Ovarian metastatic lung adenocarcinoma： a retrospective clinicopathological analysis of a consecutive 10-year case series

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Its clinicopathological features, molecular genetics, and prognosis have not been well characterized. Results Seventeen patients diagnosed with ovarian metastatic lung adenocarcinoma between 2013 and 2022 were analyzed retrospectively. All patients were non-smokers, with a median age of 46 years (range, 30 to 71y). Unilateral ovarian involvement was more frequent than bilateral involvement (58.8% vs 41.2%). Lesions presented as solid ovarian or mixed cystic and solid masses, and nearly two-thirds of the tumors (64.7%) had a diameter greater than 10 cm. More than one-third of the patients (41.2%) initially presented with pelvic masses with abdominal distension and/or lower abdominal pain, 100% of patients had elevated CA125 levels, and 76.5% had ascites. Most patients (76.5%) harbored driver gene alterations, including eight cases with EML4-AL K gene fusion and five cases with EGFR mutation. ALK rearrangement tumors showed solid adenocarcinomas (6/8,75.0%) and mucinous adenocarcinomas (2/8, 25.0%); however, acinar adenocarcinoma (6/9, 66.7%) was the most common type in non- ALK rearrangement cases. The 3-year overall survival (OS) of patients with ALK rearrangement and non-ALK rearrangement was 80.0% and 30.0%, respectively (p < 0.05). Conclusion Ovarian metastatic lung adenocarcinoma exhibits distinctive clinicopathological features and can mimic primary ovarian carcinoma. ALK rearrangement is the most common molecular alteration, and these patients have a better prognosis than those with non- ALK rearrangement. Genetic testing is recommended in all patients with ovarian metastatic lung adenocarcinoma to provide them with an opportunity to undergo targeted therapy. Ovary Metastatic carcinoma Lung cancer ALK rearrangement Figures Figure 1 Figure 2 Figure 3 Background Lung cancer is the second most common cancer and the leading cause of cancer deaths; the 5-year survival rate is only 10–20% [ 1 ]. The most frequent metastatic site in lung cancer patients is the brain, followed by the bone, liver, and adrenal glands. However, it rarely involves the ovary [ 2 ]. In previous reports, small cell carcinoma accounted for the most significant proportion of ovarian metastasis from lung carcinoma [ 3 ]. Ovarian metastatic lung adenocarcinoma is rare, and the incidence is not yet known. Moreover, driving genetic alterations (such as ALK and EGFR ) in these patients have also been only occasionally reported [ 4 , 5 ]. As a result, systematic analysis and data on ovarian metastatic lung adenocarcinoma are lacking. Lung cancer involves different metastatic sites and presents with distinct clinicopathological features depending on the primary site of involvement. For instance, intracranial metastatic lesions often present with headache, nausea, or vomiting, and metastatic bone lesions with multiple bone destruction. Thus, we hypothesized that ovarian metastatic lung adenocarcinoma might have distinct clinicopathologic features that differentiate it from other metastatic sites. In this study, we retrospectively analyzed the clinicopathological and molecular features of 17 patients with ovarian metastasis from lung adenocarcinoma together with previously reported cases with molecular information. To our best knowledge, this study explored the largest panel of ovarian metastatic lung adenocarcinoma cases with genetic alterations. Results Patients’ clinical characteristics All patients were non-smokers, with a median age of 46 years (range, 30 to 71y), and most had not reached menopause yet (13/17, 76.5%). The radiological results revealed that unilateral ovarian involvement was more frequent than bilateral ovarian involvement (58.8% vs 41.2%) (Fig. 1 A-C). Metastatic lesions presented as solid ovarian tumors or mixed cystic and solid masses. The median length of the metastatic ovarian tumors was 7.9 cm (range 1.8–16.0 cm) in the greatest dimension, and nearly two-thirds of the tumors (11/17,64.7%) were greater than 10 cm. Seven patients (7/17,41.2%) were clinically suspected of having primary ovarian cancer at the first hospital visit because they initially presented with pelvic masses with abdominal distension and/or lower abdominal pain, along with elevated CA125 levels (197.1–820.2 U/ml). In 12 cases (12/17,70.6%), the lung adenocarcinoma and metastatic ovarian tumors co-occurred. In the remaining five cases (5/17, 29.4%), metastatic ovarian tumors were discovered at 2 ~ 52 months (median three months) after the diagnosis of lung adenocarcinoma. Concurrent metastases were present in other organs in most cases (14/17, 82.4%), and multiple bone metastases were the most frequent (11/17,64.7%), followed by metastases to the brain (five cases) and adrenal gland (four cases). Out of 17 patients, 13 patients (13/17,76.5%) had ascites, and lung adenocarcinoma cells were detected in 71.4% (5/7) patients who underwent testing of the ascites fluid. The above-mentioned data are summarized in Table 1 . Table 1 Clinicopathological features of 17 cases with ovarian metastatic lung adenocarcinoma analyzed in the present study Case Age Menopause Smoking history Side Tumor size of ovary (cm) Surgery/ Biopsy (ovary) Imaging features ( ovary) Initially presented with pelvic / ovarian mass Time interval ※ Other organ involvement CA125 (U/ml) Gene alteration (site) Radiochemotherapy Targeted treatment Follow-up* A1 37 No No U L, 11.9 Biopsy solid Yes Synchronous Bone, liver, left AG, pancreas, 820.2 EML4-ALK (Ovary) Brain RT Crizotinib followed by alectinib, ensartini, and lorlatinib 68 mo, Alive A2 40 No No B L, 6.5 R, 10.3 Biopsy Mixed No 9 mo Bone, brain, right AG 49.0 EML4-ALK (Ovary and lung) Brain RT Crizotinib followed by ensartinib 67 mo, Alive A3 39 No No U R, 2.0 Biopsy solid No Synchronous Bone, brain NA EML4-ALK (Lung) PeCa Crizotinib followed by lorlatinib 24 mo, DOD A4 68 Yes No U R, 1.8 Biopsy solid No Synchronous Brain NA EML4-ALK ( Lung) Brain RT Crizotinib followed by lorlatinib 45 mo, DOD A5 54 Yes No B L, 15.0 R, 10.0 TAH-BSO solid Yes Synchronous Pleura, peritoneum 423.0 EML4-ALK (Ovary) None Crizotinib 56 mo, Alive A6 32 No No B L, 3.2 R, 4.0 Biopsy Mixed yes Synchronous Bone, brain, pericardium 709.9 EML4-ALK (Ovary and lung) None Alectinib 20 mo, Alive A7 48 No No U L, 16.0 TAH-BSO Mixed yes Synchronous Bone 796.0 EML4-ALK (Ovary) None Alectinib 6 mo, Alive A8 44 No No U R, 3.2 Biopsy solid No 52 mo None 39.0 EML4-ALK (Lung) None None 2 mo, Alive E1 44 No No U L, 14.8 Biopsy solid No Synchronous Bone, left AG, double kidney NA EGFR 19del (Lung) GCa Gefitinib 5 mo, DOD E2 46 No No B L, 14.0 R, 5.0 Biopsy solid No 3 mo Bone 362.0 EGFR 19del ( Lung) None Osimertinib 12 mo, DOD E3 71 Yes No B L, 3.3 R, 4.0 Biopsy solid Yes Synchronous Both lungs, bone, peritoneum 253.0 EGFR 19del (Ovary) PaCa None 14 mo, DOD E4 51 No No U L, 10.4 Biopsy Mixed No Synchronous Brain, bilateral AG NA EGFR L858 (Lung and ovary) PeCa Osimertinib followed by anlotinib 13 mo, Alive E5 61 Yes No U L, 15.9 Biopsy Mixed Yes Synchronous Bone, liver, spleen, peritoneum 352.0 EGFR 19del (Ovary) PaCa Osimertinib followed by anlotinib 12 mo, Alive N1 44 No No B L, 11.6 R, 7.7 Biopsy solid No 4 mo Bone, 914.0 Negative PeCi and RT None 5 mo, DOD N2 30 No No U R, 7.9 RSO Mixed No Synchronous Bone 2340.0 Negative PeCa, followed by DoCi None 10 mo, Alive N3 49 No No U R, 10.1 Biopsy solid No 2 mo None 116.2 Negative PeCa None 3 mo, Alive N4 55 No No B L, 12 R, 7 TAH-BSO Mixed Yes Synchronous None 197.1 Negative NA None 37 mo, DOD * Follow-up time was calculated from the date of diagnosis based on an ovarian sample to the date of death or last follow-up. ※ Time interval between primary lung cancer and metastasis to the ovary. Abbreviations: AG indicates adrenal gland; B, Bilateral; BSO, bilateral salpingo-oophorectomy; DoCi, Docetaxel + cisplatin; DOD, dead of disease; GCa, gemcitabine + cisplatin; L, left; mo, month; NA, not available; PaCa, paclitaxel + carboplatin; PeCa, pemetrexed + carboplatin; PeCi, Pemetrexed + cisplatin; R, right; RT, radiotherapy; RSO, Right salpingo-oophorectomy; U, unilateral; TAH-BSO total abdominal hysterectomy and bilateral salpingo-oophorectomy. Pathological features and molecular findings Four cases (4/17, 23.5%) of metastatic ovarian tumors were treated with surgical resection. The tumors were solid or mixed cystic and solid masses with smooth outer surfaces and gray or a gray-yellow appearance on the section (Fig. 1 D-E). In three cases (Case A5, A7, and N4), the tumor sections showed a small cystic cavity containing mucus, while another (Case N2) demonstrated visible necrosis and turbid liquid. Morphologically, seven cases (7/17,41.2%) were solid adenocarcinoma (Fig. 2 A), six acinar adenocarcinomas (6/17, 35.3%) (Fig. 2 B), and one micropapillary adenocarcinoma (Fig. 2 C). Another three cases were mucinous adenocarcinoma, with variable sizes of the cystic cavity, similar to primary ovarian mucinous tumor (Fig. 2 D-E). Eight cases were ALK (D5F3) positive on immunohistochemical staining (Fig. 2 G), and the majority of them were solid adenocarcinoma (6/8,75.0%), while the remaining two cases were mucinous adenocarcinoma. The majority of ALK-negative cases were acinar adenocarcinoma (6/9, 66.7%). In addition, adenocarcinoma cells were detected in the pericardial effusion in one case (case A6) (Fig. 2 H). All cases were positive for TTF-1 (16/16,100.%) (Fig. 2 F) and CK7 (17/17,100.0%). Most were NapsinA positive (11/15, 73.3%), but were negative for the remaining antibodies, including PAX-8, ER, CK20, and Villin (Table 2 ). Table 2 Morphological and immunohistochemical features of 17 ovarian metastatic lung adenocarcinoma cases Case# Morphological features Immunohistochemical characteristics ALK (D5F3) TTF-1 CK7 NapsinA PAX-8 ER CK20 Villin A1 Solid + + + ND - ND - - A2 Solid + + + + - ND ND ND A3 Solid + ND + - - - - - A4 Solid + + + + - - - - A5 Mucinous with signet-ring cells + + + + - - - - A6 Solid with Intracytoplasmic mucinous and signet-ring cells + + + + - - - - A7 Mucinous + + + + - - - - A8 Solid + + + + - - - ND E1 Acinar - + + - - ND ND ND E2 Acinar ND + + + - ND ND ND E3 Acinar - + + + - - - - E4 Acinar - + + - - - ND ND E5 Acinar - + + - - - - - N1 Acinar ND + + ND - - - - N2 Micropapillary - + + + - - - - N3 Solid - + + + -- - - - N4 Mucinous with signet-ring cells - + + + - - - - Abbreviations: ND indicates not done; +, positive; -, negative. Thirteen cases (13/17,76.5%) had driver gene alterations. Eight cases had EML4-ALK fusion genes, and five showed EGFR gene mutations (four had 19del, and one had an exon 21 L858 mutation) (Fig. 2 I). The ALK and EGFR gene mutations were mutually exclusive. Followup and survival analysis All 17 cases underwent follow-up and survival analysis. The median follow-up interval was 13 months (range, 3 to 68 mo). The treatment regimens are listed in Table 1 . The 3-year overall survival (OS) of all patients was 57.4% (Fig. 3 A).In the ALK rearrangement group, the 3-year OS was 80.0%, and seven of these patients with ALK rearrangement (7/8, 87.5%)underwent treatment with ALK inhibitors. In the non-ALK rearrangement group (including five cases with EGFR mutation and four cases with double negative for EGFR and ALK gene), the 3-year OS was only 30.0%, and four out of five cases with EGFR mutation received EGFR-targeted drug therapy.The 3-year OS was significantly different between the above two groups (p < 0.05) (Fig. 3 B). Review of the reported cases of ovarian metastatic lung adenocarcinoma with survival analysis We identified 19 cases of ovarian metastatic lung adenocarcinoma (including 12 ALK rearrangement cases and seven non-ALK rearrangement cases) with sufficient clinicopathological data in the literature [ 4 – 15 ]. The clinicopathological features of these cases and those evaluated in our study are summarized in Table 3 (also see supplemental Table S2 - 3 , which summarizes these features in detail). A total of 36 cases (including our cohort and cases from the literature) were collected, including 20 ALK rearrangement cases and 16 non-ALK rearrangement cases (including 10 cases with EGFR mutation and six cases with double negative for EGFR and ALK gene). All patients were adults with a median age of 44 years (range, 23 to 71y). The vast majority (33/36, 91.7%) were Asian and non-smokers (30/32,93.8%). There are only 14 cases of bilateral ovarian metastatic tumors (14/35, 40.0%). The maximum tumor diameter was more than 10 cm in 20 patients (20/32, 62.5%). Metastatic ovarian tumors and primary lung cancer were simultaneously detected in 19 patients (19/36, 52.8%), and nine (9/30, 30.0%) patients initially presented with pelvic or ovarian masses. Morphologically, more than two-thirds (13/19, 68.4%) of the ALK -rearrangement cases showed solid or mucinous adenocarcinoma; however, the majority of non- ALK -rearrangement cases (12/15, 80.0%) exhibited acinar adenocarcinoma or adenocarcinoma with a predominant acinar structure. The 3-year OS of all patients was 57.9% (Fig. 3 C). In the ALK rearrangement group, 77.8% of patients (14/18) were treated with ALK inhibitors, 18 cases were available for survival analysis, and the 3-year OS was 80.0%. For the non- ALK rearrangement group, the 3-year OS was only 33.7%, and eight patients were treated with EGFR inhibitors. The 3-year OS was significantly different between the two groups (p < 0.05) (Fig. 3 D). Table 3 Clinical Features of ALK rearrangement and non- ALK rearrangement ovarian metastatic lung adenocarcinoma cases in the present study and literature Characteristics ALK rearrangement group Non- ALK rearrangement group Total Number of cases 20 16 36 Median age (range) (y) 41 (range, 23 ~ 68 ) 49 (range, 29 ~ 71) 44 (range, 23 ~ 71) Origin (Asian/non-Asian) 18/2 15/1 33/3 Smoking history (yes/no) 2/14 0/16 2/30 Side (Bilateral/unilateral) 8/12 6/9 14/21 Tumor > 10 cm (yes/no) 10/8 10/4 20/12 Imaging features (Solid/Mixed) 10/8 7/7 17/15 Initially presented with pelvic/ovarian mass (yes/no) 6/10 3/11 9/21 The interval between primary lung cancer and metastasis to the ovary (Synchronous/Non-synchronous) 11/9 8/8 19/17 Morphological features (solid or mucinous/another pattern) 13/6 3/12 16/18 Discussion Metastatic ovarian lung cancer is a small probability event. Previous studies that evaluated the sites of distribution of secondary ovarian neoplasms reported that primary lung carcinoma only accounted for 0.4% of the cases, and the ovary is usually one of the multiple organs involved in advanced lung cancer [ 16 – 19 ]. In our cohort, the tumor was limited to the lung and one or both ovaries in only three cases (3/17,17.6%). In contrast, most metastatic ovarian tumors (14/17, 82.4%) were concurrent with other metastatic sites, especially the bone and brain. Whether the prognosis of cases with only ovarian metastasis is better than those with multiple organ metastases still needs further observation. Multiple bone metastases in this study were the most common event (11/17, 64.7%); however, according to the literature [ 20 ], the most common non-small cell lung cancer (NSCLC) metastatic sites are the brain, followed by the bone and liver. The reason for the above discrepancy is not known, but may be related to the limited sample size of this study. Although ovarian metastases from lung cancer are rare, clinicians should consider the possibility, especially in women with a history of lung cancer. An abdominal color ultrasound examination and serum CA125 test are recommended at a regular follow-up visit. Ovarian metastatic tumors from lung cancer potentially mimic a primary ovarian neoplasm. Usually, metastatic tumors of the ovary tend to show bilateral masses, and the most common source is the digestive tract [ 21 ]. Our results showed that in ovarian metastatic lung adenocarcinoma, unilateral ovarian metastasis was more common than bilateral (58.8% vs 41.2%). In addition, more than one-third of the patients (7/17, 41.2%) initially presented with pelvic masses with abdominal distension and/or lower abdominal pain, 100% presented with elevated CA125 level, and 76.5% of patients had ascites. The above patients had no symptoms related to primary lung cancer. Our results are consistent with those of previous reports [ 3 , 6 ]. These clinical manifestations indicate that ovarian metastatic lung cancer has unique clinicopathological features. Differentiation between metastatic ovarian lung cancer and primary ovarian tumor is essential. The two diseases have different treatment strategies, especially in ovarian metastatic lung adenocarcinoma, which mostly have driver gene ALK or EGFR changes (total mutation rate of 76.5% in our study); therefore, most of them can receive targeted therapy. Ovarian metastatic lung adenocarcinoma can mimic ovarian surface epithelial tumors, such as serous, endometrioid, mucinous, and clear cell-type tumors. A biopsy is the most accurate preoperative method for differentiation. In this study, we found that solid adenocarcinoma with mucous cells and acinar structures of varying size with high-grade nuclear features suggested metastatic carcinoma rather than high-grade serous carcinoma of the ovary. Case N2 showed micropapillary adenocarcinoma with high-grade nuclear features and necrosis; such areas of frank adenocarcinoma are exceptionally uncommon in a borderline serous tumor. In contrast, foci of microinvasion in primary serous borderline tumors are typically single cells or small discrete nests, often lying in empty spaces with no associated stromal reaction. Another three cases were mucinous adenocarcinoma, with variable sizes of the cystic cavity, similar to a primary ovarian mucinous tumor. However, small acini and irregular glands infiltrating around the capsule suggested the possibility of metastasis. Because of the above diverse morphologic spectrum of the tumor, when an ovarian tumor exhibits unusual histologic features, a metastatic ovarian tumor should always be strongly considered. Applying a panel of immunohistochemical antibodies helps to distinguish primary ovarian tumor from metastases. In our study, 100% of cases were positive for TTF-1, showing diffuse nuclear-positive tumor cells, and the NapsinA positivity rate was also as high as 73.3% (11/15). CK7 is expressed in 63% of lung tumors and only 5% of gastrointestinal tumors [ 22 ]. In contrast, gastrointestinal tumors have a high rate of CK20 expression. The combination of CK7 (+)/CK20 (-)/TTF-1 (+)/NapsinA (+) immunophenotype is highly specific for primary pulmonary tumors [ 22 , 23 ]. Positive CK20 and Villin indicate a tumor of digestive tract origin; meanwhile, the positive expression of PAX-8 and/or ER indicates a primary ovarian tumor. In addition, if ALK (D5F3) is positive, it is highly suggestive of ALK -positive lung adenocarcinoma metastasis because there is no report of ALK -positive ovarian cancer to date. The presence of driver gene alterations in ovarian metastatic lung adenocarcinoma is not an uncommon event. In the present study and literature, the majority of cases (30/36, 83.3%, including our cohort and cases from the literature) demonstrated genetic alterations, including 20 cases with ALK rearrangement and 10 cases with EGFR mutation. ALK rearrangement is common in young patients and non-smokers with lung adenocarcinoma, accounting for about 3–5% of NSCLC cases [ 24 ]. However, in our study, 55.6% (20/36) cases harbored ALK rearrangements as the most frequent molecular alteration in an unselected rare ovarian metastasis from lung adenocarcinoma. ALK inhibitors have shown excellent efficacy in treating metastatic lung adenocarcinoma, especially alectinib. In the global phase III (ALEX) study, when alectinib was used as the first-line treatment for patients with advanced ALK -positive NSCLC, it showed excellent efficacy, with progression-free survival (PFS) as high as 34.8 months [ 25 , 26 ].According to the results of the present study, the 3-year OS was significantly better in ALK -positive than ALK -negative patients (80.0% vs 33.7%, P < 0.05). Nevertheless, further follow-up and observation are required to evaluate the long-term efficacy of ALK inhibitors, along with the collection of more cases for further study. We also recommend that all patients with ovarian metastatic lung adenocarcinoma should undergo genetic mutation testing, particularly for the ALK and EGFR genes, to provide patients with an opportunity for receiving targeted therapy. The mechanism of lung cancer metastasis to the ovary has not been elucidated. An increasing trend of young lung cancer patients with ovarian metastases may be attributed to vigorous ovarian function as well as abundant lymphatic and blood supply in young patients [ 3 ]. In each ovulatory cycle, follicle rupture and repair are associated with the development of an inflammatory microenvironment rich in inflammatory cells, chemokines, and growth factors [ 27 ]. The inflammatory milieu of the ovulatory wound site may not only promote migration and adhesion of malignant cells to the ovary but also offers tumorigenic factors that support malignant transformation and maintain cancer cell survival [ 28 ]. Moreover, the defects formed on the ovarian surface during ovulation may also promote tumor cell cultivation [ 29 ]. In our study, more than three-quarters (13/17, 76.5%)of the patients had not reached menopause, with a median age of 46 years. The vast majority of patients (13/17,76.5%) had ascites, and ascites cancer cells were detected in five out of seven patients. The ovaries are located in the lower part of the pelvic and abdominal cavity, and this may make them prone to cancer cell implantation and metastasis. The mechanism of ovarian metastasis from lung cancer may involve multiple transfer mechanisms and needs more case accumulation and in-depth studies in the future. Conclusions In conclusion, ovarian metastatic lung adenocarcinoma is a rare event and clinicopathologically may mimic primary ovarian tumors. Combining medical history and morphology with a panel of immunohistochemistry is an essential tool for differential diagnosis. ALK rearrangement is the most common molecular alteration. These patients also exhibit a better prognosis than those with non- ALK rearrangement. Moreover, this study may also help clinicians and pathologists to better recognize patients presenting with rare lung adenocarcinoma metastasis in clinical practice. Methods Case selection All the included 17 cases were diagnosed with lung adenocarcinoma metastasis to the ovary between 2013 and 2022. The diagnosis was confirmed in 13 cases through ovarian biopsy specimens, and four cases through surgical excision specimens ( including three total abdominal hysterectomy and bilateral salpingo-oophorectomy, and one right salpingo-oophorectomy). All cases were reviewed by two senior pathologists who verified the diagnosis. Detailed clinical information, such as age, clinical course, symptoms, laboratory tests, imaging findings, and treatment details, were collected from electronic medical records. Follow-up data were obtained through medical records and telephone interviews. This study was approved by the Ethics Committee of Fujian Cancer Hospital. Immunohistochemical Staining Four-micrometer thick tissue sections cut from 10% formalin-fixed, paraffin-embedded tissue blocks were used for immunostaining (Ventana Autostainer BenchMark ULTRA). The antibodies used were as follows: ALK (D5F3), TTF-1 (SPT24, Leica), CK7 (EP16, Zhongshan, China), NapsinA (IP64, Zhongshan), PAX-8 (EP298, Maixin, China), ER (SP1, Maixin), CK20 (EP23, Zhongshan), Villin (EP163, Zhongshan). Positive and negative controls were employed in this study. EGFR mutation and ALK rearrangement analysis The mutational status of ALK and EGFR (exons 18, 19, 20, and 21) was determined by TaqMan-based real-time PCR using the EGFR/ALK/ROS1 Gene Mutation Joint Detection kit (Amoy Diagnostics Co., Ltd., Xiamen, China) or Next-generation sequencing (solid tumors 56 gene detection kit, Burning Rock Biotech Ltd., Guangzhou, China) (supplemental Table S1 ). Statistical and Survival Analysis Follow-up period was calculated from the date of diagnosis from an ovarian sample to the date of death or last follow-up. SPSS software (version 23.0; SPSS Inc.) was used for the analysis. Survival duration was determined using Kaplan-Meier analysis. A value of P < 0.05 was considered statistically significant. Abbreviations ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; EML4, Echinoderm microtubule-associated protein-like 4; NSCLC, non-small cell lung cancers; OS, overall survival Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Availability of data and materials All data generated or analyzed during the current study are included in this published article. Competing interests The authors declare that they have no competing interests. Funding This study was supported by the Natural Science Foundation of Fujian Province (2022J01432), Excellent Young Talents Funding program of Fujian Cancer Hospital(2020YNYQ003), High-level Talents Training Program of Fujian Cancer Hospital(2022YNG16), and the Joint Funds for the Innovation of Science and Technology, Fujian province (2021Y9195). Authors’ contributions WL and DH conceived and designed the study. 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Supplementary Files SupplementalTableS1.docx Supplemental Table S 1. Gene panel used in this study (n=56) SupplementalTableS2.docx Supplemental Table S2. Clinical features of cases with ALK rearrangement ovarian metastatic lung adenocarcinoma in the present study and literature SupplementalTableS3.docx Supplemental Table S3. Clinical Features of cases with non-ALK rearrangement ovarian metastatic lung adenocarcinoma in the present study and literature Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2685548","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":237751369,"identity":"8b0c5e6b-6dfa-4f7c-8924-53520577901f","order_by":0,"name":"Wei Liu","email":"","orcid":"","institution":"Department of Pathology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Liu","suffix":""},{"id":237751370,"identity":"2efa8e34-eba2-429d-8091-a8c7f7e2ff77","order_by":1,"name":"Yan-mei Cui","email":"","orcid":"","institution":"Department of Pathology, People`s Hospital Affiliated to Fujian University of Traditional Chinese Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yan-mei","middleName":"","lastName":"Cui","suffix":""},{"id":237751371,"identity":"ec9752dd-0d7d-47a0-862a-7d87a39119fa","order_by":2,"name":"Xiao-jiang Wang","email":"","orcid":"","institution":"Department of Molecular Pathology Laboratory, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xiao-jiang","middleName":"","lastName":"Wang","suffix":""},{"id":237751372,"identity":"6d22e2b6-5f7c-4b99-9128-92983bea4866","order_by":3,"name":"Xian-dong Lin","email":"","orcid":"","institution":"Laboratory of Radiation Oncology and Radiobiology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xian-dong","middleName":"","lastName":"Lin","suffix":""},{"id":237751373,"identity":"c74ac609-0b7f-465c-bec7-d3bcdd0598bd","order_by":4,"name":"Li-bin Zhang","email":"","orcid":"","institution":"Medical Records Room, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Li-bin","middleName":"","lastName":"Zhang","suffix":""},{"id":237751374,"identity":"b19fb3ba-a94d-4eec-9f01-f5508db19981","order_by":5,"name":"Jing-cheng Liu","email":"","orcid":"","institution":"Department of Pathology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jing-cheng","middleName":"","lastName":"Liu","suffix":""},{"id":237751375,"identity":"450de30d-1310-4806-9a87-c189a87d6ce0","order_by":6,"name":"Qing-hu Lyu","email":"","orcid":"","institution":"Department of Nuclear Medicine, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Qing-hu","middleName":"","lastName":"Lyu","suffix":""},{"id":237751376,"identity":"1eff60fd-fb43-41aa-be83-3e177c433a6a","order_by":7,"name":"Wei Chen","email":"","orcid":"","institution":"Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Chen","suffix":""},{"id":237751377,"identity":"cf49a515-320a-491f-9ece-360155c8d587","order_by":8,"name":"Dan Hu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvUlEQVRIiWNgGAWjYBACAzCqkGMG83iI13LGmFQtjG3GDMRrMZdI3vi5cJ4Bu+6MBMYHb9sY5M0JabGckVYsPXObAbPZjQRmw7ltDIY7Gwg57EaOgTTvtj8gLWzSvG0MCQYHCGsx/s07B2wL+29itZhJ8zaAtbAxE6flzLMya55jQC1nHjZLzjknYbiBoJbjyZtv89QYJJsdTz744U2ZjTxBW2AgmYGBsQFISxCpHgjsiFc6CkbBKBgFIw4AAI14O1MpDTJ2AAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-6288-816X","institution":"Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Dan","middleName":"","lastName":"Hu","suffix":""}],"badges":[],"createdAt":"2023-03-13 05:59:30","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2685548/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2685548/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":44326237,"identity":"f9dd0504-54b8-420e-b7de-87c224889978","added_by":"auto","created_at":"2023-10-09 22:11:22","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":2970611,"visible":true,"origin":"","legend":"\u003cp\u003eClinical and radiological features of ovarian metastatic lung adenocarcinoma (Case A7). A, Positron emission tomography-computed tomography (PET-CT) scan shows a nodular mass with a diameter of 1.0 cm in the posterior apex of the left lung with unclear boundaries. B, A huge mixed cystic and solid mass is visible in the pelvic cavity with a maximum cross-section of 13.1 cm×9.5 cm. C, In addition to the lung and ovarian lesions, lymph node metastases in the mediastinum and multiple bone metastases were also observed. D, The capsule of the pelvic mass appears intact with a smooth surface. E, The tumor sections showed a small cystic cavity containing mucus.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-2685548/v1/d9f0a23f0c20099196cc12dc.jpeg"},{"id":44326238,"identity":"f49158f9-eff9-4d76-9631-bbf73b07a93e","added_by":"auto","created_at":"2023-10-09 22:11:22","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":4004940,"visible":true,"origin":"","legend":"\u003cp\u003eHistological subtypes of ovarian metastatic lung adenocarcinoma. A, Solid with signet-ring cells (Case A6). B, Acinar subtype (Case E5). C, Micropapillary subtype (Case N2). D, Mucinous with signet-ring cells (Case A5). E, Mucinous subtype (Case A7). F, Tumor cells showing positive staining for TTF-1 (Case A7). G, Tumor cells showing positive staining for ALK (D5F3) (Case A7). H, Adenocarcinoma cells in the pericardial effusion (Case A6). I, The patient had the EGFR 19del mutation and developed the T790M mutation four months after targeted therapy (Case E1). (Original magnification: x\u003cimg height=\"16\" src=\"file:///C:/Users/smt8250/AppData/Local/Temp/msohtmlclip1/01/clip_image002.gif\" width=\"10\"/\u003e40 [E, F, G]; ×100 [C, B, D]; ×400 [A, H]).\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-2685548/v1/b214326c7dc600e793ec0556.jpeg"},{"id":44326235,"identity":"d3affa59-439a-42d4-aae9-9447435e1f3d","added_by":"auto","created_at":"2023-10-09 22:11:21","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":90213,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier survival and log-rank analysis of patients with ovarian metastatic lung adenocarcinoma. A, In the present study, the 3-year overall survival (OS) of patients was 57.4%. B, Kaplan-Meier curves demonstrate significantly better OS of patients with \u003cem\u003eALK\u003c/em\u003e rearrangement than those with non-\u003cem\u003eALK\u003c/em\u003e rearrangement. C, In the present study and cases reported in the literature, the 3-year OS of all patients was 57.9%. D, Patients with \u003cem\u003eALK \u003c/em\u003erearrangement show a better OS than those with non-\u003cem\u003eALK \u003c/em\u003erearrangement.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2685548/v1/315950db9ea526f9a770c0a8.jpg"},{"id":45429707,"identity":"8cf1b64f-cd9b-4750-9ff0-ea47d1d3ee41","added_by":"auto","created_at":"2023-10-30 07:53:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":960525,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2685548/v1/3a63948c-b4e9-4a10-a88d-0118176d14e2.pdf"},{"id":44326233,"identity":"20e9d463-eafb-4d09-924e-3b556977a6c2","added_by":"auto","created_at":"2023-10-09 22:11:21","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":22115,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplemental Table S 1\u003c/strong\u003e. Gene panel used in this study (n=56)\u003c/p\u003e","description":"","filename":"SupplementalTableS1.docx","url":"https://assets-eu.researchsquare.com/files/rs-2685548/v1/d92c4b93f0747760b8a5da7f.docx"},{"id":44326651,"identity":"3bf70c23-933c-41e3-a50c-4b01aa40e214","added_by":"auto","created_at":"2023-10-09 22:19:21","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":30332,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplemental Table S2. \u003c/strong\u003eClinical features of cases with ALK rearrangement ovarian metastatic lung adenocarcinoma in the present study and literature\u003c/p\u003e","description":"","filename":"SupplementalTableS2.docx","url":"https://assets-eu.researchsquare.com/files/rs-2685548/v1/bca7ebb25881e6d0736dacaf.docx"},{"id":44326652,"identity":"654a00da-9292-4baf-b62e-bd466929e0f6","added_by":"auto","created_at":"2023-10-09 22:19:21","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":29490,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplemental Table S3\u003c/strong\u003e. Clinical Features of cases with non-ALK rearrangement ovarian metastatic lung adenocarcinoma in the present study and literature\u003c/p\u003e","description":"","filename":"SupplementalTableS3.docx","url":"https://assets-eu.researchsquare.com/files/rs-2685548/v1/a9e5c2fd098bb96270333581.docx"}],"financialInterests":"","formattedTitle":"Ovarian metastatic lung adenocarcinoma： a retrospective clinicopathological analysis of a consecutive 10-year case series","fulltext":[{"header":"Background","content":"\u003cp\u003eLung cancer is the second most common cancer and the leading cause of cancer deaths; the 5-year survival rate is only 10\u0026ndash;20% [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The most frequent metastatic site in lung cancer patients is the brain, followed by the bone, liver, and adrenal glands. However, it rarely involves the ovary [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn previous reports, small cell carcinoma accounted for the most significant proportion of ovarian metastasis from lung carcinoma [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Ovarian metastatic lung adenocarcinoma is rare, and the incidence is not yet known. Moreover, driving genetic alterations (such as \u003cem\u003eALK\u003c/em\u003e and \u003cem\u003eEGFR\u003c/em\u003e) in these patients have also been only occasionally reported [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. As a result, systematic analysis and data on ovarian metastatic lung adenocarcinoma are lacking.\u003c/p\u003e \u003cp\u003eLung cancer involves different metastatic sites and presents with distinct clinicopathological features depending on the primary site of involvement. For instance, intracranial metastatic lesions often present with headache, nausea, or vomiting, and metastatic bone lesions with multiple bone destruction. Thus, we hypothesized that ovarian metastatic lung adenocarcinoma might have distinct clinicopathologic features that differentiate it from other metastatic sites.\u003c/p\u003e \u003cp\u003eIn this study, we retrospectively analyzed the clinicopathological and molecular features of 17 patients with ovarian metastasis from lung adenocarcinoma together with previously reported cases with molecular information. To our best knowledge, this study explored the largest panel of ovarian metastatic lung adenocarcinoma cases with genetic alterations.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u0026rsquo; clinical characteristics\u003c/h2\u003e \u003cp\u003eAll patients were non-smokers, with a median age of 46 years (range, 30 to 71y), and most had not reached menopause yet (13/17, 76.5%). The radiological results revealed that unilateral ovarian involvement was more frequent than bilateral ovarian involvement (58.8% \u003cem\u003evs\u003c/em\u003e 41.2%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA-C). Metastatic lesions presented as solid ovarian tumors or mixed cystic and solid masses. The median length of the metastatic ovarian tumors was 7.9 cm (range 1.8\u0026ndash;16.0 cm) in the greatest dimension, and nearly two-thirds of the tumors (11/17,64.7%) were greater than 10 cm.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eSeven patients (7/17,41.2%) were clinically suspected of having primary ovarian cancer at the first hospital visit because they initially presented with pelvic masses with abdominal distension and/or lower abdominal pain, along with elevated CA125 levels (197.1\u0026ndash;820.2 U/ml). In 12 cases (12/17,70.6%), the lung adenocarcinoma and metastatic ovarian tumors co-occurred. In the remaining five cases (5/17, 29.4%), metastatic ovarian tumors were discovered at 2\u0026thinsp;~\u0026thinsp;52 months (median three months) after the diagnosis of lung adenocarcinoma. Concurrent metastases were present in other organs in most cases (14/17, 82.4%), and multiple bone metastases were the most frequent (11/17,64.7%), followed by metastases to the brain (five cases) and adrenal gland (four cases). Out of 17 patients, 13 patients (13/17,76.5%) had ascites, and lung adenocarcinoma cells were detected in 71.4% (5/7) patients who underwent testing of the ascites fluid. The above-mentioned data are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinicopathological features of 17 cases with ovarian metastatic lung adenocarcinoma analyzed in the present study\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"16\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c15\" colnum=\"15\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c16\" colnum=\"16\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCase\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMenopause\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSmoking history\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSide\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTumor size of ovary\u003c/p\u003e \u003cp\u003e(cm)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSurgery/ Biopsy (ovary)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eImaging features\u003c/p\u003e \u003cp\u003e( ovary)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eInitially presented with pelvic / ovarian mass\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eTime interval\u003csup\u003e※\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eOther organ involvement\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eCA125 (U/ml)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003eGene alteration\u003c/p\u003e \u003cp\u003e(site)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c14\"\u003e \u003cp\u003eRadiochemotherapy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c15\"\u003e \u003cp\u003eTargeted treatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c16\"\u003e \u003cp\u003eFollow-up*\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eL, 11.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eBiopsy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003esolid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSynchronous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eBone, liver, left AG, pancreas,\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e820.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cem\u003eEML4-ALK\u003c/em\u003e\u003c/p\u003e \u003cp\u003e(Ovary)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eBrain RT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eCrizotinib followed by alectinib, ensartini, and lorlatinib\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e68 mo,\u003c/p\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eL, 6.5\u003c/p\u003e \u003cp\u003eR, 10.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eBiopsy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMixed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e9 mo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eBone, brain, right AG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e49.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cem\u003eEML4-ALK\u003c/em\u003e\u003c/p\u003e \u003cp\u003e(Ovary and lung)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eBrain RT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eCrizotinib followed by ensartinib\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e67 mo, Alive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eR, 2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eBiopsy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003esolid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSynchronous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eBone, brain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cem\u003eEML4-ALK\u003c/em\u003e\u003c/p\u003e \u003cp\u003e(Lung)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003ePeCa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eCrizotinib followed by lorlatinib\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e24 mo, DOD\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eR, 1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eBiopsy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003esolid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSynchronous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eBrain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cem\u003eEML4-ALK\u003c/em\u003e\u003c/p\u003e \u003cp\u003e( Lung)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eBrain RT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eCrizotinib followed by lorlatinib\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e45 mo, DOD\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eL, 15.0\u003c/p\u003e \u003cp\u003eR, 10.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTAH-BSO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003esolid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSynchronous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003ePleura, peritoneum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e423.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cem\u003eEML4-ALK\u003c/em\u003e\u003c/p\u003e \u003cp\u003e(Ovary)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eCrizotinib\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e56 mo, Alive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eL, 3.2\u003c/p\u003e \u003cp\u003eR, 4.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eBiopsy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMixed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSynchronous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eBone, brain, pericardium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e709.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cem\u003eEML4-ALK\u003c/em\u003e\u003c/p\u003e \u003cp\u003e(Ovary and lung)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlectinib\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e20 mo, Alive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eL, 16.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTAH-BSO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMixed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSynchronous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eBone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e796.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cem\u003eEML4-ALK\u003c/em\u003e\u003c/p\u003e \u003cp\u003e(Ovary)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlectinib\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e6 mo, Alive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eR, 3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eBiopsy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003esolid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e52 mo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e39.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cem\u003eEML4-ALK\u003c/em\u003e\u003c/p\u003e \u003cp\u003e(Lung)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e2 mo, Alive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eL, 14.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eBiopsy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003esolid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSynchronous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eBone, left AG, double kidney\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cem\u003eEGFR\u003c/em\u003e 19del\u003c/p\u003e \u003cp\u003e(Lung)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eGCa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eGefitinib\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e5 mo, DOD\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eL, 14.0\u003c/p\u003e \u003cp\u003eR, 5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eBiopsy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003esolid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e3 mo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eBone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e362.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cem\u003eEGFR\u003c/em\u003e 19del\u003c/p\u003e \u003cp\u003e( Lung)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eOsimertinib\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e12 mo, DOD\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eL, 3.3\u003c/p\u003e \u003cp\u003eR, 4.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eBiopsy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003esolid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSynchronous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eBoth lungs, bone, peritoneum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e253.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cem\u003eEGFR\u003c/em\u003e 19del (Ovary)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003ePaCa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e14 mo, DOD\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eL, 10.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eBiopsy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMixed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSynchronous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eBrain, bilateral AG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cem\u003eEGFR\u003c/em\u003e L858\u003c/p\u003e \u003cp\u003e(Lung and ovary)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003ePeCa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eOsimertinib followed by anlotinib\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e13 mo, Alive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eL, 15.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eBiopsy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMixed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSynchronous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eBone, liver, spleen, peritoneum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e352.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cem\u003eEGFR\u003c/em\u003e 19del\u003c/p\u003e \u003cp\u003e(Ovary)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003ePaCa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eOsimertinib followed by anlotinib\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e12 mo, Alive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eL, 11.6\u003c/p\u003e \u003cp\u003eR, 7.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eBiopsy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003esolid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e4 mo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eBone,\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e914.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003ePeCi and RT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e5 mo, DOD\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eR, 7.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRSO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMixed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSynchronous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eBone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e2340.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003ePeCa, followed by DoCi\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e10 mo, Alive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eR, 10.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eBiopsy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003esolid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2 mo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e116.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003ePeCa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e3 mo, Alive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eL, 12\u003c/p\u003e \u003cp\u003eR, 7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTAH-BSO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMixed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSynchronous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e197.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e37 mo, DOD\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"16\"\u003e\u003csup\u003e*\u003c/sup\u003eFollow-up time was calculated from the date of diagnosis based on an ovarian sample to the date of death or last follow-up.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"16\"\u003e\u003csup\u003e※\u003c/sup\u003eTime interval between primary lung cancer and metastasis to the ovary.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"16\"\u003eAbbreviations: AG indicates adrenal gland; B, Bilateral; BSO, bilateral salpingo-oophorectomy; DoCi, Docetaxel\u0026thinsp;+\u0026thinsp;cisplatin; DOD, dead of disease; GCa, gemcitabine\u0026thinsp;+\u0026thinsp;cisplatin; L, left; mo, month; NA, not available; PaCa, paclitaxel\u0026thinsp;+\u0026thinsp;carboplatin; PeCa, pemetrexed\u0026thinsp;+\u0026thinsp;carboplatin; PeCi, Pemetrexed\u0026thinsp;+\u0026thinsp;cisplatin; R, right; RT, radiotherapy; RSO, Right salpingo-oophorectomy; U, unilateral; TAH-BSO total abdominal hysterectomy and bilateral salpingo-oophorectomy.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003ePathological features and molecular findings\u003c/h2\u003e \u003cp\u003eFour cases (4/17, 23.5%) of metastatic ovarian tumors were treated with surgical resection. The tumors were solid or mixed cystic and solid masses with smooth outer surfaces and gray or a gray-yellow appearance on the section (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD-E). In three cases (Case A5, A7, and N4), the tumor sections showed a small cystic cavity containing mucus, while another (Case N2) demonstrated visible necrosis and turbid liquid.\u003c/p\u003e \u003cp\u003eMorphologically, seven cases (7/17,41.2%) were solid adenocarcinoma (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA), six acinar adenocarcinomas (6/17, 35.3%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB), and one micropapillary adenocarcinoma (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC). Another three cases were mucinous adenocarcinoma, with variable sizes of the cystic cavity, similar to primary ovarian mucinous tumor (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD-E). Eight cases were ALK (D5F3) positive on immunohistochemical staining (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eG), and the majority of them were solid adenocarcinoma (6/8,75.0%), while the remaining two cases were mucinous adenocarcinoma. The majority of ALK-negative cases were acinar adenocarcinoma (6/9, 66.7%). In addition, adenocarcinoma cells were detected in the pericardial effusion in one case (case A6) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eH). All cases were positive for TTF-1 (16/16,100.%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eF) and CK7 (17/17,100.0%). Most were NapsinA positive (11/15, 73.3%), but were negative for the remaining antibodies, including PAX-8, ER, CK20, and Villin (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMorphological and immunohistochemical features of 17 ovarian metastatic lung adenocarcinoma cases\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCase#\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMorphological features\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"8\" nameend=\"c10\" namest=\"c3\"\u003e \u003cp\u003eImmunohistochemical characteristics\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eALK (D5F3)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTTF-1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCK7\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNapsinA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePAX-8\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eER\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCK20\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eVillin\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSolid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSolid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSolid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSolid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMucinous with signet-ring cells\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSolid with Intracytoplasmic\u003c/p\u003e \u003cp\u003emucinous and signet-ring cells\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMucinous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSolid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAcinar\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAcinar\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAcinar\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAcinar\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAcinar\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAcinar\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMicropapillary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSolid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMucinous with signet-ring cells\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003eAbbreviations: ND indicates not done; +, positive; -, negative.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThirteen cases (13/17,76.5%) had driver gene alterations. Eight cases had \u003cem\u003eEML4-ALK\u003c/em\u003e fusion genes, and five showed \u003cem\u003eEGFR\u003c/em\u003e gene mutations (four had 19del, and one had an exon 21 L858 mutation) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eI). The \u003cem\u003eALK\u003c/em\u003e and \u003cem\u003eEGFR\u003c/em\u003e gene mutations were mutually exclusive.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eFollowup and survival analysis\u003c/h2\u003e \u003cp\u003eAll 17 cases underwent follow-up and survival analysis. The median follow-up interval was 13 months (range, 3 to 68 mo). The treatment regimens are listed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The 3-year overall survival (OS) of all patients was 57.4% (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA).In the ALK rearrangement group, the 3-year OS was 80.0%, and seven of these patients with ALK rearrangement (7/8, 87.5%)underwent treatment with ALK inhibitors. In the non-ALK rearrangement group (including five cases with EGFR mutation and four cases with double negative for EGFR and ALK gene), the 3-year OS was only 30.0%, and four out of five cases with EGFR mutation received EGFR-targeted drug therapy.The 3-year OS was significantly different between the above two groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eReview of the reported cases of ovarian metastatic lung adenocarcinoma with survival analysis\u003c/h2\u003e \u003cp\u003eWe identified 19 cases of ovarian metastatic lung adenocarcinoma (including 12 \u003cem\u003eALK\u003c/em\u003e rearrangement cases and seven non-ALK rearrangement cases) with sufficient clinicopathological data in the literature [\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The clinicopathological features of these cases and those evaluated in our study are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e (also see supplemental Table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e-\u003cspan refid=\"MOESM3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, which summarizes these features in detail). A total of 36 cases (including our cohort and cases from the literature) were collected, including 20 ALK rearrangement cases and 16 non-ALK rearrangement cases (including 10 cases with EGFR mutation and six cases with double negative for EGFR and ALK gene). All patients were adults with a median age of 44 years (range, 23 to 71y). The vast majority (33/36, 91.7%) were Asian and non-smokers (30/32,93.8%). There are only 14 cases of bilateral ovarian metastatic tumors (14/35, 40.0%). The maximum tumor diameter was more than 10 cm in 20 patients (20/32, 62.5%). Metastatic ovarian tumors and primary lung cancer were simultaneously detected in 19 patients (19/36, 52.8%), and nine (9/30, 30.0%) patients initially presented with pelvic or ovarian masses. Morphologically, more than two-thirds (13/19, 68.4%) of the \u003cem\u003eALK\u003c/em\u003e-rearrangement cases showed solid or mucinous adenocarcinoma; however, the majority of non-\u003cem\u003eALK\u003c/em\u003e-rearrangement cases (12/15, 80.0%) exhibited acinar adenocarcinoma or adenocarcinoma with a predominant acinar structure. The 3-year OS of all patients was 57.9% (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC). In the \u003cem\u003eALK\u003c/em\u003e rearrangement group, 77.8% of patients (14/18) were treated with ALK inhibitors, 18 cases were available for survival analysis, and the 3-year OS was 80.0%. For the non-\u003cem\u003eALK\u003c/em\u003e rearrangement group, the 3-year OS was only 33.7%, and eight patients were treated with EGFR inhibitors. The 3-year OS was significantly different between the two groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eD).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical Features of \u003cem\u003eALK\u003c/em\u003e rearrangement and non-\u003cem\u003eALK\u003c/em\u003e rearrangement ovarian metastatic lung adenocarcinoma cases in the present study and literature\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eALK\u003c/em\u003e rearrangement group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-\u003cem\u003eALK\u003c/em\u003e rearrangement group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of cases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian age (range) (y)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41 (range, 23\u0026thinsp;~\u0026thinsp;68 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49 (range, 29\u0026thinsp;~\u0026thinsp;71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44 (range, 23\u0026thinsp;~\u0026thinsp;71)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOrigin (Asian/non-Asian)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18/2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15/1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33/3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking history (yes/no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2/14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0/16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2/30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSide (Bilateral/unilateral)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8/12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6/9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14/21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor\u0026thinsp;\u0026gt;\u0026thinsp;10 cm (yes/no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10/8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10/4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20/12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImaging features (Solid/Mixed)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10/8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7/7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17/15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInitially presented with pelvic/ovarian mass (yes/no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6/10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3/11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9/21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThe interval between primary lung cancer and metastasis to the ovary (Synchronous/Non-synchronous)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11/9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8/8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19/17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMorphological features (solid or mucinous/another pattern)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13/6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3/12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16/18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eMetastatic ovarian lung cancer is a small probability event. Previous studies that evaluated the sites of distribution of secondary ovarian neoplasms reported that primary lung carcinoma only accounted for 0.4% of the cases, and the ovary is usually one of the multiple organs involved in advanced lung cancer [\u003cspan additionalcitationids=\"CR17 CR18\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e–\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In our cohort, the tumor was limited to the lung and one or both ovaries in only three cases (3/17,17.6%). In contrast, most metastatic ovarian tumors (14/17, 82.4%) were concurrent with other metastatic sites, especially the bone and brain. Whether the prognosis of cases with only ovarian metastasis is better than those with multiple organ metastases still needs further observation. Multiple bone metastases in this study were the most common event (11/17, 64.7%); however, according to the literature [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], the most common non-small cell lung cancer (NSCLC) metastatic sites are the brain, followed by the bone and liver. The reason for the above discrepancy is not known, but may be related to the limited sample size of this study. Although ovarian metastases from lung cancer are rare, clinicians should consider the possibility, especially in women with a history of lung cancer. An abdominal color ultrasound examination and serum CA125 test are recommended at a regular follow-up visit.\u003c/p\u003e \u003cp\u003eOvarian metastatic tumors from lung cancer potentially mimic a primary ovarian neoplasm. Usually, metastatic tumors of the ovary tend to show bilateral masses, and the most common source is the digestive tract [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Our results showed that in ovarian metastatic lung adenocarcinoma, unilateral ovarian metastasis was more common than bilateral (58.8% \u003cem\u003evs\u003c/em\u003e 41.2%). In addition, more than one-third of the patients (7/17, 41.2%) initially presented with pelvic masses with abdominal distension and/or lower abdominal pain, 100% presented with elevated CA125 level, and 76.5% of patients had ascites. The above patients had no symptoms related to primary lung cancer. Our results are consistent with those of previous reports [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. These clinical manifestations indicate that ovarian metastatic lung cancer has unique clinicopathological features.\u003c/p\u003e \u003cp\u003eDifferentiation between metastatic ovarian lung cancer and primary ovarian tumor is essential. The two diseases have different treatment strategies, especially in ovarian metastatic lung adenocarcinoma, which mostly have driver gene \u003cem\u003eALK\u003c/em\u003e or \u003cem\u003eEGFR\u003c/em\u003e changes (total mutation rate of 76.5% in our study); therefore, most of them can receive targeted therapy. Ovarian metastatic lung adenocarcinoma can mimic ovarian surface epithelial tumors, such as serous, endometrioid, mucinous, and clear cell-type tumors. A biopsy is the most accurate preoperative method for differentiation. In this study, we found that solid adenocarcinoma with mucous cells and acinar structures of varying size with high-grade nuclear features suggested metastatic carcinoma rather than high-grade serous carcinoma of the ovary. Case N2 showed micropapillary adenocarcinoma with high-grade nuclear features and necrosis; such areas of frank adenocarcinoma are exceptionally uncommon in a borderline serous tumor. In contrast, foci of microinvasion in primary serous borderline tumors are typically single cells or small discrete nests, often lying in empty spaces with no associated stromal reaction. Another three cases were mucinous adenocarcinoma, with variable sizes of the cystic cavity, similar to a primary ovarian mucinous tumor. However, small acini and irregular glands infiltrating around the capsule suggested the possibility of metastasis. Because of the above diverse morphologic spectrum of the tumor, when an ovarian tumor exhibits unusual histologic features, a metastatic ovarian tumor should always be strongly considered.\u003c/p\u003e \u003cp\u003eApplying a panel of immunohistochemical antibodies helps to distinguish primary ovarian tumor from metastases. In our study, 100% of cases were positive for TTF-1, showing diffuse nuclear-positive tumor cells, and the NapsinA positivity rate was also as high as 73.3% (11/15). CK7 is expressed in 63% of lung tumors and only 5% of gastrointestinal tumors [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In contrast, gastrointestinal tumors have a high rate of CK20 expression. The combination of CK7 (+)/CK20 (-)/TTF-1 (+)/NapsinA (+) immunophenotype is highly specific for primary pulmonary tumors [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Positive CK20 and Villin indicate a tumor of digestive tract origin; meanwhile, the positive expression of PAX-8 and/or ER indicates a primary ovarian tumor. In addition, if ALK (D5F3) is positive, it is highly suggestive of \u003cem\u003eALK\u003c/em\u003e-positive lung adenocarcinoma metastasis because there is no report of \u003cem\u003eALK\u003c/em\u003e-positive ovarian cancer to date.\u003c/p\u003e \u003cp\u003eThe presence of driver gene alterations in ovarian metastatic lung adenocarcinoma is not an uncommon event. In the present study and literature, the majority of cases (30/36, 83.3%, including our cohort and cases from the literature) demonstrated genetic alterations, including 20 cases with \u003cem\u003eALK\u003c/em\u003e rearrangement and 10 cases with \u003cem\u003eEGFR\u003c/em\u003e mutation. \u003cem\u003eALK\u003c/em\u003e rearrangement is common in young patients and non-smokers with lung adenocarcinoma, accounting for about 3–5% of NSCLC cases [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. However, in our study, 55.6% (20/36) cases harbored \u003cem\u003eALK\u003c/em\u003e rearrangements as the most frequent molecular alteration in an unselected rare ovarian metastasis from lung adenocarcinoma. ALK inhibitors have shown excellent efficacy in treating metastatic lung adenocarcinoma, especially alectinib. In the global phase III (ALEX) study, when alectinib was used as the first-line treatment for patients with advanced \u003cem\u003eALK\u003c/em\u003e-positive NSCLC, it showed excellent efficacy, with progression-free survival (PFS) as high as 34.8 months [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].According to the results of the present study, the 3-year OS was significantly better in \u003cem\u003eALK\u003c/em\u003e-positive than \u003cem\u003eALK\u003c/em\u003e-negative patients (80.0% \u003cem\u003evs\u003c/em\u003e 33.7%, P \u0026lt; 0.05). Nevertheless, further follow-up and observation are required to evaluate the long-term efficacy of \u003cem\u003eALK\u003c/em\u003e inhibitors, along with the collection of more cases for further study. We also recommend that all patients with ovarian metastatic lung adenocarcinoma should undergo genetic mutation testing, particularly for the \u003cem\u003eALK\u003c/em\u003e and \u003cem\u003eEGFR\u003c/em\u003e genes, to provide patients with an opportunity for receiving targeted therapy.\u003c/p\u003e \u003cp\u003eThe mechanism of lung cancer metastasis to the ovary has not been elucidated. An increasing trend of young lung cancer patients with ovarian metastases may be attributed to vigorous ovarian function as well as abundant lymphatic and blood supply in young patients [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In each ovulatory cycle, follicle rupture and repair are associated with the development of an inflammatory microenvironment rich in inflammatory cells, chemokines, and growth factors [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. The inflammatory milieu of the ovulatory wound site may not only promote migration and adhesion of malignant cells to the ovary but also offers tumorigenic factors that support malignant transformation and maintain cancer cell survival [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Moreover, the defects formed on the ovarian surface during ovulation may also promote tumor cell cultivation [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. In our study, more than three-quarters (13/17, 76.5%)of the patients had not reached menopause, with a median age of 46 years. The vast majority of patients (13/17,76.5%) had ascites, and ascites cancer cells were detected in five out of seven patients. The ovaries are located in the lower part of the pelvic and abdominal cavity, and this may make them prone to cancer cell implantation and metastasis. The mechanism of ovarian metastasis from lung cancer may involve multiple transfer mechanisms and needs more case accumulation and in-depth studies in the future.\u003c/p\u003e "},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion, ovarian metastatic lung adenocarcinoma is a rare event and clinicopathologically may mimic primary ovarian tumors. Combining medical history and morphology with a panel of immunohistochemistry is an essential tool for differential diagnosis. \u003cem\u003eALK\u003c/em\u003e rearrangement is the most common molecular alteration. These patients also exhibit a better prognosis than those with non-\u003cem\u003eALK\u003c/em\u003e rearrangement. Moreover, this study may also help clinicians and pathologists to better recognize patients presenting with rare lung adenocarcinoma metastasis in clinical practice.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eCase selection\u003c/h2\u003e \u003cp\u003eAll the included 17 cases were diagnosed with lung adenocarcinoma metastasis to the ovary between 2013 and 2022. The diagnosis was confirmed in 13 cases through ovarian biopsy specimens, and four cases through surgical excision specimens ( including three total abdominal hysterectomy and bilateral salpingo-oophorectomy, and one right salpingo-oophorectomy). All cases were reviewed by two senior pathologists who verified the diagnosis. Detailed clinical information, such as age, clinical course, symptoms, laboratory tests, imaging findings, and treatment details, were collected from electronic medical records. Follow-up data were obtained through medical records and telephone interviews. This study was approved by the Ethics Committee of Fujian Cancer Hospital.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eImmunohistochemical Staining\u003c/h2\u003e \u003cp\u003eFour-micrometer thick tissue sections cut from 10% formalin-fixed, paraffin-embedded tissue blocks were used for immunostaining (Ventana Autostainer BenchMark ULTRA). The antibodies used were as follows: ALK (D5F3), TTF-1 (SPT24, Leica), CK7 (EP16, Zhongshan, China), NapsinA (IP64, Zhongshan), PAX-8 (EP298, Maixin, China), ER (SP1, Maixin), CK20 (EP23, Zhongshan), Villin (EP163, Zhongshan). Positive and negative controls were employed in this study.\u003c/p\u003e \u003cp\u003e \u003cb\u003eEGFR\u003c/b\u003e \u003cb\u003emutation and\u003c/b\u003e \u003cb\u003eALK\u003c/b\u003e \u003cb\u003erearrangement analysis\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe mutational status of \u003cem\u003eALK\u003c/em\u003e and \u003cem\u003eEGFR\u003c/em\u003e (exons 18, 19, 20, and 21) was determined by TaqMan-based real-time PCR using the EGFR/ALK/ROS1 Gene Mutation Joint Detection kit (Amoy Diagnostics Co., Ltd., Xiamen, China) or Next-generation sequencing (solid tumors 56 gene detection kit, Burning Rock Biotech Ltd., Guangzhou, China) (supplemental Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eStatistical and Survival Analysis\u003c/h2\u003e \u003cp\u003eFollow-up period was calculated from the date of diagnosis from an ovarian sample to the date of death or last follow-up. SPSS software (version 23.0; SPSS Inc.) was used for the analysis. Survival duration was determined using Kaplan-Meier analysis. A value of P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; EML4, Echinoderm microtubule-associated protein-like 4; NSCLC, non-small cell lung cancers; OS, overall survival\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during the current study are included in this published article.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the Natural Science Foundation of Fujian Province (2022J01432), Excellent Young Talents Funding program of Fujian Cancer Hospital(2020YNYQ003), High-level Talents Training Program of Fujian Cancer Hospital(2022YNG16), and the Joint Funds for the Innovation of Science and Technology, Fujian province (2021Y9195).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWL and DH conceived and designed the study. QHL contributed to the radiological imaging. XJW, XDL contributed to the molecular detection; YMC, WC, JCL and LBZ collected and analyzed clinical information. YMC, WL, DH made the pathological diagnosis of the patients. WL analyzed the data, performed the literature review, and then DH rechecked it. WL wrote the initial draft of the manuscript. DH revised it. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. 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Pathologe. 2007;28:215\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Ovary, Metastatic carcinoma, Lung cancer, ALK rearrangement","lastPublishedDoi":"10.21203/rs.3.rs-2685548/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2685548/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eOvarian metastatic lung adenocarcinoma is rarely detected in clinical practice, and only a few cases have been reported. Its clinicopathological features, molecular genetics, and prognosis have not been well characterized.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eSeventeen patients diagnosed with ovarian metastatic lung adenocarcinoma between 2013 and 2022 were analyzed retrospectively. All patients were non-smokers, with a median age of 46 years (range, 30 to 71y). Unilateral ovarian involvement was more frequent than bilateral involvement (58.8% \u003cem\u003evs\u003c/em\u003e 41.2%). Lesions presented as solid ovarian or mixed cystic and solid masses, and nearly two-thirds of the tumors (64.7%) had a diameter greater than 10 cm. More than one-third of the patients (41.2%) initially presented with pelvic masses with abdominal distension and/or lower abdominal pain, 100% of patients had elevated CA125 levels, and 76.5% had ascites. Most patients (76.5%) harbored driver gene alterations, including eight cases with \u003cem\u003eEML4-AL\u003c/em\u003eK gene fusion and five cases with \u003cem\u003eEGFR\u003c/em\u003e mutation. \u003cem\u003eALK\u003c/em\u003e rearrangement tumors showed solid adenocarcinomas (6/8,75.0%) and mucinous adenocarcinomas (2/8, 25.0%); however, acinar adenocarcinoma (6/9, 66.7%) was the most common type in non-\u003cem\u003eALK\u003c/em\u003e rearrangement cases. The 3-year overall survival (OS) of patients with \u003cem\u003eALK\u003c/em\u003e rearrangement and non-ALK rearrangement was 80.0% and 30.0%, respectively (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eOvarian metastatic lung adenocarcinoma exhibits distinctive clinicopathological features and can mimic primary ovarian carcinoma. \u003cem\u003eALK\u003c/em\u003e rearrangement is the most common molecular alteration, and these patients have a better prognosis than those with non-\u003cem\u003eALK\u003c/em\u003e rearrangement. Genetic testing is recommended in all patients with ovarian metastatic lung adenocarcinoma to provide them with an opportunity to undergo targeted therapy.\u003c/p\u003e","manuscriptTitle":"Ovarian metastatic lung adenocarcinoma： a retrospective clinicopathological analysis of a consecutive 10-year case series","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-10-09 22:11:16","doi":"10.21203/rs.3.rs-2685548/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d6407093-22ff-4506-a486-9e37dd6f8438","owner":[],"postedDate":"October 9th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-10-30T07:45:38+00:00","versionOfRecord":[],"versionCreatedAt":"2023-10-09 22:11:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2685548","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2685548","identity":"rs-2685548","version":["v1"]},"buildId":"wLkW0s4AflPzk-lpfg-fK","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}