{"paper_id":"1755ecc5-9d4c-4d55-880f-78b6b91e4890","body_text":"This is an open access article under the CC BY 4.0 license ( https://creativecommons.org/licenses/by/4.0/).\nEur. J. Gynaecol. Oncol. 2022 vol.43(6), 113-121 ©2022 The Author(s). Published by MRE Press. https://www.ejgo.net/\nSubmitted: 14 September, 2022 Accepted: 18 November, 2022 Published: 15 December, 2022 DOI:10.22514/ejgo.2022.065\nC A S E R E P O R T\nSynchronous serous carcinoma arising in adenomyosis\nand small cell carcinoma of ovary-pulmonary type\n(SCCOPT): a case report and literature review\nQiuyang Jing1, Ying He 1,*\n1Department of Pathology, West China\nSecond University Hospital, Sichuan\nUniversity, Key Laboratory of Birth\nDefects and Related Diseases of Women\nand Children (Sichuan University),\nMinistry of Education, 610041 Chengdu,\nSichuan, China\n*Correspondence\nheying626@163.com\n(Ying He)\nAbstract\nSerous carcinoma arising in adenomyosis is rare, with only 8 cases reported in the\nliterature. Primary small cell carcinoma of the ovary-the pulmonary type (SCCOPT) is a\nrare and aggressive entity associated with poor outcomes and limited treatment options.\nThe presence of two malignant tumors synchronously happening in one patient has never\nbeen reported before. In this study, we summarized and analyzed the clinicopathological\nfeatures of a serous carcinoma arising in adenomyosis synchronous with SCCOPT\nand reviewed the corresponding literature. A 60-year-old postmenopausal woman\npresented to our hospital with abdominal distension, abdominal pain, and constipation.\nA colonoscopy and lung computed tomography (CT) scan showed no abnormalities.\nUltrasonography and CT scans revealed a solid-cystic mass in the pelvic cavity, with\na slightly thickened uterine myometrium at the fundus with heterogeneous echo. She\nunderwent total abdominal hysterectomy, bilateral salpingo-oophorectomy and pelvic\nand para-aortic lymphadenectomy, and the final pathology showed serous carcinoma\noriginating from adenomyosis, while the eutopic endometrium and both fallopian\nepithelia had no cancer infiltrations. The solid-cystic mass in the right ovary was\ndiagnosed with SCCOPT, which was found to metastasize to the uterine myometrium.\nThe prognosis of previously reported cancers of adenomyosis origin and SCCOPT\nwere poor, while our case was alive without disease during an 18-month follow-up.\nFindings from this case report could expand our recognition on the coexistence of serous\ncarcinoma arising in adenomyosis with small cell carcinoma of the ovary-pulmonary\ntype.\nKeywords\nSerous carcinoma; Adenomyosis; Malignant transformation; Small cell carcinoma of the\novary; Pulmonary type; Immunohistochemistry\n1. Background\nAdenomyosis is defined as ectopic endometrial glands and\nstroma invading the myometrium. It is a common benign\ngynecological disease, usually identified in hysterectomy spec-\nimens and often coexists with other diseases, such as en-\ndometrioid adenocarcinoma, leiomyoma, etc. The malignant\ntransformation of adenomyosis was first reported by Rolly\n[1] in 1897, and only dozens of cases have been reported\nsince then, with most of them malignantly transformed into\nendometrial adenocarcinoma [ 2–6]. Serous adenocarcinoma\noriginating from adenomyosis was first reported by Griffin et\nal. [ 7] in 1996, and only 8 cases have been reported so far [3, 6,\n8–11]. Due to the rarity of serous adenocarcinoma originating\nfrom adenomyosis and the current reports are mostly individual\ncases, little is known about its etiology, pathogenesis and\ngenetic alterations.\nThe gynecologic tract, including the cervix, endometrium,\novary, fallopian tube, vagina and vulva, is one of the extra-\npulmonary systems where extrapulmonary small cell carci-\nnoma (EPSCC) frequently occurs, representing <1% of all\ngynecologic malignancies [ 12, 13]. Small cell carcinoma of\nthe ovary (SCCO) is an uncommon, highly aggressive cancer\nwith an incidence of <1% of ovarian tumors [ 14]. Small\ncell carcinoma of the ovary consists of two different types:\nthe hypercalcemic type (SCCOHT) and the pulmonary type\n(SCCOPT). SCCOHT is often associated with hypercalcemia,\nwhile SCCOPT shows the characteristic morphologic features\nof lung small cell carcinoma [ 12].\nSerous carcinoma arising from adenomyosis and SCCOPT\nare rare tumors of the female genital tract, with little known\nabout them, let alone both occurring simultaneously in the\nsame patient. Herein, we reported the first case of these two\ncancers in one patient and performed an analysis of previous\nliterature on serous adenocarcinoma originating from adeno-\nmyosis to increase our understanding of the two diseases.\n\n114\n2. Case presentation\n2.1 Clinical features of the patient and\nsurgical findings\nA 60-year-old postmenopausal woman (gravida 2, para 1)\nattended the local community hospital following complaints\nof abdominal pain, abdominal distention and constipation for\nabout 1 month. Her gastroenterological endoscopy at the\nlocal community hospital showed no abnormalities. Ultra-\nsonography found a solid cystic heterogeneous mass in her\npelvic cavity, indicating that it might be originated from the\nadnexa. She had dyspnea due to abdominal distension a few\ndays later, following which she underwent abdominal puncture\ndecompression in the emergency department of our hospital.\nThe patient had regular menstruation in the past and became\nmenopausal 4 years ago. She denied having breast cancer or\nreceiving hormone replacement therapy. She was diagnosed\nwith hypertension 10 years ago and treated with amlodipine\norally. Both her parents and siblings have had a history of\nhypertension. She had a negative cervical smear one month\nago.\nPelvic examination showed a moderately enlarged uterus\nand an unmovable mass of about 9 cm in the right adnexa.\nComputed tomography (CT) scan of the pelvic and abdomen\ncavity revealed irregular solid cystic masses in the right adnexa\narea, with sizes of 9.3 cm× 7.6 cm × 6.6 cm. (Fig. 1) Contrast-\nenhanced CT scan showed that the tumor had heterogeneous\nenhancement, signs of “ovarian blood vessel pedicle”, and the\nboundary between the serosal surface of the uterus and the\nlateral adnexa area was unclear. The peritoneum and the omen-\ntum majus were thickened, and a large amount of ascites were\npresent in the pelvic and abdominal cavities. No abnormalities\nwere observed in the liver, spleen, pancreas and kidneys under\nultrasonography. The contrast-enhanced CT scan of the lungs\nshowed no mass or ground-glass opacity. Her preoperative\nserum CA125 (cancer antigen 125) was 284.2 U/mL, serum\nAFP (alpha foetoprotein) was 16.1 ng/mL, and serum calcium\nwas 2.06 mmoL/L (normal 2.15–2.70 mmoL/L). After com-\npleting all preoperative examinations, she underwent a total\nabdominal hysterectomy and bilateral salpingo-oophorectomy\n(TAHBSO).\nThe surface of the uterus and left ovary were found to be\nsmooth during the operation, and the size of the left ovary was\n4.0 cm × 4.0 cm × 3.0 cm. The right ovary adhered to the\nposterior lobe of the broad ligament and the pelvic floor and\nwas about 10.0 cm × 8.0 cm × 8.0 cm. A solid cystic mass\nwas seen in the right ovary. The solid part of the mass was\nfish-like, fragile, and easy to hemorrhage. The cystic cavity\nwas filled with dark red cyst fluid. The fallopian on both sides\nwere slightly edemateous.\n2.2 Gross pathology\nWe observed that the mass appeared to be a cyst with a fibrous\ncapsule, irregular shape and solid gray-tan color, sized about\n11.0 cm × 7.0 cm × 6.0 cm and had replaced the right ovary.\nThe cut surface of the mass was gray-tan, with hemorrhage,\ncyst formation, and necrosis. The mass was predominantly\nsolid, with scattered small cysts ranging from 0.1 cm to 0.5\nF I G U R E 1. CT scan of the pelvis shows a solid-cystic\nheterogeneous mass.\ncm in diameter. The serosal surface of both fallopian tubes\nwas smooth, and no abnormalities were found in the lumen or\nfimbria. The myometrium at the fundus was slightly thickened\nand harder than the surrounding myometrium, with a gray-\nwhite cut surface. There were no polyps, rough areas, or\nmasses in the eutopic endometrium and endocervical canal.\nThe specimens of the left adnexa, the right fallopian tube, the\nendometrium, and the cervix were all extensively sectioned for\nhistopathological examination.\n2.3 Microscopic pathology and\nimmunohistochemical staining\nHistologically, the tumor cells of the right ovary grew in\norgan-like nests, showing the typical microscopic structure of\nsmall cell neuroendocrine carcinoma. The tumor comprised\nmonomorphic small cells with indistinct cellular borders,\novoid nuclei with vesicular chromatin, hyperchromatic\nnucleoli, scanty cytoplasm, and brisk mitotic activity.\n(Fig. 2A) Lymphovascular space invasion was present around\nthe tumor.\nMicroscopically, ectopic endometrium glandular and stroma\nwere found in the thickened myometrium of the fundus, sup-\nporting the diagnosis of adenomyosis. Within the adeno-\nmyosis, serous carcinoma was observed and demonstrated a\ndestructive growth pattern and desmoplastic reaction. The\nneoplastic glands were lined by markedly atypical, cuboidal\nto columnar cells with hyperchromasia, conspicuous nucleoli,\nand irregular nuclear membranes. The tumor component was\nlocated in the deep half of the myometrium and was adjacent\nto the serosal layer. (Fig. 2F–G) Metastatic SCCOPT was\nfound in the myometrium. Lymphovascular space invasion\ncould also be occasionally found in the myometrium. There\nwas no serous carcinoma, serous endometrial intraepithelial\ncarcinoma (SEIC) or endometrial glandular dysplasia (EmGD)\n\n115\nF I G U R E 2. Microscopic pathology and immunohistochemical staining of small cell carcinoma of the ovary-pulmonary\ntype (SCCOPT) and serous carcinoma originating from adenomyosis. A. SCCOPT; hematoxylin and eosin stain (40X). B.\nSCCOPT; SMARCA4 positivity (200 × magnification). C. SCCOPT; CgA positivity (200 × magnification). D. SCCOPT; Syn\npositivity (200 × magnification). E. SCCOPT; CD56 positivity (200 × magnification). F. Serous carcinoma originating from\nadenomyosis; ectopic endometrium glandular and stroma and one glandular with atypic proliferation. Green arrows indicate\nnormal endometrial glands, and red arrows indicate endometrial glands with malignant adenomyosis. The left upper illustration\nshows the different expressions of p53 in the same gland. The normal glandular epithelium is of the wild type (green arrow), while\nthe atypical glandular epithelium is of the mutant type (red arrow). G. Serous carcinoma of the uterus. The left upper illustration\nshows strong positivity and diffuse expression of p53.\n\n116\nin the eutopic endometrium or the fallopian epithelial.\nImmunohistochemical staining of the small cell carcinoma\nof the ovary showed diffuse positivity of SMARCA4 (SWI/SNF\nRelated, Matrix Associated, Actin Dependent Regulator Of\nChromatin, Subfamily A, Member 4 ) (Fig. 2B), CgA (chro-\nmogranin A) (Fig. 2C), Syn (synaptophysin) (Fig. 2D), CD56\n(Cluster of differentiation 56) (Fig. 2E), and focal positiv-\nity of SF-1 (steroidogenic factor 1 ), but was negative for\nEMA (epithelial membrane antigen), vimentin, FOXL-2 (fork-\nhead transcription factor2), α-inhibin, CD10, CyclinD1, LCA\n(leukocyte common antigen), CD117, DOG-1 (discovered on\nGIST-1) and SALL-4 (Sal-like protein 4). The Ki67 prolif-\neration index was about 95%. Immunohistochemical staining\nof the serous carcinoma arising from adenomyosis showed\ndiffuse positivity of EMA, PAX-8 (paired box gene 8) and p53\n(Fig. 2F–G), while p16, ER (estrogen receptor), PR (proges-\nterone receptor), WT-1 (Wilms tumor gene ), Vimentin, PTEN\n(phosphatase and tensin homolog ), CgA, and Syn were all\nnegative. Both the ectopic endometrial glands and bilateral\nfallopian tube epithelium showed wild-type expression of P53.\nNo recurrence or metastasis occurred during the 18-month\nfollow-up after the operation. The patient is currently receiving\nchemotherapy at the local hospital and has shown no evidence\nof disease recurrence or metastasis. Her serum CA125, AFP\nand calcium were all within normal ranges after operation.\n3. Discussion\nAdenomyosis is a common presentation in hysterectomy speci-\nmens, and its common symptoms include dysmenorrhea, irreg-\nular menstruation, etc. Adenomyosis is histologically defined\nas the presence of ectopic endometrial glands and stroma\nwithin the myometrium. It is not uncommon for adenomyosis\nto merge with malignant tumors of the female genital tract,\nbut the incidence of malignant transformation of adenomyosis\nis low [ 5]. The malignant transformation of adenomyosis\nis mostly endometrioid adenocarcinoma [ 4, 15, 16]. Com-\nparatively, the malignant transformation of adenomyosis into\nserous adenocarcinoma or clear cell adenocarcinoma is even\nrarer [5, 17].\nThe widely agreed diagnostic criteria for malignant transfor-\nmation of adenomyosis are the Sampson criteria, and the Scott\nand Colman supplementary criteria. These criteria include the\nfollowing: (1) the presence of endometrial glands and/or stro-\nmal cells deep in the myometrium to support the diagnosis of\nadenomyosis, or endometrial glands or stromal cells around the\nmalignant lesions; (2) transformation evidence between benign\nand malignant glands structure, i.e., coexistence of normal en-\ndometrial epithelium, borderline and invasive carcinoma; (3)\nexclusion of other sources of tumor invasion or metastasis, i.e.,\nendometrium and other parts of the pelvis; (4) coexistence of\ncancer and ectopic endometrial tissues in the same lesion. Due\nto the peculiar diagnostic criteria of malignant transformation\nof adenomyosis, it is almost impossible to make an accurate\ndiagnosis before surgery [ 2, 18, 19]. Thus, a final diagnosis\nis only achieved by complete pathological examinations of\npostoperative specimens.\nOur case met all the diagnostic criteria mentioned above.\nWe observed clear ectopic endometrial glands and stroma\nbetween the myometrium and visualized a transition zone from\nbenign glandular epithelium to serous adenocarcinoma. Based\non the complete gross examination, microscopic examination,\nand appropriate immunohistochemistry staining, we excluded\nmetastatic serous adenocarcinoma of the endometrium, ovaries\nand fallopian tubes.\nThe clinicopathological characteristics of serous adenocar-\ncinoma originating from adenomyosis are presented in Table1.\nMost cases occurred in postmenopausal women [ 5]. The most\ncommon symptoms are irregular vaginal bleeding and abdom-\ninal discomfort. All reported cases underwent total abdominal\nhysterectomy and bilateral salpingo-oophorectomy, most of\nwhich underwent lymph node dissection. A study that reported\nendometrial cancer arising from adenomyosis showed that this\ncondition was associated with a significantly poorer disease-\nfree survival than endometrial cancer with adenomyosis (5-\nyear rate, p = 0.014), and it was an independent prognostic\nfactor for decreased disease-free survival ( p = 0.001) [ 11].\nMachida et al. [ 20] also found that the prognosis of endometri-\noid adenocarcinoma arising in adenomyosis was significantly\nworse than that of patients with endometrioid adenocarcinoma\ncoexisting with adenomyosis. Comparatively, Table 1 shows\nthat the prognosis of serous carcinoma from adenomyosis\nseems good, and all patients were still alive without recurrence\nat the end of follow-up. These contrasting prognostic results of\nadenomyosis malignant transformation of endometrioid ade-\nnocarcinoma and serous carcinoma might be due to the rarity of\nthe latter, with only a few reported cases. The patient reported\nin this case report was followed up for only 18 months and is\ncurrently undergoing chemotherapy; thus, her data might not\nreflect the true prognosis of the disease.\nPreoperatively, the malignant transformation of\nadenomyosis shows no prominent symptoms, specific\nlaboratory indications or imaging features [ 6, 21, 22].\nSome cases can be found through cervical smears [ 7, 23].\nThe clinical manifestations of carcinoma originating\nfrom adenomyosis are the same as those of conventional\nadenomyosis, manifested as abnormal vaginal bleeding,\nmenorrhea, or anemia [ 5, 6, 21, 22, 24], indicating a\npossible high risk of misdiagnosis. Further, as the malignant\ntransformation of adenomyosis is inside the myometrium\nrather than forming an exogenous mass and lacks positive\nfindings in hysteroscopy and curettage specimens, these\nmight also contribute to a missed diagnosis [ 6]. Our patient\ncame to the hospital due to gastrointestinal symptoms, and\nher main complaint for surgical treatment was pelvic mass.\nThere was no indication of malignant transformation of\nadenomyosis before the complete pathological examination.\nNearly all the cases underwent surgery for other reasons and\nare only accurately diagnosed after a complete pathological\nexamination [ 6, 9, 10, 16]. Although this disease can be\neasily misdiagnosed, standardized sampling, careful reading\nof all the slides and appropriate immunohistochemistry could\nincrease the accuracy and provide more indications for proper\ndiagnosis of this disease.\n\n117\nTA B L E 1. Clinicopathological characteristics of serous adenocarcinoma arising from adenomyosis in the literature.\nAuthor, time Case no. Age\n(years)\nChief complaint Findings in the\nadenomyosis\nType of surgery Follow-up Clinico-pathological features\nMiriam Griffin [ 7],\n1996\n1 68 Postmenopausal\nbleeding.\nPapillary serous\ncarcinoma\nTAH and BSO NA Cervical smear was positive for\nadenocarcinoma.\nMasafumi Koshiyama\n[8], 2002\n2 69 Postmenopausal\nbleeding\nPapillary serous\ncarcinoma\nTAH and BSO, pelvic and\npara-aortic\nlymphadenectomy\n96 months,\nAWOD\nER-, PR-, P53+++\nNarges Izadi-Mood [9],\n2007\n3 61 Postmenopausal\nbleeding\nPapillary serous\ncarcinoma\nTHA and BSO 30months,\nAWOD\nHad a history of breast cancer\n(invasive lobular carcinoma),\nunderwent a mastectomy, and received\ntamoxifen for the past five years.\nReceived pelvic and intracavitary\nradiation.\nNisreen Abushahin [ 3],\n2011\n4 58 Low abdominal\ndiscomfort\nSerous EIC THA and BSO;\nlaparoscopic staging with\nomentectomy\n68 months,\nAWOD\nNo history of breast cancer;\nNo hormone replacement was taken\nuntil the age of 55 years;\nEndometriosis in uterine\nserosa and ovaries\nIHC: P53+++, IMP3+++,\nER+, PR-, WT-1-\n5 64 Left low\nabdominal pain\nSerous carcinoma TAH and BSO, complete\nstaging surgery\nNA\nLeft ovary metastasis, leiomyoma,\nendometriosis in the rectum.\nER-, PR-, CK7+++, CK20-, PAX-8+++,\nWT-1-, CA125++, P53+++,\nPTEN++, β-catenin membrane+,\nP16+++, Ki67 >80%.\nBingjian Lu [10], 2016 6 55 Postmenopausal\nvagina bleeding\nMinimal SC; serous\nEIC; EmGD\nTAH and BSO, and\ncomplete staging surgery\nNA\nLymphovascular space invasion,\nLeiomyoma.\nER-, PR-, PAX-8+++, WT-1-,\nP53+++, PTEN++,\nβ-catenin membrane+, P16+++,\nHNF1β-, Ki67 >70%.\n7 55 V aginal bleeding Serous EIC; EmGD Radical resection of the\ncervical stump + BSO +\ncomplete staging surgery\n44 months,\nAWOD\nER-, PR-, PAX-8+++, WT-1-, P53+++,\nP16+++, Ki67 >80%\nLeft ovarian endometriotic cyst;\nEndometriosis in the rectum.\n\n118\nTA B L E 1. Continued.\nAuthor, time Case no. Age\n(years)\nChief complaint Findings in the\nadenomyosis\nType of surgery Follow-up Clinico-pathological features\nChia-Hao Liu, [6] 2017 8 67 Right inguinal\nmass and\npostmenopausal\nbleeding.\nSerous carcinoma laparoscopic complete\nstaging surgery and inguinal\nLN dissection.\n8 months,\nAWOD\nMetastatic serous carcinoma to the\ninguinal lymph node.\nCase of this present\nstudy\n9 60 Postmenopausal\nbleeding.\nSerous carcinoma TAH and BSO, complete\nstaging surgery\n18 months,\nAWOD\nAccompanied by small cell carcinoma\nof the ovary-pulmonary type.\nNA, not available; TAH, total abdominal hysterectomy; BSO, bilateral salpingo-oophorectomy; LN, lymph node; AWOD, alive without disease; EIC, endometrial intraepithelial\ncarcinoma; EmGD, endometrial glandular dysplasia; ER, estrogen receptor; PR, rogesterone receptor; IHC: immunohistochemical staining; IMP3, insulin-like growth factor II mRNA\nbinding protein 3; CK7, cytokeratin 7;CK20, cytokeratin 20; WT-1, Wilms tumor gene; P AX-8, paired box gene 8; CA125, cancer antigen 125;PTEN, phosphatase and tensin homolog.\n\n119\nUterine serous carcinoma commonly demonstrates alter-\nations in ERBB2 (erb-b2 receptor tyrosine kinase 2 ), TP53\n(Tumor protein p53 ), FBXW7 (F-box and WD repeat domain\ncontaining 7 ) and PPP2R1A (protein phosphatase 2 scaffold\nsubunit Aalpha ), and the phosphoinositide 3-kinase (PI3K)\npathway [25]. However, the etiology, pathogenesis or molec-\nular alteration of the malignant transformation of adenomyosis\nis poorly understood. At present, only a few studies have\nsuggested gene changes and inactivation of specific tumor\nsuppressor genes in adenomyosis, which might be related to its\nmalignant transformation, including the loss of heterozygosity\n(LOH), DNA mismatch repair genes, low expression of Bcl-2\n(B-cell lymphoma 2) and epigenetic changes in the promoter\nregion of the progesterone receptor gene [ 26–28]. Serous\nadenocarcinoma derived from adenomyosis also showed P53\nmutant expression and WT-1 negativity, indicating that it might\nhave similar molecular changes with serous adenocarcinoma\nof endometrial origin. Nevertheless, there is no study on\nthe molecular alterations of the malignant transformation of\nadenomyosis into serous carcinoma because of its rarity.\nDue to the low incidence of this disease and the existing\nstudies being mostly case reports, the associated risk factors of\nthe malignant transformation of adenomyosis are still unclear.\nUpon reviewing previous literature, we found a patient with\nadenomyosis malignant transformation who was treated with\ntamoxifen for a long time in the past [ 9]. Coincidentally,\nthere was also a SCCOPT case that had previously received\ntamoxifen treatment for breast cancer [ 29]. These findings\nindicated that tamoxifen could be a potential risk factor for\nmalignant transformation of adenomyosis and SCCOPT.\nPrimary small cell carcinoma of the ovary is a highly ma-\nlignant tumor, divided into two types: small cell carcinoma\nof the ovary-the pulmonary type (SCCOPT) and the hyper-\ncalcemia type (SCCOHT). Both types are rare, but compared\nwith SCCOHT, SCCOPT is rarer, with only <30 cases have\nbeen reported. SCCOHT is often accompanied by elevated\nserum calcium levels and may have the symptoms of hy-\npercalcemia [ 30]. SCCOPT is similar to pulmonary small\ncell carcinoma and is considered a neuroendocrine tumor,\nconsistent with pulmonary small cell carcinoma in morphology\nand immunophenotype. The case reported in this study was\nSCCOPT.\nIt is necessary to exclude metastatic cancer of the pul-\nmonary, digestive tract, cervix, etc., which requires a combina-\ntion of the patient’s gastrointestinal endoscopy, imaging, phys-\nical examination, intraoperative findings, morphology, and im-\nmunohistochemical staining. Gastrointestinal endoscopy and\nenhanced CT scan of the chest showed no tumorous lesions,\nand no other masses in the pelvic and abdominal cavities were\nseen during the operation in our case, which can rule out the\npossibility of metastasis. Although some studies have shown\nthat primary small cell carcinoma of the ovary does not express\nTTF-1 (thyroid transcription factor 1) [ 31, 32], its positivity\ndoes not exclude it as ovarian primary [ 13].\nBased on the clinical characteristics, morphological features\nand immunohistochemical staining of this case, we could dis-\ntinguish it from SCCOHT. Briefly, SCCOPT does not have\nfollicular-like spaces and large cell components [ 12, 30, 33].\nIn addition, SMARCA4 always shows diffuse positivity in\nSCCOPT, while SMARCA is always negative in SCCOHT\n[34, 35]. On the other hand, the expression of vimentin could\nbe opposite that of SMARCA4 in these two different types [12].\nIn addition, approximately 70% of SCCOHT patients generally\nhave hypercalcemia, which is absent in SCCOPT patients\n[12, 14, 36]. According to previous reports, the average age of\nSCCOPT patients is 59 years old [ 36], while that of SCCOHT\npatients is 23.9–30 years old [ 30, 33].\nSCCOPT also needs to be differentiated from ovarian germ\ncell tumors and lymphoma. Lymphoma specifically expresses\nlymphoma-related markers, such as LCA, Bcl-2, CD20, etc.\n[13]. Ovarian germ cell tumors always showed positivity of\ngerm cell markers, such as SALL-4 and OCT 3/4 (octamer-\nbinding transcription factor 3/4) [ 13].\nPrevious studies using flow cytometry found that SCCOPT\nwere aneuploid or diploid [ 36], while SCCOHT were all\ndiploid [30]. Recent studies showed that germline or somatic\nmutations in the SMARCA4 gene were highly correlated with\nSCCOHT [ 35, 37, 38]. Unfortunately, there is currently no\ntherapy for this mutation. There is only one literature that\nrevealed TP53 mutations in 25 % of small cell carcinoma\nof ovary (SCCO) (1/4) patients and BRCA2 (breast cancer\nsusceptibility gene 2) mutations in 50 % of SCCO (1/2)\npatients by using NGS (next-generation sequencing) and\nSanger sequencing of the 47-gene panel [ 39]. Although the\nauthors reported that TP53 mutation could be oncogenic, it\nis not persuasive to conclude that the TP53 mutation was the\nrepresentative molecular alteration of SCCOPT from only one\ncase.\nThe prognosis of SCCOPT is very poor. Even for patients\nwith FIGO (International Federation of Gynecology and Ob-\nstetrics) stage IA, the long-term survival is only 30% to 40%\n[14]. According to a study by Eichhorn [ 36], 5 of 7 cases\nsuccumbed from the disease 1–13 months (average 8 months)\nafter surgery, possibly due to the biological behavior similarity\nbetween extrapulmonary and lung small cell carcinoma, which\ncontributed to their treatment approaches being generally sim-\nilar [40, 41].\nSynchronous tumors of the ovaries and uterus are rare,\naccounting for about 1–2% of female reproductive genital tract\nmalignancies, of which endometrioid adenocarcinoma is the\nmost commonly diagnosed. This is the first study to report\nthe co-occurrence of SCCOPT and serous adenocarcinoma of\nadenomyosis; however, further investigations are required to\nclarify whether there could be a genetic correlation between\nthe two.\n4. Conclusion\nDue to the low incidence of SCCOPT and malignant trans-\nformation of adenomyosis into serous adenocarcinoma, little\nis known about their etiology, pathophysiology, pathogenesis\nand genetic alterations. To the best of our knowledge, this is\nthe first case reporting the occurrence of serous adenocarci-\nnoma arising from adenomyosis synchronous with SCCOPT.\nBecause of the high possibility of misdiagnosis, careful and\ncomplete pathological analysis, immunohistochemical stain-\ning and imaging examination are essential to accurately diag-\nnose this condition. Lastly, it is worth collecting more cases\n\n120\nfor systematic review and in-depth analysis to uncover their\nclinicopathological characteristics and molecular changes.\nA U T H O R CO N T R I B U T I O N S\nQYJ—Manuscript writing, data collection; YH—Revision of\nmanuscript, support of funding. All authors read and approved\nthe final manuscript.\nE T H I C S A P P R OVA L A N D CO N S E N T TO\nPA R T I C I PAT E\nThis study met the requirements of the Helsinki Declaration\non human material and data. The study protocol was reviewed\nand approved by the institutional research ethics committee of\nWest China Second University Hospital, approval number 326.\nThe patient agreed to the publication of this case.\nAC K N OW L E D G M E N T\nNot applicable.\nF U N D I N G\nThis project was supported by Natural Science Foundation of\nSichuan Province (No. 2022NSFSC0708).\nCO N F L I C T O F I N T E R E S T\nThe authors declare no conflict of interest.\nR E F E R E N C E S\n[1] Rolly F. Ueber einen Fall von Adenomyoma uteri mit Uebergang in\nCarcinom und Metastasenbildung. Virchows Arch Pathol Anat. 1897;\n150: 555–582.\n[2] Sampson JA. Endometrial carcinoma of the ovary, arising in endometrial\ntissue in that organ. American Journal of Obstetrics & Gynecology. 1925;\n9: 111–114.\n[3] Abushahin N, Zhang T, Chiang S, Zhang X, Hatch K, Zheng W. Serous\nendometrial intraepithelial carcinoma arising in adenomyosis: a report\nof 5 cases. 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