{"paper_id":"80ecf63b-4d75-45bb-a847-c3f499fc28ba","body_text":"Well-differentiated papillary mesothelioma (WDPM) is an abnormal mesothelial proliferation\nmost commonly encountered as an incidental finding in the peritoneal cavity, pericardium, or\ntunica vaginalis. WDPM occurs within a wide age range, is especially found during the\nreproductive years, and affects more women than men. 1  The lesions may be single or multiple but, by definition, do not invade the\nunderlying stroma and usually behave in a benign or indolent fashion, sometimes persisting\nfor many years. 2 , 3  Patients with WDPM are\nmostly asymptomatic; thus, WDPM is rarely seen in patients with infertility.\n\nFour years prior to this reporting, a 37-year-old woman (gravida 0) consulted our\nDepartment of Gynecology for primary infertility that she had experienced for 12 years.\nPhysical examination was normal, ovulation occurred in the natural cycle,\nhysterosalpingography revealed unilateral patency, and transvaginal ultrasound revealed\nchylous echo pelvic effusion, measuring 47 mm anterior and 46 mm posterior to the uterus.\nHer serum CA125 level was 43.53 U/mL (normal range: 0–35 U/mL). Before proceeding with\nassisted reproductive technology, we performed a diagnostic laparoscopy.\nIn the pelvis, approximately 200 mL of dark red, free fluid was observed, along with more\nthan 10 yellow-white polypoid nodules or papillary formations, with a maximum diameter of\n1.5 cm, on the surface of the round ligament, sacrum ligament, right fallopian tube, and\nboth sides of the uterus. No obvious abnormality was found in the appearance of the left\nfallopian tube and bilateral ovaries, whereas the surface of the right fallopian tube was\ncovered in miliary tumors of different sizes. The serous surface lesions of the fallopian\ntube were removed and sent to the lab for pathological analysis. The pathology report\nindicated WDPM with adenomatoid tumor ( Figure 1 ). Immunohistochemical staining showed that the lesions were positive for\nAE1/AE3, vimentin, cytokeratin 5/6 (CK5/6), calretinin, podoplanin (D2-40), Wilms’ tumor\nprotein (WT-1), p53 (>50%), and Ki-67 (<15%); partially positive for Pax-8; and\nnegative for desmin, estrogen receptor (ER), progesterone receptor (PR), and\ncarcinoembryonic antigen (CEA) ( Figure\n2 ). The patient was monitored by computed tomography and serum CA125 level for 49\nmonths with no recurrence.\nLaparoscopic images, with arrows indicating well-differentiated papillary mesothelioma\n(WDPM).\nUT, uterus; MUT, myoma of uterus; AS, ascites; rt FT, right fallopian tube; rt Ov,\nright ovary; rt BL, right broad ligament; rt UL, right uterosacral ligament.\nPhotomicrographs of hematoxylin and eosin (h&e; panels a and b, 200× and 400×\nmagnification, respectively) and immunohistochemical stains (panels c–k, 200×\nmagnification). Positive staining for vimentin (c) and AE1/AE3 (d) illustrated tumor\ncharacter and epithelial origin; positive results for other stains confirmed a\nmesothelial proliferation: cytokeratin 5/6 (CK5/6) (e), calretinin (f), podoplanin\n(D2-40) (g), and Wilms’ tumor protein (WT-1) (h). Staining for p53 was >50% positive\n(I) and staining for Ki-67 was <15% positive (j). Partly positive staining for Pax-8\n(k) was helpful in the differential diagnosis.\n\nThere are rare case reports of WDPM progressing to true malignant peritoneal mesothelioma.\nClinically, WDPM is often discovered incidentally during pelvic examination or surgery.\nImaging features of WDPM are not well documented, but complete resection, when possible,\nusually leads to normal survival. 1 , 4 – 6  Genome-wide sequencing analysis shows that\nWDPM has a genetic profile distinct from that of malignant mesothelioma, with a lack of copy\nnumber alterations in genes characteristic of peritoneal and pleural mesothelioma:\n BAP1 ,  SETD2 ,  PBRM1 ,\n SMARCC1 ,  CDKN2A/B ,  LATS1/2 , and\n NF2 . 7 , 8  Adenomatoid\ntumors are also relatively uncommon benign tumors of mesothelial origin that usually occur\nin the male or female genital tract. 9  Although the American Society of Clinical Oncology published a clinical practice\nguideline on fertility preservation for adults and children with cancer in 2006, which has\nbeen updated periodically, 10 , 11 \ntherapeutic strategies for WDPM with adenomatoid tumor are not currently described.\nTherefore, treatment that allows patients with WDPM with adenomatoid tumor to become\npregnant is a new challenge.\nOvulation, good oviduct function, a suitable endometrium for embryo implantation, and\nappropriate luteal support before and after pregnancy are prerequisites for pregnancy. In\nthe present case, although the patient had natural ovulation, the surface of the right\nfallopian tube was covered with miliary tumors of different sizes, which may have affected\nfallopian tube function. Moreover, salpingography showed that one side of the fallopian tube\nwas blocked, which reduced the probability of pregnancy by 50%. Immune and other factors\ncannot be excluded as possible causes of the patient’s 12-year history of infertility.\n In vitro  fertilization is the first choice for treating infertility.\nHowever, it is not known whether the process of oocyte retrieval in a case such as that\ndescribed here could lead to pelvic tumor spread and whether an invisible tumor implanted on\nthe surface of the ovary could migrate inside the ovary. There are no reports on the effect\nof estrogen and progesterone on the prognosis of WDPM. Estrogen has been shown to aggravate\ndisease progression in multiple cancer cell lines and mouse models, such as lung cancer,\ngastric cancer, skin cancer, and others. 12  Therefore, caution is required when considering adding or stimulating the production\nof supraphysiological estrogen for these patients.\n\nAlthough our patient’s diagnosis does not affect her daily life, she has been infertile for\n12 years and cannot become pregnant using assisted reproductive technology because of the\nlack of effective radical treatment for WDPM. Over time, ovarian failure may occur and the\npatient may never achieve fertility. This is an urgent problem that infertility doctors\nshould address.\n\nClick here for additional data file.\nSupplemental material, sj-pdf-1-imr-10.1177_0300060520986680 for Peritoneal\nwell-differentiated papillary mesothelioma associated with infertility in a 37-year-old\nwoman by Bo Pang, Cong Hu, Qian Liu, Jinyu Yu, Zhentong Wei and Xiaowei Yu in Journal of\nInternational Medical Research","source_license":"CC0","license_restricted":false}