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Primary Ovarian Serous Carcinomas With Sun et al. BMC Women’s Health (2021) 21:193 https://doi.org/10.1186/s12905-021-01336-y CASE REPORT Open Access Primary ovarian serous carcinomas with extensive squamous diferentiation: a case report and literature review Yao Sun1, Yuezhou Chen2, Xiaofei Zhang1, Hao Chen3 and Feng Zhou1,4* Abstract Background: Primary ovarian serous carcinomas (OSC) with extensive squamous diferentiation is a rare, and histo- logical diagnostic criteria and biological behavior have not been fully established. We present an extremely rare case of primary OSC of the ovary with squamous diferentiation. Case presentation: A 58-year-old (gravidity 3, parity 2) female was admitted complaining of abdominal distention for 6 months. No apparent tumor in the cervix was found by a physical examination. Serum levels of cancer antigen 125 (CA125) was elevated (2723.0 IU/L). Macroscopically, a 7 cm tumor of the left uterine adnexa, a 5 cm tumor of the right adnexa, and a 3 cm tumor of the omentum were found. Histological and immunochemical tests confrmed a diagnosis of OSC with squamous diferentiation. Debulking surgery with tumor resection was performed. The patient was subsequently received postoperative chemotherapy. Conclusions: In summary, OSC with extensive squamous diferentiation is a rare, and the inter- and intratumor het- erogeneity may be the reason for this phenomenon. Histological diagnostic criteria and biological behavior have not been fully established because of the limited data. Keywords: Ovary, Serous carcinoma, Squamous diferentiation Background Case presentation Squamous diferentiation is frequently present in endo- A 58-year-old (gravidity 3, parity 2) female was admit- metrioid adenocarcinoma, but not in certain varieties of ted complaining of abdominal distention for 6 months. ovarian epithelial tumors, notably serous types. As far as No apparent tumor in the cervix was found by a physi- we know, only three published cases of serous carcinoma cal examination. Tinprep cytologic test and HPV E6/ with squamous diferentiation were found [1]. In the pre- E7 mRNA (tested by Aptima assay) were negative in the sent study, we report a rare case of ovarian serous car- cervix. Her serum level of cancer antigen 125 (CA125) cinoma (OSC) with extensive squamous diferentiation, was elevated (2723.0 IU/L). Her serum carcinoembryonic which was confrmed by immunohistochemical staining. antigen and CA19-9 levels were in normal. Computed tomography identifed a tumor on the left uterine adnexa, a tumor in the right adnexa and a tumor from the omen- tum. Pelvic and periaortic lymph nodes were normal. Tus, surgical treatment was suggested. *Correspondence: [email protected] Macroscopically, the uterus measuring 4 Departments of Pathology, School of Medicine, Women’s Hospital, 9.0 × 6.0 × 5.0 cm with a normal endometrium. A 7 cm Zhejiang University, Hangzhou, Zhejiang Province, China tumor on the left uterine adnexa, a 4 cm tumor of the Full list of author information is available at the end of the article right adnexa, and a 5 cm tumor of the omentum were © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://crea- tivecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdo- main/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Sun et al. BMC Women’s Health (2021) 21:193 Page 2 of 4 evident. Other tumors (0.5-3 cm) in the mesentery, nuclear pleomorphism with eosinophilic cytoplasm. omentum, and paracolic sulcus were also detected. On Nuclei were pleomorphic in size and shape, and often cutting, the ovarian tumor surface was predominantly had one or two prominent central nucleoli (Fig. 1). solid and gray in color, accompanied by obvious hemor- Immunohistochemically, paired box 8 (PAX8), p16, rhage and necrosis. No cervical mass was apparent. p53 (mutations), Wilms tumor 1 (WT1), estrogen recep- Microscopically, the ovarian tumors showed poorly tor (ER), p63, and cytokeratin 5/6 (CK5/6) was strongly defned islands growing in sheets or nests with numerous positive and the Ki67 index signifcantly decreased in the mitotic fgures. Some tumor cells had marked pleomor- squamous diferentiation area (Fig. 2). phism and bizarre forms with high nuclear to cytoplas- Taking into account the above features, we made mic ratio and prominent nucleoli; others had severe the diagnosis of high-grade OSC with squamous Fig. 1 The tumors showed an infltrative pattern of stromal invasion growing in sheets or nests. Representative area of serous diferentiation: these atypical cells had large round to oval nuclei (a, 10 , b, 20 ). Representative area of ovarian serous carcinomas with squamous diferentiation: the × × tumor cells had severe nuclear pleomorphism with eosinophilic cytoplasm and numerous mitotic fgures (c, 10 , d, 10 , e 20, f 40) × × × × Fig. 2 The immunochemical photograph of ovarian serous carcinomas with squamous diferentiation. p16 (a, 20 ), paired box 8 (b, 20 ), p53 (c, × × 20 ), Wilms tumor 1 (d, 20 ), estrogen receptor (e, 20 ), cytokeratin 5/6 (f, 20 ), p63 (g, 20 ), Ki67 (h, 20 ), stained in the tumor cells × × × × × × Sun et al. BMC Women’s Health (2021) 21:193 Page 3 of 4 Table 1 The clinical and pathological features of primary ovarian serous carcinomas with extensive squamous diferentiation Authors [References] Age (yr) Symptom Figo stage Transitional area Immunostain Treatment Fllow-up Thomas et al. [1] 63 Postmenopausal IIB 70% 35βH11 , 34βE12 TAH-BSO OT Died at 4 yr bleeding + + RT CTX+ + + 46 Abdominal swelling III 5% 35βH11 , 34βE12 BSO OT CTX Died at 2 yr + + + + Daniel et al. [2] 61 Lower IIIC Foci p16 , PAX8 , TAH-BSO RT Na abdominal pain p53+, WT1 +, + ER +, CK5/6+, p63 + + + Present case 58 Abdominal fullness IIIC Extensive p16 , PAX8 , TAH-BSO OT CTX Ned at 1 yr p53+, WT1 +, + + ER +, CK5/6+, p63 + + + yr year, PAX8 paired box 8, WT1 Wilms tumor 1, ER estrogen receptor, CK5/6 cytokeratin 5/6, TAH-BSO total abdominal hysterectomy and bilateral salpingo- oophorectomy, OT omentectomy, RT radiation therapy, CTX chemotherapy, na not available, ned no evidence of disease. diferentiation. Te patient was subsequently received p63 and CK5/6 are typically expressed in human squa- postoperative chemotherapy. mous epithelium and SCC, but not OSC [11]. In addition, endometrioid carcinoma should be excluded, where confrmatory endometrioid features Discussion and conclusions include squamous diferentiation can be present in Te surface epithelium of the ovary, which is considered about half of cases [12]. Most OSCs can readily be dis- as the source of common epithelial tumors of the ovary, tinguished from endometrioid carcinoma by the pres- can diferentiate into squamous cells. Primary squamous ence of specifc morphologic features and immunostain cell carcinoma (SCC) of the ovary can occur as an endo- profle. PAX8, p53 (mutations), WT1, and p16 were posi- metriosis, teratoma, or Brenner’s tumor [2, 3]. However, tive in most ovarian tumor cells described herein, which we found no evidence of these in present study. is a typical feature of OSC. Interestingly, the tumor cells A typical area of OSC was confrmed, as demonstrated with severe nuclear pleomorphism and eosinophilic cyto- by its solid growth morphology, marked pleomorphism, plasm also showed intense cytoplasmic CK5/6 expres- and prominent nucleoli with numerous mitotic fgures. sion and strong nuclear p63 staining. Such a fnding of However, the ovarian tumor described here bore some immunohistochemical staining is sufcient to constitute resemblance to SCC in terms of its morphological char- evidence of both patterns of OSC and SCC. Interestingly, acter. Tus, we used several immunohistochemical mark- the Ki67 index signifcantly decreased in the squamous ers, such as PAX8, p16, p53, WT1, ER, p63, and CK5/6, diferentiation area, which indicates a decreased activity. to make a distinction between the primary OSC and We reviewed the current English literature and found ovarian metastatic SCC. only 3 similar cases [1, 2]. Te clinical and pathologi- Te immunohistochemistry p53/p16 index was a good cal features were summarized in Table 1. Ulbright et al. marker for high-grade OSC, which are defned as tumors [1] frst described two cases of OSC with squamous dif- with difuse p53 expression or complete absence of p53 ferentiation that were confrmed by the immunohisto- expression (null type) associated with difuse p16 expres- chemical markers 35βH11 and 34βE12, and by electron sion [4]. Notably, p16 overexpression is more frequently microscopy. SCC arising in association with an OSC found in serous carcinomas [5]. p53, a tumor suppressor was recently reported in a 72-year-old woman [2]. His- gene, is typically overexpressed in OSC and is regarded tological and immunochemical studies have confrmed as a useful marker of such carcinomas [4, 6]. TP53 gene distinct areas of OSC and SCC, and several small foci of mutations are present in nearly 100% of high-grade OSCs the tumor showing transitional features between serous [4]. WT1 has been proved to play an important role in and squamous diferentiation may also be seen. Interest- the normal development of the kidneys and gonads and ingly, OSC with extensive squamous diferentiation occu- more usually found in OSC.
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