A Case Report of Bilateral Ovarian Collision Tumors: Serous Carcinomas and Fibrothecomas T Ivković-Kapicl 1, AV Bojana 2, D Ninčić 3, A Mandić 3
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1 A Case Report of Bilateral Ovarian Collision Tumors: Serous Carcinomas and Fibrothecomas T Ivković-Kapicl 1, AV Bojana 2, D Ninčić 3, A Mandić 3 ABSTRACT A patient had both ovaries affected by a clearly demarcated colliding tumor masses of different gross appearance, histological features and immunohistochemical profile, corresponding to bilateral collision papillary serous high grade adenocarcinoma and fibrothecoma. Despite the applied chemotherapy, it has led to a lethal outcome of the patient after nearly a year after the surgery. Bilateral ovarian tumors raise a question: are they primary tumors or metastases? Simultaneous bilateral occurrence of surface epithelial tumors with other types of ovarian tumors is rare, and, therefore, it poses a great challenge in proper differential diagnostics. Keywords: Fibrothecoma, multiple primary neoplasms, ovarian neoplasms, serous carcinoma From: 1 Department of Pathology, Oncology Institute of Vojvodina, 2 Department of histology and embryology, Medical Faculty, Novi Sad, and 3 Clinic of Oncological Surgery, Oncology Institute of Vojvodina, Serbia. Correspondence: Dr AV Bojana, Hajdu Veljkova 3, Novi Sad, Serbia. Fax: , andrejic.bojana@gmail.com West Indian Med J DOI: /wimj
2 Bilateral Ovarian Collision Tumors INTRODUCTION Two out of three main categories of primary ovarian tumors are epithelial tumors and sex cordstromal tumors (1). Serous epithelial tumors are determined as a gynecological malignancy with the highest case-to-fatality ratio, while ovarian fibrothecomas are an intermediate form (2, 3, 4). The presence of two colliding tumor masses in both ovaries is a major diagnostic challenge (5, 6). To the best of our knowledge, this is a first case of serous carcinoma and fibrothecoma presenting as synchronous bilateral collision tumors. CASE REPORT Clinical history A 50 year old perimenopausal women with lower abdominal pain was admitted after the ultrasound verification of tumor-like mass of left ovary. Serum CA-125 levels were extremely high ( U/l). Bilateral salpingo-oophorectomy with subtotal hysterectomy and omentectomy was performed. Lymph node extraction was not performed. Postoperative course was uneventful and Oncological Committee of the Institute prescribed a following chemotherapy protocol: Taxol 270mg and Carboplatin 450mg, trough six cycles. Three months after the operation a tumor mass (2x1cm), was noted in the rectouterine pouch. Four months after the operation (after the 6 th cycle of therapy), cytological analysis of the ascites was negative, CA125 levels were within the normal reference values (according to the laboratory that conducted the testing) but magnetic resonance revealed progression of the disease (massive peritoneal implants, lymphadenomegaly, ascites). The Council of the Clinic for Gynecology of the Oncology Institute prescribed another therapeutic approach: weekly cisplatin and etoposid. 2
3 Ivkovic-Kapicil et al After the third cycle of cisplatin (8 th post-operative month), clinical progression of the disease was verified (CA125 levels were elevated, tumor mass enlarged). Eleven months after the operation only palliative symptomatic therapy was recommended, and we got a confirmation that patient had passed away, nearly a year after the surgery. Histology findings Uterus had regular morphology with two whitish nodes of storiform appearance in the myomerium and polypoid formation of the endometrium. The left ovary (Fig. 1A) was enlarged, lobulated (13x11x6cm, 426g). On the cross section, a part of the tumor (8cm in diameter) was solid, elastic, white-yellow. The second part of the tumor tissue was at intimate contact with previously described, but sharply demarcated. It was 6cm in diameter and had papillary, necrotic consistency with areas of hemorrhage. The right ovary (Figure 1B) (9x7x7cm, 315g), was involved by tumor lesions of same characteristics as the left sided. On cross sections of omentum, three nodes were found, measuring 4.5cm, 3cm and 1cm. Upon microscopic examination, two leiomyomas and one endometrial polyp were diagnosed. Ovarian tissue bilaterally was completely replaced by two different tumors. One, papillary and solid, composed of medium to large cells with bizarre nuclei, prominent nucleoli, significant cytological atypia, mitotic activity (Fig. 2A), and extensive necrosis. This type of tumor was found in the omentum. These bilaterally present histological features indicated the diagnosis of papillary high grade serous carcinoma (HGSC). The second tumor type (clearly demarcated from HGSC) was highly cellular, comprised of fascicles of cells in a storiform and whorl arrangement (Fig. 2B). Cells were spindlelike or plump and some had a clear cytoplasm with cytoplasmic lipid vacuoles. Mitoses were rare (1/10 HPF), and necrosis or hemorrhage were 3
4 Bilateral Ovarian Collision Tumors absent. The described morphologic pattern of tumor, indicating a fibrothecoma, was present bilaterally. Additionally, immunohistochemical panel of antibodies (DAKO) (6, 7) was applied (Table, Fig. 4) in order to confirm HGSC and FT. Table. Proliferative index and immunohistochemical reactivity of ovarian tumor masses (negative (-); faintly or focally positive (+); moderately (++) or strongly positive (+++)). Ki-67 αsma Vimentin S100 CD34 CD117 CD10 CK 5/6 CK 8/18 WT1 calretinin AE1/AE3 HGSC 60% FT <3% DISCUSSION Most patients with HGSC when diagnosed present some of the signs of the advanced stage of the disease, and less than 10% are confined to the ovary (2). The omentum, as in our case, is almost always affected by tumor, causing the patients significant pain (3). In our case, lymphadenectomy was not performed, according to national Good Clinical Practice Guide for diagnostics and treatment of ovarian neoplasms (6). Recent studies report that patients who underwent systematic lymphadenectomy had significantly improved progression-free and overall 4
5 Ivkovic-Kapicil et al survival in patient with no gross residual disease (optimal surgery) or residual disease 0.1-1cm (near optimal) (7). In addition to morphological features, marked cytological and nuclear atypia, epithelial tumor mass had high proliferative index and positive immunohistochemical staining of WT1 and AE1AE3 that supported the diagnosis of high grade serous carcinoma. Sex-cord stromal tumors of the ovary arise from the ovarian stroma, sex-cord elements or both. By Mondal et al. tumors of the fibroma-thecoma group (including fibrothecoma) are the second most common type of SCST, with 13.3% cases of bilaterality (4, 5). Salemis et al. reported a case of bilateral fibrothecomas with the argument that fibrothecomas should be considered in postmenopausal women with a pelvic/ovarian mass and abdominal pain, as in our case (4). Low mitotic count and proliferative index, lack of cytologic and nuclear atypia, necrosis and hemorrhage in sex-cord stromal mass, indicated a benign nature. Fibrothecomas usually show inhibin, vimentin and calretinin positivity, but these markers are not specific compared to other SCST which may show similar immunohistochemical profile (8). It is not rare to find a bilateral serous carcinomas or bilateral fibrothecomas, but simultaneous occurrence of surface epithelial tumors of the ovary with other types of ovarian tumors is rare (9, 10). So far, to the best of our knowledge, this article is the first one to report collision tumors, HGSC and fibrothecoma, present in both ovaries at the same time. The ovary is a very interesting location for formation of collision tumors due to possibility of coexistence of tumors with varying histogenesis (10). However, pathogenesis of the collision tumors of epithelial and stromal origin is unclear (9). One of the proposed theories is accidental meeting of two independent primary lesions. A different theory claims that two different tumors may occur in contiguity due to the fact that the ovaries were affected by the 5
6 Bilateral Ovarian Collision Tumors same carcinogenic stimulus, or that the presence of one tumor alter the local environment and a second tumor is more likely to develop nearby (10). ACKNOWLEDGEMENTS This paper was supported by the Ministry of Science and Technological Development of Republic of Serbia (grant No ). 6
7 Ivkovic-Kapicil et al REFERENCES 1. Zaloudek CF. Tumors of the female genital tract. In: Fletcher CDM, editor. Diagnostic histopathology of tumors. 2 nd ed. Philadelphia: Elsevier Limited; 2007: Prat J. Ovarian carcinomas: five distinct diseases with different origins, genetic alterations and clinicopathological features. Wirchows Arch 2012; 460: Lengyel E. Ovarian cancer development and metastasis. Am J Pathol 2010; 177: Salemis NS, Panagiotopoulos N, Papamichail V, Kiriakopoulos K, Niakas E. Bilateral ovarian fibrothecoma. An uncommon cause of a large pelvic mass. Int J Surg Case Rep 2011; 2: Mondal SK, Banyopadhyay R, Nag DR, Roychowdhury S, Mondal PK, Sinha SK. Histologic pattern, bilaterality and clinical evaluation of 957 ovarian neoplasms: a 10- year study in a tertiary hospital of eastern India. J Cancer Res Ther 2011; 7: Nacionalni vodiči dobre kliničke prakse [Internet]. Ministarstvo zdravlja Republike Srbije; 2002 [cited 2013 Mar 23]. Available from: 7. Chang SJ, Bristow RE, Ryu H-S. Prognostic significance of systematic lymphadenectomy as part of primary debulking surgery in patients with advanced ovarian cancer. Gynecol Oncol 2012; 126: Sills ES, Doan TB, Mock RJ, Dixson GR, Rohlfing MB. Immunohistochemical localization patterns for vimentin and other intermediate filaments in calcified ovarian fibrothecoma. Diagn Pathol 2006; 11:
8 Bilateral Ovarian Collision Tumors 9. Ozbey C, Erdogan G, Pestereli HE, Simsek T, Karaveli S. Serous papillary adenocarcinoma and adult granulose cell tumor in the same ovary. APMIS 2005; 113: Kajo K, Macháleková K. Collision of invasive serous adenocarcinoma and mature cystic teratoma in the ovary. APMIS 2007; 115:
9 Ivkovic-Kapicil et al Fig. 1.Gross appearance of ovaries with distinct two different types of tumor (A - left sided ovary; B - right sided ovary). Fig. 2. Histologic fetures of tumors on standard hematoxylin&eosin stain (A - high grade serous carcinoma, B fibrothecoma). Fig. 3. High grade serous carcinoma and fibrothecoma showing a distinct boundaries without histologic admixture (hematoxylin and eosin). 9
10 Bilateral Ovarian Collision Tumors Fig. 4. Immunohistochemical profile of fibrothecoma (FT) and high grade serous carcinoma (HGSC) of the ovaries (A WT1 in FT and HGSC (x100); B CK8/18 in FT and HGSC (x100); C AE1/AE3 in HGSC (x200); D Ki67 in HGSC (x100); E Ki67 in FT (x200); F Calretinin in FT (x200); G Reticulin in FT (x200); H CD10 in FT (x200)). 10
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