Distinct Immunophenotypic Features of Ovarian Microcystic Stromal Tumor

Case Report

Austin Biomark Diagn. 2015;2(1): 1017.

Distinct Immunophenotypic Features of Ovarian Microcystic Stromal Tumor

Niu S and Peng Y*

Department of Pathology, University of Texas Southwestern Medical Center, USA

*Corresponding author: Peng Y, Department of pathology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390- 9072, USA,

Received: April 09, 2015; Accepted: May 25, 2015; Published: June 04, 2015

Abstract

Ovarian Microcystic Stromal Tumor (MCST) is a newly recognized entity with only 19 reported cases, in which only 3 cases showed a solid growth pattern and 1 with concurrent endometrial carcinoma. Recent studies suggested the involvement of the Wnt/β-catenin pathway in MCST tumorigenesis through mutated β-catenin. Here we report another MCST case with a solid growth pattern, distinct immunophenotypes including β-catenin and cyclin D1 (a known β-catenin regulated oncogene), and a coexisting endometrial carcinoma. Macroscopically, the tumor was a well-circumscribed, solid mass. Microscopically, it consisted of predominantly lobulated cellular nodules separated by hyalinized fibrous stroma. Immunophenotypically, the tumor was diffusely and strongly positive for CD10, β-catenin (nuclear) and cyclin D1, and completely negative for inhibin, calretinin, ER, PR, cytokeratins, EMA and c-Myc. To our knowledge, this is the first report to demonstrate the co-over expression of β-catenin and cyclin D1 in case with MCST and concurrent endometrial carcinoma, which may provide new insights to the tumor biology.

Keywords: Microcystic stromal tumor; Ovary; β-catenin; Cyclin D1; Endometrial carcinoma

Introduction

Ovarian Microcystic Stromal Tumor (MCST) is a newly recognized entity with only 19 reported cases [1-3]. Of the 19 cases, 7 cases with follow-up data (1.5 to 12 years) revealed that the tumors had no metastasis or recurrence [1]. Grossly, MCST tumors were solid-cystic (14/19), solid (3/19), or predominantly cystic (2/19) [1-3]. Microscopically, the neoplasms were characterized by a microcystic growth pattern with variably solid cellular areas separated by fibrous stroma. The characteristic immunophenotypes was CD10+/vimentin+/inhibin-/calretinin-/EMA-(19/19). Two recent studies demonstrated diffuse and strong β-catenin protein nuclear expression in cases with MCST (3/3) [2,3]. Meanwhile a point mutation, CTNNB1 S33C, was identified (2/2), and the authors proposed a potential involvement of the Wnt/β-catenin pathway in MCST tumorigenesis [2].

Here we report another MCST case with a pure solid growth pattern grossly and microscopically, and with a distinct immunophenotypes including cyclin D1 (diffusely positive) and c-Myc (completely negative). Both cyclin D1 and c-Myc are wellestablished oncogenes involved in various tumor developments and have been shown to be direct Wnt/β-catenin targets [4-6]. Therefore, our findings may provide new insights to the MCST tumorigenesis.

Case Report

The patient is a 42-year-old obese woman (BMI 33.7) with a life-long history of heavy, irregular menses. An endometrial biopsy was performed; an endometrioid adenocarcinoma was diagnosed. On pre-surgery imaging work up, a 4.5-cm left ovarian mass was incidentally found. The patient underwent a total hysterectomy and bilateral salpingo-oophorectomy procedure. The specimens revealed FIGO grade I endometrioid adenocarcinoma with minimal myometrial invasion and focal cervical stromal involvement as well as a microcystic stromal tumor of the left ovary. The right ovary and bilateral fallopian tubes were unremarkable.

Tissue manipulation

All the tissue samples were fixed in formalin and embedded in paraffin. Full tissue sections were used for immunohistochemistry. Immunohistochemical staining was performed on an automated immunostainer (Dakoautostainer, Carpentaria, CA). Appropriate positive and negative controls were included. A list of antibodies used in this case is as follows: CD10 (Clone 56C6, Predilute);Cyclin D1 (Clone EP12, Predilute);Inhibin (Clone R1, Predilute);Calretinin (Clone DAK Calret1, 1:100); Cytokeratin (Clone AE1/AE3, Predilute); EMA (Clone E29, Predilute);Vimentin (Clone V9, 1:200); WT1 (Clone 6F-H2, Predilute); Estrogen receptor (Clone EP1, Predilute); Progesterone receptor (Clone PgR636, 1:350); Melan A (Clone A103, Predilute); and CD56 (Clone 123C3, 1:100). The above antibodies were from DAKO North America (Carpinteria, CA).C-Myc (Clone EP121, Predilute, Cell Marque, Rocklin, CA); CK14 (Clone LL002, Predilute, Cell Marque, Rocklin, CA); β-catenin (Clone 14, 1:1600, BD Biosciences, SanJose, CA).

Pathologic Findings

Macroscopically, the tumor was well circumscribed and had a white-tan, solid and nodular appearance (Figure 1A). It was confined to the left ovary. The tumor was extensively sampled and multiple tissue blocks were submitted for histologic evaluation. Microscopically, at low power of view, the tumor consisted of predominantly lobulated, cellular nodules separated by hyalinized fibrous stroma (Figure 1B). A rim of unremarkable ovarian parenchyma was present at the periphery of the lesion (Figure 1C). The lesion showed a pure solid growth pattern and no microcystic formation (Figure 1D). Rare foci of the tumor cells had abundant intracellular vacuoles (Figure 1E). At high magnification, the tumor cells were uniform and had round nuclei, open chromatin, inconspicuous nucleoli, and focally clear cytoplasm (Figure 1F). The vast majority of the tumor cells showed no nuclear grooves and nuclear membrane irregularity; only occasional nuclear grooves were appreciated. Mitotic count was up to 3 mitoses/10HPFs.