A 56-year-old woman presented for the evaluation of a pelvic mass. PET scan showed intense activity in the mass along the left side of the rectum. She had a prior diagnosis of right tubo-ovarian high-grade serous carcinoma status post hysterectomy and bilateral salpingo-oophorectomy 10 years ago and multiple local recurrences in the past decade. A pelvic mass biopsy was performed, and the hematoxylin and eosin-stained (H&E) slides were reviewed. Several immunohistochemical (IHC) studies were also performed and the pictures are shown below.
The correct answer is ...
STK11 adnexal tumor.
The tumor shows closely packed tubules with solid and sieve-like areas composed of ovoid tumor cells with scant eosinophilic cytoplasm, and nuclear hyperchromasia with conspicuous nucleoli. Occasional pseudo-inclusions are also identified. There is a characteristic background of the myxoid stroma. The neoplastic cells are positive for CK7 (focal), WT1, and calretinin. P53 shows a wild-type staining pattern. CK5, EMA, and SF1 showed rare positive cells. The IHC stains for Pax-8, CDX2, CK20, Napsin A, and S100 are negative. Mayo Clinic solid tumor panel (next-generation sequencing) was also performed that demonstrated an STK11 c.580G>A (p.D194N) (VAF: 91%) mutation. The combined histology along with immunohistochemistry and molecular studies is most consistent with STK11 adnexal tumor.
STK11 adnexal tumor is a novel, usually para tubal, adnexal tumor occurring in females with a median age of 39 years. Very few cases are reported in the literature. Approximately 50% of these tumors are associated with the Peutz-Jeghers syndrome that harbors STK11 mutation, however, the histogenesis is still unclear. Tumors show diverse histological patterns with inter-anastomosing cords and trabeculae. Prominent myxoid stroma imparts a distinct appearance. These tumors are overtly malignant with atypical cytologic features often with prominent nucleoli and a variable mitotic index. Half of these cases are associated with metastatic disease at the time of diagnosis. The tumor variably expresses CK and sex cord-stromal markers (inhibin, calretinin, and WT1). The tumor can be easily confused with other ovarian tumors including high-grade serous carcinoma and female adnexal tumor of probable Wolffian origin (FATWO).
High-grade serous carcinoma is a malignant epithelial tumor showing serous (tubal type) differentiation with papillary, solid and/or glandular growth and moderate to severe nuclear atypia. It is associated with TP53 mutation (>97%). The tumor showed wild type p53 staining making a diagnosis of high-grade serous carcinoma less likely.
FATWO arises in the broad ligament or ovary and is considered Wolffian in origin. Morphologically, the tumor shows an admixture of hollow to solid tubules, sieve-like cysts, or diffuse growth with interspersed hyalinized bands. Eosinophilic luminal secretions may be present but cytological atypia and mitoses are usually minimal. Rarely, metastasis has been reported. When considering a diagnosis of malignant FATWO, consider the possibility of STK11 adnexal tumor if architectural patterns are not those typical of FATWO.
Qandeel Sadiq, M.B.B.S.
Fellow, Surgical Pathology
Maryam Shahi, M.D.
Senior Associate Consultant, Anatomic Pathology
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science