The diagnosis of endometrioid intraepithelial neoplasia (EIN) is challenging owing to limited sampling, hormonal status, and other confounding histologic variables. Markers such as PTEN or PAX2 can delineate EIN in some cases, but are not wholly reliable. Clearly, new markers of EIN are needed. We explored several potential markers of EIN based rationally on molecular pathways most frequently misregulated in endometrial cancer: the 3-phosphoinositide kinase (PI3K)/AKT, β-catenin, and mismatch repair pathways. We studied PTEN, PAX2, β-catenin, and MLH1, in conjunction with 2 new markers—FOXO1 and phosphorylated AKT (pAKT)—not previously investigated in EIN. Benign (n=14) and EIN (n=35) endometria were analyzed by immunohistochemistry. Staining patterns were interpreted, tabulated, and scored by “clonal distinctiveness” in neoplastic lesions; that is, pattern alterations relative to normal glands. In normal endometria, FOXO1 was cytoplasmic in proliferative phase, but nuclear in secretory phase, showing that PI3K/FOXO1 participates in endometrial cycling and that FOXO1 is a readout of PI3K status. pAKT expression was low across normal endometria. FOXO1 or pAKT expression was altered in the majority of EINs (27/35, 77%), with FOXO1 and pAKT being co-altered only in some (20/35, 57%). β-catenin or MLH1 also exhibited clonal distinctiveness in EINs, showing that these are also useful markers in some cases. This is the first study to demonstrate the potential of pAKT and FOXO1 as biomarkers in the histopathologic evaluation of EIN. However, variability in expression poses challenges in interpretation.
Large cell neuroendocrine carcinoma (LCNEC) of the endometrium is an exceedingly rare histologic subtype of endometrial cancer (0.8%). These tumors are highly aggressive with a propensity for metastasis and have a poor prognosis. Among the 17 cases reported to date, 9 cases were pure large cell neuroendocrine tumors and 8 were collision tumors of LCNEC with endometrial carcinomas (7 endometrioid and 1 serous). In this article, we report a case of collision tumor composed of an endometrial LCNEC and a low-grade endometrial stromal sarcoma (LGESS). The patient was a 48 year-old woman who presented with a large abdominal mass for about 10 years and underwent total hysterectomy, bilateral salpingo-oophorectomy, and tumor debulking. Microscopic evaluation demonstrated an LGESS with extensive osseous metaplasia that penetrated through the myometrium and invaded into pelvic and abdominal cavity, forming a 40.0-cm mass. Cytogenetic analysis of the LGESS revealed an abnormal female karyotype (45, XX) with multiple structural abnormalities. Incidentally, small foci of LCNEC were identified within the endometrium. The LCNEC focally invaded the myometrium with involvement of the endocervix, extensive lymph-vascular space invasion, and metastases to bilateral ovaries. Subsequently, the patient was treated with cisplatin/etoposide chemotherapy and had been doing well for about a year until presenting with recurrence of LCNEC in the abdomen. She passed away a month later due to medical complications. This report reveals an extremely rare endometrial collision tumor with unusual pathologic features and clinical presentations.
Lymphangioleiomyomatosis (LAM) is a rare lung disease traditionally affecting women during their childbearing years. It can be sporadic or be associated with tuberous sclerosis syndrome. It is usually manifested in the lungs, kidneys, and/or lymphatic system. It consists of an overgrowth of abnormal smooth muscle-like cells, usually along the bronchovascular structures, resulting in the formation of cysts and the destruction of the lung parenchyma. We present the case of a 43-year-old woman with a history of pleural effusion and dyspnea. A computed tomographic scan revealed a mediastinal mass, chylothorax, and multiple pulmonary cysts. A diagnosis of LAM was rendered on a pleural fluid sample.
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