Molecular Evaluation of Low-grade Low-stage Endometrial Cancer With and Without Recurrence.

Low-grade, low-stage endometrioid carcinomas (LGLS EC) demonstrate 5-yr survival rates up to 95%. However, a small subset of these tumors recur, and little is known about prognostic markers or established mutation profiles associated with recurrence. The goal of the current study was to identify the molecular profiles of the primary carcinomas and the genomic differences between primary tumors and subsequent recurrences. Four cases of LGLS EC with recurrence and 8 cases without recurrence were evaluated via whole-exome sequencing. Three of the 4 recurrent tumors were evaluated via Oncomine Comprehensive Assay. The resulting molecular profiles of the primary and recurrent tumors were compared. Two of the 3 recurrent cases showed additional mutations in the recurrence. One recurrent tumor included an additional TP53 mutation and the other recurrent tumor showed POLE and DDR2 kinase gene mutation. The POLE mutation occurred outside the exonuclease domain. PIK3CA mutations were detected in 4 of 4 primary LGLS EC with recurrence and in 3 of 8 disease-free cases. LGLS EC with recurrence showed higher MSIsensor scores compared with LGLS without recurrence. The level of copy number gains in LGLS EC with recurrence was larger than LGLS EC without recurrence. This pilot study showed 1 of 3 recurrent cases gained a mutation associated with genetic instability (TP53) and 1 of them also acquired a mutation in the DDR2 kinase, a potential therapeutic target. We also noted a higher level of copy number gains, MSIsensor scores and PIK3CA mutations in the primary tumors that later recurred.

Absence of Distinct Immunohistochemical Distribution of Annexin A5, C3b, C4d, and C5b-9 in Placentas From Patients With Antiphospholipid Antibodies, Preeclampsia, and Systemic Lupus Erythematosus.

INTRODUCTION: In pregnancy, the presence of preeclampsia (PEC), systemic lupus erythematosus (SLE), and/or antiphospholipid antibody syndrome (APLS) is characterized by poor obstetric outcomes, with potential adverse effects for both mother and fetus. Although the histopathologic changes observed in these entities have been well established, the pathogenic mediators associated with tissue injury are poorly understood. METHODS: Forty placentas were evaluated, including 10 patients with preeclampsia, 9 with SLE, 11 with APLS, and 10 disease-free controls. Each case was subjected to a panel of immunohistochemical markers including C3b, C4d, Annexin A5, and C5b-9. Staining was graded on intensity and distribution. RESULTS: C4d staining was distinctly different among disease groups and controls. Moreover, 6/10 PEC cases, 3/9 SLE cases, and 4/11 APLS cases showed at least focal staining for C4d. All controls were negative. Annexin A5 (AnxA5) staining showed intrinsic variability in all disease groups, while 10/10 controls showed diffuse, strong staining (2+ or 3+). C3b staining was heterogeneous among groups. DISCUSSION: Previously, antiphospholipid antibody (aPLA)-associated pregnancy complications have been thought to be a consequence of a unique aPLA-mediated pathogenic mechanism. However, the immunohistochemical similarity (increased complement and decreased AnxA5 staining) observed in placentas from patients with APLS, PEC, and SLE suggests that aPLA-associated pregnancy complications may reflect a more general autoimmune mechanism.

Gynecologic Organ Involvement During Radical Cystectomy for Bladder Cancer: Is It Time to Routinely Spare the Ovaries?

PURPOSE: To determine a subset of women who could undergo ovary-sparing radical cystectomy (OSRC) for bladder cancer without compromising oncologic safety. PATIENTS AND METHODS: A retrospective review was performed of 164 consecutive women who underwent cystectomy at a single tertiary-care center from 1997 to 2018. Clinicopathologic and preoperative radiographic data were reviewed. Univariable and multivariable logistic regression models adjusting for pathologic stage, lymphovascular invasion (LVI), and carcinomain-situ were performed to evaluate the risk of ovarian and reproductive organ (RO) involvement. RESULTS: A total of 123 women with a median age of 71 years underwent radical cystectomy (RC) with removal of ROs for primary bladder cancer. Nineteen women (15%) had RO involvement by bladder cancer, and 5 of them (4%) were specifically found to have ovarian involvement. Patients with ovarian involvement of bladder cancer had more locally advanced disease (P = .01), LVI (P = .003) and positive margins (P = .003). On multivariable logistic regression, ≥ pT3 (odds ratio = 10.2; 95% confidence interval, 2.0-51.6; P = .005) and LVI (odds ratio = 3.9; 95% confidence interval, 1.1-14.2; P = .037) were associated with increased risk of RO involvement. Among 15 patients excluded for having a nonbladder primary malignancy, a third had RO involvement, and 2 (13%) had ovarian metastases. No women in our cohort had a primary ovarian malignancy detected at the time of RC. CONCLUSION: Women with ovarian involvement by malignancy at the time of RC either had locally advanced disease with LVI or a non-bladder primary malignancy. The risk of incompletely resecting the primary malignancy would be rare if OSRC was performed on women with organ-confined (≤T2) urothelial carcinoma.

Palliative hysterectomy for vaginal bleeding from breast cancer metastatic to the uterus.

Breast cancer is the most prevalent cancer in the United States. With an increasing rate of survivorship and extended life span for patients with metastatic disease, the demand for palliative care is increasing. Although uncommon, metastases to gynaecologic organs have been reported and are often present with post-menopausal bleeding. Post-menopausal bleeding can become clinically significant and have a detrimental effect on quality of life. We report the case of a 70-year-old woman with symptomatic vaginal bleeding caused by breast cancer metastatic to her uterus, cervix, fallopian tubes and ovaries. She was successfully treated with minimally invasive hysterectomy, resolving her vaginal bleeding and anemia and allowing her to resume chemotherapy.

Despite Diagnostic Morphology, Many Mixed Endometrial Carcinomas Show Unexpected Immunohistochemical Staining Patterns.

Historically, endometrial carcinomas have been classified primarily according to their histology. However, the use of immunohistochemistry has become commonplace in their evaluation, particularly in diagnostically challenging cases. Our objective was to evaluate mixed endometrial carcinomas using a well-established panel of biomarkers to assess the consistency and utility of these stains in clinical diagnosis. Eighteen cases comprised of various combinations of classical serous (SC), endometrioid (EC), and clear cell (CC) morphologies were identified and subjected to a panel of immunohistochemical markers including p53, p16, Ki67, estrogen receptor, progesterone receptor, and Napsin A. Intensity and extent of staining were evaluated on 4-tiered and 5-tiered scales, respectively. The typical immunostaining pattern expected for the individual tumor components was seen in only 3 cases, while in 15 cases an unexpected pattern was observed with at least one immunomarker. By tumor type, the most common unexpected finding in EC/SC carcinoma cases was diffuse positivity for p16 and/or estrogen receptor/progesterone receptor in both components, while in SC/CC, diffuse positivity for p53 in both components was most frequently seen, and in SC/CC/EC, Napsin A negativity was most commonly observed. Despite displaying diagnostic morphology, components of many mixed endometrial carcinomas may not exhibit expected immunohistochemical features. This may be due to the fact that these carcinomas arise from a single clone with subsequent divergence, resulting in a tumor with both mixed histologic and genetic features. It is important to note that these tumors may not demonstrate the immunohistochemical prototype of their constituents and should be approached accordingly from a diagnostic perspective.