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Malignant things you can miss
CAP 2011, Course AP104. The High Risk Benign Endometrium Neoplastic Things You Can Miss If You Don’t Think of Them! Marisa R. Nucci, M.D. Associate Professor of Pathology Division of Women’s and Perinatal Pathology Department of Pathology Brigham and Women’s Hospital Boston, MA Müllerian Adenosarcoma • Low grade müllerian tumor with a biphasic growth of benign or atypical epithelium and malignant stroma (usually low grade sarcoma) • Uterus > Ovary > Extragenital sites • Extragenital tumors particularly associated with endometriosis • Outcome depends on site and whether sarcomatous overgrowth is present Mutter and Nucci Benign Endometrial Polyp VS Müllerian Adenosarcoma, Low Grade Uterine Adenosarcoma • Age distribution – Typically postmenopausal women (mean 58 yrs) – 30% arise in premenopausal women – Younger age (mean 38 yrs) if arise in cervix • Clinical features – – – – Abnormal vaginal bleeding, pelvic pain History of recurring polyps Enlarged uterus Hyperestrinism (including tamoxifen) and prior XRT are risk factors 1 CAP 2011, Course AP104. The High Risk Benign Endometrium Müllerian Adenosarcoma • Diagnostic features – Phyllodes-like architecture – Intraglandular papillary projections – Marked stromal cellularity (with condensation) – Significant cytologic atypia – Mitoses > 2 per 10 high power fields – Altered epithelial differentiation Phyllodes-Like Architecture Mutter and Nucci Papillary projections 2 CAP 2011, Course AP104. The High Risk Benign Endometrium Stromal hypercellularity with condensation Significant cytologic atypia Mitotic Activity Altered differentiation Müllerian Adenosarcoma Differential Diagnosis – Uterine Corpus Endometrial polyp with cellular stroma – homogeneously cellular, no architectural changes, no cuffing, no cytologic atypia Endometrial polyp with bizarre stromal cells – No architectural changes, no cuffing, no mitoses Endometrial polyp with adenomyomatous stroma – Smooth muscle component, no architectural changes, no cuffing Atypical polypoid adenomyoma – smooth muscle is predominant component, squamous morules common, no periglandular cuffing, no intraluminal polypoid projections, no heterologous components Mutter and Nucci 3 CAP 2011, Course AP104. The High Risk Benign Endometrium EMP with cellular stroma Mutter and Nucci EMP with cellular stroma EMP with Stromal Atypia EMP with Stromal Atypia Adenomyomatous Polyp Adenomyomatous Polyp 4 CAP 2011, Course AP104. The High Risk Benign Endometrium Atypical Polypoid Adenomyoma Non-Diagnostic Cases • Endometrial polyp with atypical features, see COMMENT. COMMENT: The polyp is remarkable for X (cellular stroma, stromal atypia, unusual architectural feature); however, the findings are not diagnostic of an adenosarcoma. Clinical followup and consideration of followup sampling in 6 months is recommended to exclude the possibility of regrowth. Mutter and Nucci High Grade Squamous Intraepithelial Lesion (HSIL) VS Atrophy 5 CAP 2011, Course AP104. The High Risk Benign Endometrium High Grade SIL vs Atrophy • • • • • Highly cellular Crowded nuclei Irregular contour Uniformly hyperchromatic Mitotic activity • • • • • Highly cellular Well spaced nuclei Uniform contour Open chromatin No mitoses Atrophy p16 Ki-67 Mutter and Nucci p16 6 CAP 2011, Course AP104. The High Risk Benign Endometrium Conventional Atrophy Ki-67 Atrophy p16 HSIL p16 Mutter and Nucci Metastatic Tumors to Endometrium 7 CAP 2011, Course AP104. The High Risk Benign Endometrium Metastatic Tumor to Uterus • • • • • • • Breast Cancer (47%) Stomach (29%) Melanoma (5%) Lung (4%) Colon (3%) Pancreas (3%) Kidney (3%) Histopathologic Features of Metastatic Tumor • No grossly apparent lesion • Diffusely infiltrative pattern with sparing of normal endometrial glands • Capillary/lymphatic space invasion • Usually poorly differentiated • Lack squamous differentiation Kumar NB, Hart WR Cancer 1982 Metastatic Colonic Adenocarcinoma VS Primary Endometrioid Carcinoma Diagnostic Pearls • • • • • Abundance of acute inflammatory cells Necrosis in absence of solid growth Goblet cell differentiation Lack of squamous differentiation Well formed glands associated with uniform high nuclear grade Mutter and Nucci 8 CAP 2011, Course AP104. The High Risk Benign Endometrium Metastatic Breast (Lobular) Carcinoma VS Histiocytes Diagnostic Pearls • • • • Atypical nuclear features Cell clusters (cohesion) Single file growth Prominent intracytoplasmic vacuoles Consider Keratin, GCDFP Mutter and Nucci 9 CAP 2011, Course AP104. The High Risk Benign Endometrium Spread from an Upper Genital Tract Primary Diagnostic Pearls • • • • Mutter and Nucci Detached clusters of cells, papillary fronds Nests of cells within cleft like spaces No grossly visible lesion Benign endometrial background 10 CAP 2011, Course AP104. The High Risk Benign Endometrium Infarcted Leiomyoma VS Leiomyosarcoma Mutter and Nucci 11 CAP 2011, Course AP104. The High Risk Benign Endometrium Focused Ultrasound Degenerated Leiomyoma (Embolized) Degeneration Mimicking Malignancy Geographic Appearance Evaluation of Necrosis Coagulative Tumor Cell Necrosis • Multifocal • “Geographic” appearance with angulated outline • Sharp transition (< 5 cells) • Atypical “ghost” cells Mutter and Nucci 12 CAP 2011, Course AP104. The High Risk Benign Endometrium Mutter and Nucci Sharp Transition Sharp Transition Atypical Ghost Cells Atypical Ghost Cells Smooth, rounded contour Blurred Transition 13 CAP 2011, Course AP104. The High Risk Benign Endometrium Bland Ghost Cells Fibroblastic Repair Tumor Necrosis vs. Degeneration Interobserver variability in the interpretation of tumor cell necrosis in uterine leiomyosarcoma (USCAP 2011) Coagulative Tumor Cell Necrosis Ischemic Necrosis • Multifocal • Single, often central • Irregular, “map-like” • Smooth, rounded contour Number of cases diagnosed as indeterminate for TCN by: contour • Sharp transition • Blurred transition • Atypical “ghost” cells • Bland “ghost” cells • Fibroblastic repair • Fibroblastic repair ≥1pathologist No. of cases uncommon 20 ≥2pathologists 10 ≥3pathologists 4pathologists 4 1 Pearls • Leiomyosarcomas can have ischemic change • Coagulative necrosis is rare in a banal appearing smooth muscle tumor • Do not rely solely on CTN – Evaluate for atypia and mitoses – Consider STUMP (sparingly) Mutter and Nucci Early Serous Carcinoma VS Benign Endometrium (atrophy, polyp) 14 CAP 2011, Course AP104. The High Risk Benign Endometrium Serous Endometrial Intraepithelial Carcinoma • • • • • • • • Non-invasive variant of serous carcinoma Stratified/exfoliating High N/C ratio Cellular crowding Irregular nuclear contours Hyperchromatic nuclei p53 positive (most) High MiB-1 index Mutter and Nucci 85 15 CAP 2011, Course AP104. The High Risk Benign Endometrium Differential Diagnosis • Reactive/Degenerative epithelial changes • Arias-Stella effect • Exfoliation artifact Nuclear atypia Abundant cytoplasm Variable, typically low p53 immunostaining Reactive surface changes in polyps Mutter and Nucci Arias-Stella and ASE-like 16 CAP 2011, Course AP104. The High Risk Benign Endometrium Exfoliation Artifact Mutter and Nucci 17
