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Uterine Leiomyomas Presenting During Pregnancy and Delivery: Comprehensive Characterization of Features Helpful in
Ekaterina Olkhov-Mitsel1, Yutaka Amemiya2, Arun Seth1,3
1Department of Laboratory Medicine and Molecular Diagnostics, Division of Anatomic Pathology, Precision Diagnostics and Therapeutics Program, Sunnybrook Health Sciences Center.
Abstract:
A subset of uterine leiomyomas becomes clinically apparent during pregnancy/delivery and is typically excised during Cesarean section. Although benign, these leiomyomas excised during pregnancy and/or delivery (LEPs) can pose diagnostic challenges due to morphologic changes that mimic malignant mesenchymal neoplasms, such as leiomyosarcoma. This study analyzed 97 LEPs to characterize their histopathologic and immunohistochemical features. Histologic examination revealed predominantly low mitotic activity (mean: 0.5 mitoses/10 HPFs) and mild (87.6% of tumors) to at most focal moderate (9.3% of tumors) nuclear atypia. Ischemic necrosis occurred in 57.7% of tumors. Features attributed to coagulative necrosis were common, including sharp viable-nonviable transition (22.7%), perivascular tumor preservation (9.3%), and ghost outlines of tumor cell nuclei (50.5%). Focal myxoid changes, affecting ≤30% of tumor volume, were seen in 42.3% of tumors. Rare, bizarre cells were identified in 48.5% of tumors. Immunohistochemistry demonstrated the absence of estrogen receptor staining in 65% of tumors, with focal staining in 35.2%, and progesterone receptor expression in 97.7%. Caldesmon (98.9%) and desmin (100%) were positive, with the majority diffuse. CD10 (100%) showed variable staining intensity. Wild-type p53 expression was seen in all tumors tested. Expression of ATRX, MTAP, RB1, and PTEN was predominantly retained with equivocal staining in 35.3% (ATRX) and 3.4% (RB1) of tumors. Although Cyclin D1 expression was common (97.4%), it was always focal, with no diffuse (≥70%) strong nuclear staining. FH loss occurred in 3.2% of tumors. All tumors were negative for MelanA, and 92.4% were negative for HMB45. Calretinin expression was observed in 39% of tumors, typically focal and strong, while only 1 tumor showed positive inhibin staining in <5% of cells. ALK expression was focally positive or equivocal in 9.6% of cases, but no gene rearrangements were identified by in situ hybridization. Follow-up data were available for 71 patients (mean: 56 mo), with no malignant transformation or recurrence. These findings confirm that LEPs exhibit distinct morphologic and immunophenotypic alterations, including features typically attributed to coagulative tumor cell necrosis. However, given benign clinical outcomes, low mitotic activity, and lack of significant atypia, such a finding does not warrant designation as leiomyosarcoma or smooth muscle tumor of uncertain malignant potential in the context of concurrent pregnancy.
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