Immunohistochemical Analysis of HMB-45, MelanA and CathepsinK in a Series of 35 Uterine Leiomyosarcoma
Brooke E Howitt, J Kenneth Schoolmeester, Bradley J Quade, Marisa R Nucci. Brigham and Women's Hospital, Boston, MA
Background: Morphologic overlap between uterine leiomyosarcoma (uLMS) and perivascular epithelioid cell tumor (PEComa) may occur, particularly in cases of uLMS with epithelioid morphology. HMB-45 positivity can be seen in both uLMS and PEComa, so this marker is not considered discriminatory. As other markers frequently expressed in PEComa have not been systematically analyzed in uLMS, we chose to study expression of a panel of melanocytic markers and correlate the immunoprofile with tumor morphology.
Design: 35 uLMS (25 spindled, 5 myxoid, 4 epithelioid, and 1 spindled and epithelioid; consultation and in-house archives 1997-2012) were assessed for features described in PEComa, including abundant eosinophilic granular cytoplasm, multinucleated giant tumor cells, melanoma-like macronucleoli, prominent nuclear pseudo-inclusions, and typical vasculature. Based on H&E morphology, the tumors were classified into those having classic (uLMS-C), or those with either PEComa-like (uLMS-P), or lymphangioleiomyomatosis-like (uLMS-LAM) features. In addition, 3 uterine STUMP with PEComa like features were also evaluated (STUMP-P). Cases were stained for HMB-45, MelanA, and CathepsinK. Staining was scored as follows: rare cells (<1%), focal (1-10%), patchy (11-50%), or diffuse (>50%).
Results: Of the 35 cases, 15 (43%) were classified as uLMS-C, 18 (51%) as uLMS-P, and 2 (6%) as uLMS-LAM. All uLMS-C were negative for HMB-45 and MelanA, and 8/11 were Cathepsin K + (3 patchy, 5 focal). Of 18 uLMS-P, 3 were HMB-45 + (focal); however, no uLMS-P showed staining with MelanA. CathepsinK was + in 15/17 uLMS-P (2 diffuse, 8 patchy, 5 focal). Of uLMS-LAM, 1/2, 0/2 and 2/2 were + for HMB-45, MelanA, and CathepsinK (1 diffuse, 1 patchy) respectively. 1 of 3 STUMP-P was + for HMB-45 (rare cells), none for MelanA, and 1 for CathepsinK (patchy).
Conclusions: Uterine smooth muscle tumors (uSMT) with PEComa-like morphology are more likely to be positive, albeit focally, for HMB-45 than those with classic morphology. CathepsinK is more likely to show patchy to diffuse positivity in this subset as well. None of the uterine smooth muscle tumors, regardless of morphology, were positive for MelanA, which may be useful diagnostically. Nevertheless, the overlap in morphology and immunoprofile suggests a closer relationship between uterine PEComa and uSMT which may represent a morphologic continuum. Whether uSMT with PEComa-like features share a common pathogenesis and would be responsive to mTOR inhibitors merits further study.
Category: Gynecologic & Obstetrics
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 245, Tuesday Afternoon