Myxoid Leiomyosarcoma of the Uterus

Abstract

Myxoid leiomyosarcoma (mLMS) of the uterus is a rare neoplasm; thus, knowledge of its clinical behavior and morphology remains limited. We therefore reviewed 30 cases initially diagnosed as uterine mLMS to better characterize its clinicopathologic features. Diagnosis was confirmed in 25 subjects (average age 51.5 y), of whom 80% were stage 1 at presentation. The average tumor size was 10.8 cm. An infiltrative tumor border was observed microscopically in 24 cases (96%); the border in 1 case could not be assessed. Fourteen cases (56%) had >10 mitoses per 10 high-power fields, 8 (32%) had between 2 and 10, and 3 cases (12%) had <2 mitoses. Geographic tumor necrosis and moderate to severe nuclear pleomorphism were seen concurrently in 12 cases (48%). All tumors expressed smooth muscle markers. Estrogen receptor was expressed in 29.4% of cases. Eighteen of 21 cases (85.7%) were negative for ALK by immunohistochemistry. Follow-up information was available in 18 subjects: 8 died of disease, 6 were alive with local and/or distant recurrence, and 4 were alive with no evidence of disease. Individuals who died of disease tended to have tumors with >10 mitoses per 10 high-power fields. Among cases with ≥5-year follow-up, overall survival was 11.1%, significantly worse compared with reported survival rates for conventional LMS. The initial diagnosis of mLMS was revised in 5 cases. Four had a distinctive loose myxoid appearance, nuclei with vesicular chromatin, and ALK positivity by immunohistochemistry, suggesting, suggesting inflammatory myofibroblastic tumor. This diagnosis was confirmed by in situ hybridization in 2 cases. One additional myxoid tumor lacked smooth muscle or myofibroblastic features and could not be classified further. mLMS is an aggressive neoplasm characterized by infiltrative tumor borders and variability of other features (mitotic count, atypia, and necrosis). The differential diagnosis includes myxoid leiomyoma and inflammatory myofibroblastic tumor. Attention to distinguishing morphologic features and immunohistochemistry will aid in the interpretation. An illustrated algorithm with criteria for diagnosis is proposed.

Inflammatory Myofibroblastic Tumors of the Female Genital Tract Are Under-recognized

“…However, as evidenced by patient 6 in this series and multiple previous reports, some gynecologic IMTs can behave aggressively with local recurrence or metastasis, 12 , 23 – 27 and it can be extremely difficult to prospectively identify which tumors are at high risk of metastasis. In other sites molecular testing may provide a clue to the risk of aggressive disease.…”

“…Indeed, at the time of writing we are aware of only 42 reported cases. 6 , 19 – 27 Furthermore all large series are multi-institutional and show a very strong bias toward consultation and referral cases. For example, Haimes et al’s 6 recent series of 11 IMTs included consultation cases from at least 4 renowned consultation pathologists and in Parra-Herran et al’s 23 series of 10 cases, 9 (90%) were external consultation cases.…”

“…Although morphologic clues to the diagnosis of IMT including myxoid change and a lymphoplasmacytic infiltrate have been described, uterine IMTs may have fascicular areas which closely mimic uterine smooth muscle tumors. 23 In this context it is particularly interesting to note that of the 42 reported cases of uterine IMTs, 6 (14.3%) were initially categorized as leiomyosarcoma (n=4), 27 smooth muscle tumor of uncertain malignant potential (STUMP) (n=1) 26 or leiomyoma (n=1) 6 before ALK IHC, FISH, or molecular testing was performed either on archived material solely for the studies 26 , 27 or as part of a comprehensive molecular panel performed as part of a personalized medicine approach for metastatic disease. 26 …”

Novel High-grade Endometrial Stromal Sarcoma

“…Myxoid LMS can also exhibit spindled cells with fascicular architecture, nonpleomorphic nuclei and minimal mitotic activity. 46–48 In contrast to myxoid LMS, however, our ESS tumors lacked long fascicles, thick-walled blood vessels, dense eosinophilic cytoplasm and cigar-shaped nuclei with blunted ends, features which typify smooth muscle neoplasms. Two tumors in our series were SMA positive, and 1 was focally desmin positive.…”

“…Although it is acknowledged that CD10 is not an entirely specific marker for endometrial stromal differentiation, it is also worthwhile mentioning that in 2 of the largest series of myxoid LMS, 10/18 (55%) and 7/18 (39%) of tumors showed moderate to strong (2+ to 3+) staining for CD10, similar to our ESS. 48 The investigation for BCOR and ZC3H7B rearrangements in histologically classified myxoid LMS would be an interesting endeavour and merits further study.…”