“Malignant Mesenchymoma” Revisited

Abstract

Leiomyosarcoma (LMS) is the most common sarcoma in adults. Rarely, LMS dedifferentiates into an undifferentiated sarcoma. Very few cases of LMS with heterologous osteosarcomatous differentiation (OS) have been reported. The purpose of this study was to evaluate the clinicopathologic features of LMS with OS. Of 5570 LMS cases diagnosed from 2006 to 2022, 15 cases (0.2%) of LMS with OS were identified, affecting 13 females and 2 males; ages ranged from 32 to 66 years (median: 53 y). Ten tumors arose in the uterus, 2 in the retroperitoneum, and 1 each in the mesentery, mediastinum, and rectum. Primary tumors ranged from 7 to 20 cm (mean: 16 cm). The LMS components showed conventional spindle cell morphology in most cases; 3 cases showed marked pleomorphism; 3 cases contained an epithelioid component; and 1 case showed myxoid features. In 5 cases OS was identified in the primary tumor, whereas in 10 cases OS was first detected in metastases. One metastatic and 2 primary LMS showed both OS and chondrosarcomatous differentiation. Prominent osteoclastic giant cells were seen in the OS components in 11 cases. Mitotic activity ranged from 17 to 61/10 HPF with tumor necrosis in 10 cases. Twelve patients developed metastases; sites included lungs, diaphragm, kidney, adrenal glands, colon, small intestine, liver, bone, and pancreas. At last follow-up, 8 patients had died of disease, and 4 patients were alive with metastases. The interval between OS and death ranged from 3 weeks to 18 months (median: 6.5 mo). Development of OS in LMS is exceptionally rare. This form of heterologous differentiation may occur in both primary tumors and metastases. LMS with OS is highly aggressive with poor outcomes. Awareness of this phenomenon is important to avoid misdiagnosis as osteosarcoma.

Dedifferentiated leiomyosarcoma of the uterus: a clinicopathologic and immunohistochemical analysis of 23 cases

“…In keeping with prior publications of dedifferentiated soft‐tissue LMS, 12 dedifferentiated uterine LMS was defined by two distinct components: One or more differentiated smooth muscle components, showing morphological features of smooth muscle differentiation, including fascicular architecture, abundant eosinophilic cytoplasm, and cigar‐shaped nuclei, or features characteristic of epithelioid or myxoid smooth muscle tumours, and immunophenotypic evidence of smooth muscle differentiation, defined as ≥5% tumour cells staining for smooth muscle actin (SMA), desmin, or caldesmon. A dedifferentiated component, without diagnostic smooth muscle morphology and with at most rare cells positive for any smooth muscle immunomarker. Heterologous differentiation was regarded as a form of dedifferentiation, in keeping with prior reports 13,16,22 …”

“…Review of the literature identified 11 primary dedifferentiated uterine LMS. 12,[16][17][18][19][20][21] Follow-up was available in six cases, of whom three had died of disease at 4, 6, and 17 months, 16,17 one had died of other causes at 12 months, 12 and two were alive without disease at 12 and 28 months. 12,19 The literature also contains eight additional cases of primary conventional uterine LMS with subsequent dedifferentiation at metastatic sites, 16,21 with death from disease at median 7 months (range 1-18 months) after dedifferentiation.…”

“…Review of the literature identified 11 primary dedifferentiated uterine LMS 12,16–21 . Follow‐up was available in six cases, of whom three had died of disease at 4, 6, and 17 months, 16,17 one had died of other causes at 12 months, 12 and two were alive without disease at 12 and 28 months 12,19 .…”

“…Published series indicate that prospective recognition of dedifferentiated LMS is prognostically relevant, due to significantly shorter survival than LMS without dedifferentiation 14 . Across five series totalling 90 tumours, 12–16 74 (82%) dedifferentiated LMS had recurred or metastasised at median 8 months after initial diagnosis (range, 1–45 months), 49 (54%) had died of disease at median 11 months, and only six (7%) had greater than 60 months recurrence‐free survival. In published series, dedifferentiated and pleomorphic LMS appear predisposed to comparably aggressive behaviour 12–14 .…”

“…[12][13][14][15] In contrast, reports of dedifferentiated uterine LMS are limited. 12,[16][17][18][19][20][21] We hypothesised that dedifferentiation in uterine LMS is likely underrecognised, and that, when present, it heralds particularly aggressive behaviour, warranting prospective recognition.…”