Departments of *Dermatology, and
†Pathology, Coimbra University Hospital, Portugal
‡Dermatology Department, Faculty of Medicine, University of Coimbra, Coimbra University Hospital, Portugal
The authors declare no conflicts of interest.
To the Editor:
Most cases of epithelioid leiomyosarcomas (LMSs) reported to date are located in the uterus or in the gastrointestinal tract, being rarely described in somatic soft tissue.
A 42-year-old woman presented with a firm erythematous nodular lesion, 30 mm in diameter, strongly adherent to the adjacent tissue planes, with central ulceration, located on her left lower leg. The lesion had developed progressively for 2 years, and it had become painful 1 month previously to our observation. Histopathological examination showed a proliferation composed predominantly of epithelioid cells with eosinophilic cytoplasm, irregular vesicular nuclei, and marked pleomorphism, occupying the dermis and extending to the subcutaneous fat (Figs. 1A–C). Focally, lesional cells had a more spindled morphology. Mitotic figures were frequent (32 per 10 high-power fields). Macroscopically, a vessel was identified and confirmed microscopically to be a medium-sized vessel infiltrated by the tumor, with atypical cells seen in probable continuity with the muscular layer (Figs. 1D, 2A, D). Immunohistochemical study revealed diffuse positivity for smooth muscle actin, desmin, and muscle-specific actin (HHF35), and focal staining for cytokeratin cocktail MNF-116 (Figs. 2B, C), and very weak and focal positivity for epithelial membrane antigen (EMA). Ki-67 revealed a proliferation fraction of approximately 50%. Immunohistochemistry was negative for S100, HMB45, CD31, CD34, ERG, and CD68. Expression of INI-1 was preserved. Based on these findings, the diagnosis of high-grade epithelioid LMS, likely of vascular origin, was established.
The patient was submitted to wide excision of the primary tumor with a 2-cm lateral margin down to fascia. Imaging studies (ultrasonography of the inguinal lymph node basin and thoraco-abdomino-pelvic computed tomography) did not show any evidence of secondary lesions. Treatment was complemented with adjuvant radiotherapy. After 2 years, the patient remains disease free and is still under follow-up.
LMSs account for approximately 10% of soft tissue sarcomas, with predilection for the lower limbs.1 LMSs that may involve the skin are usually divided in cutaneous (or dermal) and subcutaneous, with distinct features regarding origin, location, and prognosis. Cutaneous LMSs are thought to arise from the arrector pili muscles, mainly on the neck and head (50%).2 However, the deep subcutaneous type arises from the muscular layer of vessel walls, often on the lower extremities and trunk. Some authors believe that the proximity of the tumor to the vessel wall facilitates hematogenous spread of the tumor, which occurs in up to 30% of cases.3 This is clearly distinct from the more benign nature of the dermal subtype, which rarely metastasizes.2 Local recurrences can occur in both, although this is less likely if complete excision has been achieved.1
Histopathological findings are similar in both types, being characterized by fascicular arrangement of hyperchromatic spindle-shaped cells with blunt-ended nuclei.4 Unusual morphological variants, which may pose significant diagnostic problems to the pathologist, include epithelioid, granular cell, desmoplastic, inflammatory, and myxoid LMSs.
Our case displayed some unusual features because it had not only a predominance of epithelioid cells but also significant (although focal) cytokeratin expression. These findings warranted exclusion of epithelioid sarcoma, which was one of the main differential diagnoses considered initially. However, EMA had only minimal expression (much less than would be expected for epithelioid sarcoma), and CD34 (which may be present in about 50% of epithelioid sarcomas) was equally negative. Furthermore, nuclear INI-1 expression was maintained, and the tumor expressed muscle markers, including smooth muscle actin, HHF35, and desmin.
It has been previously described that epithelioid LMS has distinct features from classical LMS, namely the predominance of round and polygonal cells over the spindled component (variably present).5 By immunohistochemistry, markers of smooth muscle such as muscle-specific actin are positive, but desmin is not always expressed, namely in the more undifferentiated tumors.
Cytokeratin positivity had already been described in epithelioid LMS, although this is a rare finding.6 We speculate that epithelial markers like cytokeratins and EMA may be more frequently positive in epithelioid LMS than in conventional LMS, similarly to what happens with other epithelioid tumors of mesenchymal origin like, for example, epithelioid angiosarcoma. We highlight this unusual finding in our case as a potential diagnostic pitfall, namely in the differential diagnosis with metastatic carcinomas and epithelioid sarcoma, underlining the importance of using a wide immunohistochemical panel in unusual tumors such as this, to avoid misdiagnosis.
In conclusion, we describe a case of epithelioid LMS arising in a medium-sized vessel of the leg, an entity that may prove a diagnostic challenge due its rarity and unusual morphological and immunohistochemical features. We also highlight the potential for malignant behavior of these tumors, which makes prompt treatment and close follow-up mandatory in their management.
We are much indebted to Prof. Christopher D. M. Fletcher, from the Pathology Department of the Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, for performing additional immunohistochemistry and giving his expert opinion on this case.
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