FINAL DIAGNOSIS: CUTANEOUS LEIOMYOSARCOMA
Leiomyosarcomas comprise approximately 7% of all soft tissue sarcomas. The vast majority of these lesions occur in the uterus and gastrointestinal tract. Within the soft tissue, cutaneous and subcutaneous leiomyosarcomas occur most commonly. Superficial leiomyosarcomas are usually divided into the two subcategories of cutaneous and subcutaneous leiomyosarcomas due not only to their difference in location, but also due to their differences in prognosis and their likely site of origin.
Cutaneous leiomyosarcomas, the type presented in this case, are believed to derive from precursor cells associated with the arrector muscles of the hair, the smooth muscle surrounding sweat glands or the genital dartos muscle. The majority occur between 40 and 60 years of age and occur more frequently in males. Cutaneous leiomyosarcomas often present as a solitary nodule smaller than 2cm, usually on the extremities, particularly on the hairbearing extensor surfaces and on the lower extremities. The overlying epidermis may exhibit a pink, purple, brown, or red discoloration; crusting; or ulceration. As many as 95% of patients report pain in association with the lesion, although some report itching, burning or bleeding. Some patients are even asymptomatic.
Histologically, cutaneous leiomyosarcomas are usually well-to moderately-differentiated neoplasms that may exhibit subcutaneous extension. However, metastatic leiomyosarcomas may exhibit prominent atypia. The proliferating cells are arranged in cellular poorly circumscribed fascicles of spindle cells with elongated nuclei with blunt ends and inconspicuous nucleoli. Some areas may be less differentiated with anaplastic nuclei and/or bizarre multinucleated giant cells. According to Fields and Helwig, more than 2 mitoses/10 HPF occur in approximately 80% of these tumors. Identification of the smooth muscle may be facilitated with a Masson's trichrome stain or a phosphotungstic acid-hematoxylin stain. The vast majority of these lesions are desmin, muscle specific actin, and vimentin positive. Diffuse S-100 immunostaining is often observed with cutaneous leiomyosarcomas, although they may be negative, as was this case; focal or no S-100 staining were commonly seen. Generally, cutaneous leiomyosarcomas are associated with a good prognosis. Metastases are rare, but, recurrences occur in up to 50% of cases with the most important prognostic factor being the depth of invasion. If subcutaneous extension does occur, metastasis occurs in up to 40% of cases. When metastasis is present, it most commonly is seen in the lungs. Neither tumor size nor histopathologic features have been correlated with the rate of local recurrence.
Subcutaneous leiomyosarcomas presumably derive from precursor in the muscular walls of veins and arteries. The inferior vena cava and veins of the lower extremities are the most common sites. This type of leiomyosarcoma has a more rapid growth rate than cutaneous leiomyosarcomas. Pain and numbness are common symptoms. In contrast to cutaneous leiomyosarcomas, these lesions may appear well-circumscribed. The risk of metastasis is greater than in cases of cutaneous leiomyosarcomas and the risk appears to increase with depth.
An unusual variant of superficial leiomyosarcomas is the epithelioid leiomyosarcoma. These lesions are composed predominantly of round epithelioid cells with abundant eosinophilic cytoplasm. The neoplastic cells stain with muscle actin and vimentin. Interestingly, however, the desmin and S-100 stains were negative in 5 of 5 recently reported cases. The differential diagnosis of this rare variant includes a variety of neoplasms such as malignant melanoma, epithelioid sarcoma, and metastatic disease.
Contributed by Valerie A. Holst, M.D., Paulina Quintana, M.D., and Mirka W. Jones, M.D.