Primary cutaneous leiomysarcoma.

Primary cutaneous leiomyosarcoma of the skin is a rare soft tissue neoplasm, accounting for about 2-3% of all superficial soft tissue sarcomas. It arises between the ages of 50 and 70 years, and shows a greater predilection for the lower extremities. Clinically, it presents with solitary, well-circumscribed nodule and, microscopically, consists of fascicles of spindle-shaped cells with "cigar-shaped" nuclei. Local recurrence is known in this tumor. We document a case of primary cutaneous leiomyosarcoma in a 77-year-old man and discuss the histological features and immunohistochemical profile of this uncommon neoplasm.

Introduction

Leiomyosarcoma is a malignant neoplasm arising from the smooth muscle. It represents about 7% of all soft tissue sarcomas[1] and when it affects the skin, this tumor may be subdivided into two main categories: primary and secondary. Primary cutaneous leiomyosarcoma (PCL) of the skin is a rare soft tissue tumor that accounts for about 2–3% of all superficial soft tissue sarcomas.[12]

Case Report

A 77-year-old male, a farmer and a chronic tobacco chewer, presented with a sacral mass since 3 months. To begin with, he developed a small nodule in the sacral region 8 months back and was operated for the same. After the operation, there was an ulcerative lesion that increased in size to develop into the present sacral mass. There was no history of diabetes mellitus, hypertension or tuberculosis. Clinical examination revealed a mass in the sacral region measuring 7 cm × 5 cm × 5 cm with ulceration of the skin measuring 3 cm × 2 cm. A systemic examination of the cardiovascular, respiratory and central nervous systems was unremarkable. His hemoglobin, complete blood count, liver and kidney function tests were normal and he was nonreactive for human immunodeficiency virus and hepatitis B surface antigen. The wedge biopsy of the mass was reported as spindle cell carcinoma.

Pathological findings

Grossly, a specimen of an excised mass covered with skin measuring 10 cm × 8 cm × 6.5 cm was received. The skin showed brownish discoloration and ulceration of 3 cm × 2 cm [Figure 1a]. The cut surface revealed a nodular grayish-white, soft fleshy tumor measuring 7 cm × 5 cm × 5 cm [Figure 1b]. Microscopically, the tumor comprised of fascicles of spindle cells with focal areas of hemorrhage and necrosis. The spindle cells had eosinophilic cytoplasm with hyperchromatic “cigar-shaped” nuclei with inconspicuous to prominent nucleoli [Figure 2a]. The tumor showed marked nuclear pleomorphism with tumor giant cells. The mitotic activity was 20/10 high-power fields, with the presence of atypical mitosis [Figure 2b]. The inflammatory component was present throughout the tumor. The surgical cut margins except the base were free of tumor.

Figure 1

A specimen of an excised mass covered with skin measuring 10 cm × 8 cm × 6.5 cm. The skin showed brownish discoloration and ulceration of 3 cm × 2 cm (a). Cut surface revealed a nodular grayish-white, soft, fleshy tumor measuring 7 cm × 5 cm × 5 cm (b)

Figure 2a

Microscopically, the tumor comprised of fascicles of spindle cells with cigar-shaped nuclei (hematoxylin and eosin stain; ×100)

Figure 2b

The tumor showed marked nuclear pleomorphism with tumor giant cells, mitosis and presence of inflammatory infiltrate (hematoxylin and eosin stain; ×400)

Immunohistochemistry

The tumor cells were immunoreactive for smooth muscle actin (SMA) while being negative for S-100, desmin, CK-7 and CD34 Figure 3.

Figure 3

The tumor cells were immunoreactive for smooth muscle actin (IHC, ×400)

Discussion

PCL arises between the ages of 50 and 70 years, with a male to female ratio of 2:1 to 3:1.[1] This tumor shows a greater predilection for the lower limbs; 50–75% of the lesions appear on the lower limbs, 20–30% on the upper limbs and 10–15% on the trunk. The cause of PCL is unknown, but the most common predisposing factors suggested are physical trauma and exposure to radiation.[2-4] Cutaneous leiomyosarcomas are divided into two subtypes depending on the location of the tumor. The superficial dermal form of leiomyosarcoma is thought to arise from the arrector pili muscle whereas the deep subcutaneous type is thought to arise from the smooth muscle of the vascular wall.[12] They clinically present with solitary, well-circumscribed nodules ranging from 0.4 to 6 cm. The skin over the dermal type is usually erythematous or brownish in color and, in the subcutaneous form, has a normal appearance. In general, dermal tumors appear adhered to the epidermis with frequent ulceration of skin with or without crusts, while subcutaneous tumors are mobile.[15] Our patient was a 77-year-old male who presented with a sacral mass of 7 cm × 5 cm × 5 cm, with brownish discoloration and ulceration of the skin. As he was a farmer by occupation, there is possibility of trauma, which might have gone unnoticed in his case. Histologically, they consist of fascicles of spindle-shaped cells bearing “cigar–shaped” nuclei. The degree of differentiation may vary within a single tumor. Generally accepted features of malignancy include the presence of mitoses of 2/ 10 high-power fields, high cellularity, significant nuclear atypia and tumor giant cells.[34] Kaddu[3] has described two different growth patterns: a nodular pattern that is quite cellular with nuclear atypia, many mitoses and a diffuse pattern that is less cellular with well-differentiated smooth muscle cells and less mitoses. Unusual morphological variants of cutaneous leiomyosarcoma that have been described include epithelioid, granular cell, desmoplastic, inflammatory and myxoid leiomyosarcoma. In poorly differentiated tumors, immunohistochemical studies can differentiate the muscular origin of the lesion. Classical immunophenotyping of PCL comprises of positive vimentin, desmin and SMA staining. Cutaneous leiomyosarcoma may show different immunophenotypes thus emphasizing the importance of using a large panel of antibodies (SMA, HHF-35, desmin, vimentin, cytokeratins and S-100 protein) in immunohistologic diagnosis.[3] The histological findings in this case were that of a poorly differentiated inflammatory leiomyosarcoma with high mitotic activity and necrosis. The tumor also had a diffuse inflammatory component because of which the histological diagnosis of malignant fibrous histiocytoma was favored.

The benign and malignant tumors that have to be differentiated from PCL are schwannoma, plexiform neurofibroma, dermatofibroma, leiomyoma, fibroacanthoma, malignant melanoma, spindle cell synovial sarcoma, spindle cell carcinoma and malignant fibrous histiocytoma. Immunohistochemistry will be helpful in difficult cases.

The most effective treatment for PCL is wide excision, with a 3–5 cm lateral margin and a depth that includes subcutaneous tissue and fascia.[5] Local excision without adequate margins leads to recurrence and increases the risk for metastatic and fatal disease. While superficial dermal leiomyosarcoma have been reported to show local recurrence rates of 30–50% and rarely metastasize, subcutaneous leiomyosarcoma recur up to 70%, and the metastatic rate has been reported in 30–40% of the cases.[6] It is important to ascertain that excision is complete by pathologic examination because the quality of the surgical treatment influences the prognosis. Adjuvant therapies such as radiation therapy and chemotherapy have been unsuccessful.[4]

Recent studies have provided greater understanding of prognostic factors and the risk of recurrence. Jensen et al.[6] had identified several poor prognostic factors, namely tumor size more than 5 cm, deep location with fascia involvement, high malignancy grade and acral distribution.[7] All the above poor prognostic factors were present in this case and thus the patient came back with a local recurrence after 8 months.

Conclusion

Primary cutaneous leiomyosarcoma is an uncommon tumor with a misleading histomorphology.