A case of desmoplastic leiomyosarcoma: A rare variant of cutaneous leiomyosarcoma
1. Department of Pathology, Baylor College of Medicine, Houston, Texas
Desmoplastic leiomyosarcoma is a rare histologic variant of cutaneous leiomyosarcoma seen more commonly in men in their 50s and 60s. This neoplasm typically presents as a solitary, enlarging red-pink nodule or plaque on the extensor surfaces of lower extremities. Its unusual histology mimics other cutaneous desmoplastic lesions and the knowledge of this entity and use of an appropriate immunohistochemical panel is essential to arrive at the correct diagnosis. We report a rare case of desmoplastic leiomyosarcoma of the left flank in a 66-year-old male who presented with itching and pain in a long-standing skin lesion. Histopathology showed the presence of individual and small aggregates of spindle to pleomorphic cells with numerous mitoses in a densely fibrotic stroma. Immunohistochemically, the cells were positive for smooth muscle actin, heavy chain myosin, and desmin, confirming their smooth muscle origin. A diagnosis of desmoplastic leimyosarcoma was made. We discuss the case with a short review of the literature.
Leiomyosarcoma (LMS) of the skin and subcutaneous tissue is a rare soft tissue malignant neoplasm of middle-aged individuals. It is most commonly seen in the extremities and can also be seen in the head, neck, and scrotal regions [1, 2]. Clinically, these neoplasms can present as small, firm to hard nodules, plaques, or large ulcerated to exophytic tumors. Histologically, Kaddu et al. described two types of growth patterns of cutaneous LMSs a nodular and a diffuse pattern. The nodular lesions are cellular spindle cell tumors with numerous mitoses, cellular pleomorphism, and with either individual cell or large areas of necrosis. The diffuse pattern, on the other hand, is less cellular with rare mitoses and minimal pleomorphism .
The desmoplastic variant of superficial LMS is a very rare entity and there are only five reported cases in the literature excluding our case. The desmoplastic variant is unique in that it clinically presents as an indurated plaque and histologically shows the presence of sparse tumor cells separated by desmoplastic stroma. Based on the literature the tumor cells can have minimal to marked pleomorphism and mitoses can be few to frequent. The clinical and histologic features show a striking resemblance to other desmoplastic lesions of skin and knowledge of this entity with performance of appropriate immunohistochemical stains is required for a correct diagnosis.
A 66-year-old man presented to our dermatology clinic with a long- standing left flank plaque that had been present since the patient was 5-6 years old. Eighteen months prior to presentation he noticed itching in the lesion and a month before his presentation he noticed increase in the size of the plaque with onset of redness and pain. On clinical examination, a 6 cm x 3 cm obliquely oriented erythematous indurated plaque with irregular edges was noted on the left flank (Figure 1). On palpation, the surface appeared rough to touch and the patient complained of increases sensitivity. No axillary or inguinal lymphadenopathy was noted. The patient’s clinical history and physical examination suggested the following differential diagnosis: dermatofibrosarcoma protuberans and desmoplastic melanoma.
A punch biopsy of the plaque showed fascicles of spindle cells with atypical pleomorphic hyperchromatic nuclei in a collagenous, lightly eosinophilic fibrous stroma. Immunohistochemically, the neoplastic spindle cells were negative for pancytokeratin AE1/AE3, melan-A, HMB45, CD68, factor XIII, and CD34. However, a minority of neoplastic spindle cells were positive for S-100. This pattern suggested a differential diagnosis of a desmoplastic melanoma versus other atypical spindle cell neoplasm. The neoplasm was surgically excised with 2 cm margins.
The histologic examination of the excision specimen showed a sparsely cellular lesion within a desmoplastic stroma. It was predominantly dermis- based (Figure 2) with extension into the superficial subcutaneous tissue. The tumor cells were arranged in interlacing bundles of spindle cells. In addition, individual cells were observed infiltrating a dense collagenous stroma (Figure 4). The cells had pale eosinophilic cytoplasm and the nuclei ranged in morphology from oval to irregular and angulated. Scattered hyperchromatic and pleomorphic forms (Figure 4) including tumor giant cells were present. Focal areas showed bundles of spindle cells with elongated cigar-shaped nuclei. Frequent mitoses including atypical forms were present. The mitotic count was as high as 8 per 10 high power fields (HPF) (Figure 5). The spindle cells were seen wrapping around the adnexal structures, vessels, and nerve fibers. Focal perineural invasion was also identified. No lymphovascular invasion or large foci of necrosis were present. Scattered lymphocytic infiltrates were seen within and around the tumor.
A panel of immunohistochemical stains was performed on the tumor to evaluate the nature of these cells. The cells were strongly positive for three smooth muscle markers including smooth muscle actin, heavy chain myosin, and desmin (Figure 6). The cells were negative for S-100, tyrosinase, HMB-45, p63, CAM 5.2, pancytokeratin, CD68, CD99, and CD117. Of note, the rare S-100 positive cells on the biopsy may have been entrapped dendritic cells and the neoplastic spindle cells in the excision specimen were S-100 negative. Based on the histological picture and the immunohistochemical stains a diagnosis of desmoplastic LMS was rendered.
The primary LMSs of the skin are of two types, cutaneous and subcutaneous. The cutaneous LMSs are derived from the arrectores pilar muscle of the hair follicle except in the scrotum where they arise from the dartos muscle; the subcutaneous LMSs arise from muscle lining of the blood vessels .
Desmoplastic LMS is one of the rare variants of cutaneous LMS. Desmoplastic LMS is important to consider in the differential diagnosis of desmoplastic malignant spindle cell lesions of skin, especially when the immunohistochemistry fails to identify the more common desmoplastic skin tumors. Desmoplastic malignant melanoma and spindle cell or desmoplastic squamous cell carcinoma are two major histopathologic differential diagnoses for desmoplastic LMS. Other spindle cell neoplasms of fibroblastic and myofibroblastic differentiation may also be considered in the differential, especially on a small biopsy specimen.
A desmoplastic melanoma is a dermal based, ill-defined tumor composed of fascicles of spindle cells within a desmoplastic stroma; it may show the presence of neurotropism of neoplastic melanocytes . Positive staining with S-100 and lack of muscle markers helps to distinguish these lesions from desmoplastic leiomyosarcoma. Cutaneous spindle cell carcinoma is characterized by spindle and pleomorphic cells infiltrating the dermis as single cells and nests lacking keratinization. Immunohistochemically, a positive staining for p63 (rare positivity in desmoplastic LMS) and cytokeratin such as 34betaE12 are useful to confirm the squamous nature of these cells [4, 5]. In contrast to these lesions, desmoplastic LMS shows positive staining for smooth muscle markers and a lack of staining with the above described markers.
Desmoplastic LMS was first described by Karroum et al. in 1995 as sclerotic primary cutaneous LMS . The term desmoplastic LMS was suggested by Diaz-Cascajo et al. in 2000 . In all the reported cases these tumors presented as long standing lesions ranging from several months to years and were noticed because of enlargement or development of symptoms such as itching and tenderness, as seen in our patient. Histologically, all the tumors were dermal based with extensions into the subcutaneous tissue. They all shared the presence of striking sclerotic stroma with sparse tumor cells arranged in small clusters or as individual cells. The tumor cells on high power examination displayed blunt-ended nuclei and fibrillary eosinophilic cytoplasm. Within different cases, the cellular pleomorphism and mitoses varied from minimal to frequent. One of the two cases discussed by Diaz-Cascajo et al. showed cellular pleomorphism and scattered tumor giant cells; both of the cases had significant mitotic counts, 5 and 6 per 10 HPF, respectively. Our case, similarly demonstrated cellular pleomorphism and tumor giant cells as well as frequent mitoses. The cases discussed by Berzel-Cantalejo et al. and C Choy et al. showed subtle features of malignancy with rare mitoses and no necrosis [8, 9]. None of the reported cases including ours showed large areas of necrosis within the tumor. The clinical and immunohistochemical features of all the cases are summarized in Table 1.
Criteria for malignancy in cutaneous LMS are not well established. Features such as high cellularity, significant nuclear atypia, tumor giant cells, and at least 1 mitosis per 10 HPF are considered to be features of malignancy . Cutaneous LMSs recur in 30-50 percent of cases and there are only two reported cases of metastatic cutaneous LMSs. Subcutaneous LMSs recur in up to 50-70 percent of cases and metastasize in up to 30 percent of cases, the most common site of metastasis being lungs .
The management of desmoplastic LMS primarily involves wide surgical excision with 3-5 cm margins. Another treatment option that is available is Mohs micrographic surgery (MMS). As of 2004, there are 15 cases of superficial LMS treated with MMS. The recurrence of LMS after MMS is only 13 percent compared to a rate of 30-50 percent after wide surgical excision. However, the number of cases used to determine this recurrence rate is significantly smaller for MMS. In addition, there is a greater chance of sparing more tissue with MMS compared to wide excision .
All the cases of desmoplastic LMS including ours were treated by wide surgical excision. In two cases (Berzel-Cantalejo et al. and C Choy et al.), the margins of resection were positive. In the cases where follow-up information was available there were no metastases and recurrence was seen only in one case reported by Berzel-Cantalejo et al., which followed incomplete excision of the primary lesion due to patient’s refusal of further surgery. However, even in this case it was after a significant period of time (6 years) [6, 7, 8, 9].
In summary, desmoplastic LMS is a rare malignant smooth muscle neoplasm of the skin. There are only five cases reported in the literature; our case provides additional insight into this rare variant. The diagnosis of this neoplasm is difficult to determine based on clinical presentation and histopathology alone. Our case alerts readers about the importance of considering this entity in the differential diagnosis of desmoplastic spindle cell lesions of the skin.
ACKNOWLEDGEMENTS: We thank Dr. Yve Thaller Huttenbach for critically reviewing the manuscript.
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