23.3 Histologic Features

The accepted derivation of cutaneous LMS is from arrector pili, dartoic, or breast smooth muscle, and the subcutaneous variant from vascular mural muscle. While a definitive derivation has not been conclusively proven, the frequency of cutaneous LMS on sites with greatest hair density supports this hypothesis. The vast majority of cutaneous LMS exhibit nodular aggregates and densely packed bundles of spindled smooth muscle cells (Fig. 23.2a, b). The superficial cutaneous variant tends to exhibit a diffuse infiltrative growth pattern with neoplastic cells splaying collagen bundles [3].

Subcutaneous LMS displays a characteristic circumscription and compressed collagen pseudocapsule [3]. Often, localized “hot spots” within the tumor demonstrate aggregates of atypical myocytes with bizarre mitotic figures interweaving chaotically between the more benign-appearing areas. Myxoid changes are not uncommon. Large thin-walled vessels may be noted within the neoplasm, and vascular invasion represents a poor prognostic indicator, as does involvement of deeper tissue planes, such as fascia and skeletal muscle [7].

Differentiating leiomyosarcoma from leiomyoma can be difficult; minimum criteria for malignancy include crowding, hyperchromatic nuclei, cellular atypia, irregular or asymmetric growth pattern with extension into the dermis, and mitoses (>1/hpf) [3]. Multinucleated giant cells with bizarre nuclei may be noted. Tumor depth, more so than grade, is correlated with metastases, local recurrence, and poor prognosis [2, 8–10]. A three-level grading system for soft tissue sarcomas has been developed by the French National Cancer Center, which takes into account differentiation (mature, certain, or uncertain), mitoses (0–9, 10–19, or 20+), and necrosis (<50% or >50%), though the unpredictable biological behavior of LMS based on grade alone limits the utility of this classification system [11].

The histologic differential diagnosis of LMS also includes other cutaneous and subcutaneous spindle cell neoplasms: atypical fibroxanthoma, malignant fibrous histiocytoma, hemangiopericytoma, fibrosarcoma, rhabdomyosarcoma, dermatofibroma, dermatofibrosarcoma protuberans, malignant schwannoma, nodular fasciitis, and synovial sarcoma [7]. The more common atypical fibrous xanthoma and malignant fibrous histiocytoma lack thin blunt-ended cells with tapered nuclei characteristic of smooth muscle. Due to its vascularity, the subcutaneous variant may resemble a hemangiopericytoma,

but close inspection should reveal cells with characteristic smooth muscle morphology.

While phosphotungstic acid hematoxylin or Masson’s trichrome staining can reveal the presence of muscle. LMS typically stains positively for vimentin, desmin, and smooth muscle actin (Fig. 23.2c). Subcutaneous and high-grade tumors may stain poorly or not at all. Staining for H-caldesmon, a regulatory protein specific for smooth muscle, has been shown to be positive in 60–73% of LMS [6]. Rare S-100 and cytokeratin positivity may make differentiating these tumors from melanoma and squamous cell carcinoma difficult [3]. Other reported variants include epithelioid, granular, and osteoclast-like giant cell predominant [3].

Summary: Prognosis

•LMS is characterized by a high local recurrence rate, which is greater for deeper subcutaneous tumors. While metastasis has been reported in up to 30% of subcutaneous tumors, the metastatic potential of superficial cutaneous tumors is thought to be minimal.

23.4 Prognosis

Due to the paucity of large studies and lack of consistent subtyping by histologic depth in the existing literature, the biological behavior of LMS is difficult to accurately assess. The prognosis of patients with superficial LMS depends on whether the tumor is cutaneous or subcutaneous in origin and whether the tumor is primary or recurrent. Early case reports suggested local recurrence rate for cutaneous LMS was 30–50% while up to 70% of subcutaneous tumors recurred [12–14]. The recurrent lesions tend to be larger, deeper, and more mitotically active than their primary lesions [13, 15].

In recent large case series, recurrence (or persistence of the tumor) following conventional wide excision has been shown to occur in about 16% of superficial LMS overall (6% for cutaneous and 18% for subcutaneous) [6, 16]. Recurrences of subcutaneous tumors after local excision are significantly greater than those limited to the dermis [3, 13, 14, 17], and greater tumor thickness is significantly associated with decreased disease-free survival [16]. Early literature suggested metastatic rates as

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Fig. 23.2 (a) Low-power view of leiomyosarcoma. Note depth of tumor involving entire reticular dermis and extending into the subcutis. (b) High-power view (200×). Fascicles of elongated cells with blunt-tipped nuclei. (c) Positive immunohistochemical staining with actin (200×)

M. Rubenzik et al.

high as 60% for subcutaneous LMS [12, 18], though this figure has been attenuated by larger, more recent investigations. These later studies suggest that subcutaneous LMS may metastasize to distant sites in up to 30% of cases, whereas the strictly cutaneous variant is considered to have very limited, if any, metastatic potential [2, 6, 9, 16]. The lungs are the most common site for metastases, liver and bone are following; however, lymphangitic spread may occur [3, 14, 19, 20].

23.4.1 Treatment

Owing to the rarity of LMS, standards for treatment have not been firmly established. Standard treatment for superficial LMS has been wide local excision

despite local recurrence rates of up to 45% (Table 23.1) [13]. While standard excisional margins have not been established, published margins range from 3.0 to 5.0 cm down to subcutaneous tissue or fascia [10, 13, 22, 23]. As stated above, recurrence rates correlate with the depth of invasion.

23.4.2 Mohs Micrographic Surgery (MMS)

A growing body of evidence supports the utility of Mohs micrographic surgery in reducing local recurrences. MMS has played a part in the treatment of LMS since 1987 [24]. Because of the ill-defined margins and infiltrative histology of LMS, conventional wide excision is not ideal. Since standard histological