(1)
Department of Pathology, University of Manitoba Max Rady College of Medicine, Winnipeg, MB, Canada
Keywords
Cutaneous leiomyomaCutaneous leiomyosarcomaDeep leiomyosarcomaGlomus tumorLeiomyomaSmooth muscle is present in almost any part of the body, including the gastrointestinal, genitourinary, and vascular systems. Similarly, smooth muscle tumors can also be found in almost any anatomic location. Morphologically, the neoplastic cells of smooth muscle tumors are noted to have eosinophilic cytoplasm and elongated or ovoid nuclei (Fig. 7.1a).
Fig. 7.1
(a) Smooth muscle cells with a spindled appearance and long, ovoid, “cigar-shaped ” nuclei. (b) Perivascular glomus cells with a more rounded and epithelioid appearance
Perivascular tumors contain a modified type of myoid cell that is associated with the vascular system. These are identified as glomus cells and can have an epithelioid or spindled appearance (Fig. 7.1b) [1].
7.1 Glomus Tumor
Glomus tumors are neoplasms that show differentiation analogous to the glomus body , a structure that is intimately associated with the vascular system and regulates body temperature by altering blood flow in the distal extremities. Glomus tumors often arise as painful lesions measuring less than 1.0 cm in greatest dimension. They tend to occur in the distal extremities, particularly beneath the fingernail [2]. Numerous other sites of occurrence, such as the gastrointestinal tract, have been described [3].
Pathology
Grossly, glomus tumors are well-circumscribed lesions that can be blue or red in appearance. Microscopically, these neoplasms are composed of vascular spaces surrounded by cells with clear to purple cytoplasm and round nuclei (Fig. 7.2). These cells can be enlarged and have an epithelial-like appearance (Fig. 7.3) [2].
Fig. 7.2
Glomus tumor of the skin with epithelioid-like cells in close proximity to vascular spaces
Fig. 7.3
High-power view of glomus tumor. The epithelioid-like cells contain vesicular and bland nuclei
Morphologic Variants
Glomuvenous malformation (Glomangioma ) – In this variant, the vascular spaces are enlarged and have a thin rim of associated glomus cells (Fig. 7.4). These usually arise in the hand or forearm of children. This entity is particularly known to arise in patients who have a familial history of glomus tumors [4].
Fig. 7.4
In this glomuvenous malformation, the vascular spaces are more dilated and have a thinner rim of glomus cells
Ancillary Studies
The cells of glomus tumors are diffusely positive for smooth muscle markers such as h-caldesmon , muscle-specific actin, and smooth muscle actin.
Comment
- 1.
Positive staining for smooth muscle markers differentiates glomus tumors from adnexal and melanocytic neoplasms.
- 2.
Glomus tumors are usually benign lesions and are treated with simple excision. Following surgery, approximately 11% recur [7].
- 3.
Glomus tumors can behave more aggressively. Malignant glomus tumors are defined as lesions with cells containing nuclei with moderate to severe atypia and having over five mitosis per 50 high power fields (hpf). Alternatively, a designation of malignant can be given if a glomus neoplasm has atypical mitotic figures. Malignant tumors have a metastatic rate of 38% [8].
- 4.
Glomus tumors of uncertain malignant potential are lesions which contain over five mitosis per 50 hpf without nuclear atypia or lesions that are deeply situated and measure over 2 cm. Since they rarely metastasize, patients should be closely monitored following excision [6].
7.2 Cutaneous Leiomyoma
Cutaneous leiomyomas are benign neoplasms of smooth muscle that either arise from the smooth muscle cells of the pilar arrector muscles (pilar leiomyoma) or from the smooth muscle cells in the genital region or nipple area (genital leiomyoma) [9].
Clinically, pilar leiomyomas manifest as skin papules in adolescents that measure less than 2 cm and are painful when exposed to low temperatures [6, 10]. Patients who have multiple cutaneous leiomyomas may have hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC ), which is associated with a germline mutation in the fumarate hydratase gene . Consequently, these patients should be referred for appropriate testing and screening for renal tumors [11].
Genital leiomyomas can arise in the vulva, scrotum, nipple, and perianal areas. These are often deeper and more nodular than their pilar counterpart [9].
Pathology
Microscopically, pilar leiomyomas are composed of spindle cells with “cigar-shaped” nuclei that are haphazardly arranged and infiltrate the surrounding dermis (Fig. 7.6a, b). Genital leiomyomas contain a similar smooth muscle cell proliferation but are usually more circumscribed (Fig. 7.7).
Fig. 7.6
(a) Pilar leiomyoma extending outward from the adnexal structures of the skin. (b) Pilar leiomyoma with small fascicles of smooth muscle with associated fibrotic tissue
Fig. 7.7
Well-circumscribed genital leiomyoma arising from the dartos muscle in the scrotum
Ancillary Studies
Leiomyomas are positive for desmin and smooth muscle markers such as smooth muscle actin and caldesmon.
Differential Diagnosis
Leiomyosarcoma
Atypical intradermal smooth muscle neoplasm
Comments
- 1.
When encountering smooth muscle tumors in the skin or subcutaneous tissue, a pathologist should exclude the possibility of a leiomyosarcoma, which has metastatic potential.
- 2.
Cutaneous leiomyoma lacks the cellular atypia and substantial mitoses of leiomyosarcoma or atypical intradermal smooth muscle neoplasm. Furthermore, these are usually limited to the dermis [12].
- 3.
Cutaneous leiomyomas are benign and simple excision is the general approach to treatment.
- 4.
Patients with multiple lesions are sometimes treated with laser therapy, given that multiple excisions are not possible [6].
- 5.
Patients with multiple cutaneous leiomyomas should be assessed for a mutation in the fumarate hydratase gene, which is associated with hereditary leiomyomatosis and renal cell cancer syndrome.
7.3 Deep Leiomyoma
Leiomyomas arising in the deep soft tissue are rare and are divided into two separate categories. Leiomyomas arising deep in the upper and lower extremities (of both males and females) are extraordinarily rare and are designated somatic leiomyomas. Leiomyomas arising in the abdominal cavity or retroperitoneum of females (separate from the uterus) are termed gynecologic leiomyomas [13].
Pathology
Microscopically, somatic leiomyomas (such as those arising in the extremities) contain spindle cells that are organized in bundles. Sometimes calcifications can be seen in these tumors (Fig. 7.8). Importantly, substantial nuclear atypia is not identified, and less than one mitosis is found in 50 hpf examined.
