Rhabdomyoma of neck. a Cut surface of lobulated soft tissue mass with a meaty appearance and a red and white-gray color. The mass had a soft rubbery consistency and absence of necrosis. b Tumor cells have the appearance of well-differentiated rhabdomyoblasts, some with visible striations (seen between arrowheads and in inset)
The classic immature form, is identified by the presence of a mixture of bland primitive spindle cells with elongated muscle cells containing indistinct cytoplasm and muscle fibers. These spindle cells are haphazardly arranged in a fibromyxoid stroma and resemble myoblasts at 6–10 weeks of embryonic development. Myoblasts may be seen at different stages of differentiation.
The intermediate form shows a greater degree and a greater number of cells with skeletal muscle differentiation, “rhabdomyoblastic maturation”. Overlapping features can also be seen between the two forms. Immunohistochemically fetal rhabdomyoma typically expresses desmin, muscle specific actin and myoglobin. Primitive mesenchymal cells unpredictably express S-100 protein, glial fibrillary acidic protein, smooth muscle actin, and vimentin.
This is characterized by the presence of sheets of well-differentiated large cells that resemble striated muscle cells. The cells are deeply eosinophilic polygonal cells, with small peripherally placed nuclei and occasional intracellular vacuoles. Cross-striations are a hallmark of identification and minimal or no mitotic activity is present. Muscle specific actin, desmin, and myoglobin are expressed to a higher degree than fetal rhabdomyomas, but vimentin is not expressed in the adult form .
The diagnosis of fetal rhabdomyoma is complicated due to the paucity of cases and the similarities between rhabdomyosarcoma. Distinction from the spindle cell variant of embryonal rhabdomyosarcoma can be notoriously difficult. Unlike fetal rhabdomyomas, which are well circumscribed and do not invade and destroy adjacent soft tissue, rhabdomyosarcomas, have infiltrative margins and invade normal tissues. Histologically, rhabdomyosarcomas can be differentiated by the presence of cellular atypia, increased mitotic activity, lack of differentiation, and similarity to other sarcomas. Foci of necrosis and hemorrhage are often also present in rhabdomyosarcoma.
Other tumors in the differential diagnosis include benign hamartomatous lesions, such as neuromuscular hamartomas and rhabdomyomatous mesenchymal hamartomas of the skin , teratoma, vascular malformation, neurofibroma, schwannoma, granular cell tumor, hibernoma, paraganglioma, and malignant tumors with skeletal muscle differentiation. Immunohistochemical stains including S-100, desmin, and myoglobulin may also be helpful in making exclusive diagnosis (Table 38.2). For example, granular cell tumors express S-100 protein but skeletal muscle markers usually are absent .
Histological characteristics of tumors in the differential diagnosis
Primitive spindle cells, myoblasts, no mitotic figures
Express muscle specific actin, desmin, and myoglobin.
Weak S-100, vimentin expression
Well-differentiated skeletal muscle cells, cross striations
Strong actin, desmin and myoglobin expression.
Do not express vimentin
Cellular pleomorphism, nuclear atypia, mitotic figures, necrosis, invasion
Granular cell tumor
Strong staining for S-100
Mixture of granulated and smaller vacuolated cells, lipocytes (resembles fetal fat)
May express S-100,
Do not express muscle immunostains
Clinical diagnosis of fetal rhabdomyoma can be challenging due to the absence of distinctive clinical characteristics.
Diagnosis is made histologically via trucut biopsy (under radiographic guidance), open biopsy or excision biopsy of the lesion. Fine needle aspiration may also be a helpful tool in the work-up of rhabdomyomas. Cytological features suggestive of rhabdomyomas include cohesive clusters of spindle cells and rhabdomyoblasts with abundant eosinophilic granular cytoplasm, often peripherally located nuclei, cross-striations, elongated intracytoplasmic inclusions, and absence of mitotic figures. It is important to differentiate findings from a rhabdomyosarcoma, which will typically show pleomorphic nuclei and cellular atypical. There have been number of reports of solitary rhabdomyomas, which were correctly diagnosed with fine needle aspiration cytology preoperatively [11, 12].