Skeletal Muscle Tumors





Benign tumors


Rhabdomyomatous Mesenchymal Hamartoma


Definition





  • A rare dermal or subcutaneous benign lesion composed of disordered mature elements, including skeletal muscle, adipose tissue, nerve bundles, blood vessels, adnexal tissue, and collagen



  • Initially reported as striated muscle hamartoma



  • Additional terms used in the past include congenital midline hamartoma and hamartoma of cutaneous adnexa and mesenchyme



  • Could reflect abnormalities in the migration of mesoderm during embryogenesis



Clinical features


Epidemiology





  • Slight male predominance



  • Most cases are congenital or discovered during infancy or early childhood



  • Rarely diagnosed in young adults



  • Mostly sporadic but may occur as part of a syndrome such as Goldenhar (oculoauriculovertebral) and Delleman (oculocerebrocutaneous) syndromes



  • Other associated conditions include persistent thyroglossal duct, amniotic band syndrome, spinal dysraphism, cleft lip, and cleft gum



Presentation





  • Majority of cases discovered incidentally



  • Solitary lesions by far predominate (over 80%)



  • Size ranges from a few millimeters to 2 cm



  • Skin-colored papule, nodule, pedunculated lesion, or mass, exceptionally as an atrophic plaque mimicking morphea “en coup de sabre”



  • The head and neck area is the most common affected location, particularly the periorbital and perioral regions



  • Rare cases described in perineal area, vagina, digits, oral cavity, and nares



Prognosis and treatment





  • Benign lesion



  • Cured by total surgical excision



  • No recurrences documented



  • An instance of complete spontaneous regression reported



Pathology


Histology





  • Subcutaneous or dermal lesion with spared overlying epidermis



  • Proliferation of mature skeletal muscles with regular cross-striations arranged in bands, single muscle fibers, or haphazard fashion



  • Additional components in variable proportions include




    • Mesodermal tissue: mature fat, elastic fibers, collagen, blood vessels, arrector pili muscles



    • Ectodermal tissue: eccrine glands, pilosebaceous units, vellus hair follicles, nerves




  • Calcification or ossification rarely seen



Immunohistochemistry/special stains





  • The skeletal muscle component expresses desmin, myoglobin, and myogenin



Main differential diagnoses





  • Accessory tragus



  • Rhabdomyoma



  • Rhabdomyosarcoma



  • Nevus lipomatosis superficialis



  • Fibrous hamartoma of infancy



  • Infantile myofibromatosis



  • Neuromuscular choristoma


Fig. 1


Rhabdomyomatous mesenchymal hamartoma.

Skin with disorganized skeletal muscle fibers in the reticular dermis.

(Courtesy of Tricia Peters, Houston, Texas, USA.)



Fig. 2


Rhabdomyomatous mesenchymal hamartoma.

Skin with disorganized skeletal muscle fibers in the reticular dermis.

(Courtesy of Tricia Peters, Houston, Texas, USA.)



Fig. 3


Rhabdomyomatous mesenchymal hamartoma.

Skin with disorganized skeletal muscle fibers in the reticular dermis.

(Courtesy of Tricia Peters, Houston, Texas, USA.)




Rhabdomyoma


Definition





  • An uncommon benign tumor of either mature (adult type) or immature (fetal type) striated skeletal muscle arising in the dermis or subcutaneous tissue



Clinical features


Epidemiology





  • Cutaneous lesions are divided into




    • Adult type: more common; affects the head and neck of middle-aged or elderly males



    • Fetal type: most commonly located at the periorbital, periauricular, and perioral areas of male infants




Presentation





  • Slowly growing, painless, solitary



  • Small nodular or lobulated mass



  • Periorbital lesions present with proptosis



  • Size ranges from 0.5 to 10 cm



Prognosis and treatment





  • Benign tumor



  • Cured by complete surgical excision



  • Recurs only if incompletely excised



Pathology


Histology





  • Well-circumscribed, nonencapsulated, subcutaneous tumor composed of variable proportion of large polygonal cells with abundant eosinophilic cytoplasm and small, round or spindle-shaped cells



  • Intracytoplasmic crystalline, rodlike inclusions may be seen



  • Cytoplasm may be vacuolated (spider cells)



  • Small, round vesicular nuclei with prominent nucleoli



  • Adult rhabdomyoma




    • Mainly large and polygonal cells with abundant eosinophilic cytoplasm



    • A scant stroma



    • Mitoses absent or rare



    • Intracytoplasmic crystalline, rodlike inclusions (corresponding to the Z-lines) are commonly seen




  • Fetal rhabdomyoma




    • A predominance of immature, round to spindle-shaped rhabdomyoblasts with a wide spectrum of skeletal muscle differentiation



    • Cross-striation in the cytoplasm of skeletal muscle fibers usually present at the periphery of the tumor, consistent with maturation of lesional cells



    • A variably myxoid stroma



    • Variation in cell size and shape without prominent atypia



    • Mitoses can be frequent



    • Necrosis is usually absent



    • A cellular variant is recognized




Immunohistochemistry/special stains





  • Tumor cells express desmin, myogenin, and muscle specific actin



  • Vimentin, S100 protein, and smooth muscle actin are less commonly positive



Ultrastructure





  • The adult type




    • Muscle cell differentiation with actin and myosin bundles



    • Cytoplasmic glycogen and crystalline rod-shaped inclusions




  • The fetal type




    • Muscle cell differentiation with actin and myosin bundles



    • Rod-shaped cytoplasmic inclusions are less common



    • Undifferentiated spindle cells also seen




Main differential diagnoses





  • Rhabdomyosarcoma



  • Granular cell tumor



  • Hibernoma



  • Infantile fibromatosis


Fig. 1


Adult rhabdomyoma.

This neoplasm is composed of large polygonal cells arranged in sheets with scant intervening stroma.



Fig. 2


Adult rhabdomyoma.

Polygonal cells have abundant eosinophilic cytoplasm and eccentrically located small, round nuclei.



Fig. 3


Adult rhabdomyoma.

Eosinophilic and vacuolated cytoplasm is characteristic. The cells lack nuclear atypia and mitoses.



Fig. 4


Fetal rhabdomyoma.

The cells are more spindled and less mature. This example lacks a more primitive component with zonal maturation.






Malignant tumors


Embryonal Rhabdomyosarcoma


Definition





  • A malignant mesenchymal tumor with predominant primitive cell morphology and evidenced skeletal muscle differentiation



  • Primary cutaneous tumors that arise in the dermis or subcutaneous tissue and lack deep soft tissue involvement are extremely rare



Clinical features


Epidemiology





  • Strong predilection for children and young adults



  • Rarely affects older individuals



  • Both sexes approximately equally affected



Presentation





  • Small, painless, solitary dermal or subcutaneous nodule



Prognosis and treatment





  • Limited information about prognosis, and clinical behavior is incompletely defined



  • Generally aggressive type of sarcoma despite small size and superficial location



  • Recent series of 11 primary cutaneous rhabdomyosarcomas revealed the presence of regional lymph node or distant metastases in over 50% of the patients and overall mortality of 36% in the mean follow-up period of 38 months



  • A combination of surgical excision, chemotherapy, and radiotherapy is employed



Pathology


Histology





  • Sheets of small, round to ovoid, uniform primitive cells with indistinct cell borders predominate



  • Well-differentiated muscle cells exhibiting cytoplasmic cross-striations may be focally seen



  • Typical cells include (not all cell types necessary are present)




    • Ribbon- or strap-shaped cells with elongated nuclei and bipolar cytoplasmic processes



    • “Tadpole” cells with eccentric nuclei and a single cytoplasmic process



    • “Spider-web” epithelioid cells with paranuclear periodic acid–Schiff (PAS)–positive intracytoplasmic vacuoles and threadlike cytoplasm




  • Brisk mitotic activity



  • Perivascular accentuation/condensation of tumor cells is typical



  • A variably myxoid stroma



  • Three histological variants exist




    • Botryoid rhabdomyosarcoma: characterized by dense subepithelial “cambium” layer



    • Anaplastic rhabdomyosarcoma: exhibiting marked atypia, hyperchromasia, and pleomorphism



    • Spindle cell rhabdomyosarcoma: composed almost entirely of spindle-shaped cells; currently recognized as a separate subtype of rhabdomyosarcoma (see Spindle cell/sclerosing rhabdomyosarcoma )




Immunohistochemistry/special stains





  • Tumor cells express desmin, myogenin, and myoD1



  • Aberrant cytokeratin expression can be seen



Genetic profile





  • More structural (but not recurrent) and copy number alternations from alveolar rhabdomyosarcomas, including gains of chromosomes 2, 8, 12, 13, and 20, and regional losses of 11p



  • MYOD1 mutations that may cooperate with PI3K-AKT pathway mutations in a subset of more aggressive cases



  • Intragenic deletions of DMD, which encodes dystrophin



  • The botryoid form can be seen in the familial cancer susceptibility syndrome of DICER1 -related disorders



  • Association with neurofibromatosis type 1 ( NF1 mutations) and Costello syndrome ( HRAS mutations)



Main differential diagnoses





  • Alveolar rhabdomyosarcoma



  • Ewing sarcoma



  • Neuroblastoma



  • Cutaneous lymphoma


Fig. 1


Embryonal rhabdomyosarcoma.

The neoplasm is composed of sheets of rhabdomyoblasts at different stages of differentiation, from small primitive cells to scattered cells with cytoplasmic cross-striations characteristic of mature skeletal muscle.



Fig. 2


Embryonal rhabdomyosarcoma.

Sheets of neoplastic cells, most of which are primitive with round nuclei and scanty cytoplasm. Occasional cells exhibit eccentrically located nuclei and abundant eosinophilic cytoplasm. Note the brisk mitotic activity.



Fig. 3


Embryonal rhabdomyosarcoma.

An area of more differentiated component. Note the “tadpole” cells with eccentrically located nuclei and the cytoplasmic cross-striations.



Fig. 4


Embryonal rhabdomyosarcoma.

Markedly pleomorphic cells, multinucleated giant tumor cells, and atypical mitosis are seen.



Fig. 5


Embryonal rhabdomyosarcoma.

Botryoid variant showing the typical dense subepithelial “cambium layer.”



Fig. 6


Embryonal rhabdomyosarcoma.

The neoplastic cells demonstrate nuclear staining with myogenin. This is a specific marker for skeletal muscle differentiation.



Fig. 7


Embryonal rhabdomyosarcoma.

A dermal embryonal rhabdomyosarcoma depicting the characteristic alternating dense hypercellular and loose hypocellular areas.



Fig. 8


Embryonal rhabdomyosarcoma.

High-power view of the alternating dense and loose cellularity. This example shows predominantly small primitive tumor cells.




Alveolar Rhabdomyosarcoma


Definition





  • A malignant mesenchymal tumor often with a distinct alveolar-like growth pattern and skeletal muscle differentiation



  • Primary cutaneous tumors that arise in the dermis or subcutaneous tissue and lack deep soft tissue involvement are extremely rare



  • PAX3 or PAX7 FOXO1 fusion gene is characteristically seen in vast majority of cases



  • Previously, tumors with combined embryonal and alveolar features were considered variants of alveolar rhabdomyosarcoma. Most such tumors lack the specific PAX FOXO1 fusion gene and tend to behave more like embryonal tumors



Clinical features


Epidemiology





  • Strong predilection for children and young adults



  • Rarely affects older individuals



  • Both sexes equally affected



Presentation





  • Small, painless solitary dermal or subcutaneous nodule



Prognosis and treatment





  • Limited information about prognosis, and clinical behavior is incompletely defined



  • Generally aggressive type of sarcoma despite small size and superficial location



  • Recurrence, distant metastasis and lymphnode involvement reported



  • A combination of surgical excision, chemotherapy, and radiotherapy is employed



Pathology


Histology





  • Nests of large rounded cells with readily recognizable rhabdomyoblastic differentiation separated by fibrous septa



  • Alveolar growth pattern with central cellular dissociation and necrosis



  • Nuclei are hyperchromatic and larger than nuclei in embryonal type



  • Multinucleated giant cells with wreathlike nuclei are common



  • Abundant mitoses



  • Epidermotropism reported in a single case



  • A solid variant lacking cellular discohesion is recognized



Immunohistochemistry/special stains





  • Tumor cells express desmin, myogenin, and myoD1



  • Aberrant cytokeratin expression can be seen



Ultrastructure





  • Skeletal muscle differentiation with actin and myosin cytoplasmic filaments



Genetic profile





  • t(2;13)(q35;q14) resulting in PAX3-FOXO1 fusion gene



  • t(1;13)(p36;q14) resulting in PAX7-FOXO1 fusion gene is less common



  • An estimated 15% to 20% of tumors lack PAX-FOXO1 fusion; in some other variant translocations are seen



Main differential diagnoses





  • Metastatic rhabdomyosarcoma



  • Embryonal rhabdomyosarcoma



  • Triton tumor (malignant peripheral nerve sheath tumor with heterologous rhabdomyoblastic component)



  • Ewing sarcoma



  • Neuroblastoma



  • Cutaneous lymphoma


Fig. 1


Alveolar rhabdomyosarcoma.

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Oct 29, 2019 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Skeletal Muscle Tumors
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