Case 138 - Discussion

Uploaded: 2007-10-28, Updated: 2007-11-02

 
  • Positive: Desmin
  • Negative: Cytokeratin, CD30, PLAP
 

Rhabdomyosarcoma

CLINICAL FEATURES
 
  • Most common soft tissue sarcoma in children, adolescents and young adults.
  • Locations: head and neck (35-44%), genitourinary tract (18-24%, most commonly paratesticular region), extremities (15-19%) and trunk (chest and lungs) (10-15%).
  • Age incidence: embryonal and botryoid variants, 0-15 year-old; alveolar variant, 10-25 year-old; pleomorphic variant, 50-56 year-old.
  • Site predilection: Head and neck, 90% embryonal subtype; Genitourinary tract, 71% embryonal subtype; Extremities, alveolar subtype more common; botryoid variant arises in mucosal cavities (bladder, vagina, nasopharynx, and middle ear); most pleomorphic variants arise in the extremities of the adults;
Embryonal Rhabdomyosarcoma
 
  • Most common subtype of all rhabdomyosarcoma (49%);

  • Mostly affect young children under 10 year-old, average 7.9 years;

  • Most commonly sites, head and neck > genitourinary region > extremities, pelvis and retroperitoneum;

  • Histologically, various stages of embryogenesis of skeletal muscle morphogenesis. (1), alternating cellular and myxoid regions; (2), a mixture of poorly differentiated cells (poorly oriented, small, hyperchromatic, round or spindle, indistinct cytoplasm, 1-2 nucleoli, high mitotic rate) and differentiated cells (rhabdomyoblasts, abundant eosinophilic cytoplasm with granular, stingy or fibrillary materials concentrically surrounding the eccentric vesicular nuclei); (3), a matrix containing little collagen and various amounts of myxoid material; (4), occasionally cartilaginous differentiation.  Degenerated rhabdomyoblasts, glassy or hyalinized deeply eosinophilic cytoplasm with a pyknotic nucleus.

  • Spindle cell subtype of embryonal rhabdomyosarcoma: 3% of all cases, more differentiated, better prognosis. M/F=6/1. predominantly in the paratesticular region followed by the head and neck. Histologically, It is predominantly composed of elongated fusiform cells with cigar-shaped nuclei and prominent nucleoli. Eosinophilic cytoplasm with distinct cellular borders. Cross-striations are more readily discernible in this type. Consistently express myogeic antigens (MSA, desmin and myoglobin).

  • Botryoid subtype of embryonal rhabdomyosarcoma: 6% of all cases of rhabdomyosarcoma. This subtype characteristically arises under the mucosal surfaces of body orifices; therefore, it is most commonly observed in areas such as the vagina, bladder, and nares. It is distinguished by the formation of polypoid and grapelike tumor masses. On histologic study, botryoid rhabdomyosarcoma demonstrates malignant cells in an abundant myxoid stroma. "Cambium" layer, subepithelial condensation of tumor cells separated from an intact surface epithelium by a zone of loose stroma. Strong reaction to myogeic antigens.

  • Embryonal rhabdomyosarcoma has a unique molecular alteration, loss of heterozygosity at chromosome 11p15.5.

Alveolar Rhabdomyosarcoma
 
  • Second most common subtype, 31% of rhabdomyosarcomas;

  • Most frequently observed in adolescents, 10-25 years of age;

  • Most commonly in the deep tissue of the extremities, and accounts for approximately 50% of all extremity rhabdomyosarcomas;

  • On microscopy, the poorly differentiated round/oval tumor cells with scant indistinct cytoplasm are arranged in ill-defined aggregates. The individual aggregates are separated and outlined by a framework of dense fibrous/hyalinized septa that surround dilated vascular channels. The cells in the periphery of the cluster are well preserved and adhere to the fibrous septa, and the cells In the center of the clusters are arranged loosely, and therefore, they appear in an alveolar pattern. These cells stain intensely with eosinophilic stain. Multinucleated giant cells, multiple peripherally placed nuclei with pale or weakly eosinophilic cytoplasm. Cross-striated malignant rhabdomyoblasts are observed in 25% of cases, which is less frequent than what is observed with the embryonal form.

  • Alveolar rhabdomyosarcoma has distinct molecular characteristics, t(2;13)(q35;q14) (70%, PAX3 -FKHR ) and t(1;13)(p36;q14) (30%, PAX7-FKHR).

Pleomorphic Rhabdomyosarcoma

 
  • The least common of all subtypes, most often occurs in patients >45 years of age, mean 56 years. Rarely observed in children.

  • Most commonly seen in the deep soft tissue of the extremities;

  • Histologically, loosely arranged, haphazardly oriented, large, round or pleomorphic cells with hyperchromatic nuclei, deeply eosinophilic cytoplasm and multipolar mitotic figures. Rare cross-striations.

  • Positive for myogenic antigens (desmin, MSA, myoglobin, MyoD1), which are useful in differentiating this tumor from pleomorphic leiomyosarcoma and MFH.

IMMUNOHISTOCHEMISTRY AND SPECIAL STAINS
 
  • Rhabdomyosarcomas contain glycogen and are positive for PAS stain;
  • Positive antibodies: desmin, sarcomeric alpha-actin, myoglobin, MyoD1.
ELECTRON MICROSCOPIC FINDINGS
 
  • Thin myofilament (actin), thick myofilament (myosin) and Z-bands.

TREATMENT AND PROGNOSIS
 
  • The 5-year survival is highest for children aged 1-4 years (77%) and worst for infants and adolescents (47% and 48%, respectively). Orbital and GU sites are the most favorable (86% and 80%, respectively). Unfavorable sites included tumors of the extremities (50%), retroperitoneum (52%), and trunk (52%).

  • Botryoid and spindle variants > conventional embryonal variant > alveolar and undifferentiated variants.

REFERENCES
 
  • Enzinger and Weiss's Soft Tissue Tumors, 4th Edition. By Drs. Sharon Weiss and John Goldblum.