Soft tissue
Skeletal muscle
Alveolar rhabdomyosarcoma

Author: Vijay Shankar, M.D. (see Authors page)

Revised: 26 September 2016, last major update November 2012

Copyright: (c) 2002-2016,, Inc.

PubMed Search: Alveolar rhabdomyosarcoma [title]

See also: anaplastic, solid

Cite this page: Alveolar rhabdomyosarcoma. website. Accessed October 27th, 2016.
Definition / General
  • High grade round cell malignancy with solid and alveolar growth and partial skeletal muscle differentiation
  • Resembles lymphoma
  • Deep muscles of extremities, axial muscles or perineum
Clinical Features
  • 20% of all rhabdomyosarcomas
  • More common in early to mid-teens but all ages affected
  • Neonatal cases have poor prognosis, are associated with skin and brain metastases (Cancer 2001;92:1613)
  • Rapid growing, often high stage at presentation
Case Reports
  • Overall poorer prognosis than embryonal subtype
  • Intergroup Rhabdomyosarcoma Study grouping (staging) is predictive of outcome
  • Poor prognostic factors: N-myc amplification, PAX3 fusion transcripts (J Clin Oncol 2002;20:2672)
  • Mixed forms with alveolar component are classified as alveolar for staging and diagnosis
Clinical Images

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Retro-orbital, courtesy of Mark R. Wick, M.D.

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Multiple nodules on foot

Progressive enlargement of skin lesions

Gross Description
  • Fleshy, tan-gray, mean 5 cm
Gross Images

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Courtesy of Mark R. Wick, M.D.

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Congenital post-auricular tumor

Micro Description
  • Thin fibrous septae lined by small round blue cells (resembling lymphoma) in an alveolar growth pattern (resembles pulmonary alveoli)
  • Loss of cellular cohesion so cells appear to float in alveolar spaces
  • Also peripheral cracking artifact at borders of cell clusters
  • Amount of alveolar tissue present is NOT significant (i.e. diagnose as alveolar even if only focal alveolar pattern)
  • Deep eosinophilic cytoplasm and presence of occasional multinucleated giant cells are important diagnostic features
  • 1/3 have rhabdomyoblasts with cytoplasmic cross striations
  • Often foci of coagulative tumor cell necrosis
  • May have neuroendocrine differentiation (Int J Surg Pathol 2009;17:135)
  • Mixed embryonal / alveolar: have foci with embryonal histology (spindle cell myoblasts, myxoid stroma)
  • Rarely has rhabdoid features (pink, ground-glass or fibrillar round to oval cytoplasmic bodies, large eosinophilic nucleoli)
Micro Images

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Tumor cells grow in nests or clusters separated by fibrous septa (AFIP)

Solid growth (AFIP)

Solid growth with giant cells

Desquamated multinuclear giant cells (AFIP)

May resemble lipoblasts

Focal rhabdoid cells

Predominantly solid areas with
only focal alveolar pattern
resembles embryonal
rhabdomyosarcoma (AFIP)

May resemble embryonal RMS
due to small round spindled cells
with hyperchromatic nuclei and
vacuolated spider cells

Alveolar type spaces contain desquamated small, round and poorly differentiated skeletal muscle cells; fibrovascular stroma is lined by undifferentiated round cells and differentiating cells with abundant eosinophilic cytoplasm, but only rare cross striations (AFIP)

Courtesy of Mark R. Wick, M.D.:





Nasopharynx, desmin

Nasopharynx, PAS


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Perineal skin of infant

Cytology Images

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Alveolar structures

Neoplastic cells

Cellular exudate with reactive mesothelial cells (double arrow),
lymphocytes (arrowhead), bizarre giant cells (single arrow) and
mitotic figures (double arrowhead), cells have vacuolated cytoplasm (inset),
tumor cells are desmin+ (3A), myogenin+ (3B), karyotype shows t(2;13) (fig 4)

Positive Stains
Electron Microscopy Description
  • Skeletal muscle differentiation
Electron Microscopy Images

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Courtesy of Mark R. Wick, M.D.

Molecular / Cytogenetics Description
  • t(2;13)(q35;q14): PAX3-FKHR in 60-85% (note: FKHR is now known as FOXO1)
  • t(1;13)(p36;q14): PAX7-FKHR in 15-20%
  • PAX/FKHR fusion negativity in 20% (associated with totally solid alveolar architecture, Am J Surg Pathol 2007;31:895)
  • N-myc amplification in 50%
  • P-cadherin is a direct PAX3-FOXO1A transcriptional target involved in alveolar RMS aggressiveness (Oncogene 2013;32:1876)
Molecular / Cytogenetics Images

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t(2;13) ISH, courtesy of Mark R. Wick, M.D.

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t(2;13): G-banding above
R- banding below

t(2;13)(q35;q14) and

Comparison of wild type
and fusion products
associated with t(2;13)
and t(1;13)


Differential Diagnosis
  • Alveolar soft parts sarcoma: PAS+ intracytoplasmic crystalline rods and granules; no pleomorphism, no giant cells, no fibrous septa, negative for muscle specific actin and myoglobin
  • Merkel cell carcinoma: negative for muscle specific actin, desmin, myogenin and Myo-D1, lacks fusion gene
  • Metastatic neuroendocrine carcinoma: keratin+, EMA+, desmin-, muscle specific actin-, lacks fusion gene