Soft tissue
Skeletal muscle
Alveolar rhabdomyosarcoma

Author: Erdener Ozer, M.D., Ph.D. (see Authors page)

Revised: 15 August 2017, last major update August 2017

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: Alveolar rhabdomyosarcoma [title]

See also: anaplastic rhabdomyosarcoma, solid rhabdomyosarcoma

Cite this page: Ozer, E. Alveolar rhabdomyosarcoma. PathologyOutlines.com website. http://pathologyoutlines.com/topic/softtissuealvrhabdo.html. Accessed December 15th, 2017.
Definition / general
  • A subtype of the rhabdomyosarcoma soft tissue cancer family whose lineage is from mesenchymal cells and which is related to skeletal muscle cells
  • Two fusion proteins can be associated with alveolar rhabdomyosarcoma (ARMS): ~60% of cases are positive for PAX3-FOXO1 fusion gene, 20% for PAX7-FOXO1 fusion gene, and 20% are fusion negative ARMS cases
ICD-10 coding
  • M8920/3
Epidemiology
  • Roughly 20 to 30% of all rhabdomyosarcoma tumors
  • Roughly 1% of malignancies found in children and adolescents
Sites
  • Commonly found in the head and neck region, male and female urogenital tracts, torso and extremities
Pathophysiology
  • Derived from precursor cells within muscle (Cancer Lett 2009;279:126)
  • Several genetic recombination events acting together cause the fusion protein, which leads to dysregulation of transcription and acts as an oncogene
Etiology
  • Most cases occur sporadically with no genetic predisposition
Clinical features
  • More common in early to mid teens but all ages affected
  • Primary tumor often presents as a painless soft tissue mass; tumor may also cause pressure symptoms on other structures in the primary site
  • 25 - 30% have metastases at diagnosis, including bone marrow, bones, distal nodes
  • PAX3-FOXO1 positive subset of ARMS occurs mostly in older children and young adults
Prognostic factors
  • Overall poorer prognosis than the embryonal subtype
  • Intergroup Rhabdomyosarcoma Study grouping (staging) is predictive of outcome
  • Patients who have metastatic ARMS positive with PAX3-FOXO1 fusion often have a poorer outcome (Adv Anat Pathol 2013;20:387)
  • Other variables that affect survival are anaplastic features, site and size of primary tumor, degree of local invasion, number of involved distal lymph nodes and other metastases
Case reports
Treatment
  • Standard surgery, radiation therapy and intensive chemotherapy
  • Patients who are fusion protein negative with low risk clinical features should be treated with reduced therapy
Clinical images

Images hosted on PathOut servers:

Retro-orbital, contributed by Mark R. Wick, M.D.



Images hosted on other servers:

Multiple nodules on foot

Progressive enlargement of skin lesions

Gross description
  • Fleshy, tan gray tumor
Gross images

Images hosted on PathOut servers:

Courtesy of Mark R. Wick, M.D.



Images hosted on other servers:

Congenital post-auricular tumor

Alveolar rhabdomyosarcoma

Microscopic (histologic) description
  • Cells are often small with little cytoplasm
  • Nuclei of the cells are round with normal, dull, chromatin structures
  • Classical subtype
    • Nests of neoplastic cells arranged in alveolar spaces
    • Amount of alveolar spaces present is not significant
    • Cells adhere to the periphery of the alveoli
      • Hobnail or tombstone appearance
      • May look like a non cohesive papillary pattern
    • Non cohesive cells appear to float in the center
    • Multinucleated giant cell forms may be seen
      • Nuclei usually peripheral, wreath-like
    • Normal muscle fibers may be entrapped
  • Solid subtype
    • Sheets of neoplastic cells
    • Nests separated by thin fibrovascular septae but alveoli are not seen
  • Occasional rhabdomyoblasts seen in 30% of cases
  • Often foci of coagulative tumor cell necrosis
  • Anaplastic cellular features may be seen
Microscopic (histologic) images
Scroll to see all images.


Images hosted on PathOut servers:

Classic subtype, contributed by Dr. Erdener Ozer

Myogenin, contributed by Dr. Erdener Ozer

Desmin, contributed by Dr. Erdener Ozer



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.:

Leg

Orbit

Unspecified



Myogenin

Nasopharynx, desmin

Nasopharynx, PAS

Desmin



Images hosted on other servers:

Perineal skin of infant

Cytology description
  • Uniform cellular pattern, multinucleate giant cells and incipient alveolar features
Cytology images

Images hosted on other servers:

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

Images hosted on PathOut servers:

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/FOX1 fusion negativity (in 20% cases) is associated with totally solid histologic subtype
  • N-myc amplification is seen in 50% (more aggressive cases)
Molecular / cytogenetics images

Images hosted on PathOut servers:

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



Images hosted on other servers:

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

t(2;13)(q35;q14) and
t(1;13)(p36;q14)

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

FISH

Videos


Histopathology skeletal muscle, face
Differential diagnosis
  • Alveolar soft part sarcoma: PAS+ intracytoplasmic crystalline rods and granules; no pleomorphism, no giant cells, no fibrous septa, negative for muscle specific actin and myoglobin
  • Embryonal rhabdomyosarcoma (ERMS): in contrast to solid variant ARMS, dense ERMS is characterized by variation in cellular and nuclear size and shape within a tumor. ARMSs typically show strong, robust, homogeneous expression with myogenin immunoperoxidase stains, as compared with the relatively weak to heterogeneous pattern seen with ERMS and have P3F or P7F gene fusions (Am J Clin Pathol 2013;140:82)
  • Merkel cell carcinoma: negative for muscle specific actin, desmin, myogenin and MyoD1, lacks fusion gene
  • Metastatic neuroendocrine carcinoma: keratin+, EMA+, desmin-, muscle specific actin-, lacks fusion gene
Board review question #1
Which immunostaining has been described as a more useful marker of the alveolar subtype of rhabdomyosarcoma?

A. ALK
B. Desmin
C. MyoD1
D. Myogenin
E. Smooth muscle actin
Board review answer #1
D. Myogenin (typically shows strong and homogeneous expression)