Soft tissue
Skeletal muscle
Rhabdomyosarcoma
Alveolar rhabdomyosarcoma
Author: Erdener Özer, M.D., Ph.D.
Topic Completed: 1 August 2017
Minor changes: 25 May 2021
Copyright: 2002-2021, PathologyOutlines.com, Inc.
PubMed Search: Alveolar rhabdomyosarcoma [title]
Table of Contents
Definition / general | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Cytology images | Positive stains | Electron microscopy description | Electron microscopy images | Molecular / cytogenetics description | Molecular / cytogenetics images | Videos | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Ozer E. Alveolar rhabdomyosarcoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/softtissuealvrhabdo.html. Accessed June 19th, 2021.
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 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
- Neonatal alveolar rhabdomyosarcoma in 4 patients (Cancer 2001;92:1613)
- Infant with perineal tumor (Arch Pathol Lab Med 2002;126:982)
- 2 year old girl with pleural effusion and ovarian mass (Arch Pathol Lab Med 2003;127:e56)
- 9 and 17 year old boys with primary alveolar rhabdomyosarcoma of bone (Diagn Pathol 2016;11:99)
- 18 year old boy with rhabdomyosarcoma mimicking Burkitt-like lymphoma (Ann Hematol 2016;95:1017)
- 21 year old female patient with metastatic alveolar rhabdomyosarcoma to the thyroid gland (Acta Cytol 2014;58:288)
- 49 year old man with no significant medical history, presenting with symptoms of nasal obstruction (Case of the Month #494)
- 60 year old woman with primary cutaneous tumor of leg (Am J Surg Pathol 2002;26:938)
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
Contributed by Mark R. Wick, M.D.
Retro-orbital
Images hosted on other servers:
Multiple nodules on foot
Progressive enlargement of skin lesions
Gross description
- Fleshy, tan gray tumor
Gross images
Contributed by Mark R. Wick, M.D.
Alveolar rhabdomyosarcoma
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
Contributed by Erdener Özer, M.D., Ph.D.
Classic subtype
Myogenin
Desmin
Contributed by Dr. Farres Obeidin and Dr. Borislav Alexiev - Case #494:
MyoD1
Myogenin
AFIP images
Tumor cells grow in nests or clusters separated by fibrous septa
Solid growth
Solid growth with giant cells
Desquamated multinuclear giant cells
May resemble lipoblasts
Focal rhabdoid cells
Foci of anaplastic cells
(nuclei are hyperchromatic
and 3x larger than
surrounding cells)
Predominantly solid areas with
only focal alveolar pattern
resembles embryonal
rhabdomyosarcoma
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
Cytology description
- Uniform cellular pattern, multinucleate giant cells and incipient alveolar features
Cytology images
Images hosted on other servers:
Alveolar structures
Neoplastic cells
Positive stains
- Myogenin (typically strong and homogeneous expression, Pathol Oncol Res 2008;14:233); also desmin, muscle specific actin, MyoD1, P-cadherin (in translocation positive cases)
- Also ALK1, CAM 5.2, wide spectrum cytokeratin, neuroendocrine markers, p80, PAX5
Electron microscopy description
- Skeletal muscle differentiation
Electron microscopy images
Contributed by Mark R. Wick, M.D.
Alveolar rhabdomyosarcoma
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
Contributed by Mark R. Wick, M.D.
insituhybridization.jpg)
t(2;13) ISH
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
Additional references
Board review style 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
A. ALK
B. Desmin
C. MyoD1
D. Myogenin
E. Smooth muscle actin
Board review style answer #1
D. Myogenin (typically shows strong and homogeneous expression)
Reference: Soft tissue - Alveolar rhabdomyosarcoma
Comment here
Reference: Soft tissue - Alveolar rhabdomyosarcoma
Comment here
Board review style question #2
Which of the following molecular aberrations may be seen in alveolar rhabdomyosarcoma?
- COL1A1-PDGFB
- SS18-SSX1
- EWSR1-FLI1
- FOXO1-PAX7
- PAX3-MAML3
Board review style answer #2
