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Soft Tissue Tumors Part 3 - Muscle, Vascular, Nerve, Other
Alveolar rhabdomyosarcoma
Author: Nat Pernick, M.D, PathologyOutlines.com, Inc.
Revised: 17 July 2009, last major update July 2009
Copyright: (c) 2002-2009, PathologyOutlines.com, Inc.
Subtypes discussed below: Anaplastic variant, Solid variant
Definition
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● High grade round cell malignancy with solid and alveolar growth and partial skeletal muscle differentiation
● Resembles lymphoma
Clinical
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● 20% of all rhabdomyosarcomas
● More common in early to mid-teens but all ages affected
● Sites: deep muscles of extremities, axial muscles or perineum
● 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
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● Infant with perineal tumor (Archives 2002;126:982)
● 2 year old girl with pleural effusion and ovarian mass (Archives 2003;127:e56)
● 60 year old woman with primary cutaneous tumor of leg (AJSP 2002;26:938)
Treatment and prognosis
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● 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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Neonate has nodules on foot Neonate with metastatic skin disease
Gross description
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● Fleshy, tan-gray, mean 5 cm
Gross images
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Tumor in skeletal muscle Congenital post-auricular tumor
Micro description
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● 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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Primitive round cells appear to float Fig B: nuclei are large and uniform,
within nests lined by fibrous septa compared to embryonal subtype (Fig A)
Tumor cells grow in nests or clusters separated by fibrous septa (AFIP)
Solid growth (AFIP) Solid growth with giant cells
Predominantly solid areas with only focal
alveolar pattern resembles embryonal
rhabdomyosarcoma (AFIP)
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)
Desquamated multinuclear Multinucleated giant cell Some cells may resemble
giant cells (AFIP) lipoblasts (AFIP)
Tumor cells may resemble embryonal Focal rhabdoid cells
rhabdomyosarcoma due to small round
and spindled cells with
hyperchromatic nuclei and
vacuolated spider cells (AFIP)
Perineal skin of infant H&E, keratin and CD56
H&E, ALK1 and p80 Desmin
Myogenin
Cytology images
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Cellular exudate (fig 2), 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+ (fig 3A), myogenin+ (fig 3BB), karyotype shows t(2;13) (fig 4)
Videos
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Positive stains
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● Muscle specific actin, desmin, myogenin (strong nuclear staining, AJSP 2001;25:1150)
● Myo-D1 (AJSP 2006;30:962), ALK1
● Also CAM 5.2 and broad spectrum cytokeratin (50%), neuroendocrine markers (43% express at least one, Mod Pathol 2008;21:795), p80 (25%, cytoplasmic dot-like pattern, Mod Path 2002;15:931), PAX5 (67%, Am J Surg Pathol 2009;33:775)
Electron microscopy
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● Skeletal muscle differentiation
Molecular / cytogenetics
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● 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%
Molecular images
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Karyotype Diagram of translocations Hybrid genes
FISH
Differential diagnosis
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● 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
● Alveolar soft parts sarcoma - no pleomorphism, no giant cells, no fibrous septa, negative for muscle specific actin and myoglobin, PAS+ intracytoplasmic crystalline rods and granules
Variants
Definition
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● Alveolar rhabdomyosarcoma with anaplastic nuclei; not a well characterized entity
Treatment and prognosis
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● Prognosis may be worse than typical alveolar rhabdomyosarcoma
Micro description
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● Anaplastic nuclei are 3x larger than surrounding nuclei
Micro images
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Foci of anaplastic cells (nuclei are hyperchromatic and
3x larger than surrounding cells)
Clinical
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● Rarely occurs in adults in head and neck (Hum Pathol 2009;40:341)
Case reports
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● 16 year old girl with chest and foot masses (UPMC Case #256)
Micro description
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● Poorly developed alveolar pattern, lacks fibrovascular septa; alveolar pattern may be missed on small biopsies
● May resemble lymphoma (J Pediatr Hematol Oncol 2008;30:772)
Micro images
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Solid variant Various images
Positive stains
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● Desmin and muscle specific actin are most helpful; may be CD56+ (J Clin Exp Hematop 2008;48:61)
Molecular
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● Associated with lack of fusion gene (Am J Surg Pathol 2007;31:895)
Molecular images
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FISH and karyotype show t(2;13)
End of Soft Tissue Tumors Part 3 - Muscle, Vascular, Nerve, Other > Alveolar rhabdomyosarcoma
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