Soft tissue

Skeletal muscle

Rhabdomyosarcoma

Alveolar rhabdomyosarcoma



Last author update: 18 April 2023
Last staff update: 20 July 2023

Copyright: 2002-2024, PathologyOutlines.com, Inc.

PubMed Search: Alveolar rhabdomyosarcoma

Alka Rani, M.B.B.S.
Nasir Ud Din, M.B.B.S.
Page views in 2024 to date: 12,098
Cite this page: Rani A, Qureshi MB, Ud Din N. Alveolar rhabdomyosarcoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/softtissuealvrhabdo.html. Accessed April 14th, 2024.
Definition / general
  • Highly aggressive type of rhabdomyosarcoma characterized by uniform, primitive, round cells showing skeletal muscle differentiation (Cancer 1969;24:18)
Essential features
  • High grade, cellular, round cell sarcoma with evidence of skeletal muscle differentiation
  • Nests and sheets of monomorphic cells may have pseudoalveolar pattern (Curr Top Pathol 1995;89:273)
  • Diffuse strong myogenin expression
  • Detection of PAX3::FOXO1 (60%) or PAX7::FOXO1 (20%) gene fusions by molecular analysis (Oncogene 2001;20:5736)
  • Predilection for deep soft tissue of lower extremities
  • High stage at presentation with overall worse prognosis
Terminology
  • Alveolar rhabdomyosarcoma
  • Preference towards switching to fusion positive and fusion negative rhabdomyosarcoma terminology among oncologists (Cancer Discov 2014;4:216)
ICD coding
  • ICD-O: 8920/3 - alveolar rhabdomyosarcoma
  • ICD-10: C49.9 - malignant neoplasm of connective and soft tissue, unspecified
  • ICD-11: 2B55.Z & XH7099 - rhabdomyosarcoma, unspecified primary site & alveolar rhabdomyosarcoma
Epidemiology
Sites
  • Commonly involves deep soft tissue of extremities, typically forearm
  • Other sites include head and neck, trunk, paraspinal, pelvic, genitourinary regions and retroperitoneum
  • Can present with widespread involvement, such as bone marrow infiltration (leukemia-like presentation) and lymphadenopathy (Diagn Pathol 2017;12:77)
  • 25 - 30% of patients present with metastatic disease
  • Most common metastatic sites include lung and lymph nodes (Int J Clin Oncol 2014;19:536)
  • Can metastasize to other sites such as the bone; however, rare visceral metastases to brain, breast, kidney and pancreas have also been reported (Arch Argent Pediatr 2021;119:e349)
Pathophysiology
  • Derived from cells with phenotypic and biologic features of myogenic lineage (undifferentiated mesodermal cells) (Cancer Lett 2009;279:126)
  • Genetic fusion events including translocations t(2;13)(q36;q14) and t(1;13)(p36;q14) lead to expression of fusion proteins PAX3::FOXO1 and PAX7::FOXO1
  • These proteins act as transcriptional activators, causing dysregulation of transcription affecting myogenesis
  • PAX::FOXO1 proteins behave as oncoproteins and contribute to tumor development by alteration of cell growth pathways and apoptosis, modulation of myogenic differentiation and stimulation of motility and other downstream pathways (Skelet Muscle 2012;2:25)
Etiology
  • Unknown
Diagrams / tables

Images hosted on other servers:
Role of PAX proteins in cell biology

Role of PAX proteins in cell biology

Clinical features
Diagnosis
  • Diagnosis is based on histologic features / immunomarkers expression in correlation with age, site and clinical findings (Mod Pathol 2001;14:506)
  • Small, round, blue cell tumor with diffuse positivity for desmin and myogenin
  • Molecular studies (PAX3::FOXO1 / PAX7::FOXO1 gene fusions) in morphologically challenging cases and cases with inconclusive immunohistochemistry (Skelet Muscle 2012;2:25)
  • WHO essential and desirable diagnostic criteria
    • Uniform round cells with or without alveolar growth pattern, diffuse homogenous expression of myogenin; heterogeneous expression for desmin or MyoD1; detection of PAX3::FOXO1 / PAX7::FOXO1 fusion by molecular analysis
Laboratory
  • Nonspecific
Radiology description
  • Radiological features are nonspecific in differentiating from other sarcomas (Clin Radiol 1978;29:53)
  • Location and demographics are most useful in truncating differentials
  • Plain radiograph: soft tissue density mass
  • Ultrasound: well defined heterogeneous nonuniform mass of low to medium echogenicity
  • CT: soft tissue density lesion with contrast enhancement
  • MRI:
    • T1: low to medium intensity lesion, isointense to adjacent muscle; prominent vascularity (Pediatr Radiol 2019;49:1516)
    • T2: hyperintense lesion; conspicuous vascularity (Radiographics 2020;40:791)
    • Postcontrast sequences: heterogeneous enhancement; ring-like enhancement when necrosis
Radiology images

Images hosted on other servers:
Left deltoid mass; exhibits restricted diffusion

Left deltoid mass; exhibits restricted diffusion

Hyperintense left thigh mass

Hyperintense left thigh mass

Prognostic factors
Case reports
Treatment
Clinical images

Images hosted on other servers:
Right facial swelling and nasal cavity mass

Right facial swelling and nasal cavity mass

Huge right submandibular mass

Huge right submandibular mass

Gross description
Gross images

Images hosted on other servers:
Fleshy, soft, gray-white tumor with necrosis

Fleshy, soft, gray-white tumor with necrosis

Large, pale, fleshy mass

Large, pale, fleshy mass

Frozen section description
  • Sensitive but not very specific (Turk Patoloji Derg 2015;31:16)
  • Clusters and single tumor cells with variable fibrous component
  • Dense cytoplasm with cytoplasmic vacuolation
  • Irregular, hyperchromatic nuclei with conspicuous nucleoli
Microscopic (histologic) description
  • Cellular round cell tumor
  • Large clusters, nests, cords and trabeculae of primitive round cells, separated by variably thick fibrovascular septa
  • Loss of cellular cohesion in the center forms alveolar-like, cystic and vague papillary appearance (Histopathology 2022;80:98)
  • Layer of cells adheres to the periphery of the spaces and fibrous septa
  • Small to intermediate sized monomorphic cells with scant cytoplasm
  • Hyperchromatic nuclei with variable conspicuous small nucleoli
  • Cells in the center have poor preservation and are necrotic; may appear floating
  • Multinucleated tumor giant cells with wreath-like lineup of nuclei are common (Acta Pathol Microbiol Immunol Scand A 1982;90:345)
  • Round to oval rhabdomyoblasts with abundant acidophilic cytoplasm may be present
  • Brisk mitosis and variable tumor necrosis
  • Occasional cases may show clear cell morphology with pale, glycogenated cytoplasm
  • Rare anaplasia
  • Some cases may show histologic features of embryonal rhabdomyosarcoma; molecular studies are essential to characterize such cases (Am J Clin Pathol 2013;140:82)
  • Solid variant:
    • Sheets of neoplastic cells
    • Lack fibrovascular septa, pseudoalveolar spaces and dyscohesion (Cancer Genet Cytogenet 2005;163:138)
    • May show rhabdomyoblastic differentiation
    • Abundant mitotic activity
Microscopic (histologic) images

Contributed by Nasir Ud Din, M.B.B.S.
Cellular round cell tumor

Cellular round cell tumor

Pseudoalveolar architecture

Pseudoalveolar architecture

Vague papillary appearance

Vague papillary appearance

Rhabdomyoblasts

Rhabdomyoblasts

Wreath-like multinucleated giant cells

Wreath-like multinucleated giant cells


Clear cell change

Clear cell change

Central floating cells

Central floating cells

Round blue cells

Round blue cells

Solid variant

Solid variant

Brisk mitosis

Brisk mitosis


Fibrovascular septa

Fibrovascular septa

Desmin

Desmin

Myogenin

Myogenin

CK AE1 / AE3

CK AE1 / AE3

Cytology description
  • Cellular smear with dyscohesive loose clusters of small to intermediate sized monotonous cells; may show pseudoalveolar pattern (Diagn Cytopathol 2014;42:1069)
  • Cells have scant cytoplasm, round to irregular hyperchromatic nuclei (Diagn Cytopathol 1992;8:465)
  • Variable fibrous tissue, wreath-like multinucleated cells and rhabdomyoblastic differentiation
Cytology images

Images hosted on other servers:
Alveolar structures

Alveolar structures

FNA biopsy of cervical lymph node

FNA biopsy of cervical lymph node

Positive stains
Negative stains
Electron microscopy description
Electron microscopy images

Images hosted on other servers:
Alveolar structures Alveolar structures

Copious intracytoplasmic actomyosin filaments and dark Z bands

Molecular / cytogenetics description
  • PAX3::FOXO1 / PAX7::FOXO1 fusion (85% of cases):
    • t(2;13)(q36;q14): PAX3::FOXO1 in 70 - 90% (Curr Mol Med 2007;7:47)
    • Amplification of MYCN and CDK4 in PAX3::FOXO1 positive cases
    • t(1;13)(p36;q14): PAX7::FOXO1 in 10 - 30%
    • Amplification of PAX7 and MIR17HG in PAX7::FOXO1 positive cases
  • Other fusions:
    • PAX3::FOXO4 fusion
    • PAX3::NCOA1 fusion
    • PAX3::INO80D fusion
    • FOXO1::FGFR1 fusion
  • Inactivating mutation of TP53 and CDKN2 (J Clin Oncol 2021;39:2859)
  • Activating mutation of FGFR4
  • Overexpression of ALK protein (Pediatr Dev Pathol 2009;12:275)
Molecular / cytogenetics images

Images hosted on other servers:
t(2;13) translocation and karyotype

t(2;13) translocation and karyotype

Disruption of <i>FOXO1</i> gene

Disruption of FOXO1 gene

Videos

Alveolar rhabdomyosarcoma

Sample pathology report
  • Forearm, wide margin excision:
    • Features are consistent with alveolar rhabdomyosarcoma (see comment)
    • Tumor size: 6 x 5 x 4.5 cm
    • Margins: superior margin: 1.8 cm
      • Inferior margin: 2.1 cm
      • Medial margin: 2 cm
      • Lateral margin: 2.2 cm
      • Anterior margin: 1.9 cm
      • Posterior margin: 2.2 cm
    • Comment: Histology shows an infiltrative cellular tumor composed of large clusters and nests of primitive round cells, separated by variably thick fibrovascular septa. Irregular pseudoalveolar spaces and cystic change are present within the nests. Scattered wreath-like multinucleated giant cells and rhabdomyoblasts are present along with brisk mitosis and necrosis. Tumor cells show strong and diffuse desmin and myogenin expression, focal MyoD1 and alpha smooth muscle actin positivity, whereas CD34, S100, CK AE1 / AE3, CD99, SALL4, LCA, TdT and synaptophysin are negative. Morphological features and immunoprofile strongly support the diagnosis of alveolar rhabdomyosarcoma. It is a malignant high grade soft tissue sarcoma with myogenic differentiation and an overall worse prognosis.
Differential diagnosis
Board review style question #1

An 18 year old boy presented with a rapidly growing mass in the right forearm, which was resected. Gross examination showed a skin covered fibromuscular tissue with an infiltrative, soft, fleshy gray-white tumor of 6 x 5 x 4.5 cm. Histology showed a small, round, blue cell tumor arranged in nests and aggregates separated by fibrous septa. Pseudoalveolar spaces with cystic change were present along with frequent mitoses and focal necrosis. Immunostains desmin and myogenin were diffuse strong positive. CD34, S100, CK AE1 / AE3, CD99, SALL4, LCA, TdT and synaptophysin were negative. Focal muscle specific actin and MyoD1 expression was present. What is the most likely diagnosis?

  1. Alveolar rhabdomyosarcoma
  2. Embryonal rhabdomyosarcoma
  3. Pleomorphic rhabdomyosarcoma
  4. Sclerosing rhabdomyosarcoma
  5. Spindle cell rhabdomyosarcoma
Board review style answer #1
A. Alveolar rhabdomyosarcoma. Alveolar rhabdomyosarcoma shows small, round, blue cell morphology with pseudoalveolar change, diffuse desmin and myogenin expression and focal MyoD1. Answer B is incorrect because embryonal rhabdomyosarcoma has round and spindle cell morphology with scattered differentiated rhabdomyoblasts as well as desmin positivity and heterogeneous nuclear staining for myogenin and MyoD1. Answer C is incorrect because pleomorphic rhabdomyosarcoma has sheets of large, atypical pleomorphic and frequently multinucleated polygonal, spindle or rhabdoid eosinophilic cells as well as diffuse strong desmin positivity with focal myogenin and MyoD1. Answer D is incorrect because sclerosing rhabdomyosarcoma has cords and trabeculae of round to ovoid cells in a sclerotic collagenous background as well as diffuse MyoD1 positivity, focal desmin and myogenin. Answer E is incorrect because spindle cell rhabdomyosarcoma has fascicles of spindle cells as well as diffuse MyoD1, focal desmin and myogenin.

Comment Here

Reference: Alveolar rhabdomyosarcoma
Board review style question #2

Which particular type of multinucleated giant cells is associated with alveolar rhabdomyosarcoma?

  1. Floret-like giant cells
  2. Langhans giant cells
  3. Osteoclast-like giant cells
  4. Touton type giant cells
  5. Wreath-like giant cells
Board review style answer #2
E. Wreath-like giant cells. Wreath-like giant cells are seen in alveolar rhabdomyosarcoma and clear cell sarcoma. Answer A is incorrect because floret-like giant cells are present in spindle cell / pleomorphic lipoma, neurofibroma and giant cell fibroblastoma. Answer B is incorrect because Langhans giant cells are seen in tuberculosis and sarcoidosis. Answer C is incorrect because osteoclast-like giant cells are seen in giant cell tumor and tenosynovial giant cell tumor. Answer D is incorrect because Touton type giant cells are seen in xanthoma, xanthelasma and myxofibrosarcoma.

Comment Here

Reference: Alveolar rhabdomyosarcoma
Back to top
Image 01 Image 02