Soft tissue

Uncertain differentiation

Alveolar soft part sarcoma


Editorial Board Member: Nasir Ud Din, M.B.B.S.
Deputy Editor-in-Chief: Borislav A. Alexiev, M.D.
Laura Warmke, M.D.
Jeanne Meis, M.D.

Last author update: 7 April 2022
Last staff update: 19 July 2022

Copyright: 2002-2022, PathologyOutlines.com, Inc.

PubMed Search: Alveolar soft part sarcoma soft tissue pathology

Laura Warmke, M.D.
Jeanne Meis, M.D.
Page views in 2021: 20,521
Page views in 2022 to date: 14,386
Cite this page: Warmke L, Meis J. Alveolar soft part sarcoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/softtissuealveolarsoft.html. Accessed August 14th, 2022.
Definition / general
  • Alveolar soft part sarcoma (ASPS) is a rare sarcoma of uncertain histogenesis
  • First formally described by Christopherson et al. in 1952 (Cancer 1952;5:100)
  • Characterized by a specific translocation, der(17)t(X;17)(p11.2;q25), resulting in ASPSCR1-TFE3 gene fusion
Essential features
  • Rare malignant mesenchymal neoplasm frequently composed of large, polygonal cells with abundant eosinophilic cytoplasm, a nested or pseudoalveolar growth pattern and PASD+ intracytoplasmic rhomboid or rod shaped crystals
  • Predominantly affects the deep soft tissues of the extremities (thigh and buttock) in young adults and head and neck region (tongue and orbit) in children
  • Characterized by ASPSCR1-TFE3 gene fusion
ICD coding
  • ICD-O: 9581/3 - alveolar soft part sarcoma
  • ICD-11: 2B5F.2 & XH8V95 - sarcoma, not elsewhere classified of other specified sites & alveolar soft part sarcoma
Epidemiology
Sites
Pathophysiology
  • ASPSCR1-TFE3 fusion protein localizes to the nucleus, functioning as an aberrant transcription factor, resulting in c MET overexpression and activation of c MET signaling, making the tumor cells sensitive to c MET inhibition (Cancer Res 2007;67:919, J Pathol 2013;229:743, PLoS One 2017;12:e0185321)
  • Mouse model demonstrated the dependance of ASPS on lactate for growth, which may relate to its common occurrence in muscle with the expression of lactate transporter, monocarboxylate transporter (MCT1) protein and CD147 (Cancer Cell 2014;26:851, Am J Pathol 2002;160:1215)
  • Defined by a specific genetic alteration, der(17)t(X;17)(p11;q25) that results in the fusion of the TFE3 transcription factor gene (from Xp11) with ASPSCR1 at 17q25.3 (Oncogene 2001;20:48)
Etiology
  • ASPSCR1-TFE3 translocation is an instigating genetic event (Oncogene 2001;20:48)
  • No association with radiation or a cancer predisposition syndrome has been reported
Clinical features
  • Presents as a slow growing, painless mass (Clin Orthop Surg 2014;6:80)
  • Proptosis can be seen with orbital tumors
  • Vaginal bleeding can be seen with female genital tract tumors
  • At presentation, the tumor can be localized (38%), regional (11%) and metastatic (43%) (J Surg Oncol 2016;113:581)
Diagnosis
  • Eosinophilic polygonal cells with a nested growth pattern, rich capillary network and intracytoplasmic rod shaped crystals
  • TFE3 nuclear expression by immunohistochemistry
  • Confirmation of TFE3 gene rearrangement or ASPSCR1-TFE3 gene fusion (Arch Pathol Lab Med 2015;139:1459)
Radiology description
Radiology images

Contributed by Jeanne Meis, M.D. and Mark R. Wick, M.D.
Left leg mass

Left leg mass

Pulmonary metastases

Pulmonary metastases

CT scan, orbital



Images hosted on other servers:

MRI ankle mass T1

MRI ankle mass T2

Nuclear medicine bone scan

Chest CT

Thyroid gland ultrasound

MRI, tongue mass

Prognostic factors
Case reports
Treatment
  • Radical surgical resection is the treatment of choice
  • Excision of lung and brain metastasis may prolong survival (Cancer 1989;63:1)
  • Adjuvant chemotherapy does not seem to be effective
  • Radiation may reduce the risk of local recurrence (Cancer 2001;91:585)
  • Clinical trial of crizotinib (c MET inhibitor) showed disease stabilization without much tumor shrinkage (Ann Oncol 2018;29:758)
  • Multiple pulmonary metastases in select patients have responded to interferon alfa 2a (Br J Cancer 2003;89:243, Med Pediatr Oncol 2001;37:482)
  • Long term clinical follow up is mandatory given the risk of metastasis > 10 years after diagnosis
Clinical images

Contributed by Mark R. Wick, M.D.

Orbital



Images hosted on other servers:

Tongue

Orbital tumor

Nose and thigh

Gross description
  • Solid, partially circumscribed mass with fleshy nodules and fibrotic bands
  • Usually yellow to gray to white-tan
  • Tumor size varies from 1.2 to 24 cm (median: 6.5 cm) (Cancer 2001;91:585)
  • Frequently has large vessels at the periphery
Gross images

Contributed by Mark R. Wick, M.D.

Deep soft tissue mass

Frozen section description
  • Large polygonal cells with abundant eosinophilic cytoplasm
  • Eccentric nuclei with prominent nucleoli
  • Nests of tumor cells with surrounding vascular channels
  • Scrape preparations can demonstrate cytomorphology (Cancer 2009;117:500)
Frozen section images

Contributed by Laura Warmke, M.D.
Touch prep

Touch prep

Frozen section

Nest of tumor cells

Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Laura Warmke, M.D., Jeanne Meis, M.D. and Mark R. Wick, M.D.
Polygonal cells

Polygonal cells

Prominent nucleoli

Prominent nucleoli

Eosinophilic cytoplasm

Eosinophilic cytoplasm

Pseudoalveolar-like structures

Pseudoalveolar-like structures

Central discohesion

Central discohesion

Fibrous septa

Fibrous septa


Clear cell change

Clear cell change

Capillary network

Capillary network

Vascular network

Vascular network

Lymphovascular invasion

Lymphovascular invasion

Fibrous septa

Fibrous septa

Pseudogland formation

Pseudogland formation


Pleomorphic foci

Pleomorphic foci

Large nests

Large nests

Uniform cells

Uniform cells

Hemangiopericytomatous vasculature

Hemangio-pericytomatous vasculature

Cytoplasmic vacuolization

Cytoplasmic vacuolization

Conventional and pleomorphic areas

Conventional and pleomorphic areas


Intracytoplasmic crystals

Intracytoplasmic crystals

TFE3 TFE3

TFE3

SMA

SMA

PAS

PAS

PASD

Virtual slides

Images hosted on other servers:

39 year old man with a distal extremity mass

Cytology description
Cytology images

Contributed by Laura Warmke, M.D. and Mark R. Wick, M.D.
Prominent nucleoli

Prominent nucleoli

Granular cytoplasm

Granular cytoplasm

Polygonal cells

Polygonal cells

FNA



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Fine needle aspiration

Clusters of tumor cells

Positive stains
Negative stains
Electron microscopy description
  • Tumor cells have numerous mitochondria and well developed Golgi apparatus
  • Characteristic rhomboid or rod shaped intracytoplasmic crystals with a regular lattice pattern (Arch Pathol Lab Med 2007;131:488)
  • Ultrastructural immunohistochemistry has shown that the crystals consist of aggregates of MCT1 and CD147 (Am J Pathol 2002;160:1215)
Electron microscopy images

Contributed by Mark R. Wick, M.D.

Rhomboid crystals



Images hosted on other servers:

Rod shaped crystals

Intracytoplasmic crystal

Molecular / cytogenetics description
Molecular / cytogenetics images

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FISH for TFE3

ASPL-TFE3 (ASPSCR1-TFE3) gene fusion

Videos

Alveolar soft part sarcoma versus alveolar rhabdomyosarcoma, by Dr. Gardner

Sample pathology report
  • Soft tissue, mass, anterior right thigh, core biopsy:
    • Alveolar soft part sarcoma (see comment)
    • Comment: This biopsy is composed of round to polygonal tumor cells with abundant eosinophilic cytoplasm and round nuclei with vesicular chromatin and prominent macronucleoli. The tumor cells grow in a nested or pseudoalveolar pattern with nests of cells separated by fibrous bands and delicate, thin walled blood vessels. Focal lymphovascular invasion is present. Immunohistochemical stains show that the tumor cells are positive for TFE3 (strong nuclear staining), while they are essentially negative for pancytokeratin, S100 protein, SMA, desmin, synaptophysin, MelanA and HMB45. Fluorescence in situ hybridization (FISH) confirms the presence of a TFE3 gene rearrangement. These results support the above diagnosis.
Differential diagnosis
Board review style question #1

Which of the following special stains is most helpful in diagnosing alveolar soft part sarcoma (ASPS)?

  1. Colloidal iron
  2. GMS
  3. PAS with diastase
  4. PAS without diastase
  5. Warthin-Starry
Board review style answer #1
C. PAS with diastase can highlight the characteristic rhomboid or rod shaped intracytoplasmic crystals within the tumor cells in approximately 80% of cases.

Comment Here

Reference: Alveolar soft part sarcoma
Board review style question #2

Metastases to which of the following locations are more common in alveolar soft part sarcoma (ASPS) than in any other soft tissue sarcoma?

  1. Bone
  2. Brain
  3. Liver
  4. Lung
  5. Lymph node
Board review style answer #2
B. Brain. While ASPS frequently metastasizes to the lungs and bone, as do many other sarcomas, metastases to the brain are much more common in ASPS than any other sarcoma. Metastatic involvement of the liver and lymph nodes is unusual in ASPS.

Comment Here

Reference: Alveolar soft part sarcoma
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