Cervix

Mesenchymal / mixed epithelial & mesenchymal tumors

Alveolar soft part sarcoma



Last author update: 23 May 2024
Last staff update: 23 May 2024

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PubMed Search: Alveolar soft part sarcoma

Katharina Wiedemeyer, M.D.
David B. Chapel, M.D.
Page views in 2024 to date: 1,469
Cite this page: Wiedemeyer K, Chapel DB. Alveolar soft part sarcoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/cervixalveolarsoftpartssarcoma.html. Accessed June 16th, 2024.
Definition / general
  • Alveolar soft part sarcoma (ASPS) is a morphologically distinctive neoplasm of unknown histogenesis / cell lineage, which may rarely occur in the female genital tract
  • Alveolar soft part sarcoma is a high grade sarcoma by definition (no formal grading system available)
Essential features
  • Rare malignant mesenchymal neoplasm exhibiting nested or solid growth patterns with pseudoalveolar spaces
  • Composed of large, polygonal cells with abundant eosinophilic cytoplasm and PASD+ intracytoplasmic granules or crystals
  • Harbors characteristic ASPSCR1::TFE3 gene fusion
Terminology
  • Alveolar soft part sarcoma is the preferred WHO terminology
ICD coding
  • ICD-O: 9581/3 - alveolar soft part sarcoma
  • ICD-10: C49.9 - malignant neoplasm of connective and soft tissue, unspecified
  • ICD-11: 2B5F.2 & XH8V95 - sarcoma, not elsewhere classified of other specified sites & alveolar soft part sarcoma
Epidemiology
Sites
Pathophysiology
  • Unbalanced translocation: der(17)t(X:17)(p11;p25)
  • Translocation results in fusion of ASPSCR1 (ASPL) gene on chromosome 17 to the TFE3 gene on X chromosome
  • ASPSCR1 gene is joined in frame upstream of either the third or fourth exon of TFE3, yielding 2 fusion variants (type 1 and type 2) (J Clin Pathol 2006;59:1127)
Etiology
  • No risk factors have been identified
  • No associated germline mutations
Clinical features
Diagnosis
  • Characteristic histomorphology: eosinophilic, polygonal cells with a nested or solid growth pattern, delicate vasculature and intracytoplasmic PASD positive material
  • TFE3 nuclear expression by immunohistochemistry
  • Molecular confirmation of TFE3 rearrangement or ASPSCR1::TFE3 fusion
  • Reference: JAMA Oncol 2019;5:254
Radiology description
  • Hypervascular tumors with high signal intensity on T2 weighted magnetic resonance imaging
  • Contrast enhanced masses on computed tomography
  • Lobulated contours
  • Well defined tumors of the uterine corpus or cervix (compared to more ill defined alveolar soft part sarcoma of other sites) (Korean J Pathol 2014;48:361)
Radiology images

Images hosted on other servers:
Lobulated, hypervascular mass originating in the cervix

Lobulated, hypervascular mass originating in the cervix

Well defined mass extending from cervix into vagina

Well defined mass extending from cervix into vagina

Prognostic factors
  • Prognostic information on ASPS of the female genital tract is limited by short median follow up in published studies
  • ASPS of the uterine corpus, cervix or adnexa appear to have a more favorable prognosis than their soft tissue counterparts, likely reflecting early clinical detection, small size or resectability (Korean J Pathol 2014;48:361, Am J Surg Pathol 2017;4:622, Int J Gynecol Pathol 1995;14:283)
  • Vulvar and vaginal tumors appear to have a prognosis more comparable to their soft tissue counterparts, with disease related mortality in ~33% of cases
Case reports
Treatment
  • Complete surgical resection is first line therapy
  • Most vulvovaginal ASPS reported in the literature have been treated with adjuvant radiation and a subset with adjuvant chemotherapy, though objective data are scarce (Int J Gynecol Pathol 2014;33:263)
  • Surgical staging offers little prognostic benefit (Arch Gynecol Obstet 2009;279:263)
  • Given the propensity for late recurrence or metastasis, long term follow up is recommended
Gross description
Gross images

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Well circumscribed, lobulated mass

Well circumscribed, lobulated mass

Frozen section description
  • Large, round to polygonal cells with abundant eosinophilic granular cytoplasm and round, vesicular nucleus with prominent nucleolus
  • Organoid / nest-like growth pattern or solid growth pattern
  • Central discohesion results in characteristic pseudoalveolar-like structures
  • Rich capillary network
  • Reference: Cancer 2009;117:500
Frozen section images

Contributed by Katharina Wiedemeyer, M.D.
ASPS shows delicate vasculature

Delicate vasculature

ASPS cytopathological features

Cytopathological features

ASPS nuclear pleomorphism

Nuclear pleomorphism

Microscopic (histologic) description
  • ASPS of the female genital tract is indistinguishable from its soft tissue counterpart (Int J Gynecol Pathol 1995;14:283, Am J Surg Pathol 2017;4:622)
  • Multinodular to lobular architecture with intervening fibrous septa
  • Pushing or infiltrative invasion into surrounding tissues
  • Well delineated tumor cell nests surrounded by thin walled vessels
  • Loss of tumor cell cohesion results in pseudoalveolar pattern
  • Subset show areas of solid sheet-like growth
  • Tumor cells are large and polygonal with ample granular eosinophilic or clear cytoplasm and monomorphic, round to ovoid nuclei with prominent nucleoli
  • Mitoses are rare (typically 0 - 1 per 10 HPF)
  • Features seen in a minority of tumors: necrosis, nuclear hobnailing, nuclear pleomorphism (typically focal), bi or multinucleated tumor cells
Microscopic (histologic) images

Contributed by Katharina Wiedemeyer, M.D. and W. Glenn McCluggage, M.D.
Nested pattern

Nested pattern

Solid pattern

Solid pattern

Vasculature

Vasculature

ASPS consists of polygonal cells

Polygonal cells

ASPS, cells with granular cytoplasm

Cells with granular cytoplasm


ASPS, cells with monomorphic nuclei and moderate atypia

Cells with monomorphic nuclei and moderate atypia

TFE3

TFE3

Cathepsin K

Cathepsin K

SMA

SMA

Positive stains
Negative stains
Electron microscopy description
Electron microscopy images

Images hosted on other servers:
Cytoplasmic electron dense secretory granules / rod shaped crystals

Cytoplasmic electron
dense secretory
granules / rod shaped
crystals

Molecular / cytogenetics description
  • FISH confirms TFE3 gene rearrangement
  • Reverse transcription polymerase chain reaction (PCR) can detect ASPSCR1::TFE3 fusion transcripts
  • ASPSCR1::TFE3 gene fusions are characteristic for ASPS but the same fusion has been reported in a subset of PEComas (tumors with Perivascular and epithelioid cell differentiation) and a small subset of renal cell carcinomas
  • References: Am J Surg Pathol 2013;37:1619, Nat Commun 2023;14:1957
Molecular / cytogenetics images

Images hosted on other servers:
FISH test detecting ASPL::TFE3 fusion gene in tumor cells

ASPL::TFE3 fusion gene in tumor cells

Sample pathology report
  • Uterus and cervix, hysterectomy:
    • Uterus:
      • Proliferative endometrium, negative for hyperplasia and malignancy
      • Myometrium and serosa without pathologic findings
    • Cervix:
      • Alveolar soft part sarcoma (see comment)
      • Max tumor size: 4 cm (grossly)
      • Lymphovascular invasion present
      • Negative for perineural invasion
      • All margins negative for tumor, closest margin: proximal (0.7 cm)
      • Comment: Alveolar soft part sarcoma rarely affects the cervix or other sites of the female genital tract. It is a neoplasm of unknown differentiation but is defined as a high grade sarcoma. Molecular analysis confirmed the characteristic gene fusion involving ASPSCR1 and TFE3.
Differential diagnosis
Board review style question #1

Which statement about alveolar soft part sarcoma (ASPS) is correct?

  1. Cervix is commonly affected
  2. It is a rapidly growing high grade sarcoma
  3. It often shows ALK rearrangement
  4. It shows histopathologic overlap with TFE3 rearranged PEComa
Board review style answer #1
D. It shows histopathologic overlap with TFE3 rearranged PEComa. The entities show considerable morphologic and genetic overlap. ASPS and TFE3 rearranged PEComa are considered 2 distinctive entities despite their known morphological overlap. Recent studies have suggested a potential histogenetic relationship between them. PEComa can be ruled out with appropriate immunohistochemical stains (MelanA, HMB45, S100). Answer A is incorrect because ASPS typically affects the soft tissue of the extremities and the head and neck area. The female genital tract, including the cervix, is a very rare site of ASPS. Answer B is incorrect because ASPS grows slowly despite of being defined as a high grade sarcoma. Answer C is incorrect because ALK rearrangements have not been described in ASPS. ASPS shows the translocation der(17)t(X;17)(p11.2;q25), resulting in ASPSCR1::TFE3 gene fusion.

Comment Here

Reference: Cervix - Alveolar soft part sarcoma
Board review style question #2
Which statement about alveolar soft part arising in the cervix is true?

  1. It is diffusely positive for S100 protein, CD68 and SOX10
  2. It typically harbors the ASPSCR1::TFE3 fusion protein
  3. It typically stains negative for PASD
  4. It typically stains positive for myogenin and MyoD1
Board review style answer #2
B. It typically harbors the ASPSCR1::TFE3 fusion protein. Like ASPS of other sites, ASPS arising in the cervix is characterized by the translocation der(17)t(X;17)(p11.2;q25), resulting in ASPSCR1::TFE3 gene fusion; therefore, ASPS of the cervix overexpresses the fusion protein ASPSCR1::TFE3 and it stains positive for TFE3 (nuclear positivity). Answer D is incorrect because ASPS is consistently negative for myogenin and MyoD1. These markers are positive in alveolar rhabdomyosarcoma and help distinguish this entity from ASPS. Answer C is incorrect because PASD highlights the cytoplasmic granular and crystalline material in ASPS. It is positive in ASPS and is useful in making the diagnosis. Answer A is incorrect because S100, CD68 and SOX10 are consistently negative in ASPS. Granular cell tumor is diffusely positive for S100 protein, CD68 and SOX10. These markers help to distinguish the entity from granular cell tumor.

Comment Here

Reference: Cervix - Alveolar soft part sarcoma
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