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Mesenchymal / mixed epithelial & mesenchymal tumors

Alveolar soft part sarcoma

Authors: Katharina Wiedemeyer, M.D., David B. Chapel, M.D.

Editorial Board Member: Kyle Devins, M.D.

Deputy Editor-in-Chief: Gulisa Turashvili, M.D., Ph.D.

Last author update: 23 May 2024

Last staff update: 23 May 2024

Copyright: 2007-2025, PathologyOutlines.com, Inc.

PubMed Search: Alveolar soft part sarcoma

Table of Contents

Cite this page: Wiedemeyer K, Chapel DB. Alveolar soft part sarcoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cervixalveolarsoftpartssarcoma.html. Accessed January 1st, 2025.

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

Alveolar soft part sarcoma of the female genital tract is rare; 50 - 60 cases published to date (Int J Womens Health 2024;16:17)
Affects women over a wide age range (8 - 68 years), with most cases diagnosed in the third and fourth decades (Am J Surg Pathol 2017;4:622)
Alveolar soft part sarcoma of nongenital sites also shows a ~2:1 female predilection (J Surg Oncol 2016;113:581)

Sites

ASPS can affect any site in the female genital tract, most commonly cervix (cervix > uterine corpus > vagina) (Int J Gynecol Pathol 1995;14:283, Am J Surg Pathol 2017;4:622, Int J Gynecol Pathol 2014;33:263)
- Vulvar, perineal and adnexal tumors are very rare
Overall, ASPS is much more common in deep soft tissues of the extremities and head and neck than in the female genital tract

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

Uterine, cervical and vaginal tumors typically present with vaginal / abnormal uterine bleeding or menstrual cycle shortening (Int J Clin Exp Pathol 2017;10:9812, Int J Gynecol Pathol 1995;14:283)
- May also be discovered incidentally during pregnancy or at surgery for an unrelated cause
Rare vulvar or perineal tumors present as a painless mass (Int J Gynecol Pathol 2014;33:263)

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

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

10 year old girl with alveolar soft part sarcoma occurring in the uterine cervix (Diagnostics (Basel) 2022;12:1102)
33 year old woman with alveolar soft part sarcoma of the uterine corpus (Taiwan J Obstet Gynecol 2023;62:769)
57 year old postmenopausal woman with uterine alveolar soft part sarcoma with pelvic lymph node metastasis (Int J Clin Exp Pathol 2012;5:715)
68 year old postmenopausal woman with alveolar soft part sarcoma of the uterine cervix (Int J Clin Exp Pathol 2017;10:9812)

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

Circumscribed or infiltrative, solid, lobular mass with white to tan-gray cut surface
Size variation in female genital tract: 0.5 - 9 cm (median: 5.5) (Int J Gynecol Pathol 2014;33:263)
Ulceration reported in half of vaginal tumors (Int J Gynecol Pathol 1995;14:283)

Gross images

Images hosted on other servers:

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.

Delicate vasculature

Cytopathological features

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

Solid pattern

Vasculature

Polygonal cells

Cells with granular cytoplasm

Cells with monomorphic nuclei and moderate atypia

TFE3

Cathepsin K

SMA

Positive stains

TFE3 (staining percentage 100%, strong nuclear staining) (Int J Gynecol Pathol 2005;24:131, Am J Surg Pathol 2017;4:622, Int J Gynecol Pathol 2014;33:263)
Cathepsin K (100%) (Mod Pathol 2011;24:1313)
PASD highlights intracytoplasmic granules and crystals
INI1 retained (positive)
PR positive in alveolar soft part sarcomas of uterus and cervix (Diagnostics (Basel) 2022;12:1102)

Negative stains

Muscle markers
- SMA (unspecific, weak staining possible)
- Desmin (can be focally positive [50%]) (J Clin Pathol 2006;59:1127)
- h-caldesmon
- Myogenin
- MyoD1
Melanocytic markers
- HMB45 (rarely focal positivity) (Am J Surg Pathol 2017;4:622)
- MelanA
- MITF
- S100
Pancytokeratin
EMA
PAX8
CD34
Inhibin
Calretinin
Chromogranin
Synaptophysin

Electron microscopy description

Intracytoplasmic rhomboid or rod shaped crystals (Arch Gynecol 1987;240:125)

Electron microscopy images

Images hosted on other servers:

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:

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

PEComa:
- Coexpression of melanocytic (HMB45, MelanA) and myoid markers (SMA, desmin)
- May show nuclear expression of TFE3 as there are TFE3 rearranged subtypes (PSF / SFPQ::TFE3 and other TFE fusions) (Histopathology 2024;84:482, Am J Surg Pathol 2017;4:622)
Melanoma:
- Expression of melanocytic markers (S100, SOX10, HMB45 and MelanA, MITF)
- Frequent nuclear pleomorphism, high mitotic activity
- Necrosis is common
Clear cell carcinoma:
- Tubulocystic, papillary and solid growth patterns
- Uniformly atypical cells with clear to eosinophilic cytoplasm
- Expression of CK7, EMA, PAX8, HNF-1B and Napsin A
Metastatic renal cell carcinoma:
- Expresses PanCK, PAX8
- Subset with Xp11 translocation renal cell carcinoma can express TFE3 (nuclear positivity)
Paraganglioma:
- Positive for chromogranin and synaptophysin
- S100 protein stains sustentacular cells
- Can show nuclear expression with TFE3 but molecular studies for TFE3 translocation are negative
Granular cell tumor:
- Granular cell tumor of the female genital tract principally affects the vulva, where ASPS is rare
- Expresses S100, CD68 and SOX10
- Majority shows nuclear expression of TFE3 but molecular studies for TFE3 translocation are negative (Hum Pathol 2015;46:1242)
- Granular cytoplasm is negative for PASD
Rhabdomyoma:
- Round to polygonal cells with eosinophilic cytoplasm and frequent cross striations
- Positive for desmin, myogenin and MyoD1
Alveolar rhabdomyosarcoma:
- Small round blue cell tumor
- Positive for desmin, myogenin and MyoD1
- No intracytoplasmic granular material / crystals
- Translocations involving t(2;13) and t(1;13)

Additional references

WHO Classification of Tumours, Editorial Board: Soft Tissue and Bone Tumours, 5th Edition, 2020, Med Oncol 2024;41:76

Board review style question #1

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

Cervix is commonly affected
It is a rapidly growing high grade sarcoma
It often shows ALK rearrangement
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?

It is diffusely positive for S100 protein, CD68 and SOX10
It typically harbors the ASPSCR1::TFE3 fusion protein
It typically stains negative for PASD
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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