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Alveolar Soft Part Sarcoma

Definition

  • Sarcoma with large poorly cohesive cells with distinctive regular alveolar pattern

Diagnostic Criteria

  • Large poorly cohesive round cells in nests
    • Nodular growth pattern
    • Composed of small nests or packets
      • At least focally, sometimes completely
    • 25-50 cells per nest in cross-section on average
      • May vary from single cells to large numbers of cells
    • Peripheral layer of cells frequently adheres to surrounding septum
    • Rarely spindled or pseudoglandular pattern
  • Nests surrounded by thin walled vessels rather than connective tissue
    • May produce sinusoidal pattern
  • Cytoplasm abundant, granular, eosinophilic
    • Crystals reported in up to 80% of cases
      • Rod shaped
      • PAS positive, diastase resistant
      • May be irregular
    • Glycogen usually present at least focally
      • PAS positive, diastase sensitive
    • May have vacuoles
    • May be clumped with clear areas
    • May form globular inclusions
  • Nuclei large, regular, round and vesicular
    • Nucleoli prominent
    • Pleomorphism may be focal but not widespread
    • Mitotic figures rare
    • Multinucleated cells may be present
  • Vascular invasion frequent

Richard L Kempson MD
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting/updates:: 7/19/07, 8/4/10

Supplemental studies

Immunohistology

  • Muscle markers
    TFE3 100% positive
    Desmin About 50% positive
    Muscle specific actin Variable, occasional cases positive
    Smooth muscle actin Variable, occasional cases positive
    Myoglobin Variable, occasional cases positive
    MyoD1 All recent reports negative
  • S100 variable, occasional cases positive
  • HMB45 negative
  • Keratin negative
  • Chromogranin 1/5 positive
  • TFE3 also stains Xp11 translocation renal cell carcinoma
    • Focal and less intense reactions seen in melanoma, clear cell sarcoma, PEComa and angiomyolipoma

Genetic analysis

  • Unbalanced translocation der(17)t(X;17)(p11.2;q25) present in all cases studied, produces TFE3-ASPL gene product.
    • Detectable with two color break-apart FISH
  • Identical fusion transcript resulting from a balanced translocation is found in translocation-associated renal carcinomas.

Differential Diagnosis

Alveolar rhabdomyosarcoma Alveolar Soft Part Sarcoma
Variably shaped alveolar spaces Regular alveolar spaces
Fibrous septa around nests Thin walled vascular septa
Cells generally 10-30 microns diameter Cells larger
Pleomorphic nuclei Only mild pleomorphism
Dense nuclei Vesicular nuclei
Small nucleoli Prominent nucleoli
No crystals Crystals in up to 80% of cases
Uniformly desmin, actin positive Occasionally desmin, actin positive
Frequently MyoD1 positive MyoD1 rare or negative
Translocations t(2;13) or t(1;13) der(17)t(X;17)(p11.2;q25)

 

Granular cytoplasm and / or nesting pattern of cells in the following may raise the question of alveolar soft part sarcoma

Metastatic Carcinoma Alveolar Soft Part Sarcoma
Keratin positive Keratin negative
Desmin, actin negative Occasionally desmin, actin positive
May have pleomorphic nuclei Only mild pleomorphism
Unusual in young adults Usually young adults
Morphologically similar carcinomas include renal cell and ovarian clear cell

 

Metastatic melanoma Alveolar Soft Part Sarcoma
Uniformly S100 positive S100 variable
HMB45 85% positive HMB45 negative
Desmin, actin negative Occasionally desmin, actin positive
Pleomorphic nuclei Only mild pleomorphism
Unusual in young adults Usually young adults

 

Granular Cell Tumor Alveolar Soft Part Sarcoma
Uniformly S100 positive S100 variable
No regular nests of cells Regular nests of cells
Dense granular cytoplasm Variable granularity, frequent vacuoles

 

Paraganglioma Alveolar Soft Part Sarcoma
Usually small nests (zellballen) Usually large nests
Surrounded by fibrous tissue Surrounded by thin walled vessels
Small to medium size cells Large cells
Dense nuclei, often spiculated chromatin Vesicular nuclei
Inconspicuous nucleoli Prominent nucleoli
Chromogranin positive One case reported chromogranin positive
S100 sustentacular cells frequent No sustentacular cells
Desmin, actin negative Occasionally desmin, actin positive
Does not occur on extremities Frequently involves extremities

Clinical

  • Age range 2-70 years, most are 15-35 years
  • Location
    • 60% extremities (frequently thigh)
    • 20% trunk
    • 12% head and neck
    • 8% retroperitoneum
    • Unusual sites include oral cavity, uterus
  • Over half present with metastases
    • Frequent metastatic sites lung and brain
    • Primary may be occult
    • Metastasis and death may occur late (>10 years), even if clearly excised with no local recurrence
  • 5 year survival 60% but 20 year survival 15%
  • Pediatric cases may have better survival

Grading / Staging / Report

According to the guidelines of the ADASP, alveolar soft part sarcoma is not considered gradable although it often metastasizes

French Federation of Cancer Centers System grading scheme for adult sarcomas

  • Tumor differentiation score = 3 for alveolar soft part sarcoma
  • Mitotic index
    • Score 1 0-9 mitoses per 10 hpf (0.1744 sq mm)
    • Score 2 10-19 mitoses per 10 hpf
    • Score 3 >19 mitoses per 10 hpf
  • Tumor cell necrosis
    • Score 0 No necrosis on any slide (one slide per 2 cm tumor diameter)
    • Score 1 <50% of tumor is necrotic on slides examined
    • Score 2 >50% of tumor is necrotic on slides examined
  • Final Grade (add the three scores above)
  • Grade 1 Sum of scores = 2 or 3
  • Grade 2 Sum of scores = 4 or 5
  • Grade 3 Sum of scores = 6 or more

Use TNM Staging

The surgical pathology report should contain or address the following:

  • Location
  • Type of resection or biopsy
  • Histologic diagnosis
  • Managerial category IV (Systemic disease assumed to be present at the outset)
  • Extent of tumor cell necrosis
  • Size
  • Depth (dermis, subcutis, below fascia, body cavity)
  • Margins
    • Involved
    • Not involved
      • If under 2 cm give all such distances and sites
      • If over 2 cm give minimum distance and site
  • Results of supplementary studies if performed
  • Relationship to other specimens from the same patient

Lists

Pending

Bibliography

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