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Peripheral Primitive Neuroectodermal Tumor

Definition

  • Small cell neoplasm with a spectrum of appearance from undifferentiated to forming rosettes. CD99 positive and contains characteristic translocations involving 22q12.

Alternate/Historical Names

  • PNET
  • Primitive neuroectodermal tumor
  • Peripheral neuroectodermal tumor
  • Ewing sarcoma
  • Askin tumor
  • Peripheral neuroepithelioma
  • Ectomesenchymoma (variant of PPNET)
  • Biphenotypic sarcoma (variant of PPNET)

Diagnostic Criteria

  • CD99 positive in >90% of cases
  • Glycogen present in 90% of cases
  • Mitotic figures frequent (5-50/10 HPF)
  • Undifferentiated appearance
    • Small cells
    • Round to oval nuclei
      • Smooth nuclear membrane
      • Fine chromatin
      • Small nucleoli
    • Small amount of clear to amphophilic cytoplasm
      • Cell borders may be distinct
  • Differentiated appearance
    • Medium sized cells
    • Moderate sized nuclei with moderate atypia
      • Irregular nuclei
      • Small to medium sized nucleoli
    • Moderately abundant eosinophilic or amphophilic cytoplasm
    • Homer-Wright rosettes
      • Radiating fibrillar material surrounded by a ring of nuclei
    • Pseudorosettes
      • As for Homer-Wright rosettes but with a central blood vessel
  • Other patterns
    • May form alveolar or angiomatoid patterns
    • Metaplastic cartilage or bone may infrequently be seen
    • Skeletal muscle differentiation may be seen in the ectomesenchymoma variant

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

Original posting:: February 2, 2007

Variant: Primitive malignant ectomesenchymoma or biphenotypic sarcoma

Definition

  • Variant of Peripheral Primitive Neuroectodermal Tumor with divergent skeletal muscle differentiation

Diagnostic Criteria

  • Muscle differentiation at least focal
    • May be desmin, actin, myogenin positive
    • May have cross striations
    • May have alveolar growth pattern
  • Otherwise same histologic, immunologic and genetic features as PPNET / Ewing sarcoma
  • Clinical significance not clear
  • Rare

Supplemental studies

Immunohistology

CD99 >90% membrane
Keratin 5-15% scattered cells
NSE 40-90%
Synaptophysin 40-50%
Chromogranin 0-25%
CD57 15-40%

Histochemical stains

  • PAS with and without diastase reveals abundant glygogen in 90% of cases

Genetic study

  • Five chromosomal translocations may be seen, all involving EWS gene at 22q12
    • t(11;22)(q24;q12) Most common (>80% of cases)
    • t(21;22)(q22;q12) Most of the remaining cases
    • t(7;22)(p22;q12) Rare
    • t(17;22)(q12;q12) Rare
    • t(2;22)(q33;q12) Rare
  • Under 5% of PPNET / Ewing sarcoma lack detectable translocations involving the EWS gene

Differential Diagnosis

Neuroblastoma Peripheral Primitive Neuroectodermal Tumor
CD99 negative CD99 positive
Dense chromatin Fine chromatin
Serum catecholamines elevated Normal catecholamines

 

Rhabdomyosarcoma Peripheral Primitive Neuroectodermal Tumor
Usually irregular nuclei Usually uniform nuclei
Usually dense chromatin Usually fine chromatin
Variable amounts of cytoplasm Usually scant cytoplasm
No rosettes May have rosettes
CD99 rare to 50% CD99 >90%
Muscle markers positive Muscle markers only in ectomesenchymoma variant
Translocations t(2;13) or t(1:13) in alveolar rhabdomyosarcoma Translocations involving 22q12

 

Lymphoma Peripheral Primitive Neuroectodermal Tumor
LCA or lineage markers positive LCA, B and T markers negative
CD99 may be positive in >50% of T leukemias and T lymphoblastic lymphomas

 

The small cell pattern of DSCT may be confused with PPNET
Peripheral Primitive Neuroectodermal Tumor Desmoplastic Small Cell Tumor
CD99 positive CD99 35%
WT1 negative WT1 positive
Desmin only in ectomesenchymoma variant Desmin positive
Keratin 5-15% Keratin positive
EMA negative EMA positive
No desmoplastic stroma Prominent desmoplastic stroma
Various translocations involving 22q12 (no translocations involving 11p13) t(11;22)(p13;q12)

 

Esthesioneuroblastoma Peripheral Primitive Neuroectodermal Tumor
CD99 negative CD99 >90%
S100+ sustentacular cells in 75% of cases No sustentacular cells

 

Small Cell Osteosarcoma Peripheral Primitive Neuroectodermal Tumor
CD99 negative to rare CD99 >90%
Malignant osteoid present at least focally No osteoid

 

Mesenchymal Chondrosarcoma Peripheral Primitive Neuroectodermal Tumor
Islands of hyaline cartilage Hyaline cartilage rare
Cartilaginous areas S100 positive S100 negative
No translocations involving 22q12 Various translocations involving 22q12
Mesenchymal chondrosarcoma may be CD99 positive

 

Nephroblastoma Peripheral Primitive Neuroectodermal Tumor
CD99 rare to 50% CD99 >90%
Kidney primary Wide variety of sites
No translocations involving 22q12 Various translocations involving 22q12

 

Oat Cell Carcinoma Peripheral Primitive Neuroectodermal Tumor
CD99 <10% positive CD99 >90%
Age usually >50 years Age nearly always <40 years
Keratin positive Keratin rare
Very scant cytoplasm Cytoplasm clearly discernable
Nuclear molding No nuclear molding
No translocations involving 22q12 Various translocations involving 22q12

Clinical

  • Mean age 14-20 years
    • Nearly all occur between 5 and 40 years
  • May occur at any site

Grading / Staging / Report

According to the guidelines of the ADASP, PPNET is definitionally high grade

French Federation of Cancer Centers System grading scheme for adult sarcomas

  • Tumor differentiation score = 3 for PPNET
  • 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
  • Grade
  • Stage
  • 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

Small round blue cell tumors

CD99 positive tumors (>50%)

Bibliography

  • Kempson RL, Fletcher CDM, Evans HL, Henrickson MR, Sibley RS. Tumors of the Soft Tissues, Atlas of Tumor Pathology, AFIP Third Series, Fascicle 30, 2001
  • Fletcher CDM, Unni KK, Mertens F. Pathology and Genetics of Tumours of Soft Tissue and Bone, World Health Organization Classification of Tumours 2002
  • Weiss SW, Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors, 4th edition, 2001
  • Nascimento AG, Unii KK, Pritchard DJ, Cooper KL, Dahlin DC. A clinicopathologic study of 20 cases of large-cell (atypical) Ewing's sarcoma of bone. Am J Surg Pathol. 1980 Feb;4(1):29-36.
  • Ushigome S, Shimoda T, Nikaido T, Nakamori K, Miyazawa Y, Shishikura A, Takakuwa T, Ubayama Y, Spjut HJ. Primitive neuroectodermal tumors of bone and soft tissue. With reference to histologic differentiation in primary or metastatic foci. Acta Pathol Jpn. 1992 Jul;42(7):483-93.
  • Delattre O, Zucman J, Melot T, Garau XS, Zucker JM, Lenoir GM, Ambros PF, Sheer D, Turc-Carel C, Triche TJ, et al. The Ewing family of tumors--a subgroup of small-round-cell tumors defined by specific chimeric transcripts. N Engl J Med. 1994 Aug 4;331(5):294-9.
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