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
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
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
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
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.
