Bone
Other tumors of bone
Ewing sarcoma / primitive or peripheral neuroectodermal tumor (PNET)

Author: Erdener Özer, M.D., Ph.D. (see Authors page)

Revised: 27 April 2017, last major update April 2017

Copyright: (c) 2003-2016, PathologyOutlines.com, Inc.

PubMed search: ewing sarcoma [title] bone

Cite this page: Ewing sarcoma / primitive or peripheral neuroectodermal tumor (PNET). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/boneewing.html. Accessed August 21st, 2017.
Definition / general
Terminology
  • Ewing sarcoma family of tumors (Pediatr Dev Pathol 2012;15:108)
  • Ewing sarcoma
  • Atypical Ewing sarcoma
  • Primitive neuroectodermal tumor (PNET)
  • Askin Tumor
Epidemiology
  • Typically found in patients 5 - 25 years of age
  • Second most common malignant bone tumor in children
Sites
  • Particularly common locations include the paraspinal tissues, pelvis, chest wall and extremities
  • Most common bone locations are pelvis, distal femur, proximal tibia, femoral diaphysis and proximal humerus
  • ~50% are found in the diaphysis of long bones
Pathophysiology
Clinical features
  • May present with pain, fever, weight loss, leukocytosis and increased erythrocyte sedimentation rate mimicking osteomyelitis
Diagnosis
Radiology description
  • Plain film and CT
    • Permeative: 76%
    • Laminated (onion skin) periosteal reaction: 57%
    • Sclerosis: 40%
  • MRI (Radiographics 2013;33:803)
    • T1: low to intermediate signal
    • T1 C+ (Gd): heterogeneous but prominent enhancement
    • T2: heterogeneously high signal, may see hair on end low signal striations
Radiology images

Images hosted on PathOut server:

Upper end of femur

Destruction of cortex

Subperiosteal defect



Images contributed by Mark R. Wick

Humerus xray

Phalanx of foot xray

Femur xray

Metatarsal MRI

Ulna xray

Prognostic factors
  • Of all prognostic factors, age at onset, tumor size, site and stage have proven to be the most important in predicting outcome (EFS: event free survival)
    • Age
      • Favorable prognosis: < 10 years (EFS 69%); 10 - 17 years (EFS 74%)
      • Unfavorable prognosis: ≥ 18 years (EFS 44%)
    • Site
      • Favorable prognosis: distal extremity (EFS 74%); proximal extremity (EFS 62%)
      • Unfavorable prognosis: pelvis (EFS 50%)
    • Size
      • Favorable prognosis: < 8 cm greatest diameter (EFS 75%)
      • Unfavorable prognosis: ≥ 8 cm in greatest dimension (EFS 55%)
    • Stage
      • Favorable prognosis: nonmetastatic tumor (EFS 70%)
      • Unfavorable prognosis: metastatic tumor (EFS approximately 20%)
  • Necrosis predicts long term outcome in excised specimens after therapy
Case reports
Treatment
  • Systemic chemotherapy is the mainstay of treatment with surgery or radiotherapy
Gross description
  • White, fleshy, ill defined tumor with extensive involvement of medulla and cortex with periosteal elevation
  • May be necrotic or resemble pus
  • Specimens are usually excised after therapy, and show fibrosis, hemorrhage and necrosis
  • Necrosis can be used as a predictor of long term outcome
Gross images

Images hosted on PathOut server:

Contributed by Erdener Özer, M.D., Ph.D.

Contributed by Dr. Mark R. Wick



Images hosted on other servers:

Untreated specimen with ill defined tumor

26 year old man with Ewing sarcoma of knee

Microscopic (histologic) description
  • Classical Ewing sarcoma
    • At lower power, is undifferentiated and densely cellular with "light" cell and "dark" cell appearance
    • Sheets of small, round, uniform cells with scant clear cytoplasm, divided into irregular lobules by fibrous strands
    • Indistinct cell membranes
    • Cytoplasm frequently has glycogen vacuoles; may be amphophilic
    • Round nuclei with indentations, small nucleoli
    • Minimal amounts of stroma
    • Few mitoses
    • May have large pleomorphic cells, organoid pattern, filigree pattern (large areas of perivascular tumor necrosis with "ghost cells")
  • Primitive neuroectodermal tumor (PNET)
    • Oval to plump spindle cells
    • Variably arrayed in rosettes
    • Encircle either neurofibrillary cores (Homer Wright rosette) or central lumens (Flexner-Wintersteiner rosette)
  • Atypical Ewing sarcoma
    • Cytologic features dissimilar to the uniformly round classical form
    • Limited neural differentiation but without histologically recognizable neural features
    • Often contain increased amounts of stroma and may appear nodular, even to the point of resembling alveolar rhabdomyosarcoma
    • More mitoses
  • Extremely rare lesions may resemble ganglioneuroblastoma: Schwannian and neuronal features
  • Rarely also show heterologous differentiation such as cartilage, melanin and muscle (ectomesenchymomas)
  • Rarely epithelial differentiation resembling adamantinoma
  • Posttreatment specimens may show marked pleomorphism, tumor giant cells and neural differentiation or rhabdomyosarcomatous transformation
Microscopic (histologic) images
Images hosted on PathOut server:

Contributed by Erdener Özer, M.D., Ph.D.



Small cell Ewing sarcoma

Large cell Ewing sarcoma

Neuroectodermal tumor


Extends between normal trabeculae

Wilder reticulin stain

PAS stain



Images contributed by Dr. Mark R. Wick

Foot

PNET

     

Sheets of small, round, uniform cells
with scant clear cytoplasm, divided into
irregular lobules by fibrous strands


Ewing sarcoma

CD99

PAS stain



Images hosted on other servers:

Quiz case

Univ Pittsburgh Case #103

PAS staining: cytoplasmic glycogen

CD99 immunopositivity

Xray, MRI, H&E, EM

Xray, CT, H&E, PAS, CD99

Cytology images
Images hosted on PathOut server:

Contributed by Erdener Özer, M.D., Ph.D.

Touch imprint

Touch prep - contributed by Dr. Mark R. Wick

PNET FNAB - contributed by Dr. Mark R. Wick

PNET lung FNAB - contributed by Dr. Mark R. Wick

Positive stains
  • CD99 is positive in virtually all cases and diffusely expressed in the vast majority of cases in a membranous pattern
    • Staining results using monoclonal antibodies O13, HBA71 and 12E7 are similar
  • FLI1 is touted as a sensitive marker showing nuclear staining
  • Vimentin is always diffusely immunopositive
  • Cytokeratin may be diffusely positive in the adamantinoma-like variant
Negative stains
Molecular / cytogenetics description
  • The characteristic translocations involve the EWSR1 gene at 22q12 and either the FLI1 gene at 11q24 or the ERG gene at 21q22 (Annu Rev Pathol 2012;7:145)
  • The most common gene fusion is the EWSR1-FLI1 (90% to 95% of patients)
  • There are numerous other EWSR1 gene partners that occur in a minority (5% to10%) of cases
Molecular / cytogenetics images
Images hosted on PathOut server:

Images contributed by Dr. Mark R. Wick

Translocation FISH

Differential diagnosis