Peripheral Neuroectodermal tumours (PNET/Ewing´s Sarcoma-)/Ewing Family tumours-EFT

Clinical features

  • Mainly affect adolescents and young adults
  • No sex predilection
  • One-third of cases has a major nerve involvement with neurological symptoms
  • Common sites: paravertebral region, lower extremities and retroperitoneum

 

Fig 50 – PNET - Discohesive monomorphic small round cells. Tigroid background (Giemsa)
Fig 51 - PNET – Monotonous small cell population. Remark the presence of dark and light nuclei. Absence of fibrillary background (H&E)
Fig 52 - PNET –Nuclei with coarse “salt and pepper” chromatin and inconspicuous nucleoli (H&E)
Fig 53 - PNET – CD99 immunocytochemical stain - intense positivity with a membranous pattern

 

  • Discohesive or in groups of monomorphic small round cells
  • Dimorphic population of smaller and darker cells and lighter staining cells
  • Lighter cells have
    •  Pale chromatin and small nucleoli
    • Membranous cytoplasmic blebs (Diff-Quick staining)
  • Darker cells have condensed chromatin and scarce cytoplasm (they are probably cells in degeneration)
  • Absence of neuropil and ganglion cells
  • Rosettes are seen, even though rarer than in neuroblastoma
  • Tigroid background can be seen
  • Necrosis

 

Immunocytochemistry

  • CD56 (NCAM): negative
  • CD99: positive (membranous pattern)-not specific but the most useful marker
  • Caveolin-1 :positive, even in CD99 negative cases
  • FLI-1 : positive (nuclear-only 70% of the cases)
  • Cytokeratin’s: focal positivity in 20%
    • CK20: negative – useful differentiating with Merkle tumour
  •  Vimentin: positive
  • AE1AE3:positive
  • P63: positive in some cases
  • Synaptophysin: positive (focal)
  • Chromogranin: in most cases negative
  • NSE: positive

Low diagnostic utility 

 

List of CD99 positive tumours

Ewing/PNET

Alveolar rhabdomyosarcoma

Desmoplastic small round-cell tumour

Atypical teratoid rhabdoid tumour

Synovial sarcoma

Mesenchymal chondrosarcoma

Merkel cell carcinoma

Non-Hodgkin lymphoma

 

Genetic studies

  •  t(11;22)(q24;q12) in 90% of the cases
  •  t(21;22) or t(7;22) - 15% of the cases
  • C-myc over expression
  • N-myc: no expression

 

Differential diagnosis

  • Neuroblastoma
    • Younger patients
    • Usually secretes catecholamine’s
    • Neuroblasts are generally present at different stages of differentiation
    • Neuropil frequently present
    • Rosettes frequently present
    • Vimentin: negative
    • Fli1: negative
    • CD56 N-CAM: positive
    • N-myc: may be over expressed
    • No t(11;22)
  • Atypical teratoid rhabdoid tumour
    • Malignant central nervous system neoplasm
    • In 2% of the cases  located in the spine
    • Huge nucleoli
    • Rhabdoid cytoplasm
    • Areas with eosinophilic cytoplasm globoid “inclusions”
    • Para nuclear whorls of intermediate filaments(EM)
    • EMA: positive
    • Vimentin : positive
    • Synaptophysin: positive
    • MIC 2: positive- it may stain cellular membrane
    • INI1: negative (rare cases of positivity in the CNS are described)
    • 22q11 deletions
  • Wilms´ Tumour
    • In visceral (kidney) presentation of Ewing Family Tumours
    • CD99: negative
  • Alveolar rhabdomyosarcoma
    • Actin: positive
    • Rare cases of PNET may have myogenic differentiation (ectomesenchymoma)
    • Desmin: positive
    • Myogenin :positive
    • CD99 may be positive (20-25%)
  • Lymphoma
    • Lymphoglandular bodies
    • CD45: positive
    • CD99: positive in lymphoblastic lymphomas (90%)
    • CD3, Tdt and CD43: positive
    • Neuroendocrine markers: negative
  • Small cell osteosarcoma
    • Presence of osteoid
    • Neuroendocrine markers: negative
  • Desmoplastic small cell tumour
    • More frequent in an intra-abdominal location
    • Divergent differentiation
    • Wt1: positive
  • Undifferentiated Synovial sarcoma
    • EMA: positive (even in cases negative to other keratins)
    • Keratins: positive, mainly high molecular weight cytokeratin’s (60-70%)
    • CD99: positive in 50-100% in spindle and poorly differentiated pattern (absence of membranous pattern)
    • Bcl-2: positive (79%)

 

Main points

  • PNET/ Ewing´s Sarcoma-Well and poorly differentiated ends of a spectrum of round-cell sarcomas with a partial neuroectodermal phenotype-Ewing Family Tumours (EFTs)
  • Neural crest origin
  • 1% of all soft tissue sarcomas
  • PNET and Ewing’s sarcoma are related entities and nowadays form a single group of bone and soft-tissue tumours (electron microscopic, immunohistochemical and cytogenetic features are remarkably similar)
  • Surgical resection and/or radiotherapy and chemotherapy have increased survival from less than 10% to 40%
  • Lack of responsiveness to preoperative chemotherapy
  • Prognosis:
    • Stage; site; size; age; response to therapy
    • EWS exon7 fusion with FLI1 exon 6)- better prognosis
    • Deletion 1p-poor prognosis
    • P53 mutation - poor prognosis
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