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)

• 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

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