Rhabdoid tumour

Clinical features

  • Rare tumour that accounts for less than 2% of paediatric renal tumours
  • 60% are diagnosed in the first year of age
  • Striking clinical associations:
    • Hypercalcemia in 15%,- associated with tumour production of parathormone and parathormone-like substances
    • 15% of synchronous or metachronous  genetically independent primary embryonal brain tumour (PNET–like neoplasm)
  • Often compromises the renal hilum at presentation
  • No relation with Wilms’ tumour or any syndrome
  • First description in the kidney; it is now well-documented in other locations such as liver, soft tissues, brain, genitourinary tract and skin
    • Often metastasized at presentation (bone, brain and regional lymph nodes)
  • High-risk tumours (SIOP-2001 revised working classification of renal tumours of childhood)

 

Fig 7a (H&E) – Rhabdoid tumor- Round to polygonal rhabdoid dispersed cells in a background of necrosis. Eccentric nuclei with an intracytoplasmic eosinophilic inclusion can be seen
Fig 7b - (Giemsa) – Rhabdoid tumor- Round to polygonal rhabdoid dispersed cells in a background of necrosis. Eccentric nuclei with an intracytoplasmic eosinophilic inclusion can be seen
Fig 8- Rhabdoid tumor- Cytoplasm is fragile and as a consequence single nude nuclei are numerous. Single eosinophilic macro nucleoli are evident. (H&E)

 

 

  • Round to polygonal rhabdoid-like dispersed cells or in clusters:
    • Bare nuclei
    • Cell with irregular nuclei
    • Reticular chromatin
    • Single eosinophilic macronucleoli
    • Clear area around the macronucleoli
    • Fragile, pale, and eccentric cytoplasm
    • Intracytoplasmic eosinophilic inclusions

 

Immunocytochemistry

  • Vimentin: positive (dot)
  • Cytokeratin: positive (dot)
  • EMA: positive
Coexpression
  • Desmin: rarely positive
  • CD99: positive
  • Synaptophysin: positive (variable)
  • CD10:positive
  • Myogenin: negative
  • Smooth muscle actin: negative
  • CD56(NCAM): negative
  • CD57: negative
  • INI1: negative-loss of nuclear positivity (most other tumours with rhabdoid features have detectable INI1 protein).
 

 

Genetic studies:

Variable findings:

  • Frequent monosomy 22
  • Deletion at 22q11 in chromosome 22
  • Biallelic inactivation of the tumour suppressor gene locus of hSNF5/INI1 gene
  • Association with alterations on the short arm of chromosome 11
  • Patients with germline mutation of HSNF5/INI1 are more prone to have malignant embryonal tumours of posterior fossa

 

Differential Diagnosis

  • Nephroblastoma, predominantly blastemal
    • Regular nuclei with fine chromatin
    • Inconspicuous nucleoli
    • No cytoplasmic inclusions
    • Absence of coexpression of vimentin and cytokeratin’s
    • INI 1 : positive
  • Rhabdomyosarcoma
    • Anisokaryosis
    • Trap cells
    • Tigroid background
    • Desmin: strongly positive
    • Myogenin: positive
    • INI 1 : positive
    • Rhabdomyoblastic differentiation on electron microscopy
  • Neuroblastoma
    • Nuclei with salt-and-pepper chromatin
    • Neuroblasts in different stages of maturation
    • Fibrillary matrix
    • Cytokeratin: negative
    • Vimentin:  usually negative
  • Renal PNET
    • Most common in young adults
    • Nuclei with coarse chromatin
    • CD99: positive
    • INI1: positive
    • t (11:22) (q24; q12)
  • Renal cell carcinoma
    • Rarely affects children under the age of two years
    • High degree of cellular cohesion
    • Absence of intermediate filaments (electron microscopy)
  • Lymphoma
    • Lymphoglandular bodies
    •  CD45: positive
    • Cytokeratin: negative

Main points

  • Initially described in the kidneys by Beckwith and Palmer as a possibly sarcomatous variant of Wilms’ tumour
  • Later described in soft tissues and other organs
  • Most likely of primitive epithelial derivation
  • Highly aggressive tumour:
    • 82% with metastases at presentation
    • 90% of patients die within two years
  • Age affects prognosis: age under six months of age –poor prognosis; age older two years of age have better prognosis
  • Occur in patients with germline mutations in hSNF5/INI1
  • A familial “rhabdoid predisposition syndrome” has been described in families with constitutional inactivating mutations of hSNF5/INI1. 
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