Pheochromocytoma

Clinical features

  • Known as “10% tumour”: 10% bilateral; 10% extra-adrenal; 10% malignant; and 10% in children.
  • Peak age is the fifth decade
  • 90% are sporadic and 10% have a familial history of multiple endocrine tumours (MEN syndromes)
  • Frequent clinical manifestations: paroxysmal hypertension, headaches, nausea, vomiting, diaphoresis, palpitations, tremors, fatigue, anxiety, chest and abdominal pain and visual disturbances.
  • Children are more affected with clinical symptoms than adults are; 90% suffer from hypertension, convulsions, polydipsia or polyuria
  • Bilateral cases are more frequent in children
  • Secretion of norepinephrine and epinephrine; rare cases with production of ACTH or VIP

 

Cytopathology

  • Hypercellular smears, with single cells and loose clusters
  • Variation in cell size or shape
  • Nuclear pseudo inclusions
  • Granular cytoplasm with frayed borders
  • Poorly defined reddish granular cytoplasm (Giemsa stain)

 

Immunocytochemistry

  • Neurofilaments: positive
  • Vimentin: positive
  • Chromogranin: positive
  • Synaptophysin: positive
  • CD56 N-CAM: positive
  • NSE: positive
  • S-100 protein: positive in sustentacular cells
  • Cytokeratin: controversial; sparse when present
  • EMA: negative
  • Alpha-inhibin: generally negative
  • Indicators of malignancy
    • p53: positive
    • Ki-67: positive

 

Genetic studies

  • 10% of sporadic pheochromocytomas harbour somatic mutations involving proto-oncogene
  • MEN 2a and 2b are associated with the chromosome 10q11.2-ret proto-oncogene site

 

Differential diagnosis

  • Sarcomatoid renal cell carcinoma
    • Cytokeratin’s are generally intensely positive
  • Adrenocortical carcinoma
    • Bcl-2: positive
    • Inhibin A: positive
    • Chromogranin: negative
    • EMA: positive

 

Main points

  • Malignant pheochromocytomas are slow-growing neoplasms: five-year survival rate of 40-50%
  • Common sites for metastasis: lymph nodes, bone and liver
  • Mutations of the neurofibromin gene seem to contribute to the development of pheochromocytomas in patients with Von-Recklinghausen’s disease
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