FFinalistSouthampton · 2027
Endocrine
AKT · Endocrine/Paraneoplastic & neuroendocrinelow yield

Paraneoplastic polycythaemia (ectopic EPO)

Ectopic erythropoietin secretion by a tumour

Overview

Secondary polycythaemia from inappropriate (ectopic) erythropoietin production by a tumour — classically renal cell carcinoma, hepatocellular carcinoma, cerebellar haemangioblastoma (and uterine fibroids). Raised haemoglobin/haematocrit with a HIGH EPO and a normal JAK2 (distinguishing it from polycythaemia vera). Treated by removing the tumour.

Recognise

  • Raised haemoglobin/haematocrit (polycythaemia) — hyperviscosity symptoms (headache, plethora, thrombosis)
  • Features of the underlying tumour (haematuria/flank mass — renal cell; liver disease — HCC; cerebellar signs — haemangioblastoma)
  • HIGH erythropoietin (inappropriate) with NEGATIVE JAK2

Red flags

  • Thrombosis from hyperviscosity
  • Occult renal/hepatic/cerebellar tumour → investigate

Differentials & how to tell them apart

Polycythaemia veraprimary (JAK2-positive) with LOW EPO, splenomegaly, raised WCC/platelets
Hypoxic secondary polycythaemiaCOPD/OSA/altitude — appropriate EPO rise to hypoxia
Relative (apparent) polycythaemiadehydration/diuretics — reduced plasma volume, normal red cell mass

Investigations

FBC (raised Hb/Hct), serum EPO (HIGH — vs low in polycythaemia vera), JAK2 (negative); imaging to find the tumour (renal/liver/CNS).

Management

Treat the underlying tumour (± venesection for hyperviscosity)

  1. 1Confirm true polycythaemia with a HIGH EPO and negative JAK2; image to find the tumour (renal/liver/CNS). Treat the tumour (often curative).Gate: HIGH EPO with negative JAK2 points to a secondary/ectopic cause (find the tumour) rather than polycythaemia vera (JAK2-positive, low EPO)
  2. 2Resect the tumour (resolves the polycythaemia); venesection for symptomatic hyperviscosity meanwhile.
Treat the tumour — resection (e.g. nephrectomy) usually resolves the polycythaemia
Venesection — symptomatic hyperviscosity control

Key points

Raised Hb + HIGH EPO + JAK2-negative = secondary/ectopic polycythaemia — hunt the tumour (renal cell, HCC, cerebellar haemangioblastoma). Polycythaemia vera is the opposite (low EPO, JAK2-positive).

Monitor & prognosis

Hb/Hct; tumour treatment.

Resolves with tumour treatment.

Source: BSH; StatPearls