Glottis oedema and interstitial pulmonary disease as a result of extramedullary haemopoiesis in polycythaemia vera rubra causing asphyctic death

Polycythaemia vera rubra (PV) is a clonal disorder of the pluripotent haemopoietic progenitor cell, with overproduction of phenotypically normal erythrocytes, granulocytes, and platelets in the absence of recognisable stimuli.¹ PV usually becomes clinically apparent as a result of splenomegaly, hyperuricaemia, or aquagenic pruritus, in addition to the most important complications and leading causes of death—symptoms related to the raised blood cell mass and increased blood viscosity, such as hypertension, erythromelalgia, vertigo, visual disturbances, myocardial, mesenteric and cerebral infarctions, hepatic vein thrombosis, pulmonary thromboembolism, and heart failure.^1,2 Ten per cent of patients with PV die of an acute leukaemic transformation and about 2% develop severe myelofibrosis, with extramedullary haemopoiesis in the liver and spleen.² An aggressive systemic spread is a rare complication of PV. Asphyxia caused by infiltration of the respiratory organs by PV has not been reported, although both extramedullary haemopoiesis in the subglottis and in the pulmonary interstitium have been observed.^3,4

We report a 58 years old male patient suffering from PV and supportively treated by phlebotomies. His disease was stable and he had moderate splenomegaly, hyperuricaemia, and polycythaemia, with greatly decreased concentrations of erythropoietin. Trephine bone marrow biopsies showed erythroid hyperplasia, clustered polymorphous megakaryocytes, depleted iron stores, and minimal argyrophilic myelofibrosis.⁵ After an indolent disease course for 12 years, unexpectedly the patient became dyspnoic, with head and neck oedema and threatening asphyxia, without preceding medical manipulations or medication. Despite intubation, aggressive diuresis, and the application of corticosteroids he died of a treatment resistant asphyxia with respiratory acidosis. Laboratory examination revealed polyglobulia with 0.5% blasts in addition to 4% myeloid precursor cells at that time. Nasopharyngeal, laryngeal, and oral mucosae appeared to be extensively swollen at necropsy. Both subendocardial petechiae in the left outflow tract and cerebral oedema were observed. The spleen was moderately enlarged (16 cm). Microscopic examination of the laryngeal, pharyngeal, and oral mucosae revealed dense predominantly perivascular, factor VIII, glycophorin C, and myeloperoxidase positive haemopoietic cell infiltrates—extramedullary haemopoiesis (fig 1). Haemopoietic cells also infiltrated the neck lymph nodes, the spleen, and the liver, in addition to the pulmonary interstitium, even the alveolar septa. Postmortem bone marrow examination revealed a 95% cellularity with moderate fibrosis and 1% CD34 positive blasts. Asphyxia caused by treatment resistant respiratory insufficiency on the background of laryngeal and interstitial pulmonary infiltration by PV was determined as the cause of death. Both factors impaired external and internal respiration, perturbing ventilation and gas diffusion.⁶ Concerning adequate treatment in such circumstances, a good response to local radiotherapy has been described in one less dramatic case.³

Figure 1.

Extramedullary haemopoietic infiltration of the laryngeal submucosa consisting of megakaryocytes, myelopoietic cells, and erythropoietic cells. Original magnification, ×400.

Clinicians should be aware that PV can progress to an uncontrollable generalised disease and infiltrate the respiratory organs.