Chromosome 17p deletion in aplastic anaemia with paroxysmal nocturnal haemoglobinuria clone: a diagnostic challenge

Aplastic anaemia (AA) and paroxysmal nocturnal haemoglobinuria (PNH) are closely related acquired bone marrow failure syndromes sharing an immune-mediated pathogenesis. Cytogenetic abnormalities are uncommon in AA-PNH overlap syndrome, and their significance remains uncertain. We report a case of non-severe AA-PNH overlap syndrome harbouring a low-level chromosome 17p deletion in the absence of morphologic or molecular evidence of myeloid neoplasm.

A 56-year-old female presented with recurrent aphthous ulcers and pancytopenia. Complete blood count revealed haemoglobin of 6.3 g/dL, total leukocyte count of 2800/µL with an absolute neutrophil count of 982/µL, and platelet count of 10,000/µL. Bone marrow aspirate showed adequate erythropoiesis with normoblastic to megaloblastic maturation and active myelopoiesis. Bone marrow biopsy revealed a markedly hypocellular marrow (10% cellularity) with focal erythroid prominence. No dysplasia, excess blasts, ring sideroblasts, and abnormal topography were identified. Flow cytometric PNH evaluation demonstrated a large type III clone involving 78% of neutrophils and 64% of monocytes. FISH analysis using TP53/CEP17 probes revealed chromosome 17p deletion in 12 of 200 nuclei (6%). Next-generation sequencing did not identify TP53 or other myeloid-associated mutations. The patient was treated with horse anti-thymocyte globulin, cyclosporine, romiplostim, erythropoietin, and irradiated blood products. She achieved transfusion independence and remains clinically stable on follow-up of 27 months.

Low-level chromosome 17p deletion may occur in AA-PNH overlap syndrome without morphologic or molecular evidence of myeloid neoplasm. Careful clinicopathologic correlation and long-term surveillance are essential before attributing such abnormalities to clonal evolution.