Importance of Morphology in the Era of Molecular Biology: Lesson Learnt from a Case of Chediak–Higashi Syndrome

Excerpt

A 4-years-old boy presented with recurrent episodes of fever since 6 months of age associated with bilateral neck swellings, scalp abscesses and intermittent bilateral ear discharge requiring recurrent hospital admissions. On examination, he had microcephaly, diffuse skin hypopigmentation (Fig. 1a), silver-grey hair, pallor, periodontitis (Fig. 1b), generalized lymphadenopathy and hepatosplenomegaly. Investigations revealed hemoglobin of 70 g/L, platelet count 88 × 10⁹/L, and total leukocyte count 6.7 × 10⁹/L with an absolute neutrophil count of 0.873 × 10⁹/L. Peripheral blood examination revealed discrete to multiple irregular large round-to-oval purple colored peroxidase positive intra-cytoplasmic inclusions (~ 1–2µ in diameter) in the neutrophils, lymphocytes and monocytes (Fig. 1c, d). Considering above findings, a diagnosis of Chédiak–Higashi syndrome (CHS) was considered. Hair-shaft microscopy revealed small regularly distributed clumps of melanin in the cortex (Fig. 1e). Bone marrow aspiration was done to identify the cause of cytopenia which showed similar granules in neutrophils and its precursors, monocytes and lymphocytes along with few haemophagocytic histiocytes (Fig. 1f). He was diagnosed as a case of CHS in accelerated phase and initiated on high-dose ascorbic acid (500 mg/day) with cotrimoxazole prophylaxis (60 mg/day). Genetic testing revealed mutation in LYST gene (c.10371delT), confirming the diagnosis of CHS.

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