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A 79-year-old man with myelofibrosis presented with progressive renal insufficiency (serum creatinine, 1.48 mg/dL) and nephrotic-range proteinuria (5.2 g/d), prompting a kidney biopsy. The biopsy revealed prominent coarse, brightly eosinophilic (panel A; hematoxylin and eosin stain; 20× objective), and periodic acid–Schiff (PAS)–positive (panel B; PAS stain; 20× objective) reabsorption granules within the proximal tubular epithelial cells, consistent with a protein-storing tubulopathy. Immunofluorescence results for κ and λ light chains were negative, ruling out light-chain proximal tubulopathy. Immunohistochemistry (IHC) revealed intense tubular staining for lysozyme within the granules, consistent with lysozyme-associated nephropathy (LyN), and additionally revealed aggregates of monocytic cells in the interstitium (panel C; lysozyme IHC; 40× objective). These cells were also positive for CD68 (panel D; CD68 IHC; 20× objective), CD117, and MPO.

The discovery of LyN, usually found in association with systemic monocytic proliferations and myelomonocytic leukemias and only very rarely described in association with myelofibrosis, together with the accompanying interstitial monocytic infiltrates, raised concern for unrecognized leukemic transformation. An urgent bone marrow biopsy was performed and confirmed acute myeloid leukemia with monocytic differentiation. This case illustrates the finding of LyN on kidney biopsy as the diagnostic key in unmasking myeloid blast phase in the setting of previously stable myelofibrosis.

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