Microscopic Description -- Acute Leukemia, Nodular Skin Lesions and Splenomegaly


Bone marrow aspirate and biopsy reveal 83% blast forms and a marked decrease in hematopoietic elements. There are occasional dyserythropoietic forms and rare intermediate myeloid forms seen. Megakaryocytes are present in markedly decreased numbers. Flow cytometric and immunophenotypic studies strongly suggest a B-cell lineage. Genotypic studies demonstrate biallelic rearrangement of the immunoglobulin heavy chain gene both by Southern blot and PCR analyses.

Punch biopsy of a papular skin lesion reveals superficial and deep perivascular lymphoplasmacytic infiltrates as well as an interstitial neutrophilic infiltrate. A Grocott stain demonstrates a dermal infiltrate of fungal hyphal and yeast forms. There is no evidence of leukemia.

Fungal cultures of the skin biopsy yield cream-colored yeastlike colonies that grow rapidly at 30 degrees C on Sabouraud's dextrose agar but which are inhibited by cyclohexamide. Microscopic examination following growth on cornmeal agar reveals round blastoconidia with long chains of rectangular arthroconidia. There is no fermentation of dextrose, glucose, maltose, sucrose, or trehalose. Using an API 20C yeast strip, the following sugars are reading assimilated: glucose, glycerol, z-keto-D-gluconate, L-arabinose, xylose, adonitol, xylitol, galactose, inositol, sorbitol, methyl-D-glucoside, N-acetyl-D-glucosamine, cellobiose, lactose, maltose, sucrose, trehalose, melezitose and raffinose. Nitrate is not assimilated. Minimal inhibitory concentration (MIC) assays are conducted at the University of Texas Health Center, San Antonio, with the following susceptibilities:

Amphotericin B0.5 mcg/ml
Fluconazole4 mcg/ml
Miconazole0.25 mcg/ml
Itraconazole0.5 mcg/ml

Subsequent blood, sputum, and spleen cultures grow the same organism. All viral cultures are negative.

The spleen contains numerous granulomas (see images 07 and 08), some of which are suppurative and many of which are necrotic with numerous fungal and yeast forms. Branching hyphae (some of which are septate) and pseudohyphae are present. In some hyphae, there is central eosinophilic material. Blastoconidia and arthroconidia are present. The portions of spleen less involved by the infectious process demonstrate chronic inflammatory cells and mononuclear cells that are difficult to classify with certainty.

The liver parenchyma shows maintenance of normal architecture. Scattered subcapsular and intraparenchymal inflammatory cells are present. No leukemic infiltrate is present. Extensive iron deposits are present in Kupffer cells and hepatocytes. Patchy mild centrilobular sinusoidal fibrosis is present. There is no evidence of either leukemic or fungal infiltrates.





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