Cystinosis

The patient was a 23-year-old white man who underwent a renal transplant at age 12 years for end-stage renal disease secondary to nephropathic cystinosis. The patient had been taking several immunosuppressive medications since receiving the transplant. The patient's clinical course was complicated by episodes of gout and pancytopenia. At a follow-up examination in July 2001, the patient was noted to have a decreased white blood cell count of 3100/muL; hemoglobin, 6.7 g/dL; and platelets, 221 x 10^sup 3^/muL. A bone marrow biopsy was performed, revealing a hypocellular bone marrow with mild megaloblastoid erythropoiesis, 3+ stainable iron with no ringed sideroblasts, and numerous macrophages containing clusters of hexagonal, tubular, and rectangular cystine crystals (Figure 1). The crystals appeared birefringent using polarizing and first-order compensator filters (Figures 2 and 3). Flow cytometry and chromosome analysis revealed no abnormalities.

Nephrotic cystinosis is a rare autosomal-recessive disorder characterized by a defect in the transport of the amino acid cystine out of lysosomes, leading to an accumulation of free cystine in various tissues.1 The stored cystine is poorly soluble and crystallizes within the lysosomes, leading to widespread tissue and organ damage. Cystinosis is classified into 3 variants. Infantile nephropathic cystinosis is the most common and most severe variant. Patients usually present during the first year of life with polyuria, polydipsia, dehydration, acidosis, and failure to thrive. If untreated, these children develop rickets, grow poorly, and progress to renal failure by 7 to 10 years of age. The diagnosis is confirmed by the demonstration of crystals in the cornea and conjunctiva on slit-lamp examination and by measuring cystine levels in cultured fibroblasts or polymorphonuclear leukocytes. The diagnosis can also be established by the demonstration of cystine crystals in macrophages in bone marrow aspirate.2 The solubility of cystine in acid solutions and in formalin contributes to the wide variation in the amount of crystal formation observed in histologic specimens.

Other causes of bone marrow crystals include precipitated fixatives that may be crystalline, silicosis (silica crystals), oxalosis, and myeloma (immunoglobulin crystals).3 Oxalate crystals are extracellular in most instances and have a variable shape and variable birefringence to polarized light.

References

1. Elenberg E. Cystinosis. EMedicine [serial online]. September 7, 2001;2:111.

2. Varan A, Tuncer M. The importance of the bone marrow examination in cystinosis. Pediatr Hematol Oncol. 1991;8:373-374.

3. Foucar K. Bone Marrow Pathology. 2nd ed. Chicago, III: ASCP Press; 2001: 549-550.

Fadi Gebrail, MD; Mark Knapp, MD; Gerardo Perrotta, MT(ASCP); Hernani Cualing, MD

Accepted for publication March 19, 2002.

From the Departments of Pathology and Laboratory Medicine (Dr Gebrail and Mr Perrotta) and Hematology/Oncology (Dr Knapp), University of Cincinnati College of Medicine, Cincinnati, Ohio; and the Interdisciplinary Oncology Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Fla (Dr Cualing).

Reprints: Hernani Cualing, MD, 12902 Magnolia Dr, Tampa, FL 33612 (e-mail: cualinhd@moffitt.usf.edu).

Copyright College of American Pathologists Sep 2002
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