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Chronic Myelomonocytic Leukemia Revealed by Uncontrollable Hematuria.


A 72-year-old man presented with a 2-day history of persistent frank hematuria and vague right flank pain. The results of physical examination were unremarkable, and he was afebrile and normotensive.

The patient's hemoglobin level was 0.88 g/L (mean corpuscular volume, 85.7 fL), the white blood cell count was 4.8 x [10.sup.9]/L (neutrophils, 2.6 x [10.sup.9]/L; lymphocytes, 2.1 x [10.sup.9]/L; monocytes, 0.1 x [10.sup.9]/L), and the platelet count was 74 x [10.sup.9]/L. Biochemical parameters were normal apart from mildly elevated serum urea and creatinine levels (10 and 129 mmol/L, respectively). The international normalized ratio was 1.4. An intravenous urogram revealed a filling defect in the right renal pelvis, and cystoscopy showed blood emerging from the right ureteric orifice only. Persistent heavy hematuria and a presumptive diagnosis of a urothelial tumor prompted nephrectomy.

Following identification of infiltration of the kidney by myelomonocytic leukemia, a bone marrow aspirate and biopsy were performed, and the patient was diagnosed as having chronic myelomonocytic leukemia (CMML).

The patient was treated conservatively with observation and regular hematological review. Subsequent abdominal computed tomography failed to reveal any hepatomegaly or splenomegaly. Four months later, the patient was admitted with epistaxis and renal failure. A presumptive diagnosis of leukemic infiltration of the remaining kidney was made, biopsy was not undertaken, and the patient underwent dialysis. Seven months after the initial presentation, the patient died as a result of marrow replacement by CMML and overwhelming sepsis.


The kidney was fixed in 10% formalin for 24 hours. Blocks were taken according to standard protocol, fixed in 10% formalin, processed routinely, sectioned, and stained with hematoxylin-eosin. Immunohistochemical staining for myeloperoxidase, common leukocyte antigen, [Kappa] and [Lambda] light chains, glycophorin C, and CD34 was performed. Direct immunofluorescence for immunoglobulin A (IgA), IgM, and IgG was performed on sections of formalin-fixed tissue. Relevant blocks of formalin-fixed tissue were transferred to glutaraldehyde, postfixed in ossium tetroxide, stained with uranyl lead acetate, and examined with a Hitachi 7100 transmission electron microscope (Hitachi, Japan).

The bone marrow trephine biopsy specimen was fixed in Bouin fixative, processed routinely, and stained with hematoxylin-eosin, periodic acid--Schiff, iron, reticulin, and myeloperoxidase.


The kidney weighed 210 g and appeared normal externally. The pelvocalyceal system was found to be completely filled with blood clot. The renal parenchyma appeared normal. The histologic structure of the renal cortex and medulla was normal. The suburothelial connective tissue in the pelvis of the kidney was markedly hemorrhagic and extensively infiltrated by sheets of dyshesive cells with vesicular nuclei, inconspicuous nucleoli, and modest amounts of eosinophilic granular cytoplasm (Figures 1 and 2). These cells were negative for lymphoid markers and positive for myeloperoxidase. In some areas, there were small aggregates of cells that had the variegated appearance of hematopoietic elements (Figure 3). Within these areas of extramedullary hematopoiesis, there were scattered cells positive for CD34 and glycophorin C. In the area of infiltration, several arterioles were seen with fibrinoid necrosis of their walls (Figure 4). These vessels were focally positive for IgM and IgG on immunofluorescence. Electron microscopy revealed scattered primary lysosomes in the cytoplasm of the leukemic cells, confirming their myeloid lineage.


On microscopy, the bone marrow trephine biopsy specimen had a cellularity of 98% (fat cell ratio, 2:98), and the marrow space was almost completely effaced by an infiltrate of myeloid and monocytic cells, which immunohistochemically were positive for myeloperoxidase.

The bone marrow aspirate was similar to the trephine, with 15% of blasts showing monocytoid differentiation together with an absolute monocytosis (20%) and mild dyserythropoiesis.


Twenty years ago renal leukemic infiltration was identified in 40% to 80% of cases at autopsy.[1] Chronic myelomonocytic leukemia was not recognized as a distinct entity until 1982, and it is not possible to ascertain what proportion of cases in the earlier study were in fact CMML. Most cases of CMML present as a peripheral cytopenia with obvious monocyte proliferation and relatively few myeloblasts in the marrows. The disease is included in the World Health Organization classification as a form of myelodysplastic syndromes (MDS).[2] A recent report suggests that CMML be placed in a different category with juvenile myelomonocytic leukemia as a disorder with both myeloproliferative and myelodysplastic features.[3] In recent years, it has become apparent that the clinical presentation of CMML is more protean than originally thought. During the last 16 years, however, 5 cases of CMML have been recorded in which renal impairment was a prominent clinical feature.[4,5]

In only one of these cases was renal infiltration by leukemia demonstrated by a biopsy specimen.[5] Both cutaneous and systemic vasculitis are well-recognized features of CMML,[6] although the origin remains obscure. Mechanisms that have been suggested include vasculitis due to a primary defect in leukocyte function particular to MDS, vasgulitis due to infection permitted by neutrophil dysfunction,[7] qualitative and quantitative abnormalities of T-cell function, and immune complex deposition. The last theory is supported by the presence of immune complexes in the serum of 50% of patients with MDS, cases of CMML with polyclonal hypergammaglobulinemia,[8] and the association of CMML with other autoimmune conditions.[9]

The spectacular mode of presentation of CMML in this case was clearly due to immune-mediated vasculitis in a kidney infiltrated by primitive myelomonocytic cells and aggravated by the systemic coagulopathy and thrombocytopenia. Lack of clinical evidence of vasculitis elsewhere suggests that the infiltrate per se was instrumental in initiating the local vasculitic damage, although the precise mechanism of this phenomenon remains to be elucidated.

Another puzzling aspect of this case is the presence of extramedullary hematopoiesis in the kidney. Long-standing congenital anemias and myeloproliferative disorders are well-recognized situations in which extramedullary hematopoiesis may occur in the liver and spleen. The occurrence of extramedullary hematopoiesis in the kidney without hepatic or splenic involvement is very unusual. A recent article[10] has made reference to autonomous colony formation in the bone marrow of patients with MDS due to, it is thought, an overproduction of granulocyte-macrophage colony-stimulating factor; this same phenomenon may help to explain the presence of hematopoiesis in a kidney infiltrated by malignant myeloid cells, or alternatively it may merely reflect the similarities between CMML and the myeloproliferative disorders.

In conclusion, CMML fits uncomfortably into the category of myelodysplasia alone, because it has features common to myeloproliferative disorders. It is traditionally defined by a combination of bone marrow features together with a peripheral monocytosis. However, it can, as this article highlights, assume a varied clinical presentation, including organ infiltration, and elicit a number of poorly understood autoimmune phenomena, all of which serve to illustrate that the spectrum of pathologic features seen in CMML is broader than has previously been appreciated.


[1.] Vidana E, Bross IDJ, Pricken JW. An autopsy study of metastatic patterns of human leukaemia. Oncology. 1978;35:87-96.

[2.] Bennett JM, Catovsky D, Daniel MT, et al [The French-American-British Co-Operative Group]. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol. 1982;51:189-199.

[3.] Harris NL, Jaffe ES, Diebold J, et al. The World Health Organization classification of neoplastic diseases of the haematopoietic and lymphoid tissues: report of the Clinical Advisory Committee Meeting, Airlie House, Virginia, November 1997. Histopathology. 2000;36:69-87.

[4.] Morschhauser F, Wattel E, Paginez D, et al. Glomerular injury in chronic myelomonocytic leukaemia. Leuk Lymphoma. 1995;18:479-483.

[5.] Paydas S, Tuncer I, Zorludemir S, et al. A case with membranous glomerulonephritis and myelodysplastic syndrome. Nephron. 1992;62:231-232.

[6.] Green AR, Shuttleworth D, Bowen DT, et al. Cutaneous vasculitis in patients with myelodysplasia. Br J Haematol. 1990;74:364-370.

[7.] Boogaerts MA, Neilssen V, Roelant C, et al. Blood neutrophil function in primary myelodysplastic syndromes. Br J Haematol. 1983;55:217-227.

[8.] Mufti GJ, Figes A, Hamblin TJ, et al. Immunological abnormalities in myelodysplastic syndromes: serum immunoglobulins and autoantibodies. Br J Haematol. 1986;63:143-147.

[9.] Enright H, Jacob HS, Vercellotti G, et al. Paraneoplastic autoimmune phenomena in patients with myelodysplastic syndromes: response to immunosuppressive therapy. Br J Haematol. 1995;91:403-408.

[10.] Bincoletto C, Saad STO, Soars DA, et al. Autonomous proliferation and bcl-2 expression involving haematopoietic cells in patients with myelodysplastic syndrome. Br J Cancer. 1998;78:621-624.

Accepted for publication September 25, 2000.

From the Department of Histopathology, St. James's Hospital (Drs Bane and Sweeney), and Department of Hematology, The Meath and Adelaide Hospitals Incorporating The National Childrens Hospital (Dr Enright), Dublin, Ireland.

Reprints: A. L. Bane, Department of Histopathology, Central Pathology Laboratory, St. James's Hospital, Dublin 8, Ireland (e-mail:
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Author:Bane, A. L.; Enright, H.; Sweeney, E. C.
Publication:Archives of Pathology & Laboratory Medicine
Date:May 1, 2001
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