Colonic lymphocytic infiltration in chronic lymphocytic leukemia

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Colonic lymphocytic infiltration in chronic lymphocytic leukemia Somashekar G. Krishna1, M.D., M.P.H., Srinivas Rami Reddy1, M.D., Rachel L. Sargent M.D.2, Rei Suzuki1, M.D., , Manoop S. Bhutani1, M.D., FASGE, FACG, AGAF 1Department of Gastroenterology, Hepatology and Nutrition 2Department of Hematopathology University of Texas MD Anderson Cancer Center Houston, TX [email protected] Disclosures: None of the authors have any financial disclosures. Colonic involvement in patients with chronic lymphocytic leukemia (CLL) is extremely rare. Diarrhea in immunosuppressed patients with hematological malignancies presents a unique challenge when routine testing fails to identify the etiology. Amongst various causes for diarrhea in such a patient population, involvement of the gastrointestinal tract by primary hematological malignancy should be considered in the differential diagnosis.

endoscopic evaluation. Colonoscopy demonstrated mild diffuse nodularity of the colonic mucosa in the cecum, ascending and transverse colon (figures 1, 2). The mucosal nodularity was less evident in the descending and sigmoid colon. Representative

Case Report: An 80-year-old woman with a history of CLL diagnosed 5 years ago presented with chronic diarrhea. Patient was initially treated with a combination of prednisone and Rituximab for approximately one year and was on observation since hematological parameters remained stable. Staging evaluation revealed a white blood cell count of 10,900 cells/ UL (55% lymphocytes), platelet count of 199000/ UL and imaging evidence of pelvic lymphadenopathy consistent with Rai’s stage I. Preliminary laboratory and microbiological evaluation for diarrhea did not reveal any specific cause. Thus, patient underwent

Figure 1. Colonoscopy: Diffuse nodularity of colonic folds in the ascending colon. random biopsies were obtained from all segments of the colon. The histologic sections from the biopsy specimens showed a multifocal, dense, diffuse infiltrate that distorted and effaced the normal colonic architecture. The infiltrate was composed of numerous

Figure 2. Colonoscopy: Diffuse nodularity seen in transverse colon.

Figure 3. Histopathology: H and E stain, at 4x and 40x. A multifocal, dense infiltrate with effacement of the normal colonic architecture. small monotonous lymphocytes with scant cytoplasm, round nuclei, clumped chromatin and inconspicuous nucleoli (figure 3). Immunohistochemical staining revealed numerous CD20 positive cells that were also CD5 and CD23 positive (figure 4). Staining for CD3 revealed many scattered small T-cells within the infiltrate. The morphologic and immunohistochemical findings were diagnostic of CLL. After elimination of common causes for diarrhea and with the biopsy proven findings, chronic diarrhea in this patient was secondary to CLL involvement of the colon. Patient was subsequently restarted on Rituximab with early documentation of resolving diarrhea.

Figure 4. Immunohistochemical staining with CD5, CD23 and CD20.

Discussion: Chronic lymphocytic leukemia is a disease of the elderly. Being the most common of the adult lymphocytic leukemias, it is a proliferative disease characterized by a progressive accumulation of non-

Differential diagnosis for diarrhea in immunocompromised patients with hematological malignancies.2 Etiology Essential Workup Infections • Clostridium difficile stool toxin assay • Clostridium difficile infection (most common infec- Endoscopy and biopsy tion) • Stool ova and parasites • Viral infections: herpes simplex, cytomegalovirus, • Small bowel aspirate adenovirus, enteric viruses (coxsackie, echovirus, and • Stool Giardia antigen rotavirus) • Viral polymerase chain reaction studies • Fungal colonization • Other bacterial infections: Salmonella, Escherichia coli, Campylobacter • Reactivation of parasitic infections (strongyloidiasis and cryptosporidiosis) Infiltration by primary hematological malignancy Lactose Intolerance (Secondary to Mucosal Injury) Hormonal Disturbances Worsening of Preexisting Diseases: Inflammatory Bowel Disease, Celiac Disease, Microscopic Colitis Irritable Bowel Syndrome functional monoclonal lymphocytes.1 Common etiologies for diarrhea in immunocompromised patients with hematological malignancies not receiving chemotherapy are listed in Table 1. The necessary laboratory investigations and endoscopic evaluations are also detailed.2 Chronic diarrhea in a patient with CLL is usually of infectious origin because of a compromised immune system. Lymphocytic infiltration of the gastrointestinal tract is generally due to Richter’s transformation which is development of diffuse large B-cell lymphoma in patients with CLL.3, 4 There are very few reports of patients with colonic infiltration by References: 1. Hernandez JA, Land KJ, McKenna RW. Leukemias, myeloma, and other lymphoreticular neoplasms. Cancer 1995;75:381-94. 2. Krishna SG, Barlogie B, Lamps LW, Krishna K, Aduli F, Anaissie E. Recurrent spontaneous gastrointestinal graft-versus-host disease in autologous hematopoietic stem cell transplantation. Clin Lymphoma Myeloma Leuk;10:E17-21.

Endoscopy and biopsy Stool electrolytes for osmolarity, oral breath test, trial of lactose-free diet Thyroid-stimulating hormone, cortisol Endoscopy and biopsy, serum markers Diagnosis of exclusion leukemic cells. Endoscopically, the colonic mucosa, when involved, could have any of the following morphological appearances – (a) normal, (b) nodular, (c) whitish plaques, (d) hypertrophic mucosal folds, and (e) multiple polyposis.5 Histopathology and immunohistochemical studies are necessary for conclusive diagnosis. In conclusion, patients with CLL when presenting with chronic diarrhea will require a detailed evaluation to eliminate infectious etiologies. Thereafter, continued management should include endoscopy and random biopsies irrespective of mucosal morphology.

3. Abella E, Gimenez T, Gimeno J, et al. Diarrheic syndrome as a clinical sign of intestinal infiltration in progressive B-cell chronic lymphocytic leukemia. Leuk Res 2009;33:159-61. 4. Tsimberidou AM, Keating MJ, Wierda WG. Richter’s transformation in chronic lymphocytic leukemia. Curr Hematol Malig Rep 2007;2:265-71. 5. Cornes JS, Jones TG. Leukaemic lesions of the gastrointestinal tract. J Clin Pathol 1962;15:305-13.