Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disorder in the United States. It has a variable presentation with most patients having asymptomatic lymphocytosis. Many other patients present with lymphadenopathy or enlargement of other organs of the reticuloendothelial system. However, CLL can present with extramedullary involvement. Most commonly, this is in the form of skin or central nervous system involvement, though rarely it can present with gastrointestinal involvement. Here, we present the case of a 70-year-old Caucasian male who presented with chronic diarrhea for over 4 months. After failing conservative treatment, a colonoscopy was performed which showed diffuse mucosal nodularities with a biopsy revealing CLL. The patient was treated successfully with chemotherapy and his diarrhea improved. This is a differential to keep in mind in patients with chronic diarrhea, once the more common causes have been ruled out.
B-cell chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the United States, accounting for almost 25 to 30% of all leukemias [
Extramedullary involvement of CLL is rare, but if it occurs, it most commonly involves the skin and central nervous system [
A 70-year-old Caucasian male presented with complaints of diarrhea for the last 4 months. He had associated fecal urgency and incontinence at times. He was having 4-5 bowel movements a day ranging from semisolid to watery stools. He denied any history of fevers, abdominal pain, vomiting, weight loss, night sweats, or skin rashes. He denied any recent travel history or exposure to anyone with similar symptoms.
On physical examination, his abdomen was soft and nontender. There was no apparent hepatomegaly or splenomegaly. The rest of the cardiovascular, respiratory, and nervous system examinations were unremarkable. Initial laboratory evaluation showed a hemoglobin of 15.5 g/dL (14–18), WBC of 8.3 K/uL (4.5–11), leucocyte fraction of 45.7% (15–50%), platelet count of 187 K/uL (140–440), creatinine of 0.9 mg/dL (0.7–1.3), AST of 34 U/L (13–39), ALT of 25 U/L (4–33), ALP of 102 U/L (34–104), albumin of 4 g/dL (3.5–5.7), and globulin of 3.1 g/dL (1.5–4.5).
Further workup was done for finding the etiology of the chronic diarrhea. Work up for infection, including parasitic infection and bacterial infections including
Colonoscopy showing submucosal nodularity.
Hematoxylin and eosin stain showing lymphoid aggregate with normal colon mucosa.
Lymphoid aggregate positive for PAX5 stain.
Lymphoid aggregate negative for cyclin D1.
The patient then underwent CT chest, abdomen, and pelvis with IV contrast for evaluation which revealed extensive bilateral axillary, hilar, abdominal, and pelvic lymphadenopathy. He subsequently underwent bone marrow biopsy histopathology which revealed hypercellular bone marrow, with 50% involved by lymphoid cells; flow cytometric immunophenotyping studies revealed monoclonal B-cell lymphoid population with kappa light chain restriction with CD5 and CD23 coexpression consistent with CLL. The patient did not have any abnormal cell clone harboring deletion of 11q, 13q, or 17p. His Rai staging was Stage I and Binet staging was Stage B, putting him at intermediate risk. The patient was referred to oncology that started him on obinutuzumab and venetoclax chemotherapy for the CLL.
The patient went into remission from his CLL on treatment with chemotherapy. The patient improved significantly, and the diarrhea resolved. On 3- and 6-month follow-ups, the patient experienced significant symptomatic improvement with resolution of chronic diarrhea.
A review of the literature revealed a total of
All the prior reported cases of CLL presenting with chronic diarrhea.
Case | Age | Sex | Initial presentation | History of CLL | Colonoscopy | Histopathology | Imaging | Treatment | Outcome |
---|---|---|---|---|---|---|---|---|---|
1 | 75 years [ | M | Watery diarrhea, abdominal pain for 4 months | CLL 4 years after treatment-remission | 4 cm polypoidal mass, located at the area of the cecum | B-cell small lymphocytic lymphoma | CT abdomen and pelvis revealed multiple lymphadenopathies in the abdominal and pelvic region | Polypectomy | Resolution of diarrhea after polypectomy. Outpatient follow-up |
2 | 65 years [ | M | Worsening diarrhea, fecal urgency for 6 months | No hx of CLL | An ulcer measuring 2 cm in diameter was noted at the cecum/ileocecal valve junction and multiple nonbleeding, superficial, linear ulcers were observed in the rectal mucosa | Dense, atypical, lymphoid infiltrate suggestive of a low-grade lymphoproliferative disorder | CT imaging showed mild splenomegaly and enlarged portacaval, precaval, periaortic, mesenteric, bilateral supraclavicular, axillary, and inguinal lymph nodes | Weekly rituximab | Resolution of diarrhea after 4 weeks of treatment |
3 | 81 years [ | M | Diarrhea for 6 weeks and 10-pound weight loss | No hx of CLL | Moderate mucosal inflammation, friability, and a few ulcerations, more pronounced in the sigmoid colon | Lamina propria expanded by small lymphocytes | Inflammation and colonic wall thickening and possible narrowing of the rectosigmoid colon with surrounding fat stranding and significant retroperitoneal and mesenteric lymphadenopathy | Palliative care, trial of chlorambucil | Died after 10 days at home |
4 | 66 years [ | M | Hematochezia, intermittent left lower abdominal pain of 1-month duration | No hx of CLL | Huge, round, reddish intraluminal mass covered with blood clots in the ascending colon just proximal to hepatic flexure that occupied nearly the entire colonic lumen | Dense cellular infiltrate in the mucosa. The infiltrating cells were darkly stained, uniformly small and round lymphocytes that had infiltrated the lamina propria but spared the crypts | Initial ultrasound: right midabdomen that had alternating hypoechoic and hyperechoic rings surrounding an echogenic center (doughnut sign), findings suggestive of intussusception | — | Died several weeks from presentation |
5 | 70 years | M | Diarrhea for 4 months | No hx of CLL | Normal mucosa but diffuse submucosal nodularity through the large intestine | Multiple aggregates for small mature lymphocytes in the submucosa | CT chest, abdomen, and pelvis revealed extensive bilateral axillary, hilar, abdominal, and pelvic lymphadenopathy | Obinutuzumab and venetoclax chemotherapy | Asymptomatic on 6 months follow-up |
Endoscopic evaluation with colonoscopy was notable for variable findings ranging from polypoid mass, multiple linear ulcerations, and ulcerations with mucosal inflammation and friability. Imaging with contrast enhanced CT in all cases revealed abdominal and pelvic lymphadenopathy. Colonic histopathology in all cases revealed lymphocytic infiltration. Treatment details were available for two patients; polypectomy was done for one patient, and rituximab was used to treat for the other patient with resultant resolution of symptoms. In the remaining two patients, one patient decided to pursue comfort care measures and passed away shortly after hospital discharge. No treatment details were available for the other patient who also passed away few weeks after diagnosis.
Of these cases, there are two cases of CCL involving the large intestine including our patient [
(1) Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disorder in the United States. (2) It has a very variable presentation with most patients having asymptomatic lymphocytosis. (3) CLL can also present with extramedullary involvement, most commonly the skin or central nervous system. (4) Rarely, it can also present with chronic diarrhea, which typically resolves after treatment of the CLL.
The abstract of this case report was presented at the American College of Gastroenterology Annual 2020 Conference and the abstract was published in The American Journal of Gastroenterology October 2020 Volume 115.
The authors declare that they have no conflicts of interest.