History of Present Illness 43 y/o Caucasian man presented with 1 month of intermittent diarrhea and abdominal pain Stools described as liquid, watery, brown in color 3-4 episodes per day not mixed with blood or mucous. No tenesmus. Associated with lower abdominal cramps. No fever or chills. No nausea or vomiting. No recent H/O sick contact. No antibiotic recently. Initial Stool studies done initially- Ova and parasite- negative, C diff- negative, Culture- negative, Leuko-test- positive. Empirically treated with Metronidazole- got better for 3 days but symptoms recurred
Past Medical and Surgical History History of foot surgery many years ago Arthritis, joint pain Allergies: PCN and sulfa- rash Social history: Non smoker, drinks maybe 6 beers a week. He works as a janitor. Married, 3 kids. Family history: Unknown, he is adopted Medications: Tramadol as needed Flonase daily AM
Review Of Systems CONSTITUTIONAL: Fatigue. No fever, chill, anorexia, weight loss or night sweats insomnia. HEENT: Denies changes in vision or hearing, hoarseness, epistaxis, postnasal drip, vertigo, or recurrent sinusitis. CARDIOVASCULAR AND RESPIRATORY: Denies chest pain, palpitations, claudication, edema, dyspnea, orthopnea GASTROINTESTINAL: Intermittent diarrhea and abdominal cramps. Denies dysphagia, early satiety, heartburn, vomiting, excessive flatus. melena, rectal bleeding, hemorrhoids or laxative abuse. GENITOURINARY: Denies dysuria, urinary frequency, urgency, nocturia, hematuria, MUSCULOSKELETAL: Chronic Muscle pain, joint pain. INTEGUMENTARY: Denies changes in skin or nails NEUROLOGIC: Denies headaches, dizziness, paresthesias, weakness
Physical Examination Vital signs: Temp-98F, BP 120/90, HR- 64, RR- 16, Weight - 190 Lb HEENT: wnl Oral cavity: unremarkable NECK: No anterior cervical lymphadenopathy. There are 2 occipital lymph nodes, each approximately 1 cm soft, mobile, and non tender No thyroid enlargement No axillary lymphadenopathy Chest- Clear CVS- S1 S2 regular Abdomen- Soft, non tender, No rebound, guarding, rigidity,BS +ve, No Hepatosplenomegaly. NEUROLOGIC: Cranial nerves II through XII are intact and functioning symmetrically. MS 5/5, and sensations were intact. Symmetrical reflexes. Gait was normal.
Hospital Course The patient underwent cervical lymph node FNA (6/25/2012) which showed Low grade B cell Lymphoma Nodal excision on 7/5/12 showed Mantel Cell Lymphoma Staging LN on both sides of Diaphragm (max size 2cm) BM biopsy negative but Flow cytometry showed 2% of CD5/CD19 positive B cells PET scan done for staging revealed an abnormal focus in terminal ileum. He was referred for Colonoscopy which showed a mass in terminal ileum I-C valve and sigmoid colon, biopsy showed Mantle Cell Lymphoma. Sent to Northwestern hospital-enrolled in a clinical trial 2 arms: R-hyper CVAD alternating with MTX/Ara-C for 4 cycles+1 Compared with R-Bendamustine q28days X6 cycles Both arms followed by Stem cell transplantation
Mantle Cell Lymphoma Mantle cell lymphoma (MCL) is a non-Hodgkin lymphoma and represents 2-10% of all non-Hodgkin lymphomas Characterized by involvement of the lymph nodes, spleen, blood, and bone marrow, tonsils and adenoids, the liver or the gastrointestinal tract. MCL cells may enter the brain, lungs and spinal cord. Whites at higher risk than blacks and Asian Americans Male-to-female ratio is 4:1 Age range at presentation is 35-85 years, with median age being 60 years Short remission duration to standard therapies and a median overall survival of 4–5 years. No causative factor has been identified for mantle cell lymphoma
Clinical Features loss of appetite and weight loss fever, night sweats, nausea and/or vomiting, indigestion, abdominal pain or bloating, a feeling of “fullness” or discomfort due to an enlarged tonsils, liver or spleen pressure or pain in the lower back often extending down one or both legs, Disease complications from disease progression may include Cytopenias (neutropenia,anemia,thrombocytopenia) GI, Pulmonary, CNS complications- if extranodal. In the GIT a condition known as “multiple small-intestine polyps” may result. Leucocytosis
Diagnosis Diagnosis is based on lymph node, bone marrow, or tissue morphology of Centrocytic lymphocytes, small cell type, or blastoid variant cells. MCL is characterized by expansion of the mantle zone that surrounds the lymph node germinal centers by small-to-medium atypical lymphocytes. A chromosomal translocation t(11:14) is the molecular hallmark of MCL, resulting in the overexpression of cyclin D1. Cyclin D1 is detected by immunohistochemistry in 98% of cases. (cyclin regulates CDK kinases->control mitosis) The differential diagnosis of MCL includes small lymphocytic lymphoma, marginal zone lymphoma, and follicular lymphoma.
Risk Stratification The mantle cell lymphoma international prognostic index (MIPI) is the prognostic model most often used and incorporates – ECOG performance status – age – leukocyte count, and – lactic dehydrogenase. A modification of the MIPI also adds the Ki-67 proliferative index if available. The median overall survival (OS) for the low-risk group was not reached (5-year OS of 60%). The median OS for the intermediate risk group was 51 and 29 months for the high-risk group.
GI involvement The frequency of gastrointestinal (GI) tract involvement in mantle cell lymphoma (MCL) at diagnosis is reported to be below 30%. In a prospective series of 13 patients with MCL – Abnormal mucosa was identified in 38% of cases by upper endoscopy (mainly mild nonspecific gastritis) and in 54% of cases by lower endoscopy (mostly micropolyps). – Histologically, infiltration by MCL was demonstrated in the stomach in 77% of cases and in the colon in 77% of cases. As a whole, 92% of patients showed upper or lower GI tract infiltration by MCL. – Histologic evidence of MCL involvement was present in all cases with endoscopically abnormal mucosa, but it was also observed in two-thirds of cases with endoscopically unremarkable mucosa. In conclusion, the great majority of MCL patients showed GI tract involvement at the time of diagnosis, not uncommonly in the form of minute lymphoid infiltrates Am J Surg Pathol. 2006 Oct;30(10):1274-80
Risk-Adapted Therapy For selected indolent, low MIPI MCL patients, initial observation may be appropriate therapy. For younger patients with intermediate or high risk MIPI MCL, aggressive therapy with a Cytarabine containing regimen ± autologous stem cell transplantation should be considered. For older MCL patients with intermediate or high risk MIPI, combination chemotherapy with R-CHOP, R-Bendamustine, or a clinical trial should be considered. At the time of relapse, agents directed at activated pathways in MCL cells such as bortezomib (NFkB inhibitor), BTK inhibitors or CAL-101 (B- cell receptor inhibitors) or lenalidamide (antiangiogenesis) have clinical activity in MCL patients.