3History of Present Illness 43 y/o Caucasian man presented with 1 month of intermittent diarrhea and abdominal painStools 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
4Past Medical and Surgical History History of foot surgery many years agoArthritis, joint painAllergies:PCN and sulfa- rashSocial history:Non smoker, drinks maybe 6 beers a week.He works as a janitor . Married, 3 kids.Family history:Unknown, he is adoptedMedications:Tramadol as neededFlonase daily AM
5Review Of SystemsCONSTITUTIONAL: 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, orthopneaGASTROINTESTINAL: 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 nailsNEUROLOGIC: Denies headaches, dizziness, paresthesias, weakness
6Physical ExaminationVital signs: Temp-98F, BP 120/90, HR- 64, RR- 16, Weight LbHEENT: wnlOral cavity: unremarkableNECK: No anterior cervical lymphadenopathy. There are 2 occipital lymph nodes , each approximately 1 cm soft, mobile, and non tenderNo thyroid enlargementNo axillary lymphadenopathyChest- ClearCVS- S1 S2 regularAbdomen- 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.
13Hospital CourseThe patient underwent cervical lymph node FNA (6/25/2012) which showed Low grade B cell LymphomaNodal excision on 7/5/12 showed Mantel Cell LymphomaStaging LN on both sides of Diaphragm (max size 2cm)BM biopsy negative but Flow cytometry showed 2% of CD5/CD19 positive B cellsPET 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 trial2 arms: R-hyper CVAD alternating with MTX/Ara-C for 4 cycles+1Compared with R-Bendamustine q28days X6 cyclesBoth arms followed by Stem cell transplantation
25Mantle Cell LymphomaMantle cell lymphoma (MCL) is a non-Hodgkin lymphoma and represents 2-10% of all non-Hodgkin lymphomasCharacterized 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 AmericansMale-to-female ratio is 4:1Age range at presentation is years, with median age being 60 yearsShort remission duration to standard therapies and a median overall survival of 4–5 years.No causative factor has been identified for mantle cell lymphoma
26Clinical 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 spleenpressure or pain in the lower back often extending down one or both legs,Disease complications from disease progression may includeCytopenias (neutropenia,anemia,thrombocytopenia)GI, Pulmonary, CNS complications- if extranodal. In the GIT a condition known as “multiple small-intestine polyps” may result.Leucocytosis
27DiagnosisDiagnosis 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.
28Risk StratificationThe mantle cell lymphoma international prognostic index (MIPI) is the prognostic model most often used and incorporatesECOG performance statusageleukocyte count, andlactic 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.
29GI involvementThe 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 MCLAbnormal 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 infiltratesAm J Surg Pathol Oct;30(10):
30Risk-Adapted TherapyFor 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.