Resident CPCPresenter: Dr. Nilofer RahmanFacilitator: Dr. Neha Agrawal

Faculty: Radiology: Dr. Aziz AhmedPathology: Dr. Ben Yan

Chief Complaints• Intermittent diarrhea for 1 month• Lower abdominal cramping pain.

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 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 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.

HematologyWBC 7.3HGB 16HCT 44.9MCV 85.1Platelet 328

Neutrophils 61%Lymphocytes 28%Monocytes 8%Eosinophils 1%Basophils 2%

Complete Metabolic Panel

Na 140K 4.2Cl 105CO2 25BUN 16Cr 0.8Ca 9.0

Total protein 7.7Albumin 4.3

AST 24

ALT 33

Alk ph 74

T bili 0.5

Other labs

TSH 0.54 (0.35-4.94)ESR 3CRP <0.5Celiac disease panel Negative

CT Scan Abdomen/Pelvis

CT Scan Of Abdomen And Pelvis

Dr. Nilofer Rahman

Hospital Course• The patient underwent cervical lymph node FNA (6/25/2012)

which showed Low grade B cell LymphomaNodal 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

Radiology Dr. Aziz Ahmed

Pathology Dr. Benjamin Yan

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.

Thank You

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