NYU Medicine Grand Rounds Clinical Vignette

1. NYU Medicine Grand Rounds Clinical Vignette Benjamin P. Geisler, MD, MPHPGY-22/5/2014 UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

2. Chief Complaint UNITED STATES DEPARTMENT OF VETERANS AFFAIRS • 59 year old woman with epigastric pain for four days

3. History of Present Illness UNITED STATES DEPARTMENT OF VETERANS AFFAIRS • For the past 4 days, has had multiple episodes of non-bloody, non-bilious vomiting • Thirteen days prior had stay in observation unit for diarrhea and dehydration, empirically started on metronidazole • Intense, sharp, crampy right foot pain for three days after walking half a block, relieved by rest

4. History of Present Illness (continued) UNITED STATES DEPARTMENT OF VETERANS AFFAIRS • Previous workup for celiac disease: • Transglutaminase IgA (92 [normally <4] U/ml) • Esophagogastroduodenoscopy 4/2013 (↑ intraepithelial lymphocytes, mild-moderate villous atrophy) • Capsule endoscopy 5/2013 consistent with active Celiac disease in the small bowel • Improved with gluten-free diet; transglutaminase IgA decreased to 30 U/ml

5. UNITED STATES DEPARTMENT OF VETERANS AFFAIRS Additional History • Past Medical History: • Celiac Disease • Osteoporosis • Osteoarthritis • Past Surgical History: • Status post total right hip arthroplasty 2010 • Social History: • From Ireland • Denis toxic habits • Family History: • Celiac Disease in multiple relatives • Father died from unknown lymphoma at age 42 • Brother with diabetes and myocardial infarction at age 51

6. Additional History (continued) UNITED STATES DEPARTMENT OF VETERANS AFFAIRS • Allergies: • Aspartame – urticaria • Medications: • Metronidazole 500 mg three times per day • Bismuth subsalicylate 524 mg every hour as needed • Ibuprofen-diphenhydramine 600/114 mg nightly • Ergocalciferol 50,000 once per week • Folic acid 1 mg daily

7. Physical Examination UNITED STATES DEPARTMENT OF VETERANS AFFAIRS • General: anxious-appearing, pale, in painful distress • Vital Signs: T:97.8°F BP:176/92 HR:71 RR:20 and O2 sat:100% on room air • Epigastric tenderness • Right first toe cyanotic, sluggish capillary refill on right lower extremity without palpable dorsalis pedis pulse • Remainder of Physical Exam was normal

8. Laboratory Findings UNITED STATES DEPARTMENT OF VETERANS AFFAIRS • CBC: white cell count 16,500/µl (82% neutrophils, 14% lymphocytes), platelets 756,000/µl • Remainder of CBC was within normal limits • Basic Metabolic panel: CO2 21 mmol/L, BUN 9 mg/dL • Remainder of basic was within normal limits • Hepatic panel: alkaline phosphatase 147 U/L, albumin 3.1 g/dL • Remainder of hepatic panel was within normal limits

9. Other Studies UNITED STATES DEPARTMENT OF VETERANS AFFAIRS • Arterial duplex: mild femoral-popliteal and mild to moderate tibio-peroneal occlusive disease • CT abdomen/pelvis: diffuse calcific atherosclerosis, unchanged right adnexal cyst, scattered mesenteric lymph nodes without intestinal inflammation or obstruction, new non-occlusive 1.9 cm thrombus in the infrarenal aorta

10. UNITED STATES DEPARTMENT OF VETERANS AFFAIRS Working or Differential Diagnosis • Infrarenal aortic thrombus of unclear etiology • Myeloproliferative disorder • Essential thrombocytemia • Polycytemia vera • Primary myelofibrosis • Chronic leukocytemic leukemia • Reactive thrombocytosis, e.g., from refractory celiac disease or lymphoma

11. UNITED STATES DEPARTMENT OF VETERANS AFFAIRS Hospital Course • Hospital Day 1-2: • Heparin and aspirin started • Peripheral blood sent for JAK2 (V617F) mutation and t(9;22) translocation with BCR-ABL fusion; both subsequently returned negative

12. UNITED STATES DEPARTMENT OF VETERANS AFFAIRS Hospital Course (continued) • Hospital Day 3-6: • Open aortic thrombectomy, aortoplasty, and mesenteric lymph node biopsy • Hydroxyurea started for persistent thrombocytosis

13. UNITED STATES DEPARTMENT OF VETERANS AFFAIRS Hospital Course (continued) • Hospital Day 16: • Colonoscopy: mildly congested mucosa throughout; nodular ileal mucosa; congested, friable fold in the ascending and adenomatous-appearing fold in the descending colon; hyperemic rectum • Small bowel enteroscopy: diffuse scalloped and friable mucosa in the proximal and mid-jejunum without nodules, lesions, or masses

14. UNITED STATES DEPARTMENT OF VETERANS AFFAIRS Hospital Course (continued) • Hospital Day 20: • Biopsies with abnormalities in mesenteric lymph node and small bowel • Slight excess of B-cells, felt non-diagnostic of lymphoma • Increased number of γδ-T cells especially in ileum with presence of large cells • Molecularly and immunopheno typically unclear • Corticosteroids started

15. UNITED STATES DEPARTMENT OF VETERANS AFFAIRS Pathological Re-evaluation • Duodenum and jejunum: • Partial villous atrophy, crypt hyperplasia, moderate inflammation, and patchy intraepithelial lymphocytosis • Terminal ileum, ascending/left/sigmoid/rectum: • Lymphocytic infiltrate of intermediate to large, atypical, pleomorphic CD3+, CD4(subset)+, CD5-, CD30(subset)+ cells • Kappa-restricted HLA-DR+, CD5-, CD19+, CD20dim, CD30- CD79a+, CD103- clone • Bone marrow: • Positive for T-cell receptor-beta gene rearrangement

16. UNITED STATES DEPARTMENT OF VETERANS AFFAIRS Final Diagnosis • Enteropathy-associated T-cell lymphoma • Possible concurrent B-cell lymphoproliferative disorder, likely low-grade B-cell lymphoma