CLINICOPATHOLOGICAL CASE

1. CLINICOPATHOLOGICAL CASE NilofarRahman, PGY 3

2. History of Present Illness • 43 y/o Caucasian M presented with c/o intermittent diarrhea for last 1 month, associated with lower abdominal cramps. • Stools are liquid, watery, brown in color 3-4 episodesper day not mixed with blood or mucous. No tenesmus. No h/o fever, chills, nausea or vomiting. • No h/o sick contacts or recent antibiotic use. • 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 and again started having diarrhea and cramps .

3. Review Of Systems • CONSTITUTIONAL:Fatigue. No fever, chill, anorexia, weight loss or night sweats insomnia. • HEENT: No changes in vision or hearing, hoarseness, epistaxis, postnasal drip, vertigo, or recurrent sinusitis. • CVS and RS:Denies chest pain, palpitations, claudication, edema, phlebitis, dyspnea, orthopnea, cough, asthma, or pneumonia. • GI: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. Denies decreased range of motion, arthritis, back pain, morning or night cramps. • INTEGUMENTARY: Denies changes in skin lesions, presence of unusual skin lesions, pruritus, nail changes, hair changes. • NEUROLOGIC: Denies headaches, dizziness, paraesthesias, weakness, fainting, coordination difficulty, cranial nerve problems, or gait disturbance.

4. …CASE • Past Medical and Surgical History • Significant for history of foot surgery when he was young. • Arthritis, joint pain. History of trigger fingers. • History of allergies • Social history • Does not smoke, drinks maybe 6 beers a week. He works as a janitor . Married, has 3 children. • Family history • He does not know much. He is adopted.

5. …CASE • Allergies: • PCN- rash as child • Sulfa- rash • Medications: • Tramadol as needed • Flonase daily AM

6. Physical Examination • Vital signs: Temp-98F, BP 120/90, HR- 64, RR- 16, Weight - 190 Lb • HEENT: • Head: Normocephalic with no unusual masses; • Ears: No pre or postauricular masses or lymphadenopathy. External auditory canal is within normal limits. Normal tympanic membrane. • Nose: septum is midline with normal septal mucosa. • Oral cavity: unremarkable. • Neck: No anterior cervical lymphadenopathy. There are 2 occipital lymph nodes, each approximately 1 cm soft, mobile, and non tender ( pt stated that the LN are present for >1 year, wax and wane, initially started after an URI). No thyroid enlargement • No axillary lymphadenopathy • Chest -Clear to auscultation, no wheezes or crackles. • CVS - S1, S2 heard, RRR. No murmurs, rubs or gallop. • Abdomen - Soft, non tender, no rebound or guarding, no signs of peritonitis, BS +ve. No hepatosplenomegaly. • Neurologic:Cranial nerves II through XII are intact and functioning symmetrically. Motor strength 5/5, and sensations were intact. Symmetrical reflexes. Gait was normal.

7. My questions • Diarrhea: ?recurrence, alternating with constipation, nocturnal diarrhea, fasting diarrhea, stools were foul smelling or greasy • PMH: h/o recurrent infections, duration of arthritis • Family history: colon cancer, autoimmune conditions, CAD, DM, IBD • Dietary history: exposure to impure water source, intake of smoked foods, raw milk • Social history: IV drug use, secondary gain from illness, travel, exposure to TB, occupation • Sexual history: promiscuity, h/o STDs • Therapeutic interventions – Radiation, OTC medications

8. More questions • Rectal exam: anal fissures, fistula, abnormal anal sphincter pressure • Eye exam: evidence of episcleritis • Skin: rashes, erythema nodosum • Exam of joints: range of motion, effusion

9. Hematology

10. Complete Metabolic Panel

11. Other labs

12. CT Scan Abdomen/Pelvis Filling defect

13. CT Scan Abdomen/Pelvis

14. Case summary 43 y/o Caucasian M with PMH of arthritis and allergies presented with c/o intermittent diarrhea for one month. Stools were watery, non bloody and associated with lower abdominal cramps. Initial assessment revealed two palpable, soft, non tender occipital lymph nodes which were 1 cm in size. The lymph nodes were noticed > 1 year ago, waxing and waning type, initially brought about by an URI. Labs showed some hemoconcentration. CT scan of abdomen and pelvis revealed filling defect in ileum and abdominal and inguinal lymphadenopathy.

15. Additional workup • FOBT, stool electrolyte • Baseline Hb and Hct and magnesium levels • Colonoscopy with biopsy • Plasma peptides: Gastrin, Somatostatin • Urine 5HIAA, serotonin

16. Broad differential diagnosis • Inflammatory: • IBD – crohn’s disease • Ischemic colitis • Tumors • Benign: adenomas, leiomyomasand lipomas • Malignant • Adenocarcinoma • Lymphoma • Drugs • Chronic infections: • HIV associated opportunistic infections • Tubercular enteritis • Secretory diarrhea • Laxative abuse • Post cholecystectomy • Neuroendocrine tumors • Gastrinoma • Somatostatinoma • VIPoma • Carcinoid syndrome • Malabsorption syndromes • Small bowel bact overgrowth, short bowel syndrome, pancreatic exocrine insufficiency • Disordered motility • Hyperthyroidism • Diabetic autonomic neuropathy • Irritable bowel syndrome

17. Drugs causing diarrhea

18. Drugs causing diarrhea Tramadol causes diarrhea in < 5% of cases

19. Broad differential diagnosis • Inflammatory: • IBD-crohn’s • Ischemic colitis • Tumors • Benign: adenomas, leiomyomas, and lipomas • Malignant • Adenocarcinoma • Lymphoma • Drugs • Chronic infections: • HIV associated opportunistic infections • Tubercular enteritis • Secretory diarrhea • Laxative abuse • Neuroendocrine tumors • Gastrinoma • Somatostatinoma • VIPoma • Carcinoid syndrome • Malabsorptionsyndromes • Small intestinal bact overgrowth, short bowel syndrome, pancreatic exocrine insufficiency • Disordered motility • Hyperthyroidism • Diabetic autonomic neuropathy • Irritable bowel syndrome

20. Ischemic colitis • Mesenteric ischemia: reduction in blood flow, acute and chronic • Risk factors: h/o smoking, atherosclerotic vascular disease • Chronic mesenteric ischemia is due to episodic or constant hypoperfusion • Symptoms: • Abdominal pain – symptoms out of proportion to signs • Sitophobia – weight loss • Diarrhea • Diagnosis is due by CT or MR angiography

21. Broad differential diagnosis • Inflammatory: • IBD – crohn’s • Ischemic colitis • Tumors • Benign: adenomas, leiomyomasand lipomas • Malignant • Adenocarcinoma • Lymphoma • Chronic infections: • HIV associated opportunistic infections • Tubercular enteritis • Secretory diarrhea • Laxative abuse • Neuroendocrine tumors • Gastrinoma • Somatostatinoma • VIPoma • Carcinoid syndrome • Malabsorption syndromes • Small intestinal bact overgrowth, short bowel syndrome, pancreatic exocrine insufficiency • Disordered motility • Hyperthyroidism • Diabetic autonomic neuropathy • Irritable bowel syndrome

22. Other neuroendocrine tumors • Gastrinoma: well differentiated NET • Duodenum and pancreas • Gastrin is predominant peptide • Symptoms: peptic ulcers, diarrhea, weight loss • Diagnosis: serum fasting gastrin, secretin stimulation test, gastric acid secretion studies • Somatostatinoma: rare NET of D cell origin – secretes somatostatin • Mainly found in duodenum or pancreas • Symptoms: diarrhea with steatorrhea, abdominal pain, diabetes, cholelithiasis • VIPoma: Rare NET, secretes VIP • Watery diarrhea, hypokalemia, hypochlorhydria • Imaging of NET • CT scan, octreotide scan

23. Broad differential diagnosis • Inflammatory: • IBD – crohn’s • Tumors • Benign: adenomas, leiomyomasand lipomas • Malignant • Adenocarcinoma • Lymphoma • Chronic infections: • HIV associated opportunistic infections • Tubercular enteritis • Secretory diarrhea • Laxative abuse • Neuroendocrine tumors • Carcinoid syndrome • Gastrinoma • Somatostatinoma • VIPoma • Malabsorption syndromes • Small intestinal bact overgrowth, short bowel syndrome, pancreatic exocrine insufficiency • Disordered motility • Hyperthyroidism • Diabetic autonomic neuropathy • Irritable bowel syndrome

24. Irritable bowel syndrome • Important cause of functional diarrhea, 2:1 female predominance • Clinical manifestations: • Diarrhea, constipation or alternating bowel habits • Diarrhea is associated with mucus • LARGE, VOLUMINOUS, BLOODY OR NOCTURNAL DIARRHEA ARE NOT ASSOCIATED WITH IBS. • Diagnosis by ROME criteria

25. Broad differential diagnosis • Inflammatory: • IBD – crohn’s • Tumors • Benign: adenomas, leiomyomas and lipomas • Malignant • Adenocarcinoma • Lymphoma • NET: Carcinoid • Chronic infections: • HIV associated opportunistic infections • Tubercular enteritis • Disordered motility • Irritable bowel syndrome

26. Inflammatory bowel disease • Crohn’s disease: transmural inflammation of GI tract • 80% ileum • 50% ileum and colon • Clinical manifestations: • Abdominal pain • Diarrhea with or without bleeding • Fistulas • phlegmon • Perianal disease • Other GI involvement: oral ulcers, esophageal, gastroduodenal and gallstones • Systemic manifestations: fatigue, weight loss, fever

27. Clinical manifestations • Extraintestinal manifestations: • Arthritis: large joints or central/axial skeleton • Eye involvement: uveitis, episcleritis, iritis • Skin: erythema nodosum and pyodermagangrenosum • Primary sclerosingcholangitis • Venous and arterial thrombosis • Renal stones • Vitamin B12 deficiency

28. Diagnosis of crohn’s disease • Iron deficiency anemia, elevated ESR/CRP, Vitamin B12 deficiency, elevated WBC • Serologic tests: p ANCA, ASCA • Wireless capsule endoscopy • Imaging: • CT abdomen • MRI Diagnostic accuracy of serological assays in inflammatory bowel disease. RuemmeleFM, Targan SR, Levy G, Dubinsky M, Braun J, SeidmanEG. Gastroenterology. 1998;115(4):822.

29. Diagnosis of crohn’s disease Colonoscopy findings: Endoscopic features in Crohn'sdisease: Aphthousulcers, which are the earliest lesions seen in Crohn's disease (panel A); large ulcers interspersed with normal mucosa, which are typical for the segmental distribution of Crohn's disease (panel B); a cobblestone appearance (panel C); and strictures due to fibrosis (panel D).

30. Tumors of small bowel • Types: • Benign: adenomas, leiomyomas and lipomas • Malignant: • Duodenum: adenocarcinoma, carcinoid, lymphoma, sarcoma • Jejunum: adenocarcinoma, lymphoma, carcinoid • Ileum: carcinoid, adenocarcinoma, lymphoma

31. Adenocarcinomas • Risk factors: Hereditary conditions, crohn’s disease, dietary factors • Clinical manifestations:

32. Carcinoid tumor • Arise from intraepithelial endocrine cells • Ileum – 60 cm from ileocecal valve • Symptoms/signs: asymptomatic, abdominal pain, diarrhea, obstruction • Metastasis to liver – carcinoid syndrome • Diagnosis: • 24 hr urinary excretion of 5HIAA, urine serotonin • Serum chromogranin A, B, C levels • CT scan • Octreotide scan CT scan: soft tissue mass containing coarse central calcifications (short arrow) in the RLQ. This is a classic desmoplastic response with spiculation of the adjacent mesenteric fat (long arrow).

33. Lymphoma • May arise as a primary GI lymphoma or as a part of systemic disease • Primary GI tract lymphoma- stomach, small intestine • Risk factors: Autoimmune, crohn’s, immunodeficiency syndromes, chronic immunosuppression, radiation • Classified as • Immunoproliferative small intestinal disease (IPSID) • Enteropathy associated T cell lymphoma (EATL) • Non immunoproliferative small intestinal disease (non IPSID) • Clinical features differ according to histologic type • IPSID: abdominal pain, diarrhea, weight loss • EATL: acute GI bleed, intestinal obstruction or perforation • Non IPSID: abdominal pain, GI bleed, obstruction or perforation

34. Diagnosis of small bowel tumors • Small bowel follow through may show a mass or mucosal defect • CT scan • Endoscopy with biopsy • Tumor markers: CEA

35. Chronic infections • Small bowel manifestation of HIV is enteritis • Opportunistic infections likely occur when CD4 < 50 /microL • Common organisms: • Bacterial: salmonella, shigella, campylobacter and c. diff • Parasites like giardia, cryptosporidium, microsporidia, isospora • Enteric pathogens like mycobacterium aviumintracellulare

36. HIV • Cryptosporidium and microsporidia: transmitted as zoonosis or feco oral • involves small bowel, microsporidia – has extraintestinal involvement • High output diarrhea and malabsorption like vit B12 deficiency • Villous atrophy on biopsy • therapy – under investigation • Isospora: feco oral route of transmission • Acid fast stains – large oocysts, charcotleyden crystals • Biopsy: intracellular forms, eosinophils and villous atrophy • Giardia: diarrhea, severe in those who practice oral-anal sex • Stool exam and duodenal aspirates: cysts, trophozoites

37. HIV • CMV: ususally involves esophagus and colon • Mycobacterium aviumintracellulare: CD4<100/microL • Fever, weight loss, abdominal pain, diarrhea • Small bowel biopsy: macrophages with acid fast organisms • CT scan: lymphadenopathy with central necrosis • Intestinal involvement – kaposi’s sarcoma – HHV8 • NHL: • involves the small intestine • Abdominal pain, diarrhea or mass lesions

38. Final diagnosis • Tumors • Benign: adenomas, leiomyomas, lipomas • Malignant • Adenocarcinoma • Lymphoma • NET: carcinoid • Metastatic lesions • Chronic infections: • HIV associated opportunistic infections • Tubercular enteritis • Inflammatory: • IBD – crohn’s

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