CLINICOPATHOLOGICAL CASE

CLINICOPATHOLOGICAL CASE

Nilofar Rahman, PGY 3

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 episodes per 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 .

History of Present Illness

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.

Review Of Systems

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.

…CASE

Allergies:◦ PCN- rash as child

◦ Sulfa- rash

Medications:◦ Tramadol as needed

◦ Flonase daily AM

…CASE

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.

Physical Examination

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

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

WBC 7.3HGB 16HCT 44.9MCV 85.1Platelet 328

Hematology

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

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

Complete Metabolic Panel

Total protein 7.7Albumin 4.3AST 24ALT 33Alk ph 74T bili 0.5

Other labs

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

CT Scan Abdomen/Pelvis

Filling defect

CT Scan Abdomen/Pelvis

Case summary43 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.

Additional workup

FOBT, stool electrolyte

Baseline Hb and Hct and magnesium levels

Colonoscopy with biopsy

Plasma peptides: Gastrin, Somatostatin

Urine 5HIAA, serotonin

Broad differential diagnosis Inflammatory:

IBD – crohn’s disease

Ischemic colitis

Tumors Benign: adenomas, leiomyomas

and 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

Drugs causing diarrheaCardiovascular Antiarrhythmics Quinidine,

Procainamide, Digitalis

Antihypertensives ACEi, ARBs, Bblockers, Hydralazine, methyldopa

Cholesterol lowering agents

Statins, cholestyramine, gemfibrozil

Diuretics Acetazolamide, ethacrynic acid, furosemide

Central nervous system AntianxietyAntiparkinsonianOthers

LorazepamLevodopaAnticholinergics, Lithium, floxetine

Endocrine Oral hypogycemicsThyroid replacement

MetforminSynthroid

Drugs causing diarrheaGastrointestinal Antiulcer

Bile acids

Laxatives

H2 blockers, PPIs, mag containing antacids

Ursodeoxycholic acid

Lactulose, sorbitol

Musculoskeletal Gold salts

NSAIDS

Gout

Auronofin

Ibuprofen, naproxen

Cochicine

Antibiotics Ampicillin, amoxycillin, clindamycin, cephalosporins, neomycin

Antineoplastic several

Dietary Alcohol, sugar substitutesVitamins Magnesium,

Vitamin C

Tramadol causes diarrhea in < 5% of cases


• IBD-crohn’s

Ischemic colitis

Tumors Benign: adenomas, leiomyomas,

and lipomas Malignant


Drugs



Secretory diarrhea• Laxative abuse• Neuroendocrine tumors


Malabsorption syndromes• Small intestinal bact


Disordered motility• Hyperthyroidism• Diabetic autonomic

neuropathy• Irritable bowel syndrome

Ischemic colitisMesenteric 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


• IBD – crohn’s

Ischemic colitis

Tumors Benign: adenomas, leiomyomas and

lipomas Malignant








Disordered motility• Hyperthyroidism• Diabetic autonomic neuropathy• Irritable bowel syndrome

Other neuroendocrine tumorsGastrinoma: 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




lipomas

Malignant• Adenocarcinoma• Lymphoma




• Carcinoid syndrome• Gastrinoma• Somatostatinoma• VIPoma



Disordered motility• Hyperthyroidism• Diabetic autonomic

neuropathy• Irritable bowel syndrome

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




lipomas

Malignant • Adenocarcinoma• Lymphoma• NET: Carcinoid



Disordered motility• Irritable bowel syndrome

Inflammatory bowel diseaseCrohn’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

Clinical manifestations Extraintestinal manifestations:

Arthritis: large joints or central/axial skeleton

Eye involvement: uveitis, episcleritis, iritis

Skin: erythema nodosum and pyoderma gangrenosum

Primary sclerosing cholangitis

Venous and arterial thrombosis

Renal stones

Vitamin B12 deficiency

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. Ruemmele FM, Targan SR, Levy G, Dubinsky M, Braun J, Seidman EG. Gastroenterology. 1998;115(4):822.

Diagnosis of crohn’s diseaseColonoscopy findings:

Endoscopic features in Crohn's disease: Aphthous ulcers, 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).

Tumors of small bowel

Types:

Benign: adenomas, leiomyomas and lipomas

Malignant:

Duodenum: adenocarcinoma, carcinoid, lymphoma, sarcoma

Jejunum: adenocarcinoma, lymphoma, carcinoid

Ileum: carcinoid, adenocarcinoma, lymphoma

Adenocarcinomas

Risk factors: Hereditary conditions, crohn’s disease, dietary factors

Clinical manifestations:

abdominal painnausea/vomitinganemiaGI bleed

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).

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

Diagnosis of small bowel tumors Small bowel follow through may show a mass or mucosal defect

CT scan

Endoscopy with biopsy

Tumor markers: CEA

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 avium intracellulare

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, charcot leyden 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

HIV CMV: ususally involves esophagus and colon

Mycobacterium avium intracellulare: 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

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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CLINICOPATHOLOGICAL CASE