Peutz-Jeghers syndrome differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hamid Qazi, MD, BSc [2]

Overview

Peutz-Jeghers syndrome must be differentiated from other diseases that cause hamartomatous polyps and mucocutaneous pigmentation, such as Cowden syndrome, Bannayan–Riley–Ruvalcaba syndrome, juvenile polyposis, and McCune-Albright syndrome.

Differentiating Peutz-Jeghers Syndrome from other Diseases

Peutz-Jeghers syndrome must be differentiated from the following diseases:

• Cowden syndrome
• Cronkhite-Canada syndrome
• Bannayan–Riley–Ruvalcaba syndrome
• Juvenile polyposis
• McCune-Albright syndrome

Differential diagnosis according to polys:

Diseases	History and Symptoms				Physical Examination			Laboratory Findings				Other Findings
	Abdominal Pain	Rectal Bleeding	Hyperpigmentation	Fatigue	Abdominal Tenderness	Hyperpigmentation	Anemia	Gene(s)	Sertoli Cell Tumors	Gastrointestinal Tumors	Cancers
Juvenile Polyposis Syndrome	+		-	+	-	-	-	SMAD4 BMPR1A	-	Adenoma+  Hamartoma+++	Colon
Cowden Syndrome	-	-	Axillary+ Inguinal+ Facial+	-	-	Axillary+ Inguinal+ Facial+	-	PTEN	-	Adenoma+  Hamartoma+++	Breast, Thyroid, Endometrium	Trichilemmoma, skin hamartoma, hyperplastic polyps, macrocephaly, breast fibrosis
Carney Syndrome	-	-	Facial+ Mucosal+	-	-	Facial+ Mucosal+	-	PRKAR1A	++		Thyroid	Myxomas of skin and heart
Familial Adenomatous Polyposis	+	+	-	+	+/-	-	+	APC	-	Adenoma+++	Colon, brain	Desmoid tumors, osteomas
Hereditary Non-Polyposis Colon Cancer	-	+	-	+	+/-	-	+	MLH1 MSH2 MSH3 MSH6 PMS1 PMS2	-	Adenoma+	Endometrial, gastric, renal pelvis, ureter, and ovarian	Sebaceous adenoma

Differential of gastrointestinal bleeding

Disease Clinical manifestations Diagnosis Comments Symptoms Signs Abdominal Pain Fever Rigors and chills Nausea or vomiting Jaundice Constipation Diarrhea Weight loss GI bleeding Hypo- tension Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging Peutz-Jeghers syndrome Depends on location of polyps it maybe present ± - ± - ± ± ± Rectal bleeding may be present due to polyp - - - + Hamartomatous polyps present on endoscopy Iron deficiency anemia on CBC STK11 mutation Intra-operative enteroscopy (laparatomy with endoscopy Double balloon eneteroscopy Colonoscopy Barium Swallow Can lead to colon cancer, breast cancer, ovarian cancer, cervical cancer, and testicular cancer Peptic ulcer disease Diffuse ± − + − − − + Gastric ulcer- melena and hematemesis Duodenal ulcer- melena and hematochezia Positive if perforated Positive if perforated Positive if perforated N Ascitic fluid LDH > serum LDH Glucose < 50mg/dl Total protein > 1g/dl Air under diaphragm in upright CXR Upper GI endoscopy for diagnosis Gastritis Epigastric ± − + − − − Positive in chronic gastritis + − − − N H.pylori infection diagnostic tests Endoscopy H.pylori gastritis guideline recommendation Gastrointestinal perforation Diffuse + ± - ± − − − + + + ± Hyperactive/hypoactive WBC> 10,000 Air under diaphragm in upright CXR Hamman's sign Acute diverticulitis LLQ + ± + − + ± − + Positive in perforated diverticulitis + + Hypoactive Leukocytosis CT scan Ultrasound History of constipation Inflammatory bowel disease Diffuse ± − − ± − + + + − − − Normal or hyperactive Anti-neutrophil cytoplasmic antibody (P-ANCA) in Ulcerative colitis Anti saccharomyces cerevisiae antibodies (ASCA) in Crohn's disease String sign on abdominal x-ray in Crohn's disease Extra intestinal findings: Uveitis Arthritis Infective colitis Diffuse + − ± − − + − + Positive in fulminant colitis ± ± Hyperactive Stool culture and studies Shiga toxin in bloody diarrhea PCR CT scan Bowel wall thickening Edema Colon carcinoma Diffuse/localized − − − − ± ± + + ± − − Normal or hyperactive if obstruction present CBC Carcinoembryonic antigen (CEA) Colonoscopy Flexible sigmoidoscopy Barium enema CT colonography  PILLCAM 2: A colon capsule for CRC screening may be used in patients with an incomplete colonoscopy who lacks obstruction Budd-Chiari syndrome RUQ ± − − ± − − − Positive in liver failure leading to varices − − − N Elevated serum aspartate aminotransferase and alanine aminotransferase levels may be more than five times the upper limit of the normal range. Elevated serum alkaline phosphatase and bilirubin levels, decreased serum albumin level. Findings on CT scan suggestive of Budd-Chiari syndrome include: Early enhancement of the caudate lobe and central liver around the inferior vena cava Delayed enhancement of the peripheral liver with accompanying central low density (flip-flop appearance) Peripheral zones of the liver show reversed portal venous blood flow In the chronic phase, there is caudate lobe enlargement and atrophy of the peripheral liver in affected areas Ascitic fluid examination shows: Total protein more than 2.5 g per deciliter White blood cells are usually less than 500/μL. Hemochromatosis RUQ − − − − − − − Positive in cirrhotic patients − − − N >60% TS >240 μg/L SF Raised LFT Hyperglycemia Ultrasound shows evidence of cirrhosis Extra intestinal findings: Hyperpigmentation Diabetes mellitus Arthralgia Impotence in males Cardiomyopathy Atherosclerosis Hypopituitarism Hypothyroidism Extrahepatic cancer Prone to specific infections Cirrhosis RUQ − − − + − − + + + − − N Hypoalbuminemia Prolonged PT Abnormal LFTs Hyponatremia Thrombocytopenia US Nodular, shrunken liver Ascites Stigmata of liver disease Cruveilhier- Baumgarten murmur Mesenteric ischemia Periumbilical Positive if bowel becomes gangrenous − + − − + + + Positive if bowel becomes gangrenous Positive if bowel becomes gangrenous − Hyperactive to absent Leukocytosis and lactic acidosis Amylase levels D-dimer CT angiography SMA or SMV thrombosis Also known as abdominal angina that worsens with eating Acute ischemic colitis Diffuse + ± + − − + + + + + + Hyperactive then absent Leukocytosis Abdominal x-ray Distension and pneumatosis CT scan Double halo appearance, thumbprinting Thickening of bowel May lead to shock Ruptured abdominal aortic aneurysm Diffuse ± − + − − − + + + − − N Fibrinogen D-dimer Focused Assessment with Sonography in Trauma (FAST)  Unstable hemodynamics Intra-abdominal or retroperitoneal hemorrhage Diffuse ± − ± − − − − + + − − N ↓ Hb ↓ Hct CT scan History of trauma