Small intestine cancer differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Qurrat-ul-ain Abid, M.D.[2]

Overview

Small intestine cancer must be differentiated from Crohn's disease, intestinal tuberculosis, ulcerative colitis, large intestine cancer, peptic ulcer disease, and irritable bowel syndrome (IBS).

Differential Diagnosis

• Crohn's disease
• Intestinal tuberculosis
• Ulcerative colitis
• Colorectal cancer
• Irritable bowel syndrome (IBS)
• Peptic ulcer disease
• Pancreatic cancer
• Colon cancer
• Intestinal polypoid adenomas
• Intestinal leiomyosarcoma
• Gastric cancer

Table for Differential Diagnosis of Small Intestine Cancer

ABBREVIATIONS:

N/A: Not available, NL: Normal, Hb: Hemoglobin, Abd: Abdominal

Diseases	Clinical manifestations				Para-clinical findings						Gold standard
	Symptoms
					Lab Findings		Imaging			Histopathology
	Bowel Frequency	Blood in stool	Abd pain	Other symptoms	Hb	Tumor marker	Endoscopy	CT scan	Other diagnostic study
Adenocarcinoma of small intestine	↑↓	+	+/-	Tenesmus Diminished caliber of stools Mucus in stools	↓	CEA+	Polyps (villous, tubular, tubulo-villous) Ulcerating polyps cancerous lesions	Luminal narrowing and bowel obstruction Circumferential thickening of the bowel wall Enlarged lymph nodes Pulmonary metastases Peritoneal metastases Hepatic metastases	PET scans: Detailed images and metastasis Barium enema: Cancer or a precancerous polyp Genetic testing: hereditary nonpolyposis colorectal cancer (HNPCC) or familial adenomatous polyposis (FAP)	Different grades of differentiation of glandular structures Sheets or cords of malignant cells, Cellular atypia, pleomorphism High mitotic rate Necrotic debris in glandular lumina Desmoplastic reaction (sign of invasion)	Biopsy and histopathological analysis
Carcinoids	↑	+/-	+	Flushing Wheezing Shortness of breath Palpitations Weight gain Hirsutism Weakness Leg edema	↓	Urinary 5-hydroxyindoleacetic acid (5-HIAA) Chromogranin A (CgA) Other biochemical markers include: Substance P Neurotensin Bradykinin Human chorionic gonadotropin Neuropeptide L Pancreatic polypeptide	Infiltrating, ulcerating or fungating lesions in the wall of colon	Well-defined single or multiple lesions Round or ovoid in shape Variable in size ranges between 2-5 cm	PET scan 11C-5-hydroxytryptophan (11C-5-HTP): Deetects metastasis MRI: Nodular mass originating from the bowel wall or regional uniform bowel wall thickening with moderate intense enhancement on post gadolinium T1-weighted fat-suppressed images Mesenteric metastases presents as nodular masses with mesenteric stranding Liver metastases may show hypointense precontrast T1- and hyperintense T2-weighted images Liver metastases are commonly hypervascular Ki-67 index	Solid or spongy nests of cells accentuated by neatly outlined luminal spaces Peripheral nuclear palisading Granular eosinophilic cytoplasm.	Biopsy and histopathological analysis
Intestinal Lymphoma	-	+/-	+	Weight loss	↓	Non-Hodgkin lymphomas: CD-20	Polypoid or ulcerated mass, intramural lesion, aphthous ulcer, stricture, extraluminal mass, or diffuse, multiple polypoid lesions	CT scan: polypoid mass, circumferential-cavitary lesions, focal mucosal nodularity, diffuse ulcerative or nodular lesions, regional lymph node involvement	Biopsy: Diffuse large B-cell lymphoma Extranodal marginal zone lymphoma (MALT) Mantle cell lymphoma Burkitt’s lymphoma Follicular lymphoma Double-contrast enema: Subtle mucosal changes, gross tumor morphology	Diffuse large B-cell lymphoma: Extranodal marginal zone lymphoma (MALT) Mantle cell lymphoma Burkitt’s lymphoma Follicular lymphoma	Biopsy and histopathological analysis
Gastrointestinal Stromal Tumors (GIST)	↑↓	+/-	-	Mostly asymptomatic Are discovered incidentally Non-specific symptoms Early satiety and bloating	↓/-	KIT protein CD 117 antigen	Subepithelial round masses Smooth margins Normal overlying mucosa may be intact or ulcerated Bulging into gastrointestinal lumen	Small GIST (< 5 cms) are homogeneous with clear boundaries and have an intraluminal pattern of growth. Intermediate GIST (size of 5-10 cms) are heterogeneous with irregular borders and intra or extra-luminal pattern of growth. Large GISTs (>10 cms) are heterogeneous with irregular borders and have local or distant spread Malignant GIST with metastasis: Size greater than 10 cm Calcifications Irregular margins Heterogeneous and lobulated Lymphadenopathy Ulceration Extraluminal and mesenteric fat infiltration	MRI: Hemorrhage, necrosis, surrounding structures and metastasis. Endoscopic ultrasonography: Mucosal ulceration or bleeding Smooth submucosal mass as hypoechoic mass Malignant GIST lesions present with: Heterogeneous mass >4 cm in size Irregular borders Intra and extraluminal growth Multiple cysts within the main lesion	Spindle cell type are eosinophilic cells arranged in the form of whorls or fascicles. Epithelioid GISTs are rounded cells with oval nuclei and vesicular chromatin and appears nested On immunohistochemical staining they are positive for molecular markers CD117 antigen and KIT protein.	Endoscopic ultrasound withBiopsy and histopathological analysis
Peutz-Jeghers syndrome	↑↓	+	+	Mucocutaneous hyperpigmentation (mouth, hands, and feet) Fatigue Weight loss Rectal prolapse	↓	N/A	Multiple polyps mucocutaneous pigmentation	Multiple polyps Intussusception Bowel obstruction	Barium enema: Multiple polyps. MRI: Multiple hamartomatous polyps	Hamartomatous mucosal polyps with central core of branching smooth muscle associated with mucosa Smaller polyps may lack the prominent arborizing smooth muscle	Genetic testing for STK11 Colonoscopy
Juvenile Polyposis Coli	↑	+	+	Prolapsing polyp Intussusception Macrocephalus Hypotonia Bowel obstruction Heart or brain abnormalities Cleft palate Polydactyly Abnormalities of the genitalia or urinary tract.	↓	N/A	>5 juvenile polyps in the colon and rectum Multiple juvenile polyps in gastrointestinal tract	Multiple polyps in gastrointestinal tract	Barium study: Multiple polyps in GI tract Stool DNA test: SMAD4 or BMPR1A Diagnose if any of the following positive: More than five juvenile polyps of the colorectum Multiple juvenile polyps throughout the GI tract Any number of juvenile polyps and a family history of juvenile polyposis Heterozygous pathogenic variant in SMAD4 or BMPR1A	Numerous cystic and dilated crypts or glands with inspissated mucin and intraluminal neutrophils Lamina propria edematous with associated lymphocytes, plasma cells, eosinophils and neutrophils Filiform, multilobated forms with increased glandular-to-stroma ratio in nonclassic or atypical polyps Areas of conventional dysplasia	If any of the following positive: More than five juvenile polyps of the colorectum Multiple juvenile polyps throughout the GI tract Any number of juvenile polyps and a family history of juvenile polyposis Heterozygous pathogenic variant in SMAD4 or BMPR1A
Kaposi's sarcoma	↑	+	+	Melena Hematochezia Abdominal pain N/V	↓	CD34 CD31 D2-40 HHV-8 FHI-1 antibody LANA-1	Localized purpuric lesion	N/A	Electrophoresis: antibodies against Kaposi sarcoma herpes virus (HHV-8) Biopsy: Vascular proliferation, red blood cell and hemosiderin extravasation,lymphocytes and monocytes, neovascular lesion wrapped around a pre-existing space, intracytoplasmic PAS +ve hyaline globules	Vascular proliferation Red blood cell and hemosiderin extravasation Lymphocytes and monocytes Premonitory sign (a neovascular lesion wrapped around a pre-existing space) Intracytoplasmic PAS +ve hyaline globules	Biopsy
Arteriovenous malformation	-	+	-	N/A	↓	N/A	Bright red, flat lesions Rarely, polypoid	N/A	N/A	Aberrant vessels with thickened, hypertrophic walls in the mucosa and the submucosa. Arteries directly connected to veins without capillary beds	Accidental fining
Infectious colitis	↑	+	+	Fever, chills N/V Bloating	-	N/A	Patchy or diffuse erythematous mucosa Edema, hemorrhage, with or without ulcers of mucosa	N/A	Stool cultures in adequate culture media Stool analysis: Leukocytosis	N/A	Stool culture
Hamartoma	↑	+	+	Tenesmus	-	S100 (mucosal Schwann cell hamartoma (MSCH)	Large polypoid mass	Isodense or hypodense solid masses Heterogeneous mass Presence of fat in a well circumscribed nodule Calcification	Biopsy: Proliferation of bland spindle cells in the lamina propria (mucosal schwann cell hamartoma (MSCH))	poorly circumscribed, short fascicles of uniform spindle cells replacing the colonic lamina propria, separating and entrapping the crypts The nuclei are bland and mostly uniform, occasional larger nuclei are found. The cytoplasmic borders are indistinct Involvement of mucosa but never the submucosa	Biopsy
Ulcerative colitis	↑	+	+	Diarrhea mixed with blood and mucus Weight loss Urgency Tenesmus	↓	N/A	Continuous lesions Erythema (or redness of the mucosa) and friability of the mucosa Crypts, formation of residual mucosal tissue Pseudopolyps	N/A	N/A	Mucosal and submucosal inflammation Hemorrhage or inflammatory polymorphonuclear cells aggregate in the lamina propria Distorted crypts Crypt abscess	Endoscopy and a mucosal biopsy
Crohn's disease	↑	+	+	Tenesmus N/V Bowel obstruction Fever	↓	N/A	Discontinuous lesions Strictures Linear ulcerations	N/A	N/A	Transmural pattern of inflammation Mucosal damage Focal infiltration of leukocytes into the epithelium Granulomas	Endoscopy and a mucosal biopsy
Irritable bowel syndrome	↑↓	+	+	Straining during defecation Urgency Sensation of incomplete evacuation Mucus passage Bloating Weight loss	-	N/A	Not recommended	N/A	Diagnosis of exclusion with fulfillment of Rome criteria	N/A	Clinical diagnosis (Rome criteria)
Bowel endometriosis	↓↑	+	+	Dyschezia Tenesmus	↓	N/A	N/A	N/A	Transvaginal ultrasonography: heterogeneous, hypoechoic, spiculated mass Barium enema: Extrinsic mass compressing the bowel, fine crenulation of the mucosa, bowel strictures at the rectosigmoid junction T1-weighted or fat-suppression T1-weighted MRIs: Contrast enhanced mass or hyperintense foci, hemorrhagic foci or hyperintense cavities	N/A	Transvaginal ultrasonography
Intestinal tuberculosis	Chronic ↑	+/-	+	Fever Fatigue, Weight loss Anorexia Night sweats Bowel obstruction Abdominal distension Lymph node enlargement	↓	N/A	To get sample for histolopathology and culture Forms on endoscopy: Hypertrophic Ulcerative Endoscopic findings: Ulcers in mucosa Nodules in mucosa Strictures in intestinal wall Pseudopolyps formation Adhesions Fistulas Deformed ileocecal valve	Concentric thickening at the site of lesion with proximal intestinal dilatation asymmetric thickening of the intestinal wall Lymphadenopathy Thickening of the peritoneum Ascites	Small bowel follow-through or barium enema: Mucosal ulcerations Strictures in the intestinal wall Cecal deformations Incompetency of ileocecal valve Ultrasound: Bowel thickening Peritoneal nodules Peritoneal thickening Lymphadenopathy Ascitic fluid analysis: Straw-colored ascites Lymphocytes in ascitic fluid Cell count is 150 to 4000 cells/mcL with leukocyte count of 150 to 4000 cells/mm3 AFB smear ADA level Protein >3.0 g/dL Mycobacterial culture NAAT for M. tuberculosis SAAG <1.1 g/dL Ascitic fluid NAAT Ascitic fluid polymerase chain reaction (PCR)	Submucosal caseation granulomas	Endoscopic biopsy and histopathology analysis
Peptic ulcer disease	↑↓	+ Melena	+	Heartburn Asymptomatic Chest discomfort Early satiety Nausea and vomiting Anorexia Bloating Perforation	↓	N/A	Smooth ulcers in mucosa of intestine Ulcers with round edges Flat ulcer base filled with exudate	Shows ulcers (perforated or non-perforated) when done for the investigation of abdominal pain	.Barium swallow (infrequent) H. Pylori testing Hydrogen breath test	Endoscopic biopsy sample may show positive H. Pylori by H&E stain	Endoscopic visualization of ulcer
Pancreatic cancer	Chronic ↑	+	+	Asthenia and depression Jaundice Anorexia Weight loss Nausea and vomiting Steatorrhea Dark urine Back pain Thrombophlebitis	↓	Cancer-associated antigen 19-9 (CA 19-9)	Endoscopic retrograde cholangiopancreatography (ERCP) is used: To collect tissue sample For imaging of biliary tree and pancreatic ducts Obstruction and strictures of common bile duct and pancreatic duct is suggestive of cancer ("double duct" sign)	Mass within the pancreatic parenchyma or duct Atrophy of the parenchyma	Transabdominal US Billiary dilatation Mass in pancreas Hypoechoic hypovascular mass with irregular borders Magnetic resonance cholangiopancreatography(MRCP) : Better than CT to visualize pancreatic and billiary anatomy and hepatic lesions Biopsy: Percutaneous FNA biopsy Transduodenal Endo US-guided FNA biopsy	Pancreatic tumor can show two type of histology depending on the location: Intraductal papillary mucinous neoplasms Papillary lesions Disseminated or segmental dilation of the pancreatic duct Pancreatic ductal adenocarcinoma Duct-like structures Mucin production Cell atypia Dense stromal fibrosis	Biopsy and histological analysis
Gastric cancer	↓/-	+ Melena	+	Weight loss Early satiety Dysphagia Anorexia Weakness and fatigue	↓	Carcinoembryonic antigen (CEA) Glycoprotein CA 125 Carbohydrate antigen 19-9 (CA 19-9) Alpha-fetoprotein (AFP)	On endoscopy gastric cancer may appear as: Polypoid mass Ulcerating lesion Infiltrating lesion Diffuse thickening	CT is used to stage the disease extent CT can also visulaize primary lesion: Polypoid mass Ulcerating lesion Diffuse thickening (tunica plastica) Infiltrating mass	PET scan: Useful to confirm malignant involvement of CT-detected lymphadenopathy. Directly visualizes the liver surface, the peritoneum, and local lymph nodes for metastasis MRI: Better T staging of stomach cancer (better soft tissue visualization and of individual layers of stomach wall) Ultrasonography	Histologically, there are two major types of gastric cancer: Intestinal type adenocarcinoma Irregular tubular structures Multiple lumens Reduced stroma ntestinal metaplasia cellular pleomorphism Diffuse type adenocarcinoma Discohesive Secrete mucus Pools of mucus/colloid Signet ring cell appearance	Biopsy and histopathological analysis