Colorectal cancer differential diagnosis

To view the differential diagnosis of familial adenomatous polyposis (FAP), click here
To view the differential diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC), click here

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]: Associate Editor(s)-in-Chief: Trusha Tank, M.D.[2], Qurrat-ul-ain Abid, M.D.[3]

Overview

Colorectal cancer must be differentiated from other diseases that cause unexplained weight loss, unexplained loss of appetite, nausea, vomiting, diarrhea, anemia, jaundice, and fatigue, such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), hemorrhoids, anal fissures, and diverticular disease. There are less common conditions that may be confused as colorectal cancer such as infectious colitis and gastrointestinal lymphoma.

Colorectal Cancer Differential Diagnosis

• Colorectal cancer must be differentiated from other diseases that cause lower abdominal pain and fever like appendicitis, diverticulitis, inflammatory bowel disease, cystitis, and endometritis.

Other conditions that can be mistaken for colorectal cancer include the following:

• Benign colon polyps
• Infectious colitis
• Arteriovenous malformation (AVM)
• Carcinoid/neuroendocrine tumors
• Small intestine carcinomas
• Gastrointestinal lymphoma
• Pregnancy
• Appendicitis
• Hernia
• Lactose intolerance
• Flatulence
• Ulcer
• Cholecystitis

ABBREVIATIONS:N/A: Not available , N/V: Nausea/vomiting, M/C: Most common, DRE: Digital rectal exam, RLQ: Right lower quadrant, LLQ: Left lower quadrant
Diseases	Clinical manifestations					Para-clinical findings					Gold standard
	Symptoms
						Lab Findings	Imaging			Histopathology
	Bowel frequency	Blood in stool	Abdominal pain	Tenesmus	Other symptoms	Anemia	Colonoscopy	CT scan	Other diagnostic study
Colorectal carcinoma (Adenocarcinoma)	↑ or ↓	+	+/-	+	Weight loss Fatigue Low caliber of stools Mucus in stools	+	Polyps (villous, tubular, tubulo-villous) Ulcerating polyps Cancerous lesions	Luminal narrowing Bowel obstruction Thickening of the bowel wall Lymphadenopathy Metastases	PET scans Metastasis Barium enema Cancer or precancerous polyp	Different grades of differentiation of glandular structures Sheets or cords of malignant cells Cellular atypia and pleomorphism High mitotic rate Necrotic debris in glandular lumina Desmoplastic reaction (sign of invasion)	Biopsy, genetic testing, and histopathological analysis
Peutz-Jeghers syndrome	↑ or ↓	+	+	-	Weight loss Fatigue Mucocutaneous hyperpigmentation Rectal prolapse	+	Multiple polyps Mucocutaneous pigmentation	Multiple polyps Intussusception Bowel obstruction	Barium enema Multiple polyps MRI Multiple hamartomatous polyps	Hamartomatous mucosal polyps with core of smooth muscle associated with mucosa Smaller polyps lack the prominent arborizing smooth muscle	Genetic testing for STK11 and colonoscopy
Carcinoids	↑	+/-	+	-	Weight loss Weakness Flushing Wheezing Shortness of breath Palpitations Leg edema	+	Infiltrating, ulcerating or fungating lesions in the wall of colon	Well-defined single/multiple lesions Round/ovoid in shape Variable in size between 2-5 cm	PET scan (11C-5-hydroxytryptophan, 11C-5-HTP) Detects metastasis MRI Nodular mass Wall thickening Metastasis Ki-67 index	Solid/spongy nests of cells accentuated by neatly outlined luminal spaces Peripheral nuclear palisading Granular eosinophilic cytoplasm	Biopsy and histopathological analysis
Diseases	Bowel frequency	Blood in stool	Abdominal pain	Tenesmus	Other symptoms	Anemia	Colonoscopy	CT scan	Other diagnostic study	Histopathology	Gold standard
Juvenile Polyposis Coli	↑	+	+	-	Prolapsing polyp Intussusception Macrocephalus Hypotonia Bowel obstruction Heart or brain abnormalities Cleft palate Polydactyly Genitalia or urinary abnormalities	+	>5 juvenile polyps in the colon and rectum Multiple juvenile polyps in gastrointestinal tract	Multiple polyps in GI 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	Cystic and dilated crypts or glands with inspissated mucin and intraluminal neutrophils Lamina propria edematous with associated lymphocytes, plasma cells, eosinophils, and neutrophils Filiform, multilobed forms with increased glandular-to-stroma ratio in nonclassic or atypical polyps Areas of conventional dysplasia	Diagnostic criteria fulfilment
Gastrointestinal Stromal Tumors (GIST)	-	+/-	-	-	Asymptomatic Early satiety Bloating	+/-	Subepithelial round masses Smooth margins Normal overlying mucosa may be intact or ulcerated Bulging into gastrointestinal lumen	Benign Small, < 10 cms Homogeneous Clear boundaries intraluminal or extraluminal growth Malignant GIST with metastasis: Size > 10 cm Calcifications Irregular margins Heterogeneous and lobulated Lymphadenopathy Ulceration Extraluminal and mesenteric fat infiltration	Endoscopic ultrasonography Benign: Mucosal ulceration or bleeding Smooth submucosal mass as hypoechoic mass Malignant GIST: Heterogeneous mass >4 cm in size Irregular borders Intra/extraluminal growth Multiple cysts	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 biopsy and histopathological analysis
Hamartoma	↑	+	+	+	N/A	-	Large polypoid mass	Isodense/hypodense solid masses Heterogeneous mass Presence of fat 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
Diseases	Bowel frequency	Blood in stool	Abdominal pain	Tenesmus	Other symptoms	Anemia	Colonoscopy	CT scan	Other diagnostic study	Histopathology	Gold standard
Colorectal Lymphoma	-	+/-	+	-	Weight loss	+	Polypoid or ulcerated mass, intramural lesion, aphthous ulcer, stricture, extraluminal mass, or diffuse, multiple polypoid lesions	Polypoid mass Circumferential-cavitary lesions Focal mucosal nodularity Diffuse ulcerative or nodular lesions Lymphadenopathy	Double-contrast enema Subtle mucosal changes Gross tumor morphology Biopsy	Diffuse large B-cell lymphoma: Extranodal marginal zone lymphoma (MALT) Mantle cell lymphoma Burkitt’s lymphoma Follicular lymphoma	Biopsy
Kaposi's sarcoma	↑	+	+	-	Nausea and vomiting	+	Localized purpuric lesion	N/A	Serology Antibodies against Kaposi sarcoma herpes virus (HHV-8) Biopsy	Vascular proliferation RBC and hemosiderin extravasation Lymphocytes and monocytes Premonitory sign (neovascular lesion wrapped around a pre-existing space) Intracytoplasmic PAS +ve hyaline globules	Biopsy
Arteriovenous malformation	-	+	-	-	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 finding
Diseases	Bowel frequency	Blood in stool	Abdominal pain	Tenesmus	Other symptoms	Anemia	Colonoscopy	CT scan	Other diagnostic study	Histopathology	Gold standard
Diverticular diseases	↑ or ↓	+/-	+ RLQ	-	Fever Chills N/V	-	Not recommended	Outpouchings of the colonic wall (diverticula) Inflamed diverticula Abscess formation Intraperitoneal free air (microperforation)	Barium enema Circumferential narrowing Spiculated contour Tapered margins	N/A	CT scan
Hemorrhoids	↓	+	+	-	Perianal Itching Pain with defecation Painful-hard lump in anus	+	Anoscopy Protruding mass from the anus	N/A	DRE Palpable mass, tender if thrombosed	N/A	Clinical
Anal fissure	-	+	+	-	Painful defecation Itching Irritation	+/-	Anoscopy Anal wall laceration	N/A	N/A	N/A	Clinical
Diseases	Bowel frequency	Blood in stool	Abdominal pain	Tenesmus	Other symptoms	Anemia	Colonoscopy	CT scan	Other diagnostic study	Histopathology	Gold standard
Infectious colitis	↑	+	+	-	Fever, chills N/V Bloating	-	Patchy or diffuse erythematous mucosa Edema, hemorrhage, with or without ulcers of mucosa	N/A	Stool analysis Leukocytosis Stool cultures	N/A	Stool culture
Ulcerative colitisV	↑	+	+ LLQ	+	Weight loss Diarrhea withmucus Urgency	+	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	Endoscopic biopsy
Crohn's disease	↑	+	+ RLQ	+	N/V Bowel obstruction Fever	+	Discontinuous lesions Strictures Linear ulcerations	N/A	N/A	Transmural pattern of inflammation Mucosal damage Focal infiltration of leukocytes into the epithelium Granulomas	Endoscopic biopsy
Irritable bowel syndrome	↑ ↓	+	+	+	Weight loss Straining Urgency Mucus passage Bloating	-	Not recommended	N/A	Diagnosis of exclusion Fulfilment of Rome criteria	N/A	Clinical diagnosis (Rome criteria)
Diseases	Bowel frequency	Blood in stool	Abdominal pain	Tenesmus	Other symptoms	Anemia	Colonoscopy	CT scan	Other diagnostic study	Histopathology	Gold standard
Appendicitis	↑	-	+ RLQ	-	Pain starting periumbilical before localizing to the RLQ N/V Fever Chills Loss of appetite	-	N/A	Appendiceal wall thickening (≥ 3mm) Periappendiceal fat stranding Thick lateral conal fascia and mesoappendix Extraluminal fluid Phlegmon Abscess	Ultrasound Aperistaltic, noncompressible, dilated appendix (>6 mm) Appendicolith Echogenic prominent pericaecal fat Periappendiceal fluid collection	N/A	CT scan
Strangulated hernia	↓	-	+ RLQ	-	N/V Heaviness/dull discomfort in the groin, with straining, lifting, coughing, or exercising Weakness, heaviness, burning, or aching in the groin Swelling Fever	-	N/A	Defect in the abdominal wall muscles Bowel loops within the lesion Lateral crescent sign The hernia neck superolateral to the course of the inferior epigastric vessels	Ultrasound: Hypoechoic mass suggesting dilated and edematous intestinal segment	N/A	Ultrasound
Bowel endometriosis	↑ or ↓	+	+ Pelvic	+	Dyschezia	+	N/A	N/A	Transvaginal ultrasound Heterogeneous, hypoechoic, spiculated mass T1-weighted or fat-suppression T1-weighted MRIs Contrast enhanced mass Hyperintense hemorrhagic Hyperintense cavities	N/A	Transvaginal ultrasound
ABBREVIATIONS:N/A: Not available , N/V: Nausea/vomiting, M/C: Most common, DRE: Digital rectal exam, RLQ: Right lower quadrant, LLQ: Left lower quadrant

References

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