Colorectal cancer differential diagnosis

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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

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

Diseases Clinical manifestations Para-clinical findings Gold standard
Symptoms
Lab Findings Imaging Histopathology
Constipation/
Diarrhea
Blood in stool Abdominal pain Other symptoms Anemia Colonoscopy CT scan Other diagnostic study
Adenocarcinoma[7]

and/or

+
  • Diffuse abdominal pain +/-
+
  • 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)
Peutz-Jeghers syndrome
[8][9][10][11][12]

and/or

+
  • Abdominal pain
+
Carcinoids
[13][14][15][16][17]
+/-
  • Abdominal pain
+
  • 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)
    • Detects 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.
Juvenile Polyposis Coli[18][19][20][21][22] +
  • Diffuse abdominal pain
+
  • 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
Gastrointestinal Stromal Tumors (GIST)[23][24][25][26][27]
  • Normal
+/-
  • No pain
  • Mostly asymptomatic
  • Are discovered incidentally
  • Non-specific symptoms
  • Early satiety and bloating
+/-
Hamartoma[30] +
  • Depending on location
-
  • Large polypoid mass
  • 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
Colorectal Lymphoma[31][32]
  • Normal
+/-
  • Depending on location
  • Weight loss
+
  • 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
Kaposi's sarcoma[33] +
  • Diffuse abdominal pain
+
  • Localized purpuric lesion
  • N/A
  • Biopsy
Arteriovenous malformation[34]
  • Normal
+
  • No pain
  • 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
Diverticular diseases[35][36][37]

and/or

+/-
  • Pain in RLQ
-
  • Not recommended
  • Outpouchings of the colonic wall (Diverticula)
  • Inflamed diverticula
  • Abscess formation
  • Intraperitoneal free air (microperforation)
  • Barium enema: Circumferential narrowing, spiculated contour and tapered margins
  • N/A
  • CT scan
Hemorrhoids[38] +
  • Localized pain
  • Perianal Itching
  • Pain with defecation
  • Painful, hard lump in anus
+
  • N/A
  • N/A
  • Clinical
Anal fissure[39]
  • Normal
+
  • Localized pain
+/-
  • N/A
  • N/A
  • N/A
  • Clinical
Infectious colitis[40] +
  • Diffuse abdominal
-
  • N/A
  • N/A
  • Stool culture
Ulcerative colitis[41] + +
  • N/A
  • N/A
  • Mucosal and submucosal inflammation[41]
  • Hemorrhage or inflammatory polymorphonuclear cells aggregate in the lamina propria
  • Distorted crypts
  • Crypt abscess
  • Endoscopy and a mucosal biopsy[42]
Crohn's disease[41] +
  • Lain in RQ
+
  • 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[43]

and/or

+
  • Diffuse abdominal pain
-
  • Not recommended
  • N/A
  • N/A
Appendicitis[44] -
  • Pain in RLQ
-
  • N/A
  • Tc-99m labeled anti-CD15 antibodies
  • Ultrasound
    • Aperistaltic, noncompressible, dilated appendix (>6 mm outer diameter)
    • Appendicolith
    • Echogenic prominent pericaecal fat
    • Periappeniceal fluid collection
  • N/A
Strangulated hernia
  • Constipation
- N/V

Heaviness or dull discomfort in the groin, with straining, lifting, coughing, or exercising

Weakness, heaviness, burning, or aching in the groin

Pain and swelling

Fever

-
  • N/A
  • Defect in the abdominal wall muscles
  • Appearance of bowel loops within the lesion
  • Lateral crescent sign
  • The hernia neck will be superolateral to the course of the inferior epigastric vessels.
  • N/A
  • N/A
  • Ultrasound: Hypoechoic mass suggesting dilated and edematous intestinal segment
Bowel endometriosis[45]

and/or

+
  • Pelvic pain
  • Dyschezia
  • Tenesmus
+
  • 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

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