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)
Arteriovenous malformation[8]
  • 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[9][10][11]

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[12] +
  • Localized pain
  • Perianal Itching
  • Pain with defecation
  • Painful, hard lump in anus
 +
  • N/A
  • N/A
  • Clinical
Anal fissure[13]
  • Normal
 +
  • Localized pain
 +/-
  • N/A
  • N/A
  • N/A
  • Clinical
Infectious colitis[14] +
  • Diffuse abdominal
 -
  • N/A
  • N/A
  • Stool culture
Peutz-Jeghers syndrome[15][16][17][18][19]

and/or

+
  • Abdominal pain
 +
Carcinoids[20][21][22][23][24] +/-
  • 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): 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.
Juvenile Polyposis Coli[25][26][27][28][29] +
  • 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)[30][31][32][33][34]
  • Normal
 +/-
  • No pain
  • Mostly asymptomatic
  • Are discovered incidentally
  • Non-specific symptoms
  • Early satiety and bloating
 +/-
Hamartoma[37] +
  • 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[38][39]
  • 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[40] +
  • Diffuse abdominal pain
 +
  • Localized purpuric lesion
  • N/A
  • Biopsy
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

References

  1. ↑ Laurell H, Hansson LE, Gunnarsson U (2007). "Acute diverticulitis--clinical presentation and differential diagnostics". Colorectal Dis. 9 (6): 496–501, discussion 501-2. doi:10.1111/j.1463-1318.2006.01162.x. PMID 17573742.
  2. ↑ Hardin, M. Acute Appendicitis: Review and Update. Am Fam Physician".1999, Nov 1;60(7):2027-2034
  3. ↑ Hanauer SB (1996). "Inflammatory bowel disease". N Engl J Med. 334 (13): 841–8. doi:10.1056/NEJM199603283341307. PMID 8596552.
  4. ↑ Cystitis-acute. MedlinePlus.https://www.nlm.nih.gov/medlineplus/ency/article/000526.htm Accessed on February 9, 2016
  5. ↑ Prostatitis - bacterial. NLM Medline Plus 2016. https://www.nlm.nih.gov/medlineplus/ency/article/000519.htm. Accessed on March 2, 2016
  6. ↑ Ford GW, Decker CF (2016). "Pelvic inflammatory disease". Dis Mon. 62 (8): 301–5. doi:10.1016/j.disamonth.2016.03.015. PMID 27107781.
  7. ↑ Secco GB, Fardelli R, Campora E, Lapertosa G, Gentile R, Zoli S, Prior C (1994). "Primary mucinous adenocarcinomas and signet-ring cell carcinomas of colon and rectum". Oncology. 51 (1): 30–4. doi:10.1159/000227306. PMID 8265100.
  8. ↑ Lee HH, Kwon HM, Gil S, Kim YS, Cho M, Seo KJ, Chae HS, Cho YS (2017). "Endoscopic resection of asymptomatic, colonic, polypoid arteriovenous malformations: Two case reports and a literature review". Saudi J Gastroenterol. 23 (1): 67–70. doi:10.4103/1319-3767.199111. PMC 5329980. PMID 28139503.
  9. ↑ Shen SH, Chen JD, Tiu CM, Chou YH, Chiang JH, Chang CY, Lee CH (September 2005). "Differentiating colonic diverticulitis from colon cancer: the value of computed tomography in the emergency setting". J Chin Med Assoc. 68 (9): 411–8. doi:10.1016/S1726-4901(09)70156-X. PMID 16187597.
  10. ↑ Shen, Shu-Huei; Chen, Jen-Dar; Tiu, Chui-Mei; Chou, Yi-Hong; Chiang, Jen-Huei; Chang, Cheng-Yen; Lee, Chen-Hsen (2005). "Differentiating Colonic Diverticulitis from Colon Cancer: The Value of Computed Tomography in the Emergency Setting". Journal of the Chinese Medical Association. 68 (9): 411–418. doi:10.1016/S1726-4901(09)70156-X. ISSN 1726-4901.
  11. ↑ Sheiman, Laura; Levine, Marc S.; Levin, Alicia A.; Hogan, Jonathan; Rubesin, Stephen E.; Furth, Emma E.; Laufer, Igor (2008). "Chronic Diverticulitis: Clinical, Radiographic, and Pathologic Findings". American Journal of Roentgenology. 191 (2): 522–528. doi:10.2214/AJR.07.3597. ISSN 0361-803X.
  12. ↑ Jacobs, Danny; Solomon, Caren G. (2014). "Hemorrhoids". New England Journal of Medicine. 371 (10): 944–951. doi:10.1056/NEJMcp1204188. ISSN 0028-4793.
  13. ↑ Schlichtemeier S, Engel A (2016). "Anal fissure". Aust Prescr. 39 (1): 14–7. doi:10.18773/austprescr.2016.007. PMC 4816871. PMID 27041801.
  14. ↑ DuPont HL (January 2012). "Approach to the patient with infectious colitis". Curr. Opin. Gastroenterol. 28 (1): 39–46. doi:10.1097/MOG.0b013e32834d3208. PMID 22080825.
  15. ↑ Zhong ME, Niu BZ, Ji WY, Wu B (June 2016). "Laparoscopic restorative proctocolectomy with ileal pouch-anal anastomosis for Peutz-Jeghers syndrome with synchronous rectal cancer". World J. Gastroenterol. 22 (22): 5293–6. doi:10.3748/wjg.v22.i22.5293. PMID 27298573.
  16. ↑ Kopacova, Marcela; Tacheci, Ilja; Rejchrt, Stanislav; Bures, Jan (2009). "Peutz-Jeghers syndrome: Diagnostic and therapeuticapproach". World Journal of Gastroenterology. 15 (43): 5397. doi:10.3748/wjg.15.5397. ISSN 1007-9327.
  17. ↑ Giardiello, F; Trimbath, J (2006). "Peutz-Jeghers Syndrome and Management Recommendations". Clinical Gastroenterology and Hepatology. 4 (4): 408–415. doi:10.1016/j.cgh.2005.11.005. ISSN 1542-3565.
  18. ↑ Beggs, A. D.; Latchford, A. R.; Vasen, H. F. A.; Moslein, G.; Alonso, A.; Aretz, S.; Bertario, L.; Blanco, I.; Bulow, S.; Burn, J.; Capella, G.; Colas, C.; Friedl, W.; Moller, P.; Hes, F. J.; Jarvinen, H.; Mecklin, J.-P.; Nagengast, F. M.; Parc, Y.; Phillips, R. K. S.; Hyer, W.; Ponz de Leon, M.; Renkonen-Sinisalo, L.; Sampson, J. R.; Stormorken, A.; Tejpar, S.; Thomas, H. J. W.; Wijnen, J. T.; Clark, S. K.; Hodgson, S. V. (2010). "Peutz-Jeghers syndrome: a systematic review and recommendations for management". Gut. 59 (7): 975–986. doi:10.1136/gut.2009.198499. ISSN 0017-5749.
  19. ↑ Kopacova, Marcela; Tacheci, Ilja; Rejchrt, Stanislav; Bures, Jan (2009). "Peutz-Jeghers syndrome: Diagnostic and therapeuticapproach". World Journal of Gastroenterology. 15 (43): 5397. doi:10.3748/wjg.15.5397. ISSN 1007-9327.
  20. ↑ Chung TP, Hunt SR (May 2006). "Carcinoid and neuroendocrine tumors of the colon and rectum". Clin Colon Rectal Surg. 19 (2): 45–8. doi:10.1055/s-2006-942343. PMC 2780103. PMID 20011309.
  21. ↑ Diagnostics: Biochemical Markers, Imaging, and Approach. National cancer institute. http://www.cancer.gov/types/gi-carcinoid-tumors/hp/gi-carcinoid-treatment-pdq
  22. ↑ Rindi G, Falconi M, Klersy C, Albarello L, Boninsegna L, Buchler MW, Capella C, Caplin M, Couvelard A, Doglioni C, Delle Fave G, Fischer L, Fusai G, de Herder WW, Jann H, Komminoth P, de Krijger RR, La Rosa S, Luong TV, Pape U, Perren A, Ruszniewski P, Scarpa A, Schmitt A, Solcia E, Wiedenmann B (May 2012). "TNM staging of neoplasms of the endocrine pancreas: results from a large international cohort study". J. Natl. Cancer Inst. 104 (10): 764–77. doi:10.1093/jnci/djs208. PMID 22525418.
  23. ↑ Fang C, Wang W, Zhang Y, Feng X, Sun J, Zeng Y, Chen Y, Li Y, Chen M, Zhou Z, Chen J (June 2017). "Clinicopathologic characteristics and prognosis of gastroenteropancreatic neuroendocrine neoplasms: a multicenter study in South China". Chin J Cancer. 36 (1): 51. doi:10.1186/s40880-017-0218-3. PMC 5480192. PMID 28637502.
  24. ↑ Signs and symptoms of carcinoid syndrome. National Cancer Institute. http://www.cancer.gov/types/gi-carcinoid-tumors/patient/gi-carcinoid-treatment-pdq
  25. ↑ Grotsky HW, Rickert RR, Smith WD, Newsome JF (March 1982). "Familial juvenile polyposis coli. A clinical and pathologic study of a large kindred". Gastroenterology. 82 (3): 494–501. PMID 7054044.
  26. ↑ Brosens LA, Langeveld D, van Hattem WA, Giardiello FM, Offerhaus GJ (November 2011). "Juvenile polyposis syndrome". World J. Gastroenterol. 17 (44): 4839–44. doi:10.3748/wjg.v17.i44.4839. PMC 3235625. PMID 22171123.
  27. ↑ Latchford AR, Neale K, Phillips RK, Clark SK (October 2012). "Juvenile polyposis syndrome: a study of genotype, phenotype, and long-term outcome". Dis. Colon Rectum. 55 (10): 1038–43. doi:10.1097/DCR.0b013e31826278b3. PMID 22965402.
  28. ↑ Latchford AR, Neale K, Phillips RK, Clark SK (October 2012). "Juvenile polyposis syndrome: a study of genotype, phenotype, and long-term outcome". Dis. Colon Rectum. 55 (10): 1038–43. doi:10.1097/DCR.0b013e31826278b3. PMID 22965402.
  29. ↑ Latchford AR, Neale K, Phillips RK, Clark SK (October 2012). "Juvenile polyposis syndrome: a study of genotype, phenotype, and long-term outcome". Dis. Colon Rectum. 55 (10): 1038–43. doi:10.1097/DCR.0b013e31826278b3. PMID 22965402.
  30. ↑ Niazi AK, Kaley K, Saif MW (May 2014). "Gastrointestinal stromal tumor of colon: a case report and review of literature". Anticancer Res. 34 (5): 2547–50. PMID 24778074.
  31. ↑ Niazi AK, Kaley K, Saif MW (May 2014). "Gastrointestinal stromal tumor of colon: a case report and review of literature". Anticancer Res. 34 (5): 2547–50. PMID 24778074.
  32. ↑ Medeiros F, Corless CL, Duensing A, Hornick JL, Oliveira AM, Heinrich MC, Fletcher JA, Fletcher CD (July 2004). "KIT-negative gastrointestinal stromal tumors: proof of concept and therapeutic implications". Am. J. Surg. Pathol. 28 (7): 889–94. PMID 15223958.
  33. ↑ Kamiyama Y, Aihara R, Nakabayashi T, Mochiki E, Asao T, Kuwano H, Oriuchi N, Endo K (November 2005). "18F-fluorodeoxyglucose positron emission tomography: useful technique for predicting malignant potential of gastrointestinal stromal tumors". World J Surg. 29 (11): 1429–35. doi:10.1007/s00268-005-0045-6. PMID 16222452.
  34. ↑ Miettinen M, Sobin LH, Lasota J (January 2005). "Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up". Am. J. Surg. Pathol. 29 (1): 52–68. PMID 15613856.
  35. ↑ Fletcher CD, Berman JJ, Corless C, Gorstein F, Lasota J, Longley BJ, Miettinen M, O'Leary TJ, Remotti H, Rubin BP, Shmookler B, Sobin LH, Weiss SW (April 2002). "Diagnosis of gastrointestinal stromal tumors: a consensus approach". Int. J. Surg. Pathol. 10 (2): 81–9. doi:10.1177/106689690201000201. PMID 12075401.
  36. ↑ Fletcher CD, Berman JJ, Corless C, Gorstein F, Lasota J, Longley BJ, Miettinen M, O'Leary TJ, Remotti H, Rubin BP, Shmookler B, Sobin LH, Weiss SW (April 2002). "Diagnosis of gastrointestinal stromal tumors: a consensus approach". Int. J. Surg. Pathol. 10 (2): 81–9. doi:10.1177/106689690201000201. PMID 12075401.
  37. ↑ Cauchin E, Touchefeu Y, Matysiak-Budnik T (September 2015). "Hamartomatous Tumors in the Gastrointestinal Tract". Gastrointest Tumors. 2 (2): 65–74. doi:10.1159/000437175. PMC 4668787. PMID 26672891.
  38. ↑ Quayle FJ, Lowney JK (May 2006). "Colorectal lymphoma". Clin Colon Rectal Surg. 19 (2): 49–53. doi:10.1055/s-2006-942344. PMC 2780105. PMID 20011310.
  39. ↑ Quayle, Frank; Lowney, Jennifer (2006). "Colorectal Lymphoma". Clinics in Colon and Rectal Surgery. 19 (2): 049–053. doi:10.1055/s-2006-942344. ISSN 1531-0043.
  40. ↑ Arora M, Goldberg EM (July 2010). "Kaposi sarcoma involving the gastrointestinal tract". Gastroenterol Hepatol (N Y). 6 (7): 459–62. PMC 2933764. PMID 20827371.
  41. ↑ 41.0 41.1 41.2 41.3 41.4 Fakhoury M, Negrulj R, Mooranian A, Al-Salami H (2014). "Inflammatory bowel disease: clinical aspects and treatments". J Inflamm Res. 7: 113–20. doi:10.2147/JIR.S65979. PMC 4106026. PMID 25075198.
  42. ↑ Collins P, Rhodes J (August 2006). "Ulcerative colitis: diagnosis and management". BMJ. 333 (7563): 340–3. doi:10.1136/bmj.333.7563.340. PMC 1539087. PMID 16902215.
  43. ↑ Iwańczak B, Iwańczak F (August 2017). "[Functional gastrointestinal disorders in children and adolescents. The Rome IV criteria]". Pol. Merkur. Lekarski (in Polish). 43 (254): 75–82. PMID 28875974.
  44. ↑ Choi D, Park H, Lee YR, Kook SH, Kim SK, Kwag HJ, Chung EC (2003). "The most useful findings for diagnosing acute appendicitis on contrast-enhanced helical CT". Acta Radiol. 44 (6): 574–82. PMID 14616200.
  45. ↑ Wolthuis AM, Meuleman C, Tomassetti C, D'Hooghe T, de Buck van Overstraeten A, D'Hoore A (November 2014). "Bowel endometriosis: colorectal surgeon's perspective in a multidisciplinary surgical team". World J. Gastroenterol. 20 (42): 15616–23. doi:10.3748/wjg.v20.i42.15616. PMC 4229526. PMID 25400445.


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