Appendix cancer pathophysiology

Jump to navigation Jump to search

Appendix cancer Microchapters


Patient Information


Historical Perspective




Epidemiology and Demographics

Differentiating Appendix cancer from other Diseases

Risk Factors


Natural History, Complications and Prognosis


Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings




CT scan

Echocardiography and Ultrasound

Other Imaging Findings

Other Diagnostic Studies


Medical Therapy


Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Appendix cancer pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides


American Roentgen Ray Society Images of Appendix cancer pathophysiology

All Images
Echo & Ultrasound
CT Images

Ongoing Trials at Clinical

US National Guidelines Clearinghouse

NICE Guidance

FDA on Appendix cancer pathophysiology

CDC on Appendix cancer pathophysiology

Appendix cancer pathophysiology in the news

Blogs on Appendix cancer pathophysiology

Directions to Hospitals Treating Appendix cancer

Risk calculators and risk factors for Appendix cancer pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Soroush Seifirad, M.D.[2]


The pathophysiology of appendix cancer depends on the histological subtype. There are two major subtypes of appendix cancer, adenocarcinomas and carcinoid tumors. While carcinoid tumors arises from enterochromaffin cells (Kulchitsky cells), which are secretory cells that are normally involved in neuroendocrine hormonal secretions, adenocarcinomas are the result of mutations in mucus producing epithelial cells. Their physiology, pathophysiology, genetic pathways, prognosis as well as epidemiology are different and hence, discussed separately. The progression to adenocarcinoma usually involves the KRAS, APC, TP53, and RAF pathways, while β-catenin, NF1, and MEN1 genes are major contributors of carcinoid tumors progression.





Genes involved in the pathogenesis of carcinoid tumors of appendix include:[4][5]

The development of appendiceal adenocarcinoma is the result of multiple genetic mutations such as:[5]

Associated Conditions

  • Conditions associated with appendiceal cancers include:

Gross Pathology

Appendix carcinoid gross pathology. Courtesy of Dr.Robertson. Uploaded by James Heilman, MD.
  • On gross pathology, findings of appendix cancer, include:[3]
  • Well-demarcated mass
  • Average size between 1 and 5 cm
  • Gray or yellowish color
  • Deformed appendix
  • Adenocarcinoma
  • Gray/yellow color
  • Cystic structures with angiolymphatic invasion
  • Appendix might be buried within the mass
  • Carcinoid tumors
  • Prevalent at the tip of appendix
  • Generally less than 1 cm
  • Gray or yellow
  • Well-demarcated firm
  • Intramural nodules that may narrow or obliterate appendiceal lumen
  • Proximal tumors may cause obstruction and appendicitis
  • Goblet cell carcinoids
  • No gross tumor might be present
  • Thickened appendiceal wall

Microscopic Pathology

The images below demonstrate different
histopathological findings of appendix cancer

Low grade appendiceal mucinous neoplasm, MUC2 staining. Courtesy of Carlos Parra-Herran, M.D.
Appendiceal adenocarcinoma, H and E staining. Courtesy of Carlos Parra-Herran, M.D.
Typical microscopic appearance of a well differentiated carcinoid tumor (terminal illeum, H and E staining).Case courtesy of Dr Andrew Ryan, <a href=""></a>. From the case <a href="">rID: 16308</a>
  • Cystic structures
  • Angiolymphatic invasion
  • Adenocarcinoma
  • Intestinal, mucinous or signet ring cell types
  • Coexisting acute appendicitis is common
  • immunohistochemistry (IHC) might be positive for the following stains:[6]
  • MUC 2
  • MUC5AC
  • CK 8/18
  • CK 13
  • CK 19
  • CK 20
  • Carcinoid tumor
  • Insular growth pattern of solid islands of uniform polygonal cells with minimal pleomorphism
  • Retraction of peripheral tumor cells from stroma
  • Angiolymphatic invasion is common
  • Granular eosinophilic cytoplasm with either diffusely scattered or peripherally clumped granules
  • Two types of well differentiated tumors: EC cell (serotonin producing) and rarely L-cell (enteroglucagon or peptide YY producing)[7]
  • IHC might be positive for S100
  • Goblet cell
  • GCC generally spares mucosa and infiltrates muscularis propria and periappendiceal fat
  • Tumor cell clusters
  • Crypt-like structures
  • Tubules of mucus-secreting cells distended with mucin resembling goblet cells
  • Eosinophilic cytoplasm resembling carcinoid tumors
  • Pools of extracellular mucin
  • Scattered Paneth cells in tumors with crypt like structures
  • Extensive perineural invasion
  • Carcinomatous growth pattern:
    • Cribriform growth pattern, solid sheets of infiltrating signet ring cells
    • Nuclear pleomorphism
    • Increased mitotic activity
  • IHC might be positive for the followings:


  1. 1.0 1.1 Gunawardene AR, Corfe BM, Staton CA (2011) Classification and functions of enteroendocrine cells of the lower gastrointestinal tract. Int J Exp Pathol 92 (4):219-31. DOI:10.1111/j.1365-2613.2011.00767.x PMID: 21518048
  2. Modlin IM, Lye KD, Kidd M (2003) A 5-decade analysis of 13,715 carcinoid tumors. Cancer 97 (4):934-59. DOI:10.1002/cncr.11105 PMID: 12569593
  3. 3.0 3.1 3.2 Ruoff C, Hanna L, Zhi W, Shahzad G, Gotlieb V, Saif MW (2011). "Cancers of the appendix: review of the literatures". ISRN Oncol. 2011: 728579. doi:10.5402/2011/728579. PMC 3200132. PMID 22084738.
  4. Modlin IM, Kidd M, Latich I, Zikusoka MN, Eick GN, Mane SM et al. (2006) Genetic differentiation of appendiceal tumor malignancy: a guide for the perplexed. Ann Surg 244 (1):52-60. DOI:10.1097/01.sla.0000217617.06782.d5 PMID: 16794389
  5. 5.0 5.1 5.2 Hassan MM, Phan A, Li D, Dagohoy CG, Leary C, Yao JC (2008) Family history of cancer and associated risk of developing neuroendocrine tumors: a case-control study. Cancer Epidemiol Biomarkers Prev 17 (4):959-65. DOI:10.1158/1055-9965.EPI-07-0750 PMID: 18398037
  6. Lee MJ, Lee HS, Kim WH, Choi Y, Yang M (2003) Expression of mucins and cytokeratins in primary carcinomas of the digestive system. Mod Pathol 16 (5):403-10. DOI:10.1097/01.MP.0000067683.84284.66 PMID: 12748245
  7. Iwafuchi M, Watanabe H, Ajioka Y, Shimoda T, Iwashita A, Ito S (1990) Immunohistochemical and ultrastructural studies of twelve argentaffin and six argyrophil carcinoids of the appendix vermiformis. Hum Pathol 21 (7):773-80. PMID: 2193876

Template:WH Template:WS