Appendiceal Mucinous Neoplasm with High Risk of Recurrence

Definition

• Neoplasm of the appendix with features of mucinous adenoma but with evidence of epithelial spread beyond the muscularis propria

Alternate/Historical Names

• Borderline mucinous tumor
• Disseminated peritoneal adenomucinosis
• Low grade mucinous neoplasm (WHO preferred term, includes low and high risk of recurrence neoplasms, see Controversy)
• Mucinous carcinoma (see Controversy)
• Mucinous neoplasm of low malignant potential
• (Note that ovarian involvement has by some been taken to represent a primary ovarian carcinoma, see Controversy)

Diagnostic Criteria

• Epithelial lesion oexhibiting features of mucinous adenoma (see detailed adenoma criteria)
  • Simple mucinous columnar epithelium
  • Low grade dysplasia
  • Sessile, usually circumferential, lining of appendiceal luminal surface
• Extra-appendiceal mucinous implants containing epithelium
• Frequent mucin dissection of the wall
  • Neoplastic epithelium may be present in intramural mucin
• Commonly associated with luminal dilation
• Implants largely intraperitoneal
  • Implants frequently paucicellular
  • Frequently involves surface of liver and spleen
  • Frequently involves ovary
    • May produce mucinous cysts that have the appearance of primaries (see Controversy)
  • May involve lining of fallopian tubes
• No metastases to nodes or parenchyma of organs other than ovary
• Mucinous neoplasm with high risk of recurrence is the most frequent cause of pseudomyxoma peritonei
  • Extensive mucin secretion producing abdominal distension
• Specimen may need to be entirely submitted to make this diagnosis
• Occasional cases may have discrepant findings of invasive carcinoma in implants but typical low grade neoplasm in the appendix
  • Clinical significance is unclear

Original posting/updates : 10/7/10, 2/10/12

Controversy

• Low grade mucinous neoplasm - WHO proposed alternate name
• Term proposed to encompass mucinous neoplasms with low and high risks of recurrence
• Proposed because all are composed of histologically identical adenomatous appearing epithelium
• We prefer not to combine these processes as their clinical behavior is quite different
• Mucinous neoplasm with low risk of recurrence has very low morbidity and mortality
• Mucinous neoplasm with high risk of recurrence has considerable morbidity and mortality
• Furthermore, the term could be confused with low grade adenocarcinoma
  • This is an ordinary colonic type adenocarcinoma, which has a more aggressive course
• Mucinous carcinoma - proposed alternate name
  • Term proposed as alternate to mucinous neoplasm with high risk of recurrence
  • We prefer to reserve this term for neoplasms capable of metastasis to organs such as lymph node, lung and liver (parenchyma)
  • Mucinous carcinoma of all GI sites behaves aggressively, with metastases
• Does ovarian involvement represent spread from the appendix?
  • Alternative possibilities include
    • Simultaneous primaries, perhaps due to a field defect
    • Ovarian primary with spread to appendix in some cases
    • No clinical importance to the distinction as long as:
      • Frequent association of appendiceal and ovarian disease is recognized
      • Frequent association with pseudomyxoma peritonei is recognized

Supplemental studies

Immunohistology

Differential Diagnosis

Appendiceal Mucinous Neoplasms

Mucinous Adenoma/Cystadenoma	Mucinous Low Risk of Recurrence	Mucinous High Risk of Recurrence	Mucinous Adenocarcinoma
No extra-appendiceal mucin	No epithelium in extra-appendix mucin	Epithelium present in extra-appendiceal mucin	Epithelium may be present in extra-appendiceal mucin
Non-invasive epithelium may be present in intramural mucin	Non-invasive epithelium may be present in intramural mucin	Non-invasive epithelium may be present in intra and extramural mucin	Invasion by jagged neoplastic glands
Margin of resection must be clear	Margin may be involved	Margin may be involved	Margin may be involved
Benign, no recurrences	Very few recur, 0% mortality	Frequently recur, 50% 5 year, 20% 10 year survival	<10% 10 yr survival

The distinctions are critical

 

Appendiceal Mucinous Neoplasm with High Risk of Recurrence	Appendiceal Endometriosis with Mucin Extravasation
Lacks endometrioid epithelium	Associated with endometrioid epithelium
Lacks endometrial stroma	Associated with endometrial stroma

Clinical

• Frequent cause of pseudomyxoma peritonei
• Abundant mucin secretion by implants
• Causes abdominal distention
• Long clinical course
• Multiple recurrences
• Surgical debulking is worthwhile, both at presentation and for recurrences
• 50% 5 year, 20% 10 year survival
• Death usually caused by intestinal obstruction after multiple recurrences
• Some question as to whether or not right colectomy is indicated
• Frequent involvement of ovary
• In all cases of appendiceal mucinous neoplasms, the ovaries should be examined
• In all cases of ovarian mucinous neoplasms, the appendix should be examined (or removed)
• In all cases of pseudomyxoma peritonei the appendix and the ovaries should be examined

Lists

Appendiceal Epithelial Neoplasms and Proliferations

• Adenocarcinoma
• Carcinoid / well differentiated neuroendocrine neoplasm
• Carcinoma ex-goblet cell carcinoid
• Goblet cell carcinoid
• Hyperplastic polyp / mucosal hyperplasia
• Mucinous adenoma / cystadenoma
• Mucinous neoplasm with high risk of recurrence
• Mucinous neoplasm with low risk of recurrrence
• Sessile serrated polyp / adenoma
• Traditional serrated adenoma

Clinical / Descriptive Terms

• Mucocele
• Pseudomyxoma peritonei

Bibliography

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• Bosman FT, Carneiro F, Hruban RH, Thiese ND (Eds). WHO Classifiication of Tumors of the Digestive System, IARC, Lyon 2010
• Seidman JD, Elsayed AM, Sobin LH, Tavassoli FA. Association of mucinous tumors of the ovary and appendix. A clinicopathologic study of 25 cases. Am J Surg Pathol. 1993 Jan;17(1):22-34.
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• Ronnett BM, Zahn CM, Kurman RJ, Kass ME, Sugarbaker PH, Shmookler BM. Disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis. A clinicopathologic analysis of 109 cases with emphasis on distinguishing pathologic features, site of origin, prognosis, and relationship to "pseudomyxoma peritonei". Am J Surg Pathol. 1995 Dec;19(12):1390-408.
  
• Ronnett BM, Yan H, Kurman RJ, Shmookler BM, Wu L, Sugarbaker PH. Patients with pseudomyxoma peritonei associated with disseminated peritoneal adenomucinosis have a significantly more favorable prognosis than patients with peritoneal mucinous carcinomatosis. Cancer. 2001 Jul 1;92(1):85-91.
• Yantiss RK, Shia J, Klimstra DS, Hahn HP, Odze RD, Misdraji J. Prognostic significance of localized extra-appendiceal mucin deposition in appendiceal mucinous neoplasms. Am J Surg Pathol. 2009 Feb;33(2):248-55