Cytologically bland appendiceal neoplasm consisting of cohesive clusters composed of cells exhibiting intracytoplasmic mucin and scattered cells witih neuroendocrine differentiation
Alternate/Historical Names
Adenocarcinoid
Crypt cell carcinoma
Mucinous carcinoid
Diagnostic Criteria
Classification is based on the appearance of the primary tumor, not on the metastases
Metastases may appear poorly differentiated or undifferentiated
Cytologically bland
Mitotic figures infrequent
Many cells resemble goblet cells or signet ring cells
Mucin positive cytoplasm
Nucleus displaced by mucin
Rare to scattered neuroendocrine cells always present
<25% of cells
Seen on synaptophysin or chromogranin stains
Cohesive clusters and cords of cells
Discohesive, single cells rare
Cohesive cord or linear pattern usually seen within invaded muscularis propria
Well formed gland lumens not seen
Paneth cells and foci resembling Brunner glands have been reported
Frequently little architectural distortion of appendix
Invasion of appendix wall shows scant desmoplasia
Invasion frequently circumferential and lateral
May not form a well defined tumor mass
Perineural invasion common
Pools of extracellular mucin may be seen
Clusters of bland goblet cells may be in and around the pools
Regional lymph node involvement is frequent (19%)
Extra-appendiceal spread is frequent (33%)
Usually to right colon, peritoneal surfaces and ovary
Other neuroendocrine markers have been reported positive also
Neuroendocrine cells are positive with both argentaffin and argyrophil stains
Immunohistochemistry is not particularly useful for these distinctionsn
Small clusters and cords, no poorly differentiated or undifferentiated carcinoma
Irregular large clusters, no poorly differentiated or undifferentiated carcinoma
May have confluent sheets of cells OR >1 low power field or >1 mm2 of conventional type adenocarcinoma, usually poorly differentiated or undifferentiated
Based on histopathologic findings in primary tumor
All must have at least focal typical goblet cell carcinoid
Based on Tang 2008
Chromogranin and synaptophysin stain rare to scattered cells only
No intracytoplasmic mucin (lumenal mucin may be present in tubular carcinoid)
Intracytoplasmic mucin in goblets
CK7 negative, CK20 variable
CK7 variable, CK20 100%
Rare mitotic figures at most
Mitotic figures may be numerous in carcinoma ex-GCC
Cohesive nests and cords
Single cell infiltration or sheet like growth in carcinoma ex-GCC
No desmoplasia
Desmoplasia may be present in carcinoma ex-GCC
Clinical
Spread is primarily to the right colon, over the peritoneal surface and to ovaries
33% present at stage IV
If no carcinoma component is present, the prognosis appears to be very good, even with distant spread or positive nodes (96% overall disease specific survival)
Right hemicolectomy recommended, especially for the following:
Tumor recognized intraoperatively
Appendiceal margin positive
Involvement beyond muscularis propria
Perforation
Presence of carcinoma component (see carcinoma ex-goblet cell carcinoid LINK)
It has been suggested that tumors confined to the appendiceal wall with a clear surgical margin can be treated by appendectomy alone
Must not have a carcinoma component
Grading/Staging/Report
Pure goblet cell carcinoid (GCC) is by definition low grade
Tang 2008 has proposed separating the following based on the histopathologic findings in the primary tumor (see Diagnostic Criteria at left):
DSS = Disease Specific Survival
Entries marked with * represent only 1 or 2 cases
Stage IIA represents invasion of muscularis propria without node involvement
Stage IIIB represents node involvement without metastasis
Based on Tang 2008
Classification/Lists
Gastrointestinal Endocrine Cell Proliferations and Neoplasms
Well differentiated processes including carcinoids
Riddell RH, Petras RE, Williams GT, Sobin LH. Tumors of the Intestines, Atlas of Tumor Pathology, AFIP Third Series, Fascicle 32, 2003.
Bosman FT, Carneiro F, Hruban RH, Thiese ND (Eds). WHO Classifiication of Tumors of the Digestive System, IARC, Lyon 2010
Isaacson P. Crypt cell carcinoma of the appendix (so-called adenocarcinoid tumor). Am J Surg Pathol. 1981 Apr;5(3):213-24.
Burke AP, Sobin LH, Federspiel BH, Shekitka KM, Helwig EB. Goblet cell carcinoids and related tumors of the vermiform appendix. Am J Clin Pathol. 1990 Jul;94(1):27-35.
Varisco B, McAlvin B, Dias J, Franga D. Adenocarcinoid of the appendix: is right hemicolectomy necessary? A meta-analysis of retrospective chart reviews. Am Surg. 2004 Jul;70(7):593-9.
Tang LH, Shia J, Soslow RA, Dhall D, Wong WD, O'Reilly E, Qin J,Paty P, Weiser MR, Guillem J, Temple L, Sobin LH, Klimstra DS. Pathologic classification and clinical behavior of the spectrum of goblet cell carcinoid tumors of the appendix. Am J Surg Pathol. 2008 Oct;32(10):1429-43.
Plöckinger U, Couvelard A, Falconi M, Sundin A, Salazar R, Christ E, de Herder WW, Gross D, Knapp WH, Knigge UP, Kulke MH, Pape UF; Frascati Consensus Conference participants. Consensus guidelines for the management of patients with digestive neuroendocrine tumours: well-differentiated tumour/carcinoma of the appendix and goblet cell carcinoma. Neuroendocrinology. 2008;87(1):20-30.
Pai RK, Longacre TA. Appendiceal mucinous tumors and pseudomyxoma peritonei: histologic features, diagnostic problems, and proposed classification. Adv Anat Pathol. 2005 Nov;12(6):291-311.
Kende AI, Carr NJ, Sobin LH. Expression of cytokeratins 7 and 20 in carcinomas of the gastrointestinal tract. Histopathology. 2003 Feb;42(2):137-40.
Alsaad KO, Serra S, Schmitt A, Perren A, Chetty R. Cytokeratins 7 and 20 immunoexpression profile in goblet cell and classical carcinoids of appendix. Endocr Pathol. 2007 Spring;18(1):16-22.
Chetty R, Klimstra DS, Henson DE, Albores-Saavedra J. Combined classical carcinoid and goblet cell carcinoid tumor: a new morphologic variant of carcinoid tumor of the appendix. Am J Surg Pathol. 2010 Aug;34(8):1163-7
