Stanford School of Medicine

Surgical Pathology Criteria
http://surgpathcriteria.stanford.edu/

 use browser back button to return

Carcinoma Ex-goblet Cell Carcinoid of the Appendix

Definition

  • Biphasic appendiceal neoplasm exhibiting both areas of typical GCC and areas of infiltrating adenocarcinoma

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 often appear more poorly differentiated or undifferentiated
  • Typical goblet cell carcinoid is at least focally present
    • Typical cohesive nests of bland goblet cells may be only very focally preserved
    • Rare to scattered neuroendocrine cells always present
      • Seen on synaptophysin or chromogranin stains
      • Present in typical goblet cell carcinoid areas
      • Less reliably seen in carcinomatous components
  • Carcinoma is present with the following features (criteria proposed by Tang 2008)
    • Signet ring cell type
      • Infiltrating signet ring cell carcinoma is present with at least one of the following features
        • Goblet cells / signet ring cells in irregular large clusters
        • Confluent sheets of cells indicates poorly differentiated carcinoma type, see below
      • Discohesive single file or single cell infiltration
        • Desmoplastic response
      • Significant cytologic atypia
        • Irregular hyperchromatic nuclei
    • Poorly differentiated type exhibits at least one of the following features
      • Confluent sheets of atypical cells
        • May or may not be signet cells
      • >1 low power field or >1 mm2 of conventional type adenocarcinoma, usually poorly differentiated or undifferentiated
        • May form glands
    • Features that may be shared by both types, but are not seen in pure goblet cell carcinoid
      • Cytologically atypical signet ring cells
      • Discohesive single file or single cell infiltration
      • Desmoplastic response
      • Significant cytologic atypia
        • Irregular hyperchromatic nuclei
  • Regional lymph node involvement frequent
    • 73% in signet ring cell type
    • 100% in poorly differentiated type
  • Extra-appendiceal spread to right colon, peritoneal surfaces and ovary is frequent
    • 88% in signet ring cell type
    • 100% in poorly differentiated type
  • Hematogenous metastases rare

Robert V Rouse MD
Teri A Longacre MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting : 7/12/10, last update 3/26/14

Supplemental studies

Immunohistology

Marker Pure GCC Areas Signet Ring Type of Ca ex-GCC Poorly Differentiated Type of Ca ex-GCC
Synaptophysin 100% of cases, rare to 25% of cells Same as GCC Same as GCC
Chromogranin 100% of cases, rare to 25% of cells Same as GCC Same as GCC
CDX2 no data no data no data
CK7 Variable no data no data
CK20 100% no data no data
p53 Negative Positive Positive
MUC1 Negative Positive Positive
MUC2 Positive Negative Negative
Other neuroendocrine markers have been reported positive also
Neuroendocrine cells are positive with both argentaffin and argyrophil stains

Differential Diagnosis

Goblet Cell Carcinoid, Pure Carcinoma ex GCC, Signet Ring Cell Type Carcinoma ex GCC, Poorly Differentiated Carcinoma Type
Bland cytology Atypical cytology Atypical cytology
Cohesive clusters and cords Discohesive cells with single cell infiltration May have discohesive cells
No desmoplasia Desmoplastic response to invasion Desmoplastic response to invasion
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

Appendiceal Adenocarcinoma Carcinoma Ex-goblet Cell Carcinoid
No typical goblet cell carcinoid At least focal typical goblet cell carcinoid
Usually low grade Usually high grade
Based on histopathologic findings in primary tumor

Appendiceal Carcinoid / Well Differentiated Neuroendocrine Cell Neoplasm Goblet Cell Carcinoid and/or Carcinoma ex-GCC
Chromogranin or synaptophysin positive 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
    • Regional nodes frequently positive
  • Right hemicolectomy, debulking surgery and possible oophorectomy are recommended
  • Adjuvant chemotherapy is generally given
  • 5 year disease specific survival for stage IV patients
    • 38% for signet ring type
    • 0% for poorly differentiated type

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):
  • TNM 7th edition staging should follow that of non-carcinoid appendiceal adenocarcinomas
  • Findings relevant to extent of disease should be included in the report
    • Involvement of mesoappendix
    • Involvement of surgical margin
    • Involvement of lymph nodes
    • Involvement of other organs or tissues

    Goblet Cell Carcinoid, Pure vs. Carcinoma Ex-GCC Incidence by Stage at Presentation with Survival
    Type Stage I Stage IIA Stage IIIB Stage IV
    GCC, pure

    1%*
    5 yr DSS 100%

    60%
    5 yr DSS 100%
    3%*
    5 yr DSS 100%
    33%
    5 yr DSS 100%
    Ca ex-GCC, signet ring cell type 0% 4%*
    5 yr DSS 100%
    8%*
    5 yr DSS 100%
    88%
    5 yr DSS 38%
    Ca ex-GCC, poorly diff. 0% 0% 0% 100%
    5 yr DSS 0%
    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

Appendiceal Epithelial Neoplasms and Proliferations

Clinical / Descriptive Terms

Bibliography

  • Riddell RH, Petras RE, Williams GT, Sobin LH. Tumors of the Intestines, Atlas of Tumor Pathology, AFIP Third Series, Fascicle 32, 2003.
  • Hamilton SR, Aaltonen LA eds. Pathology and genetics of tumours of the digestive system. World Health Organization classification of tumours, Vol. 2. Lyon: IARC Press 2000.
  • 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.
Printed from Surgical Pathology Criteria: http://surgpathcriteria.stanford.edu/
© 2005  Stanford University School of Medicine