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Gastrin Cell Neoplasm / Gastrinoma of the Duodenum

Definition

  • Duodenal neoplasm of gastrin producing cells, termed gastrinoma if there is clinical evidence of gastrin secretion

Alternate/Historical Names

  • G cell neoplasm

Diagnostic Criteria

  • Histologic appearance is indistinguishable from other GI well differentiated endocrine neoplasms
    • Uniform cells with bland round regular nuclei
    • Trabecular and pseudo glandular growth patterns
    • Perivascular pseudo rosettes
    • Gastrin can be immunohistologically identified in both functioning and non-functioning neoplasms
      • Other markers variably demonstrable include pancreatic polypeptide, insulin and somatostatin)
  • Non-functioning gastrin cell (G cell) neoplasms nearly all solitary and located in bulb of duodenum
    • Usually benign
  • 15% of duodenal G cell neoplasms are gastrinomas (functioning) with associated Zollinger-Ellison (ZE) syndrome
    • G cell neoplasms are termed gastrinomas if there is clinical evidence of gastrin secretion(ZE syndrome)
    • Increasing numbers of ZE patients are reported to be associated with duodenal gastrinomas (up to 70%)
      • Remainder appear to be due to pancreatic neoplasms
      • Earlier reports of primary nodal gastrinomas and of diffuse gastrin overproduction in the stomach appear to be due instead to very small (<1 mm) duodenal neoplasms
    • Functioning G cell neoplasms (gastrinomas) may be solitary or multiple and may be located throughout the duodenum or into proximal jejunum
      • Local lymph nodes frequently involved (50-80%)
        • May occur even if primary neoplasm is <1 mm
      • Liver involved at presentation in about 5%
    • Most cases of ZE syndrome due to sporadic gastrinomas
      • Approximately 20% associated with MEN1
        • Duodenal G cell neoplasms associated with MEN1 are more often multiple
          • Same behavior as sporadic neoplasms if matched for function and stage
      • Sporadic G cell neoplasms more often solitary and <1 cm
  • 10 year survival >90% for duodenal gastrinomas without liver metastases (Weber 1995, Stabile 1985)
    • 10 year survival if liver metastases found at presentation 30%
    • Local lymph node involvement not predictive of poor behavior
      • 10 year survival if regional nodes involved also >90%
      • Same behavior even if incompletely resected
    • Note that WHO 2008 incorrectly gives 10 year survival of 59% for duodenal gastrinomas without liver metastases, referencing Weber 1995 who actually reported 94% survival

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

Original posting/updates : 7/27/10, 11/22/11, 12/28/11

Grading

WHO recommends the following grading scheme, but a number of other factors are predictive of behavior, see Criteria

    Proposed grading scale based on proliferation

    Grade Mitotic count per 10 hpf % of cells Ki67+
    G1 <2 ≤2
    G2 2-20 3-20
    G3 >20 >20
    • Mitotic counts based on 50 hpf
    • Ki67 % based on 500-2000 cells
    • If discrepant, use higher grade
    • Scale proposed by European Neuroendocrine Society (ENETS)
      • Carcinoids / neuroendocrine tumors may be G1 or G2
      • G3 is definitional for high grade neuroendocrine carcinoma
    • Progression from G1/2 to G3 is quite rare
      • G3 appears to be a separate process

    Grading/Staging References

    • Rindi G, Klöppel G, Couvelard A, Komminoth P, Körner M, Lopes JM, McNicol AM, Nilsson O, Perren A, Scarpa A, Scoazec JY, Wiedenmann B. TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system. Virchows Arch. 2007 Oct;451(4):757-62.
    • Rindi G, Klöppel G, Alhman H, Caplin M, Couvelard A, de Herder WW, Erikssson B, Falchetti A, Falconi M, Komminoth P, Körner M, Lopes JM, McNicol AM, Nilsson O, Perren A, Scarpa A, Scoazec JY, Wiedenmann B; and all other Frascati Consensus Conference participants; European Neuroendocrine Tumor Society (ENETS). TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch. 2006 Oct;449(4):395-401.
  • Staging
    • Use TNM

Differential Diagnosis

Determination of common sites of origin for metastatic well differentiated endocrine neoplasms
  TTF1 CDX2 PDX1 ISL1 PAX8
Lung 40-50% Negative Negative Negative Negative
Pancreas Negative 0-18% 28% 68% 50-67%
Stomach Negative 0-17% 60% Negative 20%
Duodenum Negative 0-17% 60% Negative 100%
Ileum Negative >90% Negative Negative Negative
Appendix Negative >90% 55% Negative 21%
Rectum Negative 0-55% 17% Negative 85%
Detection of specific islet hormones may be useful; PAX8 data has been questioned (see Pancreas).

 

Determination of common sites of origin for metastatic well differentiated endocrine neoplasms-keratins
  CK7 CK20
Lung Variable Negative
Pancreas Variable Variable
Stomach Variable Negative
Duodenum Negative Variable
Ileum Negative Variable
Appendix Negative Variable
Rectum Variable Variable
CK7/20 staining is only helpful in instances of positivity where a negative result is expected

Lists

Gastrointestinal Endocrine Cell Proliferations and Neoplasms

Bibliography

  • 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
  • Weber HC, Venzon DJ, Lin JT, Fishbein VA, Orbuch M, Strader DB, Gibril F, Metz DC, Fraker DL, Norton JA, et al. Determinants of metastatic rate and survival in patients with Zollinger-Ellison syndrome: a prospective long-term study. Gastroenterology. 1995 Jun;108(6):1637-49.
  • Donow C, Pipeleers-Marichal M, Schröder S, Stamm B, Heitz PU, Klöppel G. Surgical pathology of gastrinoma. Site, size, multicentricity, association with multiple endocrine neoplasia type 1, and malignancy. Cancer. 1991 Sep 15;68(6):1329-34.
  • Delcore R Jr, Cheung LY, Friesen SR. Outcome of lymph node involvement in patients with the Zollinger-Ellison syndrome. Ann Surg. 1988 Sep;208(3):291-8.
  • Anlauf M, Enosawa T, Henopp T, Schmitt A, Gimm O, Brauckhoff M, Dralle H, Musil A, Hauptmann S, Perren A, Klöppel G. Primary lymph node gastrinoma or occult duodenal microgastrinoma with lymph node  metastases in a MEN1 patient: the need for a systematic search for the primary tumor. Am J Surg Pathol. 2008 Jul;32(7):1101-5.
  • Anlauf M, Garbrecht N, Henopp T, Schmitt A, Schlenger R, Raffel A, Krausch M, Gimm O, Eisenberger CF, Knoefel WT, Dralle H, Komminoth P, Heitz PU, Perren A, Klöppel G. Sporadic versus hereditary gastrinomas of the duodenum and pancreas: distinct clinico-pathological and epidemiological features. World J Gastroenterol. 2006 Sep 14;12(34):5440-6.
  • Srivastava A, Hornick JL. Immunohistochemical staining for CDX-2, PDX-1, NESP-55, and TTF-1 can help distinguish gastrointestinal carcinoid tumors from pancreatic endocrine and pulmonary carcinoid tumors. Am J Surg Pathol. 2009 Apr;33(4):626-32.
  • Stabile BE, Passaro E Jr. Benign and malignant gastrinoma. Am J Surg. 1985 Jan;149(1):144-50.
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