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carcinoid (argentaffinoma)

Etiology: risk factors - hereditary syndromes - multiple endocrine neoplasia type 1 (MEN1) - neurofibromatosis type 1 - tuberous sclerosis - von Hippel-Lindau syndrome - hypergastrinemia Epidemiology: - uncommon, but most common neuroendocrine tumors in U.S. [8] - 2% of lung tumors, with higher percentage in younger patients - 0.5% of all newly diagnosed cancers [8] - generally occur in the 7th decade of life - slight female preponderance - blacks are affected more frequently than whites - no association with smoking - incidence of carcinoid appears to be increasing - imaging for screening/diagnosis of other conditions may play a role [8] - incidental finding in appendectomy specimens from children [8] Pathology: - low-grade malignancy consisting of cells of neuroendocrine origin [5,6] - derived from primitive stem cells in the gut wall [8] - histologically described as typical or atypical [5] - common sites of carcinoid (different sources differ) - carcinoid tumors may occur - anywhere in the gastrointestinal tract (2/3) - appendix (most common (90%) in children, 7% in adults) [8] - most others are in the ileum - small intestines (39%) [8] - rectum (15%) [8] - colon (5%-7%) [8] - stomach (2%-4%) [8] - pancreas (2%-3%) [8] - liver (1%) [8] - lung (1/3) - lung tumors tend to be endobronchial in location [5] - bronchopulmonary system (10%) - thymus (one of foregut carcinoids involving lung, thymus, stomach, proximal duodenum, or pancreas) - thyroid, gallbladder, kidney, testes, ovaries less frequently affected [8] - generally small, slow growing neoplasm consisting of islands of rounded, oxyphilic or medium-sized spindle-shaped cells with moderately small vesicular nuclei - intact mucosa covers the tumor with a yellow cut surface - neoplastic cells frequently form pallisades at the periphery & have a tendency to infiltrate surrounding tissue - carcinoid tumors are generally incidental findings at autopsy or appendectomy - transformation of carcinoid tumors generally occurs in the appendix, terminal ileum, rectum, & bronchi & less commonly in the jejunum, duodenum, stomach, liver, pancreas, & gonads - tumor orginating in the appendix seldom metastasize, but those from other sites & tumors > 2.0 cm in size may metastasize chiefly to abdominal lymph nodes & the liver Microscopic pathology: (colon & rectum) 1) EC cell tumors - serotonin & substance P producing - absence of S100 staining sustentacular cells - type A solid nest pattern with some peripheral pallisading 2) L cell tumors (most frequently in rectum) - glucagon-like peptides (GLP1&2, enteroglucagons glicentin & oxyntomodulin) & PP/PYY producing - type B ribbon pattern often admixed with type C (tubuloacini or broad irregular trabeculae with rosettes) - argentaffin negative - Grimelius stain positive 3) strong positive reaction to keratin & neuroendocrine markers (chromogranin & synaptophysin) [8] 4) 5 distinct histopathologic patters [8] a) insular (common): - solid, nodular nests (favorable prognosis) b) trabecular (common): - ribbons, bands, or loops with anastomosing features (favorable prognosis) c) glandular (uncommon): - tubules with acinar or rosettelike patterns (poor prognosis) d) undifferentiated: - oorly differentiated or atypical patterns (poor prognosis) e) mixed patterns Genetics: - intestinal carcinoid is associated with defects in SDHD Clinical manifestations: - lung tumors - hemoptysis - bronchial obstruction resutling in atelectasis or focal bronchiectasis - patients may present with history of recurrent pneumonia [5,6] - 5% of patients with carcinoid tumors manifest carcinoid syndrome Laboratory: - tumor biopsy - mitotic count & Ki-67 proliferation index are used in the WHO classification system - 5-hydroxytryptamine in serum - gastrin in serum (fasting) - chromogranin A in serum - 24-hour urine 5-hydroxyindoleacetic acid - MEN1 gene mutation [8] - neurofibromatosis-1 genotyping [8] - see ARUP consult [4] Special laboratory: as needed - bronchoscopy for bronchial carcinoid - upper gastrointestinal endoscopy - endoscopic retrograde cholangiopancreatography (ERCP) - colonoscopy - capsule endoscopy - echocardiography Radiology: - computed tomography (CT), multiphasic - abdominal CT, CT of pelvis, &/or CT of thorax - lung tumors endobronchial with smooth borders - repeat imaging every 3-4 months for asymptomatic, well-differentiated diffuse or metastatic carcinoid [5] - magnetic resonance imaging (MRI) vs CT - as needed - octreotide scintigraphy - gallium-68 positron emission tomography - technetium-99m bone scintigraphy Complications: - foregut carcinoids most likely to metastasize & produce carcinoid syndrome or other symptoms [8] - bone metastases - carcinoid syndrome - acromegaly - Cushing disease - telangiectasia or skin hypertrophy of face & upper neck [8] Staging: World Health Organization (WHO) assigns nuroendocrine tumors 1 of 3 broad grades on the basis of tumor differentiation [8]: - G1: Well differentiated, low grade - G2: Well differentiated, intermediate grade - G3: Poorly differentiated, high grade Management: - treatment of choice is observation vs surgical excision [8] - surgical resection of lung tumors [5,6] - prognosis - typical carcinoid has excellent prognosis with surgical resection [5] - 10 year survival of lung carcinoid is >90% [5,6] - asymptomatic, well-differentiated diffuse or metastatic carcinoid can be managed by observation [5] with repeat evaluation every 3-4 months - well-differentiated carcinoid tumor discovered upon appendectomy should be observed for symptoms of carcinoid syndrome - for symptomatic local or regional carcinoid - octreotide (long-acting) 20-30 mg IM every 4 weeks or - lanreotide 120 mg deep SC injection every 4 weeks - chemotherapy limited to unresectable & metastatic tumors - interferon alfa-2b - 5-Fluorouracil - capecitabine - dacarbazine - oxyaliplatin - streptozotocin - termozolomide - everolimus - radiation therapy generally not used for treatment [8] - may be an option for palliative therapy - emerging molecular-targeted therapies [8] - bevacizumab - VEGF tyrosine kinase inhibitors - sunitinib - vatalanib - sorafenib prognosis: 5-year survival rates - GI carcinoid tumors - nonmetastatic: 65-90% - with regional metastasis: 46-78% - with distant metastasis: 14-54% - typical lung carcinoid tumor: 85-90% - atypical lung carcinoid tumor: 50-70%

Related

carcinoid syndrome enterochromaffin cell (argentaffin cell)

Specific

benign carcinoid bronchial carcinoid gastric carcinoid malignant carcinoid

General

ectopic hormone secretion neuroendocrine neoplasm

References

  1. Stedman's Medical Dictionary 26th ed, Williams & Wilkins, Baltimore, 1995
  2. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 587
  3. WHO Classification Tumours of the Digestive System. IARC Press 2000
  4. ARUP Consult: Neuroendocrine Tumors of the Gastrointestinal Tract, Lung, and Thymus - Carcinoid Tumors The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/carcinoid-tumors
  5. Medical Knowledge Self Assessment Program (MKSAP) 16, 17, 18, 19. American College of Physicians, Philadelphia 2012, 2015, 2018, 2021.
  6. Cao C, Yan TD, Kennedy C, Hendel N et al Bronchopulmonary carcinoid tumors: long-term outcomes after resection. Ann Thorac Surg. 2011 Feb;91(2):339-43 PMID: 21256263
  7. Moertel CG, Weiland LH, Nagorney DM, Dockerty MB. Carcinoid tumor of the appendix: treatment and prognosis. N Engl J Med. 1987 Dec 31;317(27):1699-701. PMID: 3696178
  8. Ahmad A (slide show) Carcinoid Tumors: Cancers in Slow Motion. Medscape. March 30, 2016 http://reference.medscape.com/features/slideshow/carcinoid-tumors

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