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.
• 2% of lung tumors, with higher percentage in younger patients
• 0.5% of all newly diagnosed cancers
• 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
• incidental finding in appendectomy specimens from children

Pathology

• low-grade malignancy consisting of cells of neuroendocrine origin
• derived from primitive stem cells in the gut wall
• histologically described as typical or atypical
• 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)
        • most others are in the ileum
      • small intestines (39%)
      • rectum (15%)
      • colon (5%-7%)
      • stomach (2%-4%)
      • pancreas (2%-3%)
      • liver (1%)
  • lung (1/3)
    • lung tumors tend to be endobronchial in location
    • bronchopulmonary system (10%)
  • thymus (one of foregut carcinoids involving lung, thymus, stomach, proximal duodenum, or pancreas)
  • thyroid, gallbladder, kidney, testes, ovaries less frequently affected
• 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)

• EC cell tumors
  • serotonin & substance P producing
  • absence of S100 staining sustentacular cells
  • type A solid nest pattern with some peripheral pallisading
• 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
• strong positive reaction to keratin & neuroendocrine markers (chromogranin & synaptophysin)
• 5 distinct histopathologic patters
  • insular (common):
    • solid, nodular nests (favorable prognosis)
  • trabecular (common):
    • ribbons, bands, or loops with anastomosing features (favorable prognosis)
  • glandular (uncommon):
    • tubules with acinar or rosettelike patterns (poor prognosis)
  • undifferentiated:
    • oorly differentiated or atypical patterns (poor prognosis)
  • 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% 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
• neurofibromatosis-1 genotyping
• see ARUP consult

Diagnostic procedures

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
• magnetic resonance imaging (MRI) vs CT
• as needed
  • octreotide scintigraphy
  • gallium-68 positron emission tomography
  • technetium-99m bone scintigraphy

Staging

World Health Organization (WHO) assigns nuroendocrine tumors 1 of 3 broad grades on the basis of tumor differentiation:

• G1: Well differentiated, low grade
• G2: Well differentiated, intermediate grade
• G3: Poorly differentiated, high grade

Complications

• foregut carcinoids most likely to metastasize & produce carcinoid syndrome or other symptoms
• bone metastases
• carcinoid syndrome
• acromegaly
• Cushing disease
• telangiectasia or skin hypertrophy of face & upper neck

Management

• treatment of choice is observation vs surgical excision
• surgical resection of lung tumors
• prognosis
  • typical carcinoid has excellent prognosis with surgical resection
    • 10 year survival of lung carcinoid is >90%
• asymptomatic, well-differentiated diffuse or metastatic carcinoid can be managed by observation 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
  • may be an option for palliative therapy
• emerging molecular-targeted therapies
  • 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%

More general terms

• neuroendocrine neoplasm
• ectopic hormone secretion

More specific terms

• benign carcinoid
• bronchial carcinoid
• gastric carcinoid
• malignant carcinoid

Additional terms

• carcinoid syndrome
• enterochromaffin cell (argentaffin cell)

Patient information

carcinoid patient information

Database

• OMIM: https://mirror.omim.org/entry/114900