Definition/General
Introduction:
Pulmonary carcinoid tumors are well-differentiated neuroendocrine neoplasms
Represent 1-2% of all lung tumors
Show indolent behavior
Excellent prognosis for typical carcinoids
Part of lung neuroendocrine tumor spectrum.
Origin:
Arise from neuroendocrine cells (Kulchitsky cells)
Located in bronchial epithelium
Show neuroendocrine differentiation
No smoking association
Younger age group.
Classification:
WHO 2021: Typical carcinoid (<2 mitoses/2 mm², no necrosis)
Atypical carcinoid (2-10 mitoses/2 mm², ± necrosis)
Grade 1 and 2 neuroendocrine tumors.
Epidemiology:
Peak incidence 4th-5th decades
No gender predilection
No smoking association
Central location (typical)
Peripheral (atypical)
Rare familial syndromes.
Clinical Features
Presentation:
Chronic cough
Hemoptysis
Wheezing
Recurrent pneumonia
Carcinoid syndrome (rare, 2%)
Asymptomatic (peripheral lesions).
Symptoms:
Persistent cough
Shortness of breath
Chest pain
Wheeze/stridor
Post-obstructive pneumonia
Carcinoid syndrome: flushing, diarrhea.
Risk Factors:
No known risk factors
MEN-1 syndrome (rare)
Family history (rare)
No tobacco association
No environmental factors.
Screening:
Chest imaging
Bronchoscopy
24-hour urine 5-HIAA
Chromogranin A levels
Octreotide scan
68Ga-DOTATATE PET.
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Gross Description
Appearance:
Well-circumscribed
Tan-yellow color
Firm consistency
Homogeneous cut surface
Hemorrhage possible
Central location (typical).
Characteristics:
Smooth surface
Fleshy consistency
Pink-tan color
No necrosis (typical)
Focal necrosis (atypical)
Vascular appearance.
Size Location:
Central/endobronchial (typical carcinoid)
Peripheral (atypical carcinoid)
Variable size (0.5-8 cm)
Polypoid growth
Bronchial obstruction.
Multifocality:
Usually solitary
Multiple tumors (MEN-1)
Synchronous lesions rare
Metachronous tumors
Tumorlets (microscopic foci).
Microscopic Description
Histological Features:
Uniform neuroendocrine cells
Organoid/trabecular pattern
Salt-and-pepper chromatin
Inconspicuous nucleoli
Moderate eosinophilic cytoplasm
Rich vascularity.
Cellular Characteristics:
Polygonal cells
Round to oval nuclei
Finely granular chromatin
Absent/small nucleoli
Moderate cytoplasm
Uniform appearance.
Architectural Patterns:
Organoid pattern
Trabecular arrangement
Ribbon-like cords
Rosette formation
Solid nests
Prominent vasculature.
Grading Criteria:
Typical carcinoid: <2 mitoses/2 mm², no necrosis
Atypical carcinoid: 2-10 mitoses/2 mm², ± necrosis
Grade 1 (typical) vs Grade 2 (atypical).
Immunohistochemistry
Positive Markers:
Chromogranin A - positive
Synaptophysin - positive
CD56 - positive
TTF1 - positive (bronchial origin)
INSM1 - positive.
Negative Markers:
CK7 - variable
CK20 - negative
p63 - negative
Napsin A - negative
CDX2 - negative.
Diagnostic Utility:
Neuroendocrine markers confirm diagnosis
TTF1 positivity supports lung origin
Ki-67: Low in typical (<3%), higher in atypical (5-20%)
p53: Usually negative.
Molecular Subtypes:
Typical carcinoid: Low Ki-67, stable genetics
Atypical carcinoid: Higher Ki-67, more genetic alterations
All carcinoids: Neuroendocrine markers positive.
Molecular/Genetic
Genetic Mutations:
MEN1 mutations (sporadic and familial)
ARID1A mutations
EIF1AX mutations
Chromatin remodeling genes
Low mutational burden.
Molecular Markers:
Stable genome
Neuroendocrine differentiation
Serotonin production
Chromogranin expression
Low proliferation.
Prognostic Significance:
Typical carcinoid: Excellent (95% 5-year survival)
Atypical carcinoid: Good (70% 5-year survival)
Size and nodal status important
Metastases rare.
Therapeutic Targets:
Surgical resection
Bronchoscopic removal (small, endobronchial)
Octreotide (symptomatic)
Everolimus
Peptide receptor radionuclide therapy.
Differential Diagnosis
Similar Entities:
Large cell neuroendocrine carcinoma
Small cell carcinoma
Paraganglioma
Metastatic neuroendocrine tumor
Adenoid cystic carcinoma.
Distinguishing Features:
Carcinoid: Low Ki-67, organoid pattern
LCNEC: High Ki-67, large cells
SCLC: Small cells, high Ki-67
Paraganglioma: S-100+ sustentacular cells
Metastatic: Clinical correlation.
Diagnostic Challenges:
Typical vs atypical distinction
Mitotic counting
Crush artifact
Small biopsies
Necrosis assessment.
Rare Variants:
Oncocytic carcinoid
Clear cell carcinoid
Melanotic carcinoid
Composite tumors.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
[Lobectomy/wedge resection/bronchoscopic biopsy] with tumor
Tumor Description
Well-circumscribed neuroendocrine tumor measuring [X] cm in [central/peripheral] location
Microscopic Features
Organoid arrangement of uniform neuroendocrine cells with salt-and-pepper chromatin
Mitoses and Necrosis
Mitotic count: [X] per 2 mm², Necrosis: [present/absent]
Grade
[Typical carcinoid (Grade 1)/Atypical carcinoid (Grade 2)]
Immunohistochemistry
Chromogranin A: Positive, Synaptophysin: Positive, TTF1: Positive, Ki-67: [%]
Stage
pT[stage]N[stage]M[stage]
Final Diagnosis
[Typical/Atypical] carcinoid tumor, WHO Grade [1/2], pT[stage]