Lung neuroendocrine neoplasms

Group of lung tumors arising from neuroendocrine cells, ranging from indolent carcinoid tumors (typical and atypical) to highly aggressive small cell and large cell neuroendocrine carcinomas.

• Lung NENs account for ~20% of lung cancers (SCLC ~15%, carcinoids ~2%, LCNEC ~3%). They span some of the best and worst prognoses in pulmonary oncology – e.g. low-grade carcinoids often curable, versus small cell lung cancer (one of the most aggressive malignancies). Many have unique features like paraneoplastic syndromes (ectopic ACTH, SIADH) that make them high-yield for exams.

• Carcinoid tumors (typical & atypical): usually patients <60 and often non-smokers; present as central airway masses causing cough, wheezing, hemoptysis, or recurrent pneumonia from bronchial obstruction. Many are found incidentally on imaging; true carcinoid syndrome (flushing, diarrhea, bronchospasm) is rare (<3%) in lung carcinoids.
• Small cell lung carcinoma (SCLC): occurs almost exclusively in heavy smokers (typically in their 60s–70s). Presents with a central lung mass, early metastases, weight loss, and often paraneoplastic phenomena (e.g., Cushing syndrome from ACTH, SIADH with hyponatremia, or Lambert–Eaton myasthenic syndrome).
• Large cell neuroendocrine carcinoma (LCNEC): a rare high-grade NSCLC variant in older smokers, often appearing as a large peripheral mass. Clinically behaves like SCLC (aggressive growth, poor prognosis), though it may be identified after surgical resection of what was thought to be NSCLC.

1. Imaging + biopsy: Investigate persistent pulmonary symptoms or nodules with chest CT and obtain tissue diagnosis. Use bronchoscopy for central lesions or CT-guided needle biopsy for peripheral lesions. Pathology will show neuroendocrine morphology; confirm with immunohistochemistry (chromogranin A, synaptophysin, CD56).
2. Grade the tumor: Determine mitotic count (per 2 mm²) and look for necrosis to classify the tumor: typical carcinoid (<2 mitoses, no necrosis), atypical carcinoid (2–10 mitoses or focal necrosis), or high-grade NEC (>10 mitoses, extensive necrosis). If biopsy is small/crushed, use the Ki-67 labeling index to help gauge proliferation.
3. Evaluate hormone production: If symptoms suggest hormonal syndrome, check relevant labs (e.g., 24-hr urine 5-HIAA for carcinoid syndrome, serum ACTH/cortisol for ectopic Cushing). Note that most lung NETs are "functional" only in a minority of cases.
4. Staging work-up: Do a thorough metastasis evaluation once diagnosis is confirmed. This includes CT (or PET-CT) scans of chest/abdomen, brain MRI, and bone scan if needed. Well-differentiated tumors may also be imaged with somatostatin receptor scintigraphy (octreotide or Gallium-68 DOTATATE scan) to detect occult metastases.

1. Carcinoid (typical/atypical): first-line is surgical resection (often curative for localized disease). Atypical carcinoids (higher grade or nodal spread) may receive adjuvant platinum-etoposide chemotherapy. Metastatic carcinoid tumors can be managed with somatostatin analogs (octreotide/lanreotide) to control symptoms and targeted therapies (e.g., everolimus) to slow tumor growth.
2. Small cell lung cancer: primarily treated with chemotherapy (e.g., cisplatin or carboplatin + etoposide) and radiation therapy. Surgery is rarely an option (only in very limited stage SCLC). SCLC responds initially to chemo but often recurs; prognosis remains poor.
3. Large cell neuroendocrine carcinoma: if diagnosed at limited stage, treat similar to other NSCLC (surgical resection followed by adjuvant chemo). For advanced LCNEC, therapy mirrors SCLC (platinum-based chemo), recognizing its high metastatic potential.

• Recurrent localized pneumonia or asthma-like symptoms (wheezing) in a non-smoker should prompt evaluation for a bronchial carcinoid blocking an airway.
• Bronchial carcinoids are highly vascular ("raspberry" red lesion); biopsy can cause bleeding – be prepared to control hemorrhage.
• Carcinoid tumors rarely cause carcinoid syndrome in the lung – paradoxically, ectopic Cushing (ACTH) is more common. Don't jump to flushing/diarrhea unless the case clearly suggests it.
• SCLC is usually not treated with surgery – if an answer choice offers surgery for a smoker's small cell tumor, it's likely a trap (surgery is only for extremely limited cases).

• Severe hyponatremia in a lung cancer patient (e.g., Na <120) suggests paraneoplastic SIADH – can cause confusion, seizures, and requires urgent management (fluid restriction, hypertonic saline) along with cancer therapy.
• Carcinoid tumor during surgery or biopsy can precipitate carcinoid crisis (flushing, bronchospasm, hemodynamic instability); ensure prophylaxis with octreotide and have vasoactive support ready if needed.

1. Pulmonary nodule or suspicious symptoms → CT chest to localize lesion; consider bronchoscopy if central.
2. If a lung NE tumor is suspected → obtain biopsy for definitive diagnosis (with NE marker studies and Ki-67 index for grading).
3. After diagnosis of lung NEN → perform staging (CT/PET scans, brain MRI) to determine extent of disease.
4. Localized well-differentiated tumor → surgery (preferred for carcinoids, and even for LCNEC if resectable). High-grade or metastatic disease → systemic therapy (chemotherapy ± radiotherapy); add octreotide for functional symptoms.

• Middle-aged non-smoker with recurrent pneumonia in the same lobe, wheezing not responding to asthma therapy, and hemoptysis → Bronchial carcinoid (central vascular tumor causing airway obstruction).
• Older heavy smoker with a rapidly growing hilar mass, weight loss, and hyponatremia (paraneoplastic SIADH) → Small cell lung carcinoma.