Primary and metastatic tumors of the lung

A) Benign Tumors of the Lung

Hamartoma

• Most common benign tumor of the lung
• Focal, excessive overgrowth of cells/tissues native to the organ; mature cellular elements, but do not reproduce normal architecture
• Arise from CT; compress surrounding lung tissue; usually asymptomatic
• Treatment: surgical resection (excellent prognosis)

Adenomas

• Benign epithelial neoplasms producing gland patterns:
  • Alveolar adenoma: peripheral lung; small cystic spaces lined by type II pneumocytes
  • Bronchial gland adenoma: from mucous glands/ducts of trachea or bronchi
  • Papillary adenoma: peripheral lung; type II pneumocytes
  • Pleomorphic adenoma: trachea and major bronchi

Solitary Fibrous Tumor (SFT)

• Rare mesenchymal tumor from visceral pleura (80%) or parietal pleura (20%)
• Can be very large (up to 40 cm); >50% asymptomatic
• Treatment: surgical resection (great prognosis)

Carcinoid Tumorlets

• Hyperplasia of neuroendocrine cells ≤5 mm, no mitotic activity, no necrosis
• Tiny peripheral carcinoid; rarely metastasize; arise near bronchioles
• Differential: small cell carcinoma, peripheral carcinoid tumor

Sclerosing Hemangioma

• From incompletely differentiated respiratory epithelium
• Asymptomatic, peripheral, solitary, well-circumscribed; women ~50 years of age
• Histology: 2 cell types (surface + round cells); 4 patterns (papillary, sclerotic, solid, hemorrhagic)
• Benign; treatment: surgical excision

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B) Metastatic Tumors of the Lung

• Entire cardiac output flows through lungs → high risk of hematogenous metastases
• Metastatic steps: tumor cell migration → vascular invasion → extravasation → distant metastasis
• Common primaries metastasizing to lung:
  • Breast carcinoma, GI tumors, renal cell carcinoma, malignant melanoma, sarcomas, lymphomas, germ cell tumors
• Lung carcinoma metastasizes to: Brain, Bone, Liver, Adrenals

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C) Malignant Lung Tumors (Lung Carcinomas)

• #1 cause of cancer-related deaths in industrialized countries
• 5-year survival rate ~15% (all stages)
• Symptoms: dyspnea, coughing (sometimes hemoptysis), weight loss
• 95% originate from bronchial epithelium
• Risk factors: cigarette smoking, asbestos, radon, formaldehyde, radiation, recurrent inflammation

SCLC vs. NSCLC

	SCLC	NSCLC
Cell types	Neuroendocrine / anaplastic	SCC, adenocarcinoma, large cell carcinoma
Cell of origin	Kulchitsky (enterochromaffin) cells	SCC: metaplasia/dysplasia; ADC: pneumocyte II
Therapy	Chemo (+/- radio) — not operable	Surgery

Pathogenesis

• Stepwise accumulation of genetic abnormalities → inactivation of tumor suppressor genes on chromosome 3p (early); p53 mutation + KRAS inactivation (late)
• Cigarette smoking: strongest association with squamous cell + small cell carcinoma

The 4 Major Histological Types

1. Squamous Cell Carcinoma

• More common in men; closely related to cigarette smoking
• Central location in major bronchi (around tracheal bifurcation)
• Preceded by squamous metaplasia/dysplasia → carcinoma in situ → obstructing mass → atelectasis + infection
• Histology: well-differentiated to poorly differentiated squamous neoplasms

2. Adenocarcinoma

• Most common primary lung cancer
• More common in women and non-smokers
• Usually peripheral (bronchioles); grows slowly; early widespread metastasis
• Histology: acinar, papillary, solid types; precursor = atypical adenomatous hyperplasia (AAH)
• Broncho-alveolar carcinoma (BAC): peripheral; grows along preexisting alveolar structures (preserves architecture)

3. Small Cell Lung Carcinoma (SCLC)

• Pale gray, centrally located masses
• Early dissemination → hilar and mediastinal lymph nodes
• Cells: round to fusiform, little cytoplasm, finely granular chromatin; many mitotic figures
• Precursor: Kulchitsky (neuroendocrine) cells
• Usually non-operable (already metastasized at diagnosis)

4. Large Cell Carcinoma

• Undifferentiated malignant epithelial tumors; lack cytological features of small cell
• Large nuclei, prominent nucleoli, moderate cytoplasm
• Probably represents undifferentiated SCC or ADC

Pancoast Tumor

• Tumor of the pulmonary apex (usually NSCLC)
• Invades brachial/cervical sympathetic plexus → severe pain in ulnar nerve distribution
• Horner syndrome: ptosis (drooping eyelid) + miosis (pupil constriction) + enophthalmos (sunken eyes)

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D) Carcinoid Tumors

• Malignant tumors of neuroendocrine cells (Kulchitsky cells)
• Contain dense neurosecretory granules; may secrete hormonally active peptides
• Morphology: arise in main bronchi; 2 patterns: (1) obstructing polypoid intraluminal mass; (2) mucosal plaque penetrating bronchial wall

Two types:

• Typical carcinoid: nests of uniform cells; round nuclei; little pleomorphism; grow slowly; rarely metastasize
• Atypical carcinoid: higher mitotic rate; cytological variability; focal necrosis; higher metastatic spread
• Progression: typical → atypical → small cell carcinoma

Clinical: men ~40 years; coughing, hemoptysis, recurrent infections; carcinoid syndrome (rare): diarrhea, flushing, cyanosis

💡 High-yield: Lung carcinoma = #1 cancer death; 5-yr survival ~15%. ADC = most common, women/non-smokers, peripheral. SCC = men, smokers, central. SCLC = Kulchitsky cells, chemo only, already metastasized. Pancoast = apical tumor + Horner (ptosis, miosis, enophthalmos). Carcinoid = neuroendocrine; typical (benign-ish) → atypical → SCLC.