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Chapter: Pathology: Respiratory Pathology

Pulmonary Neoplasia

Lung cancer is the leading cause of cancer death among both men and women; it hasbeen increasing in women (increased smoking) in the past few decades.


Lung cancer is the leading cause of cancer death among both men and women; it hasbeen increasing in women (increased smoking) in the past few decades. It occurs most commonly age 50–80. Major risk factors include cigarette smoking, occu-pational exposure (asbestosis, uranium mining, radiation, etc.), passive smoking, and air pollution. Clinical features include cough, sputum production, weight loss, anorexia, fatigue, dyspnea, hemoptysis, and chest pain. Obstruction may produce focal emphysema, atelectasis, bronchiectasis, or pneumonia.

Common genetic mutations in lung cancer involve the oncogenes MYCL (small cell carcinomas) and KRAS (adenocarcinomas); tumor suppressor genes: TP53 and RB1.

Adenocarcinoma is more commonly seen in women and nonsmokers. Grossly, itcauses a peripheral gray-white mass, and the tumor may develop in areas of paren-chymal scarring (scar carcinoma). Microscopically, common patterns include ­acinar, papillary, mucinous, and solid. The precursor lesion—atypical adenomatous hyper-plasia—progresses to adenocarcinoma in situ (noninvasive well- differentiated tumor <3 cm) and to minimally invasive tumor (invasion no more than 5 mm) before progressing to invasive adenocarcinoma.

Squamous cell carcinoma (SCC) is strongly related to smoking and affects malesmore than females. Squamous cell carcinoma arises from bronchial epithelium after a progression:

metaplasia → dysplasia → carcinoma in situ → invasive carcinoma

Pathologically, the tumor grossly causes a gray-white bronchial mass, usually cen-trally located. Microscopically, well-differentiated tumors show invasive nests of squamous cells with intercellular bridges (desmosomes) and keratin production (“squamous pearls”).

Small cell carcinoma has a strong association with smoking, and affects males morethan females. This neuroendocrine tumor is very aggressive, with rapid growth and early dissemination. Small cell carcinoma is commonly associated with paraneo-plastic syndromes.

Pathologically, gross examination demonstrates central, gray-white masses. Micro-scopic examination shows small round or polygonal cells in clusters, and electron microscopy shows cytoplasmic dense-core neurosecretory granules.

Large cell carcinoma has large anaplastic cells without evidence of differentiation.

Intrathoracic spread of lung cancer is to lymph nodes, particularly hilar, bronchial,tracheal, and mediastinal; pleura (adenocarcinoma); and lung apex causing Horner syndrome (Pancoast tumor).

·            Obstruction of the superior vena cava by tumor causes superior vena cavasyndrome, characterized by distended head and neck veins, plethora, andfacial and upper arm edema.


·            Esophageal obstruction can cause dysphagia.


·            Recurrent laryngeal nerve involvement causes hoarseness, while phrenic nerve damage causes diaphragmatic paralysis.

Extrathoracic sites of metastasis include adrenal (>50%), liver, brain, and bone.

Paraneoplastic syndromes

·            Endocrine/metabolic syndromes include Cushing syndrome secondary to ACTH production, SIADH secondary to ADH production, and hypercalcemia secondary to PTH production (squamous cell carcinoma).


·            Eaton-Lambert syndrome


·            Acanthosis nigricans


·            Hypertrophic pulmonary osteoarthropathy is characterized by periosteal new bone formation with clubbing and arthritis.

Treatment of non–small cell lung cancer is with surgery, and treatment of small cell lung cancer is with chemotherapy and radiation. Despite treatment, the prognosis is poor, with overall 5-year survival 16%.

Bronchial carcinoids occur in a younger age group (mean age 40 years) and typi-cally produce a polypoid intrabronchial mass or plaque; it is characterized on light microscopy by small, round, uniform cells growing in nests (organoid pattern), and on electron microscopy by cytoplasmic dense-core neurosecretory granules. Atypi-cal carcinoid is more aggressive than typical carcinoid.

Metastatic carcinoma is the most common malignant neoplasm in the lung. It typi-cally causes multiple, bilateral, scattered nodules; common primary sites include breast, stomach, pancreas, and colon.

Hamartomas are benign tumors; they occur more commonly in middle-aged adultsbut also occur in children. They can appear as coin lesions on chest x-ray. Micro-scopically, they are comprised of nonencapsulated fibromyxoid tissue. Carney triad is the finding of a hamartoma with a predominantly cartilaginous component (pul-monary chondroma), an extra-adrenal paraganglioma and a gastric gastrointestinal stromal tumor.

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