History of Lung Diseases: Cancers

Disease Category & Link Progress, Diagnosis, Treatment, & Notable People
NSCLC: Adenocarcinoma

Wikipedia: Lung Adenocarcinoma

Progress: Now the most common type, even in non-smokers. Historically grouped with other cancers, its rise in the late 20th century was a mystery. The modern era began in 2004 with the discovery of EGFR mutations by multiple teams (Meyerson, Varmus, Thomas, Pao), proving this was a disease of specific genetic pathways.

Diagnosis & Imaging:

  • X-ray/CT: Classically presents as a peripheral nodule or mass. Early-stage (lepidic) adenocarcinoma is famous for appearing as a faint “ground-glass opacity” (GGO) on CT, which is very difficult to see on X-ray.
  • PET/CT: Used for staging to find lymph node and distant metastases.

Treatment: Revolutionized by targeted therapies (like Osimertinib for EGFR) and immunotherapy (like Pembrolizumab for PD-L1), which have dramatically improved survival.

NSCLC: Squamous Cell Carcinoma

Wikipedia: Squamous-cell lung carcinoma

Progress: The classic “smoker’s cancer.” Its incidence soared with the rise of cigarette smoking. Drs. Richard Doll and Austin Bradford Hill (1950s) definitively linked smoking to this cancer type.

Diagnosis & Imaging:

  • X-ray/CT: Classically presents as a central mass near the hilum, often arising from a main bronchus.
  • This type is notorious for cavitation (the center of the tumor dies and creates an air-filled hole) and for causing post-obstructive pneumonia (blocking an airway, causing infection downstream).
  • Pancoast tumors (at the very top of the lung) are often squamous cell.

Treatment: Dr. Evarts Graham performed the first successful pneumonectomy (lung removal) for this cancer in 1933. Today, treatment involves surgery, chemotherapy, and immunotherapy.

NSCLC: Large Cell Carcinoma

Wikipedia: Large-cell lung carcinoma

Progress: This is an “undifferentiated” cancer, meaning it’s a diagnosis of exclusion. It lacks the features of small cell, adeno, or squamous cancer. It’s known for being large and growing rapidly.

Diagnosis & Imaging:

  • X-ray/CT: Often presents as a large peripheral mass, frequently with central necrosis or cavitation.
  • Its undifferentiated nature means it can be very aggressive and metastasize early.

Treatment: Generally treated with surgery (if caught early) and chemotherapy. It often lacks the specific mutations for targeted therapy, making it a difficult-to-treat subtype.

Small Cell Lung Cancer (SCLC)

Wikipedia: Small-cell carcinoma

Progress: The most aggressive lung cancer, strongly linked to smoking. It is a neuroendocrine tumor, meaning it can secrete hormones and cause paraneoplastic syndromes (like SIADH or Cushing’s).

Diagnosis & Imaging:

  • X-ray/CT: Rarely a “coin lesion.” The classic presentation is a large hilar/mediastinal mass with extensive “bulky” lymphadenopathy.
  • It grows extremely fast (high mitotic rate) and is often widespread (metastatic) at diagnosis, especially to the brain, liver, and bones.
  • Can cause Superior Vena Cava (SVC) syndrome by compressing the large vein in the chest.

Treatment: It is not a surgical disease. It is highly sensitive to initial chemotherapy and radiation, but it almost always relapses quickly. Immunotherapy is a recent addition to its treatment.

Malignant Carcinoid Tumor

Wikipedia: Lung Carcinoid Tumour

Progress: A rare, low-grade (slow-growing) neuroendocrine tumor, distinct from SCLC. Not strongly linked to smoking.

Diagnosis & Imaging:

  • X-ray/CT: Classically appears as a highly vascular central, endobronchial (inside the airway) nodule.
  • Because it’s in the airway, it can cause hemoptysis (coughing up blood) or block a lobe, causing recurrent pneumonia.

Treatment: The primary treatment is surgery, which is often curative. These tumors are highly resistant to chemotherapy and radiation.

Malignant Mesothelioma

Wikipedia: Mesothelioma

Progress: An aggressive cancer of the pleura (the lining around the lung), not the lung itself. In the 1960s, Drs. J.C. Wagner and Irving Selikoff definitively linked it to asbestos exposure.

Diagnosis & Imaging:

  • X-ray: Often first seen as a large, one-sided pleural effusion (fluid).
  • CT/PET: This is the gold standard. It shows the hallmark finding: a nodular, rind-like thickening of the pleura that encases the entire lung, often “squeezing” it and shrinking the chest cavity on that side. This appearance is highly characteristic.

Treatment: Very difficult. Often involves a combination of surgery (pleurectomy), chemotherapy, and radiation, with a historically poor prognosis.

1. Notables Who Advanced the Diagnosis & Management of Lung Cancer

Name & Wikipedia Link Comment on Contribution
Evarts Graham (1883–1957) A pioneering thoracic surgeon. In 1933, he performed the first successful pneumonectomy (removal of an entire lung) to cure a patient with squamous cell lung cancer. This proved that lung cancer was a surgically treatable disease.
Richard Doll & Austin Bradford Hill (1912–2005) & (1897–1991) British epidemiologists whose “British Doctors Study” in the 1950s provided the first definitive, large-scale scientific proof that cigarette smoking was the direct cause of the lung cancer epidemic.
J.C. Wagner & Irving Selikoff (1912–1996) & (1914–1992) These two researchers (Wagner in South Africa, Selikoff in the US) independently and definitively linked asbestos exposure to malignant mesothelioma, a rare and aggressive cancer of the pleura (lung lining).
Meyerson, Varmus, Pao, et al. (2004) These are several of the key researchers (on separate teams) who simultaneously discovered that a subset of adenocarcinoma patients (often non-smokers) had EGFR mutations. This launched the modern era of “targeted therapy” (e.g., Iressa, Tarceva) for lung cancer.
James P. Allison & Tasuku Honjo (b. 1948) & (b. 1942) Awarded the 2018 Nobel Prize for their discovery of checkpoint inhibition (CTLA-4 and PD-1). Their work is the foundation of immunotherapy, which has revolutionized the treatment of advanced lung cancer.

2. Notables Who Suffered From Lung Cancer

Name & Wikipedia Link Comment on Disease
Walt Disney (1901–1966) A lifelong, heavy cigarette smoker. He was diagnosed with lung cancer (likely squamous cell or small cell) and had his entire left lung removed, but he died from the disease just 34 days later.
King George VI (1895–1952) The King of England (featured in The King’s Speech) was a very heavy smoker. He underwent a pneumonectomy for lung cancer in 1951 (an event hidden from the public) but died a few months later from the disease.
Yul Brynner (1920–1985) The star of The King and I was a famous smoker. After being diagnosed with inoperable lung cancer, he recorded a famous anti-smoking PSA, stating “Now that I’m gone, I tell you: Don’t smoke.” It was released after his death.
Paul Newman (1925–2008) The actor and philanthropist was a heavy smoker for much of his life. He quit in the 1970s but was diagnosed with and ultimately died from lung cancer.
Peter Jennings (1938–2005) The ABC News anchor was a heavy smoker who quit for a time but resumed after 9/11. He announced on-air in April 2005 that he had been diagnosed with lung cancer (adenocarcinoma) and died just four months later.
Dana Reeve (1961–2006) The wife of Christopher Reeve, she was a lifelong non-smoker. Her death from lung adenocarcinoma at age 44 was a major public event that highlighted the tragic reality that non-smokers can and do get lung cancer.