Lung Cancer | Lung Pathologies

Smoking-Associated Lung Cancer

Lung cancer stands as the most common cause of cancer-related deaths globally, claiming a staggering 1.76 million lives each year. Tobacco use, as numerous studies have shown, plays a pivotal role in this grim reality. According to research published in The Lancet, approximately 22% of cancer deaths are attributable to tobacco use.

The correlation between smoking and lung cancer is undeniable.

In fact, an estimated 90% of lung cancer cases can be directly

linked to tobacco consumption. And it's not just the nicotine in

cigarettes that's the culprit here. The secondary components of

cigarette smoke, including carbon monoxide and tar, play

significant roles in causing harm to the lungs. Carbon monoxide,

for instance, interferes with the blood's ability to carry oxygen,

while tar, a complex mixture of chemicals apart from nicotine

and carbon monoxide, is laden with carcinogens.

Carcinogens such as polycyclic aromatic hydrocarbons,

N-nitrosamines, and aromatic amines, among others, wreak

havoc on lung tissue, leading to the development of cancerous

cells. And what's more concerning is that these carcinogens

can be detected not only in the lungs but also in bodily fluids

like urine, blood, and breath, underscoring the pervasive

damage caused by smoking.

The repercussions of lung cancer extend beyond the lungs themselves. Metastasis, the spread of cancer to distant sites, can occur in various organs, including the brain, bones, liver, and adrenal glands. Despite advances in treatment, advanced-stage lung cancer often poses significant challenges in terms of management and prognosis.

By understanding the intricate mechanisms linking smoking to lung cancer and spreading awareness about the risks involved, we can strive towards reducing the burden of this devastating disease.It's imperative that we continue to educate individuals about the detrimental effects of tobacco use and advocate for policies aimed at curbing its prevalence. Through ongoing research and public health initiatives, we can work towards a future where lung cancer ceases to be a leading cause of mortality worldwide.

Lung affected by lung cancer. Photo Credit: Human Protein Atlas

Small cell carcinoma is a high-grade neuroendocrine tumor that predominantly arises in the hilum of smokers. It's characterized by its aggressive nature and poor prognosis, with limited targeted therapy options currently available.

Small cell carcinoma is associated almost exclusively with smoking or tobacco exposure, constituting around 10-15% of all lung cancer cases. A striking 70% of patients present with metastasis at the time of diagnosis, underscoring the advanced stage at which this cancer is often detected. Common sites of metastasis include the liver, adrenals, bone, bone marrow, and brain. Additionally, small cell carcinoma typically arises from the neuroendocrine cells of the basal bronchial epithelium.

Diagnosis relies heavily on biopsy findings, with characteristic hematoxylin and eosin morphology guiding the process. Staging is typically conducted via radiological imaging, such as chest CT scans, brain MRIs, or bone scans.

Symptoms can vary but often include:

Cough
Dyspnea
Weight loss
Paraneoplastic syndromes such as Cushing syndrome and superior vena cava syndrome.

From a pathological standpoint, small cell carcinoma presents as a mass of white-tan soft friable necrosis, with peripheral nodules displaying a circumscribed, fleshy cut surface. Microscopically, it's characterized by round or oval blue cells with minimal cytoplasm, along with distinctive nuclear features and patterns such as sheets, clusters, and rosettes. Prognosis tends to be more favorable in women, although overall survival rates remain relatively low. Treatment typically involves combined chemotherapy, often platinum-based, and radiation therapy. Unfortunately, targeted immunotherapy options are currently lacking.

Female, 78, small cell lung carcinoma. Photo Credit: The Human Protein Atlas

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Adenocarcinoma is a subtype of non-small cell lung carcinoma characterized by glandular differentiation, mucin production, or pneumocyte marker expression.

It manifests in five main histologic patterns, including: acinar, papillary, micropapillary, lepidic, and solid.

Notably, adenocarcinoma is more prevalent in certain demographics, such as females, nonsmokers, and individuals aged 60 to 70. Adenocarcinoma often arises from toxic cellular exposures leading to genetic mutations and subsequent proliferation of endobronchial cells. While smoking remains a significant risk factor for all types of lung cancer, including adenocarcinoma, the association is lower compared to other lung cancer subtypes. Additional risk factors include exposure to secondhand smoke, cooking oil fumes, and asbestos.

Clinical presentations of adenocarcinoma may include:

Cough (often productive with mucinous adenocarcinoma)
Hemoptysis
Dyspnea
Weight loss
Chest pain.

Unlike small cell lung carcinoma, adenocarcinoma is less frequently associated with paraneoplastic or endocrine syndromes. Diagnosis relies heavily on histological examination, often guided by radiological findings such as well-defined borders, lobulated or spiculated appearance, and presence of air bronchograms.

Prognosis for adenocarcinoma is generally favorable, especially when detected and treated early. Treatment strategies vary depending on the stage of the disease. Surgical resection, often followed by adjuvant radiation therapy, is recommended for early-stage disease. For more advanced cases, a combination of surgical resection, chemotherapy, and radiation therapy may be employed. Molecular-dependent chemotherapy has shown promise in inoperable or metastatic cases.

Male, 80 years, Adenocarcinoma, clear cell type. Photo Credit: The Human Protein Atlas.

Large cell carcinoma is a subtype of non-small cell lung carcinoma characterized by tumors that lack morphologic or immunohistochemical differentiation toward small cell carcinoma, adenocarcinoma, or squamous cell carcinoma.

It tends to affect individuals around 65 years old, with a higher incidence in males and a strong association with cigarette smoking.

Large cell carcinoma primarily arises in the peripheral lung, often presenting as solitary nodules.

Common symptoms include:

Cough
Chest pain
Shortness of breath.

Diagnosis is typically achieved through exclusion, ruling out other subtypes of lung cancer.

Diagnosis of large cell carcinoma often involves a combination of radiological imaging, histological examination, and immunohistochemical analysis. Once diagnosed, treatment options may include surgery, chemotherapy, and radiation therapy, depending on the stage and extent of the disease.

Grossly, large cell carcinoma typically presents as large, circumscribed tumors with well-defined borders and a homogeneous gray-white "fish flesh" cut surface. Microscopically, they consist of sheets or solid nests of round to polygonal cells with moderately abundant cytoplasm, vesicular nuclei, and prominent nucleoli. Foci of central necrosis and hemorrhage may also be present.

Fig. 1. Examples of undifferentiated LCC with a solid (A) and discohesive (B) growth pattern. Photo Credit: Science Direct.

Squamous cell carcinoma is a malignant tumor arising from epithelial cells with squamous differentiation. It can manifest as either keratinizing or nonkeratinizing forms.

This type of cancer has a strong association with a history of tobacco smoking, with approximately 80% of men and 90% of women affected. It primarily affects patients over 50 years of age and accounts for around 30% of non-small cell lung carcinomas.

Squamous cell carcinoma can arise in any site but is commonly found in central locations within the lung.

Common symptoms reported by patients include:

Cough
Chest pain
Shortness of breath
Hemoptysis
Wheezing
Weight loss
Recurrent infections
Loss of appetite, and
Fatigue.
Note: These symptoms can vary widely and are often nonspecific, making diagnosis challenging.

Diagnosis can be made through biopsy or cytology specimens. Imaging, particularly CT scans, is often used to evaluate lung cancer, revealing nonspecific masses with irregular borders, often accompanied by central cavitation.

Treatment may involve surgical excision through wedge resection, lobectomy, or pneumonectomy, depending on the extent of the disease. Additionally, systemic chemotherapy, including immunotherapy targeting PDL1 if applicable, and radiation therapy may be employed to manage the disease.

Grossly, squamous cell carcinoma often presents as a cavitary mass with white, smooth cut surfaces containing hemorrhage and necrosis. Microscopically, characteristics such as keratinization, intercellular bridging, inflammation, and necrosis are frequently observed, though not required for diagnosis.

Male, 72 years, poorly differentiated squamous cell carcinoma. Photo Credit: The Human Protein Atlas.

Test Your Knowledge

1. What are the main histologic patterns associated with adenocarcinoma?

a) Squamous, sarcomatoid, and neuroendocrine

b) Acinar, papillary, micropapillary, lepidic, and solid

c) Small cell, large cell, and bronchioloalveolar

d) Clear cell, chromophobe, and oncocytic

2. What is a significant risk factor for adenocarcinoma besides smoking?

a) Exposure to radon gas

b) Consumption of grilled meat

c) Exposure to secondhand smoke, cooking oil fumes, and asbestos

d) Lack of physical exercise

3. Which of the following is NOT typically a clinical presentation of adenocarcinoma?

a) Cough

b) Hemoptysis

c) Dyspnea

d) Palpitations

4. Which of the following is NOT a characteristic feature of large cell carcinoma on histological examination?

a) Sheets or solid nests of round to polygonal cells

b) Prominent nucleoli

c) Thin fibrous capsules

d) Moderately abundant cytoplasm

5. What is the primary method for diagnosing large cell carcinoma?

a) Blood tests

b) Genetic testing

c) Radiological imaging, histological examination, and immunohistochemical analysis

d) Urine analysis

6. What percentage of non-small cell lung carcinomas does squamous cell carcinoma account for?

a) Approximately 10%

b) Roughly 30%

c) Roughly 10%

d) Approximately 40%

7. Which diagnostic method is typically used to evaluate lung cancer?

a) CT scans

b) X-rays

c) Blood Test

d) MRI scans

8. What are common characteristics observed in squamous cell carcinoma on microscopy?

a) Glandular formation

b) Keratinization, intercellular bridging, inflammation, and necrosis

c) Papillary structures

d) Mucin production

PATHOLOGIES OF THE LUNGS

Smoking-Associated Lung Cancer

Test Your Knowledge