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Large-cell lung carcinoma (LCLC), or large-cell carcinoma (LCC) in short, is a heterogeneous group of undifferentiated malignant neoplasms that lack the cytologic and architectural features of small cell carcinoma and glandular or squamous differentiation. LCC is categorized as a type of NSCLC (non-small-cell lung carcinoma) that originates from epithelial cells of the lung. LCLC is histologically characterized by the presence of large, undifferentiated cells that lack distinctive features of either squamous cell carcinoma or adenocarcinoma (other types of cancers). Typically seen in LCLC tumor cells are abundant pale staining cytoplasm and prominent nucleoli.

Presentation

The clinical presentation of LCLC is nonspecific and can include symptoms such as:

1. Persistent cough
2. Shortness of breath/pain with breathing
3. Chest pain
4. Unintentional weight loss
5. General fatigue
6. Coughing up blood (hemoptysis)
7. Frequent upper respiratory infections (URIs)
8. Difficulty swallowing
9. Hoarseness

Diagnosis

LCC is, in effect, a "diagnosis of exclusion", in that the tumor cells lack light microscopic characteristics that would classify the neoplasm as a small-cell carcinoma, squamous-cell carcinoma, adenocarcinoma, or other more specific histologic type of lung cancer.

Tools used for diagnosis:

Imaging Studies: Chest X-rays, CT scans, PET, or PET-CT scans are the most commonly used imaging modalities to help identify the size, location, and extent of the tumor.

Biopsy: Done by obtaining a piece of tissue from the tumor, classically done through bronchoscopy or CT guided needle biopsy, to study the histology of the tissue and confirm diagnosis.

Classification

The newest revisions of the World Health Organization (WHO) "Histological Typing of Lung Cancer schema" include several variants of LCC, including:

• large cell neuroendocrine carcinoma
• basaloid carcinoma
• lymphoepithelioma-like carcinoma
• clear cell carcinoma
• large cell carcinoma with rhabdoid phenotype.

Large-cell neuroendocrine carcinoma (LCNEC)

One clinically significant subtype is "large-cell neuroendocrine carcinoma" (LCNEC), which is believed to derive from neuroendocrine cells.

In addition, a "subvariant", called "combined large-cell neuroendocrine carcinoma" (or c-LCNEC), is recognized under the new system. To be designated a c-LCNEC, the tumor must contain at least 10% LCNEC cells, in combination with at least 10% of other forms of NSCLC.

Pathology images

Incidence

In most series, LCLC's comprise between 3%-9% of all primary lung cancers.

According to the Nurses' Health Study, the risk of large cell lung carcinoma increases with a previous history of tobacco smoking, with a previous smoking duration of 30 to 40 years giving a relative risk of approximately 2.3 compared to never-smokers, and a duration of more than 40 years giving a relative risk of approximately 3.6.

Another study concluded that cigarette smoking is the predominant cause of large cell lung cancer. It estimated that the odds ratio associated with smoking two or more packs/day for current smokers is 37.0 in men and 72.9 in women.

Notable people with the condition include American comedian Andy Kaufman, who died from the disease in 1984.

Treatment options

Treatment often requires a multidisciplinary approach, which will vary based on factors such as the extent of the tumor and the condition and comorbidities of the patient.

1. Surgery: Surgical resection may be considered for local tumors.
2. Chemotherapy: Standard treatment of LCLC. Often use of platinum-based agents with other cytotoxic drugs are used to target the tumor. Due to overall prognosis chemotherapy often may offer increased chance to improve survival.
3. Targeted Therapy: A type of treatment that targets specific features of the cell to minimize damaging healthy cells and to reduce side effects of the treatment.
4. Immunotherapy: A form of treatment that boosts the body's natural immune defense system to apprehend the cancer cells.

References

1. ^ Midthun. "UpToDate". www.uptodate.com.
2. Tazelaar. "UpToDate". www.uptodate.com.
3. "Lung Cancer - Non-Small Cell - Symptoms and Signs". Cancer.Net. 25 June 2012.
4. ^ Weissferdt, Annikka. "ClinicalKey". www.clinicalkey.com.
5. Fernandez FG, Battafarano RJ (October 2006). "Large-cell neuroendocrine carcinoma of the lung". Cancer Control. 13 (4): 270–275. doi:10.1177/107327480601300404. PMID 17075564.
6. Cotran RS, Kumar V, Fausto N, Robbins SL, Abbas AK (2005). Robbins and Cotran pathologic basis of disease. St. Louis, Mo: Elsevier Saunders. p. 762. ISBN 978-0-7216-0187-8.
7. Smokers defined as current or former smoker of more than 1 year of duration. See image page in Commons for percentages in numbers. Reference:
   • Table 2 in: Kenfield SA, Wei EK, Stampfer MJ, Rosner BA, Colditz GA (June 2008). "Comparison of aspects of smoking among the four histological types of lung cancer". Tobacco Control. 17 (3): 198–204. doi:10.1136/tc.2007.022582. PMC 3044470. PMID 18390646.
8. Kenfield SA, Wei EK, Stampfer MJ, Rosner BA, Colditz GA (June 2008). "Comparison of aspects of smoking among the four histological types of lung cancer". Tobacco Control. 17 (3): 198–204. doi:10.1136/tc.2007.022582. PMC 3044470. PMID 18390646.
9. Muscat JE, Stellman SD, Zhang ZF, Neugut AI, Wynder EL (July 1997). "Cigarette smoking and large cell carcinoma of the lung". Cancer Epidemiology, Biomarkers & Prevention. 6 (7): 477–480. PMID 9232332.
10. "Large Cell Lung Carcinoma". Lung Cancer Foundation of America.

External links

• . World Health Organization Histological Classification of Lung and Pleural Tumours. 4th Edition.

• Lung cancer