Large-cell lung carcinoma

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Large-cell carcinoma
Specialty Oncology/pulmonology

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. [1] LCC is categorized as a type of NSCLC (non-small-cell lung carcinoma) which 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. [2]

Contents

Presentation

The clinical presentation of LCLC is nonspecific and can include symptoms such as: [3]

  1. Persistent cough
  2. Shortness of breathe/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. [1]

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. [1]

Classification

The newest revisions of the World Health Organization (WHO) "Histological Typing of Lung Cancer schema" include several variants of LCC, including: [4]

Large-cell neuroendocrine carcinoma (LCNEC)

One clinically significant subtype is "large-cell neuroendocrine carcinoma" (LCNEC), [5] which is believed to derive from neuroendocrine cells. [6]

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

Pie chart showing incidence of large-cell lung cancer (shown in green at upper left) as compared to other lung cancer types, with fractions of smokers versus non-smokers shown for each type. Pie chart of lung cancers.svg
Pie chart showing incidence of large-cell lung cancer (shown in green at upper left) as compared to other lung cancer types, with fractions of smokers versus non-smokers shown for each type.

In most series, LCLC's comprise between 3%-9% of all primary lung cancers. [4]

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. [8]

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. [9]

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

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. [10]

Related Research Articles

<span class="mw-page-title-main">Lung cancer</span> Malignant tumor characterized by uncontrolled cell growth in lung tissue

Lung cancer, also known as lung carcinoma, is a malignant tumor that begins in the lung. Lung cancer is caused by genetic damage to the DNA of cells in the airways, often caused by cigarette smoking or inhaling damaging chemicals. Damaged airway cells gain the ability to multiply unchecked, causing the growth of a tumor. Without treatment, tumors spread throughout the lung, damaging lung function. Eventually lung tumors metastasize, spreading to other parts of the body.

<span class="mw-page-title-main">Adenocarcinoma</span> Medical condition

Adenocarcinoma is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, or both. Adenocarcinomas are part of the larger grouping of carcinomas, but are also sometimes called by more precise terms omitting the word, where these exist. Thus invasive ductal carcinoma, the most common form of breast cancer, is adenocarcinoma but does not use the term in its name—however, esophageal adenocarcinoma does to distinguish it from the other common type of esophageal cancer, esophageal squamous cell carcinoma. Several of the most common forms of cancer are adenocarcinomas, and the various sorts of adenocarcinoma vary greatly in all their aspects, so that few useful generalizations can be made about them.

<span class="mw-page-title-main">Small-cell carcinoma</span> Type of malignant cancer

Small-cell carcinoma is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tract. Compared to non-small cell carcinoma, small cell carcinoma is more aggressive, with a shorter doubling time, higher growth fraction, and earlier development of metastases.

<span class="mw-page-title-main">Grading (tumors)</span> Measure of the cell appearance in tumors and other neoplasms

In pathology, grading is a measure of the cell appearance in tumors and other neoplasms. Some pathology grading systems apply only to malignant neoplasms (cancer); others apply also to benign neoplasms. The neoplastic grading is a measure of cell anaplasia in the sampled tumor and is based on the resemblance of the tumor to the tissue of origin. Grading in cancer is distinguished from staging, which is a measure of the extent to which the cancer has spread.

<span class="mw-page-title-main">Non-small-cell lung cancer</span> Any type of epithelial lung cancer other than small-cell lung carcinoma

Non-small-cell lung cancer (NSCLC), or non-small-cell lung carcinoma, is any type of epithelial lung cancer other than small-cell lung cancer (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to small-cell carcinoma. When possible, they are primarily treated by surgical resection with curative intent, although chemotherapy has been used increasingly both preoperatively and postoperatively.

<span class="mw-page-title-main">Adenocarcinoma in situ of the lung</span> Medical condition

Adenocarcinoma in situ (AIS) of the lung —previously included in the category of "bronchioloalveolar carcinoma" (BAC)—is a subtype of lung adenocarcinoma. It tends to arise in the distal bronchioles or alveoli and is defined by a non-invasive growth pattern. This small solitary tumor exhibits pure alveolar distribution and lacks any invasion of the surrounding normal lung. If completely removed by surgery, the prognosis is excellent with up to 100% 5-year survival.

Neuroendocrine carcinoma of the cervix is best defined separately:Neuroendocrine: Of, relating to, or involving the interaction between the nervous system and the hormones of the endocrine glands.Carcinoma: An invasive malignant tumor derived from epithelial tissue that tends to metastasize to other areas of the body.

<span class="mw-page-title-main">Combined small-cell lung carcinoma</span> Medical condition

Combined small cell lung carcinoma is a form of multiphasic lung cancer that is diagnosed by a pathologist when a malignant tumor, arising from transformed cells originating in lung tissue, contains a component of;small cell lung carcinoma (SCLC), admixed with one components of any histological variant of non-small cell lung carcinoma (NSCLC) in any relative proportion.

Treatment of lung cancer refers to the use of medical therapies, such as surgery, radiation, chemotherapy, immunotherapy, percutaneous ablation, and palliative care, alone or in combination, in an attempt to cure or lessen the adverse impact of malignant neoplasms originating in lung tissue.

Large cell lung carcinoma with rhabdoid phenotype (LCLC-RP) is a rare histological form of lung cancer, currently classified as a variant of large cell lung carcinoma (LCLC). In order for a LCLC to be subclassified as the rhabdoid phenotype variant, at least 10% of the malignant tumor cells must contain distinctive structures composed of tangled intermediate filaments that displace the cell nucleus outward toward the cell membrane. The whorled eosinophilic inclusions in LCLC-RP cells give it a microscopic resemblance to malignant cells found in rhabdomyosarcoma (RMS), a rare neoplasm arising from transformed skeletal muscle. Despite their microscopic similarities, LCLC-RP is not associated with rhabdomyosarcoma.

Epithelial-myoepithelial carcinoma of the lung is a very rare histologic form of malignant epithelial neoplasm ("carcinoma") arising from lung tissue.

Targeted therapy of lung cancer refers to using agents specifically designed to selectively target molecular pathways responsible for, or that substantially drive, the malignant phenotype of lung cancer cells, and as a consequence of this (relative) selectivity, cause fewer toxic effects on normal cells.

HOHMS is the medical acronym for "Higher-Order HistoMolecular Stratification", a term and concept which was first applied to lung cancer research and treatment theory.

Mucinous cystadenocarcinoma of the lung (MCACL) is a very rare malignant mucus-producing neoplasm arising from the uncontrolled growth of transformed epithelial cells originating in lung tissue.

<span class="mw-page-title-main">Adenocarcinoma of the lung</span> Medical condition

Adenocarcinoma of the lung is the most common type of lung cancer, and like other forms of lung cancer, it is characterized by distinct cellular and molecular features. It is classified as one of several non-small cell lung cancers (NSCLC), to distinguish it from small cell lung cancer which has a different behavior and prognosis. Lung adenocarcinoma is further classified into several subtypes and variants. The signs and symptoms of this specific type of lung cancer are similar to other forms of lung cancer, and patients most commonly complain of persistent cough and shortness of breath.

Adenosquamous lung carcinoma (AdSqLC) is a biphasic malignant tumor arising from lung tissue that is composed of at least 10% by volume each of squamous cell carcinoma (SqCC) and adenocarcinoma (AdC) cells.

Basaloid squamous cell carcinoma (Bas-SqCC) is an uncommon histological variant of lung cancer composed of cells exhibiting cytological and tissue architectural features of both squamous cell lung carcinoma and basal cell carcinoma.

Basaloid large cell carcinoma of the lung, is a rare histological variant of lung cancer featuring certain distinctive cytological, tissue architectural, and immunohistochemical characteristics and clinical behavior.

<span class="mw-page-title-main">Squamous-cell carcinoma of the lung</span> Medical condition

Squamous-cell carcinoma (SCC) of the lung is a histologic type of non-small-cell lung carcinoma (NSCLC). It is the second most prevalent type of lung cancer after lung adenocarcinoma and it originates in the bronchi. Its tumor cells are characterized by a squamous appearance, similar to the one observed in epidermal cells. Squamous-cell carcinoma of the lung is strongly associated with tobacco smoking, more than any other forms of NSCLC.

Pulmonary neuroendocrine tumors are neuroendocrine tumors localized to the lung: bronchus or pulmonary parenchyma.

References

  1. 1 2 3 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. 1 2 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:
  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.
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