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Pulmonary Pathology Online

Pathology of Bronchogenic Carcinoma (Lung Cancer)

Dr Sampurna Roy MD    

 

                                                                                                                      

 

Bronchogenic carcinoma the lung are by far the most common malignancies of this organ and constitute the leading cause of cancer morbidity and mortality worldwide.

Histologically, adenocarcinomas appear to be the most common histologic type of lung cancer diagnosed, while squamous cell carcinoma appears to be more commonly associated with tobacco use.

Bronchogenic carcinoma constitutes 90 to 95% of lung tumours.

It is the most common cause of cancer death in both men and women.

New pathologic classification of lung cancer: relevance for clinical practice and clinical trials. J Clin Oncol. 2013 Mar 10;31(8):992-1001

We summarize significant changes in pathologic classification of lung cancer resulting from the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) lung adenocarcinoma classification. The classification was developed by an international core panel of experts representing IASLC, ATS, and ERS with oncologists/pulmonologists, pathologists, radiologists, molecular biologists, and thoracic surgeons. Because 70% of patients with lung cancer present with advanced stages, a new approach to small biopsies and cytology with specific terminology and criteria focused on the need for distinguishing squamous cell carcinoma from adenocarcinoma and on molecular testing for EGFR mutations and ALK rearrangement. Tumors previously classified as non-small-cell carcinoma, not otherwise specified, because of the lack of clear squamous or adenocarcinoma morphology should be classified further by using a limited immunohistochemical workup to preserve tissue for molecular testing. The terms "bronchioloalveolar carcinoma" and "mixed subtype adenocarcinoma" have been discontinued. For resected adenocarcinomas, new concepts of adenocarcinoma in situ and minimally invasive adenocarcinoma define patients who, if they undergo complete resection, will have 100% disease-free survival. Invasive adenocarcinomas are now classified by predominant pattern after using comprehensive histologic subtyping with lepidic, acinar, papillary, and solid patterns; micropapillary is added as a new histologic subtype with poor prognosis. Former mucinous bronchioloalveolar carcinomas are now called "invasive mucinous adenocarcinoma." Because the lung cancer field is now rapidly evolving with new advances occurring on a frequent basis, particularly in the molecular arena, this classification provides a much needed standard for pathologic diagnosis not only for patient care but also for clinical trials and TNM classification.

Pathogenesis:

Tobacco smoking is well established as the most important and common etiologic factor in the development of lung cancer.

- Statistically, there is an unequivocal link between the frequency of lung cancer and the number of pack-years of smoking.

- Clinically, hyperplastic and atypical changes can be seen in the bronchial epithelium of smokers and in the vicinity of bronchial cancer.

- Experimentally, there are numerous known carcinogens in cigarette smoke (Eg., polycyclic aromatic hydrocarbons).

Other etiologic factors include exposure to radiation (atomic bomb survivors, uranium miners), asbestos (especially combined with smoking), air pollution (radon, particulates), and miscellaneous occupational inhaled substances (Example: Nickel, chromates, arsenic).

Genetic mechanisms implicated include dominant oncogenes (Example: K-ras, in adenocarcinomas) and loss of tumor-suppressor genes.

Read: The new IASLC/ATS/ERS lung adenocarcinoma classification from a clinical perspective: current concepts and future prospects. J Thorac Dis. 2014 Oct;6

The new the International Association for the Study of Lung Cancer (IASLC)/the American Thoracic Society (ATS)/the European Respiratory Society (ERS) pathologic classification of lung cancer has markedly changed the pathologic diagnosis of lung adenocarcinoma. This classification deals with many aspects that directly affect clinical practice, and opens new gateways for future research. By means of a multidisciplinary approach, it differs significantly from the former 2004 the World Health Organization (WHO) classification, which was mainly written by pathologist. The present review, in line with the consensus article, is divided in two components: the diagnosis and classification of lung adenocarcinoma in resection specimens and the diagnosis of lung cancer in small biopsies and cytology. Resection specimens are currently classified according to the predominant histologic pattern after comprehensive subtyping in 5% increments. This approach has led to the addition of new pathologic subtypes [adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and micropapillary predominant adenocarcinoma)] and to the discontinuation of some heterogeneous entities included in the former 2004 WHO classification (mixed subtype adenocarcinoma and bronchioloalveolar carcinoma). Overall, these changes have resulted in a better stratification of lung adenocarcinoma tumors in more homogeneous morphologic, clinical and biological subgroups. Pathologic subtyping has demonstrated prognostic utility in resected stage I-III patients, and recent data support their predictive role for the benefit of adjuvant chemotherapy. Moreover, comprehensive pathologic subtyping may potentially affect TNM staging and surgical management or early-stage tumors. On the other hand, for the first time, the novel pathologic classification provides standardized terminology and diagnostic criteria of small biopsies and cytology. Criteria are proposed not only for adenocarcinoma but also for other histologies, but special emphasis was put on the distinction between adenocarcinoma and squamous-cell carcinoma due to its major clinical implications.

 

Clinical features of Bronchogenic Carcinoma:

They usually occur in the sixth to seventh decades of life.

The clinical symptoms depend largely on the anatomic location of the tumour and its size.

Tumours with a central location are more likely to produce early symptoms such as cough, dyspnea, wheezing, hemoptysis, and pneumonia.

Tumours that are located in the periphery of the lung need to attain a relatively large size before they become symptomatic.

Some types of symptoms may be correlated with certain types of malignancy. For instance, bronchorrhea (expectoration of large amounts of mucus) is more commonly seen in invasive mucinous adenocarcinoma.

In other instances, symptoms such as pleuritic pain, Pancoast syndrome, or superior vena cava syndrome develop when there is extensive tumour burden within the thorax.

In addition, non–small cell carcinomas may also be associated with other conditions such as bronchiectasis, pulmonary fibrosis, tuberculosis and other infectious processes.

Bronchogenic carcinomas usually present with cough, weight loss, chest pain, and dyspnea.

Paraneoplastic syndromes associated with bronchogenic carcinoma often occur due to release of the following hormones:

- Antidiuretic hormone (syndrome of inappropriate antidiuretic hormone release).

- Adrenocorticotropic hormone (Cushing’s syndrome).

- Parathormone or prostaglandin E (hypercalcemia)

- Calcitonin (hypocalcemia)

- Gonadotropin (gynecomastia)

- Serotonin (carcinoid syndrome)

Other paraneoplastic syndromes include myopathy, peripheral neuropathy, acanthosis nigricans, and hypertrophic osteoarthropathy (Example: clubbing of fingers).

Overall 5-year survival is approximately 9%. Surgical resection of solitary (non-small cell) tumours offers some improved survival (30 to 40% - 5-year survival) for a minority of patients with localized disease.

The use of more advanced radiological techniques such as magnetic resonance imaging and computerized tomography has greatly improved the detection of lung cancer.

Further reading:

Preoperative serum carcinoembryonic antigen level is a prognostic factor in women with early non-small-cell lung cancer.

Clinicopathologic study of resected, peripheral, small-sized, non-small cell lung cancer tumors of 2 cm or less in diameter: pleural invasion and increase of serum carcinoembryonic antigen level as predictors of nodal involvement.

Non-small cell lung cancer in the young: a retrospective analysis of diagnosis, management and outcome data.

Impact of large tumor size on survival after resection of pathologically node negative (pN0) non-small cell lung cancer. 

Pattern of recurrence after curative resection of local (stage I and II) non-small cell lung cancer: difference according to the histologic type.

Long-term results of pathological stage I non-small cell lung cancer: validation of using the number of totally removed lymph nodes as a staging control.

Characteristics and prognosis of patients after resection of nonsmall cell lung carcinoma measuring 2 cm or less in greatest dimension.

The prognostic significance of intranodal isolated tumor cells and micrometastases in patients with non-small cell carcinoma of the lung.

Prognostic markers in resectable non-small cell lung cancer: a multivariate analysis.

Predictive survival markers in patients with surgically resected non-small cell lung carcinoma. 

Conventional clinicopathologic prognostic factors in surgically resected nonsmall cell lung carcinoma. A comparison of prognostic factors for each pathologic TNM stage based on multivariate analyses. 

Pathological-radiological correlations: pathological and radiological correlation of endobronchial neoplasms: part II, malignant tumors.

Tumour regression in non-small-cell lung cancer following neoadjuvant therapy. Histological assessment. 

How reliable is the diagnosis of lung cancer using small biopsy specimens? Report of a UKCCCR Lung Cancer Working Party. 

Bronchogenic carcinoma: radiologic-pathologic correlation.

Pathology of carcinoma of lung: an update on current concepts.

Changing patterns of lung cancer incidence by histological type.

 

 

Dr Sampurna Roy  MD

Consultant  Histopathologist (Kolkata - India)

 


 

 

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