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A case of sudden death of a young woman with a lipoma of the pontocerebellar angle has been illustrated. The deceased presented episodes of migraine, which were never clinically investigated. The post-mortem examination depicted a single pathological cause responsible for the death, which consisted of an expansive intr... |
## Footnotes |
## REFERENCES |
8a7962212ffe7aa27ea9cfe482da42f7b49d7705a0ab49373e74b10a7c3eed89 pmc9422988.txt |
TITLE: Adenocarcinoma of the lung |
REVID: 1368833512 |
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 an... |
Adenocarcinoma is more common in patients with a history of cigarette smoking, and is the most common form of lung cancer in younger women and Asian populations. The pathophysiology of adenocarcinoma is complicated, but generally follows a histologic progression from cells found in healthy lungs to distinctly dysmorphi... |
Treatment of this lung cancer is based upon the specific subtype and the extent of spread from the primary tumor. Surgical resection, chemotherapy, radiotherapy, targeted therapy and immunotherapy are used in attempt to eradicate the cancerous cells based upon these factors. |
== Signs and symptoms == |
The majority of patients who are diagnosed with lung cancer usually present with locally advanced or metastatic disease. Only about one third of patients have stage I disease when diagnosed. The symptoms that the patient exhibits usually reflect the extent of the cancer's spread. Lung cancers that are discovered early ... |
Cough that does not go away or gets worse |
Weight loss |
Dyspnea (shortness of breath or difficulty breathing) |
Chest pain, which may be aggravated by deep breathing, coughing, or laughing |
Hemoptysis (coughing up blood or rust-colored phlegm) |
Bone pain |
Clubbing |
Fever |
Generally feeling tired or weak |
Superior vena cava obstruction- facial, neck, upper torso swelling. This is caused by compression of vasculature by the lung tumor that restricts blood return from the upper body. |
Dysphagia (trouble swallowing or the sensation that something is caught in the throat) and hoarseness |
New onset of wheezing without history of asthma |
Clinicians should have a high level of suspicion for lung cancer, especially in patients with a smoking history. Patients with recurring or unresolving lung infections (e.g. bronchitis and pneumonia) that are unresponsive to antibiotics should also be further evaluated for lung cancer. In nonsmokers, women and East Asi... |
Importantly, many of these signs are commonly due to other causes that are not cancer. |
=== Extrapulmonary manifestations === |
The most common paraneoplastic syndromes associated with adenocarcinoma of the lung are described below: |
Hypercalcemia of malignancy is more common in squamous cell carcinoma of the lung, but can occur in adenocarcinoma as well. Parathyroid hormone-related peptide (PTHrP) is produced by tumor cells and functions similarly to parathyroid hormone (PTH). The production of this hormonally active peptide by cancer cells causes... |
Hypertrophic pulmonary osteoarthropathy (HPO) is fairly rare in adenocarcinoma. Less than 1% of patients with adenocarcinoma of the lung will exhibit this finding, but when it does occur, it is a poor prognostic factor. The exact mechanism of HPO is unknown but it is thought to be hormonal or neurogenic in etiology. Th... |
== Causes == |
=== Risk factors === |
According to the Nurses' Health Study, the risk of pulmonary adenocarcinoma increases substantially after a long duration of tobacco smoking: smokers with a previous smoking duration of 30–40 years are more than twice as likely to develop lung adenocarcinoma compared to never-smokers (relative risk of approximately 2.4... |
This cancer usually is seen peripherally in the lungs, as opposed to small cell lung cancer and squamous cell lung cancer, which both tend to be more centrally located, although it may also occur as central lesions. For unknown reasons, it often arises in relation to peripheral lung scars. The current theory is that th... |
== Mechanism == |
=== Pathogenesis === |
Large scale studies such as The Cancer Genome Atlas (TCGA) have systematically characterized recurrent somatic alterations likely driving lung adenocarcinoma initiation and development. |
==== Gene mutations and copy number alterations ==== |
Since smoking is a strong mutagenic factor, lung adenocarcinoma is one of the tumor types with the highest number of mutations. Common somatic mutations in lung adenocarcinoma affect many oncogenes and tumor suppressor genes, including TP53 (mutated in 46% of cases), EGFR (27%), KRAS (32%), KEAP1, STK11 and NF1. EGFR a... |
Copy number amplifications in oncogenes such as TERT, Mdm2, EGFR, MET, and Myc have been reported, as well as deletions of tumor suppressor genes such as CDKN2A. |
Frequent alterations occur in genes belonging to the receptor tyrosine kinase pathway, of which EGFR is the most prominent example. This pathway is involved in cell proliferation and survival and it is often deregulated in cancer. As a consequence, targeted therapies have been developed to inhibit mutant pathway compon... |
==== Chromosomal rearrangements ==== |
Three membrane associated tyrosine kinase receptors are recurrently involved in fusions or rearrangements in adenocarcinomas: ALK, ROS1, and RET, and more than eighty other translocations have also been reported in adenocarcinomas of the lung. |
In ALK rearrangements, the most common partner gene is EML4. |
=== Pathophysiology === |
The respiratory tract can be divided into two main components: the conducting airways and the gas exchange airways. The gas exchange airways are made of alveoli, small microscopic air sacs that are responsible for the exchange of oxygen and carbon dioxide during normal breathing. Alveoli are composed of two cell types,... |
There are several factors that contribute to the transformation of normal alveolar epithelium into dysplastic, or pre-cancerous, lesions. Adenocarcinoma of the lung develops in a step-wise progression as type II pneumocytes undergo consecutive molecular changes that disrupt normal cell regulation and turnover. Atypical... |
== Diagnosis == |
A diagnosis of lung cancer may be suspected on the basis of typical symptoms, particularly in a person with smoking history. Symptoms such as coughing up blood and unintentional weight loss may prompt further investigation, such as medical imaging. |
=== Classification === |
The majority of lung cancers can be characterized as either small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC). Lung adenocarcinoma is one of the three major subtypes of NSCLC, which also include squamous carcinoma and large cell carcinoma. |
Historically, there has been much debate in the most accurate method of describing adenocarcinoma of the lung and several revisions of classification systems have been published. Most recently, the International Multidisciplinary Classification of Lung Adenocarcinoma was published in 2011 and represents the consensus o... |
The tumor size, pattern of cell growth, and depth of cell invasion into normal lung tissue are considered in determining classification. The following names represent a step-wise pathologic progression in the natural course of adenocarcinoma development; Adenocarcinoma in situ (AIS), Minimally invasive adenocarcinoma (... |
The 2011 consensus describes five subtypes of invasive adenocarcinomas based on the cell pattern that is most predominant. These subtypes are described below: |
lepidic predominant |
acinar predominant |
papillary predominant |
micropapillary predominant |
solid predominant with mucin production |
Cell patterns identifying subtypes are associated with prognosis, ranging from favorable (lepidic) to intermediate (acinar and papillary) to poor (micropapillary and solid). |
Four discrete variants of invasive adenocarcinomas not assignable to these five subtypes are also included in the current classification: |
invasive mucinous adenocarcinoma |
colloid adenocarcinoma |
fetal adenocarcinoma |
primary pulmonary enteric adenocarcinoma |
=== Imaging === |
CT imaging provides better evaluation of the lungs, with higher sensitivity and specificity for lung cancer compared to chest radiograph (although still significant false positive rate). Computed tomography (CT) that is specifically aimed at evaluating lung cancer includes the chest and the upper abdomen. This allows f... |
Nuclear medicine imaging, such as PET/CT and bone scan, may also be helpful to diagnose and detect metastatic disease elsewhere in the body. PET/CT uses a metabolically active tracer that allows clinicians to identify areas of the body that are hypermetabolic. Increased uptake of the tracer occurs in malignant cells an... |
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