Clinical manifestations
The common first symptoms of lung cancer in women are mainly cough, hemoptysis, fever, chest pain, chest tightness and shortness of breath, etc. Some of them start with extra-pulmonary symptoms, such as back pain, bone pain, bone and joint swelling, limb pain, muscle weakness, convulsions, ataxia, nausea and vomiting, hoarseness, swelling of upper limbs and face, drooping eyelids, etc.
Other less common first symptoms include abdominal pain, neck mass, electrolyte disturbance, and personality changes. Other patients do not have any symptoms and are only found to have the disease during routine physical examination. In addition, the clinical manifestations of lung cancer in women have the following special features.
A number of studies suggest that female patients are more common among young and middle-aged lung cancer patients. It was found that among 20,561 lung cancer patients, the average age of onset of female patients was less than that of male patients (60 years vs. 62 years), and women were more common among patients <50 years old; young women accounted for 23.3% of the total number of female lung cancer patients, compared to 12.6% for men.
Most lung cancers are prone to misdiagnosis and most of the first symptoms are atypical, as is the case with female lung cancers, and some of them also start with extra-pulmonary symptoms, making the diagnosis more difficult. It is worth noting that because women are prone to autoimmune diseases, some of those who start with limb pain and joint swelling are sometimes misdiagnosed as autoimmune diseases such as rheumatoid arthritis.
A study analyzed the clinical characteristics of 198 female lung cancer patients and found that 109 cases had metastasis at the time of first diagnosis. Common metastatic sites of lung cancer include brain, bone, intrapulmonary, liver, neck and supraclavicular lymph nodes, while women should also be alert to ovarian metastasis.
Specific clinical manifestations.
The age of onset is young, easy to be misdiagnosed, and metastasis has already occurred by the time of detection.
Pathology and markers.
The common pathological type is adenocarcinoma, and the attention to CEA should be enhanced.
Imaging and fibrinoscopy.
Mainly peripheral type, often combined with medium-large amount of pleural fluid; microscopically, infiltrative type is more common.
Molecular biology: p53, K-ras mutation rate is high, EGFR mutation is more frequent in Eastern, female, non-smoking, adenocarcinoma patients.
Diagnosis
Early diagnosis
Sputum cytology conventional sputum exfoliative cytology screening for lung cancer has low sensitivity, and the sputum detection rate may be even lower in women because of the predominance of peripheral type of lung cancer, but there are no relevant reports in the literature.
Tumor markers CEA are more significant for the diagnosis of lung adenocarcinoma, while CYFRA211 and SCC-Ag are mostly seen in squamous lung cancer, and ProGRP and NSE are commonly seen in small cell lung cancer (SCLC). Because the common pathological type of lung cancer in women is adenocarcinoma, the attention to CEA should be enhanced.
Hormone levels in SCLC in women may also secrete a variety of ectopic hormones, including gonadotropins, adrenocorticotropins, antidiuretic hormones, and chorionic gonadotropins, which should be differentiated from pulmonary metastases from choriocarcinoma.
Imaging examination
Chest X-ray and chest CT female lung cancer also has certain characteristics in chest X-ray and chest CT, mainly peripheral type, which is commonly seen as lung masses, but also as lamellar shadows, pulmonary atelectasis and obstructive pneumonia, widened mediastinal shadow, cavity, etc. A few may have no abnormalities. Because peripheral type lung cancer easily invades the pleura, pleural effusion is also an important manifestation. It is now believed that low-dose spiral CT can reduce the radiation dose and does not significantly affect the detection and diagnostic accuracy of lung lesions, which is of greater importance for female patients.
Ultrasound is generally used for localization prior to pleural fluid puncture, determination of pericardial effusion, and examination of superficial lymph nodes and masses. Women with lung cancer often have a combination of moderate-to-large amounts of pleural fluid, and often require ultrasound localization followed by pleural fluid puncture for symptomatic relief.
Head MRI, bone scan, PET-CT Female patients should undergo head magnetic resonance imaging (MRI) and bone scan at the first visit to determine whether there are brain metastases and bone metastases, and positron emission tomography (PET)-CT is also necessary to clarify the metastases throughout the patient’s body.
Invasive tests
Fiberoptic bronchoscopy is the most commonly used invasive examination method for lung cancer diagnosis because of its simpler operation and less invasive nature.
Female lung cancer lesions are mostly located in the right lung, but may also occur in the left lung or both lungs, and less frequently in the trachea and ramus. The microscopic manifestations can be broadly divided into four types, with the infiltrative type being the most common.
(1) Proliferative type, with cauliflower-like or polyp-like neoplasms in the bronchi;
(2) Infiltrative type, with congestion, edema, thickening and erosion of the bronchial mucosa, centripetal narrowing of the lumen, and indistinct tracheal rings;
③External pressure type, the trachea or bronchial wall is deformed by pressure, but the mucosal surface is normal;
In the normal type, the bronchial lumen and mucosa are not abnormal, and a small amount of secretion and bleeding can be seen individually. Given that peripheral type lung cancer is more common in women, the positive rate of fiberoptic bronchoscopy alone may be low, and transbronchoscopic needle aspiration biopsy (TBNA) may also be considered as appropriate.
Percutaneous transluminal lung biopsy is more common in women with peripheral lung cancer. When bronchoscopy is more difficult to diagnose, percutaneous transluminal lung biopsy may be considered as a priority.
Other invasive examinations can be considered more actively when pathology may not be obtained by the above methods, such as mediastinoscopy for clarifying the nature of enlarged mediastinal lymph nodes; medical thoracoscopy mainly for checking whether there is pleural fluid and pleural invasion; open chest biopsy, although more invasive, should be performed as much as possible if the patient’s general condition allows when there is a high clinical suspicion of lung tumor and other methods cannot make a definite diagnosis.
Examination of extra-pulmonary metastases
Some female lung cancer patients already have metastases from other sites at the first visit, so when it is difficult to obtain tissues from the primary site, we can also consider obtaining tissues from metastatic sites to assist in diagnosis, such as pleural fluid, pericardial effusion, pleura, lymph nodes, liver, bone marrow and cerebrospinal fluid.
Clinicopathology and molecular biology
The molecular variation of female lung cancer also has its own characteristics. Currently in clinical work, the routine detection of gene mutations is relatively limited and still needs to be further explored.
P53 gene mutations are present in lung cancer patients and are strongly associated with smoking. Some studies have shown that the rate of p53 mutations is significantly higher in women who smoke than in non-smoking women and men who smoke.
K-ras gene mutations are higher in female smokers than in male smokers and are mostly associated with adenocarcinogenesis, which may suggest a poor prognosis, but in nonsmoking women with lung cancer, K-ras is hardly expressed.
EGFR mutations EGFR is the first tyrosine kinase erB family member found to be encoded by a proto-oncogene. Current studies suggest that EGFR mutations are more prevalent in Eastern, female, non-smoking, adenocarcinoma patients and that EGFR-tyrosine kinase inhibitors (TKI) may be effective.
HER2/neuHER2/neu is mostly expressed in adenocarcinoma in non-small cell lung cancer (NSCLC) and has a higher mutation rate in oriental, female, non-smokers.HER2 is associated with prognosis in female lung cancer patients.
Estrogen receptor (ER) An increasing number of studies suggest that estrogen may play an important role in the development of lung cancer. there are two main subtypes of ER, ERα and ERβ. However, it is still controversial whether there are gender differences in ERβ expression in lung cancer tissues.
DNA hypermethylation studies revealed that some genes were hypermethylated in lung cancer tissues, among which hypermethylation of KCNH5, CNH8, and RARB was more common in women.
The expression of c-Met is present in C-Met lung cancer tissues, but there are no reports on whether there are gender differences in its expression. Some studies suggest that c-Met is significantly expressed in lung adenocarcinoma, but not strongly expressed in squamous carcinoma. However, the difference in c-Met expression between pathological subtypes was not significant. Therefore, it is also more difficult to try to infer expression differences in gender from the differences in c-Met expression in different pathological types).
EML4-ALK is currently considered a new target for NSCLC. Shaw (Shaw) et al. selectively selected 141 NSCLC cases based on the criteria of at least 2 of female, Asian, mild or nonsmoking adenocarcinoma, and detected 19 (13%) EML4-ALK cases, 18 of which were adenocarcinomas and 1 adenosquamous carcinoma; there was no overlap in the occurrence of the 3 mutations. Therefore, the investigators concluded that EML4-ALK is mostly seen in adenocarcinoma, young, non-smokers or light smokers, but its expression characteristics in women need to be further investigated.