OVERVIEW
是一组主要起源于气管和支气管壁小涎腺的肿瘤
可出现呼吸困难、咳嗽、咳痰、咯血、喘息等症状
病因不明，可能与基因突变有关
诊断一旦明确应尽早开始治疗，以手术治疗为主
Definition
Lung salivary gland tumors are a group of tumors that originate mainly in the minor salivary glands of the tracheal and bronchial walls.
Salivary glands, also known as salivary glands, are divided into major and minor salivary glands, with three pairs of major salivary glands: parotid, submandibular, and sublingual glands; and minor salivary glands, which are mainly located in the oral cavity, paranasal sinuses, and bronchi, under the mucosa.
The histologic features of this disease are similar to those of salivary gland tumors, and the incidence is low.
Staging
Depending on whether they originate in the lung tissue or not, they can be divided into primary pulmonary salivary gland tumors and secondary pulmonary salivary gland tumors.
Primary pulmonary salivary gland tumors
According to the World Health Organization (WHO) 2021 criteria for histologic staging of lung tumors, the disease can be staged as follows.
腺样囊性癌（adenoid cystic carcinoma，ACC）
Low-grade ACC has a favorable prognosis, and high-grade MEC behaves similarly to other non-small cell carcinomas.
It consists of two cellular components, adenoepithelial and myoepithelial, arranged in three structures, sieve, tubular and solid, with sieve structure being the most common and an important morphologic clue for diagnosis.
黏液表皮样癌（mucoepidermoid carcinoma，MEC）
This type can be further categorized into two types, low-grade and high-grade, with a relatively good prognosis.
Low-grade MEC contains 3 cellular components, namely mucous cells, epidermal cells and intermediate cells, with cystadenoid and solid nested mass structures, and unremarkable nuclear schizophrenia and cellular anisotropy.
High-grade MEC consisted mainly of atypical epidermal and intermediate cells, with variable numbers of mucous cells and predominantly solid nested structures, accompanied by readily apparent nuclear schizophrenia and marked cellular anisotropy.
上皮肌上皮癌（myoepithelioma carcinoma，EMC）
Lung Primary EMC Clinically very rare, it is a low-grade malignant epithelial tumor with a biphasic morphology that is usually clinically inert with rare cases of metastasis. It consists of spindle-shaped, clear or plasma cell-like myoepithelial cells and cuboidal ductal epithelial cells.
多形性腺瘤（Pleomorphic adenoma，PA）
The tumor consists of ductal epithelial cells, myoepithelial cells, and mucinous cartilage-like stroma. Most PAs are benign tumors, and malignant changes are rare.
其他
Other rare types are clear cell carcinoma with vitreous transformation and myoepithelioma and myoepithelial carcinoma.
Secondary pulmonary salivary gland-type tumors
This refers to the metastasis of salivary gland-type tumors from other sites to the lungs, such as parotid and submandibular glands.
Pathogenesis
Primary pulmonary salivary gland tumors are a rare group of lung tumors, accounting for less than 1% of primary lung tumors [1] .
They develop in the trachea and bronchi and can be central or peripheral, with a higher incidence in the lower lobe of the left lung.
The most common clinical pathologic types of primary pulmonary salivary gland type tumors are MEC and ACC.
Etiology
Pathogenesis
Primary pulmonary salivary gland tumors
The etiology of primary pulmonary salivary gland-type tumors is currently unknown and may be related to genetic mutations.
It has been found that MYB gene translocations are detected in primary adenoid cystic carcinoma of the lung.
Approximately 38% to 81% of MECs have a gene mutation [t(11; 19)(q21; p13)], which leads to the expression of the fusion oncogene CRTC1-MAML2 [3].
Secondary pulmonary salivary gland-type tumors
Most of them have a clear etiology and are caused by metastasis of primary tumors from other sites to the lungs.
It can be through blood metastasis, lymphatic metastasis and direct infiltration.
Symptoms
The clinical manifestations of primary pulmonary salivary gland tumors are not specific, and the tumor may be asymptomatic when it occupies <30% of the tracheal lumen, and respiratory symptoms may appear when it occupies >75%; secondary pulmonary salivary gland tumors may have symptoms caused by the primary tumor in addition to respiratory symptoms.
Main symptoms
Dyspnea
Dyspnea is the first symptom in some patients.
Most of them manifest as chest tightness, shortness of breath, and some patients may have chest pain.
Cough and sputum
Cough is the most common symptom of lung cancer patients when they visit the doctor, and many patients have coughing symptoms at the time of consultation.
It is mostly irritating dry cough without sputum or with a little white mucus sputum.
Hemoptysis or blood in sputum
Some patients may experience hemoptysis.
It usually manifests as blood in the sputum, hemoptysis is rare.
Wheezing
This is characterized by shortness of breath, and in severe cases, a wheezing sound may be heard.
Hoarseness
Hoarseness is caused when the recurrent laryngeal nerve is involved.
Foreign body sensation in the pharynx
Most often caused by direct tumor invasion or lymph node metastasis compressing the esophagus.
Fever
It can be caused by necrosis of tumor tissue or secondary pneumonia (such as obstructive pneumonia).
Fever is characterized by delayed and repeated, sometimes good and sometimes bad, and difficult to be cured.
Intermittent moderate or low fever is common, and high fever may be present when combined with infection.
Other symptoms
Patients with secondary pulmonary salivary gland type tumors may have symptoms caused by the primary tumor.
The tumor may cause consumption, loss of appetite, etc., resulting in the patient experiencing malaise with weight loss.
Medical Treatment
Department of Medicine
Respiratory Medicine
Please consult the Department of Respiratory Medicine when symptoms such as dyspnea, cough, hemoptysis or blood in sputum, wheezing, etc. occur.
Thoracic Surgery
Please consult the Department of Thoracic Surgery when nodules or space-occupying lesions in the lungs are detected by chest imaging (X-ray, chest CT, etc.), or when surgical treatment is required after diagnosis.
Medical Oncology
When a patient is diagnosed with a salivary gland-type tumor of the lung, he/she can go to the Department of Medical Oncology to receive systematic and standardized treatment if he/she needs drug treatment.
Preparation
Consultation: Registration, Preparation of Documents, Frequently Asked Questions
Consultation Tips
Chest X-rays or CT scans may be required. Please avoid wearing metallic clothing such as buttoned shirts, sequined tops, and dresses with zipper openings.
Checklist for preparing for medical treatment
症状清单
The time of onset of symptoms, special manifestations, etc., should be taken into consideration.
Has there been coughing and sputum, and for how long?
Is there any blood in the sputum or hemoptysis?
Is there any chest tightness, shortness of breath or even dyspnea, and how long has it been?
Is there any unexplained weight loss?
Is there any fever and what is the highest temperature?
病史清单
Is there any past history of other malignant tumors? For example, parotid adenocarcinoma, cancer of submaxillary gland, etc.
Are you a smoker, for how long and how many cigarettes per day?
Any drug or food allergies?
检查清单
Test results in the last six months, which can be brought to the doctor’s office
Laboratory tests: routine blood, urine, stool, blood biochemistry tests
Imaging tests: lung biopsy pathology report, chest X-ray or CT report, magnetic resonance imaging (MRI), PET-CT, tumor markers.
Diagnosis
Diagnosis is based on
Medical history.
The patient may have the following medical history:
History of parotid adenocarcinoma.
History of cancer of the submandibular gland.
Clinical manifestations
症状
Patients may present with dyspnea, cough, hemoptysis or blood in sputum, and wheezing.
体征
Early patients may have no obvious signs.
Some patients may have palpable enlarged superficial lymph nodes.
Laboratory tests
血常规检查
Can clarify whether the patient has infection, anemia, thrombocytopenia, etc., to help determine the condition of the disease, the next step in the treatment.
生化检查
Help to initially determine whether the liver and kidney functions are abnormal, whether there are electrolyte disorders, dyslipidemia, etc., to guide the next step of treatment.
肿瘤标志物检查
Tumor marker test can help the auxiliary diagnosis of the disease, efficacy judgment and follow-up monitoring.
Imaging
胸部X线
It is still the basic examination method to detect lesions including lungs, especially in primary hospitals.
It has limited diagnostic value for early lung salivary gland type tumors, and once suspected, chest CT should be performed promptly.
CT检查
Chest CT is the most important and commonly used imaging examination method in the diagnosis, staging, efficacy evaluation and post-treatment follow-up of this disease.
For lung lesions that are difficult to be diagnosed qualitatively, percutaneous lung puncture biopsy can be performed under CT guidance, and lung tissue can be removed for pathological biopsy.
CT examination of other parts of the body, including the brain, liver, and adrenal glands, can help doctors clarify whether there are distant metastases.
MRI检查
It can help determine whether the chest wall or mediastinum has been invaded by a tumor, and differentiate the boundary between hilar masses and atelectasis and obstructive pneumonia.
MRI of the cranium, brain, abdomen and other parts of the body can help determine whether there are metastases.
超声检查
Ultrasonography is mainly applied to the observation of metastasis in superficial lymph nodes, liver, adrenal glands, kidneys and other parts and organs, providing information for tumor staging.
Ultrasound-guided puncture can be used for puncture biopsy of metastases in lung occupancy, enlarged lymph nodes, and parenchymal organs, and specimens can be obtained for histological examination.
正电子发射计算机断层显像（PET-CT）
PET-CT is the best method for diagnosis, staging and restaging, efficacy evaluation and prognosis assessment.
Histologic examination
Pathological diagnosis of lung biopsy specimens is mainly to clarify the presence or absence of tumor and the histological type of tumor, which is the “gold standard” for final diagnosis.
Differential diagnosis
Lung salivary gland tumors are mainly differentiated from other types of lung tumors, such as lung adenocarcinoma and lung adenosquamous carcinoma.
Lung adenocarcinoma
Similarity: both may present with symptoms such as dyspnea, cough, sputum, hemoptysis and blood in sputum.
Differences:
肺腺癌细胞异型性较大，肺泡上皮标志物（TTF1、Napsin A）阳性。
腺样囊性癌细胞异型性较小，TTF1和Napsin A阴性，腺上皮细胞标志物（CK8/18、CK7）和肌上皮细胞标志物（S-100蛋白、Calponin、CD10）均为阳性。
Lung adenosquamous carcinoma
Similarity: both may present with symptoms such as dyspnea, cough, sputum, hemoptysis, and blood in sputum.
Differences:
高级别MEC需重点与肺腺鳞癌相鉴别。
MEC的黏液细胞TTF1和Napsin A阴性，肺腺鳞癌的腺上皮细胞常TTF1和Napsin A阳性。
如果腺鳞癌中的腺癌成分为黏液型和肠型腺癌，则TTF1和Napsin A均可阴性，在这种情况下，基因检测对鉴别诊断至关重要，检测到MAML2基因易位则可排除腺鳞癌，支持MEC。
Treatment
Aim of treatment: maximize the resection of the tumor, improve the therapeutic effect, and improve the quality of life of the patients.
Treatment principle: once the diagnosis of pulmonary salivary gland tumor is clear, the treatment should be started as early as possible, and surgery is the main treatment.
Tips: For more information about treatment, please refer to the related disease articles.
Surgery
At present, primary pulmonary salivary gland-type tumors are low-grade malignant tumors, and surgical treatment is the mainstay, and complete resection of the tumor is applicable to tumors of all pathological grades. There is no uniform understanding of the need for adjuvant treatment such as radiotherapy and chemotherapy after surgery.
Some studies point to surgical resection as the best initial treatment option. When removing the lesion site by surgery, care is taken to maintain the integrity of the tumor resection and negative margins.
Surgical resection modalities include lobectomy, bronchial segmental resection + end-to-end anastomosis, and localized resection of bronchial masses.
For tumors that cannot be resected surgically, partial tumor resection or palliative treatment can be used.
Other treatments
Bronchoscopic interventions may be used as an initial treatment for patients who are clinically at a higher clinical stage or as a transitional treatment to initial treatment prior to surgery. Thermal therapies such as ablation or coagulation of tumors in the airways include electrocautery, argon plasma coagulation (APC), and cryotherapy.
For secondary pulmonary salivary gland-type tumors, different treatment measures such as radiotherapy, chemotherapy, and targeted therapy are used depending on the primary tumor.
Prognosis
Cure
The prognosis for different types of salivary gland tumors varies.
Primary pulmonary salivary gland tumors have a long course, slow progression, usually low-grade tumors, less likely to develop distant metastases, with 5-year and 10-year survival rates of 65% and 35%, respectively [8].
肺原发黏液表皮样癌（MEC）通常外科手术治疗可以治愈，但部分病例会在几年后复发。
低级别腺样囊性癌（ACC）具有良好的预后，高级别MEC的表现与其他非小细胞癌相似。
肺原发ACC具有惰性生物学行为，局部复发（通常是多次）可能在手术切除后10～15年，最终可能发生远处转移。
大部分多形性腺瘤（PA）为良性肿瘤，经过手术切除并保证肿瘤切除的完整性和切缘的阴性，常预后较好。
Secondary pulmonary salivary gland tumors are metastatic tumors of salivary gland origin from other parts of the body that metastasize to the lungs, and most of them are in the advanced stages of the disease with a relatively poor prognosis.
Special reminder.
The 5-year/10-year survival rate refers to the proportion of patients whose tumors survive for more than 5/10 years after various comprehensive treatments, and does not mean that patients can only survive for 5 or 10 years.
Survival rates are statistics used in clinical research, usually based on the results of previous studies of large populations with a particular cancer (e.g., staging), and these statistics do not predict nor represent the survival of any individual.
Prognostic Factors
Prognostic factors
The smaller the tumor diameter and the younger the patient, the better the prognosis.
Low-grade MEC has a better prognosis than high-grade MEC.
Poor prognostic factors
Patients with incomplete surgical resection (positive resection margins) have a poorer prognosis.
The larger the tumor diameter and the older the patient, the worse the prognosis.
Patients who develop lymph node metastases have a relatively poor prognosis.
Daily
Daily Management
Dietary management
Reasonable arrangement of diet, pay attention to eat more nutritious and easy-to-digest food.
Intake of fresh fruits and vegetables rich in vitamins can supplement the vitamins needed by the body and promote recovery.
Eat more protein-rich foods, such as eggs, milk, lean meat and fish.
Cold, raw, stimulating, pickled, fried and deep-fried foods, such as fried chicken and chili peppers, should be avoided.
Life management
Avoid exertion, regular work and rest, and ensure sufficient sleep.
Proper exercise is needed in daily life to improve physical fitness and avoid low immunity.
Maintain a healthy body weight and take appropriate activities, such as slow walking, tai chi, qigong and breathing exercises.
Psychological support
Maintain a good mood and mindset to face the disease positively.
Learn to confide in friends and family members to avoid excessive pressure, which may cause mental illness, and seek help from a psychiatrist if necessary.
Patients should establish a correct understanding of the disease, accept treatment positively, and do work and housework to the best of their ability during and after treatment, so as to reintegrate into social roles.
Family members should provide adequate companionship to the patient, create a cozy family atmosphere, comfort the patient and help him/her get through the difficult time.
Disease monitoring
Patients should pay attention to observe their own condition in daily life. If symptoms such as dyspnea, cough, sputum, hemoptysis, blood in sputum, wheezing, etc. recur, they should consult a doctor in time.
Follow-up
The main purpose of follow-up is to detect tumor recurrence or second primary cancer earlier and intervene in a timely manner to improve the overall survival and quality of life of patients.
It is recommended to follow the doctor’s instructions for regular checkups, and if there is any discomfort, please consult the doctor at any time.
Prevention
The etiology of pulmonary salivary gland tumors is unknown, and there is no precise and effective preventive measure, it is recommended that annual health checkups may help to reduce the incidence of the disease.
参考文献
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