Sarcomatoid carcinoma of the lungs



OVERVIEW

Definition.

Pulmonary sarcomatoid carcinomas (PSCs) are a group of very poorly differentiated non-small cell lung cancers (NSCLCs) with sarcoma or sarcomatoid components.

It usually occurs in older men who are heavy smokers.

PSCs have a poor prognosis compared to other types of NSCLC, even in the early stages of the disease.

Classification.

According to the World Health Organization (WHO 2015 version) histologic classification of lung tumors, the disease can be divided into five subtypes.

Pleomorphic carcinoma (PC)

The most common, accounting for more than 50% of cases, is a group of NSCLC containing spindle and/or giant cells or consisting only of spindle and/or giant cell components, with at least a 10% spindle and/or giant cell component; these NSCLC can be squamous cell carcinomas, adenocarcinomas, or large cell carcinomas.

Spindle cell carcinoma (SCC)

NSCLC composed almost entirely of spindle-shaped tumor cells that lack the architecture of adenocarcinoma, squamous cell carcinoma, giant cell carcinoma, or large cell carcinoma is clinically rare.

Giant cell carcinoma (GCC)

NSCLC composed of polymorphic multinucleated and or mononuclear tumor giant cells, the tumor consists of large, multinucleated and odd-nucleated cells, the nuclei of the tumor cells have obvious polymorphism, the nuclei are lobulated, the adherence between the tumor cells is poor, and abundant inflammatory cell infiltration can be seen in the mesenchyme, which is extremely rare.

Carcinosarcoma (CS)

It is a mixed malignancy consisting of a non-small cell lung cancer component (mainly squamous or adenocarcinoma) and a sarcoma component (rhabdomyosarcoma, chondromyxoid sarcoma, and osteosarcoma). The tumor shows bidirectional differentiation, and the two may be clearly demarcated from each other, or they may be present in a mixed manner, and it accounts for only 4% of lung sarcomatoid carcinomas.

Pulmonary blastoma (PB)

A rare malignant tumor containing a primitive epithelial component and a primitive mesenchymal component resembling a well-differentiated fetal adenocarcinoma, occasionally a bi-directional tumor of chondrosarcoma, chondroma, or rhabdomyosarcoma. Pneumoblastoma histologically shows a bi-directional differentiated form of malignant gland.

Incidence

Sarcomatoid carcinoma of the lung is very rare, accounting for 0.1% to 1.3% of all lung malignancies [2].

It can occur in both lungs, with a prevalence of the peripheral type in the upper lobe of the right lung [3].

It is prevalent in middle-aged and elderly males and is more common in smokers, with the majority of cases occurring at an age of <80 years [3].

Etiology

Causes

Smoking

Smoking is the most common cause of lung sarcomatoid carcinoma. Smoking tobacco in the form of cigarettes, cigars or pipes can lead to the disease.

The longer you smoke and the more you smoke, the higher the incidence and mortality of lung sarcomatoid cancer.

Genetic Abnormalities

Patients with lung sarcomatoid cancer may have multiple genetic abnormalities, the most common of which are EGFR, TP53, KRAS, ALK, PIK3CA and MET.

Environmental factors

Long-term exposure to asbestos and electrically insulating substances are also important risk factors for lung sarcomatoid carcinoma.

Symptoms

Main Symptoms

Clinical symptoms and signs of lung sarcomatoid carcinoma are nonspecific, mainly related to the location of the lesion and the size of the mass, and may have the following manifestations.

Cough and sputum

Cough is a common symptom of lung sarcomatoid cancer.

Most of them have dry cough, no sputum or a little white mucus sputum.

Blood in sputum

Usually manifested as blood in sputum, hemoptysis is rare.

Chest pain, dyspnea

Some patients may present with chest pain, chest tightness, shortness of breath, or even dyspnea.

Fever

It can be caused by necrosis of tumor tissues or by secondary pneumonia (e.g. obstructive pneumonia).

Fever is characterized by delayed and repeated, sometimes good and sometimes bad, difficult to cure.

Other symptoms

Some advanced cancer patients may develop malignant disease, which is characterized by extreme emaciation, weakness, general exhaustion and other symptoms.

Consultation

Department of Medicine

Thoracic Surgery

Please consult the Department of Thoracic Surgery if nodules or space-occupying lesions in the lungs are found on chest imaging (X-ray, chest CT, etc.) during a routine physical examination or other tests.

Oncology

When lung sarcomatoid carcinoma is diagnosed and anti-tumor treatment such as radiotherapy and chemotherapy is required, please consult the Department of Medical Oncology.

Respiratory Medicine

Please consult the Department of Respiratory Medicine when symptoms such as dry cough, blood in sputum and chest pain occur.

Preparation for medical treatment

Preparation for consultation: registration, preparation of documents, common problems

Tips for Medical Treatment: Registration, Preparation of Documents, Frequently Asked Questions

Patients may need to undergo a chest X-ray or CT examination. Please avoid wearing metal clothing such as shirts with buttons, blouses with sequins, and dresses with zipper buttons.

Patients who need a lung puncture should stop taking aspirin for at least 7 days before the puncture to avoid bleeding, please consult your doctor for details.

Checklist for Preparing for a Visit to the Doctor

Particular attention should be paid to the time of onset of symptoms, special manifestations, etc.

Is there a cough and for how long?

Is there blood in the sputum? What is the amount of blood?

Is there any chest pain, dyspnea?

Has there been a recent change in weight? How is your appetite?

Are you a smoker, for how long and how many cigarettes per day?

Any exposure to carcinogens such as asbestos?

Is there a family history of malignant tumors such as lung cancer?

Any allergies to medications or foods?

Test results in the last six months, which can be brought to the doctor’s office

Specialized tests: lung biopsy pathology report, chest X-ray or CT report, tumor markers.

Laboratory tests: blood test, urine test, stool test, biochemical test.

Imaging tests: magnetic resonance imaging (MRI), PET-CT.

Diagnosis

Diagnosis is based on

Medical history

The patient may have the following medical history.

History of prolonged heavy smoking.

History of exposure to carcinogens such as asbestos.

Family history of cancer.

Clinical manifestations

In the early stage, there are mostly no obvious symptoms. As the disease progresses, symptoms such as dry cough, coughing up sputum, blood in sputum, chest pain, dyspnea, fever, weight loss, and generalized weakness may appear.

Imaging

The most commonly used examinations in clinic are chest CT and PET-CT.

Lung sarcomatoid carcinoma lacks specificity in imaging manifestations, and can occur in any lung lobe or segment, with peripheral type predominating, preferably in the upper lobe of the right lung.

Most of them are isolated round or round-like soft tissue density masses with a diameter of >3cm, mostly lobulated, with uneven density, clear borders and relatively few burr signs.

After enhancement, the tumor periphery shows uneven thickness ring enhancement, and necrosis is common in the center, and it often invades the pleura, chest wall, and adjacent mediastinal or intrapulmonary blood vessels.

Positron emission tomography CT (PET-CT) may be performed if the patient has multiple metastases or if the indication for enhanced CT is unclear.

Fiberoptic bronchoscopy

For central lung sarcomatoid carcinoma, bronchoscopy can directly observe the lesion inside the bronchus and can take part of the tissue for pathological biopsy.

However, the tumors of this disease are mostly located in the periphery, so sputum cytology and bronchoscopy are not very helpful in diagnosing this disease.

Pathologic examination

The diagnosis of lung sarcomatoid carcinoma relies on surgery or biopsy specimens to be clarified by pathology and immunohistochemistry, which is the “gold standard” for final diagnosis.

Microscopically, the tumor is mainly composed of epithelium and sarcoma or sarcomatoid mesenchyme, and the sarcoma or sarcomatoid component is dominant, and the epithelial component is mostly squamous or adenocarcinoma.

Immunohistochemistry: ripple protein, a biological marker of mesenchymal cells, is often positively expressed in the carcinoma component, and cytokeratin, an epithelial marker, is often positively expressed in the sarcomatoid component.

Differential diagnosis

Pulmonary synovial sarcoma

Similarities: Both may present with cough, blood in sputum, and chest pain.

Differences: synovial sarcoma is usually characterized by heterogeneous CK staining, non-expression of TTF-1, and the presence of SS18-SSX gene fusion or X;18 translocation.

Intrapulmonary thymoma

Similarities: Both may present with cough, blood in sputum, and chest pain.

Differences: thymoma cells are mild, without naive mesenchymal components, without obvious nucleoli and nuclear schizophrenia, immunohistochemistry expresses CD20, and also expresses broad-spectrum CK, EMA, vimentin, and low or no expression of p53 and Ki-67.

Pneumocystic myofibroblastoma

Similarity: Both may present with cough, sputum or blood in sputum.

Differences: Pneumocystic myofibroblastoma mostly occurs in children and young adults, and the immunophenotype may cross with PSC, but most express ALK with ALK gene rearrangement.

Pulmonary spindle cell malignant melanoma

Similarities: Both may have symptoms of cough and blood in sputum.

Differences: pulmonary spindle cell malignant melanoma has a prominent nucleus, visible pigmentation, and expresses Melan-A, S-100, and HMB-45. primary malignant peripheral nerve sheath tumor of the lung: expresses S-100, NSE, etc., and does not express CK.

Treatment

Aim of treatment: maximize the elimination of tumor, improve the quality of life of patients and prolong the survival time.

Treatment principle: once the diagnosis of lung sarcomatoid carcinoma is clear, treatment should be started as early as possible, with surgical resection as the first choice of treatment.

Surgery

Surgery is a more effective treatment option for early-stage patients, but the recurrence rate after surgery is still high.

Meanwhile, because this disease is not sensitive to radiotherapy, complete resection of tumor is very necessary.

[Tips] This disease is a special type of lung cancer, for more about surgical treatment, please refer to read Lung Cancer.

Radiotherapy and chemotherapy treatment

Since PSC is easily resistant to conventional chemotherapy and has low response to radiotherapy, it is rarely applied alone in general clinical practice.

Further exploration and support from evidence-based medicine and clinical evidence is needed regarding the role of neoadjuvant therapy.

Frontline treatment

Currently, the treatment of pulmonary sarcomatoid carcinoma is still a major challenge, and studies have shown that targeted therapy and immunotherapy are expected to be novel treatment strategies for patients with this disease.

Targeted therapy

Some studies have reported that the mutation rates of EGFR, KRAS and MET in patients with lung sarcomatoid carcinoma are 8%, 22% and 16%, respectively, and therefore better therapeutic effects may be obtained by applying the corresponding target inhibitors [7].

For example, EGFR exon 19 deletion can be treated with gefitinib; ALK fusion gene positivity and post-transcriptional deletion of exon 14 of MET gene mutation, the application of crizotinib is highly effective.

Immunotherapy

Retrospective studies have reported a high incidence of PD-L1 expression in patients with this disease. 69.2% (9/13) of patients were reported to be positive for PD-L1 [8]. This implies that the application of PD-L1 monoclonal antibody for the treatment of this disease may benefit patients, but further clinical trials and studies are needed to confirm this.

Prognosis

Cure

Lung sarcomatoid carcinoma has an insidious onset, nonspecific clinical manifestations, low incidence, high aggressiveness, easy early metastasis, high mortality rate, short average survival, and poor prognosis.

It has been reported in the literature that the 5-year survival rate of surgical resection of pulmonary sarcomatoid carcinoma ranges from 12.6% to 54.3%, with nearly half of them experiencing postoperative recurrence [1].

Vascular invasion is present in 90% of patients with lung sarcomatoid carcinoma, so early metastases to lung, bone, adrenal gland and brain are likely to occur [1].

Prognostic factors

Prognostic factors are factors that have an impact on the overall survival and quality of life of patients.

The prognosis of this disease is related to age, tumor size and tissue type, and the older the age, the larger the tumor (length diameter > 5 cm), and the more mesenchymal components, the worse the prognosis.

KRAS gene mutations suggest poor prognosis and treatment resistance.

Daily

Daily management

Lifestyle

Abstain from smoking and alcohol, avoid exertion, have a regular routine, avoid staying up late, and ensure sufficient sleep.

Maintain a healthy weight, take appropriate activities such as slow walking, tai chi, qigong, breathing exercises, etc., and avoid crowded places.

Diet management

Reasonable dietary arrangements, so as to achieve a light diet, balanced nutrition, and a variety of food types.

Intake of vitamin-rich fresh fruits and vegetables can supplement the vitamins needed by the body and promote recovery.

Eat more protein-rich food, 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.

Psychological support

Maintain a good mood and mindset and 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 psychiatrists 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 their social roles.

Family members should provide adequate companionship to the patient, create a cozy family atmosphere, comfort the patient and help him/her to tide over the difficult times.

Disease monitoring

Patients should pay attention to the sputum condition and seek medical advice if there is blood in the sputum or even hemoptysis again.

Follow-up

Follow-ups are very important for patients to help the doctor assess the efficacy of the treatment and to monitor whether there is a recurrence of the disease.

The time for follow-up should be set by the specialist.

Review items: tumor markers, chest X-ray, chest CT, brain MRI and other tests can help determine whether there is recurrence and metastasis.

Prevention

There is no specific preventive measure for lung sarcomatoid carcinoma, which can start from reducing or avoiding the risk factors causing the disease.

Smoking cessation

Smoking is an important risk factor for the disease, you should quit smoking (including cigarette, e-cigarette, etc.) and stay away from passive smoking.

Take occupational precautions

People who are at risk of occupational exposure should take proper protective measures to avoid exposure to carcinogenic substances such as asbestos and electrical insulation.

Regular screening

Annual health checkups are recommended to help detect diseases at an early stage.