2 Pathology and classification

The lungs are respiratory organs located above the diaphragm within the thoracic cavity, on both sides of the mediastinum, one on the left and one on the right. The lungs are cone-shaped, with one apex, one base, three surfaces, and three edges. The structure of the left lung root from top to bottom: left pulmonary artery, left main bronchus, left inferior pulmonary vein; the structure of the right lung root from top to bottom: right main bronchus, right pulmonary artery, right inferior pulmonary artery. The physiological functions of the lungs mainly include external respiration (lung ventilation and gas exchange) and internal respiration (transport of gases in the blood and regulation of respiratory movements). (2) Pathology and classification

1. Classified by anatomical location Those located at the periphery of the lung are called peripheral type, accounting for about 30% of all lung cancers, usually more common in adenocarcinoma, with cancer tissue often growing below the segmental bronchi and their branches; those near the hilum are called central type, accounting for about 70% of all lung cancers, with cancer tissue growing in the main bronchi or lobar bronchi, usually more common in squamous cell carcinoma and undifferentiated carcinoma. In addition, there are also very few lung cancers that grow in the trachea or at the bifurcation of the bronchi, but this is extremely rare.
2. Classified by histopathology (1) Non-small cell lung cancer ① Squamous cell carcinoma (commonly referred to as squamous carcinoma): commonly seen in middle-aged and elderly men, closely related to smoking, more common in the central type because it often invades the bronchi above the segmental level and grows under the mucosa, easily causing bronchial stenosis, leading to atelectasis and obstructive pneumonia in the early stages of the disease. Squamous carcinoma tissue is prone to degeneration and necrosis, forming cavities, abscesses, and bleeding. Typical squamous carcinoma cells are arranged in a squamous epithelial pattern, with polygonal shapes and nuclear division, and intercellular bridges or keratin pearls may appear between cancer cells. Squamous carcinoma cells grow relatively slowly and metastasize later, but often cause local rib destruction. Because metastasis occurs late, there are more opportunities for surgery, resulting in a higher five-year survival rate. ② Adenocarcinoma: including alveolar adenocarcinoma, papillary adenocarcinoma, bronchioloalveolar carcinoma, etc., this type of cancer is more common in women, especially middle-aged and elderly women, and is not closely related to smoking. Cancer tissue tends to invade the bronchi below the segmental level, so among peripheral lung cancers, this type is more common. Cancer cells often have a papillary structure, with relatively consistent cell size, large nuclei and clear nucleoli, darker staining, and clearer nuclear membranes. Cancer tissue is prone to metastasis, mainly through hematogenous spread, so metastatic lesions are often found in the brain, liver, bones, and other organs, and of course also frequently metastasize to the pleura, causing bloody pleural effusion. ③ Large cell carcinoma: including giant cell carcinoma and transparent cell carcinoma. Can occur in the bronchi near the hilum or at the periphery of the lung. Cells are larger, metastasis is less common than in undifferentiated carcinoma, and there are greater chances for surgical removal. ④ Others: adenosquamous carcinoma, carcinoid tumor, sarcomatoid carcinoma, salivary gland carcinoma, etc. (2) Small cell lung cancer: including oat cell type, intermediate cell type, and composite oat cell type. Cancer cells are mostly round or rhomboid, with little cytoplasm, resembling lymphocytes. Oat cell type and intermediate type may originate from the neural ectoderm. The cytoplasm contains neuroendocrine granules, with secretory and chemical receptor functions, capable of secreting peptide substances, which can cause carcinoid syndrome. Small cell lung cancer often has already metastasized to the hilum and lymph nodes in the early stages of development, and because it invades blood vessels, most cases already have extra-pulmonary metastases at the time of diagnosis. II. Diagnosis and treatment (---) Clinical diagnosis Anyone aged 40 or above, especially men with a long history of smoking, who presents with any of the following symptoms, should undergo further examination to rule out lung cancer. ① Irritative cough lasting more than two weeks. ② Persistent hemoptysis. ③ Unilateral or localized wheezing. ④ Recurrent pneumonia in the same area. ⑤ Pulmonary abscess of unknown cause, recurring repeatedly, with ineffective drug treatment. ⑥ Limb joint pain and clubbing of fingers of unknown cause. ⑦ Localized emphysema or atelectasis on X-ray. If any of the above symptoms exist, diagnosis can be confirmed through X-rays, CT scans, exfoliative cytology, bronchoscopy, and biopsy. X-ray examination shows that peripheral lung cancers are circular or nearly circular, with lobes inside, serrated edges or umbilical-like indentations, lighter density in the early stages and increasing in the later stages, with clear boundaries. Central lung cancers often show irregular masses at the hilum, formed by the fusion of primary cancer with metastases from hilar lymph nodes and mediastinal lymph nodes; CT scan advantages lie in its ability to detect small lesions and lesions located behind the heart, beside the spine, at the lung apex, near the diaphragm, and at the rib heads, and CT can also detect enlargement of hilar and mediastinal lymph nodes early, making it easier to determine whether tumors have invaded adjacent organs, thus enhancing the value of CT compared to plain radiography; magnetic resonance imaging has superiority over CT in clarifying the relationship between tumors and major blood vessels; PET-CT, by injecting contrast agents, accelerates the metabolism of lung cancer cells compared to normal cells, increasing glucose uptake, and the injected glucose accordingly accumulates in large quantities within tumor cells, thus being useful for qualitative diagnosis of lung cancer and lymph node metastasis; the more times exfoliative cytology samples are submitted, the higher the positive rate, but sputum samples must be fresh and smear staining completed within one hour, otherwise cells dissolve and are difficult to identify, affecting detection rates. Pleural fluid can be subjected to exfoliative cytology after centrifugal sedimentation; bronchoscopy is particularly important for diagnosing central lung cancers, directly allowing observation of the condition of bronchial tumors and enabling pathological biopsy of suspicious tissues, as well as brushing for exfoliative cytology; biopsy involves surgically removing superficial enlarged lymph nodes, such as supraclavicular and axillary lymph nodes, performing pathological examination, which can determine the type of primary cancer cells and is helpful for judging the possibility of surgical removal and further determining chemotherapy plans. Biopsy can also be performed via fine needle percutaneous puncture under CT guidance; endoscopic examination is an important diagnostic method for lung cancer; bronchoscopic ultrasound endoscopy uses ultrasound to perform percutaneous biopsy of tumors closely attached to the bronchi and trachea; thoracoscopy is a minimally invasive surgical technique; tumor markers such as carcinoembryonic antigen (CEA), squamous cell antigen (SCC), sialic acid (SA), and neuron-specific enolase (NSE) all have certain reference value for diagnosing lung cancer; thoracotomy is for patients with strong suspicion of lung cancer, such as those who, despite examination by the above methods, still cannot be diagnosed and meet all conditions for lobectomy, should promptly undergo thoracotomy to avoid delaying treatment. (2) Western medical treatment Western medical treatment plans are mainly based on the type of tumor tissue and the stage of the tumor. Usually, when small cell lung cancer is discovered, it has already metastasized, making radical surgical cure difficult, so reliance is mainly placed on chemotherapy, radiotherapy, and interventional therapy. In contrast, non-small cell lung cancer can often be cured by surgery or radiotherapy, but the response to chemotherapy is poorer than that of small cell lung cancer. Interventional therapy can achieve good results in the treatment of lung cancer. 1. Treatment of non-small cell lung cancer Stage I and II non-small cell lung cancer should be treated surgically. Stage IIIa patients, if age, cardiopulmonary function, and anatomical position are suitable, can also consider surgery. Stage III patients or Stage I and II patients who cannot tolerate surgery can consider radical radiotherapy. Radiotherapy radiation can damage lung parenchyma and other organs in the chest, such as the spinal cord, heart, and esophagus, which is one of its drawbacks. Preoperative chemotherapy, radiotherapy, and interventional therapy can improve efficacy for some patients. For some patients, especially Stage III patients, postoperative chemotherapy, radiotherapy, and interventional therapy are also necessary. For disseminated lesions, non-small cell lung cancer patients who cannot undergo surgery have a 70% poor prognosis. (1) Chemotherapy: Common chemotherapy regimens for non-small cell lung cancer include NP regimen, TP regimen, DP regimen, PC regimen, TCB regimen, etc. (2) Targeted therapy: For patients with EGFR mutations and those with ≥3 brain metastases, first-line recommended TKIs include first-generation (gefitinib, erlotinib, icotinib), second-generation (afatinib), third-generation (osimertinib), TKI+ chemotherapy, and chemotherapy + bevacizumab (non-squamous), while anlotinib can be chosen as third-line. ALK inhibitors such as crizotinib, ceritinib, and alectinib, anti-angiogenic drugs such as bevacizumab, and ROS1 gene-positive advanced NSCLC patients should prioritize crizotinib treatment. (3) Immunotherapy: Immune checkpoint inhibitors such as pembrolizumab, nivolumab, and atezolizumab have been approved by the FDA for treating advanced NSCLC. (4) Interventional therapy ① Intravascular interventional therapy: mainly includes bronchial arterial infusion chemotherapy (BAI) and bronchial arterial chemoembolization (BAE). ② Non-intravascular interventional therapy: non-intravascular interventional therapy mainly includes intratumoral local

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Ablation techniques include chemical ablation (anhydrous ethanol, acetic acid) and physical ablation (argon-helium knife, radiofrequency, microwave, etc.). With the development of interventional techniques, particle implantation technology can also achieve good therapeutic effects.

Chemical ablation for tumors: This usually refers to percutaneous anhydrous ethanol injection therapy (PEIT) and percutaneous acetic acid injection therapy (PAIT). Applying this technique to treat solid tumors has the characteristics of a large coagulation range, high efficiency in coagulating cancerous tissue, clear boundaries, almost no side effects, and good controllability during treatment. Compared with other ablation therapies, it shows considerable application prospects. Isolated pulmonary masses, especially those close to the lung surface, are suitable for chemical ablation.

Radiofrequency ablation (RFA): This involves using an ablation electrode, guided by instruments such as ultrasound or CT, to perform percutaneous puncture and insert it into the tumor tissue. Through radiofrequency output, ion oscillation and friction in the lesion area generate heat, raising the local temperature to over 90°C. The high temperature kills tumor tissue, causing coagulative necrosis of the lesion, ultimately forming liquefied foci or fibrotic tissue. At the same time, the temperature is monitored and adjusted in real-time to achieve local elimination of tumor tissue. Finally, the puncture tract is heated and ablated to prevent tumor implantation.

Argon-helium knife: This is a minimally invasive ultra-low-temperature cryoablation technique for tumors, which has certain efficacy for solid tumors such as lung cancer, liver cancer, brain tumors, and breast cancer.

Others: In addition to the aforementioned interventional treatments and methods, microwave ablation and particle implantation technologies have also shown certain efficacy in the treatment of lung cancer and other tumors. Treatment can be administered according to relevant chapters, specific circumstances, and the patient's condition.

2. Treatment of Small Cell Lung Cancer Small cell lung cancer is still primarily treated with comprehensive therapy, with chemotherapy being the main treatment method for SCLC. Studies on patients in the limited stage show that early radiotherapy or chemotherapy, or concurrent radiotherapy and chemotherapy, yield better results. For patients in the extensive stage and those in the limited stage who still fail to achieve PR after chemotherapy, single-agent chemotherapy is mainly used. Commonly used chemotherapy regimens include the EP regimen and the IP regimen. Research shows that the combination of nivolumab and ipilimumab can achieve an ORR of around 20%. The combination of atezolizumab and durvalumab with chemotherapy for extensive-stage small cell lung cancer also demonstrates good efficacy.

3. Professor Pei Zhengxue’s Thinking Method Professor Pei Zhengxue believes that the lungs belong to metal, and only fire can overcome it; hence the ancient saying, “When the lungs are diseased, heat is the primary culprit.” When heat invades the lungs, symptoms include high fever, wheezing and coughing, copious purulent and foul-smelling sputum, and blood in the sputum.

The heat that overcomes the lungs is considered “strong fire,” which both consumes qi and damages yin. Consuming qi leads to deficiency of lung qi, while damaging yin depletes lung yin. Prolonged lung qi deficiency can lead to secondary illness affecting the spleen, resulting in symptoms such as poor appetite, fatigue, shortness of breath, reluctance to speak, cough with phlegm, spontaneous sweating, aversion to cold, and mild edema of the face and lower limbs—this is spleen-lung qi deficiency. If lung yin is depleted for a long time, the mother disease will affect the child, leading to lung-kidney deficiency, manifested as chest tightness, shortness of breath, cough with phlegm, sticky and difficult-to-expectorate phlegm, blood in the phlegm, bone-steaming heat, five-center vexation, night sweats—this is lung-kidney yin deficiency. Deficiency of the lungs easily invites wind-cold pathogens to take advantage of the weakness, as the saying goes, “Where evil gathers, qi must be deficient.” Once cold pathogen invades the lungs, it immediately transforms from yang to fire, presenting symptoms such as headache, chills and fever, body pain, and cough with phlegm—this is wind-cold invading the lungs. When lung disease persists for a long time, it enters the meridians. Besides chest pain and hemoptysis, and physical debility, lumps may accumulate under the ribs. Lung cancer, due to deficiency of righteous qi and invasion of pathogenic factors, along with phlegm-stasis-toxic heat, damages the lungs and lung meridians, leading to lump formation, lung qi deficiency, and overall righteous qi deficiency as the root cause of the disease. The disease is characterized by deficiency of the root and excess of the manifestation, with both deficiency and excess intertwined, and the site of the disease is in the lungs, related to the spleen and kidneys. Diagnosis should first distinguish between deficiency and excess, as well as the strength of pathogenic factors. In the early stages of lung cancer, the focus is on excess pathogenic factors, treating to eliminate pathogenic factors while supporting righteous qi; in the middle stages, righteous qi deficiency becomes dominant, treating to support righteous qi while eliminating pathogenic factors; in the late stages, pathogenic factors are strong and righteous qi is weak, with all three organs—the lungs, spleen, and kidneys—being deficient, so the focus is on supporting righteous qi and strengthening the foundation, nourishing the spleen and tonifying the kidneys.