Practice 15 structured short- and long-answer medical questions on Lung Tumours Conti.... Review model answers for exam revision.
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Answer: - Peripheral carcinoids are less common. - 5–15% have metastasised to hilar nodes at presentation; distant metastases are rare. - **Typical carcinoid:** Characterized by nests of uniform cells with regular round nuclei exhibiting "salt and pepper" chromatin, absent or rare mitoses, and minimal pleomorphism. - **Atypical carcinoid:** Shows a higher mitotic rate, small foci of necrosis, and a higher incidence of lymph node and distant metastasis. **TP53 mutations are found in 20–40%** of cases. - These tumours exist on a **spectrum of neuroendocrine neoplasms**, increasing in aggressiveness: typical carcinoid → atypical carcinoid → large cell neuroendocrine carcinoma → SCLC. **Clinical Features:** - Signs and symptoms related to intraluminal growth include cough, haemoptysis, and recurrent bronchial/pulmonary infections. - Peripheral tumours are often asymptomatic and discovered incidentally on chest radiographs. - **Carcinoid syndrome** (characterized by intermittent diarrhoea, flushing, and cyanosis) is rarely produced by pulmonary carcinoids. - **5-year and 10-year survival rates:** - Typical carcinoids: Above 85%. - Atypical carcinoids: 56% and 35% respectively. --- ## 10. Pleural Lesions **Conditions covered:** Pleural Effusion and Pleuritis · Pneumothorax · Haemothorax · Chylothorax · Malignant Mesothelioma ### Pleural Effusion and Pleuritis - Pleural effusions can be classified as **transudates or exudates**. - **Hydrothorax** refers to a transudate; the most common cause is **congestive heart failure**, typically presenting bilaterally. - An **exudate** has a protein content >30 g/L and contains inflammatory cells, suggesting pleuritis. **Four principal causes of pleural exudate:**
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Answer: **Other causes** include SLE, rheumatoid arthritis, uraemia, and previous thoracic surgery. - **Malignant effusions** are characteristically large and often bloody (haemorrhagic pleuritis). Cytologic examination may reveal malignant cells. - Transudates and serous exudates are usually resorbed without residual effects if the inciting cause is controlled. - Fibrinous, haemorrhagic, or suppurative exudates can lead to fibrous organization, resulting in adhesions or fibrous pleural thickening (sometimes with calcification). ### Pneumothorax, Haemothorax, and Chylothorax **Pneumothorax:** Refers to air or other gas in the pleural sac. - **Simple (spontaneous) pneumothorax:** Occurs in young, apparently healthy adults, usually men, with no known pulmonary disease. - **Secondary pneumothorax:** Arises in the context of a thoracic or lung disorder (e.g., emphysema, fractured rib, lung abscess, TB, carcinoma). It occurs due to the rupture of a pulmonary lesion close to the pleural surface, allowing inspired air to enter the pleural cavity. It can also result from high-pressure mechanical ventilation. **Complications of Pneumothorax:** - **Tension pneumothorax:** A life-threatening condition where a ball-valve leak allows air to enter but not exit the pleural space, leading to mediastinal shift and compromised pulmonary circulation. - **Failure to re-expand:** If the lung fails to re-expand within a few weeks, scarring can occur, preventing full re-expansion. This can lead to serous fluid collection, resulting in **hydropneumothorax**. - **Empyema (pyopneumothorax):** Prolonged lung collapse increases the risk of infection. **Haemothorax:** A collection of whole blood in the pleural cavity, distinguished from a bloody effusion by the presence of clots. It may complicate a ruptured intrathoracic aortic aneurysm and is almost always fatal. **Chylothorax:** A pleural collection of milky lymphatic fluid containing microglobules of lipid. It is always significant, implying obstruction of major lymph ducts, typically by an **intrathoracic cancer** (primary or secondary mediastinal neoplasm, such as lymphoma). ### Malignant Mesothelioma - A rare cancer of mesothelial cells, usually arising in the **parietal or visceral pleura**, but can also occur in the peritoneum and pericardium. - **80–90%** of cases have a history of **asbestos exposure**. - Individuals at greatest risk include shipyard workers, miners, and insulators. The risk also extends to those living near asbestos factories or relatives of asbestos workers. - **Latent period:** There is a significant latent period of 25–40 years after initial exposure, suggesting that causative driver mutations are acquired slowly. - **Cigarette smoking combined with asbestos exposure does NOT increase mesothelioma risk**, unlike its synergistic effect on lung carcinoma risk. - Once inhaled, asbestos fibres remain in the body for life, meaning the **lifetime risk does not diminish over time**, unlike smoking risk which decreases after cessation. - Asbestos fibres preferentially accumulate near the mesothelial cell layer, generating reactive oxygen species that cause DNA damage and mutations. - **BAP1** is one of the most commonly mutated genes in sporadic mesothelioma. It is a tumour suppressor gene involved in DNA repair and is also affected by germline mutations in familial mesothelioma. **Morphology:** - Often preceded by extensive pleural fibrosis and plaque formation. - The tumour typically begins in a localised area and then spreads widely by contiguous growth or diffuse seeding of the pleural surfaces. - At autopsy, the affected lung is ensheathed by **yellow-white, firm, variably gelatinous tumour** that obliterates the pleural space. - The tumour may directly invade the thoracic wall or subpleural lung tissue; distant metastases are uncommon. - **Three morphologic appearances** are described:
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Answer: --- ## 11. Lesions of the Upper Respiratory Tract **Conditions covered:** Acute Infections · Nasopharyngeal Carcinoma · Laryngeal Tumours · Carcinoma of the Larynx ### Acute Infections of the Upper Respiratory Tract - These are among the most common afflictions of humans, often referred to as the "common cold." - Symptoms typically include nasal congestion, watery discharge, sneezing, a scratchy sore throat, and a slight fever (which can be more pronounced in young children). - The **most common pathogen is rhinovirus**, but others include coronaviruses, RSV, parainfluenza, influenza, adenovirus, enteroviruses, and group A β-haemolytic streptococci. In about 40% of cases, the causative agent cannot be determined. - Most infections occur in the fall and winter and are self-limiting, usually resolving within a week. - A minority of cases are complicated by bacterial otitis media or sinusitis. **Acute Pharyngitis:** - **Mild pharyngitis with minimal findings** is the most common form and often accompanies colds. - **Severe pharyngitis with tonsillitis** can be caused by β-haemolytic streptococcal and adenovirus infections, presenting with marked hyperaemia and exudates. - **Streptococcal tonsillitis** is important to recognize and treat early due to the risk of peritonsillar abscesses ("quinsy") or progression to **poststreptococcal glomerulonephritis and acute rheumatic fever**. - **Coxsackievirus A** can cause pharyngeal vesicles and ulcers (herpangina). - **Infectious mononucleosis**, caused by EBV, is an important cause of pharyngitis and is known as the "kissing disease." **Acute Bacterial Epiglottitis:** - Primarily affects young children and is caused by **H. influenzae**. - Key findings include pain and airway obstruction, with abrupt onset. - Failure to maintain an open airway can be **fatal**. - Vaccination against H. influenzae has significantly decreased its incidence. **Acute Laryngitis:** - Can be caused by irritant inhalation, allergic reactions, or common cold agents. - **Tuberculous laryngitis** is almost always a consequence of protracted active TB, resulting from infected sputum being coughed up. - **Diphtheritic laryngitis:** Uncommon due to widespread immunization, it is caused by *Corynebacterium diphtheriae*. The potent exotoxin leads to necrosis of the mucosal epithelium and a dense fibrinopurulent exudate, forming the **classic dirty-grey pseudomembrane of diphtheria**. The major hazards are aspiration of the sloughed pseudomembrane (causing airway obstruction) and absorption of exotoxins, which can lead to myocarditis and peripheral neuropathy. - **Croup (laryngotracheobronchitis):** The most common cause in children is **parainfluenza virus**, but RSV can also be involved. It is generally self-limited but can cause frightening inspiratory stridor and a harsh, persistent cough. In occasional cases, laryngeal inflammation narrows the airway, leading to respiratory failure. Viral upper respiratory tract infections can predispose to secondary bacterial infections by staphylococci, streptococci, or H. influenzae. ### Nasopharyngeal Carcinoma - A rare neoplasm with notable characteristics:
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Answer: - EBV first replicates in the nasopharyngeal epithelium and then infects nearby tonsillar B lymphocytes, leading to the transformation of epithelial cells. - The **EBV genome is found in virtually ALL nasopharyngeal carcinomas**, including those outside Asian endemic areas, which is distinct from Burkitt lymphoma. - **Three histologic variants** are recognized:
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Answer: - These tumours invade locally, spread to **cervical lymph nodes**, and can cause distant metastases. - They are **radiosensitive**, with 5-year survival rates of 50% even for advanced cancers. Immune checkpoint inhibitor responses have also been reported. ### Laryngeal Tumours **Conditions covered:** Vocal Cord Nodules · Laryngeal Papilloma · Carcinoma of the Larynx **Vocal Cord Nodules ("Polyps"):** - Smooth, hemispherical protrusions, usually less than 0.5 cm, located on the true vocal cords. - They are composed of fibrous tissue covered by stratified squamous mucosa, which may be ulcerated from contact trauma. - They occur primarily in **heavy smokers or singers (singer's nodes)** as a result of chronic irritation or overuse. **Laryngeal Papilloma (Squamous Papilloma):** - A benign neoplasm, typically found on the true vocal cords. It presents as a soft, raspberry-like excrescence rarely exceeding 1 cm. - Histologically, it shows multiple slender fingerlike projections with central fibrovascular cores covered by orderly stratified squamous epithelium. - **Single in adults but multiple in children** (recurrent respiratory papillomatosis - RRP). RRP in children typically recurs after excision. - These papillomas are caused by **HPV types 6 and 11** and often spontaneously regress at puberty. - Cancerous transformation is rare. - **In children:** Vertical transmission from an infected mother during delivery is the likely route. The HPV vaccine, which protects against types 6 and 11, offers an opportunity for **prevention of RRP in children**. ### Carcinoma of the Larynx - Represents only **2% of all cancers**. - Most commonly occurs after age 40, with a **higher prevalence in men (7:1 gender ratio)**. - Nearly all cases are found in **smokers**. Alcohol and asbestos exposure also play contributing roles. - HPV sequences are detected in ~15% of cases, and these tumours **tend to have a better prognosis**. - **Approximately 95% are squamous cell carcinomas**; adenocarcinomas (arising from mucous glands) are rare. **Location and Prognosis:** | Location | Frequency | Key Features | | :--------- | :----------- | :--------------------------------------------------------------------------------------------------------------------------------------------------------------------- | | **Glottic** (on vocal cords) | 60–75% | Early symp
Answer: This section provides a comprehensive overview of primary lung tumours, focusing on carcinomas as the most prevalent type. It details the aetiology, pathogenesis, and molecular aspects of lung cancer, including the significant impact of smoking and other environmental factors. The morphology of major histological subtypes like adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and small cell lung carcinoma is described, alongside their respective precursor lesions and characteristic genetic mutations. The comparison between small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCL C) highlights their distinct clinical behaviours and treatment implications. The section also covers the spread patterns, clinical manifestations, paraneoplastic syndromes, and treatment strategies for lung tumours, emphasizing the advent of targeted therapies and immune checkpoint inhibitors. Additionally, it discusses carcinoid tumours, a less common but distinct group of neuroendocrine neoplasms originating in the lungs. ## Key Points - **~95% of primary lung tumours are carcinomas**, with the remaining 5% comprising carcinoids, mesenchymal malignancies, lymphomas, and benign lesions. - **Hamartoma** is the most common benign lung tumour, appearing as a discrete "coin lesion" on imaging. - **Carcinoma of the lung** is the leading cause of cancer-related deaths in industrialized countries, with peak incidence in the fifties and sixties. - **Four Major Histologic Types** of lung carcinoma are Adenocarcinoma, Squamous cell carcinoma, Small cell carcinoma, and Large cell carcinoma. - **Smoking** is the most important aetiological factor, accounting for ~90% of lung cancers. - **Asbestos exposure** synergizes with tobacco smoke, significantly increasing lung cancer risk. - **Key Targetable Mutations** in lung adenocarcinomas include EGFR, KRAS, and ALK rearrangements, driving personalized treatment approaches. - **Small Cell Lung Carcinoma (SCLC)** is highly aggressive, virtually always metastatic at diagnosis, and treated with systemic chemotherapy. - **Non-Small Cell Lung Carcinoma (NSCLC)** is more likely to be resectable and may respond to targeted therapies. - **Carcinoid Tumours** are low-grade neuroendocrine carcinomas, often resectable and curable, with typical and atypical subtypes. - **Pleural lesions** include effusions (transudates and exudates), pneumothorax, haemothorax, chylothorax, and malignant mesothelioma. - **Malignant Mesothelioma** is a rare cancer of mesothelial cells, strongly linked to asbestos exposure with a long latent period. - **Upper Respiratory Tract Lesions** encompass acute infections (pharyngitis, epiglottitis, laryngitis) and neoplasms like nasopharyngeal carcinoma, laryngeal papilloma, and carcinoma of the larynx. - **Carcinoma of the Larynx** is predominantly squamous cell carcinoma, with glottic tumours having a better prognosis due to early symptoms and less lymphatic spread. ## Detailed Notes ### Overview of Primary Lung Tumours - **~95%** of primary lung tumours are carcinomas. - The remaining 5% consist of carcinoids, mesenchymal malignancies (fibrosarcomas, leiomyomas), lymphomas, and benign lesions. - The **most common benign tumour** is **Hamartoma**. It is typically spherical, small (1–4 cm), and appears as a discrete "coin lesion" on imaging. It is composed mainly of mature cartilage admixed with fat, fibrous tissue, and blood vessels. Clonal cytogenetic abnormalities have been confirmed, technically classifying it as a benign neoplasm rather than a true hamartoma. ### Carcinoma of the Lung - **Most important cause of cancer-related deaths** in industrialised countries. - Leading cause of cancer deaths in both men and women. - Estimated ~221,200 new cases and 158,040 deaths in the USA (2016 figures). - Peak incidence occurs in the **fifties and sixties**. - At diagnosis, >50% of patients already have distant metastases, and an additional 25% have regional lymph node disease. - The **overall 5-year survival is approximately 16%**, a figure that has not changed significantly over 35 years. - Even with disease localised to the lung, the 5-year survival is only 45%. **Four Major Histologic Types:** | Type | Key Features | | :---------------------- | :------------------------------------------------------------------------------- | | Adenocarcinoma | Most common overall; most common in women, non-smokers, and those <45 years old. | | Squamous cell carcinoma | Strong smoking association; typically central location. | | Small cell carcinoma | Strongest smoking association; neuroendocrine in nature; almost always metastatic at diagnosis. | | Large cell carcinoma | Undifferentiated; diagnosis of exclusion. | - The historical division between **SCLC (Small Cell Lung Carcinoma)** and **NSCLC (Non-Small Cell Lung Carcinoma)** is clinically important: - **SCLC:** Virtually always metastasised at diagnosis. Treatment involves systemic chemotherapy ± radiation; it is NOT surgical. - **NSCLC (adenocarcinoma, squamous, large cell):** More likely to be resectable. May respond poorly to conventional chemotherapy but can respond to targeted therapies. ### Aetiology and Pathogenesis **Smoking:** - Approximately **90% of lung cancers occur in active smokers or recent quitters**. - There is a nearly linear correlation between lung cancer frequency and pack-years of smoking. - The risk is **60 times greater** in heavy smokers (2 packs/day for 20 years) compared to non-smokers. - **Women are more susceptible** to the carcinogens in tobacco smoke than men. - Cessation of smoking reduces risk over time but **never returns to the baseline** risk of a never-smoker. - Passive smoking also increases risk. - Pipe and cigar smoking also lead to a modest increase in risk. **Other Carcinogenic Influences:** - Exposure to uranium mines, asbestos, arsenic, chromium, nickel, and vinyl chloride dusts. - **Asbestos + Tobacco Synergy:** Asbestos alone in non-smokers increases risk 5-fold; heavy smokers exposed to asbestos face a **~55-fold increased risk**. - Importantly, smoking + asbestos increases lung carcinoma risk but does **NOT** increase mesothelioma risk. **Genetic Factors:** - Polymorphisms in the **P-450 monooxygenase enzyme system** can increase the capacity to activate procarcinogens in cigarette smoke, leading to greater carcinogen exposure and a higher lung cancer risk. - A **mutagen-sensitive genotype** (characterized by chromosomal breakage after carcinogen exposure) is associated with a >10-fold increased risk. **Molecular Pathogenesis — Sequential Mutations:** - The stepwise accumulation of driver mutations parallels the histologic progression of lung cancer. - An **early event** involves the inactivation of tumour suppressor genes on **chromosome 3p**, which can be found even in the benign bronchial epithelium of smokers, indicating a "field effect." - **Late events** include mutations in the **TP53** tumour suppressor and the **KRAS** oncogene. - Loss of 3p is found in benign bronchial epithelium, suggesting that large areas of respiratory mucosa are mutagenised. **Key Targetable Mutations (mainly in adenocarcinomas):** - **EGFR mutations:** Found in ~10% of whites and ~30% of Asians, particularly in non-smoking women. Tumours with these mutations are sensitive to EGFR inhibitors, though responses are often short-lived. EGFR and KRAS mutations are **mutually exclusive** as KRAS lies downstream of EGFR. - **KRAS mutations:** Occur in ~30% of adenocarcinomas. - **ALK rearrangements:** Found in 4–6% of adenocarcinomas, often in non-smokers, and can present with signet ring morphology. - **ROS1, HER2, c-MET mutations:** Each can be targeted by specific drugs, contributing to the era of "personalised" lung cancer treatment. Each kinase is optimally targeted by a different drug. **Precursor Lesions:** - **Adenocarcinoma sequence:** Atypical adenomatous hyperplasia (AAH) → adenocarcinoma in situ (AIS) → minimally invasive adenocarcinoma → invasive adenocarcinoma. - **Squamous cell carcinoma sequence:** Basal cell hyperplasia → squamous metaplasia → squamous dysplasia → carcinoma in situ → invasive carcinoma. This sequence shows a linear correlation with cigarette smoke intensity. - **Bronchioalveolar stem cells (BASCs):** These multipotent cells at the bronchioloalveolar duct junction are postulated to incur the initiating hit (e.g., a somatic KRAS mutation) after lung injury, escape checkpoint mechanisms, and lead to pulmonary adenocarcinomas. ### Morphology of Individual Subtypes **Adenocarcinoma:** - Usually **peripherally located**, although they can also occur near the hilum. - They grow slowly and form smaller masses than other subtypes but **metastasise widely at an early stage**. - Growth patterns include acinar (gland-forming), papillary, mucinous (often multifocal with a pneumonia-like consolidation), and solid (requires mucin stains to confirm adenocarcinomatous differentiation). - **Atypical Adenomatous Hyperplasia (AAH):** A well-demarcated focus ≤5 mm, composed of cuboidal to low-columnar cells with nuclear hyperchromasia, pleomorphism, and prominent nucleoli. It is monoclonal and shares molecular aberrations (e.g., KRAS mutations) with adenocarcinomas. - **Adenocarcinoma in situ (AIS)** (formerly bronchioloalveolar carcinoma): ≤3 cm, characterized by growth along pre-existing alveolar structures (lepidic growth) with preservation of alveolar architecture. Tumour cells grow in a monolayer along alveolar septa without stromal invasion or desmoplasia (if present, it indicates invasive adenocarcinoma). AIS can be nonmucinous, mucinous, or mixed. - **TTF-1 (thyroid transcription factor-1)** is positive in the majority of pulmonary adenocarcinomas and is an important immunohistochemical marker. **Squamous Cell Carcinoma:** - More common in men and closely correlated with smoking history. - **Centrally located**, arising in major bronchi. - They spread to local hilar nodes first and **disseminate outside the thorax later** than other histologic types. - Large lesions may exhibit central necrosis, leading to **cavitation**. - The precursor lesion is squamous metaplasia/dysplasia in the bronchial epithelium, progressing to carcinoma in situ, which can persist for several years. Atypical cells may be detectable in sputum cytology or bronchial lavage before the tumour is symptomatic or radiologically detectable. - Histologically, it ranges from well-differentiated (with keratin pearls and intercellular bridges) to poorly differentiated. - It can produce **PTH-related peptide**, leading to hypercalcaemia as a paraneoplastic syndrome. **Large Cell Carcinoma:** - An undifferentiated malignant epithelial tumour that lacks the cytologic features of neuroendocrine carcinoma and shows no evidence of glandular or squamous differentiation. - Characterized by large nuclei, prominent nucleoli, and moderate amounts of cytoplasm. - It is a diagnosis of exclusion. **Small Cell Lung Carcinoma (SCLC):** - Appears as pale gray, **centrally located** masses extending into lung parenchyma. - Composed of relatively small tumour cells with round to fusiform shapes, scant cytoplasm, finely granular chromatin with a **"salt and pepper"** appearance, numerous mitotic figures, and invariably present necrosis (which can be extensive). - **Cells are fragile**, leading to fragmentation and **"crush artifact"** in small biopsy specimens. - **Nuclear molding** (close apposition of tumour cells with scant cytoplasm) is a characteristic feature, best appreciated in cytologic specimens. - **Expresses neuroendocrine markers:** chromogranin, synaptophysin, CD56. Dense-core granules are seen on electron microscopy. - By the time of diagnosis, most SCLC patients have metastasised to hilar and mediastinal lymph nodes. - The **Azzopardi effect** is observed, characterized by basophilic staining of vascular walls due to encrustation by DNA from necrotic tumour cells. ### Comparison: SCLC vs NSCLC | Feature | SCLC | NSCLC | | :----------------------- | :----------------------------------------------------------------- | :------------------------------------------------------------------------- | | **Histology** | Scant cytoplasm; small hyperchromatic nuclei; fine chromatin; indistinct nucleoli; diffuse sheets. | Abundant cytoplasm; pleomorphic nuclei; coarse chromatin; prominent nucleoli; glandular or squamous architecture. | | **Neuroendocrine markers** | Present | Absent | | **Mucin** | Absent | Present in adenocarcinomas | | **Peptide hormone production** | ACTH, ADH, gastrin-releasing peptide, calcitonin | PTH-rp in squamous cell carcinoma | | **3p deletions** | >90% | >80% | | **RB mutations** | ~90% | ~20% | | **TP53 mutations** | >90% | >50% | | **KRAS mutations** | Rare | ~30% in adenocarcinomas | | **EGFR mutations** | Absent | ~20% in adenocarcinomas (non-smokers, women) | | **ALK rearrangements** | Absent | 4–6% in adenocarcinomas | | **Response to chemotherapy** | Often complete but invariably recur | Incomplete | ### Spread and Clinical Features **Local and Regional Spread:** - Each subtype of lung cancer spreads to lymph nodes, including those in the carina, mediastinum, neck (scalene nodes), and clavicular regions. - Involvement of the **Virchow node** (left supraclavicular node) is characteristic and can sometimes call attention to an occult primary tumour. - Advanced tumours can extend into the pleural or pericardial space, leading to inflammation and effusions. - Compression or infiltration of the **superior vena cava** causes venous congestion, resulting in **superior vena cava syndrome**. - **Pancoast tumour:** An apical neoplasm invading the brachial or cervical sympathetic plexus. It presents with severe pain in the distribution of the ulnar nerve and **Horner syndrome** (ipsilateral enophthalmos, ptosis, miosis, anhidrosis). It may also be associated with destruction of the first and second ribs and sometimes thoracic vertebrae. The clinical findings collectively are known as **Pancoast syndrome**. **Clinical Features:** - The presentation is often insidious, with many cases unresectable before symptoms appear. - Early symptoms include chronic cough and expectoration, which may indicate localised, resectable disease. - Late or poor-prognosis symptoms include hoarseness, chest pain, superior vena cava syndrome, pericardial/pleural effusion, and persistent segmental atelectasis or pneumonitis. - Lung cancer frequently presents with symptoms from **metastatic spread**: - Brain: Mental or neurological changes. - Liver: Hepatomegaly. - Bones: Pain. - Adrenal glands: Adrenal glands can be nearly obliterated by metastases, but adrenal insufficiency is uncommon as islands of cortical cells persist. **Paraneoplastic Syndromes (3–10% of patients):** - **Hypercalcaemia:** Most often associated with squamous cell carcinoma, due to secretion of PTH-related peptide. - **Cushing syndrome:** Most often associated with SCLC, due to increased ACTH production. - **SIADH** (syndrome of inappropriate ADH secretion): Most often associated with SCLC. - **Neuromuscular syndromes:** Including myasthenic syndrome, peripheral neuropathy, and polymyositis; most often associated with SCLC. - **Clubbing of fingers and hypertrophic pulmonary osteoarthropathy.** - **Coagulation abnormalities:** Such as migratory thrombophlebitis, nonbacterial endocarditis, and DIC; most often associated with adenocarcinoma. - A general rule of thumb: hypercalcaemia suggests squamous cell carcinoma; haematologic syndromes suggest adenocarcinoma; neurologic syndromes suggest SCLC, though exceptions are common. **Treatment and Prognosis:** - Squamous cell carcinoma and adenocarcinoma generally have a more favourable prognosis than SCLC. - NSCLC detected before metastasis may be curable by lobectomy or pneumonectomy. - Unresectable adenocarcinomas with targetable mutations (e.g., EGFR) can show remarkable responses to EGFR inhibitors, though relapse within months to a year is typical, often due to new mutations or circumventing mechanisms. - **Immune checkpoint inhibitors** are approved for a subset of NSCLC, particularly smoking-related tumours with a high neoantigen burden. Encouraging responses are also seen in advanced SCLC. - **SCLC** is rarely amenable to surgery due to its tendency to spread early. While highly sensitive to chemotherapy, it invariably recurs. Currently, there are no specific targeted therapies for SCLC. The median survival with treatment is approximately 1 year, with only 5% alive at 10 years. ### Carcinoid Tumours - These are malignant tumours composed of cells containing **dense-core neurosecretory granules** in their cytoplasm. They rarely secrete hormonally active polypeptides. - They are best considered **low-grade neuroendocrine carcinomas**. - They are subclassified into **typical or atypical** carcinoids, both of which are often resectable and curable. - They occur in young adults (mean age 40 years) and represent ~5% of all pulmonary neoplasms. - Occasionally, they are part of a **multiple endocrine neoplasia (MEN) syndrome**. **Morphology:** - Most originate in the main bronchi and present in one of two growth patterns: