Case 17: lung, mets, MM Flashcards
Lung cancer risk factors
- Smoking even passive, this risk is proportional to pack years
- Age: 60-70, male
- Radiation exposure
- Chemicals: asbestos, acetaldehyde, beryllium, arsenic, nickle, chromium, formaldehyde
- Air pollution
- Family history
- HIV
- Beta carotene supplements in heavy smokers
Lung cancer symptoms
- Shortness of breath
- Cough
- Haemoptysis(coughing up blood)
- Finger clubbing
- Wheeze or stridor
- Recurrent pneumonia
- Weight loss, malaise and lethargy
- Hoarseness (invasion of recurrent laryngeal nerve) and dysphagia (compression)
- Lymphadenopathy - supraclavicular then axillary
Lung cancer examination
- Reduced expansion on affected side
- Diminished breath sounds
- hepatomegaly
- Clubbing: in NSCLC
- Hands: nicotine staining, clubbing
- Neck: lymphadenopathy
- Chest: signs of pulmonary collapse, pleural effusion or consolidation
- Superior vena caval obstruction
Paraneoplastic syndrome
- Hypercalcaemia: Often due to production of parathyroid hormone-related peptide (PTHrP).
- Cushing’s syndrome: Due to ectopic adrenocorticotropic hormone (ACTH) production.
- SIADH (Syndrome of Inappropriate Antidiuretic Hormone secretion): Leading tohyponatraemia
- Lambert-Eaton myasthenic syndrome (LEMS): A neuromuscular disorder caused by antibodies directed against voltage-gated calcium channels in the presynaptic nerve terminals. Muscles weakness, bilateral ptosis and autonomic symptoms
- Clubbing
Paraneoplastic syndrome in NSCLC
Hypertrophic pulmonary osteoarthropathy - presents with clubbing and arthralgia (esp wrists and ankles)
What lymph nodes may be affected by lung cancer
- Initially: ipsilateral peribronchial, ipsilateral hilar nodes
- Later: mediastinal nodes, contralateral hilar nodes, supraclavicular nodes
Pancoasts tumour
- Cancer in the top of the lung - usually non small cell
- Chest wall pain
- Horner’s syndrome: miosis, anhydrosis, partial ptosis and enophthalmos
- Pain in T1 dermatomal distribution due to apical tumour invading chest wall, interrupting sympathetic chain and invading T1 nerve root
Lung cancer investigations (not imaging)
bedside: full set of obs, sputum culture, pulmonary function tests (spirometry)
bloods:
- FBC to look for anaemia and raised platelets
- U+Es
- LFTs to look for liver mets
- LDH may be raised in SCLC
- calcium may be raised in squamous NSCLC
Lung cancer imaging
- CXR
- contrast enhanced CT chest abdo pelvis for staging
- PET CT for metastases
- bronchoscopy with endobronchial ultrasound- take biopsy
- Transthoracic biopsy (CT guided)
- Fine Needle aspiration (FNA) of affected lymph node
- Fluid cytology from a pleural effusion if present
- Plain bone x-ray and bone scans to exclude metastasis
Lung cancer special tests
- sputum and pleural effusion cytology
- biopsy via bronchoscopy, needle or surgery
- lung function tests
Imaging in different types of lung cancer
- SCLC: imaging of upper abdomen as cancer can spread to the liver and adrenal glands
- NSCLC considered for radical treatment: Pulmonary function tests, Contrast CT TAP, V/Q scan, US, mediastinoscopy, laryngoscopy, PET-CT
Molecular features of lung cancer
- Adenocarcinomas can have specific mutations in: EGFR, MAPK and PI3K signalling pathways. Can determine treatment
- Adenocarcinomas: EGFR and ALK mutations develop in non-smokers, KRAS and BRAF mutations are more associated with smokers
- NSCLC: Translocation of ALK and EML4
Lung cancer: features associated with adverse features
- Large tumor size (>3 cm)
- Nonsquamous histology
- Metastases to multiple lymph nodes
- Brain metastasis
- Age
- Vascular invasion
- Poor performance status and weight loss >10%
- Increased LDH
Management of lung cancer
- conservative:- smoking cessation
- medical:- radiotherapy for stages 1-3- chemotherapy as adjunct to surgery/ radiotherapy
- surgical:- lobectomy (1st line for stages 1-2)
- Advanced disease: Systemic therapy with tyrosine kinase inhibitors or immunotherapy
Extrapulmonary manifestations of lung cancer
- Small cell lung cancer: can cause paraneoplastic syndrome
- RLN palsy: hoarse voice due to a tumour pressing on the nerve
- Phrenic nerve palsy: diaphragm weakness causing SOB
- Horner’s syndromeis a triad of partial ptosis, anhidrosis and miosis. It can be caused by aPancoast tumour(tumour in thepulmonary apex) pressing on thesympathetic ganglion.
- Syndrome of inappropriate ADH(SIADH) can be caused byectopic ADHsecreted by asmall cell lung cancer. It presents withhyponatraemia.
- Cushing’s syndromecan be caused byectopic ACTHsecretion by asmall cell lung cancer.
- Hypercalcaemiacan be caused byectopic parathyroid hormonesecreted by asquamous cell carcinoma.
Lung cancer: compressive and obstructive symptoms
- Compressive symptoms: dysphagia due to oesophageal compression. Hoarseness due to recurrent laryngeal nerve compression
- Local invasion: pleural effusion, SVC obstruction
- SVC obstruction: bulging veins on forehead, papilloedema, Pemberton sign
- Pemberton’s sign: worsening of SOB/ facial congestion/cyanosis when raising arms until they touchside of face (seen in SVC obstruction)
- Metastatic: liver, bone, brain, adrenal gland
Lambert-Eaton Myasthenic syndrome
- Caused by antibodies produced by the immune system against small cell lung cancer cells
- Causes weakness in proximal muscles, diplopia, ptosis, slurred speech and dysphagia
- Autonomic dysfunction: dry mouth, blurred visi
Referral criteria for lung cancer (2 week wait): patients over 40 with
- Clubbing
- Lymphadenopathy(supraclavicularor persistent abnormal cervical nodes)
- Recurrent or persistent chest infections
- Raised platelet count (thrombocytosis)
- Chest signs of lung cancer
- Consider a CXR in patients >40 who have two or more unexplained symptoms in patients that have never smoked or one or more unexplained symptoms in patient that have smoked
- Unexplained symptoms: cough, SOB, fatigue, chest pain, weight loss, loss of appetitie
Investigations for lung cancer
- CXR: first line, show hilar enlargement, peripheral opacity, pleural effusion and collapse
- Staging CT of chest, abdomen and pelvis: assesses stage, lymph node involvement and metastasis
- PET-CT
- Bronchoscopy with endobronchial ultrasound (EBUS): detailed assessment of tumour and US guided biopsy
- Histological diagnosis: either bronchoscopy or percutaneous biopsy
Treatment options: NSLC
- MDT meeting discussion
- Surgery: first line in stages 1,2 and 3A, followed by adjuvant chemo. Remove primary tumour and regional lymph nodes
- Radiotherapy: Stages I-III not suitable for surgery aiming for cure. Use high dose CHART or cure.
- Chemotherapy: in addition to surgery or radiotherapy (adjuvant chemotherapy). Used in stage III-IV (palliative). Uses either carboplatin or cisplatin with gemcitabine or vinorelbine
- Endobronchial treatment with stents and debulking: palliative in bronchial obstruction
- Brain metastasis: steroids
- SVC obstruction: stent insertion or radiotherapy
Treatment options for SCLC
- Surgery: only considered in stage I-II
- Majority treatment with chemotherapy and radiotherapy
- In relapses SCLC consider further chemotherapy or palliative radiotherapy
- Systemic chemotherapy includes etoposide combines with carboplatin or cisplatin: 3 weekly intervals for 4-6 cycles
- Poor prognosis: survival is 14 months
Lung cancer: molecular targeted therapy
- EGFR tyrosine kinase inhibitors (gefitinib, erlotinib) can be offered to patients with EGFR mutations.
- Translocation of ALK and EML4 respond to crizotinib
- Fusions involving the ROS1 gene respond to treatment with crizotinib and entrectinib
- NTRK gene fusion: treated with TRK inhibitors, larotrctinib and entrectinib
Lung cancer surgery
- Segmentectomyorwedge resectioninvolves taking a segment or wedge of lung (a portion of one lobe)
- Lobectomyinvolves removing the entire lung lobe containing the tumour (the most common method)
- Pneumonectomyinvolves removing an entire lung
- A chest drain is left in after thoracic surgery: allows air and fluid to exit and the lungs to expand
Palliative care for lung cancer
- Palliative radiotherapy for symptom control
- Endobronchial stenting or debulking for bronchial obstruction
- Pleural drainage or aspiration for pleural effusion
- Dexamethasone therapy for those with symptomatic brain metastasis
- Opioid therapy to relievecough and breathlessness
Disease related complications in NSCLC
- Local invasion: SVC obstruction, pleural effusion
- Distant metastasis: brain, liver, bone
- Non-metastatic: Hypercalcaemia, Cushing’s syndrome, SIAD, Neurological syndrome
SVC obstruction
- Obstruction of blood flow through the SVC
- Caused by compression, invasion, or thrombosis in the superior mediastinum
- Symptoms are increased by bending forward, stooping, or by lying down
- Treatment is at the underlying cause (mostly lung cancer)
- Initial management: Dexamethasone
- Symptoms: Dyspnoea, facial swelling, head fullness, venous distension of neck, facial oedema, cyanosis, cough
- X-ray: superior mediastinal widening, pleural effusion, right hilar mass, bilateral diffuse infiltrates
Malignant melanoma
skin cancer arising from the melanocytes which are responsible for producing melanin
Risk factors for malignant melanoma
- Family history or prior personal history of melanoma
- Genetic syndromes, such as Familial Atypical Multiple Mole Melanoma Syndrome
- Skin type prone to burning and not tanning (Fitzpatrick type I or II)
- Immunosuppression
- High levels of sun or UV exposure
- Presence of atypical melanocytic naevi or multiple moles
- Smoking
- Advanced age and male sex
Types of malignant melanoma
- Superficial spreading
- Nodular
- Lentigo maligna
- Acral Lentiginous
Malignant melanoma- superficial spreading
- 70% of cases
- Typically affects: arms, legs, back and chest, young people. Long radial phase
- A growing mole
Malignant melanoma: nodular
- Second most common
- Typically affects: sun exposed skin, middle aged people. Most aggressive type, no radial phase
- Appearance: red or black lump or lump which bleeds or oozes
Malignant melanoma: Lentigo maligna
- Less common
- Affects: chronically sun exposed skin, older people. Very long radial phase
- A growing mole
Malignant melanoma: acral lentiginous
- Rare form
- Typically affects: nails, palms or soles. People with darker skin pigmentation. Short radial phase
- Appearance: Subungal pigmentation (Hutchinson’s sign) or on palms or feet
Malignant melanoma ABCDE
- Asymmetry of the lesion
- Border irregularity
- Colour variation
- Diameter >6mm
- Elevation/evolution over time
Clinical features of mole in malignant melanoma
- Major criteria: change in size, change in shape, change in colour
- Minor features: Diameter ≥7mm, inflammation, oozing or bleeding, altered sensation
- Can also be itchy
Malignant melanoma: investigations
- Excisional biopsy of the lesion with a 2mm margin
- Sentinel lymph node biopsy if the Breslow thickness is >1mm
- PET or CT scans may be necessary in the presence of clinical suspicion for metastases
malignant melanoma: treatment
- Suspicious lesions: excision biopsy, remove the lesion completely and it undergoes histopathological assessment
- Lymph node clearance if lymph nodes involved
- Radiotherapy in some cases
- Adjuvant Immunotherapy/chemotherapy in metastatic disease (Stage III/IV), such as pembrolizumab (PD-1 blocking drug)
- Mole-mapping and lifestyle advice to prevent recurrence in those at risk
Breslow thickness
determined histologically, most important prognostic indicator. Measured in mm from top of granular layer in the epidermis to the deepest point the tumour extends
Malignant melanoma: excision clearance
- Excision with a 2mm margin
- Melanoma in situ: 5 – 10 mm
- Melanoma < 1 mm: 10 mm
- Melanoma 1–2 mm: 10 – 20 mm
- Melanoma > 2 mm: 20 mm
Brain metastasis: origins and symptoms
- Origins (in order of likelihood): Lung, Breast, CUP, Melanoma, GI
- Presenting features: Headache, Cognitive dysfunction, Neurological deficit, Seizures
Treatment for brain metastasis
- Dexamethasone IV: decreases oedema
- Anticonvulsant IV or PO: of the patient needs, normally Phenytoin
- Surgery: only if solitary met
- Radiotherapy: palliative
- Chemotherapy: little role as cant pass blood-brain barrier
Bone metastasis
- Most common tumours causing bone metastases (in descending order: breast, prostate, lung
- Most common site (in descending order): spine, pelvis, ribs, skull, long bones
- Features: bone pain, pathological fractures, hypercalcaemia, raised ALP
- X-ray: sclerotic appearance
Lung metastasis
- Seen in breast, colorectal, renal cell, bladder, prostate
- Multiple, round well-defined lung secondaries are often referred to as ‘cannonball metastases’. They are most commonly seen withrenal cell cancerbut may also occur secondary to choriocarcinoma and prostate cancer.
- Calcification in lung metastases is uncommonexcept in the case of chondrosarcoma or osteosarcoma.
Spinal metastasis
- Can develop into metastatic spinal cord compression
- Symptoms and findings: unrelenting lumbar back pack pain, any thoracic or cervical back pain. Worse with sneezing, coughing or straining. Nocturnal, associated with tenderness
- If neurological features suspect spinal cord compression and act quickly
- Without neuro symptoms a whole spine MRI within one week
Carcinoid syndrome
- Paraneoplastic syndrome due to neuroendocrine tumour
- Investigations of carcinoid syndrome: urinary 5-HIAA (as tumour secretes serotonin)
- Presents: flushing, diarrhoea, flushing, bronchospasm, hypotension, weight loss
Management of VTE in cancer: 6 months of DOAC
Oesophageal cancer
- Malignant neoplasm in the oesophagus
- Poor prognosis due to late presentation and aggressive behaviour
- Two main histological subtypes: squamous cell carcinoma and adenocarcinoma
Risk factors for oesophageal cancer
- Age, male, obesity, high fat diet, smoking, alcohol, GORD, Barett’s oesophagus, achalasia and strictures
- H.pylori infection may reduce the risk
Oesophageal cancer: adenocarcinoma
- Most common type in the UK
- In the lower third of the oesophagus: near the gastro-oesophageal junction
- Risk factors: GORD, Barrett’s oesophagus, smoking, obesity
Oesophageal cancer: squamous cell cancer
- Most common type in the developing world
- In the upper 2/3rds of the oesophagus (can occur at any level)
- Risk factors: smoking, alcohol, achalasia, Plummer-Vinson syndrome, diets rich in nitrosamines, hot drinks
Oesophageal cancer: clinical features
- Presents at advanced stage as initially asymptomatic
- Dysphagia: solids and progressing to liquids, is the most common presenting symptom.
- Cough when eating can cause aspiration pneumonia (upper 1/3 of oesophagus)
- Weight loss
- Odynophagia: Painful swallowing
- Hoarseness: compression of the recurrent laryngeal nerve. (upper 1/3 of oesophagus)
- Retrosternal pain or discomfort
- Regurgitation or vomiting: Obstruction of the oesophagus.