Computer generated transcript

Warning!
The following transcript was generated automatically from the content and has not been checked or corrected manually.

OncologyRapidReview Joanna Kucharczak, Eric Jou, Helene Greenwood May 4 2023Case1 A 64 year-old man with 20-pack year smoking A chest x-ray was performed. history presented to the emergency department with nausea and vomiting for 3 days. Whatotherinvestigationsareusefulto reachthediagnosis? dyspnoea on exertion, and a constant dry cough, fatigue and diminished appetite. He denied fever or weight loss. Physical examination was normal except for left lung end-expiratory wheezing. What are the most likelydifferential diagnoses? • Malignancy • Pulmonary fibrosis • Heart failureInvestigationsforsuspectedlungcancer Bloods Imaging Histology Staging General including: CXR Biopsyor brushing Whole body FDG-PET - U&E for sodium and other integrated - Coagulation screen for biopsy CT scans (which Bronchoscopyfor central tumours – this can be PET scans allows biopsy endobronchialultrasound guided scan (EBUS) Serological tumour markers: planning) Brain CT or MRI - Pro-gastrin releasing peptide (ProGRP) Thoracoscopyor percutaneousfine needle - Neuron-specific enolase (NSE) aspiration (FNA) for peripheral tumours - Soluble fragment of cytokeratin 19 (CYFRA 21-1) Effusionaspiration and cytology - Carcinoembryonic antigen (CEA) - Squamous cell carcinoma antigen (SCCA) NeoplasticMass Metastasis Malignant Benign • Breast • Colorectal Hamartoma • Prostate Primary • Well circumscribed • Sarcoma • Well differentiated • Bladder • Limited cytological atypia • Low mitotic index without atypical mitotic figures • Absenceof coagulative necrosis Low grade Carcinoid High grade Most common cause of cancer death in • Neuroendocrinetumours in digestive tract or lungs the UK • In lungs: usually on bronchial wall – cough, haemoptysis • Usually asymptomatic for many years Carcinoidsyndrome Small cell Non-small cell • Release of serotonin,histamine,prostaglandins, bradykininsetc. • Usually metabolisedby lungs and liver • No release into systemic circulation until metastasis • In only 10% of patients with carcinoid tumours • Symptoms:flushing,diarrhoea, tachycardia, bronchospasm,hypotension Adenocarcinoma Squamous cell Large cell carcinoma carcinoma • Diagnosis: 24 hour urine 5-HIAA + Functional imaging Case1:Biopsyresults hyperchromatic nuclei, minimal cytoplasm – “oat cells” positive for TTF-1 Diagnosis: small cell lung cancerCancercells:histologicalfeatures High Nuclear: cytoplasmic ratio disorganised architecture hyperchromatic nuclei mitotic figures pleomorphism Lungcancerclassification:SmallCellvsNSCLC SmallCellLungCarcinoma(15%) Adenocarcinoma(40%) ● Centrallylocated (arises from neuroendocrine cells of basal bronchial epithelium) ● Peripherallesions ● Usually advanced at diagnosis and likely only ● Can develop in non-smokers ● Histology: back-to-back large amenable to chemotherapy ● Almost exclusively associated with smoking glandular structures filled with mucin Squamouscellcarcinoma(30%) Largecellcarcinoma(10%) ● Often arises ● Prognosis less favourable than centrally/proximally in large other forms of NSCLC bronchi, M>F ● Usually develop in outer regions ● Can cause obstruction of of lung airway/collapsed lung ● Histology: large, poorly ● Histology: malignant differentiated cells without squamous cells with squamous or glandular features keratinization – “keratin ● Most common subtype: pearls” and intercellular neuroendocrine carcinoma bridges ● Synaptophysin +veCasecontinued… Initial blood results showed: The clinical picture is consistent with SIADH. ● sodium110 ↓ ● serumosmolarity227 ↓ This is most likely due to a paraneoplastic manifestation of his underlying small cell ● urineosmolarityof 579 ↑ lung cancer. Clinically he was euvolaemic. Fluid restriction led to normalization of his sodium and resolution of nausea & vomiting. Whatdoes this mean?ParaneoplasticSyndromes • Remote complications of cancer, not as a direct result of tumour invasion • Most arise due to secretion of hormones, cytokines or growth factors • Can also arise when normal cells secrete products in response to tumour cells e.g. antibodies Endocrine Neurological ● Cushing’s syndrome: ectopic secretion of ACTH ● Mostly immune mediated ○ Most commonly in small cell lung cancer (>50%) ○ Central obesity, proximal muscle weakness, Lambert Eaton syndrome: striae, hypertension, insulin resistance ● Associated with small cell lung cancer ○ Elevated urinary free cortisol and failure of ● Caused by antibodies against presynaptic voltage suppression by low dose dexamethasone gated calcium channels -> reduced release of ACh ● SIADH ● Proximal muscle weakness sparring eyes; power ○ Most commonly in SCLC increasewith repetition ● Hypercalcemia due to production of parathyroid hormone-related protein (PTHrP) ○ Associated with squamous cell carcinoma Dermatological ○ High calcium, low phosphate ● Next slideParaneoplasticdermatologicalconditions dermatomyositis Heliotrope rash Shawl sign Gottron papules acanthosis nigricans – adenocarcinoma, predominantly gastric Leser-Trélat sign – explosive onset of seborrhoeic keratosesNext steps after diagnosis? MDTmeeting (Surgeons, MDT Coordinator, Medical Oncologists, Histopathologists, Specialist Nurses, Clinical Oncologists) performance status Treatmentplanning type of cancer and Treatments with a curative intent vs Palliative therapy oncological stage patient preference and quality of life Treatments with a curative intent: Palliative therapy ● radiotherapy ● symptom management (pain, ● chemotherapy breathlessness, anxiety) ● surgery ● palliative radiotherapy/chemotherapy ● immunotherapyCase2 As the junior doctor at the GP surgery, you see Miss A, a 37-year-old lady, who is worried about her risks of breast cancer and asks you about breast cancer screening. Please outline the breast cancer screening programmein the UK. CancerscreeningintheUK Breast Cervical Bowel All women between 50-70. Women from age 25 to 64 All aged between 60-74. Mammogram every 3 years. - every 3 years between 25-49 Faecal immunochemical Can request if over 70 just - every 5 years between 50-64 test (FIT) test every 2 years. not automatically allocated. - can ask for one over 65 if never had before Can request over 74. HPV primary screening May start younger (using MRI) People at high risk of bowel if strong FH/other RF e.g. cancer have screening with ● BRCA1/2 -> Annual MRI colonoscopy e.g. annually if from age 30. FAP or Lynch, between 35- ● Some women who have 45 if strong other strong FH had RTx for HL <30yrs to check for polyps. start screening earlier Other groups: IBD, Hx of with annual MRIs - polyps, previous Hx of depends on risk. bowel cancer.Whatmakesagoodscreeningprogramme? General screening programme 1. Test is sensitive 2. Can actually intervene/treatment available 3. Specificity 4. Test is acceptable 5. Cost effective 6. Practical to deliver at a large scale 7. Screening is minimally harmful 8. Understanding biology of disease e.g. recognise precursor -> earlier detection must improve outcome 9. Family member considerations 10. Disease in question is sufficiently prevalent in the publicMissAisnowinher50sandreportsabreastlump What do all patients that present with a breast mass undergo at the breast clinic?MissAisnowinher50sandreportsabreastlumpMiss B screening mammogramMRI-basedscreeningforbreastcancerinthefuture? Baltzer et al 2010Fine-needleaspiration ACS Shigematsu et al 2011CorebiopsyCorebiopsy Diagnosis: invasiveductal carcinoma At lower magnification: Loss of normal breast architecture. Evidence of neoplastic cells (pleomorphic, mitotic figures, nuclear hyperchromatism) forming cords and nests, extending irregularly through stroma. Microcalcification in lower centre right. At higher magnification: Pleomorphic cells forming nests and irregular gland like structures Infiltrating through collagenous stroma LCIS: Solid, monotonous proliferation of DCIS: duct proliferation, malignant features, no stroma invasion small, discohesive cells expanding terminal duct lobular units and small ducts. Bound by basement membrane. Loss of E-cadherin staining. Lobularcarcinoma More commonly multifocal and no mass. Medullarycarcinoma Cells are arranged in slender Most common type in BRCA1 patients. linear strands. Well circumscribed (pushing borders), syncytial growth of cells. Prominent lymphoid infiltrate. Abundant eosinophilic cytoplasm (with a hint of squamous differentiation). Large pleomorphic nuclei + prominent nucleoli + frequent mitoses.Spot diagnosisHistopathological grade Tubules, pleomorphism, mitoses; Grade 1 = 3-5, Grade 2 = 6 or 7, Grade 3 = 8 or 9Summaryofbreastcancer Lump- Non-lump forming forming Medullary Ductal carcinoma carcinoma Paget’s Lobular Inflammatory diesaea carcinomaBreastcancertreatmentFurthercomplications 10 years later Miss A presents to the GP with a 2 day history of ‘heavy legs’, reduced bilateral sensation in lower limbs on a background of 6 weeks of back pain that keeps her up at night and is unresponsive to analgesia given to her by the GP. On further inquiry she has lost 3kg of weight over last few months. O/E: Mid spine tenderness, bilateral lower limb reduced power (⅘), hyperreflexia, reduced sensation L4- S1. Normal upper limb neurology. GP organises urgent admission to the hospital for MRI. Whatis thelikelydiagnosisfromthepresentationand imaging,andtheinitialmanagement?Metastaticspinalcordcompression Presentation Most common Back pain keeping awake at night cancers: ● Prostate Hyperreflexia -> UMN sign ● Breast ● Lung Sensory and motor loss bilaterally Mid thoracic tenderness ● Myeloma The MRI spine shows a collapsed vertebral body at T9 with retropulsion causing compression of the thoracic cord. Other bony Thoracic 70% metastases are visible. Cervical 10% Lumbar 20% With her history of malignancy and systemic symptoms (weight loss) this is likely to be metastatic. 1. High dose steroids: dexamethasone 16mg/d PO stat 2. Urgent MRI + consult neurosurgeons 3. Analgesia, catheter, laxatives, bed rest 4. Definitive management: Surgical decompression appropriate if one site, limited disease, histology needed, skeletal instability. Most pt: urgent radiotherapy – initially induces oedema so things worsen before get better.Morecomplications… Miss A has a bone scan and CT-CAP and wide spread metastasis in her lung, liver and bone are found. Decision is made for palliative management and Miss A goes home to be with her family. A few months later her husband brings her back to the hospital as he is concernedthat she has deteriorated quite opioid dose. Blood tests are done for reversible causes and her Calcium is found to be 3.5.sing her Explainthe possible pathologyof the abnormal finding and management of this.Hypercalcaemia CancersmostfrequentlyassociatedwithhyperCa: ● Breast Symptoms(bones, stones, groansandpsychicmoans) ● Myeloma ● Renal cell • General: fatigue, malaise, anorexia, dehydration, polyuria, polydipsia, ● Squamous cell tumours – esp. bronchus hypercalciuria and renal stones • Neurological: confusion, depression, headache, drowsiness, coma Management • GI: anorexia, nausea, vomiting, constipation, abdo pain <3: watch/wait, rx if sx troublesome • Life threatening: bradycardia, coma, heart block >3: recommend treatment to reduce distressing sx: 1. Rehydration with 1-2L IV normal saline. • Non specific sx - important to monitor Ca on unwell pt. Commonly need 4L. 2. IV bisphosphonates (zoledronic acid) Causes of hyperCainmalignancy If don’t respond - denosumab - particularly for bony mets. •Paraneoplastic syndrome of Parathyroid Hormone-related protein: • Less likely to respond to bisphos. Maintain hydration and repeat Ca/U+Es at 48h. Normalisation can take 3 days. Check not rising again • 80% of cancer associated cases. after 3 weeks - sometimes monthly rx required. • Osteolysis by tumour • Local resorption of bone by osteoclasts in areas of marrow with malignant cells. •Treatable but a poor prognostic sign in metastatic disease - median survival approx. 3 months. Case 3 History: Examination: A 14-year-old girl (Miss H) is brought into A&E by her O/E: HR 110/min, BP 110/70, RR 28/min, temp 36.9 . mother with increasing shortness of breath and facial Marked facial oedema and swelling of upper limbs and swelling. chest wall, distended neck veins, raised JVP and prominent veins present on whole of the chest wall. Her mother reports increasing breathlessness and dry cough over the last month. Over the last 2 weeksshe Resp exam: dullness on percussion, reduced vocal has been puffy around the eyes in the morning, and in resonance, and decreased breath sounds over upper the past week this has been more persistent and has right side of chest and upper sternum. Rest of exam spread to include her whole face and arms too. normal. CVS, CNS and abdo examinations normal. No significant She is now breathless on standing up, and symptoms lymphadenopathy present in neck, axilla or inguinal worsen if she raises her arms,aand when lishedliwsd.own. region. No hx of fever, weight loss, neck swellings. Reference: https://casereports.bmj.com/content/2012/bcr.01.2012.5487.fullBased on presenting complaint and examination findings, what is the clinical diagnosis and initial acute management? ● Dyspnoea and cough ● Facial swelling +/- upper limb swelling ● Dilated/distended neck and chest wall veins ● Symptoms exacerbated by raising arms either side of face = Pemberton’s sign (facial congestion, cyanosis and resp distress) ● Examination findings (dullness to percussion, reduced resonance and decreased breath sounds) SUPERIOR VENA CAVA ONBSTRUCTION(SVCO) ONCOLOGICAL EMERGENCY SVCO Features: Causes: Presents over weeks-months with: Malignant (60-80%): - Dyspnoea, orthopnoea, cyanosis - Lung cancers (70-80%) - NSCLC - Cough, headaches (worse leaning forward), hoarseness 50%, SCLC 25% (though greater - Dusky skin colour over chest, arms, face, overall incidence) - Swelling of face, neck, arms/chest - Lymphoma (NHL (10%) >HL), - Facial oedema and plethora - Other: Mediastinal Germ Cell - Distended neck and arm veins Tumour, Thymoma, Metastatic LN Complications: laryngeal oedema (stridor, airway Non-malignant: catheter associated obstruction), cerebral oedema (cognitive thrombus, sarcoid, aneurysm, LNpathy, dysfunction), PE, reduced CO mediastinitis SVCO Investigations: Management: - Usually CXR 1. Sit patient upright and give high - CT to confirm flow O2 - Histological diagnosis (if first 2. Start high dose steroids (Dex 8- presentation) helpful for management 16mg stat) to reduce swelling +/- loop diuretics 3. Analgesia for pain + anticoag (high risk thrombus) 4. Histological dx guides further mx: chemoresponsive tumour (e.g. SCLC)-> chemo 5. Otherwise - RT to shrink tumour Describe and interpret Miss H’s imaging ● The CXR shows widened mediastinum and large well- defined opacity in the right upper and middle zone. ● CT imaging shows a large homogenously enhancing mass lesion in the anterior mediastinum, compressing and displacing adjacent right lung, along with superior vena cava. https://casereports.bmj.com/content/2012/bcr.01.2012.5487.fullDifferential diagnosis of a mediastinal mass: ● Malignancy ○ Lymphoma - NHL/Hodgkins ○ Leukemia ○ Lung cancer (very young for this) ○ Mediastinal Germ cell tumour ○ Thymus: Thymoma, Thymic carcinoma ○ Neuroblastoma (quite old) ○ Thyroid cancer ● Vascular ○ Thoracic aortic aneurysm ○ Aortic dissection ● Sarcoidosis ● Infection ● Pericardial/bronchogenic/oesophageal cyst Miss H undergoes CT guided biopsy. Histology shown below. Describe the images and suggest the likely diagnosis. Source: https://webpath.med.utah.edu/Miss H Bands of pink collagenous tissue ● Lymphocytes dividing up the field = nodular ● Reed Sternberg cells = Hodgkin Lymphoma. sclerosis. ● Cancer buzzwords: pleomorphic cells, hyperchromatic nuclei, mitotic figures etc. https://www.cap.org/member-resources/case-of-the-month/t- lymphoblastic-leukemia-lymphoma-tlbll-2019 Lymphoma - Histopathology Hodgkin Lymphoma Non-Hodgkin lymphoma Teens/adolescents/young adults Key = Reed Sternberg cells: ● Lymphoblastic lymphoma (T>B) - have ≥2 nucleoli in 2 separate nuclear lobes. CD15+ - Lymphoblasts - scanty cytoplasm, irregular nuclei, Tdt+, 1. Classic HL- RS cells that are CD15+ CD30+ CD45- CD3/20+ a. Nodular sclerosis - 60-80%: bands of fibrosis, lacunar cells ● DLBCL (Diffuse large B cell) (large cells large with clear space surounding nucleus (fixation - Large cells artefact)) - (≥ 2x size of lymphocyte). b. Mixed cellularity (15-30%) - older, lots of different cells - Moderately abundant cytoplasm c. Lymphocyte rich: (5%) mostly reactive lymphocytes + RS cells. ● Burkitt lymphoma d. Lymphocyte depletion: (<1%) many RS cells and variants/fibrous tissue. Poor prognosis. - t(8,14) is characteristic - ‘Starry sky’ appearance 2. Nodular lymphocyte predominant - mostly B cells and few - (tangible-body macrophages) variant CD20+ CD15- CD30-. RS cells. (5%) Acts like low grade. - Endemic version in jaw Popcorn/LP cells (lobular nuclear contour) ● Anaplastic large cell lymphoma https://webpath.med.utah.edu/ - T cell - Large, pleomorphic cells - ALK + CD30+. ALK translocation ● Low grade e.g. SLL, FL, Marginal, Mantle cell https://www.pathologyoutlines.com/topic/lymphomanonBanaplastic.htm lMiss H is rapidly started on treatment with ABVD chemotherapy and local radiotherapy. Day 2 feels nauseous, starts vomiting and is noted to have a reduced urine output. She says has palpitations and an ECG shows tented T waves. Repeat bloods are shown below. Which likely complication of treatment ABVD chemotherapyincludes: has occurred? •A – doxorubicin (Adriamycin) •V – vinblastine •D – dacarbazine (DTIC) Patient’s blood Normal values Serum Na (mmol/l) 138 135-145 Serum K (mmol/l) 6.2 3.5-5.0 Creatinine (micromol/l) 315 55-120 Corrected Ca (mmol/l) 1.6 2.1-2.6 Phsophate (mmol/l) 2.52 0.8-1.4Answer ● Blood results show hyperkalaemia, hyperphosphataemia and hypocalcaemia ● Creatinine is raised + reduced urine output -> AKI ● This suggests that Miss H has developed tumour lysis syndrome due to the rapid destruction of a large number of tumour cells. ● Pathophysiology: rapid death of large number of cells releasing K+, phosphate and purines. The phosphate binds Ca and precipitates, causing hypoCa and the purines are converted to uric acid ● Deposition of uric acid crystals and calcium phosphate contribute to causing an AKI. ● Hyperkalaemia causes arrhythmias and tented T waves.Tumour Lysis Syndrome (TLS) Acute destruction of large number of cancer cells in bulky chemosensitive disease (e.g. lymphoma, leukemia, GCT) -> TLS. Release from cells: ● K -> HyPER K+ ● Phosphate -> binds calcium -> HyPERphosphate + HyPO Ca ● Purines -> uric acid metabolism -> HyPERuricaemia Renal failure due to crystallisation of uric acid and coprecipitation of Ca-phosphate Sx: fatigue, nausea, vomiting, arrhythmia, HF, tetany, seizures, sudden death http://www.learnpicu.com/oncology/tumor-lysis-syndrome Treat with: ● Allopruinol (reduces conversion of purines to uric acid) Intermediate - high risk cancers: - high grade NHL e.g. Burkitts, DLBCL, ● Rasburicase converts urate to allantoin lymphoblastic lymphoma ● Treat hyperK : IV Ca gluconate, insulin + dextrose etc. - ALL ● Reduce phosphate: oral phosphate binders, dextrose + insulin, may give Calcitriol. - AML Low risk: Hodgkin’s lymphoma, low grade NHL, solid tumours, chronic leukemia, MM If not responding: urinary alkalinisation, haemodialysis.In high risk disease, how could this complication be prevented? ● Regular monitoring of serum biochemistry ● Give initial chemo slowly ● Hydration (start 48h before in high risk) ● Allopurinol prophylaxis (reduces conversion of purines to uric acid)Case 4 • Mr C, a 25-year-old presents with one episode of haematochezia. He is concerned because his mother died of colorectal cancer at 50 years of age. He has no further information about his family history. Physical examination is normal. He undergoes colonoscopy and is found to have 20 adenomas ranging in size from 4 to 15 mm. • What are you suspecting? Familial adenomatous polyposis Hereditary colorectal cancer syndromes characterised by the development of hundreds to thousands of colorectal adenomas. The attenuated form leads to the formation of fewer than 100 polyps Investigations • Colonoscopy • Genetic testing Differentials: • MRI/CT - MUTYH polyposis - Peutz-Jeghers syndrome Presentation • Constipation/diarrhoea • Haematochezia • Extraintestinal features: skin cysts, lipomas and fibromas, supernumerary teeth, thyroid nodules and cancer, osteomas, desmoid tumours, adrenal adenomas, and congenital hypertrophy of the retinal pigment epithelium Management • Total prophylactic proctocolectomyFamilial cancer syndromesThank you! Feedback please 😇 Big thanks to previous CU OncSoc committee members for the content! www.facebook.com/cambridgeoncsoc www.instagram.com/cambridgeoncsoc www.twitter.com/cuoncsoc