15 & 16 - Lung Cancer Flashcards
Second most common type of cancer in each men and women
Lung Cancer
Leading cause of cancer death
Lung Cancer
Screening - CT vs CXR
CT catches more, catches them earlier, helps more people survive
More false positives!! (noncalcified granulomas or benign intrapulmonary LN)
Cytology specimens
Fine needle aspiration
An assortment of cells
Core biopsy
Tissue in context!
Minimally invasive procedures
CT guided biopsy - FNA & Core, only peripheral
EBUS - EndoBronchial Ultrasound-Guided Something - FNA, but not Core. Central only. Can stage.
Electromagnetic navigational bronchoscopy - FNA & Core, Peripheral & Central, can’t stage, though
Classifications of Tumors in the Lung
Epithelial Mesenchymal Lymphohistiocytic Ectopic origin Metastatic
Mesenchymal Tumors
Not epithelial cells
Most common Mesenchymal Tumor in Lungs
Hamartoma
Hamartoma
Tissue elements normally found in lung but occurring as disorganized proliferation
Benign
“Coin lesions” with popcorn calcifications
Well-circumscribed
Slow-growing
Hamartoma - Morphology
Varying amounts of mesenchymal elements (Cartilage, fat, connective tissue, bone)
Entrapped respiratory epithelium
Categories of Epithelial Tumors of the Lung
Neuroendocrine Tumors
XXX
XXX
Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH
Proliferation of neuroendocrine cells Confined to mucos aof airways Invade locally to form tumorlets Develop into carcinoids Rarely associated with small cell carcinoma and large cell neuroendocrine carcinoma
Neuroendocrine Tumors - Low-intermediate grade
Typical carcinoid
Atypical carcinoid
Neuroendocrine Tumors - High Grade
Small cell carcinoma
Large cell neuroendocrine carcinoma
Neuroendocrine - Typical Carcinoid
Central Airways > Peripheral
Well-circumscribed
Fill bronchial lumens
Morphology:
Monomorphic
Fine “salt and pepper” chromafin
Immunostains:
Synaptophysin
Chromogranin
CD56
Neuroendocrine - Small Cell Lung Cancer
Large central mass with bulky mediastinal adenopathy
Morphology: Scant cytoplasm Inconspicuous/Absent nucleoli Nuclear molding Crush artifact Numerous mitoses
Immunostains: Neuroendocrine markers Synaptophysin Chromogranin CD56
Squamous Cell Carcinoma
Preinvasive: Squamous cell carcinoma in situ
Invasive: Keratinizing, Non-Keratinizing, Basaloid squamous cell carcinoma
Adenocarcinoma
Preinvasive: Atypical adenomatous hyperplasia (AAH), Adenocarcinoma in situ
Invasive: Adenocarcinoma, classification based on predominant subtype:
Lepidic, acinar, papillary, micropapillary, solid
Squamous Cell Carcinoma - Life cycle
Early:
Normal - Ciliated epithelium
Hyperplasia
Squamous metaplasia
Intermediate:
Dysplasia
Late:
Carcinoma in situ
Invasive carcinoma
Squamous Cell Carcinoma - Histo
Morphology:
Keratinization
Intercellular bridges
Immunostains:
P40
P63
CK5/6
Adenocarcinoma - Life Cycle
Pre-invasive:
Atypical Adenomatous Hyperplasia (AAH) (less than .5cm)
Adenocarcinoma in Situ (less than 3cm)
Invasive:
Minimally invasive adenocarcinoma
Adenocarcinoma - Histo
Morphology:
Glands/acini
(micro)papillae
Mucin
Immunostains
TIF-1
Napsin A
Which two molecular tests do you do on an adenocarcinoma?
EGFR Mutation
ALK rearrangement
Large Cell Carcinoma
Non-small cell carcinoma
Lacks cytological architectural and immunohistochemical features of small cell carcinoma, adenocarcinoma and squamous cell carcinoma
Catch-all
Sarcomatoid Carcinoma
Pleomorphic Carcinoma
Non-small cell carcinoma, with at least 10% spindle and/or giant cells
Lung Metastases - Presentation
Single or multiple
Lymphangitic
Lung parenchyma or pleura>endobronchial mass
Lung Metastases - Common sites
Breast Prostate GI tract Gynecological Head & Neck
Lung Metastases - Pathological Diagnosis
Clinical
Morphological
Immunohistochemical
Lung Cancer Presentation - Local Symptoms
Cough Dyspnea Hemoptysis Chest pain Hoarseness (recurrent laryngeal nerve) SVC Syndrome Wheezing
Lung Cancer Presentation - Systemic Symptoms
Constitutional:
Weight loss
Malaise
Skeletal:
Clubbing
Hypertrophic Pulmonary Osteoarthropathy
Endocrine:
SIADH (SCLC)
Hypercalcemia (Squamous)
Cushings Syndrome (SCLC)
Neurologic:
Horner’s Syndrome
Eaton-Lambert Syndrome (SCLC)
Vascular:
Hypercoagulable state of malignancy
Thrombophlebitis
DIC
NSCLC Staging - Determination
Size
Invasion of adjacent structures
Separate nodules with the same morphology
Lung Cancer - Clinical Staging
PET scan
MRI
TNM - Nodes N1 vs N2
N1 = Double Digit Station (more peripheral) N2 = Single Digit Station (more central)
Dr. Bosl’s Rules of Cancer
It’s not cancer until proven to be cancer
If it’s cancer, it’s curable until proven otherwise
If it’s not curable, the cancer is treatable until proven otherwise
Even if the cancer is not treatable, the patient is always treatable.
Definitive Management - Early Stage Disease
Surgery
Anatomical resections:
Pneumonectomy - High M&M, especially a right pneumonectomy. MAJOR functional consequences (60% function loss)
Lobectomy - Preferred surgical option for most patients
Lung-preserving surgery:
Wedge Resection - Least morbidity, commonly done, but recurrence rate higher. Can be safe in patients with limited lung function. First surgical step if pathology is unclear.
Techniques:
Conventional open
VATS (Video-Assisted Thoracoscopic Surgery)
Robotic
Adjuvant Treatment
Given after surgery to decrease risk of recurrence
Chemotherapy (eliminate micrometastatic disease)
Radiotherapy (eliminate localized disease at resection margins/mediastinal nodes)
Curative intent, but no guarantee
Lung Cancer - Adjuvant Treatment (Stage I - II)
Platinum Doublet
No major difference in efficacy between various chemotherapy doublets in advanced disease
Cisplatin with: Premetrexed Docetaxel Gemcitabine Etc
4cm cutoff for adjuvant chemotherapy
Lung Cancer - Adjuvant Treatment (Stage III)
Involves local and distant therapy
Surgery → Adjuvant chemo → PORT
Neoadjuvant Chemo → Surgery → +/- PORT
Chemo + XRT → Surgery
Chemo + XRT
PORT
Post-Operative RT
When you discover mid-surgery that there is N2 lymph node involvement, causing them to be a higher stage than you thought.
PORT has not been shown to improve survival
Increases mortality in N0 and N1
Stage IIIB
Involvement of the contralateral lymph nodes
Prognosis poor
They are essentially at stage 4, so only treat with chemo & XRT or XRT alone. No surgery.
Platinum Doublets for Stage IIIB treatment
Cisplatin and Paclitaxel
Cisplatin and Gemcitabine
Cisplatin and Docetaxel
Carboplatin and Paclitaxel
Which platinum doublet is best?
THEY ARE ALL THE SAME
Cisplatin - Mechanism
Platinum agent
Inhibits DNA synthesis by the formation of DNA cross-links, disrupts DNA function
Cisplatin - Side effects
Neurotoxicity Nausea/vomiting Ototoxicity Nephrotoxicity (must hydrate) Electrolyte disturbances
Paclitaxel - Mechanism
It’s a taxane
Disrupts microtubule function (stabilizer), cell cycle arrest & apoptosis
Paclitaxel - Side Effects
Alopecia Decreased blood count Neuropathy Hypersensitivity reaction Arthralgias/myalgias Fatigue Nail changes
Pemetrexed - Mechanism of Action
Antimetabolite
Inhibits folate-dependent enzymes involved in purine & pyrimidine synthesis:
Thymidylate Synthase (TS)
Dihydrofolate Reductase (DHFR)
Glycinamide Ribonucleotide Formyltransferase (GARFT)
Multi-targeted folate analogue
Adenocarcinoma does better with this than other drugs
Premetrexed - Side Effects
Well tolerated, for the most part Decreased blood counts Nausea Fatigue Rash Supplementation with B12 and folic acid to reduce side effects.
EGFR Pathway
Member of the HER family of cell surface TKRs
Downstream signaling via RAS/MAPK, PI3K/AKT pathways
Inappropriate signaling leads to:
Increased/uncontrolled cell proliferation
Decreased apoptosis
Enhanced cancer cell motility
Angiogenesis
Lung cancer with an EGFR mutation
Predictive AND prognostic
Better prognosis
Responds well to an EGFR TKI
Give an EGFR TKI to Lung Cancer with EGFR mutation
Higher response rates in:
Females
Never smokers
Asians
ALK+ NSCLC - Treatment
Crizotinib (WAY BETTER THAN CHEMO)
Small Cell Lung Cancer - Staging
Limited Vs Extensive stage disease based on radiation fields
Limited: 40% of patients 14 - 20 months median survival 40% 2-year survival 10 - 20% long-term survival
Extensive: 60% of patients 8 - 12 months median survival 5 - 10% 2-year survival Very few long-term survivors
Limited Stage Small Cell Lung Cancer - Treatment
Surgery is rarely an option Standard of care: Chemo & XRT Chemo = Platinum + Etoposide (4 - 6 cycles) Concurrent > Sequential BID may be more effective than daily RT?
Limited Stage Small Cell Lung Cancer - During Remission
Give Prophylactic Cranial Irradiation (PCI)
10 - 30% of patients entering complete remission relapse with isolated CNS mets
PCI (20 - 40 Gy) improves survival
Long-term neuropsychiatric defects commonly noted
Extensive Stage SCLC
Very poor outcome
9 - 12 months medical survival
Standard treatment is chemo (4 - 6 treatments of platinum/etoposide)
60 - 80% response rate
Patients quickly relapse
2nd line chemotherapies provide only short-term benefits
Etoposide - Mechanism of action
Topoisomerase inhibitor
Forms complex with DNA andtopoisomerase II
Prevents re-ligation of DNA strands causing breakage
Etoposide - Side effects
Alopecia Nausea Decreased blood counts Fatigue Secondary leukemia
