ICL 3.6: Pathology of Pulmonary Tumors Flashcards
what are the 2 types of primary lung tumors?
- small cell lung cancer (SCLC)
treated with chemo, with or without radiation – usually when you discover them they’re at an advanced stage with mets
- non-small cell lung cancer (NSCLC)
treated with surgical resection if localized at the time of the diagnosis; less often metastatic
what is the relationship of primary lung tumors with smoking?
increases incidence of all types of primary lung tumors
strongest association with squamous cell and small cell carcinomas
cancer which most likely occurs in non-smokers is adenocarcinoma
what are the risk factors for developing primary lung tumor?
- smoking
- industrial hazards
asbestos, radiation, nickel, arsenic, chromium
- air pollution
second hand smoke
which genetic factors are associated with primary lung tumor?
oncogenes and tumor suppressor genes associated include:
- small cell carcinoma = p53, C-MYC, RB
- non-small cell carcinoma = p53, RAS, p16
- familial clustering = Polymorphism in the cytochrome P-450 gene CYP1A1
what are the precursor lesions associated with primary lung tumors?
- squamous dysplasia = cells have undergone aggressive changes, large nuclei, but only part of the surface epithelium is involved
- carcinoma in situ = entire surface epithelium is involved but dysplastic cells don’t cross BM
- atypical adenomatous hyperplasia = associated with adenocarcinoma
what is the morphology of primary lung tumors?
squamous and small cell carcinoma usually arise most often in and around the hilum
it begins as a small area of in-situ atypia and progress <1.0 cm of mucosal thickening
progresses to an irregular*, warty lesion which elevates or erodes lining epithelium
what is the location of primary lung tumors?
adenocarcinomas are mostly peripheral (25%)
squamous cell and small cell carcinomas are usually centrally located in the 1st, 2nd and 3rd order bronchi (75% of primary tumors)
what is squamous cell carcinoma?
primary lung tumors more common in men
close association with smoking
occurs in larger, more central bronchi, but incidence in periphery is increasing
paraneoplastic syndrome: hypercalcemia due to tumor producing parathyroid hormone like peptide
50 year old woman, non smoker, presents with cough and hemoptysis for three months. PE negative
Chest x ray peripheral coin lesion in RT middle lobe.
diagnosis?
tests?
adenocarcinoma of the lung
common in women non-smokers and presents with peripheral lesions
what are adenocarcinomas?
non-small cell lung cancer most common type in women and in nonsmokers
> 75% found in smokers
more peripherally located; arise from bronchi
80% mucin secreting
grow slower than squamous cell carcinomas; tend to be smaller so better prognosis
may be associated with scars
the majority are positive for TTF1 = thyroid transcription factor 1 –> can be used as a marker for diagnosing adenocarcinoma
what is a common mutation associated with adenocarcinoma?
EGFR mutations (epidermal growth factor receptor gene)
common in Asian women
can be treated with EGFR inhibitors (promising response)
what is a bronchioloalveolar carcinoma?
a subtype of adenocarcinoma with relatively good prognosis
1-9% of all lung cancers
arises in pulmonary parenchyma in terminal bronchioloalveolar regions
equal incidence in males and females
start in second decade of life
symptoms appear late and include cough, hemoptysis and pain
metastases – late; in 45% of cases
what are the gross and microscopic changes seen in bronchioloalveolar carcinoma?
gross = solid gray white area(s)
microscopic:
1. no evidence of stromal, vascular, or pleural invasion
- growth along preexisting bronchioles without destruction of alveolar architecture
60 year old female smoker presents with a seizure, she had a cough with blood streaked sputum for two months. CXR shows hilar lesion in the right lung.
diagnosis?
cause of seizure?
tests?
small cell-cancer of the lung
hyponitremia paraneoplastic syndrome causing seizure
what is small cell carcinoma?
occurs in cigarette smokers, only 1% in non-smokers
M > F
most aggressive of lung cancers, rapid growth, metastasize, widely and are incurable by surgical resection because by the time we’ve found it, it’s already metastasized –> metastasize early to lymph nodes and hematogenously
hilar or central location
most common pattern associated with ectopic hormone production (ACTH SIADH) = paraneoplastic syndrome
what is the histology of small cell carcinoma?
very undifferentiated; looks like purple cells everywhere
round, blue cells with “salt and pepper” chromatin
neurosecretory granules (EM) because it’s a neuroendocrine tumor
where do small cell carcinomas spread to?
more than 50% spread to lymph nodes: tracheal, bronchial and mediastinal
can extend to the pleural surface and then pleural cavity or into the pericardium
distant spread; favorite sites include:
1. adrenal (>50%)
- liver (30-50%)
- brain (20%)
- bone (20%)
metastases may be first sign of disease**
A 70 year old lady present with ptosis of her left eye for two weeks. She has been coughing for the last three months.
PE: miosis of the left pupil.
What would you like to ask her?
diagnosis?
lung cancer pressing on the sympathetic ganglion = Horner syndrome
miosis = pupil constriction
ptosis = droopy eyelid
what are the local effects of a small cell carcinoma spreading to other parts of the body?
- pneumonia*, abscess, lobar collapse –> tumor obstruction of airway
- lipoid pneumonia –> tumor obstruction, accumulation of cellular lipid in foamy macrophages
- pleural effusion –> tumors spread into pleurae
- hoarseness –> recurrent laryngeal nerve invasion
- diaphragm paralysis –> phrenic nerve invasion
- rib destruction –> chest wall invasion
- SVC syndrome* –> SVC compression by tumor; patient presents with face and arm swelling with purple discoloration
- Horner syndrome* –> ptosis, miosis and anhydrous due to sympathetic ganglion invasion
- pericarditis, tamponade
what is a paraneoplastic syndrome?
clinical syndromes that cannot readily be explained, either by the local or distant spread of the tumor or by the elaboration of hormones indigenous to the tissue from which the tumor arose
they occur in 1 to 10% of patients with lung cancer
may precede the development of a gross pulmonary lesion
may cause significant clinical problems
what are some of the paraneopalstic syndromes associated with lung cancer?
- SIADH*
- parathormone, parathyroid hormone-related peptide, prostaglandin E* –> cause hypercalcemia and is associated with squamous cell carincoma
- calcitonin-hypocalcemia
- gonadotropins - gynecomastia
- serotonin-carcinoid syndrome
- adrenocorticotrophic hormone (ACTH)* –> Cushing’s syndrome; small cell carcinoma
what is SIADH?
secretion of inappropriate ADH
patient will have hyponatremia which is associated with small cell carcinoma
what are the systemic manifestations of small cell lung cancer?
- Lambert-Eaton
- dermatologic changes (acanthosis nigricans)
- hypertrophic pulmonary osteoarthropathy
- infiltration of the sympathetic plexus causing Horner’s related to Pancoast tumors
what is Lambert-Eaton?
antibodies to neuronal calcium channels
muscles weakness that gets better with use (MG gets worse with use!)
this is a systemic manifestation of small cell lung cancer
what metastatic disease is associated with lung cancer?
common sites of metastases include:
- brain
- bone
- adrenal
- liver
cervical and supraclavicular (Virchow’s node) lymphadenopathy
what are the complications of lung cancer?
- atelectasis if obstructing the main bronchus
- pneumonia
- lung abscess
- bleeding
- esophago-pleural fistula
- effects of metastases on other organs
- compression of the superior vena cava (Pancoast tumor)
Horner’s syndrome
pancoast tumor
what are neuroendocrine tumors of the lungs? what are the 2 types?
they are tumors that arise form neuroendocrine cells
two types:
1. carcinoid
2 small cell carcinoma
what is a carcinoid lung tumor?
most patients < 40 yrs.; M=F;
20-40% non-smokers
generally located in the main stem bronchus
what are the microscopic changes seen in carcinoid lung tumors?
arise from neuroendocrine cells in the bronchial epithelium
- contain dense neurosecretory granules in the cytoplasm
- cells grow in clusters, uniform round nuclei
- epithelial cells twice the size of lymphocytes, round or oval, scant cytoplasm
- in some cases spindle shaped or polygonal
what is carcinoid syndrome?
intermittent attacks of:
1. flushing
- diarrhea
- cyanosis because they get asthmatic
- right sided heart lesions
what causes carcinoid tumors?
- intraluminal growth – dyspnea, infections, bronchiectasis, etc.
- capacity to metastasize – distant metastases rare.
- ability to elaborate vasoactive amines – carcinoid syndrome –rare
what is the most common tumor of the lung?
metastatic tumors
can be spread hematogenous, lymphatics or direct spread
what are the 3 patterns of metastatic tumors in the lungs?
- multiple nodules in the lung periphery
- peribronchiolar and perivascular lymphatics
diffuse infiltration of lung septa and connective tissue
lymphangitis carcinomatosis – subpleural lymphatics
- no macroscopic change, microscopic only at autopsy
what is a coin lesion of the lung?
a solitary, circumscribed mass greater than 1.5 cm in diameter on a chest x-ray
can be malignant or benign
malignant = bronchogenic carcinoma, metastasis
benign = hamartomas, granulomas, abscess
what is malignant mesothelioma?
tumor involving the visceral or parietal pleura usually caused by asbestos exposure
90% asbestos related; lifetime risk 7-10%
late period 25-45 years after exposure
risk not increased in smokers** –> risk of lung cancer with asbestos exposure IS increased in smokers
what is the clinical presentation of mesothelioma?
dyspnea, chest pain, recurrent pleural effusions
pulmonary asbestosis in 20%
death within 12 months of diagnosis in 50%
invades lung directly
metastases to hilar LN, liver
what are the central tumors of the lungs?
- small cell (pst aggressive, hilarious, smoking, usually metastasized by the time we find it, SIADH, hyponitremia, Lambert-Eaton, Cushing Syndrome)
- squamous cell (smoking, hilar, paraneoplastic parathyroid hormone peptide with hypercalcemia and constipation)
usually associated with smoking
what are the peripheral tumors of the lungs?
- adenocarcinoma (usually nonsmoker, women, +TTF1, mutation of EGF)
- bronchioalveolar carcinoma (nonsmoker, very young males, good prognosis)
what are the 3 paraneoplastic syndromes associated with small cell carcinoma?
- SIAHD = hyponatremia
- Lambert-Eaton
- ACTH: Cushing Syndrome
A six year old child puts the contents of a bag of peanuts in his mouth and then takes a deep breath with the idea of blowing the peanuts out all over his sister. However, he aspirates a peanut during this maneuver. One day later, he has slight dyspnea. On physical examination, his temperature is 36.8° C, pulse 70/min, respirations 17/min, and blood pressure 90/60 mm Hg. There are decreased breath sounds on auscultation and increased tympany on percussion over the right lower lung posteriorly. A chest CT scan shows a hemicircular area of density in the right lower lobe. Laboratory studies show a hemoglobin concentration of 13.6 g/dL and WBC count of 6175/mm3 . Gram stain of sputum shows normal flora. Which of the following complications has this child most likely developed?
atelectasis due to inhaled peanut obstructing bronchiole
what is atelectasis?
incomplete expansion or collapse of previously inflated lung, producing areas of relatively airless pulmonary parenchyma
can occur at birth or anytime afterwards
reversible, since collapsed lung can be reinflated EXCEPT with contraction atelectasis associated with scaring
what are the 3 types of atelectasis?
- obstructive
- compression
- contraction
local or diffuse fibrotic changes in the lung or pleura prevent lung expansion
what is obstructive atelectasis?
complete obstruction of an airway causes resorption of oxygen distally
can occur due to excessive bronchial secretions and mucus plugging (bronchial asthma, chronic bronchitis, post-op complication) or aspirated foreign bodies
tumors produce incomplete obstruction and localized emphysema
mediastinum may shift toward affected lung**
what is compression atelectasis?
filled pleural cavity (fluid, tumor, blood clot, or air)- partial or complete like from cardiac failure or neoplastic effusions or neumothorax
abnormally elevated diaphragm -basal atelectasis
mediastinum may shift away affected lung**
sand blaster
silicosis
shipyard worker
asbestos
pleural plaque
asbestos
increased REID index
chronic bronchitis
acute CORE pulmonale
PE
aspirin
intrinsic asthma
foul smelling sputum
bronchiestasis
failure to clear surfactant
pulmonary alveolar proteinosis
mucin, young age, good prognosis
bronchoalveolar carcinoma
hypercalcemia
squamous cell carcinoma of the lung
and sarcoidosis
most common lung cancer in women
adenocarcinoma
