ICL 3.6: Pathology of Pulmonary Tumors Flashcards Preview

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what are the 2 types of primary lung tumors?

1. 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

2. 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?

1. smoking

2. industrial hazards

asbestos, radiation, nickel, arsenic, chromium

3. air pollution

second hand smoke


which genetic factors are associated with primary lung tumor?

oncogenes and tumor suppressor genes associated include:

1. small cell carcinoma = p53, C-MYC, RB

2. non-small cell carcinoma = p53, RAS, p16

3. familial clustering = Polymorphism in the cytochrome P-450 gene CYP1A1


what are the precursor lesions associated with primary lung tumors?

1. squamous dysplasia = cells have undergone aggressive changes, large nuclei, but only part of the surface epithelium is involved

2. carcinoma in situ = entire surface epithelium is involved but dysplastic cells don't cross BM

3. 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.



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)

1. no evidence of stromal, vascular, or pleural invasion

2. 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.


cause of seizure?


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%)

2. liver (30-50%)

3. brain (20%)

4. 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?


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?

1. pneumonia*, abscess, lobar collapse --> tumor obstruction of airway

2. lipoid pneumonia --> tumor obstruction, accumulation of cellular lipid in foamy macrophages

2. pleural effusion --> tumors spread into pleurae

3. hoarseness --> recurrent laryngeal nerve invasion

4. diaphragm paralysis --> phrenic nerve invasion

5. rib destruction --> chest wall invasion

6. SVC syndrome* --> SVC compression by tumor; patient presents with face and arm swelling with purple discoloration

7. Horner syndrome* --> ptosis, miosis and anhydrous due to sympathetic ganglion invasion

8. 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?


2. parathormone, parathyroid hormone-related peptide, prostaglandin E* --> cause hypercalcemia and is associated with squamous cell carincoma

3. calcitonin-hypocalcemia

4. gonadotropins - gynecomastia

5. serotonin-carcinoid syndrome

6. 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?

1. Lambert-Eaton

2. dermatologic changes (acanthosis nigricans)

3. hypertrophic pulmonary osteoarthropathy

4. 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:

1. brain
2. bone
3. adrenal
4. liver

cervical and supraclavicular (Virchow’s node) lymphadenopathy


what are the complications of lung cancer?

1. atelectasis if obstructing the main bronchus

2. pneumonia

3. lung abscess

4. bleeding

5. esophago-pleural fistula

6. effects of metastases on other organs

7. 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

1. contain dense neurosecretory granules in the cytoplasm

2. cells grow in clusters, uniform round nuclei

3. epithelial cells twice the size of lymphocytes, round or oval, scant cytoplasm

4. in some cases spindle shaped or polygonal