Pulmonary pathology tumor pleura
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Pulmonary pathology tumor pleura

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Pulmonary pathology tumor pleura Pulmonary pathology tumor pleura Presentation Transcript

    • Lung Tumors
    • ~ 95% are carcinomas (parenchyma)
    • a) ~ 5% are bronchial
    • b) ~ 2-5 % mesenchymal + miscellaneous
    • Carcinoma
    • a) most common cause of cancer mortality worldwide
    • i) CA effects of cigarette smoke
    • ii) ~ 172,000 new cases in USA in 2003
    • whereas it was ~ 18,000 in 1950
    • iii) in women, more deaths from lung cancer vs. breast cancer (in 2003)
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    • b) occurs more often between 40-70 yrs
    • i) peak incidence 50-60 yrs
    • ii) < 2 % occur before 40 yrs
    • c) 5 yr survival rate  5-10 % !!
    • Etiology & Pathogenesis
    • a) “stepwise accumulation of genetic abnormalities that transform benign epithelium to neoplastic tissue”
    • i) similar to other tissues
    • b) unlike other tissues, environmental insult IS KNOWN
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    • Tobacco smoke
    • Causal relationship established !!
    • a) based on statistical data
    • i) 87 % carcinomas occur in active smokers or stopped recently
    • ii) avg. smokers  10x  risk compared to non smokers
    • iii) heavy smokers (> 2 packs/day - - 40 cigarettes)  60x  risk
    • iv) women have  susceptibility
    • v) association with cancer of mouth, larynx, pharynx, esophagus, pancreas, cervix, kidney, bladder
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  • vi) ~ 3000 deaths/yr in USA from second hand smoke vii) cigar, pipe also  incidence of cancer, but smaller than cigarettes viii) smokeless tobacco  oral cancers + nicotine addiction b) clinical data i) sequential changes in respiratory epithelium ii) linear correlation between extent or intensity of exposure and worrisome epithelial changes - squamous metaplasia  dysplasia  in situ  invasive www.freelivedoctor.com View slide
    • 2. Industrial Hazards
    • High dose ionizing radiation
    • a) uranium workers have 4x  risk
    • b) smoking miners have 10x  risk
    • Asbestos  risk of lung cancer
    • a) non smoking  risk by 5x
    • b) smoking  risk by 50-90x
    • c) latent period of 10-30 yrs.
    • d) of asbestos workers, death due to:
    • i) 20 % to lung cancer
    • ii) 10 % to pleural or peritoneal mesothelioma
    • iii) 10 % to GI cancers
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    • 3. Air Polution
    • Indoor air pollution
    • a) radon
    • i) inhalation of radioactive decay particles attached to bronchial epithelium
    • - correlation of lung cancers of non smokers
    • 4. Molecular Genetics
    • ~ 10-20 genetics mutations by the time the tumor is clinically apparent
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    • Lung cancers divided into 2 categories
    • a) small cell
    • b ) non-small cell
    • c) frequently involved oncogenes
    • i) c-MYC
    • ii) K-RAS
    • iii) EGFR
    • iv) HER-2/neu
    • d) common deleted tumor suppressor genes
    • i) p53
    • ii) RB
    • iii) p16
    • iv) multiple sites on chromosome 3p
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    • e) p53 mutations common to both small cell and non-small cell cancers
    • f) small cell cancers have more common
    • i) c-MYC
    • ii) RB
    • g) non-small tumors have more common
    • i) RAS
    • ii) p16
    • 5. Precussor Lesions
    • 3 types of precursor epithelial lesions
    • a) squamous dysplasia and carcinoma in situ
    • b) atypical adenomatous hyperplasia
    • c) diffuse idiopathic pulmonary neuroendocrine cell hyperplasia
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    • d) not known which pre-invasive lesions will progress or remain localized
    • 6. Classification
    • Proportions of major categories
    • a) Squamous cell CA (25-40 %)
    • b) Adenocarcinoma (25-40 %)
    • c) Small cell CA (20-25 %)
    • d) Large cell CA (10-15 %)
    • Adenocarcinoma has  incidence
    • a) most common type in women (men as well in several studies)
    • i) due to  # of women smokers
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    • ii) with different types of cigarettes (i.e., filter, low nicotine, etc) inhale
    • more deeply  expose more peripheral airways and cells (susceptible sites to adenocarcinoma) to carcinogens.
    • Mixed types occur in tumors (e.g., small
    • cell + adenocarcinoma + squamous cell
    • CA can occur in ~ 10 % of patients)
    • With these various cell type, lung cancer
    • clustered into 2 groups (based on
    • metastases and response to Tx):
    • a) small cell carcinoma
    • i) most often metastatic, high initial response to chemotherapy
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    • b) non-small cell carcinoma
    • i) less metastatic; less responsive.
    • Strongest relationship to smoking is with
    • a) squamous cell and
    • b) small cell CA
    • Morphology
    • a) Lung CA arise most often in/near hilus
    • i) ~ 75% arise from 1 st -3 rd order bronchi
    • ii) small % arise in periphery of lung; alveolar septa to near terminal bronchioles
    • - mostly adenocarcinomas !!
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  • b) squamous cell CA begins as area of in situ cytologic dysplasia i) develops along a variety of pathways ii) patterns show gray-white and firm to hard; keratinization (squamous ** pearls), and/or intracellular bridges iii) metastasize outside of the thorax late in its development. Most lung CA metastasize early. iv ) more often found in men v) strong correlation w/ smoking vi) highest frequency of p53 mutations - over expression may precede invasion vi) cavitation (abscess, TB diff. ???) www.freelivedoctor.com
  • viii) p53 staining (i.e., activity) increases as stage of tumor increases - 60-90 % of in situ CA ix) over expression of epidermal growth factor receptor detected in ~ 80% of squamous cell CA c) Distant metastasis of lung CA involve all tissues and organs i) adrenals most often (~ 50%) ii) liver (30-50 %);brain/bone (~20 %) d) Distant metastasis usually first sign of overt lung CA www.freelivedoctor.com
  • e) Adenocarcinoma i) malignant epithelial tumor - mucin production - glandular differentiation ii) most common type of lung CA in women and nonsmokers iii) more peripherally located compared with squamous cell CA iv) several growth patterns - acinar, papillary, bronchioalveolar (only one with distinct features) and solid with mucin production - ~ 80% contain mucin www.freelivedoctor.com
  • v) grow more slowly vs. squamous - metastasize widely and early vi) less frequently associated with smokers (~ 75%) as compared with squamous or small cell CA (~ 98%) vii) K-RAS mutations are seen primarily in adenocarcinomas; p53, RB and p16 mutations, etc seen in squamous cell CA viii) bronchioalveolar CA grow along preexisting structures w/out destruction - “lepidic” growth pattern (butterflies sitting on a fence) www.freelivedoctor.com
  • ix) two subtypes: mucinous and nonmucinous (amenable to surgical resection) f) Small cell CA i) highly malignant tumor ii) grading is inappropriate since all small cell CA are of the HIGH grade iii) strong correlation to cigarette smoking - ~1 % in nonsmokers iv) most aggressive of lung tumors v) metastasize widely and essentially incurable via surgery vi) frequent mutations of p53;RB www.freelivedoctor.com
  • vii) expression of anti-apoptotic gene (i.e., BCL2) in > 90% of tumors; low frequency of expression of pro- apoptotic gene, BAX ** viii) round to oval cells with pleomorphic, hyperchromatic nuclei g) Large cell CA i) undifferentiated malignant epithelial tumor ii) probably represent squamous and adenocarcinoma tumors that are so undifferentiated that they can no longer be identified microscopically www.freelivedoctor.com
  • h) Combined CA i) ~ 10% of all lung CA have combined histology from at lease 2 or more of the preceding CA i) secondary pathology i) obstruction (focal emphysema with partial obstruction); atelectasis with total obstruction ii) pulmonary abscess - bronchiectasis due to decreased drainage iii) compression of vena cava (dusky head and arm edema) www.freelivedoctor.com
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    • Staging
    • a) uniform TNM system
    • i) anatomic extent of CA
    • - T tumor description
    • - N node involvement
    • - M metastases
    • b) lung CA: symptoms of several months’ duration
    • i) cough (75%); weight loss (40%);
    • ii) chest pain (40%); dyspnea (20%)
    • c) usually found by secondary spread of CA
    • d) bronchioalveolar CA do not metastasize and are noninvasive  kill by suffocation
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    • Outlook for lung CA is poor
    • a) 5 yr survival is ~ 15% !!
    • adenocarcinoma and squamous cell pattern have better prognosis  localized longer than undifferentiated forms
    • a) ~ 50% survival when cases detected when still localized
    • Untreated patients with small cell CA 
    • 6-17 weeks
    • a) sensitive to radiation Tx
    • i) many distant metastases by time of diagnosis  1 yr survival at best
    • Some patients cured with lobectomy or
    • pneumonectomy (early detection !!!)
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    • Paraneoplastic Syndromes
    • a) lung CA associated with hormones or hormone-like factors
    • i) ADH   Na due to ADH 
    • ii) ACTH  Cushing syndrome
    • iii) calcitonin   Ca
    • iv) gonadotropin  gynecomastia
    • v) serotonin and bradykinin  carcinoid syndrome
    • vi) PTH, PGE, cytokines  implicated in  Ca, often seen with lung CA
    • Associated with 1-10% of all lung CA
    • a) tumors which produce ADH and ACTH usually are small cell CA
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    • b) tumors producing  Ca are most often squamous cell CA
    • Other systemic manifestations
    • a) Lambert-Eaton myasthenic syndrome
    • i) muscle weakness due to auto- antibodies  neuronal Ca channels
    • b) peripheral neuropathy
    • c) dermatologic abnormalities  acanthosis nigricans
    • d) hematological abnormalities  leukemoid reactions
    • e) connective tissue  hypertropic pulmonary osteoarthropathy  clubbing of fingers
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    • Apical lung CA (Pancoast Tumor)  invade neural structures around trachea  cervical sympathetic plexus
    • a) severe pain in ulnar nerve (Pancoast Syndrome)
    • b) Horner syndrome  enophthalmos, ptosis, miosis, anhidrosis
    • i) all on same side as lesion
    • Neuroendocrine
    • a) normal lung has these cells w/in epithelium as single cells or clusters of “neuroepithelial bodies”
    • i) all neuroendocrine hyperplasia is secondary to airway fibrosis
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    • ii) rare disorder called “diffuse idiopathic pulmonary neuroendocrine cell hyperplasia”
    • - precursor to multiple small tumors (tumorlets) or carcinoids
    • Carcinoid tumors
    • a) 1-5 % of all lung CA
    • b) younger age (~ 40 yrs)
    • c) ~ 20-40 % are nonsmokers
    • d) low grade malignant epithelial cell CA
    • i) typical (no p53 or BCL2/BAX) ii) atypical (show changes listed above in ~ 10-40 % of cases)
    • e) intraluminal growth  characteristic
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    • Miscellaneous tumors
    • a) mesenchymal
    • i) fibroma, fibrosarcoma, lipoma
    • ii) leiomyoma, leiomyosarcoma, etc…
    • b) lung harmartoma
    • i) common ( rounded “coin” lesion)
    • ii) asymptomatic (found on CXR)
    • iii) peripheral, solitary, < 3-4 cm dia.
    • iv) cartilage most common connective tissue component
    • v) rare in children, increased incidence with age
    • vi) BENIGN
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    • Mediastinal tumors
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    • Pleura
    • a) usually secondary complication of underlying disease
    • b) primary disorders include:
    • i) intrapleural infections
    • ii) neoplasias  mesothelioma
    • Pleural effusion
    • a) normally ~ 15 ml serous fluid
    • b) increased pleural fluid occurs:
    • i) CHF (i.e.,  hydrostatic pressure)
    • ii)  permeability  pneumonia
    • iii)  oncotic pressure  nephrotic
    • iv)  (-) intrapleural press  atelectasis
    • v)  lymph drainage  mediastinal
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  • c) inflammatory or noninflammatory effusions 1) inflammatory (serous or serofibrinous pleuritis) - TB - abscess - pneumonia - bronchiectasis - RA - SLE - uremia - diffuse systemic infections - metastases (pleural) - radiation therapy www.freelivedoctor.com
  • i) purulent pleural exudate (empyema) - bacterial or mycotic seeding usually resulting from pulmonary infection - lymphatic or hematogenous - subdiaphragmatic or liver abscess bulging into pleura; usually occurring on the right side ii) hemorrhagic pleuritis (sanguineous) - differentiate  hemothorax - presence of tumor cells !! www.freelivedoctor.com
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  • 2. Noninflammatory pleuritis i) hydrothorax - CHF most common cause; usually collects at the base; causing compression and atelectasis of surrounding lung ii) hemothorax (blood in pleura) - fatal complication of ruptured aortic aneurysm / vascular trauma - rare to find inflammatory milieu iii) chylothorax - accumulation of milky lymph - more often confined to left side www.freelivedoctor.com
    • - Lymphatic obstruction, trauma, lymphoma
    • - distant metastases may grow in right lymphatic or thoracic duct
    • c) pleural effusion may be associated with ascites of any cause
    • i) pressure difference favors movement of fluid into pleura via lymphatics or across diaphragmatic defects
    • Pneumothorax
    • a) air/gas in pleural space
    • i) spontaneous
    • ii) traumatic
    • iii) therapeutic
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  • b) more often associated with: i) emphysema ii) asthma iii) TB c) spontaneous idiopathic pneumothorax i) young people ii) rupture of apical blebs iii) recurrent attack common iv) flap valve - when defect allows air to enter but not to escape - results in increasing pressure - “tension pneumothorax” - may compress contralateral lung www.freelivedoctor.com
    • Pleural tumors
    • a) primary or secondary tumors
    • i) secondary  metastatic
    • - more common vs. primary
    • - arise from primary CA of lungs and breast
    • - can arise from any organ (i.e., ovarian CA implant in thorax and abdomen
    • ii) tumors produce serous / serosanguineous fluid
    • - fluid good marker of tumor type
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  • b) solitary (localized) fibrous tumors i) “benign mesothelioma” - soft fibrous tumors mainly in pleura and rarely in lung - remains confined to surface of lung - do not produce pleural effusions - usually benign - tumor cells  CD34+; keratin negative staining (good differential from malignant mesotheliomas) - NO relationship to asbestos exposure !! www.freelivedoctor.com
  • c) Malignant mesothelioma i) arise from either pleura ii) asbestos exposure related iii) long latent period (25-50 yrs) iv) smoking does NOT increase risk - smoking  risk of lung CA in asbestos workers !! v) produces pleural effusions vi) diffuse and covers lung; invades thoracic cavity and structures vii) S & S - chest pain, dyspnea and recurrent pleural effusions viii) outcome poor  death w/in 2 yrs www.freelivedoctor.com
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