Lung Cancer Pathology & Clinical


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Lung tumor pathology

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Lung Cancer Pathology & Clinical

  1. 1. + Lung Tumors Shahd AlAli Pathology and Clinical
  2. 2. + Pathology
  3. 3. +  Most common cause of cancer-related deaths in industrialized countries  1/3 of cancer deaths in men  Risk factors:  Cigarette smoking “contain 60 carcinogens”  Radon “formed by radioactive decay of uranium”  Asbestos
  4. 4. + Histological Types:  Small cell carcinoma (19%)  Non small cell carcinoma (85%)  Squamous cell carcinoma 30%  Adenocarcinoma 40%  Large cell carcinoma 10%  Carcinoid tumor 5%
  5. 5. + Source: A.Sattar,Hussain, Fundamental of Pathology
  6. 6. + Etiology & Pathogenesis  Smoking is the leading cause; 85% of lung cancer occurs in smokers in “ sp: Small cell carcinoma & Squamous cell carcinoma”  Step wise progression metaplasia>dysplasia>carcinoma in situ > carcinoma  3p suppression gene loss very early event  P53 mutation / activation of KRAS oncogene > late event  Adenocarcinoma: activation of Epidermal growth factor receptor (EGFR) + KRAS
  7. 7. + Morphology of Small Cell Carcinoma “Oat Cell Carcinoma”  Poor differentiation arise from neuroendocrine cells “Kulchtisky cells”  Correlated with smoking  Centrally located masses > extension to lung parenchyma  Involvement of hilar & mediastinal nodes  Can cause ACTH (Cushing syndrome), ADH (hypernatremia) and Eaton-Lambert syndrome  Amplicfication of myc oncogen is common Usually respond to chemo and radiotherapy
  8. 8. + Small Cell Carcinoma  Grossly: Pale gray Central location  Micro  Sheets of round fusiform cell with scant cytoplasm & finely granular chromatin Nuclear molding Mitotic figure Necrosis Cush artifact in small biopsy Express neuroendocrine markers (chromogranin, synpatophysin, NSE and CD56)
  9. 9. + Gross “Arising centrally in this lung and spreading extensively is a small cell anaplastic (oat cell) carcinoma. The cut surface of this tumor has a soft, lobulated, white to tan appearance. The tumor seen here has caused obstruction of the main bronchus to left lung so that the distal lung is collapsed. Oat cell carcinomas are very aggressive and often metastasize widely before the primary tumor mass in the lung reaches a large size.” - webpath
  10. 10. + “Here is an oat cell carcinoma which is spreading along the bronchi. The speckled black rounded areas represent hilar lymph nodes with metastatic carcinoma. These neoplasms are more amenable to chemotherapy than radiation therapy or surgery, but the prognosis is still poor. Oat cell carcinomas occur almost exclusively in smokers.” -webpath
  11. 11. + Microscopic pattern This is the microscopic pattern of a small cell anaplastic (oat cell) carcinoma in which small dark blue cells with minimal cytoplasm are packed together in sheets.
  12. 12. + Tips Small cell carcinoma & Squamous cell carcinoma  Smoking  Central  Syndrome
  13. 13. + Squamous cell carcinoma  Associated with smoking  Arise centrally in major bronchi  Spread to local hilar nodes  Central necrosis > cavitation  Squamous cell metaplasia>dyplasia>carcinoma in situ  Can cause distal atelectasis & infection  May produce PTHrp > hypercalcemia
  14. 14. + Histologically: Squamous CC Keratin pearls Intercellular bridges
  15. 15. + Pathoma Squamous cell carcinoma A, Keratin pearls. B, Interceltular bridges. C Central location.
  16. 16. + Gross “This is a squamous cell carcinoma of the lung that is arising centrally in the lung (as most squamous cell carcinomas do). It is obstructing the right main bronchus. The neoplasm is very firm and has a pale white to tan cut surface.” -webpath
  17. 17. + “This is a larger squamous cell carcinoma in which a portion of the tumor demonstrates central cavitation, probably because the tumor outgrew its blood supply.Squamous cell carcinomas are one of the more common primary malignancies of lung and are most often seen in smokers.” -webpath
  18. 18. + Adenocarcinoma  Most common lung cancer in nonsmokers and females  Activating mutation of K-Ras  Associated with hypertrophic osteoarthropathy “clubbing”  Located peripherally with central scar  Glandular differentation with tubules or papillae and mucin secretion  Histological examination:  Acinar (gland forming)  Papillary  Mucinous  Metastasis widely at an early stage
  19. 19. +  Atypical adenocarcinoma (AAH) > Adenocarcinoma in situ (AIS) > minimally invasive adenocarcinoma > invasive adenocarcinoma  AAH: well demarcated focus of epithelial proliftation 5 mm or less composed of cuboidal to low-columnar cells with cytological atypia.  AIS: (bronchoalveolar carcinoma) involve peripheral parts of the lung. Diameter of 3 cm or less, growth along preexisting structures & preservation of alveolar architecture. Can be nonmucinous, mucinous or mixed.
  20. 20. + Adenocarcinoma Precursors Minimally invasive adenocarcinoma Invasive adenocarcinoma Tumor less than 3 cm, invasive component is 5mm or less Tumor any size, invaded to depth > 5mm
  21. 21. + Gross “This is a peripheral adenocarcinoma of the lung. Adenocarcinomas and large cell anaplastic carcinomas tend to occur more peripherally in lung. Adenocarcinoma is the one cell type of primary lung tumor that occurs more often in non-smokers and in smokers who have quit. If this neoplasm were confined to the lung (a lower stage), then resection would have a greater chance for cure. The solitary appearance of this neoplasm suggests that the tumor is primary rather than metastatic.”
  22. 22. + “This is another less common type of adenocarcinoma of lung known as adenocarcinoma-in-situ (formerly bronchioloalveolar carcinoma). Seen here is variant that appears grossly (and on chest radiograph) as a less well- defined area resembling pneumonic consolidation. The poorly defined mass involving the upper lobe toward the right here has a pale tan to grey appearance.”
  23. 23. + Microscopically “Microscopically, the adenocarcinoma-in-situ (formerly bronchioloalveolar carcinoma) is composed of columnar cells that proliferate along the framework of alveolar septae, a so-caled "lepidic" growth pattern. The neoplastic cells are well-differentiated. These neoplasms, a form of adenocarcinoma, in general have a better prognosis than most other primary lung cancers, but they may not be detected at a low stage.”
  24. 24. +
  25. 25. + Atypical adenocarcinoma Adenocarcinoma in situ
  26. 26. + (A) Acinar growth pattern; (B) Papillary growth pattern; (C) Lepidic growth pattern; (D) Solid growth pattern
  27. 27. + Large Cell Carcinoma  Undifferentiated malignant epithelial tumors that lack the cytological features of small cell carcinoma, adenocarcinoma and squamous cell carcinoma  The cell have large prominent nuclei & moderate amount of cytoplasm  Has poor prognosis  Can be central or peripheral  On ultrastructure examination minimal glandular or squamous differentiation is common
  28. 28. + Combined Patterns  More than one line cell differentiation  Occur in 10%  Involves of the left supraclavicular node (Virchow node)  These cancers when advanced often extend to the pleura or pericardial space leading to inflammation and effusion  Compress or infiltrate the superior vena cava and cause venous congestion or the vena caval syndrome  Apical neoplasm may invade the brachial or cervical sympathetic plexus to cause severe pain in the distribution of the ulnar nerve or produce Horner syndrome.  Apical neoplasms (Pancoast tumors) destruct the 1st and 2nd rib and sometimes the thoracic vertebra
  29. 29. + Bronchial Carcinoid Tumor  Represents 5% of all pulmonary tumors  Malignant tumors composed of cells that contain dense- core neurosecretory granules in their cytoplasm  Rarely secrete hormone active polypeptides  Classified into typical (low grade) & atypical (intermediate- grade)  Has excellent prognosis; metastasis is rare  Rarely produce carcionid syndrome serotonin secretion (flushing, diarrhea and cyanosis)
  30. 30. + Morphology  Most originate in main bronchi and grow in one of two patterns:  Obstructive polypoid intraluminal mass  Mucosal plaque penetrating the bronchial wall to fan out in the peribronchial tissue (collar-button lesion)  5% to 15% metastasize to hilar nodes at presentation  Distant metastases are rare
  31. 31. + Histologically  Typical: Nests of uniform cells that have regular round nuclei salt and pepper cromatin rare mitoses, and little pleomorphism.  Atypical: high mitotic rate (but less than small cell or large cell carcinomas) & focal necrosis.  Unlike typical carcinoids, the atypical subset may demonstrate TP53 mutation (20% to 40%) Both express neuroendocrine markers (chromogranin, synpatophysin, NSE and CD56)
  32. 32. + Carcinoid Tumors A.Carcinoid growing as sphercal, pale mass B. Appearance of small, rounded, uniform nuclei and moderate cytoplasm
  33. 33. + Carcinoid tumor A, Microscopic appearance. B, Chromogranin expression by immunohistochemistry. C, Polyp-like growth in the bronchus pathoma
  34. 34. + All Lung cancer types except ronchioloalveolar and ronchial carcinoid are associated with smoking.
  35. 35. + Clinical
  36. 36. + Clinical  Presentation :  Hemoptysis  Bronchial obstruction  Wheezing  Coin lesion on x-ray film  Noncalcificated nodule on CT
  37. 37. + Metastatic disease “sites of metastases”  Bones > pain & spinal cord compression  Adrenal  Brain > changes in personality & epilepsy  Liver > jaundice and hepatomegaly
  38. 38. + Metastatic Tumors in The Lungs Prostate Colon Cervix Breat Bone Bladder
  39. 39. + Complications SPHERE  S: superior vena cava syndrome  P: pancoast tumor “slide 26”  H: horner syndrome  E: pleural effusion  R: recurrent laryngeal symptoms (hoarseness) “left”  E: endocrine  ADH > hypernatremia  ACTH> Cushing’s syndrome PTH> hypercalcemia HCG> gyncomastia
  40. 40. + Investigations: CXR to confirm the diagnosis  Abnormal CXR tumors appear as round shadow, with fluffy or spiked appearance edges  Evidence of cavitation, lobar collapse, pleural effusion or 2ry pneumonia  Spread to lymphatic channels give rise to lymphangitis carcinomatosis appearing like a streaky shadowing throughout the lung
  41. 41. + CXR Intrapulmonary Mediastinal
  42. 42. + Determine the histology  Sputum examination by a cytologist for malignant cells  Bronchoscopy is used to obtain biopsies  Transthoracic fine needle aspiration biopsy under radiographic or CT screening is useful for obtaining tissue diagnosis from peripheral lesions
  43. 43. + Thank you :)