L7, Resp Pathology PDF - Lung Tumors Lecture Notes

pathology - respiratory Lung tumors LECTURE (7) Lung tumors Dr. M. Shalaby pathology - respiratory Lung tumors  Lung cancer is currently the most frequently diagnosed major canc...

pathology - respiratory Lung tumors LECTURE (7) Lung tumors Dr. M. Shalaby pathology - respiratory Lung tumors  Lung cancer is currently the most frequently diagnosed major cancer and the most common cause of cancer mortality worldwide.  At diagnosis, more than 50% of patients already have distant metastatic disease.  Each year, lung cancer kills more people than colon, breast, and prostate cancer combined.  It is generally a disease of older adults, most often between ages 55 and 84 years.  Most (but not all) lung cancers are associated with a well-known carcinogen -cigarette smoke. In addition, there are other genetic and environmental factors.  Smoking is the most important risk factor for lung cancer.  Responsible for the mutations that give rise to lung cancer.  About 80% of lung cancers occur in active smokers or those who stopped recently, and there is a nearly linear correlation between TOBACCO the frequency of lung cancer and pack-years of cigarette smoking  Not all heavy smokers develop lung cancer (Mutagenic effect of carcinogens modified by genetic factors.  It appears that women are more susceptible to carcinogens in tobacco than men. PIPE AND CIGAR  Also incur an elevated risk. SMOKERS  Not a safe substitute for smoking cigarettes or cigars. CHEWING TOBACCO  The long-term effects of electronic cigarette aerosols are not known, as "vaping" is a relatively recent phenomenon. SECONDHAND SMOKE,  Contains numerous human carcinogenis for which there is no safe OR ENVIRONMENTAL levels of exposure. TOBACCO SMOKE Dr. M. Shalaby pathology - respiratory Lung tumors  Molecular characterization of lung adenocarcinoma identifies oncogenic mutations  The frequency of these alterations in lung adenocarcinoma has been studied by sex, age, smoking status, and geographic regions. EGFR MUTATIONS & ALK, ROS1, AND KRAS MUTATIONS RET TRANSLOCATIONS ADENOCARCINOMA found in cigarette smokers. found in light or never smokers. EGFR ALTERATIONS ALK, ROS1, AND RET ALTERATIONS Young patients Young patients Women Without sex predilection BRAF AND MET Both smokers and nonsmokers  Most tumors have mutation in P53. SQUAMOUS CELL  Also EGFR and MET mutation, and ALK or ROS1 rearrangement can CARCINOMA occur in lung squamous cell carcinoma especially young non smoker.  Associated with inhibition of TP53 & RB1. SMALL CELL  Occupational exposure : CARCINOMA Asbestos, arsenic, chromium, uranium, nickel , radiation.  Lepidic, acinar, micropapillary, papillary, solid ADENOCARCINOMA  Invasive mucinous adenocarcinoma SQUAMOUS CELL  Keratinizing, nonkeratinizing, basaloid CARCINOMA ① Small cell carcinoma ② Combined small cell carcinoma NEUROENDOCRINE ③ Large cell neuroendocrine carcinoma TUMORS ④ Combined large-cell neuroendocrine carcinoma ⑤ Carcinoid tumor: Typical, atypical ① Large cell carcinoma ② Adenosquamous carcinoma OTHER UNCOMMON ③ Sarcomatoid carcinoma TYPES ④ Others such as lymphoepithelioma-like carcinoma, NUT carcinoma and Thoracic SMARCA4-deficient undifferentiated tumor Dr. M. Shalaby  pathology - respiratory Lung tumors  The right lung in more affected. The tumor is greyish white and hard.  More often squamous cell carcinomas: arises from the main bronchus as fungating, infiltrating or ulcerating mass. CENTRAL (HILAR)  Focal areas of hemorrhage or necrosis may appear to produce red or TYPE yellow-white mottling and softening.  Sometimes these necrotic foci cavitate.  More often adenocarcinomas: arises from the peripheral bronchus as PERIPHERAL TYPE single or multiple nodules. DIFFUSE TYPE  Rare, multifocal and shows massive infiltration of a lobe or whole lung ① Adenocarcinoma (50%) NON SMALL CELL ② Squamous Cell Carcinoma (20%) CARCINOMA (NSCLC) ③ Large Cell Carcinoma (2%) SMALL CELL (15%) CARCINOMA (SCLC) Dr. M. Shalaby pathology - respiratory Lung tumors 1 ADENOCARCINOMA ① Atypical adenomatous hyperplasia: Small precursor lesion (≤5 mm). Characterized by dysplastic pneumocytes lining alveolar walls that are mildly fibrotic. Can be single or multiple and can be in the lung adjacent to invasive PRECURSOR tumor or away from it. LESIONS ② Adenocarcinoma in situ: Lesion that is less than 3 cm in size Composed of dysplastic cells growing along pre-existing alveolar septa. The cells have more dysplasia than atypical adenomatous hyperplasia and may or may not have intracellular mucin  Invasive malignant epithelial tumor with glandular differentiation or mucin production by the tumor cells.  Adenocarcinomas grow in various patterns: ① Acinar. ② Lepidic. ③ Papillary. ④ Micropapillary. ⑤ Solid. CHARACTERS  THEY VARY HISTOLOGICALLY: From well-differentiated tumors with obvious glandular elements to papillary lesions To solid masses with only occasional mucin-producing glands NB  Micropapillary, solid and cribriform patterns are high grade patterns. Dr. M. Shalaby pathology - respiratory Lung tumors GRADING OF INVASIVE NONMUCINOUS ADENOCARCINOMAS GRADE 1  Lepidic predominant with no or