Pathology of Lung Neoplasms and Infections Flashcards
causes of pneumonia
- impaired local defense mechanisms:
-suppression of cough reflex
-dysfunction of mucociliary apparatus
-accumulation of secretions
-interference with phagocytic alveolar macrophages
-pulmonary congestion, edema - immunodeficiency:
-chronic diseases, immunologic deficiencies
-immunosuppressive agents
-leukopenia
pneumonia - clinical features
*fever, chills
*productive cough
*tachypnea, pleuritic chest pain
*decreased breath sounds
*dullness to percussion
diagnosis of pneumonia
*labs:
-CBC with elevated WBC
-sputum gram stain
-cultures (sputum, tissue, blood)
*CXR:
-lobar pneumonia
-bronchopneumonia
-interstitial pneumonia
lobar bacterial pneumonia
*consolidation (solid, airless) of ENTIRE LOBE
*alveoli filled with neutrophils; congested septa
*most common pathogen = Strep pneumo (gram positive diplococci)
bronchopneumonia
*PATCHY consolidation around bronchioles
*often multifocal and bilateral
*most common pathogen = Staph aureus (gram positive cocci)
lobar pneumonia vs. bronchopneumonia
*lobar pneumonia (left) most commonly strep pneumo
*bronchopneumonia (right) most commonly staph aureus
viral pneumonia - overview
*nearly all also cause upper-respiratory tract infections
*risk factors: extremes of age, malnutrition, debilitating illness
*organisms: INFLUENZA (types A and B), COVID19, RSV, adenovirus, etc
viral pneumonia - morphology
*congested lung w/ lymphocytic and monocytic reaction
-may be patchy or involve whole lobes, bilaterally or unilaterally
*severe infections lead to diffuse alveolar damage with hyaline membranes (ARDS)
viral pneumonia - pathogenesis
*viruses infect and damage respiratory epithelium; impaired local defenses predisposes to secondary bacterial infections
tuberculosis - primary infection
*previously un-sensitized
*clinical: asymptomatic in 95% of patients
*pathology: GHON COMPLEX on CXR
-focal caseation in parenchyma + hilar nodes
-undergoes fibrosis/calcification for imaging
*leads to PPD+
tuberculosis - secondary infection
*previously sensitized individuals
*YEARS after initial infection, reactivation of latent infection (or reinfection in the face of waning host immunity)
*clinical: fever, night sweats, cough, hemoptysis
*APICES OF LUNG are infected, causing poor lymphatic drainage and high O2 tenssion
tuberculosis - secondary infection PATHOLOGY
*cavitary lesion with CASEATING NECROSIS (caseous necrotizing granulomas)
*diagnosis: acid-fast positive bacilli
tuberculosis - progressive infection
*blood-borne spread (subsequent to primary or secondary infections)
*more common in immunosuppressed patients
*pathology: MILIARY (disseminated granulomas; spleen, liver, other organs)
*diagnosis: AFB+ bacilli, NUMEROUS
spectrum of tuberculosis pathologies
- primary: Ghon complex (lower lobe + hilar nodes)
- secondary: granuloma with caseation
- progressive: miliary = disseminated granulomas
spectrum of granulomas
- non-necrotizing:
-think of sarcoid, fungi, foreign bodies, or autoimmune - caseous, necrotizing:
-think of TB - suppurative, necrotizing:
-think of bacteria, fungi, or foreign bodies
non-necrotizing granulomas
*think of sarcoid, fungi, foreign bodies, or autoimmune conditions
caseous, necrotizing granulomas
*think of TB
suppurative, necrotizing granulomas
*think of bacteria, fungi, or foreign bodies
*suppurative means neutrophils/bacteria
pulmonary abscess - overview
*local suppurative process, causing necrosis of lung tissue
pulmonary abscess - causes
*aspiration
*antecedent lung infection
*septic embolism
*secondary infection from obstructing neoplasm
*traumatic penetrations
*hematogenous seeding by pyogenic organisms
pulmonary abscess - clinical features
*cough with copious amounts of foul-smelling purulent or sanguineous sputum
*fever, chest pain, and weight loss are common
*diagnosis confirmed radiographically
pulmonary abscess - morphology
*suppurative parenchymal destruction with cavitation
opportunistic pulmonary infections
*serious infections in immunocompromised individuals
*common organisms include:
-CMV
-pneumocystis jiroveci
-cryptococcus neoformans
-aspergillus
pathology of opportunistic pulmonary infections: CYTOMEGALOVIRUS (CMV)
*huge cells with intranuclear inclusions surrounded by halo
pathology of opportunistic pulmonary infections: PNEUMOCYSTIS JIROVECI
*intra-alveolar, foamy exudate
*silver+ cup-shaped cysts
pathology of opportunistic pulmonary infections: CRYPTOCOCCUS NEOFORMANS
*granulomas with PAS+ encapsulated yeasts
pathology of opportunistic pulmonary infections: ASPERGILLUS
*angio-invasive silver+ molds causing hemorrhage, necrosis
hypertrophic pulmonary osteoarthropathy (HPO)
*aka digital clubbing (clubbing of the fingers)
*painful periosteal elevation at several bony and joint sites, especially the fingers
*elevation of the nail bed to form a pronounced curvature is characteristic
*associated with some pulmonary carcinomas, especially adenocarcinomas
lung carcinoma - overview & epidemiology
*malignant neoplasm of pulmonary epithelial cells
*most frequently diagnosed major cancer and most common cause of cancer mortality worldwide
*incidence gradually decreasing (possibly due to changes in smoking habits?)
*peak incidence in adults 50+ in age
*prognosis remains dismal
major causes of cavitary lesions in the lung
- pulmonary tuberculosis (most common)
- malignancy, especially squamous cell carcinoma
- lung abscess
major histologic types of lung carcinoma
- small cell carcinoma
- non-small cell carcinoma:
a. adenocarcinoma
b. squamous cell carcinoma
c. large cell carcinoma
lung carcinoma - pathogenesis
*stepwise accumulation of carcinogen-induced driver mutation:
-“Field Effect” = genetic alterations seen in benign epithelium
-precursor lesions = preinvasive, antedate carcinoma:
~asymptomatic and undetectable on radiographs
~atypical cells identified in sputum, cytologic smears, tissue biopsies
~changes may last for years
squamous cell carcinoma - overview
*malignant neoplasms of bronchial epithelium with SQUAMOUS CELL DIFFERENTIATION
*most common tumor in male smokers
*arise CENTRALLY in major bronchi:
-segmental/subsegmental bronchi
-become symptomatic with bronchial obstruction
-eventually spread to hilar nodes
squamous cell carcinoma - pathogenesis
*highly associated with exposure to tobacco smoke
*diverse genetic aberrations:
-TP53 mutation
-CDKN2A tumor suppressor gene
-FGFR1 amplification
squamous cell carcinoma - gross pathology
*large lesions, variegated color
*may have CENTRAL NECROSIS leading to CAVITATION
squamous cell carcinoma - microscopic pathology
*sputum: orange-staining, keratinized squamous cells
*tissue:
-nests of polygonal cells with pink cytoplasm, distinct cell borders
-well differentiated = squamous KERATINIZING PEARLS
-poorly differentiated = anaplasia, pleomorphism, increased atypical mitoses
keratin pearls are associated with what type of lung carcinoma
squamous cell carcinoma
adenocarcinoma - overview
*malignant epithelial tumor with GLANDULAR DIFFERENTIATION and/or MUCIN PRODUCTION
*most common type in women, young patients, non-smokers
*arise more PERIPHERAL:
-bronchioles, alveoli
-produce fewer symptoms in early course of disease
adenocarcinoma - pathogenesis
*less associated with tobacco smoking than other subtypes
*oncogenic mutations of growth factor receptor pathways (EGFR, ALK, ROS1)
-mutations are important for prognosis because there is targeted therapies
adenocarcinoma - gross pathology
*tend to be smaller lesions
*may be solitary or multiple nodules
*may involve entire lobe, mimicking lobar pneumonia
adenocarcinoma - microscopic pathology
*GLANDULAR EPITHELIAL CELLS +/- mucin
*peripheral lepidic pattern of spread = tumor cells “crawl” along normal-appearing alveolar septa
*need to determine mutations present to determine treatment
large cell carcinoma - overview
*UNDIFFERENTIATED malignant epithelial tumor lacking features of other forms of lung cancer
*associated with smoking
*arise central OR peripheral
large cell carcinoma - pathology
*large, polygonal ANAPLASTIC cells
-growing in sheets or solid nests
-foci of central necrosis and hemorrhage
*diagnosis of exclusion (no glandular/mucin, squamous, or neuroendocrine differentiation)
small cell carcinoma - overview
*malignant neoplasm of PULMONARY NEUROENDOCRINE CELLS
-in physiologic states, these cells secrete serotonin, calcitonin, and gastrin-releasing peptide
-in tumors, secrete ACTH, other neuropeptides
*may arise in MAJOR BRONCHI or PERIPHERY
*MOST AGGRESSIVE OF LUNG TUMORS
small cell carcinoma - pathogenesis
*exposure to carcinogens and other stimuli cause PEC proliferation
*virtually ALWAYS associated with exposure to tobacco smoke
*highest mutational burden among lung cancers (universal inactivation of both p53 and RB; loss of chromosome 3p also occurs)
small cell carcinoma - gross pathology
*arising centrally
*may cause obstruction of main bronchus or spread along the bronchi (peribronchial spread)
small cell carcinoma - microscopic pathology
*small cells with scant cytoplasm, ill-defined cell borders
-nuclear molding prominent
-fine chromatin “salt and pepper”
*sheet of tiny blue cells
*numerous mitoses
*extensive necrosis
*NO glandular or squamous differentiation
lung carcinoma: metastases
*systemic metastatic spread of lung neoplasm
*lung carcinomas have predilection to metastasize
*hematogenous or direct extension
*sites:
-BRAIN / leptomeningeal (small cell carcinoma, adenocarcinoma)
-bone/bone marrow
-adrenal gland: (non-small cell carcinomas)
metastatic disease of lung
*lung is most common site of metastatic neoplasms (more common than primary lung neoplasms)
*hematogenous spread, lymphatic spread, or direct extension
*variable patterns:
-multiple: “cannonball lesions” scattered throughout
*biopsy recapitulates the neoplasm of origin (ex. if metastatic colon cancer, it will look like colon pathology)
mesothelioma - overview
*malignant epithelial neoplasm of MESOTHELIAL CELL ORIGIN
*history of ASBESTOS EXPOSURE (direct or secondary)
*arise in PARIETAL OR VISCERAL PLEURA
-tumor usually encases lung
mesothelioma - pathogenesis
*asbestosis with long latency period after initial exposure, 25-40 years later
*asbestos preferentially accumulate in subpleural alveoli near mesothelial cell layer
*induce production of ROS, leading to DNA damage and multiple driver mutations
mesothelioma - gross pathology
*preceded by pleural fibrosis/plaque
*dense white encircling tumor mass:
-big bulky tumors filling chest cavity
-obliterates pleural cavity
mesothelioma - microscopic pathology
*microscopic appearance is variable:
-epithelial (left) = carcinomatous appearance
-spindle (right) = sarcomatous appearance
-biphasic = epithelial + spindle
