1. impaired local defense mechanisms: -suppression of cough reflex -dysfunction of mucociliary apparatus -accumulation of secretions -interference with phagocytic alveolar macrophages -pulmonary congestion, edema 2. immunodeficiency: -chronic diseases, immunologic deficiencies -immunosuppressive agents -leukopenia

Pathology of Lung Neoplasms and Infections Flashcards by Kyra Porter

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

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pneumonia - clinical features

*fever, chills
*productive cough
*tachypnea, pleuritic chest pain
*decreased breath sounds
*dullness to percussion

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diagnosis of pneumonia

*labs:
-CBC with elevated WBC
-sputum gram stain
-cultures (sputum, tissue, blood)
*CXR:
-lobar pneumonia
-bronchopneumonia
-interstitial pneumonia

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lobar bacterial pneumonia

*consolidation (solid, airless) of ENTIRE LOBE
*alveoli filled with neutrophils; congested septa
*most common pathogen = Strep pneumo (gram positive diplococci)

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bronchopneumonia

*PATCHY consolidation around bronchioles
*often multifocal and bilateral
*most common pathogen = Staph aureus (gram positive cocci)

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lobar pneumonia vs. bronchopneumonia

*lobar pneumonia (left) most commonly strep pneumo
*bronchopneumonia (right) most commonly staph aureus

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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

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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)

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viral pneumonia - pathogenesis

*viruses infect and damage respiratory epithelium; impaired local defenses predisposes to secondary bacterial infections

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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+

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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

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tuberculosis - secondary infection PATHOLOGY

*cavitary lesion with CASEATING NECROSIS (caseous necrotizing granulomas)
*diagnosis: acid-fast positive bacilli

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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

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spectrum of tuberculosis pathologies

primary: Ghon complex (lower lobe + hilar nodes)
secondary: granuloma with caseation
progressive: miliary = disseminated granulomas

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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

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non-necrotizing granulomas

*think of sarcoid, fungi, foreign bodies, or autoimmune conditions

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caseous, necrotizing granulomas

*think of TB

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suppurative, necrotizing granulomas

*think of bacteria, fungi, or foreign bodies
*suppurative means neutrophils/bacteria

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pulmonary abscess - overview

*local suppurative process, causing necrosis of lung tissue

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pulmonary abscess - causes

*aspiration
*antecedent lung infection
*septic embolism
*secondary infection from obstructing neoplasm
*traumatic penetrations
*hematogenous seeding by pyogenic organisms

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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

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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

1. pulmonary tuberculosis (most common) 2. malignancy, especially squamous cell carcinoma 3. lung abscess

major histologic types of lung carcinoma

1. small cell carcinoma 2. 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