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LUNGS PATHOLOGY 2 - Coggle Diagram

- - - - increased by factors like cigarette smoking
    - - the most dangerous particles are 1-5 microns, as they can reach the terminal small airways, in the end depositing in their linings
    - - influenced by particles size
  - - - dust reduction measures are available today
      - morphology: dark black deposits are visible grossly and microscopically
    - - coal macules (1-2 mm): carbon-laden macrophages
      - coal nodules (>2 mm): delicate network of collagen fibers
    - - progressive massive fibrosis
      - many years to develop
      - intensely blackened scars 1-10 cm
      - necrosis in the centre of the lesion
    - - carbon pigment is engulfed by alveolar or interstitial macrophages, which accumulate in the connective tissue adjacrnt to the lymphatics and in organized lymphoid tissue adjacent to the bronchi or in the lung hilus or in regional lymph nodes
      - usually benign, little decrement in lung function
        
        in <10% of cases, progressive massive fibrosis, pulmonary hypertension, cor polmonare
  - - - slowly progressing nodular fibrosinig pneumoconiosis
    - - heavy exposition, accumulation of aboundant lipoproteinaceous material within alveoli
    - - phagocytosis of inhaled silica crystals by macrophages activates the inflammasome and stimulates the release of inflammatory mediators (IL1 and IL8)
        
        recruitment of additional inflammatory cells and interstitial fibroblasts actication, leading to collagen deposition
    - - slow and insidious onset, accelerated or rapid
      - chest radiographs: fine nodularity in the upper zones of the lung
      - pulmonary function is either normal or only moderately affected (early phases)
        
        then, progression occurs even in the absence of the stimuli
    - - tiny palpable discrete pale-to-blackened nodules in the hylar lymph nodes and upper zones of the lungs
        
        as the disease progresses, nodules coalesce into hard collagenous scars
        
        progressive massive fibrosis
        
        under polarized dark field microscopy, weakly birefringent silicate particles
  - - - consider concentration, size, shape and solubility of asbestos fibers
        
        serpentine forms --> 90%
        
        amphibole forms --> less prevalent, more pathogenic
      - asbestos acts both as a tumor initiator and as a tumor promoter
        
        once phagocytosed by macrophages, asbestos fibers activate the inflammasome and stimulate the release of proinflammatory factors and fibrogenic mediators
        
        macrophages attempt to ingest and clear the fibers
        
        long-term deposition of fibers and persistent release of mediators eventually lead to generalized interstitial pulmonary inflammation and fibrosis
    - - diffuse pulmonary interstitial fibrosis
      - ASBESTOS BODIES
        
        golden brown, fusiform or beaded rods with a translucent centre consisting of asbestos fibers coated with an iron-containing proteinaceous material
        
        they arise when macrophages phagocytose asbestos fibers
      - fibrosis around the respiratory bronchioles and alveolar ducts in the beginning
        
        then, it extends to involve adjacent alveolar sacs and alveoli
        
        architecture distortion
        
        UIP pattern: enlarged airspaces enclosed by thick fibrous walls,eventually becoming honeycombing, fibroblastic foci and varying degrees of fibrosis
      - PLEURAL PLAQUES
        
        most common manifestation
        
        well-circumscribed plaques of dense collagen
        
        often calcified
        
        size and number do not correlate with the level of exposure to asbestos
        
        no identifiable asbestos bodies content
- - - - increased hydrostatic pressure (congestive heart failure)
        
        increased vascular permeability (pneumonia)
        
        decreased osmotic pressure (nephrotic syndrome)
        
        increased intraplural negative pressure (atelectasis)
        
        decreased lymphatic drainage (mediastinal carcinomatosis)
    - - inflammatory
        (pleuritis)
        
        inflammation of the lung (TBC, pneumonia, lung infarction, abscess and bronchiectasis
        
        connective tissue diseases (RA, SLE)
        
        diffuse systemic infections
        
        metastatic involvement of the pleura
        
        purulent exudate (empyema)
        
        hemorrhagic pleuritis
      - non-inflammatory
        
        collection of serous fluid in the pleural cavities (hydrothorax)
        
        most common cause: heart failure
        
        accompanied by: pulmonary congestion and edema
        
        escape of blood in the pleural cavity
        (hemothorax)
        
        complication of trauma or less commonly surgery, aortic aneurysm rupture
        
        accumulation of milky fluid, usually of lymphatic origin, in the pleural cavity (chylothorax)
        
        high amounts of finely emulsified fats
        
        more often caused by thoracic duct trauma or by obstruction of a major lymphatic duct
        
        pneumothorax
        
        air or gas go into the pleural cavities
        
        associated with emphysema, asthma and TBC
        
        types
        
        spontaneous
        
        young patients
        
        rupture of small, peripheral, apical subpleural blebs
        
        spontaneous recovery
        
        recurrent attacks
        
        marked respiratory distress due to collapse and atelectasis
        
        traumatic
        
        perforating injury of the chest wall
        
        spontaneous recovery
        
        tension
        
        when the pleural defect acts as a flap valve and permits the entrance of air during inspiration, but not its escape during expiration
        
        progressively increasing of intra-pleural pressure, compressing vital mediastnal structures and the contralateral lung
  - - - more common than primary tumors
      - generally arising from primary neoplasms of lung and breast, sometimes also ovarian carcinomas
      - serous or metastatic effusions often containing neoplastic cells
        
        it is very important to perform a careful cytological examination
    - - SOLITARY FIBROUS TUMOR
        
        soft tissue tumor
        
        propensity to occur in the pleura, less commonly in the lung
        
        often attached to the pleural surface by a pedicle
        
        from 1 to 30 cm
        
        confined to the surface of the lung
        
        no relationship to asbestos exposure
        
        malignant form (rare): pleomorphism, increased mitotic activity, hypercellularity, necrosis, large size
        
        IHC: CD34+, STAT6+, keratin- and calretinin-
        
        pathogenesis: cryptic inversion of ch12 involving NAB2 and STAT6 genes
        
        macro
        
        dense whitish fibrous tissue with occasional cyst filled with viscid fluid
        
        micro
        
        spirals of reticulin and collagen fibers among which there are interspersed cells resmbling fibroblasts
      - MALIGNANT MESOTHELIOMA
        
        increased incidence among people with heavy exposure to asbestos (--> asbestos bodies)
        
        it arises from visceral / parietal pleura
        
        latency: 25-45 years from exposure
        
        symptoms: chest pain, dyspnea, recurrent pleural effusions
        
        often metastatic spread to the hylar lymph nodes, eventually also the liver
        
        50% pts die in 12 months
        
        aggressive therapy: extrapleural pneumonectomy, chemotherapy, radiation therapy
        
        cytogeneric abnormalities: homozygous deletion of ch9p, leading to loss of CDKN2A (also consider NF2, BAP1)
        
        IHC: keratin+, calretinin+, WT1+, cytokeratin 5/6+, podoplanin+, claudin4-, TTF1-, CEA-
        
        macro
        
        diffuse lesion arising from visceral / parietal pleura, then spreading in the pleural space; extensive pleural effusion and invasion of thoracic structures
        
        the affected lung gets covered by a thick layer of soft, gelatious, grayish-pink tumor tissue
        
        micro
        
        mesothelial cells can develop as epithelium-like cells or mesenchymal stromal cells
        
        epithelioid type: cuboidal, columnar or flattened cells forming tubular or papillary structures;
        adenocarcinoma-like
        
        sarcomatoid type: fibrosarcoma-like
        
        biphasic type: both epithelioid and sarcomatoid patterns
        
        WHO 2021
        
        localized pleural mesothelioma
        
        no more "malignant"
        
        circumscribed mass with no clinical or histological evidence of diffuse serosal spread
        
        epithelioid, sarcomatoid, biphasic histology
        
        BAP1 mutations, TRAF7 mutations, genomic near-haploidization
        
        median survival --> 29-134 months
        
        BAP1 is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations
        
        mesothelioma in situ
        
        preinvasive single-layer surface proliferation of neoplastic mesothelial cells
        
        layer of flat or cuboidal cells with/without minimal cytological atypia, without evidence of invasion
        
        loss of BAP1 nuclear expression and/or MTAP staining by IHC or homozigous delesion of CDKN2A by FISH