Pulmonary/Mediastinum Flashcards
What are key diagnostic features of the following major noninfectious causes of granulomatous lung disease? Sarcoidosis, hypersensitivity pneumonitis, hot tub lung, Wegener granulomatosis, Churg-Strauss syndrome, aspiration pneumonia, talc granulomatosis, and rheumatoid nodule.
SARCOIDOSIS: Prominent, well-formed, discrete, nonnecrotizing granulomas in pleura, interlobular septa, and walls of bronchioles. Normal lung away from granulomas. HYPERSENSITIVITY PNEUMONITIS: Prominent interstitial chronic inflammation. Scattered, small, poorly formed granulomas or multinucleated giant cells in interstitium. HOT TUB LUNG: Granulomas within bronchiolar lumens. History of hot tub use. WEGENER GRANULOMATOSIS: Supperative granulomas with “dirty” necrosis. Necrotizing vasculitis. CHURG-STRAUSS SYNDROME: Necrotizing granulomas. Necrotizing vasculitis. Prominent eosinophils. ASPIRATION PNEUMONIA: Vegetable material surrounded by foreign body-type granulomas or multinucleated giant cells. TALC GRANULOMATOSIS: Interstitial foreign body-type granulomas containing talc, microcrystalline cellulose, or crospovidone. RHEUMATOID NODULE: Active, seropositive rheumatoid arthritis. Multiple, bilateral lung nodules. Subpleural necrotizing granuloma.
Aspiration pneumonia. What is seen histologically?
Surgical lung bxs from pts with chronic recurrent aspiration of gastric contents commonly show patchy BOOP. The specific finding that distinguishes aspiration from other causes of BOOP comprises airway-centered granulomas with central suppuration or foreign-body giant cells with exogenous material. These can be very focal and sometimes require a diligent search. Less commonly, organizing pneumonia is minimal or absent, and instead, the findings are those of acute bronchiolitis with or without bronchopneumonia characterized by airway-centered acute inflammation and necrosis. Aspirated materials comprise vegetable matter, skeletal muscle, or crystalline inorganic fillers found in oral medications. Depending on the age of the process, organic material ranges from recognizable plant cellular structures and skeletal muscle to amorphous, degenerated, pale eosinophilic material within peribronchiolar interstitium. Inorganic fillers from medications usually take the form of either microcrystalline cellulose, which is chunky and strongly birefringent, or crospovidone, which are small, round, hematoxyphilic globules. Occasionally, bxs demonstrate only airway-centered, suppurative granulomas without exogenous material, a combination of findings that raises the possibility of aspiration but is not conclusive. In such cases, special stains should be used to exclude granulomatous infection.
Carney Triad.
Characterized by the presence of at least 2 of the following 3: Gastric epithelioid leiomyosarcoma (now called GIST), extraadrenal paraganglioma, pulmonary hamartoma/chondroma. Primarily affects young women. Not familial.
Ciliocytophthoria is classically seen in what infection?
Adenovirus infection in the respiratory system. Ciliocytophthoria are decapitated ciliated columnar cells, where only the terminal bar and cilia are seen.
Describe the histologic appearance of chronic necrotizing pulmonary aspergillosis and allergic bronchopulmonary aspergillosis.
In CNPA, Aspergillus infection results in semi-invasive, chronic, indolent, cavitary disease in patients who have preexisting lung disease or are mildly immunocompromised. It is characterized by necrotizing granulomas containing Aspergillus hyphae. The granulomas may cause extensive parenchymal consolidation, may lead to bronchiectatic cavities, or may be exclusively bronchocentric. The bronchocentric cases may be accompanied by nonnecrotizing granulomas in a lymphangitic distribution. A nonnecrotizing vasculitis can occur. Eosinophils are not prominent. ABA is a noninvasive form of Aspergillus lung disease characterized by a hypersensitivity response to Aspergillus antigens, occuring mostly in asthmatic patients. Less commonly, other fungi such as Curvularia and Candida may cause similar morphologic changes. ABA results in a distinctive tissue reaction characterized by the triad of mucoid impaction of bronchi, bronchocentric granulomatosis, and eosinophilic pneumonia. However, an individual component of the triad may be present in isolation. Also, each of the features of the triad can occur in isolation in other conditions.
Erdheim-Chester disease and the lung?
A rare nonfamilial histiocytic disorder of unknown etiology. It primarily affects middle-aged and older adults. There are sclerotic changes in long-bone diaphyses and metaphyses with bone pain. About half of cases have involvement of nonosseous tissue, and lung involvement occurs in ~20% of cases. Histologically, there is accumulation of foamy or clear histiocytes with variable amounts of associated fibrosis and a variable lymphoplasmacytic infiltrate. Histiocytes and associated fibrosis and inflammation lie in a characteristic lymphangitic distribution: subpleural, intralobar septal, and bronchovascular. Generally immunopositive for CD68 and factor XIIIa and negative for CD1a. S-100 is variably positive.
Examples of pseudoneoplastic lesions in the lower airway and their related neoplastic mimes.
Pseudocarcinomatous epithelial hyperplasia (squamous cell carcinoma and adenocarcinoma). Fibrohyaline plaques of pleura (desmoplastic mesothelioma). Florid mesothelial hyperplasia (epithelial mesothelioma). Localized tumefactive organizing pneumonia (inflammatory sarcomatoid carcinoma). Selected examples of lymphocytic interstitial pneumonia (lymphoma). Pulmonary chondroid/lipomatous/muscular hamartomas (metaplastic carcinomas). Other examples include inflammatory pseudotumor, nodular lymphoid hyperplasia, apical cap AKA apical scar, round atelectasis, sclerosing (fibrosing) mediastinitis, and hyalinizing granuloma,
Examples of pseudoneoplastic lesions in the upper airway and their related neoplastic mimes.
Pseudocarcinomatous epithelial hyperplasia (squamous cell carcinoma). Oral organ of Chievitz (low-grade squamous or mucoepidermoid carcinoma). Necrotizing sialometaplasia (squamous or mucoepidermoid carcinoma). Radiation effects on mucosal epithelia (squamous carcinoma). Benign lymphoepithelial lesion of salivary gland (lymphomas). Traumatized antral/choanal polyps (polypoid sarcomatoid carcinomas). Glial heterotopias (peripheral nerve sheath tumors). Benign fibroosseous lesions (low-grade fibrosarcoma or osteosarcoma).
How can you tell granulomas in Wegener granulomatosis from infectious granulomas?
In Wegener granulomatosis, there are necrotizing granulomas with necrotizing vasculitis. The granulomas are supperative with a highly irregular contour. Vasculitis is primarily neutrophils. No lymph node involvement. No organisms found. Clinical picture of upper respiratory tract symptoms, multifocal lung involvement, kidney disease, and positive ANCA. Infectious granulomas are more likely solitary lesions. Admixed compact, sarcoid-like, nonnecrotizing granulomas with regular contours. Vasculitis is non-necrotic and primarily lymphocytes. Lymph node involvement present. Organisms found.
IHC for separating reactive mesothelial proliferations from mesothelioma?
Desmin positive in ~85% of reactive mesothelial proliferations and ~10% of mesothelioma. EMA positive in ~20% of reactive mesothelial proliferations and ~80% of mesothelioma. p53 positive in 0% of reactive mesothelial proliferations and ~45% of mesothelioma. GLUT-1 positive in 0% of reactive mesothelial proliferations and ~90% of mesothelioma.
Mesothelioma types.
Benign (3): Benign (papillary) mesothelioma. Benign multi cystic mesothelioma. Adenomatoid tumor. (All 3 are more common in the peritoneal cavity than in the pleural cavity.)
Malignant (4): –Epithelioid mesothelioma. MC histologic type of malignant mesothelioma. Common secondary patterns of epithelioid MM are: tubulopapillary, acinar (glandular), adenomatoid (microglandular), and solid. Uncommon secondary patterns are: clear cell, deciduoid, adenoid cystic, signet ring, small cell, and rhabdoid. –Spindle cell or sarcomatoid mesothelioma. Are predominantly or entirely composed of spindle tumor cells. They tend to be more nodular and less plaque-like than those composed of cuboidal mesothelial cells and are often accompanied by hemorrhage, necrosis, and cystic change. Secondary patterns of sarcomatoid MM may have anaplastic and giant cells, osteosarcomatous areas, chondrosarcomatous areas, or be lymphohistiocytoid.
–Desmoplastic mesothelioma. Most are a subtype of sarcomatoid MM, but rare epithelioid desmoplastic MM can occur. Is accompanied by abundant deposition of fibrous tissue. Must be distinguished from areas of dense inflammatory fibrosis (fibrous pleuritis). –Variants with unresolved histogenetic questions: MM with squamous differentiation (pleural squamous cell carcinoma). Mucoepidermoid carcinoma of the pleura.
Pulmonary Langerhans-cell histiocytosis.
Previously called histiocytosis X or pulmonary eosinophilic granuloma. Characterized by infiltration in lung parenchyma of CD1a-positive histiocytes = Langerhans cells. The earliest abnormality is an interstitial infiltrate of Langerhans cells, predominantly around small airways. With progression of PLCH, the infiltrates develop into temporally heterogenous, roughly symmetrical, stellate nodules containing variable numbers of Langerhans cells, eosinophils (which may be scant to absent), lymphocytes, and fibroblasts. The surrounding lung parenchyma may be normal. The nodules may become cystic. Central scarring eventually develops. Generally immunopositive for CD1a and S-100 and negative for CD68.
Rosai-Dorfman disease and the lung?
AKA sinus histiocytosis with massive lymphadenopathy, is a rare, acquired, pseudoneoplastic hematopoietic proliferation of distinctive histiocytic/phagocytic cells within lymph node sinuses and lymphatics in extranodal sites. Typically affects children and young adults but not always. Unknown etiology. Most often involves cervical lymph nodes. ~3% of patients have lung involvement and lesions may arise as one or more masses involving the trachea and bronchi, or as diffuse involvement of pulmonary interstitium in some. Nodular areas contain dense infiltrates of lymphocytes with intermixed large pale histiocytes, arranged both singly and in small clusters. Rosai-Dorfman histiocytes have abundant eosinophilic cytoplasm and exhibit round to oval nuclei with one or more prominent nucleoli. Nuclei may be multilobulated and may exhibit mild atypia. Emperipolesis is present and may be conspicuous. Generally immunopositive with CD68, CD14, CD15, CD64, S-100, HAM56. Generally negative with markers of dendritic differentiation such as CD1a, CD21, CD23, and CD35.
Two non-Langerhans-cell histiocytoses with pathology in the lung?
Erdheim-Chester disease and Rosai-Dorfman disease.
Usual interstitial pneumonia.
UIP is the MC of the idiopathic interstitial pneumonias, which include respiratory bronchiolitis interstitial pneumonia/desquamative interstitial pneumonia, acute interstitial pneumonia (AKA Hamman-Rich disease) and nonspecific interstitial pneumonia. UIP is the histologic counterpart of the clinical syndrome referred to as idiopathic pulmonary fibrosis and is typically diagnosed in pts 50-70 yo. UIP is a disease of pathologic fibrosis. Some degree of interstitial inflammation is usually present, especially in areas of honey comb change, but the very patchy inflammation is overshadowed by fibrosis as the dominant finding. The most notable feature at low magnification is the variegated nature of the fibrosis. UIP typically has spatial heterogeneity, where minimally affected areas are juxtaposed with dense and often confluent fibrosis. UIP can also have temporal heterogeneity, where most of the fibrosis consists of dense collagen deposits that contrast with scattered, small, interstitial, subepithelial foci of pale blue, immature collagen with admixed myofibroblasts, so-called fibroblast foci. Fibrosis in UIP is often sufficiently advanced by the time of bx to result in architectural distortion in the form of collagenous scarring and honeycomb change. Honeycomb change refers to cystically dilated airspaces within zones of scar. A mucopurulent exudate is often present within the dilated airspaces, accumulating as a consequence of the stasis of secretions in these areas.
What are 3 tumors in the PEComa famiy that are seen in tuberous sclerosis?
Angiomyolipoma, clear cell “sugar” tumor, and lymphangioleiomyomatosis.
What are the 2 most common forms of pulmonary Aspergillosis with granuloma formation?
Aspergillus may cause invasive, saprophytic, or allergic lung disease, depending primarily on the immune status of the host. The 2 most common forms of lung involvement by Aspergillus (aspergilloma and invasive aspergillosis) do not feature granulomas. However, granulomas are a prominent feature of 2 less common forms of pulmonary aspergillosis: chronic necrotizing pulmonary aspergillosis and allergic bronchopulmonary aspergillosis).
What nuclear features and types of inclusions are seen in pulmonary viral infections (herpes simplex and herpes zoster, CMV, measles, RSV, and adenovirus)?
Herpes simplex and herpes zoster: Nuclear features are multinucleation, molding, and peripheral margination of chromatin. Inclusions are intranuclear and eosinophilic (Cowdry type A). CMV: Nuclear feature is enlargement. Intranuclear inclusions are large and basophilic with a halo, and cytoplasmic inclusions are small and basophilic. Measles: Nuclear feature is multinucleation. Intranuclear inclusions are eosinophilic, and intracytoplasmic inclusions are multiple and eosinophilic. RSV: Nuclear feature is multinucleation. Inclusions are cytoplasmic and basophilic with a halo. Adenovirus: One type of nuclear inclusion seen is a large basophilic inclusion usually filling the entire nucleus and obscuring chromatin detail (smudge cell). The other type of nuclear inclusion seen are eosinophilic inclusions that resemble the Cowdry A inclusion of HSV.
Why are transbronchial biopsies so effective in detecting sarcoidosis?
There is a lymphantic distribution to the granulomas of sarcoidosis. In the lung, lymphatics run in the pleura, interlobular septa, and bronchovascular bundles (bronchi/bronchioles and arteries).
Why is “talc granulomatosis” a misnomer?
Because talc (hydrated magnesium silicate) is not the only excipient used in medications. Excipients are inactive substances used as carriers for the active ingredients of medications. In oral pills/tablets, they act as fillers, binders, and disintegrants. Other excipients are microcrystalline cellulose and crospovidone. Microscopically the inclusions are: large sheet/platelike and strongly birefringent (talc), fiber/rod-like and strongly birefringent (microcrystalline cellulose) or deep blue and coral-like (crospovidone). In contrast, while sarcoidosis can have birefringent foreign material in granulomas as well, they are often small, crystalline, and are present in less amounts than with the excipients.
What is Austrian syndrome?
Austrian syndrome was first described by Robert Austrian in 1957. The classical triad consists of meningitis, pneumonia, and endocarditis all caused by Streptococcus pneumoniae. It is associated with alcoholism, due to the presence of hyposplenia, and can been seen in males between 40–60 years old.
Organizing pneumonia (Bronchiolitis Obliterans Organizing Pneumonia). What causes it?
Organizing pneumonia, formerly referred to as BOOP, is seen secondary to a variety of lung injuries and as a component of several specific lung diseases. The same histologic pattern occurs as an idiopathic clinical syndrome called cryptogenic organizing pneumonia (COP; formerly referred to as idiopathic bronchiolitis obliterans organizing pneumonia), classified with the idiopathic interstitial pneumonias. Organizing pneumonia is a common response to infectious or inflammatory injury to lungs, including viral or other infections, as a drug reaction, as a reaction to chemotherapy or radiation therapy, after inhalation of fumes or toxic compounds, as a postobstructive finding distal to an obstructed airway, as a result of aspiration, and in bone marrow transplant recipients. This pattern can also be a component of specific lung diseases, including hypersensitivity pneumonia, eosinophilic pneumonia, collagen vascular diseases involving the lungs, and Wegener granulomatosis. Cause cannot be determined from biopsy; clinical history is needed. Clinically, acute onset with cough, shortness of breath, fever, and malaise. Some patients have self-limited disease; excellent prognosis with steroid treatment; steroid resistance can lead to death.
Organizing pneumonia (BOOP) histologic features?
On low power, there are evenly spaced nodules or plugs of organizing connective tissue and inflammation that obliterates terminal airways. There are plugs of granulation tissue (fibroblasts in an edematous or myxoid stroma) in the lumens of bronchioles, alveolar ducts, and adjacent alveoli. The fibroblastic plugs in bronchioles and alveolar ducts is the “bronchiolitis obliterans” component and the fibroblastic plugs in alveoli is the “organizing pneumonia” component. The plugs are formed by spindled fibroblasts in pale-staining matrix with serpiginous or elongated shape. Rounded nodules of granulation tissue in alveolar spaces are called Masson bodies. There may be accompanying interstitial lymphocytes or other inflammation. Thickened alveolar septae and rare neutrophils can be seen. Transbronchial biospy may fail to sample bronchioles, and the only finding may be the granulation tissue in the alveoli. Intra-alveolar collections of foamy macrophages may result from the bronchiolar obstruction. There may be findings that suggest the etiology, such as viral inclusions in viral pneumonias, foreign-body giant-cells in aspiration, or poorly formed granulomas and multinucleated giant-cells in hypersensitivity pneumonitis. Histopathologic clues to the etiology of organizing pneumonia may not be present, and clinical correlation is necessary to determine the underlying cause. If an identifiable etiology is excluded, then the diagnosis is cryptogenic organizing pneumonia. The organizing pneumonia may resolve with or without residual scarring.
Cryptogenic organizing pneumonia/Idiopathic bronchiolitis obliterans organizing pneumonia. What causes it?
Cryptogenic organizing pneumonia (COP), formerly termed idiopathic BOOP, consists of proliferation of granulation tissue within small airways, alveolar ducts, and alveoli. The clinical syndrome occurs most often in middle-aged to older adults and is often preceded by a flu-like illness. Persistent nonproductive cough and shortness of breath are the usual presenting symptoms. Most, but not all, patients respond rapidly to steroids, and in most cases the prognosis is excellent. COP is an idiopathic clinical syndrome, but similar lesions can be seen in various specific pulmonary injuries. These identifiable causes of organizing pneumonia must be excluded clinically and pathologically before a diagnosis of COP can be made.
Usual interstitial pneumonia. Definition and histologic features.
UIP is the pathologic abnormality essential to the diagnosis of the distinct clinical disorder idiopathic pulmonary fibrosis (IPF), also known as cryptogenic fibrosing alveolitis. IPF is a chronic progressive form of interstitial pulmonary fibrosis that occurs in middle-aged to elderly patients and does not respond to immunosuppressive therapy, unlike many other interstitial lung diseases, and has a poor prognosis. It is probable that smoking has a causative role. UIP is characterized histologically by: Chronic interstitial fibrosis composed predominantly of mature collagen with relatively minimal to mild interstitial chronic inflammation. Patchy pattern of interstitial fibrosis with areas of normal or nearly normal lung parenchyma mixed with areas of minimal to mild interstitial fibrosis and areas of architectural distortion consisting of honeycomb lung or solid scars. Fibrosis and honeycombing of UIP are more prominent in the lower lung zones, in the peripheral (subpleural) areas, and in the periphery of the lobule. Fibroblast foci consisting of small tufts of granulation tissue (fibroblasts in a myxoid or edematous stroma), typically on the fibrotic walls at the interface between fibrotic and normal lung. Most of the fibrosis observed in UIP is mature collagen, including areas of honeycomb lung and solid scars, but the scattered small fibroblast foci represent the active areas of ongoing disease (temporal heterogeneity, which is essential to the concept and diagnosis of UIP). Honeycomb areas may show lymphoid aggregates, smooth-muscle hyperplasia, bronchiolar or squamous metaplasia of cyst linings and neutrophils or macrophages or debris in the cystic spaces, or desquamative interstitial pneumonia-like reactions. Granulomas, hyaline membranes, extensive areas of organizing pneumonia, foreign-body giant cells, bronchiolocentric fibrosis, and other specific findings suggest that the fibrosis has another cause.
What diseases/factors can cause a usual interstitial pneumonia pattern of fibrosis in the lung?
Lung involvement in collagen vascular diseases, particularly RA and scleroderma. Drug reactions. Chronic aspiration. Radiation fibrosis. “Burnt out” chronic infections. Sarcoidosis. Chronic hypersensitivity pneumonia. Langerhans histiocytosis.
Nonspecific interstitial pneumonia. Definition and histologic features?
NSIP is defined as a chronic idiopathic interstitial pneumonia that is temporally uniform. NSIP occurs most often in middle-aged adults and usually presents as shortness of breath. Histologically, NSIP is divided into cellular and fibrotic forms. In cellular NSIP, the alveolar septa have lymphoplasmacytic infiltrates that may vary from minimal to severe and may be accompanied by lymphoid nodules, but the underlying alveolar architecture is relatively preserved and recognizable. In fibrotic NSIP, the alveolar septa have fibrosis that may vary from minimal to severe, but the underlying alveolar architecture is relatively preserved and recognizable. Some cases may show varying amounts of both cellular interstitial infiltrates and interstitial fibrosis. In contrast to UIP, NSIP has minimal or absent honeycombing and lacks the fibroblast foci that represents the temporal heterogeneity of UIP. Organizing pneumonia may be present. Cellular NSIP has a good response to steroids and a good prognosis. Fibrotic NSIP may respond to steroids but generally has a much worse prognosis than the cellular form. Biopsies of several specific entities can also show features that meet the criteria for NSIP.
Mediastinal germinoma/seminoma. What does it look like on FNA?
Germinomas occur exclusively in males. The typical aspirate from a geminoma grossly appears slimy or viscous. Microscopically, smears are usually fairly cellular, containing large, round or polygonal, poorly cohesive cells with a moderate amount of pale cytoplasm with distinct cell membranes. The cells have relatively round nuclei and prominent nucleoli. The background typically has a characteristic “tigroid” appearance on Diff-Quik-stained smears that corresponds to the viscous appearance of the aspirate. The granular background is likely composed of cytoplasmic remnants. Lymphocytes are usually present, and granulomas and syncytiotrophoblast-like multinucleated giant cells may also be observed.
Mechanisms of injury in alpha-1-antitrypsin deficiency, and types of systemic disease associated with alpha-1-antitrypsin deficiency.
The pathologic consequences of deficient alpha-1-antitrypsin are primarily restricted to the lungs and liver. In the lung, deficiency of serum alpha-1-antitrypsin results in unopposed proteolytic destruction of alveolar tissue by neutrophil elastase, and therefore results in progressive panacinar emphysema, typically presenting in the fifth or sixth decade of life in non-smokers and fourth decade of life in smokers. Other pulmonary manifestations include chronic bronchitis, bronchiectasis, and asthma. In the liver, endoplasmic reticulum storage of the abnormal protein results in progressive liver injury, hepatitis, liver failure, and cirrhosis. The pathogenesis of liver cell injury is thought to be secondary to mitochondrial injury, activation of autophagy, and caspase activation leading to apoptosis. Hepatocellular carcinoma is also an associated complication. Other reported systemic diseases associated with AAT deficiency include necrotizing panniculitis, glomerulonephritis, arterial aneurysms, gastrointestinal bleeding, rheumatoid arthritis, anti-proteinase3-associated vasculitis (Wegener granulomatosis), and other immune-mediated vasculitis.The pathologic consequences of deficient alpha-1-antitrypsin are primarily restricted to the lungs and liver. In the lung, deficiency of serum alpha-1-antitrypsin results in unopposed proteolytic destruction of alveolar tissue by neutrophil elastase, and therefore results in progressive panacinar emphysema, typically presenting in the fifth or sixth decade of life in non-smokers and fourth decade of life in smokers. Other pulmonary manifestations include chronic bronchitis, bronchiectasis, and asthma. In the liver, endoplasmic reticulum storage of the abnormal protein results in progressive liver injury, hepatitis, liver failure, and cirrhosis. The pathogenesis of liver cell injury is thought to be secondary to mitochondrial injury, activation of autophagy, and caspase activation leading to apoptosis. Hepatocellular carcinoma is also an associated complication. Other reported systemic diseases associated with AAT deficiency include necrotizing panniculitis, glomerulonephritis, arterial aneurysms, gastrointestinal bleeding, rheumatoid arthritis, anti-proteinase3-associated vasculitis (Wegener granulomatosis), and other immune-mediated vasculitis.
__% of patients with NSCLC test positive for ALK by break-apart FISH probes; an additional __% may test positive by RT PCR due to ALK variants.
3-5% of patients with NSCLC test positive for ALK by break-apart FISH probes; an additional 1-2% may test positive by RT PCR due to ALK variants.
How do carcinoid tumors of pulmonary, gastric and duodenal, ileal, appendiceal, and rectal types stain with TTF-1, CDX-2, and PDX-1 (Pancreatic and Duodenal Homeobox factor-1)?
Pulmonary carcinoids are positive for TTF-1 (only sometimes though) and negative for the others. Gastric and duodenal carcinoids are mostly positive for PDX-1 and negative for the others. Ileal carcinoids are positive for CDX-2 and negative for the others. Appendiceal carcinoids are positive for CDX-2 and negative for the others. Rectal carcinoids are negative for TTF-1 and CDX-2 and and almost all are negative for PDX-1.
What features distinguish benign mesothelial proliferations from diffuse malignant mesothelioma?
Entrapment occurs when organizing pleuritis layers lie over a pleural surface lined by reactive mesothelial hyperplasia, giving an initial impression of invasive mesothelial cell, but closer examination discloses that the hyperplastic mesothelial cells are arranged in a linear pattern (which, in fact, is along the original pleural surface). The proliferating fibroblasts, endothelial cells, and spindled mesothelial cells of organizing pleuritis may mimic sarcomatoid DMM, and fibrocytes and spindled mesothelial cells within mature, dense, fibrous pleuritis may mimic desmoplastic DMM. The storiform pattern that may be seen in sarcomatoid DMM is lacking in benign pleuritis. Zonation of the proliferating cells, with more toward the surface and tapering off in the deeper tissues, is characteristic of benign pleuritis. Another feature that is suggestive of organizing pleuritis, as opposed to DMM, is the presence of parallel capillaries perpendicular to the pleural surface within the granulation tissue. A few significant features are considered confirmatory of DMM on pleural biopsy and decortication specimens and apply to both epithelioid cells and sarcomatoid cells: Invasion into underlying tissues, specifically adipose tissue and/or skeletal muscle under the parietal pleura and lung tissue under the visceral pleura, is diagnostic of DMM. Proliferating cellular nodules that expand the surrounding stroma are confirmatory of a neoplasm rather than a reactive process. In addition, cancer can be diagnosed if there are unequivocal histopathologic features of malignancy, such as severe pleomorphism and atypical mitoses. Bland necrosis with foci of ‘‘clean,’’ ischemic-type necrosis of the proliferating cells is characteristic of DMM and differs from the ‘‘dirty,’’ leukocytoclastic necrosis often seen with infections and other types of cancer, such as colon cancer.
In AJCC (7th edition) staging of lung cancer: What are the tumor sizes for T1a, T1b, T2a, T2b, and T3? Direct tumor invasion into an adjacent ipsilateral lobe (i.e., invasion across a fissure) is classified as __. Multiple tumor nodules in the same lobe are classified as __. Multiple tumor nodules in the same lung but a different lobe are classified as __. Malignant pleural and pericardial effusions are classified as __. Separate tumor nodules in the contralateral lung are classified as __. Distant metastases are classified as __.
T1a is ≤2.0 cm in size, T1b is >2.0 to ≤3.0 cm in size, T2a is >3.0 to ≤5.0 cm in size, T2b is >5.0 to ≤7.0 cm in size, T3 is >7 cm in size. Direct tumor invasion into an adjacent ipsilateral lobe (i.e., invasion across a fissure) is classified as T2a. Multiple tumor nodules in the same lobe are classified as T3. Multiple tumor nodules in the same lung but a different lobe are classified as T4. Malignant pleural and pericardial effusions are classified as M1a. Separate tumor nodules in the contralateral lung are classified as M1a. Distant metastases are classified as M1b.
In AJCC (7th edition) staging of lung cancer, what are definitions of PL0, PL1, PL2, and PL3?
PL0 is defined as tumor located within the lung parenchyma or only superficially invading in the pleural connective tissue, but not beyond the elastic layer of the visceral pleura (i.e., falls short of completely traversing the elastic layer). PL1 is defined as tumor invading into the visceral pleura beyond the elastic layer, and PL2 is defined as tumor invading to the visceral pleural surface. Either PL1 or PL2 status allows classification of the primary tumor as T2. PL3 is defined as tumor invading into the parietal pleura or the chest wall, and PL3 status categorizes the tumor as T3.
What is Lambertosis?
Peribronchiolar metaplasia (also known as Lambertosis) is a condition wherein bronchiolar epithelial metaplasia occuring in peribronchiolar regions of scarred bronchioles extensively colonizes adjacent alveolar spaces, presumably extending through Lambert’s canals. Occasionally, this process may be so marked as to raise serious concern over the histopathologic diagnosis of adenocarcinoma. When peribronchiolar metaplasia is seen in the setting of emphysema in cigarette smokers, that worry is heightened even further. Nevertheless, the metaplastic elements in peribronchiolar metaplasia are more columnar than those of bronchioloalveolar carcinoma, and not as atypical as those of ordinary pulmonary adenocarcinomas. Focal retention of ciliation in the cells of peribronchiolar metaplasia further supports its reactive benign nature, inasmuch as cilia virtually exclude a diagnosis of carcinoma.
Hypersensitivity pneumonia, also known as ___, is a form of diffuse interstitial lung disease. The pathologic basis is an immune complex and cell-mediated immunologic response to a variety of inhaled
organic antigens. The most common antigens are ___. The category of animal proteins is almost always avian (bird) antigens. Cats and dogs do not cause hypersensitivity pneumonia. The list of entities or unusual exposures that are reported to cause hypersensitivity pneumonia increases every year. Exposure to certain inorganic compounds, mainly isocyanates, may also cause hypersensitivity pneumonia in a small percentage of exposed individuals. Through the years specific names have been applied to patients with hypersensitivity pneumonia based on the unique circumstances of antigenic exposure, such as ___. Chronic hypersensitivity pneumonia results from repeated exposures to antigens and can be lethal.
Hypersensitivity pneumonia, also known as extrinsic allergic alveolitis, is a form of diffuse interstitial lung disease. The pathologic basis is an immune complex and cell-mediated immunologic response to a variety of inhaled organic antigens. The most common antigens are molds, thermophilic bacteria, and animal proteins. The category of animal proteins is almost always avian (bird) antigens. Cats and dogs do not cause hypersensitivity pneumonia. The list of entities or unusual exposures that are reported to cause hypersensitivity pneumonia increases every year. Exposure to certain inorganic compounds, mainly isocyanates, may also cause hypersensitivity pneumonia in a small percentage of exposed individuals. Through the years specific names have been applied to patients with hypersensitivity pneumonia based on the unique circumstances of antigenic exposure, such as farmer’s lung, bird fancier’s lung, or pigeon breeder’s lung. Chronic hypersensitivity pneumonia results from repeated exposures to antigens and can be lethal.
What is the classic triad of histologic features seen in chronic hypersensitivity pneumonia?
Cellular interstitial pneumonia, chronic bronchiolitis, and poorly formed granulomas. Cellular interstitial pneumonia: Expansion within the interstitium by a cellular process; should be mostly lymphocytes. Chronic bronchiolitis: Variable dense infiltrate of mononuclear cells that expands the peribronchiolar interstitium with or without fibrosis. Composed of predominately lymphocytes and often with granulomatous features. Poorly formed granulomas: Located in the interstitium, not airways, except in hot tub lung. Isolated giant cells, loose congregation of histiocytes. Well-formed granulomas are not characteristic. May contain Schaumann bodies, cholesterol clefts, asteroid bodies, and calcium oxalate crystals.
The solid variant of pulmonary adenocarcinoma is defined in the WHO classification as ___.
The solid variant of adenocarcinoma is defined in the WHO classification as having intracytoplasmic mucin in at least 5 tumor cells in each of two high power fields. This definition is, however, arbitrary, and there is debate regarding whether tumors that fall short of this definition should be classified as adenocarcinoma or large cell carcinoma.
Pulmonary adenosquamous carcinoma is defined in the WHO as ___.
Adenosquamous carcinoma is defined in the WHO as “a carcinoma showing components of both squamous cell carcinoma and adenocarcinoma with each comprising at least 10% of the tumor.” Each component should have definitive diagnostic features before assigning this designation.
What are 3 benign epithelial lesions, and 3 benign mesenchymal neoplasms seen in the lung?
3 benign epithelial lesions seen in the lung are papilloma, sclerosing hemangioma/pneumocytoma, and alveolar adenoma. 3 benign mesenchymal lesions seen in the lung are hamartoma, solitary fibrous tumor, and clear cell tumor (“sugar tumor”).
Papillomas in the lung.
These epithelial proliferations can be divided into those that involve the large airways and those that arise more distally. Squamous papillomas occur in the large airways and are generally exophytic proliferations that can partially occlude the airway. They are associated with human papillomavirus; they can be seen in both pediatric and adult patients but are more frequently encountered in the pediatric population. Involvement of the lower respiratory tract without involvement of the upper tract is unusual. Histologically, these proliferations consist of stratified squamous epithelium with surface koilocytic atypia, growing on fibrovascular cores in an arborizing pattern. Mixed squamous and glandular papillomas are not associated with human papillomavirus and are lesions of the bronchioles; the fibrous cores are lined by columnar and glandular cells, and in some instances, vaguely resemble transitional-type epithelium. It is important to recognize the bland lining cells of these distal papillomas, as they can be confused with adenocarcinoma. The main differential diagnosis of papillomas in the large airways is a tumorlike condition known as a fibroepithelial polyp. While the fibroepithelial polyp also has a fibrous core, the arborizing structures are lined with respiratory epithelium. The fibroepithelial polyp is likely a tumorlike condition, a postinflammatory reactive process.
What are the 4 common patterns seen in sclerosing hemangiomas/pneumocytomas of the lung?
There are 4 common patterns seen in these tumors: telangiectatic, epithelial/papillary, solid, and sclerotic. Not all tumors have all 4 patterns. It is the telangiectatic hemorrhagic pattern that led to the morphologic classification of this tumor as a hemangioma. While the sclerotic areas are not usually the predominant pattern, it is the combination of sclerosis in a bland papillary and solid-growing tumor that leads to the consideration of this entity, even on frozen section.
Sclerosing hemangioma/pneumocytoma of the lung. IHC characteristics?
While this tumor has the historical name of hemangioma, electron microscopy and immunohistochemistry have shown an epithelial origin for this tumor. It is most frequently a solitary lung nodule, more common in women. Both radiographically and grossly these are well-circumscribed tumors. While they can be multiple and can involve lymph nodes, sclerosing hemangioma/pneumocytoma is a benign neoplasm clinically. There are 4 common patterns seen in these tumors: telangiectatic, epithelial/papillary, solid, and sclerotic. The immunohistochemistry profile of this tumor is distinctive, as the combination of cytokeratin and thyroid transcription factor 1 is generally diagnostic. While cytokeratin shows reactivity in the papillary proliferations, the bland solid areas are negative for this marker. In contrast, thyroid transcription factor 1 shows positivity in both the epithelial/papillary pattern and in the solid pattern. While foci can be positive for neuroendocrine markers (which at one point led to the speculation of a neuroendocrine tumor), these are not diffusely positive as in a carcinoid tumor. In addition, solid-growing areas of a carcinoid tumor are generally strongly cytokeratin positive.
Sclerosing hemangioma/pneumocytoma of the lung is IHC positive for __ and __, the combination of which is generally diagnostic.
Sclerosing hemangioma/pneumocytoma of the lung is IHC positive for cytokeratin and TTF-1, the combination of which is generally diagnostic.
Alveolar adenoma of the lung.
While included among epithelial neoplasms, it is not clear that alveolar adenoma is in fact an epithelial neoplasm. Like sclerosing hemangiomas, alveolar adenomas are usually solitary nodules, seen more commonly in women. The dilated spaces have been described as resembling a lymphangioma, but they are lined by type II epithelial cells. In contrast to the sclerosing hemangioma, the solid growing interstitial cells are mesenchymal, not type II epithelial cells, and as a result, only the lining cells are immunoreactive with thyroid transcription factor 1.
Pulmonary hamartoma.
While a hamartoma is defined as disordered growth of tissues normally present within the organ, pulmonary hamartomas are clonal proliferations and therefore neoplastic. They contain chromosomal rearrangements of 12p15 and 6p21. Among the benign neoplasms of lung, which are overall rare, hamartomas are the exception. They can occur in the periphery or endobronchially and can vary in size, although they are usually less than 4 cm. Their distinct radiologic appearance (lobulated, ‘‘popcorn’’ calcification) can be diagnostic, therefore avoiding the need for resection. Pulmonary hamartomas contain at least 2 benign/mature mesenchymal tissues, one of which is often cartilage. Adipose tissue is also frequently present, especially in central lesions. The epithelium is thought to be entrapped reactive epithelium. In tumors with only 1 mesenchymal element, a corresponding benign mesenchymal neoplasm, such as a lipoma or chondroma, should be the main diagnostic consideration.
Intrapulmonary solitary fibrous tumor.
While most commonly a tumor of pleura, intraparenchymal solitary fibrous tumor of lung can also occur. Aside from the location, solitary fibrous tumor of the lung is histologically identical to that of the pleura, with the exception that intrapulmonary solitary fibrous tumor has ingrowth of epithelial cells along clefts in the tumor. This can impart a leaflike growth pattern, which should not cause confusion with other neoplasms. The bland spindle cell population of a solitary fibrous tumor, alternating with areas of hyalinized collagen, is fairly distinctive; the addition of strong CD34 positivity is confirmatory.
What are some common and uncommon mass-forming tumorlike conditions in the lung?
Common: Granulomatous lesions, with infectious necrotizing granulomas being the most common, with AFB and fungi being the most commonly identified causes. Also, vasculitides such as Wegener granulomatosis, nodular sarcoid, and rheumatoid nodules. Pulmonary infarcts. Localized/focal organizing pneumonia. Intraparenchymal lymph node. Uncommon: Minute meningothelial nodules. Nodular lymphoid hyperplasia. Nodular amyloid. Inflammatory pseudotumor, plasma cell granuloma type and IgG4-related sclerosing disease. Pulmonary hyalinizing granuloma. Tracheopathia osteoplastica. Apical cap. Rounded atelectasis.
What are pulmonary minute meningothelial nodules?
While these are commonly encountered lesions, as incidental findings in lung tissue resections for other reasons, they are not generally the target lesion of a nodule or mass resection. There are rare cases in which these proliferations exceed 5 mm and are resected for concern of malignancy. They typically expand alveolar walls, imparting a stellate appearance to the lesions; the cellular expansion consists of bland cells with indistinct borders in nested and whorled patterns. They are typically positive for epithelial membrane antigen by immunohistochemistry. Despite their name and morphologic similarity, the even rarer true meningioma of the lung appears to harbor different molecular alterations from those of minute meningothelial nodules, raising the question as to whether they actually have related pathogenesis.
Nodular lymphoid hyperplasia in the lung.
Dense proliferations of lymphocytes in the lung, forming a mass lesion, should be ruled out for lymphoma. With this in mind, areas of lymphoid hyperplasia can form a localized or multinodular mass in lung. The inciting trigger for lymphoid hyperplasia has been proposed to be a foreign body/foreign antigen, and this can sometimes be demonstrated. These proliferations are composed of well formed follicles with organized B-cell and T-cell zones without invasion of pleura or bronchus. Involvement of epithelium can be present, mimicking a lymphoepithelial lesion, but in contrast to B-cell lymphoma, the infiltrating cells are T cells. The plasma cells within the lesion can have Russell bodies but not Dutcher bodies.
Pulmonary hyalinizing granuloma.
This is a localized lesion of the lung seen in adults and characterized by a central area of dense, ropy collagen surrounded by a rim of inflammatory cells, which are usually lymphocytes. While at low power this can resemble a granuloma, these lesions do not have a rim of histiocytes at the periphery, nor do they have central necrosis or calcification. They are negative for CD34 and therefore do not represent paucicellular solitary fibrous tumor. There is a pleural lesion called calcifying fibrous pseudotumor in which a rim of inflammation is also present, but the center contains dense hyalinized collagen with small calcifications. This is seen in young adults and is pleural based, usually visceral pleura.
Tracheopathia osteoplastica.
This is usually an incidental asymptomatic tracheal and bronchial multinodular growth arising from the cartilaginous components of the airway. Its distribution along the cartilaginous surfaces of the airway is radiographically and bronchoscopically distinct, sparing the membranous surface of the trachea. Cases that involve the bronchus can cause obstruction necessitating resection. The nodules are composed of cartilage and ossification, with or without adipose tissue. Bone marrow elements can also be seen.
Apical cap.
Lesions of nodular fibroelastosis can occur at the apices of the upper lobes of lung as well as the upper portions of the lower lobes. While these lesions yield negative findings on PET scan, their irregular spiculated appearance and their persistence can lead to resection for concern of malignancy. Histologically, apical cap represents a localized area of fibroelastosis that is directly subpleural, extending focally into lung parenchyma. While lesions can be fairly broad and bilateral, multifocality within a given lobe is not generally seen. Fibroelastosis that is associated with multifocality, causing diffuse or multifocal pleural thickening with parenchymal involvement, is outside the spectrum of apical cap/fibroelastosis. In such cases, especially those in which there is a history of pneumothorax, idiopathic pleural parenchymal fibroelastosis needs to be considered, a rare pleural and interstitial lung disease manifested by progressive fibroelastosis.
Rounded atelectasis.
This is a nonneoplastic lesion of lung tissue that is rolled into or folded into an area of fibrous adhesion between parietal and visceral pleura. It is associated with conditions that cause hyalinized parietal pleural plaque with resulting adhesion to the visceral pleura. The lung gets trapped in that adhesion. Asbestos exposure can be the cause of hyalinized plaque. Radiologically, the folded lung shows airways leading into it, with a vaguely radial configuration that has been described as the ‘‘comet tail’’ sign. If the adhesion is removed surgically, the lung can reexpand and the nodule disappears. The histologic profile that remains is often that of relatively normal lung with visceral pleural fibrosis.
What are 6 causes of hemorrhagic pleural effusion?
Malignancy. Infection (especially TB). Pulmonary embolism/infarction. Trauma. Pneumothorax. Benign asbestos effusion.
Malignancy. Infection (especially TB). Pulmonary embolism/infarction. Trauma. Pneumothorax. Benign asbestos effusion.
Necrosis is usually an indicator of malignancy in mesothelial proliferations. However, it can occasionally be seen in what 3 conditions/situations?
Necrosis is usually an indicator of malignancy in mesothelial proliferations. However, it can occasionally be seen in bacterial empyemas (where the necrotic tissue typically is made up of inflammatory cells with relatively few mesothelial cells), mycobacterial and fungal infections in the pleura, and as a reaction to talc poudrage/pleurodesis. Talc can also induce cytologically worrisome mesothelial reactions, so considerable caution should be exercised in diagnosing (de novo) a mesothelioma after talc instillation.
Spindle cell mesothelial proliferations fall into what 3 categories?
Organizing pleuritis (OP, also called fibrous pleurisy or fibrosing pleurisy). Desmoplastic mesotheliomas (DMM)/sarcomatous mesotheliomas. Atypical mesothelial proliferations (atypical mesothelial hyperplasia), used for lesions worrisome for, but not diagnostic of, DMM or sarcomatous mesotheliomas.
What is the “fake fat phenomenon” that can be seen in mesothelial proliferations?
Keratin stains are very helpful in diagnosing desmoplastic mesotheliomas because they typically show spindled cells running downward (ie, away from the pleural surface) into fat. Care should be taken to ensure that what appears to be fat really is fat. Old paucicellular organizing pleuritis may show deep, fatlike spaces running parallel to the pleural surface, with keratin-positive cells between the ‘‘fat’’ cells. This “fake fat phenomenon” is really a biopsy/tissue processing artifact and the spaces are not fat but rather, traction artifacts in a fibrotic stroma. These traction/cutting artifacts may contain pale-staining ground substance. By contrast, true DMMs are both more cellular and have downward growth of spindle cells between fat cells rather than growth parallel to the pleural surface. S100 stains can be helpful because true fat is S100 positive and artifactual spaces are not.
What are nonmalignant medical conditions associated with reactive eosinophilia?
Allergic reactions (drug reactions, asthma), parasitic infections (strongyloidiasis), schistosomiasis, filariasis, toxocariasis), metabolic abnormalities (adrenal insufficiency), humoral immunodeficiency (hyperimmunoglobulin E syndrome (Job syndrome), Wiskott-Aldrich syndrome, hyperimmunoglobulin M syndrome, immunoglobulin A deficiency), pulmonary eosinophilias (eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome), allergic bronchopulmonary aspergillosis, chronic and acute idiopathic eosinophilic pneumonias), autoimmune blistering skin diseases (dermatitis herpetiformis, bullous pemphigoid).
Lymphangioleiomyomatosis. Locations? Association with a syndrome?
Lymphangioleiomyomatosis (or lymphangiomyomatosis) (LAM) occurs almost exclusively in reproductive age women and consists of a proliferation of immature myoid cells which are currently thought to derive from perivascular epitheliod cells (PEC). LAM may involve the lungs and axial thoraco-abdominal lymphatic system including both lymph nodes and the thoracic duct. Supraclavicular and inguinal nodes may rarely be involved. In most cases, the pulmonary manifestations dominate but LAM may occasionally present exclusively in the abdomen. Abdominal LAM may mimic ovarian carcinoma radiographically and patients may present with pain, often due to hemorrhage. LAM may occur in association with tuberous sclerosis (TS) or in isolation (sporadic LAM), although in either form the LAM cells may be associated with mutations of the TS genes, TSC-1 or TSC-2. Whether LAM is sporadic or associated with TS, the histologic appearance is the same but lymph node involvement is more frequent in patients without TS.
___ is the most common primary pulmonary lymphoma, comprising up to 70% of all cases.
MALT lymphoma is the most common primary pulmonary lymphoma, comprising up to 70% of all cases. MALT lymphomas may have a deceptively heterogenous appearance microscopically, including germinal center formation and a mixture of T-cells and B-cells by IHC.
