Pulmonary/Mediastinum Flashcards

Question

Usual interstitial pneumonia. Definition and histologic features.

Answer 1

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.

Answer 2

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.

Answer 3

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.

Answer 4

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.

Answer 5

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.

Answer 6

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.

Answer 7

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.

Answer 8

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.

Answer 9

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.

Answer 10

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.

Answer 11

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.

Answer 12

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.

Answer 13

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.

Answer 14

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.

Answer 15

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.

Answer 16

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").

Answer 17

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.

Answer 18

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.

Answer 19

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.

Answer 20

Sclerosing hemangioma/pneumocytoma of the lung is IHC positive for cytokeratin and TTF-1, the combination of which is generally diagnostic.

Answer 21

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.

Answer 22

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.

Answer 23

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.

Answer 24

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.

Answer 25

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.

Answer 26

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.

Answer 27

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.

Answer 28

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.

Answer 29

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.

Answer 30

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.

Answer 31

Malignancy. Infection (especially TB). Pulmonary embolism/infarction. Trauma. Pneumothorax. Benign asbestos effusion.

Answer 32

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.

Answer 33

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.

Answer 34

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.

Answer 35

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).

Answer 36

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.

Answer 37

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.

Answer 38

The primary entity in the differential diagnosis of pulmonary MALT lymphoma is nodular lymphoid hyperplasia (NLH). Such lesions are extremely rare. The most important caveat is that any mass-forming lesion effacing the underlying lung architecture should be considered a lymphoma until proven otherwise, so careful exclusion of lymphoma is of paramount importance before rendering a diagnosis of NLH.

Answer 39

Typically, NLH presents as solitary peripheral nodules but may be multiple on occasion. NLH is well-circumscribed in comparison to MALT lymphoma, and lacks peripheral lymphangitic spread of the lymphoproliferative process. Additionally, lymphoepithelial lesions should be absent or very rare in NLH, and plaque-like infiltration of the pleura and Dutcher bodies should not be seen. Germinal center formation may be quite pronounced and plasma cells are prominent between the reactive follicles. Immunostains show a distribution of B- and T-cells typical of reactive follicles and the plasma cells lack light chain restriction. Similarly, no evidence of clonality should be evident by flow cytometry or molecular studies.

Answer 40

LYG is an angiocentric lymphoproliferative disorder which may involve multiple organs, but frequently involves the lungs. LYG is comprised of a mixture of neoplastic, large, morphologically atypical B-cells admixed with variable numbers of background T-cells. LYG is traditionally divided into three grades (LYG 1, 2, and 3) depending on the percentage of each cell type present, with LYG grade 3 being comprised essentially entirely of large B-cells and generally regarded as a B-cell lymphoma. Grade 1 LYG, however, is comprised primarily of small background T-cells and only a small percentage of large atypical B-cells, and therefore may be considered in the differential of MALT lymphoma. LYG occurs most commonly in immunocompromised individuals and typically presents as multiple masses, often with cavitation.

Answer 41

Lymphocytic interstitial pneumonia (LIP) is a diffuse interstitial lung disease generally restricted to a narrow range of clinical senarios, and is most commonly encountered in patients with collagen vascular disease or immunodeficiency.

Answer 42

Primary pulmonary lymphoma can be diagnosed when there is a clonal lymphoid proliferation affecting one or both lungs (parenchyma and/or bronchi) without evidence of mediastinal lymphadenopathy or a mass on chest imaging in a patient with no previous extrathoracic involvement at the time of diagnosis or during the subsequent 3 months. Primary lymphoma of the lung is a rare disorder and represents only 0.3% of all primary pulmonary malignancies, <1% of all the cases of non-Hodgkin lymphoma, and 3-4% of all the extranodal manifestations of non-Hodgkin lymphoma.

Answer 43

It is a rare EBV-positive DLBCL arising in patients with long-standing chronic pyothorax (treated with iatrogenic pneumothorax), secondary to tuberculosis. Patients present with a mass in the pleura accompanied rarely by lung mass or pleural effusion. On microscopic examination, the tumor shows diffuse proliferation of large atypical cells, with centroblastic and/or immunoblastic or plasmacytoid features with areas of necrosis. Neoplastic cells express pan-B-cell antigens and MUM1; rarely are CD138 positive; and are negative for CD10, bcl-6, and HHV-8. These patients have a dismal prognosis.

Answer 44

Hantavirus pulmonary syndrome. During the HPS prodrome, thrombocytopenia is the only dependable finding. Once pulmonary edema is established, however, there is a highly reproducible pentad of findings: thrombocytopenia, left-shifted neutrophilia, neutrophils with lack of significant toxic granulation, increased hemoglobin concentration (hemoconcentration), and >10% of lymphocytes having immunoblastic morphology. Having 4 of these 5 has a high sensitivity and specificity for HPS.

Answer 45

Several named syndromes are associated with eosinophilia and eosinophilic infiltration of specific organs: eosinophilic cellulitis (Well syndrome), eosinophilic pneumonia (Loeffler syndrome), eosinophilic fasciitis (Shulman syndrome), and eosinophilic vasculitis (Churg-Strauss syndrome).

Answer 46

Fetal adenocarcinoma consists of glandular elements with tubules composed of glycogen-rich, nonciliated cells that resemble fetal lung tubules. The malignant glandular cells grow in tubules and papillary structures with endometrioid morphology. Some tumor cells have prominent clear cytoplasm. Subnuclear vacuoles are common and characteristic. Squamoid morules may be in the lumens. Most are low grade with a favorable outcome. This tumor typically occurs in younger patients than do other adenocarcinomas. Uniquely, the low-grade fetal adenocarcinomas appear to be driven by mutations in the beta-catenin gene and the epithelial cells express aberrant nuclear and cytoplasmic staining with this antibody.

Answer 47

Enteric differentiation can occur in lung adenoCA and when this component exceeds 50%, the tumor is classified as pulmonary adenoCA with enteric differentiation. The enteric pattern shares morphologic and IHC features with CRC. In contrast to metastatic colorectal adenoCA, these tumors are histologically heterogeneous with some component that resembles primary lung adenoCA such as lepidic growth. The enteric pattern consists of glandular and/or papillary structures, sometimes with a cribriform pattern, lined by tumor cells that are mostly tall columnar with nuclear pseudostratification, luminal necrosis, and prominent nuclear debris. Poorly differentiated tumors may have a more solid pattern. These tumors show at least 1 IHC marker of enteric differentiation (CDX-2, CK20, or MUC2). Consistent positivity for CK7 and expression of TTF-1 in ~50% of cases help in the distinction from metastatic CRC. CK7 negative cases may occur. CDX-2 is reduced or absent in most poorly differentiated CRC and more than half show the high-frequency MSI phenotype. Although this type of tumor will rarely metastasize to lung, since IHC detection of MMR proteins (MLH1, MSH2, MSH6, and PMS2) gives a predictive value that is virtually equivalent to MSI testing, this may be worth testing in selected cases as MSI in primary lung adenoCA is extremely rare. Primary lung adenoCA that histologically resemble CRC but lack IHC markers of enteric differentiation are probably better regarded as lung adenoCA with enteric morphology rather than lung adenoCA with enteric differentiation.

Answer 48

Lymphoma with artifactual signet ring cells due to cytoplasmic shrinkage (CD45 is usually positive in lymphoma). Metastases from breast or lung (clinical history, plus the use of appropriate immunostains such as TTF1 or GCDFP-15 is helpful). Reactive epithelial atypia associated with radiation treatment or chemotherapy. Xanthoma.

Answer 49

Peutz-Jeghers polyps (hamartomatous polyps) are supported by broad bands of muscularis mucosa smooth muscle, which is thicker centrally, and resembles a Christmas tree at low power. The polyp has superficial columnar and goblet cells, but Paneth and endocrine cells at its base. Peutz-Jeghers polyps are large, pedunculated polyps of the gut almost always seen in association with Peutz-Jeghers syndrome. This rare autosomal dominant disorder is usually diagnosed at ages 20-30, with hamartomatous polyps in the small bowel (100%), stomach and colon (25%), and associated adenomatous lesions that may give rise to adenocarcinoma of the stomach, large or small bowel; adenoma malignum of the cervix, ovarian mucinous tumors, and carcinoma of the breast, lung and pancreas. The syndrome is also associated with sex-cord tumor with annular tubules (almost all patients) and melanotic pigmentation of the digits, genitalia, lips, oral mucosa, palms and soles. Peutz-Jeghers syndrome is caused by mutations in STK11/LKB1, a serine threonine kinase that may play a role in cell polarity.

Answer 50

For GI tract and pancreas, WHO 2010 classification: Low grade (G1): 20 mitoses/10 HPF, OR >20% Ki-67 index. For lung and thymus, WHO 2004 classification: Low grade (G1): 10 mitoses/10 HPF.

Answer 51

Primary ciliary dyskinesia AKA immotile cilia syndrome is associated in ~50% of patients with Kartagener syndrome AKA situs inversus totalis. Chronic bronchitis, recurrent pneumonia, and atelectasis is virtually pathognomonic for Kartagener syndrome, and in this situation, cilia evaluation is not required for diagnosis.

Answer 52

According to the World Health Organization (WHO), thymic epithelial tumors with predominant neuroendocrine differentiation are classified as Neuroendocrine carcinomas (NEC) of the thymus. Thymic neuroendocrine carcinomas are classified as well-differentiated NEC (typical carcinoid and atypical carcinoid) and poorly differentiated NEC(large cell NEC and small cell NEC). The main differential diagnosis includes: Metastatic pulmonary NEC (TTF1+ may be helpful). Thymic carcinoma with focal neuroendocrine differentiation. Nerve sheath tumor (CK-, chromo-, synapto-). Paraganglioma (CK-).

Answer 53

It has initial and acute phases. The initial phase is characterized by mild flu-like symptoms (e.g., malaise, fatigue, low-grade fever) followed by a period of apparent wellness for about a day. This is immediately followed by the acute phase, which eventually leads to more serious symptoms (e.g., acute respiratory distress). The incubation period can vary from 1–5 days, depending on the number of spores inhaled, but can be as long as 60 days. Shock and death usually occur 24–36 hours after the onset of respiratory distress. The fatality rate of inhalation anthrax approaches 90%, even with antibiotic therapy.

Answer 54

The fatality rate of inhalation anthrax approaches 90%, even with antibiotic therapy. Untreated cutaneous anthrax can have a fatality rate of up to 20%, but fatalities are rare (1%) with proper antibiotic treatment. The fatality rate for GI anthrax is 25%–60%.

Answer 55

Inhalation, cutaneous, and GI anthrax can be complicated by meningitis, which occurs in about 5% of cases.

Answer 56

Type I pneumocytes are large, flat, squamous alveolar lining cells; covering ~93% of alveolar surface area. Type I cells are incapable of division. They provide a thin air-blood interface for gas transfer. Type I pneumocytes stain with epithelial markers such as AE1/AE3, caveolin, and aquaporin. Type II, or granular, pneumocytes are cuboidal to columnar alveolar lining cells. Gas exchange takes place across the cytoplasm of type I cells. Type II cells are the progenitors for type I cells, synthesize and secrete surfactant (lamellar ultrastructural inclusions), and proliferate after injury to restore alveolar epithelial integrity. Type II cell hyperplasia (alveolar cell hyperplasia) represents a nonspecific marker of alveolar injury and repair. Type II pneumocytes stain with epithelial markers such as AE1/AE3, and surfactant protein C.

Answer 57

Type II pneumocytes are the progenitors for type I pneumocytes.

Answer 58

MNPH is defined by the WHO (1999) as "a multifocal micronodular proliferation of type II cells with mild thickening of the interstitium". This condition is rare and generally an incidental finding in a bx taken for another lesion (usually lymphangioleiomyomatosis). Rarely, MNPH is the sole lesion present. The lesions are typically <5 mm in size. They can usually be distinguished from AAH and other causes of alveolar cell hyperplasia by their distinct rounded nodular character at scanning microscopy, the large plump eosinophilic type II cells lacking significant atypia, the slight interstitial collagen deposition within the lesions, and the presence of airspace histiocytes in the regions of the nodules.

Answer 59

Blue bodies are intra-alveolar, lamellated, basophilic, calcified structures found in airspaces associated with alveolar macrophages and giant cells. They are a nonspecific finding in a number of diffuse lung diseases related to accumulation of macrophages and are of no diagnostic significance. They are thought to be related to macrophage catabolism; they are composed primarily of calcium carbonate.

Answer 60

Tracheobronchial cartilage ossification, submucosal fatty metaplasia, oncocytic metaplasia and/or hyperplasia in bronchial glands, and elastotic appearance of the submucosa. Pulmonary arterial and venous intimal thickening and hyalinization of arterioles. Alveolar enlargement (rarely appreciated in biopsy material). Medical calcification in bronchial arteries. Senile vascular amyloidosis. Anthracosis (urban dwellers).

Answer 61

Cartilaginous hamartoma. Alveolar adenoma. Mucous gland adenoma. Endobronchial lipoma. Pulmonary adenofibroma/adenomyoma. Intrapulmonary solitary fibrous tumor. Glomus tumor. Intrapulmonary thymoma. Pulmonary paraganglioma. Pulmonary meningioma. Minute meningothelial-like nodule. Granular cell tumor. Sclerosing hemangioma (pneumocytoma). Clear cell "sugar" tumor (PEComa).

Answer 62

Villin is an actin binding protein present in cytoskeleton of intestinal microvilli; has critical role in maintaining brush border organization. It is relatively specific for GI epithelium with brush border microvilli or adenocarcinomas derived from them. Positive staining (normal): Digestive tract epithelium, proximal renal tubules, hepatic bile ducts. Positive staining (disease): Colonic adenocarcinoma, renal cell carcinoma, pulmonary adenocarcinomas. Negative staining: Renal distal tubules, bronchiolar epithelium, pulmonary alveolar cells, bronchial gland cells. Uses: Primary bladder adenocarcinoma (villin-, CDX2-) vs. colorectal carcinoma to bladder. Ovarian adenocarcinoma (villin-) vs. colorectal adenocarcinoma.

Answer 63

Facial angiofibromas (adenoma sebaceum) or forehead plaque. Nontraumatic ungual or periungual fibroma. >3 hypomelanotic macules. Shagreen patch (connective tissue nevus). Multiple retinal nodular hamartomas. Cortical tuber. Subependymal nodule. SEGA. Cardiac rhabdomyoma, single or multiple. LAM. Renal AML. Definite TSC is either 2 major features or one major plus 2 minor features.

Answer 64

H. influenzae and M. catarrhalis.

Answer 65

In most cases, the basic valvular abnormality is due to rheumatic heart disease, most often affecting the mitral valve. Other cases are related to mitral valve prolapse, nodular dystrophic (age-related) calcification of the aortic valve, and congenital heart disease.

Answer 66

Infants/children: RSV. Adults: Influenza A (orthomyxovirus).

Answer 67

Community-acquired: S. pneumoniae, L. pneumoniae, H. influenzae, S. aureus, M. pneumoniae. Chronic alcoholics: K. pneumoniae. Cystic fibrosis: P. aeruginosa. Atypical/walking pneumonia: M. pneumoniae, Chlamydia pneumoniae. Nosocomial pneumonia: E. coli, P. aeruginosa, S. aureus, L. pneumoniae.

Answer 68

SPEP can be used to screen for AAT deficiency, in which the serum will display a markedly diminished alpha-1 band.

Answer 69

It refers to bleeding that originates in the pulmonary microvasculature instead of the parenchyma or bronchial circulation. Bleeding into the alveolar spaces characterizes the syndrome of DAH and is due to disruption of the alveolar-capillary basement membrane. This is caused by injury or inflammation of the arterioles, venules, or alveolar septal (alveolar wall or interstitial) capillaries. Pulmonary renal syndromes, connective tissue disorders and drugs make up the majority of the cases of DAH.

Answer 70

The 3 histologic patterns recognized in alveolar hemorrhage are pulmonary capillaritis, diffuse alveolar damage, and bland pulmonary hemorrhage. Pulmonary capillaritis is the most frequent pattern described. It is characterized by the leak of red blood cells into the alveolar spaces through damaged alveolar-capillary basement membrane. The interstitium is edematous with necrotic debris, inflammatory cells and red blood cells. There is a striking neutrophilic component in pulmonary capillaritis. Most cases of pulmonary capillaritis will be caused by collagen vascular diseases, autoimmune disorders or vasculitis. DAD is identical to the histopathology seen in acute respiratory distress syndrome. There is edema, capillary congestion, and microthrombi in the alveolar septa and intra-alveolar hyaline membrane formation. The third histologic pattern is bland pulmonary hemorrhage, which in contrast to capillaritis and DAD, shows hemorrhage into alveolar spaces without any alveolar damage. Alveolar hemorrhage from anticoagulant therapy, idiopathic pulmonary hypertension, Goodpasture syndrome and congestive heart failure will demonstrate this pathology.

Answer 71

Three variants of primary pulmonary hemosiderosis are recognized: (1) pulmonary hemosiderosis associated with antibody to the basement membrane of the lung and kidney (ie, Goodpasture syndrome), (2) pulmonary hemosiderosis associated with hypersensitivity to proteins in cow's milk (ie, Heiner syndrome), and (3) idiopathic pulmonary hemosiderosis (IPH).

Answer 72

Type I (cystic). Type II (cystic and solid). Type III (solid).

Answer 73

Type 0 CPAM to type 4 CPAM. Type 4 is now thought to represent a regressed or undersampled form of type I (cystic) pleuropulmonary blastoma.

Answer 74

FLIT is a congenital pulmonary mass typically identified prenatally or within the first 3 months of life. Histologically, the tumor has immature airspace structures separated by widened cellular septa giving the tumor a microcystic appearance. The spaces are lined by flat to cuboidal non-ciliated epithelium with clear cytoplasm. The septa contain a monotonous population of immature, round to ovoid mesenchymal cells in the interstitium. The interstitial cells are PAS positive diastase sensitive, positive for vimentin, and there is variable positivity for SMA and desmin in cases with myofibroblastic morphology.

Answer 75

For bone tumors, metastases are far more common than primary bone tumors in a ratio of 25:1. The 5 most common primary sites are lung, breast, prostate, kidney, and thyroid. After lungs and liver, skeleton is 3rd most frequent site of metastatic disease.

Answer 76

Malignant melanoma, followed by lung and gynecologic cancers.

Answer 77

Mature type II pneumocytes produce a mixture of phospholipids composed predominantly of lecithin. The vast majority of lecithin is disaturated phosphatidylcholine (DSPC). Lesser amounts of phosphatidylglycerol (PG), phosphatidylinositol (PI), phosphatidylethanolamine (PE), and sphingomyelin also comprise lecithin.

Answer 78

It is an issue for gestation between 34 to 37 weeks. Prior to 34 weeks, fetal lung maturity is unlikely, and the risk of RDS is very high. After 37 weeks the risk of RDS is exceedingly low, and fetal lung maturity testing is generally not indicated, except in the presence of poorly controlled maternal diabetes.

Answer 79

Lecithin/sphingomyelin ratio. Phosphatidylglycerol concentration. Foam stability. Lamellar body number density. Disaturated phosphatidylcholine concentration. Fluorescence polarization assay.

Answer 80

Lecithin increases with gestational age, while sphingomyelin remains at a relatively constant 2% of total surfactant phospholipid. Until 26 wks, the ratio is 1:1. After that, the L:S ratio increases until 2:1 is reached around 35 wks. This ratio is generally taken to indicate fetal lung maturity. Above 2:1, 2% of premature infants will develop RDS. Below 2:1, nearly 60% will.

Answer 81

In DM, a ratio of 2:1 does not ensure FLM. The phosphatidylglycerol concentration is more reliable in this senario. The presence of meconium falsely decreases the L:S ratio. The presence of blood normalizes the L:S ratio to ~1.5. The CV of the L:S ratio is high.

Answer 82

Phosphatidylglycerol concentration.

Answer 83

PG is first detected around 36 wks and its presence is indicative of FLM. Neither blood nor meconium interfere with PG determinations, making it the test of choice when the only available specimen is a contaminated one. PG can be measured by TLC or agglutination.

Answer 84

When pulmonary surfactant is present in amniotic fluid in sufficient concentration, the fluid is able to form a highly stable film that can support the structure of a foam. The amniotic fluid is serially diluted with ethanol, and the highest concentration of ethanol at which a complete ring of bubbles is seen is the foam stability index (FSI). An FSI greater than 0.47 is considered indicative of fetal lung maturity.

Answer 85

Surfactant lamellar bodies are about the size of platelets, and the platelet channel of a cell counter can be used to quantify them. An LBND greater than 50,000/mL is predictive of maturity.

Answer 86

An alternative to the L/S ratio is to determine the DSPC concentration, the major component of lecithin, directly. Since it doesn't rely on a ratio with sphingomyelin, it is unaffected by meconium and blood contamination.

Answer 87

This is now the most commonly used method; it is rapid and at least as predictive of FLM as the L/S, with considerably lower CV. A fluorescence polarization value less than 260 is considered mature. Values greater than 290 are considered immature. If these is less than 0.5% blood, results are unaffected. Greater amounts tend to lower high values and raise low values. Even in the presence of blood, values less than 230 are considered mature.

Answer 88

Mortality is increased in pregnancy women with SLE, with most deaths occuring as a result of pulmonary hemorrhage due to lupus pneumonitis and other complications (transverse myelitis, stroke, corticosteroid complications).

Answer 89

Upper respiratory tract (80% of cases). Other less common locations include GI tract, urinary bladder, CNS, breast, parotid gland, thyroid gland, lymph node, testis, and skin.

Answer 90

MI (due to cocaine-induced vasoconstriction). Pneumothorax (due to inhalation barotraumas). Aortic dissection (due to HTN). PE (due to clotting activation). Endocarditis (due to injection of cocaine).

Answer 91

Goodpasture disease refers to the triad of pulmonary (alveolar) hemorrhage, glomerulonephritis of any severity, and serum anti-GBM production. The treatment of choice is plasmapheresis.

Answer 92

The NC1 domain of collagen IV in glomerular and alveolar basement membranes.

Answer 93

Anti-GBM disease, ANCA disease, and immune complex-mediated diseases (such as SLE).

Answer 94

The combination of acute glomerulonephritis and pulmonary hemorrhage. Causes: ANCA-positive vasculitis (granulomatosis with polyangiitis/Wegener's, microscopic polyangiitis). Anti-GBM disease (Goodpasture's). Pulmonary hemorrhage is a rare finding in lupus, HSP (IgAV), and infective endocarditis. Acute glomerulonephritis complicated by pulmonary edema due to fluid overload, as can occur in poststreptococcal glomerulonephritis.

Answer 95

Primary: Infectious mononucleosis. X-linked lymphoproliferative disorder. Hepatitis. Latent: Burkitt lymphoma (100% of endemic BL, 25% of sporadic BL). Hodgkin lymphoma (EBV in 50-70% of cases). Primary effusion lymphoma (EBV in 70% of cases, HHV8 in 100% of cases). Lymphomatoid granulomatosis. Post-transplant lymphoproliferative disorder (EBV in >95%). Oral hairy leukoplakia. Nasopharyngeal carcinoma (nearly 100% EBV positive in Chinese and Inuit populations, 75% EBV positive in US).

Answer 96

In primary effusion lymphoma, HHV8 is positive in 100% of cases, and EBV is positive in 70% of cases.

Answer 97

Adenoviruses are grouped into over 40 serotypes. Most of the respiratory infections are caused by serotypes 1-14, with types 4 and 7 associated with epidemic outbreaks of respiratory disease. Types 11 and 21 are associated with hemorrhagic cystitis. Types 40 and 41 are associated with childhood gastroenteritis.

Answer 98

ANCA disease accounts for ~55% of cases, anti-GBM for 7%, and both ANCA and anti-GBM present in 8% of cases.

Answer 99

Clinical features. Patient's lacking signs of asthma, lung and sinus inflammation, or peripheral blood eosinophilia are best classified as having microscopic polyangiitis. Necrotizing inflammatory lesions involving the lungs, nasal sinuses and kidneys are typically seen in cases of Wegener's granulomatosis. Peripheral blood eosinophilia and asthma are defining features of Churg-Strauss syndrome.

Answer 100

Mucoid impaction of bronchi is characterized by obstruction of proximal bronchi by large, laminated, gelatinous mucus plugs filled with viable and necrotic eos, neuts, fibrin, and necrotic debris. Charcot-Leyden crystals are often present. Aspergillus hyphae may be found within the mucus. Bronchocentric granulomatosis is characterized by necrotizing granulomas centered exclusively on bronchi and bronchioles distal to the bronchi affected by mucoid impaction. The necrotic centers of the granulomas are rich in eos and necrotic debris. Eosinophilic pneumonia is usually a focal finding in ABA. The main histologic feature is filling of the alveolar spaces with eos, often accompanied by histiocytes. The interstitium is usually thickened by a combination of eos, lymphs, and plasma cells. A mild nonnecrotizing vasculitis may be present. (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.)

Answer 101

Juvenile-onset form (presents at 2-4 years of age), in which HPV is thought to be acquired during passage through the birth canal and is more aggressive. Adult form (presents at 20-40 years of age), thought to be sexually transmitted, in which papillomas are fewer.

Answer 102

The papillomas arise most often on the true vocal cords. Malignant transformation is rare, but the lesions can be life-threatening because of airway obstruction, particularly in children. An HPV subtype is sometimes requested as HPV 11 is associated with more aggressive disease than HPV 6.

Answer 103

Unlike the more common flu strains, H5N1 affects predominantly children and young adults, with a median age of 15 yrs. Lymphopenia is characteristic, without significant changes in the neutrophil, RBC, or platelet counts. The virus has tropism for non-ciliated epithelial cells of the lower respiratory tract, leading to an ARDS/DAD-like clinicopathologic picture and may explain the low rate of human-to-human transmission.

Answer 104

Parainfluenza viruses 1 and 2 cause the most cases of croup in children between the ages of 2 and 6. RSV is the most common cause of respiratory bronchiolitis ("viral pneumonia") in infants under age 2.

Answer 105

Classic measles infection in immunocompetent patients. Modified measles (an attenuated infection in patients with preexisting, but incompletely protective, anti-measles antibody). Atypical measles (in patients immunized with the killed virus vaccine and subsequently exposed to wild-type measles virus; is rare since the killed virus vaccine was used in the US from 1963-67). Neurologic syndromes following measles infection, including acute disseminated encephalomyelitis (ADEM) and subacute sclerosing panencephalitis (SSPE). Severe measles. Complications of measles including secondary infection, giant cell pneumonia, and measles inclusion body encephalitis.

Answer 106

RSV causes 90% of respiratory bronchiolitis in infants and almost 50% of lower respiratory tract infections in children. Immunity to RSV is short-lived, and recurrence throughout childhood is the rule, although infections are progressively less severe with bronchiolitis uncommon after 12 mos.

Answer 107

Coxsackie A virus causes hand-foot-mouth disease and herpangina. Coxsackie B virus causes myocarditis, pericarditis, and epidemic pleurodynia (the grippe).

Answer 108

Also called anti-tRNA synthetase. Implies high likelihood of developing interstitial lung disease in polymyositis/dermatomyositis.

Answer 109

Goodpasture syndrome; the epitope is the M2 subunit of type IV collagen.

Answer 110

High specificity for Wegener syndrome; cANCA is anti-proteinase 3 (PR3).

Answer 111

c-ANCA is positive in 90% of Wegener granulomatosis. Its presence does correlate with activity, and c-ANCA titers can be monitored to follow disease activity. It is highly (95-99%) specific for Wegener granulomatosis.

Answer 112

Sarcoidosis. ACE is nearly always elevated in active sarcoidosis. Inactive sarcoidosis is associated with normal levels of ACE.

Answer 113

Primary biliary cirrhosis, Gaucher disease, and leprosy. All of these have in common the formation of granulomas; however, most other granulomatous diseases are not associated with an elevated ACE.

Answer 114

Type I (allergic, immediate-type): IgE; atopy, asthma, anaphylaxis. Type II (antibody-dependent, cytotoxic, antibody-mediated cellular cytotoxicity): IgM or IgG, complement, MAC; Goodpasture syndrome, autoimmune hemolytic anemia, erythroblastosis fetalis, rheumatic heart disease (also Graves disease and myasthenia gravis, but some classify these as type V). Type III (immune complex): IgG, complement, neutrophils; SLE, serum sickness, Arthus reaction, PSGN. Type IV (delayed-type, cell-mediated immune memory response, antibody-independent): T cells; tuberculin skin test, contact dermatitis, MS. Type V (an additional subtype sometimes used as a distinction from type II) (receptor mediated autoimmune disease): IgM or IgG, complement; Graves disease, myasthenia gravis.

Answer 115

ANA, anti-nucleolar, anti-Scl-70 (anti-topoisomeraseI). IIF on C. luciliae or HEp-2 cells; ELISA.

Answer 116

It binds avidly to pulmonary surfactant.

Answer 117

Oxalic acid is a fermentation by-product of Aspergillus, and the precipitation of calcium oxalate crystals in alkaline tissue environments infected by the fungus is a recognized phenomenon. The crystals are themselves potent agents of tissue destruction, causing extensive necrosis. Oxalate deposition is most commonly associated with A. niger, but it has been observed in association with other Aspergillus species, including A. fumigatus and A. flavus. Visualization of oxalate crystals in respiratory tract cytological specimens has been described as a reliable marker for the presence of Aspergillus infection and may precede the appearance of positive fungal culture results or radiographic identification of an aspergilloma by 1 year. The typical appearance of calcium oxalate crystals is that of birefringent needlelike crystals in rosette, wheat-sheaf, or fanlike arrangements; they are nonstaining and difficult to identify by ordinary light microscopy. Of greatest diagnostic value is the observation of both oxalate crystals and typical fungal elements in a single specimen.

Answer 118

Squamous cell carcinoma, seminoma, and thymoma.

Answer 119

Characterized by the progressive proliferating and infiltrating smooth musclelike cells (lymphangioleiomyomatosis cells/LAM cells) which lead to the cystic destruction of the lung parenchyma; obstruction of airways, blood vessels, and lymphatics; and loss of pulmonary function. LAM cells were recently recognized as perivascular epithelioid cells, and LAM is categorized as one of the perivascular epithelioid cell tumor family, which includes angiomyolipomas, clear cell "sugar" tumors of the lung and extrapulmonary sites, clear cell myomelanocytic tumors of the falciform ligament or ligamentum teres, and rare clear cell tumors of other anatomic sites. LAM occurs in 2 main forms: tuberous sclerosis complex (TSC-)-associated LAM, and sporadic LAM (S-LAM), with most being the latter form. Primarily affects women of childbearing age and worsens during pregnancy and following the administration of estrogens. Dyspnea on exertion and recurrent pneumothorax are the MC clinical features.

Answer 120

Macroscopic features are enlarged lungs with a cystic, honeycomb appearance. The cysts are usually evenly distributed through the lung and may contain air or fluid (serosanguinous or chylous). Microscopically, the LAM cells are characteristically found in small clusters or nests at the edges of the cysts and along the alveolar walls, pulmonary blood vessels, lymphatics, and bronchioles. The proliferating LAM cells are morphologically heterogenous and can be classified into 2 types: spindle-shaped cells (usually centrally located) and epithelioid cells (usually in the peripheral regions of the LAM cell nodules). Lymphangioleiomyomatosis cells coexpress smooth muscle markers and melanocytic markers. Somatic or genetic mutations of tumor suppressor genes TSC1 or TSC2 (Tuberous Sclerosis Complex 1 or 2) are closely related to LAM.

Answer 121

Tuberculous effusions typically appear turbid, with a yellow or silvery green metallic appearance grossly. In the later phase, an abundance of lymphocytes is present. The fibrin in the exudate traps mesothelial cells, and tuberculous pleural effusions therefore characteristically have few or no mesothelial cells. In addition, the high fibrin content of the fluid causes some of the lymphocytes to appear in clusters, and uncommon feature of lymphocytes in other conditions. Multinucleated giant cells are uncommon, although histiocytes may be evident. Because of the predominance of lymphocytes, lymphoma may enter into the differential diagnosis.

Answer 122

An adequate bronchoalveolar lavage requires more than 10 macrophages per high-power field.

Answer 123

Abscesses containing nuclear dust and neutrophils. Bacteria are difficult to see, even with special stains such as Giemsa or Gram. Histiocytes surround the abscesses and are also seen in the walls of bronchi filled with pus. Venous thrombosis is common.

Answer 124

CK7+ and CK20-. 97% are CK7 positive, and only 7% are CK20 positive.

Answer 125

UIP is in older patients; NSIP is in younger patients.

Answer 126

Airway-centric. Chronic inflammation. Granulomata. Organizing pneumonia. Giant cells.

Answer 127

Innate immune resistance and adaptive immune resistance. In innate immune resistance, the up-regulation of PD-L1 expression is secondary to constitutive oncogenic signaling within tumor cells including EGFR mutations and ALK rearrangements. In adaptive immune resistance, PD-L1 expression is induced on tumor cells secondary to local inflammatory signals, which in turn induces PD-1 on T cells.

Answer 128

When engaged by PD-L1 or other ligands, PD-1 inhibits kinases that are involved in T cell activation through the phosphatase SHP250 leading to apoptosis of T cells, although additional signaling pathways are likely also induced. Thus, blockade of PD-1/PD-L1 interaction will reinstitute the active anti-tumor immune response. KRAS-mutated NSCLC, especially those with significant smoking history, may harbor large mutation burdens (large numbers of neoantigens) leading to adaptive immune resistance (due to immune microenvironment with significant local inflammatory signals).

Answer 129

KRAS-mutated NSCLC, especially those with significant smoking history, may harbor large mutation burdens (large numbers of neoantigens) leading to adaptive immune resistance (due to immune microenvironment with significant local inflammatory signals).