anatomy and histology of the normal lung and airways
TRANSCRIPT
Anatomy and histology of the normal lung and airways
The trachea is approximately 22 cm long, with a cross-sectional area of 2 cm. Pulmonary Pathology Online
At the tracheal carina it divides into two major bronchi.
The right bronchus diverges at a lesser angle from the trachea, which is why foreign material is more frequently aspirated on the right side.
On entering the lung the bronchus divide into lobar bronchi and then into segmental bronchi, which supply the 19 segments of the lung.
Because the segments are individual units with their own bronchovascular supply, they can be resected individually. The number of further ramifications of the bronchi depends on the distance from the hilum. Thus, there is a substantial number of ramifying bronchi in axial pathways that traverse the long distance to the periphery of the lung, such as the posterior basal segment, whereas there are far fewer in lateral pathways supplying the lung close to the hilum.
The tracheobronchial tree has cartilage and tracheobronchial mucous glands in the wall.
The glands are compound tubular glands that display both mucous (pale cells) and serous cells (granular, more basophilic cells).
Between them, both types of cell secrete most of the mucus that is found in the tracheobronchial tree.
The tracheobronchial tree is lined by a pseudostratified epithelium, which appears as layers, although all cells reach the basement membrane. Most of the cells are ciliated, but mucus-secreting (goblet) cells also exist, as well as basal cells that do not reach the surface. The basal cells are thought to be precursor cells that differentiate to form the more specialized cells of the tracheobronchial epithelium.
K (for Kulchitsky-like) cells which resemble the argentaffin and argyrophil cells found in the gut and elsewhere, are neuroendocrine cells that contain a variety of hormonally active polypeptides and vasoactive amines. Although at one time these cells were thought to derive from the neural crest and migrate to the epithelium of the bronchus, it is now clear that they share a common stem cell with other cells of the bronchus and gut.
Succeeding the bronchi are the (membranous) bronchioles, which differ from bronchi in that they contain neither cartilage nor mucus-secreting glands.
As with bronchi, the number of branchings and their length depends on the pathway from the hilus to the periphery of the lung.
In axial pathways there may be up to 25 branchings of conducting airways and a length of approximately 23 cm, whereas in lateral pathways there are only seven generations and a total length of about 8 cm.
The epithelium of the bronchioles becomes thinner, until only one cell layer is apparent.
The last purely conducting structure is the terminal bronchiole, after which the airways have alveoli in their walls.
A major change then occurs as the gas-exchanging unit, the acinus, is encountered.
This unit consists of, in series:
1) Respiratory bronchioles, airways with both alveolated and nonalveolated epithelium in their walls,
2) Alveolar ducts, conducting structures with only alveoli in their walls,&
3) Alveolar sacs, terminal structures lined entirely by alveoli.
The acinus is the unit of gas exchange in the lung.
Understanding this structure is critical to understanding the very important condition known as emphysema.
Alveoli, the gas-exchanging structures of the lung, are lined by two types of epithelium.
- Type I cells cover 95% of the alveolar surface, although they comprise only 40% of all the epithelial cells of the alveolus. They are thin and have a large surface area, a combination of that facilitates gas exchange.
- Type II cells comprise 60% of the alveolar lining cells, but because they are more cuboidal they contribute only a small part to the total alveolar surface area. These cells secrete the surfactant material of the alveolar surface that maintains the patency of alveoli.
It should be noted that bronchioles are also line by surfactant and that displacement of surfactant by inflammatory exudates leads to the bronchiolar instability and thus impairs their function.
Type I cells are very vulnerable to injury, and when they die, type II cells multiply and differentiate to form type I cells, thereby reconstituting the alveolar surface area.
The alveolar epithelial cells are connected by tight junctions that prevent the passage of even small molecules through the epithelial surface.
The alveolar wall contains a dense network of capillaries, each alveolus having approximately 1000 capillary segments, about 15 micrometer long and 8 micrometer in diameter. The capillaries are lined by endothelial cells that resemble type I epithelial cells in that they have abundant flat cytoplasm but differ in that their junctions are “leaky” or “semitight”.
Because the junctions are tighter on the arterial side and looser in the small venules, molecules the size of albumin can pass through the capillary endothelium.
Both the endothelium and epithelium have basal laminae, and when they are adjacent they fuse into a single basal lamina that forms the thin side of the alveolar capillary membrane where gas exchange is most efficient.
On the opposite side (the thick side), the basal laminae are separate, and collagen, elastin, and proteoglycans are found there.
In addition, fibroblasts, some of which contain muscle filaments (myofibroblasts), are also found on the thick side of the alveolar capillary membrane.
This region, which constitutes the interstitial space of the alveolar wall, is where significant fluid and molecular exchange occurs and where edema begins.
The pulmonary arteries accompany the airways in a sheath of connective tissue known as the bronchovascular bundle.
The more proximal arteries are elastic and then become transitional (four or fewer elastic laminae in their walls).
They are succeeded by arteries whose walls have two elastic laminae with a layer of muscle between them.
In vessels about 100 micrometer in diameter or less, muscle extends in a spiral fashion between the elastic laminae, so that the arterial wall is partly muscular and partly non-muscular where the elastic laminae fuse.
The smallest arteries have no muscle.
The smallest veins, which resemble the smallest arteries, join with other veins and drain into the lobular septa, connective tissue partitions that subdivide the lung into small respiratory units.
The veins then continue in the lobular septa, joining other veins to form a network that is separate from the bronchovascular bundles.
There are no lymphatics in most alveolar walls. The lymphatics commence in alveoli at the periphery of the acinus, which lies along a lobular septum, the bronchovascular bundle, and the pleura.
The lymphatics of the lobular septa and bronchovascular bundle accompany these structures, and the pleural lymphatics drain toward the hilus via bronchovascular lymphatics.
A crucial concept in understanding the lung pathology is that of the interstitium of the lung.
This is composed of the connective tissue that surrounds the veins and bronchovascular bundle and the tissue on the thick side of the alveolar capillary membrane.
NOTE:
The proximal airways are lined by pseudostratified ciliated columnar epithelium and the distal airways by non-ciliated cuboidal epithelium. Specialized cells found in the lining of the airways include Kulchitsky cells, Clara cells and goblet cell. The proportion of goblet cells is lower in the distal airways than in the proximal airways, and there is a corresponding increase in the number of Clara cells after bronchial injury, they are recognized by PAS-positive, diastase-resistant granules in the apical part of their cytoplasm. Kulchitsky cells form part of the diffuse neuroendocrine system and so contain cytoplasmic dense core granules.
Inflammatory changes such as active bronchitis, bronchiolitis, and areas of granulation tissue can be seen in biopsy or excision specimens as a result of previous instrumentation.
The trauma of biopsy or open surgery commonly causes fresh intra-alveolar hemorrhage, and so this feature should not be interpreted as a pathological process.
Age-related changes in the lung include calcification and ossification of cartilage in the large airways, intimal thickening in pulmonary vessels and oncocytic metaplasia of submucous glands.
Indications and techniques:
The lung biopsy is widely recognized as a valuable tool for the diagnosis and management of diverse pulmonary disorders. The transbronchial lung biopsy, open lung biopsy, and video assisted thoracoscopic surgery biopsy are the principal tools that have been developed for obtaining lung tissue for histopathological examination.
INDICATIONS:
Specimens from lungs are taken:
-For the diagnosis, treatment and palliation of neoplasms.
Pleural biopsy is usually taken:
-To help in the differential diagnosis of pleural effusions and pleural tumours.
Other reasons for lung biopsy include:
i) Assessment of inflammatory lesions such as sarcoidosis , tuberculosi s and fungal infections.
ii) Fibrosing lung diseases and
iii) Rejection changes in heart / lung transplants.
iv) Rarely biopsies are taken in the investigation of asthma and its response to treatment.
Along with the lung or pleural biopsy specimen following clinical information should be provided by the clinician to the histopathologist :
Lung Biopsy Specimen:
- Age and sex of the patient;
- Clinical signs and symptoms and their duration.
- History of smoking;
- History of tuberculosis , systemic malignancy or other diseases (Cushing’s syndrome, diabetes insipidus, hypertrophic osteoarthropathy, rheumatoid arthritis & other connective tissue disease);
- Occupation
- History of previous instrumentation in the lung
- Results of other investigations :(radiological and microbiological ).
Pleural biopsy specimen:
- Age and sex of the patient;
- Clinical signs and symptoms and their duration.
- Clinical examination - hilar lymphadenopathy;
- Occupation (especially history of asbestos exposure);
- History of smoking;
- History of tuberculosis or systemic malignancy.
- History of hilar lymphadenopathy
- Results of other investigation:( radiological and microbiological).
Correlation between the clinical and pathohistologic diagnosis in "small biopsies" of the lung.Med Pregl. 1998 Sep-Oct;51(9-10):431-5. Med Pregl. 1998 Sep-Oct;51(9-10):431-5.
INTRODUCTION: During the last 20 years routine application of various methods of multiple "small biopsies" of the lungs such as forceps, transbronchial, trucut percutaneous and so on, has significantly increased the efficacy of diagnostics of bronchopulmonary and pleural diseases. Tissue samples, not bigger than 3-4 mm, in which diagnostic pathological changes are expected on the basis of previous clinical, radiological and bronchoscopic examinations, can be the basis for making a definite therapeutical decision only if a skillful surgeon has performed the biopsy by correct instruments and from the right place and sent it for histological analysis with other important clinical information. This study is a comment on quality, significance and possibilities of improving clinical-pathological cooperation in this field of clinical pathology. MATERIAL AND METHODS: By correlation of clinical and histological diagnoses we analyzed the diagnostic efficiency of microscopic examinations of "small biopsies" of the respiratory tract in 319 patients (175 bronchial forceps biopsies, 31 transbronchial biopsies, 22 percutaneous needle pleural biopsies and 91 combined forceps and transbronchial biopsies) in whom biopsies were performed during 1996 in the Specialized Hospital for Lung Diseases Brezovik. RESULTS: Overall concordance between the clinical and histopathological diagnosis was 82.2%. In 99 cases (73.3%) out of 135 clinically "obvious" neoplasms, the histopathological examination confirmed existence of malignant tumor: squamous cell carcinoma in 80%, small cell carcinoma in 9.6% and adenocarcinoma in 5.6% of patients. In other patients it was not possible to perform a more precise classification. Endoscopic specimens of 29 patients (9.1%) were not representative. CONCLUSION: The level of diagnostic efficiency (73.3%) of definitive
histopathological verification of bronchopulmonary lesions, which have been clinically diagnosed as malignancies, is rather high, but the increase of diagnostic efficiency requires application of more sophisticated histological diagnostic methods (immunohistochemical) and more frequent utilization of bioptic procedures which are more convenient for detection of peripheral pulmonary lesions (transbronchial and percutaneous fine needle aspiration biopsies of the lungs).
Bronchoscopic diagnosis and staging of lung cancer.Chest Surg Clin N Am. 2001 Nov;11(4):701-21, vii-viii
In the past 2 decades, flexible bronchoscopy (FB) with forceps biopsy and transbronchial needle aspiration (TBNA); computed tomography (CT)-guided, transthoracic fine-needle aspiration (FNA); and endoscopic ultrasonography (EUS) have revolutionized lung cancer diagnosis and staging by facilitating precise biopsy of lung lesions and virtually all mediastinal lymph-node stations. In this article the authors present an algorithm for the diagnosis and staging of lung cancer that addresses sampling of suspicious lesions and lymph nodes by means of FB, CT, ultrasonography, fluoroscopy, and EUS, emphasizing tissue-based diagnosis and staging by means of image-guided technology with the highest diagnostic yield. They discuss the approach to the diagnosis and staging of lung cancer by techniques guided by FB, with particular attention to the increasing role of TBNA in this field. Additionally, the authors propose a rating scale based on the degree of invasiveness and diagnostic yield, comparing FB with other diagnostic techniques.
Bronchoscopic needle aspiration biopsy.Am J Clin Pathol. 2000 May;113(5 Suppl 1):S97-108
Bronchoscopic needle aspiration biopsy, which encompasses transbronchial needle aspiration, transtracheal needle aspiration, and endobronchial needle aspiration, is a minimally invasive technique used to diagnose mediastinal and pulmonary masses and to stage lung cancer patients with mediastinal lymphadenopathy. Since it is safe, accurate, and potentially cost-efficient, its use may increase in the coming years. It is important that pathologists who examine cytology specimens understand this procedure, its limitations, and ways that it may be optimized.
Bronchoscopy in diffuse lung disease: evaluation by open lung biopsy in nondiagnostic transbronchial lung biopsy.Ann Otol Rhinol Laryngol. 1987 Nov-Dec;96(6):654-7
Transbronchial lung biopsy through the flexible bronchoscope is used widely for the diagnosis of diffuse lung disease; however, a significant number of specimens obtained by the bronchoscopic 2-mm biopsy forceps will reveal nonspecific findings, eg, interstitial fibrosis or nonspecific pneumonitis. Such a report may be an accurate reflection of the presence of idiopathic pulmonary fibrosis or nonspecific pneumonitis, but may merely indicate that the true diagnosis has been missed. We retrospectively studied 38 patients with diffuse lung disease whose transbronchial lung biopsies yielded nonspecific abnormalities. Subsequently, these patients were subjected to open lung biopsies. Nineteen of the 38 patients (50%) had a specific diagnosis made by open lung biopsy. The diagnoses included bronchiolitis obliterans, alveolar proteinosis, metastatic carcinoma, lymphoma, tuberculosis, and bronchioloalveolar cell carcinoma. Although transbronchial lung biopsy is useful in the diagnosis of many diffuse lung diseases, it is not a replacement for open lung biopsy. When nonspecific findings by transbronchial lung biopsy do not correlate with the clinical picture, open lung biopsy should be performed.
HISTOCHEMICAL STAIN:
Periodic acid schiff (PAS):
PAS- Glycogen : Fungi
PAS with diastase pretreatment (Neutral mucin): Pulmonary Alveolar Proteinosis
Grocott : For Fungi ; Pneumocystis infection;
Ziel-Neelsen stain: For mycobacterial organisms; Tuberculosi s
Elastic/van Gieson stain for:
(collagen) - Fibrosis ; (elastin) - Vasculature.
Eg. Interstitial fibrosis; Organizing pneumonia; Vasculitis;
Pulmonary Hypertension ; chronic lung rejection
Congo red : for amyloid (primary / secondary);
Perls’ prussian stain: for ferric iron. Eg. Pulmonary Hemorrhage ; ferruginous bodies.
von Kossa stain phosphate;
IMMUNOHISTOCHEMICAL / FLUORESCENCE:
Pneumocystis antibodies : Pneumocystis carinii
Cytomegalovirus antibody : Cytomegalovirus infection
OTHER ANALYSIS:
Polarising microscopy for birefringent material:
Talc ; Mica ; Pneumoconiosis .
Mineral analysis: (light or electron microscope)- Diagnosis in Asbestos-related diseases.
HISTOCHEMICAL STAIN:
Periodic acid Schiff (PAS): Clear cell tumours
PAS with diastase pretreatment (Neutral mucin): Adenocarcinoma
(Alcian blue pH 2.5 (Acid mucin): Mesothelioma (Mesothelioma -Online )
Combined Alcian blue/diastase PAS.(basement membrane / neutral mucin): Adenoid cystic Ca.
Argyrophil stains such as Grimelius for neuroendocrine granules of carcinoid tumours.
IMMUNOHISTOCHEMICAL STAIN:
Immunohistochemical stains for NSE and PGP 9.5 have limited value in distinguishing small cell carcinoma from other types of carcinoma in small biopsies as they are often non-specific and unreliable.
More specific markers, such as chromogranin and N-CAM, are not easily identified in poorly differentiated tumours and small cell carcinoma.
CAM 5.2 and other cytokeratins give paranuclear dot positivity in small cell carcinoma and can be used as part of a panel.
Immunostains can be usefully applied in typing of neoplasms - CAM 5.2, leucocyte common antigen, desmin, synaptophysin, chromogranin, N-CAM, S100, surfactant;
Lymphocyte markers - B and T cell markers, light chains.
SUMMARY OF IMMUNOSTAINS USEFUL IN THE DIAGNOSIS OF PULMONARY TUMOURS: Histochemistry and Immunohistochemistry in the diagnosis of Mesothelioma: click here
Carcinoembryonic antigen Adenocarcinoma
Leu-M1
Ber-EP4
Surfactant apoprotein A
Thyroid transcription Factor 1 (Thyroid and pulmonary origin)
Calretinin ; Mesothelioma
Cytokeratin 5 / 6 ;
Thrombomodulin ;
Chromogranin A ; Synaptophysin ; CD56 : Neuroendocrine Tumours.
An approach to histopathological reporting of the pulmonary parenchymal biopsies:
I) In the bronchioles:
- Peribronchial or peribronchiolar inflammation:
Non-specific: Reactive lymphoid follicles as in follicular bronchiectasis or follicular bronchiolitis ; Granulomatous .
- Obliterative changes in bronchioles with fibrous scarring, as in bronchiolitis obliterans:
- Organizing granulation tissue in bronchiolar lumina, as in cryptogenic organizing pneumonia (also known as bronchiolitis obliterans organizing pneumonia or BOOP).
II) In the alveoli and interstitium:
- Architecture:
-Destruction of alveolar walls without fibrosis in emphysema ;
-Destruction of alveolar walls with interstitial and intra-alveolar fibrosis, alveolar collapse, and bronchiolization in advanced interstitial lung disease;
-Alveolar walls:
- Interstitial inflammatory infiltration ;
- Focal acute inflammation with central necrosis and scattered giant cells in fungal pneumonias;
- Heavy lymphocytic infiltrate, as in lymphoid interstitial pneumonia (LIP), extrinsic allergic alveolitis, monomorphic and atypical lymphoid infiltrate, as in malignant lymphoma;
- Non-necrotizing well formed granulomas in sarcoidosis ;
- Non-necrotizing poorly formed granulomas in e xtrinsic allergic alveolitis ;
- Necrotizing granulomas in mycobacterial and fungal infection ;
- Palisaded granulomas in Wegener’s granulomatosis and rheumatoid nodules ;
- Interstitial fibrosis;
- A sbestos bodies ;
- Amyloid;
- Smooth muscle cells in lymphangioleiomyomatosis ;
- Lymphatic infiltration by tumour cells as in extra-pulmonary primary adenocarcinoma (lymphangitis carcinomatosa), lymphoma, Kaposi's sarcoma , epithelioid hemangioendothelioma ;
- Calcification- metastatic in the elastic of alveolar walls, dystrophic in areas of long-standing fibrosis;
- Calcified bodies (Schaumann bodies) in areas of hyaline fibrosis in sarcoidosis;
- Hemosiderin deposition in areas of hemorrhage;
- Alveolar lining cells:
- Hyaline membranes in diffuse acute alveolar damage;
- Proliferation of type II pneumocytes in the reparative phase of hyaline membrane disease;
- Multinucleate giant cells:
-giant cell interstitial pneumonia (hard metal disease);
-giant cell pneumonia ( measles infection in children, occasionally respiratory syncytial virus infection or parainfluenza B);
-viral inclusions, such as cytomegalovirus or measles;
- cytoplasmic hyaline in type II pneumocytes, first identified in asbestosis but also seen in other conditions;
-atypical cells: seen with some cytotoxic drugs such as busulfan or bleomycin;
-bronchiolisation of distal air spaces in advanced diffuse pulmonary fibrosis;
-squamous metaplasia as a result of chronic inflammation ;
-tumour cells lining alveoli in bronchioloalveolar carcinoma, which may be mucus secreting or non-mucus secreting.
- Alveolar lumina:
-Inflammatory cells:
-polymorphs in bacterial pneumonias ;
-eosinophils in eosinophilic pneumonia ;
-histiocytes/macrophages - foamy in obstructive pneumonitis or lipid pneumonia , containing fine lipofuscin pigment in desquamated interstitial pneumonia, ‘blue bodies’ associated with lysosomal accumulation in such conditions as DIP ;
-multinucleate foreign body giant cells, often associated with cholesterol crystal clefts, in obstructive pneumonitis or pulmonary alveolar proteinosis ;
-Granular eosinophilic debris, often with cholesterol crystals, in pulmonary alveolar proteinosis,
- Granular and foamy lightly eosinophilic material in pneumocystis pneumonia ;
- Hemorrhage or accumulation of haemosiderin- laden macrophages in hemorrhagic diathesis, pulmonary capillaritis, idiopathic pulmonary hemosiderosis, pulmonary venous hypertension;
- Intra-alveolar irregular laminated calcospherites in pulmonary microlithiasia;
- Organizing exudates (Masson bodies -Masson's Tumour) in organizing pneumonia;
III) In the blood vessels:
- Vasculitis:
-Eosinophil infiltration with granuloma formation in Churg-Strauss syndrome;
-Extravascular granulomas and areas of necrosis in Wegener’s granulomatosis;
-Granulomas in vessel walls in sarcoidosis , necrotizing sarcoidal granulomatosis, and reaction to talc particles in drug addicts;
- Capillaritis with alveolar hemorrhage in Wegener’s granulomatosis, microscopic polyarteritis and hypersensitivity vasculitis;
- Infiltration of vessel walls by atypical lymphoid cells in angiocentric lymphoma (lymphomatoid granulomatosis);
- Pulmonary hypertension and thromboembolic disease:
- Muscular arteries - medial hypertrophy in hypoxic pulmonary hypertension, pulmonary venous hypertension and plexogenic pulmonary arteriopathy; subintimal longitudinal muscle fibres in hypoxic pulmonary hypertension;
- Intimal thickening-eccentric in thromboembolic pulmonary hypertension, associated with organizing thrombus or other embolic material, concentric in plexogenic pulmonary arteriopathy ; dilatation lesions, plexiform lesions and fibrinoid necrosis in plexogenic pulmonary arteriopathy;
- Muscularization of arterioles in hypoxic pulmonary hypertension ;
- Veins:
- Obliteration by connective tissue in pulmonary veno-occlusive disease;
- Thickening of the media with arteriolization in pulmonary venous hypertension;
- Replacement of the vein wall by a network of capillaries with abnormal capillaries in alveolar walls in pulmonary capillary hemangiomatosis.
Histopathological reporting of pulmonary biopsy in cases of idiopathic lung fibrosis
- Trans-bronchial lung biopsy (TBLB) is the initial procedure of choice in those patients likely to have diffuse parenchymal lung disease in which small samples may be diagnostic.
- These biopsies are not useful for the diagnosis or staging of the various histopathological subsets of Idiopathic Pulmonary Fibrosis .
- By open/video assisted thoracoscopic (VATS) lung biopsies it is possible to adequately examine the secondary lobules and the distribution of the disease process.
- These biopsies should be at least 4 cm in maximum diameter when inflated and include a depth of at least 1.5 cm.
- Biopsy samples from the middle lobe or lingula may be taken provided they are of adequate size, contain deep alveolar tissue and are from a site involved by active disease.
Histological interpretation of lung biopsies and what to look for - a brief practical guide:
1. Detailed clinical history and radiological findings should always be obtained and taken into consideration in the interpretation of lung biopsies.
2. Low power magnification:
- The distribution, intensity, and nature of fibrosis and inflammation.
- Is the disease process temporally uniform Eg. Non-specific interstitial pneumonia (NSIP) or temporally and spatially heterogeneous Eg. Usual Interstitial Pneumonia (UIP)?
- Are the changes predominantly centri-lobular Eg. Respiratory bronchiolitis-interstitial lung disease (RBILD) , diffuse throughout the secondary lobule (Eg. NSIP ), or predominantly sub-pleural (Eg. UIP )?
3. Bronchi or bronchioles (any abnormality such as bronchiolitis obliterans?).
4. Alveolar lumina (any abnormality, such as organizing exudates, accumulation of macrophages, giant cells, hemorrhage, hyaline membrane?)
5. Epithelial lining (any hyperplastic, metaplastic or neoplastic changes? Any viral inclusions?)
6. Blood vessels (any evidence of veno-occlusive disease which may produce parenchymal changes similar to IPF? Any vasculitis? Or thrombi?), lymphatics (any abnormality?).
7. Interlobular septa (any abnormality?).
8. Pleura (is there any fibrosis/chronic inflammation e.g. in collagen vascular disease and asbestosis?).
9. Any ferruginous bodies (particularly asbestos)/ Any pigment (e.g. hemosiderin)? A sbestosis
10. Are there any granulomata, or scattered individual giant cells? Any foreign material?
11. Is there any smooth muscle proliferation? Are the smooth muscle fibers mature?
12. Any other abnormality (e.g. amyloid).
Transbronchial biopsy interpretation in the patient with diffuse parenchymal lung disease. Arch Pathol Lab Med. 2007 Mar;131(3):407-23.
CONTEXT: The most common lung tissue samples seen by pathologists worldwide are obtained with the flexible bronchoscope. Specimens taken for examination of diffuse or multifocal parenchymal lung abnormalities pose special challenges for the general surgical pathologist, and these challenges are often compounded by high clinical expectations for accurate and specific diagnosis. OBJECTIVE: To present and discuss the most common histopathologic patterns and diagnostic entities seen in transbronchial biopsy specimens in the setting of diffuse or multifocal lung disease. Specifically, acute lung injury, eosinophilic pneumonia, diffuse alveolar hemorrhage, chronic cellular infiltrates, organizing pneumonia, alveolar proteinosis, sarcoidosis, Wegener granulomatosis, intravenous drug
abuse-related microangiopathy, Langerhans cell histiocytosis, and lymphangioleiomyomatosis are presented. Clinical and radiologic context is provided for the more specific diagnostic entities. DATA SOURCES: The published literature and experience from a consultation practice. CONCLUSIONS: The transbronchial biopsy specimen can provide valuable information for clinical management in the setting of diffuse or multifocal lung disease. Computed tomographic scans are useful for selecting appropriate patients to undergo biopsy and in limiting the differential diagnosis. Knowledge of the clinical context, radiologic distribution of abnormalities, and histopathologic patterns is essential. With this information, the surgical pathologist can substantially influence the diagnostic workup and help guide the clinician to an accurate clinical/radiologic/pathologic diagnosis.
Mortality and risk factors for surgical lung biopsy in patients with idiopathic interstitial pneumonia.Eur J Cardiothorac Surg. 2007 Jun;31(6):1115-9. Epub 2007 Apr 5.
Background: The overall safety of surgical lung biopsy in patients with idiopathic interstitial pneumonia (IIP) remains controversial. This study was performed to investigate the mortality and complication rate and identify the risk factors for surgical lung biopsy in patients with IIP. Methods: A total of 200 patients with IIP who underwent surgical lung biopsy at the Asan Medical Center, Korea, from April 1990 to August 2003, were enrolled. Complications and mortality were analyzed retrospectively. Results: (1) The mortality rate 30 days after the surgical lung biopsy was 4.3%, which was significantly higher than the control group. Biopsy performed at the time of acute exacerbation (AE) resulted in higher 30-day mortality (28.6%) compared to non-AE (3.0%; p<0.05). AE was followed by biopsy itself in three cases. (2) Univariate analysis indicated that lower FVC, lower DL(CO), and presence of AE were significant risk factors for 30-day mortality (p<0.05). However, multivariate analysis revealed that only AE (OR: 11.334, 95% CI: 1.727-74.365, p=0.011) was an independent risk factor. (3) The patients with low DL(CO) (<50% predicted) had higher mortality and complication rate than high DL(CO) group. Conclusion: Our data suggested that the presence of acute exacerbation at the time of biopsy and lower DL(CO) were predictors of higher mortality after the surgical lung biopsy.
Low-Dose CT-Guided Transthoracic Lung Biopsy for Evaluation of Non-Infectious Chronic Interstitial Lung Disease in Children. Pneumologie. 2007 May 25.
BACKGROUND: Children with interstitial pneumonitis (IP) of unknown origin often have to undergo open lung biopsy to establish a final diagnosis. Open lung biopsy is an invasive procedure with major potential complications. In the meantime, CT-guided transthoracic lung biopsy (TLB) has become a common diagnostic procedure in adults. OBJECTIVE: The aim of this study was to retrospectively evaluate the efficacy and radiation exposure of low-dose CT-guided TLB in children with non-infectious IP of unknown origin. METHODS: Twelve children (7-males, age range: 7 months-15 years) with non-infectious IP of unknown origin and inconclusive clinical tests underwent CT-guided TLB with a 20-gauge biopsy instrument. A low-dose protocol with acquisition of single slices was used on a 16-row CT scanner: 80 kVp, 20 mAs, slice thickness 10 mm. Biopsy specimens were processed by standard histopathological and immunohistochemical techniques and effective doses were individually calculated. RESULTS: All biopsies were performed without major complications. Two children (17 %) developed a small pneumothorax/pulmonary haemorrhage that resolved spontaneously. A final diagnosis could be established in 9/12 patients (75 %) by CT-guided TLB. In 2 patients (17 %) the results of TLB were inconclusive; however, the clinical suspicion could be disproved. Open lung biopsy was performed in 1 patient (8 %), which demonstrated idiopathic pulmonary fibrosis. On average, the effective dose of CT-guided TLB was 0.78 mSv (0.4 - 1.1 mSv). CONCLUSION: Low-dose CT-
guided TLB can be a helpful method for investigating children with non-infectious IP of unknown origin thus making open lung biopsy unnecessary. Application of a low-dose protocol leads to a significant reduction of radiation exposure in CT-guided TLB.
Complications of video-assisted thoracoscopic lung biopsy in patients with interstitial lung disease.Ann Thorac Surg. 2007 Mar;83(3):1140-4.
BACKGROUND: Current guidelines recommend surgical lung biopsy for diagnosis of interstitial lung diseases (ILDs) in selected patients. To shed light on the risk-benefit ratio for this recommendation, we examined the morbidity and mortality associated with video-assisted thoracoscopic surgical (VATS) lung biopsy in a group of outpatients. METHODS: A retrospective cohort study was conducted of 68 consecutive ambulatory patients with radiographically apparent interstitial lung disease (ILD) referred for VATS biopsy during a 6-year period. Incidence of postoperative mortality, prolonged air leaks, pneumonias, and re-admissions were calculated. Risk factors for complications of surgery were examined. RESULTS: Three deaths occurred within 60 days after biopsy for a mortality rate of 4.4% (95% confidence interval [CI], 1% to 12%), and 19.1% (95% CI, 11% to 31%) experienced one or more complications of surgery. Risk factors for morbidity included preoperative dependence on oxygen therapy and pulmonary hypertension. The three patients who died had usual interstitial pneumonia on their biopsy specimen and were reintubated postoperatively for acute lung injury. Aggregation of articles published over the past 10 years reporting on surgical lung biopsy for the diagnosis of ILD yielded a postoperative mortality rate of 2% to 4.5%. CONCLUSIONS: VATS lung biopsy for diagnosis of ILD, even in ambulatory patients, is not an entirely benign procedure. Biopsy rarely may trigger an acute exacerbation of usual interstitial pneumonitis. The risk of postoperative complications appears to be greatest in those dependent on oxygen and those who have pulmonary hypertension. This information may be used in weighing the risk-benefit ratio of biopsy in individual patients.
Diffuse interstitial lung disorders in systemic diseases.Verh K Acad Geneeskd Belg. 2003;65(6):350-65.
Diffuse parenchymal lung disorders (DPLD) can develop in a variety of systemic disorders. Schematically grouped, these include connective tissue disorders, vasculitis, neoplastic disorders, sarcoidosis and a group of inherited or other rare miscellaneous disorders. This overview focuses on sarcoidosis, systemic sclerosis and Churg Strauss vasculitis. Pulmonary involvement occurs in more than 90% of all patients with sarcodosis. Grading into 4 stages is based on the chest radiograph. Forms characterised by an acute clinical onset or a low grade lung involvement have the highest spontaneous remission rate. The cause of sarcoidosis remains unknown. The diagnosis therefore is descriptive, based on the combination of clinical observations, chest X ray, and the histological documentation of non-caseating epitheloid granulomas in tissue biopsies. Treatment with steroids is only indicated if organ involvement leads to functional impairment. Lung fibrosis is the most important complication of both the "limited" and "diffuse cutaneous form" of systemic sclerosis, involving 90% of all patients. The histological pattern is that of "Usual Interstitial Pneumonia" (UIP) or "Non-specific Interstitial Pneumonia" (NSIP). The pathogenesis of the disorder is thought to consist of an abnormal, excessive regenerative response to an auto-immune mediated lung injury. Churg Strauss vasculitis is characterised by asthma, blood eosinophilia and vasculitis of the small vessels. The affected vessels wall shows signs of fibrinoid necrosis and are infiltrated by eosinophils. pANCA (anti-myeloperoxidase) is considered to play a role in the pathogenesis of the disease. Concern has risen that CysLT1 receptor antagonists might induce production of pANCA. To date, this has not been substantiated.
Histopathological reporting of pleural biopsy
Closed pleural biopsy for neoplasm or inflammatory lesions:
Indication: Closed pleural biopsy is done to determine causes of pleural effusion after fluid analysis has been nondiagnostic. It is an efficient method in diagnosis of Tuberculosis and malignant pleural effusions.
Closed pleural biopsy has fairly low sensitivity for diagnosis of cancer but it can be increased by adding cytologic evaluation. It is necessary to do further investigations and follow-up in patients that have inflammation in pleural biopsy.
Specimens: These are either needle biopsies (e.g. Trucut), punch biopsies or material obtained by thoracoscopy.
Tissues present include : Pleura, adipose tissue, skeletal muscle, nerves and lung parenchyma.
Distinction can be difficult in the following conditions:
1) A florid reactive mesothelial proliferation and a mesothelial neoplasm
2) A tubuloglandular mesothelioma and metastatic adenocarcinoma.
- Indicators towards mesothelioma as opposed to a reactive proliferation are a single population of frankly malignant cells arranged in papillary, tubulopapillary or microcystic pattern.
- Invasion of underlying tissue with transition to spindle cell forms ( a biphasic pattern) is also a useful feature.
- Involvement of the pleura by metastatic adenocarcinoma is suggested by a separate population of malignant cells, distinct from mesothelial cells.
- In areas of pleural fibrosis and adhesions blood vessels can appear thick walled and sclerosed, or may take on a pseudoangiomatous appearance.
An approach to histopathological reporting of pleural biopsy:
Comments should be made on the following features:
- Pleural thickening:
-Hyaline fibrous tissue with a basket weave pattern in pleural plaques:
-Cellular fibrous tissue in an inflammatory process or neoplasia:
- Features of inflammatory lesions:
- Reactive proliferation of mesothelial cells - non-specific.
- Palisaded histiocytes, which can be multinucleate, with fibrinoid necrosis in rheumatoid disease :
- Necrotizing granulomas in tuberculous pleurisy :
- Presence of neoplasm:
- Localized fibrous tumor of pleura, benign or malignant :
- Mesothelioma : epithelial; mixed (biphasic); fibrous (sarcomatoid) or desmoplastic :
- Metastatic carcinoma.
Open pleural biopsy - pleural strip:
Open pleural biopsy is often necessary for the diagnosis of mesothelioma as a confident diagnosis can usually be made only when adequate tissue is available.
When underlying lung is included, the report should comment on the following features:
- It is involved by spread of tumor ;
- There is fibrosis ;
- Asbestos bodies are present.
Specimens taken for treatment of recurrent pneumothorax:
Pneumonectomy or pleural stripping may be performed for recurrent pneumothoraces. In young patients, pneumothoraces are often spontaneous but malignancy becomes more likely with increasing age.
The microscopical report should comment on:
- The type and severity of inflammatory infiltrate.
- Eosinophils often seen in pneumothorax (eosinophilic pleuritis);
-The presence of specific features such as granulomas
-The presence of neoplasia.
Value of closed pleural biopsy in diagnosis of pleural effusion.Przegl Lek. 2005;62(12):1325-7.
The aim of the study was to assess closed pleural biopsy (CPB) as a diagnostic method of pleural effusion. CPB using Cope needle was performed in 62 patients, proceeded by ultrasound examination. It helped to obtain specimen for histological and microbiological examination even with cases of small amount of fluid. In all 62 patients CPB enabled to diagnose 13 cases with neoplasmatic effusions (majority being adenocarcinomas) and 16 cases of tuberculosis in histological and/or microbiological examination. There were 33 cases with non-specific inflammatory changes. In 7 patients we confirmed neoplastic pleural
infiltrates in cytological examination of pleural effusion. In 26 patients videothoracoscopy (VTS) was carried out and 20 of those had post-inflammatory changes. In 4 cases, however we confirmed neoplasmatic effusions and in next 2 cases--tuberculosis. Closed pleural biopsy proves to be an efficient method in diagnosis of Tuberculosis and malignant pleural effusions. However, in 23% of cases with post-inflammatory changes, malignancy and tuberculosis were undiagnosed. This in turn implicates the necessity for further diagnostic procedures including VTS.
Diffuse malignant pleural mesothelioma.Kyobu Geka. 2007 ;60(1):35-9
Malignant pleural mesothelioma is an uncommon neoplasm that caused 647 deaths in Japan in 2004. The incidence of the disease is increasing and is estimated to reach its peak in 2025. We reviewed the clinical features in 11 consecutive patients with pathologically confirmed diffuse malignant pleural mesothelioma in our institution from January 1997 to December 2002. Of the 11 patients, 9 were male and 2 were female with a mean age of 66 (range, 55 to 90) years. Symptoms included dyspnea in 4 patients, chest pain in 3, dyspnea plus chest pain in 2, and cough in 2. Median period between symptom onset and presentation was 1 (range, 0 to 6) month. A history of asbestos exposure was identified in 3 patients and suspected in 5. A definitive diagnosis was made by closed pleural biopsy in 8 patients, pleural fluid cytology in 2, and autopsy in 1. Histological subtypes included epithelioid in 6 patients, sarcomatoid in 2, biphasic in 1, and unknown in 2. International Mesothelioma Interest Group (IMIG) staging included stage II in 6 patients, stage III in 3, and stage IV in 2. Median period between presentation and diagnosis was 1 (range, 0 to 22) month. Treatment included intrapleural chemotherapy in 4 patients, extrapleural pneumonectomy in 3, pleural drainage in 2, and best supportive care in 2. During the follow-up period, 9 patients died and 2 survived. Median survival time after diagnosis was 3 (range, 0 to 51) months. Of the 11 patients, 7 (64%) died within 6 months after the first presentation, and only 1 (9%) lived longer than 2 years after diagnosis.
Current problems in the diagnosis of malignant pleural mesothelioma. Kyobu Geka. 2007 Jan;60(1):14-8.
The diagnosis of malignant pleural mesothelioma (MPM) is challenging although MPM is highly aggressive tumor. The current diagnostic gold standard is principally based on light microscopic examination of hematoxylin-eosin and immunohistochemical stains of large tissue sections. However, pathological diagnosis of MPM and classification of histological findings into 1 of the 3 subtypes (epithelial, sarcomatoid, biphasic) are difficult. We studied correlation between initial and final histological diagnosis retrospectively from the records of 21 cases with MPM from 1989 to 2005. The diagnosis of MPM was confirmed by histopathological examination of pleural tissue samples obtained by closed biopsy under computed tomography (CT) or ultrasonography-guided (5 cases), by biopsy under thoracoscopy with local anesthesia (9), by open biopsy via thoracotomy (2), and by video-assisted thoracoscopic surgery (VATS) [5] . Pleural biopsy under those diagnostic methods led to initial diagnosis of MPM in 15 of 21 cases (71.4%) . In 6 cases (28.6%) , initial diagnosis of MPM were not confirmed because of missing malignant tissue (1 case) and relatively small and sarcomatous element (5). In 2 cases examined by closed biopsy and in 3 examined by thoracoscopy under local anesthesia, initial diagnosis of MPM were not confirmed. To get the accurate diagnosis of MPM, obtaining large tissue samples in the initial examination by less invasive thoracoscopy is recommended.
Diagnostic value of thoracoscopic pleural biopsy for pleurisy under local anaesthesia. ANZ J Surg. 2006 Aug;76(8):722-4
BACKGROUND: We find pleural effusion in clinical practice frequently. However, it is difficult to make a diagnosis definitively by thoracocentesis or closed pleural biopsy. We directly examine the thoracic cavity by thoracoscopy under local anaesthesia, carry out pleural biopsy and make a definitive pathological diagnosis in pleurisy. METHOD: A retrospective study of 138 patients who had been diagnosed by thoracoscopy in our hospital was carried out between January 1995 and January 2005. RESULTS: The patients were 114 men and 24 women, ranging in age from 21 to 85 years, with a mean of 59 years. The right side was involved in 83 patients and the left side in 55. The operations took 11-145 min, with a mean of 46 min. Thoracoscopy directly without thoracocenteses was carried out in 28 of 138 patients. Lung cancer with pleural dissemination was diagnosed in 27, malignant pleural mesothelioma in 10, tuberculous pleurisy in 32, non-specific pleurisy in 58, other tumour in 2 and pyothorax in 9 patients. The overall diagnostic efficacy was 97.1% (134/138). The diagnostic efficacy in the cases of carcinoma was 92.6% (25/27), in malignant pleural mesothelioma it was 100% (10/10) and in tuberculosis it was 93.8% (30/32). No major complications occurred during the examination. CONCLUSION: Pleural biopsy by thoracoscopy under local anaesthesia should be actively carried out in patients with pleurisy, because the technique has a high diagnostic rate and can be easily and safely carried out.
Diagnostic yield of closed pleural biopsy in exudative pleural effusion.Saudi Med J. 2003 Mar;24(3):282-6.
OBJECTIVE: Closed pleural biopsy is known to be diagnostic in approximately 75% of pleural effusion undiagnosed by thoracocentesis or pleural fluid evaluation. The purpose of this study was to determine the efficacy of closed pleural biopsy in a Saudi tertiary care teaching hospital. METHODS: We retrospectively reviewed the diagnostic utility of all closed pleural biopsies performed from January 1988 to December 1997 at the King Fahad National Guard Hospital, Riyadh, Kingdom of Saudi Arabia. RESULTS: One hundred and twenty-two pleural biopsies were performed in 116 patients using cope needle in 39, Abram's needle in 82, and Trucut needle in one patient. Twelve cases were excluded due to transudative effusion (N=6) and obtaining no pleural tissue (N=6). Specific diagnoses were obtained in 54 cases giving a diagnostic yield of 49.1%. Of these 10 revealed neoplasia, 35 tuberculosis, and 9 empyema. A non-specific diagnosis was obtained in 56 (50.9%) cases. CONCLUSION: By closed pleural biopsy 49.1% of undiagnosed exudative pleural effusions could be diagnosed. This shows that closed pleural biopsy is still of value as a diagnostic procedure, and should be carried out prior to invasive procedures such as thoracoscopy or open pleural biopsy.
Closed pleural needle biopsy: predicting diagnostic yield by examining pleural fluid parameters.Respir Med. 2002 Nov;96(11):890-4
OBJECTIVE: Pleural fluid parameters that predict a diagnostic closed pleural needle biopsy were investigated. DESIGN: A retrospective analysis. SETTING: The Institute of Pulmonology, Hadassah University Hospital. PATIENTS AND METHODS: Forty-four patients who underwent closed pleural needle biopsies were included in this study. Pleural fluid values of protein, glucose, lactate dehydrogenase (LDH), pH, and white blood cell count with differential cell counts, from patients with diagnostic and non-diagnostic pleural biopsies were compared. RESULTS: Thirteen patients (29%) had diagnostic biopsies. Malignancy was identified in 10 patients (23%), of whom 70% had adenocarcinoma. Three other patients had non-malignant specific diagnosis. LDH levels in pleural fluid from patients with diagnostic pleural biopsy were higher than in patients with non-diagnostic pleural biopsies (1436 +/- 333 U l(-1) vs. 775 +/- 109 U l(-1); P < 0.05). LDH levels less than 510 U l(-1) were highly predictive of a negative biopsy (negative predictive value of 86.6%). Follow up revealed malignancy including mesothelioma and lymphoma, in 10 of 30 (33%) patients with non-diagnostic biopsies, and one
patient died of unrelated cause, while the pleural effusion either resolved, remained stable or an alternative benign process was identified in 19 patients (63%). CONCLUSIONS: Low levels of LDH (< 510 U l(-1)) were highly predictive of a negative pleural needle biopsy. Thus, LDH may serve as a useful guide in deciding whether to perform closed pleural biopsy or to proceed to thoracoscopically guided biopsy.
Diagnostic value of medical thoracoscopy in pleural disease: a 6-year retrospective study.Chest. 2002 May;121(5):1677-83.
STUDY OBJECTIVES: Unlike thoracocentesis and closed pleural biopsy (CPB), medical thoracoscopy permits biopsy with direct visualization. In a 6-year retrospective study of patients having undergone at least one medical thoracoscopy, we analyzed the diagnostic yield of thoracoscopy and its value in the management of pleural disease. SETTING/PATIENTS: From January 1, 1989, to December 31, 1994, 168 medical thoracoscopies were performed on 154 patients (123 men; mean age +/- SE, 61 +/- 1 years), of which 149 were diagnostic and 19 were indicated for therapeutic assessment in malignant mesothelioma (MM). Prior to thoracoscopy, at least one CPB had been performed in 120 of 149 cases, yielding a diagnosis in 96 cases. RESULTS: Thoracoscopy challenged the CPB-based diagnosis in 43 of 96 cases. In 66 cases of nonspecific inflammation diagnosed by CPB, thoracoscopy revealed MM in 16 cases, adenocarcinoma in 10 cases, undetermined carcinoma in 3 cases, and pleural tuberculosis in 3 cases. In 18 cases in which the CPB diagnosis was MM, thoracoscopy, performed for precise staging, challenged the diagnosis in 4 cases. In 12 cases of carcinoma diagnosed by CPB, thoracoscopy specified the histologic type in 7 cases. Thoracoscopic diagnoses were found to be erroneous in 10 of 149 cases, mainly owing to pleural adhesions that limited access to the pleural cavity. There was one thoracoscopy-related death, one case of sepsis, and six cases of empyema. CONCLUSIONS: Medical thoracoscopy appears to be efficient and relatively safe in the management of pleural disease. Pleural adhesions can lower its diagnostic value.
Determining the optimal number of specimens to obtain with needle biopsy of the pleura.Respir Med. 2002 Jan;96(1):14-7
The aim of this study was to define the number of pleural biopsy samples necessary for optimum diagnostic performance and determine to what extent they are complementary. Eighty-four closed pleural biopsies were performed in our department between June 1996 and January 1998 on 55 males and 29 females with an average age of 64.4 +/- 16.7 years.The study of the pleural fluid included: pH, biochemical testing of pleura/serum (proteins, lactate dehydrogenase, glucose, cholesterol, triglycerides, albumin and adenosine deaminase), haemogram, cytology and microbiological testing (Gram-staining, aerobes, anaerobes and mycobacteriae cultures). The biopsies were performed using a Cope needle, with a total of five biopsies for each patient: four for pathological examination (taken numerically in the order in which they were performed: D1, D2, D3 and D4) and one for microbiological testing. In those cases in which the diagnosis was uncertain or effusion persisted, a thoracoscopy or thoracotomy was performed.There were no significant differences in the diagnostic yield of each individual sample (D1, D2, D3 and D4), but there were differences in the sum of the samples, depending on the number of biopsies performed.This was true for total group and the group with carcinomas, but not for the group with tuberculosis. The increase in diagnostic yield with the number of biopsies was more remarkable in the carcinoma cases, where it increased by 35% when four biopsies were performed (54% with one biopsy versus 89% with four biopsies, P < 0.002). In conclusion, the diagnostic yield increased with the number of biopsy samples in the total group and the group with malignancy but not in the group with tuberculous effusions. The best diagnostic performance for malignant pathology was obtained with four samples. In pleural tuberculosis, the
diagnostic yield did not increase with more biopsy samples. One high quality sample should be enough to obtain a diagnosis.
Blind pleural biopsy using a Tru-cut needle in moderate to large pleural effusion--an experience.Singapore Med J. 1998 May;39(5):196-9
BACKGROUND: Pleural biopsy is invaluable for the etiological diagnosis of pleural diseases in the presence of an exudative pleural effusion. Conventionally, pleural biopsy is either performed with the Cope's or the Abrams pleural biopsy needles. A few investigators have used the Tru-cut biopsy needle with or without ultrasound guidance. We report our experience in performing closed pleural biopsy using a Tru-cut needle without ultrasound guidance in moderate to large exudative pleural effusion. We used a perpendicular approach to biopsy the pleura instead of the tangential approach described earlier. METHODS: Closed Tru-cut biopsy was performed in 27 consecutive patients with exudative pleural effusion who volunteered to undergo the procedure. The biopsy specimen was sent for histopathology. Pleural fluid analysis and other relevant investigations required to obtain a specific diagnosis were carried out. RESULTS: A specific diagnosis of tuberculosis was obtained on histopathology of pleural tissue in 12 out of 16 patients (diagnostic yield 75%) and in 5 out of 7 patients with malignancy (diagnostic yield 71%). Among the other 4 patients, other causes of exudative pleural effusion were detected in 3 and in 1 patient, no specific diagnosis could be made, despite extensive investigation. CONCLUSION: Closed pleural biopsy using a Tru-cut needle is effective for the specific diagnosis of exudative pleural effusion. The use of a perpendicular approach to biopsy the pleura does not seem to increase the complication in moderate to large pleural effusion.
Anatomical distribution of pulmonary diseases
Conducting airways: Bronchial / Bronchiolar Disorders:
1.Granulomatous :
Mycobacterial (Tuberculosis), fungal (Fungal Infections), bronchocentric granulomatosis (allergic, fungal, mucoid impaction, connective tissue disease)
2.Non-granulomatous:
Bronchopneumon ia , lymphocytic and obliterative bronchiolitis (Transplant rejection, viral, toxin, foreign body, connective tissue disease).
3.Extracellular deposits:
Bone/cartilage (tracheobronchopathia osteoplastica),)amyloid (tracheobronchial).
Angiocentric Disorders:
1. Vasculitides:
Wegener’s granulomatosis ; Churg - Strauss syndrome ; Necrotizing sarcoid granulomatosis ; Lymphomatoid Granulomatosis .
2. Hypertensive:
Pulmonary Hypertension Plexigenic arteriopathy ; Thrombotic arteriopathy ; Hypoxic arteriopathy ; Congestive vasculopathy ; Vaso-occlusive disease.
Lymphangiocentric Disorders:
Pneumoconioses; Lymphangitis carcinomatosa / malignant lymphoma ; L ymphangioleiomyomatosis ; Sarcoidosis.
Alveolar Disorders :
1. Acellular :
Edema , Pulmonary Alveolar Proteinosis , pneumocystis.
2. Cellular :
Erythrocytes: Hemorrhagic - Goodpasture’s syndrome, systemic lupus erythematosus , drugs , chronic mitral stenosis, pulmonary venous occlusion, pulmonary hypertension , pulmonary hemosiderosis.
Neutrophils: Bacterial pneumonia. (Lobar Pneumon ia ; Broncho-pneumon ia )
Eosinophils: Eosinophilic pneumonia, allergy, parasites.
Macrophages: Desquamative interstitial pneumonia , smoking, Tuberculosi s , Legionella , Lipid Pneumonia.
Giant cells: Foreign body ; Granulomatous disease ; Hard metal disease.
3. Fibrosis:
Organizing pneumonia
Interstitial Disorders :
1. Non-granulomatous:
Acute interstitial pneumonia , non-specific interstitial pneumonia , usual interstitial pneumonia (+/-), asbestosis , viral pneumonitis, Langerhans cell histiocytosis.
2. Granulomatous:
Tuberculosi s , fungi, sarcoid , extrinsic allergic alveolitis, pneumoconiosis ( talc ,hard metal beryllium, aluminium ).
3. Extracellular Deposits:
Calcium (calcinosis, dystrophic, psammoma bodies, blue bodies); Amyloid (nodular - amyloidoma, diffuse - alveolar septal)
Mixed intraalveolar and interstitial disorders:
Diffuse alveolar damage, Eosinophilic Pneumonia, Pulmonary Alveolar Microlithiasis.
Pleural Disorders:
Mesothelioma -Online
1. Mesothelium:
Reactive / Neoplastic - (primary ; secondary)
2. Submesothelial connective tissue:
Connective tissue disease ; infection ; neoplasia