Normal Anatomy and Histology of the Lung and Airways

Anatomical Distribution of Pulmonary Disease

Useful chromatic and immunostains in pulmonary pathology

Percutaneous Needle and Trucut Biopsy Specimen:

Bronchial Biopsy Specimen:

Transbronchial Biopsy Specimen:

Transbronchial biopsy in lung transplant recipients: 

Open lung biopsy:

Lobectomy and pneumonectomy specimen

Histopathological reporting of pulmonary parenchymal biopsies:

Closed pleural biopsy for neoplasm or inflammatory lesions  ; Open pleural biopsy and pneumonectomy or pleural stripping:

Congenital Cystic Adenomatoid  Malformation

Chronic Obstructive Pulmonary Disease

Bronchial Asthma

Bronchiectasis

Chronic Bronchitis

Emphysema

Bronchiolitis

Lipid Pneumonia

Pulmonary Alveolar Proteinosis

Pulmonary Thromboembolism

Other forms of  Pulmonary Embolism

Pulmonary Infarction

Pulmonary Hypertension

Pulmonary Collapse (Atelectasis) and Pneumothorax

Pulmonary Edema

Pulmonary Hemorrhage (Eg. Goodpasture's Syndrome)

Sarcoidosis

Extrinsic Allergic Alveolitis (Hypersensitivity Pneumonitis)

Lymphangio leiomyomatosis

Pulmonary Mesenchymal Tumours

Primary Pulmonary Leiomyosarcoma

Primary Pulmonary Rhabdomyosarcoma

Primary Monophasic Synovial Sarcoma of the Lung

Neurogenic Tumours of the Lung

Pulmonary Malignant Fibrous Histiocytoma

Bone and Cartilage- forming Sarcoma of the Lung

Kaposi's Sarcoma and Angiosarcoma of the Lung

Epithelioid Hemangioendothelioma of the Lung

Intrapulmonary Solitary Fibrous Tumour

Localized Fibrous Tumour of the Pleura

Pulmonary Lymphoproliferative Disease

Lymphomatoid Granulomatosis

Post-Transplant Lymphoproliferative Disease

Biphasic Epithelial/ Mesenchymal Lung Tumours

Pulmonary Carcino sarcoma

Pulmonary Blastoma

Large Cell Neuro endocrine tumour

Chondroid Hamartoma

Alveolar Adenoma

Endobronchial Lipoma

Bronchial 'mucous gland' adenoma

Pulmonary Papillary Adenoma

Pulmonary Adenofibroma

Minute Pulmonary Meningothelial-like Nodules

Metastatic Tumours of the Lung

Pulmonary vasculitis describes a number of distinct disorders that are pathologically characterized by the destruction of blood vessels. The clinical manifestations of each disorder are defined by the size, type, and location of the affected vasculature. The clinical approach to these disorders rests upon an astute clinician considering the diagnosis and identifying the specific patterns of clinical, radiologic, laboratory, and pathologic abnormalities. Lung involvement is most commonly seen with the primary, idiopathic, small-vessel, or antineutrophil cytoplasmic antibody-associated vasculitides; Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. However, primary, idiopathic medium and large-vessel vasculitis, primary immune complex-mediated vasculitis, and secondary vasculitis are all capable of presenting with lung involvement. In this article, we focus on the more common, antineutrophil cytoplasmic antibody-associated disorder, vasculitides.

Antineutrophil cytoplasmic antibody(ANCA).Rinsho Byori. 2003 Jul;51(7): 644-8.

ANCA are associated with small sized vessel vasculitis; one subtype is an antibody against myeloperoxidase(MPO), which stains in a perinuclear pattern(P-ANCA) indirect immunofluorescence(IIF) using a neutrophil substrate, and the other subtype is an antibody against proteinase-3(PR-3), which stains in a diffuse granular cytoplasmic pattern ANCA by IIF. PR-3 ANCA is more specific in Wegener's granulomatosis(WG) than the other primary vasculitides. MPO-ANCA can be found in microscopic polyangiitis (MPA), Churg Strauss Syndromes(CSS), drug-induced vasculitis, and environmental factor-induced such as silicosis vasculitis more frequently than WG. The value of the IIF test for ANCA detection can be greatly increased by the addition of a standardized antigen-specific ELISA. The intra-assay and inter-assay CV of the MPO and PR-3 ELISA were 6.6 to 4.8%, respectively. Close ANCA titer correlation was shown between MPO-ANCA ELISA and the activity of ANCA associated vasculitis. Renal manifestations and pulmonary manifestations are observed in 70-90% of AAV as the initial manifestation. The changes in titers of ANCA seem to reflect disease activity in 60-70% of AAV patients. A combination of steroids and immunosuppressive drugs is effective in relieving the clinical symptoms of AAV.

Update in the diagnosis and management of pulmonary vasculitis.Chest. 2006 Feb;129(2):452-65.

The term vasculitis encompasses a number of distinct clinicopathologic disease entities, each of which is characterized pathologically by cellular inflammation and destruction of the blood vessel wall, and clinically by the types and locations of the affected vessels. While multiple classification schemes have been proposed to categorize and simplify the approach to these diseases, ultimately their diagnosis rests on the identification of particular patterns of clinical, radiologic, laboratory, and pathologic features. While lung involvement is most commonly seen with the primary idiopathic, small-vessel or antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides of Wegener granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome, one should remember that medium-vessel vasculitis (ie, classic polyarteritis nodosa), large-vessel vasculitis (ie, Takayasu arteritis), primary immune complex-mediated vasculitis (ie, Goodpasture syndrome), and secondary vasculitis (ie, systemic lupus erythematosus) can all affect the lung. However, for the purpose of this review, we will focus on the ANCA-associated vasculitides.

BACKGROUND AND AIM OF THE WORK: The respiratory system may be involved in all systemic vasculitides (SV), although with a variable frequency. Lung disease is a very common and important feature of the antineutrophil cytoplasmic antibodies (ANCA)-associated SV (AASV), such as Wegener's granulomatosis (WG), Churg-Strauss syndrome (CSS), and microscopic polyangiitis (MPA). The aim of the work is to review the clinical findings, as well as the radiological and pathological features of respiratory system involvement in AASV. METHODS: A detailed search via the PubMed index from the National Library of Medicine, covering the period from 1980 to December 2004, was accomplished. RESULTS: In WG, almost all patients have either upper airway or lower respiratory tract disease. Solitary or multiple nodules and masses are the most common findings on chest radiograph. Asthma is a main symptom of CSS, often preceded by allergic rhinitis, frequently complicated by nasal polyposis and sinusitis. Pulmonary transient and patchy alveolar infiltrates are the most common radiographic findings. In MPA, diffuse alveolar haemorrhage (DAH) due to alveolar capillaritis is the most frequent manifestation of the respiratory involvement, clinically expressing with haemoptysis, respiratory distress and anaemia. CONCLUSIONS: The involvement of the respiratory system is a very common and important feature of AASV. There is substantial overlap in many of the clinical pulmonary features of AASV. In some cases, distinguishing between these diseases on the basis of the clinical features alone is difficult and pathological assessment is needed.

Wegener's granulomatosis (WG), microscopic polyangiitis (MPA) and Churg- Strauss syndrome (CSS) are small-vessel vasculitides that, because of their frequent association with antineutrophil cytoplasmic antibodies (ANCA), are usually referred to as ANCA-associated systemic vasculitides (AASV). The diagnosis of AASV is made on the basis of clinical findings, biopsy of an involved organ and the presence of ANCA in the serum. Lung disease is a very common and important clinical feature of AASV. In WG, almost all patients have either upper airway or lower respiratory tract disease. Solitary or multiple nodules, frequently cavitated, and masses are the most common findings on chest radiography. Asthma is a cardinal symptom of CSS, often preceded by allergic rhinitis. Pulmonary transient and patchy alveolar infiltrates are the most common radiographic findings. In MPA, diffuse alveolar haemorrhage as a result of alveolar capillaritis is the most frequent manifestation of respiratory involvement, and is clinically expressed as haemoptysis, respiratory distress and anaemia. However, diffuse alveolar haemorrhage may also be subclinical and should be suspected when a chest radiograph demonstrates new unexplained bilateral alveolar infiltrates in the context of falling haemoglobin levels. Normal and high-resolution CT have a higher sensitivity than chest radiography for demonstrating airway, parenchymal and pleural lesions. However, many of these radiological findings are nonspecific and, therefore, their interpretation must take into account all clinical, laboratory and pathological data. Therapy of AASV is commonly divided into two phases: an initial 'remission induction' phase, in which more intensive immunosuppressant therapy is used to control disease activity, and a 'maintenance' phase, which uses less intensive therapy, for maintaining disease remission while lowering the risk of adverse effects of immunosuppressant drugs. In patients with AASV refractory to standard therapy with corticosteroids and oral cyclophosphamide, new therapeutic options are now available. Recurrence of pulmonary symptoms suggesting a flare indicates the need for a careful search for an opportunistic lung infection or iatrogenic pulmonary complications. In conclusion, involvement of the respiratory system is a very common and important organ manifestation of AASV. Respiratory system involvement comprises a wide spectrum of clinical features and radiological findings, and because of its frequency and prognostic significance, a complete assessment of the respiratory system should be included in the work-up of all patients with AASV.

Respiratory system involvement in systemic vasculitides.Clin Exp Rheumatol. 2006 Mar-Apr;24(2 Suppl 41):S48-59.

The respiratory system may be involved in all systemic vasculitides (SV), although with a variable frequency. Lung disease is a very common and important feature of the antineutrophil cytoplasmic antibodies (ANCA)-associated SV (AASV), such as Wegener's granulomatosis (WG), Churg-Strauss syndrome (CSS), and microscopic polyangiitis (MPA). In WG, almost all patients have either upper airway or lower respiratory tract disease. Solitary or multiple nodules and masses are the most common findings on chest radiograph. Asthma is a cardinal symptom of CSS, often preceded by allergic rhinitis, frequently complicated by nasal polyposis and sinusitis. Pulmonary transient and patchy alveolar infiltrates are the most common radiographic findings. In MPA, diffuse alveolar hemorrhage (DAH) due to alveolar capillaritis is the most frequent manifestation of the respiratory involvement, clinically expressing with hemoptysis, respiratory distress and anemia. However, DAH may be subclinical and has to be suspected when chest radiograph demonstrates new unexplained bilateral alveolar infiltrates, in the face of falling hemoglobin levels. In giant cell arteritis, the most frequent respiratory symptom is cough, usually non-productive, persistent, and responsive to corticosteroids. In Takayasu arteritis, pulmonary involvement is frequently subclinical and detectable by non-invasive techniques. Pulmonary involvement is rare in polyarteritis nodosa, Kawasaki disease, Henoch-Schonlein purpura and cryoglobulinemic vasculitis.In conclusion, the involvement of the respiratory system is a very common and important feature of AASV, whereas is less frequent in other SV. It comprises a wide spectrum of clinical features and radiological findings, and may have a prognostic significance. The assessment of the respiratory system should be included in the work-up of all patients with SV, especially of those with AASV.

Immune mediated intra-alveolar haemorrhage in the adult.Rev Mal Respir. 2006 Feb;23(1 Suppl):3S61-73.

INTRODUCTION: The diagnosis of diffuse intra-alveolar haemorrhage (DAH) is suggested by the combination of haemoptysis, anaemia and pulmonary infiltrates. Broncho-alveolar lavage produces macroscopically haemorrhagic fluid and/or haemosiderin laden macrophages. The diagnostic approach should allow distinction between immune mediated and other causes on account of the therapeutic implications. BACKGROUND: The main immunological causes are small and medium vessel vasculitis (Wegener's granulomatosis, microscopic polyangeitis), lupus and Goodpasture's syndrome. Other immune disorders are only rarely involved. The association of DAH with an acute glomerulonephritis, indicating the pulmonary-renal syndrome, extra-thoracic involvement and immunological abnormalities suggest an immune aetiology. Immunosuppressant treatment should be started as soon as possible with corticosteroids often combined with intravenous cyclophosphamide. Plasmapharesis is indicated for Goodpasture's syndrome and poorly responding lupus. Aggravating factors such as hypervolaemia and disorders of haemostasis should be searched for and treated. Hospital mortality is close to 20%. VIEWPOINT AND CONCLUSION: Immune mediated DAH is a disorder whose rarity justifies the establishment of a national registry with the aim of developing standardised diagnostic and therapeutic strategies.

Update in the diagnosis and management of pulmonary vasculitis.Chest. 2006 Feb;129(2):452-65.

The term vasculitis encompasses a number of distinct clinicopathologic disease entities, each of which is characterized pathologically by cellular inflammation and destruction of the blood vessel wall, and clinically by the types and locations of the affected vessels. While multiple classification schemes have been proposed to categorize and simplify the approach to these diseases, ultimately their diagnosis rests on the identification of particular patterns of clinical, radiologic, laboratory, and pathologic features. While lung involvement is most commonly seen with the primary idiopathic, small-vessel or antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides of Wegener granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome, one should remember that medium-vessel vasculitis (ie, classic polyarteritis nodosa), large-vessel vasculitis (ie, Takayasu arteritis), primary immune complex-mediated vasculitis (ie, Goodpasture syndrome), and secondary vasculitis (ie, systemic lupus erythematosus) can all affect the lung. However, for the purpose of this review, we will focus on the ANCA-associated vasculitides.

Diagnosis and treatment of primary small vessel vasculitis with involvement of lungs. Zhonghua Jie He He Hu Xi Za Zhi. 1999 Jun;22(6):347-50.

OBJECTIVE: To investigate the clinical characteristics of primary small vessel vasculitis with involvement of lungs. METHODS: 13 cases of primary small vessel vasculitis with involvement of lungs from 1993 to 1998 were analyzed retrospectively. RESULTS: Among 13 cases 7 were microscopic polyangiitis (MPA) and 6 were Wegener granulomatosis (WG). The ages of onset were from 17 to 68 years old with average age 48.8 years old. 69%(9/13) were ANCA positive, among them 100%(7/7) MPA were ANCA positive (6/7 were P-ANCA positive, 1/7 was C-ANCA positive), while 33%(2/6) WG were ANCA positive (one case of P-ANCA and another case of C-ANCA was positive respectively). The major symptoms of respiratory system included hemoptasis 69% (9/13), dyspnea 23%(3/13), dry cough 15%(2/13) and chest pain 15%(2/13). The chest x-rays showed multiple patchy shadows in both lungs were mainly found in MPA (3/7) and single or multiple masses or nodular shadows were mainly found in WG (5/6) with or without cavity formation. The appearance of lungs in MPA 71% (5/7) had been explained as "pulmonary infection" and that of WG had been explained as "primary lung cancer or metastatic carcinoma". Symptoms of respiratory system might occur before (3/5) or after (2/5) occurrence of acute renal failure. The treatments with corticosteroid and CTX were effective in these cases, in particularly, pulmonary lesions improved obviously. CONCLUSIONS: It is very difficult to make diagnosis of primary small vessel vasculitis with involvement of lungs and this should be paid more attention. ANCA detection is very useful in diagnosis of MPA. Corticosteroid and CTX are most effective in treating these diseases.

Pulmonary vasculitis.Semin Respir Crit Care Med. 2004 Oct;25(5):483-9.

This review summarizes the radiological manifestations of the vasculitides of proven or presumed immunologic origin in which the inflammatory reaction is directed primarily against the vessel wall. These include Wegener's granulomatosis, Churg-Strauss syndrome, Takayasu's arteritis, Behcet's syndrome, Goodpasture's syndrome, and microscopic polyangiitis. Chest radiography is used routinely in the initial evaluation and follow-up of these patients. The radiographic findings however are nonspecific and need to be interpreted together with the clinical findings. Computed tomography (CT) plays an increasingly important role in the assessment of patients with vasculitis and, in the proper clinical context, allows a confident diagnosis of some of these entities. Magnetic resonance imaging and positron emission tomography play a limited role. The characteristic imaging manifestations of the various vasculitides are reviewed and illustrated.

Pathology of pulmonary vasculitis.Semin Respir Crit Care Med. 2004 Oct;25(5):475-82.

There are three major vasculitis syndromes that affect the lung: Wegener's granulomatosis (WG), Churg-Strauss syndrome (CSS), and microscopic polyangiitis (MPA). The pathology of pulmonary vasculitis is complicated because it requires correlation with clinical, laboratory, and radiological features; there is overlap in some histological features among the vasculitis syndromes; biopsies early in the course of disease or after therapy may show atypical or incomplete histological features; the differential diagnosis is complex and includes infection that should not be treated with corticosteriods or immunosupressive agents; and few pathologists have much experience with these cases. Major histological features of necrosis, granulomatous inflammation, and vasculitis characterize WG. The inflammatory consolidation consists of a mixture of neutrophils, lymphocytes, plasma cells, macrophages, giant cells, and eosinophils. Necrosis may take the form of neutrophil microabscesses or geographic necrosis. Granulomas may take several forms, including scattered or loose clusters of giant cells, palisading histiocytes or giant cells lining the border of geographic necrosis or microabscesses, and palisading microgranulomas. Sarcoidal granulomas are very rare. CSS may show eosinophilic pneumonia, allergic granulomas, and eosinophilic vasculitis. Asthmatic bronchitis may also be present. Biopsies from CSS patients are rare because this syndrome is usually diagnosed clinically. Microscopic polyangiitis demonstrates neutrophilic capillaritis and diffuse alveolar hemorrhage.

Pathogenesis of pulmonary vasculitis.Semin Respir Crit Care Med. 2004 Oct;25(5):465-74.

Vasculitis is inflammation of blood vessels and can affect any type of vessel in any organ. Pulmonary vasculitis usually is a component of a systemic small vessel vasculitis. Three major forms of small vessel vasculitis that often affect the lungs are Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. These forms of vasculitis are strongly associated with antineutrophil cytoplasmic autoantibodies (ANCA) directed against enzymes contained in the primary granules of neutrophils and peroxidase-positive lysosomes of monocytes. This review discusses the evidence for a pathogenic role of ANCA. In vitro, ANCAs can activate cytokine-primed neutrophils and monocytes resulting in oxygen radical formation and release of lysosomal enzymes. In vivo, antimyeloperoxidase ANCA has been shown to induce crescentic glomerulonephritis and systemic vasculitis. Overall, the available data suggest that ANCA are indeed a pathogenic factor in the development of small-vessel vasculitis. Antiglomerular basement membrane (anti-GBM) disease also causes pulmonary vasculitis through immune attack on alveolar capillaries and glomerulonephritis through antibody mediated injury to glomerular capillaries. Thus, there is evidence that antibodies are important pathogenic factors in both ANCA disease and anti-GBM disease, however, there are also indications that T cells may play important pathogenic roles in both categories of disease as well.

Pulmonary vasculitis.Am Rev Respir Dis. 1986 Jul;134(1):149-66.

The granulomatous vasculitides frequently involve the lung. These syndromes include Wegener's granulomatosis, allergic angiitis and granulomatosis, and the polyangiitis overlap syndrome. Although not a true systemic vasculitis, necrotizing sarcoid granulomatosis also represents a type of pulmonary vasculitis. It is clear that many infectious agents can cause a picture in the lung that can be confused with granulomatous vasculitis and that an infectious process must be ruled out before a diagnosis of pulmonary vasculitis can be established. Pulmonary vasculitis can be associated with the hypersensitivity vasculitides, and pulmonary hemorrhage can be secondary to pulmonary capillaritis. Therapy of the hypersensitivity vasculitides consists of removing the offending antigen and instituting a limited course of corticosteroids. If the vasculitis is secondary to an underlying disease, such as lymphoma, therapy should be directed at the primary disease. Combination therapy with cyclophosphamide and corticosteroids is effective in the systemic vasculitides and the 5-yr survival rate is approximately 90%.

The spectrum of pulmonary vasculitis.Monaldi Arch Chest Dis. 1996 Feb;51(1):35-8.

Wegener's granulomatosis and Churg-Strauss syndrome are the predominant pulmonary vasculitides. Next in frequency are the various diffuse alveolar haemorrhage syndromes, which may be related to the antineutrophil cytoplasmic autoantibody (ANCA)-associated diseases, such as Wegener's granulomatosis and Churg-Strauss syndrome, or may be a part of a collagen vascular disease, such as lupus erythematosus, or associated with antiglomerular basement membrane antibody (AGBM) and fall within the definition of Goodpasture's syndrome. Whereas Behclet's disease and Takayasu's arteritis have major pulmonary manifestations, they are rare diseases. Entities previously confused with pulmonary vasculitis include lymphomatoid granulomatosis or polymorphic reticulosis, and benign lymphocytic angiitis and granulomatosis, which are probably in the spectrum of T-cell lymphomas. Necrotizing sarcoid and sarcoidosis can involve blood vessels, but do not follow a typical course associated with the traditional concept of vasculitis.

Cavitating lung lesions in the course of ANCA-associated vasculitis: differential diagnostic aspects. Aktuelle Radiol. 1998 May;8(3):114-8.

Antineutrophil cytoplasmatic antibodies (ANCA)-associated vasculitides (Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome) show quite variable courses. Clinical features of the full blown generalized systemic vasculitis are usually found in the respiratory tract and the kidney. Pulmonary involvement of Wegener's granulomatosis shows commonly nodules and cavitations but also diffuse alveolar hemorrhage. We report the case of a 57 year-old man suffering from dyspnea, thoracal pain, arthralgia, purpura, scleritis and tinitus. Specimen of the kidney showed segmental glomerulosclerosis and tubulointerstitial nephritis. Because of the presence of cANCA Wegener's disease was assumed. Pulmonary infiltrates developed under immunosuppressive treatment with cyclophosphamid. As differential diagnosis of the pulmonary infiltrates, we considered invasive pulmonary aspergillosis as well as infiltrates due to Wegener's granulomatosis. In spite of maximal therapeutic management of patient died of respiratory and cardiovascular failure. The findings at autopsy showed distinct invasive pulmonary aspergillosis and perifocal hemorrhage.