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Interstitial granulomatous pulmonary diseases: a diagnosticapproach for the general pathologist*

Alosio S. Felipe da SilvaI; Danieli Cheke da RosaI; Vera Luiza CapelozziII

IResident Physician of Pathological Anatomy.IIAssociated Professor of the Department of Pathology.

Correspondence

ABSTRACT

Some kinds of interstitial pneumonia present a histopathological pattern dominated bysarcoid - necrotizing or non-necrotizing - granulomas, which can be divided into two maingroups: infectious and non-infectious. The infectious causes include tuberculosis,histoplasmosis, fungi in general, paracoccidioidomycosis, ascaridiasis, echinococcosis and

dirophilariosis. The non-infectious causes include histiocytosis-X, hipersensitivitypneumonia, vasculitis, lymphomas, sarcoidosis, and pneumoconioses such as silicosis andberylliosis. The purpose of this review is to provide a practical guideline to enable generalpathologists to make the differential diagnosis of granulomatous pulmonary diseases. Forthis purpose, anatomical-clinical-radiological correlations will be presented and targeted toeach diagnosis discussed. Whenever a granulomatous inflammatory process is in progress,the search for infective agents by direct observation, by culture, and by histochemicalmethods should be mandatory. The histological aspects of infectious granulomas to beanalyzed should include their random histo-anatomical location, the type of inflammatoryreaction, and necrosis. A panel of complementary reactions (immunohistochemistry andPCR) should identify the infectious agent and, whenever their results and the culture arenegative, the possibility of non-infectious granulomatous diseases has to be evaluated. Insuch cases, the histo-anatomical distribution (bronchocentric, lymphangitic, angiocentric,random), the qualitative characteristics of the lesions (type of necrosis and inflammatoryreaction), and the correlation with the X-ray findings will help the diagnosis.

Key words: Granulomatous diseases. Histologic diagnosis. Interstitial pulmonary diseases.Pathology. Granuloma.
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Acronyms and abbreviations used in this workPCR Polymerase chain reactionBCG Bacillus Calmette-GurinCHP Chronic hypersensitivity pneumoniaIgG-Fc HLA-DR ANCA anti-neutrophil cytoplasm auto-antibodyBALT Bronchial associated lymphoid tissue

Introduction

Diffuse granulomatous pulmonary diseases form a heterogeneous group of clinical andphysiopathological entities.(1-5) However, the formation of granulomas as a commonhistopathological feature constitutes an important diagnostic element, since it orients theclinical reasoning towards a relatively limited group of etiologies.(6) An accurate diagnosis isbased on a correlation between clinical and radiological data and the specific histological,histochemical and microbiological characteristics of each disease.(7-9) Molecular andimmunohistochemical methods may be necessary. The path to the final histopathologicaldiagnosis should be systematized, considering both physiopathology and the differentialmorphological aspects of granulomatous diseases.

Granulomatous inflammation as a pulmonary defense mechanism

The respiratory system is exposed to a variety of potentially harmful agents, many of whichare environmental and aggress the organism by inhalation. There are several lines ofdefense against such agents, covering from the upper airways to the alveolar spaces.

The first line of defense of the respiratory system consists of mechanical factors, such ashair and the coughing reflex, mucociliary transport, and biochemical mucus componentssuch as immunoglobulins and complement. Although unspecific, these mechanisms preventmost of the external agents from reaching the alveolar space. Among the unspecific defensemechanisms of the alveolar space, there are the pulmonary surfactant and the alveolarmacrophages.(10) The latter can stimulate the rapid migration of neutrophils into the alveolarlumen, as initial phagocytes.

Once exposed to the antigen, the alveolar macrophage can activate the specific immune

response, through antigenic presentation. This response is characterized by cytokine-mediated clonal lymphocyte expansion, migration of lymphocytes, plasmacytes andmonocytes into the interstitium and the alveolar space. Effector mechanisms mediated byspecific immunoglobulins, effector T-cells, and macrophage activation are also triggered.

The granulomatous inflammatory process is one of the effector mechanisms of the immuneresponse and the last line of pulmonary defense. This response pattern arises as a result ofcertain aggressive agents or antigens, which could not be eliminated by the previouslymentioned mechanisms. The formation of a granuloma is determined by an interaction


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between macrophages and T- lymphocytes, triggered by antigenic presentation, andmediated by cytokines. The process culminates with the recruiting, proliferation andactivation of both cell types, besides fibroblast migration.(11,12)

Although previously exemplified for preferentially inhaled agents, granuloma formation alsooccurs in a group of diseases in which the immune response plays a crucial role in the

clinical and anatomicopathological manifestations, even though their etiological aspectsremain poorly elucidated, such as, for example, sarcoidosis.

Granulomatous pulmonary diseases

The granulomatous pulmonary diseases are summarized inChart 1, divided into two maingroups: infectious and non-infectious.

Infectious causes include tuberculosis, histoplasmosis, fungi in general,paracoccidioidomycosis, ascaridiasis, echinococcosis, and dirophilariosis.

Non-infectious causes include histiocytosis-X, hypersensitivity pneumonia, vasculitis,lymphomas, sarcoidosis, and pneumoconioses, such as silicosis and berylliosis.

Initial approach: infectious diseases

Once a granulomatous inflammatory process is detected, the search for infectious agentsthrough direct observation, culture, and histochemical methods is mandatory. Infectiousgranulomatous diseases are important differential diagnoses, considering their prevalence,clinical-pathological heterogeneity, and the available therapeutic possibilities.
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The initial approach usually includes a search for the alcohol-acid-resistant bacillus (Ziehl-Neelsen staining) and mycobacteria detection, and silver-methenamine staining (Grocottstaining) to identify fungi.(6,11,12) Nocardia can also be detected by these methods.

Actinomyces sp can be identified by Gram staining.(12)

The search for possible infectious agents causing certain histopathological pictures of the

granulomatous disease also counts on resources provided by immunohistochemistry andmolecular biology. If there is a clinical-radiological suspicion, a search for BCG antigen canbe performed for mycobacteria, and for fungus antigens ofP. brasiliensis and P. carinii. TheBCG antigen has been intensely used by some groups, whereas the use ofP. brasiliensisand P. cariniiantigens is less common. Many pathologists are particularly critical regardingthe first one, and many do not know it, but there are data from the literature attesting to itsvalidity.(13,14) PCR (polymerase chain reaction) can be used in histological pictures suspectedof mycobacteriosis, where the infectious agent was not identified by other methods.(13,14) Itis estimated that 106 microorganisms per millimeter of tissue are required for Ziehl-Neelsenstaining to be positive.(13) A positive PCR result is not considered valid from the diagnosticviewpoint, unless one or more microorganisms can be identified inside the tissue by theZiehl-Neelsen technique.

If the panel of complementary reactions was unable to identify an infectious agent, thehistological and radiological characteristics(9) are fundamental for the clinical managementand establishment of diagnostic hypotheses, while waiting for the microbiological cultureresult.

Tissue culture techniques require from three to six weeks to identify themicroorganism.(13,15)

Chart 2exemplifies the sequence of events in the diagnosis of granulomatous diseases.
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Differential histological characteristics: infectious diseases

The histological aspects of infectious granulomas include their random histo-anatomiclocation and the presence of an inflammatory reaction (Figure 1) and necrosis (Figure 2).
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In tuberculosis and pulmonary mycoses, the distribution of granulomas is random, i.e., thepathological process can affect any region of the pulmonary lobes, without any preferential

location.(8,12)

A random granulomatous process with the presence of both necrosis andinflammation, although not pathognomonic, increases the probability of an infectiousdisease diagnosis. However, a few comments are necessary.

In immunosuppressed patients, inflammation is frequently discreet or absent (Figure 1).Necrosis is predominant, with only outlines of granulomas, and there may be no giantcells.(12)

Different types of necrosis can suggest the etiological agent. Thus, caseous necrosis istypical for tuberculosis and also for nocardiosis (Figure 2). Suppurative (liquefactive)necrosis is present in mycoses, while dirophilariosis is accompanied by coagulative necrosis.Figures 3 to 5exemplify the radiological distribution of the lesions in tuberculosis.
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If the panel of complementary reactions (histochemistry, immunohistochemistry, and PCR)was unable to identify an infectious agent and the culture results were negative, thepossibility of a non-infectious granulomatous disease has to be evaluated. To this effect, theanatomical-clinical-radiological correlation is fundamental.(9)

Differential histological characteristics: non-infectious diseases

Each non-infectious granulomatous pulmonary disease presents distinctive clinical andradiological characteristics, particularly in the classical form. However, these characteristicsmay present various degrees of overlapping, being even mistaken for possible infectiousdiseases. In this context, the histopathological test is of fundamental importance to confirmthe granulomatous nature, and to rule out a possible infectious cause. Moreover, theetiopathogenic differences are reflected by the histological presentation of each disease,allowing to differentiate them morphologically with a certain degree of accuracy.


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The histological characteristics evaluated are the histo-anatomical distribution ofgranulomas and the presence of necrosis.Charts 3and4summarize the differentcategories.

Bronchocentric distribution

Diseases with a bronchocentric or inhalation distribution, like chronic hypersensitivitypneumonia and histiocytosis-X, tend to affect the axial region of the pulmonary lobe, beingcharacterized as airway-centered diseases.(8)
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Chronic hypersensitivity pneumonia (CHP) is characterized by a chronic interstitialinflammatory process, usually secondary to prolonged exposure to inhaled organic dustsand occupational antigens. CHP can present a distinctive histopathological pattern when allthree characteristics are present: 1) interstitial cellular bronchiolocentric pneumonia, 2)non-caseating granulomas, and 3) intraluminal fibrosis or organizing pneumonia (Figure6).(16,17) The formation of incomplete non-necrotizing granuloma occurs, and can be

accompanied by obliterating bronchiolitis in 25% to 50% of the cases, and by obliteratingbronchiolitis with organizing pneumonia in 15% to 25%.(18) The radiological presentationcan be seen inFigures 7and8.
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Histiocytosis-X or Langerhans cell histiocytosis is characterized by the clonal expansion of

antigen-presenting dendritic cells (Langerhans cells), a kind of histiocytes. There aredifferent forms of clinical presentation: acute disseminated children s disease (Letterer-Siwe syndrome), chronic multifocal children s disease (Hand-Schller-Christian syndrome),indolent localized disease (eosinophilic granuloma), systemic disease with pulmonaryinvolvement, and primary pulmonary Langerhans cell histiocytosis. Pulmonary affection(Figure 9) is characterized by stellate nodules or granulomas, formed by dendritic cells withvarying proportions of lymphocytes, plasmacytes, neutrophils e eosinophils.(19-21) Thedendritic cells express proteins S100 and CD1a, and can be identified byimmunohistochemistry.(20-21) They exhibit a broad and frequently granulous cytoplasm andnuclei with invaginations (Figure 10). Electron microscopy reveals characteristiccytoplasmatic Birbeck granules (Figure 11).(22) Sometimes, they can be accompanied bynecrosis. Other characteristics of the Langerhans cells include the presence of C3, receptorsfor IgG-Fc and Ia antigen (HLA-DR).(22,23)Figure 12shows the radiological aspect of

histiocytosis-X.
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Angiocentric distribution

In this group of diseases, the affection is centered in the pulmonary vessels, sometimes inthe arteries and veins, sometimes in the capillaries.(8) Wegener s granulomatosis,microscopic polyangiitis, the Churg-Strauss syndrome, and drug-induced ANCA-associatedvasculitis belong to this group. They are characterized by inflammatory vascular affectionand by the association with positive titles of the anti-neutrophil cytoplasm auto-antibody(ANCA). Although they are distinct clinical entities, they have several histopathological andetiopathogenic aspects in common.

Wegener s granulomatosis is characterized by a triad consisting of necrotizinggranulomatous inflammation of the upper and lower respiratory tract, focal necrotizing

vasculitis of small- and medium-caliber vessels, and renal disease, in the form of focalnecrotizing or crescentic glomerulitis.(24) In the pulmonary parenchima, the necrotizinggranulomas can flow together, leading to a characterisitic pattern of basophilic geographicalnecrosis (Figure 13). The formation of neutrophilic micro-abscesses with a variable numberof giant cells also occurs. The pulmonary vessel damage occurs as necrotizing vasculites(Figure 14) or granulomatous vasculites of the arterioles and venules, with or withoutcapillaritis (Figure 15). There may be cutaneous damage by leukocytoclastic vasculitis.Figures 16 to 18present the radiographic aspect of Wegener s granulomatosis.
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Microscopic polyangiitis affects arterioles, venules and capillaries, the lesion being rarer in

larger vessels.(25) Necrotizing glomerulitis and pulmonary capillaritis are common. Isolatedcutaneous leukocytoclastic vasculitis may occur.

In allergic granulomatosis and angiitis (Churg-Strauss syndrome), the vascular lesionsresemble those of microscopic polyangiitis, mainly with necrotizing vasculitis andextravascular granulomas.(26) There is, however, a strong association here with allergicconditions like severe asthma and rhinitis.(27) There is systemic hypereosinophilia, that canbe detected in peripheral blood. Severe renal alterations are rare, and there may be fever.In stage 1, diffuse pulmonay infiltration by eosinophils occurs, while in stage 2 vasculitis,necrosis and granulomas are more pronounced (Figure 19).

Lymphangitic distribution
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This group of diseases, which includes sarcoidosis and some pulmonary lymphomas,presents granulomas distributed along the pulmonary lymph ways, both on the central axisand along the peripheral lobular interstitium, the septa, and subpleural regions.(8)

Pulmonary lymphomas account for 0.5% of the primary lung tumors.(28) They are classifiedin ways as variable as systemic lymphomas; however, the most common histological type is

the low-degree small lymphocyte lymphoma (Figure 20). This category comprises 50% to90% of the primary pulmonary lymphomas.(29) They are B-cell neoplasias originated fromBALT (bronchial associated lymphoid tissue), which involve, in up to 20% of cases, the bonemarrow, and are related to monoclonal serum proteins. Radiologically, they can be diffuseor localized. They affect mainly patients in their sixties, usually asymptomatic; such patientshave a long survival.

Angiocentric immunoproliferative lesions (angiocentric lymphomas or lymphomatoidgranulomatosis) constitute the second most common group.(30)Figure 21shows theirradiological aspect. Clinically, they affect men in their fifties, presented as bilateralpulmonary nodules, sometimes involving other organs such as the central nervous systemand the skin. Histopathologically, they are T-cell or B-cell lymphomas infected by theEpstein-Barr virus, usually of a high degree, which form nodules and perilymphaticinfiltrates. Necrosis and polymorphonuclear infiltrates may also develop.


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Sarcoidosis is characterized by the presence of non-necrotizing epithelioid granulomas indifferent organs and systems affecting, in the great majority of cases, the lungs and hilarlymph nodes.(31) Its etiology remains unknown.(32) Histologically, it is characterized by"hard" granulomas, in which the epithelioid cell is the dominant element (Figure 22),distributed within the pulmonary interstitium along the pleura and interlobular septa, andaround the vasculo-bronchial axis.(33) Differential diagnosis is made with othergranulomatous diseases, such as mycobacterioses(13) and berylliosis,(34) usually being adiagnosis by exclusion.Figure 23exemplifies the radiological aspect of sarcoidosis.


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Nodular diseases

Rheumatoid pulmonary nodule is uncommon in patients with rheumatoid disease, occurringin less than 1% of the cases.(35) Its frequency is higher in men with active articular disease,and involves an increase of the rheumatoid factor. Histologically, it resembles thesubcutaneous rheumatoid nodules, which are more common, and are characterized by acentral area of fibrinoid necrosis surrounded by a belt of epithelioid macrophages andnumerous lymphocytes and plasmacytes, characterizing the palisade granuloma.(36) Itsdifferential diagnosis with infectious diseases or malignant granulomatoses is difficult.Figure24shows the radiological aspect of rheumatoid nodule.

Conclusion
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Interstitial pneumonia can present a histopathological pattern dominated by sarcoidgranulomas, caseating or not, which can be grouped into infectious and non-infectiouscases. The infectious causes include tuberculosis, histoplasmosis, fungi in general,paracoccidioidomycosis, ascaridiasis, echinococcosis, and dirophilariosis. The non-infectiouscauses include histiocytosis-X, hypersensitivity pneumonia, vasculites, lymphomas,sarcoidosis, and pneumoconioses such as silicosis and berylliosis. The histological aspects of

infectious granulomas to be analyzed include their random histo-anatomic location, the kindof inflammatory reaction, and necrosis. A panel of complementary reactions(immunohistochemistry and PCR) should identify any infectious agent and, if both theirresults and the culture are negative, the possibility of a non-infectious granulomatousdisease will have to be evaluated. In such cases, the histo-anatomic distribution(bronchocentric, lymphangitic, angiocentric, random), the qualitative characteristics of thelesions (kind of necrosis and inflammatory reaction) and the correlation with X-rays will helpin the diagnosis.

References

1. Cushley MJ, Davison AG, du Bois RM, Egan J, Flower CD, Gibson GJ, et al. The diagnosis,assessment and treatment of diffuse parenchymal lung disease in adults. Thorax

1999;54:S1-S300. [Links]

2. Capelozzi V. Dificuldades na interpretao da bipsia pulmonar nas doenas intersticiais

difusas dos pulmes. J Pneumol 1998;24:30-42. [Links]

3. Capelozzi V. Progressos recentes na patologia das doenas intersticiais pulmonares

difusas. Pulmo RJ (Supl) 1998;12-26. [Links]

4. Capelozzi V. Asbesto, asbestose, cncer. J Pneumol 2001;27:206-17. [Links]

5. American Thoracic Society/European Respiratory Society. International MultidisciplinaryConsensus Classification of the Idiopathic Interstitial Pneumonia. Am J Respir Crit Care Med

2002;165:277-304. [Links]

6. Katzenstein ALA. Granulomatous diseases of the lung. In: Katzenstein ALA, editor.Katzenstein and Askin s surgical pathology of non-neoplastic lung disease. Philadelphia,USA: W.B. Saunders, 1997;48-80. [Links]

7. Schettino IAL, Ab Saber AM, Kairalla RA, Carvalho CRR, Saldiva PHN, Capelozzi VL.Correlation between CT scan and open lung biopsy in idiopathic pulmonary fibrosis: a

morphometric study. Pathol Pract Res 2002;198:347-57. [Links]

8. Colby T, Lombard C, Yousem AS, Kitaichi M. Interstitial diseases. In: Atlas of pulmonary

surgical pathology. WB Saunders, 1991;227. [Links]

9. Muller NL, Fraser RS, Lee KS, Johkoh T. Pulmonary infection. In: Diseases of the lung.Radiologic and pathologic correlations. Philadelphia, USA: Lippincott Williams & Wilkins,

2003;17. [Links]


21/23

10. Weibel ER. Lung cell biology. In: Fishman AP, editor. Pulmonary diseases and disorders.

3rd ed. New York: McGraw Hill, 1997;25. [Links]

11. Capelozzi VL. Pulmes. Pleura. In: Bogliolo Patologia. 6a ed. Ed. Geraldo Brasileiro Filho,Guanabara Koogan, 2000. [Links]

12. Gutierrez EB, Zanett DMT, Saldiva PHN, Capelozzi VL. Autopsy-proven determinants ofdeath in HIV-infected patients treated for pulmonary tuberculosis in Sao Paulo, Brazil.Pathol Res Pract 2002;198:339-46. [Links]

13. Hruban RH, Hutchins GM. Mycobacterial infections. In: Dail DH, Hammar SP, editors.

Pulmonary pathology. 2nd ed. New York: Springer-Verlag, 1994;331-50. [Links]

14. Lack EE, Connor DH, Chandler FW, Manz HJ. Pathology of infectious diseases. Stamford:Appleton & Lange, 1997;857-68. [Links]

15. Hopewell PC, Bloom BR. Tuberculosis and other mycobacterial diseases. In: Murray JF,

Nadel JA, Mason RJ, Boushey HA Jr, editors. Textbook of respiratory medicine. 3rd ed.Philadelphia: WB Saunders, 2000;1043-105. [Links]

16. Colby TV, Coleman A. The histologic diagnosis of extrinsic allergic alveolitis and its

differential diagnosis. Prog Surg Pathol 1989;10:11-25. [Links]

17. Kawanami O, Basset F, Barrios R, Lacronique JG, Ferrans VJ, Crystal RG.Hypersensitivity pneumonitis in man. Light- and electron-microscopic studies of 18 lung

biopsies. Am J Pathol 1983;110:275-89. [Links]

18. Bertorelli G, Bocchino V, Olivieri D. Hypersensitivity pneumonitis. Eur Respir Mon

2000;14:120-36. [Links]

19. Colby TV, Lombard C. Histiocytosis X in the lung. Hum Pathol 1983; 14:847-

56. [Links]

20. Hage C, Willman CL, Favara BE, Isaacson PG. Langerhan s cell histiocytosis(histiocytosis X): immunophenotype and growth fraction. Hum Pathol 1993;24:840-

5. [Links]

21. Travis WD, Borok Z, Roum JH. Pulmonary Langerhans cell granulomatosis (histiocytosis

X). A clinicopathologic study of 48 cases. Am J Surg Pathol 1993;17:971-86. [Links]

22. Ye F, Huang SW, Dong HJ. Histiocytosis X. S100 protein, peanut agglutinin, andtransmission electron microscopy study. Am J Clin Pathol 1990;94:627-31. [Links]

23. Klareskog L, Tjernlund U, Forsum U, Peterson PA. Epidermal Langerhan s cells express

Ia antigens. Nature 1997;268:248-50. [Links]

24. Travis WD, Hoffman GS, Leavitt RY, Pass HI, Fauci AS. Surgical pathology of the lung inWegener s granulomatosis. Review of 87 open lung biopsies from 67 patients. Am J Surg

Pathol 1991;15:315-33. [Links]


22/23

25. Jennette JC, Falk RJ. Small-vessel vasculitis. N Engl J Med 1997;337: 1512-

23. [Links]

26. Lanham JG, Churg J. Systemic vasculitides. New York: Igaku-Shoin, 1991;101-20. [Links]

27. Churg J, Strauss L. Allergic granulomatosis, allergic angiitis and periarteritis nodosa. Am

J Pathol 1951;27:277-94. [Links]

28. Habermann TM, Ryu JH, Inwards DJ, Kurtin PJ. Primary pulmonary lymphoma. SeminOncol 1999;26:307-15. [Links]

29. Fiche M, Captron F, Berger F. Primary pulmonary non-Hodgkin s lymphomas.

Histopathology 1995;26:529-37. [Links]

30. Guinee JR DG, Perkins S, Travis W, Holden JA, Tripp SR, Koss MN. Proliferation andcellular phenotype in lymphomatoid granulomatosis. Am J Surg Pathol 1998;22:1093-

100. [Links]

31. Rosen Y, Vuletin JC, Pertschurk, LP, Silverstein E. Sarcoidosis from the pathologist svantage point. Pathol Annu 1979;14 Part I]:405-39. [Links]

32. Statement on Sarcoidosis. Joint Statement of the American Thoracic Society (ATS), theEuropean Respiratory Society (ERS) and the World Association of Sarcoidosis and OtherGranulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERSExecutive Committee, February 1999. Am J Respir Crit Care Med 1999; 160:736-

55. [Links]

33. Rosen Y, Vuletin JC, Pertschurk, LP, Silverstein E. Sarcoidosis from the pathologist s

vantage point. Pathol Annu 1979;14[Part I]:405-39. [Links]

34. Jones Williams WA. A histological study of the lungs in 52 cases of chronic beryllium

disease. Br J Ind Med 1958;15:84-91. [Links]

35. Wiedemann HP, Matthay RA. Pulmonary manifestations of systemic lupus

erythematosus. J Thorac Imaging 1992;7:1-18. [Links]

36. Yousem AS, Colby TV, Carrington CB. Lung biopsy in rheumatoid arthritis. Am Rev

Respir Dis 1985;131:770-7. [Links]

Correspondence toVera Luiza CapelozziProfessora Associada do Departamento de Patologia, Faculdade de Medicina da USPAv. Dr. Arnaldo, 455, 1 andar, sala 1.14301246-903 So Paulo, SP Brazil
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0102-35862003000300008


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Phone: +55 11 3066-7427; fax: +55 11 5096-0761E-mail:[email protected]

Received for publication on 11/06/02Approved, after revision, on 02/21/03.

*Lecture given during the III Annual Course on Interstitial Pulmonary Diseases March 1and 2, 2002. Scientific support: Fapesp Fundao de Amparo Pesquisa do Estado de SoPaulo (So Paulo State Foundation for the Support of Reseach). LIM05-HCFMUSP MedicalInvestigation Laboratory Hospital das Clnicas da Faculdade de Medicina da Universidadede So Paulo. CNPq Conselho Nacional de Desenvolvimento Cientfico e Tecnolgico(National Council for Scientific and Technological Development).

Sociedade Brasileira de Pneumologia e Tisiologia

Faculdade de Medicina da Universidade de So Paulo

Departamento de Patologia

Laboratrio de Poluio AtmosfricaAv. Dr. Arnaldo, 455

01246-903 So Paulo SP Brazil

Tel: +55 11 3060-9281

[email protected]
mailto:[email protected]:[email protected]:[email protected]://www.scielo.br/scielo.php?script=sci_arttext&pid=S0102-35862003000300008#tophttp://www.scielo.br/scielo.php?script=sci_arttext&pid=S0102-35862003000300008#topmailto:[email protected]:[email protected]:[email protected]://www.scielo.br/scielo.php?script=sci_arttext&pid=S0102-35862003000300008#topmailto:[email protected]

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