Abstract
Pathologists are frequently involved in the diagnosis of sarcoidosis on conventional biopsies or examining bronchoalveolar lavage fluid and assisting bronchoscopists when performing bronchial or transbronchial biopsies or transbronchial needle aspiration (TBNA)/endobronchial ultrasound (EBUS)-guided biopsies of enlarged lymph nodes. Histology generally does not pose difficult tasks in the correct clinical and imaging scenario, but atypical forms of sarcoidosis exist, and in these cases, the diagnosis may become difficult. When faced with granulomas in the lung, the evaluation of their qualitative features, anatomic distribution, and accompanying findings usually allows the pathologist to narrow considerably the differential diagnosis. The final diagnosis always requires the careful integration of the histology with the clinical, laboratory, and radiologic findings. How robust is the histologic component of the diagnosis varies from case to case, and the pathologist should always clearly discuss this point with the clinician; in general, the weaker the histology is, the stronger should be the clinical–radiologic findings, and vice versa. The differential diagnosis of sarcoidosis includes granulomatous infections, hypersensitivity pneumonitis, pneumoconiosis, autoimmune diseases (e.g., inflammatory bowel disease, primary biliary cirrhosis, several collagen vascular diseases (particularly Sjögren), drug reactions, chronic aspiration, and even diffuse fibrosing diseases. In this review, conventional and unusual histologic findings of pulmonary sarcoidosis are presented, highlighting the role of the pathologist and discussing the main differential diagnoses.
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Introduction
With the exception of classic Lofgren’s syndrome, in which a clinico-radiologic diagnosis is often acceptable, the diagnosis of sarcoidosis generally requires a histologic biopsy or a cytologic specimen showing granulomas in the correct clinico-radiologic context [1, 2]. As a consequence, pathologists are frequently involved in the workup of these patients, and sarcoidosis represents one of the granulomatous diseases they encounter most commonly. In many cases, the pathologist’s role in this setting is not particularly difficult, providing that a strict collaboration with clinicians and radiologists is ensured. However, examples of sarcoidosis with atypical histology present diagnostic difficulties. Moreover, the widespread diffusion of transbronchial needle aspiration (TBNA) requires pathologists to recognize granulomas in limited cytologic material [3]. Herein, we provide a practical review on the role of pathologists in the diagnosis of sarcoidosis, focusing particularly on these problematic areas.
Classical and Atypical Histologic Features
The histology of sarcoidosis is well described in textbooks [4–9] and review articles [10–14]. Classical sarcoidosis (Fig. 1) consists in well-formed, tightly packed, non-necrotizing granulomas surrounded by lamellar hyaline collagen. Occasionally, granulomas are rimmed by a more edematous, myofibroblastic-rich tissue. In the lung, sarcoid granulomas typically coalesce along the lymphatic routes in the pleura, interlobular septa, and bronchovascular bundles. One of these anatomic compartments may be more involved than the others, generally the bronchovascular bundles but sometimes the pleura. This typical distribution of granulomas, together with their qualitative features (non-necrotizing, compact and associated with hyaline fibrosis), is the main histologic clue of pulmonary sarcoidosis. The disease tends to have an upper lung zone distribution, and this is a helpful feature in differential diagnosis with other granulomatous processes.
The fact that sarcoid granulomas tend to localize in the interstitium along lymphatic routes, where bronchovascular structures are found, with relative sparing of alveolar parenchyma, has some important consequences: First, it closely correlates with the “perilymphatic” distribution seen on high-resolution computer tomography (HR-CT) of the chest [15]; second, it is the reason of the high diagnostic yield of bronchoscopic biopsies; third, it explains why some patients have few/no symptoms and normal function tests in spite of a significant pathology radiologically; fourth, it explains why in some patients the clinical picture is dominated by airway involvement (wheezing, functional obstruction) [16]; fifth, it is the reason for the frequent occurrence of vascular involvement in sarcoidosis, reported in 53 % of transbronchial biopsies [17], in 69 % of surgical lung biopsies [18], and in 100 % of autopsies [19]. Vascular involvement generally consists of granulomas variably involving the adventitia, media, or intima of pulmonary arteries and/or veins (Fig. 2). Occasionally, a more pronounced vasculitic inflammation may be present, but necrosis of the vessel wall is distinctly unusual. Vascular involvement likely accounts for the rare occurrence of pulmonary hypertension in sarcoidosis, sometimes with features of veno-occlusive disease [20].
Intracytoplasmic inclusions (Schaumann bodies, birefringent calcium oxalate crystals, cholesterol crystals, and asteroid bodies) are frequent in giant cells of sarcoid granulomas (Fig. 3). Although Schaumann bodies are relatively more common in sarcoidosis than in other granulomatous diseases [21], none of these inclusions is specific and they can occur in granulomas of any cause. They are endogenous by-products of macrophage metabolism, and they should not lead the pathologist to the erroneous diagnosis of foreign material and foreign-body granulomas.
Sarcoid granulomas may fuse into large fibrogranulomatous masses, so-called nodular sarcoid, which can simulate a neoplastic process radiologically (Fig. 4). In nodular sarcoid, the lymphatic distribution of granulomas may not be readily apparent: A clue is to look at the periphery of the mass, where sometimes the lymphatic localization is still recognizable. Nodules may become extensively fibrotic, and it is important to do not misinterpret this hyaline, acellular fibrosis as necrosis. Occasionally, the fibrosis assumes a lamellar configuration and incorporates dust, simulating a silicotic nodule.
Although classically described as non-necrotizing, some necrosis is in fact quite common in sarcoid granulomas, being present in about 20 % of transbronchial biopsies [11] and more frequently in surgical biopsies. It generally consists of small foci of fibrinoid (“rheumatoid-like”) necrosis punctuating occasional granulomas, but larger areas of fibrinoid, infarct, or suppurative (“Wegener-like”) necrosis may be rarely seen (Fig. 5). The controversial entity necrotizing sarcoid granulomatosis [22, 23] is probably just an unusual variant of sarcoidosis in which necrosis is particularly prominent. In general, the presence of necrosis in granulomas should always raise the possibility of infection, and a diagnosis of necrotizing sarcoid granulomatosis should not even be considered until an infection has been rigorously excluded.
In sarcoidosis, inflammation is generally inconspicuous and limited to a thin rim of lymphocytes around granulomas: A significant cellular infiltrate with organizing pneumonia is unusual and should suggest an alternative diagnosis. However, rare examples of sarcoidosis are characterized by a significant inflammation (Fig. 6), particularly in early phases or as an expression of obstructive pneumonia when granulomas occlude the bronchial tree.
With time, hyaline collagen penetrates the granulomas, which may become so fragmented to be barely recognizable. Occasionally, scattered giant cells (or even just isolated Schaumann bodies) entrapped within dense fibrosis may remain as the only marker of an old sarcoidosis. In some of these cases, the lymphatic distribution of the fibrosis is still recognizable, and when this occurs, it is a helpful diagnostic clue (Fig. 7). Sarcoidosis generally heals leaving normal or slightly scarred lung but occasionally progresses to significant fibrosis with traction bronchiectasies and honeycombing [24]. Aspergilloma may colonize these chronic cystic cavities.
Being frequently asymptomatic, sarcoidosis may occasionally represent just a background incidental finding in a biopsy performed for another disease.
Differential Diagnosis
The diagnosis of sarcoidosis cannot be rendered solely by the pathologist (except perhaps at autopsy), since there are several other granulomatous disorders that mimic sarcoidosis, particularly infections (Table 1 and Fig. 8) [11, 25], and in individual cases, the clinical, laboratory, and radiologic findings are critical in determining a final diagnosis.
Mycobacteria and some fungi are an important cause of granulomatous inflammation, most commonly necrotizing. However, when non-necrotizing infectious granulomas occur, a random rather than lymphangitic distribution of granulomas in the lung parenchyma as well as the presence of polymorphonucleates in and around granulomas are further histologic findings favoring an infection. Non-tuberculous mycobacteria lung involvement (e.g., Mycobacterium avium-intracellulare) may mimic sarcoidosis, forming bronchiolocentric non-necrotizing granulomas, as seen in hot tub lung [26].
Several fungal infections (e.g., Aspergillosis, Coccidioidomycosis, Blastomycosis, Histoplasmosis, and others) may produce granulomas in the lungs, but suppurative necrosis is often present and organisms apparent on methenamine silver staining [27, 28].
Although rare, Pneumocystis jiroveci infection may be responsible of granulomas (sometimes non-necrotizing), in patients with AIDS or bone marrow transplant recipients [29].
Hypersensitivity pneumonia may enter in differential diagnosis with sarcoidosis, but it is characterized by the presence of bronchiolocentric and/or interstitial, ill-defined, tiny, discohesive non-necrotizing granulomas and/or scatterd multinucleated giant cells. Moreover, the cellular infiltrate is generally much more prominent than the granulomas in hypersensitivity pneumonitis [11, 30].
Bronchiolocentric and vascular-centered non-necrotizing granulomas may be observed in chronic aspiration pneumonia and intravenous drug/talc injection, respectively. A careful search for exogenous matter and birefringent material (e.g., talc, microcrystalline cellulose) in the cytoplasm of foreign body giant cells can confirm the diagnosis (for both aspiration and IV talcosis [31, 32]. Pulmonary involvement from systemic extrapulmonary granulomatous disorders, such as Crohn’s disease or primaty biliary cirrhosis, may pose some diagnostic problems, but knowledge of clinical history and the finding of chronic bronchiolitis with non-necrotizing granulomas without the classic lymphangitic pattern are key features in differential diagnosis [33, 34].
An occupational history of chronic exposure to beryllium may be the only finding in discriminating berylliosis from sarcoidosis [35].
Invasive Diagnostic Procedures
The demonstration of granulomas in the correct clinico-radiologic context is generally required for the diagnosis of sarcoidosis [1, 2]. The biopsy should be directed to the most accessible affected site: For example, if the skin is involved, a cutaneous biopsy may lead to a rapid diagnosis. Frequently, however, the lung or the mediastinal lymph nodes are the target organs, because they are almost universally involved. The localization of the granulomas along the lymphatics in the lung enables a high diagnostic yield of the bronchoscopic procedures. The different bronchoscopic procedures can be combined together, further increasing their diagnostic yield [36]. Surgical lung and mediastinal lymph node biopsies should be reserved for atypical cases and for those patients in whom the diagnosis remains uncertain after bronchoscopy.
Bronchoalveolar Lavage (BAL)
Since a CD4 + T-helper 1 (Th1) lymphocytic alveolitis represents the early immunologic feature of sarcoidosis, a careful examination of bronchoalveolar lavage (BAL) fluid in patients with suspected sarcoidosis may be very helpful. Although the results of BAL cell count should always be interpreted together with clinical, imaging, and laboratory data, macrophages and lymphocytes are the main cells observed in BAL, with few neutrophils, about 1 % of eosinophils and lack of plasma cells and foamy macrophages [37]. This is particularly true in early phase of sarcoidosis, while an increase of neutrophils and mast cells is often found in advanced or chronic phase of the disease. Although the percentage of lymphocytes (ranging from 20 to 80 % with a mean value of 40 %) and an elevated CD4/CD8 ratio (≥3.5) may represent important findings (Fig. 9), about 10–15 % of patients with sarcoidosis may show normal or even decrease CD4/CD8 ratio in BAL. Increased CD4/CD8 ratio (over 3.5) on BAL has a sensitivity of 60 % and a specificity of 90–95 %, similar to that reported for transbronchial biopsy [38, 39].
More than 90 % of patients with sarcoidosis at diagnosis may show a lymphocytic alveolitis with a slightly increased total cell count. Nevertheless, several diseases in differential diagnosis with sarcoidosis may show lymphocytosis on BAL, such as hypersensitivity pneumonia (HP), connective tissue diseases (CTD), drug toxicity, or even extrapulmonary conditions involving the lung (e.g., Crohn disease or primary biliary cirrhosis) [38, 40].
The presence of plasma cells in BAL does exclude sarcoidosis, but it favors HP, CVD, or drug reaction. The finding of lymphocytosis with hemosiderin-laden macrophages is more consistent with vasculitis, CTD, idiopathic hemosiderosis, or drug toxicity [37, 38]. Immunocytochemistry using lymphoid markers (e.g., CD3, CD20, CD30) works quite well on BAL and may be useful to rule out lymphoproliferative disorders.
In summary, BAL fluid examination is a useful tool in the diagnostic workup of sarcoidosis. In addition, BAL examination together with the use of special stains (e.g., methenamine silver stain, Ziehl-Neelsen, periodic-acid Shiff) is particularly important in excluding a possible opportunistic infection in patients with sarcoidosis who show clinical deterioration while undergoing long-term immunosuppression.
Bronchial and Transbronchial Biopsies
Good-quality bronchial and transbronchial biopsies have a diagnostic yield (i.e., granulomas are present) of about 50 % (higher if a macroscopic lesion is seen) and 90 %, respectively, in patients with sarcoidosis [41–43]. Bronchial and transbronchial cryobiopsies, which obtain larger pieces of lung tissue, may further increase these percentages [44]. Since sarcoidosis may involve l the entire respiratory tree, it is not surprising to observe tiny granulomas at histology even in biopsies from “normal” or nearly normal appearing mucosa (e.g., localized erythema or slight thickening). So, it is useful to perform multiple endobronchial biopsies in all cases of suspected sarcoidosis, particularly when transbronchial biopsy is contraindicated [45].
When examining transbronchial biopsies, if the first section is negative, the pathologist should obtain additional levels to increase the probability to detect granulomas [46]. Sometimes, a transbronchial biopsy shows features which are almost diagnostic of sarcoidosis per se, namely numerous compact, non-necrotizing granulomas embedded within hyaline collagen. More often, however, bronchial or transbronchial biopsies show just a few tiny granulomas or even a single giant cell or a Schaumann body: In these cases, the pathologist can say just there is a granulomatous lesion, but the differential diagnosis among the different granulomatous diseases should be based on clinical data (Fig. 10).
Transbronchial Needle Aspiration (TBNA)
Sarcoidal granulomas may be reliably seen in smeared aspirates from transbronchial needle aspiration (TBNA) of hilar and mediastinal lymph nodes (Fig. 11). This technique is a useful diagnostic procedure in sarcoidosis, and non-necrotizing epithelioid granulomas may be observed in about 80 % of stage I and stage II disease. Sampling of at least two different lymph nodes and rapid-on-site evaluation (ROSE) of transbronchial aspirates significantly increase the diagnostic yield and reduce the complication rate of bronchoscopy, respectively [47, 48].
Cell block preparation from TBNA is an excellent method to better appreciate the architectural morphology of granulomas sampled from hilar or mediastinal lymph nodes, also consistently permitting immunostains when required (i.e., to exclude lymphoproliferative diseases).
The presence of a necrotic background around granulomas favors an infectious agent, mainly tuberculosis [3].
Final Remarks
-
Sarcoidosis is probably the most common cause of non-necrotizing granulomas in the lungs.
-
On histology, tightly packed, non-necrotizing granulomas surrounded by lamellar hyaline fibrosis and displaying a lymphangitic distribution are quite characteristic of sarcoidosis.
-
BAL fluid examination may be a diagnostic tool in the adequate clinico-radiologic scenario, either in supporting a diagnosis of sarcoidosis and in ruling out opportunistic infections in deteriorated patients with sarcoidosis treated with steroids.
-
Sarcoidal granulomas may be reliably identified on cytology obtained from TBNA of mediastinal lymph nodes (with or without EBUS).
-
Atypical forms of sarcoidosis may occur and knowledge of unusual histologic features (Table 2) is mandatory to prevent misdiagnoses.
References
Costabel U, Ohshimo S, Guzman J (2008) Diagnosis of sarcoidosis. Curr Opin Pulm Med 14:455–461
Judson MA, Baughman RP (2004) Sarcoidosis. In: Baughman RP, du Bois RM, Lynch JP, Wells AU (eds) Diffuse lung disease: a practical approach. Arnold, London, pp 109–129
Cancellieri A, Leslie KO, Tinelli C, Patelli M, Trisolini R (2013) Sarcoidal granulomas in cytological specimens from intrathoracic adenopathy: morphologic characteristics and radiographic correlations. Respiration 85:244–151
Colby TV, Carrington CB (1995) Interstitial lung disease. In: Thurlbeck WM, Churg AM (eds) Pathology of the lung. Thieme, New York, pp 589–738
Travis WD, Colby TV, Koss MN, Rosado-de-Christenson ML, Muller NL, King TE (2002) Atlas of nontumor pathology. Non-neoplastic disorders of the lower respiratory tract. ARP, New York
Myers JL (2005) Other diffuse lung diseases. In: Churg AM, Myers JL, Tazelaar HD, Wright JL (eds) Thurlbeck’s pathology of the lung. Thieme, New York, pp 601–674
Fukuoka J, Leslie KO (2011) Chronic diffuse lung diseases. In: Wick MR (ed) Practical pulmonary pathology. A diagnostic approach, Leslie, K., O. Elsevier, Philadelphia, pp 213–276
Katzenstein ALA (2006) Surgical pathology of non-neoplastic lung disease. Saunders, Philadelphia
Farver CF (2008) Sarcoidosis. In: Tomashefski JF, Cagle PT, Farver CF, Fraire AE (eds) Dail and Hammar’s pulmonary pathology. Springer, New York
Ma YL, Gal A, Koss MN (2007) The pathology of pulmonary sarcoidosis: update. Semin Diagn Pathol 24:150–161
Cheung OY, Muhm JR, Helmers RA et al (2003) Surgical pathology of granulomatous interstitial pneumonia. Ann Diagn Pathol 7:127–138
El-Zammar OA, Katzenstein ALA (2007) Pathological diagnosis of granulomatous lung disease: a review. Histopathology 50:289–310
Myers JL, Tazelaar HD (2008) Challenges in pulmonary fibrosis: 6. Problematic granulomatous lung disease. Thorax 63:78–84
Cavazza A, Harari S, Caminati A et al (2009) The histology of pulmonary sarcoidosis: a review with particular emphasis on unusual and underrecognized features. Intern J Surg Pathol 17:219–230
Criado E, Sanchez M, Ramirez J et al (2010) Pulmonary sarcoidosis: typical and atypical manifestations at high-resolution CT with pathologic correlation. Radiographics 30:1567–1586
Chambellan A, Turbie P, Nunes H, Brauner M, Battesti JP, Valeyre D (2005) Endobronchial stenosis of proximal bronchi in sarcoidosis. Chest 127:472–481
Takemura T, Matsui Y, Oritsu M et al (1991) Pulmonary vascular involvement in sarcoidosis: granulomatous angitis and microangiopathy in transbronchial biopsies. Virchows Arch A Pathol Anat Histopathol 418:361–368
Rosen Y, Moon S, Huang C, Gourin A, Lyons HA (1977) Granulomatous pulmonary angitis in sarcoidosis. Arch Pathol Lab Med 101:170–174
Takemura T, Matusi Y, Saiki S, Mikami R (1992) Pulmonary vascular involvement in sarcoidosis: a report of 40 autopsy cases. Hum Pathol 23:1216–1223
Nunes H, Humbert M, Capron F et al Pulmonary hypertension associated with sarcoidosis: mechanisms, haemodynamics and prognosis. Thorax 61:68-74
Hsu RM, Connors AF, Tomashefski JF (1996) Histologic, microbiologic, and clinical correlates of the diagnosis of sarcoidosis by transbronchial biopsy. Arch Pathol Lab Med 120:364–368
Churg A, Carrington CB, Gupta R (1979) Necrotizing sarcoid granulomatosis. Chest 76:406–413
Shirodaria CC, Nicholson AG, Hansell DM, Wells AU, Wilson R (2003) Necrotizing sarcoid granulomatosis with skin involvement. Histopathology 43:91–93
Xu L, Klingerman S, Burke A (2013) End-stage sarcoid lung disease is distinct from usual interstitial pneumonia. Am J Surg Pathol 37:593–600
Gal AA, Koss MN (2002) The pathology of sarcoidosis. Curr Opin Pulm Med 8:445–51
Khoor A, Leslie KO, Tazelaar HD, Helmers RA, Colby TV (2001) Diffuse pulmonary disease caused by nontuberculous mycobacteria in immunocompetent people (hot tub lung). Am J Clin Pathol 115:755–762
Mukhopadhyay S (2011) Role of histology in the diagnosis of infectious causes of granulomatous lung disease. Curr Opin Pulm Med 17:189–196
Mukhopadhyay S, Aubry MC (2013) Pulmonary granulomas: differential diagnosis, histologic features and algorithmic approach. Diagn Histopathol 19:288–297
Gal AA, Plummer AL, Langston AA, Mansour KA (2002) Granulomatous Pneumocystis carinii pneumonia complicating hematopoietic cell transplantation. Pathol Res Pract 198:553–558
Coleman A, Colby TV (1988) Histologic diagnosis of extrinsic allergic alveolitis. Am J Surg Pathol 12:514–518
Mukhopadhyay S, Katzenstein AL (2007) Pulmonary disease due to aspiration of food and other particulate matter: a clinicopathologic study of 59 cases diagnosed on biopsy or resection specimens. Am J Surg Pathol 31:752–759
Barnes TW, Vassallo R, Tazelaar HD, Hartman TE, Ryu JH (2006) Diffuse bronchiolar disease due to chronic occult aspiration. Mayo Clin Proc 81:172–176
Casey MB, Tazelaar HD, Myers JL et al (2003) Noninfectious lung pathology in patients with Crohn’s disease. Am J Surg Pathol 27:213e9
Cavazza A, Rossi G, Corradi D et al (2010) Cellular non-specific interstitial pneumonia as a pulmonary manifestation of primary biliary cirrhosis. Pathology 46:596–598
Freiman DG, Hardy HL (1970) Beryllium disease: the relation of pulmonary pathology to clinical course and prognosis based on a study of 130 cases from the U.S. beryllium case registry. Hum Pathol 1:25–44
Shorr AF, Torrington KG, Hnautiuk OW (2001) Endobronchial biopsy for sarcoidosis: a prospective study. Chest 120:109–114
Drent M, Mansour K, Linssen C (2007) Bronchoalveolar lavage in sarcoidosis. Semin Respir Crit Care Med 28:486–495
Costabel U, Guzman J (2001) Bronchoalveolar lavage in interstitial lung disease. Curr Opin Pulm Med 7:255–261
Winterbauer RH, Lammert J, Selland M et al (1993) Bronchoalveolar lavage cell population in the diagnosis of sarcoidosis. Chest 104:352–361
Camus P, Colby TV (2000) The lung in inflammatory bowel disease. Eur Respir J 15:5–10
Leslie KO, Gruden JF, Parish JM, Scholand MB (2007) Transbronchial biopsy interpretation in the patient with diffuse parenchymal lung disease. Arch Pathol Lab Med 131:407–423
Colby TV (2010) The pathologist’s approach to bronchoscopic biopsies. Pathologica 102:432–442
Poletti V, Chilosi M, Olivieri D (2004) Diagnostic invasive procedures in diffuse infiltrative lung diseases. Respiration 71:107–119
Poletti V, Casoni GL, Gurioli C, Ryu JH, Tomassetti S (2014) Lung cryobiopsies: a paradigm shift in diagnostic bronchoscopy? Respirology 19(5):645–54
Chapman JT, Mehta AC (2003) Bronchoscopy in sarcoidosis: diagnostic and therapeutic interventions. Curr Opin Pulm Med 9:402–7
Takamaya K, Nagata N, Miyagawa Y, Hirano H, Shigematsu N (1992) The usefulness of step sectioning of transbronchial biopsy specimen in diagnosing sarcoidosis. Chest 102:1441–1443
Trisolini R, Tinelli C, Cancellieri A et al (2008) Transbronchial needle aspiration in sarcoidosis: yield and predictors of a positive aspirate. J Thorac Cardiovasc Surg 135:837–842
Trisolini R, Cancellieri A, Tinelli C et al (2011) Rapid on-site evaluation of transbronchial aspirates in the diagnosis of hilar and mediastinal adenopathy: a randomized trial. Chest 13:395–401
Compliance with Ethical Standards
The manuscript has not been submitted to more than one journal for simultaneous consideration.
The manuscript has not been published previously (partly or in full), unless the new work concerns an expansion of previous work (please provide transparency on the re-use of material to avoid the hint of text-recycling (“self-plagiarism”)).
A single study is not split up into several parts to increase the quantity of submissions and submitted to various journals or to one journal over time (e.g., “salami publishing”).
No data have been fabricated or manipulated (including images) to support your conclusions.
No data, text, or theories by others are presented as if they were the author’s own (“plagiarism”). Proper acknowledgements to other works must be given (this includes material that is closely copied (near verbatim), summarized, and/or paraphrased); quotation marks are used for verbatim copying of material, and permissions are secured for material that is copyrighted.
Consent to submit has been received explicitly from all co-authors, as well as from the responsible authorities—tacitly or explicitly—at the institute/organization where the work has been carried out, before the work is submitted.
Authors whose names appear on the submission have contributed sufficiently to the scientific work and therefore share collective responsibility and accountability for the results.
This is a review article that does not involve human participants and does not require informed consent.
The study does not involve animals.
Conflict of Interest
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Rossi, G., Cavazza, A. & Colby, T.V. Pathology of Sarcoidosis. Clinic Rev Allerg Immunol 49, 36–44 (2015). https://doi.org/10.1007/s12016-015-8479-6
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12016-015-8479-6