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A 66-Year-Old Man With Mediastinal Mass and Dyspnea FREE TO VIEW

Narendra Kumar Narahari, MD, FCCP; Paramjyothi K. Gongati, MD; Shantveer G. Uppin, MD; Anu Kapoor, MD; Bhaskar Kakarla, MD; Ramakrishna Dev Tella, MS, MCh
Author and Funding Information

aDepartment of Respiratory Medicine, Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad, Telangana, India

bDepartment of Pathology, Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad, Telangana, India

cDepartment of Radiology and Imaging, Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad, Telangana, India

dDepartment of Cardiothoracic Surgery, Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad, Telangana, India

CORRESPONDENCE TO: Narendra Kumar Narahari, MD, FCCP, Department of Respiratory Medicine, Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad, Telangana, 500082, India


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;150(4):e109-e115. doi:10.1016/j.chest.2016.07.002
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A 66-year-old man presented with dry cough and shortness of breath on exertion of 6 months' duration. There were no complaints of fever and hemoptysis. His history was significant for recurrent episodes of respiratory tract infections over the previous 4 years. He had also had episodes of recurrent otitis media and pus discharge from the left ear for 3 years, with progressive loss of hearing. There was no history of recurrent skin infections or diarrhea. He was treated symptomatically with antibiotics by local general practitioners. He was a nonsmoker and did not drink alcohol, and there was no history of environmental or occupational exposure. He had been known to have diabetes for 10 years. He had negative results for the presence of HIV and hepatitis B surface antigen.

Figures in this Article

General examination showed pallor and clubbing. On oral examination, the buccal mucosa and tongue showed white and violaceous lacy plaques, a few coalescing to form a reticulate pattern on an erythematous base. A few erosions were also seen on the buccal mucosa (Fig 1). Punch biopsy samples of the lesion confirmed lichen planus. The patient's blood test results revealed a normal hemoglobin value and total leukocyte count, with 86% neutrophils and 7% lymphocytes. Auscultation revealed bilateral basal fine crepitation.

Figure 1
Figure Jump LinkFigure 1 A, Buccal mucosa. B, Inferior labial mucosa. C, Tongue showing white and violaceous lacy plaques, a few coalescing to form reticulate pattern on an erythematous base. A few erosions are also seen on the buccal mucosa. Plaque formation and brownish discoloration of teeth and gingivae also noted, indicating poor oral hygiene.Grahic Jump Location

His chest radiograph showed a well-defined homogeneous opacity in the right paracardiac region silhouetting the right cardiac border, suggestive of an anterior mediastinal mass (Fig 2A). Chest CT imaging confirmed a dense soft-tissue mass with calcification located in the right anterior mediastinum. The mass showed mild homogeneous enhancement with no infiltration of adjacent pleura or mediastinal structures. There was no significant mediastinal lymphadenopathy (Fig 2B). Fine-needle aspiration of this lesion confirmed the diagnosis of thymoma (type A). High-resolution CT (HRCT) images in lung window settings revealed multiple tiny ill-defined randomly distributed nodules in both lungs, with areas of diffuse ground-glass attenuation (Figs 2C-E).

Figure 2
Figure Jump LinkFigure 2 A, Chest radiograph shows a homogeneous opacity in right paracardiac region, with indistinct right cardiac border suggestive of an anterior mediastinal mass. In addition, faint nodularity is noted in both lung fields. B, Contrast-enhanced axial CT image of the chest shows a homogeneous soft-tissue lesion with calcification in right anterior mediastinum. C-E, High-resolution CT (HRCT) images in lung window settings reveal diffuse ground-glass attenuation of lung parenchyma with multiple tiny ill-defined randomly distributed nodules in both centrilobular and subpleural locations along the fissures (white arrows in C and D).Grahic Jump Location

Pulmonary function tests confirmed the restrictive pattern, with an FEV1 of 2.05 L (82% of predicted), FVC of 2.34 L (67% of predicted), FEV1/FVC of 121% of predicted, and diffusion capacity for carbon monoxide 41% of predicted. A 6-minute walk test was performed during which the patient ambulated 271 m against a predicted distance of 557.65 m. At the end of the test, his oxygen saturation fell from 98% to 94%, and his respiratory rate increased from 24 breaths per minute to 32 breaths per minute. The rest of his vital signs did not show any significant change.

He underwent thymectomy and a surgical lung biopsy procedure. Sections from the thymic mass showed diffusely arranged monomorphous plump spindle cells admixed with a few lymphocytes, consistent with type A thymoma (Figs 3A, 3B). Sections from the lung biopsy showed peribronchiolar and interstitial infiltrates composed mainly of lymphocytes along with some histiocytes (Figs 3C, 3D). In addition, there were scattered interstitial aggregates of epithelioid cells and giant cells forming ill-defined loose nonnecrotizing granulomas (Figs 3E, 3F). Acid-fast bacilli and Gomori methenamine silver staining were negative for any microorganisms. Immunohistochemistry (IHC) showed the infiltrating lymphocytes to be only T cells (CD3 positive) without any CD20-positive B lymphocytes (Figs 3G, 3H) IHC also highlighted CD68-positive interstitial histiocytes (Fig 3I).

Figure 3
Figure Jump LinkFigure 3 A and B, Section from the anterior mediastinal mass shows diffusely arranged monomorphous plump spindle cells admixed with lymphocytes. C, Section from lung biopsy sample shows peribronchiolar and interstitial lymphomononuclear infiltrates. D, Section shows thickened alveolar septa with infiltrates of predominantly lymphocytes and a few histiocytes. E and F, Interstitial aggregate of epithelioid cells and giant cells (arrow) forming ill-defined loose nonnecrotizing granuloma. G, CD3 positivity of lymphocytes in the interstitial infiltrate. H, Negative staining for CD20 in the interstitial lymphocytic infiltrate. I, CD68 highlights the histiocytes within the interstitial infiltrate.Grahic Jump Location

What is the diagnosis and what other tests are recommended to establish the diagnosis?

Diagnosis: Good syndrome (thymoma with immunodeficiency) with rare association of granulomatous lymphocytic interstitial lung disease. Further investigations recommended include determination of serum immunoglobulin levels and flow cytometric analysis of T- and B-cell subsets.

In view of a history of recurrent respiratory tract infections, the presence of autoimmune manifestations such as lichen planus along with thymoma, a possible thymoma-associated immunodeficiency disorder was considered. He was further investigated for serum immunoglobulin levels and quantification of T- and B-cell subsets by flow cytometry. His immunoglobulin profile revealed panhypogammaglobulinemia, and flow cytometry showed a complete absence of B cells, which confirmed the diagnosis of Good syndrome (GS).

Clinical Findings

GS is an extremely rare adult-onset primary immunodeficiency associated with thymoma. This association was first described by Dr Robert Good in 1954. It is classified as a distinct clinical entity separate from common variable immunodeficiency (CVID). Although there are no definite diagnostic criteria, it is characterized clinically by an increased propensity for infections and immunologically by hypogammaglobulinemia, absent or reduced B cells, and variable defects in cellular immunity such as CD4 T-cell lymphopenia, an abnormal or inverted CD4:CD8+ T-cell ratio, and impaired T-cell proliferation in response to mitogens and antigens in the presence of thymoma. A list of B-cell disorders and their important features are provided in Table 1.

Table Graphic Jump Location
Table 1 B-Cell Disorders: Age of Presentation and Important Clinical and Laboratory Findings

The etiopathogenesis of GS remains unknown. Evidence in the literature suggests that a basic defect in the bone marrow, autoimmune phenomena, and a T-cell defect probably play major roles. Sinopulmonary infections are the hallmark of GS due to B-cell deficiency, and defects in cell-mediated immunity cause opportunistic fungal and viral infections. Diarrhea is commonly seen in GS in about one-third of patients. Noninfectious pulmonary complications such as autoimmune manifestations and ILD are known to occur in immunodeficiency syndromes like CVID but are rarely reported with GS. These complications are now being recognized as important prognostic indicators, as immunoglobulin replacement therapy reduces the frequency of infections. Autoimmune manifestations are reported in 59% of patients with GS and mainly include myasthenia gravis, lichen planus, pure red cell aplasia, and various other hematologic manifestations. In a systematic review of GS by Kelesidis and Yang, oral lichen planus was reported in 11 cases, comprising 12.4% of total autoimmune manifestations. The patient in our study also had histologically confirmed oral lichen planus.

Granulomatous lymphocytic interstitial lung disease (GL-ILD), a variant of ILD, is frequently observed in patients with CVID and carries a very grave prognosis. It is speculated that GL-ILD in GS occurs due to a pathogenesis of immune deficiency that is similar and shared by the two entities. Only two cases reported in the literature showed GL-ILD associated with GS., GL-ILD usually presents at the time of diagnosis or within the first 5 years after diagnosis, as was observed in CVID, and carries a worse overall prognosis. The lung is the most commonly affected organ in GL-ILD, along with the spleen and lymph nodes. The main presenting features of GL-ILD include dry cough and dyspnea, with splenomegaly as the predominant clinical finding. Pulmonary function shows a restrictive pattern with a reduced diffusion capacity, but occasionally patients with normal lung function have some degree of interstitial involvement, making HRCT an important tool in diagnostic evaluation.

The main conditions to be considered in adults with frequent respiratory infections include chronic rhinosinusitis, primary immunodeficiency (eg, CVID, thymoma-associated immunodeficiency, chronic granulomatous disease [CGD]), secondary immunodeficiency, primary ciliary dyskinesia, cystic fibrosis, structural airway abnormalities, recurrent aspiration syndromes, allergic airway disease).

Among the patients with primary immunodeficiency presenting with frequent respiratory infections, an absent or reduced number of peripheral B cells, opportunistic infections due to defects in cell-mediated immunity, old age, association with thymoma, and high mortality differentiate GS from CVID. Conversely, patients with CGD usually present in the first 2 years of life. This is primarily a disorder of phagocytic function leading to recurrent bacterial and fungal infections in various body sites along with recurrent skin infections and diarrhea. Unlike GS, CGD does not have any association with thymoma.

Radiologic Findings

Thoracic imaging in the patient in our study confirmed the presence of thymoma, with no evidence of pleural, lung, or mediastinal invasion. The lung parenchyma showed ground-glass attenuation and multiple ill-defined randomly distributed nodules in both centrilobular and subpleural locations. The presence of reticular opacities and nodules are not typical of GS and are more suggestive of GL-ILD. Hence, based on these findings, a differential diagnosis of granulomatous infection/GL-ILD was offered. Differentiating invasive from noninvasive thymoma using imaging criteria is difficult unless there is clear evidence of extension into the mediastinum or adjacent pleura or lung, and these findings were not observed in the patient in our study. Therefore, the possibility of lung metastasis from thymoma was not considered in this case for the following reasons: (1) CT imaging features were suggestive of noninvasive thymoma, (2) histopathologic features confirmed benign type A thymoma, and (3) nodular pulmonary metastasis from thymoma are extremely rare.

The characteristic radiologic findings in GL-ILD have been described by Park et al as generalized diffuse reticulation with lower-zone predominance (seen in 80% of patients) and large ill-defined bronchocentric nodules or small randomly distributed nodules (seen in 50% of patients). Nodules on imaging represent granulomatous or lymphoproliferative disease, and ground-glass attenuation represents lymphocytic interstitial pneumonia (LIP).

Lung imaging plays a major role in excluding an infective cause and guides appropriate selection of the lesions for histopathologic evaluation. Any deterioration in lung function may be due to interstitial involvement (apart from bronchiectasis, which is commonly observed in GS resulting from hypogammaglobulinemia). Therefore, HRCT of the chest is recommended in all patients with GS, as it helps in better appreciation and complete assessment of the respiratory complications.

Pathologic Findings

The histologic features noted in the present case were consistent with findings that have been reported in GL-ILD. There was no evidence of follicular bronchiolitis or lymphoid hyperplasia. The infiltrates were patchy and of variable density. The granulomatous lung disease in CVID is well documented, but the clinical and pathologic significance of GL-ILD in GS is not yet known and remains investigational. GL-ILD exhibits both nonnecrotizing granulomatous and lymphoproliferative histologic patterns, consisting of LIP, follicular bronchiolitis, and lymphoid hyperplasia. LIP is characterized by diffuse interstitial inflammatory infiltrates consisting of mature lymphocytes, plasma cells, and histiocytes. The proposed mechanism for the formation of granulomatous disease may be due to impaired T-cell function, and lymphoproliferative lesions may be due to aberrant B-cell homeostasis, disordered immune regulation, and chronic antigenic stimulation. The possible role of human herpes virus type 8 in the pathogenesis is speculated to trigger lymphocyte proliferation.

The histologic differential diagnosis in the present case included sarcoidosis, hypersensitivity pneumonitis, infection, and LIP with granulomas. The granulomas in GS, although also nonnecrotizing, are loose and poorly circumscribed in contrast to the compact and well-circumscribed granulomas of sarcoidosis., In addition, the granulomas in sarcoidosis have a lymphatic distribution in contrast to the random distribution in GS. The clinical findings of hypersensitivity pneumonitis are distinct enough to differentiate it from GS. The closest and most difficult histologic differential diagnosis is LIP with granulomas. LIP usually shows more dense and diffuse interstitial lymphocytic infiltration compared with that noted in GL-ILD, as was seen in this case. However, we personally believe it may be impossible at times to histologically differentiate between these two entities. The absence of any identifiable microorganisms on special staining made the possibility of infectious granulomatous disease less likely in this case. LIP in patients with HIV may have similar histologic findings but is more common in the pediatric population than in adults, and unlike GS, these patients commonly have serum polyclonal hypergammaglobulinemia.

The patient in our study was given IV immunoglobulin (IVIG) therapy and is receiving regular follow-up. He is being closely monitored for his lung condition without any active management at present. Treatment of GS involves thymectomy, IVIG therapy to maintain adequate trough IgG values, and aggressive antimicrobial therapy to combat infections. Thymectomy does not reverse the immunologic abnormalities in GS but is found to be beneficial in parathymic syndromes such as myasthenia gravis and pure red cell aplasia and is recommended because of its potential to reduce local and distant metastases.

Currently there are no guidelines for optimal treatment and standard of care in GL-ILD. Treatment options are variable based on the clinical condition of the patient and the decline in lung function. Corticosteroids are commonly used, and some of the literature has shown a response rate of 50% to 60% in patients with CVID. Some studies did not show long-lasting remission with corticosteroids, and because of significant side effects, other options such as therapy aimed at eliminating T cells and B cells are chosen. Recently, Chase et al showed that combination chemotherapy with rituximab and azathioprine resulted in significant improvement in pulmonary function and parenchymal abnormalities on lung imaging. Apart from establishing the diagnosis, IHC findings on lung biopsy samples may provide information about the type of the lymphocyte population present in lung infiltrates, which can help tailor the immunosuppressive therapy. Rituximab therapy may be ineffective and unnecessary in patients whose lung infiltrates lack CD20-positive B cells, as was seen in the patient in our study. Although the significance of GL-ILD in GS is not known at present because there have been only a few reported cases, it has become an important prognostic entity in patients with CVID, in whom an early diagnosis is considered essential to improving mortality and survival.

Noninfectious complications in immunodeficiency disorders are of major concern at present because of increasing mortality and morbidity. GL-ILD has become an important prognostic entity because of the worse prognosis observed in this condition. More research is warranted to unravel the mystery of its hidden pathogenesis and to develop firm conclusions, with an aim of providing the best standard of care. A surgical lung biopsy procedure is mandatory with diffuse lung involvement in GS and is essential to make a definitive diagnosis.

Financial/nonfinancial disclosures: None declared.

Other contributions:CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.

Good R.A. . Agammaglobulinaemia—a provocative experiment of nature. Bull U Minnesota. 1954;26:1-19 [PubMed]journal
 
Primary immunodeficiency diseases Report of an IUIS scientific committee. International Union of Immunological Societies. Clin Exp Immunol. 1999;118:1-28 [PubMed]journal
 
Kelleher P. .Misbah S.A. . What is Good’s syndrome? Immunological abnormalities in patients with thymoma. J Clin Pathol. 2003;56:12-16 [PubMed]journal. [CrossRef] [PubMed]
 
Kelesidis T. .Yang O. . Good's syndrome remains a mystery after 55 years: a systematic review of the scientific evidence. Clin Immunol. 2010;135:347-363 [PubMed]journal. [CrossRef] [PubMed]
 
Prasse A. .Kayser G. .Warnatz K. . Common variable immunodeficiency-associated granulomatous and interstitial lung disease. Curr Opin Pulm Med. 2013;19:503-509 [PubMed]journal. [CrossRef] [PubMed]
 
Lee S.H. .Lee S.M. .Yang S.C. .et al A case of granulomatous lung disease in a patient with Good's syndrome. Korean J Intern Med. 2008;23:219-222 [PubMed]journal. [CrossRef] [PubMed]
 
Jensen ML, Bendstrup E, Hilberg O. Granulomatous-lymphocytic interstitial lung disease and recurrent sinopulmonary infections in a patient with Good’s syndrome [published online ahead of print September 30, 2015].BMJ Case Rep.http://dx.doi.org/10.1136/bcr-2014-205635.
 
Park J.H. .Levinson A.I. . Granulomatous-lymphocytic interstitial lung disease (GLILD) in common variable immunodeficiency (CVID). Clin Immunol. 2010;134:97-103 [PubMed]journal. [CrossRef] [PubMed]
 
Park J.E. .Beal I. .Dilworth J.P. .Tormey V. .Haddock J. . The HRCT appearances of granulomatous pulmonary disease in common variable immune deficiency. Eur J Radiol. 2005;54:359-364 [PubMed]journal. [CrossRef] [PubMed]
 
Tarr P.E. .Sneller M.C. .Mechanic L.J. .et al Infections in patients with immunodeficiency with thymoma (Good syndrome). Report of 5 cases and review of the literature. Medicine (Baltimore). 2001;80:123-133 [PubMed]journal. [CrossRef] [PubMed]
 
Roos D. .de Boer M. . Molecular diagnosis of chronic granulomatous disease. Clin Exp Immunol. 2014;175:139-149 [PubMed]journal. [CrossRef] [PubMed]
 
Bates C.A. .Ellison M.C. .Lynch D.A. .Cool C.D. .Brown K.K. .Routes J.M. . Granulomatous- lymphocytic lung disease shortens survival in common variable immunodeficiency. J Allergy Clin Immunol. 2004;114:415-421 [PubMed]journal. [CrossRef] [PubMed]
 
Rao N. .Mackinnon A.C. .Routes J.M. . Granulomatous and lymphocytic interstitial lung disease: a spectrum of pulmonary histopathological lesions in common variable immunodeficiency—histologic and immunohistochemical analysis of 16 cases. Hum Pathol. 2015;46:1306-1314 [PubMed]journal. [CrossRef] [PubMed]
 
Das S. .Miller R.F. . Lymphocytic interstitial pneumonitis in HIV infected adults. Sex Transsm Infect. 2003;79:88-93 [PubMed]journal. [CrossRef]
 
Chase N.M. .Verbsky J.W. .Hintermeyer M.K. .et al Use of combination chemotherapy for treatment of granulomatous and lymphocytic interstitial lung disease (GLILD) in patients with common variable immunodeficiency (CVID). J Clin Immunol. 2013;33:30-39 [PubMed]journal. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1 A, Buccal mucosa. B, Inferior labial mucosa. C, Tongue showing white and violaceous lacy plaques, a few coalescing to form reticulate pattern on an erythematous base. A few erosions are also seen on the buccal mucosa. Plaque formation and brownish discoloration of teeth and gingivae also noted, indicating poor oral hygiene.Grahic Jump Location
Figure Jump LinkFigure 2 A, Chest radiograph shows a homogeneous opacity in right paracardiac region, with indistinct right cardiac border suggestive of an anterior mediastinal mass. In addition, faint nodularity is noted in both lung fields. B, Contrast-enhanced axial CT image of the chest shows a homogeneous soft-tissue lesion with calcification in right anterior mediastinum. C-E, High-resolution CT (HRCT) images in lung window settings reveal diffuse ground-glass attenuation of lung parenchyma with multiple tiny ill-defined randomly distributed nodules in both centrilobular and subpleural locations along the fissures (white arrows in C and D).Grahic Jump Location
Figure Jump LinkFigure 3 A and B, Section from the anterior mediastinal mass shows diffusely arranged monomorphous plump spindle cells admixed with lymphocytes. C, Section from lung biopsy sample shows peribronchiolar and interstitial lymphomononuclear infiltrates. D, Section shows thickened alveolar septa with infiltrates of predominantly lymphocytes and a few histiocytes. E and F, Interstitial aggregate of epithelioid cells and giant cells (arrow) forming ill-defined loose nonnecrotizing granuloma. G, CD3 positivity of lymphocytes in the interstitial infiltrate. H, Negative staining for CD20 in the interstitial lymphocytic infiltrate. I, CD68 highlights the histiocytes within the interstitial infiltrate.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 B-Cell Disorders: Age of Presentation and Important Clinical and Laboratory Findings

References

Good R.A. . Agammaglobulinaemia—a provocative experiment of nature. Bull U Minnesota. 1954;26:1-19 [PubMed]journal
 
Primary immunodeficiency diseases Report of an IUIS scientific committee. International Union of Immunological Societies. Clin Exp Immunol. 1999;118:1-28 [PubMed]journal
 
Kelleher P. .Misbah S.A. . What is Good’s syndrome? Immunological abnormalities in patients with thymoma. J Clin Pathol. 2003;56:12-16 [PubMed]journal. [CrossRef] [PubMed]
 
Kelesidis T. .Yang O. . Good's syndrome remains a mystery after 55 years: a systematic review of the scientific evidence. Clin Immunol. 2010;135:347-363 [PubMed]journal. [CrossRef] [PubMed]
 
Prasse A. .Kayser G. .Warnatz K. . Common variable immunodeficiency-associated granulomatous and interstitial lung disease. Curr Opin Pulm Med. 2013;19:503-509 [PubMed]journal. [CrossRef] [PubMed]
 
Lee S.H. .Lee S.M. .Yang S.C. .et al A case of granulomatous lung disease in a patient with Good's syndrome. Korean J Intern Med. 2008;23:219-222 [PubMed]journal. [CrossRef] [PubMed]
 
Jensen ML, Bendstrup E, Hilberg O. Granulomatous-lymphocytic interstitial lung disease and recurrent sinopulmonary infections in a patient with Good’s syndrome [published online ahead of print September 30, 2015].BMJ Case Rep.http://dx.doi.org/10.1136/bcr-2014-205635.
 
Park J.H. .Levinson A.I. . Granulomatous-lymphocytic interstitial lung disease (GLILD) in common variable immunodeficiency (CVID). Clin Immunol. 2010;134:97-103 [PubMed]journal. [CrossRef] [PubMed]
 
Park J.E. .Beal I. .Dilworth J.P. .Tormey V. .Haddock J. . The HRCT appearances of granulomatous pulmonary disease in common variable immune deficiency. Eur J Radiol. 2005;54:359-364 [PubMed]journal. [CrossRef] [PubMed]
 
Tarr P.E. .Sneller M.C. .Mechanic L.J. .et al Infections in patients with immunodeficiency with thymoma (Good syndrome). Report of 5 cases and review of the literature. Medicine (Baltimore). 2001;80:123-133 [PubMed]journal. [CrossRef] [PubMed]
 
Roos D. .de Boer M. . Molecular diagnosis of chronic granulomatous disease. Clin Exp Immunol. 2014;175:139-149 [PubMed]journal. [CrossRef] [PubMed]
 
Bates C.A. .Ellison M.C. .Lynch D.A. .Cool C.D. .Brown K.K. .Routes J.M. . Granulomatous- lymphocytic lung disease shortens survival in common variable immunodeficiency. J Allergy Clin Immunol. 2004;114:415-421 [PubMed]journal. [CrossRef] [PubMed]
 
Rao N. .Mackinnon A.C. .Routes J.M. . Granulomatous and lymphocytic interstitial lung disease: a spectrum of pulmonary histopathological lesions in common variable immunodeficiency—histologic and immunohistochemical analysis of 16 cases. Hum Pathol. 2015;46:1306-1314 [PubMed]journal. [CrossRef] [PubMed]
 
Das S. .Miller R.F. . Lymphocytic interstitial pneumonitis in HIV infected adults. Sex Transsm Infect. 2003;79:88-93 [PubMed]journal. [CrossRef]
 
Chase N.M. .Verbsky J.W. .Hintermeyer M.K. .et al Use of combination chemotherapy for treatment of granulomatous and lymphocytic interstitial lung disease (GLILD) in patients with common variable immunodeficiency (CVID). J Clin Immunol. 2013;33:30-39 [PubMed]journal. [CrossRef] [PubMed]
 
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