GLILD Revisited: Pulmonary Pathology of Common Variable and Selective IgA Immunodeficiency.

Common variable immunodeficiency (CVID) and selective immunoglobulin A deficiency (IgAD) often cause chronic lung disease, but the pulmonary pathologic features of these systemic diseases are poorly recognized by pathologists. It has been claimed that CVID cases show a characteristic combination of noncaseating granulomas-lymphoid proliferations termed granulomatous-lymphocytic interstitial lung disease (GLILD). We present 34 surgical lung biopsy cases of CVID and 4 of IgAD. Noncaseating granulomas were seen in 23/34 (68%) CVID and 2/4 (50%) IgAD cases. A statistically identical pattern of benign lymphoid proliferation was found in CVID and IgAD whether or not granulomas were present. Organizing pneumonia, sometimes considered a part of GLILD, was seen in 25/34 (74%) CVID and 2/4 (50%) IgAD cases and did not correlate with the presence of granulomas. On follow-up, 3 CVID patients died (only 1 of pulmonary disease), while 21 others are alive at 1 to 300 months with no difference by presence or absence of granulomas. Three IgAD patients with follow-up are alive. We conclude that CVID and IgAD are indistinguishable in surgical lung biopsies and a subset of both show patterns that would qualify as GLILD, while other cases lack granulomas but have identical patterns of lymphoid infiltration and organizing pneumonia. We suggest that GLILD is neither a specific nor a useful entity, and biopsies from CVID and IgAD patients should be diagnosed simply by microscopic pattern(s) observed. The prognosis of CVID with lymphoid infiltrates with or without granulomas in this series was good, contrary to claims in the literature about GLILD.

The Necessity of Anti-Tuberculosis Therapy after Resection of Pulmonary Tuberculous Nodules: A Single Center Retrospective Study.

PURPOSE: To discuss the necessity of anti-tuberculosis therapy after resection of asymptomatic pulmonary tuberculous nodules: is postoperative anti-tuberculosis therapy is over-treatment? METHODS: This is a single-center retrospective study. Patients with solitary pulmonary nodule (SPN) and diagnosed as tuberculosis by pathology were included. Clinical features are collected. The primary end point is tuberculosis relapse and the secondary is adverse drug reactions. Patients are divided into two groups according to the acceptance of anti-tuberculosis treatment after operation (A: treated; B: untreated). Recurrence is diagnosed by multi-disciplinary discussion. The difference of recurrence rate will be compared and the incidence of adverse drug reactions in Group A will be calculated. RESULTS: A total of 98 patients were enrolled, 66 in Group A and 32 in Group B. No significant difference between two groups was found in the past history of tuberculosis, erythrocyte sedimentation rate (ESR), T-spot positive rate, and the uptake value of 18F-glucose. No relapse of tuberculosis was found in both groups. The incidence of adverse drug reactions in Group A was 61% (40/66), and the rate of severe adverse reaction was 14% (9/66). CONCLUSIONS: Postoperative recurrence of tuberculosis is rare, anti-tuberculosis treatment seems unnecessary for asymptomatic pulmonary tuberculous nodules. Adverse drug reactions should not be ignored.

Pleuroparenchymal Fibroelastosis: A Review of Histopathologic Features and the Relationship Between Histologic Parameters and Survival.

Pleuroparenchymal fibroelastosis (PPFE) is now a defined clinicopathologic entity in the updated 2013 ATS/ERS classification of idiopathic interstitial pneumonias (IIPs), which has led to a significant increase in cases being diagnosed at our institution. We have therefore reviewed 43 PPFE cases (58 biopsies in total) to assess whether any clinical or histopathologic features provide prognostic information. A semiquantatitive grading system was used to assess extent of fibroblastic foci, intra-alveolar fibroelastosis, visceral pleural fibrosis, chronic inflammation in areas of fibrosis, vascular fibrointimal thickening, and presence of granulomas. Other patterns of interstitial lung disease were also noted, if present. All biopsies showed intra-alveolar fibroelastosis, fibroblastic foci at the leading edge of fibrosis and chronic inflammation within areas of fibrosis, 91% showed vascular fibrointimal thickening of vessels, 73% showed pleural fibrosis, and 35% showed granulomas. Ten cases showed a coexistent IIP (5 showed usual interstitial pneumonia, 5 showed features of hypersensitivity pneumonitis). There was no significant correlation with mortality and severity of histologic parameters, other than a significant decrease in mortality in PPFE with coexistent granulomas, after adjusting for age and gender (hazard ratio, 0.27; P=0.049). Male gender was also associated with an increased risk of mortality, after adjusting for age (hazard ratio, 4.8; P=0.045). PPFE is more common than previously thought, not infrequently showing coexistent pathology, specifically usual interstitial pneumonia and granulomatous lung disease, our data suggesting the latter may have prognostic significance.

Transplant Pulmonary Interventions: Translating Lung Transplant Interventions to Nontransplant Patients.

Roughly 10% of lung transplant recipients experience airway complications. Although the incidence has decreased dramatically since the first lung transplants were performed in the 1960s, airway complications have continued to adversely affect outcomes. Bronchoscopic interventions such as balloon dilation, airway stenting, and endobronchial electrocautery play an important role in ameliorating the morbidity and mortality associated with these complications. This review describes the array of bronchoscopic interventions used to treat airway complications after lung transplant and how these techniques can be used in nontransplant settings as well.

Versatile myeloid cell subsets contribute to tuberculosis-associated inflammation.

Tuberculosis (TB), a chronic bacterial infectious disease caused by Mycobacterium tuberculosis (Mtb), typically affects the lung and causes profound morbidity and mortality rates worldwide. Recent advances in cellular immunology emphasize the complexity of myeloid cell subsets controlling TB inflammation. The specialization of myeloid cell subsets for particular immune processes has tailored their roles in protection and pathology. Among myeloid cells, dendritic cells (DCs) are essential for the induction of adaptive immunity, macrophages predominantly harbor Mtb within TB granulomas and polymorphonuclear neutrophils (PMNs) orchestrate lung damage. However, within each myeloid cell population, diverse phenotypes with unique functions are currently recognized, differentially influencing TB pneumonia and granuloma functionality. More recently, myeloid-derived suppressor cells (MDSCs) have been identified at the site of Mtb infection. Along with PMNs, MDSCs accumulate within the inflamed lung, interact with granuloma-residing cells and contribute to exuberant inflammation. In this review, we discuss the contribution of different myeloid cell subsets to inflammation in TB by highlighting their interactions with Mtb and their role in lung pathology. Uncovering the manifold nature of myeloid cells in TB pathogenesis will inform the development of future immune therapies aimed at tipping the inflammation balance to the benefit of the host.

[Granulomatous interstitial lung diseases]. / Pneumopathies interstitielles granulomateuses.

Sarcoidosis is sometimes severe and, in this setting, some investigations like thoracic computed tomography and pulmonaruy function tests constitute an angular stone. In 25% of cases, the presentation is not typical and diagnosis may be difficult. Some lung granulomatosis may share a very similar presentation with sarcoidosis according to clinic, imaging, serum biology, broncho-alveolar lavage and pathology (berylliosis, immuno-deficiency and drug- induced lung granulomatosis). Eventually, lung Langerhans histiocytosis is a very rare disease observed in young adults with heavy smoking habits and thoracic CT is the crucial investigation to reach diagnosis in 80% of cases.

A case of granulomatous lung disease in a patient with Good's syndrome.

Good's syndrome is extremely rare. This adult-onset condition is characterized by a thymoma with immunodeficiency, low B- and T-cell counts, and hypo-gammaglobulinemia. The initial clinical presentation is either a mass-lesion thymoma or a recurrent infection. Patients with Good's syndrome are very susceptible to infections; common respiratory and opportunistic infections can be life-threatening. There are no reports of granulomatous lung disease in patients with Good's syndrome, although it has been observed in patients with common variable immunodeficiency, of which Good's syndrome is a subset. We describe a 53-year-old male thymoma patient who presented with respiratory symptoms caused by granulomatous lung disease and an opportunistic infection. He died of uncontrolled fungal infection despite repeated intravenous immunoglobulin and supportive care. Clinicians should look for evidence of immunologic dysfunction in thymoma patients presenting with severe recurrent infections, especially opportunistic infections.

Pulmonary sarcoidosis.

Sarcoidosis, a granulomatous disorder of unknown etiology, characteristically involves multiple organs. However, pulmonary manifestations typically dominate. Chest radiographs are abnormal in 85 to 95% of patients. Abnormalities in pulmonary function tests are common and may be associated with cough, dyspnea, and exercise limitation. However, one third or more of patients are asymptomatic, with incidental abnormalities on chest radiographs. The clinical course and expression of pulmonary sarcoidosis are variable. Spontaneous remissions occur in nearly two thirds of patients. The course is chronic in up to 30% of patients. Chronic pulmonary sarcoidosis may result in progressive (sometimes life-threatening) loss of lung function. Fatalities ascribed to sarcoidosis occur in 1 to 4% of patients. Although the impact of treatment is controversial, corticosteroids may be highly effective in some patients. Immunosuppressive, cytotoxic, or immunomodulatory agents are reserved for patients failing or experiencing adverse effects from corticosteroids. Lung transplantation is a viable option for patients with life-threatening disease failing medical therapy.

Interferon-induced granulomatous lung disease.

PURPOSE OF REVIEW: Interferon therapy can induce or exacerbate sarcoidosis. With the increasing use of interferons it is highly likely that more cases of sarcoidosis will be encountered by clinicians. We describe three unusual cases of interferon-induced sarcoidosis and review the most recent relevant literature on this subject. RECENT FINDINGS: Interferons, on account of their antiviral antigrowth and immunomodulatory effects, are used to treat various internal and dermatological diseases. Exogenously administered interferons stimulate the Th-1 response, which plays a major role in granuloma formation. In most of the patients with interferon-induced sarcoidosis, the disease subsides when interferon is discontinued. Occasionally, treatment with corticosteroids may become necessary. SUMMARY: Interferon therapy can induce or exacerbate sarcoidosis, the disease disappears when interferon is discontinued, sometimes treatment with corticosteroids is required.

Necrotizing sarcoid granulomatosis: a rarity in childhood.

Necrotizing sarcoid granulomatosis (NSG) is characterized by pulmonary nodular infiltrates, a typical histology, and a benign clinical course. The etiology and pathogenesis of the disease are still unknown. In childhood, it is extremely rare, with only three reported cases so far. Here we report on an 8-year-old girl, who to our knowledge is the youngest reported patient with NSG. The girl presented with shortness of breath and a sore throat. Chest X-ray and computed tomography (CT) scan revealed multiple nodular opacities of the lung. The symptoms and radiological findings disappeared within 6 months without any treatment. The diagnosis was based on the typical signs and symptoms of NSG and on the exclusion of other diseases. As abnormal immunological findings such as the lack of specific diphtheria antibodies in spite of vaccination against diphtheria were present, we suggest that immunologic mechanisms could play an etiologic role in the pathogenesis of NSG. In addition, the ratio of CD4+/CD8+ T-cells in the peripheral blood was significantly reduced, whereas the CD4+/CD8+ T-cell ratio in the immunohistochemical staining of the lung tissue was elevated. Since this compartmentalization is a typical finding in sarcoidosis, it supports the theory that NSG may represent a variant of sarcoidosis. However, because some characteristics of NSG are uncommon in typical sarcoidosis, NSG may also be an entity in its own right.

Primary lymphoepithelioma-like carcinoma of the lung.

Primary lymphoepithelioma-like carcinoma (LELC) of the lung is a neoplasm seen most commonly in the nasopharynx of individuals from south China and Taiwan, and is strongly associated with the Epstein-Barr virus. The case of a 62-year-old Chinese man with a rare primary lung T2N1M0 LELC of the left lower lobe is presented. The lesion was further notable because of the presence of necrotizing granulomatous inflammation. The patient was treated with surgical resection. After it was determined that the neoplasm was of primary lung origin, adjunctive chemotherapy was initiated. The role of adjunctive chemotherapy in this setting is discussed.

Isolated endobronchial atypical mycobacterium in a child: a case report and review of the literature.

Isolated endobronchial lesions caused by Mycobacterium avium are rare, especially in the pediatric population. We share the case of a 10-month-old boy who, after 1 week of cough and low-grade fever, had a radiographic examination showing endobronchial obstruction. At bronchoscopy, a granuloma of the left bronchus intermedius was found. Histopathologic examination revealed necrotizing granulomatous inflammation. Kinyoun Acid Fast stain revealed acid fast bacilli. Cultures were positive for M. avium. Current treatment options and controversies are presented. The roles of antibiotics and steroids in preventing progressive disease are discussed. The need for serial bronchoscopy and the potential benefits of surgical resection are discussed. Isolated endobronchial M. avium infection remains a rare and challenging problem. The paucity of clinical experience, and variation in patient presentation, obligates a high index of suspicion, and frequent follow-up with bronchoscopic examination and pulmonary assessment, for the child diagnosed with isolated endobronchial atypical mycobacterial infection.

Bronchocentric granulomatosis as a first clinical manifestation in an adult patient with p67phox deficiency.

We report on a case of adult chronic granulomatous disease which first manifested as a pulmonary mass, and was histologically diagnosed as bronchocentric granulomatosis associated with aspergillosis in a patient with a deficiency of p67phox and a low oxidative response. Antifungal treatment was required for clinical resolution.

Differential expression and cross-regulatory function of RANTES during mycobacterial (type 1) and schistosomal (type 2) antigen-elicited granulomatous inflammation.

The role of RANTES in Th1 and Th2 cell-mediated immune responses has been enigmatic. To approach this question, we analyzed RANTES expression and function in murine models of types 1 and 2 cell-mediated pulmonary granulomas elicited with Mycobacterium bovis or Schistosoma mansoni egg Ag-coated beads, respectively. Compared with type 2, type 1 lesions had up to 4-fold greater RANTES protein and mRNA production. Type 1 draining lymph nodes also produced up to 7-fold higher levels of RANTES. Anti-RANTES Ab treatments had opposite effects, decreasing type 1 lesion area by 25% and augmenting type 2 lesions by 50%. The latter was associated with increased IL-4, IL-5, IL-10, and IL-13 production by lymph nodes. Infusion of rRANTES (1 mg/kg/day) did not affect type 1 lesions, but reduced type 2 lesion area by 27% and eosinophils by 40%. Lymph node cultures from RANTES-treated mice had augmented type 1 and impaired type 2 responses. In vitro, RANTES caused selective, dose-related inhibition of IL-4 that was largely dependent on CCR1 receptors. In conclusion, RANTES plays different roles in types 1 and 2 granuloma formation, promoting the former and mediating cross-regulatory inhibition of the latter. Moreover, RANTES may have therapeutic potential in the treatment of established type 2 hypersensitivity.