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.

Significance of coexistent granulomatous inflammation and lung cancer.

AIMS: Coexistence of lung cancer and granulomatous inflammation in the same patient confuses clinicians. We aimed to document the prevalence, clinicopathological features, treatment outcomes and prognosis in patients with coexisting granulomatous inflammation undergoing curative lung resection for lung cancer, in a tuberculosis (TB)-endemic country. METHODS: An observational cohort study of patients with lung cancer undergoing curative resection between 2012 and 2015 in a tertiary centre in Singapore. RESULTS: One hundred and twenty-seven patients underwent lung resection for cancer, out of which 19 (14.9%) had coexistent granulomatous inflammation in the resected specimen. Median age was 68 years and 58.2% were males. Overall median (range) survival was 451 (22-2452) days. Eighteen (14%) patients died at median duration of 271 days after surgery. The postsurgery median survival for those alive was 494 (29-2452) days in the whole group. Subgroup analysis did not reveal any differences in age, gender, location of cancer, radiological features, type of cancer, chemotherapy, history of TB or survival in patients with or without coexistent granulomatous inflammation. CONCLUSIONS: Incidental detection of granulomatous inflammation in patients undergoing lung resection for cancer, even in a TB-endemic country, may not require any intervention. Such findings may be due to either mycobacterial infection in the past or 'sarcoid reaction' to cancer. Although all patients should have their resected specimen sent for acid-fast bacilli culture and followed up until the culture results are reported, the initiation of the management of such patients as per existing lung cancer management guidelines does not affect their outcome adversely.

Disease Recurrence and Acute Cellular Rejection Episodes During the First Year After Lung Transplantation Among Patients With Sarcoidosis.

INTRODUCTION: Sarcoidosis is reported to recur after lung transplantation (LT). We sought to determine the frequency of recurrent disease after LT and predictors of recurrence. We also evaluated the incidence and severity of acute cellular rejection (ACR) episodes among these patients. METHODS: The database of LT patients at Cleveland Clinic was interrogated for sarcoidosis patients who underwent LT between May 1993 and 2011. Charts were reviewed for demographics, type of transplant, posttransplant biopsy findings, and outcomes. RESULTS: Data were available for 30 patients (mean age, 50 ± 9.3 years; range, 30-65 years; M-to-F ratio, 17:13; single-to-double-to-heart lung ratio, 5:24:1). Recurrence of sarcoidosis was noted among 7 patients (pathological recurrence in all and radiological findings suggesting recurrence in 1 patient) with no impact on overall outcomes. Presence of granulomas on explanted lungs was the only predictor of recurrence (85.7% vs 30.4%, odds ratio, 13.7; 1.4-136.2; P = 0.02).Overall burden of ACR episodes on all bronchoscopies was significantly lower in patients with disease recurrence (7.6 % vs 21.3% of biopsies, P = 0.038). Among patients with recurrent disease, ACR did not develop once disease recurrence had been seen on transbronchial biopsy. CONCLUSIONS: A significant proportion of sarcoidosis patients have disease recurrence after LT and presence of active granulomas on explant is associated with subsequent recurrence. There may be an association of recurrence with lower frequency of ACR episodes. There does not appear to be any impact of sarcoidosis recurrence on 1-, 3-, or 5-year survivals.

Incidence and aetiologies of pulmonary granulomatous inflammation: a decade of experience.

BACKGROUND AND OBJECTIVE: Granulomatous lung disease (GLD) is caused by a wide range of conditions. Often there is a need to correlate pathological findings with clinical, microbiological or radiological data to determine an aetiology. The aim of this study was to determine the different aetiologies of GLD over the past decade. METHODS: Among 2228 consecutive lung specimens from 1999 to 2011, 226 cases (10.1%) were positive for GLD. One hundred ninety patients were retrospectively reviewed and diagnoses were assigned based on availability of histological/clinical/microbiological correlation. RESULTS: A confident, probable and uncertain diagnosis was made in 68.4%, 13.2% and 18.4% patients. The aetiologies comprised infectious, non-infectious and uncertain in 54.7%, 26.8% and 18.4% patients. Mycobacterial infections constituted 27% of all patients, and included atypical, tuberculous and unclassified mycobacteria in order of frequency. Acid-fast bacilli (AFB) were visualized in tissue sections in 29% cases and cultured in 73% cases. Fungal infections comprised 27% of all cases, which included Coccidioides, Cryptococcus, Aspergillus and Histoplasma in order of frequency. Fungi were visualized in tissue sections with Gomori methenamine silver (GMS) stain in 83% patients and cultured in 52% cases. Sarcoidosis was the major non-infectious aetiology, constituting 21% of all patients. Necrosis in granulomas was associated with the presence of infection (P < 0.001). CONCLUSIONS: The aetiology in necrotizing GLD with negative AFB and GMS stains is most likely infectious due to atypical mycobacteria. Coccidioidomycosis was the most common fungal infection. The aetiology in non-necrotizing GLD is most likely non-infectious, probably sarcoidosis.

Common variable immunodeficiency-associated granulomatous and interstitial lung disease.

PURPOSE OF REVIEW: Common variable immunodeficiency (CVID) is the most common primary immunodeficiency characterized by a deficiency of immunoglobulins. Approximately 30% of the patients develop autoimmune and granulomatous disease. Similar to sarcoidosis, granulomatous disease in CVID can potentially affect all organs, but the lung is the most common. Interstitial lung disease (ILD) manifests in 5-15% of CVID patients, and is present already at the initial diagnosis in the majority of patients. The number of published studies addressing ILD in CVID is limited. However, recently, several studies added substantial knowledge to the field and are discussed within this review in the context of the literature. RECENT FINDINGS: Histologically, ILD in CVID presents within the known patterns of sarcoid-like granuloma, organizing pneumonia, lymphocytic interstitial pneumonitis and nonspecific interstitial pneumonia. Often, these patterns are concomitantly found in the same patients. Three new articles were published which analyzed high-resolution computed tomography findings and response to treatment. SUMMARY: In a considerable number of patients, ILD is stable over years and patients may not need any immunosuppressive treatment. Prednisone treatment is often used as the first-line treatment and studies suggest response to treatment in 50-66% of cases. In progressive disease with lung function impairment, combined immunosuppressive treatment is recommended.

FDG PET/CT evaluation of pathologically proven pulmonary lesions in an area of high endemic granulomatous disease.

PURPOSE: The goal of this study is to assess how reliable the threshold maximum standardized uptake value (maxSUV) of 2.5 on positron emission tomography-computed tomography (PET/CT) is for evaluation of solitary pulmonary lesions in an area of endemic granulomatous disease and to consider other imaging findings that may increase the accuracy of PET/CT. MATERIALS AND METHODS: The staging PET/CT of 72 subjects with solitary pulmonary lesions (nodules (less than 3 cm) or masses (greater than 3 cm)) were retrospectively reviewed. Pathology proven diagnosis from tissue samples was used as the gold standard. Logistic regression was used to assess whether the subject's age, maxSUV, size of lesion, presence of emphysema, or evidence of granulomatous disease was predictive of malignancy. RESULTS: Malignant lesions were identified in 84.7 % (61/72) of the 72 subjects. A threshold maxSUV of 2.5 had a sensitivity of 95.1 % (58/61), specificity of 45.5 % (5/11), positive predictive value of 90.6 % (58/64), negative predictive value of 62.5 % (5/8) and an accuracy of 87.5 % (63/72). The false negative rate was 4.9 %, and the false positive rate was 54.5 %. All 3 false negatives were less than or equal to 1.0 cm; however, false positives ranged from 1.1 to 5.6 cm. The false negatives had a mean (SD) maxSUV of 2.0 (0.4), whereas the false positives had a mean (SD) maxSUV of 5.6 (3.0). Emphysema was associated with 1.1 higher odds of malignancy, and evidence of granulomatous disease was associated with 0.34 lower odds of benign disease, however, neither was statistically significant (p = 0.92 and p = 0.31, respectively). Higher maxSUV was significantly associated with increased risk of malignancy (p = 8.3 × 10(-3)). Older age and larger size of lesion were borderline associated with increased risk of malignancy (p = 0.05 and p = 0.07, respectively). CONCLUSION: In an area of high endemic granulomatous disease, the PET/CT threshold maxSUV of 2.5 retains a high sensitivity (95.1 %) and positive predictive value (90.6 %) for differentiating benign from malignant pulmonary lesions; however, the specificity (45.5) and negative predictive value (62.5) decrease due to increased false positives. The presence of emphysema and absence of evidence of granulomatous disease increases the probability that a pulmonary lesion is malignant; however, these were not statistically significant.

Epidemiology of sarcoidosis: recent advances and future prospects.

Sarcoidosis is by definition a disease of "unknown causes," but recent epidemiologic advances suggest that the long-standing definition of sarcoidosis may soon need to be amended. The recently completed ACCESS (A Case-Control Etiologic Study of Sarcoidosis) study was not able to definitively identify the "cause" of sarcoidosis, but yielded important findings regarding familial and environmental risks that have advanced our understanding of this disease. The HLA-DRB1 associations reported in ACCESS along with the results of two recently completed genome scans of sarcoidosis in German Caucasians and African-Americans, respectively, have further defined the genetics of sarcoidosis. These studies suggest genetic heterogeneity of sarcoidosis risk between Caucasians and African-Americans and multiple susceptibility genes that interact together and with environmental factors in the disease pathogenesis. Genes that influence sarcoidosis clinical phenotypes may also be largely separate from sarcoidosis susceptibility genes. Although genetic studies of sarcoidosis in African-American populations are confounded by Caucasian admixture, this same admixture may be useful in identifying sarcoidosis genes linked with African ancestry. Case-only methods may be useful in identifying recent acute exposures linked to disease, genetic variants of risk, and gene-environment interactions. In summary, the epidemiology of sarcoidosis has a promising future that should eventually provide the answers to the etiologic origins of this complex disease.

[Immunophenotyping of epithelioid-cell granulomas in sarcoidosis].

The specimens of biopsy of the lung and lymph nodes from 24 patients with sarcoidosis were immunophenotyped. The monoclonal antibody panel for immunophenotyping the monocyte-macrophage cells included HLA-DR, CD64, CD163; CD7, CD3, CD4, CD8, HLA-DR, and CD20 were used to assess lymphocytic populations. In sarcoidosis, the majority of cell elements of a granuloma are in a state of activation, as evidenced by HLA-DR expression on the epithelioid, giant cells, T lymphocytes (which was observed in more than in 90% of cases), the extent of this expression decreasing as fibrosis develops. There is a statistically significant correlation between the presence of individual lymphocytic subpopulations and monocyte-macrophage cells in the granuloma. No clear relationship of the phenotype of a granuloma to the clinical form (stage) of sarcoidosis suggests that is based on the common self-sustaining process of formation, functioning, and involution of granulomas, which has no direct agreements in the X-ray and laboratory manifestations of the disease.

Pulmonary sarcoidosis: new genetic clues and ongoing treatment controversies.

The wide-ranging, multisystemic manifestations of sarcoidosis can make diagnosis and management difficult. Corticosteroid treatment is effective, but the optimal time to start, the dose, and the duration of treatment are controversial. We are just beginning to understand the genetic basis of sarcoidosis.