Characteristics of culture-negative subclinical pulmonary tuberculosis: a single-center observation.

BACKGROUND: Little is known about culture-negative subclinical pulmonary tuberculosis (TB), and its diagnosis remains challenging. Therefore, this study aimed to identify the characteristics and the extent of disease associated with culture-negative subclinical pulmonary TB. METHODS: This retrospective cohort study was conducted on immunocompetent individuals with subclinical pulmonary TB at a university hospital in Thailand from January 2014 to December 2019. Subclinical pulmonary TB was diagnosed based on the presence of radiographic abnormalities consistent with TB in the absence of TB symptoms. All subjects demonstrated significant improvement or resolution of radiographic abnormalities following the completion of treatment. At least two negative sputum cultures were needed to fulfill the definition of culture-negative pulmonary TB. Data were analyzed using univariate and multiple logistic regression analyses to determine the characteristics of those with culture-negative subclinical pulmonary TB compared to culture-positive ones. RESULTS: Out of the 106 individuals identified with subclinical pulmonary TB, 84 met the criteria for inclusion in the analysis. The study found lower radiographic extent and increasing age were key attributes of culture-negative subclinical pulmonary TB. The odds ratios (95% confidence interval) were 7.18 (1.76 to 29.35) and 1.07 (1.01 to 1.13), respectively. They tend to have lower rates of bilateral involvement in both chest x-ray (8.5% vs. 32.0%, p=0.006) and computed tomography (15.4% vs. 42.9%, p=0.035). However, no other specific radiographic findings were identified. CONCLUSIONS: People with culture-negative subclinical pulmonary TB were likely to have less radiographic -severity, reflecting early disease. Nevertheless, no radiographic patterns, except for unilaterality, were related to culture-negative subclinical pulmonary TB.

Primary pulmonary lymphoepithelioma-like carcinoma treated with immunotherapy: A case report and literature review.

Here, we report a case of metastatic Epstein-Barr virus (EBV)-related primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) in a young, nonsmoking female who responded well to treatment with two types of immune checkpoint inhibitors (ICIs). This is the first case report of a favorable outcome to ICIs in the late-line treatment of advanced PPLELC patients with programmed cell death-ligand 1 (PD-L1) expression.

Nonspecific interstitial pneumonia in refractory systemic juvenile idiopathic arthritis responded to tocilizumab treatment.

BACKGROUND: Nonspecific interstitial pneumonia (NSIP) is a rare pulmonary complication in systemic juvenile idiopathic arthritis (SJIA). OBJECTIVE: To present a case with NSIP in SJIA. METHODS: Case report. RESULTS: We report the case of a 4-year-old boy with SJIA complicated by macrophage activation syndrome (MAS) refractory to conventional therapy, and who later developed NSIP confirmed by high-resolution computerized tomography of the chest and lung histopathology. The patient received tocilizumab, a monoclonal antibody to interleukin-6 receptor, to control his disease. Data relating to tocilizumab treatment of NSIP in refractory SJIA is limited. CONCLUSIONS: The data from this case report suggests that NSIP could be a pulmonary complication of SJIA complicated by MAS that is refractory to conventional therapy. Early initiation of tocilizumab should be considered to achieve disease remission in this pediatric patient population.

A rare case of mediastinal lymphatic venous malformations in children.

We report a case of mediastinal lymphatic venous malformations (LVM) in a 11-year-old boy who presented with chest pain after jumping into a swimming pool, with review of the literature. A superior mediastinal mass was incidentally found from the chest x-ray. Chest computed tomography revealed a large heterogenous mass at the left-sided mediastinum containing fat, minimal enhancing solid portion, non-enhancing cystic portion and calcification. Because of the large size of the mass, the patient underwent tumour removal. Operative findings gave a definitive diagnosis of mediastinal LVM. The patient had an uneventful clinical course and was discharged without complication. This report highlights that it is possible to misdiagnose mediastinal LVM especially if its predominant portion is lymphatic tissue with only minimal contrast enhancement. Tissue biopsy must be avoided because it may lead to haemorrhagic complication.

Clinical Characteristics of Sarcoidosis in Asian Population: A 14-year Single Center Retrospective Cohort Study from Thailand.

BACKGROUND: Little is known about epidemiology and clinical characteristics of sarcoidosis in Asian population. OBJECTIVES: This study aimed to examine the epidemiology and clinical characteristics of Thai patients with sarcoidosis, using databases of a tertiary care medical center. METHODS: Potential cases of sarcoidosis were identified from two sources, the medical record-linkage system and the pathology database of Siriraj Hospital, Mahidol University in Bangkok, Thailand. Patients with ICD-10-CM codes for sarcoidosis were identified and retrieved from the medical record-linkage system from 2005 to 2018. Patients with histopathology positive for non-caseating granuloma were identified and retrieved from the pathology database from the same time period. All potential cases underwent individual medical record review to confirm the diagnosis of sarcoidosis which required compatible clinical pictures supported by presence of non-caseating granuloma, radiographic evidence of intrathoracic sarcoidosis and exclusion of other granulomatous diseases. RESULTS: From 2005 to 2018, 89 confirmed cases of sarcoidosis were identified. 80.9% of them were female and mean age at diagnosis was 46.8 years (standard deviation (SD) 13.9 years). The majority of patients had intrathoracic disease (81 cases; 91.0%) but less than half had respiratory symptoms (34 cases; 41.9%). Extrathoracic disease was common in this cohort that pulmonary sarcoidosis was accompanied by extrathoracic involvement in 53 patients (65.4%). Sarcoid uveitis was the most common extrathoracic disease (35 cases; 39.3%), followed by cutaneous sarcoidosis (24 cases; 26.9%), extrathoracic lymphadenopathy (18 cases; 22.5%) and sarcoid arthropathy (4 cases; 4.5%). CONCLUSION: The current study examined clinical characteristics of sarcoidosis in an Asian population and found high prevalence of uveitis and marked female predominance. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (4): e2020011).

Enhanced surveillance for severe pneumonia, Thailand 2010-2015.

BACKGROUND: The etiology of severe pneumonia is frequently not identified by routine disease surveillance in Thailand. Since 2010, the Thailand Ministry of Public Health (MOPH) and US CDC have conducted surveillance to detect known and new etiologies of severe pneumonia. METHODS: Surveillance for severe community-acquired pneumonia was initiated in December 2010 among 30 hospitals in 17 provinces covering all regions of Thailand. Interlinked clinical, laboratory, pathological and epidemiological components of the network were created with specialized guidelines for each to aid case investigation and notification. Severe pneumonia was defined as chest-radiograph confirmed pneumonia of unknown etiology in a patient hospitalized ≤48 h and requiring intubation with ventilator support or who died within 48 h after hospitalization; patients with underlying chronic pulmonary or neurological disease were excluded. Respiratory and pathological specimens were tested by reverse transcription polymerase chain reaction for nine viruses, including Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and 14 bacteria. Cases were reported via a secure web-based system. RESULTS: Of specimens from 972 cases available for testing during December 2010 through December 2015, 589 (60.6%) had a potential etiology identified; 399 (67.8%) were from children aged < 5 years. At least one viral agent was detected in 394 (40.5%) cases, with the most common of single vial pathogen detected being respiratory syncytial virus (RSV) (110/589, 18.7%) especially in children under 5 years. Bacterial pathogens were detected in 341 cases of which 67 cases had apparent mixed infections. The system added MERS-CoV testing in September 2012 as part of Thailand's outbreak preparedness; no cases were identified from the 767 samples tested. CONCLUSIONS: Enhanced surveillance improved the understanding of the etiology of severe pneumonia cases and improved the MOPH's preparedness and response capacity for emerging respiratory pathogens in Thailand thereby enhanced global health security. Guidelines for investigation of severe pneumonia from this project were incorporated into surveillance and research activities within Thailand and shared for adaption by other countries.

Pathological confirmed diagnosis of asbestosis: the first case report in Thailand.

Asbestosis is an occupational lung disease defined as pulmonary fibrosis caused by asbestos. Asbestosis was previously reported in Thailand based on radiologic findings, which demonstrated interstitial lung with calcified pleural plaques, and the patient worked in a fiber cement factory. However there was some doubt about the diagnosis because clinical and radiological findings are nonspecific; there was no data support of asbestos exposure in the patient and no histologic confirmed diagnosis. Histologic diagnosis is most useful when an equivocal of ahistory of asbestos exposure in patients with interstitial lung diseases take place. The authors report a patient presenting with progressive dyspnea for 2 years. She worked in an electric, wire, mesh fan cover factory to check quality of protective wire mesh for 10 years until the factory was closed 6 years ago. This type of factory had never officially reported asbestos use. Her clinical manifestations and radiologic findings are compatible with interstitial lung disease. She subsequently underwent thoracotomy with wedge lung resection. Pathology revealed interstitial fibrosis with honeycombing. Asbestos bodies were found more than 10 per cm2 in the fibrosis. She was diagnosed asbestosis. The patient is suffering from dyspnea, severe hypoxemia and cor pulmonale. The patient is put on waiting lists for heart lung transplantation. The authors thus confirmed that asbestosis exists in Thailand. A policy to protect workers and people who may have risk of asbestos exposure is necessary, since diseases related to asbestos are incurable, but preventable.

Extensive pulmonary alveolar microlithiasis.

Pulmonary alveolar microlithiasis is a rare pulmonary disorder that is caused by abnormal sodium-dependent phosphate co-transporter from the mutation of SLC34A2 gene, leading to accumulation of microliths in the alveoli. We report the extensive pulmonary alveolar microlithiasis in an elderly woman who presented with progressive dyspnea for 2 months. Chest radiograph revealed diffuse pulmonary calcification. Tissue histopathology from open lung biopsy demonstrated widespread intra-alveolar laminated calcium deposits compatible with pulmonary alveolar microlithiasis.

Highly sensitive EGFR mutation detection by specific amplification of mutant alleles.

Mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene predict benefit from tyrosine kinase inhibitors in patients suffering from non-small-cell lung cancer. In this study, we developed a fast, simple, cost-effective and highly sensitive assay for detection of five clinically important EGFR mutations in exon 19 (2235_2249del and 2236_2250del), exon 20 (C2369T) and exon 21 (T2573G and c.2573_2574 TG > GT). We designed EGFR mutation detection assays by combining allele-specific PCR amplification with the detection of SYBR Green I fluorescence, and optimized PCR conditions to specifically amplify mutant alleles. These one-step assays were able to detect the mutations at levels as low as 1.5 mutant copies in a DNA sample. Commercially available probe-based allele-specific PCR exhibited relatively poor performance when detecting very low copies of mutated DNA, especially in exon 19 and 20. Our assays offered dramatically less reagent cost than that of the commercial kit and generated results in less than 90 min after DNA extraction. These protocols can also be applied to conventional thermal cyclers followed by gel electrophoresis detection.

A case series of sarcoidosis with pulmonary involvement: various clinical and radiographic manifestations.

BACKGROUND: Sarcoidosis is a multisystem granulomatous disease of unknown etiology. The disease is rare in East Asian populations. Patients have many clinical presentations and 90% of patients have pulmonary involvement. There are few reports in Thailand that collected the data about chest imaging and pathological findings of sarcoidosis. MATERIAL AND METHOD: The data of patient with sarcoidosis with pulmonary involvement, who followed-up between September 2008 and December 2011, were retrospectively reviewed. RESULTS: Ten patients with sarcoidosis and pulmonary involvement were reviewed. Three patients presented with abnormal chest x-ray without respiratory symptom or other organ involvement. One patient was suspected to be sarcoidosis secondary to etanercept therapy. The majority of patients had cutaneous involvement. The most common finding on chest x-ray is bilateral hilar lymphadenopathy (90%). Seven patients had stage 2 disease and three patients had stage 1 disease. The diagnoses of all patients were confirmed by histopathology and exclusion of tuberculosis and fungal infection. Spirometry showed normal in seven patients, irreversible obstruction in one patient, and impaired diffusing capacity in six patients. There was no indication of systemic corticosteroids or immunosuppressive drug in most patients. CONCLUSION: Sarcoidosis has various clinical manifestations. The pulmonary and cutaneous involvement is common and the diagnosis is made by a combination of clinical, radiological, and histopathologic findings. The treatment of systemic corticosteroids is not required in most patients. The patients should be regularly followed-up in order to follow the course of disease.

Prosthetic valve endocarditis caused by Histoplasma capsulatum: the first case report in Thailand.

The authors report a rare case of fungal endocarditis caused by Histoplasma capsulatum in an immunocompetent woman with mitral valve prosthesis. The patient presented with chronic fever and embolic phenomenon. Transthoracic and transesophageal echocardiography revealed a mobile mass attached to mitral prosthetic valve and her blood cultures were negative for both bacteria and fungi. The diagnosis was made by presence of budding yeasts in the histopathological findings of the vegetation and recovery of H. capsulatum from tissue culture of the excised vegetation. The patient was improved after a 6-week course of amphotericin B. Fungal endocarditis caused by Histoplama capsulatum is rare but should be considered as a possible causative organism in culture-negative endocarditis. To our knowledge, this is the first case report of H. capsulatum endocarditis in Thailand.

Influenza A(H1N1)pdm09-associated pneumonia deaths in Thailand.

BACKGROUND: The first human infections with influenza A(H1N1)pdm09 virus were confirmed in April 2009. We describe the clinical and epidemiological characteristics of influenza A(H1N1)pdm09-associated pneumonia deaths in Thailand from May 2009-January 2010. METHODS: We identified influenza A(H1N1)pdm09-associated pneumonia deaths from a national influenza surveillance system and performed detailed reviews of a subset. RESULTS: Of 198 deaths reported, 49% were male and the median age was 37 years; 146 (73%) were 20-60 years. Among 90 deaths with records available for review, 46% had no identified risk factors for severe influenza. Eighty-eight patients (98%) received antiviral treatment, but only 16 (18%) initiated therapy within 48 hours of symptom onset. CONCLUSIONS: Most influenza A(H1N1)pdm09 pneumonia fatalities in Thailand occurred in adults aged 20-60 years. Nearly half lacked high-risk conditions. Antiviral treatment recommendations may be especially important early in a pandemic before vaccine is available. Treatment should be considered as soon as influenza is suspected.

Benign metastasizing leiomyoma.

Pulmonary metastases from benign-appearing smooth muscle tumors of the uterus are rare, and are termed benign metastasizing leiomyoma (BML). Affected patients usually present with single or multiple lung nodules and are usually women who have undergone hysterectomy. Only a few cases of BML with lung cysts have been reported, with 2 patients presenting with spontaneous pneumothoraces. We report a case of BML in a 29-year-old woman with an abnormal preoperative chest radiograph who several years after hysterectomy developed spontaneous bilateral pneumothoraces.

Pathologic characteristics of resected squamous cell carcinoma of the trachea: prognostic factors based on an analysis of 59 cases.

While squamous cell carcinoma (SCC) is the most common tracheal malignancy, few reports describe the pathologic considerations that may guide intraoperative decisions and prognostic assessment. We reviewed 59 tracheal SCC treated between 1985 and 2008 by segmental resection of the trachea, including resection of the carina in 24% and inferior larynx in 14%. We classified these tumors by grading histologic differentiation and microscopic features used in SCC of other sites. Of 59 tumors, 24% (14 of 59) were well differentiated, 49% (29 of 59) were moderately differentiated, and 27% (16 of 59) were poorly differentiated. Unfavorable prognostic factors were tumor extension into the thyroid gland (all of five so-afflicted patients died of tumor progression within 3 years) and lymphatic invasion (mean survival 4.6 versus 7.6 years). Keratinization, dyskeratosis, acantholysis, necrosis, and tumor thickness did not predict prognosis. As surgical resection is the only curative treatment; the surgeon should establish clean lines of resection using, as appropriate, intraoperative frozen section. The pathologist can provide additional important prognostic information, including tumor differentiation and extent, invasion of surgical margins, and extension into the thyroid.

Lymphangiomatoid pattern in diffuse malignant mesothelioma of the pleura: a report of six cases.

The multiplicity of epithelioid and mesenchymal forms of diffuse malignant mesothelioma includes patterns that may mimic another process. Identification of the multiplicity of patterns may help in the diagnosis of diffuse malignant mesothelioma. One pattern that has not been described is lymphangiomatoid. We observed six cases with ovoid or elongated or irregular anastomosing vascular-like spaces lined by flattened cells simulating lymphangioma. The luminal spaces could contain proteinaceous material simulating lymph but not erythrocytes. The cells lining the spaces were mesothelial by immunohistochemical staining. The lymphangiomatoid areas never constituted more than 40% of the area of the tumor on the slides. When seen in more solid areas of tumor, the lymphangiomatoid structures generally did not produce diagnostic difficulty. However, when seen at the edge of solid tumor or forming an irregular nodule or invading into adjacent adipose tissue, these lymphangiomatoid structures could be confusing. All six patients had been exposed to asbestos either by occupation or by spousal exposure. Three patients received chemotherapy. One patient died of diffuse malignant mesothelioma of the pleura.

Nodular amiodarone lung disease.

The antiarrhythmic drug amiodarone accumulates in many organs of the body. Amiodarone lung disease (ALD) most commonly manifests clinically as an interstitial pneumonitis. The few reports of nodular ALD generally have been in the clinical and radiographic literature. No detailed histopathologic analysis of nodular ALD is available. We report 4 patients with nodular ALD, all of whom had excision of a nodule and none had a preoperative diagnosis of ALD. The radiographic suspicion before excisional biopsy in all 4 cases was malignancy. The initial pathologic suspicion in all 4 cases was either an abscess or vasculitis. In 3 of the 4 cases, where the dosages were known, each patient received 800 mg/d for 7 or more months. All cases have strikingly similar histopathology, with vacuolated histiocytes massed within alveoli to form macroscopic nodules with tissue breakdown. Ultrastructural examination of lung and peripheral nerve in 1 case showed the characteristic inclusions of amiodarone in the cytoplasm of swollen histiocytes. Vacuolated histiocytes filled with these inclusions indicate the effect of the drug, but in these 4 cases there was tissue destruction, which indicated disease. The necrotizing nature of the massed histiocytes in the absence of infection or obstruction suggests the correct etiologic diagnosis even when the history of administration of the drug is not available at initial review.

Bronchiolitis interstitial pneumonitis: a pathologic study of 31 lung biopsies with features intermediate between bronchiolitis obliterans organizing pneumonia and usual interstitial pneumonitis, with clinical correlation.

Bronchiolitis combined with interstitial pneumonitis generally has been equated with bronchiolitis obliterans organizing pneumonia (BOOP). We describe our experience with lung biopsies that had both bronchiolar and interstitial diseases. We studied 31 patients who had respiratory difficulty leading to open lung biopsy, which showed a combination of both prominent bronchiolitis and prominent interstitial pneumonitis. We compared these cases clinically and pathologically with 6 other pulmonary diseases, namely, bronchiolitis obliterans, BOOP, nonspecific interstitial pneumonitis, usual interstitial pneumonitis, airway-centered interstitial fibrosis, and idiopathic bronchiolocentric interstitial pneumonia, and with 10 cases of cystic fibrosis, an unrelated disease with both bronchiolar and interstitial pathology. The commonality of our cases was a combination of bronchiolitis and interstitial inflammation and fibrosis but little or no intra-alveolar organizing pneumonia. Bronchiolitis obliterans with organizing pneumonia involved less area than the interstitial pneumonitis in each case. All 19 patients for whom we had follow-up received corticosteroids for their pulmonary diseases. Seven patients had improvement in symptoms and pulmonary function test results and radiographic findings, 5 patients experienced subjective improvement with unchanged results of pulmonary function tests or chest x-ray, 1 patient's condition was unchanged, 6 patients' disease worsened, and 4 of these 6 died. The natural history of these cases, which we have designated bronchiolitis interstitial pneumonitis, seems more sanguine than usual interstitial pneumonitis and worse than BOOP at least in the short term. On the one hand, response to corticosteroids was not as frequent as generally accepted for BOOP. On the other hand, disease did not progress in most patients on corticosteroids.

Shirt-sleeve or scanning magnification as an aid to the diagnosis of commonly encountered medical lung diseases.

Shirt-sleeve magnification (holding a slide over a white sleeve) and low-power magnification serve as useful adjuncts in the general categorization of noninfectious medical lung disease. This article divides medical lung disease into chronic and acute, where the temporality is determined first by clinical circumstances and then confirmed by histopathology. The low-power patterns of various lung diseases overlap, sometimes greatly. Nevertheless, classic examples of chronic disease can be sorted as linear, lobular filling, nodular dispersed, nodular lymphangitic, or cystic patterns at shirt-sleeve or low-power magnification. Classic examples of acute disease generally produce a solidifying pattern at shirt-sleeve or low-power magnification, which can be followed by a determination as to whether alveolar filling is principally fibrotic or principally fluid or cells at higher magnification. This article gives a simple system for the categorization of medical lung disease by this approach, with an emphasis on the most common diseases to be encountered in a general surgical pathology practice. In our experience, this system also proves useful in arriving at some therapeutic decisions.

Pitfalls in classifying lymphomas.

BACKGROUND: Although the WHO classification (2001) requires a great deal of morphologic, immunophenotypic, genetic, and clinical features for classifying lymphomas, it is still feasible to misdiagnose under limited resources, especially a limited panel of antibodies used for immunophenotyping. To identify pitfalls in classifying lymphomas among hematopathologist, general pathologists, and pathology residents under this situation. MATERIAL AND METHOD: Newly diagnosed lymphoma cases from 1 July 2002 to 30 June 2003 at Siriraj Hospital were included for two rounds of individually blinded review by a hematopathologist, two general pathologists, and three pathology residents. Final diagnoses were given by consensus. Pitfalls were determined from misdiagnosis, in each case analyzed in terms of frequency. RESULTS: One hundred and four lymphoma cases included 61 diffuse large B-cell lymphoma (DLBCL, 58.6%), 12 MALT lymphoma (11.5%), eight follicular lymphoma (FL, 7.7%), seven classical Hodgkin lymphoma (HL, 6.7%), four unspecified peripheral T-cell lymphoma (PTCL, 3.8%), three Burkitt lymphoma (BL, 2.9%), two subcutaneous panniculitis-like T-cell lymphoma (SPTCL, 1.9%), and seven other uncommon types (1% each). Pitfalls were low infrequency on diagnosis of DLBCL, nodular sclerosis HL, and SPTCL (8% each), but not different among the participants only in DLBCL. Pitfalls in diagnosis of MALT lymphoma, mixed cellularity HL, BL, unspecified PTCL, and FL were 60%, 50%, 33%, 29%, and 24%, respectively. However, considering hematopathologist and non-hematopathologist groups, pitfalls in the former were lower, especially in the uncommon types of lymphoma. CONCLUSION: Pitfalls in classifying lymphomas are common. Interest in hematopathology reduces misdiagnosis in lymphomas other than DLBCL.