GLPG1205 for idiopathic pulmonary fibrosis: a phase 2 randomised placebo-controlled trial.

BACKGROUND: GLPG1205 is a selective functional antagonist of G-protein-coupled receptor 84, which plays an important role in fibrotic processes. This study assessed the efficacy, safety and tolerability of GLPG1205 for treatment of idiopathic pulmonary fibrosis (IPF). METHODS: PINTA (ClinicalTrials.gov: NCT03725852) was a phase 2, randomised, double-blind, placebo-controlled, proof-of-concept trial. Patients with IPF were randomised 2:1 to once-daily oral GLPG1205 100 mg or placebo for 26 weeks and stratified to receive GLPG1205 alone or with local standard of care (nintedanib or pirfenidone). The primary end-point was change from baseline in forced vital capacity (FVC); other end-points were safety and tolerability, and lung volumes measured by imaging (high-resolution computed tomography). The study was not powered for statistical significance. RESULTS: In total, 68 patients received study medication. Least squares mean change from baseline in FVC at week 26 was -33.68 (95% CI -112.0-44.68) mL with GLPG1205 and -76.00 (95% CI -170.7-18.71) mL with placebo (least squares mean difference 42.33 (95% CI -81.84-166.5) mL; p=0.50). Lung volumes by imaging declined -58.30 versus -262.72 mL (whole lung) and -33.68 versus -135.48 mL (lower lobes) with GLPG1205 versus placebo, respectively. Treatment with GLPG1205 versus placebo resulted in higher proportions of serious and severe treatment-emergent adverse events and treatment-emergent discontinuations, most apparent with nintedanib. CONCLUSIONS: Treatment with GLPG1205 did not result in a significant difference in FVC decline versus placebo. GLPG1205 demonstrated a poorer safety and tolerability profile than placebo.

Cervico-Dorsal Intramedullary Spinal Cord Abscess with Aspergillus fumigates following Pulmonary Infection in an Immunocompetent Patient.

Invasive forms of aspergillosis of the nervous system are relatively rare and are usually diagnosed in immunocompromised patients. We present the case of a young female patient, treated in the last two months with corticosteroids and antifungal drug for pulmonary aspergillosis, who developed progressive paraparesis. An intramedullary abscess at the C7-D1 level was identified and the lesion was treated with a combination of surgery and antifungal therapy. Histopathologic findings of surgical specimens showed myelomalacia with Aspergillus hyphae and a peripheral rim of neutrophils. We consider that the use of multiple drugs and corticosteroids for our patient's initial community pneumonia could be the factor that transformed her into a mildly immunocompromised individual and permitted the Aspergillus spp. to disseminate through the blood and into the spinal cord. Moreover, we highlight the fact that more attention should be paid to living and working conditions of the patients, as a simple colonization of the lung with Aspergillus spp. could develop, in a short time, into an invasive disease with a high risk of mortality.

Phase II Study of Single/Repeated Doses of Acumapimod (BCT197) to Treat Acute Exacerbations of COPD.

Mitogen-activated protein kinase p38 is a key regulator in the inflammation pathway and is activated in the lungs of chronic obstructive pulmonary disease (COPD) patients. Acumapimod is a potent, selective, oral, p38 inhibitor under investigation for treatment of acute exacerbations of COPD (AECOPD). In this Phase II, double-blind, randomized, placebo-controlled dose-exploration study of acumapimod in patients with moderate or severe AECOPD (NCT01332097), patients presenting with AECOPD were randomized to receive single-dose acumapimod (20 mg or 75 mg) on Day 1, repeated single-dose acumapimod (20 mg or 75 mg) on Days 1 and 6, oral prednisone 40 mg (10 days), or placebo. Primary outcome: improvement in forced expiratory volume in 1 s (FEV1) versus placebo at Day 5 (single doses) and Day 10 (repeated doses). N = 183 patients were randomized; 169 (92%) patients completed the study. Although the primary endpoint (FEV1 at Day 10) was not met (p = 0.082), there was a significant improvement in FEV1 with acumapimod repeat-dose 75 mg versus placebo at Day 8 (p = 0.022) which, though not a prespecified endpoint, was part of an overall trend. Differences at lower doses did not achieve significance. Mean change in FEV1 AUC from baseline to Day 14 in the 75 mg repeat-dose group was significantly higher versus placebo (p = 0.02), prednisone (p = 0.01), and 20 mg single-dose groups (p = 0.015) (post-hoc analysis). EXACT-PRO showed numerical differences versus placebo that did not reach significance. Acumapimod was well tolerated. In conclusion, repeated single-dose acumapimod showed a clinically relevant improvement in FEV1 over placebo at Day 8, along with consistent numerical differences in EXACT-PRO. These data can be used to determine dose regimens for a proof-of-clinical-concept trial.

The TB Portals: an Open-Access, Web-Based Platform for Global Drug-Resistant-Tuberculosis Data Sharing and Analysis.

The TB Portals program is an international consortium of physicians, radiologists, and microbiologists from countries with a heavy burden of drug-resistant tuberculosis working with data scientists and information technology professionals. Together, we have built the TB Portals, a repository of socioeconomic/geographic, clinical, laboratory, radiological, and genomic data from patient cases of drug-resistant tuberculosis backed by shareable, physical samples. Currently, there are 1,299 total cases from five country sites (Azerbaijan, Belarus, Moldova, Georgia, and Romania), 976 (75.1%) of which are multidrug or extensively drug resistant and 38.2%, 51.9%, and 36.3% of which contain X-ray, computed tomography (CT) scan, and genomic data, respectively. The top Mycobacterium tuberculosis lineages represented among collected samples are Beijing, T1, and H3, and single nucleotide polymorphisms (SNPs) that confer resistance to isoniazid, rifampin, ofloxacin, and moxifloxacin occur the most frequently. These data and samples have promoted drug discovery efforts and research into genomics and quantitative image analysis to improve diagnostics while also serving as a valuable resource for researchers and clinical providers. The TB Portals database and associated projects are continually growing, and we invite new partners and collaborations to our initiative. The TB Portals data and their associated analytical and statistical tools are freely available at https://tbportals.niaid.nih.gov/.

Challenges of cardiac sarcoidosis.

Sarcoidosis is a multisystem granulomatosis of unknown origin, which can involve almost any organ. Most frequently the disease involves the lungs and mediastinal lymph nodes, but it can affect the skin, the eyes, nervous system, the heart, kidneys, joints, muscles, calcium metabolism, and probably any other anecdotical organ involvement. Cardiac sarcoidosis is one of the most challenging involvements, as it can lead to cardiac mortality and morbidity, and also because the diagnosis may be difficult. With no specific symptoms, cardiac sarcoidosis may be difficult to suspect in a patient with no previous extra-cardiac sarcoidosis diagnosis. This manuscript reviews the current knowledge of the diagnosis and decision to treat cardiac sarcoidosis, and illustrates the information with a case presentation of a young adult with no risk factors, no previous diagnosis of sarcoidosis, and with cardiac symptoms impairing his quality of life.

Validation of the Sarcoidosis Diagnostic Score in a Multicontinental Study.

Rationale: The Sarcoidosis Diagnostic Score (SDS) has been established to quantitate the clinical features consistent with sarcoidosis in a monocentric study. Objectives: We aimed to confirm the diagnostic value of SDS in a large, multicontinental study and to assess the utility of SDS in differentiating sarcoidosis from alternative diagnoses, including infectious and noninfectious granulomatous diseases. Methods: We included patients with biopsy-confirmed sarcoidosis at nine centers across the world. Patients without sarcoidosis seen at the same sites served as control patients. Using a modified World Association of Sarcoidosis and Other Granulomatous Disorders organ assessment instrument, we scored all patients for the presence of granuloma on biopsy, highly probable symptoms, and least probable symptoms for each area. Two sarcoidosis scores were generated: SDS Biopsy (with biopsy) and SDS Clinical (without biopsy). SDS Clinical and Biopsy were calculated for all patients. We calculated and compared the area under the curve (AUC) for SDS Clinical and Biopsy according to different diagnosis scenarios. Results: A total of 1,041 patients with sarcoidosis and 1,035 without sarcoidosis were included. The results for SDS Clinical (AUC, 0.888; 95% confidence interval [CI], 0.874-0.902) and SDS Biopsy (AUC, 0.979; 95% CI, 0.973-0.985) according to AUC were good to excellent for differentiating sarcoidosis from alternative diagnosis. SDS Clinical was less discriminatory in males (P = 0.01) and in high tuberculosis prevalence centers (P < 0.001). However, SDS Clinical (AUC, 0.684; 95% CI, 0.602-0.766) and SDS Biopsy (AUC, 0.754; 95% CI, 0.673-0.835) were not sufficiently discriminative for noninfectious granulomatous diseases, but both SDSs could differentiate sarcoidosis from infectious granulomatous diseases. Algorithms were proposed for the SDS Clinical and SDS Biopsy to assist the clinician in the diagnostic process, and cutoff values were proposed for the SDS Clinical and SDS Biopsy, allowing the diagnosis of sarcoidosis to be safely confirmed or rejected in most cases except for noninfectious granulomatous disease. Conclusions: This multicontinental study confirms that both SDS Clinical and SDS Biopsy have good to excellent performance in discriminating sarcoidosis from alternative diagnoses. Differences in the AUC were seen for high tuberculosis prevalence versus low tuberculosis prevalence centers and for males versus females. Both SDSs had good discriminatory function for infectious granulomatous disease but failed in cases of noninfectious granulomatous disease such as berylliosis.

A Rare Thymic Tumor - Lipofibroadenoma - Always a Postoperative Surprise.

BACKGROUND/AIM: Thymic lipofibroadenoma is a benign growth of unknown etiology extremely rarely described in the literature, morphologically resembling lipofibroadenoma of the breast. The diagnosis is usually a postoperative surprise and is made by the anatomopathologist. Surgical resection is curative. CASE REPORT: The presented case is the first reported in a woman, to date. The patient was successfully submitted to surgery and complete resection of the giant intrathoracic tumor was performed. The histopathological and immunohistochemical studies came to demonstrated the presence of a thymic lipofibroadenoma while the postoperative outcomes were favorable. CONCLUSION: In cases presenting large intrathoracic tumors complete resection is able to provide a significant improvement of the general condition of the patient, as well as a chance for cure.

Patient Reported Experiences and Delays During the Diagnostic Pathway for Pulmonary Fibrosis: A Multinational European Survey.

Introduction: Pulmonary fibrosis includes a spectrum of diseases and is incurable. There is a variation in disease course, but it is often progressive leading to increased breathlessness, impaired quality of life, and decreased life expectancy. Detection of pulmonary fibrosis is challenging, which contributes to considerable delays in diagnosis and treatment. More knowledge about the diagnostic journey from patients' perspective is needed to improve the diagnostic pathway. The aims of this study were to evaluate the time to diagnosis of pulmonary fibrosis, identify potential reasons for delays, and document patients emotions. Methods: Members of European patient organisations, with a self-reported diagnosis of pulmonary fibrosis, were invited to participate in an online survey. The survey assessed the diagnostic pathway retrospectively, focusing on four stages: (1) time from initial symptoms to first appointment in primary care; (2) time to hospital referral; (3) time to first hospital appointment; (4) time to final diagnosis. It comprised open-ended and closed questions focusing on time to diagnosis, factors contributing to delays, diagnostic tests, patient emotions, and information provision. Results: Two hundred and seventy three participants (214 idiopathic pulmonary fibrosis, 28 sarcoidosis, 31 other) from 13 countries responded. Forty percent of individuals took ≥1 year to receive a final diagnosis. Greatest delays were reported in stage 1, with only 50.2% making an appointment within 3 months. For stage 2, 73.3% reported a hospital referral within three primary care visits. However, 9.9% reported six or more visits. After referral, 76.9% of patients were assessed by a specialist within 3 months (stage 3) and 62.6% received a final diagnosis within 3 months of their first hospital visit (stage 4). Emotions during the journey were overall negative. A major need for more information and support during and after the diagnostic process was identified. Conclusion: The time to diagnose pulmonary fibrosis varies widely across Europe. Delays occur at each stage of the diagnostic pathway. Raising awareness about pulmonary fibrosis amongst the general population and healthcare workers is essential to shorten the time to diagnosis. Furthermore, there remains a need to provide patients with sufficient information and support at all stages of their diagnostic journey.

The impact of demographic disparities in the presentation of sarcoidosis: A multicenter prospective study.

OBJECTIVE: To study how demographic differences impact disease manifestation of sarcoidosis using the WASOG tool in a large multicentric study. METHODS: Clinical data regarding 1445 patients with sarcoidosis from 14 clinical sites in 10 countries were prospectively reviewed from Feb 1, 2020 to Sep 30, 2020. Organ involvement was evaluated for the whole group and for subgroups differentiated by sex, race, and age. RESULTS: The median age of the patients at diagnosis was 46 years old; 60.8% of the patients were female. The most commonly involved organ was lung (96%), followed by skin (24%) and eye (22%). Black patients had more multiple organ involvement than White patients (OR = 3.227, 95% CI: 2.243-4.643) and females had more multiple organ involvement than males (OR = 1.238, 95% CI: 1.083-1.415). Black patients had more frequent involvement of neurologic, skin, eye, extra thoracic lymph node, liver and spleen than White and Asian patients. Women were more likely to have eye (OR = 1.522, 95%CI: 1.259-1.838) or skin involvement (OR = 1.369, 95%CI: 1.152-1.628). Men were more likely to have cardiac involvement (OR = 1.326, 95%CI: 1.096-1.605). A total of 262 (18.1%) patients did not receive systemic treatment for sarcoidosis. Therapy was more common in Black patients than in other races. CONCLUSION: The initial presentation and treatment of sarcoidosis was related to sex, race, and age. Black and female individuals are found to have multiple organ involvement more frequently. Age at diagnosis<45, Black patients and multiple organ involvement were independent predictors of treatment.

The clinical-morphological profile of tuberculous pleurisies - our experience in relation to literature data.

AIM: The authors made a morphological evaluation of pleural tissue fragments from patients hospitalized in Thoracic Surgery Department of the Emergency County Hospital of Craiova, Romania, over a period of 26 years, diagnosed with tuberculous lesions in the Pathology Department of the same Hospital. PATIENTS, MATERIALS AND METHODS: The studied material consisted of pleural tissue samples taken by biopsy or surgical excision from 39 cases coming out of 841 patients investigated in the above-mentioned period of time and diagnosed from histological point of view with tuberculosis (TB). Granuloma cell population was assessed using immunohistochemical method. For diagnostic confirmation, Ziehl-Neelsen staining has been used as a rule but, in some cases, immunohistochemistry was also used. RESULTS: TB lesions predominated in men usually around or over 50 years old. The diagnostic was suspected in almost half of the cases. Right cavity was more affected and the extended fibrosis was present in a significant number of cases. The inflammatory conflict was of reactive type, with giant Langhans cells granulomas and acidophilic necrosis but sometimes with superinfection or significant fibrous sequelae. CONCLUSIONS: Pleural effusions of TB origin are a reality more and more present due to the recrudescence of pulmonary TB in the last decades. Their presence should be suspected if faced to a unilateral pleural effusion with free-flowing fluid occurred almost often to a man of any age from youth to elderly.

New advances in the development of sarcoidosis models: a synopsis of a symposium sponsored by the Foundation for Sarcoidosis Research.

Sarcoidosis is a complex disease with variable phenotypes that will require a multisystem approach to understand pathophysiology. One of the most challenging problems in sarcoidosis research is the absence of valid and widely accepted experimental models that accurately simulate human disease. The Foundation of Sarcoidosis Research (FSR) has funded five projects for the development of novel experimental models for sarcoidosis, presented and discussed in a workshop organized during the European Respiratory Society Congress held in Milan from September 9th to 13th. The experimental, in vivo or in sillico models presented may be quite helpful for investigating specific pathogenic and therapeutic questions, addressing especially severe forms of sarcoidosis. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 2-4).

Large pleural tumor revealed by severe hypoglycemia: Doege-Potter syndrome.

AIM: Doege-Potter syndrome is a rare condition consisting of a mesenchymal tumor, either benign or malignant, accompanied by severe hypoglycemia. The syndrome was first described independently by two American physicians, Karl Walter Doege (1867-1932) and Roy Pilling Potter (1879-1968), in 1930, but it was not before 1988 that it was associated with non-islet cell tumor production of insulin growth factor (IGF) that induces hypoglycemia as a paraneoplastic syndrome. CASE PRESENTATION: We present the case of a 61-year-old woman with severe hypoglycemia that induced seizures. On the general check-up, a massive tumor occupying the lower part of left hemi-thorax was discovered. Initially, corticosteroids, glucose i.v. and high carbohydrate diet managed to prevent the severe blood glucose drop. Surgery exposed a massive well-defined pleural tumor. After surgical removal, blood glucose stabilized. Histological examination confirmed the fibrous tumor that proved to be malignant on immunochemistry. DISCUSSION: The authors discuss other cases reported in the literature of this rare condition and its pathogenic mechanisms, the presented case being the first reported in Romania. CONCLUSIONS: The clinician should be aware of the possible existence of a pleural tumor in a patient presenting an unexplained hypoglycemia because the surgical removal of the tumor can solve the clinical manifestations.

Antacid therapy in idiopathic pulmonary fibrosis: more questions than answers?

Idiopathic pulmonary fibrosis (IPF) is a progressive parenchymal lung disease of complex cause. Gastro-oesophageal reflux (GER) and microaspiration have been proposed as risk factors for the development and progression of IPF, but robust definitive data are few. A recent international guideline conditionally recommended the use of antacid therapy (proton pump inhibitors or histamine-2-receptor antagonists) for patients with IPF, in the absence of oesophageal reflux or symptoms. In this Position Paper, we summarise the literature addressing the association between GER and IPF, and also identify future research priorities that could clarify this issue. We shed light on the process through which the guideline recommendation was achieved and aim to contextualise the recommendation for providers caring for patients with IPF.

New treatments in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis is a chronic fibrotic pulmonary disease of unknown origin, with an unfavourable prognosis, leading to death by respiratory failure in most patients within 3-5 years ofdiagnosis. Several drugs were studied for the treatment of this disease, and most of them were not able to stop the relentless evolution of the disease (warfarin, corticosteroids in combination with azathioprine, N-acetylcysteine, ambrisentan, bosentan, sildenafil, antiacids). Two novel drugs, pirfenidone and nintedanib, proved effective in reducing lung function decline, improving the patient's quality of life, and increasing the patient's probability of survival. These drugs were approved by international health authorities for use in the treatment of IPF patients. The paper refers also to the status of IPF patients in Romania, where epidemiological data are not known, and where the disease is most likely severely underdiagnosed. Patients are typically diagnosed late, and are therefore in advanced stages of the disease. A proactive attitude, in favour of identification and early diagnosis of IPF patients is highly needed in order to offer to these patients the opportunity of treatment, improved survival, and a better quality of life.

Tissue prints for the rapid diagnosis of malignancy in lung cancer.

UNLABELLED: Rapid diagnosis of malignancy during oncological surgery is crucial for making decisions related to the extension of the resection. The tissue prints, used initially for plant biology but also for prostate or breast cancer diagnosis, might be useful as a rapid cytological diagnosis. MATERIALS AND METHODS: Tissue prints were done from freshly sectioned excised tissue fragments in patients operated between March 2010 and February 2012 in the Department of Surgery for cancer or benign lesions. Tissue prints were examined by a cytologist and considered as malignant or benign. Same fragments were then processed in the pathology laboratory using the typical paraffin-embedding method. All slides were examined by the same pathologist and considered the golden standard for malignancy and histological type. RESULTS: Three hundred and eleven fragments were examined, obtained from lung masses, lymph nodes, pleura and mediastinal masses, pathology showed 208 malignant and 103 benign. Tissue prints identified 227 malignant and 84 benign. For identifying malignancy, tissue prints had a sensibility of 0.91, specificity 0.64. Positive predictive value was 0.86 and negative predictive value 0.78. For lymph nodes, the specificity was better. In lymphomas and adenocarcinomas, tissue prints identified also the histology type in most cases. CONCLUSIONS: Tissue prints are rapid, easy to perform, cheap, with high sensibility but specificity lower than literature data on frozen sections. This might be improved by a better selection of cases where tissue prints are used for rapid diagnosis.

Morphological aspects in tuberculosis of oral cavity - our experience and a review of the literature attempt.

AIM: The authors continue a started series of articles about extrapulmonary tuberculosis (EPTB) with the assessment of the mycobacterial lesions discovered on tissue samples of the oral cavity structures in the Department of Pathology of the Emergency County Hospital of Craiova, Romania, and the review of the cases reported in the literature available, between 1990 and 2013. MATERIALS AND METHODS: The studied material consisted, for our series, of samples obtained by biopsy or surgical excision, including the salivary glands and excluding the lymph nodes from 17 patients histopathologically diagnosed with tuberculosis and, for review series, 190 papers selected from PubMed database. RESULTS: The number of cases reported increased throughout the studied period. Most cases came from departments connected with oral pathology but also from various medical and surgical departments. In general, patients were adults with a mean age of around 40 years, with twice as many men than women, without no information or no clinical suspicion of tuberculosis (TB) at the admission. When reported, the provisional diagnostic was oriented most often towards neoplastic proliferation. There was no information about human immunodeficiency virus (HIV) testing in more than half of the case reports but when existed the result was two-fold more frequently negative than positive. TB lesions of the oral cavity were more often primary infections than secondary. From morphological point of view, the granuloma cellular population included both epithelioid and Langhans cells in most of the cases, the necrosis, present in most of the cases, displayed the whole range of morphological features, but mainly the acidophilic, microgranular one and the perilesional fibrosis was absent in almost all of the cases. As a whole, well-differentiated granulomas were the most frequent, usually of grade II - reactive type ("homeostatic") but with a significant contingent of grade I - hyperplastic ("protective") granulomas. Local extension was usually not present and, when present, regional lymph nodes were mainly involved. Coexistence of TB lesions with a neoplastic proliferation was very rare and when present it was mainly located in the parotid gland. Apart from this general profile, particular, individual profiles were observed for each of the oral cavity segments. CONCLUSIONS: TB lesions in the oral cavity are indeed a rare event but no swelling or ulcer in the oral cavity should be disregarded by the medical practitioners because it could be tuberculosis.

[REGIS--Romanian National Registry for Interstitial Lung Diseases and Sarcoidosis: launch of the website and building-up the database]. / REGIS--Registrul National de Pneumopatii Interstitiale Difuze si Sarcoidoza: lansarea site-ulu web si modul de alcatuire a bazei de date.

REGIS--Romanian National Registry for Interstitial Lung Diseases and Sarcoidosis: launch of the website and building-up the database Interstitial lung diseases (ILD) comprise about 200 different diseases with low prevalence, some evolving towards irreversible lung fibrosis. The diagnostic of each disease involves complex investigations (high resolution CT scan, broncho-alveolar lavage, complex lung function testing, surgical biopsy), but the main element is the expertise of the clinician and the multidisciplinary diagnostic approach. The creation of a national registry for ILD and sarcoidosis allows putting together in the same database numerous cases, now spread around the country. REGIS is the initiative of a group of physicians from "Marius Nasta" Institute of Pulmonology Bucharest and from the Pulmonology Dept. of "Victor Babes" Infectious Diseases Hospital, Timisoara. REGIS is an online registry, available at www. regis.ro, consisting of several components: 1. The registry per se, in which the accredited physicians will be able to feed information about their patients, by filling-in a questionnaire 2. Educational platform, containing a collection of clinical cases organized according to diagnosis, which is generated anonymously from the data from the registry 3. Patients' page, with information on ILD in general and on the most frequent diseases in the group. Expected results are: increasing the physicians' knowledge on ILDs, informing correctly the patients, bringing up to light new cases previously not diagnosed, building up a database for research (prevalence studies, risk factor studies, selection of patients for clinical trials), creating a base for a future national health programme dedicated to idiopathic pulmonary fibrosis patients, preparing future projects for development of a Romanian centre for lung transplantation.

[Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs): short update]. / Reactii de hipersensibilitate la antiinflamatorii nesteroidiene: scurta actualizare.

Hypersensitivity reactions to aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are a challenge to the clinicians, due to their severity. In susceptible individuals, NSAIDs induce a wide spectrum of reactions with various timing and organ manifestations, involving immunological and non-immunological mechanisms. Diagnosis of hypersensitivity to NSAID is based on characteristic symptoms precipitated with ASA/NSAIDs. Oral challenge with NSAID is the "gold standard" for the diagnosis and can be performed in order to confirm hypersensitivity to the culprit drug or to confirm or exclude tolerance to an alternative drug. Diagnosis process includes understanding of the underlying mechanism, and is mandatory for prevention of future events.

Lymph node tuberculosis - an attempt of clinico-morphological study and review of the literature.

AIM: The authors assessed the mycobacterial lesions in the lymph nodes discovered on tissue samples coming from the surgical stage in the Department of Pathology, Emergency County Hospital of Craiova, Romania, starting from 1990 until 2012. MATERIALS AND METHODS: The studied material consisted of lymph node (LN) tissue samples obtained by biopsy or surgical excision from 362 patients histopathologically diagnosed with tuberculosis. For confirming the diagnosis, Ziehl-Neelsen staining was carried out and, in some cases, PCR technique was used. RESULTS: Patients were mainly women, with a mean age of 35 years. The suspicion of diagnosis at admission was reduced, the most usual diagnosis being a very general and uncertain one of "adenopathy/polyadenopathy". In only few cases, other tissues/organs have been affected in the same time with the LN determination. Also, multiple LN group involvement was present in only five cases. The most affected LN groups were: the lateral cervical, submandibular, axillary, inguinal, supraclavicular and mesenteric. In paired LN groups, there was no predilection for any of the body sides. Epithelioid cells (ECs) and giant Langhans cells (GLCs) were present together in most of the granulomatous reactions. However, the presence of neutrophils in 10% of the cases should be noticed. Necrosis was present in almost all cases, displaying the whole range of morphological features, but usually the acidophilic, microgranular one. Fibrosis was rarely encountered. As a whole, well-differentiated granulomas were the most frequent but the presence of hyporeactive granulomas in more than a quarter of the cases and that of non-reactive granulomas in more than 10% of the cases should be noticed. The extension of TB process was not a rare event. CONCLUSIONS: LNs seem to be the favorite location of TB besides the lung. The overall morphological picture revealed an active and destructive profile of the bacillary aggression in the LN parenchyma, which could mean either a higher sensitivity of the LN tissue or a more vulnerable background of the patients with TBLN lesions.