Pulmonary sarcoid granulomas are characterised by their elective distribution along collecting lymphatics. However, relationships between granulomas and intralobular lymphatics or blood ...microvascularisation have not been investigated. Therefore, we undertook a specific analysis of blood capillaries and lymphatics supplying sarcoid granulomas to identify additional clues to understanding the pathophysiogenesis of these lesions. Six pulmonary samples were immunolabelled with D2-40, anti-CD34 and anti-CD31 antibodies, paying particular attention to the relationships between lymphatics and granulomas, and the pattern of blood microvessels supplying sarcoid lesions. A morphometric study of granulomas included their distance to lymphatics and a three-dimensional reconstruction of a granuloma in its lymphatic context. Intralobular granulomas were closely associated with lymphatics; apart from a few granulomas, blood capillaries stopped at the outer border of the fibrous ring surrounding granulomas, and perigranuloma capillaries were particularly scarce. Our observations of the lymphatic and blood microvascular environment of intralobular pulmonary sarcoid granulomas provide evidence for the critical role of lymphatics in the emergence of these lesions. Moreover, pulmonary sarcoid lesions could be considered avascular structures, thereby providing new insights into the understanding of the granuloma physiology and the distribution of blood-borne therapeutic agents.
Diagnosis issues in sarcoidosis Jeny, F.; Bernaudin, J.-F.; Cohen Aubart, F. ...
Respiratory medicine and research,
03/2020, Letnik:
77
Journal Article
Recenzirano
Odprti dostop
Multiple problems may be encountered during the diagnosis of sarcoidosis: at first diagnose sarcoidosis in an appropriate clinical setting, secondly, identify any manifestation to be linked to ...sarcoidosis at diagnosis work-up and during evolution; thirdly, recognize “danger” in sarcoidosis and parasarcoidosis syndromes, and finally, diagnose sarcoidosis recovery. Diagnosis is often delayed as presentation may be diverse, non-specific, or atypical. Diagnosis of sarcoidosis is based on three criteria: a compatible presentation; evidence of non-caseating granulomas and exclusion of any alternative diagnosis. However, even when all criteria are fulfilled, the probability of sarcoidosis diagnosis varies from definite to only possible depending upon the presence of more or less characteristic radio-clinical and histopathological findings and on the epidemiological context. Bilateral hilar lymphadenopathy and/or diffuse lung micronodules mainly along lymphatics are the most frequent highly suggestive findings. Evidence of granulomas relies on superficial biopsies of clinically suspected lesion when present or most often by bronchial endoscopy. The diagnosis of sarcoidosis may be difficult in absence of thoracic or skin manifestations and may require the benefit of hindsight before being definitive. Differential diagnoses, mainly tuberculosis, must be considered. The diagnosis of events during evolution relies on serial clinical, pulmonary function, radiographic evaluation and on extrapulmonary manifestations work-up, including electrocardiogram and blood biology. Affected organs need to be related to sarcoidosis using an appropriate diagnostic assessment instrument. To declare the recovery of sarcoidosis, all manifestations must have disappeared spontaneously or after 3–5 years post-treatment without relapse.
Background
Sarcoidosis, characterized by epithelioid granulomas, is considered to be caused by a complex interplay between genetics and environmental agents. It has been hypothesized that exogenous ...inorganic particles as crystalline silica could be a causal or adjuvant agent in sarcoidosis onset.
Objectives
To investigate the location, frequency and physicochemical characteristics of foreign materials and mineral tissue deposits in the granulomatous area of cutaneous sarcoidosis.
Methods
Skin biopsies (n = 14) from patients diagnosed with cutaneous sarcoidosis (mean age 43 years; 11 patients with extracutaneous involvement) were investigated using polarized light examination (PLE), μFourier Transform Infra‐Red (μFT‐IR) spectroscopy and Field Emission Scanning Electron Microscopy coupled with Energy Dispersive X‐ray Spectroscopy (FE‐SEM/EDX).
Results
Combined PLE, μFT‐IR, FE‐SEM/EDX analysis allowed to characterize mineral deposits in 7/14 biopsies (50%). It identified crystalline silica (SiO2) inside granulomas in three biopsies and calcite (CaCO3) at their periphery in 4.
Conclusion
This study emphasizes the need of using combined methods for assessment of mineral deposits in granulomatous diseases. According to the location and characteristics of deposits, we can hypothesize that SiO2 particles contribute to the granuloma formation, whereas CaCO3 deposits are related to the granuloma biology. However, the significance of the association between SiO2 deposits and sarcoidosis is still disputed.
Fine-needle aspiration cytology, which is well established to be accurate for the diagnosis of thyroid cancer, may be inconclusive for the follicular thyroid neoplasms. As galectin-3 was suggested to ...be a marker of malignant thyrocytes, we investigated whether this protein might be helpful in the diagnosis of aspirates classified as undeterminate by cytology. After establishing an easy processing of aspirates for galectin-3 immunodetection, a series of aspirates categorised as benign (n=63), malignant (n=17) or undeterminate (n=34) was prospectively analysed for galectin-3. Only the patients with malignant or undeterminate lesions underwent surgery. Most lesions (86%) diagnosed as malignant by cytology or after surgery were positive for galectin-3. The majority of lesions (94%) classified as benign by cytology or after surgery was negative for galectin-3. The positive and negative predictive values were 83 and 95%, respectively. When focusing on the undeterminate lesions, the sensitivity and specificity were 75 and 90%, respectively, while the positive and negative predictive values were 82 and 87%, respectively. The specificity and the positive predictive value were higher (100%) when considering the percentage of stained cells. Altogether these results show that galectin-3 constitutes a useful marker in the diagnosis of thyroid lesions classified as undeterminate by conventional cytology.
In humans, interferon γ (IFN-γ) receptor deficiency leads to a predisposition to mycobacterial infections and impairs the formation of mature granulomas. Interleukin-12 (IL-12) receptor deficiency ...was found in otherwise healthy individuals with mycobacterial infections. Mature granulomas were seen, surrounded by T cells and centered with epithelioid and multinucleated giant cells, yet reduced IFN-γ concentrations were found to be secreted by activated natural killer and T cells. Thus, IL-12-dependent IFN-γ secretion in humans seems essential in the control of mycobacterial infections, despite the formation of mature granulomas due to IL-12-independent IFN-γ secretion.
It can be hypothesised that inherited polymorphisms in the drug-transporter ABCB1 gene may interfere with interindividual variations in drug response in breast cancer patients. Docetaxel is a ...substrate for ABCB1 whose function has been shown to be modulated by oestrogen and progesterone.
Whether ABCB1 polymorphisms including T-129C, A61G, C1236T, G2677T/A and C3435T polymorphisms could account for variations in the disposition of docetaxel and whether menopausal status at the time of diagnosis might interact with this effect were analysed in women receiving neoadjuvant chemotherapy for breast cancer (n=86).
A highly significant association was observed, but restricted to premenopausal women (n=53), between the pharmacokinetics of docetaxel and C3435T polymorphism, as patients with CC genotype had lower mean values of the area under the plasma concentration-time curve (AUC) of docetaxel than patients with CT and TT genotypes (P<0.0001). Comparison between pre- and postmenopausal women with the same C3435T genotype yielded a significant difference in docetaxel AUC only for CC genotype (P<0.0001).
These results suggest that C3435T polymorphism genotyping and menopausal status at the time of diagnosis might be useful when considering chemotherapy regimens including docetaxel in breast cancer patients.
Background: It has been suggested that histologically undetectable or ‘occult’ metastases in the lymphatic system could explain some recurrences. HPV DNA screening by means of the polymerase chain ...reaction (PCR) has been proposed as a method to detect occult metastases. This study was designed to determine the frequency of HPV DNA detection by PCR in sentinel lymph node (SN), and its relation to the clinical characteristics and outcome of women with cervical cancer. Patients and methods: The primary cervical tumor and SN were tested for HPV DNA by means of PCR in 59 patients. Results: Fifteen (25.4%) of the 59 women undergoing the SN procedure had an involved SN. HPV DNA was more frequent in positive SN than in negative SN (P < 0.0001). Seven patients had a recurrence, after a mean delay of 17 months (range: 10–26). One of seven patients with a recurrence had an involved SN. HPV DNA was detected in an SN of one of seven patients with recurrence and nine (19.5%) of 46 patients without recurrence (not significant). Conclusion: In women with cervical cancer, HPV DNA screening of sentinel nodes might help to identify patients at risk of lymph node metastases and recurrence.
Tumor infiltrate, predominantly constituted by lymphocytes, may represent an important prognostic factor in bronchioloalveolar carcinoma (BAC), in addition to tumor extension and histological type. ...In the present study, we determined the presence, the origin, and the prognostic importance of neutrophils that also participate in leukocyte infiltrates of BAC. Neutrophil alveolitis was determined immunohistochemically in both lung biopsies and bronchoalveolar lavage (BAL) fluid samples from 29 patients with histologically proved BAC. The local expression of interleukin (IL)-8 was determined by immunohistochemical and immunoenzymatic techniques. Neutrophil counts were analyzed in relation to the clinical outcome of patients by the Kaplan-Meier method and Cox's univariate and stepwise multivariate models. Lymphocytes and neutrophils dominated the inflammatory cell population in the lower respiratory tract of patients with BAC. Neutrophils were located mainly in the alveolar lumen and seldom in alveolar wall whereas lymphocytes were exclusively present in alveolar wall. A relationship was observed between the number of neutrophils and the level of IL-8 in BAL fluid suggesting the involvement of that chemokine in neutrophil recruitment. The tumor cells were the predominant cells that appeared to express IL-8 by immunolocalization. The presence of increased numbers of neutrophils was significantly associated with a poorer outcome in patients with BAC (P = 0.02). In a multivariate analysis, the neutrophil percentage in BAL fluid was an independent predictor of clinical outcome. The risk of death was increased substantially (rate ratio, 5.2; 95% confidence interval, 1.1 to 24.7) among patients with BAL neutrophil percentage of > or = 39% (median of the distribution) as compared with the others. In BAC, neutrophils accumulate in the alveolar lumen. Elaboration of IL-8 by tumor cells may be responsible for this event, which is associated with a significantly higher risk of death.
PDF
