Immunohistochemical analysis of axillary skin biopsies for the detection of adrenergic innervation of sweat glands in normal subjects and Parkinson’s disease patients

Beside the typical motor symptoms Parkinson’s disease (PD) is characterized, with varying severity, by autonomic dysfunction. Several studies have shed light on the anatomical and molecular changes that underlie the peripheral neuronal degeneration associated with PD and other Lewy body (LB) diseases (LBDs). By using skin biopsies from LBDs patients it was possible to detect misfolded phospho-α-synuclein (p-syn) deposits within dermal nerve fibers and correlate them with a reduced density of small nerve fibers. (1, 2). The skin biopsy approach is an inexpensive and minimally invasive technique. To date, there is not a standardized procedure for sampling site, tissue processing and nerve fibre assessment, so the goal of a diagnostic instrument for an early diagnosis of (LBDs) still remains a challenge. We have carried out a retrospective study setting up a novel protocol based on 10 µm thick serial sections from FFPE axillary skin biopsies. This choice take advantage from the presence of apocrine glands in the axillary region, as they receive a dense sympathetic adrenergic innervation, exploitable for a clear nervous fibers tracking. The biopsies were taken from 14 individuals who had been, in the first instance, diagnosed with various traits of motor and neurological dysfunction and two control subjects. Serial tissue sections were analysed by IHC (DAB chromogen) and by immunofluorescent labelling, using anti-p-α-synuclein (S129), anti- α -synuclein, anti-PGP9.5 and anti-tyrosine hydroxylase antibodies. This particular setting has proven useful to well highlight the adrenergic fibers surrounding the apocrine sweat glands and to visualize the fibers α -synuclein deposition. Our results enabled us to support the first diagnosis in various cases with probable PD but gave a negative p-Syn-S129 immunoreactivity results for samples from vascular Parkinson, multiple system atrophy, essential tremor and frontotemporal dementia. Our methodological setting is able to detect the adrenergic innervation of sweat apocrine glands and both the presence of Lewy bodies and Lewy neurites in axillary skin biopsies

Calcitonin-producing well-differentiated neuroendocrine carcinoma (carcinoid tumor) of the urinary bladder: case report

BACKGROUND: The occurrence of calcitonin-secreting primary carcinoid tumor of the urinary bladder is extremely rare. CASE PRESENTATION: The case of a 68-year-old male with carcinoid tumor arising in the urinary bladder is presented. Transurethral resection of a polypoid small tumor 0.4 cm in diameter was performed. Immunohistochemical study using neuroendocrine markers allowed a straightforward diagnosis of a low-grade neuroendocrine carcinoma (carcinoid tumor) of the urinary bladder. Immunohistochemistry demonstrated calcitonin immunoreactivity in the most of the tumor cells. CONCLUSION: This tumor shows specific clinical, macroscopical and histological features and must be considered in the differential diagnosis of bladder neoplasms

Hypoxia induces Galectin-3 and Bcl-2 over-expression in human umbilical vein endothelial cells (HUVECs)

Angiogenesis, the growth of new blood vessels from pre-existing endothelium, is a critical phenomenon occurring during development and tissue regeneration. In pathological conditions such as inflammation and malignancies, hypoxia represent one of the most important driver of angiogenesis, mainly via the release of nitric oxide [1]. Here we investigate the behavior of human umbilical vein endothelial cells (HUVECs) treated with 100 mM CoCl2 for 24 hours, a condition mimicking hypoxia by the stabilization of HIF-1α and HIF-2α [2,3]. MTT and wound healing assays were performed to evaluate cell migration and proliferation, respectively, while Bcl-2 and Galectin-3 expression levels were analyzed by western blotting. We showed that hypoxic condition resulted in reduced proliferation and migration with increased expression of Galectin-3 and Bcl-2. These preliminary results provide new insights in the characterization of Galectin-3/Bcl-2 interplay in endothelial cell survival under hypoxic condition, and will contribute to a better understanding of hypoxia influences on tumor angiogenesis

Surprising autopsy diagnosis in unclear initial situation. A case of intravascular B cell lymphoma

Intravascular large B cell lymphoma (IVLBCL) is a rare extranodal non-Hodgkin lymphoma characterized by proliferation of malignant cells within the lumen of small vessels, with a predilection for the central nervous system and the skin [1]. IVLBCL clinical course is highly aggressive, clinical signs and symptoms are not specific and may consist in neurological deficits, fever of unknown origin, cutaneous lesions, lacking of a typical neuroimaging pattern [1]. For all these reasons the diagnosis is frequently missed and the exitus is frequent, therefore post-mortem evaluation is necessary to clarify the clinical history. We present a case of IVLBCL in a 62-year-old female with unusual symptomatology, mimicking a vascular multinfarctual cerebropathy; post-mortem autopsy was diriment to define the nature of the disease. Immu- nohistochemical analysis for anti-CD20 revealed the ubiquitary presence of malignant lymphoid B-cells into the vessels of all organs analyzed, allowing the definitive diag- nosis. Although the diagnostic procedure for such pathology is still a matter for fur- ther studies, adequate interpretation of neuro-imaging and morphological findings, as well as of systemic symptoms can provide a right diagnostic hypothesis, suggest- ing focused biopsy in vivo

Impairment of T cell development and acute inflammatory response in HIV-1 Tat transgenic mice

Immune activation and chronic inflammation are hallmark features of HIV infection causing T-cell depletion and cellular immune dysfunction in AIDS. Here, we addressed the issue whether HIV-1 Tat could affect T cell development and acute inflammatory response by generating a transgenic mouse expressing Tat in lymphoid tissue. Tat-Tg mice showed thymus atrophy and the maturation block from DN4 to DP thymic subpopulations, resulting in CD4(+) and CD8(+) T cells depletion in peripheral blood. In Tat-positive thymus, we observed the increased p65/NF-κB activity and deregulated expression of cytokines/chemokines and microRNA-181a-1, which are involved in T-lymphopoiesis. Upon LPS intraperitoneal injection, Tat-Tg mice developed an abnormal acute inflammatory response, which was characterized by enhanced lethality and production of inflammatory cytokines. Based on these findings, Tat-Tg mouse could represent an animal model for testing adjunctive therapies of HIV-1-associated inflammation and immune deregulation

Early invasive vulvar squamous cell carcinoma arising in a woman with vulvar pemphigus vulgaris and systemic lupus erythematosus

Pemphigus vulgaris (PV) is an autoimmune blistering disease of the skin and mucous membranes. Genital involvement occurs when most other common sites are concurrently affected or are in remission. Systemic lupus erythematosus (SLE) is an autoimmune disease that may affect many parts of the body and the skin with occasional bullous lesions. Pemphigus vulgaris and SLE may be associated, albeit rarely. Here, we report the first case of a woman affected with SLE presenting with early invasive squamous cell carcinoma (SCC) arising from Pemphigus Vulgaris of the vulva

Anxiety and depression in keratotic oral lichen planus: a multicentric study from the SIPMO

Objectives: Oral lichen planus with exclusive keratotic reticular, papular, and/or plaque-like lesions (K-OLP) is a clinical pattern of OLP that may be associated with a complex symptomatology and psychological alteration. The aim of the study was to evaluate the prevalence of anxiety (A) and depression (D) in patients with K-OLP, analyzing the potential predictors which can affect mental health status. Methods: Three hundred K-OLP patients versus 300 healthy controls (HC) were recruited in 15 Italian universities. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), and Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A) were administered. Results: The K-OLP patients showed statistically higher scores in the NRS, T-PRI, HAM-D, and HAM-A compared with the HC (p-value < 0.001**). A and D were found in 158 (52.7%) and 148 (49.3%) K-OLP patients. Strong linear correlations were identified between HAM-A, HAM-D, NRS, T-PRI, and employment status and between HAM-D, HAM-A, NRS, T-PRI, employment status, and female gender. Multivariate logistic regression revealed that HAM-D and HAM-A showed the greatest increase in the R2 value for A and D in the K-OLP patients, respectively (DR2 = 55.5% p-value < 0.001**; DR2 = 56.5% p-value < 0.001**). Conclusions: The prevalence of A and D is higher in the K-OLP patients compared with the HC, also found in K-OLP subjects without pain, suggesting that the processing of pain may be in a certain way independent of the processing of mood. Clinical relevance: Mood disorders and pain assessment should be carefully performed in relation to K-OLP to obtain a complete analysis of the patients

AIRO Breast Cancer Group Best Clinical Practice 2022 Update

Introduction: Breast cancer is the most common tumor in women and represents the leading cause of cancer death. Radiation therapy plays a key-role in the treatment of all breast cancer stages. Therefore, the adoption of evidence-based treatments is warranted, to ensure equity of access and standardization of care in clinical practice.Method: This national document on the highest evidence-based available data was developed and endorsed by the Italian Association of Radiation and Clinical Oncology (AIRO) Breast Cancer Group.We analyzed literature data regarding breast radiation therapy, using the SIGN (Scottish Intercollegiate Guidelines Network) methodology (www.sign.ac.uk). Updated findings from the literature were examined, including the highest levels of evidence (meta-analyses, randomized trials, and international guidelines) with a significant impact on clinical practice. The document deals with the role of radiation therapy in the treatment of primary breast cancer, local relapse, and metastatic disease, with focus on diagnosis, staging, local and systemic therapies, and follow up. Information is given on indications, techniques, total doses, and fractionations.Results: An extensive literature review from 2013 to 2021 was performed. The work was organized according to a general index of different topics and most chapters included individual questions and, when possible, synoptic and summary tables. Indications for radiation therapy in breast cancer were examined and integrated with other oncological treatments. A total of 50 questions were analyzed and answered.Four large areas of interest were investigated: (1) general strategy (multidisciplinary approach, contraindications, preliminary assessments, staging and management of patients with electronic devices); (2) systemic therapy (primary, adjuvant, in metastatic setting); (3) clinical aspects (invasive, non-invasive and micro-invasive carcinoma; particular situations such as young and elderly patients, breast cancer in males and cancer during pregnancy; follow up with possible acute and late toxicities; loco-regional relapse and metastatic disease); (4) technical aspects (radiation after conservative surgery or mastectomy, indications for boost, lymph node radiotherapy and partial breast irradiation).Appendixes about tumor bed boost and breast and lymph nodes contouring were implemented, including a dedicated web application. The scientific work was reviewed and validated by an expert group of breast cancer key-opinion leaders.Conclusions: Optimal breast cancer management requires a multidisciplinary approach sharing therapeutic strategies with the other involved specialists and the patient, within a coordinated and dedicated clinical path. In recent years, the high-level quality radiation therapy has shown a significant impact on local control and survival of breast cancer patients. Therefore, it is necessary to offer and guarantee accurate treatments according to the best standards of evidence-based medicine