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Eosinophilic fasciitis (EF) remains a diagnostic challenge due to its rarity and resemblance to scleroderma. This case report aims to provide a cohesive exploration of EF's clinical nuances, emphasizing the importance of accurate diagnosis and effective management. A 52-year-old male developed bilateral forearm and calf hardening, along with erythema, pruritus, and pain four months prior to the presentation in our Clinic. The symptoms initially debuted bilaterally in the forearms and progressed to involve the calves, distal arms, and thighs. Clinical examination revealed symmetrical plaques on forearms and calves, featuring erythematous, hyper, and hypopigmented elements extending proximally, a positive "groove sign" and a moderate difficulty in knee joint flexion. Despite these findings, the patient was generally in good condition, without any other notable clinical signs. Initial laboratory findings showed slightly increased percentual eosinophil levels, elevated C-reactive protein (CRP), normal erythrocyte sedimentation rate (ESR), and negative antinuclear and scleroderma specific antibodies. Magnetic resonance imaging (MRI) demonstrated enhanced fascial signal and thickening while the fascia-muscle biopsy revealed marked edema and inflammatory lymphoplasmacytic infiltrate, consistent with the diagnosis of EF. The patient showed a favorable response to systemic corticosteroids. EF predominantly affects males aged 30 to 60 and is characterized by a sudden onset and unclear etiological factors. Differential diagnosis requires careful exclusion of scleroderma and other mimicking conditions. Diagnostic modalities such as skin-muscle biopsy and MRI reveal characteristic findings like inflammatory infiltrate and fascial thickening. Accurate diagnosis and differentiation from scleroderma are crucial, with early intervention involving glucocorticoids and immunosuppressive agents improving long-term outcomes.
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Eosinofilia , Fasciite , Humanos , Fasciite/patologia , Fasciite/diagnóstico , Masculino , Eosinofilia/patologia , Eosinofilia/diagnóstico , Pessoa de Meia-Idade , Imageamento por Ressonância MagnéticaRESUMO
The first lung transplant (LT) was made in Romania in 2018 at a 36-year-old male patient with chronic obstructive pulmonary disease (COPD). The study follows the first LT rehabilitation by describing the physical therapy program (PTP), the measurements of body mass and appendicular skeletal muscle mass (ASM) by bio-impedancemetry analysis (BIA) and the functional capacity assessment realized by the six-minute walk test (6MWT) and by the functional respiratory tests (FRTs) in order to evaluate the effectiveness of functional respiratory rehabilitation in this case during a period of one year. In parallel, repeated transbronchial biopsies were performed after six weeks, three months, six months and one year since the transplant. Only the first biopsies showed injuries suggesting an acute rejection, all the rest revealing mild, unspecific lesions. The patient followed 15 sessions of respiratory exercises, joints mobilizations and progressive global muscle strength started one month after LT surgery and was also instructed to perform the exercises at home, using a tablet given at discharge and under monthly guidance through telemedicine. All the measurements were performed before and after the rehabilitation cure, and it was repeated at three different evaluations for one year. The results showed that at the end of follow-up, the 6MWT was significantly increased from 59% of predicted distance at the intake in post-acute hospitalization to 166% at one year after LT, without desaturation that represent a very good evolution; the FRTs increased to normal, and the body weight increased with 18 kg (from severe underweight to normal weight) with constant increasement of skeletal muscle mass. The use of PTP after LT surgery significantly improves functional capacity and increases body mass and skeletal muscle mass.
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Transplante de Pulmão , Modalidades de Fisioterapia , Humanos , Masculino , AdultoRESUMO
Skin malignant melanoma (MM) is one of the most frequent and aggressive neoplasia worldwide. Its associated high mortality rates are mostly due to its metastases, while diagnosis and treatment of MM in its early stages is of favorable prognostic. Even skin superficial MMs at incipient local stages can already present with lymph node invasion and distant metastases. Therefore, knowledge of the controllable risk factors and pathogenic mechanisms of MM development, spreading, and metastatic pattern, as well as early diagnosis, are essential to decrease the high mortality rates associated with cutaneous malignant melanoma. Genetic factors are incriminated, although lifetime-acquired genetic mutations appear to be even more frequently involved in the development of MM. Skin melanocytes divide only twice per year and have time to accumulate genetic mutations as a consequence of environmental aggressive factors, such as UV exposure. In the search for more promising therapies, matrix metalloproteinases have become of significant interest, such as MMP-1, MMP-2, MMP-9, and MMP-13, which have been linked to more aggressive forms of cancer and earlier metastases. Therefore, the development of specific synthetic inhibitors of MMP secretion or activity could represent a more promising and effective approach to the personalized treatment of MM patients.
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Metaloproteinases da Matriz , Melanoma Maligno Cutâneo , Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/terapia , Melanoma/patologia , Melanoma/genética , Melanoma/metabolismo , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/genética , Metaloproteinases da Matriz/metabolismo , Animais , Inibidores de Metaloproteinases de Matriz/uso terapêutico , Inibidores de Metaloproteinases de Matriz/farmacologiaRESUMO
BACKGROUND: Matrix metalloproteinase (MMP)1, MMP9, MMP11, and MMP13 are overexpressed in malignant melanoma (MM), being associated with tumor invasive phase, metastases, and more aggressive neoplastic phenotypes. AIM: The main objective of the current study was to correlate the expression of the MMPs with the evolution of MM toward distant metastasis. PATIENTS, MATERIALS AND METHODS: We designed a retrospective cohort study, including 13 patients with metastatic MM. Data concerning age, sex, localization of the primary lesion and metastasis, and histological and immunohistochemical features (intensity of expression and percent of positive cells for MMPs) were statistically processed. RESULTS: The time between the diagnosis of primitive melanoma and the diagnosis of metastasis ranged between 0 and 73 months, with a mean value of 18.3 months. The metastases rich in MMP1- and MMP9-positive cells occurred earlier than the metastases with low levels of positive cells. The mean period until metastasis was shorter for the MMP1-expressing tumors than the ones without MMP1 expression. MMP13 expression in the tumor and its metastasis was significantly linked with the time until the metastasis occurrence. CONCLUSIONS: This study emphasizes the roles of MMP1, MMP9, and MMP13 in the process of metastasis in melanoma and the opportunity to use them as therapeutic targets and surveillance molecules.
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Metaloproteinase 13 da Matriz , Metaloproteinase 1 da Matriz , Metaloproteinase 9 da Matriz , Melanoma , Humanos , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 11 da Matriz/genética , Metaloproteinase 11 da Matriz/metabolismo , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Melanoma/genética , Melanoma/metabolismo , Estudos RetrospectivosRESUMO
The presence of lymphovascular invasion (LVI) in urothelial carcinoma (UC) is a poor prognostic finding. This is difficult to identify on routine hematoxylin-eosin (H&E)-stained slides, but considering the costs and time required for examination, immunohistochemical stains for the endothelium are not the recommended diagnostic protocol. We developed an AI-based automated method for LVI identification on H&E-stained slides. We selected two separate groups of UC patients with transurethral resection specimens. Group A had 105 patients (100 with UC; 5 with cystitis); group B had 55 patients (all with high-grade UC; D2-40 and CD34 immunohistochemical stains performed on each block). All the group A slides and 52 H&E cases from group B showing LVI using immunohistochemistry were scanned using an Aperio GT450 automatic scanner. We performed a pixel-per-pixel semantic segmentation of selected areas, and we trained InternImage to identify several classes. The DiceCoefficient and Intersection-over-Union scores for LVI detection using our method were 0.77 and 0.52, respectively. The pathologists' H&E-based evaluation in group B revealed 89.65% specificity, 42.30% sensitivity, 67.27% accuracy, and an F1 score of 0.55, which is much lower than the algorithm's DCC of 0.77. Our model outlines LVI on H&E-stained-slides more effectively than human examiners; thus, it proves a valuable tool for pathologists.
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In the present study, we employed the ddPCR and IHC techniques to assess the prevalence and roles of RAS and RAF mutations in a small batch of melanoma (n = 22), benign moles (n = 15), and normal skin samples (n = 15). Mutational screening revealed the coexistence of BRAF and NRAS mutations in melanomas and nevi and the occurrence of NRAS G12/G13 variants in healthy skin. All investigated nevi had driver mutations in the BRAF or NRAS genes and elevated p16 protein expression, indicating cell cycle arrest despite an increased mutational burden. BRAF V600 mutations were identified in 54% of melanomas, and NRAS G12/G13 mutations in 50%. The BRAF mutations were associated with the Breslow index (BI) (p = 0.029) and TIL infiltration (p = 0.027), whereas the NRAS mutations correlated with the BI (p = 0.01) and the mitotic index (p = 0.04). Here, we demonstrate that the "young" ddPCR technology is as effective as a CE-IVD marked real-time PCR method for detecting BRAF V600 hotspot mutations in tumor biopsies and recommend it for extended use in clinical settings. Moreover, ddPCR was able to detect low-frequency hotspot mutations, such as NRAS G12/G13, in our tissue specimens, which makes it a promising tool for investigating the mutational landscape of sun-damaged skin, benign nevi, and melanomas in more extensive clinical studies.
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Melanoma Maligno Cutâneo , Nevo de Células Epitelioides e Fusiformes , Neoplasias Cutâneas , Humanos , Análise Mutacional de DNA , Mutação , Nevo de Células Epitelioides e Fusiformes/genética , Projetos Piloto , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/genética , Melanoma Maligno Cutâneo/genéticaRESUMO
BACKGROUND: Histologic activity has emerged as an aspirational therapeutic goal in ulcerative colitis management. It is not yet a formal treatment target in ulcerative colitis. However, it could be used as an adjunct to mucosal healing to represent a deeper level of healing. We investigated mucosal and histologic remission rates and potential predictors of these outcomes in a cohort of UC patients. METHODS: We conducted a retrospective analysis of data collected from UC patients enrolled in an ongoing prospective cohort study. Mucosal healing was defined as Mayo endoscopic score = 0. RESULTS: A total of 131 patients with ulcerative colitis were enrolled in our study and were prospectively followed for a median length of 2 years (range 0-5 years), totaling 266 study visits. Mucosal healing was recorded for 27 patients at 70 (26%) different study visits. For patients with mucosal healing, histologic remission was achieved in 18/27 (66%) patients. On univariate analysis, sustained clinical remission, SIBDQ scores ≥ 5.5, CRP ≤ 5 mg/dL and absence of corticotherapy were associated with mucosal healing and SIBDQ scores ≥ 5.5 and CRP ≤ 5 mg/dL with histologic healing, respectively. After logistic regression analysis, none of the investigated factors were associated with mucosal and histologic healing. The number of CD8+ intraepithelial lymphocytes (IELs) was significantly greater than the number of CD4+ IELs in periods of disease activity, as well as during mucosal healing (p < 0.01 in both cases). CONCLUSIONS: Mucosal healing and histologic remission rates are low in real-life settings. The results of univariate analysis indicate that a good quality of life (SIBDQ score) and normal inflammatory markers (CRP) are associated with mucosal and histologic healing. However, frequently used patient- and disease-related factors, including mucosal healing, are not reliable predictors for histologic remission. Greater CD8+ lymphocyte involvement and higher CD8+/CD4+ distribution can have a meaningful impact on understanding the pathogenesis and natural history of ulcerative colitis, as well as future treatment options for lymphocyte-targeting medications.
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Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UC-OGC) is a rare subtype of pancreatic cancer, accounting for less than 1% of all pancreatic tumors. Preoperative diagnosis is cumbersome as cross-sectional imaging is often not capable to distinguish between UC-OGC and other pancreatic tumors such as pancreatic adenocarcinoma, mucinous carcinoma or neuroendocrine tumors and specific tumor markers seem to be lacking. Endoscopic ultrasound r `m(EUS) with tissue acquisition via fine-needle aspiration (FNA) or biopsy (FNB) with microscopic HE staining and immunohistochemistry allows for an accurate diagnosis, thus influencing further treatment. We present herein the cases of two patients with osteoclast-like giant cells tumors of the pancreas diagnosed by EUS-guided fine needle biopsy and perform a literature review on the role of EUS-guided biopsy for diagnosis.
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Adenocarcinoma , Carcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/diagnóstico por imagem , Osteoclastos/patologia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Carcinoma/patologia , Células Gigantes/patologia , Neoplasias PancreáticasRESUMO
Cutaneous melanoma is the most aggressive form of skin cancer and its incidence is unfortunately increasing. In the last decades, a progressive increase of new cases of diagnosed thin melanoma has been noted. This may be due to earlier detection, better surveillance, improved diagnostic criteria or increased exposure to sunlight. Despite the fact that Breslow tumor thickness has the strongest proven prognostic significance, there are still thin melanomas that metastasize and thick melanomas with favorable evolution. Therefore, the identification of strong predictive factors for survival is mandatory, particularly for patients with thin melanoma.
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Mycobacteria identification is crucial to diagnose tuberculosis. Since the bacillus is very small, finding it in Ziehl-Neelsen (ZN)-stained slides is a long task requiring significant pathologist's effort. We developed an automated (AI-based) method of identification of mycobacteria. We prepared a training dataset of over 260,000 positive and over 700,000,000 negative patches annotated on scans of 510 whole slide images (WSI) of ZN-stained slides (110 positive and 400 negative). Several image augmentation techniques coupled with different custom computer vision architectures were used. WSIs automatic analysis was followed by a report indicating areas more likely to present mycobacteria. Our model performs AI-based diagnosis (the final decision of the diagnosis of WSI belongs to the pathologist). The results were validated internally on a dataset of 286,000 patches and tested in pathology laboratory settings on 60 ZN slides (23 positive and 37 negative). We compared the pathologists' results obtained by separately evaluating slides and WSIs with the results given by a pathologist aided by automatic analysis of WSIs. Our architecture showed 0.977 area under the receiver operating characteristic curve. The clinical test presented 98.33% accuracy, 95.65% sensitivity, and 100% specificity for the AI-assisted method, outperforming any other AI-based proposed methods for AFB detection.
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Non-melanoma skin cancer (NMSC) is the most common type of neoplasm affecting Caucasian individuals, with squamous-cell carcinoma (cSCC) being the second most common type of NMSC after basal-cell carcinoma. The immunohistochemical study of cSCC is of particular importance, especially for the diagnosis of its rare forms, for which accurate and early diagnosis is crucial for survival. In the present review of the literature, the potentially significant value of immunohistochemical markers were highlighted to more accurately assess the biological behaviour, the prognosis of cSCC and to optimize case management. The immunohistochemical markers were classified from a pathophysiological point of view in order to present the mechanism by which carcinogenesis occurs with its subsequent evolution and therefore, to develop a more accurate novel risk staging criteria for this type of neoplasm.
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Concomitant diagnosis of non-Hodgkin lymphoma (NHL) and acute myeloid leukemia secondary to chronic myeloproliferative neoplasms (MPNs) is rarely reported. Patients with MPNs may have a second neoplasm, and the risk of lymphoid line neoplasms is 2.5-3.5 times for lymphoid line neoplasms. The explanation for this association is the genetic instability of hematopoietic progenitors in MPNs. An 80-year-old Caucasian man, with many comorbidities, presents for physical asthenia, sweating. The right inguinal adenopathy was known one month before the examination. The patient was diagnosed concomitantly with diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) secondary to primary myelofibrosis (PMF) and presented trisomy 8, trisomy 13, and triple-negative PMF status. The patient initially received two well-tolerated R mini CHOP series. This type of treatment was selected to treat DLBCL for one unfit patient for intensive chemotherapy due to his age and comorbidities. R mini CHOP administration was followed by severe aplasia that lasted approximately two weeks followed by severe thrombocytosis that reached 4000 x109/L, and Thromboreductin recommendation was mandatory. The result of the treatment was a partial response but with severe adverse events like neutropenia G4, due to the delay of the treatment the patient lost the response. It was mandatory to select another treatment line and the chosen was venetoclax; it was selected for the simultaneous treatment of DLBCL and the underlying AML. It was obtained a significant reduction in the size of the inguinal lymph node block in two weeks of treatment. Severe neutropenia was diagnosed and complicated with sepsis. The evolution is unfavorable with the installation of multiple organ dysfunction. The presence of a complex karyotype (trisomy 8, trisomy 13) in a patient with myeloid metaplasia with triple-negative PMF was associated with blast transformation and severe thrombocytosis. The patient was diagnosed concomitantly with DLBCL, making the therapeutic decision difficult. Venetoclax has been shown to be useful in the treatment of DLBCL but has been associated with severe neutropenia, which has led to infectious complications.
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Background and aims. Patients with COVID-19 frequently present abnormal elevated liver function tests of unknown clinical significance. We aimed to investigate the characteristics and factors influencing outcome in patients with confirmed SARS-CoV-2 infection and liver injury on admission.Methods. This is a retrospective observational study of patients hospitalized in two COVID units in Romania. Relevant data on clinical and laboratory parameters and medication administered during the admission were analyzed to identify predictors of a negative outcome. Patients with confirmed COVID-19 and liver function tests (LFTs) above the upper limit of normal were included in the analysis.Results. From 1,207 patients, we identified 134 patients (11%) with abnormal LFTs during hospitalization. The majority of patients had mildly elevated levels and a predominantly cholestatic pattern of liver injury. Patients who received lopinavir/ritonavir were more likely to have increased ALAT levels (p<0.0001). Sixteen patients had pre-existing chronic liver disease, and they were more likely to suffer from severe COVID-19 (p=0.009) and have a negative outcome (p<0.001), but on multivariate analysis, only the severity of COVID-19 was predictive of death (OR 69.9; 95% CI 6.4-761.4).Conclusions. Mild liver injury is relatively common in COVID-19 and possibly influenced by medication. Patients with chronic liver disease are at high risk for negative outcome, but the severity of the infection is the only predictor of death.
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COVID-19 , Antivirais/uso terapêutico , COVID-19/complicações , Humanos , Fígado , Estudos Retrospectivos , SARS-CoV-2RESUMO
(1) Background: The immune microenvironment plays an important role in carcinogenesis and has prognostic potential in many types of cancer. In this study we assess the prognostic character of tumor-infiltrating immune cells CD4+, CD8+ and CD56+ in resectable oral squamous cell carcinoma (OSCC); (2) Methods: We have evaluated the densities of CD4+, CD8+ and CD56+ in two distinct compartments, intratumor and invasion front, in 90 patients with OSCC; (3) Results: Significant differences were found between the tumor compartments for the CD4+ and CD8+ lymphocytes. An improved outcome (OS) was seen in patients with high densities of intratumor CD8+ lymphocytes (p = 0.0086), CD8+ lymphocytes at the front of invasion (p = 0.0011) and for intratumor CD56+ cells (p = 0.0016). Multivariate analysis confirmed the independent prognostic role of CD8+ at the front of invasion (OR = 3.75, CI95% 1.17-12.35, p = 0.026) and for intratumor CD56+ cells (OR = 3.669, CI95% 1.09-15.37, p = 0.035); (4) Conclusions: Tumor-infiltrating CD8+ lymphocytes at the front of invasion and CD56+ in the intratumor compartment display predictive traits in OSCC. A reach immune infiltration with these types of cells is associated with an improved patient outcome.
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Given the current outbreak of coronavirus disease 2019 (COVID19) and the development and implementation of mass vaccination, data are being obtained by analyzing vaccination campaigns. In the present study, 69 healthcare workers who were exposed to patients with severe acute respiratory syndrome coronavirus2 were monitored for specific immunoglobulin (Ig)G and IgA levels at different time periods. Prior to vaccination, after the first round of vaccination at 21 days (when the second dose of vaccine was administrated) and 24 days after the second round of vaccination, with an mRNAbased vaccine. The basal IgG and IgA levels in previously infected subjects and noninfected subjects notably differed. Vaccination increased the IgG and IgA levels after the first dose in most subjects from both groups, the levels of which further increased following the second round of vaccination. The associations between IgG and IgA levels following the first and second rounds of vaccination demonstrated that in the entire vaccination group, regardless of prior exposure to the infectious agent, the increment and levels of IgG and IgA were similar. Thus, the levels upon vaccination were statistically similar irrespective of the starting base line prior to vaccination. In the present study, seroconversion was achieved in all subjects following the second round of vaccination, with similar antibodies levels.
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Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Adulto , Anticorpos Antivirais/sangue , COVID-19/patologia , COVID-19/virologia , Vacinas contra COVID-19/efeitos adversos , Feminino , Pessoal de Saúde , Humanos , Masculino , Dor/etiologia , SARS-CoV-2/isolamento & purificação , Fatores de Tempo , Vacinação , Vômito/etiologiaRESUMO
BACKGROUND AND AIM: Colonic serrated lesions are premalignant lesions, using an alternative malignization pathway, including multiple genetic and epigenetic alterations, as: mismatch repair deficiency due to MutL homolog 1 (MLH1) promoter methylation, tumor protein p53 (TP53) mutations, activating mutations of v-Raf murine sarcoma viral oncogene homolog B (BRAF) and Kirsten rat sarcoma viral oncogene homolog (KRAS). Our study aims to evaluate MLH1, BRAF and p53 immunohistochemical (IHC) status in sessile serrated lesions (SSLs), with and without dysplasia. MATERIALS AND METHODS: This is a retrospective case-control study including 20 SSLs with dysplasia and 20 SSLs without dysplasia (matching sex and age). IHC expression of MLH1, BRAF and p53 was evaluated as the percent of nuclear loss of MLH1, cytoplasmic positivity of BRAF and nuclear positivity of p53. Data concerning age, sex, localization of the lesion, dysplasia and IHC results were statistically processed using Microsoft Excel. RESULTS: We had very polymorphous patterns of IHC expression for BRAF, MLH1 and p53, especially in the dysplastic group. Thus, two patients were BRAF+∕MLH1-∕p53+, three were BRAF+∕MLH1-∕p53-, one was BRAF+∕MLH1+∕p53- and six were BRAF+∕MLH1+∕p53+. Dysplastic lesions without BRAF mutation exhibited the following phenotype: one case BRAF-∕MLH1-∕p53+, four BRAF-∕MLH1-∕p53- and three BRAF-∕MLH1+∕p53+. In the control group (SSLs without dysplasia), there was a more homogenous distribution of cases: eight cases BRAF+∕MLH1+∕p53-, seven BRAF-∕MLH1+∕p53-, one BRAF-∕MLH1-∕p53+, two BRAF-∕MLH1-∕p53- and two BRAF-∕MLH1+∕p53+. CONCLUSIONS: There are more routes on the serrated pathway, with different mutations and time of acquisition of each genetic or epigenetic lesion with the same morphological result. These lesions should be stratified according to their risk to poor outcome and their need to further surveillance.
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Adenocarcinoma , Adenoma , Pólipos do Colo , Neoplasias Colorretais , Proteína Supressora de Tumor p53/metabolismo , Adenocarcinoma/patologia , Adenoma/patologia , Animais , Estudos de Casos e Controles , Pólipos do Colo/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Humanos , Hiperplasia , Camundongos , Proteína 1 Homóloga a MutL/genética , Mutação/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Estudos Retrospectivos , Proteína Supressora de Tumor p53/genéticaRESUMO
Ulcerative colitis and Crohn's disease are the inflammatory bowel diseases with a continuously increasing of prevalence. Their exact causes are still not well known and, more than that, they are raising up serious issues of diagnosis. The same difficulties of diagnosis are encountered in the case of the colonic angiodysplasia or ischemic colitis (IC). Colonic angiodysplasia is a common vascular abnormality of the gastrointestinal tract, being diagnosed mostly in the elderly persons, in a similar manner to the IC. For all these diseases comorbidities plays their important role both as causes of the onset and aggravating factors during the evolution. The differential diagnosis between these three conditions needs a complex and multidisciplinary approach, involving at least clinical evaluation, endoscopic and imaging assessments, and histopathological exam.
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Angiodisplasia , Colite Isquêmica , Colite Ulcerativa , Idoso , Angiodisplasia/diagnóstico , Colite Isquêmica/diagnóstico , Colite Ulcerativa/complicações , Colite Ulcerativa/diagnóstico , Diagnóstico Diferencial , HumanosRESUMO
Hepatocellular carcinoma (HCC) is the main primary liver malignancy, being associated with both health and economic burden worldwide. Recently, novel molecular markers and possible therapeutic targets were identified. Different adhesion molecules, as well as possible angiogenesis-associated targets can be prime candidates when investigating novel therapies. Considering these premises, our goal was to study the co-existence of E-cadherin and aquaporin 1 (AQP1) in a series of HCC diagnosed patients. Utilizing archived tissue fragments from 17 patients diagnosed with well-to-moderate and poorly differentiated HCC, as well as four samples of normal liver tissue and using a highly specific biotin-free tyramide amplification technique, we have assessed here the expression of E-cadherin and AQP1 during HCC carcinogenesis. Moreover, as we have observed that some of the AQP1 expression seems membrane-bound, we have sought to evaluate their co-localization. Our data showed, as expected, that E-cadherin decreases from control tissue to low-grade and respectively, high-grade HCC. AQP1 was expressed, also as already known, at the level of endothelial blood vessels and bile ducts epithelia, however, we have showed here for the first time that this water pore is also expressed in the cytoplasm and membranes of hepatocytes, both in control and HCC tissue. Moreover, AQP1 expression parallels the decrease of E-cadherin expression during carcinogenesis, but together with this downregulation, we have also found a spatial decrease in the colocalization of the two proteins. Altogether, utilizing a biotin-free tyramide signal amplification technique, this study shows for the first time that AQP1 is expressed at the level of liver epithelia, in both control and HCC tissue.
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Aquaporina 1 , Caderinas , Carcinoma Hepatocelular , Neoplasias Hepáticas , Antígenos CD , Aquaporina 1/genética , Caderinas/genética , Carcinoma Hepatocelular/genética , Humanos , Neoplasias Hepáticas/genética , Projetos PilotoRESUMO
Cutaneous melanoma is a significant immunogenic tumoral model, the most frequently described immune phenomenon being tumor regression, as a result of the interaction of tumoral antigens and stromal microenvironment. We present a retrospective cohort study including 52 cases of melanoma with regression. There were evaluated correlations of the most important prognostic factors (Breslow depth and mitotic index) with FOXP3 expression in tumor cells and with the presence of regulatory T cells and dendritic cells in the tumoral stroma. FOXP3 expression in tumor cells seems an independent factor of poor prognosis in melanoma, while regression areas are characterized by a high number of dendritic cells and a low number of regulatory T cells. FOXP3 is probably a useful therapeutical target in melanoma, since inhibition of FOXP3-positive tumor clones and of regulatory T cells could eliminate the ability of tumor cells to escape the immune defense of the host.
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Fatores de Transcrição Forkhead/metabolismo , Melanoma/metabolismo , Melanoma/patologia , Linfócitos T Reguladores/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Biomarcadores Tumorais , Feminino , Fatores de Transcrição Forkhead/genética , Expressão Gênica , Humanos , Imuno-Histoquímica , Imunomodulação/genética , Masculino , Melanoma/etiologia , Pessoa de Meia-Idade , Prognóstico , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/patologia , Linfócitos T Reguladores/imunologiaRESUMO
Suppurative hidradenitis and pyoderma gangrenosum are rare disorders that can be seen isolated or even more rare, as part of different autoinflammatory syndromes: Pyoderma gangrenosum, acne, and hidradenitis suppurativa (PASH), pyoderma gangrenosum, acne, pyogenic arthritis, and hidradenitis suppurativa (PAPASH) or psoriatic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PsAPASH). Although they have different clinical features, suppurative hidradenitis and pyoderma gangrenosum seem to share similar pathogenic pathways involving a dysregulated innate immune system, with neutrophilic inflammation, mediated by IL-1ß, controlled by NALP3 inflammasome pathway. We report a case of a 53-year-old male patient previously diagnosed with HS in inguinal-scrotal area that developed rapidly after a traumatic injury on his left anterior calf, a painful inflammatory plaque with pustules on the surface that rapidly progressed (24-48 h) to form ulcers. The lesions ended up healing with a large scarring plaque with cribriform openings, multiple fibrous bridges, open comedones, and double-ended pseudo-comedones. Although the clinical aspect at presentation together with the aspect on the first biopsy were suggestive for pyoderma gangrenosum, the healing aspect is more commonly seen in suppurative hidradenitis. Commonly seen in acne, in the healing phase of suppurative hidradenitis but more rarely in pyoderma gangrenosum, the formation of comedones seem to be a complex process and raise the question if these entities represent in our patient an association, an overlap or the spectrum of the same disease.