Search

Malignant melanoma (MM) is known to avoid the host's immune response. Studies on in vitro melanoma cell lines link the microphthalmia-associated transcription factor (MITF) with the regulation of the PD-L1 expression. It seems that MITF affects the activation of the gene responsible for PD-L1 protein expression. Several proteins, including Bcl-2 and Cyclin D1, play major roles in malignant melanoma cell cycle regulation and survival. Our study aims to assess the relationship between MITF, Bcl-2, and cyclin D1 protein expression and the expression of the PD-L1 molecule. Additionally, we examined the association of BRAF mutation, MITF, and CCND1 gene amplification with PD-L1 protein expression. We performed immunohistochemical staining on fifty-two tumour samples from patients diagnosed with nodular melanoma (NM). BRAF V600 mutation, MITF, and CCND1 gene amplification analyses were analyzed by the Sanger sequencing and QRT-PCR methods, respectively. Statistical analyses confirmed the significant inverse correlation between cyclin D1 and PD-L1 expression (p = 0.001) and correlation between PD-L1 and MITF protein expression (p = 0.023). We found a statistically significant inverse correlation between the present MITF gene amplification and PD-L1 (p = 0.007) and MITF protein expression (p = 3.4 ×10-6), respectively. Our study, performed on clinical NM materials, supports the in vitro study findings providing a rationale for the potential MITF-dependent regulation of PD-L1 expression in malignant melanoma., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Background: The spread and invasion of malignant melanoma cells involve degradation and reorganization of the extracellular matrix by the activation of several matrix metalloproteinases (MMPs). This study analyzed the expression of MMP-1, MMP-2, and MMP-13 proteins in primary nodular melanoma (NM) and dysplastic nevi (DN) as a significant risk factor for melanoma development. The secondary goal was to analyze the correlation of MMPs protein expression in NM with tumor invasion, BRAF V600 mutation status, and overall survival., Methods: Immunohistochemistry for MMP-1, MMP-2, and MMP-13 was performed on nodular melanoma (n = 52) and dysplastic nevi (n = 28) on tissue microarray (TMA). BRAF V600 mutation analysis on NM samples was performed by the Sanger sequencing method., Results: A high level of MMPs expression in NM samples (>30%) compared with DN (<8%) was statistically significant (P < 0.001). BRAF V600 mutations were detected in 15 of 39 (38.5%) NM samples. This study revealed an interesting finding that MMP-1 and MMP-13 protein expression in the BRAF V600 mutated melanomas were significantly lower than in the BRAF V600 wild type (P < 0.05)., Conclusion: Cox analysis revealed that Clark categories, Breslow thickness, and MMP-1 high protein expression are predictive factors for shorter overall survival (P < 0.05)., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The aim of this report is to present a case of a patient with a recurrent nasal cavity amelanotic melanoma (AM), with emphasis on diagnosis and therapy options of this clinical entity. A 65-year-old female patient presented with pain in the right cheek region and nasal obstruction. In 2013, she was diagnosed with mucosal melanoma (MM) of the left nasal cavity. After endoscopic surgery and radiotherapy, the patient was followed by the oncology team. Five years after the initial diagnosis, rhinoscopy showed a tumorous formation in the right nasal cavity. The tumor mass was without black discoloration and was the same color as the surrounding nasal mucosa. Microscopic examination after biopsy of the tumor confirmed amelanotic MM. The patient underwent an additional endoscopic surgery. A complete standard diagnostic workup for MM found metastases in head and neck lymph nodes, on both sides. MMs of head and neck are uncommon malignancies. Unique biology of MM cells causes a high rate of recurrences. This report presents an example of recurrent AM of the nasal cavity, in treatment with checkpoint inhibitor (pembrolizumab), which could provide a good therapy option for patients with MM., Competing Interests: Conflict of interest: the authors declare no potential conflict of interest.

We report the case of a 31-year-old female who was admitted to the emergency department with symptoms of cardiac arrest and ultimately died in spite of enormous resuscitation efforts. During resuscitation, pulmonary embolism was considered as a possible non-cardiac cause of cardiac arrest, and following its extremely unfavorable prognosis, the fatal outcome was not so surprising. However, since acute pulmonary emboli obstructing blood flow to a lobe or multiple lung segments was suspected, alteplase was indicated and administered. At the autopsy, no venous thrombosis in the vena cava, pelvic veins, or any of the lower extremity veins was documented; conversely, nor were specific signs of pulmonary thromboembolism (PTE) found macroscopically, until this was confirmed by histopathological staining which is not used as a routine diagnostic tool in forensic medicine. In this study, we conclude that PTE is generally overlooked as the principal diagnosis and the cause of death. Rightful postmortem diagnosis could lead to increased vigilance and a change in management in many of such cases, which could result in improved survival. Motivated by providing better awareness of PTE, this study aimed to illustrate unrecognized PTE and pathological findings that were masked by thrombolytic drugs.

Purpose: The goal of this study was to identify risk factors for wound infections in patients with oral cancer who underwent surgical procedures., Materials and Methods: This study included 195 patients who underwent surgical treatment of oral and oropharyngeal cancer over a 7-year period. Wound infection was defined as the occurrence of purulent content from the wound or as an appearance of exudate with signs of local infection and positive cultures taken from the wound. For every patient who was suspected to have a wound infection, a swab from the wound was taken, and microbiological analysis was performed. The patients were divided into 2 groups: patients with postoperative wound infections, and patients with postoperative wound infection., Results: Wound infection was present in 155 patients (59%). Univariate analysis indicated that the following factors were significantly related to the occurrence of wound infection: gender, smoking, tumor localization, size and stage of the tumor, type of surgery, neck dissection, type of reconstruction, nasogastric sonde, gastrostomy and tracheotomy. On multivariate analysis, statistically significant predictors of wound infection were gender, tumor localization and type of reconstruction., Conclusions: The occurrence of wound infection is high despite antibiotic prophylaxis. To minimize the risk of wound infection and for prompt recognition of risk factors, surgeons managing oral tumor patients should have a better understanding of the risk factors such as gender, tumor localization and type of reconstruction., (Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Since there are no standardized protocols regarding the detection of microscopic melanoma deposits in sentinel lymph nodes (SLN), the aim of this study was to present our experience with intraoperative cytological evaluation of SLN in patients with melanoma. The study included 475 SLN biopsies (SLNB) from 201 patients with primary cutaneous melanoma of intermediate thickness. Each lymph node was cut in half; touch imprint cytology (TIC) preparations of all cut surfaces were performed and stained according to a modified May-Grünwald-Giemsa method. The results were compared to definitive postoperative histology. Twenty of 25 SLNB positive on TIC proved to be metastatic when compared to definitive histology. Most of 32 SLN that were suspicious but not diagnostic on TIC were proven negative (23/32, 71.8%), while 7 nodes had metastases (one micrometastasis and one with isolated tumor cells only). The majority (94%) of SLNBs negative on TIC remained negative on final histology, while 6% or 25 nodes were positive, mostly with micrometastases or isolated tumor cells (17/25). In frozen sections performed in cases of suspicious or positive SLN cytology, metastasis was confirmed in 80% of positive and in 21.9% of suspicious TIC. Altogether, 49% (27/55) of positive SLNB were identified intraoperatively in 57% (24/42) of patients, and in those cases a complete regional lymph node dissection was performed in the first step. TIC assessment of SLNB with 99% specificity and 57% sensitivity for intraoperative identification of metastasis is useful and beneficial for avoiding a second operative procedure.

The genetic etiology and the contribution of rare genetic variation in multiple sclerosis (MS) has not yet been elucidated. Although familial forms of MS have been described, no convincing rare and penetrant variants have been reported to date. We aimed to characterize the contribution of rare genetic variation in familial and sporadic MS and have identified a family with two sibs affected by concomitant MS and malignant melanoma (MM). We performed whole exome sequencing in this primary family and 38 multiplex MS families and 44 sporadic MS cases and performed transcriptional and immunologic assessment of the identified variants. We identified a potentially causative homozygous missense variant in NLRP1 gene (Gly587Ser) in the primary family. Further possibly pathogenic NLRP1 variants were identified in the expanded cohort of patients. Stimulation of peripheral blood mononuclear cells from MS patients with putatively pathogenic NLRP1 variants showed an increase in IL-1B gene expression and active cytokine IL-1β production, as well as global activation of NLRP1-driven immunologic pathways. We report a novel familial association of MS and MM, and propose a possible underlying genetic basis in NLRP1 gene. Furthermore, we provide initial evidence of the broader implications of NLRP1-related pathway dysfunction in MS.

Melanoma ulceration is the third most powerful survival predictor in the analysis for the currently valid 2010 AJCC melanoma staging system. However, there is still no detailed explanation for melanoma ulceration mechanism. Although thicker tumors are more commonly ulcerated, ulceration is a factor that predicts the disease outcome independently of melanoma thickness. It is our hypothesis that EGFR activates melanoma cell mobility. Melanoma cells with increased mobility move through tissue in diverse direction. Cells moving toward the epithelium weaken the intercellular bonds between the cells causing the loss of epithelium and subsequently ulceration., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Considering that nodular melanoma (NM) has the potential to show an early distant metastasis, there is an urgent need for the discovery and evaluation of new diagnostic and prognostic biomarkers. We aimed to investigate the protein expression of membrane and nuclear epidermal growth factor receptor (EGFR), cyclin D1, and the corresponding gene status in NM samples and correlate the results obtained with clinicopathological parameters and overall survival of patients. Immunohistochemical and fluorescence in-situ hybridization analyses were carried out on tissue microarrays constructed from 110 NM samples, 30 compound nevi, and 38 dysplastic nevi. NM samples showed 24% strong cyclin D1 and 37% strong Ki67 protein expression compared with 3 and 0% strong cyclin D1 and Ki67 expression in the control group. Membrane EGFR expression was detected in 50% of NM cases, whereas EGFR gene amplification was detected in only 4% of NM cases. Multiple NM samples presented simultaneous membrane and nuclear EGFR expression. We found a negative correlation between tumor thickness and membrane EGFR expression. It was also observed that membrane EGFR 3+ NM samples presented ulceration significantly more often than membrane EGFR-negative (0) NM samples. In univariate analysis, carried out on 44 patients with follow-up data, both nuclear and membrane EGFR overexpression showed a correlation with a shorter overall survival. Nuclear EGFR (++, +++) showed 3.06 and membrane EGFR (2+, 3+) showed 2.76 higher risk of mortality compared with patients with low and negative nuclear and membrane EGFR expression (P<0.05).

Chronic recurrent multifocal osteomyelitis (CRMO) is an extremely rare and most severe form of chronic nonbacterial osteomyelitis of unknown etiology. Here we present the first case of a six-year-old girl in which was observed that the stress fracture mimic osteomyelitic foci in the course of CRMO.

Angiogenesis, the growth and proliferation of new blood vessels, is important in a variety of pathophysiological processes. However the role of angiogenesis in allergic rhinitis has not been well studied. Hence, the aim of this study was to compare the vascularisation of the nasal mucous membrane of non-allergic, non-treated allergic and allergic patients treated with mometasone furoate. A small piece of the nasal mucous membrane was taken from the frontal pole of the lower nasal shell from 90 patients. The patients were divided in three groups, each containing 30 patients. First group of patients (GP1) had a negative inhalatory allergen test, patients in second group (GP2) had positive test but were not under treatment and the third group of patients (GP3) had positive results with the same test and were treated with mometasone furoate for 15 days before analysis. Immunhistochemical staining with anti-CD31 and VEGF-C was performed. Vascular phase was determined by using length density. Differences in expression of CD31 and VEGF-C were compared using one-way ANOVA and Tukey HSD post-hoc tests. Significantly lower values of CD31 and VEGF-C expression were observed in GP1 in compare with GP2 and GP3 (p < 0.001, p = 0.013, resjpectively). In GP3 the microvessel density was significantly lower than in GP2 (p < 0.001), but higher than in GP1. Our results demonstrated that 15-day treatment with mometasone furoate results in a significant reduction of the density of vascular parameters in allergic patients.

There is a global rising incidence of melanoma. For different reasons, the patterns of the incidence, appearance, gender, anatomical distribution and outcome vary among different geographic areas. Screening programs have led to better early detection of melanoma in Australia and some world areas. National Cancer Registry and practice data show the incidence in Croatia to be constantly rising. Despite public education programs about early detection, at clinical departments there are still many new advanced stage melanoma patients. We analyzed data on 157 patients treated and followed up for 10 years for T1b-T4aN0 skin melanoma. There was a difference in anatomical distribution of melanoma lesions in correlation with patient age (ANOVA test, F=3.51, p=0.009). A higher prevalence of shoulder melanoma was found in young people and of head/neck melanoma in the elderly (post-hoc Sheffe test, p=0.038). T4 lesions were more commonly found in men and T1 mainly in women (Pearson χ(2)-test, χ(2)=12.08, p=0.016). There was no difference in Clark level, but a significantly higher Breslow stage was found in men (t=-2.52, p=0.013). Men were much more prone to have head and neck, body and shoulder melanoma, whereas women had more melanoma on their legs and arms. Clark and Breslow levels were strongly correlated in leg melanoma; head localization showed no correlation at all. In conclusion, more attention should be devoted to improve the results in melanoma detection in men, especially considering the prevalence of body (back) and head/neck localizations, sometimes not readily accessible for visual detection. The pattern of distribution also pointed to the need for more attention to pay to shoulder melanoma in younger people.