Cutaneous melanoma is a public health problem. Efforts to reduce its incidence have failed, as it continues to increase. In recent years, many risk factors have been identified. Numerous diagnostic systems exist that greatly assist in early clinical diagnosis. The histopathological aspect illustrates the grim nature of these cancers. Currently, pathogenic pathways and the tumor microclimate are key to the development of therapeutic methods. Revolutionary therapies like targeted therapy and immune checkpoint inhibitors are starting to replace traditional therapeutic methods. Targeted therapy aims at a specific molecule in the pathogenic chain to block it, stopping cell growth and dissemination. The main function of immune checkpoint inhibitors is to boost cellular immunity in order to combat cancer cells. Unfortunately, these therapies have different rates of effectiveness and side effects, and cannot be applied to all patients. These shortcomings are the basis of increased incidence and mortality rates. This study covers all stages of the evolutionary sequence of melanoma. With all these data in front of us, we see the need for new research efforts directed at therapies that will bring greater benefits in terms of patient survival and prognosis, with fewer adverse effects.

Adult low-grade gliomas are a rare and aggressive pathology of the central nervous system. Some of their characteristics contribute to the patient’s life expectancy and to their management. This study aimed to characterize and identify the main prognostic factors of low-grade gliomas. The six-year retrospective study statistically analyzed the demographic, imaging, and morphogenetic characteristics of the patient group through appropriate parameters. Immunohistochemical tests were performed: IDH1, Ki-67, p53, and Nestin, as well as FISH tests on the CDKN2A gene and 1p/19q codeletion. The pathology was prevalent in females, with patients having an average age of 56.31 years. The average tumor volume was 41.61 cm³, producing a midline shift with an average of 7.5 mm. Its displacement had a negative impact on survival. The presence of a residual tumor resulted in decreased survival and is an independent risk factor for mortality. Positivity for p53 identified a low survival rate. CDKN2A mutations were an independent risk factor for mortality. We identified that a negative prognosis is influenced by the association of epilepsy with headache, tumor volume, and immunoreactivity to IDH1 and p53. Independent factors associated with mortality were midline shift, presence of tumor residue, and CDKN2A gene deletions and amplifications.

(1) Background: Because melanoma is an aggressive tumor with an unfavorable prognosis, we aimed to characterize the PD-L1 expression in melanomas in association with T cell infiltrates because PD-1/PD-L1 blockade represents the target in treating melanoma strategy. (2) Methods: The immunohistochemical manual quantitative methods of PD-L1, CD4, and CD8 TILs were performed in melanoma tumor microenvironment cells. (3) Results: Most of the PD-L1 positive, expressing tumors, have a moderate score of CD4+ TILs and CD8+TILs (5−50% of tumor area) in tumoral melanoma environment cells. The PD-L1 expression in TILs was correlated with different degrees of lymphocytic infiltration described by the Clark system (X² = 8.383, p = 0.020). PD-L1 expression was observed often in melanoma cases, with more than 2−4 mm of Breslow tumor thickness being the associated parameters (X² = 9.933, p = 0.014). (4) Conclusions: PD-L1 expression represents a predictive biomarker with very good accuracy for discriminating the presence or absence of malign tumoral melanoma cells. PD-L1 expression was an independent predictor of good prognosis in patients with melanomas.

Grade 4 adult gliomas are IDH-mutant astrocytomas and IDH-wildtype glioblastomas. They have a very high mortality rate, with survival at 5 years not exceeding 5%. We aimed to conduct a clinical imaging and morphogenetic characterization of them, as well as to identify the main negative prognostic factors that give them such aggressiveness. We conducted a ten-year retrospective study. We followed the clinical, imaging, and morphogenetic aspects of the cases. We analyzed immunohistochemical markers (IDH1, Ki-67, and nestin) and FISH tests based on the CDKN2A gene. The obtained results were analyzed using SPSS Statistics with the appropriate parameters. The clinical aspects representing negative prognostic factors were represented by patients’ comorbidities: hypertension (HR = 1.776) and diabetes mellitus/hyperglycemia (HR = 2.159). The lesions were mostly supratentorial, and the temporal lobe was the most affected. The mean volume was 88.05 cm³ and produced a midline shift with an average of 8.52 mm. Subtotal surgical resection was a negative prognostic factor (HR = 1.877). The proliferative index did not influence survival rate, whereas CDKN2A gene mutations were shown to have a major impact on survival. We identified the main negative prognostic factors that support the aggressiveness of grade 4 gliomas: patient comorbidities, type of surgical resection, degree of cell differentiation, and CDKN2A gene mutations.

Background and Aims: High-grade gastrointestinal neuroendocrine neoplasms (GI-NENs) are divided into well-differentiated G3 neuroendocrine tumors (NETs G3) and neuroendocrine carcinomas (NECs), having identical cut-offs of proliferation, but different biomolecular origins. This translates in distinct treatment choices. Our aim was to establish if p53/Rb1 immunohistochemical status in GI-NENs with Ki67 index >20% can predict the histopathological diagnosis. Methods: p53/Rb1 immunolabelling was performed on 42 cases of high-grade GI-NENs, diagnosed as NET G3, NEC and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) with NEC component. Immunolabeled slides were digitally scanned, with automatic quantification of p53 and Rb1, blind to the diagnosis. Results: The p53 positive percentage was stratified; two cut-offs were selected, naming the intervals as N (null, 20%). The Rb1 expression loss in >90% of neoplastic cells was considered mutational. NETs G3 mainly showed the T status (14/16, 87.5%), followed by N (1/16, 6.25%) and C (1/16, 6.25%); NECs and NEC components in MiNENs predominantly expressed the C status (19/26, 73.08%), followed by N (5/26, 19.23%) and T (2/26, 7.69%) (p<0.001, χ 2 =27.017). NET G3s showed positive expression for Rb1; 73.08% of NECs expressed negative Rb1 (p<0.001, χ 2 =21.351). NECs and NEC components in MiNENs showed Rb1 mutational status in 13 C cases (13/19, 68.42%), 4 N cases (4/5, 80%) and in both the T cases (p=0.002, χ 2 =11.187). Conclusions: Our results highlight the correlations between the p53/Rb1 immunostainings and the histopathological diagnosis of high-grade GI-NENs. NECs and NEC components in MiNENs showed a p53 mutational status (0% or 21-100%) and predominantly negative Rb1 expression. NETs G3 showed a p53 wild-type status (1-20%) and retained Rb1 expression. These findings suggest that the differential diagnosis of high-grade GI-NENs may benefit from p53/Rb1 immunohistochemical tests in everyday practice.

Necrosis and increased microvascular density in glioblastoma IDH-wild-type are the consequence of both hypoxia and cellular immaturity. Our study aimed to identify the main clinical-imaging and morphogenetic risk factors associated with tumor necrosis and microvascular in the prognosis of patient survival. We performed a retrospective study (10 years) in which we identified 39 cases. We used IDH1, Ki-67 and Nestin immunomarkers, as well as CDKN2A by FISH. The data were analyzed using SPSS Statistics. The clinical characterization identified only age over 50 years as a risk factor (HR = 3.127). The presence of the tumor residue, as well as the absence of any therapeutic element from the trimodal treatment, were predictive factors of mortality (HR = 1.024, respectively HR = 7.460). Cellular immaturity quantified by Nestin was associated with reduced overall survival (p = 0.007). Increased microvascular density was associated with an increased proliferative index (p = 0.009) as well as alterations of the CDKN2A gene (p < 0.001). CDKN2A deletions and cellular immaturity were associated with an increased percentage of necrosis (p < 0.001, respectively, p = 0.017). The main risk factors involved in the unfavorable prognosis are moderate and increased Nestin immunointensity, as well as the association of increased microvascular density with age over 50 years. Necrosis was not a risk factor.