A Misdiagnosed Desmoplastic Neurotropic Melanoma of the Scalp: A Challenging Case for the Pathologist and Surgeon

Desmoplastic neurotropic melanoma (DNM) is a rare melanoma subtype that shows tropism for the nerves, perineural invasion correlates to higher rate of local recurrence, poorer prognosis and worse morbidity. Given the paucity of typical melanoma features, both clinical and pathological, this confusing skin cancer may act as a pretender, thus leading clinician to misdiagnosis and subsequent inappropriate conservative treatment. Sarcomatoid- like cells rearrangement and absence of pigmentation can lead towards sarcoma diagnosis, so specific skills are required to pathologist to properly recognize this melanoma subtype. In this case report, we present an example of how challenging can be the diagnosis, and how it can affect clinical outcom

A Misdiagnosed Desmoplastic Neurotropic Melanoma of the Scalp: A Challenging Case for the Pathologist and Surgeon

Desmoplastic neurotropic melanoma (DNM) is a rare melanoma subtype that shows tropism for the nerves, perineural invasion correlates to higher rate of local recurrence, poorer prognosis and worse morbidity. Given the paucity of typical melanoma features, both clinical and pathological, this confusing skin cancer may act as a pretender, thus leading clinician to misdiagnosis and subsequent inappropriate conservative treatment. Sarcomatoid- like cells rearrangement and absence of pigmentation can lead towards sarcoma diagnosis, so specific skills are required to pathologist to properly recognize this melanoma subtype. In this case report, we present an example of how challenging can be the diagnosis, and how it can affect clinical outcom

Western Diet-Induced Metabolic Alterations Affect Circulating Markers of Liver Function before the Development of Steatosis

Since nutrition might have a significant impact on liver function, we analyzed the early effect of Western-type diet on hepatic tissue and lipid and drug metabolism in Wistar-Kyoto rats (n = 8); eight rats fed with a standard diet were used as controls. Histological analysis of liver tissue was performed, and plasma biochemical parameters were measured. Plasma concentration of six bile acids was determined by ultra-liquid chromatography-tandem mass spectrometry UHPLC-MS/MS. Hepatic gene expressions of enzymes involved in drug and lipid metabolism were assessed by means of real-time reverse transcription (qRT)-PCR. Liver of rats fed with a Western diet did not show macroscopic histological alterations, but number and diameter of lipid droplets increased, as well as DGAT1, GPAT4, SCD, FASN and SREBP2 expression. Furthermore, Western diet-fed animals showed an increase in the activation of hepatic stellate cells and macrophage number in liver tissue, as well as a significant increase in AST and bilirubin levels (p < 0.01), and in the LDL:HDL cholesterol ratio (p < 0.001). Plasma chenodeoxycholic acid concentration increased significantly, whereas cholic acid decreased (p < 0.05), and cytochrome P450 genes were generally downregulated. Significant changes in hepatic lipid and drug metabolism are early induced by the Western diet, prior to steatosis development. Such changes are associated with a peculiar alteration in circulating bile acids, which could represent an early marker of non-alcoholic fatty liver disease (NAFLD) development

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P &lt; .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Neutralizing antibodies to Omicron after the fourth SARS-CoV-2 mRNA vaccine dose in immunocompromised patients highlight the need of additional boosters

IntroductionImmunocompromised patients have been shown to have an impaired immune response to COVID-19 vaccines.MethodsHere we compared the B-cell, T-cell and neutralizing antibody response to WT and Omicron BA.2 SARS-CoV-2 virus after the fourth dose of mRNA COVID-19 vaccines in patients with hematological malignancies (HM, n=71), solid tumors (ST, n=39) and immune-rheumatological (IR, n=25) diseases. The humoral and T-cell responses to SARS-CoV-2 vaccination were analyzed by quantifying the anti-RBD antibodies, their neutralization activity and the IFN-γ released after spike specific stimulation.ResultsWe show that the T-cell response is similarly boosted by the fourth dose across the different subgroups, while the antibody response is improved only in patients not receiving B-cell targeted therapies, independent on the pathology. However, 9% of patients with anti-RBD antibodies did not have neutralizing antibodies to either virus variants, while an additional 5.7% did not have neutralizing antibodies to Omicron BA.2, making these patients particularly vulnerable to SARS-CoV-2 infection. The increment of neutralizing antibodies was very similar towards Omicron BA.2 and WT virus after the third or fourth dose of vaccine, suggesting that there is no preferential skewing towards either virus variant with the booster dose. The only limited step is the amount of antibodies that are elicited after vaccination, thus increasing the probability of developing neutralizing antibodies to both variants of virus.DiscussionThese data support the recommendation of additional booster doses in frail patients to enhance the development of a B-cell response directed against Omicron and/or to enhance the T-cell response in patients treated with anti-CD20

Pathology of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of different conditions which are characterized by hepatic steatosis in the absence of secondary causes. It is currently the most common chronic liver disease worldwide, and its estimated prevalence is about 1.5-6.5%. The only histological finding of steatosis ("simple" steatosis) represents the uncomplicated form of NAFLD, while non-alcoholic steatohepatitis (NASH) is its inflammatory subtype associated with disease progression to cirrhosis and hepatocellular carcinoma (HCC), and represents the major indication for liver transplantation. NASH is still a diagnostic and therapeutic challenge for clinicians and liver biopsy is currently the only accepted method to reliably distinguish NASH from "simple" steatosis. From the histological perspectives, NAFLD and NASH continue to be an area of active interest for pathologists, with a specific focus on better methods of evaluation, morphologic clues to pathogenesis, and predictors of fibrosis progression. This review focuses on histopathology of NAFLD in adults, with the aim to provide a practical diagnostic approach useful in the clinical routine

Hepatocellular carcinoma: a clinical and pathological overview

HCC incidence rates have been rising in the past 3 decades and by 2025 &gt; 1 million individuals will be affected annually. High-throughput sequencing technologies led to the identification of several molecular HCC subclasses that can be broadly grouped into 2 major subgroups, each characterized by specific morphological and phenotypical features. It is likely that this increasing knowledge and a more appropriate characterization of HCC at the pathological level will impact HCC patient management