A Patient With Stage III Locally Advanced Pancreatic Adenocarcinoma Treated With Intra-Arterial Infusion FOLFIRINOX: Impressive Tumoral Response and Death due to Legionella pneumophila Infection: A Unique Case Report.

Patients affected by pancreatic ductal adenocarcinoma (PDAC) have very poor prognosis, whereby at a follow-up of 5 years, the mortality rate is very similar to the incidence rate. Globally, around 10% of patients are amenable to radical surgery at the time of diagnosis, which represents the only chance of cure or long-term survival for these patients. Almost 40% of patients with PDAC show locally advanced pancreatic cancer (LAPC). LAPC is not a metastatic disease, although it is not amenable to radical surgery. For these patients, systemic induction chemotherapy with intravenous FOLFIRINOX (5-fluorouracil, folic acid, irinotecan, oxaliplatin) regimen is administered, with the aim of conversion to surgery, although the conversion rate remains low, at approximately 10% to 15%. Pancreatic arterial chemotherapy has been explored to overcome the intrinsic tumor pancreatic resistance to systemic chemotherapy, where an intra-arterial port-a-cath is placed by means of interventional oncology techniques under angiographic guidance in the operating theater. Here, we treated a patient with an intra-arterially modified FOLFIRINOX regimen. Three courses were administered, and the patient experienced no adverse events. At the end of the third course, the patient rapidly developed lung failure due to nosocomial Legionella pneumophila infection, despite the impressive pathological tumor response shown in the autopsy report. This is a first and unique report that demonstrates that pancreatic intra-arterial FOLFIRINOX can be safe and efficacious. We believe that this preliminary result will be confirmed in the next patients to be enrolled and that it provides a glimmer of hope for patients with this lethal disease.

Necrotizing Fasciitis of the Thigh as Unusual Colonoscopic Polypectomy Complication: Review of the Literature with Case Presentation.

Necrotizing fasciitis (NF) is an infection characterized by necrosis of the superficial muscle fascia and surrounding soft tissues. It usually occurs following skin breaches from penetrating traumas or high-degree burns. Less frequently, it could be related to major abdominal surgery. However, no cases of thigh NF after minor abdominal procedures have ever been reported. A previously healthy 59-year-old male patient underwent a colonoscopic polypectomy. After the procedure, the patient developed an increasing right groin pain. The CT scan showed a gas collection in the right retroperitoneum space and in the right thigh soft tissues. Thus, a right colon perforation was hypothesized, and the patient was moved to the nearest surgery department and underwent a right hemicolectomy procedure. During surgery, the right thigh was also incised and drained, with gas and pus leakage. Nevertheless, the right lower limb continued to swell, and signs of systemic infection appeared. Afterward, clinical conditions continued to worsen despite the drainage of the thigh and antibiotic therapy, and the patient died of septic shock after just two days. This case shows that, although rare, lower limb NF should be considered among the causes of early post-operative local painful symptoms.

GLUT1, GLUT3 Expression and 18FDG-PET/CT in Human Malignant Melanoma: What Relationship Exists? New Insights and Perspectives.

BACKGROUND: Malignant melanoma is the most aggressive of skin cancers and the 19th most common cancer worldwide, with an estimated age-standardized incidence rate of 2.8-3.1 per 100,000; although there have been clear advances in therapeutic treatment, the prognosis of MM patients with Breslow thickness greater than 1 mm is still quite poor today. The study of how melanoma cells manage to survive and proliferate by consuming glucose has been partially addressed in the literature, but some rather interesting results are starting to be present. METHODS: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and a search of PubMed and Web of Sciences (WoS) databases was performed until 27 September 2021 using the terms: glucose transporter 1 and 3 and GLUT1/3 in combination with each of the following: melanoma, neoplasm and immunohistochemistry. RESULTS: In total, 46 records were initially identified in the literature search, of which six were duplicates. After screening for eligibility and inclusion criteria, 16 publications were ultimately included. CONCLUSIONS: the results discussed regarding the role and expression of GLUT are still far from definitive, but further steps toward understanding and stopping this mechanism have, at least in part, been taken. New studies and new discoveries should lead to further clarification of some aspects since the various mechanisms of glucose uptake by neoplastic cells are not limited to the transporters of the GLUT family alone.

Dedifferentiated Melanoma: A Diagnostic Histological Pitfall-Review of the Literature with Case Presentation.

Dedifferentiated melanoma is a particular form of malignant melanoma with a progressive worsening of the patient's clinical outcome. It is well known that melanoma can assume different histo-morphological patterns, to which specific genetic signatures correspond, sometimes but not always. In this review we address the diagnostic difficulties in correctly recognizing this entity, discuss the major differential diagnoses of interest to the dermatopathologist, and conduct a review of the literature with particular attention and emphasis on the latest molecular discoveries regarding the dedifferentiation/undifferentiation mechanism and more advanced therapeutic approaches.

HMGB1-TIM3-HO1: A New Pathway of Inflammation in Skin of SARS-CoV-2 Patients? A Retrospective Pilot Study.

The SARS-CoV-2 pandemic has completely disrupted the health systems of the entire planet. From the earliest months, it became increasingly clear that in addition to affecting the upper airways and lungs, there were other organs that could be affected. Among these, the skin became a real "sentinel signal" to be able to even suspect COVID-19. Background: this study deals with a little-explored issue for now: the study of skin immunopathology in SARS-CoV-2 positive subjects ascertained using the most reliable methods available. Methods: we used skin biopsy samples from SARS-CoV-2 positive and negative patients, studying morphology (Hematoxylin-Eosin), T lymphocyte population (CD4 and CD8), three markers such as HMGB-1, TIM-3 and HO-1 by immunohistochemistry. Results: although the presence of the CD4 and CD8 T population did not differ statistically significantly, we found greater activation and release of HMGB-1 in skin samples from SARS-CoV-2 positive patients, greater immunolabeling for TIM-3 at the level of CD4 and CD8 and a reduced expression of Heme oxygenase 1. Conclusions: these results support the possibility that there is immune deregulation in SARS-CoV-2 positive patients who develop skin manifestations of various kinds.

Purpuric Skin Rash in a Patient Undergoing Pfizer-BioNTech COVID-19 Vaccination: Histological Evaluation and Perspectives.

The COVID-19 pandemic has affected the entire planet, and within about a year and a half, has led to 174,502,686 confirmed cases of COVID-19 worldwide, with 3,770,361 deaths. Although it is now clear that SARS-CoV-2 can affect various different organs, including the lungs, brain, skin, vessels, placenta and others, less is yet known about adverse reactions from vaccines, although more and more reports are starting to emerge. Among the adverse events, we focused particularly on skin rashes. In this short report, we describe the case of a patient vaccinated with Comirnaty, who developed a purpuric rash resistant to oral steroid therapy after 2 weeks. To date, this is one of the very few cases in which skin biopsy was performed to better characterize the histopathological picture of this rash. Finally, we conduct a literature review of the cases of rashes from SARS-CoV-2 vaccines described in the literature, with the aim of laying foundations for future, larger case studies.

"Animal-Type Melanoma/Pigmented Epithelioid Melanocytoma": History and Features of a Controversial Entity.

Animal-type melanoma (ATM) was first described in the literature by Levene in 1979 in relation to a patient with a characteristic clinical presentation, and only later, rare and anecdotal case series have tried to shed light on an entity that has undergone several nosographic classification changes, and which, since 2018, is classified under the term "pigmented epithelioid melanocytoma". Here, we conduct a brief review of the current literature on ATM and present a new clinical case with histopathological, immunophenotypic, and molecular investigations.

The Multiple Faces of Nodular Trichoblastoma: Review of the Literature with Case Presentation.

Trichoblastoma (TB) is a rare biphasic benign adnexal neoplasm originating from follicular germ cells but clinically, it can simulate basal cell carcinoma (BCC), making the diagnosis more difficult. There are several variants of Trichoblastoma and a good knowledge of these is essential for correct diagnosis and management. We report two new cases observed in the last year at our Pathological Anatomy Operative Unit, and conduct a careful review of the literature, from the first description of this lesion by Headington in 1970 to the most recent classifications.

Synthesis and Biological Evaluation of Dantrolene-Like Hydrazide and Hydrazone Analogues as Multitarget Agents for Neurodegenerative Diseases.

Dantrolene, a drug used for the management of malignant hyperthermia, had been recently evaluated for prospective repurposing as multitarget agent for neurodegenerative syndromes, including Alzheimer's disease (AD). Herein, twenty-one dantrolene-like hydrazide and hydrazone analogues were synthesized with the aim of exploring structure-activity relationships (SARs) for the inhibition of human monoamine oxidases (MAOs) and acetylcholinesterase (AChE), two well-established target enzymes for anti-AD drugs. With few exceptions, the newly synthesized compounds exhibited selectivity toward MAO B over either MAO A or AChE, with the secondary aldimine 9 and phenylhydrazone 20 attaining IC50 values of 0.68 and 0.81 µM, respectively. While no general SAR trend was observed with lipophilicity descriptors, a molecular simplification strategy allowed the main pharmacophore features to be identified, which are responsible for the inhibitory activity toward MAO B. Finally, further in vitro investigations revealed cell protection from oxidative insult and activation of carnitine/acylcarnitine carrier as concomitant biological activities responsible for neuroprotection by hits 9 and 20 and other promising compounds in the examined series.

Skin Manifestation of SARS-CoV-2: The Italian Experience.

At the end of December 2019, a new coronavirus denominated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was identified in Wuhan, Hubei province, China. Less than three months later, the World Health Organization (WHO) declared coronavirus disease-19 (COVID-19) to be a global pandemic. Growing numbers of clinical, histopathological, and molecular findings were subsequently reported, among which a particular interest in skin manifestations during the course of the disease was evinced. Today, about one year after the development of the first major infectious foci in Italy, various large case series of patients with COVID-19-related skin manifestations have focused on skin specimens. However, few are supported by histopathological, immunohistochemical, and polymerase chain reaction (PCR) data on skin specimens. Here, we present nine cases of COVID-positive patients, confirmed by histological, immunophenotypical, and PCR findings, who underwent skin biopsy. A review of the literature in Italian cases with COVID-related skin manifestations is then provided.

Inflammatory Skin Lesions in Three SARS-CoV-2 Swab-Negative Adolescents: A Possible COVID-19 Sneaky Manifestation?

Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with various clinical manifestations, including skin lesions. In particular, during the COVID-19 pandemic lock-down period numerous chilblain-like lesions, mainly located on the feet, were observed in adolescents. The latter were often asymptomatic or associated with very mild respiratory symptoms. Here, we report three cases of acral nodular lesions in SARS-CoV-2 swab-negative adolescents with histological findings of chronic immune-mediated inflammation and immunohistochemical evidence of SARS-CoV-2 spike glycoproteins in endothelial cells and eccrine sweat glands. In one of these cases, the virus presence was confirmed by electron microscopy.

Advanced Cutaneous Leiomyosarcoma of the Forearm.

Leiomyosarcoma is a malignant smooth muscle neoplasm, which is traditionally divided into superficial and deep tumors. Superficial leiomyosarcomas are quite rare entities, accounting for approximately 7% of soft tissue neoplasms and 0.04% of all cancers. Here we describe a rare case of advanced primary cutaneous leiomyosarcoma (PCL) in a 93-year-old woman, highlighting the considerable size of the lesion and the correct surgical and oncological management. The clinical story began about 4 years ago, and the neoplasia was treated only with local radiotherapy, but the patient suffered from a dramatic volumetric increase of the right arm sarcoma one year ago. Then, an amputation of the limb was performed without following adjuvant chemotherapy. Currently, she does not show signs of recurrence and is in good shape.