Understanding the Dermoscopic Patterns of Basal Cell Carcinoma Using Line-Field Confocal Tomography.

Basal cell carcinoma (BCC) is the most frequent malignancy in the general population. To date, dermoscopy is considered a key tool for the diagnosis of BCC; nevertheless, line-field confocal optical coherence tomography (LC-OCT), a new non-invasive optical technique, has become increasingly important in clinical practice, allowing for in vivo imaging at cellular resolution. The present study aimed to investigate the possible correlation between the dermoscopic features of BCC and their LC-OCT counterparts. In total, 100 histopathologically confirmed BCC cases were collected at the Dermatologic Clinic of the University of Siena, Italy. Predefined dermoscopic and LC-OCT criteria were retrospectively evaluated, and their frequencies were calculated. The mean (SD) age of our cohort was 65.46 (13.36) years. Overall, BCC lesions were mainly located on the head (49%), and they were predominantly dermoscopically pigmented (59%). Interestingly, all dermoscopic features considered had a statistically significant agreement with the LC-OCT criteria (all p < 0.05). In conclusion, our results showed that dermoscopic patterns may be associated with LC-OCT findings, potentially increasing accuracy in BCC diagnosis. However, further studies are needed in this field.

A case report of complex suicide in physician: attempt drugs poisoning and adhesive tape asphyxia.

Complex suicides are rare occurrences that can be categorized into planned (or primary) cases and unplanned (or secondary) cases. Additionally, individuals often select suicide methods based on their availability and accessibility. The body of a 58-year-old man was discovered deceased inside his medical office. He was found seated on the waiting room sofa, with his airways obstructed by several layers of adhesive tape wrapped around his head. An intravenous needle was observed in his left arm, and on the table in front of him, an empty 50 ml syringe, two empty vials of 10 ml potassium chloride, and an empty 10 mg vial of Valium (diazepam) were found. A roll of adhesive tape, similar to the one around his head, was also present. The autopsy, conducted 36 h after the body's discovery, revealed therapeutic concentrations of diazepam and its metabolite nordiazepam in the blood samples, while potassium chloride was not detected. Integrating forensic findings obtained from autopsy, histology, and other postmortem investigation, including toxicological analysis, can aid in defining suicidal behavior and preventing misinterpretation, particularly in differentiating diagnosis between homicide and suicide. It is crucial to consider circumstantial data and professional knowledge in such cases.

"Immunohistochemical analysis of Sigma-1 receptor (σ-1R) expression in human pineal gland in relation to different causes of death".

Sigma-1 receptor (σ-1R) modulates cellular signaling pathways, probably acting as a ligand operated chaperone. When activated, the receptor translocates from the interface mitochondrion associated membrane of the endoplasmic reticulum to the cell membrane. σ-1R was demonstrated in some brain regions, including the pineal gland, and was proposed to be involved in several cerebral processes, including neuroprotective responses against homeostasis alterations. On this basis, the immunohistochemical expression of σ-1R in human pineal glands was evaluated, with particular regard to the different causes of death. Thirty-eight pineal glands obtained from forensic autopsies were divided into five groups according to the cause of death: sudden death, drowning, fire fatality, hanging, and hemorrhagic shock, and examined with hematoxylin-eosin stain and immunohistochemistry for σ-1R. Both pinealocytes and perivascular spaces were evaluated. The pineal glands from sudden death were only mildly positive for σ-1R, while a more evident immunopositivity was observed in hanging, fire fatality, hemorrhagic shock, and drowning. These results were confirmed in a two-by-two comparison between the sudden death group and other groups. Our data demonstrate for the first time with immunohistochemical techniques the presence of σ-1R expression in the human pineal gland and propose a direct correlation between σ-1R expression and duration of the death process, in particular when hypoxic conditions and/or excessive psychological stress are present.

Primary Cutaneous Cryptococcosis in an Immunocompetent Patient: Diagnostic Workflow and Choice of Treatment.

Cryptococcosis is an opportunistic infection in immunocompromised patients, involving mainly the lungs and central nervous system; however, the skin, eyes and genitourinary tract could also be involved as secondary sites of infection. Primary cutaneous cryptococcosis (PCC) is a distinct clinical entity that can occur in both immunocompetent and -compromised patients, usually trough skin injury. In immunocompetent patients, it is a very rare infection, presenting with non-specific clinical pictures and being challenging to diagnose. Herein, we present the case of an immunocompetent man with PCC due to Cryptococcus neoformans on his right forearm. PCC was diagnosed by a histological and cultural examination. Causes of concomitant immunosuppression were ruled out. A secondary cutaneous cryptococcosis was excluded with careful investigations. Therapy with oral fluconazole for three months was successfully performed, without evidence of recurrence in the following six months. Complete clinical recovery was achieved after three months of oral antifungal therapy, suggesting that longer courses of treatment could be avoided when faced with PCC in immunocompetent patients.

Usefulness of polymerase chain reaction analysis in a case of clinically and histologically atypical nodular granulomatous secondary syphilis.

We report a case of a nodular granulomatous secondary syphilis histologically resembling tuberculids in a patient with positive quantiferon test and serology for syphilis. Polymerase chain reaction (PCR) analysis led to the diagnosis. We underline the usefulness of PCR in clinically and histologically doubtful cases in order to avoid misdiagnosis and delay treatment.

Professional liability due to complete esophagus section during thyroidectomy: a rare case report.

Background: Several diagnostic and therapeutic processes are regulated by guidelines and recommendations provided by International and National Societies which offer standardized indications for health-care practitioners, including the treatment of pathologies that may affect the thyroid gland. These documents are very important for patient health promotion and, also, for preventing adverse events associated with patient injuries and related malpractice litigations. Particularly, thyroid surgery can be a cause of professional liability due to complications from surgical errors. Even if the most frequent complications are hypocalcemia and recurrent laryngeal nerve injury, this surgical specialty can be also burdened by other rare and serious adverse events such as esophagus lesions. Case Description: Here a case of alleged medical malpractice involving a 22-year-old woman reporting a complete esophagus section during thyroidectomy was described. The case analysis highlighted that the surgical treatment was performed for an unconfirmed Graves-Basedow disease which was then assessed as Hashimoto thyroiditis by histological exam of the removed gland. The esophagus section was treated by termino-terminal pharyngo-jejunal anastomosis and termino-terminal jejuno-esophagus anastomosis. The medico-legal analysis of the case revealed two different profiles of medical malpractice related, respectively, to the misdiagnosis of the pathology due to an inappropriate diagnostic-therapeutic procedure and the production of the complete section of the esophagus, representing an extremely rare complication of thyroidectomy. Conclusions: Clinicians should ensure an adequate diagnostic-therapeutic path based on guidelines, operational procedures, and evidence-based publications. The non-observance of the "required rules" for diagnosis and treatment of thyroid disease can be associated with a very rare and severe complication that strongly compromises the patient quality of life.

Postmortem Biochemistry and Immunohistochemistry in Anaphylactic Death Due to Hymenoptera Sting: A Forensic Case Report.

BACKGROUND: Postmortem assessment of anaphylactic death is a challenge for forensic pathologists. One of the most frequent elicitors of anaphylaxis is insect venom. Here, a case of anaphylactic death due to Hymenoptera stings is reported to highlight the contribution of postmortem biochemistry and immunohistochemistry in assessing the cause of death. CASE REPORT: A 59-year-old Caucasian man working on his farm was presumably stung by a bee and died. He had a history of previous sensitization to insect venom. The autopsy revealed no signs of insect puncture, mild edema of the larynx, and foamy edema in the bronchial tree and lungs. Routine histology showed endo-alveolar edema and hemorrhage, bronchospasm, and scattered bronchial obstruction due to mucus hyperproduction. Biochemical analysis was performed, and serum tryptase was equal to 189 µg/L, total IgE was 200 kU/L, and specific IgE dosage was positive for bee and yellow jacket species. Immunohistochemistry for tryptase detection was carried out, revealing mast cells and degranulated tryptase expression in the larynx, lungs, spleen, and heart. These findings led to the diagnosis of anaphylactic death due to Hymenoptera stings. CONCLUSIONS: The case highlights that the role of biochemistry and immunohistochemistry in the postmortem assessment of anaphylactic reactions should be stressed by forensic practitioners.

Multidisciplinary Forensic Approach in "Complex" Bodies: Systematic Review and Procedural Proposal.

The recovery of severely altered cadavers (i.e., extensively decomposed, mummified, charred or dismembered) can be a challenge for forensic pathologists due to the difficulties in identification, PMI estimation and manner and cause of death determination. In such cases, integrating routine approaches (autopsy, histology, toxicology) to more specific forensic branches can be fundamental to improving the investigative process. In this paper a systematic review using PubMed, Scopus and Web of Science databases has been performed. The aim was to evaluate the forensic approaches implemented in the management of severely altered bodies due to decomposition, mummification, skeletonization, charring or dismemberment (to which we refer to as "complex"), and the role of each approach in the solution of a case. Then, the literature revision results were used to propose a schematic flowchart summarizing the post mortem activities that can be performed in forensic practice, adaptable in relation to each case.

Suicide, depression and thyroid dysregulation: An unusual case of unplanned complex suicide.

Complex suicides are rare events pursued by the victims by means of two or more different fatal methods and can be further classified in planned or unplanned depending on the simultaneous or sequential application of the methods, respectively. The multiplicity of the injuries detected can frequently lead to misinterpretations, thus making a multidisciplinary approach of utmost importance. Here an unusual unplanned complex suicide was described discussing the post-mortem data leading to the forensic diagnosis; moreover, a focus on the depression cause was reported. The case regarded a 48-year-old man with a recent diagnosis of depression who self-stabbed his neck and, subsequentially, fallen from height. Data obtained from autopsy, histology, radiology and toxicology were described, highlighting the main findings for achieving the differential diagnosis between suicide and homicide. Moreover, microscopic findings compatible with an unrecognized thyroiditis led to consider the thyroid dysfunction as a possible substrate of depression, suggesting it potential effect on suicidal behaviour.

Folliculosebaceous units are a frequent finding in early lichen sclerosus of the foreskin.

BACKGROUND: Folliculosebaceous units (FSU) has been considered an early target of inflammation in vulvar lichen sclerosus (VLS). This diagnostic clue is not reported in lichen sclerosus (LS) of the foreskin (FLS) that is normally hairless. We evaluated the presence and inflammation of FSU and sebaceous glands (SG) in LS of the foreskin. METHODS: Histological specimens from therapeutic circumcision were assessed in order to evaluate the frequency and inflammation of FSU and SG in LS. RESULTS: Ninety-eight cases, grouped into 46 early (group 1) and 52 overt (group 2) FLS were included in the study. SG-FSU were found in 95.7% of group 1, and 65.4% of group 2 cases. Their density was inversely correlated with patient age (P=0.0014). We observed perifollicular inflammation in all cases with visible SG-FSU and frequent FSU abnormalities. CONCLUSIONS: SG and FSU were frequent in early FLS and decreased in advanced disease and adults. We hypothesize that SG and FSU are involved in the inflammatory process leading to FLS. These data, which need further investigation, could help to better understand the pathogenesis of FLS.

State of the Art on the Role of Postmortem Computed Tomography Angiography and Magnetic Resonance Imaging in the Diagnosis of Cardiac Causes of Death: A Narrative Review.

The need of a minimally invasive approach, especially in cases of cultural or religious oppositions to the internal examination of the body, has led over the years to the introduction of postmortem CT (PMCT) methodologies within forensic investigations for the comprehension of the cause of death in selected cases (e.g., traumatic deaths, acute hemorrhages, etc.), as well as for personal identification. The impossibility to yield clear information concerning the coronary arteries due to the lack of an active circulation to adequately distribute contrast agents has been subsequently overcome by the introduction of coronary-targeted PMCT Angiography (PMCTA), which has revealed useful in the detection of stenoses related to calcifications and/or atherosclerotic plaques, as well as in the suspicion of thrombosis. In parallel, due to the best ability to study the soft tissues, cardiac postmortem MR (PMMR) methodologies have been further implemented, which proved suitable for the detection and aging of infarcted areas, and for cardiomyopathies. Hence, the purpose of the present work to shed light on the state of the art concerning the value of both coronary-targeted PMCTA and PMMR in the diagnosis of coronary artery disease and/or myocardial infarction as causes of death, further evaluating their suitability as alternatives or complementary approaches to standard autopsy and histologic investigations.

The role of PMCT for the assessment of the cause of death in natural disaster (landslide and flood): a Sicilian experience.

In this report, the authors provide a contribution of PMCT in assessing the cause of death due to natural disasters. Here, the PMCT findings of 43 subjects who died during both landslide and flood were described. The post-mortem imaging revealed, clearly, traumatic injuries and/or the presence of foreign material in airways allowing to assess the cause of death of each subject, together with external inspection and the collected circumstantial data. Particularly, the PMCT has been helpful for characterization and localization of the clogging substance in airways providing findings on bronchial branches involvement. Moreover, the investigation offered detailed data on skeletal injuries in all anatomic districts and put in evidence both the precise fracturing site and the characteristics of fracture stubs for each bone fracture. This report supports the recommendation of the virtual autopsy in a case with several victims, as in natural disasters, and its role as an alternative diagnostic investigation when the standard autopsy is not feasible.

An Insight into the Role of Postmortem Immunohistochemistry in the Comprehension of the Inflammatory Pathophysiology of COVID-19 Disease and Vaccine-Related Thrombotic Adverse Events: A Narrative Review.

On 11 March 2020, the World Health Organization (WHO) declared a pandemic due to the spread of COVID-19 from Wuhan, China, causing high mortality rates all over the world. The related disease, which mainly affects the lungs, is responsible for the onset of Diffuse Alveolar Damage (DAD) and a hypercoagulability state, frequently leading to Severe Acute Respiratory Syndrome (SARS) and multiorgan failure, particularly in old and severe-critically ill patients. In order to find effective therapeutic strategies, many efforts have been made aiming to shed light on the pathophysiology of COVID-19 disease. Moreover, following the late advent of vaccination campaigns, the need for the comprehension of the pathophysiology of the fatal, although rare, thrombotic adverse events has become mandatory as well. The achievement of such purposes needs a multidisciplinary approach, depending on a correct interpretation of clinical, biochemical, biomolecular, and forensic findings. In this scenario, autopsies have helped in defining, on both gross and histologic examinations, the main changes to which the affected organs undergo and the role in assessing whether a patient is dead "from" or "with" COVID-19, not to mention whether the existence of a causal link exists between vaccination and thrombotic adverse events. In the present work, we explored the role of postmortem immunohistochemistry, and the increasingly used ancillary technique, in helping to understand the mechanism underlying the pathophysiology of both COVID-19 disease and COVID-19 vaccine-related adverse and rare effects.

Caspase 9 and Caspase 3 Immunohistochemical Pattern in Skeletal and Cardiac Muscles at Different Times after Death: An Experimental Study on PMI Estimation.

(1) Background: The estimation of the post mortem interval (PMI) is a challenge for forensic pathologists because data emerging from methods commonly applied are not always conclusive, since several conditions exist that may affect the reliability of these parameters. Thus, new approaches have been proposed to overcome such a limit. In recent years, several studies have been performed on proteins analyzing their expression/degradation patterns in relation to the progressing of the post mortem interval. (2) Methods: The immunoreactivity patterns of two apoptosis mediators-Caspase 9 and Caspase 3-have been tested in order to evaluate their potential role as markers of the post mortem interval. The immunohistochemical analysis was performed on samples of skeletal and cardiac muscles obtained from rats at 0, 4, 8, 12, 24 and 72 h after death. (3) Results: The observed immunoreactivity patterns of both Caspase 9 and Caspase 3 showed a significant correlation with increasing post mortem interval either in skeletal or cardiac muscles, while the comparison of the immunoreactivity patterns of the two apoptotic mediators within each tissue appeared consistent with a preliminary activation of the "initiator" Caspase 9, which, in turn, subsequently activates the "executioner" Caspase 3. (4) Conclusion: The different expressions and decrease immunohistochemically observed on both caspases with progressing PMI support the usefulness of the combined analysis for post mortem interval estimation.

Investigation of the skin lesions in lightning strike death.

Lightning strike-related deaths are unusual, and the victim bodies can present different lesions due to the different injury mechanisms associated with this event. Since the post mortem assessment can be challenging, the evaluation of the characteristics of the skin lesions becomes fundamental to reconstruct the event. Due to the paucity of literature on this topic, the authors report the case of a 59-year-old man found dead near his home after a thunderstorm. Initially considered a murder by gunshot, the autopsy revealed the typical lightning strike lesions, also known as Lichtenberg figures. The adequate interpretation of the autopsy data and the histological evidences allowed to reconstruct the death dynamic and to relate it to a lightning strike. The main lesions due to lightening are here reported and discussed in order to provide a workflow for the identification of lightening as cause of death in unwitnessed cases.

Forensic investigative issues in a fireworks production factory explosion.

Since their discovery in ancient China, fireworks rapidly spread throughout the world, where they have always been used to celebrate either popular or private events. Their use is nonetheless related to several risks, especially within production factories, since several injuries or even death can occur following an accidental ignition. In cases of major disasters related to fireworks explosions, stating the accidental or intentional nature of the event might prove challenging, thus raising the need of a multidisciplinary approach. In this regard, we here discuss the case of an accidental explosion that occurred in a fireworks production factory, accountable for five deaths and two hospitalisations.

Fire in operating room: The adverse "never" event. Case report, mini-review and medico-legal considerations.

The patient's security and safety represent a topic of great importance for public health that led several healthcare organizations in many Countries to share documents to promote risk management and preventing adverse events. Surgical Fire (SF) is an infrequent adverse event generally occurring in the operating room (OR) and consisting of a fire that occurs in, on, or around a patient undergoing a medical or surgical procedure. Here a medico-legal case involving a 65-year-old woman reporting burns to the neck due to an SF during a thyroidectomy was described. A literature review was performed using Pubmed and Scopus databases, focusing on epidemiology, causes, prevention activities associated with the SF, and the related best practices recommendations. The medico-legal analysis of the case led to admit the professional liability because the suggested time (3 min) to use the electrocautery after CHG application was not respected. The case analysis and the literature review suggest the importance of implementing National and Local procedures to promote the management of SF risk. Finally, it is necessary to highlight the role of incident reporting and root causes analysis in understanding the cause of the adverse events and thus enforce their prevention.

Retinoblastoma Is Characterized by a Cold, CD8+ Cell Poor, PD-L1- Microenvironment, Which Turns Into Hot, CD8+ Cell Rich, PD-L1+ After Chemotherapy.

Purpose: To investigate the impact of chemotherapy (CHT) on human retinoblastoma (RB) tumor microenvironment (TME). Cases and Methods: Ninety-four RBs were studied, including 44 primary RBs treated by upfront surgery (Group 1) and 50 primary RBs enucleated after CHT (CHT), either intra-arterial (IAC; Group 2, 33 cases) or systemic (S-CHT; Group 3, 17 cases). Conventional and multiplexed immunohistochemistry were performed to make quantitative comparisons among the three groups, for the following parameters: tumor-infiltrating inflammatory cells (TI-ICs); programmed cell death protein 1 (PD-1) positive TI-ICs; Ki67 proliferation index; gliosis; PD-1 ligand (PD-L1) protein expression; vessel number. We also correlated these TME factors with the presence of histological high-risk factors (HHRF+) and RB anaplasia grade (AG). Results: After CHT, a decrease in both RB burden and Ki67 positivity was observed. In parallel, most subsets of TI-ICs, PD-1+ TI-ICs, gliosis, and PD-L1 protein expression significantly increased (P < 0.001, P = 0.02, P < 0.001, respectively). Vessel number did not significantly vary. Age, HHRFs+ and AG were significantly different between primary and chemoreduced RBs (P < 0.001, P = 0.006, P = 0.001, respectively) and were correlated with most TME factors. Conclusions: CHT modulates host antitumor immunity by reorienting the RB TME from anergic into an active, CD8+, PD-L1+ hot state. Furthermore, some clinicopathological characteristics of RB correlate with several factors of TME. Our study adds data in favor of the possibility of a new therapeutic scenario in human RB.

Unusual attempted suicide or covered attempted homicide? A neck stabbing case report and review of literature.

A medico-legal consult is frequently required in a clinical context in order to assess the eventual compatibility of specific wounds with a self- or hetero-infliction. Accordingly, the case of a 52-year-old man with a single, penetrating stab wound of the neck, reported as self-inflicted, is here presented. The forensic aspects, taken into account in order to determine the self- or hetero-infliction nature of the wound, are further discussed and compared to cases described in the literature.

Post-Mortem Investigations for the Diagnosis of Sepsis: A Review of Literature.

To date, sepsis is still one of the most important causes of death due to the difficulties concerning the achievement of a correct diagnosis. As well as in a clinical context, also in a medico-legal setting the diagnosis of sepsis can reveal challenging due to the unspecificity of the signs detected during autopsies, especially when no ante-mortem clinical data, laboratory, and cultural results are available. Thus, a systematic review of literature was performed to provide an overview of the main available and updated forensic tools for the post-mortem diagnosis of sepsis. Moreover, the aim of this review was to evaluate whether a marker or a combination of markers exist, specific enough to allow a correct and definite post-mortem diagnosis. The review was conducted searching in PubMed and Scopus databases, and using variable combinations of the keywords "post mortem sepsis diagnosis", "macroscopic signs", "morphology", "histology", "immunohistochemical markers", "biochemical markers", and "forensic microbiology". The article selection was carried out following specific inclusion and exclusion criteria. A total of 44 works was identified, providing data on morphological aspects of the organs examined, histological findings, immunohistochemical and biochemical markers, and cultural assays. The review findings suggested that the post-mortem diagnosis of sepsis can be achieved by a combination of data obtained from macroscopic and microscopic analysis and microbial investigations, associated with the increased levels of at least two of three biochemical and/or immunohistochemical markers evaluated simultaneously on blood samples.