Type I Diabetes Mellitus Suppresses Experimental Skin Carcinogenesis.

This study explores the previously uncharted territory of the effects of ultraviolet (UV) radiation on diabetic skin, compared to its well-documented impact on normal skin, particularly focusing on carcinogenesis and aging. Employing hairless SKH-hr2, Type 1 and 2 diabetic, and nondiabetic male mice, the research subjected these to UV radiation thrice weekly for eight months. The investigation included comprehensive assessments of photoaging and photocarcinogenesis in diabetic versus normal skin, measuring factors such as hydration, trans-epidermal water loss, elasticity, skin thickness, melanin, sebum content, stratum corneum exfoliation and body weight, alongside photo documentation. Additionally, oxidative stress and the presence of hydrophilic antioxidants (uric acid and glutathione) in the stratum corneum were evaluated. Histopathological examination post-sacrifice provided insights into the morphological changes. Findings reveal that under UV exposure, Type 1 diabetic skin showed heightened dehydration, thinning, and signs of accelerated aging. Remarkably, Type 1 diabetic mice did not develop squamous cell carcinoma or pigmented nevi, contrary to normal and Type 2 diabetic skin. This unexpected resistance to UV-induced skin cancers in Type 1 diabetic skin prompts a crucial need for further research to uncover the underlying mechanisms providing this resistance.

Spongiotic Gingival Hyperplasia in a Child with Asperger Syndrome: a Case Report.

Background: Asperger syndrome is a type of autism spectrum disorder that may affect oral health and dental management. Spongiotic gingival hyperplasia is a rare lesion with unique clinicopathological features and unknown pathogenesis that has not been previously reported in a patient with autism spectrum disorder. The purpose of this case report is to present the first case of spongiotic gingival hyperplasia in a child with Asperger syndrome. Methods: A 14-year-old boy with Asperger syndrome was referred for diagnosis and management of bright red granular overgrowths of the marginal gingiva and interdental papilla of the mandibular right incisors and marginal gingiva of the mandibular left incisor. A biopsy was performed on the interdental papilla between the mandibular right incisors. Results: Microscopic examination and cytokeratin 19 immunopositivity confirmed the diagnosis of spongiotic gingival hyperplasia. The parents of the patient declined any further intervention, and four months later the gingival lesions, including the biopsied area, did not show any significant difference from the initial examination. Conclusions: Patients with autism spectrum diseases, such as Asperger syndrome, cannot achieve a good level of oral hygiene. Thus, it is expected that the incidence of spongiotic gingival hyperplasia should be higher in this group of patients, in case oral microbiome participates in its pathogenesis. Management of such lesions is challenging, as such patients do not comply with a proper oral hygiene program and do not cooperate with surgical excision.

Domestic and Community Violence in Greece After the First COVID-19 Quarantine: A Clinical Forensic Approach.

Many scientists expressed their concerns regarding the impact of COVID-19-related quarantine measures on interpersonal violence, mainly concerning children and intimate partners, as well as other negative psychological effects. During early 2020, free circulation in Greece was prohibited for 42 days, up until May 4th. The aim of our study was to investigate characteristics of bodily harm allegation cases referred to the Department of Forensic Medicine and Toxicology of the Medical School of the National and Kapodistrian University of Athens, Greece, during the first month succeeding free circulation re-establishment in the broader Attica region. We also aimed to detect any possible differences regarding bodily harm allegations by comparing the corresponding time period of 2019. A decrease in community violence (CV) allegations, especially youth violence incidents, was observed in 2020. Females' victimization, as well as allegations against strangers, were also decreased. No differences were observed concerning the injury mechanism. Victims of 2020 filed the allegations faster and, thus, were examined almost one day earlier than their 2019 counterparts. During lockdown, domestic violence (DV) hotline reporting was significantly increased, but paradoxically DV cases referred to our Department were decreased. In Greece, the legislators did not foresee any specific exemption from circulation restriction for DV victims attempting to escape abuse. Our results revealed a small, but notable, impact on non-fatal interpersonal violence.

The Anaphylactoid Syndrome of Pregnancy: Two Autopsy Cases.

The anaphylactoid syndrome of pregnancy (ASP) is a rare emergency with significant mortality and morbidity, in which the amniotic fluid and fetal cells enter the maternal circulation leading to respiratory failure, altered mental status, hypotension, and disseminated intravascular coagulation. The term ASP was recently introduced to replace the term amniotic fluid embolism since the clinical manifestations of the entity were more similar to a septic or anaphylactic shock rather than that of an embolic event. Two autopsy cases are described, regarding a 35-year-old gravida 2 para 1 and a 34-year-old gravida 1 para 0, where the cause of death was determined to be ASP.

Undifferentiated-dedifferentiated endometrial carcinoma; the reappearance of an old friend with insights into the new data.

Endometrial carcinoma is a common malignancy in women and shows increasing incidence. Except for its two main pathogenetic types I and II, the continuing evolution on molecular genetics have led to a new classification system (TCGA), that includes four main molecular subtypes: (i) POLE-mutant (ultramutated), (ii) hypermutated (MSI), (iii) copy-number low/MSS (p53wt) and (iv) copy-number high/serous-like (p53mut). The undifferentiated and dedifferentiated endometrial carcinomas are rare and clinically aggressive variants, comprising about 10% of the high-grade endometrial carcinomas and 2% of the endometrial carcinomas in general. Until recently, they were under-recognized and not fully described morphologically and immunohistochemically/molecularly. Their recognition diagnostically is crucial because of their poor prognosis; approximately 40% of patients with these subtypes will die within 0.5-20 months after diagnosis, so additional therapeutic strategies are important for an effective management. Because of their rarity, the responsiveness to other than conventional treatment, such as immunotherapy, has not been sufficiently investigated yet. The aim of this review is to provide an update on the knowledge about these two uncommon subtypes according to the current literature.

Infant Pneumonitis Due to a Tracheoesophageal Fistula: A Presentation of Two Autopsy Cases.

Both esophageal atresia (EA) and tracheoesophageal fistula (TEF) represent a rather uncommon congenital abnormality that is the result of abnormal tracheoesophageal organogenesis. Although EA, with or without TEF, is relatively uncommon, it represents the most common upper gastrointestinal birth defect. Esophageal atresia and tracheoesophageal fistula are anatomically classified into five types according to the Gross classification (types A, B, C, D, E/H). As in type E/H, the continuity of the esophagus is not interrupted, the symptom onset is consequently delayed, and therefore diagnosis is difficult. Aspiration pneumonitis is a chemical injury caused by inhaled sterile gastric contents, while aspiration pneumonia is, in part, an infectious process because the inhaled oropharyngeal secretions are rich in bacteria. This paper aims to report two infant autopsy cases of aspiration pneumonitis with TEF involvement. The main histopathological finding was interstitial pneumonitis. Upon histopathological examination, lymphocytes, plasma cells, and macrophages were discovered on the alveolar walls, which were compatible with the chemical origin of interstitial pneumonitis. No eosinophils were detected; therefore, hypersensitivity-originating interstitial pneumonitis was ruled out. The cause of death in both cases was interstitial pneumonitis.

Serum Concentration of Selected Angiogenesis-Related Molecules Differs among Molecular Subtypes, Body Mass Index and Menopausal Status in Breast Cancer Patients.

BACKGROUND: Angiogenesis is a hallmark of breast cancer (BC) and is mediated by the vascular endothelial growth factor (VEGF) signaling axis. It is regulated by different proangiogenic factors, including platelet-derived growth factor-CC (PDGF-CC) and heparin-binding EGF-like growth factor (HB-EGF), as well as co-receptors, such as neuropilin-1, which could have prognostic implications in BC patients. PATIENTS AND METHODS: We assessed the serum levels of VEGF, HB-EGF, PDGF-CC and neuropilin-1 in 205 patients with early BC (invasive, n = 187; in situ, n = 18) and in 31 healthy donors (HD) and investigated the potential associations with clinical and histopathological parameters. RESULTS: VEGF serum levels were significantly higher in patients with invasive versus ductal carcinomas in situ. PDGF-CC serum concentrations varied among BC molecular subtypes. Furthermore, we observed a differential expression of most biomarkers between overweight/obese (body mass index (BMI) ≥ 25 kg/m2) and non-obese patients among the BC molecular subtypes. Finally, the classification of subjects according to menopausal status revealed a significant difference in specific biomarker levels between patients and HD. CONCLUSION: The serum concentrations of angiogenic molecules differ among breast cancer molecular subtypes and are affected by the BMI and menopausal status, which could have possible clinical or prognostic implications.

Decoding a gene expression program that accompanies the phenotype of sporadic and basal cell nevus syndrome-associated odontogenic keratocyst.

BACKGROUND: Odontogenic keratocyst is characterized by local aggressive behavior and a high recurrence rate, as well as its potential to develop in association with the basal cell nevus syndrome. The aim of this study was to decode the gene expression program accompanying odontogenic keratocyst phenotype. METHODS: 150-bp paired-end RNA-sequencing was applied on six sporadic and six basal cell nevus syndrome-associated whole-tissue odontogenic keratocyst samples in comparison to six dental follicles, coupled with bioinformatics and complemented by immunohistochemistry. RESULTS: 2654 and 2427 differentially expressed genes were captured to characterize the transcriptome of sporadic and basal cell nevus syndrome-associated odontogenic keratocysts, respectively. Gene ontologies related to "epidermis/skin development" and "keratinocyte/epidermal cell differentiation" were enriched among the upregulated genes (KRT10, NCCRP1, TP63, GRHL3, SOX21), while "extracellular matrix organization" (ITGA5, LOXL2) and "odontogenesis" (MSX1, LHX8) gene ontologies were overrepresented among the downregulated genes in odontogenic keratocyst. Interestingly, upregulation of various embryonic stem cells markers (EPHA1, SCNN1A) and genes committed in cellular reprogramming (SOX2, KLF4, OVOL1, IRF6, TACSTD2, CDH1) was found in odontogenic keratocyst. These findings were highly shared between sporadic and basal cell nevus syndrome-associated odontogenic keratocysts. Immunohistochemistry verified SOX2, KLF4, OVOL1, IRF6, TACSTD2/TROP2, CDH1/E-cadherin, and p63 expression predominantly in the odontogenic keratocyst suprabasal epithelial layers. CONCLUSION: The odontogenic keratocyst transcriptomic profile is characterized by a prominent epidermal and dental epithelial fate, a repressed dental mesenchyme fate combined with deregulated extracellular matrix organization, and enhanced stemness gene signatures. Thus, we propose a developed epidermis-like phenotype in the odontogenic keratocyst suprabasal epithelial cells, established in parallel to a significant upregulation of marker genes related to embryonic stem cells and cellular reprogramming.

Non-Fatal Attacks by Dogs: Characteristics of Victims and Attacking Dogs, From the Forensic Perspective: A Series of 106 Cases From Athens, Greece, and Brief Review of the Literature.

INTRODUCTION: The close association of dogs with humans may explain the fact that dog bites are possibly the most common animal bites recorded. The relevant data concerning Greece is scarce. We aimed to study this phenomenon by describing its characteristics. METHODS: We performed a retrospective analysis of cases concerning dog attack victims, examined our Department, between 2011 and 2019. Recorded variables included sex, age, nationality, occupation, marital status, medical history, ownership status of the dog, injury anatomic location, incident time, the timing of clinical forensic examination, incapacitation time, and medical care provided. Statistical analysis was performed using Stata/MP 13 (Stata Corp., College Station, TX) and IBM SPSS Statistics Version 20 (IBM, Armonk, NY). Statistical significance was defined as a two-sided p value of <0.05. RESULTS: Most incidents involved male victims (54.2%). The victim's mean age was 44.9 years. The dog involved was unowned in 19.8% of cases. The most frequent anatomical site of injury was the legs (48.1%). Older victims suffered injuries in more sensitive areas of the body (head and neck), when compared to younger adults. Only 1.9% of victims required hospitalization. The mean incapacitation time was estimated at 5.39 days. CONCLUSIONS: Per our results, males tend more often to be victims of dog attacks. Typically, victims are of increased age and are attacked by a dog already known to them. Most incidents take place during late winter and spring, more specifically during February and during May. The most frequently affected anatomical sites were the legs. Older people suffered injuries in more sensitive areas of the body.

Surgical administration of multiple glomus tumors in uncommon anatomic regions in a 17-year-old female. A rare case report.

Glomus tumor (GT) constitutes a rare, benign, soft-tissue tumor emerging from neuro-myo-arterial glomus bodies. Due to its rarity, and absence of typical symptoms, GT is usually misdiagnosed, with a potential risk of rupture and infection, or even malignant transformation. The present manuscript reports a rare case of a 17-year-old young woman with multiple GTs in her lower back, breach and left thigh that was surgically treated. The manuscript aims to highlight the importance of prompt diagnosis and surgical treatment of this peculiar tumor in young patients and raise surgeons' awareness.

Immunohistochemical Study of Bladder Cancer Molecular Subtypes and Their Association with PD-L1 Expression.

The significant heterogeneity in clinical outcomes among patients with bladder cancer has highlighted the existence of different biological subtypes of muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Meanwhile, immune checkpoint proteins and their interference with tumor-related immune-evasive strategies has led to the development of several immunotherapeutic drugs targeting programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1). However, the lack of any known biomarker that could predict responses to immunotherapy has led to a more agnostic therapeutic approach. Here, we present a study conducted in 77 bladder cancer (BC) patients (n = 77), ranging from stages pTa to pT2. Tumor specimens were resected via transurethral resection of bladder tumor (TURBT) and consistuted of 24 low-grade (LG) and 53 high-grade (HG) tumors. Patients' tumors were then categorized into molecular subtypes, via immunohistochemistry (CK5/6 and GATA3). Furthermore, all tumor specimens were stained with anti-PD-L1 and demonstrated significant correlations with basal immunophenotype, stage pT2 and HG tumors. As such, we attempted to stratify patients into groups of likely-responders and likely-not-responders to immunotherapy with anti-PD-L1, based on their molecular phenotype. Finally, in acknowledging the fact that there is a universal lack of biomarkers associated with predicting BC response to immunotherapeutic drugs, we tested all tumors for deficiency of mismatch repair proteins (MMR).

SDH-deficient renal cell carcinoma: A case report associated with a novel germline mutation.

The highly syndromic nature of succinate dehydrogenase-deficient RCCs constitutes their active surveillance and molecular profiling the alpha and omega.

Cardiac Involvement and Subsequent Death due to Extranodal NK/T Cell Cutaneous T-Cell Lymphoma: An Autopsy Case and Brief Review of the Literature.

Cardiac tumors range from benign to high grade malignancies. The incidence of cardiac involvement either by primary, or secondary tumors during autopsy is reported to be extremely low. Extranodal NK/T-cell lymphoma (ENKTL), nasal type is an unusual type of lymphoma. The skin is the second most common site of involvement after the respiratory tract. We present a case of a 63-year-old male, who was recently diagnosed with ENKTL, nasal type, who received chemotherapy, and died without any evident cause. The corpse was referred for routine medicolegal examination. Macroscopical determination of the cause of death was not feasible and subsequent histopathological examination revealed heart infiltration by ENKTL that was found in vivo in cutaneous lesions. Similar infiltrations existed in the pancreatic tissue. To the best of our knowledge, myocardial infiltration of ENKTL, inducing severe myocardial lesions that eventually caused death, is rare, with limited cases reported in the literature.

Recurrence in Oral Premalignancy: Clinicopathologic and Immunohistochemical Analysis.

Oral leukoplakia (OL) has a propensity for recurrence and malignant transformation (MT). Herein, we evaluate sociodemographic, clinical, microscopic and immunohistochemical parameters as predictive factors for OL recurrence, also comparing primary lesions (PLs) with recurrences. Thirty-three patients with OL, completely removed either by excisional biopsy or by laser ablation following incisional biopsy, were studied. Selected molecules associated with the STAT3 oncogenic pathway, including pSTAT3, Bcl-xL, survivin, cyclin D1 and Ki-67, were further analyzed. A total of 135 OL lesions, including 97 PLs and 38 recurrences, were included. Out of 97 PLs, 31 recurred at least once and none of them underwent MT, during a mean follow-up time of 48.3 months. There was no statistically significant difference among the various parameters in recurrent vs. non-recurrent PLs, although recurrence was most frequent in non-homogeneous lesions (p = 0.087) and dysplastic lesions recurred at a higher percentage compared to hyperplastic lesions (34.5% vs. 15.4%). Lower levels of Bcl-xL and survivin were identified as significant risk factors for OL recurrence. Recurrences, although smaller and more frequently homogeneous and non-dysplastic compared to their corresponding PLs, exhibited increased immunohistochemical expression of oncogenic molecules, especially pSTAT3 and Bcl-xL. Our results suggest that parameters associated with recurrence may differ from those that affect the risk of progression to malignancy and support OL management protocols favoring excision and close monitoring of all lesions.

Primary Large Cell Neuroendocrine Carcinoma of the Parotid Gland. Report of a Rare Case.

Primary neuroendocrine carcinomas of the salivary glands are very rare neoplasms that present light microscopic, ultrastructural, and immunohistochemical features of neuroendocrine differentiation. Twelve cases have been published in the English language literature. We describe the pathologic features of a case of primary large cell neuroendocrine carcinoma of the parotid gland in a 91-year old male and summarize the immunophenotype of previously reported LCNECs of the major salivary glands. It is concluded that primary LCNEC of the salivary glands presents as a high-grade undifferentiated carcinoma, whose diagnosis may be hindered by its rarity and non-specific light microscopic features. A high level of awareness, immunohistochemical staining for neuroendocrine markers synaptophysin and CD56, and a thorough diagnostic work-up in order to exclude metastasis from a primary neuroendocrine carcinoma will allow its diagnosis.

Contemporary Molecular Classification of Urinary Bladder Cancer.

The significant heterogeneity in the clinical outcome among patients with bladder cancer has highlighted the existence of different biological subtypes of muscle-invasive and non-muscle-invasive bladder cancer. Transcriptional profiling studies revealed that primary bladder cancers can be grouped into 'intrinsic' basal and luminal molecular subtypes. Luminal tumors have a papillary configuration and express markers of urothelial differentiation (uroplakins, cytokeratin 20) fibroblast growth factor 3 (FGFR3), E-cadherin and early cell-cycle genes. On the contrary, basal tumors express markers of the basal layer of the urothelium (cluster of differentiation 44, cytokeratin 5/6 and cytokeratin 14); some show squamous differentiation. Patients with basal tumors respond better to immune checkpoint inhibitors and have a worse prognosis than those with luminal tumors, who respond better to FGFR3 and human epidermal growth factor receptor 2. Patients with squamous differentiation tumors show better response to agents targeting epidermal growth factor receptor. The aim of this review was to highlight the chronological order of research performed in the field of the molecular classification of bladder cancer, with particular emphasis on prototypical research projects and recent advances. If prospective studies confirm the association of bladder cancer molecular subtypes with different responses and prognoses to targeted therapies, molecular subtyping will be incorporated into bladder cancer management.

Interpersonal Violence Against Children and Adolescents: A Forensic Study From Greece.

OBJECTIVE: To investigate differences in victimization of minors after allegations of domestic violence and community violence. METHODS: This retrospective study was conducted by reviewing the archive of clinical examinations after allegations for interpersonal violence against minors that were performed at the Department of Forensic Medicine and Toxicology of our Medical School from 2012 to 2016. RESULTS: 216 cases of allegations for victimization of minors' were referred to our department, representing 8.8% of all clinical forensic examinations. Boys community violence victims were affected mainly on the head, whilst girls mainly on the genital area. Upper limbs were the predominant site of injuries on domestic violence victims of both sexes. CONCLUSIONS: Adolescents were in greater danger of sustaining injuries than younger children. Upper limb injuries may prove to be a useful screening tool for domestic violence in school-age children and adolescents, while trunk injuries may indicate domestic violence in preschool children.

Biological rhythms of fatal myocardial infarction in Greece: an autopsy study.

BACKGROUND: Biological rhythms, acting as an endogenous clock, prepare and assist the organism to function optimally during predictable seasonal and daily cycles. Many elements of the cardiovascular system exhibit specific rhythmical patterns. Besides genetic mechanisms, external stimuli may alter biological rhythms. METHODS: The aim of this study was to investigate the patterns of biological rhythms in patients who suffered a fatal myocardial Infarction (MI), ascertained by macroscopical or histopathological examination. Cases of fatal MI examined during the time 2010-2017 were included in our study sample (827 cases in total). Medical History was also obtained for each case. The assessment of seasonal variation of fatal MI was accomplished by employing three different methods, Rayleigh Uniformity Test, X2 Goodness-of-fit test and Edward's Seasonality Test. Statistical significance was defined as a 2-sided p value of <0.05. RESULTS: Regarding the distribution of total cases, fatal MIs onset occurs more often during winter, with higher incidence in December and January. The weekly distribution of cases seems uniform. The circadian pattern presents higher frequencies of fatal MIs between 08:00 and 12:00 with the acrophase between 11:00 and 12:00. Further analysis was conducted separately, depending on the method of time-of-death reporting. CONCLUSIONS: Taking under consideration the variation of the occurrence of MI related deaths, in accordance with the respective biological rhythms, public health policies more suitable to the individual requirements of every country's population may be adopted.

Hypersensitivity reaction of the gingiva to chlorhexidine: case report and literature review.

OBJECTIVE: The aim of this case report was to document a case of delayed-type hypersensitivity reaction of the gingiva to chlorhexidine and review the literature on oral mucosal hypersensitivity reactions associated to chlorhexidine-containing oral hygiene products. STUDY DESIGN: A 58-year-old man presented with a well-demarcated erythematous area on the right upper anterior gingiva. Incisional biopsy was performed. Postoperatively, chlorhexidine digluconate gel was prescribed twice a day, but the patient did not use it because he experienced intense burning immediately after the first application. The microscopic diagnosis was nonspecific mucositis. Hypersensitivity reaction was suspected. The patient reported use of 0.004% chlorhexidine digluconate-based toothpaste twice a day in the past few years. A delayed-type hypersensitivity reaction to the toothpaste was hypothesized, and its use was discontinued. Chlorhexidine, the common ingredient of both the toothpaste and the gel, was considered the allergen. The literature was reviewed on chlorhexidine-induced oral hypersensitivity reactions. RESULTS: Two weeks after cessation of toothpaste use, complete remission of the lesion was observed without additional intervention. Four years later, no recurrence has been reported. The literature review yielded 7 studies reporting 20 patients with intraoral manifestations of hypersensitivity reactions associated with chlorhexidine-containing oral hygiene products. CONCLUSIONS: Clinicians should be aware that oral hygiene products containing even low concentrations of chlorhexidine might induce hypersensitivity reactions.

Traumatic complete outer ear amputation by human bite, a forensic case report and review of the literature.

We present a case of a complete external ear amputation, caused by a human bite, that took place during a quarrel in a local farmers' market. The male victim was transferred to the Hospital. After surgical reattachment of the auricle, a forensic clinical examination was performed, as per legal obligation. During examination, the victim was found to have sustained: contusions of the orbital regions (lower eyelids), bilaterally, soft tissue oedema of the forehead (to the left of the middle line), and contusion of the right neck area. He also sustained multiple soft tissue injuries (contusions, abrasions) on the torso and on both upper and lower extremities. Clinical forensic examination of human bite injuries requires thorough description of the wound, proper photography and possibly collection of swabs for DNA identification (in case of unknown perpetrator). Nevertheless, the Forensic Pathologist is often required to perform clinical examination, only after medical care has been provided. Therefore, clinicians should be aware of the need of proper documentation and act accordingly.