Forensic Pathology and Legal Issues in COVID-19: Case Report and Literature Review.

Autopsy investigations of deaths following nosocomial coronavirus disease 2019 (COVID-19) infection have enormous medical and social significance, as autopsies are essential for the correct statistical recording of COVID-19 deaths, presenting new lessons, which is important to policymakers and in the improvement of public health in general.  Our study is based on the presentation of a case of a road traffic accident involving an elderly 73-year-old female with a complication of nosocomial COVID-19 infection and death leading to forensic pathological investigation. This involved autopsy, histopathological examinations, and other tests, and highlighting the importance of medicolegal matters, including the legal and ethical practicalities encountered in healthcare. This article highlights the fact that patients who have sustained various traumatic injuries accompanied by nosocomial COVID-19 infection have higher risks of morbidity and mortality. The significance of the role of a Forensic Pathologist in dealing with the analysis of injuries and the performance of autopsies to determine the cause, mechanism, and manner of death. In addition, the important lesson of testing patients for COVID-19 more regularly during a long hospital admission period, to offer early treatment and isolation, including avoiding the further spread of the COVID-19 infection variants to patients and healthcare professionals, thereby minimising and preventing hospital-acquired infection and death is stressed.

Monoradiculopathy Caused by Sporadic Hemangioblastoma of the Conus Medullaris: Case Report and Literature Review.

Sporadic spinal extramedullary hemangioblastomas of the conus medullaris are extremely rare. We present the case of a 40-year-old male with symptoms of severe back pain and monoradiculopathy. The magnetic resonance imaging (MRI) revealed an intradural extramedullary tumor attached to the conus medullaris. Total tumor removal was achieved via a typical posterior midline approach through laminectomy of L1 and L2 vertebrae, resulting in complete resolution of the preoperative symptoms. The histological examination was consistent with hemangioblastoma. To the best of our knowledge, this is the fifth case reported in the literature. We performed a brief literature review outlining the mainstay of diagnosis and therapeutic approach to these challenging lesions.

In search of dermatophytes - frequency and etiology of fungal infections in patients with and without diabetes mellitus.

INTRODUCTION: Onychomycosis is a frequent nail disorder, accounting for up to 50% of all nail problems. Treatment of onychomycosis is expensive and requires a long time of antifungal medications. Consequently, a proper and faster diagnosis is necessary. Especially for those patients with diabetes mellitus, where onychomycosis is among the most significant predictors of foot ulcer and possible severe complications.

Increased PD-L1 expression in high-grade bladder cancer with squamous cell differentiation in Bulgarian and French patients' samples.

Urothelial carcinomas (UC) of the bladder are biologically and clinically heterogeneous and the most common malignancy of the urinary tract in developed countries worldwide, where several checkpoint targets as programmed death ligand-1 (PD-L1) and programmed cell death protein (PD-1) have received the most attention in the treatment of bladder cancer. However, the clinicopathological impact of this biomarker has not yet been established enough. OBJECTIVE: To evaluate programmed death ligand-1 (PD-L1) expression in UCs of the bladder in Bulgarian and French patients' samples. MATERIALS AND METHODS: Urothelial bladder carcinomas cases from 2016-2020 were retrospectively were analyzed. The cohort included 105 cases: 42 (40%) low grade and 63 (60%) high grade. Immunohistochemical (IHC) staining for PD-L1 expression was performed using an anti-PD-L1 primary antibody clone 22C3pharmDx only to 73/105 cases. RESULTS: Approximately 21/73 cases (28.8%) of urothelial bladder carcinomas demonstrated positive PD-L1 expression, and in 52/73 cases (71.2%) were negative. Positive PD-L1 expression was associated with high grade and high pathologic stage (p < 0.001). We found that PD-L1 was expressed in a significant percentage in UC with squamous differentiation (40%), followed by classic UC (30%). An association between histological grading systems of bladder UC (WHO1973 and WHO 2016) and the TNM-staging system, estimated by Pearson correlation coefficients (r = 0.590 and r = 0.583, respectively, p < 0.001) was observed. CONCLUSIONS: We found that PD-L1 expression is increased in patients with muscle-invasive UC, and PD-L1 might be a new biomarker that correlates with the pathological stage of urothelial bladder cancer and might predict recurrence-free survival.

Eosinophilic metaplasia in transurethral resection of the prostate.

BACKGROUND: To investigate prostatic eosinophilic metaplasia (EM) in a large series of cases and their relationship with the basic prostate pathology in TURP-material: benign prostatic hyperplasia (BPH), National Institutes of Health category IV prostatitis (also called histologic prostatitis or HP), and prostatic adenocarcinoma (PCa). AIM: The relation between EM and basic prostate pathology: BPH, PCa, and HP. MATERIALS AND METHODS: Around 61 consecutive TURP-specimens were reviewed for the presence of EM. The tissue sections were stained routinely with hematoxylin-eosin (HE), hematoxylin-phloxine-saffron (HPS), and periodic acid-Schiff's procedure. Simultaneously BPH, HP, and PCa were evaluated. RESULTS: We found EM in 55.7% of TURP-specimens. EM is located more often in the ductal epithelium (58.8%) and is usually focal (73.5%) and in small groups (88.2%) of secretory luminal cells. They are associated with BPH and with a variable degree of HP in all cases. However, there is no association with PCa. Eosinophilic cytoplasmic granules in EM are better visualized with HPS. Zones induced by tissue electrocoagulation which mimic EM, are seen in the periphery of TURP-fragments. CONCLUSION: EM in prostate is presented by the presence of eosinophilic cytoplasmic granules in benign secretory epithelium. The study presents the first attempt to investigate EM in a large series of patients. Our results enrich the available information about the histoepidemiology of prostatic EM. Moreover, EM is more common in a focal lesion, found in small groups of ductal secretory epithelial cells while EM in TURP-specimens is associated with BPH and HP in all the cases.

Histopathology of nonspecific granulomatous prostatitis with special reference to eosinophilic epithelial metaplasia: Pathophysiologic, diagnostic and differential diagnostic correlations.

BACKGROUND: Recently, we publish two case reports about association of nonspecific granulomatous prostatitis (NSGP) and eosinophilic metaplasia (EM) in benign prostatic epithelium. There is no investigation of large series of this association in medical literature. Aim of the current study is to investigate the frequency of association of NSGP and prostatic EM in a large series of cases and their relationship with the basic prostate pathology: benign prostatic hyperplasia (BPH), National Institutes of Health-category IV prostatitis (so-called histologic prostatitis (HP)), and prostatic adenocarcinoma (PCa). MATERIALS AND METHODS: A retrospective record review for NSGP was performed on a total of 2366 prostatic specimens of all types of material. All cases of NSGP were reviewed for the presence of EM, BPH, and HP. NSGP with EM-cases and control cases with high grade PCa with endocrine differentiation (so-called Paneth cell-like changes) were evaluated immunohistochemically. RESULTS: NSGP was found in nine cases (0.38%). EM was detected in benign perigranulomatous secretory epithelial cells in 100% of cases with NSGP and were closely associated with BPH and HP. Immunohistochemically, in 55.5% of cases with EM, there was weak focal apical false-positive staining for p504s. CONCLUSION: EM is a very common lesion in NSGP and reflects histologically a nonspecific cellular response, connected with repeated inflammation, in close relation with BPH and HP. We speculate that EM might serve as a morphological precursor of the immunologic phase of NSGP. This constant morphological finding could facilitate the histopathological differential diagnosis of NSGP with other types of granulomatous prostatitis and high grade PCa with or without endocrine differentiation.

Nonspecific granulomatous prostatitis in association with eosinophilic epithelial metaplasia and prostatic adenocarcinoma.

We present the first case of nonspecific granulomatous prostatitis (NSGP) associated with both eosinophilic epithelial metaplasia (EM) in benign glands and prostatic adenocarcinoma (PCa). The patient was a 68-year old man with a history of obstructive prostatic syndrome. After a transurethral resection of the prostate, the histologic analysis revealed NSGP and PCa. EM was seen in benign peri-granulomatous secretory epithelial cells as PAS Diastase positive granular eosinophilic transformation of the apical cell cytoplasm. This unusual cell appearance closely simulated the Paneth cell-like changes found in PCa. Negative chromogranin expression and weakly positive P504S immune staining in the foci of EM, surrounded by P63 positive basal cells confirmed the benign EM - phenotype. The combination of NSGP with both EM and PCa has not been reported in medical literature so far. Some observations concerning their differential diagnosis are suggested.

Comparative Characteristics of Napsin A, TTF 1 and EGFR Mutation Expression in Mucinous Lung Cell Carcinomas.

BACKGROUND: Invasive mucinous lung adenocarcinomas are rare and account for 2%-10% of all lung adenocarcinoma cases. It is believed that Napsin A exhibits a weaker expression in mucinous adenocarcinomas compared with TTF1, but such correlation is still poorly researched. AIM: The aim of the study was to determine the frequency of mucinous to nonmucinous adenocarcinomas and compare specificity and sensitivity of monoclonal Napsin A with TTF1 in mucinous adenocarcinomas and define the frequency of EGFR mutations. MATERIALS AND METHODS: Eighty-four resected lung carcinomas were prospectively evaluated. All biopsies were analysed with p63, TTF1, monoclonal Napsin A, CK7, CK20 and CDX2 and were studied with real-time PCR technology. RESULTS: In resected material we detected 49/84 (58.3%) adenocarcinomas and selected 21 mucinous adenocarcinomas out of 46 non-mucinous adenocarcinomas (45.6%). The most common pattern of mucinous adenocarcinomas is papillary - 24% and colloidal - 24%, followed by acinar - 19.2% and lepidic - 19.2%. mNapsin A was positive in 18/21 (85.7%) mucinous adenocarcinomas v/s 17/21 TTF1 positive (80.9%). EGFR mutations were detected in 3/21 cases with mucinous adenocarcinomas (14.3%): mucinous papillary, mucinous acinar and "salivary gland-like". CONCLUSION: Our study demonstrates a high proportion of primary mucinous lung adenocarcinomas to primary non-mucinous adenocarcinomas. Sensitivity and specificity of mNapsin A and TTF1 did not show significant difference in pulmonary mucinous and non-mucinous adenocarcinomas, as mNapsin A gave greater sensitivity to mucinous adenocarcinomas. Our results indicate the same mutation frequency of EGFR in mucinous adenocarcinomas as mutation frequency detected in non-mucinous adenocarcinomas in the Bulgarian region.

Diagnostic Value of ERG in Prostate Needle Biopsies Containing Minute Cancer Foci.

BACKGROUND: Prostate carcinoma (PC) is the second most diagnosed cancer in men population worldwide. The small amount of the tissue in prostate needle biopsy is often sufficient for the correct interpretation. Novel antibodies, as ERG, could add to the diagnostic value of IHC study in analysing difficult core biopsies. AIM: The aim of the present study was to establish a diagnostic use of ERG in a work-up of prostate needle biopsies containing minute PC, individually and in combination with AMACR/34ßE12. MATERIALS AND METHODS: From total number of 1710 consecutive prostate needle biopsies based on HE stain 114 biopsies containing minute PC. Selected biopsies were incubated with anti-ERG, AMACR and 34ßE12 antibodies using immunohistochemical technique. RESULTS: Among 98 selected biopsies, 57 showed positive and 41 negative ERG staining. AMACR staining was positively expressed in 86 of the cases and completely absent in remaining 12. In 9 of the AMACR-negative cases the final diagnosis was establish by manifestation of ERG expression in the tumour foci. 95 of the biopsies demonstrated lack of 34ßE12 expression and only 3 cases showed weak patchy staining. Among these cases 2 were ERG-positive. CONCLUSION: ERG antibody could be especially helpful in the cases with controversial expression of AMACR and 34ßE12.

Lack of ERG-antibody in Benign Mimickers of Prostate Cancer.

INTRODUCTION: Prostate carcinoma (PC) is the second most diagnosed cancer in men worldwide. Prostate tissue in needle biopsy expresses a wide variety of architectural patterns some of which are difficult to interpret. Immunohistochemical markers, such as AMACR, p63 and 34ßE12 that are currently used in diagnosing prostate cancer, are of great value, but often their interpretation is ambiguous. In 2005 Tomlins et al. identified an emerging marker, erythroblastosis E26 rearrangement gene (ERG), which is a member of the family of genes encoding erythroblast-transformation specific transcription factors (ETS) with frequent expression in PC. AIM: The aim of this study was to investigate the expression of ERG in benign mimickers of PC in needle biopsies and its diagnostic value alone and in combination with AMACK and 34ßE12. RESULTS: Of the selected 46 biopsies, two were eventually diagnosed as PC Gleason score 6 as they were simultaneously ERG and AMACR-positive and 34ßE12-negative. One case was considered atypical. The remaining 43 biopsies were diagnosed as benign cases: simple atrophy in 13 cases, partial atrophy in 11, adenosis in 9, basal cell hyperplasia in 3, post-atrophic hyperplasia in 3, clear cell hyperplasia in 2 and sclerotic adenosis in 2 cases. None of the 43 benign cores showed evidence of ERG expression. CONCLUSION: ERG could be preferably used in diagnosing prostate needle biopsies, lesions that are hard to interpret and controversial expression of AMACR/34ßE12.

Cutaneous Mastocytosis with Persistent Blistering: Successful Treatment with Methylprednisolone and 3-Year Follow-Up Management.

BACKGROUND: Mastocytosis is a rare disorder with diverse clinical manifestations. In cutaneous mastocytosis the mast cell infiltration is limited to the skin, but is often associated with systemic symptoms due to the release of mast cell mediators. CASE REPORT: We report a 6-month-old male infant who had skin lesions of various morphologies (macules, papules, plaques, and nodules) and sizes, persistent blistering and frequent flushing episodes for half a year. Vital signs and physical examinations were unremarkable. No abnormalities in the laboratory tests were found except for a serum tryptase level (STL) of 11.8 ng/ml. The histological and immunohistochemical examinations confirmed the diagnosis of cutaneous mastocytosis. The patient was first treated with methylprednisolone, oral levocetirizine, and topical fusidic acid/betamethasone cream. Subsequently the treatment was tapered and stopped within 9 weeks. The child's symptoms improved and were successfully controlled with intermittent courses of ketotifen and topical hydrocortisone over 3 years. CONCLUSION: Childhood cutaneous mastocytosis usually has a favorable prognosis, but in some cases the disease can progress with skin manifestations necessitating a more active systemic and topical treatment.

Bilateral pheochromocytoma/intra-adrenal paraganglioma in von Hippel-Lindau patient causing acute myocardial infarction.

A 26-year-old male presented to the emergency department complaining of obstipation, severe headache and abdominal pain. An autopsy revealed bilateral pheochromocytoma and acute myocardial infarction. The tumor cells showed positive immunoreactivity of both chromogranin A and synaptophysin and were negative for adrenocortical markers such as SF-1, c17, scc, 3-HSD as well as SDHB, suggesting a germline mutation of the gene SDHB or SDHD. Molecular genetic analyses did not show a mutation in these two genes, but a mutation in the VHL gene, in exon 3: VHL c.499C>T. This is a missense mutation and causes an amino acid change (Arg167Trp).