Introduction Primary extramammary Paget\'s disease (EMPD) is a rare neoplasm that manifests as well-defined erythematous plaques, often misdiagnosed due to its similarity with different dermatoses. It may exhibit invasive features, involving adnexal invasions. The study aims to assess and compare the clinicopathological correlation of primary EMPD with adnexal features. Materials and methodology The monocentric observational retrospective study observed 43 confirmed primary EMPD cases in patients aged 45-95, excluding those with infectious dermatoses, pseudo-tumors, secondary lesions, or survived less than a month. Demographical, clinical and pathological observations were recorded. Expert dermatopathologists, blinded to the initial diagnosis, conducted a comprehensive histopathological evaluation yielding differential pathological diagnosis. Statistical analysis involved Pearson\'s Chi-square, Mann-Whitney U, and Spearman\'s Correlations for clinicopathological concordance and adnexal features. Recurrence was evaluated using Kaplan-Meier and log-rank tests, while multivariate recurrence analyses include Cox regression. A p-value < 0.05 was deemed significant. Results There was a significant association between adnexal involvement and the site of lesion (p < 0.05). There was a significant association (p < 0.05) between involved adnexal depth and primary EMPD subtypes. Adnexal involvement has a significant association with the concordance rates derived from clinicopathological correlations (p < 0.05). Smaller lesions and non-invasive EMPD significantly predict longer recurrence onset (p < 0.01). The primary EMPD subtype was the only independent predictor for recurrence time using the Cox regression model. Conclusion Adnexal proliferation in primary EMPD is considered vital on clinicopathological correlations and recurrence predictions, suggestive of its utility on both diagnosis and prognosis.

Fewer than 26 case reports describe hypertrophic lichen planus (HLP) misdiagnosed as cutaneous squamous cell carcinoma (cSCC). It can be difficult to distinguish between HLP and cSCC, as these two conditions share many clinical and histopathological characteristics. Patients who are misdiagnosed with cSCC often undergo unnecessary medical and/or surgical interventions before receiving a diagnosis of HLP and improving on HLP-directed therapy. This case series highlights the course of three female patients, referred to a single tertiary institution between 2018 and 2022, who were initially misdiagnosed with cSCC before receiving a diagnosis of HLP. We have emphasized the clinical and histopathological distinguishing features between HLP and cSCC, the pathogenesis of HLP, and current and new HLP-directed therapy. We hope that this case series serves as a reminder to dermatologists, dermatologic surgeons, and dermatopathologists to be aware of this diagnostic challenge.

UNASSIGNED: The haemoglobin, albumin, lymphocyte, and platelet (HALP) score, a convenient and composite laboratory biomarker, can reflect inflammation and systemic nutritional status. This study was performed to investigate the effect of the HALP score on the prognosis of patients with IgA nephropathy (IgAN).
UNASSIGNED: This is a retrospective single centre study that enrolled 895 biopsy-confirmed IgAN patients from June 2019 to June 2022 who were followed for more than 1 year. Kaplan-Meier curves and Cox regression analyses were performed to determine the relationship between HALP and adverse outcomes. The restricted cubic splines was used to identify the possible associations. The optimal cut-off value of HALP for renal poor outcome was identified by the area under the receiver operating characteristic curve (AUC).
UNASSIGNED: A total of 895 patients finally participated in the study and were divided into three groups (tertial 1-3) according to the baseline HALP score. More severe clinicopathologic features were observed in the lower HALP group, and Kaplan-Meier analysis showed patients in tertial 1 had a higher risk of kidney failure than the other groups (log-rank=11.02, P= 0.004). Multivariate Cox regression revealed that HALP score was an independent risk factor for renal prognosis in IgAN (adjusted HR: 0.967, 95% CI: 0.945-0.990, P = 0.006). The results of subgroup analysis suggested that HALP was more important in patients under the age of 50, BMI ≤ 23.9 and eGFR ≤ 90 mL/min/1.73 m2. The best cut-off HALP for renal survival was 38.83, sensitivity 72.1%, and specificity 55.9% (AUC: 0.662). Patients were further grouped according to HALP cut-off values and propensity matched. Multivariate Cox regression analysis revealed that HALP remained an independent predictor of IgAN in the matched cohort (HR 0.222, CI: 0.084-0.588, P=0.002).
UNASSIGNED: HALP is a novel and potent composite parameter to predict kidney outcome in patients with IgAN.

BACKGROUND: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease characterized by hyperphosphorylated tau (p-tau) accumulation. The clinical features associated with CTE pathology are unclear. In brain donors with autopsy-confirmed CTE, we investigated the association of CTE p-tau pathology density and location with cognitive, functional, and neuropsychiatric symptoms.
METHODS: In 364 brain donors with autopsy confirmed CTE, semi-quantitative p-tau severity (range: 0-3) was assessed in 10 cortical and subcortical regions. We summed ratings across regions to form a p-tau severity global composite (range: 0-30). Informants completed standardized scales of cognition (Cognitive Difficulties Scale, CDS; BRIEF-A Metacognition Index, MI), activities of daily living (Functional Activities Questionnaire), neurobehavioral dysregulation (BRIEF-A Behavioral Regulation Index, BRI; Barratt Impulsiveness Scale, BIS-11), aggression (Brown-Goodwin Aggression Scale), depression (Geriatric Depression Scale-15, GDS-15), and apathy (Apathy Evaluation Scale, AES). Ordinary least squares regression models examined associations between global and regional p-tau severity (separate models for each region) with each clinical scale, adjusting for age at death, racial identity, education level, and history of hypertension, obstructive sleep apnea, and substance use treatment. Ridge regression models that incorporated p-tau severity across all regions in the same model assessed which regions showed independent effects.
RESULTS: The sample was predominantly American football players (333; 91.2%); 140 (38.5%) had low CTE and 224 (61.5%) had high CTE. Global p-tau severity was associated with higher (i.e., worse) scores on the cognitive and functional scales: MI ([Formula: see text] standardized = 0.02, 95%CI = 0.01-0.04), CDS ([Formula: see text] standardized = 0.02, 95%CI = 0.01-0.04), and FAQ ([Formula: see text] standardized = 0.03, 95%CI = 0.01-0.04). After false-discovery rate correction, p-tau severity in the frontal, inferior parietal, and superior temporal cortex, and the amygdala was associated with higher CDS ([Formula: see text] sstandardized = 0.17-0.29, ps < 0.01) and FAQ ([Formula: see text] sstandardized = 0.21-0.26, ps < 0.01); frontal and inferior parietal cortex was associated with higher MI ([Formula: see text] sstandardized = 0.21-0.29, ps < 0.05); frontal cortex was associated with higher BRI ([Formula: see text] standardized = 0.21, p < 0.01). Regions with effects independent of other regions included frontal cortex (CDS, MI, FAQ, BRI), inferior parietal cortex (CDS) and amygdala (FAQ). P-tau explained 13-49% of variance in cognitive and functional scales and 6-14% of variance in neuropsychiatric scales.
CONCLUSIONS: Accumulation of p-tau aggregates, especially in the frontal cortex, are associated with cognitive, functional, and certain neurobehavioral symptoms in CTE.

Introduction Phyllodes tumor (PT) is an uncommon fibroepithelial neoplasm of the breast. It is a biphasic tumor with stromal and epithelial components, with a tendency to recur. Because of its wide range of disease manifestations, it has been subclassified into three categories, i.e., benign, borderline, and malignant, based on several histological parameters. This study was conducted to evaluate the clinicopathological features associated with malignancy in breast PTs. Methods We conducted a retrospective study at the Department of Histopathology at Liaquat National Hospital, Karachi, Pakistan. A total of 146 biopsy-proven cases of PTs were enrolled in the study. Clinical data were obtained from the clinical referral forms. Specimens were obtained from either lumpectomy or simple mastectomy. The specimens obtained were received at the laboratory where after gross examination, paraffin-embedded tissue blocks were prepared, which were sectioned, stained, and studied by a senior histopathologist. Pathological features, such as mitotic count, necrosis, stromal atypia, stromal overgrowth, and heterologous elements, were observed. Based on these features, the PTs were classified into benign, borderline, and malignant tumors. Results The mean age of the PTs in our setup was 40.65 ± 12.17 years with a mean size of 9.40 ± 6.49 cm. Malignant PT was found to be the most prevalent in our population, accounting for 63 (43.2%) cases, followed by borderline (51, 34.9%) and benign (32, 21.9%). A significant association was found between the tumor subtype and patient age, i.e., patients diagnosed with malignant and borderline PTs were found to be of older age (mean 42.82 ± 12.94 and 42.05 ± 11.31 years, respectively) than those diagnosed with benign PTs (mean age 34.12 ± 9.75 years). Moreover, malignant PTs were associated with larger tumor size (mean 11.46 ± 6.08) compared with the other two subtypes. Conclusion We found a significant association among patient age, tumor size, and PT subtype. Therefore, apart from the usual histological parameters, patient age and tumor size are important parameters for predicting the behavior of breast PT and should be considered for management.

Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target. Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis, there is considerable heterogeneity, including clinical presentation, progression, and the underlying triggers for disease initiation. Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations, it has become apparent that overt disease is preceded by a prodromal phase, possibly in years, where compensatory mechanisms delay symptom onset. Since 85-90% of amyotrophic lateral sclerosis is sporadic, there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for regeneration. Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease. Skeletal muscle, including the neuromuscular junction, manifests abnormalities at the earliest stages of the disease, before motor neuron loss, making it a promising source for identifying biomarkers of the prodromal phase. The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time. The advent of \"omics\" technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle, ranging from coding and non-coding RNAs to proteins and metabolites. This technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms. A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of disease. There are two major goals of this review. The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity, evidence of a similar dysregulation in the SOD1G93A mouse during presymptomatic stages, and evidence of progressive change during disease progression. The second goal is to review the molecular pathways these biomarkers reflect and their potential role in mitigating or promoting disease progression, and as such, their potential as therapeutic targets in amyotrophic lateral sclerosis.

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BACKGROUND: Despite the large number of articles published on skin lesions related to COVID-19, clinicopathological correlation has not been performed consistently and immunohistochemistry to demonstrate spike 3 protein expression has not been validated through RT-PCR.
METHODS: We compiled 69 cases of patients with confirmed COVID-19, where skin lesions were clinically and histopathologically studied. Immunohistochemistry (IHC) and RT-PCR was performed in skin biopsies.
RESULTS: After a careful review of the cases, 15 were found to be dermatosis not related to COVID-19, while the rest of the lesions could be classified according to their clinical characteristics as vesicular (4), maculopapular eruptions (41), urticariform (9), livedo and necrosis (10) and pernio-like (5). Although histopathological features were similar to previously reported results, we found two previously unreported findings, maculopapular eruptions with squamous eccrine syringometaplasia and neutrophilic epitheliotropism. IHC showed in some cases endothelial and epidermal staining but RT-PCR was negative in all the tested cases. Thus, direct viral involvement could not be demonstrated.
CONCLUSIONS: Despite presenting the largest series of confirmed COVID-19 patients with histopathologically studied skin manifestations, direct viral involvement was difficult to establish. Vasculopathic and urticariform lesions seem to be those more clearly related to the viral infection, despite IHC or RT-PCR negative results failed to demonstrate viral presence. These findings, as in other dermatological areas, highlight the need of a clinico-pathological correlation to increase knowledge about viral involvement in COVID-19 skin-related lesions.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect any part of the neuraxis. Many neurological conditions have been attributed to be caused by SARS-CoV-2, namely encephalopathy (acute necrotizing encephalopathy and encephalopathy with reversible splenial lesions), seizures, stroke, cranial nerve palsies, meningoencephalitis, acute disseminated encephalomyelitis (ADEM), transverse myelitis (long and short segment), Guillain-Barré syndrome (GBS) and its variants, polyneuritis cranialis, optic neuritis (ON), plexopathy, myasthenia gravis (MG), and myositis. The pathophysiology differs depending on the time frame of presentation. In patients with concomitant pulmonary disease, for instance, acute neurological illness appears to be caused by endotheliopathy and cytokine storm. Autoimmunity and molecular mimicry are causative for post-coronavirus disease 2019 (COVID-19)-sequelae. It has not yet been shown that the virus can penetrate the central nervous system (CNS) directly. This review aims to describe the disease and root pathogenic cause of the various neurological manifestations of COVID-19. We searched Pubmed/Medline and Google Scholar using the keywords \"SARS-CoV-2\" and \"neurological illness\" for articles published between January 2020 and November 2022. Then, we used the SWIFT-Review (Sciome LLC, North Carolina, United States), a text-mining workbench for systematic review, to classify the 1383 articles into MeSH hierarchical tree codes for articles on various parts of the nervous system, such as the CNS, peripheral nervous system, autonomic nervous system, neuromuscular junction, sensory system, and musculoskeletal system. Finally, we reviewed 152 articles in full text. SARS-CoV-2 RNA has been found in multiple brain areas without any histopathological changes. Despite the absence of in vivo virions or virus-infected cells, CNS inflammation has been reported, especially in the olfactory bulb and brain stem. SARS-CoV-2 genomes and proteins have been found in affected individuals\' brain tissues, but corresponding neuropathologic changes are seldom found in these cases. Additionally, viral RNA can rarely be identified in neurological patients\' CSF post hoc SARS-CoV-2 infection. Most patients with neurological symptoms do not have active viral replication in the nervous system and infrequently have typical clinical and laboratory characteristics of viral CNS infections. Endotheliopathy and the systemic inflammatory response to SARS-CoV-2 infection play a crucial role in developing neuro-COVID-19, with proinflammatory cytokine release mediating both pathological pathways. The systemic inflammatory mediators likely activate astrocytes and microglia across the blood-brain barrier, indirectly affecting CNS-specific immune activation and tissue injury. The management differs according to co-morbidities and the neurological disorder.

Following the publication of this paper, it was drawn to the Editors\' attention by a concerned reader that certain of the tumor images shown in Fig. 4G and H were strikingly similar to tumor images (albeit oriented differently) which had previously appeared in Fig. 8A in another article published in the journal International Journal of Oncology [Tang B, Li Y, Yuan S, Tomlinson S and He S: Upregulation of the δ opioid receptor in liver cancer promotes liver cancer progression both in vitro and in vivo. Int J Oncol 43: 1281‑1290, 2013], indicating that results which were purported to have been obtained under different experimental conditions had been derived from the same original source. In view of the fact that these data had already appeared in another publication prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 41: 43‑56, 2019; DOI: 10.3892/or.2018.6825].