A novel method to assess copy number variations in melanocytic neoplasms: Droplet digital PCR for precise quantitation of MYC and MYB genes.

INTRODUCTION: While most melanocytic neoplasms can be classified as either benign or malignant by histopathology alone, ancillary molecular diagnostic tests can be necessary to establish the correct diagnosis in challenging cases. Currently, the detection of copy number variations (CNVs) by fluorescence in situ hybridization and chromosomal microarray (CMA) are the most popular methods, but remain expensive and inaccessible. We aim to develop a relatively inexpensive, fast, and accessible molecular assay to detect CNVs relevant to melanoma using droplet digital polymerase chain reaction (ddPCR) technology. METHODS: In this proof-of-concept study, we evaluated CNVs in MYC and MYB genes from 73 cases of benign nevi, borderline melanocytic lesions, and primary and metastatic melanoma at our institution from 2015 to 2022. A multiplexed ddPCR assay and CMA were performed on each sample, and the results were compared. RESULTS: Concordance analysis of ddPCR with CMA for quantification of MYC and MYB CNVs revealed a sensitivity and specificity of 89% and 86% for MYC and 83% and 74% for MYB, respectively. CONCLUSION: We demonstrate the first use of a multiplexed ddPCR assay to identify CNVs in melanocytic neoplasms. With further improvement and validation, ddPCR may represent a low-cost and rapid tool to aid in the diagnosis of histopathologically ambiguous melanocytic tumors.

Anti-PL-7, anti-Ro/SSA, anti-Mi-2, and anti-TIF1-γ correlate with specific patterns of histopathologic features in dermatomyositis: An analysis of 39 skin biopsy specimens from 25 patients.

BACKGROUND: In dermatomyositis (DM), myositis-specific and myositis-associated antibodies have been correlated with clinical features. It is unknown if histopathologic findings in lesional skin biopsies correlate with serologic subtypes of DM. METHODS: A retrospective chart review of patients with DM was performed. Patients with myositis antibodies and DM lesional skin biopsies were included in the study. Skin biopsies were reviewed by blinded dermatopathologists for 20 histopathologic features. RESULTS: There was a statistically significant (p < 0.05) association between anti-PL-7 serology and decreased degree of vacuolar degeneration, necrotic keratinocytes, and thickening of the epidermal basement membrane. Anti-aminoacyl tRNA synthetase (anti-ARS) antibodies had the same significant negative association with degree of vacuolar degeneration, necrotic keratinocytes, and thickening of the epidermal basement membrane. A similar pattern was seen with an anti-cytoplasmic serology; where there was a significant association with an increased degree of vacuolar degeneration and necrotic keratinocytes, and a nonsignificant trend of minimally thickened epidermal basement membrane. There was a statistically significant association between anti-Ro/SSA serology and increased degree of vacuolar degeneration. Anti-TIF1-γ serology was significantly associated with the increased presence of necrotic keratinocytes and pigment incontinence, and displayed a pattern of increased neutrophils. There was a significant association between anti-Mi-2 antibodies and pigment incontinence, as well as between myositis-specific antibodies and pigment incontinence. A statistically significant positive association was found between nuclear antibodies and degree of vacuolar degeneration, thickened epidermal basement membrane, pigment incontinence, and epidermal atrophy. CONCLUSION: In patients with DM, some specific serotypes, including anti-PL-7, anti-Ro/SSA, anti-Mi-2, and anti-TIF1-γ, may have characteristic histopathologic features.

Unusual presentations of chronic graft versus host disease.

Skin is commonly affected by graft versus host disease (GVHD), a complication of bone marrow transplantation (BMT). One-third of hematopoietic cell transplantation recipients develop acute eruption classically described as folliculocentric, maculopapular, or morbilliform, in contrast to the more common chronic presentations of sclerotic, poikilodermic, or lichenoid dermatitides. With the wider use of non-myeloablative (reduced-intensity) transplant therapy, various atypical presentations can occur, representing a diagnostic challenge. Herein, we report an unusual case of chronic GVHD manifested by two distinct clinical and histopathological features lacking the classical presentation. Five months after her BMT, the patient presented with a papulosquamous eruption on her neck, trunk, and arms showing a psoriasiform histopathological pattern of chronic GVHD. She also demonstrated multiple small flesh-colored papules on her distal extremities showing a solitary syringotropic pattern of GVHD, demonstrated by interface dermatitis involving the superficial eccrine duct, as the only diagnostic histopathological feature of GVHD. This report, with review of literature, highlights the uncommon psoriasiform GVHD and the novel description of isolated syringotropic chronic GVHD.

Identifying global research trends on inflammation associated with traumatic brain injury by bibliometric and visualized analysis.

Background: Traumatic brain injury (TBI) is a catastrophic disease involving complex inflammatory processes. This study aimed to quantitatively analyze and visualize the global research trends on inflammation associated with TBI. Methods: All publications concerning TBI and inflammation published from 2007 to 2021 were retrieved from the Web of Science Core Collection database. Key visualization and statistical analysis were calculated and evaluated using VOSviewer, CiteSpace, R package "bibliometrix," and an online bibliometric analysis platform. Results: From 2007 to 2021, 15,138 authors from 2860 institutions in 77 countries/regions published 3154 articles on inflammation associated with TBI in 786 academic journals. The research output has significantly increased over the years despite a minor fluctuation. Among the countries, the United States showed the highest output (43.50%) with the most total citations (62,791). The author with the most published articles was Cox CS (30 articles with h-index = 20), and the most popular journal in the field was the Journal of Neurotrauma (190 papers, cited 6433 times). The high-frequency keywords were "post-traumatic brain injury," "brain edema," and "glial activation." Moreover, high-frequency keywords analysis indicated that various inflammatory cells contributed to neuroinflammation, neuroprotection, and oxidative stress after TBI. Conclusion: This study revealed the research trends, hotspots, and emerging topics in inflammation associated with TBI by quantitative and visualized analysis. The current research focuses on the crosstalk between various inflammatory cells and the brain and the associated mechanisms. This study presents the research landscape and inspires future research on inflammation associated with TBI.

Oligometastatic Melanoma Treated by Metastasectomy in Combination with Immune Checkpoint and BRAF Inhibitors: A Case Series.

BACKGROUND Early therapies for metastatic melanoma improved patient quality of life; however, median survival remained unaffected. Studies are showing that surgical excision with the combination of immune checkpoint inhibitor (ICI) therapy has better outcomes than systemic therapy alone. This single-center case series describes 7 patients with oligometastatic melanoma treated by metastasectomy in combination with ICI and BRAF inhibitors. CASE REPORT One female and 6 male patients are included in our study, with ages ranging from 34 to 82 years. Oligometastatic melanoma is defined was having no more than 5 metastatic regions. Each patient had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients received either ICI therapy with ipilimumab, nivolumab, and/or pembrolizumab, or targeted therapy with encorafenib and binimetinib, or a combination. Patients underwent metastasectomies with curative intent. The main outcome and measurements obtained were the duration of disease-free survival, based on radiographic evidence. The range of disease-free survival in our population was 13 to 67 months, with the lower end limited by patient death and the upper limit being the present day. CONCLUSIONS This case series reiterates survival benefit for patients who received metastasectomy after exhibiting good response to ICI therapy. ICI and/or BRAF inhibitor therapy combined with metastasectomy provides a possible curative option for patients who may have previously been relegated to palliative-focused care. By using a multimodal approach with oncologists and surgeons, we can challenge our understanding of what constitutes a resectable cancer.

PRAME expression in cutaneous melanoma does not correlate with disease-specific survival.

BACKGROUND: Immunohistochemistry-based protein biomarkers can provide useful prognostic information in cutaneous melanoma. The independent prognostic value of Ki-67 has been studied with variable results. PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemistry is a useful new ancillary tool for distinguishing cutaneous nevi from melanoma; however, its prognostic value has not been well studied. We evaluated PRAME as a prognostic marker in cutaneous melanoma, compared to Ki-67. METHODS: We analyzed the immunohistochemical expression of PRAME and Ki-67 in 165 melanocytic lesions, including 92 primary melanomas, 19 metastatic melanomas, and 54 melanocytic nevi using tissue microarrays. PRAME immunostaining was scored based on the percentage of positive nuclei: 0 <1%, 1+ 1%-25%, 2+ 26%-50%, 3+ 51%-75%, and 4+ >75%. The percentage of Ki-67-positive tumor nuclei was used to calculate the proliferation index. RESULTS: PRAME and Ki-67 both showed significantly increased expression in melanomas compared to nevi (p < 0.0001 and p < 0.001, respectively). There was no significant difference in PRAME expression in primary versus metastatic melanomas. By contrast, the Ki-67 proliferation index was higher in metastatic melanoma than in primary melanoma (p = 0.013). Increased Ki-67 index correlated with ulceration (p < 0.001), increased Breslow depth (p = 0.001), and higher mitotic rate (p < 0.0001), whereas increased PRAME expression correlated with higher mitotic rate (p = 0.047) and Ki-67 index (p = 0.007). Increased Ki-67 index correlated with worse disease-specific survival in patients with primary melanoma (p < 0.001), but PRAME expression did not show prognostic significance in disease-specific survival (p = 0.63). In a multivariable analysis of patients with primary melanoma, tumor Breslow depth, ulceration, mitotic rate, and Ki-67 index were each independent predictors of disease-specific survival (p = 0.006, 0.02, 0.001, and 0.04, respectively); however, PRAME expression was not predictive of disease-specific survival (p = 0.64). CONCLUSION: Ki-67 is an independent prognostic marker; although increased PRAME expression correlates with the Ki-67 proliferation index and mitotic rate, PRAME is not an independent prognostic marker for cutaneous melanoma. PRAME and Ki-67 are useful ancillary tools for distinguishing benign from malignant melanocytic lesions.

An improved ant colony optimization for solving the flexible job shop scheduling problem with multiple time constraints.

The flexible job shop scheduling problem is important in many research fields such as production management and combinatorial optimization, and it contains sub-problems of machine assignment and operation sequencing. In this paper, we study a many-objective FJSP (MaOFJSP) with multiple time constraints on setup time, transportation time and delivery time, with the objective of minimizing the maximum completion time, the total workload, the workload of critical machine and penalties of earliness/tardiness. Based on the given problem, an improved ant colony optimization is proposed to solve the problem. A distributed coding approach is proposed by the problem features. Three initialization methods are proposed to improve the quality and diversity of the initial solutions. The front end of the algorithm is designed to iteratively update the machine assignment to search for different neighborhoods. Then the improved ant colony optimization is used for local search of the neighborhood. For the searched scheduling set the entropy weight method and non-dominated sorting are used for filtering. Then mutation and closeness operations are proposed to improve the diversity of the solutions. The algorithm was evaluated through experiments based on 28 benchmark instances. The experimental results show that the algorithm can effectively solve the MaOFJSP problem.

Adnexotropic and granulomatous mycosis fungoides following TNF-α inhibitor treatment.

Recent publications have documented an increased prevalence of cutaneous T-cell lymphoma (CTCL) in patients undergoing tumor necrosis factor alpha (TNF-α) inhibitor therapy. Herein, we present an uncommon manifestation of mycosis fungoides (MF) with unique pathological findings after the initiation of adalimumab therapy for the treatment of psoriasis. One year after starting treatment, the patient noticed a slowly growing, eroded plaque on the left cheek, the biopsy of which demonstrated mixed granulomatous and adnexotropic lymphocytic infiltrate with features characteristics of MF. In the following months, the patient developed pink- and violet-colored scaly plaques on the right posterior upper arm and right medial upper arm. Biopsy of these plaques also revealed findings compatible with MF. T-cell receptor (TCR) clonality studies by PCR revealed identical T-cell clones in the samples obtained from the cheek, right posterior upper arm, and right medial upper arm. TCR clonality studies of a long-standing psoriatic plaque on the right thigh failed to reveal similar T-cell clones. Blurring of histopathologic presentation by TNF-α inhibitors could greatly complicate the identification of MF subtypes. Providers treating patients with TNF-α inhibitors must be aware of the risk of cutaneous lymphoma development and the potential deviations from their expected presentations. In patients without an initial biopsy, the possibility of pre-existing CTCL with psoriasiform presentation should be considered.

Cutaneous myoepithelioma with EWSR1 gene rearrangement and its differentials: A diagnostic challenge.

Cutaneous myoepithelioma is a rare benign soft tissue neoplasm of myoepithelial cells involving the skin and subcutis. These tumors can be diagnostically challenging. The plasticity of myoepithelial cells leads to wide variability in the cytomorphology, immunophenotype, and genetic features of myoepithelioma. Their protean presentations may mimic malignant neoplasms. Therefore, distinction from malignancy is essential. Herein, we report a case of cutaneous myoepithelioma presenting similarly to Ewing sarcoma, with small round blue cells and an EWSR1 rearrangement. Our case highlights the important morphologic, immunohistochemical, and cytogenetic features of this benign basaloid cutaneous tumor.

Histiocytoid melanoma: Diagnostic pitfall and mimicker of non-Langerhans cell histiocytoses including reticulohistiocytoma.

Melanoma and benign histiocytic proliferations can sometimes show considerable clinical and histopathologic overlap. Recently, cases of melanomas resembling xanthogranuloma and Rosai-Dorfman disease have been reported, and herein we report a case of melanoma closely mimicking reticulohistiocytoma. An 84-year-old man presented with a 1 cm purple-red nodule on his arm concerning for squamous cell carcinoma. While the biopsy findings resembled reticulohistiocytoma, the clinical context and regression changes at the lesion perimeter raised stronger concern for melanoma, which was confirmed with immunohistochemistry. We review prior rare reports of melanomas resembling non-Langerhans cell histiocytic proliferations and summarize helpful clinical and histopathologic clues to avoid a diagnostic pitfall when confronted with this unusual quandary.

Radiomics features from perihematomal edema for prediction of prognosis in the patients with basal ganglia hemorrhage.

Objective: We developed and validated a clinical-radiomics nomogram to predict the prognosis of basal ganglia hemorrhage patients. Methods: Retrospective analyses were conducted in 197 patients with basal ganglia hemorrhage (training cohort: n = 136, test cohort: n = 61) who were admitted to The First Affiliated Hospital of Shandong First Medical University (Shandong Provincial Qianfoshan Hospital) and underwent computed tomography (CT) scan. According to different prognoses, patients with basal ganglia hemorrhage were divided into two groups. Independent clinical risk factors were derived with univariate and multivariate regression analysis. Radiomics signatures were obtained using least absolute shrinkage and selection operator. A radiomics score (Rad-score) was generated by 12 radiomics signatures of perihematomal edema (PHE) from CT images that were correlated with the prognosis of basal ganglia hemorrhage patients. A clinical-radiomics nomogram was conducted by combing the Rad-score and clinical risk factors using logistic regression analysis. The prediction performance of the nomogram was tested in the training cohort and verified in the test cohort. Results: The clinical model conducted by four clinical risk factors and 12 radiomcis features were used to establish the Rad-score. The clinical-radiomics nomogram outperformed the clinical model in the training cohort [area under the curve (AUC), 0.92 vs. 0.85] and the test cohort (AUC, 0.91 vs 0.85). The clinical-radiomics nomogram showed good calibration and clinical benefit in both the training and test cohorts. Conclusion: Radiomics features of PHE in patients with basal ganglia hemorrhage could contribute to the outcome prediction. The clinical-radiomics nomogram may help first-line clinicians to make individual clinical treatment decisions for patients with basal ganglia hemorrhage.

Molecular analysis of NUT-positive poromas and porocarcinomas identifies novel break points of YAP1::NUTM1 fusions.

BACKGROUND: Poromas, and their malignant counterparts, porocarcinomas, harbor recurrent translocations involving YAP1-MAML2, YAP1-NUTM1, and infrequently WWTR1-NUTM1; YAP1-NUTM1 being the most common in porocarcinomas. NUT immunohistochemistry (IHC) can be used to identify NUTM1-translocated tumors. This study sought to investigate potential novel NUTM1-fusion partners among NUT IHC-positive poromas and porocarcinomas. METHODS: Thirteen NUT IHC-positive poroid tumors (four poromas and nine porocarcinomas) were identified within a multi-institutional international cohort. Next-generation sequencing (NGS) assessed for NUTM1 fusion partners. RESULTS: NGS detected a NUTM1 fusion in 12 of 13 cases: YAP1-NUTM1 (11/12 cases) and WWTR1-NUTM1 (1/12 cases). Two of the cases (2/12) with NUTM1 fusion were not called by the NGS algorithm but had at least one read-spanning YAP1-NUTM1 break point upon manual review. A NUTM1 fusion was not identified in one case; however, the sample had low RNA quality. The following fusion events were identified: YAP1 exon 4::NUTM1 exon 3 in six cases, YAP1 exon 6::NUTM1 exon 2 in one case, YAP1 exon 3::NUTM1 exon 3 in three cases, WWTR1 exon 3::NUTM1 exon 3 in one case, and YAP1 exon 8::NUTM1 exon 3 fusion in one case. CONCLUSION: While no novel NUTM1 fusion partners were identified within our cohort, 12 of 13 cases had discoverable NUTM1 fusions; YAP1-NUTM1 fusion was detected in 11 cases (92%) and WWTR1-NUTM1 in 1 case (8%). These data corroborate findings from other recent investigations and further substantiate the utility of NUT IHC in diagnosing a subset of poroid neoplasms. In addition, two of our cases harbored fusions of YAP1 exon 6 to NUTM1 exon 3 and YAP1 exon 8 to NUTM1 exon 2, which have not been reported before in poroid neoplasms and indicate novel break points of YAP1.

PRAME expression in melanocytic lesions of the nail.

BACKGROUND: Subungual melanoma can be diagnostically challenging. We evaluated the potential of PReferentially expressed Antigen for MElanoma (PRAME) immunoreactivity for differentiating benign from malignant nail melanocytic lesions. METHODS: Sixty cases were identified (10 invasive melanomas, 8 melanomas in situ, 14 nevi, 12 cases of lentigo, and 16 of melanocytic activation). Percentage of PRAME-positive melanocytes was evaluated as follows: 0 no staining, 1+ 1%-25%, 2+ 26%-50%, 3+ 51%-75%, and 4+ >75%. A combined score of both percentage and intensity was also evaluated. RESULTS: The difference in PRAME expression between malignant and benign lesions was statistically significant (p < 0.0001). The degree of PRAME expression significantly correlated with patients' age and clinical size. When based on percentage score, 61.1% of melanomas showed a 4+ score, 16.7% showed a 3+ score, 11.1% showed a 1+ score, and 11.1% was negative; 69.0% of the benign lesions was negative, 23.8% showed a 1+ score, 4.8% showed a 2+ score, and 2.4% showed a 4+ score. When the cutoff value for malignancy decreased from 4+ to 3+, the sensitivity increased from 61.1% to 77.8%, while specificity remained 97.6%. Combined score results were similar. CONCLUSIONS: PRAME is a relatively sensitive and highly specific marker in differentiating benign from malignant nail melanocytic lesions. However, correlation with morphology is imperative.

Resident memory CD8+ T cells in regional lymph nodes mediate immunity to metastatic melanoma.

The nature of the anti-tumor immune response changes as primary tumors progress and metastasize. We investigated the role of resident memory (Trm) and circulating memory (Tcirm) cells in anti-tumor responses at metastatic locations using a mouse model of melanoma-associated vitiligo. We found that the transcriptional characteristics of tumor-specific CD8+ T cells were defined by the tissue of occupancy. Parabiosis revealed that tumor-specific Trm and Tcirm compartments persisted throughout visceral organs, but Trm cells dominated lymph nodes (LNs). Single-cell RNA-sequencing profiles of Trm cells in LN and skin were distinct, and T cell clonotypes that occupied both tissues were overwhelmingly maintained as Trm in LNs. Whereas Tcirm cells prevented melanoma growth in the lungs, Trm afforded long-lived protection against melanoma seeding in LNs. Expanded Trm populations were also present in melanoma-involved LNs from patients, and their transcriptional signature predicted better survival. Thus, tumor-specific Trm cells persist in LNs, restricting metastatic cancer.

Eggerthella lenta Bacteremia in a Middle-Aged Healthy Man with Acute Hepatic Abscess: Case Report and Literature Review, 1970-2020.

Eggerthella lenta (E. lenta) is a rare but significant human emerging pathogen. Infections caused by it are rare and little-known, both on clinical and therapeutical aspects, in spite of new emergence of bacteria isolation and identification techniques. In this article, we report a case involving a previously healthy 52-year-old man suffering from a newly diagnosed hepatic abscess who developed E. lenta bacteremia, which was treated successfully using empirical therapy with ertapenem and teicoplanin. To the best of our knowledge, this is the first documented report of E. lenta bacteremia related specifically to liver abscess. Cases related to this bacterial species are infrequent and sporadic; thus, we reviewed English literature on E. lenta infection in PubMed/MEDLINE in the last 50 years. A total of 31 sporadic cases were identified. The majority of patients were male (71%), had an average age of 54.3 years and presented predisposing conditions, such as digestive system trouble (45.2%), immunocompromised state (25.8%) or risk factors (22.6%). Two of the cases had more than one predisposing factors. Fever was common (93.5%). Average days to diagnosis of them were 6.8 days. MALDI-TOF MS is emerging as a fast and useful tool in the identification of it. Teicoplanin, vancomycin, amoxicillin-clavulanate, metronidazole, clindamycin, cefoxitin, chloramphenicol, and carbapenems appear to be the most used antibiotic treatment options. The purpose of this review is to increase awareness about the clinical infections caused by E. lenta.

[Short-segment pedicle screw fixation combined with vertebroplasty for the treatment of Kümmell disease with kyphosis].

OBJECTIVE: To explore the clinical effects of posterior short-segment pedicle screw internal fixation combined with vertebroplasty for the treatment of Kümmell disease with kyphosis. METHODS: Twenty-four patients with Kümmell disease complicated with kyphosis treated by posterior short-segment pedicle screw internal fixation combined with vertebroplasty from January 2016 to December 2018 were retrospectively analyzed, including 6 males and 18 females, aged 63 to 85 (73.1±6.5) years old. The clinical effect was evaluate by visual analogue scale (VAS), Oswestry Disability Index (ODI), the anterior height of injured vertebral body, and the sagittal Cobb angle of the affected segment beforeoperation, at 3 days and final follow up after operation. And the surgical complications were observed. RESULTS: All 24 patients were followed up from 12 to 24 months with an average of (15.5±3.2) months. The VAS score was decreased from 5.21±1.06 preoperatively to 2.38±0.58 at 3 days postoperatively and 1.71±0.75 at final follow-up;ODI was decreased from (50.4±13.5)% preoperatively to (20.9±8.0)% at 3 days postoperatively and (16.7±9.6)% at final follow-up;the anterior height of injured vertebral body was restored from (8.0±4.2) mm before surgery to (18.1±5.0) mm at 3 days after surgery and (16.8±5.1) mm at final follow up;the sagittal Cobb angle of affected segment was decreased from (19.5±6.3)° preoperatively to (7.6±2.1)° at 3 days after surgery and(8.4±1.7)° at final follow-up. VAS, ODI, anterior height of injured vertebral body, and sagittal Cobb angle of affected segment were significantly improved at 3 days after operation and at final follow-up (P<0.05). Two patients had complications, including asymptomaticcement leakage in 1 patient and superficial wound infection in 1 patient. CONCLUSION: Posterior short-segment pedicle screw internal fixation combined with vertebroplasty for the treatment of Kümmell disease with kyphosis has relatively small surgical trauma, excellent clinical results, good vertebral height recovery, satisfactory correction of kyphotic angle, and fewer complications, etc. It is a safe and effective surgical method to treat Kümmell disease with kyphosis.

Deep Herpes.

Herpes viruses are known for infecting epithelial cells and manifesting as vesicles. However, herpes viruses can also infect stromal cells. While established in the ocular setting, cutaneous stromal herpes (deep herpes) is previously unreported and may evade clinical and microscopic detection. We searched for skin biopsies with herpes stromal disease. Clinical information was retrieved via electronic medical records and pathology records system. Hematoxylin and eosin slides, immunohistochemical staining, and polymerase chain reaction detection of viral DNA was performed. We identified 12 specimens from 10 patients with cutaneous stromal herpes simplex virus 1/2 (n=7) or varicella-zoster virus infection (n=5). The most common site involved was the buttocks/perianal region (n=6). Ulceration was a frequent dermatologic finding (n=8). Pyoderma gangrenosum was clinically suspected in 6 specimens (50%). Eight patients (80%) were immunosuppressed. Biopsies frequently demonstrated a dense dermal mixed inflammatory infiltrate with subcutaneous extension and enlarged cells with viral cytopathic changes confirmed by herpes simplex virus 1/2 or varicella-zoster virus immunohistochemistry (n=10) or polymerase chain reaction (n=2). Most specimens (67%) lacked evidence of characteristic epidermal keratinocyte infection. This study presents the first known report of the ability of herpes virus to infect deep stromal cells of the dermis. We raise awareness of cutaneous stromal herpes in patients presenting with atypical clinical lesions, particularly while immunocompromised. Establishing the correct diagnosis is critical for initiating therapy.

Resident and circulating memory T cells persist for years in melanoma patients with durable responses to immunotherapy.

While T-cell responses to cancer immunotherapy have been avidly studied, long-lived memory has been poorly characterized. In a cohort of metastatic melanoma survivors with exceptional responses to immunotherapy, we probed memory CD8+ T-cell responses across tissues, and across several years. Single-cell RNA sequencing revealed three subsets of resident memory T (TRM) cells shared between tumors and distant vitiligo-affected skin. Paired T-cell receptor sequencing further identified clonotypes in tumors that co-existed as TRM in skin and as effector memory T (TEM) cells in blood. Clonotypes that dispersed throughout tumor, skin, and blood preferentially expressed a IFNG / TNF-high signature, which had a strong prognostic value for melanoma patients. Remarkably, clonotypes from tumors were found in patient skin and blood up to nine years later, with skin maintaining the most focused tumor-associated clonal repertoire. These studies reveal that cancer survivors can maintain durable memory as functional, broadly-distributed TRM and TEM compartments.

Comparison of adipophilin and recently introduced PReferentially expressed Antigen in MElanoma immunohistochemistry in the assessment of sebaceous neoplasms: A pilot study.

BACKGROUND: We and others have noticed consistent staining of sebaceous glands with PReferentially expressed Antigen in MElanoma (PRAME). We aimed to determine whether PRAME was as sensitive, specific, and interpretable as adipophilin for distinguishing sebaceous neoplasms (SNs) from other neoplasms. METHODS: Twenty SNs and 32 control cases were stained for PRAME and adipophilin. Extent of staining was scored as follows: 0, no staining; 1, <5% positivity; 2, 5% to 50% positivity; and 3, >50% positivity. Intensity was scored as negative, weak, moderate, or strong. A composite score was determined by adding the scores for extent and intensity. RESULTS: PRAME had positive composite scores in all 20 SNs in the more differentiated areas, whereas adipophilin had positive composite scores in 19/20 cases. PRAME showed positivity in the basaloid cells in 15/16 cases, whereas adipophilin was positive in 14. Among controls, PRAME and adipophilin had positive composite scores in 3/32 cases and 6/32 cases, respectively. CONCLUSIONS: PRAME and adipophilin are comparable in terms of distribution and intensity for staining sebocytes. In the basaloid cells, PRAME expression is often more diffuse and easier to detect than adipophilin. In comparing the SNs to the controls, PRAME was more sensitive and more specific than adipophilin. PRAME could be used as an additional marker of sebaceous differentiation in everyday practice.