Lichen Planus: What is New in Diagnosis and Treatment?

Lichen planus (LP), an idiopathic, multifaceted chronic inflammatory disease with a heterogeneous clinical presentation, affects approximately 0.5-1% of the population. The various clinical manifestations of LP fall into three broad categories, namely cutaneous, appendageal, and mucosal, with further subclassification depending on the morphology and distribution patterns of individual lesions. There is mounting evidence that LP has systemic associations, including autoimmune conditions, glucose intolerance, dyslipidemia, and cardiovascular disorders. Cutaneous hypertrophic and mucosal forms of LP are at a heightened risk for malignant transformation. Familiarity with these potential associations in conjunction with long-term follow-up and regular screening could lead to a timely diagnosis and management of concomitant conditions. In addition, the frequent quality of life (QoL) impairment in LP underscores the need for a comprehensive approach including psychological evaluation and support. Several treatment strategies have been attempted, though most of them have not been adopted in clinical practice because of suboptimal benefit-to-risk ratios or lack of evidence. More recent studies toward pathogenesis-driven treatments have identified Janus kinase inhibitors such as tofacitinib, phosphodiesterase-4 inhibitors such as apremilast, and biologics targeting the interleukin-23/interleukin-17 pathway as novel therapeutic options, resulting in a dramatic change of the treatment landscape of LP. This contemporary review focuses on the diagnosis and management of LP, and places emphasis on more recently described targeted treatment options.

Local Cutaneous Scrotal Involvement of Paratesticular Mesothelioma.

ABSTRACT: Paratesticular mesothelioma (malignant mesothelioma arising from the tunica vaginalis of the testis) represents a small proportion of mesothelial neoplasms, and cutaneous involvement by paratesticular mesothelioma is very rare. Cutaneous involvement can manifest as scrotal subcutaneous nodules from regional spread, distant metastasis, or direct extension through surgical scars. Mesothelioma has 3 histopathologic classifications that include epithelioid, biphasic, and sarcomatoid, which is rarely seen in paratesticular mesothelioma. Given the rarity of this condition, cutaneous mesothelioma may be misdiagnosed as histologic mimics, such as metastatic adenocarcinoma or adnexal neoplasms; thus, appropriate immunohistochemical workup and clinical correlation are required to make an accurate diagnosis. In this case, a 75-year-old man with a history of paratesticular mesothelioma, status postorchiectomy, presented with right-sided scrotal swelling, erythema, and subcutaneous nodules. These nodules were identified as local recurrence with cutaneous involvement by paratesticular mesothelioma on histopathologic examination. This case highlights the clinical and histopathologic features of this diagnosis and underscores the importance of dermatopathologists being aware of this condition to ensure accurate diagnosis.

Treatment of lichen sclerosus with hydroxychloroquine: a Mayo Clinic experience.

BACKGROUND: There is a dearth of studies investigating the efficacy of hydroxychloroquine in the treatment of either anogenital lichen sclerosus or extragenital lichen sclerosus, a condition that, if left untreated, could lead to a greater degree of scarring and malignant transformation. OBJECTIVE: This study aims to analyze the demographic characteristics, clinicopathological features, treatment response, and outcomes of patients diagnosed with either anogenital or extragenital lichen sclerosus who received hydroxychloroquine therapy. METHODS: A retrospective analysis was conducted involving 70 patients diagnosed with lichen sclerosus who underwent treatment with hydroxychloroquine at our institution between 2018 and 2023. RESULTS: Among the cohort, 67 patients were female, and 3 were male. Extragenital lichen sclerosus was diagnosed in 23 patients, with 16 exhibiting concomitant morphea overlap. Itching was the predominant clinical presentation (67%). A notable proportion of patients (36%) had a connective tissue disorder, prompting hydroxychloroquine therapy. Among the 30 patients treated solely for lichen sclerosus, 21 demonstrated response and 9 had no response. From a broader comparison of response to hydroxychloroquine, the overall anogenital response rate was 84.6% as opposed to 50% in extragenital lichen sclerosus. The median time to initial response was 4 months. Adverse effects, predominantly mild, were observed in 10 (14.3%) patients. LIMITATION: This study is constrained by its retrospective nature and reliance on data from a single center, resulting in a limited sample size. CONCLUSION: Hydroxychloroquine demonstrates promise as a therapeutic option for anogenital lichen sclerosus because of its favorable response rates and low incidence of adverse effects. However, further investigations, including larger-scale or prospective studies, are imperative to ascertain its definitive efficacy.

Therapeutic Targets in Advanced Penile Cancer: From Bench to Bedside.

Discovery of effective systemic therapies for patients with advanced penile cancer has been slow to occur. Comprehensive genomic profiling from several studies shed light on the molecular oncogenesis of penile squamous cell carcinoma (PSCC) and differences between HPV-related and unrelated tumors. While these two subsets of PSCC appear distinct in their biology, there are not yet specific treatment strategies recommended on that basis. Cell surface proteins have been identified that may potentially serve as drug targets for monoclonal antibodies or small molecule inhibitors. Here, we review some of the new biological insights regarding PSCC that could lead to improved therapies, as well as the related clinical trials recently completed or in progress. We conclude that antibody-drug conjugates are especially promising, as are the combinations of immune checkpoint inhibitors with other types of drugs.

High-risk human papilloma virus status & outcomes for penile squamous cell carcinoma: A single institution experience.

OBJECTIVES: There is a paucity of data on North American cohorts of patients with penile squamous cell carcinoma (pSCC). Herein, we aimed to assess the sensitivity of various modalities to identify human papillomavirus (HPV) status, determine the prevalence of high-risk HPV-positivity, and evaluate the prognostic impact of relevant clinicopathologic variables. METHODS: Patients with pSCC (n = 121) consecutively treated with partial/total penectomy (2000-2022) at a single institution were included. HPV status (based on immunohistochemistry [IHC], in situ hybridization [ISH], and panviral metagenomic sequencing [PMS]), histologic features, and outcomes were reviewed. Outcome events included death due to disease and progression. RESULTS: The majority of patients were white (105/121, 86.8%). Thirty-seven (30.6%) were high-risk HPV-positive, and morphologic evaluation had a sensitivity of 97.3% (95% confidence interval [CI], 86.2-99.5) for predicting high-risk HPV status compared to IHC/ISH/PMS. Disease progression was more common among high-risk HPV-negative compared to high-risk HPV-positive patients (HR 2.74, CI 1.12-8.23, P = 0.03). Moreover, among high-risk HPV-negative patients, those with moderate-poorly differentiated tumors had increased disease-specific mortality (32.6%, CI 17.1-48.1) compared to those with well-differentiated tumors (0%). Among high-risk HPV-positive patients, those with basaloid morphology had lower disease-specific mortality (0% vs 14.4%, CI 0.0-33.1). CONCLUSIONS: We demonstrate high-risk HPV-positivity in approximately one-third of patients with pSCC. Morphologic evaluation alone had a high sensitivity in correctly determining HPV status. Our results suggest that high-risk HPV status and morphologic features (differentiation in high-risk HPV-negative, and basaloid subtype in high-risk HPV-positive pSCC) may have prognostic value.

Comparison of a modified staging system with 8th edition AJCC criteria in a North American cohort of pT2/pT3 HPV-negative penile squamous cell carcinoma.

The staging for pT2/pT3 penile squamous cell carcinoma (pSCC) has undergone major changes. Some authors proposed criteria wherein the distinction between pT2/pT3 was made using the same histopathological variables that are currently utilized to differentiate pT1a/pT1b. In this single-institution, North American study, we focused on (HPV-negative) pT2/3 pSCCs (i.e., tumors invading corpus spongiosum/corpus cavernosum), and compared the prognostic ability of the following systems: (i) AJCC (8th edition) criteria; (ii) modified staging criteria proposed by Sali et al. (Am J Surg Pathol. 2020; 44:1112-7). In the proposed system, pT2 tumors were defined as those devoid of lymphovascular invasion (LVI) or perineural invasion (PNI), and were not poorly differentiated; whereas pT3 showed one or more of the following: LVI, PNI, and/or grade 3. 48 pT2/pT3 cases were included (AJCC, pT2: 27 and pT3: 21; Proposed, pT2: 22 and pT3: 26). The disease-free survival (DFS) and progression-free survival (PFS) did not differ between pT2 and pT3, following the current AJCC definitions (p = 0.19 and p = 0.10, respectively). When the pT2/3 stages were reconstructed using the modified criteria, however, a statistically significant difference was present in both DFS and PFS between pT2 and pT3 (p = 0.004 and p = 0.003, respectively). The proposed staging system has the potential to improve the prognostication of pT2/pT3 tumors in pSCC. Each of these histopathologic variables has been shown to have a significant association with outcomes in pSCC, which is an advantage. Further studies are needed to demonstrate the utility of this modified staging system in patient populations from other geographic regions.

NTRK3-Rearranged Prostatic Acinar Adenocarcinoma: Report of a Patient and Review of the Literature.

Molecular investigations have led to increased therapeutic options for prostatic adenocarcinoma. A single case report of a PRPSAP1::NTRK3 gene fusion occurring in prostate cancer was previously reported. A review of the literature revealed that NTRK gene rearrangements are exceedingly rare molecular events in prostate cancer. NTRK gene fusions can be oncogenic drivers or develop as resistance mechanisms. The tumor-agnostic approvals of TRK inhibitors by the FDA provide additional rationale for molecular investigations of aggressive prostatic adenocarcinomas. This may prove to be an additional therapeutic option for patients with aggressive prostatic carcinomas refractory to initial therapy. We report a case of an aggressive castrate-resistant prostatic adenocarcinoma with a BMP6::NTRK3 gene fusion.

Cutaneous Malignant Mixed Tumor With Pulmonary Metastasis: A Case Report and Literature Review.

BACKGROUND: Cutaneous malignant mixed tumor (MMT) is a rare sweat gland-derived tumor characterized by admixed malignant epithelial cells and chondromyxoid stroma. Approximately 50 cases have been described in the literature. Metastasis, which may occur in more than one-third of cases, is most common in the lung. METHODS: We summarized the clinicopathologic features of a patient with cutaneous MMT metastatic to the lungs. A literature review of similar cases was completed using Web of Science, Scopus, and PubMed databases. RESULTS: A woman in her 70s presented with an enlarging mass on her left eyebrow; histopathologic examination showed large islands of atypical cells with increased mitotic activity, admixed with necrosis on a background of fibrotic and chondromyxoid stroma. Multiple lung nodules were identified during follow-up. Examination of a pulmonary core needle biopsy specimen was consistent with metastatic cutaneous MMT. Literature review identified 10 cases published between 1980 and 2017. Most primary tumors were large (≥4 cm). Local recurrence was uncommon, and the lung was the only metastatic site in 5 cases. Histopathologically, metastatic tumors were described as more cellular, with diminished stromal tissue compared with the primary lesion. CONCLUSION: This is 1 of the 11 reports of cutaneous MMT with metastasis to the lungs found in the English-language literature published after 1980. Of note, most reports were published before 1990, making this case study one of the few contemporary descriptions of cutaneous MMT with pulmonary metastases. We think that the present case report will increase the awareness of this rare tumor.

Genomic attributes of prostate cancer across primary and metastatic noncastrate and castrate resistant disease states: a next generation sequencing study of 183 patients.

Primary prostatic adenocarcinoma (pPC) undergoes genomic evolution secondary to therapy-related selection pressures as it transitions to metastatic noncastrate (mNC-PC) and castrate resistant (mCR-PC) disease. Next generation sequencing results were evaluated for pPC (n = 97), locally advanced disease (involving urinary bladder/rectum, n = 12), mNC-PC (n = 21), and mCR-PC (n = 54). We identified enrichment of TP53 alterations in high-grade pPC, TP53/RB1 alterations in HGNE disease, and AR alterations in metastatic and castrate resistant disease. Actionable alterations (MSI-H phenotype and HRR genes) were identified in approximately a fifth of all cases. These results help elucidate the landscape of genomic alterations across the clinical spectrum of prostate cancer.

Human sociality in the times of the Covid-19 pandemic: A systematic examination of change in greetings.

Using multimodal conversation analysis this article examines embodied and tactile greetings in social interaction, documenting their change during the Covid-19 pandemic. Recognizing social interaction as foundational for human sociality, we consider greetings as a crucial normative, organizational, and ritual practice for mutually engaging in intersubjective action. Analyses use video recordings made in Switzerland (featuring (Swiss-)German and English as a lingua-franca), focusing on embodied greetings of acquainted people in public spaces at the age of Covid19-a historical moment in which physical proximity and contact are targeted by official measures restricting social interactions. Studying a range of tactile embodied greetings, the paper shows how they change from routine greetings to hesitated, suspended yet still completed ones, and to projected but resisted and refused ones. Furthermore, it reveals some 'new' practices of greeting (elbow/feetbumps, hugs-in-the-air) and their non-straightforward and accountable character, as well as how they sediment and normalize during the pandemic.

Dans le cadre de l'analyse conversationnelle multimodale, cet article se penche sur les salutations incarnées et tactiles dans l'interaction sociale, pour en documenter les changements observables durant la pandémie de Covid­19. En reconnaissant que l'interaction sociale a un rôle fondateur pour la socialité humaine, nous considérons les salutations comme des pratiques normatives, organisationnelles, et rituelles cruciales pour s'engager mutuellement dans l'action intersubjective. Les analyses proposées reposent sur des enregistrements vidéo effectués en Suisse (langues impliquées: Allemand, Suisse­Allemand, Anglais lingua franca), documentant des salutations incarnées entre interconnaissances dans les espaces publics à l'ère de la Covid­19­un moment historique durant lequel la proximité physique et le contact corporel sont la cible de mesures officielles restreignant les interactions sociales. En étudiant une variété de salutations incarnées tactiles, cette étude montre comment elles changent, passant de salutations routinières à des salutations hésitantes, suspendues, tout en continuant à être complétées, aboutissant à des salutations projetées, mais faisant l'objet de résistance et de refus. Enfin, l'étude montre l'émergence de quelques "nouvelles" pratiques de salutations (avec les pieds, les coudes, et des embrassades en l'air), leur caractère initialement non­évident, puis progressivement sédimenté et normalisé au fil de la pandémie.