Successful Treatment of Metastatic Primary Cutaneous Adnexal Carcinoma With a PD-1 Inhibitor.

SUMMARY: Standard of care treatment for metastatic cutaneous adnexal carcinomas is not well established. In this case report, we highlight the successful use of anti-programmed cell death protein 1 (anti-PD-1) therapy in treating a patient with low tumor mutation burden, microsatellite stable, high programmed death-ligand 1 (PD-L1) gene expression, metastatic primary cutaneous adnexal carcinoma with significant radiographic, and circulating tumor DNA response with durable benefit. Immune checkpoint inhibitors hold promise as a future treatment option in rare instances of metastatic disease from primary skin adnexal carcinoma. Further studies are needed to identify better immune checkpoint inhibitor predictive biomarkers for rare, advanced-stage non-melanoma skin cancers.

Diffuse Large B-Cell Lymphoma, Not Otherwise Specified (DLBCL NOS) Presenting as Multiple Subcutaneous Nodules: An Unusual Cutaneous Presentation of Systemic Disease.

Diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS) is the most common lymphoid malignancy in the Western world and classically presents as a rapidly enlarging nodal or extranodal mass. Cutaneous involvement by systemic DLBCL NOS is an infrequent clinical presentation, encountered in only 1.5-3.5% of cases, while disseminated cutaneous disease with multiple subcutaneous nodules at the time of diagnosis is unusual and can present a diagnostic challenge. The differential diagnosis when encountering a high-grade B-cell malignancy at a cutaneous site is broad and includes primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), high-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL-MYC/BCL2), and other potential entities which must all be carefully considered before rendering a final diagnosis. In this report, we describe the case of a 69-year-old man who was seen at our hospital due to generalized weakness and was found to have multiple subcutaneous nodules representing disseminated DLBCL NOS. The case was complicated by concurrent monoclonal B-cell lymphocytosis involving the bone marrow.

Spatial transcriptomics of a giant pilomatricoma.

Pilomatricomas (PMs) are common benign adnexal tumors that show a predilection for the head and neck region and are characterized at the molecular level by activating mutations in the beta-catenin (CTNNB1) gene. Giant PMs are a rare histopathological variant, according to the World Health Organization, which are defined by a size greater than 4 cm and are reported to show upregulation of yes-associated protein compared to PMs of typical 1-3 cm size. We describe the case of a 67-year-old man with an 8 cm giant PM involving his temporal scalp, whose PM we characterized by 10X spatial gene expression analysis. This revealed five total transcriptomic clusters, including four distinct clusters within the giant PM, each with a unique transcriptional pattern of hair follicle-related factors, keratin gene expression, and beta-catenin pathway activity.

Delayed Injection Site Reaction to Fremanezumab for Chronic Migraine Treatment.

INTRODUCTION: Fremanezumab is a humanized monoclonal antibody administered through a subcutaneous injection. It is used for treatment of migraines, and occasional injection site reactions have developed after usage. CASE PRESENTATION: This case report describes a nonimmediate injection site reaction on the right thigh of a 25-year-old female patient after starting treatment with fremanezumab. The injection site reaction presented as 2 warm, red annular plaques 8 days following a second injection of fremanezumab and about 5 weeks following the first injection. She was prescribed a 1-month course of prednisone that relieved her symptoms of redness, itching, and pain. DISCUSSION: Similar nonimmediate injection site reactions have been reported before, but this particular injection site reaction was significantly more delayed. CONCLUSIONS: Our case illustrates that injection site reactions to fremanezumab can be delayed after the second dose and may require systemic therapy to alleviate symptoms.

Benign eccrine spiradenoma imitating a nerve sheath tumor: illustrative case.

BACKGROUND: Benign eccrine spiradenoma is a rare tumor arising from the sweat glands and is a pathology that is almost never encountered in routine neurosurgical practice. Although this is a rare pathology, it is one that should be included in the differential diagnosis for a patient presenting with a painful, subcutaneous mass, because it can guide further treatment considerations. OBSERVATIONS: The authors present a case of benign eccrine spiradenoma that mimicked a nerve sheath tumor in clinical presentation, imaging characteristics, and gross appearance. LESSONS: Complete local excision of these lesions is the gold standard treatment, because they are painful, and there are reports of local recurrence and malignant degeneration with incomplete resection. For this reason, neurosurgeons should be sure to include this in the differential diagnosis of a patient with a painful, subcutaneous mass, because it may help to guide management decisions.

Appropriate use criteria for ancillary diagnostic testing in dermatopathology: New recommendations for 11 tests and 220 clinical scenarios from the American Society of Dermatopathology Appropriate Use Criteria Committee.

BACKGROUND: Appropriate use criteria (AUC) provide patient-centered physician guidance in test selection. An initial set of AUC was reported by the American Society of Dermatopathology (ASDP) in 2018. AUC reflect evidence collected at single timepoints and may be affected by evolving evidence and experience. The objective of this study was to update and expand AUC for selected tests. METHODS: RAND/UCLA (RAND Corporation [Santa Monica, CA]/University of California Los Angeles) methodology used includes the following: (a) literature review; (b) review of previously rated tests and previously employed clinical scenarios; (c) selection of previously rated tests for new ratings; (d) development of new clinical scenarios; (e) selection of additional tests; (f) three rating rounds with feedback and group discussion after rounds 1 and 2. RESULTS: For 220 clinical scenarios comprising lymphoproliferative (light chain clonality), melanocytic (comparative genomic hybridization, fluorescence in situ hybridization, reverse transcription polymerase chain reaction, telomerase reverse transcriptase promoter), vascular disorders (MYC), and inflammatory dermatoses (periodic acid-Schiff, Gömöri methenamine silver), consensus by panel raters was reached in 172 of 220 (78%) scenarios, with 103 of 148 (70%) rated "usually appropriate" or "rarely appropriate" and 45 of 148 (30%), "appropriateness uncertain." LIMITATIONS: The study design only measures appropriateness. Cost, availability, test comparison, and additional clinical considerations are not measured. The possibility that the findings of this study may be influenced by the inherent biases of the dermatopathologists involved in the study cannot be excluded. CONCLUSIONS: AUC are reported for selected diagnostic tests in clinical scenarios that occur in dermatopathology practice. Adhering to AUC may reduce inappropriate test utilization and improve healthcare delivery.

Guidelines of care for the management of actinic keratosis: Executive summary.

BACKGROUND: Actinic keratoses (AK) are rough scaly patches that arise on chronically ultraviolet-exposed skin and can progress to keratinocyte carcinoma. Treatment options for AK include topical medications, photodynamic therapy, cryosurgery, and laser ablation. OBJECTIVE: This executive summary provides a synopsis of the 18 evidence-based recommendations for the treatment of AK detailed in the Guidelines of Care for the Management of Actinic Keratosis. METHODS: A multidisciplinary workgroup conducted a systematic review to address 5 clinical questions on the management of AKs and applied the Grading of Recommendations Assessment, Development and Evaluation approach for assessing the certainty of the evidence and formulating and grading clinical recommendations. Graded recommendations were voted on to achieve consensus. RESULTS: Analysis of the evidence resulted in 18 recommendations, suggesting there are several effective treatments available for AK. LIMITATIONS: The analysis informing the recommendations was based on the best available evidence at the time it was conducted. The results of future studies may necessitate a revision of current recommendations. CONCLUSIONS: Strong recommendations are presented for using ultraviolet protection, topical imiquimod, topical 5-fluorouracil, and cryosurgery. Conditional recommendations are presented for the use of photodynamic therapy and diclofenac for the treatment of AK, both individually and as part of combination therapy regimens.

Guidelines of care for the management of actinic keratosis.

BACKGROUND: Actinic keratoses (AK) are rough scaly patches that arise on chronically ultraviolet-exposed skin and can progress to keratinocyte carcinoma. OBJECTIVE: This analysis examined the literature related to the management of AK to provide evidence-based recommendations for treatment. Grading, histologic classification, natural history, risk of progression, and dermatologic surveillance of AKs are also discussed. METHODS: A multidisciplinary Work Group conducted a systematic review to address 5 clinical questions on the management of AKs and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of the evidence and formulating and grading clinical recommendations. Graded recommendations were voted on to achieve consensus. RESULTS: Analysis of the evidence resulted in 18 recommendations. LIMITATIONS: This analysis is based on the best available evidence at the time it was conducted. The pragmatic decision to limit the literature review to English language randomized trials may have excluded data published in other languages or limited identification of relevant long-term follow-up data. CONCLUSIONS: Strong recommendations are made for using ultraviolet protection, topical imiquimod, topical 5-fluorouracil, and cryosurgery. Conditional recommendations are made for the use of photodynamic therapy and diclofenac for the treatment of AK, both individually and as part of combination therapy regimens.

Impact of clinical photographs on the accuracy and confidence in the histopathological diagnosis of mycosis fungoides.

BACKGROUND: The histopathological diagnosis of MF is challenging, and there is significant overlap with benign inflammatory processes. Clinical features may be relevant in the assessment of skin biopsies. METHODS: We provided photomicrographs to board-certified dermatopathologists and one hematopathologist with and without accompanying clinical photographs and assessed accuracy and confidence in diagnosing MF. RESULTS: We found that access to clinical photographs improved diagnostic accuracy in both MF and non-MF (distractors); the degree of improvement was significantly higher in the non-MF/distractor category. Across all categories, diagnostic confidence level was higher when clinical images were available. CONCLUSION: These findings suggest that clinical images are useful in making an accurate diagnosis of MF, and may be particularly helpful in ruling it out when an inflammatory disorder is clinically suspected.

Diagnosis and Management of Vulvovaginal Lichen Planus.

IMPORTANCE: Genital lichen planus is a debilitating disorder that lacks definitive recommendations regarding diagnosis and treatment. OBJECTIVE: The aim of this study was to present best practices from available evidence for the diagnosis and treatment of genital lichen planus. EVIDENCE ACQUISITION: We conducted a narrative review of the literature on genital lichen planus by searching PubMed using the following search terms: "vulvar lichen planus" OR (vulvar diseases[mesh] OR vulva[mesh]) AND lichen planus[mesh] OR vulvar[ti] AND "lichen planus"[ti]. We included all languages and years in the search. RESULTS: The search resulted in 273 citations that we reviewed for relevancy and selected 60 as the foundation for this review that focuses on genital sites. Diagnosis can be made without biopsy, and when a biopsy is taken, the pathologic findings may be nonspecific. Topical ultrapotent corticosteroids are most commonly used as first-line treatment of genital lichen planus. CONCLUSIONS AND RELEVANCE: When patients present with genital lichen planus, a complete review of systems and a thorough physical examination should be performed because of the prevalence of extragenital sites. Treatment of genital disease should start with a topical, ultrapotent steroid, and follow-up visits should occur to ensure improvement and to monitor for adverse drug reactions and malignancy.

An Update on Endocrine Mucin-producing Sweat Gland Carcinoma: Clinicopathologic Study of 63 Cases and Comparative Analysis.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare, low-grade adnexal neoplasm with predilection for the periorbital skin of older women. Histologically and immunophenotypically, EMPSGC is analogous to another neoplasm with neuroendocrine differentiation, solid papillary carcinoma of the breast. Both lesions are spatially associated with neuroendocrine mucinous adenocarcinomas of the skin and breast, respectively. EMPSGC is ostensibly a precursor of neuroendocrine-type mucinous sweat gland adenocarcinoma (MSC), a lesion of uncertain prognosis. Non-neuroendocrine MSC has been deemed locally aggressive with metastatic potential, and previous works speculated that EMPSGC-associated (neuroendocrine-type) MSC had similar recurrence and metastatic potential with implications for patient follow-up. Only 96 cases of EMPSGC have been reported (12 cases in the largest case series). Herein, we present 63 cases diagnosed as "EMPSGC" in comparison with aggregated results from known published EMPSGC cases. We aim to clarify the clinicopathologic features and prognostic significance of the neuroendocrine differentiation of EMPSGC and its associated adenocarcinoma and to determine the nosological relevance of EMPSGC association in the spectrum of MSC histopathogenesis. Results established an overall female predominance (66.7%) and average presenting age of 64 years. EMPSGC lesions were associated with adjacent MSC in 33.3% of cases. The recurrence rate for neuroendocrine-type MSC was ~21%, less than the reported 30% for non-neuroendocrine MSC. There were no cases of metastasis. EMPSGC and neuroendocrine-type MSC are distinct entities with more indolent behavior than previously reported, supporting a favorable prognosis for patients.

A Cross-Sectional Study of Attitudes and Factors That Promote Medical Student Participation in Professional Medical Societies.

PURPOSE: Medical student participation in professional medical societies is an understudied extracurricular activity. The purpose of this study is to assess student characteristics associated with participation and their attitudes toward professional medical societies. METHODS: A cross-sectional study using a 21-item survey questionnaire was administered to Wisconsin medical students in the fall of 2019. Regression analysis was used to find factors associated with participation. RESULTS: A total of 308 questionnaire responses were collected with a response rate of 17.4%. Sixty-three percent of respondents participated in a professional medical society, and the most important reasons for participating included professional development, networking, and advocacy. Participation was positively associated with age (OR = 1.16; 95% CI, 1.01 - 1.33); years of medical education (OR = 1.4; 95% CI, 1.18 - 1.69); number of memberships in professional medical societies (OR = 2.02; 95% CI, 1.61 - 2.53); number of extracurricular advocacy events attended outside of professional medical societies (OR = 1.62; 95% CI, 1.17 - 2.23); belief that participation is important for professional development (OR = 1.76; 95% CI, 1.39 - 2.23), patients (OR = 1.51; 95% CI, 1.23 - 1.86), and medical education (OR = 1.43; 95% CI, 1.19 - 1.71); and the desire to participate as a physician (OR = 1.53; 95% CI, 1.25 - 1.88). Participation was negatively associated with male gender (OR = 0.51; 95% CI, 0.27 - 0.95). CONCLUSIONS: Medical students who participate in professional medical societies believe participation supports their education, their patients, and their professional development. Further study is required to elucidate reasons for nonparticipation.

Number of skin biopsies needed per malignancy: Comparing the use of skin biopsies among dermatologists and nondermatologist clinicians.

BACKGROUND: There are too few board-certified dermatologists to treat all patients with skin disease. Primary care physicians often serve at the frontline of skin cancer screening. OBJECTIVE: To compare biopsy use among dermatologist physicians, dermatology advanced practice professionals (APPs), primary care physicians (PCPs), and other nondermatology clinicians. METHODS: Pathology reports, requisition forms, and clinical notes of skin biopsies submitted to our institution during the study period were reviewed. Skin biopsies for inflammatory conditions, cosmetic or functional purposes, and re-excisions were excluded. The number needed to biopsy (NNB) was calculated as the number of biopsied lesions divided by histologically proven skin cancers. RESULTS: The NNB by clinician type was 2.82 for dermatology physicians, 4.69 for APPs, 4.55 for nondermatology PCPs, and 6.55 for other nondermatology clinicians (P < .001). The NNB was significant between clinician groups for nonmelanoma skin cancer (dermatology physicians, 2.00; APPs, 2.71; PCPs, 2.36; and other nondermatology clinicians, 3.47; P < .001) but not for melanoma (dermatology clinicians, 14.33; APPs, 20.78; PCPs, 27.80; and other nondermatology clinicians, 53.56; P = .061). LIMITATIONS: The NNB represents a measure of use but gives no insight into the number of malignant lesions that go unbiopsied and, therefore, undiagnosed. The prevalence of skin cancer varies among dermatology and nondermatology practices. The results are not generalizable to all practice settings. CONCLUSIONS: Dermatology physicians had the lowest NNB of all clinician groups. PCPs performed similarly to dermatology APPs.