Eruptive nevi and lentigines have been reported to occur in the setting of immunosuppression, which may be medication-induced. The associated histopathologic findings have not been well described in the literature. Herein, we report the case of a woman in her 60s who had been receiving chemotherapy treatment with capecitabine, a prodrug of 5-fluorouracil, for advanced pancreatic cancer. She developed multiple small, dark macules on the dorsal and plantar surfaces of both feet. An initial biopsy of one lesion showed a crowded lentiginous proliferation of predominantly single melanocytes, with poor nest formation and some pagetoid scatter. Subsequent biopsies revealed lentigines with melanocytic hyperplasia, which showed less cellularity than the initial biopsy. This case provides histopathologic correlation for eruptive acral melanocytic lesions that result from capecitabine therapy.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is an adnexal neoplasm which typically occurs on periorbital skin and demonstrates overlapping histopathologic features with primary mucinous carcinoma of the skin (MCS). Herein, we report a patient who developed five distinct lesions of EMPSGC and MCS over an eight-year period, some of which occurred on periorbital sites and others which occurred on the lower face. We further sought to better characterize these tumors on a molecular basis; targeted next generation sequencing analysis of two discrete tumors revealed identical missense variants within the ATRX gene. Our report expands on the rare prior reports of multicentric, asynchronous EMPSGC and MCS, and also provides a basis for additional genetic classification of these neoplasms.

CRTC1::TRIM11 cutaneous tumor (CTCT) is a newly identified dermal amelanotic tumor that shows epithelioid to spindle cell morphology with melanocytic differentiation and harbors an in-frame translocation, CRTC1::TRIM11. Given the limited number of reported cases describing its biologic behavior, it is crucial to distinguish this entity from histopathologic mimics, including clear cell sarcoma and metastatic or primary dermal melanoma. Herein, we report a 39-year-old woman with CTCT on the left leg histopathologically mimicking dermal melanoma. The patient developed a tender nodule on the left lateral malleolus 1 year before presentation, which enlarged gradually. A punch biopsy from the lesion and subsequent excision demonstrated a dense spindle cell tumor in the dermis. There were fascicles of achromic spindle cells, some of which showed mildly enlarged nuclei. A mitotic rate of 4/mm2 was noted. The lesional cells were diffusely positive with SOX10 and MITF, with rare S100 and HMB45 staining. Melan-A, pan cytokeratin, p63, and smooth muscle actin were negative. With detection of CRTC1::TRIM11 by next-generation sequencing and lack of CCS-associated cytogenetic translocations, a diagnosis of CTCT was established. She was treated with Mohs micrographic surgery. No metastasis or local recurrence has been found in the 22 months since treatment. Although CTCT was once thought to behave more indolently than melanoma or clear cell sarcoma, recent reports with long-term follow-up detail occurrence of regional and/or distant metastases. Further studies on treatment and follow-up management strategy are warranted.

Importance:Direct immunofluorescence (DIF) testing has been an important ancillary tool for the diagnosis of various inflammatory mucocutaneous conditions for more than 50 years. Current DIF test panels are based on historical clinical descriptions; few studies have rigorously addressed preanalytical, analytical, and/or postanalytical aspects, and even fewer have been replicated or validated. Recent unresolved key issues include whether DIF testing and test panels should be triaged or truncated based on clinical indication or histopathologic findings. Objective:To assess levels of consensus regarding practical aspects of DIF testing among immunodermatology testing specialists in the US. Design, Setting, and Participants:Using modified Delphi methods with a priori characterized criteria, a survey containing 54 statements pertaining to DIF testing was created and distributed to assess consensus. Statements not initially reaching consensus were discussed in 2 live virtual sessions, which were supplemented by relevant literature review and free-text survey comments. These statements were then reassessed in a second survey. Immunodermatology testing specialists in US academic institution-based and independent laboratories were invited based on serving as immunodermatology laboratory medical directors, authoring pertinent literature, or delivering relevant talks at major conferences or by referral. The first survey was conducted from January to February 2024, and the second survey was conducted from March to April 2024. Main Outcomes and Measures:The primary measured outcome was degree of consensus for various DIF testing practice, including DIF testing triage by histopathology/dermatopathology findings and DIF testing panel tailored truncations by clinical indication. Results:A total of 23 respondents to the survey invitation had a mean (SD) of 18.5 (11.1) years and median (range) of 20.0 (1.5-46.0) years in immunodermatology laboratory practice. Consensus was achieved for 46 of 54 statements (85.2%) in the initial survey and for an additional 4 statements in the second survey (50 of 54 [92.6%]). Strong consensus was found against tailored truncation of DIF panel based on the clinical indication in the first survey round. The general acceptability of triaging specimens for DIF testing based on histopathology findings remained without consensus after both surveys. Conclusions and Relevance:Overall, participating US specialists in immunodermatology laboratory testing agreed on many practical aspects of DIF testing, including matters not queried previously. The findings also revealed areas of continued controversy and identified issues for prioritized future study.

The 5th edition of the World Health Organization Classification of Tumours (WCT) serves as a foundation for global diagnostic standards in tumour pathology. Similar to other volumes in this series, the Skin Tumours (Skin5) edition follows a standardized approach. This edition introduces two new chapters: 'Tumours of the nail unit' and 'Metastases to skin', along with new entities across relevant chapters. This review article provides an overview of the updates in Skin5 based on currently published evidence, with emphasis on newly introduced chapters and newly described entities that involve the skin, in particular, epidermal, melanocytic and appendageal tumours.

ImportanceGermline SUFU pathogenic variants (PVs) have previously been associated with basal cell nevus syndrome (BCNS) and multiple infundibulocystic basal cell carcinoma syndrome; however, a broader spectrum of cutaneous findings in patients with SUFU PVs has not been well delineated.ObjectiveTo define the clinical and histopathologic spectrum of cutaneous findings in patients with germline SUFU PVs.Design, Setting, and ParticipantsThis case series was conducted in multiple US academic dermatology, medical genetics, and medical oncology clinics between July 2014 and July 2022. The study included patients with confirmed germline SUFU PVs who were evaluated by a dermatologist. The analysis took place from March to September 2023.Main Outcomes and MeasuresHistopathologic evaluation of skin biopsies with or without immunohistochemical staining, and targeted next-generation sequencing (NGS) on tumor specimens.ResultsAll 5 patients were women. The mean (range) age at presentation was 50.2 (31-68) years, with skin manifestations initially appearing in the fourth to sixth decades of life. None had keratocystic odontogenic tumors. A total of 29 skin pathology specimens from the 5 patients were reviewed; of these, 3 (10.3%) were diagnosed as basaloid follicular hamartomas (BFHs), 10 (34.5%) classified as infundibulocystic basal cell carcinomas (iBCCs), 6 (20.7%) classified as nodular basal cell carcinomas (nBCCs), and 1 (3.4%) as infiltrative basal cell carcinoma (BCC). Targeted NGS studies on tumor specimens suggest that an increased number of UV-signature variants is associated with basal cell carcinomas compared with more indolent basaloid follicular hamartomas.Conclusions and RelevancePatients with germline SUFU PVs may present with multiple indolent basaloid neoplasms in addition to conventional basal cell carcinomas, typically appearing in the fourth to sixth decades of life. Although there are overlapping clinical manifestations, these findings help to differentiate the clinical syndrome associated with SUFU PVs from PTCH1 BCNS. Awareness of the clinicopathologic spectrum of SUFU-associated basaloid neoplasms is important for dermatologists and dermatopathologists because many (although not all) of these lesions are indolent and do not require aggressive surgical treatment. Importantly, because SUFU lies downstream of the protein smoothened, vismodegib and other smoothened inhibitors are unlikely to be effective therapies in this subset of patients.

BACKGROUND:Mohs surgery of eyelid skin cancers requires detailed knowledge of anatomy for precise surgery and accurate evaluation of histology. OBJECTIVE:To review the histology of the peritarsal eyelid using frozen sections as encountered intraoperatively by Mohs surgeons. METHODS:The authors review the literature describing the anatomy and histology of the peritarsal eyelid from the lens of a Mohs surgeon. Histology from select Mohs cases is used to frame the discussion of the microanatomy of this region. RESULTS:The peritarsal eyelids contain a unique mixture of skin, muscle, tarsus, glandular tissue, and conjunctiva. The histologic appearance of many of these structures differs from skin found outside of this anatomic region. Tumors of the eyelid and periocular region may mimic normal histologic structures found within the peritarsal eyelid. CONCLUSION:The peritarsal eyelids have unique anatomy and associated histologic structures. Knowledge of the detailed histoanatomy is required for confident execution of Mohs surgery in this anatomic region.

BACKGROUNDFew prospective studies have evaluated local recurrence rates (LRR) after excision of desmoplastic melanoma (DM); however, several retrospective studies have reported high LRR.OBJECTIVETo determine LRR after excision of DM and evaluate factors affecting LRR.MATERIALS AND METHODSSystematic review of the PubMed, Embase, and Web of Science databases was performed to identify studies reporting local recurrence after excision of DM with conventional wide local excision (WLE), Mohs micrographic surgery (MMS), or staged excision (SE). Meta-analysis was performed to calculate summary LRR and pooled risk ratios (RR).RESULTSLiterature search identified 4 studies evaluating MMS or SE (total n = 61 DM). 53 studies assessed WLE (n = 3,080) and were analyzed quantitatively. The overall LRR after WLE of DM was 21% (95% CI, 0.16-0.28; n = 2,308). Local recurrence rate was higher with positive/unknown histologic excision margins (49%, 95% CI, 0.25-0.74; n = 91) versus negative histologic margins (11%, 95% CI, 0.07-0.17; n = 1,075; [p < .01]). Neurotropism was also associated with increased LRR (RR, 1.79; 95% CI, 1.34-2.38, p < .01; n = 644).CONCLUSIONDM has high LRR after WLE. Local recurrence risk was greatest with positive excision margins, indicating the importance of achieving negative microscopic margins. Greater study of MMS and SE for DM is required.

Journal of the European Academy of Dermatology and VenereologyVolume 37, Issue 3 p. e433-e434 LETTER TO THE EDITOR Stage II desmoplastic melanoma treated with neoadjuvant immunotherapy and Mohs micrographic surgery Daniel J. Lewis, Corresponding Author Daniel J. Lewis [email protected] orcid.org/0000-0002-1610-5785 Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA Correspondence Daniel J. Lewis, Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Hospital of the University of Pennsylvania, 3600 Spruce Street, 2 Maloney, Philadelphia, PA 19104-4283, USA. Email: [email protected]Search for more papers by this authorJunqian Zhang, Junqian Zhang Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USASearch for more papers by this authorRosalie Elenitsas, Rosalie Elenitsas Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USASearch for more papers by this authorRabie M. Shanti, Rabie M. Shanti Department of Oral & Maxillofacial Surgery and Pharmacology, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA Department of Otorhinolaryngology/Head and Neck Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USASearch for more papers by this authorChristopher J. Miller, Christopher J. Miller Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USASearch for more papers by this authorJustine V. Cohen, Justine V. Cohen Department of Oncology, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USASearch for more papers by this author Daniel J. Lewis, Corresponding Author Daniel J. Lewis [email protected] orcid.org/0000-0002-1610-5785 Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA Correspondence Daniel J. Lewis, Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Hospital of the University of Pennsylvania, 3600 Spruce Street, 2 Maloney, Philadelphia, PA 19104-4283, USA. Email: [email protected]Search for more papers by this authorJunqian Zhang, Junqian Zhang Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USASearch for more papers by this authorRosalie Elenitsas, Rosalie Elenitsas Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USASearch for more papers by this authorRabie M. Shanti, Rabie M. Shanti Department of Oral & Maxillofacial Surgery and Pharmacology, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA Department of Otorhinolaryngology/Head and Neck Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USASearch for more papers by this authorChristopher J. Miller, Christopher J. Miller Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USASearch for more papers by this authorJustine V. Cohen, Justine V. Cohen Department of Oncology, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USASearch for more papers by this author First published: 21 October 2022 https://doi.org/10.1111/jdv.18669 Reprint Requests: Please send all reprint requests to Daniel J. Lewis MD. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Volume37, Issue3March 2023Pages e433-e434 RelatedInformation

Melanoma of the nail apparatus is challenging to diagnose for both dermatologists and dermatopathologists. Misdiagnosis or delayed diagnosis of nail unit melanoma can have fatal consequences and legal ramifications. This review educates dermatopathologists on challenges and traps they should be aware of to avoid misdiagnosis of nail unit melanoma. We present illustrative difficult cases that introduce several themes regarding challenges in the diagnosis of nail unit melanoma: specimens with subtle histopathologic findings, challenges in immunoperoxidase interpretation, and how clinical knowledge and surgical procedural knowledge are mandatory to make the diagnosis. Dermatopathologists will be aware of when and how to suspect nail unit melanoma in unusual circumstances.

In the United States, 9.5 million people struggle with opioid misuse, of which 2.7 million meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for opioid use disorder.1 Intravenous drug use (IVDU) can lead to cutaneous reactions associated with injected drug contaminants or fillers, including sugars, talc, and starch.2 Puffy hand syndrome (PHS)—a phenomenon associated with chronic IVDU—clinically presents as intermittent, painless, erythematous, nonpitting edema of the hands and upper extremities.

Importance A standardized pathology classification system for melanocytic lesions is needed to aid both pathologists and clinicians in cataloging currently existing diverse terminologies and in the diagnosis and treatment of patients. The Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) has been developed for this purpose. Objective To revise the MPATH-Dx version 1.0 classification tool, using feedback from dermatopathologists participating in the National Institutes of Health-funded Reducing Errors in Melanocytic Interpretations (REMI) Study and from members of the International Melanoma Pathology Study Group (IMPSG). Evidence Review Practicing dermatopathologists recruited from 40 US states participated in the 2-year REMI study and provided feedback on the MPATH-Dx version 1.0 tool. Independently, member dermatopathologists participating in an IMPSG workshop dedicated to the MPATH-Dx schema provided additional input for refining the MPATH-Dx tool. A reference panel of 3 dermatopathologists, the original authors of the MPATH-Dx version 1.0 tool, integrated all feedback into an updated and refined MPATH-Dx version 2.0. Findings The new MPATH-Dx version 2.0 schema simplifies the original 5-class hierarchy into 4 classes to improve diagnostic concordance and to provide more explicit guidance in the treatment of patients. This new version also has clearly defined histopathological criteria for classification of classes I and II lesions; has specific provisions for the most frequently encountered low-cumulative sun damage pathway of melanoma progression, as well as other, less common World Health Organization pathways to melanoma; provides guidance for classifying intermediate class II tumors vs melanoma; and recognizes a subset of pT1a melanomas with very low risk and possible eventual reclassification as neoplasms lacking criteria for melanoma. Conclusions and Relevance The implementation of the newly revised MPATH-Dx version 2.0 schema into clinical practice is anticipated to provide a robust tool and adjunct for standardized diagnostic reporting of melanocytic lesions and management of patients to the benefit of both health care practitioners and patients.

The authors declare no conflict of interest. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

We call on dermatologists and dermatopathologists to include nail clipping histopathology as an essential component of the routine evaluation of melanonychia. This manuscript demonstrates a case where an adult woman with broad melanonychia of the right thumbnail declined a nail matrix biopsy, but was amenable to a nail clipping.The nail clipping showed pigmentation, melanocyte remnants, and small cavities in the nail plate. These features have been published previously by our group as a clue to nail unit melanoma within nail clippings.This patient was rapidly triaged for nail matrix biopsy, which demonstrated nail unit melanoma in situ. Every patient with melanonychia can benefit from a nail clipping by examination of the location of the pigmentation within the nail plate for surgical planning, and if melanocyte remnants are detected, the nail clipping also serves as a rapid triage mechanism for nail matrix biopsy to evaluate for nail unit melanoma. Fontana-stained sections will highlight the pigmentation in the nail plate, and its location in the nail plate can easily be described by the dermatopathologist. Nail clippings performed in the setting of clinically apparent melanonychia may show helpful histopathologic findings of pigmented fungi, hemorrhage, external pigmentation, features of other pigmented nail unit tumors, as well as other entities. Nail clipping histopathology can provide extensive information in the evaluation of melanonychia with minimal discomfort for a patient, and little disruption to a physician's clinic flow. With this additional case of a nail unit melanoma diagnosed after initial concern found in a nail clipping, as well as other information in the literature, it is clear that melanocyte remnants found in nail clippings are reliable concerning features related to nail unit melanoma in adults. With knowledge of these histopathologic features in nail clippings and the significance of melanocyte remnants, the dermatopathologist can play a crucial role in the use of a nail clipping as a life-saving diagnostic maneuver. Accordingly, given the potential benefit to patients in this setting, as well as other uses of a nail clipping in the evaluation of melanonychia, we call on dermatologists and dermatopathologists to innovate the routine evaluation of melanonychia through the routine employment of nail clippings for histopathologic evaluation.

BACKGROUND:Programmed cell death protein (PD-1) and programmed death-ligand 1 (PD-L1) inhibition checkpoint blockade leads to various cutaneous adverse reactions, including bullous pemphigoid and lichen-planus-like reactions. However, lichen planus pemphigoides (LPP), manifesting histopathologic features of both lichen planus and bullous pemphigoid, has more rarely been associated with immunotherapy.METHODS:The clinical and histopathologic findings of three patients were examined, and a review of cases of LPP and bullous lichen planus secondary to PD-1 inhibitor therapy was performed.RESULTS:Three patients (two with advanced non-small-cell lung adenocarcinoma and the third with metastatic breast cancer) presented with both lichenoid eruptions and bullae. Biopsy of the lesions revealed lichenoid tissue reactions in all three patients. Together with the histopathologic findings, direct immunofluorescence (DIF) showing linear C3 and IgG deposition and positive enzyme-linked immunosorbent assay (ELISA) showing BP180 positivity supported a diagnosis of LPP in two patients. The third patient in our series also showed confirmatory ELISA testing supporting LPP.CONCLUSIONS:Lichen planus pemphigoides is a distinct cutaneous toxicity to checkpoint inhibitor therapy illustrates a possible pathogenic mechanism and the importance of dermatopathology recognition to render an accurate diagnosis.

ABSTRACT:Cutaneous ganglioneuromas (GNs) are exceptionally uncommon tumors, and many reported cases describe association with overlying epidermal hyperplasia that may be interpreted as seborrheic keratosis (SK) or SK-like proliferation. We report 5 cases of cutaneous GN in adult patients; all of which were discovered incidentally in the immediate vicinity of epidermal hyperplasia. A review of the literature demonstrates the current-although likely imperfect-understanding of the etiopathogenesis of both SK and GN in the skin. We explore the putative pathophysiologies of other common, well-characterized skin lesions and, taking them into account, provide rationale for the coexistence of cutaneous GN with overlying SK and SK-like epidermal changes. However, we ultimately acknowledge a dilemma of causality and, given the rarity of their co-occurrence, objectively question whether occasional cameo appearances by GN lying subjacent to SK and SK-like hyperplasia may be due merely to chance.

Wang, Robin H. BA*; Abbott, James MD†; Jiang, Angela J. MD†; Chu, Emily Y. MD, PhD†; Elenitsas, Rosalie MD† Author Information

The authors declare no conflict of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.