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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. [ABSTRACT FROM AUTHOR]

Background: Cutaneous focal mucinosis (CFM) or focal dermal mucinosis is a benign reactive process categorized as a primary mucinosis. Skin biopsy is essential for diagnosis, as the clinical appearance is often non‐specific. Follicular induction is a phenomenon whereby the epidermis is induced by an underlying process to form primitive or mature hair follicles, and is commonly seen overlying dermatofibromas. Follicular induction has been rarely described in CFM. Methods: We performed a retrospective histological review of lesions of CFM confirmed by skin biopsy from 2010 to 2015 in our department. Results: We found that 11% (11/98) of CFM lesions showed follicular induction. Cytokeratin 20 (CK20) immunostaining was performed on all 11 of these biopsies that showed follicular induction and highlighted an increased density of CK20+ Merkel cells within the basaloid epidermal proliferations. Conclusion: As superficial basal cell carcinomas (BCC) often show a mucinous stroma around the basaloid islands, CFM with follicular induction may closely mimic a BCC histologically, particularly in superficial shave biopsies. Therefore, it is important that dermatopathologists be aware of this phenomenon. Furthermore, CK20+ staining within the basaloid epithelial proliferations may be helpful in differentiating CFM with follicular induction from a BCC. [ABSTRACT FROM AUTHOR]

Background: Primary giant cell tumor of soft tissue, also known as soft tissue giant cell tumor of low malignant potential, is a rare soft tissue tumor located in both superficial and deep soft tissue. Histologically, these lesions bear a close resemblance to their bony counterparts, giant cell tumor of bone, with round to spindle-shaped cells intimately admixed with uniformly scattered osteoclast-like multinucleated giant cells. In 1989 in the dermatology literature, two malignant giant cell tumors of soft parts were described that filled the dermis and extended into the subcutaneous tissue. Methods: The authors report the rare occurrence of a giant cell tumor of soft tissue occurring primarily in the dermis that lacks overtly malignant features and clinically was thought to be an epidermal inclusion cyst. Results: Light microscopy revealed a non-encapsulated cellular dermal tumor containing numerous osteoclast-like giant cells. Cytologic atypia was minimal and the mitotic count averaged 2–3/10 HPF. The histologic differential diagnosis is also discussed. Conclusion: Giant cell tumor of soft tissue is a rare neoplasm of the skin, however, recognition of this tumor is important due to its behavior as a low-grade malignancy. [ABSTRACT FROM AUTHOR]

To examine the effects of chronic ultraviolet light on human epidermal cells, we grafted white human skin onto recombinase activating gene-1 knockout mice. We found previously that the maximal concentration of ultraviolet 8 radiation (290-320 nm) tolerated by human skin xenografts was 500 J per m² when given three times weekly. One hundred and fifty-eight grafted mice were randomized and observed for a median of 10 mo in four groups: (i) no treatment: (ii) one treatment with the chemical carcinogen dimethy--(a)benzanthracene; (iii) ultraviolet B three times weekly; and (iv) a combination of dimethyl-(a)benzanthracene and ultraviolet B. Approximately half of the skin specimens treated with ultraviolet B developed superficial milia and epidermal cysts. Grafts contained up to seven milia lesions between 4 and 8 mo after initiation of treatment, whereas the number of larger epidermal cysts was rarely more than two. Milia and cysts developed in the skin regardless of pigmentation or tanning. Actinic keratoses arose in 9% of grafts treated with ultraviolet B alone and in 19% of grafts treated with the combination of dimethyl- (a)benzanthracene and ultraviolet B. Invasive squamous cell carcinomas developed in 10% of grafts after combined dimethyl-(a)benzanthracene and ultraviolet B treatment and lesions were restricted to skin grafts that did not tan. These findings demonstrate that (i) development of ultraviolet-induced lesions can be experimentally accelerated in human skin, (ii) xenografted recombinase activating gene-1 deficient mice are superior to severe combined immunodeficiency disease mice for chronic ultraviolet B studies, and (iii) benign cystic tumors and squamous cell carcinomas are caused by ultraviolet B. [ABSTRACT FROM AUTHOR]

SSA/Ro and SSB/La are soluble cellular proteins to which antibodies are frequently produced in patients with Sjögren's syndrome and systemic lupus erythematosus. In this investigation, we examined anti-SSA/Ro and anti-SSB/La staining patterns on synchronized WiL2 cells and mixed lymphocyte culture cells using monospecific antisera. In addition to its presence in the nucleoplasm, the SSB/La antigen was highly concentrated in the nucleolus of cells during the late G1 and early S phase and is thus cell cycle-related. In contrast, the SSA/Ro antigen was found to be independent of cell cycle, showing a nuclear speckled pattern in all phases. Blocking experiments indicated that free SSB/La is responsible for the nucleolar staining, whereas the combination of both SSA/Ro and SSB/La determines the nucleoplasmic speckled staining pattern. [ABSTRACT FROM AUTHOR]

BACKGROUND. Review of the literature reveals that malignant spiradenomas are rare and may be fatal, and typically manifest as rapid enlargement in long-standing spiradenomas. OBJECTIVE. The present tumor was removed 2 months after it was first noted by the patient. A case of what we believe is the earliest stage of malignant transformation within spiradenoma is reported. METHODS. Case report and literature review. RESULTS. The region with malignant transformation was characterized by nuclear pleomorphism, loss of two cell types, and increased mitotic activity with atypical mitoses. Small infiltrating duct-like structures were seen. The large aggregates and sheets of malignant cells described in long-standing tumors were not seen. CONCLUSION. We ascribe the early detection of this tumor to increased public awareness of the importance in seeking early treatment of skin lesions. Histologic examination of tins stage may eventually outnumber the now more commonly described latter stages. [ABSTRACT FROM AUTHOR]

While our patient, and 90% of patients included in the review, did not recall any specific trauma to the affected site, it is plausible that minor repetitive traumas secondary to footwear or activity[1] could have gone unnoticed. Keywords: acquired ungual; fibrokeratoma; ungual fibrokeratoma EN acquired ungual fibrokeratoma ungual fibrokeratoma 779 782 4 08/16/23 20230901 NES 230901 INTRODUCTION Acquired ungual fibrokeratomas are uncommon benign fibrous tumors of the nail unit. These tumors can emerge from the proximal nail fold, directly from the nail bed itself,[1] as well as from other areas of the nail unit. [Extracted from the article]

Our patient represents the first reported case of neoadjuvant immune checkpoint inhibitor (ICI) therapy for stage II melanoma. At this time, surgical resection and adjuvant therapy remain the standard of care for high-risk stage II and clinical stage III melanoma.[1] However, appropriate patients can be considered for neoadjuvant therapy in ongoing clinical trials. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

PD-1 (programmed cell death-1) inhibitors, used to treat metastatic melanoma and other malignancies, are associated with development of immune-related adverse events in the skin. Such reactions include morbilliform eruptions, vitiligo, alopecia areata and bullous pemphigoid. In this report, we describe a patient who developed a lupus-like cutaneous reaction in the setting of pembrolizumab therapy for metastatic melanoma, adding to the spectrum of reactions which may be observed in association with PD-1 inhibitor therapy. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. BACKGROUND: Few prospective studies have evaluated local recurrence rates (LRR) after excision of desmoplastic melanoma (DM); however, several retrospective studies have reported high LRR. OBJECTIVE: To determine LRR after excision of DM and evaluate factors affecting LRR. MATERIALS AND METHODS: Systematic 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). RESULTS: Literature 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). CONCLUSION: DM 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. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

BACKGROUND Extraocular sebaceous carcinoma (SC) is a rare malignancy with metastatic potential. The authors present a case of a rapidly growing extraocular SC with equivocal radiographic imaging to highlight challenges in tumor management. OBJECTIVE To examine the existing literature for evaluation and management recommendations of extraocular SC. METHODS AND MATERIALS A comprehensive review of relevant English articles in PubMed through May 2015. RESULTS Tumor-specific staging system and management guidelines do not currently exist for extraocular SC. Mohs micrographic surgery or wide local excision are the most commonly used surgical treatments. Regional/distant metastasis occurs infrequently, but systemic workup with radiographic imaging or sentinel lymph node biopsy may be warranted in select cases. Adjuvant radiation therapy can be considered for recurrent and metastatic tumors. CONCLUSION Extraocular SCs present unique challenges that may benefit from multidisciplinary management. Surgical removal with negative pathologic margins is the mainstay treatment of extraocular SC. Additional studies will help clarify the optimal diagnostic workup and adjuvant treatment of patients. [ABSTRACT FROM AUTHOR]

The article presents the case of an 11-year-old girl with a congenital melanocytic nevus on her right forearm. The lesion was asymptomatic, but the appearance and hair growth within the lesion were bothersome to the patient. She and her mother denied any prior procedures or physical trauma to the site. On physical examination, the patient had a tan-brown thin papule measuring.

Vemurafenib is a specific inhibitor of the V600E mutated BRAF protein kinase used for the treatment of unresectable or metastatic melanoma harboring this mutation. Multiple predictable side effects have been described with use of this targeted therapy, and implicate BRAF and mitogen activated protein kinase ( MAPK) signaling pathways in their pathogenesis. Herein, we report the novel finding of an interface dermatitis in radiation recall and a keratosis pilaris-like clinical reaction in a patient treated with vemurafenib. [ABSTRACT FROM AUTHOR]

In another study,7 in which different colors of nail polish and different brands of nail polish were studied, similar patterns for the nail polish were seen except that the finely granular material was mostly polarizable. In the 19th century, nail cosmetics became more commonly used worldwide; nail polish itself was popularized in the 20th century and many different forms of nail cosmetics were introduced to the fashion industry, including basic nail polish, gel nail polish, acrylics, breathable nail polish, and others.1 In the last few decades, further innovations have been made in nail art, introducing various forms of nail polish and nail stickers.2 Magnetic nail polish is a new trend in nail cosmetics that is quickly becoming popular. For example, the acrylate ingredient, which is also present in this magnetic nail polish, is the main allergenic component among most types of nail polishes, including acrylic nails, gel nails, solar nails, ultraviolet nails, nail wraps, and silk nails. [Extracted from the article]

BACKGROUND Perineural invasion (PNI) has been associated with poor prognosis in cutaneous squamous cell carcinoma (CSCC), but it is unclear how different degrees of nerve involvement affect prognosis. OBJECTIVE To determine whether the diameter of nerves invaded by CSCC affects outcomes of recurrence, metastasis, and disease-specific and overall survival. METHODS A retrospective cohort study was conducted of patients with CSCC with PNI. Dermatopathologists blinded to subject outcomes determined the diameter of the largest involved nerve. RESULTS Data were obtainable for 48 patients. Small-caliber nerve invasion (SCNI) of nerves less than 0.1 mm in diameter was associated with significantly lower risks of all outcomes of interest. Disease-specific death was 0% in subjects with SCNI, versus 32% in those with large-caliber nerve invasion (LCNI) ( p=.003). Other factors associated with significantly worse survival were recurrent or poorly differentiated tumors or tumor diameter of 2 cm or greater or depth of 1 cm or greater. On multivariate analysis, only tumor diameter and age predicted survival. CONCLUSIONS The individual prognostic significance of factors associated with poor survival remains uncertain. Small-caliber nerve invasion may not adversely affect outcomes. Defining PNI as tumor cells within the nerve sheath and routine recording of diameter of involved nerves, tumor depth, and histologic differentiation on pathology reports will facilitate further study. [ABSTRACT FROM AUTHOR]

Background: Src-family tyrosine kinases (SFKs) are signaling proteins that regulate keratinocyte proliferation and differentiation. Src-activating and signaling molecule (Srcasm) is a recently identified molecule that downregulates SFK activity and promotes keratinocyte differentiation. To determine if Srcasm expression correlates with keratinocyte differentiation, we characterized the level of Srcasm expression in some cutaneous lesions that exhibit increased keratinocyte proliferation. Methods: Formalin-fixed sections of randomly selected seborrheic keratoses (SKs) and basal cell carcinomas (BCCs) were analyzed for Srcasm and Ki-67 immunohistochemical staining. Anti-Srcasm and anti-Ki-67 stainings were performed in parallel. Results: All SKs displayed decreased Srcasm staining in areas comprised of basaloid keratinocytes that exhibited an increased Ki-67 index. Higher Srcasm staining levels were detected near pseudohorn cysts where keratinocytes exhibited a lower Ki-67 index. All multicentric and nodular BCCs displayed a prominent loss of Srcasm staining in association with a marked increase in Ki-67 staining. Conclusions: Our results support the hypothesis that Srcasm protein levels are decreased in the hyperproliferative keratinocytes found in SKs and BCCs. Increased Srcasm protein levels are detected in keratinocytes undergoing differentiation. Decreased Srcasm levels may be part of the pathophysiologic mechanism in cutaneous lesions, exhibiting keratinocyte hyperproliferation. [ABSTRACT FROM AUTHOR]

The diagnosis of ‘cellular dermal nodule in melanocytic nevi’ is challenging, as it can simulate invasive and tumorigenic melanoma. Because cellular nodules are presumed benign, it is essential to differentiate them from true malignant melanoma arising within a nevus, which portends a poor prognosis. Although presumed benign, to date, no published long-term follow-up studies have proved the benignity of this lesion. To better understand the clinical behavior and histological features of these lesions, we present a clinical pathological study of a cohort of 26 cases, for which we obtained clinical follow up by chart review and questionnaires. Clinical follow up was obtained on 16 out of 26 patients (61.5%) and ranged from 12 to 132 months (average 62.3 months). The cellular nodules in congenital pattern nevi, reported here, had an invariably benign clinical course. Features useful in differentiating cellular nodule from melanoma include: (1) lack of high-grade uniform cellular atypia; (2) lack of necrosis within the nodule; (3) rarity of mitoses; (4) evidence of maturation in the form of blending or transitional forms between the cells in the nodule and the adjacent nevus cells; (5) lack of pagetoid spread into the overlying epidermis; and (6) no destructive expansile growth. The difference between cellular nodule and melanoma arising from nevus can be very subtle, and it is important to emphasize that these lesions must be assessed on an individual case-by-case basis. Xu X, Bellucci KSW, Elenitsas R, Elder DE. Cellular nodules in congenital pattern nevi. [ABSTRACT FROM AUTHOR]

Interestingly, comparison of the histopathologic findings of the annular EO lesions in patients with and without systemic sarcoidosis showed only minor differences.5 In patients with systemic sarcoidosis, the zonal pattern on histopathology was less defined. Only 1 patient had skin lesions outside of the area of EO, but it was not reported whether this patient had systemic sarcoidosis or cutaneous lesions only. Keywords: ochronosis; exogenous; exogenous ochronosis; perforating; granulomatous EN ochronosis exogenous exogenous ochronosis perforating granulomatous 1219 1222 4 09/21/21 20211001 NES 211001 Introduction Exogenous ochronosis (EO) is a cutaneous disorder induced by cosmetic application of skin lightening agents, most commonly hydroquinone.1 The pathogenesis is secondary to inhibition of local activity of homogentisic acid oxidase by hydroquinone, leading to accumulation of homogentisic acid that polymerizes to form ochronotic pigment in the skin. AG-like change in EO has been reported in a patient who presented with annular lesions on a background of severe EO.7 Of note, in AG, elastophagocytosis is a prominent feature, which is absent in actinic granuloma-like EO. [Extracted from the article]

The role of gold in allergic contact dermatitis is poorly understood and is a subject of increasing interest. Recent studies demonstrate that gold-positive patch testing is not uncommon, but persistent patch test reactions are rarely reported. We present a case of a 53-year-old woman with a 7-year history of a scattered, pruritic papular dermatitis. Patch testing demonstrated a persistent, positive reaction to gold sodium thiosulfate. The histopathology of the patch test site and that of the cutaneous eruption were similar in nature but differing in severity. No other allergens have been identified, but gold avoidance has not yet resulted in the clearing of her eruption. This case underscores the difficulty in making a clinical correlation despite suggestive clinical pathologic evidence. [ABSTRACT FROM AUTHOR]

Fibrous hamartoma of infancy ( FHI) is a rare, benign, soft tissue tumor. The lesion's clinical resemblance to more aggressive soft tissue tumors of childhood makes histologic diagnosis paramount. We report a unique presentation of a FHI associated with localized hypertrichosis and hyperhidrosis. [ABSTRACT FROM AUTHOR]

The anti-tumor action of many chemotherapeutic agents has recently been attributed to the induction of apoptosis in the malignant cell population. In this study, we investigated the ability of extracorporeal photopheresis (ExP) and in vitro PUVA (8-methoxypsoralen + ultraviolet A) therapy to induce apoptosis in peripheral blood mononuclear cells from Sezary syndrome patients and normal controls. Flow cytometric analysis of ExP- or PUVA-treated peripheral blood lymphocytes demonstrated two distinct cell populations within 24 h of treatment. One population was similar to untreated controls with the other exhibiting characteristics of apoptotic cell death, i.e., a loss of cell volume and an accompanying increase in cell density. This latter population was comprised of cells with DNA strand breaks as determined by the Tdt-mediated deoxyuridine triphosphate-biotin nick end labeling assay. Apoptosis was also confirmed morphologically by fluorescent and electron microscopy as well as by demonstration of characteristic DNA strand breaks (laddering) using gel electrophoresis. Apoptosis was not observed with 8-methoxypsoralen (≤300 ng per ml) alone; however, ultraviolet A alone at doses ≥ 2 J per cm2 induced apoptosis in lymphocytes. Peripheral blood T-cell subpopulations of Sezary syndrome patients, including the malignant clone, were equally susceptible to apoptosis subsequent to either photopheresis or PUVA treatment. In contrast, monocytes (CD14+/ CD45+) appear to be resistant to apoptosis induction by ExP or PUVA treatment. Moreover, ExP-treated and untreated monocytes phagocytized apoptotic, but not untreated, peripheral blood mononuclear cells. ExP and PUVA have been shown to be efficacious and well-tolerated therapies in the treatment of dermatologic diseases and transplant rejection. These data suggest that induction of apoptosis may be an important event for therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Jellyfish envenomation often causes an immediate painful vesiculopapular eruption. Less commonly it can cause a type IV allergic hypersensitivity that manifests with delayed or recurrent cutaneous lesions at the primary site or distant from the primary site. These secondary reactivations may be related to high antijellyfish immunoglobulin levels, intracutaneously sequestered antigen, or cross-reacting venom. Immunomodulators such as pimecrolimus and tacrolimus and topical and intralesional corticosteroid therapy decrease this recurrent dermatitis. We report a case of a 9-year-old girl with a recurrent jellyfish dermatitis lasting more than 1 year after the initial envenomation. The dermatitis finally resolved after treatment with tacrolimus and intralesional triamcinolone acetonide therapy. [ABSTRACT FROM AUTHOR]

Mucinous nevus (MN) is a rare, benign, cutaneous hamartoma that may be congenital or acquired. There are admixed CD34-positive fibroblasts and a few factor XIIIa-positive dendritic cells.3 Many cases show an acanthotic epidermis with elongation of the rete ridges and hyperkeratosis, similar to an epidermal nevus. 4 Oiso N, Kimura M, Kawada A. Follicular mucinous nevus: a possible new variant of mucinous nevus. [Extracted from the article]

Sclerotic lipomas, a lipoma variant, are benign subcutaneous tumors, so‐named because of their resemblance to sclerotic fibromas. Previous literature has suggested that these tumors may show a predilection for middle‐aged adult males. We report an unusual case of a sclerotic lipoma diagnosed on the scalp of a 66‐year‐old female. The patient presented to the outpatient clinic with a 3‐ to 4‐year history of an enlarging and irritated 2.6‐cm nodule on the anterior crown of the scalp, clinically thought to be a pilar cyst. Histopathological examination from the excisional specimen revealed a well‐circumscribed dermal to subcutaneous tumor with ample sclerotic collagen bundles, an increased number of CD34 positive spindled cells, and prominent S‐100 positive mature adipocytes comprising greater than 50% of the tumor. We present this case given its atypical clinical and histopathological presentation, review the literature of sclerotic lipomas, and discuss the differential diagnosis to raise awareness of this rare entity. [ABSTRACT FROM AUTHOR]

Background: BRAF inhibition has improved overall survival in patients with BRAF mutant melanoma, but this is associated with a range of known and predictable cutaneous side effects, including squamous cell carcinomas associated with RAS mutations. Methods: We identified three severely dysplastic nevi, one atypical intraepidermal melanocytic proliferation, and four melanoma in situ lesions, newly arising in four patients undergoing treatment with vemurafenib. To characterize mutations in these atypical melanocytic lesions, we used a custom iPlex panel detecting 74 mutations in 13 genes known to play a role in melanoma pathogenesis. Results: We identified an NRAS mutation at codon 61 (Q61R) and a rare BRAF exon 11 mutation (G466A) in atypical melanocytic lesions that arose in patients treated with vemurafenib. Conclusion: There appears to be development or accelerated growth of atypical melanocytic lesions in the setting of BRAF inhibition. Our results underscore the need for careful surveillance for melanocytic lesions in patients on BRAF inhibitor therapy and shed light on potential mechanisms for melanoma pathogenesis in the context of BRAF pathway blockade. Further studies are warranted to show a causal relationship. [ABSTRACT FROM AUTHOR]

Background: Actinic keratosis (AK) and squamous cell carcinoma in‐situ (SCCIS) within or near melanoma in situ (MIS) can complicate diagnosis due to overlapping clinical and microscopic features. This study aimed to describe basilar melanocyte density and pagetoid spread in AK and SCCIS for improved diagnostic accuracy. Methods: A total of 22 AK and 22 SCCIS biopsies containing a margin of uninvolved epidermis were immunostained with MART‐1 (melanoma antigen recognized by T‐cells 1). The basilar melanocyte:keratinocyte ratio and the number and distribution of pagetoid melanocytes were compared in AK, SCCIS, and uninvolved epidermis. An in‐vitro human skin model was created to assess the impact of keratinocyte atypia on melanocyte distribution. Results: The median basilar melanocyte:keratinocyte ratio in SCCIS (1:11.49) was lower than in uninvolved epidermis (1:5.59, P = 0.0011), and the ratio in AK (1:6.94) was similar to uninvolved epidermis (P = 0.987). Pagetoid melanocytes were absent in perilesional skin but common in AK (21/22, P < 0.0001) and SCCIS (22/22, P < 0.0001). Pagetoid melanocytes at or above the mid‐spinous layer were more common in SCCIS (21/22) vs AK (7/22, P < 0.0001). Pagetoid melanocytes were present in the in‐vitro skin model made with neoplastic but not normal keratinocytes. Conclusions: Pagetoid melanocytes in AK and SCCIS should be interpreted with caution to avoid overdiagnosis of MIS. [ABSTRACT FROM AUTHOR]

A 20-year-old female patient was seen in consultation in the pediatric dermatology clinic for a progressive diffuse eruption, which began when she was 18 years of age. The histologic findings in our patient are similar to those that have been reported previously in stem cell transplant patients and are nearly indistinguishable from idiopathic LS.3 Our case also features a subtle vacuolar interface reaction involving the follicular epithelium as well as pigment incontinence. A clinical association between LS and morphea has also been established, as Lutz et al8 have reported that 45 percent of patients with plaque morphea had associated genital LS. [Extracted from the article]

Whereas DNSM show clear nerve sheath differentiation with expression of S100 and other nerve sheath markers, CNT do not. Large series have since shown that CNTs are morphologically and immunohistochemically distinct from true nerve sheath myxomas, and their true origin may be fibroblastic cells.2 There is decidedly no nerve sheath differentiation as they universally lack S100 expression by immunohistochemistry. Histopathologically, the differential diagnosis includes a nerve sheath myxoma, melanocytic tumors, and other fibrohistiocytic tumors. [Extracted from the article]

Background: Recently, a 23-gene signature was developed to produce a melanoma diagnostic score capable of differentiating malignant and benign melanocytic lesions. The primary objective of this study was to independently assess the ability of the gene signature to differentiate melanoma from benign nevi in clinically relevant lesions.Methods: A set of 1400 melanocytic lesions was selected from samples prospectively submitted for gene expression testing at a clinical laboratory. Each sample was tested and subjected to an independent histopathologic evaluation by 3 experienced dermatopathologists. A primary diagnosis (benign or malignant) was assigned to each sample, and diagnostic concordance among the 3 dermatopathologists was required for inclusion in analyses. The sensitivity and specificity of the score in differentiating benign and malignant melanocytic lesions were calculated to assess the association between the score and the pathologic diagnosis.Results: The gene expression signature differentiated benign nevi from malignant melanoma with a sensitivity of 91.5% and a specificity of 92.5%.Conclusions: These results reflect the performance of the gene signature in a diverse array of samples encountered in routine clinical practice. Cancer 2017;123:617-628. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Blue nevi are a heterogeneous group of dermal melanocytic proliferations that share a common clinical appearance but remain controversial in their histopathologic and biologic distinction. While common blue nevi and cellular blue nevi are well-defined entities that are classified without significant controversy, the distinction between atypical cellular blue nevi and blue nevus-like melanoma remains diagnostically challenging. We report a case of a 46-year-old female with recurrent blue nevus-like melanoma of the scalp with liver metastases; mutational analysis showed GNA11 Q209L and BAP1 Q393 mutations. To our knowledge, this is the first case of blue nevus-like melanoma with GNA11 and BAP1 mutations. These particular mutations and the predilection for liver metastases in our patient's case underscore a fundamental biological relationship between blue nevi and uveal melanoma and suggest the two entities may prove amenable to similar diagnostic and prognostic testing and targeted therapies [ABSTRACT FROM AUTHOR]

Therapeutic immune checkpoint blockade for metastatic melanoma has been associated with vitiligo, pruritus and morbilliform eruptions. Reports of other autoimmune skin disease in this setting are rare. We sought to expand the spectrum of cutaneous immune-mediated effects related to immune checkpoint inhibitor therapy. In this report, we describe two unusual cutaneous reactions related to checkpoint inhibitor therapy, namely bullous pemphigoid ( BP) and dermatitis herpetiformis. The development of BP and dermatitis herpetiformis in the context of checkpoint inhibitor therapy is consistent with previous investigations supporting the importance of effector and regulatory T cells in the pathogenesis of these diseases. [ABSTRACT FROM AUTHOR]

BACKGROUND: Published appropriate use criteria (AUC) for Mohs micrographic surgery (MMS) for melanoma are based on consensus opinion. OBJECTIVE To evaluate whether published AUC identify melanomas for which MMS may benefit patients by detecting subclinical spread or confirming clear microscopic margins before flap or graft reconstruction. MATERIALS AND METHODS: Retrospective cohort study of 591 melanomas in 556 patients evaluating the correlation between current AUC (anatomic location, recurrent status, and tumor stage) and subclinical spread or reconstruction with a flap or graft. RESULTS: Anatomic location on the head, neck, genitalia, hands, feet, or pretibial leg was associated with a significantly higher frequency of subclinical spread (odds ratio (OR) 1.89, p = .0280) and flap or graft reconstruction (OR 10.3, p = .0001). Compared with primary lesions, recurrent melanomas had a higher frequency of subclinical spread (OR 1.78, p = .0104) and reconstruction with a flap or graft (OR 1.67, p = .0217). The frequencies of subclinical spread and flap or graft reconstruction did not differ between in situ and invasive melanomas. CONCLUSION: Anatomic location and recurrent status are useful criteria to identify melanomas that may benefit from MMS. Tumor stage is not a useful criterion, as MMS has similar benefits for subsets of both invasive and in situ melanomas. [ABSTRACT FROM AUTHOR]

Several types of cutaneous reactions have been reported to arise at the site of herpes zoster ( HZ) infection weeks to years after the acute disease. Among these, granulomatous reactions are the most frequently reported. In this study, we describe the spectrum of histopathologic findings of HZ granulomatous reactions observed in 26 patients with cutaneous lesions confined to the area of previous HZ eruption and compare them with biopsy specimens taken from 25 patients with acute HZ. All patients with persistent reactions from whom history was available presented within 12 weeks of the onset of the acute eruption. The most frequent findings were interstitial granulomatous dermatitis with lymphocytes, histiocytes and multinucleated giant cells displaying elastophagocytosis and a perineural, perivascular and perieccrine mononuclear inflammatory infiltrate rich in lymphocytes and plasma cells. Less common features included intra-arrector and peri-arrector pili granulomas, follicular dilatation and hyperkeratosis, and vasculitis. Specimens from patients with acute HZ were found to have small numbers of perineural plasma cells and most had subtle granulomatous inflammation, in patterns similar to the group with late granulomatous reactions. Our findings suggest that granulomatous reactions to varicella zoster virus represent a persistent evolving inflammatory reaction after acute infection. [ABSTRACT FROM AUTHOR]

Early-stage cutaneous T-cell lymphoma (CTCL) is a skin-limited lymphoma with no cure aside from stem cell transplantation. Twelve patients with stage IA-IIA CTCL were treated in a phase 1 trial of 0.03% and 0.06% topical resiquimod gel, a Toll-like receptor 7/8 agonist. Treated lesions significantly improved in 75% of patients and 30% had clearing of all treated lesions. Resiquimod also induced regression of untreated lesions. Ninety-two percent of patients had more than a 50% improvement in body surface area involvement by the modified Severity-Weighted Assessment Tool analysis and 2 patients experienced complete clearing of disease. Four of 5 patients with folliculotropic disease also improved significantly. Adverse effects were minor and largely skin limited. T-cell receptor sequencing and flow cytometry studies of T cells from treated lesions demonstrated decreased clonal malignant T cells in 90% of patients and complete eradication of malignant T cells in 30%. High responses were associated with recruitment and expansion of benign T-cell clones in treated skin, increased skin T-cell effector functions, and a trend toward increased natural killer cell functions. In patients with complete or near eradication of malignant T cells, residual clinical inflammation was associated with cytokine production by benign T cells. Fifty percent of patients had increased activation of circulating dendritic cells, consistent with a systemic response to therapy. In summary, topical resiquimod is safe and effective in early-stage CTCL and the first topical therapy to our knowledge that can induce clearance of untreated lesions and complete remissions in some patients. This trial was registered at www.clinicaltrials.gov as #NCT813320. [ABSTRACT FROM AUTHOR]

Abstract: Angiomatoid and desmoplastic Spitz nevi are rare histologic variants of Spitz nevi that present most frequently on the extremities of children and young adults. Although Spitz nevi are clinically heterogeneous, one presenting as a keloidal nodule has not been previously published. We present a case of an angiomatoid and desmoplastic Spitz nevus clinically akin to a keloid on an African‐American teenager and describe its unique histopathologic features. [ABSTRACT FROM AUTHOR]

Presents an abstract for the article on the gene expression of RNA for beta 3 integrin and CD9 antigen in malignant melanoma and melanocytic nevi.

Diffuse dermal angiomatosis ( DDA) represents a benign, acquired, reactive proliferation of vessels. DDA is clinically characterized by painful livedoid plaques with central ulceration, and the histopathologic hallmark is diffuse endothelial cell hyperplasia in the dermis. DDA has been rarely reported in association with calciphylaxis, a condition characterized by calcification of arterial walls with accompanying thrombosis and cutaneous necrosis. We present a case of a 72-year-old man with end-stage renal disease on peritoneal dialysis who presented with painful lesions on his legs, and was found to have DDA in the setting of calciphylaxis. The possible pathogenesis linking DDA and calciphylaxis is discussed. [ABSTRACT FROM AUTHOR]

Breast carcinoma remains one of the most common sources of skin metastases in women. Cutaneous breast carcinoma metastases have variable clinical and histopathologic presentations that can make diagnosis challenging. We report a unique case of metastatic breast carcinoma with prominent clear cell features, thus mimicking a xanthomatous process. Dermatopathologists should be aware of this entity given its resemblance to other clear cell infiltrates and neoplasms. [ABSTRACT FROM AUTHOR]

Tattooing for ornamental purposes is an ancient practice that remains popular in modern times. Tattoos are encountered by the dermatopathologist either as incidental findings on skin biopsies or because of complications specific to the tattoo. A range of neoplasms and inflammatory conditions are seen in association with tattoos, many of which may be attributed to hypersensitivity to tattoo inks. The composition of tattoo inks is highly variable, and inks can contain numerous potentially allergenic or carcinogenic compounds. Infections with bacterial, viral and fungal species can occur after tattooing, sometimes after substantial delay. Atypical mycobacterial infections in particular are increasingly reported; special stains for mycobacteria should be performed and cultures recommended particularly when dense, mixed or granulomatous infiltrates are present. [ABSTRACT FROM AUTHOR]

PEComas are mesenchymal neoplasms composed of perivascular epithelioid cells (PEC) and include a spectrum of tumors. PEComas and malignant melanoma share common morphological, immunohistochemical, and ultrastructural features, such as epithelioid cell morphology and melanocytic immunophenotype. Melanocytic markers commonly expressed in PEC tumors include HMB-45, Melan-A/MART-1, tyrosinase, microphthalmia transcription factor (MITF), and occasionally, S100. Given this morphological and immunophenotypical overlap, the differential diagnosis between a PEComa and malignant melanoma can represent a challenge. Additional diagnostic difficulty is the differentiation of melanoma and PEComa from clear cell sarcoma that is indistinguishable from melanoma based on the immunohistochemical profile. Recent studies have shown that MUM-1, a known lymphocyte marker shows positive immunostaining in nevi and melanomas, its expression in PEComas and clear cell sarcoma, however, has not been previously addressed. In this study, the authors analyzed MUM-1 expression using immunohistochemistry in PEComas (n = 8), the PEComa family members, angiomyolipomas (n = 13), and clear cell sarcomas (n = 11) and compared the staining pattern with malignant melanomas (n = 25), both primary (n = 14) and metastatic (n = 11). It was found that 92.3% of primary melanomas and 81.3% of metastatic melanomas were MUM-1 positive. In contrast, MUM-1 was only weakly positive in only 25% of PEComas and negative in all angiomyolipomas. MUM-1 expression was noted in 72.7% of clear cell sarcomas. The study demonstrated differential MUM-1 expression between PEComas and other true melanocytic tumors and suggested that the addition of MUM-1 to the usual panel of melanocyte markers could be a helpful adjunctive study to aid in the differential diagnosis between these entities. [ABSTRACT FROM PUBLISHER]

The article presents a study which investigates the differences in risk factors for early metastases (EM) and late metastases (LM) in melanoma patients at different time intervals following treatment. It says that the 34 clinical and tumor characteristics of melanoma patients involved in a case-control study were analyzed through multivariate analysis. Results confirmed several risk factors for metastases such as a history of skin cancer and increasing thickness of tumors.

The article presents a case study of a 57-year-old man with a history of diabetes mellitus and psoriasis who complaint of malaise, perianal papule and occasional bright red blood per rectum.

A letter to the editor is presented related to a case with cutaneous metastasis as part of patient's presentation of late recurrence synovial sarcoma.

A perineurioma is a benign peripheral nerve sheath neoplasm thought to be derived from cells of the perineurium, the cellular sheathing of peripheral nerve fascicles. The histological, immunohistochemical (positive for epithelial membrane antigen, collagen type IV, laminin and vimentin but not S-100 protein) and ultrastructural features of a perineurioma form the basis for diagnosis. Two types of perineuriomas are recognized, intraneural and soft tissue (extraneural) forms. Sclerosing perineurioma is considered a variant of the soft tissue perineurioma. In all but one of the reported cases, this subtype presented as a solitary clinical lesion with a predilection for the fingers and palms of young adults. In 2002, Huang and Sung described a 16-year-old boy with one sclerosing perineurioma on each hand. The unusual case presented herein is a 21-year-old woman manifesting more than 30 cutaneous sclerosing perineuriomas on the hands and arms. This case is the most extensive presentation of sclerosing perineuriomas documented to date and extends the clinical presentation spectrum of these lesions. [ABSTRACT FROM AUTHOR]

Angiomatoid Spitz nevus is a recently described subtype of desmoplastic Spitz nevus. Six cases have been described in the literature thus far. Here, we describe six additional cases of angiomatoid Spitz nevus and provide a review of the literature on this entity. The features of classic angiomatoid Spitz nevus are described in the context of important differential diagnostic considerations, particularly regressed malignant melanoma. [ABSTRACT FROM AUTHOR]