Search

Competing Interests: Dr Grichnik serves as a consultant for Galileo Group, Canfield Scientific and has previously received equipment and meeting support from Caliber Imaging and Diagnostics. Dr Correa-Selm served as speaker of Accutec Blades and was a consultant for Castle Biosciences. Authors Blumstein and Hanlon and Drs Chen and Elgart have no conflicts of interest to declare.

Histologically undetermined early acral melanoma in situ (HUAMIS) is rare but a diagnostic challenge, being clinically and dermoscopically MIS (late onset, a large size (>7 mm), parallel ridges pattern) but microscopically without recognizable cytological atypia. Cyclin D1 (CCND1) gene amplification is a genetic aberration occurring in the early radial growth phase of AMs and could thus help determine malignancy for this disease. We determine the value of CCND1 amplification by FISH as a diagnostic marker for HUAMIS. CCND1 amplification was examined in paraffin-embedded skin biopsies and excisions using a dual-probes fluorescence in situ hybridization (FISH) (11q13 and CEP11). One FISH-negative case 6 was additionally examined by Mypath Melanoma (qRT-PCR). Seventeen cases (12 dysplastic nevi, 3 AMIS, and 2 invasive AM) were served as negative controls for FISH. All six patients (4 females and 2 males) were Hispanic. Pigment lesions were on the left plantar foot (4), right third finger palm (1), and right thumb subungual (1). All cases showed similar clinical and dermoscopical characteristics, including late onset (50 to 74 years old), long duration (from 2 to 15 years), large-sized pigments (from 16 to 40 mm), and a parallel ridge pattern. Junctional melanocytes with no or minimal atypia from five cases showed CCND1 amplifications. Four of 5 cases were received 1st or/and 2nd wide excisions, which demonstrated foci of histologically overt MIS. One FISH-negative case 6 demonstrated "likely malignancy" scores (>2) by Mypath Melanoma (qRT-PCR). None of negative controls showed the amplification. We propose here a simple CCND1 FISH is a practical diagnostic test to determine the malignancy of the very early progression phase of AM preceding histopathologically defined MIS. Cases presented here could be an indolent subtype of AMIS characterized by carrying a long latent radial growth phase without vertical growth, mimicking lentigo maligna., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Blister beetles are a group of insects that include the Meloidae, Oedemeridae, and Staphylinidae families. The most well-known family, Meloidae, has more than 200 species known for causing a blistering dermatitis in humans by emitting the substance cantharidin, which has been pharmacologically used as a vesicant and can cause deleterious effects if ingested. Most recently, blister beetles have been studied for their anticancer properties.

Purpose: Blue nevus is a melanocytic tumor that is commonly found in the skin. Extracutaneous presentations, including the ocular surface, are rare. As such, the purpose of this study was to characterize the clinical features and clinical course of congenital melanocytic tumor (blue nevus) of the conjunctiva., Design: Retrospective, noncomparative case series., Participants: Twenty-one patients with 23 blue nevi of the ocular surface that were excised surgically between 2000 and 2016., Methods: Chart review of patients identified from a database search of the Florida Lions Ocular Pathology Laboratory records. Pathologic diagnoses were confirmed by 2 pathologists (S.R.D. and G.E.). All specimens were bleached and, tissue permitting, stained using SOX10 (MilliporeSigma, Darmstadt, Germany) and CD68 (Leica Biosystems, Nussloch, Germany)., Main Outcome Measures: Clinical characteristics, pathologic features, and clinical course., Results: Mean age of the population was 55±15 years; 71.4% (n = 15) were white and 57.1% (n = 12) were men. One patient had 3 lesions, for a total of 23 lesions examined. Clinically, 13 lesions were on the bulbar conjunctiva, 3 were on the tarsal conjunctiva, 3 were in the fornix, 2 were caruncular, 1 was episcleral, and 1 was at the limbus. Before excision, 8 patients were thought to have primary acquired melanosis, 4 with concern for primary conjunctival melanoma, and 1 thought to have metastatic disease from a plantar melanoma. Five lesions were thought to be benign, and in 8 patients, the lesions were identified incidentally after other ocular surgeries, with no diagnosis of the lesions before excision. Pathologic features were consistent with simple blue nevi in 21 lesions and cellular blue nevus in 2 lesions. No malignant transformations were noted in any patient over the mean 20.2-month follow-up period (range, 2 weeks-103 months)., Conclusions: Blue nevus is a rare deeply pigmented congenital melanocytic lesion with a benign clinical course that can appear clinically similar to primary acquired melanosis or melanoma., (Copyright © 2018 American Academy of Ophthalmology. All rights reserved.)

Background: Skin reactions to the sting of the imported fire ant have characteristic clinicopathological features., Methods: One case of experimental envenomation was prospectively followed during 48 hours, with biopsies. In addition, 6 cases from our laboratory were retrospectively evaluated histopathologically for the following features: spongiosis, exocytosis (and type of cells), pustule formation, erosion/ulceration, epidermal necrosis, scale/crust, papillary dermal edema, inflammatory dermal infiltrate (cell type, density, depth, distribution, shape), red blood cell extravasation, vasculopathy and vasculitis., Results: The typical lesion follows a very distinctive clinical and histopathologic evolution over 48 hours, with the formation of a subepidermal pustule overlying a wedge-shaped area of dermal collagen basophilic degeneration with scattered neutrophils. In the 6 cases retrieved from our files, the main features were a superficial and deep dermal, perivascular, periadnexal and interstitial infiltrate consisting of neutrophils, with basophilic degeneration of the collagen. A subepidermal pustule was noted in half of the cases., Conclusions: In biopsies taken in a clinical setting, even in the absence of the characteristic subepidermal pustule, the diagnosis of imported fire ant sting can be suspected if there is a superficial and deep perivascular, periadnexal and interstitial infiltrate composed of neutrophils, with some basophilic denaturation of collagen., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Fungal infection is a common clinical problem in dermatology. While most cases in practice are superficial infections, invasive subcutaneous mycoses are important to recognize and treat, as these conditions often have significant morbidity and mortality. Deep fungi demonstrate species-specific syndromes and may be identified by clinical and histological features in addition to serological evaluation and culture. Identification of the common innoculation subcutaneous mycoses, as well as those associated with pulmonary primary infection and dissemination to the skin is important, as treatments vary by organism and clinical setting. This overview will help to identify the key dermatological presentations of subcutaneous fungal infection, and the clues they give to cause.

Importance: Mutations driving melanoma growth have diagnostic, prognostic, and therapeutic implications. Traditional classification systems do not correlate optimally with underlying melanoma growth-promoting mutations. Our objective was to determine whether unique dermoscopic growth patterns directly correlate with driving mutations., Observations: We evaluated common driving mutations in 4 different dermoscopic patterns (rhomboidal, negative pigmented network, polygonal, and dark homogeneous streaks) of primary cutaneous melanomas; 3 melanomas per pattern were tested. Three of the 4 patterns lacked common mutations in BRAF, NRAS, KIT, GNAQ, and HRAS. One pattern, the dark homogeneous streaks pattern, had unique KIT mutations in the second catalytic domain of KIT in exon 17 for all 3 samples tested. Two tumors with the dark homogeneous streaks pattern turned out to be different primary melanomas from the same patient and had different sequence mutations but had an impact on the same KIT domain., Conclusions and Relevance: While future study is required, these results have multiple implications. (1) The underlying melanoma-driving mutations may give rise to specific dermoscopic growth patterns, (2) BRAF/NRAS mutations in early melanomas may not be as common as previously thought, and (3) patients may be predisposed to developing specific driving mutations giving rise to melanomas or nevi of similar growth patterns.

Pemphigus vulgaris is a life-threatening autoimmune blistering disease caused by anti-desmoglein IgG autoantibodies that finally lead to acantholysis presenting clinically as progressive blistering. Whilst the production of pathogenic antibodies is key to the development of pemphigus vulgaris, many immunological steps are required prior to autoantibody induction. We review advances in the understanding of these immunologic processes with a focus on human leucocyte antigen polymorphisms and antigen recognition, epitope spreading, central and peripheral tolerance, T helper differentiation, induction of pro- and anti-inflammatory cytokines and T-cell regulation of B cells. Targeting autoaggressive T cells as regulators and stimulators of B-cell antibody production should allow for more specific therapeutic immune interventions, avoiding the global immunosuppression seen with many commonly used immunosuppressants in pemphigus vulgaris., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Idiopathic atrophoderma of Pasini and Pierini is a disorder of dermal atrophy. There is a female predominance and almost never does the condition present at birth. Histopathological examination reveals attenuated dermis. We report a case of a healthy male born with a plaque of idiopathic atrophoderma of Pasini and Pierini.

Basal cell carcinomas (BCC) have a specialized microvasculature system that can be targeted by the 585-nm pulsed dye laser (PDL) utilizing the theory of selective photothermolysis. Seven volunteers with nine well-defined, biopsy-proven BCCs, were treated with the PDL (585-nm wavelength, a single 450-μs pulse, 7-mm spot size, and 9.0 J/cm(2) energy). The lesions, along with a 4-mm border of normal skin were treated. Pain assessment was carried out immediately after the laser treatment. A deep shave biopsy with histological examination occurred 4 weeks after the laser treatment. Pain was assessed on a scale of 0 (no pain) to 10 (worst pain possible). The average patient score was 2.1 (range 1-4). On histology, 5/9 (55.6%) sites demonstrated no evidence of BCC; however, 4/9 (44.4%) sites showed residual BCC. Although the PDL was able to clear over half of the BCCs in this study, there was an unacceptably high persistence rate of 44.4%. The PDL did not achieve the clearance rate that can be attained with current standard BCC treatment modalities. At this time, we do not recommend that a single treatment with the 585-nm PDL can be used as a primary therapy for BCC.

Alopecia areata (AA) is a common autoimmune disease characterized by non-scarring hair loss. Previous studies have demonstrated an association between AA and physiological/psychological stress. In this study, we investigated the effects of heat treatment, a physiological stress, on AA development in C3H/HeJ mice. Whereas this strain of mice are predisposed to AA at low incidence by 18 months of age, we observed a significant increase in the incidence of hair loss in heat-treated 8-month-old C3H/HeJ mice compared with sham-treated mice. Histological analysis detected mononuclear cell infiltration in anagen hair follicles, a characteristic of AA, in heat-treated mouse skin. As expected, increased expression of induced HSPA1A/B (formerly called HSP70i) was detected in skin samples from heat-treated mice. Importantly, increased HSPA1A/B expression was also detected in skin samples from C3H/HeJ mice that developed AA spontaneously. Our results suggest that induction of HSPA1A/B may precipitate the development of AA in C3H/HeJ mice. For future studies, the C3H/HeJ mice with heat treatment may prove a useful model to investigate stress response in AA.

More than 70 million surgical procedures are performed annually in the USA with the majority involving a skin lesion and almost all individuals in their lifetime will have one or more surgical procedures resulting in scars. Patients and physicians alike are thereby motivated to improve the cosmetic outcome of scars. Prior studies have shown that the pulsed dye laser (PDL) is effective in improving the quality and appearance of the scar when using the 585-nm PDL immediately after the removal of sutures. Most published studies used a pulse duration of 450 micros, which along with the other study parameters, has led to an overall improvement of the scars. However, a pulse duration of 1.5 ms is also available when using the pulsed dye laser and it should theoretically cause fewer side-effects. To our knowledge, there are no other studies comparing the effectiveness of different pulse durations in the treatment of surgical scars starting on the day of suture removal. The purpose of this study is to compare the effect of different pulse durations (450 micros vs. 1.5 ms) in the treatments of postsurgical linear scars immediately after suture removal when using the 585-nm pulsed dye laser (PDL). Twenty non-hospitalized male and female patients (older than 18 years of age) with skin types I-IV and with postoperative linear scars measuring at least 2.1 cm were enrolled in this prospective study. Scars were randomly divided into three equal sections. The different fields were randomly chosen to receive treatment (two out of three fields) or remain as control (one field). The two fields chosen to be treated received treatment with the 585-nm PDL using a 7-mm spot size at 4.0 J. One of the treated sections was randomly selected to receive a pulse duration of 450 micros, and the other section to receive a 1.5-ms pulse. The remaining scar section was designated as control (no treatment). The three sections were mapped and recorded. The patient received treatment immediately after the sutures were removed from the wound and then monthly for 3 months. Evaluations were performed before each treatment and 1 month after the last treatment. The short-pulse and long-pulse 585-nm PDL-treated sections demonstrated a statistically significant overall average improvement of the VSS of 92 and 89%, respectively, compared to 67% for the control site (Fig. 1). Further, for individual parameters of the Vancouver scar scale (VSS), there were significant (p < 0.05) differences between control and treatment groups for all parameters, but there were no differences between the short- and long-pulse treatment groups for any parameter. Both short-pulse and long-pulse PDL are safe and effective in improving the quality and cosmetic appearance of surgical scars in skin type's I-IV starting on the day of suture removal with no significant difference between the two pulse durations.

Unlabelled: The aim of this study was to compare the effects of the pulsed-dye laser (PDL) at a wavelength of 585 nm with those at 595 nm in the treatment of post-surgical scars, starting on the day of suture removal. The study was a prospective, non-randomized, double-blind, controlled, clinical trial, set in an outpatient clinic. Fifteen outpatients with 21 post-operative scars at least 3 cm long were recruited, and 14 patients with 19 scars completed the study. Scars were divided into three equal portions. Each outer portion was randomly allocated to PDL at 585 nm or at 595 nm (3.5 J/cm(2), 450 micros, 10 mm spot size), and the center was an untreated control; treatment was composed of three laser sessions at 4-week intervals. A blinded examiner evaluated the three scar sections using the Vancouver scar scale for pigmentation, vascularity, pliability, and height. Cosmetic appearance was evaluated with a visual analog scale. Punch biopsies of three randomly selected scars were evaluated. Pigmentation: more scars after laser treatments were of normal color than in the control, but the difference was not statistically significant. Vascularity: after treatment, more scars had normal vascularity in all three groups than at baseline (P < 0.05); the largest increase was with a wavelength of 585 nm (10.5-94.7%), then 595 nm (15.8-78.9%), then control (5.2-36.6%). Pliability: there was more normal pliability in all three groups than at baseline (P < 0.05), with greater improvements in the laser-treated groups. Height: significantly more flat scars after 585 nm PDL (63.2%) than at baseline (21.1%) (P < 0.05). We observed a slight but non-significant decrease in the scar heights with 595 nm PDL in comparison with the control., Histology: after laser irradiation, the treated sections were more similar to a non-scarring process than the control. Cosmetic outcome: visual analog scales increased in all groups (P < 0.05), but the greatest increases were observed in the 585 nm and 595 nm laser-treated groups (50% and 60%, respectively) compared with controls (30%). There were significantly higher scores with the lasers than for the control (P < 0.001) at each visit after baseline. Both the 585 nm and 595 nm PDL treatments were effective in improving the appearance and normalizing the vascularity and pliability of post-operative scars. Both wavelengths improved the scars' visual appearance more than controls. We found that 585 nm appears to be the preferred wavelength, as it substantially normalized the height in addition to the vascularity and pliability in a significant number of scars.

Objective: To examine the expression of candidate markers for micrometastasis., Study Design: Cross-sectional analysis of subjects with oral cavity carcinomas who underwent sentinel lymph node biopsy (SLNB) and subsequent immunohistochemical (IHC) analysis., Subjects and Methods: Two groups were identified based on SLNB status: negative SLNB (19/30) and positive SLNB (11/30). Specimens underwent IHC using conjugated monoclonal antibodies for membrane type-1 matrix metalloproteinase (MT1-MMP), CD44, focal adhesion kinase-1, and E-cadherin. Staining results were evaluated to determine if a particular marker was associated with SLNB status or other histopathologic prognosticators., Results: For MT1-MMP, 21 percent (3/14) of evaluable specimens stained positively in the SLNB(-) group and 67 percent (4/6) stained positively in the SLNB(+) group (P=0.12). No statistically significant association was seen between any marker's staining pattern and SLNB status alone. When MT1-MMP staining was evaluated in tumors with SLNB(+) or perineural invasion (PNI) present on histopathology, six of nine specimens (67%) stained positively for MT1-MMP, vs one of 11 (9%) in specimens lacking either negative prognosticator (P=0.016, RR=7.33)., Conclusion: Preliminary results suggest that MT1-MMP positivity in primary tumor specimens may identify aggressive tumor types, evidenced by the presence of micrometastasis or PNI.

Excessive scar formation in keloids points to altered tissue modeling and repair mechanisms. Dysregulation of cytokine and apoptotic cascades and their downstream signaling pathways might have a role in keloid development. Total RNA was isolated from biopsied keloidal tissue and adjacent normal skin of black patients, white patient's scars, and normal skin of black and white patients, with normal wound healing. Apoptosis, cytokine and NFkB pathway microarrays were used to study and compare gene expression levels. Real-time PCR was used to verify microarray results in original samples and a separate, validation-set of samples. Significant differences were observed in the expression levels of members of caspase, cytokines and MAP kinase pathways, between the normal skin of keloid-prone and normal skin of keloid-resistant patients. Specifically, expression of caspase 6, and caspase 14 genes were different between normal skin of keloid-prone individuals and normal skin of keloid-resistant patients. Our results suggest that normal skin of keloid-prone individuals constitutively expresses a distinct gene profile which might contribute to their susceptibility to develop keloids.

A number of non-invasive approaches have been developed over the years to provide an objective means of evaluating and diagnosing skin melanoma. However, the current gold-standard in melanoma diagnosis is the examination of a skin lesion by the trained eye of a physician followed by histological examination of an invasive excisional biopsy of the skin specimen. Diagnosis of melanoma by simple visual examination is incorrect in almost 1 out of every 3 melanoma diagnoses. Therefore, the diagnosis of early stage in-depth melanoma by non-invasive methods remains an active area of research. Recent advancements in computer and digital technology have provided several sensitive tools to evaluate the different characteristics of a melanoma lesion including its contour, edge, color, size, depth, and/or elevation. These tools include (1) digital imaging systems and computer analysis instruments such as MoleMax, SIAscope, SolarScan, MelaFind; (2) tape stripping mRNA; (3) laser-based technology such as Confocal scanning laser microscopy (CSLM), optical coherence tomography (OCT), laser Doppler perfusion imaging (LDPI), (4) Ultrasonography, and (5) other imaging tools such as electrical bio-impedance, MRI and PET scan. The ultimate goal of all investigational instrumentation is the prevention of unnecessary biopsies and a decrease in the prevalence and morbidity associated with malignant melanoma.

Alopecia (hair loss) is experienced by thousands of cancer patients every year. Substantial-to-severe alopecia is induced by anthracyclines (e.g., adriamycin), taxanes (e.g., taxol), alkylating compounds (e.g., cyclophosphamide), and the topisomerase inhibitor etoposide, agents that are widely used in the treatment of leukemias and breast, lung, ovarian, and bladder cancers. Currently, no treatment appears to be generally effective in reliably preventing this secondary effect of chemotherapy. We observed in experiments using different rodent models that localized administration of heat or subcutaneous/intradermal injection of geldanamycin or 17-(allylamino)-17-demethoxygeldanamycin induced a stress protein response in hair follicles and effectively prevented alopecia from adriamycin, cyclophosphamide, taxol, and etoposide. Model tumor therapy experiments support the presumption that such localized hair-saving treatment does not negatively affect chemotherapy efficacy.

Merkel cell carcinoma (MCC) is a rare and extremely aggressive skin cancer that arises from primary neural cells. It presents most commonly in the elderly and immunocompromised patients. Pathologically, MCC should be distinguished from extrapulmonary small cell lung cancer or metastatic small cell lung cancer or a small cell variant of melanoma. The prognosis is based largely on the stage of disease at the time of presentation. Therapeutic options for MCC include wide resection with or without adjuvant radiotherapy or chemotherapy. Novel therapies based on the understanding of the molecular aspects of MCC are currently being explored.

Context: Dermatofibroma is a benign fibrohistiocytic tumor composed of a mixture of fibroblastic and histiocytic cells. The diagnosis of this tumor is generally uncomplicated; however, rare variants may be difficult to distinguish from malignant fibrohistiocytic tumors. Deep penetrating dermatofibroma may be difficult to distinguish from dermatofibrosarcoma protuberans, and pseudosarcomatous dermatofibroma and dermatofibroma with monster giant cells share morphologic similarities with malignant fibrous histiocytoma and atypical fibroxanthoma., Objective: To find an immunohistochemical marker or markers that differentiate between fibrohistiocytic lesions of skin., Design: We evaluated the immunophenotypic characteristics of 83 fibrohistiocytic tumors (36 typical dermatofibromas, 16 cases of dermatofibrosarcoma protuberans, 16 malignant fibrous histiocytomas, and 15 atypical fibroxanthomas) using antibodies against MIB-1 (Ki-67), factor XIIIa, CD34 (HPCA-1), HHF35 (muscle-specific actin), 1A4 (smooth muscle actin), cytokeratin (AE1/AE3, CAM 5.2, and 34betaE12), S100 protein, and desmin., Results: A high proliferative index detected by MIB-1 staining excluded the possibility of dermatofibroma and was diagnostically useful in separating this entity from dermatofibrosarcoma protuberans, malignant fibrous histiocytoma, and atypical fibroxanthoma. A low proliferative index, however, could not differentiate dermatofibroma from dermatofibrosarcoma protuberans. Factor XIIIa reactivity was not helpful for the diagnosis of dermatofibroma, whereas CD34 reactivity was statistically significant in the diagnosis of dermatofibrosarcoma protuberans. The sensitivity of these 2 markers is low and therefore of questionable practical diagnostic value., Conclusion: Evaluation of the proliferative index may further assist in distinguishing dermatofibroma from dermatofibrosarcoma protuberans, atypical fibroxanthoma, and malignant fibrous histiocytoma.

Necrobiotic xanthogranuloma (NXG) is a disorder characterized by indurated, yellow-red nodules or plaques, primarily involving the face and, less frequently, the trunk and extremities. NXG may be associated with paraproteinemia, multiple myeloma, and hypertension. Histologically, xanthogranulomatous features with hyaline necrosis or necrobiosis are present. No first-line treatment has been established. This disease is a chronic process, and a patient's prognosis depends on the degree of extracutaneous involvement and the presence of visceral malignancies. We describe a patient with typical cutaneous and histologic findings of NXG with an associated monoclonal gammopathy.