Melanocytic Hyperplasia Research Articles

Significance of the preferentially expressed antigen in melanoma in discriminating the conjunctival malignant melanoma and pigmented nevus

Objective: To investigate the significance of the preferentially expressed antigen in melanoma (PRAME) in the differential diagnosis of the conjunctival malignant melanoma and pigmented nevus. Methods: Specimens from 86 patients with conjunctival malignant melanoma (42 males and 44 females, aged 18 to 84 years) and 86 patients with conjunctival pigmented nevus (47 males and 39 females, aged 1 to 82 years) were collected at Zhongshan Ophthalmic Center, Sun Yat-sen University from January 2017 to July 2024. Immunohistology was performed to detect the PRAME expression. The difference of PRAME expression in the two kinds of conjunctival melanocyte hyperplasia lesions and the correlation of PRAME expression with clinical stages of the conjunctival malignant melanoma (T1 to T4) were analyzed. Results: Most patients with malignant melanoma had a positive PRAME expression (89.53%, 77/86), while only 1 patient with pigmented nevus showed a positive PRAME expression (1.16%, 1/86). The positive expression rate of the PRAME in conjunctival malignant melanoma tissues was significantly higher than that in conjunctival pigmented nevi (P<0.05). The PRAME had a sensitivity and specificity of 89.53% and 98.84%, respectively. The expression of the PRAME among patients with conjunctival malignant melanoma in different age groups (>50, 30 to 50, <30) was significantly different (P<0.05). However, the PRAME expression had no difference in different clinical stages of the conjunctival malignant melanoma (P>0.05). Conclusions: The PRAME has significance in discriminating the conjunctival malignant melanoma and pigmented nevus. It is a useful biomarker in the diagnosis of conjunctival malignant melanoma.

Oral melanoacanthoma: A new entity in 2022 WHO

: To highlight the occurrence of Melanoacanthoma in oral cavity. Melanoacanthoma of the oral cavity is rare benign reactive pigmented lesion. It has been recently considered as a distinct entity in the World Health Organization (WHO) classification. Oral melanoacanthomas are reactive and not related to seborrheic keratosis unlike their cutaneous counterparts which are variant of pigmented seborrheic neoplastic in nature. These lesions are characterized by hyperplasia of dendritic melanocytes dispersed throughout an acanthotic epithelium with buccal mucosa being the most common location. An 81-year-old female presented to us with complaint of blackish patch on hard palate. The patient underwent biopsy and the histopathological diagnosis of Melanoacanthoma was given. To the best of our knowledge this is first such case of Melanoacanthoma on the hard palate in Indian subcontinent. : Awareness about these lesions is important for apt diagnosis and preventing under diagnosis.

Intra-operative dermoscopy (onychoscopy) of the nail unit-A systematic review.

Dermoscopy of the nail unit (onychoscopy) is a method which allows for non-invasive observation of the nail structures, increasing the accuracy of clinical diagnosis. Currently, it is used in evaluation of both inflammatory and neoplastic conditions of the nail unit. However, in contrast to the skin, the anatomy of the nail unit prevents direct observation of nail bed or nail matrix structure during classic onychoscopy. Intra-operative onychoscopy is a variant of the technique which uses direct visualization of the nail unit structures after nail plate avulsion. The aim of this systematic review was to summarize the current state of knowledge on intra-operative onychoscopy. The MEDLINE, EMBASE and Cochrane databases were systematically searched in January 2024. All types of study designs assessing intra-operative dermoscopy of the nail unit were included in this study. The risk of bias in included studies was assessed using the Joanna Briggs Institute critical appraisal tools. The qualitative synthesis of 19 studies totalling a number of 218 cases in 217 patients included the following entities: melanoma, nevus, hypermelanosis (melanocytic activation), melanocytic hyperplasia, melanophages accumulation, squamous cell carcinoma, glomus tumour, lichen planus, onychomatricoma, onychomycosis and subungual exostosis. The main limitation of the study was a relatively low number of identified studies, most with low levels of evidence. Intra-operative onychoscopy does not replace histologic examination, though it may be useful in determining the modality of surgical diagnostic procedures.

A Rare Case of Diffuse Neurofibroma Mimicking as Hairy Naevus or Vascular Malformation: A Surgeon’s Perspective

Nevi are areas of melanocytic hyperplasia or neoplasia. These collections can be found in the epidermis, partially in the dermis, or completely within the dermis. They commonly develop in childhood and young adulthood and sometimes spontaneously regress. Exposure to Ultraviolet (UV) radiation is associated with increased density of these lesions. In contrast, neurofibromas are benign proliferations made up of all nerve elements and arise as fleshy and non tender, sessile, or pedunculated masses on the skin. They can arise sporadically or in association with type 1 Neurofibromatosis (NF), and in these cases, are associated with café-au-lait spots and Lisch nodules. In the present report, authors present a case diagnosed clinically as a giant naevus on the dorsum of the right hand in an adult patient (26-year-old female) with no other associated secondary swellings elsewhere in the body. However, further radiological investigations revealed a case of vascular malformation. Postoperatively, histopathological examination showed features of diffuse neurofibroma. The present case report enables the surgeon to consider various rare differential diagnosis for swelling in the extremities, even when it is not reflected in the clinical or radiological findings. Thus, a detailed history, physical examination, and various diagnostic tests, keeping in mind all possible differential diagnosis, should be performed.

Understanding the anatomy of dermoscopy of melanocytic skin tumours: Correlation invivo with line-field optical coherence tomography.

Early melanoma detection is the main factor affecting prognosis and survival. For that reason, non-invasive technologies have been developed to provide a more accurate diagnosis. Recently, line-field confocal optical coherence tomography (LC-OCT) was developed to provide an invivo, imaging device, with deep penetration and cellular resolution in three dimensions. Combining the advantages of conventional OCT and reflectance confocal microscopy, this tool seems to be particularly suitable for melanocytic lesions. The objective of this study was to identify and describe the correlation between specific dermoscopic criteria and LC-OCT features in three dimensions associated with melanocytic lesions. Dermoscopic and LC-OCT images of 126 melanocytic lesions were acquired in three different centres. The following dermoscopic criteria have been considered: reticular pattern, dots and globules, structureless areas, blue-whitish veil, regression structures, negative network, homogeneous pattern, streaks and blotches. 69 (55%) benign and 57 (45%) malignant lesions were analysed. A regular reticular pattern was found associated in the 75% of the cases with the presence of elongated rete ridges with pigmented cells along the basal layer, while atypical reticular pattern showed an irregular organization of rete ridges with melanocytic hyperplasia, broadened and fused ridges and elongated nests. Both typical and atypical dots and globules were found associated with melanocytic nests in the dermis or at the dermoepidermal junction (DEJ), as well as with keratin cysts/pseudocysts. Grey globules corresponded to the presence of melanin-containing dermal inflammatory cells (melanophages) within the papillae. Structureless brown/black areas correlated with alterations of the DEJ. We observed the same DEJ alterations, but with the presence of dermal melanophages, in 36% of the cases of blue/white/grey structureless areas. A description of each LC-OCT/dermoscopy correlation was made. LC-OCT permitted for the first time to perform an invivo, 3D correlation between dermoscopic criteria and pathological-like features of melanocytic lesions.

Report of Incidental Vulvar Malignant Melanoma Upon Dermatologic Evaluation for Vaginal Cyst

BACKGROUND: Vulvar malignant melanoma is a rare, often aggressive and recurring disease with a poorly understood prognosis. Here, we describe a patient with a longstanding vaginal cyst who was diagnosed with vulvar malignant melanoma upon a dermatologic evaluation. THE CASE: Our patient, a 53-year-old female, with a family history of a father with malignant melanoma presented for evaluation of a vaginal cyst present for over 20 years on her right labia that had become painful and began draining over the past year. She was seen twice at urgent care and was treated with oral antibiotics (unspecified) and referred to dermatology. A comprehensive dermatologic evaluation of the epidermal inclusion cyst in the right labia majora incidentally revealed a neoplasm of uncertain behavior in the right labia minora suspected for vulvar malignant melanoma (Figure 1). Shave biopsy of her right labia minora revealed a Stage 1B malignant melanoma, superficial spreading type, with a 1.1 mm depth of invasion (Breslow thickness) and 11 per 1mm2 mitotic count. Right partial radical vulvectomy and bilateral inguinal sentinel lymph node biopsies were performed. Pathology showed malignant melanoma with negative margins and negative nodes. Treatment and excision for her vaginal cyst was not initiated as her symptoms were not bothersome at the time of visit. She presented with a post-operative infection after 2 weeks which was suggestive of bilateral inguinal vulval acute cellulitis with no definitive abscess upon computed tomography (CT) scan. She was initially treated with vancomycin with additional piperacillin/tazobactam for a total of three days. Trimethoprim/sulfamethoxazole was later initiated for 14 days. Medical oncology referral for evaluation of metastasis revealed normal positron emission tomography-computed tomography scan. Notably, the patient had extensive confluent/atypical lentiginous basal melanocytic hyperplasia at the periphery which could not be distinguished from melanoma in situ. Upon tumor board consultation, scouting biopsies of her left labia majora were performed. Pathology showed melanocytic hyperplasia instead of residual malignant melanoma at the periphery. The patient now follows up every few months with dermatology and medical oncology. CONCLUSION: Given the often fast, aggressive spread of vulvar malignant melanoma, timely dermatologic evaluations are necessary. Among those at higher risk due to a personal or family history of malignant melanoma, regular total body skin cancer screenings are indicated. Further, the sensitive and typically sun-protected location of a vulvar malignant melanoma might preclude a dermatologic evaluation in this area and highlights the need for more comprehensive vaginal screenings and better communication between dermatologic and gynecologic medical care teams.

Margin status in vulvovaginal melanoma: Management and oncologic outcomes of 50 cases

ObjectivesTo determine the influence of margin status, including preinvasive disease at the margin, on local recurrence and overall survival (OS) in patients with vulvovaginal melanoma. MethodsAll patients with Stage 0-III vulvovaginal melanoma treated with primary surgical management between 1/2010–12/2019 were included. Margin status was categorized as negative, preinvasive disease (atypical junctional melanocytic hyperplasia and melanoma in situ), and invasive melanoma. Kaplan-Meier analyses were performed for local progression free survival (PFS) and OS. The impact of clinical and pathologic factors on local PFS and OS were assessed with Cox-regression analyses. ResultsFifty patients with a median follow-up of 48 months (range 3–119) were included. The median age was 63 years (range 20–83). Twenty percent (N = 10) had Stage 0 disease, 18% (N = 9) had Stage I, 46% (N = 23) had Stage II, and 16% (N = 8) had Stage III. Forty-four percent (N = 22) of patients had negative surgical margins, 46% (N = 23) had preinvasive disease at the margins, and 10% (N = 5) had invasive melanoma at the margins. The 5-year local PFS was 63% (95% CI: 42–78%) and OS was 60% (95% CI: 42–74%). Age, Breslow depth, stage, margin status, and re-resection did not significantly impact local PFS. In patients with preinvasive disease at the margin, all who recurred locally had Stage I-II disease. ConclusionPreinvasive disease at the surgical margins may play an important role in local recurrence in patients with Stage I-II vulvovaginal melanoma. Patients with early (Stage 0) and advanced (Stage III) disease rarely recur locally and may not benefit from re-resection.

Treatment of Benign Melanocytic Hyperplasia of Nail Apparatus with Dr. Hoon Hur’s Golden Parameter Therapy

Background: Benign melanocytic hyperplasia (BMH) of nail apparatus may be caused by a lentigine in the nail matrix. Traditional treatment modalities including surgical excision and CO2 laser ablation may cause a severe scar of nail apparatus.There is no clear treatment for BMH of nail apparatus. Objectives: This study was performed to investigate the efficacy and safety of Dr. Hoon Hur’s Golden Paramter Therapy (GPT) with a high fluence 1064nm Q-switched Nd:YAG laser (QSNL) for treating BMH of nail apparatus . Study design: The medical records of 52 Korean patients (age range: 21 to 60 year-old, mean age: 38.6 year-old) diagnosed with BMH of nail apparatus were reviewed retrospectively. Methods: All patients were treated with a 1064nm QSNL, on a weekly basis for 10-15 treatment sessions of Dr. HoonHur’s GPT. The parameters were a spot size of 7mm, a fluence of 2.2J/cm² and a pulse rate of 10Hz with three passes by a sliding technique (sliding GPT) and one pass by a pulse stacking technique (pulse-stacking GPT) over the BMH of nail apparatus. Results: At the time of the final treatment, all patients with BMH showed the complete removal of pigmented lesions without any side effects, such as purpura, crust, post-inflammatory hyperpigmentation (PIH), nail dystrophy and scarring. No recurrences were observed in any of the patients after a follow-up of 3-12 months. Conclusion: We suggest that Dr. Hoon Hur’s GPT with a high fluence 1064nm QSNL is a safe and effective new treatment for BMH of nail apparatus without side effects and recurrences. Keywords: Benign Melanocytic Hyperplasia; Nail;1064-nm ND:YAG laser;Dr. Hoon Hur’s GPT

Atypical Melanocytic Matricoma: A Case Report with Molecular Studies.

Melanocytic matricoma is a rare benign pilar tumor characterized by matrical differentiation and interspersed dendritic melanocytes. It may show cellular atypia and brisk mitotic activity. Histological characterization of some lesions may be difficult. In addition, because the reported cases are few and have limited follow-up, there is insufficient experience to define outcome-based criteria for malignancy. Some cases of melanocytic matricoma with more prominent atypia have been reported as malignant, but their clinical behavior is uncertain. We present a melanocytic matricoma with interspersed benign dendritic melanocytes, but moderate basaloid atypia, focally brisk mitotic activity, and atypical mitoses. Despite the apparently good delimitation of this tumor, higher magnification revealed a slightly irregular border. However, overt malignant features such as necrosis, frank asymmetry, deep infiltration, and ulceration were not present. This tumor showed a complex aberrant genomic profile with multiple whole chromosomes or chromosomal arms, losses, and duplications. The tumor mutational burden was high. A loss-of-function alteration in CDKN2A and a loss-of-function mutation in TP53 were also present. This unexpected molecular profile contrasts with the relatively bland histology of the tumor and is in line with the difficulties in microscopic differential diagnosis between melanocytic matricoma and an indolent malignant pilomatrical tumor. We suggest that molecular studies and longer follow-up periods may help to further understand and more precisely categorize borderline pilomatrical tumors with melanocytic hyperplasia.

Clinical Features and Histopathologic Examination of Lentiginosis Profusa in a Dog

An 5-year-old Yorkshire Terrier dog was presented due to a gradually developing hyperpigmented spot at the ventral abdomen, around lips, interdigital space and paws. The skin lesions appeared 2 years ago and gradually increased the numbers. The skin condition was generally dry on presentation, and several hyperpigmented macules and patches were detected. Except for the hyperpigmented skin lesions, other physical examinations and dermatological examination results were non-remarkable. Based on the history and clinical examination results, the genetic dermatological disease, lentigo was highly suspected. Skin biopsy and histopathologic examination were performed to rule out other pigmentary skin disease including tumor. The histopathologic examination revealed epidermal hyperplasia, melanocytic hyperplasia and hyperkeratosis. The dermatologic signs and histopathologic results were compatible with lentiginosis profusa. Canine lentiginosis profusa predominantly occurs in mature dogs and is generally considered a benign condition. While it is primarily a cosmetic concern, it is essential to distinguish it from other hyperpigmentation-related diseases.

A rapidly-growing erythematous nodule on the right upper neck

A rapidly-growing erythematous nodule on the right upper neck

The anatomical distribution of lentiginous melanoma (lentigo maligna and lentigo maligna melanoma): Differences according to sex.

The anatomical distribution of lentiginous melanoma (lentigo maligna and lentigo maligna melanoma): Differences according to sex.

Melanocytic Matricoma With Atypical Histopathological Features: A Case Report of an Extremely Rare Entity and Review of the Literature.

Melanocytic matricoma with atypical features is a rare, biphasic adnexal neoplasm displaying hair matrix differentiation, with only 3 reported cases worldwide. Generally, the lesion comprised a solid matrical and supramatrical cell proliferation, admixed with intermediate cell aggregates with sparse anucleated "shadow cells" and a prominent pigmented melanocytic hyperplasia. We report the case of a 78-year-old man with a slow-growing crusted lesion on the frontal left scalp, which in a matter of 1-2 months became a 0.6 cm well-defined, black purplish exophytic nodule. Histopathologically, the lesion presented a well-circumscribed border with a nodular dermal growth pattern, presenting different architectural features varying from benign pilomatricoma-like changes to atypical features such as moderate-to-high nuclear pleomorphism in both basaloid (matrical/supramatrical) and epidermal (keratinous) components. Strong nuclear and cytoplasmic positivity for β-catenin was observed in matrical cells, whereas prominent cytoplasmic membrane positivity for Melan-A in dendritic melanocytes. Owing to the evidence of atypical cytological features, we propose the "atypical/borderline" category of melanocytic matricoma as part of a possible spectrum among matrical neoplasms. Pathologists should be aware of any atypical histopathological features while reporting cases due to their potential malignant transformation.

Dendritic Melanocytic Hyperplasia in Pterygia: A Potential Source of Diagnostic Confusion with Primary Acquired Melanosis

Introduction: The aim of this study was to report the nearly ubiquitous prevalence of melanocytic hyperplasia in benign pterygia/pingueculae and establish that the entity is insufficiently recognized. Methods: This is a retrospective immunohistochemical pathology case series of 30 consecutive pterygia/pingueculae samples selected from an ophthalmic pathology database at a single institution. Histopathologic and immunohistochemistry analyses with anti-SOX-10 and anti-MART-1 antibodies were used for identifying melanocytes. The number of squamous cells intervening between melanocytes was determined. Results: The frequency of dendritic melanocytes was found to meet the criteria for dendritic melanocytic hyperplasia in 29 of 30 pterygia/pingueculae samples using specific antibodies. Melanocytes were found in several patterns: diffuse (28%), multifocal (28%), and focal (44%). In each case, the melanocytes were distributed as single melanocytes at the base; clusters of melanocytes were seen in 17% of samples. There were an average of about two intervening epithelial cells between melanocytes at the base. Conclusion: When diagnosed with immunohistochemistry, dendritic melanocytic hyperplasia is nearly ubiquitous in pterygia and pingueculae. Melanocytic hyperplasia may have a distribution that includes nests and single melanocytes above the basal layer, which can be confused with forms of primary acquired melanosis. It is important for pathologists to recognize these lesions as a distinct benign clinicopathologic entity.

Genomic Profiling of Lentigo Maligna within an Interim Registry Analysis​

Background: Pigmented lesion analysis remains a challenging aspect of dermatology. The DermTech Melanoma Test (‘the test’) is a non-invasive genomic test designed to rule-out melanoma. It consists of the pigmented lesion assay, which detects RNA products of Long Intergenic Non-Coding RNA 00518 (LINC00518) and Preferentially Expressed Antigen in Melanoma (PRAME), and an add-on assay for DNA promoter mutations in telomerase reverse transcriptase (TERT). In previous studies, the test was found to have a negative predictive value ≥99%. This interim analysis of a registry study examines the genomic patterns of the Lentigo Maligna (LM) subtype of melanoma. Methods: Between April 2021 and March 2022, multiple geographically diverse sites throughout the US submitted data to a registry to assess real-world use of the test. Approximately 8,000 clinically atypical lesions were tested. After receiving the test result, providers followed their clinical judgement for biopsy decision. Histopathologic diagnoses for biopsied lesions were correlated with test results and all melanomas were sorted into LM subtype vs non-LM subtype. In addition, lesions that were noted to be on sun exposed skin and/or noted to have solar elastosis and called atypical melanocytic hyperplasia were included. Results: At the 1-year mark of the registry, there were roughly 8000 unique entries. Of those, 1003 expressed one or more genomic markers from the DMT and had records available, and 134 (13.2%) were found to be melanoma or melanoma in-situ. More than a third (n=46, 34.3%) of the melanomas were of the Lentigo Maligna sub-type, with 7 of those being Lentigo Maligna Melanoma (LMM). Seven additional lesions were called atypical junctional melanocytic hyperplasia (AJMH) on sun-damaged skin. This group of 53 LM, LMM, and AJMH lesions were all evaluated for correlations to the DMT markers. LINC was the most commonly expressed genomic marker (n=45, 84.9%), with PRAME (n=36, 67.9%) and TERT (n=24, 45.3%) following. Most invasive tumors (LMM) expressed all three markers (n=4) and all 7 expressed LINC. Conclusion: While the original validation study included the LM subtype, this interim registry analysis demonstrates real-world use of the DMT in assessing pigmented macules concerning for LM. Over 1/3 of the melanomas reported in the registry were LM subtypes. LINC had a higher correlation with the lentigo maligna subtype of melanoma and was present in all invasive tumors. While AJMH is considered borderline, it may be worthwhile in the clinical context to group AJMH lesions with LM due to similarities in treatment.

Follicular colonization in melanocytic nevi and melanoma: A literature review.

The lentiginous spread of melanocytes into the hair follicle can be observed in a number of benign melanocytic neoplasms such as in nevi but also in sun-induced melanocytic hyperplasia and melanoma. The follicular colonization by melanocytes in melanoma is classified into three distinct patterns: primary follicular melanoma, melanoma with folliculotropism, and invasive melanoma arising from melanoma in situ with folliculotropism. The role of follicular colonization in melanoma pathologic staging is still a matter of debate though the description of the latter has been recommended by the International Collaboration on Cancer Reporting. In this review, we will discuss the role of follicular colonization in melanoma and melanocytic nevi as well as the facts and controversies regarding this topic.

Computer-Aided Diagnosis of Melanoma Subtypes Using Reflectance Confocal Images.

Lentigo maligna (LM) is an early form of pre-invasive melanoma that predominantly affects sun-exposed areas such as the face. LM is highly treatable when identified early but has an ill-defined clinical border and a high rate of recurrence. Atypical intraepidermal melanocytic proliferation (AIMP), also known as atypical melanocytic hyperplasia (AMH), is a histological description that indicates melanocytic proliferation with uncertain malignant potential. Clinically and histologically, AIMP can be difficult to distinguish from LM, and indeed AIMP may, in some cases, progress to LM. The early diagnosis and distinction of LM from AIMP are important since LM requires a definitive treatment. Reflectance confocal microscopy (RCM) is an imaging technique often used to investigate these lesions non-invasively, without biopsy. However, RCM equipment is often not readily available, nor is the associated expertise for RCM image interpretation easy to find. Here, we implemented a machine learning classifier using popular convolutional neural network (CNN) architectures and demonstrated that it could correctly classify lesions between LM and AIMP on biopsy-confirmed RCM image stacks. We identified local z-projection (LZP) as a recent fast approach for projecting a 3D image into 2D while preserving information and achieved high-accuracy machine classification with minimal computational requirements.

Determining the Association Between Melanomas and Fields of Melanocytic Dysplasia.

Some have proposed that melanomas in situ may be associated with fields of melanocytic dysplasia, particularly on sun-damaged skin, whereas others maintain that the atypical junctional melanocytic hyperplasia (MH) at the periphery of melanomas is simply background junctional MH of sun-damaged skin. The biological potential of atypical junctional MH at the periphery of melanomas is uncertain. We examined whether atypical junctional MH was intrinsic to the melanoma itself (ie, melanoma-associated field of melanocytic dysplasia) or was simply the predictable junctional MH associated with long-standing sun exposure. We retrospectively compared 106 cutaneous melanoma excisions without residual tumor with 105 nonmelanoma cutaneous tumor excisions (ie, basal cell or squamous cell carcinomas) without residual tumor. MH with atypia occurred significantly more frequently in melanoma than in nonmelanoma cutaneous tumor excisions (55.7% vs. 24.8%, P < 0.001). Solar elastosis occurred significantly less frequently in melanoma than in nonmelanoma cutaneous tumor excisions; 33.0% of melanoma excisions and 8.6% of nonmelanoma excision samples exhibited no solar elastosis, respectively (P < 0.001). After controlling for solar elastosis using multivariable linear regression, the association between MH with atypia and melanoma excisions remained significant (P < 0.001). Our results, therefore, demonstrate that melanomas were associated with atypical junctional MH that could not solely be accounted for by the extent of sun damage as measured by solar elastosis.

Staged Excision of Lentigo Maligna of the Head and Neck: Assessing Surgical Excision Margins With Melan A, SOX10, and PRAME Immunohistochemistry.

Staged excision has emerged as a superior treatment option for lentigo maligna (LM) of the head and neck when compared with conventional wide local excision. Assessing surgical excision margins for remaining LM poses a diagnostic challenge. To determine whether immunohistochemical (IHC) staining with SOX10 and preferentially expressed antigen in melanoma (PRAME) aids in diagnosing LM on excision margins compared with conventional hematoxylin and eosin and Melan A IHC staining. This study included cases of LM of the head and neck treated with staged excision. Histological findings were reviewed according to standard criteria for the diagnosis of LM and compared with the results after IHC staining for Melan A, SOX10, and PRAME. The cohort consisted of 35 sections. Based on hematoxylin and eosin and Melan A IHC staining, 23 sections were diagnosed as LM by the initial pathologist. Further staining with SOX10 IHC showed only 8 to be consistent with a diagnosis of LM and 9 revealing features of actinic melanocyte hyperplasia. PRAME was positive in 5 of the 8 cases of LM and negative in all 9 cases of actinic melanocyte hyperplasia (P = 0.009). The presence of melanocyte nests (P = 0.29) and pagetoid spread (P = 0.003) was the most reliable histological findings distinguishing LM from its mimics. SOX10 is a more specific and sensitive marker for melanocytes when assessing for LM on excision margins compared with Melan A. The addition of PRAME can be useful to confirm or exclude the diagnosis in challenging cases.

Zinc transporter Slc30a1 regulates melanocyte development by interacting with mt2 in zebrafish

The essential trace element zinc is involved in multiple biological processes including development and metabolism, while its role in melanocyte formation is still unclear. Slc30a1a and Slc30a1b are zinc exporters in zebrafish. Here, we found that melanocytes were increased in slc30a1a and slc30a1b double mutant zebrafish. SMART-seq data revealed that genes involved in the melanoma pathway and the gene mt2, which encodes zinc-binding protein, were significantly upregulated in the mutants. In addition, the expression of mt2 was specifically increased in mutant melanocytes, as detected by in situ hybridization, suggesting an essential role of this gene in the tissue. Mechanistically, we demonstrated that elevated zinc levels resulting from Slc30a1 deficiency promoted melanocyte proliferation and that mt2 played a protective role in the process of Slc30a1/zinc-mediated melanocyte hyperplasia. This study uncovered the critical function of Slc30a1-mediated zinc homeostasis in melanocyte development and suggests that accumulated zinc in melanocytes would be a risk for inducing melanoma and that mt2 is a potential target for controlling diseases related to abnormal melanocyte development.