Spitz Nevi Research Articles

Primum non nocere: MelTUMP.

The majority of melanocytic lesions can be diagnosed clinically, dermoscopically and by histology. Yet, dermato-pathologists and clinicians may face tumours that cannot be classified as bona fide benign or malignant. The World Health Organization Classification of Skin Tumours recognized this dilemma and included the term MelTUMP and melanocytoma to account for melanocytic tumours with ambiguous morphology, architecture, and cytology.1 Similar to challenges with their clinical and histologic classification, it is hard to predict the biological behaviour of MelTUMPs at the time of diagnosis. For the most part, however, they rarely cause distant metastasis and death. Nonetheless, lymph node involvement is not uncommon. This may sound like a contradiction, but actually reflects the same dilemma present in diagnosing such tumours: they are neither unequivocally good nor bad. Many terms have been introduced to reflect this grey zone in terms of diagnosis and course of the disease: MelTUMP (melanocytic tumour of uncertain malignant potential), PEM (pigmented epithelioid melanocytoma), ATM (animal type melanoma), AST (atypical Spitz tumour), and many others, all trying to tackle characteristic features for diagnosis. While it may be possible to histologically find some commonality to define subgroups within the collection of MelTUMPs, interrater agreement between dermatopathologists is typically poor. However, all terms have one thing in common: they communicate uncertainty. This also affects clinical decisions and raises several questions how to manage such lesions: Which excision margins are advisable? Should sentinel lymph node (SLN) surgery be performed? Is adjuvant systemic treatment warranted? A recently published systematic review by Varey et al.2 aimed to address some of these questions. Key messages from this article are: 5–10 mm excision margins for the primary tumour appear to be an appropriate balance between surgery-associated morbidity and adequacy of treatment for MelTUMPs. Tumour cell deposits in the SLN are frequent (even compared to clear-cut cutaneous melanomas), and even more frequent in younger patients (>50% positivity rate in patients <18 years of age). However, of the 288 patients analysed in the above study with positive SLN, only 15 developed further disease, of which three died. Thus, the prognostic value of the SLNB is poor. Altogether this paper provides a useful guidance for managing MelTUMPs and has one core message: first do no harm. We are looking forward to seeing data solving the molecular puzzle of MelTUMPs in the future, which has the potential to shed light into this grey zone of melanocyte biology. Open Access funding enabled and organized by Projekt DEAL. CP has received honoraria and travel support from BMS, MSD, Roche, Almirall, Pelpharma, Sanofi, Pfizer, Merck, Abbvie, and Novartis all unrelated to this manuscript.

Spitz Tumor With SQSTM1::NTRK2 Fusion: A Clinicopathological Study of 5 Cases.

Spitz tumors are melanocytic neoplasms characterized by specific, mutually exclusive driver molecular events, namely genomic rearrangements involving the threonine kinase BRAF and the tyrosine kinase receptors ALK , NTRK1 , NTRK2 , NTRK3 , MET , RET , ROS1 , and MAP3K8 or less commonly, mutations in HRAS or MAP2K1 . We hereby report 5 Spitz tumors with a SQSTM1::NTRK2 fusion. All patients were woman with the ages at diagnosis ranging from 30 to 50 years. Locations included the lower extremity (n = 3), forearm, and back (one each). All the neoplasms were superficial melanocytic proliferation with a flat to dome-shaped silhouette, in which junctional spindled and polygonal dendritic melanocytes were mainly arranged as horizontal nests associated with conspicuous lentiginous involvement of the follicular epithelium. Only one case showed heavily pigmented, vertically oriented melanocytic nests resembling Reed nevus. A superficial intradermal component observed in 2 cases appeared as small nests with a back-to-back configuration. In all lesions, next-generation sequencing analysis identified a SQSTM1::NTRK2 fusion. A single case studied with fluorescence in situ hybridization for copy number changes in melanoma-related genes proved negative. No further molecular alterations were detected, including TERT-p hotspot mutations.

Spectrum of Melanocytic Tumors Harboring BRAF Gene Fusions: 58 Cases With Histomorphologic and Genetic Correlations

We report a series of 58 melanocytic tumors that harbor an activating fusion of BRAF, a component of the mitogen-activated protein kinase (MAPK) signaling cascade. Cases were diagnosed as melanocytic nevus (n = 12, 21%), diagnostically ambiguous favor benign (n = 22, 38%), and diagnostically ambiguous concerning for melanoma (n = 12, 21%) or melanoma (n = 12, 21%). Three main histopathologic patterns were observed. The first pattern (buckshot fibrosis) was characterized by large, epithelioid melanocytes arrayed as single cells or “buckshot” within marked stromal desmoplasia. The second pattern (cords in whorled fibrosis) demonstrated polypoid growth with a whorled arrangement of cords and single melanocytes within desmoplasia. The third pattern (spindle-cell fascicles) showed fascicular growth of spindled melanocytes. Cytomorphologic features characteristic of Spitz nevi were observed in most cases (n = 50, 86%). Most of the cases (n = 54, or 93%) showed stromal desmoplasia. Histomorphology alone was not sufficient in distinguishing benign from malignant melanocytic tumors with BRAF fusion gene because the only histopathologic features more commonly associated with a diagnosis of malignancy included dermal mitoses (P = .046) and transepidermal elimination of melanocytes (P = .013). BRAF fusion kinases are targetable by kinase inhibitors and, thus, should be considered as relevant genetic alterations in the molecular workup of melanomas. Recognizing the 3 main histopathologic patterns of melanocytic tumors with BRAF fusion gene will aid in directing ancillary testing.

Difficult to Diagnose Cutaneous Melanoma in a Patient with BAP1 Tumor Predisposition Syndrome.

BRCA1-associated protein 1 (BAP1)-inactivated melanomas can occur sporadically or in germline contexts, particularly in recently recognized BAP1-tumor predisposition syndrome. Diagnosis represents a clinical and histopathological challenge, requiring comprehensive analysis of morphology and sometimes molecular analysis in addition to immunohistochemistry. We report a BAP1-inactivated cutaneous melanoma initially diagnosed as an atypical Spitz tumor on the auricle in a patient with BAP1-tumor predisposition syndrome. Immunohistochemistry, fluorescence in situ hybridization, and comparative genomic hybridization allowed diagnosis. Cutaneous BAP1-inactivated melanocytic tumors, previously classified as atypical Spitz Nevi, may have a dermal mitotic activity that can resemble melanoma and on the other hand, atypical Spitz tumors are sometimes difficult to differentiate from BAP1-inactivated melanoma. Specific criteria, requiring molecular diagnosis have been proposed in order to support melanoma diagnosis.

TERT Promoter Mutational Analysis as an Ancillary Diagnostic Tool for Diagnostically Challenging Melanocytic Neoplasms.

Telomerase reverse transcriptase promoter mutations (TPMs) have been shown to be common in melanoma and uncommon in benign nevi. To assess the use of TPMs as an ancillary diagnostic tool, we report the concordance of the TPM status with the final diagnosis in clinical cases with distinct differential diagnostic scenarios: dysplastic nevus versus melanoma, atypical Spitz nevus versus melanoma, atypical deep penetrating nevus (DPN) versus melanoma, and atypical blue nevus versus malignant blue nevus. In a control cohort, we found a positive TPM in 51/70 (73%) of the total melanomas with the highest frequency in vertical growth phase melanoma cases. Conversely, only 2/35 (6%) dysplastic nevi in our control cases were TPM-positive and b were severely atypical dysplastic nevi. Our clinical cohort of 257 cases had a positive TPM in 24% of cases diagnosed as melanoma and in 1% of cases with a benign diagnosis. The overall concordance of the TPM status with the final diagnosis was 86%. The TPM status had the greatest concordance (95%) with the final diagnosis in the atypical DPN versus melanoma group, with the rest of the groups ranging between 50% and 88%. Overall, our results suggest that TPMs are most useful in the differential diagnosis of atypical DPN versus melanoma. It also has some value in the differential diagnosis of atypical Spitz tumor versus melanoma and dysplastic nevus versus melanoma, whereas in our cohort, it did not contribute meaningfully to differentiating malignant blue nevus and atypical blue nevus.

Stardust Pattern as Evolution of Pigmented Spitz Nevi During Childhood.

Spitz nevi (SN) are benign melanocytic proliferations frequently occurring in children. Some pigmented SN with a starburst pattern evolve into the "stardust" one, which is characterized by a central, black to gray, hyperpigmented area and remnants of a brown network at the periphery. These dermoscopy changes are often the first alert to induce excision. The aim of this study is to enlarge the case series of stardust SN in children, in order to increase confidence with this new dermoscopic pattern and reduce unnecessary excisions. This retrospective observational study was conducted with SN cases received from IDS members. The inclusion criteria were: clinical and/or histopathologic diagnosis of Spitz naevus with starburst appearance in children <12 years old, availability of a dermoscopic image at baseline and after follow-up of at least 1 year, availability of patient data. The dermoscopic images and their changes over time were assessed by three evaluators in consensus. 38 SN were enrolled, with a median age of 7 years and a median FUP duration of 15,5 months. Comparing the evolution with time of FUP, no significant differences were found between growing and involuting lesions in terms of patient age and sex, location and palpability of lesions. The long follow-up reported in our study could really support the concept of benignity of changing SN. A conservative approach is acceptable for nevi showing the stardust pattern, because it may be considered a physiological evolution of pigmented Spitz nevus, and urgent surgeries could be avoided.

A case of angiomatoid Spitz Nevus in the elderly, with clinical and dermoscopic features.

This case was presented at the on-line telepathology meeting on the ADOI platform held on October 19th 2022 by Dr Luongo.

Spitz nevus and melanoma: evaluation with dermoscopy and reflectance confocal microscopy.

Spitz nevi (SN) include a wide range of benign melanocytic nevi, which are controversial due to their morphologic resemblance to melanoma (MM). To describe dermoscopic and reflectance confocal microscopic (RCM) features of SN compared to MM and assess the RCM utility in the differential diagnosis. We performed a multicentre retrospective analysis of MM and SN evaluated with dermoscopy and reflectance confocal microscopy. Three RCM mosaics were obtained for each lesion. Nine dermoscopic and twenty-one microscopic features were assessed for each lesion. A total of 26 lesions (15 SN and 11 MM) were included. Dermoscopically, most SN showed a "starburst" pattern. Asymmetry was marked in 8 MM. There were 6 dermoscopic features significantly more prevalent in MM than in SN. RCM showed that an atypical honeycomb pattern, atypical infiltration, and disarray of the epidermis were significant for MM. SN mostly revealed a typical honeycomb pattern. At the DEJ, most of SN had a meshwork pattern; MM revealed an atypical meshwork pattern. Atypical cells and sheet-like structures were observed in most MM. A combined approach using dermoscopy and RCM supports the differential diagnosis of SN and MM. Although our study showed some significant differences between SN and MM in RCM, further research on a larger group should be considered.

Spitz Nevus in a Nevus Spilus: Management Considerations in Pediatric Patients

Spitz Nevus in a Nevus Spilus: Management Considerations in Pediatric Patients

Spitz nevus: a childhood lesion with alarming microscopic features to the unwary

Spitz nevus: a childhood lesion with alarming microscopic features to the unwary

Multidisciplinary management of a quickly growing pediatric atypical Spitz nevus, mimicking melanoma, during the COVID-19 pandemic

Spitzoid melanoma is very rare tumour in the pediatric population, with clinical and non-uniform behaviour, different from adult melanoma [ 1 ]. It can be difficult to differentiate an atypical Spitz nevus from a Spitzoid melanoma, resulting in diagnostic problems. In addition, in our clinical case, the COVID-19pandemiccaused significant delays both in the diagnosis and in the surgical treatment of our patient. We present the clinical case of a 4-year-old child suffering from a localized polypoid cutaneous neoformation on the dorsum of the left hand, which started immediately before the lockdown and steadily increased during the COVID-19 pandemic. After a general clinical framing, the child underwent an excisional biopsy at our Department of Plastic and Reconstructive Surgery, at the Policlinico of Foggia. Subsequently, two independent anatomic pathology groups examined the specimen. Definitive diagnosis was made only after careful genetic analysis in combination with supporting histological and immunohistochemical examinations. This clinical case shows how during the pandemic we have been facing advanced forms of tumours, compared to the previous period and highlight show an interdisciplinary and multicenter collaboration allowed a quick diagnosis of certainty, demonstrating the utility of molecular pathology as a fundamental aid in clinical/surgical practice.

Reflectance confocal microscopy in paediatric patients: Applications and limits.

Reflectance confocal microscopy (RCM) is a non-invasive diagnostic tool extensively studied for adult patients. In this retrospective case series conducted at the Dermatology Unit of the University of Campania, Naples, Italy, all patients under 19 years old who were submitted to RCM from January 2011 to December 2021 where evaluated. The aim of the study was to review the most usual indications and possible benefits that it might add for children. Data collection included 215 patients (86 males and 129 females, mean age: 12). Most of the exams (n=85; 39.5%) were performed for lesions clinically compatible with Spitz nevi, congenital nevi (n=50 23,2%) and atypical melanocytic lesions (n=46; 21%) among which two melanomas were detected. RCM can be an useful instrument when evaluating paediatric patients and may help avoid unnecessary biopsy in most cases, representing an additional instrument to improve diagnostic accuracy.

Next-generation Sequencing as a Potential Diagnostic Adjunct in Distinguishing Between Desmoplastic Melanocytic Neoplasms.

Desmoplastic melanomas (DMs) are often challenging to diagnose and ancillary tests, such as immunohistochemistry, have limitations. One challenge is distinguishing DM from benign desmoplastic melanocytic neoplasms. In this study, we explored the utility of next-generation sequencing data in the diagnosis of DMs versus desmoplastic Spitz nevi (DSN) and desmoplastic nevi (DN). We sequenced 47 cases and retrieved 12 additional previously sequenced clinical cases from our dermatopathology database. The 59 total cases were comprised of 21 DMs, 25 DSN, and 13 DN. The DMs had the highest tumor mutation burden at 22 mutations/megabase (m/Mb) versus the DSN (6m/Mb) and DN (8m/Mb). Truncating mutations in NF1 resulting in a loss-of-function were exclusive to the DM cohort, identified in 8/21 (38%) cases. Importantly, missense mutations in NF1 were nonspecific and seen with similar frequency in the different cohorts. Other mutations exclusive to the DMs included truncating mutations in TP53 , CDKN2A , and ARID2 . Among the DSN, 17/25 (68%) had an HRAS mutation or receptor tyrosine kinase fusion consistent with other Spitz tumors. Two cases in the DN cohort had missense mutations in BRAF without additional progression mutations and 2 other cases had mutations in GNAQ , supporting a diagnosis of a sclerosing blue nevus. The remainder of the DN had nonspecific mutations in various signaling pathways with few progression mutations. Overall, our study provides preliminary data that next-generation sequencing data may have the potential to serve as an ancillary diagnostic tool to help differentiate malignant and benign desmoplastic melanocytic neoplasms.

Combined utility of p16 and BRAF V600E in the evaluation of spitzoid tumors: Superiority to PRAME and correlation with FISH.

Spitzoid melanocytic neoplasms are diagnostically challenging; criteria for malignancy continue to evolve. The ability to predict chromosomal abnormalities with immunohistochemistry (IHC) could help select cases requiring chromosomal evaluation. Fluorescence in situ hybridization (FISH)-tested spitzoid neoplasms at our institution (2013-2021) were reviewed. p16, BRAF V600E, and preferentially expressed antigen in melanoma (PRAME) IHC results were correlated with FISH. A total of 174 cases (1.9F:1M, median age 28 years; range, 5 months-74 years) were included; final diagnoses: Spitz nevus (11%), atypical Spitz tumor (47%), spitzoid dysplastic nevus (9%), and spitzoid melanoma (32%). Sixty (34%) were FISH positive, most commonly with absolute 6p25 gain (RREB1> 2). Dermal mitotic count was the only clinicopathologic predictor of FISH. Among IHC-stained cases, p16 was lost in 55 of 134 cases (41%); loss correlated with FISH positive (p< 0.001, Fisher exact test). BRAF V600E (14/88, 16%) and PRAME (15/56, 27%) expression did not correlate with FISH alone (p= 0.242 and p= 0.359, respectively, Fisher exact test). When examined together, however, p16-retained/BRAF V600E-negative lesions had low FISH-positive rates (5/37, 14%; 4/37, 11% not counting isolated MYB loss); all other marker combinations had high rates (56%-75% of cases; p< 0.001). p16/BRAF V600E IHC predicts FISH results. "Low-risk" lesions (p16+ /BRAF V600E- ) uncommonly have meaningful FISH abnormalities (11%). PRAME may have limited utility in this setting.

Expression of Cyclin D1 in Cutaneous Xanthogranuloma and Solitary Reticulohistiocytoma.

Expression of Cyclin D1 in Cutaneous Xanthogranuloma and Solitary Reticulohistiocytoma.

Hamartome angio-eccrine : A propos de deux observations a Dakar, Sénégal

Angio eccrine hamartoma (EAH) is a rare, benign tumoral lesion composed of eccrine glands and vascular structures in the mid dermis. We report on two observations in Dakar. Observation 1: A four-month-old infant was seen for an erythematous plaque, rounded, with a smooth surface, asymptomatic, localized to the right thigh, evolving for three months. The clinical appearance suggested a spitz tumour. Cutaneous histology confirmed the diagnosis of angioeccrine hamartoma. Observation 2: The second case was concerned with a ten-month-old infant received for an erythematous, atrophic plaque, localized at the level of the inter-gluteal fold, evolving since birth. This clinical aspect was suggestive of a sclero-atropic lichen. Cutaneous histology confirmed the diagnosis of angioeccrine hamartoma. Discussion: We reported two observations of HAE original by the rarity and the clinical presentations leading to confusion with a nevus of Spitz and the sclero-atrophic lichen. Cutaneous histology was of considerable contribution.

Dermatoscopic Features of Angiomatoid Spitz Nevus: a Case Report.

Angiomatoid Spitz nevus is an uncommon histopathological variant of Spitz nevus that is most frequently seen on the extremities of children and young adults. Dermatoscopic features of this unusual variant have rarely been reported. We presented a 19-year-old female diagnosed with angiomatoid Spitz nevus based on the clinical, dermatoscopic, and histopathological findings.&#x0D; Polarized-light dermatoscopic examination showed a red structureless background, white lines reticular, numerous coiled vessels without specific arrangement and surface scale.&#x0D; Although the dermatoscopic findings we described in this case can be observed in SN in general, we believe that the predominancy of coiled vessels may be an important clue to the angiomatoid variant of SN.

Dermoscopic Findings of the Evolving Pigmented Spitz Nevus in a Child.

According to the Authors Guidelines in case of image letters no abstract should be provided.

Malignant melanoma test results by a commercial 35-gene expression test are enriched for benign or atypical Spitz tumors.

Malignant melanoma test results by a commercial 35-gene expression test are enriched for benign or atypical Spitz tumors.

741 Paediatric Pigmented Epithelioid Melanocytoma: A Case Report

Abstract Background Pigmented epithelioid melanocytomas (PEMs) pose a challenge in terms of diagnosis and management, this is due to the wide spectrum of disease severity. Not only is management a grey area, but there is controversy over management and follow up, due to their indeterminate malignant potential. Case An 11-year-old boy presented with a six-month history of a rapidly changing pigmented naevus on his upper back. He had Fitzpatrick type 1 with no history of significant sun damage or familial history of skin cancer, and no relevant past medical history. Differential diagnoses included spitz naevus, malignant melanoma, or MelTUMP (melanocytic tumour of unknown malignant potential). An excision biopsy showed a benign pigmented epithelioid melanocytoma with local lymphatic involvement. The child was seen two months following the original surgery and no signs of local or regional recurrence was present. Discussion This is one of few cases of paediatric PEM reported in literature. This lesion has potential to metastasise through the lymphatics and mortality is very low. The management of PEMs is complicated due to their unknown malignant potential and should be decided by an MDT. Based on the limited literature on PEMs and our knowledge of ‘thin’ melanomas wide local excision is sensible, however a larger cohort if needed to fully understand prognosis. SNB should be considered on a case-by-case basis by an MDT, and regular ultrasound surveillance with clinical examination offers a safe alternative to SNB in some patients.