In 2019, YAP1::MAML2 and YAP1::NUTM1 rearrangements were demonstrated in the majority of poromas and in porocarcinomas. Recently, our group demonstrated recurrent fusions of PAK (p21 (RAC1) activated kinase) 1/2/3 genes in a subset of poromas and porocarcinomas frequently harboring hair follicle and sebaceous differentiation. To expand the spectrum of YAP1/PAK-fused tumors, we report six adnexal neoplasms with follicular differentiation with in frame YAP1::MAML2, YAP1::NUTM1, or RNF13::PAK2 fusion transcripts. Four cases of trichoblastoma and two neoplasms with panfollicular differentiation were included. Median age was 66 (range 39–76). Two patients were female. Tumors were located on the head (n = 4), chest (n = 1), or leg (n = 1). Microscopically, tumors were located in the dermis (n = 4) and/or subcutaneous tissue (n = 5), and showed macro (n = 6), micronodular (n = 5), and cystic (n = 4) structures. A delicate fibrillar stroma was present in 5 cases. Infundibulocystic structures, cell balls, and sebocytes were observed in 5, 1, and 3 cases, respectively. Immunohistochemistry revealed BerEP4 expression and Merkel cell hyperplasia in 5 and 2 cases, respectively. YAP1 (C-terminal) loss was observed in 5 cases. Accordingly YAP1::MAML2 (n = 2), YAP1::NUTM1 (n = 1), or RNF13::PAK2 (n = 1) inframe fusion transcripts were detected in the four trichoblastomas. YAP1::MAML2 fusions were also detected in the two tumors with panfollicular differentiation. In conclusion, we report six cases of follicular tumors with YAP1::MAML2, YAP1::NUTM1, or RNF13::PAK2 fusions and therefore suggest that in addition to poroid tumors, YAP1 and PAK2 fusions might be the oncogenic driver in a subset of adnexal tumors with prominent follicular differentiation.

RET-fused Spitz neoplasms represent a rare and poorly characterized category of Spitz tumors. Here we describe the clinical, histologic, and molecular findings of 31 Spitz neoplasms with RET fusion diagnosed as Spitz nevus (n = 16), atypical Spitz tumors (n =13), and Spitz melanoma (n = 2). The lesions mainly occurred in children and young adults of both sexes with a predilection for the extremities. Microscopically, they were mainly symmetrical compound melanocytic neoplasms with a domeshaped/slightly raised silhouette predominantly composed of epithelioid, spindled, and/or smaller nevoid melanocytes arranged in confluent nests. Dyscohesive melanocytes within the nests in the upper part of the lesions, prominent Kamino bodies, giant multinucleated melanocytes, variable pigmentation, and increased vascularity with vascular ectasia were frequent features. RNA sequencing detected 9 different 5' (N-terminus) fusion partners, including KIF5B (n = 8), LMNA (n = 7), CCDC6 (n = 6), OPTN (n = 3), MYO5A (n = 2), and NCOA4, ERC1, MYH9, AGAP3 (n = 1). Of these, OPTN::RET and AGAP3::RET represent novel fusions, and 3 further 5' fusion partners, namely NCOA4, ERC1, and MYH9, have never been reported in Spitz tumors. Although as a whole group, the tumors showed a heterogeneous histopathologic presentation, correlation of the morphologic features and the 5' fusion partners demonstrated certain associations. Nevoid melanocytes were exclusively encountered in cases with KIF5B fusion partner. Neuroid-like appearances with intersecting fascicles of spindled cells typified both MYO5A-fused cases. Epithelioid melanocyte population dominated cases with LMNA and CCDC6 fusion partners. Transepidermal elimination/floating intraepidermal nests of pigmented spindled and epithelioid melanocytes were observed in the OPTN subgroup. The remaining cases with less frequent 5' fusion partners manifested in general more atypical histopathologic features, including nuclear pleomorphism, high mitotic count, atypical mitoses, and sheet-like growth pattern. Melanoma fluorescence in situ hybridization probe kit targeting RREB1, MYC, CDKN2A, and CCND1, was negative for copy number variation in 4 cases tested, including 2 cases with complete p16 nuclear loss on immunohistochemistry. Array comparative genomic hybridization was performed in 3 lesions and detected numerous segmental chromosomal imbalances in 2 of them that were diagnosed as Spitz melanoma. DNA and RNA sequencing detected several further genomic alterations, including POU2F3 overexpression in 3 highly pigmented lesions. Further studies are needed to confirm possible correlations between the microscopic features and a particular fusion partner (or additional genetic events) in RET-fused Spitz neoplasms. (c) 2025 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare malignant soft tissue neoplasm typically found in the distal extremities of middle-aged adults. Histologically, MIFS presents with a myxoid stroma, a mixed inflammatory infiltrate, epithelioid/spindle cells resembling virocytes, pseudolipoblasts, and emperipolesis. Genetic alterations commonly include TGFBR3-MGEA5 rearrangements and VGLL3 amplifications. Recently, YAP1::MAML2 fusions have been identified in nodular necrotizing variants of MIFS. We report a case of a 40-year-old man presenting with right thumb pain initially suspected to be tendovaginitis. Histopathologic examination revealed a variably cellular proliferation in a fibrosclerotic-myxoid stroma with epithelioid cells displaying vesicular nuclei, spindle cells, and inflammatory infiltrates. Focal extensive necrosis was present. Immunohistochemical analysis was negative for SOX10, S100, SMA, desmin, MDM2, ALK, and CD20. Molecular genetic testing identified 2 variants of YAP1::MAML2 gene fusions and an additional TRIM24::BRAF fusion. Although BRAF rearrangements have previously been reported in MIFS, identification of TRIM24 as a fusion partner represents a novel finding. The presence of YAP1::MAML2 fusions, especially in combination with a TRIM24::BRAF fusion, has not been previously described in MIFS. TRIM24 is a transcriptional coregulator involved in p53 ubiquitination and tumorigenesis. The TRIM24::BRAF fusion has been detected in various malignancies, suggesting its potential oncogenic role. This case underscores the genetic heterogeneity of MIFS and suggests the need for further studies to elucidate the clinical implications of these molecular alterations. This report expands the molecular spectrum of MIFS and highlights the diagnostic utility of advanced sequencing technologies in identifying rare gene fusions. The TRIM24::BRAF fusion may represent a potential therapeutic target, warranting further investigation.

Hidrocystomas and cystadenomas are benign tumors, with malignant transformation being exceptionally rare, most commonly reported in the periocular region. We present a rare case of adenocarcinoma in situ arising within an apocrine papillary cystadenoma of the scalp in a 53-year-old man, without an associated nevus sebaceus. Microscopically, the tumor appeared as a predominantly cystic lesion and was located in the deep dermis. The neoplasm was composed of cuboidal to cylindrical cells, displaying decapitation secretion and forming glands, micropapillae, and occasional papillae with fibrovascular cores projecting into the cystic lumen. In addition, a considerable extraluminal proliferation of small, closely packed glands with a visible peripheral layer of myoepithelial cells was evident. Whereas most tumor cells were monomorphic, a focal area exhibited significant cellular atypia and pleomorphism. There were numerous necrotic cells, both isolated and clustered, and frequent mitotic figures, including atypical ones. RNA sequencing was performed using the Archer FusionPlex panel and revealed an HMGA2 fusion transcript of unknown significance. The lesion was surgically removed, and the patient had no evidence of disease 4 months after the diagnosis.

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

ABSTRACT:Nonmelanoma malignancies associated with congenital melanocytic nevi (CMN) are extremely rare, with only 12 reported cases of rhabdomyosarcoma (RMS) to date. We present 2 additional cases of RMS arising in giant CMN, with immunohistochemical and molecular biologic investigations. The first case was a 32-year-old woman with a personal history of melanoma in giant CMN who, after successful treatment and long remission, presented with a new 1-cm nodule within the CMN. Microscopically, the atypical areas exhibited a round cell/alveolar morphology with immunoreactivity for desmin and myogenin, and lacked PAX3/7::FOXO1 fusions typical for alveolar RMS on a reverse transcription polymerase chain reaction analysis. An identical NRAS p.Q61R mutation with comparable variant allele frequency (32% and 44%) was identified in both the nevus and the RMS tissue by next-generation sequencing. The second patient was a 5-year-old girl with a rapidly growing, bleeding, ulcerated 3 × 4 cm interscapular mass within a giant CMN that histologically seemed as a proliferation of pleomorphic spindle, polygonal and epithelioid cells with marked pleomorphism immunoreactive for myogenin, muscle-specific actin, and smooth muscle actin. Next-generation sequencing yielded an HRAS p.Q61R mutation with limited variant allele frequency (7%) in the RMS component, while ATRX p.Q2193* variant was detected in the nevus. Our study is apparently the first report of NRAS and HRAS mutations in tumors with RMS phenotype arisen in CMN.

AimsPorocarcinoma is a malignant sweat gland tumour differentiated toward the upper part of the sweat duct and may arise from the transformation of a preexisting benign poroma. In 2019, Sekine et al. demonstrated the presence of YAP1::MAML2 and YAP1::NUTM1 fusions in most poromas and porocarcinomas. Recently, our group identified PAK2‐fusions in a subset of benign poromas. Herein we report a series of 12 porocarcinoma cases harbouring PAK1/2/3 fusions.Methods and ResultsFive patients were male and the median age was 79 years (ranges: 59–95). Tumours were located on the trunk (n = 7), on the thigh (n = 3), neck (n = 1), or groin area (n = 1). Four patients developed distant metastases. Microscopically, seven cases harboured a benign poroma component and a malignant invasive part. Ductal formations were observed in all, while infundibular/horn cysts and cells with vacuolated cytoplasm were detected in seven and six tumours, respectively. In three cases, the invasive component consisted of a proliferation of elongated cells, some of which formed pseudovascular spaces, whereas the others harboured a predominant solid or trabecular growth pattern. Immunohistochemical staining for CEA and EMA confirmed the presence of ducts. Focal androgen receptor expression was detected in three specimens. Whole RNA sequencing evidenced LAMTOR1::PAK1 (n = 2), ZDHHC5::PAK1 (n = 2), DLG1::PAK2, CTDSP1::PAK1, CTNND1::PAK1, SSR1::PAK3, CTNNA1::PAK2, RNF13::PAK2, ROBO1::PAK2, and CD47::PAK2. Activating mutation of HRAS (G13V, n = 3, G13R, n = 1, Q61L, n = 2) was present in six cases.ConclusionOur study suggests that PAK1/2/3 fusions is the oncogenic driver of a subset of porocarcinomas lacking YAP1 rearrangement.

Close relationship between melanocytes and neural cells is accepted to reflect their common derivation from the neural crest and tumors combining both elements. We present a series of 10 patients with giant congenital melanocytic nevi (CMN) in which a secondary proliferation (11 lesions) with schwannian and/or perineuriomatous differentiation developed in the course of the disease. The age of the patients (4 male and 6 female) at the time of surgery and histological assessment varied from 3 months to 57 years. Histopathologically, the following subgroups were delineated: (1) nodular/tumoriform "neurotization" in CMN, (2) diffuse neurofibroma-like proliferation within CMN, (3) plexiform neurofibroma-like proliferation within CMN, and (4) diffuse perineuriomatous (hybrid schwannomatous-perineuriomatous) differentiation in CMN. We review the pertinent literature, including the role of recently identified Schwann cell precursors which are believed to represent the nerve-associated state of neural crest-like cells that persists into later developmental stages.

BRAF fusion Spitz neoplasms along with MAP3K8 fusions are among the subtypes of Spitz most likely to be diagnosed as Spitz melanoma. However, the current literature has only limited amounts of clinical follow-up on these cases. In this study, we share our experience with 39 BRAF fusion Spitz neoplasms and provide the greatest number of cases with available clinical follow-up. Among 24 patients with clinical follow-up (mean duration of 26.1 mo), none developed metastatic disease. Detailed biomarker assessment with FISH studies, TERT promoter mutational analysis, PRAME and p16 IHC also strongly favored a benign process. Only 2 of 17 cases were positive by FISH, 37 of 38 were negative for TERT promoter mutations, 24 of 24 were negative for PRAME and 16 of 21 had retained staining with p16. In addition, we identify and describe several distinct morphologic patterns, some of which are highly spitzoid in cytomorphology while others lack convincingly spitzoid cytomorphology. We address classification of those cases with less than classic spitzoid cytomorphology with a nonsupervised PCA plot which shows that independent of how spitzoid the cytomorphology is, BRAF fusions strongly cluster with other subtypes of Spitz neoplasms. In conclusion, we show with clinical follow-up, a meta-analysis of the current literature, and our biomarker analysis, that most BRAF fusion Spitz neoplasms have an indolent course and should be considered either benign or of intermediate grade. Further, our morphologic assessment and PCA plot suggest the morphologic spectrum of Spitz neoplasms may need to be expanded.

ABSTRACT:We report a very unusual case of melanocytic neoplasm appearing clinically as a 0.5-cm dome-shaped pigmented papule on the chest of a 63-year-old man. Microscopically, it was an asymmetric, entirely dermally based neoplasm characterized by a multinodular, vaguely plexiform architecture composed of moderately pleomorphic spindled melanocytes with ample, dusty pigmented cytoplasm and scattered multinucleated cells. The tumor cells were strongly positive for Melan-A, HMB45, S100, and PRAME, whereas p16 showed diffuse nuclear loss. β-catenin presented a strong and diffuse cytoplasmic staining, while nuclei were negative. Despite an increased cellularity, mitotic count was low (1/mm 2 ). Fluorescence in situ hybridization revealed no copy number alteration in melanoma-related genes ( CDKN2A, MYB, MYC, CCND1 and RREB1 ). DNA and RNA sequencing identified KIT c.2458G>T and APC c.6709C>T mutations. No further genetic alteration was detected including TERT-promoter (TERT-p ) hot-spot mutation. A re-excision was performed. A sentinel lymph node biopsy was negative. Clinical investigations revealed no extracutaneous involvement. The patient is disease-free after a follow-up period of 8 months. Given the peculiar morphologic and molecular findings, we hypothesize the lesion may represent a novel subtype of an intermediate grade melanocytic tumor (melanocytoma).

AIMS:Sebaceous neoplasms constitute a group of adnexal tumours, including sebaceous adenoma, sebaceoma and sebaceous carcinoma. Although mismatch repair deficiency may be observed, the nature of the genetic alterations contributing to the development of most of these tumours is still unknown. In the present study, we describe the clinical, microscopic, and molecular features of eight sebaceomas with GRHL gene rearrangement. METHODS AND RESULTS:Among these sebaceomas, four occurred in women and four in men; the median age was 63 years (range = 29-89). The tumours were located in the head and neck area in all cases. Microscopic examination revealed a well-demarcated lesion located in the dermis with focal extension into the subcutaneous tissue (three cases). The neoplasms displayed macronodular (eight cases), cribriform (seven cases) and organoid (six cases) growth patterns, occurring in combination. The tumours were mainly composed of immature basophilic cells associated with scattered mature sebocytes. Numerous small infundibular cysts were present in seven cases. Mitotic activity was low (none/one to four mitoses/mm2). Immunohistochemistry showed positivity for androgen receptor and p63. Preserved expression of MLH1, PMS2, MSH2 and MSH6 was observed in all cases. RNA-sequencing revealed RCOR1::GRHL2 (three cases), BCL6::GRHL1 (two cases), a BCOR::GRHL2 (one case), RCOR1::GRHL1 (one case) and TLE1::GRHL1 (one case) fusion transcript. Methylation analysis demonstrated that GRHL-fused sebaceomas form an independent cluster and highlight the proximity of such tumours with poromas with folliculo-sebaceous differentiation. CONCLUSIONS:In conclusion, we report recurrent fusions of the GRHL genes in a distinctive subset of sebaceomas harbouring infundibulocystic differentiation, a frequent organoid growth pattern and lack of mismatch repair deficiency.

Spitz tumors represent a heterogeneous group of challenging melanocytic neoplasms, displaying a range of biological behaviors, spanning from benign lesions, Spitz nevi (SN) to Spitz melanomas (SM), with intermediate lesions in between known as atypical Spitz tumors (AST). They are histologically characterized by large epithelioid and/or spindled melanocytes arranged in fascicles or nests, often associated with characteristic epidermal hyperplasia and fibrovascular stromal changes. In the last decade, the detection of mutually exclusive structural rearrangements involving receptor tyrosine kinases ROS1, ALK, NTRK1, NTRK2, NTRK3, RET, MET, serine threonine kinases BRAF and MAP3K8, or HRAS mutation, led to a clinical, morphological and molecular based classification of Spitz tumors. The recognition of some reproducible histological features can help dermatopathologist in assessing these lesions and can provide clues to predict the underlying molecular driver. In this review, we will focus on clinical and morphological findings in molecular Spitz tumor subgroups.

BAP1-inactivated melanocytoma (BIM) is a novel subgroup of melanocytic neoplasm listed in the 5th edition of WHO classification of skin tumor. BIM is characterized by two molecular alterations, including a mitogenic driver mutation (usually BRAF gene) and the loss of function of BAP1, a tumor suppressor gene located on chromosome 3p21, which encodes for BRCA1-associated protein (BAP1). The latter represents a nuclear-localized deubiquitinase involved in several cellular processes including cell cycle regulation, chromatin remodeling, DNA damage response, differentiation, senescence and cell death. BIMs are histologically characterized by a population of large epithelioid melanocytes with well-demarcated cytoplasmic borders and copious eosinophilic cytoplasm, demonstrating loss of BAP1 nuclear expression by immunohistochemistry. Recently, we have published a series of 50 cases, extending the morphological spectrum of the neoplasm and highlighting some new microscopic features. In the current article, we focus on some new histological features, attempting to explain and link them to certain mechanisms of tumor development, including senescence, endoreplication, endocycling, asymmetric cytokinesis, entosis and others. In light of the morphological and molecular findings observed in BIM, we postulated that this entity unmasks a fine mechanism of tumor in which both clonal/stochastic and hierarchical model can be unified.

A 46-year-old patient presented at our clinic with erythematous papules that had developed on both legs 2 years ago and had subsequently extended across the whole body.Over time, he developed thickening and tenseness of the skin in the face, loss of eyelashes, rarefication of eyebrows, ectropion, insufficiency of eye closure and restricted mouth opening (Figure 1).Furthermore, he had been diagnosed with a dialysis-dependent renal insufficiency, AV-block, malignant hypertension, glaucoma, and a monoclonal gammopathy type kappa.We suspected a sclerosing disease and performed skin biopsies in different affected areas.These showed abundant mucin deposition, but also extensive epithelial proliferates in all specimens (Figure 2a-h).The proliferations consisted of basosquamous cell complexes, showed primitive (Figure 2a-d) and infundibular (Figure 2e-h) follicular differentiation and were surrounded by significant fibrosis (Figure 2g,h). 1 We classified these proliferations as a secondary phenomenon of a deposition disease and diagnosed scleromyxedema with atypical histopathological presentation.In the following years, the patient developed multiple skin-colored papules on the head, trunk, and extremities (Figure 3).Some turned out to be conventional

Abstract: 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.

Kissing nevus is a congenital melanocytic neoplasm arising in those parts of the body that split at some point during embryological development (i.e., eyelid; penis), resulting in two adjacent melanocytic nevi. To date, 23 cases of kissing nevus of the penis have been described, and dermatoscopic and histological findings are available in 4/23 cases. We report a dermatoscopic, histological and confocal microscopic analysis in a new case of the kissing nevus of the penis in a 57 years old man. Dermatoscopic analysis showed large globules in the central area and a peripheral pigment network; the histological examination confirmed the presence of an intradermal melanocytic nevus with minimal junctional component and congenital features. Moreover, we reported, for the first time, confocal microscopy findings in the kissing nevus of the penis, revealing the presence of dendritic cells in correspondence with the epidermis and suggesting a state of cellular activity. Considering the clinicopathological features of the lesion, a conservative approach was adopted, and a clinical follow-up was planned after six months.

Abstract: Cuticular poroma is a rare variant of poroma composed of exclusively or predominantly cuticular cells, namely of large cells with ample eosinophilic cytoplasm. We report 7 cases of this rare tumor identified among 426 neoplasms diagnosed as poroma or porocarcinoma. The patients were 4 males and 3 females, ranging in age from 18 to 88 years. All presented with a solitary asymptomatic nodule. The location included knee (2 cases), shoulder, thigh, shin, lower arm, and neck (each 1). All lesions were surgically removed. No evidence of disease was observed in 5 patients with available follow-up (range 12–124 months). Microscopically, all neoplasms were composed of variably sized, focally closed packed, or interconnecting nodules constituted mostly of cuticular cells. Small poroid cells were a focal feature in 5 tumors, whereas in the remaining 2 cases, poroid cells with conspicuous but still in minority. Five neoplasms were somewhat asymmetric, with irregular outlines. Ductal differentiation and intracytoplasmic vacuoles were seen in 6 tumors. Other features variably encountered were conspicuous intranuclear pseudoinclusions, cystic change, occasional multinucleated cells, increased mitoses, and stromal desmoplasia. Four of the 5 tumors analyzed with next-generation sequencing yielded YAP1::NUTM1 fusions. In addition, various mutations, mostly of unknown significance were identified in one neoplasm.

ABSTRACT:We report an unusual case of schwannoma with glandular elements that demonstrated apocrine decapitation secretion. The glandular structures were embedded within the tumor, varied in shape and size, and were lined by a double-to-multilayered epithelium, with the inner layer composed of monomorphous cuboidal to columnar cells, focally with apocrine decapitation secretion, and the outer layer representing myoepithelial cells. A normal eccrine unit was observed near the lesion. Immunohistochemical studies showed that all luminal cells of the glandular structures stained positive for CK7, whereas myoepithelial cells expressed S100 and p63, and epithelial membrane antigen highlighted the luminal border. CK20 and neuroendocrine markers were negative in the glandular elements.Our findings suggest that the origin of the glandular elements in our case was represented by entrapped glands. Two theories may explain the epithelial hyperplasia observed in the present case as follows: the obstructive effect theory and the inductive ability of a mesenchymal proliferation to produce epidermal or adnexal changes. We suggest that, in a subset of cases, the origin of the glandular elements might represent entrapped glands, wherein their histomorphology/cytomorphology recapitulates the elements comprising the normal adjacent tissue. Further research is necessary to elucidate the histogenesis of glandular schwannoma.

Spitz tumors are melanocytic neoplasms morphologically characterized by spindled and/or epithelioid cells and specific stromal and epidermal changes associated with mutually exclusive fusion kinases involving ALK, ROS1, NTRK1, NTRK2, NTRK3, MET and RET, BRAF and MAP3K8 genes or, less commonly, HRAS mutation. RAF1 fusions have been recently detected in cutaneous melanocytic neoplasms, including conventional melanoma, congenital nevus and BAP-1 inactivated tumors. We report herewith three Spitz neoplasms with a RAF1 fusion, including a previously reported CTDSPL::RAF1 fusion and two novel PPAP2B::RAF1 and ATP2B4::RAF1 fusions. Two cases were classified as Spitz nevus, while the remaining neoplasm was classified as Spitz melanoma at the time of the diagnosis, given 9p21 homozygous deletion and positive sentinel lymph node biopsy. We suggest that RAF1 fused melanocytic neoplasms can represent a novel subgroup of Spitz tumors, with a RAF1 fusion representing an oncogenic driver.