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Background: Spitzoid melanocytic lesions represent a heterogeneous group of proliferations with ambiguous and overlapping terminology. The exact distinction of a Spitz nevus from a Spitzoid melanoma can be very difficult or, in some cases, impossible. Among the Spitzoid lesions, there is a lesion termed an atypical Spitz tumour (AST) that has intermediate histopathologic features between those of a Spitz nevus and a Spitzoid melanoma and thus uncertain malignant potential. There are several rare cases of patients with a Spitzoid melanoma initially misdiagnosed as a Spitz nevus or an AST with fatal consequences. It is, therefore, advised to perform a molecular characterization in cases where uncertain skin lesions are presented, as it may provide extended set of information with a possible impact on the treatment options. Furthermore, preventive measures, such as regular physical and skin examinations, as well as thorough scheduling of individual follow-up visits, are essential in patients with potentially malignant skin nevi., Case Report: We report a case of a young adult female with a history of AST excision with a negative sentinel lymph node biopsy (SLNB) and insufficient follow-up. Four years after the primary dermatological diagnosis, she presented with a giant tumour in the right hemithorax. Radical en bloc resection of the tumour with right pneumonectomy and resection of the pericardium with reconstruction of the pericardium using mesh was performed. A definitive histopathological examination revealed a metastatic melanoma. The association of the previously diagnosed AST and subsequent appearance of melanoma metastases led to a retrospective re-evaluation of the initial lesion. The suspected diagnosis of Spitzoid melanoma, however, was not confirmed. Moreover, the molecular examination revealed a major discordance between the initial lesion and the lung tumour, which most likely excluded the possible association of the lung metastasis with the initial skin lesion. The initial skin lesion was a BRAF-mutant melanoma with Spitzoid features and termed as AST, while the giant lung metastasis was NRAS-mutant melanoma. The subsequent postoperative course was complicated by the appearance of brain metastases that were stereotactically irradiated. Nevertheless, despite complex specialised medical care, the patient's clinical condition rapidly deteriorated. By this time, no active oncological treatment was possible. The patient was delegated to local hospice for palliative care six months after the surgery and died three weeks later., Conclusions: Our patient was surgically treated at the age of 20 for AST and died four years later of metastatic NRAS-mutant melanoma most likely of different occult origin. Molecular characterization, as well as the close clinical follow-up should be always precisely performed in patients with uncertain skin lesions, such as AST.

Atypical Spitz tumor (AST) is a melanocytic proliferation that shares histopathologic features of Spitz nevus and spitzoid melanoma. Distinction of AST from spitzoid melanoma is critical because the majority of ASTs will follow an indolent course. Array-based comparative genomic hybridization (aCGH) has been suggested as a potential tool for evaluating malignant potential in spitzoid tumors. We present a case of a 52-year-old woman with an AST in which aCGH was crucial in guiding correct diagnosis and management. The patient first presented with a flesh-colored papule on her arm that was changing color. Biopsy revealed a dermal nevoid melanocytic tumor of indeterminate histopathology, favored to be a severely atypical nevus. The tumor was excised. One year later, another flesh-colored papule proximal to the excision site of the first tumor was biopsied and showed a predominantly dermal atypical spitzoid melanocytic proliferation with a differential diagnosis of AST versus spitzoid melanoma. Recurrent or metastatic melanoma was also a concern given proximity to the previous excision site. Molecular analysis of both lesions by aCGH revealed distinct molecular signatures, supporting the 2 tumors to be clonally unrelated. Furthermore, the new tumor displayed limited evidence of genomic instability, supporting classification as an AST with predicted indolent behavior. This case highlights the utility of aCGH in evaluating borderline melanocytic lesions, including assessment of malignant potential in ASTs, and clonality analysis to assist in exclusion of metastatic disease.

Background: Spitz naevi may present with clinical and histopathological atypical features that do not affect patient prognosis but may become worrisome for patients ≥40 years presenting with newly appearing SN., Objective: Patient characteristics and sun behaviour patterns were investigated in correlation with age. SN characteristics and histopathological attributes were also investigated in correlation with age., Methods: Patients with histopathologically confirmed diagnosis of SN were invited for a clinical examination. Data such as skin type, number of banal/atypical naevi, sun exposure patterns and personal/family history were collected. Histopathology preparations were re-examined by two different histopathologists, and characteristics were collected based on a prespecified checklist. Patients were afterwards followed up every 6 months., Results: A total of 110 patients with SN were identified and assigned to three age groups. The most common area of presentation was the trunk, for the ≥40 years age group, and the limbs for the other age groups. Patients ≥40 years had a higher possibility of presenting with a naevus count ≥50 and at least one atypical naevus compared to the other age groups. Patients ≥40 years presented more commonly with a history of painful sunburn (100%) before the appearance of the SN, used less sunscreen, had higher sun exposure times and more clinical signs of solar skin damage compared to the other age groups. Finally, patients ≥40 years presented more commonly with signs of histopathological atypia such as the presence of mitoses, cellular atypia and prominent nucleolus., Conclusion: Patients ≥40 were more likely to report a history of longer sun exposure times, of never using a sunscreen and of having a history of painful sunburn. However, the importance of this observation remains to be elucidated as these patients also presented more commonly with lesions located on non-sun-exposed areas (trunk) and higher naevus/atypical naevus counts., (© 2017 European Academy of Dermatology and Venereology.)

Background: The solitary form of Spitz nevus is a common clinical entity in children, typically occurring on the face and extremities. However, less frequent variants of Spitz nevi, such as agminated forms and eruptive disseminated Spitz nevi (EDSN), have been described. The agminated form is characterised by localised clusters or segmental distribution of Spitz nevi on the face, back, or extremities. First described as "eruptive juvenile melanomata", EDSN is the rarest clinical variant, consisting of a widespread eruption of Spitz nevi, most frequently involving the trunk, buttocks, and proximal limbs, and usually occurs in the second to third decade of life., Objectives: To describe a case of EDSN and review the literature., Materials & Methods: Twenty-seven cases of EDSN, including a 12-year-old female patient with EDSN presented here, were reviewed., Results: EDSN generally exhibits an abrupt, eruptive onset (developing over few months), followed by a slow progressive course of new lesions that continue to appear over a long period, resulting in hundreds of papules and nodules. In all reported cases, the EDSN lesions involved the trunk, often affecting the legs and arms, and sometimes the scalp. A number of possible precipitating factors were reported., Conclusion: A periodic self-examination, total body photography, a dermoscopic 3-6-month follow-up during the eruptive phase (extending to 9-12 months during the stable phase), and prompt surgical excision of lesions that may be malignant is recommended, however, to date, no malignant transformation of EDSN has been reported.

Background: Differentiating Spitz nevi from melanoma can be difficult. Pagetoid spread of melanocytes is among the features making diagnosis difficult. Rare reports of isolated pagetoid Spitz nevi exist., Observations: We present a unique case of multiple pagetoid Spitz nevi initially diagnosed as multiple in situ melanomas. Germline karyotyping, CDK4 and CDKN2A sequencing, and comparative genomic hybridization of HRAS, BRAF, KRAS, RAF1, CDKN2A, Rb1, MAP2K1, MAP2K2, PTEN, and PTPN11 genes did not identify mutations in this case. Germline and somatic sequencing of BRAF exon 15 revealed no mutations at V600D/E/K. In addition, single-nucleotide polymorphism microarray analysis (330K) on lesional and normal skin revealed no genome-wide copy number changes or loss of heterozygosity., Conclusions: Clinicians should be aware of the occurrence of multiple pagetoid Spitz nevi to avoid morbidity associated with the misdiagnosis of multiple melanomas. The genetic mechanisms of pagetoid spread of melanocytes are not fully understood.

Pigmented epithelioid melanocytoma (PEM) is a recently described entity comprising most cases previously described as "animal-type melanoma" and epithelioid blue nevus (EBN) occurring in patients with the multiple neoplasia syndrome Carney complex (CNC). Mutations of the protein kinase A regulatory subunit type 1alpha (R1alpha) (coded by the PRKAR1A gene) are found in more than half of CNC patients. In this study, we investigated whether PEM and EBN are related at the molecular level, and whether changes in the PRKAR1A gene status and the expression of the R1alpha protein may be involved in the pathogenesis of PEM and other melanocytic lesions. Histologic analysis of hematoxylin and eosin-stained sections and immunohistochemistry (IHC) with R1alpha antibody were performed on 34 sporadic PEMs, 8 CNC-associated PEMs from patients with known PRKAR1A mutations, 297 benign and malignant melanocytic tumors (127 conventional sections of 10 compound nevi, 10 Spitz nevi, 5 deep-penetrating nevi, 5 blue nevi, 6 cellular blue nevi, 2 malignant blue nevi, 3 lentigo maligna, and 86 melanomas of various types); in addition, 170 tissue microarray sections consisting of 35 benign nevi, 60 primary melanomas, and 75 metastatic melanomas, and 5 equine dermal melanomas, were examined. Histologic diagnoses were based on preexisting pathologic reports and were confirmed for this study. DNA studies [loss of heterozygosity (LOH) for the 17q22-24 locus and the PRKAR1A gene sequencing] were performed on 60 melanomas and 7 PEMs. IHC showed that R1alpha was expressed in all but one core from tissue microarrays (169/170), and in all 127 melanocytic lesions evaluated in conventional sections. By contrast, R1alpha was not expressed in the 8 EBN from patients with CNC and PRKAR1A mutations. Expression of R1alpha was lost in 28 of 34 PEMs (82%). R1alpha was expressed in the 5 equine melanomas studied. DNA studies correlated with IHC findings: there were no PRKAR1A mutations in any of the melanomas studied and the rate of LOH for 17q22-24 was less than 7%; 5 of the 7 PEMs showed extensive 17q22-24 LOH but no PRKAR1A mutations. The results support the concept that PEM is a distinct melanocytic tumor occurring in a sporadic setting and in the context of CNC. They also suggest that PEM differs from melanomas in equine melanotic disease, further arguing that the term animal-type melanoma may be a misnomer for this group of lesions. Loss of expression of R1alpha offers a useful diagnostic test that helps to distinguish PEM from lesions that mimic it histologically.

Spitz naevi are usually solitary lesions. Multiple Spitz naevi are extremely rare and reported as widespread (disseminated) or grouped (agminated). We report two cases of multiple Spitz naevi and review their aetiology and treatment.

The epidermal nevus syndrome is the association of epidermal nevi with abnormalities in other organ systems, most commonly the central nervous system, the skeletal system, and the eyes. We present a patient with epidermal nevus syndrome associated with hypophosphatemic vitamin D-resistant rickets and multiple adnexal and spindle cell tumors.

The majority of Spitz nevi are acquired solitary lesions. Multiple Spitz nevi are rare and may develop on hyperpigmented skin. We report a 16-year-old girl with multiple Spitz nevi arranged on a café au lait macule. Immunohistochemistry showed positivity for S-100 and HMB-45. Of interest, expression of Polo-like kinase (PLK), a novel proliferation marker that recently proved to be positive in up to 98% of malignant melanoma cells, showed positivity in 40% of the nevus cells. The clinical development of multiple Spitz nevi is not yet clear, as they are preferentially excised. Reviewing 70 cases in the literature we found that multiple agminated Spitz nevi occur more frequently than reported previously. In about one-third of these cases Spitz nevi arose on congenitally hyperpigmented skin.

We report the unusual history of a young lady who, over a period of 9 years, developed 3 epithelioid neoplasms of different histiogenetic origin: a cutaneous epithelioid hemangioendothelioma, an epithelioid cell histiocytoma, and a Spitz nevus. To the best of our knowledge, such an unusual combination of neoplasms has not been reported previously and raises the question of an underlying "epithelioid" reaction pattern responsible for the epithelioid appearance in all 3 tumors; the likelihood of such a combination of tumors occurring in a single patient would be less than 1 in 1 billion.

We report an 18-year-old boy with a congenital pigmented lesion measuring 2 x 6 cm on his right thigh. About a third of the lesion was composed of numerous lentiginous macules superimposed on histologically normal and clinically nontan skin; in the remainder of the lesion, several macules and papules with histologic features of junctional and compound nevi were superimposed on clinically normal skin, which had a lentiginous pattern histologically. Some years later, eruptive intradermal Spitz nevi developed at one corner of the lesion. The combined clinical and histological features of the lesion fulfill descriptions for both segmental lentiginosis and an unusual variant of speckled lentiginous nevus. Our case points out the limitations of using strict diagnostic criteria to define speckled lentiginous nevus and offers an opportunity to consider the natural history of the lesion as a continuum from lentigines to melanocytic nevi. Moreover, the presence of eruptive intradermal Spitz nevi arising within the area of speckled lentiginous nevus lacking a distinct tan background, suggests the possibility that the entire area of the lesion per se constitutes an environment where development of nevi is enhanced.

A 40-year-old woman had a speckled lentiginous nevus on her thigh since birth. During her first pregnancy, additional papules and nodules appeared within the preexisting hyperpigmented area, histologic examination of which showed features of both junctional and compound Spitz's nevi accompanied by simple lentigolike changes. In this particular case, speckled lentiginous nevus may have constituted a particular environment for the production of multiple Spitz nevi.

A case of multiple agminated juvenile melanoma (MAJM) arising on a hyperpigmented macule is reported. The patient, a 1-year-old boy, had 9 small nodules on an irregular, hyperpigmented macule on the right shoulder. Histologically, the nodules contained nests of spindle-shaped cells in their epidermis and at the dermoepidermal junction, and the hyperpigmented macule exhibited increased melanin granules in the basal layer and small nests of epithelioid cells. We concluded that MAJM on a hyperpigmented macule is the subtype of the nevus spilus.