A reappraisal of the epidemiology of Spitz neoplasms in the molecular era: A retrospective cohort study.

BACKGROUND: Previous studies suggest that Spitz neoplasms occur primarily in younger patients, leading pathologists to shy away from diagnosing a benign Spitz neoplasm in the elderly. With the advent of genomic sequencing, there is a need for reappraisal of the epidemiology of Spitz neoplasms in the modern molecular era. OBJECTIVE: We aim to reassess the epidemiology of Spitz neoplasms incorporating next-generation sequencing. METHODS: We looked at 53,814 non-Spitz neoplasms and 1260 Spitz neoplasms including 286 Spitz neoplasms with next-generation sequencing testing and collected various epidemiologic data. RESULTS: In our general pool of cases, the proportion of Spitz neoplasm cases occurring is relatively the same in each of the first 4 decades of life with a precipitous drop in the fifth decade. In assessing a group of genomically verified cases of Spitz neoplasms, the drop was much less significant and up to 20% of all Spitz neoplasm cases occurred in patients over 50 years of age. LIMITATIONS: Limitations included the number of genetically verified Spitz neoplasm cases available and a possible bias as to which cases undergo genomic testing. CONCLUSION: Genomic verification may allow more confident diagnosis of Spitz neoplasms in patients over 50 years of age and avoid melanoma overdiagnosis.

Differences in individual and environmental factors between cutaneous melanoma and atypical Spitz tumour in children and adolescents.

It is not known if children and adolescents with atypical Spitz tumour and cutaneous melanoma differ in terms of etiological factors. The aim of this study was to explain differences in individual and environmental factors between cutaneous melanoma and atypical Spitz tumour. In the context of a study on melanocytic lesions, all subjects aged under 20 years with either cutaneous melanoma or atypical Spitz tumour were included (N = 105). Information on socio-demographic characteristics, individual and environmental factors were collected for both mother and child. The Fisher's exact test and the Mann-Whitney U test were used for categorical variables and continuous variables respectively. A multivariate logistic model was used to explain differences in outcome by differences in explanatory variables. In comparison to patients with cutaneous melanoma, patients with atypical Spitz tumour had less freckles (p = 0.020), lower number of common nevi (p = 0.002), and lower body mass index (p = 0.001) and experienced less sunburns episodes (p = 0.008). However, in the multivariate analysis, only a low number of common nevi remained statistically significant. Children and adolescents with cutaneous melanoma have a high number of nevi in comparison to the same-age group with atypical Spitz tumour.Conclusion: The results of this study suggest that the only difference in individual and environmental risk factors between cutaneous melanoma and atypical Spitz tumour in children and adolescents is the number of nevi. What is Known: •Atypical Spitz tumours and cutaneous melanoma in children and adolescents are clinically similar, but compared with melanoma, they have a good overall prognosis. •Risk factors for cutaneous melanoma in children and adolescents are similar to the ones found in adults in the literature What is New: •Differences in individual and environmental risk factors for atypical Spitz tumour in children and adolescents are described for the first time in this study. •Individual and environmental factors for atypical Spitz tumour in children and adolescents are comparable to cutaneous melanoma, except for the presence of low number of nevi.

Atypical Spitz tumours: an epidemiological, clinical and dermoscopic multicentre study with 16 years of follow-up.

BACKGROUND: Atypical Spitz tumours (ASTs) are regarded as an intermediate category distinguished from prototypical Spitz naevus by presenting one or more atypical features and often by an uncertain malignant potential. Clinical and dermoscopic features may play a relevant role in the diagnostic approach. AIM: To evaluate the clinical and dermoscopic features of ASTs, and their evolution over time. METHODS: This was a descriptive, multicentre study of the clinical and dermoscopic characteristics of ASTs. Data on clinical and dermoscopic characteristics, histopathology, local extension, therapy and follow-up, lymph node staging, complete lymph node dissection, and outcome were collected from the databases of four Italian Dermatology Units for the period 2004-2021. RESULTS: The study population consisted of 99 patients (62 female, 37 male) with a histologically confirmed diagnosis of AST, including age at presentation ranged from 2 to 70 years (mean 28.1 years, median 24 years). Of the 99 patients, 29 (29.3%) underwent sentinel lymph node biopsy, which showed evidence of micrometastases in three cases (10.3%); all three patients underwent complete lymph node dissection with no evidence of further metastasis. Considering the whole study population, the clinical outcome was excellent, as all of the patients have no evidence of recurrence or distant metastasis. The follow-up period ranged from 6 to 216 months (mean 81.6 months, median 78 months). In addition, we collected data on the clinical and dermoscopic features of 26 lesions. The most frequent dermoscopic pattern observed was the multicomponent pattern (34.6%), followed by homogeneous (26.9%) and nonspecific (23.2%). In 66.7% of amelanotic ASTs, we observed glomerular (coiled) vessels uniformly distributed within the entire lesion, without asymmetry. CONCLUSION: The results of our study with a long follow-up show no recurrence or distant metastases, confirming the good clinical outcome, even in the case of sentinel lymph node positivity. From a diagnostic point of view, our series identified a typical dermoscopic picture for amelanotic ASTs, with a glomerular vascular pattern throughout the lesion in the absence of other dermoscopic parameters, making the correct diagnosis possible.

Risk factors for the development of Spitz neoplasms.

BACKGROUND/OBJECTIVES: The principal environmental risk factor for conventional nevi and melanomas is ultraviolet exposure. However, little is known about genetic or environmental risk factors for developing Spitz tumors. This study investigates risk factors associated with Spitz neoplasms. METHODS: Patients with Spitz tumors seen at Northwestern Memorial Hospital and Lurie Children's Hospital were surveyed with a 16-item questionnaire about environmental and inherited factors. Spitz tumor patients were compared to a pediatric control cohort from a similar clinical setting. This was supplemented with a meta-analysis of genetic and environmental causes of Spitz neoplasms. RESULTS: One hundred and six Spitz and 58 control surveys were obtained and no statistically significant differences in genetic or environmental risk factors were found between Spitz and control groups. CONCLUSION: Our data and meta-analysis suggest that typical risk factors associated with melanoma are not significantly associated with Spitz tumors. Identification of relevant genetic or environmental risk factors will likely require larger and population-based studies.

Clinical features and outcomes of spitzoid proliferations in children and adolescents.

BACKGROUND: Spitzoid proliferations range from Spitz naevi to melanomas. There are few studies describing clinical features and outcomes in the paediatric population. OBJECTIVES: To determine the clinical features and outcomes of a large paediatric cohort with histopathologically confirmed Spitz tumours. METHODS: This was a retrospective cohort study of patients seen at Boston Children's Hospital who were aged < 20 years and had a histopathological diagnosis of spitzoid proliferation from 1 January 1994 to 23 October 2012. RESULTS: In total 595 patients with 622 spitzoid proliferations were identified (median age 7·4 years, interquartile range 4·6-11·7). Overall 512 proliferations (82·3%) were typical, 107 (17·2.%) were atypical and three (0·5%) were melanomas. The median ages at biopsy were 7·4, 7·2 and 17·2 years, respectively, and there was a significant difference in age at biopsy for patients with typical or atypical proliferations vs. melanoma (P < 0·01). Among samples with positive margins (n = 153), 55% (54 of 98) of typical proliferations, 77% (41 of 53) of atypical proliferations and 100% (two of two) of melanomas were re-excised. Six patients had sentinel lymph node biopsy performed, with three patients demonstrating nodes positive for melanocytic cells. Within a median follow-up of 4·1 years for the full cohort there were no related deaths. CONCLUSIONS: Spitz tumours have strikingly benign outcomes in the paediatric population, although this study is limited by the low number of melanomas and restriction to a single paediatric institution. Aggressive management recommendations should be reconsidered for children and adolescents with banal-appearing Spitz naevi, based on the clinically indolent behaviour in this cohort.

Characteristics of melanoma in white and nonwhite children, adolescents, and young adults: Analysis of a pediatric melanoma institutional registry, 1995-2018.

OBJECTIVES: To characterize clinical differences among nonwhite/multiethnic vs white children, adolescents, and young adults with melanoma or atypical melanocytic neoplasms, including atypical Spitz tumors. PATIENTS AND METHODS: A cohort of 55 patients (< 25 years of age) prospectively followed from 1995 to 2018 in the Stanford Pigmented Lesion and Melanoma Program was analyzed for differences in clinical presentation, including skin phototype, race/ethnicity, age, sex, tumor/melanoma characteristics, and outcome. RESULTS: Seventeen patients (9 males and 8 females) were classified as nonwhite (predominantly skin phototype IV) and of Hispanic, Asian, or Black/African American ethnicity, and 38 patients (21 males and 17 females) were classified as white (predominantly phototypes I/II). Ages ranged from 6 months to 24 years, and median follow-up was 36 months (range 1-180 months). Melanomas were diagnosed in 87% of whites in our cohort, compared to 65% of nonwhites, with the remainder representing mainly atypical Spitz tumors. Lesions were usually brought to the attention of a health care provider by the patient or family (P < 0.05). Compared with whites, nonwhites were more likely to present at a younger mean age (10.9 years vs 15.4 years, P < 0.05) and with pink/clinically amelanotic tumors (59% vs 24%, P = 0.02). CONCLUSIONS: This long-term prospective institutional study showed clinically relevant differences between nonwhite vs white children, adolescents, and young adults diagnosed with melanoma and atypical melanocytic neoplasms. Nonwhite patients presented at a younger age and had more clinically amelanotic melanocytic tumors. Increased recognition of clinical factors and risk of these tumors in nonwhites could result in earlier diagnosis.

Patients with Spitz naevi in the Greek population: Epidemiologic, Clinical and Histopathological characteristics.

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.

Spitz Nevi and Other Spitzoid Neoplasms in Children: Overview of Incidence Data and Diagnostic Criteria.

Spitz nevi are benign melanocytic neoplasms characterized by epithelioid or spindle melanocytes or both. In some rare cases their presentation overlaps with the clinical and histopathologic features of malignant melanoma, so a differential diagnosis can be difficult to make. Intermediate forms between Spitz nevi and malignant melanoma, with unpredictable behavior, have been called atypical Spitz tumors. A literature search was performed to review the clinical, dermoscopic, genetic, and histopathologic aspects of spitzoid tumors. Spitz nevi mainly occur in children, with no predilection for sex, and in young women. Common sites are the head and lower arms, where Spitz nevi present as pink nodules or hyperpigmented plaques. Spitzoid lesions may have diverse dermoscopic patterns: vascular, starburst, globular, atypical, reticular, negative homogeneous, or targetoid. The management of spitzoid lesions can be invasive or conservative; surgical excision is usually reserved for those with doubtful features, whereas clinical and dermoscopic follow-up is preferred for typical pediatric Spitz nevi. The role of sentinel lymph node biopsy in atypical Spitz tumors is debated. Immunohistochemistry and new molecular techniques such as comparative genomic hybridization, polymerase chain reaction, and fluorescence in situ hybridization offer new diagnostic perspectives, investigating genetic alterations that are specific for malignant melanoma or for Spitz nevi.

Spitz nevi: diverse clinical, dermatoscopic and histopathological features in childhood.

BACKGROUND AND OBJECTIVES: The characterization of clinical features and biological potential of Spitz nevi has attracted a lot of interest in past decades. The aim of our paper was to describe the clinical, dermatoscopic features as well as the clinical outcome of surgically excised Spitz nevi in three different pediatric age groups. PATIENTS AND METHODS: A retrospective study analyzing clinical features, videodermatoscopic images, histopathological diagnosis and patient outcome. The level of pigmentation was evaluated both clinically and histopathologically. RESULTS: 72 spitzoid neoplasms were excised from 71 pediatric patients. Videodermatoscopic images were available for 41 patients. The distribution of pigmentation significantly correlated with patient age: hyperpigmented lesions were rather rare in preschool children, becoming more frequent in patients aged 7 to 12 years and older than 13 years. The histopathological diagnosis of atypical Spitz nevus was uncommon. None of the patients originally diagnosed with atypical Spitz nevi developed local recurrence or metastases during subsequent follow-up. CONCLUSIONS: Pigmented Spitz nevi were more common after 13 years of age. The study confirms other reports regarding the distribution of pigmentation patterns, and underlines the low number of atypical Spitz nevi in pediatric patients as well as their low recurrence rate during long-term follow-up.

Spindle and/or epithelioid cells nevi in pediatric age: are they different from those of adults? A clinical review of 187 cases.

AIM: Spindle and/or epithelioid cells nevi represent the spectrum of a clinico-pathologic entity with different characteristics. Aim of the study is to provide information about the differences in characteristics of these nevi for different groups of age. METHODS: Two different groups are considered: younger than 15 years and older than 15 years. An analysis of 187 spindle and/or epithelioid cells nevi was performed. Forty-five pediatric patients (24 males and 21 females) and 142 adult patients (44 males and 98 females) were examined. Age, sex, type of nevus, location, clinical characteristics were evaluated. RESULTS: Spindle and epithelioid cells nevi were observed in 53% of the pediatric and in 45% of adult patients. Female more frequently presented with spindle nevus cell both in pediatric (56%) and in adult (70%) cases. In pediatric patients, the anatomical distribution was prevalent in the areas of the head and neck. Pigmentation was not a distinctive feature of pediatric cases and only interested the spindle and epithelioid cells nevi. The regularity of borders was not a distinctive character for neither of the groups of patients. Uniformity in color occurred more frequently in pediatric patients. CONCLUSION: Spindle and/or epithelioid nevi belong to the same spectrum of pathologies, they behave differently in the different groups of age thus permitting a certain degree of clinical distinction in different age groups.

Spitz naevus is rare in Korea.

BACKGROUND: Spitz naevi have not been widely studied in Asians. AIM: To compare the epidemiology and clinicopathological features of Spitz naevi in Koreans with lesions in western countries. METHODS: In total, 80 Spitz naevi in 77 patients diagnosed over 10 years at 17 university hospitals in Korea were analysed. RESULTS: The relative incidence of Spitz naevus vs. MM was 1 vs. 10.9. In most patients (75%) the Spitz naevi had been present for > 6 months. The size of the lesion was relatively large. Histologically, most of the lesions (54%) were the dermal type and pigmentation was common (49% of lesions). Immunohistochemical study found that all of the 34 lesions were positive for S-100 protein but only 14 (47%) were positive for HMB-45. CONCLUSION: Spitz naevus is rare in Korea. The lesions were more commonly larger, pigmented, and of the dermal type than reported in western countries.

Melanoma and melanocytic nevi in pediatric patients: a single institution experience.

BACKGROUND: Melanoma is an infrequent neoplasm in children and adolescents. The number of consultancies for melanocytic nevi control in the pediatric population is increased by the major anxiety of parents and pediatricians. METHODS: A retrospective chart review was performed in order to evaluate the incidence rate of melanoma, Spitz nevi, congenital and acquired melanocytic nevi in patients aged 14 years or less and referred to our institution from April 2010 to September 2015. RESULTS: A total of 32,755 dermatologic pediatric consultancies were performed in the considered 66 months period, including 4260 patients referred for mole control (13%). During the same period, a total of 5193 excisions of melanocytic lesions were performed (adults and pediatric patients), 259 of which were performed in 250 patients aged 14 years or less (4.98%). Only 1 in situ melanoma of the nail matrix was detected in a 12-year-old female patient (0.38% of surgical excisions). The number needed to excise (NNE) in our pediatric population, calculated by comparing the total number of excised lesions and the number of melanomas found, was 259. CONCLUSIONS: Our data leads to 3 major observations: 1) the rarity of melanoma in patients with 14 years of age or less is confirmed; 2) the number of excisions performed in this pediatric population is extremely high; 3) neither the cases of melanoma and atypical Spitz neoplasm (ASN) nor the majority of Spitz nevi were referred to us for a generic mole control. Mole controls in the pediatric population should be properly addressed, incrementing the attention on specific suspicious cutaneous lesions.

The large spectrum of Spitzoid tumors: a retrospective survival study.

BACKGROUND: There is no universally-accepted classification of Spitzoid tumors. This makes it difficult to assign a correct diagnosis and select a treatment that minimizes the risk of overestimating, or worse, underestimating, the malignant potential of these tumors. The aim of this study was to describe the clinical-pathological and epidemiological features of Spitzoid tumors, as well as to assess mortality in these patients. METHODS: This retrospective cohort study looked at data on Spitzoid tumors excised in 1999-2012 at the Dermatologic Clinic of the Turin University Hospital. Spitzoid melanoma specific survival curves were generated with the Kaplan-Meier method and compared using the log-rank test. RESULTS: In this time period, 1663 lesion were described at the pathologic report as Spitzoid. 262 (15.75%) were Spitz nevi, 307 (18.46%) Reed nevi, 827 (49.73%), 810 (48.71%) Spitzoid dysplastic nevi, 17(1.02%) atypical Spitzoid tumors, and 267 (16.06%) Spitzoid melanomas. Median follow-up time was 9 years. Out of the entire cohort only 24 patients died from melanoma. All of them received a diagnosis of Spitzoid melanoma. None of the patients with a diagnosis of not melanoma Spitz tumor died for melanoma during the follow-up. CONCLUSIONS: In the large majority of the cases, Spitz tumor should be considered as benign lesion and excised only if melanoma features are seen. The used clinical pathological classification avoid misdiagnoses, inappropriate treatment and the risk of death for melanoma.

Melanoma frequency among symmetrical Spitzoid-looking lesions: a retrospective study.

BACKGROUND: Many efforts have been spent attempting to define clinical, histopathological and molecular markers for differential diagnosis of Spitz nevus and melanoma. Dermoscopy has been widely used but it may be not always sufficient. METHODS: A retrospective study was performed evaluating Spitzoid-looking lesions showing symmetry at clinical and dermoscopic examination in patients ≥12 years attending our Clinic from 2004 to 2014. Demographic, clinical and dermoscopic data were assessed for each lesion in order to highlight the most common characteristics which could help the differential diagnosis between Spitz nevus and melanoma when clinical or dermoscopic asymmetry is lacking. RESULTS: A total of 760 lesions were excised. 690/760 (90.8%), were identified as typical Spitz nevi, whereas 70/760 lesions (9.2%) consisted of malignant melanocytic lesions. Our study showed that almost 9.2% of clinically and dermoscopically symmetric Spitzoid lesions revealed to be malignant melanocytic lesion. For symmetric Spitzoid looking lesions female sex, clinical palpability, the presence of an inverse network at dermoscopic examination and the involvement of lower limbs were observed as the main factors, which were linked to a higher possibility of being malignant lesions. CONCLUSIONS: In order to avoid missing diagnoses for malignant melanocytic lesions, this study remarked the importance of preventive excision for all Spitzoid-looking lesions in patients ≥12 years, even if they show symmetry at both clinical and dermoscopic level.

Paediatric melanoma.

Cutaneous melanoma occurs only rarely in children under 10 years of age. Mimics of melanoma, including Spitz naevi and proliferative nodules in congenital melanocytic naevi are much more frequent in this age group. Melanoma arising in congenital melanocytic naevus is uncommon, but can show aggressive behaviour. Although spitzoid lesions constitute the majority of 'diagnostically challenging' cases, they are an uncommon cause of mortality in this age group. Among lesions with undoubted metastatic potential, there are biologically distinct tumours which differ significantly in behaviour from the common types of melanoma seen in adults. In patients over 10 years of age and increasingly into the late adolescent years, melanoma is a relatively common neoplasm. Just as in adult patients, care should be taken to exclude melanoma mimics. Particular care is warranted in this older age group in the assessment of lesions with spitzoid morphology as there is significant potential for both over-and under-diagnosis.

The spectrum of Spitz nevi: a clinicopathologic study of 83 cases.

OBJECTIVE: To achieve a clinicopathologic classification of Spitz nevi by comparing their clinical, dermoscopic, and histopathologic features. DESIGN: Eighty-three cases were independently reviewed by 3 histopathologists and preliminarily classified into classic or desmoplastic Spitz nevus (CDSN, n = 11), pigmented Spitz nevus (PSN, n = 14), Reed nevus (RN, n = 16), or atypical Spitz nevus (ASN, n = 14); the remaining 28 cases were then placed into an intermediate category (pigmented Spitz-Reed nevus, PSRN) because a unanimous diagnosis of either PSN or RN was not reached. SETTING: University dermatology and pathology departments and general hospital pathology departments. PATIENTS: A sample of subjects with excised melanocytic lesions. MAIN OUTCOME MEASURE: Frequency of dermoscopic patterns within the different histopathologic subtypes of Spitz nevi. RESULTS: Overlapping clinical, dermoscopic, and histopathologic findings were observed among PSN, RN, and PSRN, thereby justifying their inclusion into the single PSRN diagnostic category. Asymmetry was the most frequent indicator of histopathologic ASN (79%; n = 11); in only 4 cases did dermoscopic asymmetry show no histopathologic counterpart, and in those cases the discrepancy was probably the result of an artifact of the gross sampling technique carried out with no attention to the dermoscopic features. CONCLUSIONS: Among Spitz nevi, histopathologic distinction between PSN and RN is difficult, not reproducible, and may be clinically useless. A simple clinicopathologic classification of these neoplasms might therefore be structured as CDSN, PSRN, and ASN. Asymmetry should be assessed using both dermoscopic and histopathologic analysis, and reliability in histopathologic diagnosis may be enhanced by the simultaneous evaluation of the corresponding dermoscopic images.

Spitz naevus versus Spitzoid melanoma: when and how can they be distinguished?

Spitz naevus is a benign melanocytic lesion that shares many histological features with melanoma. While Spitz naevi characteristically occur in children and young adults and melanomas in the middle-aged and elderly, either tumour can occur in patients of any age. In many cases, the histopathological diagnosis of Spitz naevus is straightforward, particularly in small lesions displaying many or all of the typical histological features and occurring in young patients. Tumours that deviate from the classic description, however, cause difficulties in diagnosis. In this review, we highlight histopathological features of Spitz naevi and those that may be useful in distinguishing Spitz naevi from melanomas. We find that the presence of good symmetry, Kamino bodies, and uniformity of cell nests or sheets from side-to-side favours a Spitz naevus. The presence of abnormal mitoses, a dermal mitotic rate of >2/mm2, and mitotic figures within 0.25 mm of the deep border of the lesion favours a melanoma. Immunohistochemical stains for HMB45 and Ki67 sometimes provide additional useful information. Despite this, in some cases it may not be possible to give an unequivocal diagnosis. Recommendations for the reporting of such cases are provided. New techniques have also demonstrated chromosomal, molecular and genetic differences between Spitz naevi and melanomas. This report highlights these new data and speculates on their possible future role in the diagnosis of borderline lesions.

Spitz nevus on the palmar surface.

Relatively little is known about the incidence of Spitz nevus on palmar surfaces. This report places a case study in the context of the Japanese literature regarding the occurrence of Spitz nevus on palmar surfaces. Although the proportion of palms and soles in relation to the body surface is about 5%, the incidence of the Spitz nevus was 2%. The mean age at onset was 17.8 years, and all 4 cases were women. The clinical features were a black macule or flatly elevated small modules. The size of the lesions was relatively small, extending from 3.5 mm to 8.0 mm. Although the backs of the hands and insteps have almost the same area as the palms and soles, the incidence of onset in these regions was 6.3% (13 cases). We thus concluded that Spitz nevus tends to be rare on palms and soles.