Novel MED15::ATF1 fusion in a pediatric melanoma with spitzoid features and aggressive presentation.

Childhood melanoma is a rare and biologically heterogeneous pediatric malignancy. The differential diagnosis of pediatric melanoma is usually broad, including a wide variety of spindle cell or epithelioid neoplasms. Different molecular alterations affecting the MAPK and PI3K/AKT/mTOR pathways, tumor suppressor genes, and telomerase reactivation have been implicated in melanoma tumorigenesis and progression. Here, we report a novel MED15::ATF1 fusion in a pediatric melanoma with spitzoid features and an aggressive clinical course.

Risk factors and outcomes of melanoma in children and adolescents: A retrospective multicenter study.

BACKGROUND: Pediatric melanoma presents with distinct clinical features compared to adult disease. OBJECTIVE: Characterize risk factors and negative outcomes in pediatric melanoma. METHODS: Multicenter retrospective study of patients under 20 years diagnosed with melanoma between January 1, 1995 and June 30, 2015 from 11 academic medical centers. RESULTS: Melanoma was diagnosed in 317 patients, 73% of whom were diagnosed in adolescence (age ≥11). Spitzoid (31%) and superficial spreading (26%) subtypes were most common and 11% of cases arose from congenital nevi. Sentinel lymph node biopsy was performed in 68% of cases and positive in 46%. Fatality was observed in 7% of cases. Adolescent patients with melanoma were more likely to have family history of melanoma (P = .046) compared to controls. LIMITATIONS: Retrospective nature, cohort size, control selection, and potential referral bias. CONCLUSION: Pediatric melanoma has diverse clinical presentations. Better understanding of these cases and outcomes may facilitate improved risk stratification of pediatric melanoma.

Features, management, and outcomes of pediatric scalp melanomas.

Pediatric melanoma of the scalp has the highest mortality of any anatomic location. We describe five pediatric patients with a diagnosis of scalp melanoma receiving care at Massachusetts General Hospital and/or Boston Children's Hospital from 2018 through 2022. Melanoma presented in diverse contexts: cellular blue nevus-associated, compound nevus-associated, spitzoid, nodular, and superficial spreading subtypes. This study describes a range of melanoma presentations and emphasizes the need for additional compilation of data on pediatric scalp melanomas to promote their recognition and improve patient care.

The elusive BAP1 mutation in pediatric melanocytic tumors.

Cutaneous BAP1-inactivated melanocytomas (BIM) are melanocytic proliferations defined histopathologically by an epithelioid, predominantly dermal melanocytic proliferation with loss of BAP1, and have been largely characterized in adult patients but less well-described in pediatric cohorts. BIM share overlapping histological features with those seen in Spitz nevi; however, unlike Spitz nevi, the majority of BIM carry both BAP1 and BRAFV600E mutations. This study investigated the potential overlap of BIMs with pediatric Spitz nevi by performing immunohistochemical staining of BAP1 and BRAFV600E on pediatric melanocytic tumors with banal Spitz and dermal features. None of the stained tumors in our study exhibited the concurrent BAP1 loss and BRAFV600E positivity that are characteristic of adult BIM, suggesting that this is a low-frequency mutation among banal tumors in the pediatric population.

Regional lymph node evaluation in pediatric conventional melanoma subtype: a single-center 10-year review.

PURPOSE: To assess the prognostic and therapeutic significance of sentinel lymph node biopsy (SLNB) and completion lymph node dissection (CLND) in pediatric conventional melanoma (CM), while evaluating potential predictive factors for outcomes. METHODS: We conducted a retrospective analysis of medical records spanning 2009-2020, focusing on patients aged 18 or younger with localized cutaneous conventional melanoma. RESULTS: Among the 33 patients, SLNB detected metastasis in 57.6% of cases, with 52.6% undergoing CLND. Positive SLN patients had higher relapse risk (HR 5.92; 95% CI 1.27-27.7; P = 0.024) but similar overall survival (HR 3.19; 95% CI 0.31-33.1, P = 0.33). No significant differences in disease-free survival (DFS) and OS were found between patients who underwent CLND and those who did not (HR 1.91; 95% CI 0.49-7.43, P = 0.35, and HR 0.52; 95% CI 0.03-8.32, P = 0.64, respectively). Univariate analysis showed age at diagnosis (P = 0.02) correlated with higher recurrence risk, with a 21% hazard increase per additional year of age. CONCLUSIONS: Positive SLN status and age at diagnosis were associated with worse DFS in CM patients. Our study did not find any prognostic or therapeutic value in CLND for pediatric melanoma. Further multicenter trials are needed to confirm our single-institution experience. LEVEL OF EVIDENCE: Level IV.

A 13-Year-Old Girl Affected by Melanocytic Tumors of the Central Nervous System-The Case.

Primary intracranial melanoma is a very rare brain tumor, especially when accompanied by benign intramedullary melanocytoma. Distinguishing between a primary central nervous system (CNS) lesion and metastatic melanoma is extremely difficult, especially when the primary cutaneous lesion is not visible. Here we report a 13-year-old girl admitted to the Neurosurgery Department of the Institute of Polish Mother's Health Centre in Lodz due to upper limb paresis. An intramedullary tumor of the cervical C3-C4 and an accompanying syringomyelic cavity C1-C7 were revealed. The child underwent partial removal of the tumor due to the risk of damage to spinal cord motor centers. The removed part of the tumor was diagnosed as melanocytoma. Eight months later, a neurological examination revealed paresis of the right sixth cranial nerve, accompanied by bilateral optic disc edema. Diagnostic imaging revealed a brain tumor. The girl underwent resection of both detected the tumors and an additional satellite lesion revealed during the surgery. The removed tumors were diagnosed as malignant melanomas in pathomorphological examination. Molecular analysis revealed NRASQ61K mutation in both the intracranial and the intramedullary tumor. It should be noted that in cases where available evidence is inconclusive, an integrative diagnostic process is essential to reach a definitive diagnosis.

Pediatric Melanoma: Geographic Trends in Incidence, Stage, and Mortality in the United States.

INTRODUCTION: Pediatric melanoma is the most commonly diagnosed skin cancer in children, with the annual incidence recently increasing by an average of 2% each year. Ultraviolet (UV) radiation from excessive sun exposure is an important carcinogenic risk factor, with penetration varying greatly throughout the country. Consequently, an individual's geographic location may play a role in how much exposure to high UV index rays they receive throughout their lifetime. The objective of this study was to use the surveillance, epidemiology, and end results SEER database to study geographic trends in incidence, staging, and mortality of pediatric melanoma between 2009 and 2019 and determine their relation to UV index in the United States. MATERIALS AND METHODS: A retrospective analysis of pediatric patients from 0 to 19 years in the surveillance, epidemiology, and end results 22 registries incidence database (17 states) and 17 registries incidence-based mortality database (12 states) was conducted from 2009 to 2019 based on a diagnosis of melanoma of the skin using the International Classification of Childhood Cancer codes for malignant melanoma. Data regarding patient demographics and incidence, staging, and mortality per state were extracted. Incidence data were geographically mapped and mean UV index distribution from www.epa.gov was superimposed. RESULTS: Incidence of pediatric melanoma was stratified regionally, with a total of 1665 new cases from 2009 to 2019. The Northeast had 393 new cases, with 244 (62.1%) localized cases, 55 (14.0%) lymph node-invasive and metastatic (advanced) cases, and 6/146 (4.1%) cases of mortality. The Midwest had 209 new cases, with 123 (58.9%) localized cases, 29 (13.9%) advanced cases, and 1/57 (1.8%) case of mortality. The South had 487 new cases, with 224 (46.0%) localized cases, 104 (21.4%) advanced cases, and 8/232 (3.4%) cases of mortality. The West had 576 new cases, with 364 (63.2%) localized cases, 82 (14.2%) advanced cases, and 23/551 (4.2%) cases of mortality. Mean UV index was 4.4 in the Northeast, 4.8 in the Midwest, 7.3 in the South, and 5.5 in the West from 2006 to 2020. The regional difference in incidence was not statistically significant. There was a statistically significant increased number of advanced cases in the South as compared to the Northeast (P = 0.005), West (P = 0.002), and Midwest (P = 0.02), with a significant correlation coefficient of 0.7204 between advanced cases and mean UV index in the South. CONCLUSIONS: There is a statistically significant increased incidence of lymph node-invasive and metastatic pediatric melanoma cases in the South as compared to the West, Northeast, and Midwest regions of the United States. There is also a significant correlation between the incidence of lymph node-invasive and metastatic pediatric melanoma cases and UV index. In the pediatric population, there is no statistically significant association between total incidence and mortality of melanoma and geographic region. There is an increased prevalence of pediatric melanoma seen in White and female patients. This suggests that an individual's geographic location in the United States during childhood may play a role in their likelihood of malignant melanoma development, advanced-stage melanoma development, and mortality.

Examining the role of wide excision margins in pediatric melanoma: A National Cancer Database analysis.

BACKGROUND: Although adult guidelines are often applied to children, age-specific surgical margins have not been defined for pediatric melanoma. PROCEDURE: Patients <20 years of age with invasive, cutaneous melanoma were identified using the 2004-2016 National Cancer Database and categorized as undergoing wide (>1 cm) or narrow (≤1 cm) excision. Unadjusted overall survival (OS) was compared using the Kaplan-Meier method and log-rank test. Multivariable Cox proportional hazard models were used to estimate the effect of excision margin on OS after adjustment for available covariates. RESULTS: In total, 2081 patients met study criteria: 1338 (64.3%) patients underwent wide excision whereas 743 (35.7%) underwent narrow excision. Unadjusted OS was improved in the narrow-excision group (log-rank p = .01), which was consistent among patients with thicker (>1 mm) and thinner (≤1 mm) tumors. After adjustment for patient and tumor characteristics, we found no evidence of a difference in OS for patients who underwent narrow excision compared to patients who underwent wide excision (adjusted hazard ratio 0.57, 95% confidence interval 0.32-1.01, p = .053). There was no interaction between excision margin width and Breslow depth (p = .85), indicating that the effect of excision margin width on OS does not differ based on Breslow depth. CONCLUSIONS: In this analysis, wide excision (>1 cm) does not appear to be associated with improved survival in children with melanoma regardless of tumor characteristics. Although further studies are needed to define optimal excision margins in pediatric melanoma, this study suggests that more narrow margins (≤1 cm) may be acceptable.

Genomic comparison of malignant melanoma and atypical Spitz tumor in the pediatric population.

BACKGROUND/OBJECTIVES: The diagnostic distinction between atypical Spitz tumor (AST) and malignant melanoma (MM) in pediatric tumors is challenging. Molecular tests are increasingly used to characterize these neoplasms; however, limited studies are available in pediatric patients. This study aimed to provide a genomic comparison of pediatric MM and AST in the context of comprehensive clinical annotation. METHODS: Pediatric patients diagnosed with MM (n=11) and AST (n=12) were compared to a cohort of 693 adult melanoma patients. DNA next-generation sequencing assessed kinase gene fusions, tumor mutational burden, sequence variants, copy number alterations, structural variants, microsatellite instability, and mutational signatures. RESULTS: Seven AST cases and eight MM cases were successfully sequenced. Kinase gene fusions were identified in both the MM and AST cohorts (NTRK1, ROS1, and MET). MM cases had TERT, BRAF, and CDKN2A alterations, which were not identified in the AST cohort. Tumor mutational burden (TMB) analysis showed pediatric ASTs had an average of 2.82 mutations/Mb, pediatric MM had an average of 5.7 mutations/Mb, and adult MM cases averaged 18.8 mut/Mb. One pediatric MM case had an elevated TMB of 15 mutations/Mb and a UV mutational signature. CONCLUSIONS: These data expand our understanding of pediatric malignant melanoma. The differences between the molecular signatures for AST and MM are not statistically significant, and histopathology remains the gold standard for the diagnosis of pediatric AST and MM at this time. With more data, molecular studies may provide additional support for diagnosis and targeted therapeutics.

Pediatric melanoma in the Hispanic population: An analysis of institutional and national data.

BACKGROUND/OBJECTIVES: Pediatric melanoma is rare and remains poorly characterized, especially in racial/ethnic minorities of whom Hispanics are the largest and fastest growing in the United States. The health care burden of melanoma in Hispanics, who often present with more advanced disease, is rising and has even been called an early epidemic in California. We sought to document key clinicopathologic features of melanoma in Hispanic pediatric patients and to compare these parameters to pediatric non-Hispanic whites (NHWs) under the a priori hypothesis that Spitzoid melanomas occur in greater proportions in Hispanics. METHODS: Single-institution cross-sectional study of pediatric melanoma cases (age < 20 years) with Hispanic stratification and comparison with matched Surveillance, Epidemiology, and End Results (SEER) data from the same time frame (1988-2016). RESULTS: Of our 61 institutional cases of pediatric melanoma, Hispanics (11), compared with NHWs (40), presented significantly younger (11.7 years, 95% CI: 2.77-8.00 years; P = .001), with lower limb predominance (46%; P < .05), mostly Spitzoid melanomas (82%; P < .05), and thicker tumors (2.34 mm, CI: 0.26-2.19 mm; P < .05). Similarly, SEER data (2499 cases) showed greater proportions of childhood/pre-pubertal adolescent melanomas (<15 years), lower limb involvement, Spitzoid subtype (36.5% vs 22.5% in NHWs; P = .001), and advanced (regional/distant) disease stages in Hispanics (212) compared with NHWs (2197). CONCLUSIONS: Pediatric melanomas may present differently in Hispanics, and heightened awareness/lower threshold to biopsy high-risk Spitzoid tumors on the lower limb may be warranted. Further investigations are needed to aid prevention and early detection in a vulnerable minority population less likely to seek outpatient dermatology specialty care.

Fatal GNAQ-mutated CNS melanoma in an adolescent with nevus of Ota.

Nevus of Ota is an uncommon benign mesodermal melanosis that involves the first and second divisions of the trigeminal nerve. Primary non-cutaneous melanoma often involves distinct genetic mutations compared to cutaneous melanoma. In primary central nervous system (CNS) melanomas associated with nevus of Ota, somatic mutations most commonly occur at the Q209 and R183 residues of GNAQ and likely induce tumorigenesis through upregulation of the MAP kinase pathway. This case underscores the importance of elucidating neurologic symptoms early in patients with nevus of Ota, as a delayed presentation of CNS melanoma could portend a devastating outcome.

Congenital Melanocytic Nevus: Considerations for Neonatal Clinicians and a Parent Perspective.

Congenital melanocytic nevus (CMN) or nevi, also known as dark moles, are present at birth. While small CMN are quite common, large and giant nevi are rare and can be associated with significant psychological distress and the potential for further clinical sequelae. Neonatal clinicians can offer anticipatory guidance to families through distribution of resources and navigation to additional consultants.

Cutaneous eyelid melanoma in an African American child.

Cutaneous melanoma of the eyelid constitutes less than 2% of all eyelid malignancies. Such cases in the pediatric population are even rarer, and exceedingly so in darkly pigmented individuals. A 9-year-old African American boy presented with a left upper eyelid lesion. Biopsy was consistent with deep penetrating melanoma, and the patient underwent a wide local excision and sentinel node biopsy. One upper parotid sentinel node was positive, leading to further parotidectomy and selective neck dissection. The eyelid defect was reconstructed by primary closure after margin clearance. This is the first reported case of cutaneous eyelid melanoma in an African American child with nodal metastasis. Clinical features of melanoma in the pediatric population can be more atypical and higher index of suspicion is indicated. While rare, the diagnosis of melanoma in darkly pigmented patients is still possible and cannot be excluded without a definitive biopsy.

A retrospective multicenter study of fatal pediatric melanoma.

BACKGROUND: Pediatric melanoma is rare and diagnostically challenging. OBJECTIVE: To characterize clinical and histopathologic features of fatal pediatric melanomas. METHODS: Multicenter retrospective study of fatal melanoma cases in patients younger than 20 years diagnosed between 1994 and 2017. RESULTS: Of 38 cases of fatal pediatric melanoma identified, 57% presented in white patients and 19% in Hispanic patients. The average age at diagnosis was 12.7 years (range, 0.0-19.9 y), and the average age at death was 15.6 years (range, 1.2-26.2 y). Among cases with known identifiable subtypes, 50% were nodular (8/16), 31% were superficial spreading (5/16), and 19% were spitzoid melanoma (3/16). One fourth (10/38) of melanomas arose in association with congenital melanocytic nevi. LIMITATIONS: Retrospective nature, cohort size, and potential referral bias. CONCLUSIONS: Pediatric melanoma can be fatal in diverse clinical presentations, including a striking prevalence of Hispanic patients compared to adult disease, and with a range of clinical subtypes, although no fatal cases of spitzoid melanoma were diagnosed during childhood.

Pediatric melanoma: Characterizing 256 cases from the Colorado Central Cancer Registry.

BACKGROUND: Melanoma is a rare diagnosis in the pediatric population. Differences in incidence, presentation, and survival distinguish pediatric melanoma from adult melanoma. In order to improve our understanding of pediatric melanoma, our case series investigates differences in incidence, age of onset, and anatomic site between male and female pediatric melanoma patients in Colorado between 1988 and 2015. METHODS: All data were gathered from the Colorado Central Cancer Registry. A request for de-identified data on pediatric melanoma patients between 1988 and 2015 was made by the University of Colorado Department of Dermatology. Chi-square tests were used to compare the differences reported in melanoma between sex, age-groups, and site of lesion. RESULTS: A total of 256 cases of melanoma were reported in Colorado in patients < 20 years of age between 1988 and 2015. Overall incidence of pediatric melanoma in Colorado increased from 1988 to 1999 but declined from 2001 to 2011. There was a significant predominance of female cases in the 10-14 age-group (P = 0.0477) and 15-19 age-group (P = 0.0472). Both groups had increased incidence of melanoma with increasing age. The mean age of onset for both sexes was 16 years old. Boys were more likely to have melanoma of the scalp and neck (P = 0.0523) and less likely to have melanoma of the leg (P = 0.0049). CONCLUSION: Among the pediatric population, girls 10-14 and 15-19 years old are at a significantly increased risk of melanoma compared to boys in these age-groups. Our study found sex-specific differences in anatomic site consistent with prior literature. Further investigations should aim to identify causes for these sex-specific differences in order to better guide public health initiatives.

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.

Pathology and genomics of pediatric melanoma: A critical reexamination and new insights.

The clinicopathologic features of pediatric melanoma are distinct from those of the adult counterpart. For example, most childhood melanomas exhibit a uniquely favorable biologic behavior, save for those arising in large/giant congenital nevi. Recent studies suggest that the characteristically favorable biologic behavior of childhood melanoma may be related to extreme telomere shortening and dysfunction in the cancer cells. Herein, we review the genomic profiles that have been defined for the different subtypes of pediatric melanoma and particularly emphasize the potential prognostic value of telomerase reverse transcriptase alterations for these tumors.

Pediatric patients with cutaneous melanoma: A European study.

INTRODUCTION: Cutaneous melanoma is rare in childhood and published studies have mainly been retrospective single-institution series or small case series. Given the absence of clinical protocols dedicated to pediatric melanoma, the treatment approach is generally extrapolated from the ones applied to adults. METHODS: Coordinated by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT), this study collected patients prospectively registered between 2002 and 2012 under national cooperative projects dedicated to rare pediatric tumors in Italy, Poland, Germany, and France. Additional cases were collected from dermatology registries in Germany and Israel. RESULTS: A total of 219 patients aged 0-18 years (median 14.4) were included in the analysis. Sentinel lymph node biopsy was performed in 112 patients (76% of those with Breslow thickness > 0.75 mm) and was positive in 37.5%. Systemic therapy was used in 33 cases. In stage III cases, survival rates were similar for patients who received (23 cases) or not (21 cases) adjuvant therapy. For the whole series, 3-year overall and disease-free survival rates were 91.4% and 84.0%, respectively (median follow-up 41.8 months). Tumor site, tumor stage, and ulceration influenced survival rates. Patients treated by pediatric oncologists (n = 140) were more likely to have advanced disease than those treated by dermatologists (n = 79). DISCUSSION: This study would suggest that the clinical history of melanoma in children and adolescents might resemble that of adult counterpart. Cooperative efforts are needed to make new drugs more readily available to pediatric patients to increase the outcome of patient with advanced disease.

Clinical and dermoscopic characterization of pediatric and adolescent melanomas: Multicenter study of 52 cases.

BACKGROUND: Knowledge regarding the morphologic spectrum of pediatric melanoma (PM) is sparse, and this may in part contribute to delay in detection and thicker tumors. OBJECTIVE: To analyze the clinicodermoscopic characteristics of PM. METHODS: Retrospective study of 52 melanomas diagnosed in patients before the age of 20 years. RESULTS: On the basis of its clinical, dermoscopic, and histopathologic characteristics, PM can be classified as spitzoid or nonspitzoid. The nonspitzoid melanomas (n = 37 [72.3%]) presented in patients with a mean age of 16.3 years (range, 8-20) and were associated with a high-risk phenotype and a pre-existing nevus (62.2%). The spitzoid melanomas (n = 15 [27.7%]) were diagnosed in patients at a mean age of 12.5 years (range, 2-19) and were mostly de novo lesions (73.3%) located on the limbs (73.3%). Whereas less than 25% of PMs fulfilled the modified clinical ABCD criteria (amelanotic, bleeding bump, color uniformity, de novo at any diameter), 40% of spitzoid melanomas did. Dermoscopic melanoma criteria were found in all cases. Nonspitzoid melanomas tended to be multicomponent (58.3%) or have nevus-like (25%) dermoscopic patterns. Spitzoid melanomas revealed atypical vascular patterns with shiny white lines (46.2%) or an atypical pigmented spitzoid pattern (30.8%). There was good correlation between spitzoid subtype histopathologically and dermoscopically (κ = 0.66). LIMITATIONS: A retrospective study without re-review of pathologic findings. CONCLUSION: Dermoscopy in addition to conventional and modified clinical ABCD criteria helps in detecting PM. Dermoscopy assists in differentiating spitzoid from nonspitzoid melanomas.

Congenital melanocytic nevi in young children: Histopathologic features and clinical outcomes.

BACKGROUND: Although only large congenital melanocytic nevi (CMN) are associated with a significantly high risk for malignant transformation, CMN of all sizes are prone to changes in clinical appearance in early childhood and thus are often biopsied or excised. While CMNs typically exhibit benign behavior, atypical histopathologic findings might be common and may prompt additional unnecessary procedures. OBJECTIVE: To assess the prevalence and associated clinical outcomes of atypical histopathologic features in CMN in children. METHODS: A single center retrospective study was conducted with patients 0-35 months of age with CMN diagnosed by histopathology between 1993-2013. RESULTS: One hundred seventy-nine patients with a total of 197 CMNs were identified. Cytologic atypia, architectural disorder, or pagetoid spread were present in 73% of CMN. With a mean follow up of 7.3 years, no cases of melanoma or CMN-related deaths were identified. LIMITATIONS: Our findings were based on a largely Caucasian population and might not apply to darker skin types. Our findings might not apply to older children or adults with CMN. CONCLUSION: Atypical histopathologic features of cytologic atypia, architectural disorder, and pagetoid spread are common in benign CMN of young children.