This clinical trial compares the effect of using risk-based stratification to guide surgical management to the usual approach in treating cutaneous melanoma, atypical Spitz/Spitzoid tumors or other atypical melanocytic tumors that have not spread to other parts of the body (localized). Melanoma is a cancer that in children is sometimes difficult to tell apart from benign (not harmful) or atypical (uncertain if harmful) skin lesions. Failure to diagnose melanoma can result in inadequate surgical removal and increase the risk of recurrence and metastatic disease (spread from where it first started to other places in the body). In addition, diagnosing a tumor a benign (not cancer) tumor as cancer may lead to unnecessary surgery and treatment. This trial reviews tumor pathology and genetic markers and classifies the tumor as not atypical, atypical but low risk for spread and/or recurrence (coming back after a period of improvement), and atypical and high risk for spread and/or recurrence. The classifications are then used to provide surgical recommendations. Tumors that are not atypical do not receive any surgical treatment. Low-risk recommendations include removing a small layer of normal skin around the tumor. High-risk recommendations include the usual adult melanoma approach of removing a larger layer of normal skin around the tumor with or without a biopsy of the sentinel lymph node (the first lymph node to which tumor cells are likely to spread from a primary tumor). Risk-based guided surgical management may help avoid unnecessary surgery while improving outcomes in younger patients with localized cutaneous melanoma, atypical Spitz/Spitzoid tumors or other atypical melanocytic tumors.

PRIMARY OBJECTIVE:

I. To study the feasibility of central risk-based stratification of malignant and atypical cutaneous melanocytic tumors to guide primary surgical management.

SECONDARY OBJECTIVES:

I. To evaluate the adherence rate to protocol-assigned surgical management in children with newly diagnosed melanoma, atypical Spitz/Spitzoid tumors, and other atypical melanocytic neoplasms.

II. To evaluate the surgery-related adverse events profile for patients treated with narrow re-excision without sentinel lymph node biopsy versus wide local excision +/- sentinel lymph node biopsy per standard adult cutaneous melanoma guidelines.

III. To describe progression free survival (PFS) and overall survival (OS) in pediatric patients with melanoma, atypical Spitz/Spitzoid tumors, and other atypical melanocytic neoplasms.

EXPLORATORY OBJECTIVES:

I. To describe surgical reconstruction techniques for pediatric patients with atypical and malignant melanocytic tumors.

II. To describe the use of sentinel lymph node biopsy and rate of completion nodal dissection vs observation following positive sentinel lymph node including number of sentinel nodes sampled, size of largest metastatic nodal deposit, location of draining lymph node basin(s), number of lymph nodes resected at completion dissection.

III. To describe surgical complications of completion nodal dissection (from time of surgery to 90 days following surgery): wound dehiscence, seroma/hematoma, hemorrhage, infection, skin graft failure, necrosis of flap used for reconstruction, lymphocele, lymphedema, deep vein thrombosis.

IV. To evaluate the concordance between local treating center pathologic diagnosis and central pathology review diagnosis.

V. To analyze the molecular characterization of melanocytic tumors to identify molecular and immunohistochemical biomarkers correlating with known clinical prognostic factors and outcome.

VI. To determine the number of Children's Oncology Group (COG) institutions that open the study within 18 months of activation.

OUTLINE: Patients with not atypical pathology are assigned to the Observation Arm. Patients with atypical low-risk tumors are assigned to Treatment Arm A and patients with atypical high-risk tumors are assigned to Treatment Arm B.

OBSERVATION ARM: Patients undergo observation throughout the study.

TREATMENT ARM A: Patients may undergo narrow margin re-excision without sentinel lymph node biopsy.

After completion of study intervention, patients are followed every 6 months for 1 year then every year for up to 5 years.

TREATMENT ARM B: Patients undergo wide local excision with or without sentinel lymph node biopsy (SLNB) per standard guidelines. Patients may also undergo blood sample collection, chest x-ray, computed tomography (CT), magnetic resonance imaging (MRI), whole-body fludeoxyglucose F-18 (FDG) positron emission tomography (PET)/CT or PET/MRI, nodal basin ultrasound, and brain MRI on study.

After completion of study treatment, patients are followed every 3-6 months for years 1 and 2, every 6 months up to year 5.

Inclusion Criteria:

• Patients ≤ 25 years old
• Newly diagnosed localized cutaneous melanoma, atypical Spitz/Spitzoid tumors, or other atypical melanocytic neoplasm by local institution pathology report
• Patients must have disease that is localized to the skin on clinical assessment. Note that staging imaging is not required for the determination of eligibility, but if obtained prior to enrollment, all imaging must be consistent with localized cutaneous disease
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients ≤ 16 years of age
• Patients must not have received any prior chemotherapy, immunotherapy, targeted therapy, radiation, or surgical therapy for melanoma other than the permitted biopsy/excision of the lesion for which they are enrolling. Note that prior biopsies/surgery for other benign melanocytic lesions is permitted

Exclusion Criteria:

• Patients ≥ 18 years old with conventional adult-type melanoma are excluded. Note that patients 18-25 years old with atypical Spitz/Spitzoid tumors, or other atypical melanocytic neoplasms are eligible

• Patients with clinical evidence of metastatic disease such as palpable malignant adenopathy or symptomatic distant metastases are not eligible

• Patients who have undergone re-excision to achieve a negative margin or sentinel lymph node biopsy for the melanocytic neoplasm under study are not eligible. Note that this does not exclude patients who have undergone the permitted diagnostic biopsy/excision, including re-biopsy, of the lesion

• Any of the following diagnoses

  • Congenital nevi-associated proliferative nodules
  • Agminated Spitz nevi/tumors
  • Dysplastic nevus
  • Combined nevus
  • CRTC1::TRIM11 and/or MED15::ATF1 fused tumors (molecular testing is not required prior to enrollment)

• Pre-existing conditions:

  • Solid organ transplant recipients
  • Known melanoma predisposition syndrome (i.e., patients with previously known pathogenic variants in moderate and high penetrance melanoma susceptibility genes [i.e., CDKN2A, CDK4, BAP1, POT1, TERT promoter, ACD, TERF2IP] or Xeroderma Pigmentosum). Note germline testing is not required prior to enrollment

• All patients and/or their parents or legal guardians must sign a written informed consent

• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met