Sentinel Lymph Node Biopsy in a Young Child With Thick Cutaneous Melanoma

The worldwide incidence of melanoma has been rising steadily at a rate of 4% to 6% per year, which is faster than all other types of cancer.[1] Melanoma affects all age groups, with the average age at diagnosis reported to be 48 years.[2] Fewer than 1% of melanomas occur in patients under age 17.[3] Lymphatic dissemination often precedes distant dissemination and is a strong indicator of prognosis.[4] Head and neck melanomas present a unique challenge because the lymphatic drainage pattern of this area is multiple, varied, and unpredictable.[5] Sentinel lymph node biopsy (SLNB) for cutaneous head and neck melanoma has the potential advantage of avoiding the morbidity of routine elective lymph node dissection while accurately staging the regional nodes at risk for micrometastases. This has clear implications for the patient's prognosis and eligibility to participate in clinical trials of adjuvant therapy.[ 6] Although the use of SLNB is accepted in adults, no evidence-based literature currently supports its use in the management of children. Case Report The patient is a 4-year-old white male with a several-month history of a growing lesion on the right cheek that was diagnosed as a large pyogenic granuloma (Figure 1). At the time of excision, the lesion was 1.5 cm in diameter, raised 2 cm above skin level, and contained an eschar. The child was referred to Brenner Children's Hospital after excision revealed a pathologic diagnosis of ulcerating malignant melanoma. The lesion was determined to be at least 5 mm deep, a Clark's level IV, with positive margins. Upon referral, an independent review of the pathology confirmed the previous diagnosis of thick melanoma. A metastatic work-up that included a positron-emission tomography scan, chest x-ray, and liver function tests revealed no evidence of metastatic disease. Family history of melanoma was negative. The recommendation for treatment was wide excision, with reconstruction, sentinel lymph node mapping, and formal modified neck dissection if the nodes were positive. On the morning of surgery, the patient was taken to the nuclear medicine department for lymphoscintigraphy. Technetium-99m sulfur(Drug information on sulfur) colloid was injected intradermally around the previously excised melanoma. The sulfur colloid localized to two areas- one located immediately inferior to the right external ear and the second at the base of the neck on the right. Hot Spots Excised
The patient was transported to the operating room. The previous injection site was then infiltrated with 1 mL of intradermal isosulfan blue (Lymphazurin). The face was massaged for 7 minutes. Using the Gamma probe (Neoprobe 2000 Gamma Detection System, Ethicon Endo-Surgery Inc, Johnson and Johnson, Cincinnati) over the primary injection site, a count was obtained, and a background count was determined. The Gamma probe was then placed over the two "hot spots" identified on lymphoscintigraphy. Hot spot number 1 at the superior jugular node chain, and hot spot number 2 over the inferior jugular node chain showed counts of 810 and 235, respectively. An incision was made over the first hot spot; two blue nodes were identified under the platisma with ex vivo counts of 748 and 746. A third node had elevated counts but no uptake of dye, with an ex vivo count of 310. The count in the basin was 90 after sentinel node dissection. Hot spot number 2 at the level IV jugular nodes was approached in a similar fashion. Four lymph nodes were found at this site. One lymph node was blue with an ex vivo count of 540, and three others showed no uptake of dye but had ex vivo countsof 238, 332, and 388. After excision, the count in the basin was 72. The nodes were submitted for touch prep, and initial evaluation showed no evidence of melanoma. The skin and subcutaneous tissue of the cheek was then excised, with 2-cm margins around the previous excision. The defect was reconstructed using a full-thickness skin graft. Final pathologic evaluation showed metastatic spread to one lymph node in the level II jugular lymph node chain. The patient underwent a right modified radical neck dissection 2 weeks later. An additional 13 nodes were obtained, and all were negative for metastatic melanoma. Following surgery, the patient was evaluated for adjuvant therapy with interferonalpha. Discussion Sentinel lymph node biopsy has revolutionized surgical management of primary melanoma. It allows accurate nodal staging and targets patients who may benefit from regional lymphadenectomy and systemic therapy. Morton et al proposed the SLNB concept.[ 7] They found that the injection of blue dye into the dermis around the primary tumor would lead to localization of an initial node within the nodal basin. The sentinel lymph node (first-echelon node) is defined as the first node in the regional basin that receives lymphatic drainage from the primary tumor site. The sentinel node can be identified intraoperatively with the aid of a vital dye injected at the site of the primary lesion, or with the use of a gamma probe after injection of radiolabeled material, or both.[7] The combined approach identifies the sentinel node in ≥ 90% of patients with cutaneous melanoma. The ability of the pathologic evaluation of the sentinel node to predict the status of the entire nodal basin has been confirmed by multiple reports.[8-10] The use of SLNB in the young child is not well established, given the small number of pediatric cases of melanoma. The data that do exist may overestimate survival because of the inclusion of Spitz nevi. A report by Trozak et al represents a comprehensive review of the literature on metastatic melanoma in prepubertal children.[11] Trozak divides childhood melanoma into three types: (I) congenital transplacentally acquired melanoma, (II) melanoma with onset before puberty, and (III) melanoma starting from a giant congenital melanocytic nevus. Patients with Trozak type II childhood melanoma (TNM stage IV disease) had a 5-year survival rate of 34%, which closely mirrors the behavior of metastatic melanoma in large series of adult patients.[11] Prognostic Indicators
The prognosis, treatment, and role of SLNB in adult patients with thick cutaneous melanoma (≥ 4.0 mm or Clark level V) have been the subject of ongoing debate. Patients with thick cutaneous, clinically node-negative melanomas carry a high risk of both regional and nodal micrometastases as well as occult systemic disease at the time of initial presentation.[12] Because the 5-year survival rates in these patients are 30% or less, treatment has often been considered palliative.[ 13] It was thought that the risk of micrometastatic or distant disease was so high in this population, it would negate any curative benefit of a regional operation. These patients had been referred for adjuvant therapy and had not been considered candidates for elective lymph node dissection. Adjuvant therapy with interferonalpha has some activity in patients with melanoma[14]; however, no clear benefit in terms of overall survival has been demonstrated.[15] Evolving data from Heaton et al support nodal status determined by elective lymph node dissection or the development of clinically apparent disease as the most important prognostic factor for overall survival.[16] Tumor thickness and the presence of ulceration are believed to be independent predictors of survival.[17] In a large retrospective analysis, Slingluff et al reported that only 36% of patients with 4-mm thick melanoma had positive nodes at elective lymph node dissection.[18] This is in contrast to the findings of Essner et al, who believe that for patients with thick cuta-neous melanoma, regional lymph node metastasis represents a marker of systemic disease. Their results suggest that sentinel node status is predictive of disease-free survival but is not reflective of overall survival.[19] Despite the controversy that surrounds SLNB as a prognostic predictor in patients with thick cutaneous melanoma, accurate nodal staging in cutaneous head and neck melanoma is essential to the diagnosis and treatment of this disease. For patients with a positive SLNB, nodal status helps select those who would benefit most from adjuvant therapy. A positive SLNB also leads to excision of nodal disease, which results in improved regional control. Subsequent adjuvant therapy may have an enhanced therapeutic effect because local disease has been removed. Patients with a negative SLNB are spared the morbidity and mortality of radical lymphadenectomy and adjuvant therapy. Conclusions The incidence and mortality rate of malignant melanoma has been increasing rapidly. Presently, fewer than 1% of head and neck melanomas occur in childhood, and therapy is largely based on the experience of melanomas in adults. The primary treatment of melanoma in children remains surgical.surgical. However, there appears to be a role for SLNB in this population.