Anatomic Pathology / NODAL NEVI

Melanocytic nevi occurring in lymph nodes create diagnostic difficulty by mimicking metastases. Few studies describe nodal nevi in sentinel lymph nodes (SLNs) excised for melanoma. We evaluated 72 cases in which patients had undergone SLN biopsy for melanoma. Lymph nodes and cutaneous melanomas were evaluated according to a standard protocol. Nodal nevi were identified in 8 patients (11%). Of these, 6 (75%) had an associated cutaneous nevus (P = .006). Of 21 patients with an associated nevus, 4 (19%) with nodal nevi had a cutaneous nevus with congenital features (P = .01). The incidence of nodal nevus correlated with a Breslow thickness greater than 2.5 mm (P = .02). Nevi were not seen in non-SLNs. Nodal nevi appear more frequently in patients with melanomaassociated cutaneous nevi, particularly if congenital features are present. The increased frequency of nodal nevi in SLNs relative to non-SLNs suggests an etiology of mechanical transport of nevus cells. Descriptions of intranodal melanocytic nevocellular inclusions (nodal nevi) have been reported periodically over the years.1-5 Nodal nevi predominantly form compact focal aggregates in the fibrous capsule and trabeculae of lymph nodes, although they recently have been described in the nodal parenchyma and sinusoids.6 The incidence in regional lymph nodes excised for malignancy has been reported to be between 1% and 22%.5,7,8 From a diagnostic standpoint, nodal nevi might mimic metastases when encountered in regional lymph nodes evaluated for staging patients with melanoma, and it has been reported that their occurrence in this group of patients is greater than in people undergoing regional lymph node excisions for other malignant neoplasms.7,9,10 The mechanism by which benign melanocytes are transported to lymph nodes is the subject of controversy. Prevailing theories include lymphatic transfer of melanocytes from a cutaneous nevus to a lymph node in the lymphatic drainage basin3,7 and an embryologic phenomenon whereby neural crest–derived melanocytes are transported to lymph nodes during in utero migration. The increasing popularity of sentinel lymph node (SLN) mapping in patients with melanoma in conjunction with more stringent evaluation techniques has led to increased frequency of discovery of nodal nevi in regional lymph nodes excised for the treatment of melanoma.7 In addition, a correlation between the frequency of nodal nevi and the presence of melanomaassociated cutaneous nevi including those with congenital features has been reported.7,11 Distinguishing benign nodal nevi from melanoma metastases to an SLN may be difficult, and it is of critical importance for the determination of prognosis and systemic treatment.12 To our knowledge, only 2 systematic studies describing the characteristics of nodal nevi Anatomic Pathology / ORIGINAL ARTICLE Am J Clin Pathol 2004;121:58-63 59 59 DOI: 10.1309/Y5QAD623MYA21PUY 59 © American Society for Clinical Pathology in SLNs excised for melanoma have been published.7,11 SLN biopsy is an accepted staging procedure, and we expect that it will be used even more widely in the future. Accordingly, the diagnostic dilemma imposed by nodal nevi will continue to be encountered in this setting.13,14 For this reason, we conducted the present retrospective study in an attempt to define further the features of nodal nevi in patients with melanoma. Materials and Methods Between December 1998 and March 2002, material from all SLN mapping procedures performed for melanoma at the Wake Forest University Baptist Medical Center, Winston-Salem, NC, was retrieved. Only cases in which the corresponding primary melanoma had been reviewed were included in the study. Melanoma was categorized by specific subtypes, Clark level, Breslow thickness, and the presence and type of preexisting melanoma-associated cutaneous nevi. The morphologic features of any associated precursor melanocytic lesion were characterized with particular attention given to the presence or absence of congenital features. For the purposes of this study, congenital features included small cutaneous nevi demonstrating the presence of nevus cells in the lower two thirds of the dermis; splaying of collagen bundles by singly or vertically oriented linear arrays of nevus cells; and extension of cells around nerves, vessels, and adnexa, as previously described.15 We acknowledge that there is overlap in the histologic features of congenital vs acquired nevi; however, for the purposes of this study, the cutaneous nevi with the aforementioned histologic features were considered to be congenital. In addition, the presence or absence of a geographically separate non–melanoma-associated melanocytic lesion in the wide excision specimen was noted. A standard protocol was used to identify the SLN. The tumor bed was injected with technetium sulfur colloid (0.51.0 mCi [18.5-37.0 MBq]) preoperatively. A lymphoscintigram was obtained in the nuclear medicine department before the patient’s arrival in the operative suite, and a gamma probe (Neoprobe 2000, Neoprobe, Dublin, OH) was used intraoperatively to detect the SLNs. In addition, in all cases, perilesional intradermal injections of isosulfan blue were used intraoperatively to provide visual identification of the SLNs. SLNs then were harvested and sent fresh to the pathology department for intraoperative evaluation and subsequent permanent section evaluation. The SLN was obtained as the initial phase of the surgical procedure, with excision of the primary lesion generally being performed during intraoperative pathologic evaluation of the SLN. This minimized the impact of intraoperative evaluation on the total surgical time. Intraoperative evaluations were performed by imprint cytology as previously described16 and, if positive, resulted in immediate regional lymph node dissection. If the intraoperative evaluation was not performed, then a lymph node dissection was not performed during the same procedure. SLNs were bisected along the long axis, fixed in 10% buffered formalin, processed in the usual manner, and paraffin embedded. A single H&E-stained section of the paraffin block was examined initially. If this section was negative for melanoma, 3 additional H&E-stained levels cut at 50-μm intervals in conjunction with immunohistochemical stains for S-100 and HMB-45 (DAKO, Carpinteria, CA) on the first of the 3 levels were evaluated. Immunohistochemical studies were performed using the avidin-biotin-peroxidase complex method.17 Primary antibodies included S-100 and HMB-45. Immunohistochemical stains were considered positive for malignant melanoma if immunoreactivity was detected in cell clusters or individual cells that demonstrated architectural and cytologic features of metastatic tumor cells ❚Image 1❚ and ❚Image 2❚. All metastases were compared with the primary melanoma. When discrepancies existed between the intraoperative and permanent section diagnoses, slides were reviewed in an attempt to determine the cause of the discrepancy. Nodal nevi were defined as bland nevocellular aggregates cytologically resembling those found in the intradermal component of the associated cutaneous nevus, when present. Generally, inclusions consisted of compact aggregates of cells with pale homogeneous eosinophilic cytoplasm and inconspicuous melanin pigment, indistinct cytoplasmic borders, round nuclei with delicate chromatin, inconspicuous basophilic nucleoli, and minimal, if any, mitotic activity ❚Image 3❚ and ❚Image 4❚. Stereotypical locations in the lymph node included the fibrous capsule and trabeculae, although care was exercised to identify nodal nevi in the parenchyma and subcapsular sinus, as recently described.6 In all cases, nodal nevi were compared with the primary melanoma and any associated cutaneous nevus to distinguish cytologic differences. Non-SLNs were examined using standard pathologic techniques. If the non-SLNs were more than 4 mm wide, they were sectioned; if they were less than 4 mm wide, the non-SLNs were submitted whole. Routinely, a single H&Estained section of the non-SLNs was examined, but in select cases, multiple levels were obtained in an attempt to verify the presence of metastases. Statistical comparisons were made using the Fisher exact test.