Intraparenchymal Nevus Cell Aggregates in Lymph Nodes: A Possible Diagnostic Pitfall With Malignant Melanoma and Carcinoma

Abstract

It is well documented that nevus cells can be found within the fibrous capsule and trabeculae of lymph nodes; however, it is less well known that nevus cells can also be found in the lymph node parenchyma. We report the findings in 13 cases of nevus cell aggregates located within the cortical and/or medullary parenchyma of lymph nodes. Seven of the 13 patients had a primary diagnosis of melanoma, three had no known malignancy, one had breast carcinoma, one had adnexal carcinoma of the skin, and one had squamous cell carcinoma of the tonsil. Of the seven patients with melanoma, four had axillary lymph node dissections and three had inguinal lymph node dissections. The patient with adnexal carcinoma had metastatic carcinoma in 14 of 20 lymph nodes that had been dissected; one of them also had intraparenchymal nevus cells. The patient with squamous cell carcinoma of the tonsil had an intraparenchymal nevus cell aggregate in one of the 21 dissected lymph nodes; all 21 were negative for carcinoma. Nests of intraparenchymal nevus cells ranged from clusters of only a few cells up to 2.1-mm aggregates. No mitotic figures, prominent nucleoli, or lymphatic-vascular invasion were detected in any of the melanocytic aggregates. The melanocytic cells of the nevus cell aggregates expressed S-100 protein and/or MART-1 but not gp100 protein (HMB-45). Less than 1% of the nevus cells expressed Ki-67. The purpose of this study was to draw attention to the finding of nevus cells in the parenchyma of lymph nodes and to alert pathologists to this as a potential diagnostic pitfall, especially in patients with concurrent melanoma or carcinoma. Awareness that nevus cells can be present in nodal parenchyma, analysis of their morphologic features (including comparison with any previous or existing melanoma or carcinoma), and immunophenotyping will help pathologists to establish the correct diagnosis in most instances.

Porcine Melanotic Cutaneous Lesions and Lymph Nodes

“…2,4,6 This theory would explain the presence of melanocytes in lymph nodes from pigs devoid of melanocytic cutaneous lesions.…”

“…In humans, the ''benign metastasis theory''-that is, nevus cells that enter dermal lymphatics and travel to assign residency in the draining lymph nodes-has been proposed to explain why benign nevus cells are sometimes found in the lymph nodes draining cutaneous nevi. 2,4,6 The benign metastasis theory also seems probable in pigs, when considering that the melan A-/PNL2-reactive cells in the trabecular sinuses were uniform, without signs of malignant behavior, and melan A-reactive melanocytes were also seen in trabecular sinuses of lymph nodes from pigs with no cutaneous melanocytic lesions.…”

“…10,20,29,40 The HMB-45 antibody is a marker of the cytoplasmic premelanosomal glycoprotein gp100. 4 HMB-45 is a specific marker for melanoma cells, but it is not reactive with normal adult melanocytes and intradermal nevus cells. 4,6,19,22,23,31,36,41,47 Positive labeling for HMB-45 has been demonstrated in porcine melanocytic tumors.…”

“…4 HMB-45 is a specific marker for melanoma cells, but it is not reactive with normal adult melanocytes and intradermal nevus cells. 4,6,19,22,23,31,36,41,47 Positive labeling for HMB-45 has been demonstrated in porcine melanocytic tumors. 20,30 Melan A is a melanocyte-differentiating protein that is recognized by cytotoxic T lymphocytes.…”

Immunohistochemistry in Dermatopathology

“…Combined MART-1-MIB-1 can improve the distinction between proliferating melanocytes in metastases and proliferating lymphocytes or histiocytes. 144 Just as HMB-45 does not label intradermal nevi, Biddle et al 178 found that an intranodal nevus is negative for HMB-45, unless it is a nodal blue nevus. Therefore, detection of HMB-45 in the melanocytic aggregate supports a diagnosis of metastatic melanoma; however, as mentioned previously, HMB-45 does not detect all metastatic melanomas, and its absence does not exclude melanoma.…”