Elsevier

Human Pathology

Volume 39, Issue 8, August 2008, Pages 1136-1142
Human Pathology

Original contribution
KBA.62: a useful marker for primary and metastatic melanomas

https://doi.org/10.1016/j.humpath.2007.12.006Get rights and content

Summary

We previously described a novel antimelanoma antibody, designated KBA.62. However, review of the literature showed that only a few studies have reported on this antibody. We report our experience in the diagnosis of melanoma using KBA.62 and its value in both primary and metastatic conditions. In addition to conventional melanomas, we included desmoplastic and spindle cell melanomas, whose diagnosis can be challenging. We also focus on identification of malignant cells in sentinel lymph node biopsies using KBA.62, by comparison with anti–S-100 protein and HMB-45 antibodies, because discrepancies in sensitivity and specificity of melanoma markers have given rise to numerous studies aiming to determine the best panel for the evaluation of sentinel lymph node from patients with melanoma. Overall, KBA.62 was positive in 93% of primary and metastatic melanomas. Interestingly, the 12 cases of desmoplastic and spindle cell melanomas had strongly positive results. In addition, the results of our study performed on a series of 215 sentinel lymph nodes showed that the sensitivity of anti–S-100 protein and KBA.62 antibodies in detecting occult metastasis was similar. Moreover, KBA.62 identified 6 patients (3%) who had confirmed sentinel lymph node metastasis but were negative for HMB-45. The resolution was higher with KBA.62 than that observed with anti–S-100 protein antibody, as the nonmelanocytic positive cells for KBA.62 in lymph nodes were only represented by endothelial cells, which therefore constituted an intrinsic positive control. We conclude that KBA.62 antibody is a useful additional marker for melanoma, specifically in desmoplastic/spindle cell cases and in the context of micrometastasis in sentinel lymph node.

Introduction

Melanoma diagnosis can be challenging, particularly in metastatic conditions, because it can mimic undifferentiated carcinoma, sarcoma, or large cell lymphoma. Furthermore, desmoplastic or spindle cell melanoma may be difficult to identify when tumor cells lack melanin pigment, when the biopsy is small, or in metastatic conditions. Moreover, these tumors sometimes display focal, equivocal staining or even negative staining for S-100 protein [1], [2], [3]. HMB-45 and Melan-A antibodies are of limited value in these cases because several studies have reported either very focal staining or virtually no staining at all with these 2 antibodies [4]. These discrepancies in sensitivity and specificity of melanoma markers have been confirmed by numerous studies on the best panel for the evaluation of sentinel lymph node (SLN) from patients with melanoma [5], [6], [7], [8], [9]. The strategy to enhance tumor detection consists of serial sections of lymph node. Several studies have shown that exhaustive sectioning permits a histologic review of the entire lymph node but does not increase significantly tumor detection [5], [10]. Although it is now recognized that immunohistochemistry is more sensitive than hematoxylin and eosin (H&E), there is no consensus regarding the optimal panel of antibodies [6], [7], [9], [11]. However, anti–S-100 protein antibody remains the gold standard and HMB-45 antibody the most commonly associated marker [12].

In 1995, we described a novel antimelanoma monoclonal antibody, designated KBA.62, which reacts with most of benign and malignant melanocytic proliferations and with well-differentiated squamous carcinomas [13]. However, the differential diagnosis between melanocytic proliferation and well-differentiated squamous carcinomas is not considered a challenging problem, easily resolved through morphological features and S-100/cytokeratin immunophenotype. Besides, other markers such as anti–S-100 protein, HMB-45, MITF, PNL2, and Melan-A antibodies known to react with nonmelanocytic tumors are nevertheless considered good melanoma markers [14], [15], [16], [17]. However, review of the literature showed that only a few studies have reported on KBA.62 antibody [1], [18], [19].

The purpose of the current study was to report our experience in the diagnosis of melanoma using KBA.62 by comparison with anti–S-100 protein and HMB-45 antibodies in both primary and metastatic conditions, including pure and combined desmoplastic melanomas, and with regard to the management of a series of 215 SLN biopsies.

Section snippets

Primary and metastatic melanomas

Cases diagnosed in 2005 were selected from the archives of the Department of Pathology, Centre Hospitalo-Universitaire (CHU) Purpan, Toulouse, France. The study was carried out in accordance with the institutional review board–approved protocol. Seventy-four primary melanomas consisted of 31 superficial spreading melanomas, 9 acral lentiginous melanomas, 15 lentigo maligna melanomas, 2 nodular melanomas, 3 pure desmoplastic melanomas (defined by fusiform melanocytes dispersed in a prominent

Primary and metastatic melanomas (Fig. 1, Table 1)

The results of KBA.62, HMB-45, and anti–S-100 protein stainings on primary and metastatic melanomas are detailed in Table 1. As expected, virtually all tumors were positive for S-100 protein. Overall, KBA.62 was positive in most cases (90/97 cases, 93%), with a moderate to strong membrane staining (Fig. 1B and E). The reactivities of KBA.62 and HMB-45 were comparable (93% versus 85.5%; P = .10), except for the 3 cases of pure desmoplastic primary melanomas and the nodal desmoplastic metastatic

Discussion

We have already reported the potential diagnostic value of KBA.62 monoclonal antibody in melanocytic neoplasms [13]. This antibody reacts with a not yet identified antigen, which can be detected on routinely fixed, paraffin-embedded tissues. However, during the past decade, only a few studies have dealt with this melanoma marker [1], [18], [19]. Interestingly, Kaufmann et al [18] compared tyrosinase, melan-A, and KBA.62 reactivity for the diagnosis of metastatic amelanotic melanomas. They

Acknowledgments

The authors acknowledge Florence Capilla, Michel March, and Jeanine Boyes for their excellent technical assistance.

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