CASE REPORT

Eruptive Melanocytic Nevi Induced by Interferon for Nodal Metastatic Melanoma: Case Report and Review of the Literature Thomas G. Salopek and Muhammad N. Mahmood Background: The rapid appearance of multiple new melanocytic nevi is known as eruptive nevi and has been well documented to occur with certain medications, in particular chemotherapeutic agents. Methods: We report a case of a woman with melanoma complicated by nodal metastasis who developed multiple melanocytic nevi while on high-dose interferon. Results: Serial photographs confirmed that the pigmented lesions were of new onset, whereas histology documented that the lesions were dysplastic nevi. A survey of the literature documented numerous causes of eruptive nevi, which we review. To date, interferon has not been linked to eruptive nevi. Conclusions: The phenomenon of eruptive nevi has been attributed to medications, bullous dermatoses, immunosuppression, and systemic conditions and is possibly a paraneoplastic disorder. Interferon appears to be another possible cause of this disorder. Contexte: L’apparition rapide de nombreux nouveaux nævus me´lanocytiques, appele´s nævus e´ruptifs, est bien documente´e en relation avec certains me´dicaments, notamment avec les agents chimiothe´rapeutiques. Me´thode: Sera expose´ ici le cas d’une femme atteinte d’un me´lanome complique´ de me´tastases ganglionnaires, chez qui sont apparus de nombreux nævus me´lanocytiques en cours de traitement par l’interfe´ron a` forte dose. Re´sultats: Des photographies en se´rie ont confirme´ que les le´sions pigmente´es e´taient d’apparition re´cente, et l’examen histologique a e´tabli qu’il s’agissait de nævus dysplasiques. Une recherche documentaire, suivie d’un examen, a fait ressortir de nombreuses causes a` l’origine des nævus e´ruptifs, mais aucun lien n’a e´te´ e´tabli jusqu’a` maintenant entre l’interfe´ron et ces nævus. Conclusions: L’apparition de nævus e´ruptifs est attribue´e aux me´dicaments, aux dermatoses bulleuses, a` l’immunode´pression et aux maladies ge´ne´rales, et il s’agirait d’un syndrome parane´oplasique. L’interfe´ron semble donc une autre cause possible du trouble.

HE TERM eruptive nevi refers to the abrupt appearance of melanocytic nevi, generally over several weeks to months, which is not related to sun exposure or known triggering factors for the appearance of nevi (eg, puberty or pregnancy). The condition is best associated with chemotherapeutic agents, primarily in children and young adults. Although previous authors have attributed

T

From the Division of Dermatology and Cutaneous Sciences, Department of Medicine, and Division of Anatomical Pathology, Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB. Address reprint requests to: Thomas G. Salopek, MD, FRCPC, Division of Dermatology and Cutaneous Sciences, Department of Medicine, University Dermatology Centre, 2-125 Clinical Sciences Building, Edmonton, AB T6G 2G3; e-mail: [email protected].

DOI 10.2310/7750.2013.13034 # 2013 Canadian Dermatology Association

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the nevi to the chemotherapeutic agents that were given, the possibility that this is a paraneoplastic phenomenon related to the underlying malignancy that is being treated cannot be dismissed.1 Interferon has been used for confirmed nodal metastasis secondary to melanoma since 1996.2 Despite over 15 years of use, there have been no reports of interferon-inducing eruptive nevi. We report a 44-yearold woman who developed multiple nevi during her maintenance therapy with interferon for stage IIIb melanoma. In addition, we review the literature for all reported associations and presumed triggers for eruptive melanocytic nevi.

Case Report A 44-year-old woman presented to the dermatology clinic with a history of multiple nevi that developed shortly after

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induction with high-dose interferon for stage IIIb melanoma. She initially presented to her family doctor with a changing pigmented lesion of the right thigh, which had increased in size and had become darker in pigmentation. This was initially interpreted as a compound nevus by the reporting pathologist. She later presented with a right inguinal mass with profound nausea, anorexia, and significant weight loss. A fine-needle aspirate biopsy of the inguinal mass was consistent with metastasis from melanoma. Subsequent review of the original lesion that had been biopsied 9 months earlier was interpreted as malignant melanoma, Clark level IV, 0.85 mm with microfocal regression, with a mitotic index of 2/mm2 and no ulceration. Clinical and radiologic staging failed to detect any distant or visceral metastasis. A complete lymph node dissection of the right groin found one of eight nodes positive for a metastatic melanoma. No wide local excision of the primary site was performed. She was started on the standard high-dose interferon-a2b regimen for stage III melanoma for 1 year. Shortly after maintenance therapy, she

and her husband noted the appearance of multiple nevi involving the face, trunk, and limbs. Photographs taken prior to the initiation of interferon or during the induction phase confirmed that the lesions did not exist prior to the introduction of interferon (Figure 1). Biopsies of representative lesions of the chest and right arm revealed compound Clark (dysplastic) nevus at each site (Figure 2).

Discussion We report on the appearance of eruptive nevi that developed after induction of high-dose interferon for nodal metastatic, stage IIIb melanoma. This has not been previously reported in the medical literature. Numerous causes and associations have been reported with eruptive nevi, including bullous disease, immunodeficiency, malignancies, toxic exposure, drugs, and miscellaneous systemic diseases (Table 1). Although it is tempting to attribute her eruptive nevi to the use of interferon, the possibility that this is a paraneoplastic phenomenon cannot be dismissed. McCourt and colleagues have

Figure 1. Photographs prior to or during treatment with interferon (A, C, E) and approximately 6 months after starting treatment (B, D, F).

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Figure 2. Punch biopsy from the right arm disclosed a nevus with a nested and lentiginous junctional component and a mainly nested dermal component showing maturation (hematoxylin-eosin stain; original magnification: A, 350; B, 3100).

Table 1. Reported Associations and Possible Causes of Eruptive Melanocytic Nevi Drug induced Chemotherapy drugs Anticonvulsants Melanotan Azathioprine Octreotide Epidermal growth factor inhibitors B-raf inhibitors (sorafenib) Interferon (current publication) Bullous diseases Stevens-Johnson syndrome Epidermolysis bullosa Immunosuppression Immunodeficiency Viral infection Leukemia Anti-TNF inhibitors Renal transplantation Concurrent medical conditions Epilepsy Crohn disease Addison disease Renal transplantation Paraneoplastic phenomena Melanoma Prostate cancer Leukemia Toxic mediated Exposure to mustard gas Adapted from references 1 and 4 to 36. TNF 5 tumor necrosis factor.

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recently raised this possibility in the context of prostate cancer.1 Interestingly, many of the previous reports that link eruptive nevi to chemotherapy may be related to an underlying malignancy, primarily leukemia. Due to the great disparity in reported causes, it is unlikely that there is a simple unifying mechanism for the development of these nevi. We speculate that eruptive nevi are due to activation of one of the genes reported to be important in the embryonic development of melanocyte lineage, which includes MITF, C-Kit, and WNT.3

Conclusion We report on the first case of interferon-induced eruptive melanocytic nevi in a patient with nodal metastasis from melanoma. This may be secondary to the drug or may be a paraneoplastic phenomenon.

Acknowledgment Financial disclosure of authors and reviewers: None reported.

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Eruptive melanocytic nevi induced by interferon for nodal metastatic melanoma: case report and review of the literature.

The rapid appearance of multiple new melanocytic nevi is known as eruptive nevi and has been well documented to occur with certain medications, in par...
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