DERMATOLOGY PRACTICAL & CONCEPTUAL
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Observation  |  Dermatol Pract Concept 2012;2(2):7 27

Regression of nevi in a melanoma patient 
treated with interferon
Ayelet Rishpon, M.D.1, Nir Nathanson, M.D.2

1 Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel
2 Department of Dermatology, Sheba Medical Center, Tel Hashomer, Israel

Key words: regression, nevi, interferon alpha2b

Citation: Rishpon A, Nathanson N. Regression of nevi in a melanoma patient treated with interferon. Dermatol Pract Conc. 2012;2(2):7. 
http://dx.doi.org/10.5826/dpc.0202a07.

Received: October 18, 2011; Accepted: January 30, 2012; Published: April 30, 2012

Copyright: ©2012 Rishpon et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, 
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: None.

Competing interests: The authors have no conflicts of interest to disclose.

All authors have contributed significantly to this publication.

Corresponding author: Ayelet Rishpon, M.D., Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel. Tel. 
97236973356. Email: arishpon@gmail.com.

Background

High-risk melanoma patients are occasionally offered adju-

vant treatment with interferon alpha 2b as a postsurgical 

treatment. This treatment is thought to improve disease-free 

survival by upgrading immunomodulatory functions, which 

cause an antitumor effect [1,2].

We describe a patient treated with adjuvant interferon 

therapy for stage III melanoma, who presented multiple 

regressing nevi after the treatment.

Case report

A 58-year-old male patient with a history of multiple basal 

cell carcinomas and a previous melanoma was diagnosed 

upon presentation with stage III melanoma, consisting of a 

primary melanoma of the lower back with inguinal lymph 

node metastases. After excision of the primary tumor, the 

patient was treated with high-dose interferon alpha 2b for 

six months. Four months after completing the interferon 

treatment, the patient sought treatment at the pigmented 

lesion clinic of Sheba Medical Center, Tel Hashomer, Israel. 

Full body skin examination revealed multiple pigmented 

nevi of the trunk and extremities. Of them, six nevi had a 

similar dermoscopic pattern, including a network and local-

ized fine and coarse gray granularity which in general rep-

resent regression (Figures 1, 2). In order to further analyze 

the lesions, confocal microscopy was performed (VivaScope 

1500, Lucid Inc, Rochester, New York). Instrumentation and 

acquisition procedures have been described previously [3,4]. 

Confocal mosaic image (5 mm X 5 mm, compatible with 

low magnification microscopy) showed a ringed pattern cor-

relating with the reticular dermoscopic pattern (Figure 3). 

Individual confocal images (0.5 mm X 0.5 mm, equivalent to 

high magnification microscopy) showed that in certain areas 

the ringed pattern is not visible and instead there are elon-

gated refractile structures compatible with dendritic cells 

(Figure 4). These dendritic cells could represent melanocytes, 

raising the possibility of pagetoid spread of a melanoma or 

http://dx.doi.org/10.5826/dpc.0202a


28 Observation  |  Dermatol Pract Concept 2012;2(2):7

Langerhans cell, as part of the inflammation. Histopatho-

logic analysis of this lesion showed a dysplastic nevus with 

areas of melanosis, fibrosis and inflammation and no sign of 

pagetoid spread (Figure 5A). In order to further identify the 

dendritic cells, CD1a and Melan-A stains were performed. 

CD1a stain was positive throughout the epidermis (Figure 

5B) and Melan-A stain was positive at the lower epidermis 

(Figure 5C), suggesting that the dendritic cells represent 

Langerhans cells as part of the inflammatory reaction.

The five other lesions were biopsied as well, all show-

ing histopathologically a dysplastic nevus with focal areas 

of regression.

Discussion

Regression of nevi in the setting of melanoma and interferon 

treatment might be induced by the melanoma, the interferon 

treatment, or both. Examples of remote regression induced 

by melanoma include halo nevi and melanoma-associated 

leukoderma. These phenomena result from an immune reac-

tion against shared antigens on benign and malignant mela-

nocytes [5,6].

Hu and colleagues described primary melanomas pre-

senting as inflamed pigmented lesions during adjuvant inter-

feron treatment for melanoma [7]. They suggest that the 

immunomodulatory effects of interferon targeting melanoma 

unmasked or “lit up” these subsequent primary melanomas. 

We hypothesize that this same effect might be responsible 

for causing inflammation, not only in melanomas, but also 

in nevi.

It has been suggested that imiquimod, which stimulates 

interferon transcription, can cause regression or resolution 

of atypical nevi [8,9]. In a previous study, four of imiquimod 

treated nevi (compared to 0 non-treated nevi) showed par-

tial regression on histopathology after 10 weeks of imiqui-

mod treatment [8]. Another study examined three patients, 

each with one atypical nevus treated with imiquimod for 12 

weeks [9]. Two lesions demonstrated inflammation on exci-

sional biopsy.

Of note, since we saw the patient for the first time only 

after he had already completed the interferon treatment, 

the concept of the regression being caused by the interferon 

treatment is merely a hypothesis. As we do not have previous 

documentation of this patient’s nevi, we cannot rule out that 

this was the patient’s original nevi pattern. In fact there are 

Figure 1. Close-up clinical images of four of the patient’s nevi (arrows), showing pigmented maculae with a distinct gray focus. [Copyright: 

©2012 Rishpon et al.]



Observation  |  Dermatol Pract Concept 2012;2(2):7 29

three possible interpretations of this regression, its being, the 

original nevi pattern of this patient, caused by the melanoma, 

or caused by the adjuvant interferon treatment. Understand-

ing the pathogenesis of the findings described could have a 

role in improved melanoma diagnosis and treatment. For 

example, regression in nevi could be a surrogate for identify-

ing patients in whom interferon mediates an inflammatory 

response against melanocytes. Future studies regarding the 

pathogenesis of nevi regression in the setting of melanoma 

and interferon treatment are needed.

Figure 2. Dermoscopic images of the four nevi showing network and localized gray granularity. [Copyright: ©2012 Rishpon et al.]

Figure 3. Confocal microscopy mosaic (5 x 5 mm) at the level of the 

dermo-epidermal junction showing a ringed pattern on the right, and 

a disorganized pattern with disappearance of the ringed pattern in 

the center (red circle). Inset: dermoscopic figure showing a network 

with localized gray granularity. [Copyright: ©2012 Rishpon et al.]

Figure 4. Individual confocal image (500 x 500 microns) showing a 

close-up view of the ringed pattern (circle) and dendritic structures 

(arrows). [Copyright: ©2012 Rishpon et al.]



30 Observation  |  Dermatol Pract Concept 2012;2(2):7

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Figure 5. (A) Histopathology image showing a dysplastic nevus with 

dermal melanosis and fibrosis (hematoxylin & eosin [H&E], X20). 

(B) CD1A stain showing positively-stained cells throughout the epi-

dermis (X40). (C) Melan A stain showing positively staining cells 

only at lower part of epidermis (X40). [Copyright: ©2012 Rishpon 

et al.]

A C

B