 |
|
Agminated Atypical (Dysplastic) Nevi
Case Report and Review of the Literature
Ashfaq A. Marghoob, MD;
Robin Blum, BS;
Robert Nossa, MD;
Klaus J. Busam, MD;
Dana Sachs, MD;
Allan Halpern, MD
Arch Dermatol. 2001;137:917-920.
ABSTRACT
| |
Background Patients with the atypical mole syndrome have multiple dysplastic nevi that appear to be randomly distributed on certain preferred anatomical sites such as the upper back. These dysplastic nevi are thought to be acquired melanocytic nevi that begin appearing at puberty. To our knowledge, the presence of agminated atypical (dysplastic) nevi has not been reported.
Observation We describe a patient with the atypical mole syndrome who has more than 100 melanocytic nevi, many of which are clinically atypical and one of which proved to be a melanoma. Among his many melanocytic nevi is a cluster of approximately 50 nevi that are distributed in an area measuring 5 x 3 cm. The histopathologic features of these nevi are consistent with the diagnosis of "dysplastic nevus."
Conclusions To our knowledge, agminated atypical (dysplastic) nevi have not been described previously. The presence of agminated atypical (dysplastic) nevi in a patient with the atypical mole syndrome can be theorized to arise because of loss of heterozygosity.
INTRODUCTION
ATYPICAL MOLES and the atypical mole (dysplastic nevus) syndrome are recognized as distinct clinical entities.1-2 Most dermatopathologists also agree on the existence of the histologic entity known as a dysplastic nevus.3-4 Clinically, most atypical nevi are solitary lesions that begin to appear around puberty. We describe a patient with the atypical mole syndrome who had multiple agminated atypical nevi that were histologically characterized as dysplastic nevi. Agminated as it pertains to melanocytic nevi is defined as a circumscribed grouping of pigmented lesions confined to a body segment. Our patient had approximately 50 nevi clustered in a 5 x 3-cm area of skin on his right arm. Although the existence of agminated melanocytic nevi has been documented,5 to our knowledge agminated atypical (dysplastic) nevi have never been reported in the literature.
REPORT OF A CASE
A 44-year-old man was referred to the dermatology clinic for evaluation of multiple irregular moles. The patient reported that his nevi developed during his teenage years. He denied a family history of multiple moles or melanoma.
On physical examination, the patient had more than 100 melanocytic nevi, and a few of these nevi appeared clinically atypical. The largest nevus, on the right side of his chest, measured 1 cm in greatest diameter (Figure 1). The patient also had an irregular melanocytic neoplasm on the right side of his mandible that on subsequent biopsy proved to be melanoma in situ.
|
|
|
|
Figure 1. Anterior chest and abdomen showing multiple melanocytic nevi. The patient's largest nevus is on the right side of his chest near the midline.
|
|
|
The patient had a cluster of approximately 50 melanocytic nevi on his right arm, all distributed in an area 5 x 3 cm in diameter (Figure 2 and Figure 3). The patient stated that this cluster of nevi first became apparent at the age of 15 years. No background café-au-lait pigmentation was noted clinically or with the aid of a Wood light examination. Dermoscopy revealed that all the nevi had a "diffuse and patchy" network pattern6 (Figure 4A). However, one area was darker (Figure 3) and on dermoscopy had black dots, globules, and structureless areas (Figure 4B). Because this area had nevi that differed from the other surrounding nevi, it was excised.7 The histopathologic findings revealed a lentiginous compound melanocytic nevus with architectural disorder of its intraepidermal component and irregular placement of nests of variable size and shape, fusion of nests, and asymmetric extension of the junctional component beyond the confines of the intradermal nevus component (Figure 5A). Several melanocytes contained abnormally large nuclei, some that were twice the normal size, and the nuclei had irregular contours. Furthermore, papillary dermal fibroplasia with a sparse lymphohistiocytic infiltrate was present (Figure 5B). In light of the presence of architectural disorder and cytologic atypia, a diagnosis of dysplastic nevus was made.
|
|
|
|
Figure 2. The agminated atypical nevi are seen on the right arm.
|
|
|
|
|
|
|
Figure 3. The agminated atypical nevi. A biopsy of the area within the oval was performed. A indicates the area from which the dermoscopic image seen in Figure 4A was taken; and B, the area from which the dermoscopic image seen in Figure 4B was taken.
|
|
|
|
|
|
|
Figure 4. A, Dermoscopy of the agminated nevi showing a "diffuse and patchy" network pattern, a feature commonly seen in dysplastic nevi. B, Dermoscopy showing an area with globules, black dots, a network, and structureless areas. A biopsy of this area was performed.
|
|
|
|
|
|
|
Figure 5. A, Histopathologic features under scanning magnification show the lesion to have a slightly asymmetric silhouette (original magnification x4). B, A higher magnification reveals a lentiginous melanocytic proliferation with papillary dermal fibrosis and scattered clusters of lymphocytes (original magnification x10).
|
|
|
COMMENT
Atypical moles (dysplastic nevi) are acquired pigmented lesions that develop during puberty and continue to develop and change throughout life. Although they may appear anywhere on the body, they primarily develop on the trunk.
Clinically, atypical nevi share many features of malignant melanoma, including asymmetry, border irregularity, color variability, and a diameter greater than 6 mm.8 They can be multiple or solitary, and can develop in patients with or without a family history of similar lesions.
We describe a patient with the atypical mole syndrome who had an unusual presentation of multiple, clustered, clinically atypical (dysplastic) nevi. To our knowledge, this is the first reported case of agminated atypical (dysplastic) nevi. In this patient, the diagnosis of atypical (dysplastic) nevi was based on clinical and histologic features. Clinically, some of the patient's nevi were irregular, demonstrated variegation of color, and were greater than 6 mm in diameter. The dermoscopic feature of a patchy network was also consistent with a diagnosis of dysplastic nevi.6 The histologic diagnosis of the biopsied section was that of a dysplastic nevus or a nevus with "architectural disorder and cytologic atypia."9
A review of the literature revealed that the term agminated has been used to describe several different cutaneous lesions. Pigmented lesions that have been described as agminated include melanocytic nevi,5 congenital melanocytic nevi,10 Spitz nevi,11-12 nevi spilus,13-14 blue nevi,15-16 and multiple lentigines.17 Other nonpigmented agminated lesions reported in the literature include xanthogranulomas,18 angiofibromas,19 and neurilemomas.20 Historically, atypical (dysplastic) nevi have not been reported to occur in an agminated distribution.
Based on this patient's clinical and histologic features, the diagnosis of agminated atypical (dysplastic) nevi, and not any of the other previously reported agminated lesions, is most accurate. By definition, congenital melanocytic nevi are melanocytic nevi that are present at birth or develop shortly after birth. Because our patient's nevi developed during his teenage years, it is unlikely that they were congenital melanocytic nevi.21 In addition, the histopathologic features were not consistent with congenital melanocytic nevi.
It is unlikely that the cluster of lesions were Spitz nevi. Although multiple agminated Spitz nevi have been reported,22 the histologic features of Spitz nevi are quite different and demonstrate admixed spindle and epitheliod cells arranged in irregular nests with occasional mitotic figures. These features were not seen in this patient's biopsy specimen. In addition, the clinical features of agminated Spitz nevi are also different. Spitz nevi tend to develop in early childhood, predominately occur on the face, and are pink.11 In our patient, the nevi did not develop until puberty, occurred on his arm, and were brown.
The diagnoses of nevus spilus,23 blue nevi, and lentiginosis can be ruled out based on clinical and histologic features. Unlike our patient, who developed his "agminated atypical moles" at the age of 15 years, nevus spilus is usually apparent by early infancy or childhood.21, 23 The diagnosis of nevus spilus is also not consistent with the clinical examination because of the obvious lack of background pigmentation, a feature commonly seen in a nevus spilus. Furthermore, the pathological features of our patient's agminated lesions also failed to demonstrate the background of lentigo, as would be seen in a nevus spilus. The diagnosis of blue nevi was not made because clinically they did not appear as blue or black dome-shaped papules, and histologically they did not demonstrate dermal melanocytes grouped in irregular bundles admixed with melanophages.16 The diagnosis of agminated lentiginosis was not made because the histologic features did not demonstrate elongation of the rete ridges and hyperplasia of melanocytes.17
It has been proposed that the atypical mole syndrome has either an autosomal dominant mode of inheritance with incomplete penetrance or a polygenic mode of inheritance.2 The specific gene or genes that predispose to the development of dysplastic nevi and the precipitants for the formation of individual melanocytic nevi have not been identified. However, sun exposure has been implicated in the development of melanocytic nevi.24 Furthermore, it has been postulated that some atypical melanocytic nevi may develop through loss of heterozygosity (LOH).25-26 Loss of heterozygosity is the loss of a normal wild-type allele, leading to the expression of a mutant or recessive allele.27 One mechanism for acquired loss of an allele may be through mutations induced by UV exposure.28 The specific etiology of agminated nevi is not known. Local environmental factors, such as UV radiation, may play a role in the development of clustered lesions. However, it is also possible that this agminated pattern may represent LOH, occurring during embryogenesis, as has been postulated to account for the segmental distribution of lesions such as neurofibromas, porokeratosis, and Becker nevi.27 In our patient, the agminated dysplastic nevi occurred in the presence of the atypical mole syndrome. Other examples of segmental clustering of skin lesions superimposed on a generalized less severe form of the condition may shed light on the pathogenesis in our case. Autosomal dominant skin disorders, such as neurofibromatosis, sometimes occur in a segmental pattern superimposed on a less severe but diffuse form of the same disorder.27 This phenomenon may be explained by an early postzygotic mutational event giving rise to LOH at the locus responsible for the trait. A person can also have a segmental manifestation of a polygenic skin disorder, such as segmental severe psoriasis, superimposed on symmetric involvement of ordinary psoriasis.27 This too can be explained by LOH occurring in a somatic cell during early embryogenesis, resulting in either homozygosity or hemizygosity for one of the genes predisposing to psoriasis. Future studies of the distribution of lesions in cases of agminated nevi such as ours coupled with genetic analysis of microdissected tissues may shed light on the timing and nature of these events.
In conclusion, based on a review of clinical entities occurring in an agminated distribution, we believe that our case is the first report of agminated atypical (dysplastic) nevi. This is a new, previously undescribed, clinical variant of atypical (dysplastic) nevi occurring in a patient with the atypical mole syndrome and adds to the phenotypic spectrum of this entity. In addition, this case raises the possibility that LOH may play a role in the development of some cases of dysplastic nevi or atypical mole syndrome.
AUTHOR INFORMATION
Accepted for publication February 26, 2001.
We thank Nathan Ellis, PhD, for reviewing the manuscript and helping us to better understand the concept of loss of heterozygosity.
Corresponding author and reprints: Ashfaq A. Marghoob, MD, Dermatology Service, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021.
From the Dermatology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY (Drs Marghoob, Busam, Sachs, and Halpern); and the Departments of Dermatology, State University of New York at Stony Brook (Dr Marghoob) and Mount Sinai Medical Center, New York (Ms Blum and Dr Nossa).
REFERENCES
| |
1. Tucker MA, Halpern A, Holly EA, et al. Clinically recognized dysplastic nevi: a central risk factor for cutaneous melanoma. JAMA. 1997;277:1439-1444.
FREE FULL TEXT
2. Slade J, Marghoob AA, Salopek TG, Rigel DS, Kopf AW, Bart RS. Atypical mole syndrome: risk factors for cutaneous malignant melanoma and implications for management. J Am Acad Dermatol. 1995;32:479-494.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
3. Clemente C, Cochran AJ, Elder DE, et al. Histopathologic diagnosis of dysplastic nevi: concordance among pathologists convened by the World Health Organization Melanoma Programme. Hum Pathol. 1991;22:313-319.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
4. Weinstock MA, Barnhill RL, Rhodes AR, Brodsky GL. Reliability of the histopathologic diagnosis of melanocytic dysplasia. Arch Dermatol. 1997;133:953-958.
FREE FULL TEXT
5. Stolz W, Braun-Falco O, Bilek P, Landthaler M, Cognetta AB. Color Atlas of Dermatoscopy. Oxford, England: Blackwell Science Ltd; 1993:64.
6. Kopf AW. Dermoscopic diagnosis of dysplastic nevi. Melanoma Res. 2001;11:521.
7. Grob JJ, Bonerandi JJ. The "ugly duckling" sign: identification of the common characteristics of nevi in an individual as a basis for melanoma screening. Arch Dermatol. 1998;134:103-104.
FREE FULL TEXT
8. Marghoob AA. The dangers of atypical mole (dysplastic nevus) syndrome. Postgrad Med. 1999;105:147-164.
9. NIH Consensus Development Panel on Early Melanoma. Diagnosis and treatment of early melanoma. JAMA. 1992;268:1314-1319.
FREE FULL TEXT
10. Brunner M, Vardarman E, Megahed M, Ruzicka T. Congenital agminated segmental naevi. Br J Dermatol. 1995;133:315-316.
PUBMED
11. Hamm H, Happle R, Brocker EB. Multiple agminate Spitz naevi: review of the literature and report of a case with distinctive immunohistochemical features. Br J Dermatol. 1987;117:511-522.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
12. Lancer HA, Muhlbauer JE, Sober AJ. Multiple agminated spindle cell nevi: unique clinical presentation and review. J Am Acad Dermatol. 1983;8:707-711.
PUBMED
13. Betti R, Inselvini E, Palvarini M, Crosti C. Agminated intradermal Spitz nevi arising on an unusual speckled lentiginous nevus with localized lentiginosis: a continuum? Am J Dermatopathol. 1997;19:524-527.
PUBMED
14. Aloi F, Tomasini C, Pippione M. Agminated Spitz nevi occurring within a congenital speckled lentiginous nevus. Am J Dermatopathol. 1995;17:594-598.
WEB OF SCIENCE
| PUBMED
15. Shenfield HT, Maize JC. Multiple and agminated blue nevi. J Dermatol Surg Oncol. 1980;6:725-728.
PUBMED
16. Velez A, del-Rio E, Martin-de-Hijas C, Furio V, Sanchez Yus E. Agminated blue nevi: case report and review of the literature. Dermatology. 1993;186:144-148.
WEB OF SCIENCE
| PUBMED
17. Micali G, Nasca MR, Innucenzi D, Lembo D. Agminated lentiginosis: case report and review of the literature. Pediatr Dermatol. 1994;11:241-245.
PUBMED
18. Tangoren IA, Weinberg JM, Humphreys T, Murphy GF, Margolis DJ, Spiers EM. Agminated xanthogranuloma: an unusual presentation of juvenile xanthogranuloma. Acta Derm Venereol. 1998;78:68-69.
PUBMED
19. Anliker MD, Dummer R, Burg G. Unilateral agminated angiofibromas: a segmental expression of tuberous sclerosis? Dermatology. 1997;195:176-178.
WEB OF SCIENCE
| PUBMED
20. Berger TG, Lapins NA, Engel ML. Agminated neurilemomas. J Am Acad Dermatol. 1987;17:891-894.
FULL TEXT
| PUBMED
21. Schaffer JV, Orlow SJ, Lazova R, Bolognia JL. Speckled lentiginous nevus: within the spectrum of congenital melanocytic nevi. Arch Dermatol. 2001;137:172-178.
FREE FULL TEXT
22. Paniago-Pereira C, Maize JC, Ackerman AB. Nevus of large spindle and/or epitheliod cells: Spitz's nevus. Arch Dermatol. 1978;114:1811-1823.
FREE FULL TEXT
23. Rhodes AR, Mihm MC. Origin of cutaneous melanoma in a congenital dysplastic nevus spilus. Arch Dermatol. 1990;126:500-505.
FREE FULL TEXT
24. Kelly JW, Rivers JK, MacLennan R, Harrison S, Lewis AE, Tate BJ. Sunlight: a major factor associated with the development of melanocytic nevi in Australian schoolchildren. J Am Acad Dermatol. 1994;30:40-48.
WEB OF SCIENCE
| PUBMED
25. Boni R, Zhuang Z, Albuquerque A, Vortmeyer A, Duray P. Loss of heterozygosity detected on 1p and 9q in microdissected atypical nevi. Arch Dermatol. 1998;134:882-883.
FREE FULL TEXT
26. Birindelli S, Tragni G, Bartoli C, et al. Detection of microsatellite alterations in the spectrum of melanocytic nevi in patients with or without individual or family history of melanoma. Int J Cancer. 2000;86:255-261.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
27. Happle R. Loss of heterozygosity in human skin. J Am Acad Dermatol. 1999;41:143-161.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
28. Boni R, Matt D, Burg G, Tronnier M, Vortmeyer A, Zhuang Z. Ultraviolet-induced acute histological changes in irradiated nevi are not associated with allelic loss. Arch Dermatol. 1998;134:853-856.
FREE FULL TEXT
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
RELATED ARTICLE
Archives of Dermatology Reader's Choice: Continuing Medical Education
Arch Dermatol. 2001;137(7):986-987.
FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
Segmental Lesions Are Not Always Agminated
Happle
Arch Dermatol 2002;138:838-838.
FULL TEXT
|
