Agminated Atypical (Dysplastic) Nevi Case Report and Review of the Literature

OBSERVATION 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

Background: Patients with the atypical mole syn- cytic nevi is a cluster of approximately 50 nevi that are drome have multiple dysplastic nevi that appear to be ran- distributed in an area measuring 5ϫ3 cm. The histo- domly distributed on certain preferred anatomical sites pathologic features of these nevi are consistent with the such as the upper back. These dysplastic nevi are thought diagnosis of “dysplastic nevus.” to be acquired melanocytic nevi that begin appearing at puberty. To our knowledge, the presence of agminated Conclusions: To our knowledge, agminated atypical atypical (dysplastic) nevi has not been reported. (dysplastic) nevi have not been described previously. The presence of agminated atypical (dysplastic) nevi in a pa- Observation: We describe a patient with the atypical tient with the atypical mole syndrome can be theorized mole syndrome who has more than 100 melanocytic nevi, to arise because of loss of heterozygosity. many of which are clinically atypical and one of which proved to be a melanoma. Among his many melano- Arch Dermatol. 2001;137:917-920

TYPICAL MOLES and the teenage years. He denied a family history atypical mole (dysplastic of multiple moles or melanoma. nevus) syndrome are rec- On physical examination, the pa- ognized as distinct clini- tient had more than 100 melanocytic nevi, cal entities.1,2 Most derma- and a few of these nevi appeared clini- topathologistsA also agree on the existence cally atypical. The largest nevus, on the of the histologic entity known as a dys- right side of his chest, measured 1 cm in plastic nevus.3,4 Clinically, most atypical greatest diameter (Figure 1). The pa- nevi are solitary lesions that begin to ap- tient also had an irregular melanocytic neo- pear around puberty. We describe a pa- plasm on the right side of his mandible that tient with the atypical mole syndrome who on subsequent biopsy proved to be mela- had multiple agminated atypical nevi that noma in situ. were histologically characterized as dys- The patient had a cluster of approxi- plastic nevi. Agminated as it pertains to me- mately 50 melanocytic nevi on his right lanocytic nevi is defined as a circum- arm, all distributed in an area 5ϫ3cmin scribed grouping of pigmented lesions diameter (Figure 2 and Figure 3). The confined to a body segment. Our patient patient stated that this cluster of nevi first had approximately 50 nevi clustered in a became apparent at the age of 15 years. No 5ϫ3-cm area of skin on his right arm. Al- background cafe´-au-lait pigmentation was though the existence of agminated mela- noted clinically or with the aid of a Wood nocytic nevi has been documented,5 to our light examination. Dermoscopy revealed From the Dermatology Service, knowledge agminated atypical (dysplas- that all the nevi had a “diffuse and patchy” Department of Medicine, tic) nevi have never been reported in the network pattern6 (Figure 4A). How- Memorial Sloan-Kettering literature. ever, one area was darker (Figure 3) and Cancer Center, New York, NY on dermoscopy had black dots, globules, (Drs Marghoob, Busam, Sachs, and structureless areas (Figure 4B). Be- and Halpern); and the REPORT OF A CASE cause this area had nevi that differed from Departments of Dermatology, the other surrounding nevi, it was ex- State University of New York at 7 Stony Brook (Dr Marghoob) A 44-year-old man was referred to the der- cised. The histopathologic findings re- and Mount Sinai Medical matology clinic for evaluation of mul- vealed a lentiginous compound melano- Center, New York (Ms Blum tiple irregular moles. The patient re- cytic nevus with architectural disorder of and Dr Nossa). ported that his nevi developed during his its intraepidermal component and irregu-

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©2001 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 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.

lar 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 ab- Figure 2. The agminated atypical nevi are seen on the right arm. normally large nuclei, some that were twice the normal size, and the nuclei had irregular contours. Further- more, papillary dermal fibroplasia with a sparse lympho- B histiocytic infiltrate was present (Figure 5B). In light of the presence of architectural disorder and cytologic atypia, a diagnosis of dysplastic nevus was made.

COMMENT A Atypical moles (dysplastic nevi) are acquired pigmented lesions that develop during puberty and con- tinue 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 irregu- larity, color variability, and a diameter greater than 6 mm.8 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 They can be multiple or solitary, and can develop in pa- in Figure 4A was taken; and B, the area from which the dermoscopic image tients with or without a family history of similar lesions. seen in Figure 4B was taken. We describe a patient with the atypical mole syndrome who had an unusual presentation of multiple, clustered, clinically atypical (dysplastic) nevi. To our knowl- mas.20 Historically, atypical (dysplastic) nevi have not been edge, this is the first reported case of agminated atypical reported to occur in an agminated distribution. (dysplastic) nevi. In this patient, the diagnosis of atypi- Based on this patient’s clinical and histologic fea- cal (dysplastic) nevi was based on clinical and histo- tures, the diagnosis of agminated atypical (dysplastic) nevi, logic features. Clinically, some of the patient’s nevi were and not any of the other previously reported agminated irregular, demonstrated variegation of color, and were lesions, is most accurate. By definition, congenital mela- greater than 6 mm in diameter. The dermoscopic fea- nocytic nevi are melanocytic nevi that are present at birth ture of a patchy network was also consistent with a di- or develop shortly after birth. Because our patient’s nevi agnosis of dysplastic nevi.6 The histologic diagnosis of developed during his teenage years, it is unlikely that they the biopsied section was that of a dysplastic nevus or a were congenital melanocytic nevi.21 In addition, the his- nevus with “architectural disorder and cytologic atypia.”9 topathologic features were not consistent with congen- A review of the literature revealed that the term ag- ital melanocytic nevi. minated has been used to describe several different cu- It is unlikely that the cluster of lesions were Spitz taneous lesions. Pigmented lesions that have been de- nevi. Although multiple agminated Spitz nevi have been scribed as agminated include melanocytic nevi,5 congenital reported,22 the histologic features of Spitz nevi are quite melanocytic nevi,10 Spitz nevi,11,12 nevi spilus,13,14 blue different and demonstrate admixed spindle and epithe- nevi,15,16 and multiple lentigines.17 Other nonpigmented liod cells arranged in irregular nests with occasional mi- agminated lesions reported in the literature include xan- totic figures. These features were not seen in this pa- thogranulomas,18 angiofibromas,19 and neurilemo- tient’s biopsy specimen. In addition, the clinical features

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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.

of agminated Spitz nevi are also different. Spitz nevi tend A 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 B 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 spi- Figure 5. A, Histopathologic features under scanning magnification show the lus. The diagnosis of blue nevi was not made because clini- lesion to have a slightly asymmetric silhouette (original magnification x4). cally they did not appear as blue or black dome-shaped B, A higher magnification reveals a lentiginous melanocytic proliferation with papules, and histologically they did not demonstrate der- papillary dermal fibrosis and scattered clusters of lymphocytes (original mal melanocytes grouped in irregular bundles admixed magnification x10). with melanophages.16 The diagnosis of agminated lentiginosis was not made because the histologic features did tribution of lesions such as neurofibromas, porokerato- not demonstrate elongation of the rete ridges and hyper- sis, and Becker nevi.27 In our patient, the agminated dysplasia of melanocytes.17 plastic nevi occurred in the presence of the atypical mole It has been proposed that the atypical mole syn- syndrome. Other examples of segmental clustering of skin drome has either an autosomal dominant mode of in- lesions superimposed on a generalized less severe form heritance with incomplete penetrance or a polygenic mode of the condition may shed light on the pathogenesis in of inheritance.2 The specific gene or genes that predis- our case. Autosomal dominant skin disorders, such as pose to the development of dysplastic nevi and the pre- neurofibromatosis, sometimes occur in a segmental cipitants for the formation of individual melanocytic nevi pattern superimposed on a less severe but diffuse form have not been identified. However, sun exposure has been of the same disorder.27 This phenomenon may be implicated in the development of melanocytic nevi.24 Fur- explained by an early postzygotic mutational event giv- thermore, it has been postulated that some atypical me- ing rise to LOH at the locus responsible for the trait. A lanocytic nevi may develop through loss of heterozygos- person can also have a segmental manifestation of a ity (LOH).25,26 Loss of heterozygosity is the loss of a normal polygenic skin disorder, such as segmental severe pso- wild-type allele, leading to the expression of a mutant riasis, superimposed on symmetric involvement of ordi- or recessive allele.27 One mechanism for acquired loss of nary psoriasis.27 This too can be explained by LOH an allele may be through mutations induced by UV ex- occurring in a somatic cell during early embryogenesis, posure.28 The specific etiology of agminated nevi is not resulting in either homozygosity or hemizygosity for one known. Local environmental factors, such as UV radia- of the genes predisposing to psoriasis. Future studies of tion, may play a role in the development of clustered le- the distribution of lesions in cases of agminated nevi sions. However, it is also possible that this agminated pat- such as ours coupled with genetic analysis of microdis- tern may represent LOH, occurring during embryogenesis, sected tissues may shed light on the timing and nature as has been postulated to account for the segmental dis- of these events.

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©2001 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 In conclusion, based on a review of clinical entities 9. NIH Consensus Development Panel on Early Melanoma. Diagnosis and treat- occurring in an agminated distribution, we believe that ment of early melanoma. JAMA. 1992;268:1314-1319. 10. Brunner M, Vardarman E, Megahed M, Ruzicka T. Congenital agminated seg- our case is the first report of agminated atypical (dys- mental naevi. Br J Dermatol. 1995;133:315-316. plastic) nevi. This is a new, previously undescribed, clini- 11. Hamm H, Happle R, Brocker EB. Multiple agminate Spitz naevi: review of the lit- cal variant of atypical (dysplastic) nevi occurring in a pa- erature and report of a case with distinctive immunohistochemical features. Br tient with the atypical mole syndrome and adds to the J Dermatol. 1987;117:511-522. phenotypic spectrum of this entity. In addition, this case 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. raises the possibility that LOH may play a role in the de- 13. Betti R, Inselvini E, Palvarini M, Crosti C. Agminated intradermal Spitz nevi aris- velopment of some cases of dysplastic nevi or atypical ing on an unusual speckled lentiginous nevus with localized lentiginosis: a con- mole syndrome. tinuum? Am J Dermatopathol. 1997;19:524-527. 14. Aloi F, Tomasini C, Pippione M. Agminated Spitz nevi occurring within a con- Accepted for publication February 26, 2001. genital speckled lentiginous nevus. Am J Dermatopathol. 1995;17:594-598. 15. Shenfield HT, Maize JC. Multiple and agminated blue nevi. J Dermatol Surg We thank Nathan Ellis, PhD, for reviewing the manu- Oncol. 1980;6:725-728. script and helping us to better understand the concept of loss 16. Velez A, del-Rio E, Martin-de-Hijas C, Furio V, Sanchez Yus E. Agminated blue of heterozygosity. nevi: case report and review of the literature. Dermatology. 1993;186:144-148. Corresponding author and reprints: Ashfaq A. 17. Micali G, Nasca MR, Innucenzi D, Lembo D. Agminated lentiginosis: case report Marghoob, MD, Dermatology Service, Memorial Sloan- and review of the literature. Pediatr Dermatol. 1994;11:241-245. 18. Tangoren IA, Weinberg JM, Humphreys T, Murphy GF, Margolis DJ, Spiers EM. Kettering Cancer Center, 1275 York Ave, New York, NY Agminated xanthogranuloma: an unusual presentation of juvenile xantho- 10021. granuloma. Acta Derm Venereol. 1998;78:68-69. 19. Anliker MD, Dummer R, Burg G. Unilateral agminated angiofibromas: a segmental expression of tuberous sclerosis? Dermatology. 1997;195:176-178. REFERENCES 20. Berger TG, Lapins NA, Engel ML. Agminated neurilemomas. J Am Acad Derma- tol. 1987;17:891-894. 1. Tucker MA, Halpern A, Holly EA, et al. Clinically recognized dysplastic nevi: a cen- 21. 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