Genital Nevi Research Articles

PRAME expression in genital melanocytic lesions – Potential diagnostic pitfall of intermediate expression in atypical genital nevi

IntroductionThe Preferentially Expressed Antigen in Melanoma (PRAME) immunostain has seen significant diagnostic use in confirming malignancy for melanocytic lesions. However, the expression of PRAME in genital melanocytic lesions have not been reported. In this study, PRAME staining was performed on a cohort of genital melanocytic lesions, aiming to investigate the diagnostic role of PRAME in genital melanocytic lesions and its expression in atypical genital nevi. MethodologyA cohort including genital invasive melanoma, melanoma-in-situ, atypical genital nevus (AGN), compound nevus, intradermal nevus, blue nevus, lentigo and melanosis was retrieved with histology reviewed and PRAME immunostaining performed. ResultsA total of 66 cases were reviewed. The average proportion expression of PRAME were 56.75 % and 57.43 % for invasive melanoma and melanoma-in-situ, with average H-scores of 153.5/300 and 163.14/300 respectively, which were greater than AGN (3.25 %, 7.75/300, p<0.001), compound/intradermal nevi, lentigo/melanosis, and background junctional melanocytes (<1 %, <1/300, p<0.001). The different cutoffs of PRAME expression, the sensitivity and specificity were 65.22 % and 100 % (>100/300); 69.57 % and 95.83 % (>10/300); and 82.61 % and 93.75 % (≥1/300) respectively. Low level PRAME expression was seen in half of the cases of AGN (n=2/4, 50 %), and at low cutoffs (>10/300 and ≥1/300) unable to differentiate invasive melanoma from AGN (p>0.05). ConclusionsFor genital melanocytic lesions, PRAME immunostain shows high specificity at strong and diffuse staining. AGN not uncommonly display low level expression. Focal and/or weak PRAME expression should not be considered as an absolute indication of malignancy, and comprehensive histological assessment remains the key to accurate diagnosis of melanocytic lesions.

Nonoverlapping Clinical and Mutational Patterns in Melanomas from the Female Genital Tract and Atypical Genital Nevi

Genital melanomas (GM) are the second most common cancer of the female external genitalia and may be confused with atypical genital nevi (AGN), which exhibit atypical histological features but have benign behavior. In this study, we compared the clinical, histological, and molecular features of 19 GM and 25 AGN. We described chromosomal copy number aberrations and the mutational status of 50 oncogenes and tumor suppressor genes in both groups. Our study showed that a pigmented lesion occurring in mucosal tissue, particularly in postmenopausal women, was more likely to be a melanoma than a nevus. GM had high levels of chromosomal instability, with many copy number aberrations. Furthermore, we found a completely nonoverlapping pattern of oncogenic mutations when comparing GM and AGN. In GM, we report somatic mutations in KIT and TP53. Conversely, AGN had frequent BRAF V600E mutations, which were not seen in any of the GM. Our results show that GM and AGN have distinct clinical and molecular changes and that GM have a different mutational pattern compared with AGN.

Genital Melanocytic Nevi in Children

Genital melanocytic nevi in children are little studied and are usually excluded from large studies of pediatric nevi. Investigators retrospectively

Genital melanocytic nevi in children: Experience in a pediatric dermatology practice

Little is known about the prevalence and clinical characteristics of genital melanocytic nevi in children. We sought to describe the epidemiology, clinical and dermoscopic features, and natural history of genital nevi in pediatric patients. We reviewed charts of 1159 children given the diagnosis of melanocytic nevi over 11 years. Those with genital nevus as a chief symptom were contacted for follow-up. Among children/adolescents evaluated for nevi, the prevalence of genital nevus was 3.5% (40/1159), with a male:female ratio of 1.3:1. There were no statistically significant differences in age, sex, total nevus number, presence of acral and scalp nevi, or family history of dysplastic nevi and melanoma between patients with and without genital nevi. Genital nevus onset was before age 2 years in 63.6% of patients. A globular dermoscopic pattern was observed in 93.3%. Most genital nevi underwent a gradual change in diameter, elevation (becoming soft papules), color, texture, or a combination of these. After median follow-up of 1.5 years, no melanoma or other adverse outcome was observed. This was a retrospective chart analysis and questionnaire-based study of a limited number of patients. Increased awareness of the clinical characteristics, dermoscopic features, and evolution ofgenital nevi in children may help to avoid unnecessary surgery.

Clinical and Histopathological Characteristics of Genital Melanocytic Nevi: A Report of 109 Cases and a Review of the Literature

Melanocytic lesions on the genital area are rare and poorly documented; they occur more frequently on the vulva and less often on the perineum, pubic area, and male genitalia. Genital melanocytic nevi exhibit features similar to nevi occurring on other areas of the body; in addition, they display high clinical and histopathological variability and are mostly classified as common nevi. However, a benign subtype of genital nevi that occurs in young women is known as atypical melanocytic nevi. These nevi exhibit distinct morphological characteristics that sometimes overlap with those of cutaneous melanoma. A retrospective systematic review was performed of 111 biopsy specimens of pigmented lesions on the vulva, perineum, pubic area, penis, and scrotum collected between 1998 and 2009 to assess their clinicopathological characteristics. In this sample, there were 101 cases of common genital melanocytic nevi, two genital melanotic macules, seven atypical melanocytic nevi, and one dysplastic melanocytic nevus; no cases corresponded to cutaneous melanoma. Of the 111 patients, 14.4% were male, and 85.6% were female with a mean age of 34.3 years. The female exhibited a larger number of atypical melanocytic nevi than the males. The nevi displayed melanocytic proliferation, forming irregular and coalescent nests with a loss of cellular cohesion at several sites in the rete ridges. Cytologic atypia was mild to moderate. Difficulties in the histological interpretation of these lesions remain to this day; thus, diagnosis relies significantly upon the experience and subjective judgment of pathologists to distinguish morphologically between atypical genital nevi and melanoma.

Melanocytic lesions of the genital area with attention given to atypical genital nevi

Melanocytic lesions of the genital area are rare. They arise mainly in the vulva, although they can also occur less frequently in the perineum, mons pubis and male genitalia and represent 10-12% of pigmented lesions of White women. These pigmented lesions include melanocytic nevi, lentigines, melanocytic nevi with architectural disorder and atypia of melanocytes (dysplastic nevi) and melanomas with microscopic features similar to those seen elsewhere on the body. There is a small subset of benign nevi named atypical melanocytic nevi of the genital type (AMNGT) that occur in young women, with distinctive histologic features in some cases overlapping morphologically with those of melanoma. Thus, it is important to distinguish AMNGT from melanomas in terms of prognosis and treatment. We retrieved 58 cases of genital pigmented lesions diagnosed at our hospital from 1986 to 2008 to evaluate their clinicopathologic features with especial consideration to those cases with atypical features. Thirty-two cases (55%) were common nevi, 10 (17%) lentigines, 6 (10%) melanomas, 3 (5%) dysplastic nevi and 1 blue nevus. Six cases (10%) corresponded to AMNGT and were taken from women with a median age of 21 years. All cases showed symmetry, and the melanocytic proliferation was well demarcated at the lateral margins. The junctional component was very prominent and formed by round or fusiform nests with common retraction artifact and/or cellular dyshesion or as a single cell proliferation with mild (33%) to moderate (67%) cytologic atypia, focal pagetoid spread (17%) and a benign-appearing dermal component (83%) with maturation and dense eosinophilic fibrosis in the superficial dermis. Neither nuclear atypia of melanocytes in the superficial dermis nor dermal mitoses were observed. AMNGT were excised, and no recurrences were recorded in the follow up (median 10.5 years). Therefore, it seems that there is no evidence that AMNGT are precursors of dysplastic nevi or melanomas.

Atypical Genital Nevi

Atypical genital nevi are rare melanocytic lesions that most commonly arise on the vulva of young women. They are currently regarded as nevi of special sites, in that despite histologically worrisome features, their clinical behavior is reportedly benign. However, only few studies with limited follow-up data are available. To better characterize the clinical presentation and behavior of these lesions and to further delineate their histologic features, we retrieved 56 atypical genital nevi arising in the lower female genital tract from our departmental and consultation files. The 56 lesions arose in 55 female patients with a median age of 26 years (range, 6 to 54 y). The dominant histologic feature was a lentiginous and nested junctional component composed of prominent round or fusiform nests, which often showed retraction artifact and/or cellular dyscohesion. Cytologic atypia was mild in 11 cases (20%), moderate in 34 (60%), and severe in 11 (20%). Ten cases (18%) showed focal pagetoid spread, with extension to the granular layer and stratum corneum in 1 case. The atypical junctional melanocytic proliferation was associated with a large common dermal nevus component that dominated the lesion in 26 cases (46%). Adnexal spread (46%) and nuclear atypia of melanocytes situated in the superficial dermis (39%) were relatively common, but dermal mitoses (7%) were uncommon and maturation was present in all cases. A broad zone of dense eosinophilic fibrosis within the superficial dermis was a frequent finding (41%). Clinical follow-up was available in 45 cases (80%) with a median follow-up period of 3.5 years (range, 1 to 16 y). Only 1 lesion recurred, 1.5 years after the initial excision. The original nevus in this patient had only mild cytologic atypia and was present at the margins of excision. The recurrent/persistent nevus was reexcised, and there was no further clinical recurrence in 11.5 additional years of follow-up. Our data support the hypothesis that atypical genital nevi have a benign clinical course despite their occasionally striking cytologic and architectural atypia. Awareness and recognition of this group of melanocytic lesions is important to avoid over diagnosis as melanoma with subsequent wide excision and possibly sentinel lymph node biopsy.

A diagnosis for maniacs.

Melanocytes originate in the neural crest and migrateto the basal layer of the epidermis, a distance that is tinyin an embryo but large in an adult human. A little im-precision in regard to where they come to rest may seemto be a small matter. It is not a small matter to a micros-copist who must decide whether or not melanocytes situ-ated in the spinous, granular or cornified layers of theepidermis are evidence of melanoma.In the last two decades there have been a number ofstudies establishing that nevi of “special sites” may haveeccentricities that, if they were detected elsewhere wouldbe evidence of melanoma. Nevi on the genitalia featurelarge and sometimes laterally confluent junctional nests,often of melanocytes with pale staining cytoplasm anddense lymphocytic infiltrates (1). Those on the umbilicusare altered by the presence of a scar in the dermis. Nevion the conjunctiva present with even more striking con-fluence of nests than genital nevi have, with clefts be-tween the epithelium and submucosa and dense infil-trates of lymphocytes, sometimes with lymphoid folliclesand eosinophils. Pigmentation may be prominent in thedeepest nests. Nevi in the neck, axillae and groins canresemble skin tags clinically and have a polypoid con-figuration microscopically (2).Of all of the nevi on “special sites”, those on the skinof the acra are most easily confused with melanoma byvirtue of suprabasal scatter of melanocytes. Thesechanges are most notable on nevi from the palms, solesand nailbeds, but also occur on the dorsal surfaces ofhands and feet and on knees and elbows as well. When Ibegan in dermatopathology in the early 1980s, this factwas little known. Many nevi on acral skin were labeledas melanoma or melanoma in situ, or with such terms as“atypical acral melanosis” that were often joined to notessuggesting re-excision. I wondered how it could be thatearly lesions of melanoma in situ could be so commonyet acral melanomas so are so rare, and seldom associ-ated with pre-existent nevi. I called a podiatric patholo-gist and a local dermatopathologist in private practicewho both told me that they routinely saw, but ignored thefinding of pagetoid scatter of melanocytes based on theexperience of seeing it so often. Clearly, some people