title: Atypical melanocytic nevi of the genital type with a discussion of reciprocal parenchymal-stromal interactions in the biology of neoplasia.
abstract: Melanocytic lesions of the genital area, especially those on the vulva, may present great difficulty in histological interpretation. A histological diagnosis of malignant melanoma was made in more than one third of 56 genital area melanocytic lesions submitted in consultation to the authors. The median age of the patients with these lesions was 25 years. This article is a clinicopathological study of these lesions and distinguishes them from malignant melanoma. The stroma of the lesions of the genital area was different from the stroma seen in the dysplastic nevi and melanoma. The differences in the stromal form in the diverse lesions is useful in diagnosis and is of profound biological significance. The stroma in the reported lesions and in some lesions of melanocytic neoplasia is described in detail, and its biological significance is discussed. Three sets of cases are used in this comparative study to delineate the clinicopathological nature and the biology of the genital nevi. The 56 cases submitted in consultation constitute the primary series of our work (The Clark Cutaneous Pathology Laboratory Series). These are compared with a series of cases from the Pigmented Lesion Group of the University of Pennsylvania and Pathology Services, Inc, and another series of cases from the Genetic Epidemiology Branch of the National Cancer Institute. The two series used for comparative study contain approximately the same number of cases of dysplastic nevi and malignant melanoma as there are atypical melanocytic nevi of the genital type in the primary series. The total number of cases was studied by comparison of their attributes in a relational database. The clinical data of the primary series was acquired through the use of a questionnaire completed by the contributors. The 56 cases presented two distinctive pathological pictures. One of these is termed atypical melanocytic nevi of the genital type (AMNGT), whereas dysplastic nevi (DN) formed the second of the two pathological pictures. There were 36 AMNGT and 14 DN. The remaining six cases were common nevi without atypia or ill-defined melanocytic hyperplasias. The lesions of AMNGT are usually located on the vulva, but they are seen on the perineum and, rarely, on the mons pubis and in the axilla. Lesions similar to AMNGT have been seen uncommonly on the male genitalia. The stromal patterns were distinctive and related to specific melanocytic lesions. An unclassified (unclass) or nonspecific stromal pattern was associated with AMNGT; a pattern of regression with differentiation (diff-regress) dominated the stroma of common dermal nevi; concentric eosinophilic fibroplasia (cef) and lamellar fibroplasia (lf) were present in dysplastic nevi; fibroplasia with a plaquelike lymphocytic infiltrate (fl) and diffuse eosinophilic fibroplasia (def) were noted in radial growth phase melanoma; and fibroplasia with angiogenesis (fa) or an absence of evidence for parenchymal stromal reciprocal interactions (nopsi) marked thick or deeply invasive vertical growth phase melanomas. Recommendations for management of the lesions are suggested.
  
  
  CONCLUSIONS
  One kind of atypical melanocytic proliferation in the genital area forms a distinctive clinicopathological entity that can be distinguished from melanoma and dysplastic nevi, the AMNGT. Such lesions are more common on the labia minora or the mucosa of the clitoral region than they are on the labia majora. The other common atypical melanocytic proliferation of this area is a dysplastic nevus, which is much more common on the labia majora than on the labia minora. The reciprocal interactions between parenchyma and stroma are discussed as homeostatic processes, a continually functioning template maintaining tissue, organ, and organismal form and function. The progressive disorganization of this template in neoplasia is illustrated and is considered to be a cardinal element in the biology of neoplasia.
authors.affiliation: Department of Pathology, Beth Israel Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: W H
authors.initials: WH
authors.lastname: Clark
authors.forename: A F
authors.initials: AF
authors.lastname: Hood
authors.forename: M A
authors.initials: MA
authors.lastname: Tucker
authors.forename: R M
authors.initials: RM
authors.lastname: Jampel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D004416:Dysplastic Nevus Syndrome / Q000473:pathology; D005260:Female; D005833:Genital Neoplasms, Female / Q000473:pathology*; D006801:Humans; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000473:pathology; D008875:Middle Aged; D009506:Nevus / Q000473:pathology; D009508:Nevus, Pigmented / Q000473:pathology*; D012878:Skin Neoplasms / Q000473:pathology*; D017154:Stromal Cells / Q000473:pathology / Q000502:physiology