Ronald M. Harris

Metastatic Melanoma in Pregnancy: Risk of Transplacental Metastases in the Infant

PURPOSE Although metastases to the fetus via the placenta are rare, melanoma is the most common culprit. When it occurs, maternally derived melanoma metastasis in the infant is almost invariably fatal. PATIENTS AND METHODS This article reviews current guidelines for placental evaluation in pregnant women with metastatic melanoma and presents surveillance recommendations for their infants. Comprehensive literature reviews were performed on melanoma in pregnancy and melanoma metastasis to the placenta and fetus. The use of interferon alfa in the pediatric population was also reviewed. A comprehensive search of the MEDLINE database (1966 to 2002) was performed. Articles were reviewed and additional references were obtained from the bibliographies. Translation of non-English articles was performed, and authors of previous publications were contacted. RESULTS Eighty-seven patients with placental or fetal metastasis were identified. Twenty-seven occurrences were attributed to melanoma (31%). The fetus was affected in six of 27 melanoma patients (22%), with five of six infants dying of disease. The use of high-dose interferon alfa adjuvant therapy in pediatric patients has not been reported. CONCLUSION The placentas of women with known or suspected metastatic melanoma should be carefully examined grossly and histologically by pathologists. With placental involvement, fetal risk of melanoma metastasis is approximately 22%. Neonates delivered with concomitant placental involvement should be considered a high-risk population. The risk-benefit ratio of adjuvant treatment for a potentially affected infant should be carefully weighed.

Usefulness (or Lack Thereof) of Immunophenotyping in Atypical Cutaneous T-Cell Infiltrates

Our purpose was to evaluate the interobserver concordance for the diagnoses of mycosis fungoides (MF), atypical dermatoses (AD), and benign dermatoses (BD) and the impact of T-cell immunophenotyping on the diagnoses MF, AD, and BD. Specimens of MF (n = 57), AD (n = 27), BD and normal skin (n = 54) were reviewed by 2 hematopathologists and 1 dermatopathologist to establish diagnostic interobserver concordance by routine morphologic examination. Immunophenotyping was performed to evaluate expression of CD2, CD3, CD4, CD5, CD7, CD8, CD20, CD30, and MIB-1. The interobserver concordance was fair to moderate compared with the original diagnosis. Partial deletion of CD2 alone was associated significantly with MF. Epidermal deletions of 2 or 3 T-cell antigens or 2 T-cell antigens not including CD7 were associated significantly with MF. An elevated CD4/CD8 ratio correlated with MF. Morphologic features were most diagnostic of MF. Immunophenotyping generally resulted in downgrading of the reaction pattern but was helpful in distinguishing MF from benign dermatoses.

Androgen receptor expression patterns in Becker's nevi: An immunohistochemical study

BACKGROUND Beckers nevus (BN) is a hyperpigmented patch that traditionally presents on the upper torso in adolescent males. Previous studies have reported an association with increased androgen receptors (ARs) in lesional skin in men and women who have associated physical abnormalities. OBJECTIVE This study was conducted to assess the presence of ARs immunohistochemically in female patients with BN but no other physical abnormalities and compare this finding with BN in males and in normal skin. METHODS Biopsy specimens from Beckers nevi in 3 women and 3 men as well as normal skin in the 3 female subjects were stained with AR antibody, and the level of expression in various cutaneous structures was measured. RESULTS ARs were increased in dermal fibroblasts in Beckers nevi compared to that found in normal skin. LIMITATIONS The major limitation of the study was the small sample size. CONCLUSION In BN there is increased AR expression in dermal fibroblasts; immunohistochemical staining may aid in making the biopsy diagnosis.

Post-transplant lymphoproliferative disorder limited to the skin.

Background:  Post‐transplant lymphoproliferative disorder (PTLD) is a condition affecting immunosuppressed transplant patients and has a variety of clinical presentations. It is rarely found in the skin, and cases of PTLD in the skin are usually linked with lymph node or other organ involvement.

Sampling of melanocytic nevi for research purposes: A prospective, pilot study to determine effect on diagnosis

BACKGROUND Research on melanocytic nevi predominantly utilizes formalin-fixed, paraffin-embedded tissue, largely limiting research to morphologic and immunohistochemical observations. Withholding portions of fresh nevus tissue for molecular studies could result in the loss of important diagnostic material. OBJECTIVE This study prospectively evaluated melanocytic nevi for histologic homogeneity to determine if using a portion for research would have affected diagnosis. METHODS Thirty-three subjects were enrolled in a prospective study in which pigmented lesions were chosen for biopsy on a clinical basis. Lesions were sectioned and each piece submitted in a separate block (mean, 2.7; range 2-5 blocks per lesion). Slides from nevi were examined in two phases. In phase I, sections of nevi were randomized and a diagnosis was rendered for each section of nevus. In phase II, the dermatopathologist reviewed all slides for each nevus as a case, similar to the original interpretation of the lesion provided to the clinician. Diagnoses from phases I and II were compared with the original diagnosis. RESULTS Case material included 51 melanocytic lesions from 31 subjects. The phase I diagnosis matched the original diagnosis for 99 of 121 slides that showed a melanocytic lesion (82%). The phase II diagnosis matched the original diagnosis for 45 of 51 specimens (88%). LIMITATIONS The study was limited by: a small number of specimens; the clinician could have chosen clinically homogeneous nevi for biopsy; effect of interobserver and intraobserver variability on diagnosis. CONCLUSIONS For the majority of melanocytic nevi in this study, the diagnostic information present in one section of a melanocytic nevus could be extrapolated to the remainder of the specimen without adverse consequences from a diagnostic or therapeutic perspective.

Increased Melanocytic Nevi and Nevus Density in a G-34T CDKN2A/p16 Melanoma-Prone Pedigree

TO THE EDITOR Cyclin-dependent kinase inhibitor 2A (CDKN2A/p16) is a high-penetrance, autosomal-dominant melanoma predisposition gene (Cannon-Albright et al., 1992; Kamb et al., 1994) and mutations of this tumor suppressor are associated with a markedly increased risk of melanoma (Goldstein and Tucker, 1995; Kefford et al., 1999). CDKN2A/ p16 activity is required for melanocyte senescence in vitro (Gray-Schopfer et al., 2006). Pathogenic mutations have been discovered in approximately 10% of Utah melanoma pedigrees (Eliason et al., 2006). We recently reported in the Journal the results of a longitudinal follow-up study of members of a Utah melanoma-prone kindred with a temperature-sensitive V126D CDKN2A/p16 mutation. Mutation carriers accumulated significantly more melanocytic nevi over a 15-year interval than non-carrier family members or spouse control subjects (Florell et al., 2004). Moreover, carrier subjects possessed more nevi on warm body regions, such as the head, neck, and trunk (Florell et al., 2005). These findings suggest that in addition to conferring melanoma susceptibility, CDKN2A/p16 mutation contributes to nevus development and distribution. To this end, we hypothesized that (1) pedigree members with a non-temperature-sensitive pathogenic CDKN2A/p16 mutation would possess more melanocytic nevi and have a larger nevus density than non-carrier subjects; and (2) a temperature-sensitive nevus distribution would not be identified. To obtain additional evidence regarding the effect of a different CDKN2A/p16 mutation on nevus formation, we studied a second Utah melanoma pedigree with a promoter-region (G-34T) CDKN2A/p16 mutation in the 50 untranslated region that results in a false initiation site with reduced translation of wild-type CDKN2A/p16 (Liu et al., 1999) and segregates with melanoma susceptibility in melanoma pedigrees (Liu et al., 1999; Harland et al., 2000). This study was approved by the University of Utah Institutional Review Board (Utah IRB no. 7916) and was conducted according to the Declaration of Helsinki principles utilizing informed written consent. Thirty-one members of the G-34T pedigree and 13 spouse control subjects participated approximately 12 years earlier in this followup examination. All subjects were examined by the same dermatologist (LJM) for the initial and follow-up studies. Neither the participants nor