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1.  Eccrine angiomatous hamartoma with elements of an arterio-venous malformation: a newly recognized variant 
Journal of cutaneous pathology  2006;33(6):433-436.
We present the case of a 54-year-old man with a brown-red nodule on the hand that had been present since early adulthood. Histology of the excisional biopsy revealed hyperplasia and proliferation of eccrine, apocrine, lipomatous, and vascular structures. These findings were most characteristic of the entity known as eccrine angiomatous hamartoma (EAH), an uncommon tumor that may present variable clinical and histological features. In addition, this particular case exhibited a prominent component of arterio-venous malformation that distinguishes it from other EAHs described in the literature and adds to the spectrum of histologic findings that can be seen with this entity.
PMCID: PMC4113075  PMID: 16776719
2.  p63 expression in Merkel cell carcinoma predicts poorer survival yet may have limited clinical utility 
p63 expression has been identified in several cohorts as a predictor of poorer prognosis in Merkel cell carcinoma. We used multivariate analysis in a large independent cohort to determine the clinical utility of this parameter. Immunohistochemistry was used to determine p63 expression on MCC tumors from 128 patients. Of these, 33% had detectable p63 expression. p63 positivity was associated with an increased risk of death from MCC (hazard ratio 2.05, p = 0.02) in a multivariate Cox regression model considering stage at presentation, age at diagnosis, and gender. Although p63 expression correlated with diminished survival in this largest cohort reported thus far, the effect was weaker than that observed in prior studies. Indeed, within a given stage, p63 status did not predict survival in a clinically or statistically significant manner. It thus remains unclear whether this test should be integrated into routine MCC patient management.
PMCID: PMC4074520  PMID: 24225752
Merkel cell carcinoma; survival; prognosis; p63
3.  Keratinocyte Dysplasia in Hematopoietic Stem Cell Transplant Recipients in the Day 28 to 84 Post Transplant Period 
Severe keratinocyte dysplasia (SKD) has been reported as a common event in the early post-transplant period of hematopoietic stem cell transplant (HCST) patients.1 The purpose of our study is to determine the possible causes of SKD during the intermediate post-transplant period, and to ascertain its prevalence in skin biopsies. Skin biopsy slides, obtained from HCST recipients who were days 28 to 84 post transplant, were evaluated for SKD. Forty-four examples of SKD were identified in 467 slides, or 9%. Thirty-seven patients were evaluated as cases in a case-control design. SKD was strongly associated with a conditioning regimen containing busulfan with an odds ratio (OR) of 7.25 (p=0.0002). In a multivariate adjusted analysis, SKD was not associated with cyclophosphamide, fludarabine, total body irradiation (TBI), or a nonmyeloablative conditioning regimen. SKD was not associated with clinical acute graft-versus-host disease (GVHD). SKD histology gradually resolved, reaching a normal histology after an average of 241 days. This study finds that severe keratinocyte dysplasia in the period 28 to 84 days post hematopoietic stem cell transplantation is strongly associated with a busulfan conditioning regimen.
PMCID: PMC3402699  PMID: 22326632
Skin; Dysplasia; Transplantation; Busulfan
4.  Analysis of Tp53 Codon 72 Polymorphisms, Tp53 Mutations, and HPV Infection in Cutaneous Squamous Cell Carcinomas 
PLoS ONE  2012;7(4):e34422.
Non-melanoma skin cancers are one of the most common human malignancies accounting for 2–3% of tumors in the US and represent a significant health burden. Epidemiology studies have implicated Tp53 mutations triggered by UV exposure, and human papilloma virus (HPV) infection to be significant causes of non-melanoma skin cancer. However, the relationship between Tp53 and cutaneous HPV infection is not well understood in skin cancers. In this study we assessed the association of HPV infection and Tp53 polymorphisms and mutations in lesional specimens with squamous cell carcinomas.
We studied 55 cases of histologically confirmed cutaneous squamous cell carcinoma and 41 controls for the presence of HPV infection and Tp53 genotype (mutations and polymorphism).
We found an increased number of Tp53 mutations in the squamous cell carcinoma samples compared with perilesional or control samples. There was increased frequency of homozygous Tp53-72R polymorphism in cases with squamous cell carcinomas, while the Tp53-72P allele (Tp53-72R/P and Tp53-72P/P) was more frequent in normal control samples. Carcinoma samples positive for HPV showed a decreased frequency of Tp53 mutations compared to those without HPV infection. In addition, carcinoma samples with a Tp53-72P allele showed an increased incidence of Tp53 mutations in comparison carcinomas samples homozygous for Tp53-72R.
These studies suggest there are two separate pathways (HPV infection and Tp53 mutation) leading to cutaneous squamous cell carcinomas stratified by the Tp53 codon-72 polymorphism. The presence of a Tp53-72P allele is protective against cutaneous squamous cell carcinoma, and carcinoma specimens with Tp53-72P are more likely to have Tp53 mutations. In contrast Tp53-72R is a significant risk factor for cutaneous squamous cell carcinoma and is frequently associated with HPV infection instead of Tp53 mutations. Heterozygosity for Tp53-72R/P is protective against squamous cell carcinomas, possibly reflecting a requirement for both HPV infection and Tp53 mutations.
PMCID: PMC3335843  PMID: 22545084
5.  Transcriptome-Wide Studies of Merkel Cell Carcinoma and Validation of Intratumoral CD8+ Lymphocyte Invasion As an Independent Predictor of Survival 
Journal of Clinical Oncology  2011;29(12):1539-1546.
Merkel cell carcinoma (MCC) is a polyomavirus-associated skin cancer that is frequently lethal and lacks established prognostic biomarkers. This study sought to identify biomarkers that improve prognostic accuracy and provide insight into MCC biology.
Patients and Methods
Gene expression profiles of 35 MCC tumors were clustered based on prognosis. The cluster of genes overexpressed in good-prognosis tumors was tested for biologic process enrichment. Relevant mRNA expression differences were confirmed by quantitative polymerase chain reaction and immunohistochemistry. An independent set of 146 nonoverlapping MCC tumors (median follow-up, 25 months among 116 living patients) was employed for biomarker validation. Univariate and multivariate Cox regression analyses were performed.
Immune response gene signatures were prominent in patients with good prognoses. In particular, genes associated with cytotoxic CD8+ lymphocytes were overexpressed in tumors from patients with favorable prognoses. In the independent validation set, cases with robust intratumoral CD8+ lymphocyte infiltration had improved outcomes (100% MCC-specific survival, n = 26) compared with instances characterized by sparse infiltration (60% survival, n = 120). Only stage and intratumoral CD8 infiltration (but not age, sex, or CD8+ lymphocytes localized to the tumor-stroma interface) were significant in both univariate and multivariate Cox regression analyses. Notably, traditional histologic identification of tumor-infiltrating lymphocytes was not a significant independent predictor of survival.
Intratumoral CD8+ lymphocyte infiltration can be readily assessed on paraffin-embedded tissue, is independently associated with improved MCC-specific survival, and therefore, may provide prognostic information that enhances established MCC staging protocols.
PMCID: PMC3082974  PMID: 21422430
6.  Detection of Human Papillomavirus DNA in Cutaneous Squamous Cell Carcinoma among Immunocompetent Individuals 
The presence of certain types of human papillomavirus (HPV) is a known risk factor for the development of anogenital squamous cell carcinomas (SCCs). A similar association has been hypothesized for cutaneous SCCs, although, to our knowledge, no studies to date have combined sensitive HPV DNA detection techniques with epidemiologic data controlling for known risk factors to explore the association. We designed a case–control study examining HPV prevalence using highly sensitive PCR-detection assays in tissue samples from 85 immunocompetent patients with histologically confirmed SCCs and 95 age-matched individuals without a prior history of skin cancer. A standardized interview was administered to all study subjects to collect information pertaining to potential confounding variables. The overall detection rate of HPV DNA was high in case lesions (54%) and perilesions (50%) and in both sun-exposed normal tissue (59%) and non-sun-exposed normal tissue (49%) from controls. In comparing case tissue to control tissue, there was no differential detection of HPV DNA across various HPV species. However, HPV DNA from β-papillomavirus species 2 was more likely to be identified in tumors than in adjacent healthy tissue among cases (paired analysis, odds ratio = 4.0, confidence interval = 1.3–12.0). The high prevalence of HPV DNA detected among controls suggests that HPV DNA is widely distributed among the general population. However, the differential detection of HPV β-papillomavirus species in tumors among cases suggests that certain HPV types may be involved in the progression of cutaneous SCCs.
PMCID: PMC3268673  PMID: 18185530

Results 1-6 (6)