Rosalie Elenitsas - Academia.edu (original) (raw)

Papers by Rosalie Elenitsas

JAMA Dermatology, Sep 1, 2013

, especially in the lower legs and forearms. Type 3 is characterized by the presence of diffuse b... more , especially in the lower legs and forearms. Type 3 is characterized by the presence of diffuse brownish discoloration of sun-exposed areas. Histopathologically, types 1 and 2 demonstrate pigment granules in the dermis, concentrated around vasculature within macrophages, and, in type 2, around myoepithelial cells as well. Perls staining is positive in type 1. In type 2, both Perls and Masson-Fontana stainings are positive. In type 3, there is increased melanin in basal keratinocytes with subjacent dermal melanophages without the presence of iron. Only Masson-Fontana staining is positive in this type. 4 Ultrastructural observations have confirmed that the clinical coloration is a result of a minocycline derivative chelated with iron that is stored within the lysosomes of macrophages. To our knowledge, there are no reports of cutaneous pigmentation due to rifampicin. Our patient's symptoms and the histologic findings were similar to those described for minocycline pigmentation type 2 and previous cases associated with levofloxacin and pefloxacin. The course of the pigmentation is unknown, but it tends to fade if levofloxacin treatment is discontinued. Months or years are necessary to achieve resolution, although in some cases the pigmentation can be permanent. Treatment with Qswitched laser has been reported with successful results. 5

Annals of Surgical Oncology, Oct 12, 2013

Background-The role for sentinel lymph node biopsy (SLNB) in patients with thin melanoma (≤1mm) r... more Background-The role for sentinel lymph node biopsy (SLNB) in patients with thin melanoma (≤1mm) remains controversial. We examined a large cohort of patients with thin melanoma to better define predictors of SLN positivity. Methods-Between 1995-2011, 781 patients with thin primary melanoma and evaluable clinicopathologic data underwent SLNB at our institution. Predictors of SLN positivity were determined using univariate and multivariate regression analyses, and patients were risk-stratified using a classification and regression tree (CART) analysis. Results-In the study cohort (n=781), 29 patients (3.7%) had nodal metastases. In the univariate analysis, mitotic rate (OR=8.11, p=0.005), Clark level (OR=4.04, p=0.003), and thickness (OR=3.33, p=0.011) were significantly associated with SLN positivity. In the multivariate analysis, MR (OR=7.01) and level IV-V (OR=3.45) remained significant predictors of SLN positivity. CART analysis initially stratified lesions by mitotic rate; non-mitogenic lesions (n=273) had a 0.7% SLN positivity rate versus 5.6% in mitogenic lesions (n=425). Mitogenic lesions were further stratified by Clark level; patients with level II-III had a 2.9% SLN positivity rate (n=205) versus 8.2% with level IV-V (n=220). With median follow up of 6.3 years, 5 SLN negative patients developed nodal recurrence and 4 SLN positive patients died of disease.

Journal of Clinical Oncology, Sep 15, 2004

The majority of invasive primary melanomas are thin (Յ 1.00 mm). Since the current staging system... more The majority of invasive primary melanomas are thin (Յ 1.00 mm). Since the current staging system imperfectly predicts outcome in patients with such lesions, we sought to develop a more effective classification scheme to better identify both patients at high risk of metastasis who are candidates for further staging and therapy and those with little risk. Patients and Methods This prospective cohort study included 884 patients who had thin invasive melanomas. A tree-structured analysis of 10-year metastasis was used to develop a new classification scheme. Results The overall 10-year metastasis rate was 6.5% (95% CI, 4.8% to 8.1%). The prognostic tree defined four risk groups: high-risk: men with vertical growth phase (VGP) lesions that had mitotic rates (MRs) greater than 0, and for whom the 10-year metastasis rate was 31% (22% to 42%; n ϭ 90); moderate-risk: women with VGP lesions that had MRs greater than 0 and for whom the rate was 13% (9% to 18%; n ϭ 136); low-risk: patients with VGP lesions that had MR of 0 for whom the rate was 4% (2% to 7%; n ϭ 247); and minimal-risk: patients with invasive lesions without VGP for whom the rate was 0.5% (0% to 1.2%; n ϭ 411). Survival curves differed significantly among the four groups (P Ͻ .001). Conclusion Growth phase, mitotic rate, and sex are important prognostic factors for patients with thin melanomas, and they identify subgroups at substantial risk for metastasis. After validation in other populations, the proposed prognostic tree will be useful in the design of clinical trials and clinical management.

Dermatologic Surgery, Apr 1, 2016

Background-Published appropriate use criteria (AUC) for Mohs micrographic surgery (MMS) for melan... more Background-Published appropriate use criteria (AUC) for Mohs micrographic surgery (MMS) for melanoma are based on consensus opinion.

JAMA Network Open

ImportanceA standardized pathology classification system for melanocytic lesions is needed to aid... more ImportanceA standardized pathology classification system for melanocytic lesions is needed to aid both pathologists and clinicians in cataloging currently existing diverse terminologies and in the diagnosis and treatment of patients. The Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) has been developed for this purpose.ObjectiveTo revise the MPATH-Dx version 1.0 classification tool, using feedback from dermatopathologists participating in the National Institutes of Health–funded Reducing Errors in Melanocytic Interpretations (REMI) Study and from members of the International Melanoma Pathology Study Group (IMPSG).Evidence ReviewPracticing dermatopathologists recruited from 40 US states participated in the 2-year REMI study and provided feedback on the MPATH-Dx version 1.0 tool. Independently, member dermatopathologists participating in an IMPSG workshop dedicated to the MPATH-Dx schema provided additional input for refining the MPATH-Dx tool. A referenc...

Dermatology Online Journal, 2014

A healthy 66 year-old man presented with a complaint of changes within a nodule on the scalp, whi... more A healthy 66 year-old man presented with a complaint of changes within a nodule on the scalp, which had first appeared over 10 years prior. He had no previous history of skin cancer. On physical examination a solitary, asymmetric, purple-black nodule with irregular borders was identified on the right vertex of his scalp. The remainder of his examination did not reveal any additional lesions.

Human Pathology, 2020

Vulvar malignant melanoma (VMM), although uncommon, comprises 5-10% of all vulvar malignancies. L... more Vulvar malignant melanoma (VMM), although uncommon, comprises 5-10% of all vulvar malignancies. Local control is notoriously poor in VMM with recurrence rates of 30-50% compared to approximately 3% in cutaneous melanomas. We studied clinicopathologic features of 37 women with VMM, after reviewing three decades of clinical follow up data in our institutional databases. Most patients were Caucasian (n=35) with an average age at diagnosis of 60.6 years (range 23-83). The most common subtype was mucosal lentiginous melanoma (n=25). We compared Kaplan-Meier survival curves of 31 patients defined by clinical and microscopic attributes using exact log-rank tests. Younger patients at diagnosis (23-64 yo), those with thin melanomas (≤1mm) and those with Clark's level II or III tumors had better 5 year survival rates than older patients (65-83 yo), and those with thick melanomas (>1mm) and those with Clark's level IV or V (p<=0.05), respectively, by exact log-rank test. Local recurrence of melanoma occurred in fifteen patients. Nine patients (24%) had eventual urethral involvement by malignant melanoma, and this feature was associated with significantly shorter survival (p=0.036). Patients with urethral involvement had shorter median time to death and worse 5-year survival rates. Given that spread to the urethra is common in VMM and urethral recurrence is also associated with

Journal of Cutaneous Pathology, 2018

BackgroundBRAF inhibition has improved overall survival in patients with BRAF mutant melanoma, bu... more BackgroundBRAF inhibition has improved overall survival in patients with BRAF mutant melanoma, but this is associated with a range of known and predictable cutaneous side effects, including squamous cell carcinomas associated with RAS mutations.MethodsWe identified three severely dysplastic nevi, one atypical intraepidermal melanocytic proliferation, and four melanoma in situ lesions, newly arising in four patients undergoing treatment with vemurafenib. To characterize mutations in these atypical melanocytic lesions, we used a custom iPlex panel detecting 74 mutations in 13 genes known to play a role in melanoma pathogenesis.ResultsWe identified an NRAS mutation at codon 61 (Q61R) and a rare BRAF exon 11 mutation (G466A) in atypical melanocytic lesions that arose in patients treated with vemurafenib.ConclusionThere appears to be development or accelerated growth of atypical melanocytic lesions in the setting of BRAF inhibition. Our results underscore the need for careful surveillanc...

Journal of cutaneous pathology, Jan 13, 2017

PD-1 (programmed cell death-1) inhibitors, used to treat metastatic melanoma and other malignanci... more PD-1 (programmed cell death-1) inhibitors, used to treat metastatic melanoma and other malignancies, are associated with development of immune-related adverse events in the skin. Such reactions include morbilliform eruptions, vitiligo, alopecia areata and bullous pemphigoid. In this report, we describe a patient who developed a lupus-like cutaneous reaction in the setting of pembrolizumab therapy for metastatic melanoma, adding to the spectrum of reactions which may be observed in association with PD-1 inhibitor therapy.

Cancer, Feb 21, 2016

Recently, a 23-gene signature was developed to produce a melanoma diagnostic score capable of dif... more Recently, a 23-gene signature was developed to produce a melanoma diagnostic score capable of differentiating malignant and benign melanocytic lesions. The primary objective of this study was to independently assess the ability of the gene signature to differentiate melanoma from benign nevi in clinically relevant lesions. A set of 1400 melanocytic lesions was selected from samples prospectively submitted for gene expression testing at a clinical laboratory. Each sample was tested and subjected to an independent histopathologic evaluation by 3 experienced dermatopathologists. A primary diagnosis (benign or malignant) was assigned to each sample, and diagnostic concordance among the 3 dermatopathologists was required for inclusion in analyses. The sensitivity and specificity of the score in differentiating benign and malignant melanocytic lesions were calculated to assess the association between the score and the pathologic diagnosis. The gene expression signature differentiated beni...

Journal of the American Academy of Dermatology, Jan 13, 2015

Various methods of tissue processing have been used to treat melanoma with Mohs micrographic surg... more Various methods of tissue processing have been used to treat melanoma with Mohs micrographic surgery (MMS). We describe a method of treating melanoma with MMS that combines breadloaf frozen sectioning of the central debulking excision with complete peripheral and deep microscopic margin evaluation, allowing detection of upstaging and comprehensive pathologic margin assessment before reconstruction. We conducted a retrospective cohort study evaluating for local recurrence and upstaging in 614 invasive or in situ melanomas in 577 patients treated with this MMS tissue processing methodology using frozen sections with melanoma antigen recognized by T cells 1 (MART-1) immunostaining. Follow-up was available in 597 melanomas in 563 patients. Local recurrence was identified in 0.34% (2/597) lesions with a mean follow-up time of 1026 days (2.8 years). Upstaging occurred in 34 of 614 lesions (5.5%), of which 97% (33/34) were detected by the Mohs surgeon before reconstruction. Limitations inc...

Journal of the American Academy of Dermatology, 2015

Background-Inherited susceptibility genes have been associated with histopathologic characteristi... more Background-Inherited susceptibility genes have been associated with histopathologic characteristics of tumors. Objective-To identify associations between histology of melanomas and CDKN2A genotype. Methods-Case-control study design comparing 28 histopathologic tumor features among individuals with sporadic melanomas (N=81) and cases from melanoma families with (N=123) and without (N=120) CDKN2A germline mutations. Results-Compared with CDKN2A-negative cases, mutation carriers tended to have histologic features of superficial spreading melanoma subtype including higher pigmentation (p trend =0.02)

Human pathology, 2008

Lymphatic invasion by tumor cells has been noted infrequently in primary melanomas. Our primary h... more Lymphatic invasion by tumor cells has been noted infrequently in primary melanomas. Our primary hypotheses were that using immunohistochemical markers of lymphatic vessels and of tumor cells would improve detection of lymphatic invasion and that lymphatic invasion would correlate with regional nodal metastatic disease. This study included 106 patients who were diagnosed between 1972 and 1991 and who had 10 years or more of follow-up. We performed dual immunohistochemical stains for podoplanin (for lymphatic vessels) and S-100 (for melanoma cells). Lymphatic invasion was identified by light microscopy and confirmed by multispectral imaging analysis. Lymphatic invasion was detected by morphology alone in 5 cases (4.7%) in contrast to immunohistochemical staining augmented by multispectral imaging analysis where 35 cases (33%) were identified (P < .0001). Lymphatic invasion was significantly associated with time to regional nodal metastatic disease, as well as first metastasis and m...

Journal of the American Academy of Dermatology, 2014

Letters e211 Open access under CC BY-NC-ND license. CORE Metadata, citation and similar papers at... more Letters e211 Open access under CC BY-NC-ND license. CORE Metadata, citation and similar papers at core.ac.uk

JAMA Dermatology, 2013

Journal of Cutaneous Pathology, 2009

Background-Src-family tyrosine kinases (SFKs) are signaling proteins that regulate keratinocyte p... more Background-Src-family tyrosine kinases (SFKs) are signaling proteins that regulate keratinocyte proliferation and differentiation. Srcasm is a recently identified molecule that downregulates SFK activity and promotes keratinocyte differentiation. To determine if Srcasm expression correlates with keratinocyte differentiation, we characterized the level of Srcasm expression in some cutaneous lesions that exhibit increased keratinocyte proliferation. Methods-Formalin-fixed sections of randomly selected seborrheic keratoses and basal cell carcinomas were analyzed for Srcasm and Ki-67 immunohistochemical staining. Anti-Srcasm and anti-Ki-67 staining were performed in parallel. Results-All seborrheic keratoses displayed decreased Srcasm staining in areas comprised of basaloid keratinocytes that exhibited an increased Ki-67 index. Higher Srcasm staining levels were detected near pseudo-horn cysts where keratinocytes exhibited a lower Ki-67 index. All multicentric and nodular basal cell carcinomas displayed a prominent loss of Srcasm staining in association with a marked increase in Ki-67 staining. Conclusions-Our results support the hypothesis that Srcasm protein levels are decreased in the hyperproliferative keratinocytes found in seborrheic keratoses and basal cell carcinomas. Increased Srcasm protein levels are detected in keratinocytes undergoing differentiation. Decreased Srcasm levels may be part of the pathophysiologic mechanism in cutaneous lesions exhibiting keratinocyte hyperproliferation.

Journal of Clinical Oncology, 2007

Purpose Most patients with melanoma have microscopically thin (≤ 1 mm) primary lesions and are cu... more Purpose Most patients with melanoma have microscopically thin (≤ 1 mm) primary lesions and are cured with excision. However, some develop metastatic disease that is often fatal. We evaluated established prognostic factors to develop classification schemes with better discrimination than current American Joint Committee on Cancer (AJCC) staging. Patients and Methods We studied patients with thin melanomas from the US population-based Surveillance, Epidemiology, and End Results (SEER) cancer registry (1988 to 2001; n = 26,291) and those seen by the University of Pennsylvania's Pigmented Lesion Group (PLG; 1972 to 2001; n = 2,389; Philadelphia, PA). AJCC prognostic factors were thickness, anatomic level, ulceration, site, sex, and age; PLG prognostic factors also included a set of biologically based candidate prognostic factors. Recursive partitioning was used to develop a SEER-based classification tree that was validated using PLG data. Next, a new PLG-based classification tree wa...

Journal of Clinical Oncology, 2004

PurposeThe majority of invasive primary melanomas are thin (≤ 1.00 mm). Since the current staging... more PurposeThe majority of invasive primary melanomas are thin (≤ 1.00 mm). Since the current staging system imperfectly predicts outcome in patients with such lesions, we sought to develop a more effective classification scheme to better identify both patients at high risk of metastasis who are candidates for further staging and therapy and those with little risk.Patients and MethodsThis prospective cohort study included 884 patients who had thin invasive melanomas. A tree-structured analysis of 10-year metastasis was used to develop a new classification scheme.ResultsThe overall 10-year metastasis rate was 6.5% (95% CI, 4.8% to 8.1%). The prognostic tree defined four risk groups: high-risk: men with vertical growth phase (VGP) lesions that had mitotic rates (MRs) greater than 0, and for whom the 10-year metastasis rate was 31% (22% to 42%; n = 90); moderate-risk: women with VGP lesions that had MRs greater than 0 and for whom the rate was 13% (9% to 18%; n = 136); low-risk: patients w...