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Biomedical subjects

R Elenitsas

Publications and source records attributed to R Elenitsas.

At least 37 records · Page 2Linked to original sources
PubMed1998

Cutaneous melanoma risk and phenotypic changes in large congenital nevi: a follow-up study of 46 patients.

BACKGROUND: Large congenital melanocytic nevi may undergo malignant transformation. Few prospective studies have evaluated the incidence of melanoma in large congenital nevi or have described how their phenotypic characteristics change over time. OBJECTIVE: We attempted to ascertain the incidence of cutaneous melanoma in a cohort of patients with large congenital nevi and to evaluate the frequency and nature of several morphologic changes over time. METHODS: Forty-six patients with large congenital nevi were prospectively followed up in our Pigmented Lesion Group. Large congenital nevi were defined as those occurring at birth and comprising 5% body surface area or greater in infants, children, and preadolescents and more than 20 cm in adolescents and adults. Information was obtained on location, satellitosis, changes in color and nodularity, and incidence of melanoma. The most atypical histologic findings from those who underwent biopsy were also noted. Standardized morbidity ratios (SMR) and 5-year cumulative risk were calculated and presented with corresponding 95% confidence intervals (CI). RESULTS: Twenty-four male and 22 female patients (age range, 7 days to 36.7 years; mean, 8.4 years) with large congenital nevi were followed up prospectively for a total of 335 person-years (range, 0.17 to 17.5 person-years; mean, 7.3 person-years). Two patients (4.3%) experienced 3 cutaneous melanomas that originated in their primary congenital nevi. We found one case of neurocutaneous melanosis. No satellite, extremity, or extracutaneous melanomas were detected. The majority of nevi in our cohort were located on the posterior trunk, were accompanied by multiple satellite congenital nevi, and became lighter over time. In the 27 patients who underwent biopsies, the most atypical histologic findings included melanoma, atypical melanocytic dysplasia, neurocristic dysplasia, atypical neural crest hamartomas, atypical spindle cell tumors, and congenital nevi with dysplasia. The SMR comparing observed-to-expected melanoma incidence was 148 (95% CI 18, 535; P = .0002) indicating a substantially increased risk of melanoma in patients with large congenital nevi. The cumulative 5-year risk of cutaneous melanoma was 5.7% (95% CI 0%, 13.5%). CONCLUSION: Our findings are consistent with the previously observed increased risk for the occurrence of cutaneous melanoma in patients with large congenital nevi. Although the number of patients with melanoma in this study is small, our observations and those of previous studies suggest that location and age correlates with melanoma risk. The majority of large congenital nevi are located on the trunk and may undergo several clinical changes as these patients age. Additional prospective studies are needed to gain more insight into the natural history and optimal management of large congenital nevi.

Adolescent↗
PubMed1998

Subcutaneous panniculitis-like T-cell lymphoma: clinicopathologic, immunophenotypic, and genotypic analysis of alpha/beta and gamma/delta subtypes.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is an uncommon cutaneous lymphoma that has been proposed as a distinct clinicopathologic entity, but studies of SPTCL are limited. We studied the clinicopathologic, immunophenotypic, and genetic features of 11 SPTCLs. All cases had a variable admixture of pleomorphic small, medium, or large lymphocytes and histiocytes infiltrating the subcutis in a lobular panniculitis-like pattern. A granulomatous reaction was seen in three cases and erythrophagocytosis in four. Karyorrhexis and fat necrosis were present in all cases. Angioinvasion was seen in seven SPTCLs; four had areas of coagulation necrosis. All cases expressed T-cell-associated antigens (CD3epsilon, CD45RO, or CD43) and T-cell receptors (TCR); nine expressed alphabeta TCRs and two expressed gammadelta TCRs. T-cell receptor-gamma, TCRbeta, or TCRdelta genes were clonally rearranged in 8 of 10 cases studied. Both gammadelta SPTCLs expressed Vdelta2+ TCRs and were CD4-, CD8- and CD56+. CD56 was negative in seven of nine alphabeta SPTCLs and inconclusive in the other two. Six of nine alphabeta SPTCLs were CD8+; the CD4/CD8 phenotypes were indeterminate in the other three. Cytolytic granule-associated proteins were expressed by all SPTCLs (11 of 11 were TIA-1+, 4 of 4 were perforin+). In situ hybridization for Epstein-Barr virus-encoded RNA (EBER-1) was negative in all cases. Most patients responded to systemic chemotherapy or local radiation therapy. Seven patients are alive: four without disease (19-73 months) and three with disease (32-72 months); four died: three of disease (3-25 months) and one without disease (42 months). We conclude that SPTCLs are clonal, EBV-, cytotoxic T-cell lymphomas derived from alphabeta T-cells or gammadelta T-cells. The gammadelta SPTCLs appear to be preferentially derived from the Vdelta2+ subset. Subcutaneous panniculitis-like T-cell lymphoma may be rapidly fatal or indolent; local therapy may be appropriate for some patients.

Adolescent↗
PubMed1998

The role of the pathologist in the diagnosis of melanoma.

The pathologist plays a vital role in patients with malignant melanoma. Dermatologists, surgeons, and oncologists must rely on the pathologist for accurate and complete diagnoses. Although most melanomas can be easily recognized with routine histopathology, special stains, including immunohistochemistry, may be necessary to differentiate melanoma from other cutaneous malignancies. Likewise, there are benign entities that can mimic melanoma microscopically, including Spitz nevi, pigmented spindle cell nevi, deep-penetrating nevi, and Monsel's reaction. Recognition of these entities is important to avoid unnecessary surgery, testing, adjuvant therapy, and unnecessary concern by the patients and their families. In addition to making an accurate diagnosis, the pathologist should report prognostic histologic attributes that may influence therapy and follow-up care for these patients. These histologic features should be recorded in the pathology report. This chapter provides a brief review of the most important histologic attributes that should be identified and reported by the pathologist.

Humans↗
PubMed1998

A case of multicentric reticulohistiocytosis in a 6-year-old child.

Multicentric reticulohistiocytosis (MR) is a rare disease in which an infiltration of histiocytic cells causes destructive polyarthritis and characteristic cutaneous lesions. It predominantly affects women between the ages of 40 and 50 years. Effective treatment has not been well established. We describe a case diagnosed in a 6-year-old girl. This is the youngest patient with MR reported to date.

Biopsy↗
PubMed1998

UVB induces atypical melanocytic lesions and melanoma in human skin.

A direct causal relationship between ultraviolet (UV) light in the B range and melanoma development has not been demonstrated in humans; this study aims to establish causality. A total of 158 RAG-1 mice, grafted with human newborn foreskin, were separated into four groups and observed for a median of 10 months: 1) no treatment, 2) a single treatment with 7,12-dimethyl(a)benzanthracene (DMBA), 3) UVB irradiation at 500 J/m2 alone, three times weekly, and 4) a combination of DMBA and UVB. Twenty-three percent of 40 normal human skin grafts treated with UVB only and 38% of 48 grafts treated with the combination of DMBA and UVB developed solar lentigines within 5 to 10 months of treatment. Melanocytic hyperplasia was found in 73% of all UVB-treated xenografts. Histological melanocytic changes resembling lentigo and lentigo maligna were seen in several skin grafts treated with both DMBA and UVB. In one graft of an animal treated with a combination of DMBA and UVB, a human malignant melanoma, nodular type, developed. This experimental system demonstrates that chronic UVB irradiation with or without an initiating carcinogen can induce human melanocytic lesions, including melanoma.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

UVB induction of epithelial tumors in human skin using a RAG-1 mouse xenograft model.

To examine the effects of chronic ultraviolet light on human epidermal cells, we grafted white human skin onto recombinase activating gene-1 knockout mice. We found previously that the maximal concentration of ultraviolet B radiation (290-320 nm) tolerated by human skin xenografts was 500 J per m2 when given three times weekly. One hundred and fifty-eight grafted mice were randomized and observed for a median of 10 mo in four groups: (i) no treatment; (ii) one treatment with the chemical carcinogen dimethyl-(a)benzanthracene; (iii) ultraviolet B three times weekly; and (iv) a combination of dimethyl-(a)benzanthracene and ultraviolet B. Approximately half of the skin specimens treated with ultraviolet B developed superficial milia and epidermal cysts. Grafts contained up to seven milia lesions between 4 and 8 mo after initiation of treatment, whereas the number of larger epidermal cysts was rarely more than two. Milia and cysts developed in the skin regardless of pigmentation or tanning. Actinic keratoses arose in 9% of grafts treated with ultraviolet B alone and in 19% of grafts treated with the combination of dimethyl-(a)benzanthracene and ultraviolet B. Invasive squamous cell carcinomas developed in 10% of grafts after combined dimethyl-(a)benzanthracene and ultraviolet B treatment and lesions were restricted to skin grafts that did not tan. These findings demonstrate that (i) development of ultraviolet-induced lesions can be experimentally accelerated in human skin, (ii) xenografted recombinase activating gene-1 deficient mice are superior to severe combined immunodeficiency disease mice for chronic ultraviolet B studies, and (iii) benign cystic tumors and squamous cell carcinomas are caused by ultraviolet B.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

Oral pigmentation representing Laugier-Hunziker syndrome.

Oral pigmentation is seen fairly commonly in dermatologic practice. Several conditions must be considered in the differential diagnosis. We present a patient whose condition highlights the clinical syndrome known as Laugier-Hunziker and provides the opportunity to review the clinical course, pathologic features, and literature of this uncommon syndrome.

Diagnosis, Differential↗
PubMed1997

Proto-oncogene c-kit expression in malignant melanoma: protein loss with tumor progression.

The c-kit gene encodes a transmembrane receptor that has tyrosine kinase activity. c-kit plays a role in hematopoiesis, gametogenesis, and melanogenesis. c-kit is found in melanocytes, and there is evidence that expression is lost in melanoma. We studied 85 melanocytic lesions for c-kit by immunohistochemical techniques using a monoclonal antibody. The lesions included banal nevi, junctional and compound nevi with melanocytic dysplasia, nontumorigenic radial growth phase melanoma, tumorigenic vertical growth phase melanoma, and metastatic melanoma. We found intense membrane staining in normal melanocytes and mast cells. Staining in compound nevi was strongest in junctional and superficial dermal components, whereas dermal nevi showed weak reactivity. Dysplastic nevi stained strongly, particularly in junctional cells. In melanoma, strong reactivity was most prominent in radial growth phase disease, but there was little or no staining in vertical growth phase and metastatic melanomas. In summary, c-kit protein is expressed in normal melanocytes, benign nevi, dysplastic nevi and nontumorigenic melanoma, but expression is lost in tumorigenic primary melanomas and metastases. The role of c-kit loss in advanced melanoma requires additional investigation.

Disease Progression↗
PubMed1996

A prognostic model for predicting 10-year survival in patients with primary melanoma. The Pigmented Lesion Group.

OBJECTIVE: To develop a prognostic model, based on clinical and pathologic data that are routinely available to the clinician, that would estimate the chance for survival of a patient with primary cutaneous melanoma after definitive surgical therapy. DESIGN: Cohort analytical study. SETTING: University medical center. PATIENTS: 488 patients with primary cutaneous melanoma who had no apparent metastatic disease. Patients were followed prospectively for at least 10 years. An independent validation sample of 142 patients was used to assess the stability of the model. MEASUREMENTS: Six clinical and pathologic variables that predict survival and are readily available to the clinician were used to develop a prediction model. The variables were tested for their association with death by using a univariate logistic regression model. Point estimates were generated for the probability of surviving melanoma at 10 years. Variables that were statistically significantly associated with survival were retained for testing in a logistic regression model. RESULTS: 488 patients were followed prospectively for a median of 13.5 years (minimum, 10.0 years; maximum, 20.5 years). The overall 10-year survival of the study group was 78%. Four variables were found to be independent predictors of survival. Presented as adjusted odds ratios, from strongest to weakest relative predictive strength, these variables were tumor thickness (odds ratio, 50.8), site of primary melanoma (odds ratio, 4.4), age of the patient (odds ratio, 3.0), and sex of the patient (odds ratio, 2.0). The four-variable model was significantly more accurate than tumor thickness alone, particularly for predicting death. Overall, use of the model reduced the error rate of the prediction of death by 50%. CONCLUSIONS: A prognostic model that uses four readily accessible variables more accurately predicts outcome in patients with primary melanoma than does tumor thickness alone. This four-variable model can identify patients at high risk for the recurrence of disease, an identification that becomes increasingly important as adjuvant therapies are developed for treatment of melanoma.

Adult↗
PubMed1996

Eczematous halo reaction in atypical nevi.

Meyerson's nevus has been described as a melanocytic nevus with an associated eczematous halo reaction. We describe four patients with eczematous halos developing around atypical nevi, a finding not previously reported. Biopsy specimens revealed eosinophilic spongiosis in addition to the previously reported spongiotic dermatitis.

Adult↗
PubMed1996

Neoplastic progression and prognosis in melanoma.

Most melanomas evolve through an initial stage known as radial growth phase (RGP), encompassing in situ and microinvasive malignancies in which the probability of cure approaches 100%. At the present time, despite a shift toward earlier recognition of melanoma, by the time of diagnosis roughly 70% of melanomas have evolved to a point, known as vertical growth phase (VGP) or tumorigenic melanoma, at which cure is not certain, and prognosis depends upon certain attributes of the neoplasm and the host. Attempts have been made to assemble these attributes into prognostic models to permit estimation of the probability of cure for individuals and for groups of patients. Attributes that have been identified as independent prognostic variables include thickness of the primary neoplasm, the numbers of mitotic figures, and the presence of tumor-infiltrating lymphocytes (TIL). Other biologically important prognostic variables are on the horizon, and some will likely be based on molecules (markers) expressed on neoplastic cells that show functional significance in mechanisms of metastasis.

Disease Progression↗
PubMed1996

Apoptosis induction of ultraviolet light A and photochemotherapy in cutaneous T-cell Lymphoma: relevance to mechanism of therapeutic action.

The anti-tumor action of many chemotherapeutic agents has recently been attributed to the induction of apoptosis in the malignant cell population. In this study, we investigated the ability of extracorporeal photopheresis (ExP) and in vitro PUVA (8-methoxy-psoralen + ultraviolet A) therapy to induce apoptosis in peripheral blood mononuclear cells from Sezary syndrome patients and normal controls. Flow cytometric analysis of ExP- or PUVA-treated peripheral blood lymphocytes demonstrated two distinct cell populations within 24 h of treatment. One population was similar to untreated controls with the other exhibiting characteristics of apoptotic cell death, i.e., a loss of cell volume and an accompanying increase in cell density. This latter population was comprised of cells with DNA strand breaks as determined by the Tdt-mediated deoxyuridine triphosphate-biotin nick end labeling assay. Apoptosis was also confirmed morphologically by fluorescent and electron microscopy as well as by demonstration of characteristic DNA strand breaks (laddering) using gel electrophoresis. Apoptosis was not observed with 8-methoxypsoralen (< or = 300 ng per ml) alone; however, ultraviolet A alone at doses > or = 2 J per cm2 induced apoptosis in lymphocytes. Peripheral blood T-cell subpopulations of Sezary syndrome patients, including the malignant clone, were equally susceptible to apoptosis subsequent to either photopheresis or PUVA treatment. In contrast, monocytes (CD14+/CD45+) appear to be resistant to apoptosis induction by ExP or PUVA treatment. Moreover, ExP-treated and untreated monocytes phagocytized apoptotic, but not untreated, peripheral blood mononuclear cells. ExP and PUVA have been shown to be efficacious and well-tolerated therapies in the treatment of dermatologic diseases and transplant rejection. These data suggest that induction of apoptosis may be an important event for therapeutic efficacy.

Apoptosis↗
PubMed1995

An unusual case of early malignant transformation in a spiradenoma.

BACKGROUND: Review of the literature reveals that malignant spiradenomas are rare and may be fatal, and typically manifest as rapid enlargement in long-standing spiradenomas. OBJECTIVE: The present tumor was removed 2 months after it was first noted by the patient. A case of what we believe is the earliest stage of malignant transformation within spiradenoma is reported. METHODS: Case report and literature review. RESULTS: The region with malignant transformation was characterized by nuclear pleomorphism, loss of two cell types, and increased mitotic activity with atypical mitoses. Small infiltrating duct-like structures were seen. The large aggregates and sheets of malignant cells described in long-standing tumors were not seen. CONCLUSION: We ascribe the early detection of this tumor to increased public awareness of the importance in seeking early treatment of skin lesions. Histologic examination of this stage may eventually outnumber the now more commonly described latter stages.

Adenoma, Sweat Gland↗
PubMed1995

Scurvy and panniculitis: a case report.

In most western countries, scurvy has become a rare clinical entity. However, it may still be encountered in selected situations. It can mimic connective tissue disease, because of multiorgan involvement. Panniculitis has not previously been described in association with scurvy.

Adult↗
PubMed1994

Familial occurrence of multiple cutaneous chondromas.

True cutaneous chondromas are rare lesions with an uncertain pathogenesis. We report an unusual case of a patient with multiple cutaneous chondromas of the face. One of the patient's siblings, a brother, and that brother's son had similar facial lesions. We conclude that this familial pattern suggests an autosomal dominant mode of transmission.

Adult↗
PubMed1994

Bleomycin-induced flagellate dermatitis: a clinical and histopathological review.

We report a case of bleomycin-induced flagellate dermatitis. Our patient developed pruritic linear lesions 4 days after her first dose of bleomycin. A closed patch test was performed, and was negative. However, on rechallenge, the linear eruption recurred in the previously involved sites, and in new sites, within 24 h. Flagellate dermatitis is a characteristic reaction to bleomycin use, but varying histological features and clinical presentations may be seen.

Adult↗
PubMed1994

Effects of topical tretinoin on dysplastic nevi.

PURPOSE: As potential precursors of melanoma and markers of increased melanoma risk, dysplastic nevi are suitable targets of strategies for melanoma chemoprevention. We report the results of a pilot study of topical retinoic acid in patients with dysplastic nevi. PATIENTS AND METHODS: Five male patients with dysplastic nevi applied tretinoin to half of the back for 6 months. Baseline photographs of dysplastic nevi were compared with posttreatment photographs and assessed for morphologic change. At study completion, each subject had four nevi excised from the treated side and four from the untreated side of the back. Biopsies were histologically evaluated for the presence of dysplasia. RESULTS: All patients developed signs of irritation as a result of treatment. One patient was not compliant with treatment due to skin irritation. The four compliant patients showed significant decreases in the clinical atypia of treated lesions, with concomitant fading and even disappearance of many treated nevi. Histologically, only four of 16 treated nevi met histologic criteria for dysplasia, in comparison to 13 of 16 untreated nevi. CONCLUSION: These results suggest that there is concomitant clinical and histologic improvement in a significant percentage of dysplastic nevi treated with topical tretinoin. However, the utility of topical tretinoin for chemoprevention of melanoma is limited by difficulty of application and associated inflammation. While new strategies in chemoprevention of melanoma are explored, sun protection and assiduous avoidance of sunburn must remain the mainstay of melanoma prevention.

Administration, Topical↗