Biomedical subjects

R L Barnhill

Publications and source records attributed to R L Barnhill.

At least 37 records · Page 2Linked to original sources

PubMed1999

Tumor microvessels in melanoma express the beta-2 chain of laminin. Implications for melanoma metastasis.

The ultrastructural localization of an amorphous matrix to the interface between microvessel endothelium and tumor cells has been recently reported in a series of melanomas. Laminin expression as documented by immunohistochemistry was localized to microvessels in melanomas showing the amorphous matrix. In order to identify more precisely the type of laminin present in this amorphous material, immunostaining was carried out on cryostat sections from 16 human melanoma specimens. Four murine monoclonal antibodies directed against the alpha-3, beta-2, beta-3 and gamma-2 laminin chains were employed. In the melanomas studied, alpha3, beta3 and gamma2 laminin chains showed only minimal focal vascular positivity. In contrast, the beta2 (16/16 cases) laminin chain exhibited a consistent positivity in an angiocentric pattern about tumor microvessels. In all melanomas, some tumor cells seemed to spread along the abluminal surface of the small vessels, exhibiting a pericytic location, particularly along the intratumoral projections formed by the beta2 laminin chain. Given the role of laminin in migration and tumor progression, the results suggest a role of the beta2 laminin chain in melanoma spread, promoting tumor migration along the abluminal surface of vessel, a phenomenon which has been termed extra-vascular migratory metastasis.

Adult↗

PubMed1999

Evaluation of factors associated with skin self-examination.

Early detection and excision of thin lesions may be important in reducing mortality from melanoma. Periodic skin self-examination may be beneficial in identifying thin lesions. The purpose of this study was to evaluate factors associated with skin self-examination. The study population was comprised of 549 Caucasian residents of Connecticut 18 years of age or older who were selected as controls as part of a population-based case-control study on skin self-examination and melanoma conducted during 1987-1989. Personal interviews were conducted to obtain information on skin self-examination, demographics, history of cancer, phenotypic characteristics, sun exposure habits, and screening and health behaviors. Nevus counts were performed by trained nurse interviewers. Logistic regression was used to model the relationship between the variables of interest and skin self-examination. Female gender was identified a priori as a predictor of skin self-examination, and thus all analyses were stratified by gender. Age, education, and marital status were also identified a priori as important predictor variables and were selected for inclusion in the final models. Skin awareness was a strong factor associated with skin self-examination for both females and males. For females, previous benign biopsy or the presence of an abnormal mole was identified as important for future skin self-examination using our criteria. A family history of cancer, physician examination, and change in diet to reduce cancer risk increased the likelihood of skin self-examination in males but not females. In women, light hair color may increase the likelihood of performing skin self-examination. Older age and college or postgraduate education was associated with a decreased likelihood of performing skin self-examination in both males and females. Identifying factors associated with skin self-examination will enable health care providers to target individuals who may not be performing skin self-examination but who are at increased risk for developing melanoma.

Adolescent↗

PubMed1998

Validation of a melanoma prognostic model.

BACKGROUND: A "clinically accessible," 4-variable (patient age, patient sex, tumor location, and tumour thickness) prognostic model has been published previously. This model evaluated variables that were commonly available to the clinician. Because models are heuristic, validity of a prognostic model should be evaluated in a population different from the original population. OBJECTIVE: To evaluate the external validity of this 4-variable melanoma prognostic model. DESIGN: To estimate the external validity of this model, we used a population-based cohort of individuals with melanoma. We also evaluated a 1-variable model (tumor thickness). Estimates of the external validity of these logistic regression models were made using the c statistic and the Brier score. SETTINGS AND PATIENTS: A total of 1261 patients with melanoma evaluated in a multispecialty, university-based practice and 650 patients with melanoma from throughout Connecticut. MAIN OUTCOME MEASURE: Death from melanoma within 5 years of diagnosis. RESULTS: The c statistics for the 4-variable model were 0.86 (95% confidence interval [CI], 0.83-0.89) for the university-based practice data set and 0.81 (95% CI, 0.75-0.86) for the Connecticut data set. For thickness alone, the c statistics were 0.83 (95% CI, 0.80-0.86) and 0.79 (95% CI, 0.74-0.85), respectively. Brier scores for the 4-variable model were 0.09 (95% CI, 0.08-0.10) and 0.08 (95% CI, 0.06-0.09) and for the 1-variable model were 0.09 (95% CI, 0.08-0.10) and 0.08 (95% CI, 0.07-0.10), respectively. No significant differences exist between the data sets for the 4- and 1-variable models. CONCLUSIONS: The 4- and 1-variable models are generalizable. The simpler 1-variable model--tumor thickness--can be used with a relatively small loss in accuracy.

Female↗

PubMed1998

Congenital melanocytic nevi with placental infiltration by melanocytes: a benign condition that mimics metastatic melanoma.

BACKGROUND: Placental metastases from cutaneous malignant melanoma from both the mother and the fetus have been reported. The finding of benign-appearing melanocytes in the placenta in association with congenital melanocytic nevi (CMN) is more exceptional, with only 6 reports in the literature. Clinically, the finding of melanocytes in the placenta in this setting can be alarming and might erroneously lead to the diagnosis of metastatic melanoma. OBSERVATIONS: Herein, we describe 3 additional patients with CMN with placental infiltration by melanocytes with a benign phenotype. In the results of immunoperoxidase stains, the melanocytic cells were positive for S-100 protein and HMB-45 in the 2 lesions available for study. Staining of placental vessels with Ulex europaeus agglutinin I (Vector Laboratories, Burlingame, Calif) failed to show intravascular melanocytes in the 1 lesion available for study. We report for the first time DNA diploidy in 2 lesions available for study, which were analyzed by DNA image cytometry. We describe the first patient with a relatively small, nongiant CMN. CONCLUSIONS: We support the notion of the aberrant migration of melanocytes from the neural crest during fetal development as the most likely explanation of this phenomenon and note the similarity to the association of CMN and leptomeningeal melanocytosis. However, the precise histogenesis of this process remains uncertain. Most importantly, our data provide further evidence for the benign nature of this condition. Awareness of this entity is of vital importance in avoiding overdiagnosis of melanoma in this clinical setting.

Adolescent↗

PubMed1998

Tumor vascularity, proliferation, and apoptosis in human melanoma micrometastases and macrometastases.

BACKGROUND: Clinically undetectable or dormant metastases (micrometastases) probably account for disease recurrence, ie, clinically evident metastases, in patients after disease-free intervals of variable length. Recently developed animal models have shown that dormancy may potentially be explained by the fact that these micrometastases are not vascularized and have comparable rates of cellular proliferation and programmed cell death (apoptosis), enabling them to remain viable indefinitely but not to show progressive growth. OBSERVATION: We report for the first time that melanoma micrometastases from humans are similarly not vascularized (mean number of microvessels, 10.2), have significantly lower rates of tumor cell proliferation (mean, 2.4%), comparable rates of proliferation and apoptosis (means, 2.4.% and 0.2%, respectively), compared with melanoma macrometastases, which have significantly greater tumor vascularity (mean number of microvessels, 18.7), higher rates of proliferation (mean, 18%), and higher rates of proliferation relative to apoptosis (means, 18% vs 1.6%). Tumor vascularity was quantified using the lectin Ulex europaeus agglutinin I to identify the number of microvessels per unit area (microscope ocular grid with an area of 7.84 x 10(-2) mm2 at x400 magnification). Melanoma cell proliferation rate was assessed with the MIB-1 antibody (Ki-67) as the number of positive nuclei per total number of tumor nuclei counted at x400 magnification. Apoptosis was quantified using the method of terminal deoxynucleotidyl transferase-medicated deoxyuridine triphosphate-biotin nick end labeling. The number of positive nuclei were quantified per total number of tumor nuclei; usually 200 tumor nuclei were counted at x400 magnification. CONCLUSION: We report, for the first time, that human micrometastases demonstrate attributes, ie, the lack of significant tumor vascularity and low but comparable rates of proliferation and apoptosis, that may explain the dormant state.

Apoptosis↗

PubMed1998

"Rush" skin biopsy specimens in a tertiary medical center: diagnostic yield and clinical utility.

BACKGROUND: Skin biopsy specimens are submitted for "rush" or "stat" processing, thereby indicating a sense of urgency about the clinical situation. OBJECTIVE: Our purpose was to determine the patient population who underwent biopsy on a "rush" basis and assess the way in which interpretation of the skin biopsy specimen influences clinical management. METHODS: A retrospective study was performed on the "rush" biopsy specimens sequentially requested during 1 year. Histologic findings, the clinical situation, and the effect of the biopsy result on clinical management were determined. RESULTS: A total of 90 adult patients, many critically ill, were identified. The majority of patients were admitted to hematology-oncology services (58%). The other 42% were admitted to a variety of clinical services. The chief clinical concerns in hematology-oncology patients were graft-versus-host disease and cutaneous infection. Only 5.5% of biopsy specimens taken to exclude graft-versus-host disease were used in immediate clinical decision-making compared with 45% of biopsy specimens for oncology patients with suspected infection and 42% for all other services. CONCLUSION: Many urgent skin biopsy specimens were not used for immediate clinical decision-making. The usefulness of skin biopsy varies with the clinical situation, and some situations are more prone to yield equivocal histologic data. Knowledge of these situations may reduce the number of unhelpful biopsy specimens. Therapy based on clinical findings had often been initiated before receiving the biopsy results, but biopsy findings are often helpful as confirmatory data. Diagnostic findings were not necessary for a biopsy specimen to provide useful data and nonspecific findings interpreted in light of clinical findings were also useful.

Adult↗

PubMed1998

Analysis of vascularity of human neurofibromas.

BACKGROUND: A common misperception is that the vascularity of a tumor can be determined by its gross appearance. Neurofibromas are grossly white in appearance. The degree of vascularity of neurofibromas has not been determined. OBJECTIVE: The purpose of this study was to determine the extent of neovascularization of neurofibromas. METHODS: Neurofibromas from patients with neurofibromatosis-1 or spontaneous neurofibromas were stained with antibodies against von Willebrand factor (factor VIII-related antigen) and vascular endothelial growth factor (VEGF). RESULTS: Neurofibromas, both spontaneous and congenital, exhibit a high degree of vascularity. In addition, perivascular cells in neurofibromas stain with antibodies to VEGF, an angiogenic factor. CONCLUSION: Neurofibromas, despite their gross appearance, are highly vascular. Their vascularity may be mediated, in part, through the angiogenic factor VEGF.

Endothelial Growth Factors↗

PubMed1998

Hormonal and reproductive influences and risk of melanoma in women.

BACKGROUND: Evidence linking female hormones to the development of malignant melanoma has been contradictory. The purpose of this study was to examine the risk of melanoma in relation to exogenous and endogenous hormonal variables in women, including oral contraceptives, replacement oestrogens, pregnancy, and menopause. METHODS: Hormonal and reproductive factors were evaluated using data from a personal-interview population-based case-control study of melanoma in women conducted in Connecticut during 1987-1989. Caucasian female incident invasive melanoma cases (n = 308) were confirmed by standardized histopathological review. Caucasian female controls (n = 233) were selected by random digit dialling and frequency-matched on age. Data were analysed using multivariate logistic regression. RESULTS: Ever being pregnant, age at first pregnancy, current use of replacement oestrogens, ever use of oral contraceptives, duration of use of oral contraceptives, and age at first use of oral contraceptives were not associated with melanoma. Among other variables, cases were more than twice as likely as controls to report a single pregnancy lasting >6 months, but this association lacked a dose-response relationship. Menopause and body mass index were not independently associated with risk of melanoma. However, this analysis did suggest that menopause and body mass index may be interactive risk factors. Melanoma cases were three times more likely than controls to be obese and report natural menopause when compared to thin/acceptable premenopausal women (OR = 3.00, 95% CI: 1.03-8.73). CONCLUSIONS: These data do not provide strong evidence that hormonal and reproductive factors are associated with risk of melanoma in women, although the few positive results should be explored further.

Adolescent↗

PubMed1998

Sunlamp use and the risk of cutaneous malignant melanoma: a population-based case-control study in Connecticut, USA.

BACKGROUND: The relationship between cutaneous malignant melanoma and sunlamp use is examined in a Caucasian population in Connecticut, United States. METHODS: Cases were diagnosed between 15 January 1987 and 15 May 1987 with a first primary cutaneous melanoma. Controls were obtained from the general population, frequency matched to cases by sex and age, through random digit dialling of Connecticut telephone numbers. RESULTS: Of all study subjects, 141 (23%) cases and 95 (19%) controls reported ever having used sunlamps. The crude odds ratio (OR) for developing malignant melanoma after ever having used sunlamps was 1.30 (95% confidence interval [CI]: 0.97-1.74). This was reduced to 1.13 (95% CI: 0.82-1.54) after further adjusting for cutaneous phenotype and recreational sun exposure. Those who used more than one type of sunlamp had a threefold higher risk for melanoma compared to never users. Subgroup analyses showed that sunlamp use was associated with a greater increase in risk for melanoma among those who used sunlamps at home and those who were first exposed to sunlamps prior to 1971. The first use of sunlamps before the age of 25 showed somewhat higher risk for melanoma compared to first use later in life. CONCLUSION: The current study provides limited evidence that use of sunlamps increases the risk of melanoma. For future studies, it is crucial that type of sunlamp, year of first use and amount of exposure are all taken into account. The association between melanoma and tanning with both UV-A and UV-B lamps and tanning under sunlamps early in life merits further investigation.

Case-Control Studies↗

PubMed1998

Small cell sweat gland carcinoma in childhood.

Sweat gland carcinomas are rare skin tumors that typically occur in older patients. The spectrum of their clinical and pathologic features is broad, and many different types of sweat gland carcinomas have been described, ranging from fairly indolent to highly aggressive neoplasms. We present two cases of sweat gland carcinoma with a predominant small cell morphology. Both tumors occurred in children. One lesion developed in an 8-year-old girl as an asymptomatic papule on her left forearm, which ultimately was evaluated using biopsy because of rapid growth and change in color. The other lesion occurred on the hand of a 12-year-old boy. Both tumors were pandermal and extended into fat. They were composed of monotonous cuboidal cells with scant cytoplasm that formed tubules and grew in anastomosing cords and trabeculae. The tumor cells were immunoreactive for cytokeratins but not for cytokeratin 20. Ultrastructural analysis (available in one case only) showed that the tumor cells lacked neurosecretory granules. This variant of sweat gland carcinoma needs to be distinguished from other small cell neoplasms of the skin, especially Merkel cell carcinoma, its closest mimic.

Biopsy↗

PubMed1998

Expression of melan-A (MART1) in benign melanocytic nevi and primary cutaneous malignant melanoma.

The Melan-A (MART1) gene encodes an antigen recognized by cytotoxic T cells. Although its expression in metastatic melanoma has been documented in the literature by several investigators, little is known about its distribution in primary melanomas and benign melanocytic nevi. In this study, we evaluated Melan-A expression immunohistochemically on sections from paraffin-embedded material of 50 benign nevi and 40 primary cutaneous melanomas using the monoclonal antibody A103. To evaluate a potential role of A103 in the differential diagnosis of melanocytic from nonmelanocytic tumors, we also analyzed a number of benign and malignant peripheral nerve sheath tumors, fibrohistiocytic tumors, and leiomyosarcomas. Immunoreactivity with A103 was present in all "nonneurotized" nevi and in all nondesmoplastic primary melanomas, both in the intraepidermal and the dermal component. Only two nevi that underwent prominent neurotization showed no staining with A103. Although all melanomas with epithelioid cells tended to be strongly positive with A103, only 4 of 13 spindle cell and desmoplastic melanomas (all positive with anti-S-100 and negative with HMB-45) were immunoreactive with A103 (two focally, two diffusely). None of the nonmelanocytic lesions expressed Melan-A. Our results confirm that Melan-A protein is broadly expressed in the majority of benign and malignant melanocytic lesions and suggest that A103 can be helpful diagnostically, not only for metastatic tumors, but also for primary skin lesions. Its use in distinguishing between melanocytic and peripheral nerve sheath tumors, however, is limited because of the low or absent expression of Melan-A in nevi that underwent neurotization and spindle cell and desmoplastic melanomas.

Antibodies, Monoclonal↗

PubMed1998

Atypical or worrisome features in cellular neurothekeoma: a study of 10 cases.

Cellular neurothekeoma is a recently characterized benign cutaneous neoplasm arising usually on the upper trunk or head and neck of children or young adults. Typical histology is that of a lobulated dermal tumor composed of spindle and epithelioid cells, arranged in fascicles and nests, lacking immunoreactivity for S-100 protein, but usually being NK1/C3 positive. We present 10 new cases of cellular neurothekeoma with atypical histologic features that have not been described previously and that suggested the possibility of malignancy. The age range of affected patients was 1 to 44 years (median, 20.5 years); sites included the head and neck (three cases), the upper limbs (two cases), the lower limbs (two cases), and the trunk (two cases). Atypical findings in individual cases included large size (up to 6 cm), deep penetration (extending into skeletal muscle or subcutaneous fat, or both), diffusely infiltrative borders, vascular invasion, high mitotic rate, and marked cytologic pleomorphism. Clinical follow-up was available in 7 of 10 cases. Although the atypical features raised concern about the biologic potential of these lesions, preliminary follow-up (1-5 years) has shown no recurrence and suggests that complete surgical excision of these lesions is curative. These new data expand the morphologic spectrum of cellular neurothekeoma.

Adolescent↗

PubMed1998

Childhood melanoma.

This article examines all cases of malignant melanoma referred to Children's Hospital, Boston, and to the author over the period 1959-1995. Criteria for inclusion in the study included (1) age up to 15 years, (2) availability of microscopic slides, and (3) availability of demographic data. There were 11 boys and 12 girls, ranging in age from 2 to 15 (mean age, 9.4) years. Histopathologically the 23 tumors were categorized into four subgroups: (1) small cell melanoma (five cases), (2) adultlike melanoma (six cases), (3) Spitz-like melanoma (three cases), and (4) atypical Spitz tumors (nine cases). The small cell melanomas were notable for localization to the scalp, significant thickness, and fatal outcome. The adultlike melanomas resembled typical tumors occurring in adults. The one fatal Spitz-like melanoma was located on the neck of a 14-year-old boy. Two tumors in this group metastasized to regional lymph nodes but have not been associated with further aggressive disease on follow-up despite having been treated with surgical excision only. The atypical Spitz tumors were characterized by significant thickness and abnormal features, including prominent cellularity and mitotic activity. Anatomic site and cell type may be important prognostic factors in addition to tumor thickness in childhood melanoma but require further study. The biological potential of atypical Spitz tumors has not been sufficiently characterized.

Adolescent↗

PubMed1997

Lesions resembling malignant atrophic papulosis in a patient with dermatomyositis.

Many consider porcelain white atrophic papules as pathognomonic for malignant atrophic papulosis (MAP), or Degos' disease. During the past three decades, five patients with a collagen vascular disease have been reported to have MAP-like lesions as a manifestation of their underlying illness. We describe a patient with dermatomyositis who had porcelain-white atrophic papules resembling malignant atrophic papulosis.

Adult↗

PubMed1997

Desmoplastic neurotropic melanoma.

Desmoplastic neurotropic melanoma (DNM) is a rare variant of a spindle cell melanoma. The majority of these tumors occur on the head and neck of elderly patients. The rather variable clinical appearance (e.g. frequent lack of pigmentation) makes initial diagnosis often difficult. Histologically, DNM may show a lentiginous melanocytic proliferation with atypia and pleomorphic spindle cells in the dermis. Immunostaining for S-100 is usually positive although staining for HMB-45 is frequently absent. As with other melanomas, surgery is the first line treatment for DNM. Unlike other melanomas, however, survival for DNM may be better compared with other forms of melanoma.

Biomarkers, Tumor↗

PubMed1997

Leukemic vasculitis: a feature of leukemia cutis in some patients.

Cutaneous involvement is common in certain subtypes of acute leukemia and may be a reflection of a capacity of these tumors for tissue infiltration. We have recently noted that leukemia cutis can be accompanied by vasculitis in a subset of patients. We describe six cases of such leukemic vasculitis with findings ranging from mild microvascular injury to necrotizing arteritis. All cases were seen in patients with acute leukemia with myelomonocytic or monocytic features. In one patient, cutaneous leukemic vasculitis represented the initial manifestation of leukemia. In most cases, leukemic infiltration of the dermal blood vessels was the predominant pattern of involvement with minimal dermal infiltration. Vascular injury seemed to be mediated by leukemic blasts and not by reactive inflammatory cells. We propose the term leukemic vasculitis to describe such lesions.

Adult↗

PubMed1997

CD99 (p30/32MIC2) immunoreactivity in the diagnosis of leukemia cutis.

The diagnosis of leukemia cutis and distinction of early myeloid cells and blasts from lymphoblasts or other lymphoid cells can be difficult, particularly if only fixed tissue is available. O13, a monoclonal antibody that recognizes CD99, the p30/32MIC2 gene product, has been used to identify a number of cell types, including lymphoblasts, in paraffin sections. To evaluate the usefulness of CD99 immunoreactivity in the diagnosis of leukemia cutis, we analyzed cases of cutaneous involvement by acute lymphoblastic leukemia/lymphoblastic lymphoma and acute myelogenous leukemia for the presence of this marker. Without the use of antigen retrieval methods, lymphoblasts in cases of cutaneous involvement by acute lymphoblastic leukemia/lymphoblastic lymphoma were immunoreactive for CD99 in 9 of 9 cases. Myeloblasts and early myeloid cells in cases of cutaneous involvement by acute myelogenous leukemia were immunoreactive for CD99 in 12 (80%) of 15 cases. We conclude that CD99 is a sensitive but nonspecific marker for cutaneous involvement by acute lymphoblastic leukemia/lymphoblastic lymphoma and that CD99 is immunoreactive in the vast majority of cases (21 [88%] of 24 cases) of leukemia cutis.

12E7 Antigen↗

PubMed1997

Reliability of the histopathologic diagnosis of melanocytic dysplasia. The Dysplastic Nevus Panel.

OBJECTIVE: To determine the reliability of the histopathologic diagnosis of melanocytic dysplasia among diverse dermatopathologists who had no joint training, agreed to abide by predetermined criteria, and who were provided reference photomicrographs illustrative of the criteria. DESIGN, SETTING, AND PARTICIPANTS: A stratified random sample of 112 melanocytic tumors were chosen from the files of the pathology department of a large staff-model health maintenance organization. The original diagnoses included typical and dysplastic melanocytic nevi and melanoma. A single representative slide for each case was interpreted independently by each of the 5 panel dermatopathologists and 2 melanoma specialists. They had no prior knowledge of the original diagnosis or the diagnoses of the other panel members. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Interrater reliability was measured by intraclass and Pearson correlation coefficients. Each case was graded on a 5-point scale from no dysplasia to melanoma. RESULTS: The intraclass correlation among the panel members was 0.67 (95% confidence interval, 0.59-0.73). The Pearson correlations of each of the 5 panel dermatopathologists with the mean of the 2 melanoma specialists ranged from 0.67 to 0.84, and the correlations of the mean of the panel with the 2 melanoma specialists were 0.79 and 0.82; the mean reading of the melanoma specialists correlated 0.89 with the mean panel reading. Apparent protocol violations occurred in 6.5% of the readings. CONCLUSIONS: Agreement was substantial to excellent for the histopathologic diagnosis of 112 melanocytic tumors by dermatopathologists. Using predetermined criteria, melanocytic dysplasia can be reproducibly graded among diverse general dermatopathologists.

Case-Control Studies↗