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R L Barnhill

Publications and source records attributed to R L Barnhill.

At least 91 records · Page 5Linked to original sources
PubMed1993

Pathology and prognostic factors.

Cutaneous malignant melanoma and its precursors were the general subjects of the National Institutes of Health Consensus Conference held in January 1992. Particular emphasis was placed on the diagnosis of early melanoma, especially melanoma in situ, and the controversies surrounding dysplastic nevi. Recent studies of unusual nevi often confused with melanoma, eg, deep-penetrating (plexiform) nevus, combined nevus, desmoplastic melanocytic nevus, and Spitz nevus in childhood, provided detailed histologic criteria for their discrimination from melanoma. Rare or unusual forms of melanoma, including desmoplastic melanoma, neurotropic melanoma, a newly described variant angiotrophic melanoma, subungual melanoma, and balloon cell melanoma have been the subject of comprehensive histologic studies. Other histopathologic investigations have described the prevalence of histologic regression and intraepidermal pagetoid spread in melanomas and the histologic features of reexcision specimens of melanoma. New evidence suggests that the predominant cell type infiltrating melanoma is the monocyte-macrophage, and the expression of monocyte chemotactic protein-1 by melanoma may explain the recruitment of this cell type. Immunopathologic studies of melanocytic lesions were performed with various melanocyte-associated antigens (eg, HMB-45), proliferation antigens (eg, Ki-67), and progression markers (eg, epidermal growth factor receptor and HLA-DR). HMB-45 binding has been localized ultrastructurally to early melanosome formation. Various prognostic factors, including gender, high-risk anatomic sites (particularly the scalp), race (black vs white patients), microscopic satellites, tumor volume, indices of proliferation and tumor cell motility, volume-weighted mean nuclear volume, DNA ploidy, and nucleolar organizer regions have been the subject of recent investigations. Analysis of many patients with long-term follow-up has facilitated better prognostic modeling of melanoma.

Diagnosis, Differential↗
PubMed1993

Histopathologic recognition and grading of dysplastic melanocytic nevi: an interobserver agreement study.

Before the controversies surrounding dysplastic melanocytic nevi are resolved, dermatopathologists must be able to reliably distinguish dysplastic nevi from common acquired nevi and malignant melanoma. To establish whether grading of melanocytic dysplasia has any biologic relevance, dermatopathologists must be able to consistently recognize two or more grades of atypia. We studied the concordance among five dermatopathologists for recognition and grading of 60 nevomelanocytic lesions. Ten cases from each of the following categories of melanocytic proliferation were retrieved from the Massachusetts General Hospital files: 1) common melanocytic nevi, 2) melanocytic nevi with features of dysplastic nevi, 3) dysplastic nevi with slight cytologic atypia, 4) dysplastic nevi with moderate cytologic atypia, 5) dysplastic nevi with severe cytologic atypia, and 6) primary malignant melanoma. The slides were reviewed independently; no discussion of diagnostic criteria preceded the review. Overall concordance for diagnosing dysplastic nevi was 77%, with a kappa statistic of 0.55-0.84. Furthermore, in grading dysplastic nevi, experienced dermatopathologists had a concordance ranging from 35% to 58% (kappa value 0.38-0.47). Those with less experience in grading dysplastic nevi had a concordance of 16-65% (kappa value 0.05-0.24). The five observers in this study reliably distinguished dysplastic nevi from common acquired nevi and malignant melanoma. Further refinement of the criteria for grading of nevo-melanocytic dysplasia and experience in grading are critical for accuracy in subcategorization of dysplastic nevi. Consistent, reproducible subcategorization of dysplastic nevi is a requisite before the issue of biologic or prognostic relevance of grading (dysplastic nevi) can be addressed. This study supports the validity of existing criteria for the diagnosis of dysplastic nevi because the problems in diagnosis were at the limits of the spectrum, namely, discrimination of slightly atypical dysplastic nevi from common nevi and severely atypical dysplastic nevi from radial growth phase melanoma.

Dysplastic Nevus Syndrome↗
PubMed1993

Common acquired melanocytic nevi, dysplastic melanocytic nevi and malignant melanomas: an image analysis cytometric study.

We used computerized image analysis cytometry to analyze 10 melanocytic lesions from each of the following categories: common acquired nevi, melanocytic nevi with architectural features of dysplasia, dysplastic melanocytic nevi (DMN) with slight atypia, DMN with moderate atypia, DMN with severe atypia, and superficial spreading melanomas. The nuclei of at least 50 consecutive nevomelanocytes in the most atypical zones were digitized at x 1000 under oil immersion, without knowledge of diagnosis by one observer. Grading of atypia was based on current practices as described in the literature. The results showed significant differences (p < 0.05) in nuclear area and standard deviation of nuclear area between melanoma and DMN with severe atypia, and between DMN with severe atypia and all other categories of nevi. There were no differences among any lesions with respect to nuclear shape. No differences in nuclear area were found among DMN with moderate, or slight atypia, nevi with features of dysplasia, and typical nevi. These results show for the first time objective distinction of low-grade (slight-moderate atypia), and high-grade or severe atypia in pre-malignant nevomelanocytic lesions of the skin.

Humans↗
PubMed1993

Histologic regression in malignant melanoma: an interobserver concordance study.

Histologic evidence for regression as a prognostic indicator in melanoma has shown conflicting results. To assess if melanoma regression is a consistently identifiable histologic feature, an interobserver concordance study was undertaken. Fifty histologic slides of melanoma with Breslow thickness of 1 mm or less were non-randomly selected from the Massachusetts General Hospital Melanoma Registry. The selection was in favor of those with regression present in 44 of 50 slides (88%). Two dermatopathologists working independently evaluated a 2 mm wide bracketed area in each tissue section and then the remainder of the non-bracketed tissue section for regression. Before and after each slide review, the evaluators were required to read criteria for early, intermediate, and late regression explicitly outlined. The overall concordance rate for the presence and absence of regression was 96% (48/50) in the bracketed area and 90% for the outside area. When the group with regression was subdivided into three stages, interobserver agreement fell to 86% for the bracketed, and 66% for the outside area. In at least 30% of cases where regression was detected in the bracketed area, both reviewers observed two or more stages of regression in the remainder of tissue section. Therefore, subdividing the process is impractical and unrealistic. Consistent histologic identification of regression in melanoma requires a simple and systematic approach which should be applied to future studies that include melanoma regression as a prognostic factor.

Humans↗
PubMed1993

Melanocytic nevi and tumor progression: perspectives concerning histomorphology, melanoma risk and molecular genetics.

Atypical variants of melanocytic nevi such as congenital nevi, acral nevi and Spitz nevi may share many architectural and cytologic abnormalities in common with conventional dysplastic nevi. Although largely undetermined, the degree of melanoma risk (if any) associated with the atypical nevus in question may correlate with the grade of atypia in the particular nevus and a variety of other factors such as the number of nevi and skin phototype.

Cell Transformation, Neoplastic↗
PubMed1993

Regressing thin cutaneous malignant melanomas (< or = 1.0 mm) are associated with angiogenesis.

In previous studies, we have shown that angiogenesis is often first noted in cutaneous malignant melanomas (CMMs) under 1.0 mm in thickness. Because angiogenesis may signal a more aggressive tumor phenotype, it is important to establish the circumstances associated with onset of angiogenesis. In the present study, we have quantified tumor vascularity in a series of CMMs under 1.0 mm in thickness and either associated with or lacking histologic regression. Microvessels were identified with the lectin Ulex europaeus agglutinin I and the vessels in five fields counted within an ocular grid (area 7.84 x 10(-2) mm2) at 400 x magnification. CMMs (mean 0.48 mm) with regression had greater microvessel counts (27.2 +/- 5.1) compared with CMMs (mean 0.61 mm) without regression (mean 20.1 +/- 7.9) (P < 0.01). However, of particular interest, CMMs in the radial growth phase only and associated with regression (mean 0.40 mm) had strikingly greater vascularity (mean 28.7 +/- 6.9) versus radial growth phase CMMs (mean 0.44 mm) lacking regression (mean 16.4 +/- 6.6) (P = 0.0013). CMMs in the vertical growth phase (mean 0.81 mm) without regression had slightly less vascularity (mean 24.4 +/- 7.3) compared with vertical growth phase CMMs with regression (mean microvessels 27.2 +/- 5.1) (P = 0.1878) but significantly greater microvessels versus radial growth phase CMMs without regression (P = 0.0213). These results suggest that the onset of angiogenesis in thin CMMs is related to at least two phenomena: 1) inflammatory regression and 2) development of the vertical growth phase.

Humans↗
PubMed1993

Clinical diagnosis of pigmented lesions using digital epiluminescence microscopy. Grading protocol and atlas.

BACKGROUND AND DESIGN: Epiluminescence microscopy (ELM) is a clinical technique that permits in vivo visual inspection of pigmented anatomic structures of the epidermis, dermoepidermal junction, and papillary dermis. A protocol is proposed for systematic visual inspection of pigmented lesions. Seventy pigmented lesions were imaged with a digital ELM camera system. Images were visually inspected for eight "global" ELM features, 23 "local" ELM features, and 18 network features. An atlas of the most clinically significant ELM features is presented with pilot estimates of their sensitivity and specificity for detecting melanoma. RESULTS: Preliminary data suggest that ELM features that may be most specific for melanoma include multicomponent pattern, nodular pattern, pseudopods, radial streaming, blue-gray areas, whitish veil (milky way), and sharp network margins. Epiluminescence microscopic features that may be most sensitive for melanoma include pigment dots, peripheral erythema, peripheral dark network patches, marked mean network irregularity, network line thickness variability, radial streaming, blue-gray areas, and whitish veil (milky way). Epiluminescence microscopic features that may be most sensitive for severe melanocyte atypia include pigment dots, peripheral erythema, hypopigmented network patches, peripheral dark network patches, marked mean network irregularity, and focal absence of network. In addition, features that may have a very high specificity for benign lesions include saccular pattern (suggests hemangioma), globular pattern (suggests a compound or dermal nevus), and multiple comedolike openings (suggests seborrheic keratosis). CONCLUSIONS: Features most sensitive for severe atypia and melanoma could form the basis for a screening test for considering biopsy. Features most specific for melanoma then could be applied to further triage management of pigmented lesions that meet initial screening criteria. In addition, features with very high specificity for benign lesions may help develop ELM criteria to avoid unnecessary surgery.

Atlases as Topic↗
PubMed1993

The histopathology of cutaneous malignant melanoma.

The vast majority of cutaneous malignant melanomas (CMM) develop from a proliferation of intraepidermal melanocytes that may progress through radial (including in situ and microinvasive stages) and vertical growth phases (VGP). The currently accepted classification of melanoma is based on the presence (eg, superficial spreading, lentigo maligna, or acral lentiginous melanoma) or absence of a radial growth phase (nodular melanoma). Although not standardized, melanoma may also be classified as to the nature of the VGP, eg, as expansile nodules composed of epithelioid cells, spindle cells, or smaller nevus-like cells supervening on one of the radial growth components previously mentioned, or developing de novo. Less common variants of the VGP include desmoplastic and neurotropic melanomas (often arising with lentiginous melanomas), and the controversial (and perhaps mainly conceptual) entity, minimal deviation melanoma. Other unusual or rare forms of melanoma are malignant blue nevus, balloon cell melanoma, and clear cell sarcoma. An extensive discussion of the differential diagnosis of the various types of melanoma is provided.

Cell Division↗
PubMed1992

Multiple primary cutaneous melanomas.

BACKGROUND: Development of multiple primary cutaneous melanomas is a well-recognized phenomenon. As with single primary melanoma, personal and family histories of melanoma and dysplastic nevi (DN) are considered important risk factors. The natural history and impact of regular follow-up evaluation of this entity were examined. METHOD: Through a search of the computerized data bank of the Pathology Department and the Melanoma Registry of the Pigmented Lesion Clinic at Massachusetts General Hospital, 41 patients with multiple cutaneous melanomas were identified. RESULTS: Mean (+/- standard error) age at first diagnosis was 49 +/- 2 years (range, 21-75 years). The male to female ratio was 2:1. The median number of primary melanomas was two (88%). Three patients had three and one had five. Melanoma types included superficial spreading (70%), nodular (8%), lentigo maligna (2%), and unclassified (10%), and in 7% the type was unknown. Nineteen (46%) patients had histologic and/or clinical evidence of DN. For the group with DN, the mean age at first diagnosis (44 +/- 3 years) was significantly less than that of patients without DN (54 +/- 3 years) (P less than 0.05). Family history of melanoma was found in 10 patients (24%). Multiple melanomas were diagnosed concurrently in 16 patients (39%), whereas in 25 (61%) diagnosis was sequential. For the latter group, the mean tumor thickness from the first (1.21 +/- 0.28 mm) to the second melanoma (0.51 +/- 0.08 mm) decreased significantly (P less than 0.05); the median time interval was 36 months (range, 2-372 months). CONCLUSION: These data confirm the need for complete skin examination for patients with newly diagnosed melanoma; and, with subsequent melanomas appearing as long as 31 years after the first melanoma, continued follow-up with complete skin examinations seems prudent.

Adult↗
PubMed1992

Interclinician agreement on the recognition of selected gross morphologic features of pigmented lesions. Studies of melanocytic nevi V.

BACKGROUND: Since the late 1970s clinical criteria for dysplastic melanocytic nevi (DMN) have been proposed and discussed. However, to our knowledge, no rigorous quantitative evaluation of the ability of examiners to agree on the gross morphologic features ascribed to DMN or atypical melanocytic lesions in general has been conducted. OBJECTIVE: The purpose of the study was to determine rates of interclinician agreement for recognizing seven clinical features associated with melanocytic lesions. METHODS: The gross morphologic features of 156 pigmented lesions, judged to be the clinically most atypical, from 156 consecutively examined patients with cutaneous melanoma were analyzed. Independent of the other clinicians' examinations, four physicians (two medical oncologists, one internist-epidemiologist, and one dermatologist-dermatopathologist) recorded seven gross morphologic features of the most atypical pigmented lesion on each patient. For up to 122 patients, the rates of interobserver agreement on recognizing these clinical features were measured by intraclass correlation. RESULTS: Among the clinical features assessed, the examiners noted macular components in 85.7% to 96.3% of lesions, asymmetry in 47.2% to 79.5%, irregular borders in 55.1% to 80.2%, ill-defined borders in 40.1% to 83.9%, and haphazard color in 40.8% to 73.9% of lesions. Despite this range of variance among examiners, there were statistically significant rates of interclinician agreement for the recognition of the latter features. There was less agreement in assessing individual colors within lesions. CONCLUSION: These findings substantiate that certain gross morphologic features routinely used in the clinical evaluation of melanocytic lesions can be recognized with a significant degree of reliability.

Adult↗
PubMed1992

Desmoplastic melanoma.

Desmoplastic melanoma is a rare tumour of which a limited number of cases have been described. The clinical and histopathological features of desmoplastic melanoma and its variants may give rise to perplexing diagnostic and therapeutic dilemmas. In the past decades, some insight has been gained into the histogenesis of these lesions and discriminating clinical and morphological features are now recognized. Review of the literature reveals an extensive list of differential diagnoses. Adequate surgical excision and close follow-up of these radioresistant, frequently-recurring tumours is strongly advocated.

Diagnosis, Differential↗
PubMed1992

Image analysis of stage 1 melanoma (1.00-2.50 mm): lymphocytic infiltrates related to metastasis and survival.

Image analysis of histologic sections of 11 patients with clinical Stage 1 melanoma, 1.00 mm-2.50 mm, who developed metastasis, was done to determine the significance of lymphocytic infiltrates relative to metastasis and survival. An age, sex, site, and thickness matched control group of non-metastasizing clinical Stage 1 melanoma revealed no significant difference in the lymphocytic infiltrate parameters from the metastasizing group with the exception of the ratio of lymphocyte infiltrate width to the tumor width (p = 0.003). Increased lymphocytic infiltrates within the tumor and subjacent to its base significantly correlated with delayed time to metastasis (p = 0.014 and p < 0.001, respectively) and longer survival period (p = 0.045 and p < 0.001, respectively). Lymphocytic infiltrate area at the tumor base in relation to tumor area was of prognostic value: the larger the ratio, the greater the time interval from metastasis to death (p = 0.008).

Humans↗
PubMed1992

Occurrence of melanoma in "dysplastic" nevus spilus: report of case and analysis by flow cytometry.

We report a case of melanoma arising in a large nevus spilus. On histologic examination, the nevus spilus had diagnostic features of melanocytic dysplasia. Further characterization by flow cytometry showed DNA-aneuploidy within the melanoma as well as in one of the darker pigmented papules within the nevus spilus. The significance of this finding and a review of melanomas originating in nevi spili are presented.

Adult↗
PubMed1992

Desmoplastic melanoma: clinicopathologic aspects of six cases.

We report 6 cases of desmoplastic melanoma. Upon removal and histologic examination, each lesion consisted of a dermal nodule of fascicles of spindle cells, many of which showed pleomorphic and hyperchromatic nuclei. Fascicles, as well as single cells, were seen infiltrating the dermal collagen. Lentiginous hyperplasia of melanocytes with varying but usually slight cellular atypia overlay the dermal proliferations in all cases. Melanophages and some pigmented cells, albeit few in number, were present in the infiltrate, whereas mitotic figures were also noted. These features are most consistent with desmoplastic melanoma, a rare tumor of which a limited number of cases has been described. The clinical and histopathologic features of the lesions presented exemplify the diagnostic and therapeutic dilemma associated with desmoplastic melanoma.

Adult↗
PubMed1992

Comparison of nonfamilial and familial melanoma.

There has been concern that individuals with nonfamilial melanoma and dysplastic melanocytic nevi (DMN) are not directly comparable to patients with hereditary melanoma and DMN. Because we have conducted a comprehensive study of nonfamilial melanoma over the past several years, we have addressed the above issue by directly comparing the characteristics of 145 nonfamilial patients, 6 patients with familial melanoma and the information available for familial melanoma in the literature. All 6 patients with familial melanoma had at least one first-degree blood relative with cutaneous melanoma. A large number of clinical and histologic variables were compared for both groups. Some pertinent variables included mean age at melanoma diagnosis 46.7 versus 52.3 years, mean Breslow thickness 2.11 versus 1.54 mm, mean total body nevi per patient 20.6 versus 18.3, mean total clinically atypical nevi per patient 2.0 versus 1.7 and total histologically confirmed DMN per group 22 (18.3%) versus 2 (33%), for patients with nonfamilial versus familial melanoma, respectively. No substantial differences were observed between the two groups. A review of the medical literature failed to reveal any quantitative data for melanocytic nevi, either clinical or histologic, at present that would allow distinction of patients with sporadic versus familial melanoma. We conclude that studies concerning the clinical characteristics of patients with DMN and nonfamilial melanoma are relevant to other persons with DMN including familial melanoma.

Adult↗
PubMed1992

Expression of sialyl-Lewis X, an E-selectin ligand, in inflammation, immune processes, and lymphoid tissues.

The carbohydrate structure sialyl-Lewis X (SLex) can function as a ligand for E-selectin, formerly known as endothelial leukocyte adhesion molecule-1 (ELAM-1). This study was performed to analyze the expression of SLex by leukocytes and other cell types in the context of inflammatory and immune processes. Human peripheral blood cells were examined by flow cytometry using monoclonal antibody CSLEX1 directed against SLex. Cell surface SLex was found in abundance on nearly all isolated polymorphonuclear leukocytes (PMN) and monocytes, and at low levels on a substantial portion (up to 40%) of natural killer cells. This moiety was expressed also on approximately 10% of peripheral blood T cells. Immunohistochemistry was performed on various human tissues involved in inflammatory or immune processes and on secondary lymphoid tissues. In acute appendicitis, endothelial cells of postcapillary venules expressed E-selectin, and most PMN, both within vessels and extravasated, expressed SLex. A substantial number of monocytes/macrophages in inflamed appendiceal, synovial, and dermal tissues also reacted with antibody CSLEX1; however, only rare tissue macrophages in uninflamed nonlymphoid sites showed expression of SLex. These observations are consistent with the concept that SLex on circulating PMN and monocytes functions as a ligand for endothelial E-selectin in the development of inflammatory reactions. SLex-positive lymphocytes also were seen, notably, T lymphocytes in inflamed skin. An unexpected finding was that the CSLEX1 antibody also reacted with venular endothelium in certain lymphoid tissues and in inflamed appendix, but not with endothelium in normal appendix. Whether the SLex antigen identified on endothelium represents de novo expression or passive adsorption remains to be determined.

Carbohydrate Metabolism↗