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Biomedical subjects

R L Barnhill

Publications and source records attributed to R L Barnhill.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Angiogenesis and tumor progression of melanoma. Quantification of vascularity in melanocytic nevi and cutaneous malignant melanoma.

BACKGROUND: The capacity of cutaneous malignant melanoma (CMM) to induce angiogenesis is well established. In addition, dysplastic melanocytic nevi (DMN) have been reported to display prominent vascularity relative to common acquired nevi; but this observation has never been verified objectively. EXPERIMENTAL DESIGN: In the following studies, papillary dermal or tumor vascularity was quantified in 10 examples of normal skin, and in a series of 18 melanocytic nevi, 29 DMN, 37 primary CMM and 5 melanoma metastases. Microvessels were identified with the lectin Ulex europaeus agglutinin I. The number of microvessels were counted with an ocular grid (area 7.84 x 10(-2) mm2) at x400 magnification, and the mean vascularity recorded for five fields for each specimen. RESULTS: Mean vascular counts were as follows: normal skin 5.9, common acquired nevus 9.1, nevus with features of DMN 10.3, DMN, slight atypia 11.8; DMN, moderate atypia 12.2; DMN, severe atypia 14.8; primary CMM 25.4; and metastatic melanoma 29.5). Significant differences were recorded for DMN, severe atypia versus melanoma (p less than 0.01), DMN, severe versus common nevi (p less than 0.02) and versus nevi with features of DMN (P less than 0.05). When microvessel counts from CMM in the radial growth phase were compared with those from CMM in the vertical growth phase, or CMM less than 1.0 mm versus those greater than 1.0 mm, no significant differences were found. However, CMM in radial growth did differ from severely atypical DMN (22.4 versus 14.8, p less than 0.05). CONCLUSIONS: These results quantify for the first time a gradual rise in vascularity with tumor progression in the melanocytic system and onset of angiogenesis during the radial growth phase of CMM. Other than severely atypical DMN, DMN did not differ substantially from common nevi with reference to overall vascularity.

Capillaries↗
PubMed1992

Primary malignant melanoma of the external auditory canal: a case report with presentation as an aural polyp.

A case of primary cutaneous melanoma of the external auditory canal and a review of the literature are reported. This is the first reported case with microstaging of the tumor. The tumor presented as a polypoid obstructive lesion of the external ear canal. Although occurrence of melanoma in this location is extremely rare, differential diagnosis of an external ear canal polyp should be expanded to include primary malignant melanoma.

Biopsy↗
PubMed1991

Correlation of clinical and histopathologic features in clinically atypical melanocytic nevi.

To define better the evolving entity of dysplastic melanocytic nevus (DMN), studies correlating clinical with histologic features of DMN are essential. However, based on a literature search, no previous quantitative analysis was found of the relationship between gross morphologic features and histologic features of DMN. The authors correlated individual clinical features with histopathologic features and histologic diagnosis of the clinically most atypical nevus in 153 melanoma patients. This nevus was identified, evaluated clinically, and removed for histologic evaluation from each patient. Gross morphologic features assessed for nevi included: size (in mm), the presence of a macular component, irregular border, ill-defined border, haphazard coloration, distortion of skin cleavage lines on tangential lighting, asymmetry, and number of colors present (12 features in all). Nineteen histologic features were assessed in each nevus by a single dermatopathologist. These included architectural, nuclear, and cytoplasmic parameters ascribed to dysplastic nevi. Each of these histologic features was correlated with the 12 individual clinical features. Seventeen percent of the nevi fulfilled the criteria for the histologic diagnosis of DMN. Among individual nevus parameters, size (in mm), irregular border, ill-defined border, macular component, and pink color were associated significantly with histologic DMN. Nevus size (in mm) and irregular borders correlated with the greatest number of individual histologic parameters. A comparison of clinicopathologic correlations for two different examiners revealed that certain clinical features are probably more important than others for the recognition of dysplastic nevi and that individual examiners have different thresholds for the perception of some gross morphologic features. These observations are relevant to the development of clinical criteria for dysplastic nevi.

Adult↗
PubMed1991

Sun-induced freckles in children and young adults. A correlation of clinical and histopathologic features.

Sun-induced freckles are a risk factor for epidermal and melanocytic neoplasia. Whereas sun-induced freckles in children and older adults may be clinically indistinguishable, and sun-induced freckles in older adults usually consist of increased numbers of intraepidermal melanocytes, the histology of sun-induced freckles in children remains unsettled. Using L-3,4 dihydroxyphenylalanine (DOPA)-paraffin sections, the authors examined six sun-induced freckles and adjacent nonpigmented skin (ANP) in as many white male subjects, ages 10 to 23 years. Melanocyte frequency was expressed as the ratio of DOPA-reactive melanocytes to total epidermal basal unit cells. For each case, melanocyte frequencies in freckles were significantly greater than in ANP. Cellular atypia of melanocytes was noticed in four of six freckles. Reactivity of melanocytes for HMB-45 was noticed in two freckles studied, compared with no reactivity in three specimens of ANP studied. The authors conclude the sun-induced freckles in the young may consist of a hyperplasia of melanocytes (i.e., similar to solar lentigines in the elderly), sometimes with cellular atypia, and that these findings may be relevant to melanocytic neoplasia.

Adolescent↗
PubMed1991

The histologic spectrum of pigmented spindle cell nevus: a review of 120 cases with emphasis on atypical variants.

The histopathologic features of 120 cases of pigmented spindled nevus (PSCN) from the years 1973 through 1988 were reviewed from a consultative practice heavily weighted with difficult nevomelanocytic lesions. The patients' mean age was 25.2 years, and females outnumbered males (68 versus 52). Extremity lesions made up 69.6% of the total, with the thigh the most common site. The lesions were categorized into one of four variants of PSCN, based on the presence or absence of various architectural and cytologic parameters and involvement of the reticular dermis. Thirteen cases (10.8%) were designated typical PSCN, and were characterized by fascicles of uniform pigmented spindle cells without cellular atypia and limited to the epidermis or papillary dermis. Ninety-five cases (79.2%) were classified as atypical PSCN (PSCN with architectural and/or cytologic atypia). Some of the latter also demonstrated substantial numbers of epithelioid cells, thus exhibiting some overlap with Spitz nevus. Eight cases showed striking features of dysplastic nevus. Ten cases had fascicles of pigmented spindle cells involving the reticular dermis ("plexiform" PSCN). Two cases were designated as combined PSCN because of the presence of banal nevus cells in addition to the spindle cell component. Clinical follow-up of a small group of patients has not suggested, to date, any aggressive behavior. Knowledge of PSCN and its atypical variants is important for discrimination from malignant melanoma.

Adolescent↗
PubMed1991

Studies on the cellular origin of neurothekeoma: clinical, light microscopic, immunohistochemical, and ultrastructural observations.

The clinical, histopathologic, and immunohistochemical features of 11 cases of neurothekeoma are reported. One case was examined by electron microscopy. The mean age of the patients was 27.1 years; the study comprised eight female and three male patients. Most lesions were nondescript papules and located on the upper part of the body, seven cases of neurothekeoma on the head. Eight cases were classified as cellular neurothekeoma on the basis of a striking fascicular pattern and three cases as myxomatous neurothekeoma because of prominent myxoid stromal change. All cellular neurothekeomas failed to express S-100 protein, whereas the three myxomatous types were strongly positive for this marker. Other than vimentin, there was no significant immunoreactivity with other immunohistochemical markers. Ultrastructural study of one case of cellular neurothekeoma was inconclusive for cell type although a perineurial origin could not be excluded. On the basis of these results, we conclude that cellular neurothekeoma differs from myxomatous neurothekeoma not only by clinical and histologic findings but also by immunoreactivity with S-100 protein. These findings also suggest the existence of two distinct subtypes of neurothekeoma and possible origin of the two variants of neurothekeoma from different cell types or at least variation in phenotypic expression of a common cell type. On the other hand, it cannot be excluded that these two variants are different stages in the natural history of neurothekeoma.

Adolescent↗
PubMed1991

Inter-clinician agreement on the recognition of clinical pigmentary characteristics of patients with cutaneous malignant melanoma. Studies of melanocytic nevi, VI.

The number and type of melanocytic nevi are among the most important known predictors of risk for cutaneous malignant melanoma. In this study, examinations of the skin were conducted by two to four clinicians on 153 patients with newly diagnosed melanoma, and the agreement among clinicians was quantified regarding number of nevi and freckling. The index of agreement (calculated as the intra-class correlation coefficient) was 59.7% and 69.0% for freckling on the right forearm and on the shoulders, respectively; agreement was above 50% for only one of six pairs of clinicians in examining freckling on the right forearm, while agreement was above 50% for four of the six pairs of clinicians in examination of freckling on the shoulder. For palpable nevi of the arms (used in at least two case-control studies as a predictor of risk), the agreement was 36.1% when computed for three examiners assessing 81 patients. However, for total arm nevi (both palpable and non-palpable), assessed on a subset of 48 patients, the agreement was 88.2%; this and other analyses indicated that the difficulty in achieving a consensus for palpable nevi lay in whether or not lesions were considered to be 'palpable' or 'non-palpable'. Agreement for total number of atypical nevi on the body and total number of all types of nevi were 87.4% and 91.8% respectively. These data suggest that the kinds of lesions on which agreement might be reached are total atypical nevi and total nevi of all types on the arms and on the entire body. Greater difficulty might be found in achieving consistency among investigators and among clinicians in examining individual patients with respect to freckling on the arms and 'palpable' nevi. However, some consistency was achieved even with these latter two clinical features.

Adult↗
PubMed1991

Correlation of clinical pigmentary characteristics with histopathologically-confirmed dysplastic nevi in nonfamilial melanoma patients. Studies of melanocytic nevi IX.

The dysplastic melanocytic nevus (DMN) is the key clinical marker for the familial dysplastic nevus syndrome and has also been associated with high risk for non-familial melanoma. Characterisations of DMN itself have been qualitative and on a case-by-case basis. In this study, we provided clinical and histological characterisations for each of 150 pigmented lesions from 150 patients with prior malignant melanoma. The steps involved in the study were as follows: (1) The two to four clinicians characterised pigmented lesions on each of 150 patients, and the lesion closest in characteristics to an atypical nevus was quantitatively described based on size, border characteristics and colour characteristics; (2) The lesion was then removed and independently quantified by a single dermatopathologist without knowledge of the clinical features; (3) We computed the correlation between each of the clinical variables and each of the histologic features for each of the 150 patients. Histologic diagnosis of dysplastic nevus was strongly associated with total number of palpable arm nevi, total number of any arm nevi, total number of nevi on the body of any type, and total number of clinically atypical nevi on the body (correlation coefficients 23.2% to 30.4% with P less than 0.01 in each instance). There were also strong correlations between the counts of numbers of nevi and certain types of architectural histologic features, including fusion (bridging of junctional nests), lymphocyte response and fibroplasia of the papillary dermis. Histologic evaluation of solar elastosis was negatively correlated with total numbers of nevi and total number of clinically atypical nevi (P less than 0.01). Freckling on forearm and on shoulders showed no significant positive or negative correlations with any of the histologic features nor with overall diagnosis of dysplastic nevus. We conclude that observations regarding total numbers of nevi (either normal or clinically atypical nevi) are correlated with nuclear and architectural histologic dysplasia on biopsy of the most atypical pigmented lesions.

Adult↗
PubMed1991

A relation between childhood sun exposure and dysplastic nevus syndrome among patients with nonfamilial melanoma.

We studied 117 patients with nonfamilial melanoma to determine whether melanoma patients with dysplastic nevus syndrome might be distinguished, on the basis of solar exposure, from melanoma patients without dysplastic nevus syndrome. Study participants were interviewed and received a skin examination, which included a total count of nevi, a standardized assessment of clinically atypical nevi, and the excision of each patient's clinically most atypical nevus. Based on the histologic review of the clinically most atypical nevus, each patient was classified as to whether dysplastic nevus syndrome was present or absent. Childhood sunburn with blistering and childhood recreational sun exposure were found to be associated with dysplastic nevus syndrome. The results suggest that childhood sun exposure increases risk of melanoma by initiating the melanoma precursor syndrome.

Adult↗