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R L Barnhill

Publications and source records attributed to R L Barnhill.

At least 73 records · Page 4Linked to original sources

Histologic spectrum of cutaneous involvement in patients with myelogenous leukemia including the neutrophilic dermatoses.

BACKGROUND: Cutaneous manifestations of myeloid leukemia can be specific or nonspecific. The study was designed to determine the prevalence and histologic appearance of cutaneous lesions in patients with myeloid leukemia and various myeloproliferative disorders. METHODS: The histologic changes of cutaneous lesions in 52 patients with myelodysplastic syndrome, polycythemia vera, and myeloid, myelomonocytic, or monocytic leukemia are presented in this study. RESULTS: Two types of cellular infiltrates were identified. In the first group, the most common pattern was a diffuse involvement by the leukemic cells through the entire dermis with preservation of a "grenz zone" in the superficial dermis. Two cases exhibited a Kaposi's sarcoma-like pattern, with prominent slit-like blood-filled spaces lined by myeloblasts against a fibrocellular stroma. The second group of lesions was characterized by dense, neutrophilic dermal infiltrates resembling acute neutrophilic dermatosis (Sweet's syndrome) or pyoderma gangrenosum. In two of these cases, scattered immature blast cells admixed with the mature neutrophilic elements were identified. CONCLUSIONS: Awareness of these different morphologic features and application of special stains are of value in the evaluation of suspicious cutaneous infiltrates in patients with myeloid leukemia and various myeloproliferative disorders.

Adult↗

Neurotropic melanoma with prominent melanization.

Neurotropic melanoma has generally been described in the context of desmoplastic melanoma. The vast majority of melanomas displaying neurotropism contain relatively little or no melanin. Herein, we report an unusual case of neurotropic melanoma with prominent melanin content. The patient developed a tumor notable for pagetoid (superficial spreading) melanoma with partial regression and a deep component characterized by perineurial aggregates of melanophages and intraneural infiltration by melanoma cells. This case serves to alert dermatopathologists to the fact that the spectrum of neurotropic melanoma includes tumors with perineurial aggregates of pigment-containing cells.

Adult↗

Pagetoid Spitz nevus. Intraepidermal Spitz tumor with prominent pagetoid spread.

A distinctive variant of melanocytic growth pattern is described, which appears to be related to Spitz nevus and is characterized by a mainly intraepidermal proliferation of large epithelioid melanocytes with a predominantly pagetoid distribution. This melanocytic lesion appears clinically as a small (< 0.4 cm) pigmented macule in young patients. Histologically, this lesion needs to be distinguished primarily from in situ or microinvasive malignant melanoma with pagetoid spread. Features favoring nevus over melanoma include small size, circumscription, symmetry, even distribution of cells, and lack of marked cytologic atypia.

Adolescent↗

Congenital melanocytic nevi and DNA content. An analysis by flow and image cytometry.

BACKGROUND: Potential risk factors for the development of melanoma in congenital melanocytic nevi (CMN) are not well established. DNA aneuploidy may constitute such a risk factor but has not been sufficiently studied in CMN. METHODS: In the present study, DNA analysis of eight giant CMN, nine medium CMN (1.5-20 cm), and eight small CMN (< 1.5 cm) was assessed by flow cytometry and selected lesions (six nevi) by DNA image cytometry. DNA content was correlated with patient age, nevus size, and degree of cytologic atypia. RESULTS: DNA aneuploidy was detected by flow cytometry in two giant CMN from adult patients and in a small CMN from a child. DNA aneuploidy was not observed in any of the six CMN studied by image cytometry, although an increased S-phase was noted in a markedly atypical giant CMN. No DNA aneuploidy was detected in medium-sized CMN or in the CMN of nine patients 1 year of age or younger. CONCLUSION: In contrast to previous studies, it was observed that abnormal DNA content does tend to correlate with cytologic atypia, particularly in giant CMN with atypia or melanoma, in adults. Conversely, frank DNA aneuploidy in any CMN in children younger than 1 year of age, irrespective of histologic findings, was not detected. Finally, based on these limited studies, greater sensitivity of image over flow cytometry for detection of DNA aneuploidy cannot be verified.

Adolescent↗

Identification of Borrelia burgdorferi in diffuse fasciitis with peripheral eosinophilia: borrelial fasciitis.

OBJECTIVE: To determine if spirochetes could be localized in biopsy specimens of patients with diffuse fasciitis and peripheral eosinophilia. PATIENTS: Tissue from two patients received in consultation and retrieved from hospital files. One patient had a history of tick bite and erythema migrans. SETTING: Tertiary care center and pathology consultation practice. METHODS: Multiple tissue sections were examined for spirochetes using the modified Dieterle or Steiner technique. One case was examined using rabbit polyclonal antibodies against Borrelia burgdorferi. One case had sufficient tissue to study for B burgdorferi DNA by polymerase chain reaction. RESULTS: We identified two cases of diffuse fasciitis associated with peripheral eosinophilia in which spirochetal organisms were identified. The two patients had positive or borderline B burgdorferi serological findings. Deep biopsy was diagnostic of diffuse fasciitis with eosinophilia. In one patient, multiple organisms were seen using a modified Dieterle silver stain, and B burgdorferi-specific DNA was amplified by polymerase chain reaction. In the other patient, no unequivocal organisms were detected on silver stain; however, organisms were detected using rabbit polyclonal antibodies against B burgdorferi. CONCLUSION: Some cases of what has previously been described as "eosinophilic" fasciitis may be an expression of Lyme disease, and we propose the more specific term borrelial fasciitis to describe such lesions.

Antibodies, Bacterial↗

Analysis of melanocytic lesions by DNA image cytometry.

BACKGROUND: There is increasing evidence that melanocytic nevi with architectural and/or cytologic atypia (dysplastic melanocytic nevi [DMN]) are lesions intermediate between banal nevi and malignant melanoma. Other studies have shown conflicting results regarding the DNA content in DMN. METHOD: In the present investigation, the authors measured DNA ploidy by image analysis (CAS-200 system, Cell Analysis Systems, Inc., Elmhurst, IL) using Feulgen staining in 54 melanocytic lesions. The lesions were categorized into 7 groups: compound nevus (CN) = 7; compound nevi with features of DMN (F) = 10; DMN with slight atypia = 8; DMN with moderate atypia = 9; DMN with severe atypia (S) = 8; melanoma in situ = 5; and malignant melanoma (CMM) = 7. The age distribution for these various lesions was also recorded. DNA histograms obtained by image analysis from these groups were examined for DNA aneuploidy by DNA index and classified according to Auer classifications (Auer I-IV). RESULTS: There was a progression of mean age for each group of melanocytic lesions, ranging from 39 years for ordinary nevi to 53 years for invasive melanoma. The Type I histogram, which is distinctly diploid, was seen in 4 of 7 cases of CN, 5 of 10 of nevi with features of dysplastic nevus, and 3 of 8 nevi with slight atypia. The Type I histogram was not observed at all in nevi with moderate atypia, severe atypia, melanoma in situ, and invasive melanoma. The Type IV histogram (aneuploid) was not identified in low grade lesions (CN, F, S), but was observed in two of nine nevi with moderate atypia, six of eight lesions with severe atypia, two of five melanomas in situ, and five of six invasive melanomas. Aneuploidy by DNA index was noted in one nevus with features of DMN, one DMN with slight atypia, one with moderate atypia, four of eight DMN with severe atypia, two of five in situ melanomas, and two of six invasive melanomas. CONCLUSION: The results show that DMN exhibit a spectrum of abnormal DNA content intermediate between banal nevi and CMM and that DNA content generally correlates with the age of patients and degree of atypia in melanocytic nevi.

Adult↗

A multiobserver, population-based analysis of histologic dysplasia in melanocytic nevi.

BACKGROUND: Nevi that are clinically atypical and histologically dysplastic have been associated with increased melanoma risk. There are few reproducibility studies or population-based studies of nevus histology. OBJECTIVE: Our purpose was to quantify concordance in histologic diagnosis of melanocytic lesions among a diverse group of pathologists, to assess intraobserver concordance by comparing readings of the same slide as well as of adjacent recuts from the same block, to correlate histology with nevus appearance and melanoma risk, and to estimate the range of prevalence of histologic dysplasia. METHODS: Histologic slides were prepared from 149 tissue blocks of pigmented lesions from melanoma cases, relatives, and controls. Six dermatopathologists independently evaluated the lesions for histologic dysplasia, without prior agreement on criteria. RESULTS: According to kappa statistics, intraobserver reproducibility was substantial, and interobserver concordance was fair, despite differences in criteria. The estimated prevalences of histologic dysplasia for the six pathologists ranged from 7% to 32%. Histologic dysplasia was correlated with nevus size for most observers, confounding the observed correlation between nevus appearance and histology. CONCLUSION: Although experienced dermatopathologists use different diagnostic criteria for histologic dysplasia, their usage is consistent. Histologic changes ascribed to melanocytic dysplasia are prevalent in the white population for all pathologists. The term nevus with histologic dysplasia should be used in preference to dysplastic nevus.

Adult↗

Very late metastasis (27 years) of cutaneous malignant melanoma arising in a halo giant congenital nevus.

We report a case of primary cutaneous melanoma with the incidental finding of a lung metastasis 27 years following the original diagnosis. The case is exceptional in that it is a late metastasis of a melanoma that arose in association with a halo giant congenital nevus. The original tumor was a large dermal/subcutaneous nodule composed of very well-differentiated cells reminiscent of type B nevomelanocytes. The metastasis displayed similar histology. This case emphasizes the unpredictable behavior of malignant melanoma. In cases with 'unusual' histology such as this one, the usual prognostic parameters are less helpful in predicting survival. Melanoma should be included in the differential diagnosis of an undiagnosed lesion suspicious for metastasis even if the primary was removed in the remote past.

Biopsy↗

Evolution of a naevus spilus.

The evolution of a naevus spilus is documented with serial photographs over a 12-year period. The lesion was remarkable for increasing numbers of macules and papules within the background of the café-au-lait macule. Biopsy of a new papule showed lentiginous melanocytic hyperplasia without atypia. We advise photography and periodic follow-up of large, clinically atypical or changing naevi spili. Indications for considering biopsy of naevi spili, irrespective of size, include atypical clinical features or change in one of the hyperpigmented macules or papules, eventuating in an atypical clinical appearance.

Adult↗

p53 expression in cutaneous malignant melanoma: an immunohistochemical study of 87 cases of primary, recurrent, and metastatic melanoma.

Recent studies on the role of the p53 gene in human melanoma have largely been contradictory. To further assess p53 expression in melanoma, we have studied p53 immunoreactivity in 87 cases of primary, recurrent, and metastatic melanoma. Routine immunostaining was performed on paraffin sections with the monoclonal antibody PAb1801 and a streptavidin-biotin method. All specimens were blindly and independently assessed by two observers for number of melanoma cells with granular nuclear staining. Seven melanomas (8%) exhibited from 1 to 50% positive cells and another eight cases (9%) showed p53 immunoreactivity in < 1% of cells. All of the melanomas found to be positive for p53 with one exception (< 1.50 mm) were either thicker than 1.50 mm, recurrent, or metastatic. We conclude that these findings provide little evidence for significant p53 alteration in the initiation and development of melanoma.

Humans↗

Melanoma risk in individuals with clinically atypical nevi.

BACKGROUND AND DESIGN: A lack of consensus as to the clinical and histologic characteristics of dysplastic nevi has resulted in the recommendation to abandon the term dysplastic nevus for the more descriptive atypical nevus or atypical mole. The significance of the presence of one or more such lesions, histologic features notwithstanding, has not been carefully examined. The risk of melanoma was assessed in individuals with atypical nevi monitored regularly in our Pigmented Lesion Clinic. Any patient enrolled in this subspecialty clinic between 1980 and 1985 without the diagnosis of melanoma who had at least one sufficiently atypical-appearing nevus and who was followed up for a minimum of 5 years was entered in the study. RESULTS: A total of 155 such individuals were identified. The mean (+/- SEM) age of the patients at first evaluation was 26 +/- 1 years. The group was followed for 7 +/- 1 years. The male-female ratio was 1:1. A family history of melanoma was present in 71 subjects (46%). Of the 155 patients, two developed melanoma. The thickness of the tumors in both patients was less than or equal to 0.8 mm. Twenty-five patients (16%), including the two with melanoma, had at least one nevus removed that showed "severe nuclear atypia." CONCLUSIONS: The risk of melanoma in individuals with atypical nevi is significantly greater than expected. The elevated risk was demonstrated even though careful, regular evaluations and removal of more atypical lesions were performed. This study provides evidence that, compared with no surveillance, the meticulous monitoring of patients with clinically atypical nevi is more likely to result in the detection of melanoma at thin stages, with an attendant improved prognosis.

Adolescent↗

Expression of monocyte chemoattractant protein-1 in delayed type hypersensitivity reactions in the skin.

BACKGROUND: Monocyte chemoattractant Protein-1 (MCP-1) is a potent chemotactic factor for monocytes. Because many inflammatory dermatoses are characterized by mononuclear cell infiltrates, it is reasonable to postulate that MCP-1 might be involved in their pathogenesis. To date, no in vivo studies have been published concerning the expression of MCP-1 in this context. The aim of this study was to elucidate the expression of MCP-1 in human inflammatory skin diseases which are thought to involve delayed type hypersensitivity reactions. EXPERIMENTAL DESIGN: Expression of MCP-1 was examined in normal skin and three classes of inflammatory skin reactions by immunohistochemistry experiments utilizing a monospecific MCP-1 antiserum. The distribution of monocytes/macrophages and T lymphocytes was determined by immunohistochemistry using antibodies to specific cell surface markers. RESULTS: Immunostaining with MCP-1 antiserum demonstrated strong MCP-1 expression in lichenoid dermatitis, dermal hypersensitivity reactions, and spongiotic dermatitis. In contrast, normal skin showed minimal MCP-1 expression in the dermis. The cell types displaying MCP-1 expression were endothelial cells of dermal microvessels that were surrounded by lymphocytic infiltrates and monocytes/macrophages at the periphery of the perivascular infiltrates. Occasionally, MCP-1-positive mononuclear cells were present both in the infiltrates and in a diffuse pattern in the surrounding dermis. Keratinocytes were found to produce MCP-1 constitutively in normal skin and in inflamed conditions. The pattern of MCP-1 expression was similar to the pattern observed for monocyte/macrophage distribution, whereas the pattern of MCP-1 expression was different from the pattern of T lymphocyte distribution. CONCLUSIONS: We observed an enhanced expression of MCP-1 in inflammatory skin conditions. The expression of MCP-1 provides a mechanistic explanation for the increased recruitment of monocytes/macrophages in cell-mediated immune response such as delayed type hypersensitivity reactions in the skin.

Chemokine CCL2↗

Familial cutaneous melanoma and two-mutational-event modeling.

BACKGROUND: According to the Knudson two-mutational-event theory, two mutations at a genetic locus may be required for the development of some cancers. Persons who have inherited a defect in one chromosome and therefore require only one more mutation for cancer development are at a higher risk of manifesting cancer at a younger age than persons without an inherited mutation, who need two acquired "hits." This difference allows one to distinguish familial and sporadic types of the same malignancy by evaluating age of disease onset. METHODS: To study the role of inheritance in the etiology of familial cutaneous melanoma, characteristics of patients with familial versus nonfamilial melanoma were analyzed according to the Knudson two-mutational-event model. RESULTS: The familial versus nonfamilial graphs, based on age of diagnosis, did not support this model. However, there was a statistically significant earlier age of diagnosis for patients with familial melanoma. Melanoma thickness was less (i.e., earlier cancer at possibly younger age) for patients with a positive versus a negative family history. Conversely, linear regression, after adjusting for tumor thickness, showed that patients with hereditary melanoma still manifested earlier ages of diagnosis of melanoma compared with sporadic patients. CONCLUSIONS: Genetic patterns other than the two-step model, additional family-related factors, patient-physician sensitization due to a family history, or a combination of these factors might explain this age difference. More complex multistep modeling of the data may be helpful in better characterizing the genetic patterns of cutaneous melanoma.

Age Factors↗

Lack of allelic deletion and point mutation as mechanisms of p53 activation in human malignant melanoma.

To investigate the role of the p53 tumor-suppressor gene in the development of human melanoma, loss of heterozygosity (LOH) of p53 was studied in 46 cases of melanoma by a polymerase-chain-reaction/restriction-fragment-length polymorphism (PCR/RFLP) analysis, and p53 mutations were assessed in 51 cases of melanoma by a polymerase-chain-reaction/single-strand-conformation polymorphism (PCR/SSCP) analysis. Frozen tumors and paraffin samples were used in the study. We were not able to detect any allelic loss in 12BstUI informative cases or any single mutation in exons 5 to 8 of the p53 gene. Our results, together with other findings at the DNA level, suggest that the p53 gene appears not to be commonly involved in the development of melanoma, at least by its most frequent mechanisms of deletion of one allele and/or mutation in the other.

Base Sequence↗

Prediction of histologic melanocytic dysplasia from clinical observation.

BACKGROUND: The dysplastic melanocytic nevus (DMN) is a putative precursor for malignant melanoma in persons with a family history of melanoma and multiple large atypical moles. Furthermore, the concept that DMN confers increased risk for melanoma has been extended to those without a family history of melanoma. Some investigators have characterized DMN in terms of size, surface topography, and irregularity of border and color and have provided definitive statements as to major and minor clinical "criteria" for DMN. OBJECTIVE: In this study we conducted a quantitative test of previously described clinical characteristics in patients diagnosed with melanoma but without a family history of melanoma in a first-degree relative (N = 153). METHODS: Two of us examined each patient independently, counting the total number of nevi, deciding on the most clinically atypical nevus, and recording quantitatively the size, surface, border, and color characteristics. The most atypical nevus was removed from each patient and diagnosed histologically without knowledge of the clinical examiner's description. RESULTS: Of the 153 nevi so examined, 91 (59.5%) were judged to be clinically atypical and 23 nevi (15%) were classified as histologically dysplastic. We then analyzed the ability of each clinical feature to predict histologic melanocytic dysplasia. A multivariate analysis was conducted with the blindly scored clinical features as independent variables. Independent variables included total number of nevi and freckles as well as the features of the particular nevus biopsied (including longest diameter, macular component, irregular border, ill-defined border, haphazard coloration). Of the many independent clinical variables, only total number of nevi and macular component were useful in the final multivariate prediction. Of 21 nevi with a macular component removed from persons with more than 24 total body nevi, 7 were histologically dysplastic, representing a positive predictive value of 33.3% (95% exact confidence limits 14.6% to 57.0%). Of the 38 nevi without a macular component to their most atypical nevus removed from patients with 12 or fewer total body nevi, 37 failed to meet histologic criteria for DMN, representing a negative predictive value of 97% (95% exact confidence limits 86.2% to 99.9%). CONCLUSION: We conclude that in nonfamilial melanoma, clinical criteria suggesting DMN when present will often fail to display histologic melanocytic dysplasia. In contrast, absence of a macular component in melanocytic nevi in a person with fewer than 13 total body nevi will accurately predict the absence of melanocytic dysplasia on histologic examination.

Adult↗