摘要:

BRAFmutations have recently been detected with a high frequency (66%) in cutaneous melanoma. All those mutations are activating, with a single substitution (T1796A) at codon 599 (V599E) accounting for over 90%. To investigate the stage in which those mutations occur in the currently proposed sequential malignant transformation of melanocytes, 22 benign melanocytic nevi, 23 melanocytic atypical nevi, and 25 primary cutaneous melanoma from 63 different patients were examined forBRAFmutations using DNA extracted from microdissected formalin-fixed and paraffin-embedded tissues, and a two-round PCR-RFLP–based strategy. A subset of samples was sequenced for mutation confirmation. Sixteen benign (73%) and eleven atypical (52%) melanocytic nevi, and thirteen melanoma (56%) demonstratedBRAFmutations at codon 599, and no statistically significant differences were detected among all three types of lesions. No mutations were demonstrated in microdissected epidermal keratinocytes adjacent to melanocytic lesions havingBRAFmutations. No correlation was detected betweenBRAFmutational status and age, sun exposure, and Clark's level in malignant melanoma. However, comparing only atypical nevi and melanoma lesions the frequency ofBRAFmutation is significantly greater in male (78%) than female (35%) patients (P= 0.0194). The previously described T1796A point mutation was detected in 17 of 18 mutated samples, and a novel mutation consisting of a substitution of valine for lysine (GT1795-96AA) was detected in one melanoma case. Our findings of a high frequency ofBRAFmutations at codon 599 in benign melanocytic lesions of the skin indicate that this mutation is not sufficient by itself for malignant transformation.

ISSN:0193-1091    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Whether partial regression of a primary melanoma has an adverse impact on prognosis is controversial. As an indirect mechanism of addressing this question we drew a correlation between the histopathological characteristics of 107 cutaneous melanomas and the presence of sub-clinical metastasis in corresponding sentinel lymph nodes. Partial regression of the primary tumor, defined as focal replacement of the lesion by a scar, unrelated to a previous biopsy, was observed in 20 (19%) cases in the group as a whole. Excluding cases in which an accurate Breslow thickness of the primary melanoma could not be established and/or the presence of a capsular nevus was detected in the sentinel node, a total of 97 remained. Seventeen cases (Breslow thickness 0.63–9.7; mean 2.4 mm) showed partial regression and 80 (Breslow thickness 0.25–7.00; mean 1.8 mm) were devoid of regression. Of the 17 cases with regression 5 (29%) had nodal metastasis (by histopathology and/or molecular analysis) and of the 80 cases without regression 23 (29%) had nodal metastasis (by one or both evaluations). Our data reveals no association between partial regression of the primary melanoma and sentinel node involvement by the disease. The Breslow thickness proved to be the only significant independent variable related to nodal metastasis. Of interest, ulceration of the primary lesion was significantly associated with nodal disease on univariate, but not on multivariate, analysis. While acknowledging that the cohort size may lack the statistical power to demonstrate subtle associations, our data supports the known relevance of tumor thickness and ulceration to regional lymph node metastasis and thereby, to outcome of melanoma in its early stages, but fails to support a similar role for partial regression.

ISSN:0193-1091    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Tissue expression of CC and CXC chemokines and chemokine receptors was investigated in 6 cases of classic non-AIDS Kaposi sarcoma (KS) using immunohistochemistry and RNase protection assay (RPA). Immunostaining of frozen sections of KS skin biopsies revealed that KS spindle cells express several chemokine receptors. In KS nodules, almost all KS spindle cells were intensely stained for CXCR4 and CCR5. Other chemokine receptors as CCR1, CXCR3, and CCR2 were also detected in the large majority of KS spindle cells. A minority of KS spindle cells also expressed the fractalkine receptor (FK-R) CX3CR1.The immunohistochemical findings were confirmed at RNA level. In fact, the RNase protection assay (RPA) revealed in 6 of 6 cases the presence of consistent amounts of mRNAs for CXCR4 and CCR1 and in 5 of 6 cases also for CCR5 and CXCR3.Expression of chemokine receptors by KS cells was associated with chemokine production within the lesions. In the same cases, RPA demonstrated the presence of mRNAs for MCP-1, RANTES, IP-10, MIP-1&agr;, and MIP-1&bgr;. Chemokine-producing cells, as detected by immunohistochemistry, were mainly spindle-shaped cells resembling tissue macrophages outside KS lesions and some scattered cells (<5%) present within KS nodules.The demonstration of chemokine receptors in KS cells raises the possibility that recruitment of KS cells in response to locally produced chemotactic stimuli may be one of the events involved in the pathogenesis of Kaposi sarcoma.

ISSN:0193-1091    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

A novel variant of endemic pemphigus foliaceus (EPF) was described among individuals in an area surrounding El Bagre, Colombia, South America. The population in this rural mining community is exposed to high environmental levels of mercury, used for gold extraction, as well as other minerals, metalloids, and trace elements (e.g., quartz, rutile, granite, magnetite, and almenite) and ultraviolet radiation. Fifty control subjects and fifty EPF patients in the endemic area were examined for the presence of mercury in skin biopsies and hair, using autometallographic and mass spectroscopic analyses, respectively. Simultaneously, serum levels of IgE were measured, and cutaneous tests for hypersensitivity reactions were performed. Using autometallography, mercuric sulfides/selenides were detected in 14 of 51 skin biopsies distributed similarly in the control and patient groups. However, significantly higher serum IgE levels and mercury concentrations in hair, urine, and nails were found in patients compared with controls. Microscopic analysis revealed mercuric sulfides/selenides concentrated within and around the sweat gland epithelium, as well as in dendritic cells. Five skin biopsies from EPF patients and five from controls that tested positive for the presence of mercuric sulfides/selenides by autometallography were randomly selected for electron microscopic analysis. This analysis revealed a mixed electron-dense and electron-light material closely associated with desmosomes in patients. However, there were intracellular vesicles containing an amalgam of electron-dense and electron-light materials only in the EPF patients. Thus, EPF-affected individuals are exposed to high levels of environmental mercuric sulfides/selenides and other elements. This is the first study reporting mercuric sulfides/selenides in skin biopsies from people living in a focus of EPF, and these compounds may play a role in the pathogenesis of autoimmunity.

ISSN:0193-1091    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Cell surface proteoglycans play a prominent role in tissue remodeling and homeostasis. Syndecans, their most prominent members, act by binding to growth factors and interstitial matrix molecules. They, thereby, modulate the effect of the primary ligand-receptor interaction at the cell membrane by increasing the affinity of cell-ligand interactions. Additionally, they influence the strength of cell–cell and cell–matrix interactions. Syndecan-1 is the prototypical member of this family of proteins. Under physiological conditions, its expression is restricted to the epidermis, the outer root sheath of the anagen hair follicle, and the sweat gland epithelium. The dermal compartment—with the exception of the follicular papilla of the anagen hair follicle—physiologically does not express syndecan-1. Dermatofibromas are mesenchymal lesions, which often exhibit hyperplastic changes in the overlying epidermis. In analogy to the hair follicle, they, thereby, can be used as a model for studying epithelial-mesenchymal interactions. In the current study, we examined dermatofibromas immunohistochemically for syndecan-1 expression. We report immunoreactivity for syndecan-1 in dermatofibromas, which correlates mainly with the deposition of intercellular matrix material. Syndecan-1 is also noted in the stroma surrounding areas of basaloid hyperplasia overlying dermatofibromas and may be important in the pathogenesis of this inductive phenomenon. In analogy to the follicular papilla of the anagen hair follicle, the staining pattern for syndecan-1 in dermatofibromas indicates that this cell surface protein is produced by stromal cells and most likely serves an essential function in the growth of these common mesenchymal cutaneous lesions.

ISSN:0193-1091    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The thesis is set forth in this treatise that there is no place in the routine practice of medicine for the procedure for melanoma known conventionally and universally as sentinel node biopsy. Our assertion is based on assessment of the extensive body of literature devoted to the subject of treatment of melanoma before any metastasis has manifested itself clinically and of that dedicated to therapy for overt metastatic melanoma by a variety of modalities, chief among those addressed here being elective lymph node dissection and sentinel lymph node biopsy. In this era of sentinel lymph node biopsy, elective lymph node dissection has been modified to include only patients with metastasis of melanoma to lymph nodes, a procedure now termed “selective complete lymph node dissection.” Among adjuvant medical therapies, the most popular today is interferon alpha-2B. Critical, incisive scrutiny of the literature leads to the conclusion, incontrovertibly, that elective lymph node dissection has no benefit for a patient and that all modifications of it also are devoid of value. The reason, logically, for the lack of utility of elective lymph node dissection becomes apparent by virtue of the route taken by cells of melanoma as they metastasize; those cells proceed in the same fashion as does lymph, bacteria, foreign material (including vital dyes and radioactive tracers), and other kinds of cells, to wit, by passing rapidly through nodes, including the sentinel one, and even bypassing entirely the nodes. In reality, cells of metastatic melanoma are not held up in nodes for any significant period of time, contrary to what is asserted repeatedly, but without any basis in fact, by many students of the subject. Moreover, not a single adjuvant medical therapy available currently is effective against metastatic melanoma and, therefore, none of them should be invoked to justify performance of sentinel node biopsy. Even if the sentinel node is found to house cells of melanoma, which, as a rule, conveys a grim message regarding the future, the finding in an individual patient is meaningless; a particular patient may live in harmony with metastases of melanoma for more than 30 years and even die of an unrelated malady. In short, no surgeon, pathologist, or oncologist is a seer, diviner, or prophet when it comes to predicting accurately the outcome for a patient with metastasis of melanoma; the end could come in weeks, months, or decades. If, however, a sentinel node is found to contain nary a cell of metastatic melanoma, it, too, means nothing for an individual patient because the existence of metastases widely is not excluded by that finding. In short, sentinel node biopsy cannot be considered the standard of care in the daily practice of medicine; it is woefully substandard because it is without benefit. There is no justification, whatsoever, for the procedure, scientifically or practically, and for that reason it should be abandoned, without delay, now.

ISSN:0193-1091    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Signet-ring cell malignant melanoma is a rare histopathologic variant of malignant melanoma with only a few described cases. We report the clinical, histopathological, and immunohistochemical features of two cases of primary cutaneous signet-ring cell malignant melanoma. Neoplastic melanocytes showed abundant clear cytoplasm compressing the nuclei to the periphery, sometimes resulting in a signet-ring appearance. Immunohistochemically, neoplastic melanocytes in both cases expressed immunoreactivity for the usual melanocytic markers S-100 protein and Melan-A, although only the second case resulted HMB-45 positive. We review the literature about this rare cytologic variant of malignant melanoma and discuss the differential diagnosis with other cutaneous neoplasms that may show a signet-ring cell appearance of their neoplastic cells.

ISSN:0193-1091    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

A previously healthy 14-year-old Korean male presented with striking hemorrhagic acral livedo associated with anti-ribonucleoprotein antibodies. His skin biopsy revealed a striking lymphocytic vascular reaction with mild superficial perivascular lymphocytic infiltrates, perivascular extravasation of red blood cells, and leukocytoclastic debris. Lymphocytic vasculitis (LV) is defined in different ways by different authors. The above biopsy findings do not fulfill the criteria for LV of all authors. Chronic lymphocyte-mediated endothelial cell injury may play an important role in the pathogenesis of collagen vascular disease. Cell-mediated cytotoxicity against endothelial cells or other vessel wall components is thought to be the possible pathologic mechanism of LV. We present a patient with early undifferentiated connective tissue disease (EUCTD) with hemorrhagic acral livedo, who finally developed systemic lupus erythematosus. Even though the histopathologic findings do not meet the most rigorous definition of LV, LV may a presenting sign of EUCTD. The purpose of this report is to suggest reconsideration of the diagnostic criteria of lymphocytic vasculitis.

ISSN:0193-1091    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

An 83-year-old patient presented herself with a ten-year history of keratotic papules on her trunk. A biopsy of this process revealed granular parakeratosis confined to the infundibulum of a follicle. Exclusive follicular involvement in granular parakeratosis has not been previously described.

ISSN:0193-1091    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0193-1091    

出版商:OVID    

年代:2003

数据来源: OVID