bluuebunny/crossref_metadata_2025 huggingface dataset:
Dermal dendritic cells in anogenital warty lesions unresponsive to an immune‐response modifier
Authors: Arrese Jorge E. , Paquet Philippe , Claessens Nadine , Piérard‐Franchimont Claudine , Piérard Gérald E.
Published: March 2003

Background: Human papilloma viruses (HPV) are responsible for a variety of proliferative epithelial lesions including anogenital condylomas. These lesions may regress during treatment with an immune‐response modifier such as imiquimod. The release of specific cytokines from the monocyte‐macrophage lineage induces a cascade of events abating the HPV replication.

Method: A total of 14 persistent warty anogenital lesions were excised 4 to 7 weeks after completing a 4‐month imiquimod treatment. Another series of 25 untreated condylomas and 8 bowenoid papulosis served as controls. All examined lesions had been excised in otherwise healthy individuals with a normal immune status. Lesions were examined for the presence of Langerhans cells and subpopulations of the monocyte/macrophage/dendrocyte lineage using immunohistochemical detection of L1‐protein, CD68, lysozyme and Factor‐XIIIa. CD45R0‐positive T lymphocytes were also identified. HPV capsid antigens and genotypes were searched for using immunohistochemistry and in situ hybridization, respectively.

Results: The persistent although treated anogenital lesions were identified as 10 viral condylomas, 3 bowenoid papulosis and 1 basal cell carcinoma. The inflammatory cell densities and distributions were similar in the untreated and imiquimod‐resistant condylomas with the exception of Factor XIIIa‐positive dendrocytes. These dermal dendritic cells were slim and rare in all imiquimod‐resistant lesions. In contrast, about two‐thirds of the untreated condylomas were enriched in these cells.

Conclusion: As dermal dendritic cells play a role in the immune surveillance, their low densities in some lesions might be a key feature responsible for low cytokine local production and failure of imiquimod treatment. The combined apparent lack of Langerhans cell activation might suggest that both intraepidermal and intradermal compartments of antigen‐presenting cells are affected in imiquimod‐resistant lesions.
Expression of Basigin in human fetal, infantile and adult skin and in basal cell carcinoma
Authors: Chen Xiang , Kanekura Takuro , Kanzaki Tamotsu
Published: March 2003

Background: Basigin is a glycosylated transmembrane protein belonging to the immunoglobulin superfamily and is thought to be associated with cell development and differentiation. We investigated the relation between Basigin expression and epidermal development in this study.

Methods: Basigin expression was immunohistochemically investigated during organogenesis of human skin and in human basal cell carcinoma (BCC).

Results: Human fetal skin showed negative staining at 10 weeks of gestation. At 20 weeks, the cytoplasm and membranes of adnexal germ and hair follicular cells were strongly positive, while epidermal basal cells showed weakly positive staining. After birth, basal cells, suprabasal cells, anagen hair follicular cells and eccrine glandular cells showed positive staining. Membranes of basal cells expressed more Basigin compared to other cell components. Basigin was not detectable in granular cells and telogen hair follicular cells. Sixteen of 30 BCCs were entirely negative for Basigin. However, cells at budding areas of tumor masses were positive in 14 of the 30 BCCs.

Conclusions: These findings suggest that 1) Basigin is associated with epidermal proliferation and differentiation, 2) most parts of BCCs might be derived from early fetal epidermal basal cells, and 3) that a part, only the budding area of BCCs, has the characteristics of epithelial germ cells.
The clonality of tumor‐infiltrating lymphocytes in African Kaposi’s sarcoma
Authors: Nihal Minakshi , Mikkola Debra , Qian Zheng , Remick Scot C. , Wood Gary S.
Published: March 2003

Background: African Kaposi’s sarcoma (KS) lesions contain human herpesvirus‐8 (HHV‐8) and Epstein‐Barr virus (EBV), both of which are associated with various types of non‐Hodgkin’s lymphomas and are known to produce several factors suspected of lymphomagenic potential. The aim of this study was to evaluate tumor‐infiltrating lymphocytes for the evidence of clonal expansion in African KS.

Methods: We used polymerase chain reaction (PCR)‐based assays to determine the clonality of tumor‐infiltrating lymphocytes in African KS lesions and compared the results to similar studies of patient‐matched uninvolved skin and peripheral blood.

Results: T cells were polyclonal in all samples tested. Peripheral blood B cells were also polyclonal; however, a minority of lesional and uninvolved skin samples exhibited evidence of restricted B‐cell clonality. Correlation with immunohistological analysis revealed that this clonal B‐cell restriction was secondary to the sparse nature of lesional B cells rather than their clonal overgrowth.

Conclusions: We conclude that, despite the putative lymphomagenic potential of HHV‐8 and EBV and their co‐existence in African KS lesions, tumor‐infiltrating lymphocytes in these cases do not show evidence of clonal expansion that might be an early manifestation of lymphoma. Nevertheless, these studies are a case in point that sparse lymphoid subpopulations in lesional and uninvolved extranodal tissues can give rise to restricted clonal patterns that must be interpreted carefully to avoid the misdiagnosis of occult lymphoma.
S100A6 expression in fibrohistiocytic lesions
Authors: Fullen D. R. , Reed J. A. , Finnerty B. , McNutt N. S.
Published: March 2003

Background: S100A6, an S100 calcium‐binding protein, has been found in a variety of cutaneous and extracutaneous lesions including: melanocytic nevi, melanoma, some salivary gland and epithelial tumors, and malignant fibrous histiocytoma (MFH). Dermal dendrocytes (DD) in the papillary dermis of skin also express S100A6 protein. We evaluated a variety of cutaneous fibrohistiocytic lesions to determine if the immunophenotype of S100A6 positivity can be expanded to include some or all of these lesions.

Methods: Formalin‐fixed, paraffin‐embedded tissues from fibrous papules (FP, 20), dermatofibromas (DF, 20), dermatofibrosarcoma protuberans (DFSP, 5), atypical fibroxanthomas (AFX, 5), oral fibromas (3), digital fibroma (1), and dermatomyofibroma (1) were evaluated with antibodies to S100A6, S100B, factor XIIIa, and MAC387 using a one‐hour capillary action‐based immunohistochemical procedure.

Results: DD in 20/20 FP, 19/20 DF, and 4/4 fibromas stained positively with anti‐S100A6 in a pattern similar to anti‐factor XIIIa. No DFSP cases stained with anti‐S100A6. Anti‐S100A6 showed superior staining to anti‐factor XIIIa in 4/5 AFX cases.

Conclusions: The immunophenotypes of some fibrohistiocytic lesions can be expanded to include S100A6 protein. With the exception of AFX, the use of anti‐S100A6 does not appear to offer added benefit over anti‐factor XIIIa in the differential diagnosis of fibrohistiocytic lesions.
Cutaneous lymphocyte‐associated antigen (CLA) expression in a lymphoblastoid mantle cell lymphoma presenting with skin lesions. Comparison with other clinicopathologic presentations of mantle cell lymphomaNote
Authors: Martí R. M. , Campo E. , Bosch F. , Palou J. , Estrach T.
Published: March 2003

Background: Cutaneous lymphocyte‐associated antigen (CLA) is a lymphocyte homing receptor selectively expressed by T cells of the cutaneous immune system and their malignant counterpart, that is to say, cutaneous T‐cell lymphomas. However it is absent in the vast mayority of other T‐cell malignancies and B‐cell lineage lymphomas irrespective on primary tumor site.

Methods: Expression of CLA was investigated on six cases of mantle cell lymphoma (MCL) which differed in their histopathological subtype (typical or blastic) and their tendency to infiltrate skin and/or central nervous system (CNS).

Results: CLA immunostaining on neoplastic cells was only observed in a 61‐year‐old female suffering from a lymphoblastoid MCL which clinically presented with specific skin lesions and further developped CNS disease. In this patient, coexpression of CLA with MCL markers (CD20 and CD5) was confirmed by conventional immunohistochemistry and double immunofluorescence studies.

Conclusions: To our knowledge, CLA immunoreactivity on B‐cell lymphomas has not beeen previously reported. The expression of this skin‐related adhesion molecule on malignant MCL cells could explain the clinical behavior of our case which presented and relapsed with cutaneous lesions. However, CLA seems not to be a MCL marker nor a CNS‐related adhesion molecule. The authors review the clinical and histopathological characteristics of MCL‐specific skin lesions and their diagnostic clues based on cell morphology, immunohistochemistry and molecular investigations.
Immunohistochemical study of inducible nitric oxide synthase in skin cancers
Authors: Kagoura Masayori , Matsui Chihiro , Toyoda Masahiko , Morohashi Masaaki
Published: March 2003

Background: Nitric oxide (NO) is synthesized from the amino acid L‐arginine by NO synthase (NOS). Experimental evidence suggests that increased express of inducible NOS (iNOS), which is an NOS isoform and calcium independent, is related to various pathological processes, such as inflammation and cancer.

Methods: In this study, we used immunohistochemistry to investigate iNOS expression in a series of basal cell carcinomas (BCC), Bowen’s disease, squamous cell carcinomas (SCC), extramammary Paget’s disease (EPD) and metastatic tumors of the skin.

Results: Only 1 of 16 BCC cases was positive for iNOS and the intensity of staining was weak. In most of the 10 cases of Bowen’s disease, iNOS was weakly expressed and there was a wide range in the percentage of positive tumor cells. Twelve of the 16 cases of SCC were positive for iNOS and the extent of positivity was greater than in Bowen’s disease. Two of the 7 cases of EPD were positive for iNOS, and 12 of the 15 cases of metastatic cancer were positive. Well‐differentiated adenocarcinomas were diffusely positive, whereas poorly‐differentiated ones showed strong and heterogeneous staining.

Conclusions: These results indicated that the expression of iNOS may reflect the proliferation of tumor cells and that a heterogeneous distribution of iNOS may correlate with a wide variety of biological behavior of tumor cells.
The cutaneous pathology of lupus erythematosus: a review
Authors: Crowson A. Neil , Magro Cynthia
Published: March 2003

The presentation of lupus erythematosus (LE) ranges from a skin rash unaccompanied by extracutaneous stigmata to a rapidly progressive lethal multiorgan disease. The diagnosis and subclassification is traditionally based on the correlation of serological and clinical findings. The latter include a photoinduced skin rash, arthralgia, arthritis, fever, Raynaud’s phenomenon, anemia, leukopenia, serositis, nephritis and central nervous sysdtem disease. The conventional classification scheme includes systemic, subacute cutaneous and discoid LE. Recent advances in our understanding of the cutaneous histopathology which correlates with the traditional forms of LE, along with certain novel LE subtypes, are the focus of this review. In addition to the main subtypes of LE, we will discuss associated vasculopathic lesions and the contribution of immunofluorescence microscopy to the diagnosis of LE and related connective tissue disease syndromes. Consideration will be given to unusual variants of LE such as anti‐Ro/SSA‐positive systemic lupus erythematosus (SLE), bullous SLE, lymphomatoid LE, lupus erythematosus profundus, drug induced LE, linear cutaneous LE, chiblains LE and parvovirus B19‐associated LE.
Heteroduplex analysis of T‐cell receptor γ gene rearrangement as an adjuvant diagnostic tool in skin biopsies for erythroderma
Authors: Cherny Sarah , Mraz Serena , Su Lyndon , Harvell Jeff , Kohler Sabine
Published: March 2003

Background: Erythroderma, defined as red skin covering most of the body surface often accompanied or followed by exfoliation, is the clinical manifestation of at least six different underlying etiologies with allergic or irritant contact dermatitis, atopic/asteotic dermatitis, pityriasis rubra pilaris (PRP), psoriasis, and seborrheic dermatitis accounting for the majority of cases. Approximately 10% of cases are due to adverse drug reactions with roughly another 10% due to cutaneous T‐cell lymphoma (CTCL), predominantly mycosis fungoides, or leukemia. It is clear from multiple studies that the clinical diagnosis of the underlying entity is often difficult, as these diseases can present in a very similar fashion. A skin biopsy is usually employed in this setting as a diagnostic tool. However, the histopathologic diagnosis of the underlying cause is complicated by the subtlety of the distinguishing histologic features. In this situation, an ancillary technique demonstrating the presence of a monoclonal T‐cell proliferation could help to rule in or out CTCL in cases that clinically and histopathologically do not allow a definitive diagnosis.

Methods: We retrospectively studied 25 biopsies from sixteen patients who presented to the Stanford Dermatology Clinic with erythroderma. We examined the specimens morphologically and analyzed the gamma chain of the T‐cell receptor (TCR‐ γ) by polymerase chain reaction (PCR) followed by heteroduplex analysis for clonality. We then correlated the results of our PCR and heteroduplex analyses with the patients’ clinical outcomes.

Results: Four biopsies, from three patients, contained clonal TCR‐γ rearrangements; the four biopsies, all of which were equivocal histologically, correlated to diagnoses of mycosis fungoides (MF) or Sézary syndrome (SS). Twenty‐one biopsies contained polyclonal T‐cell populations. Eighteen of these biopsies represent patients with inflammatory dermatoses. Three of these biopsies, all of which were taken from a single patient, correlate to a diagnosis of MF.

Conclusion: TCR‐γ PCR heteroduplex analysis seems to represent an important adjuvant diagnostic tool that, used in conjunction with histopathology and clinical history, could help to clarify the underlying etiology of erythroderma.
Polymerase chain reaction (PCR) for human herpesvirus 8 and heteroduplex PCR for clonality assessment in angiolymphoid hyperplasia with eosinophilia and Kimura’s disease
Authors: Jang Kyoung‐Ae , Ahn Se‐Jin , Choi Jee‐Ho , Sung Kyung‐Jeh , Moon Kee‐Chan , Koh Jai‐Kyoung , Shim Yong‐Hee
Published: March 2003

Background: Recently, human herpesvirus 8 (HHV‐8) has been isolated from almost all cases of Kaposi’s sarcoma. It has not been found in most cutaneous hemangioproliferative disorders other than Kaposi’s sarcoma. Benign vascular lesions including Kimura’s disease were not found to contain the HHV‐8 DNA sequence. However, there has been contradictory data concerning the presence of HHV‐8 in angiolymphoid hyperplasia with eosinophilia (ALHE). Clonality studies in ALHE and Kimura’s disease were rare.

Methods: We performed polymerase chain reaction (PCR)‐based analysis to determine whether HHV‐8 is present and heteroduplex analysis of rearranged T‐cell receptor (TCR) gene for clonality assessment in paraffin‐embedded skin biopsy samples of 7 ALHE and 2 Kimura’s disease, taken from immunocompetent patients.

Results: HHV‐8 could not be identified in all the cases of ALHE and Kimura’s disease. Although 2 cases (2/7) of ALHE and 2 cases

(2/2) of Kimura’s disease showed positive result for PCR analysis of TCR, all the cases were negative for heteroduplex‐PCR.

Conclusions: We suggest that HHV‐8 may not involve in a pathogenetic role in ALHE and Kimura’s disease and the failure to demonstrate clonality may be consistent with the reactive nature of these diseases and lack of malignant transformation. In addition, heteroduplex‐PCR can be applied to confirm doubtful cases of lymphoma in that heteroduplex‐PCR is more specific than PCR as seen in our study.
Subcutaneous nodules in Whipple’s disease
Authors: Tarroch X. , Vives P. , Salas A. , Moré J.
Published: March 2003

Background: Cutaneous findings other than hyperpigmentation are rare in Whipple’s disease.

Case report: We present the case of a 59‐year‐old man previously diagnosed with Whipple’s disease by duodenal biopsy, who developed red‐brown, painful, subcutaneous nodules on the buttocks, thighs, arms and legs. Biopsy of these nodules showed a septal panniculitis and foamy macrophages containing PAS‐positive, diastase resistant intracytoplasmic material, characteristic of Whipple’s disease and similar to that observed in the duodenal biopsy. Ultrastructurally, this material in the histiocytes corresponded to degenerated bacilli.

Conclusions: This is the fourth documented case of subcutaneous involvement by Whipple’s disease. One should consider the possibility of Whipple’s disease in any patient who presents with symptoms compatible with that condition who demonstrates septal panniculitis with a large amount of foamy histiocytes.
Malignant peripheral nerve sheath tumor with perineurial differentiation: ‘malignant perineurioma’
Authors: Rosenberg Arlene Sylvia , Langee Christena Lynn , Stevens G. Lex , Morgan Michael B.
Published: March 2003

Background:  Although benign tumors derived from the nerve sheath perineurial cell have been described from a variety of anatomic sites and are known to be a component of a number of benign neoplasms, malignant nerve sheath tumors of perineurial origin are exceedingly uncommon.

Methods: We report an unusual case of a 70‐year‐old male who presented with a rapidly growing mass of the left arm, subsequently shown to be a malignant nerve sheath tumor with perineurial differentiation. A brief microscopic differential diagnosis and review of the literature are discussed.

Results:  Histologic sections show a partially circumscribed tumor of atypical spindle cells arranged in sweeping fascicles embedded in a myxoid matrix with focal whorling. Nuclear pleomorphism was evident among scattered typical and atypical mitotic figures (mean mitotic index of 7/10 high‐power fields). The immunophenotypic profile consisted of only vimentin and epithelial membrane antigen (EMA) positivity, while antibodies to S‐100, CD34, smooth muscle actin, and pankeratins were negative. Ultrastructural features included spindle cells with long cytoplasmic processes invested by interrupted basal lamina and pinocytotic vesicles, consistent with perineurial differentiation.

Conclusions:  While the histogenic source of the benign perineurioma, the perineurial cell has only rarely been described in conjunction with malignant tumors. All cases to date have shown EMA‐positive and S‐100‐negative atypical spindled cells arranged in fascicles embedded in a myxoid matrix. In addition to immunohistochemistry, ultrastructural examination may be necessary to support the diagnosis. The diagnostic differential includes melanoma, spindle cell squamous cell carcinoma, atypical fibroxanthoma, leiomyosarcoma, and conventional malignant peripheral nerve sheath tumor, most commonly of Schwannian differentiation. Recognizing perineurial differentiation is important since few cases have been reported to date and the biological potential of these neoplasms is not known.
The histopathology of folliculitis in HIV‐infected patients
Authors: Holmes Rona Beth , Martins Ciro , Horn Thomas
Published: March 2003

Background:  Cutaneous disease referable to human immunodeficiency virus (HIV) infection has become less common with the advent of widespread administration of antiretroviral medications, particularly the protease inhibitors. Pruritic eruptions that fall into the general categorization of folliculitis continue to be problematic.

Methods: In this report, we describe 33 skin biopsy samples prospectively obtained of follicular papules and pustules from 33 HIV‐infected individuals with the clinical diagnosis of HIV‐related folliculitis.

Results:  The histopathologic findings were stratified as follows: (i) acute folliculitis with bacteria and/or yeast (n = 9); (ii) lymphocytic perifolliculitis (n = 7); (iii) eosinophilic folliculitis (n = 5); (iv) perifolliculitis with mixed inflammation (n = 11); (v) follicular rupture with predominant granulomatous inflammation (n = 1). Demodex organisms were found in 10 specimens scattered among these categories.

Conclusions:  The histopathology of folliculitis in HIV‐infected patients is protean. No single factor could be identified as the cause, making targeted antibacterial or antifungal therapy unlikely to be successful across a wide range of patients.
Disseminated cutaneous histoplasmosis in patients infected with human immunodeficiency virus
Authors: K. Ramdial Pratistadevi , Mosam Anisa , Dlova Ncoza C. , B. Satar Nasreen , Aboobaker Jamilla , Singh Shivon M.
Published: March 2003

Background: In the pre‐AIDS era disseminated histoplasmosis was rare and the cutaneous manifestations thereof were reported infrequently. A range of unusual clinical manifestations of disseminated cutaneous histoplasmosis (DCH) in AIDS patients has been documented, but the cutaneous histopathological descriptions are short and incomplete. In addition, the histopathological spectrum of AIDS‐associated DCH is poorly recognized.

Methods: This is a prospective 32‐month study of all HIV positive patients diagnosed with histoplasmosis in the Departments of Anatomical Pathology and Dermatology, Nelson R. Mandela School of Medicine and King Edward VIII Hospital, Durban, South Africa. Clinical distribution and morphology of the individual skin lesions and CD4+ lymphocyte counts in the peripheral blood were analysed in relation to the histopathological features of biopsied lesional tissue. Ultrastructural examination of tissue retrieved from the wax blocks of three cases that exhibited dermal karyorrhexis and collagen necrosis was undertaken. Fungal culture of lesional skin tissue was undertaken in all patients.

Results: Twenty‐one biopsies of papules (7), nodules (4), plaques (5), erythema multiforme‐like lesions (2), vasculitic lesions (2) and exfoliative dermatitis (1) from 14 patients were examined. Of four biopsies (CD4 range: 120–128 cells/mm3) one and three demonstrated necrotizing and non‐necrotizing granulomatous inflammation with a paucity of intrahistiocytic microorganisms. Seven biopsies (CD4 range: 2–56 cells/mm3) demonstrated diffuse dermal and intravascular accumulation of histiocytes densely parasitized by Histoplasma capsulatum var. capsulatum. Vasculitis, karyorrhexis or collagen necrosis was not present. Ten biopsies (CD4 range: 2–72 cells/mm3) demonstrated diffuse dermal karyorrhexis, collagen necrosis and interstitial, extracellular H. capsulatum var. capsulatum. Histiocytic disintegration and nuclear fragmentation and release of intact microorganisms and intact and ruptured lysosomes were identified ultrastructurally. Leucocytoclastic vasculitis was present in two biopsies of vasculitic clinical morphology. Microbiological culture confirmed histoplasmosis in all cases. Three patients died before treatment was commenced. Two patients died within the first two days of induction of therapy. Nine patients demonstrated dramatic healing of the cutaneous lesions.

Conclusions: Despite the clinicopathological spectrum of DCH and the attendant host immunocompromise, timely and appropriate treatment of DCH may be lifesaving and allows rapid healing of skin lesions. A high index of clinical suspicion and skin biopsies and culture are crucial for accurate diagnosis.
Acral pseudolymphomatous angiokeratoma of children: immunohistochemical and clonal analyses of the infiltrating cells
Authors: Hagari Yoshitaka , Hagari Shinobu , Kambe Naoto , Kawaguchi Toshio , Nakamoto Shu , Mihara Motoyuki
Published: March 2003

Background:  Acral pseudolymphomatous angiokeratoma of children (APACHE) is a disorder characterized clinically by red nodules and histopathologically by a massive subepidermal lymphohistiocytic infiltrate. Although it was initially thought to be a vascular nevus, it has never been regarded as a pseudolymphoma.

Case report: We report a 7‐year‐old‐girl with small red nodules on the dorsum of the right foot and a 73‐year‐old man with asymptomatic brown‐red nodules on the lower extremities.

Results:  Histopathologic examination revealed a massive lymphohistiocytic infiltrate with plasma cells, some eosinophils, or a multinucleated giant cell immediately beneath the epidermis. Thick‐walled vessels were observed in the infiltrate. These characteristics are identical to those of acral pseudolymphomatous angiokeratoma of children. The infiltrate was composed mainly of equal numbers of CD4+ or CD8+ T cells and equal numbers of B cells stained for κ or λ light chains. PCR amplification of rearranged immunoglobulin heavy chain genes or T‐cell receptor γ genes showed no evidence of clonality, suggesting that these infiltrates were polyclonal both for B and T cells.

Conclusions:  Our data support the idea that this disorder represents a reactive process. The modified term ‘papular angiolymphoid hyperplasia’ would define this disorder more appropriately.
CD34‐positive glomus tumor: clinicopathologic and immunohistochemical analysis of six cases with myxoid stromal changes
Authors: Mentzel Thomas , Hügel Heino , Kutzner Heinz
Published: March 2003

Background: Glomus tumors are benign, mainly superficially located perivascular neoplasms, composed of cytologically characteristic neoplastic cells staining immunohistochemically positive for vimentin and muscle actin, closely associated with often branching blood vessels.

Methods:  Six cases of glomus tumor were analysed histologically and immunohistochemically.

Results:  We report six cases of glomus tumor (three solid glomus tumors, two glomangiomas, one glomangiomyoma) arising on the fingers of adult patients (five female and one male patient; age range 35–65 years) that showed prominent myxoid stromal changes and immunohistochemically a coexpression of alpha‐smooth muscle actin and CD34 by neoplastic cells.

Conclusions: Neoplastic cells in glomus tumor may show a coexpression of alpha‐smooth muscle actin and CD34, an important finding regarding the differential diagnosis of these lesions and the relationship of perivascular neoplasms.
Cytomegalovirus neuritis in perineal ulcers
Authors: Ramdial Pratistadevi K. , Dlova Ncoza Cordelia , Sydney Clive
Published: March 2003

Background:  Although a range of cytomegalovirus (CMV)‐induced cutaneous manifestations is described in AIDS patients, skin involvement in immunocompromised patients is rare, and intraneural CMV inclusions or CMV neuritis has not been documented in skin biopsies.

Methods and results:  Cutaneous biopsies of CMV lesions were collected prospectively for 12 months. The morphology, sites and symptomatology of the individual lesions, associated systemic illnesses, treatment schedules and disease outcome were recorded. A total of nine biopsies were obtained from three females who presented with extensive painful perineal ulceration and disseminated cutaneous ulcers, nodules and plaques. Clinically, herpes simplex virus (HSV) ulceration was diagnosed and treatment with acyclovir was initiated after biopsies from the natal cleft, perineum and neck were obtained. All were superficial and demonstrated HSV infection. Only the natal cleft biopsy demonstrated coexistent CMV inclusions. Suboptimal healing necessitated two further biopsies from each patient, none of which demonstrated HSV inclusions. Three of four deep perineal biopsies demonstrated CMV inclusions within nerves attended by a lymphocytic infiltrate and architectural disturbances. Two deep cutaneous biopsies of the trunk and abdominal wall confirmed CMV in extraneural locations only. One superficial perineal biopsy did not demonstrate any viral inclusion.

Conclusions:  In documenting CMV neuritis in painful perineal ulcers, the histopathological spectrum of perineal CMV ulcers is expanded, a cutaneous neurotropic characteristic of CMV is presented and a direct role for CMV in the pathogenesis of pain is suggested. CMV latency within perineal nerves is also revisited as another potential site of CMV reactivation in immunocompromised patients, and another potential site for possible venereal transmission of CMV infection. The exclusive presence of HSV in initial superficial biopsies highlights the need for optimally biopsied tissue to confirm the coexistence of CMV infection.
p63 expression in normal skin and usual cutaneous carcinomas
Authors: Reis‐Filho Jorge S. , Torio Beatriz , Albergaria André , Schmitt Fernando C.
Published: March 2003

Background:  p63 is a p53 homologue that is mapped to chromosome 3q27. This gene encodes six different isoforms, which have either transactivating or dominant negative effects on p53‐reporter genes. It has been described that in contrast to p53, p63 seems not to be associated with tumor predisposition, as neither p63 knockout mouse models nor germline p63 mutations are related to an increased risk of tumorigenesis. It has been demonstrated that p63 is a reliable keratinocyte stem cell marker and that it is involved in the maintenance of the stem cell population. Scant data on p63 expression in normal skin, basal cell carcinomas (BCCs), keratoacanthomas and squamous cell carcinomas (SCCs) have been reported. We herein evaluated p63 expression in 16 BCCs, one keratoacanthoma and 13 SCCs.

Methods:  Immunohistochemistry according to the streptavidin‐biotin‐peroxidase technique, using the antibody 4A4 raised against all p63 isoforms, was performed. p63 expression was evaluated in epidermal cells and skin appendages. Semi‐quantitative evaluation (–, +, ++, +++) of p63 expression in BCCs, keratoacanthoma and SCCs was carried out. Only nuclear expression was considered as specific.

Results:  p63 was expressed in the nuclei of epidermal basal and suprabasal cells, in the cells of the germinative hair matrix and the external root sheath of hair follicles, in the basal cells of the sebaceous gland and in the myoepithelial/basal cells of the sweat glands. All terminally differentiated cells were negative for p63. All BCCs showed ++ to +++ immunoreactivity. At variance, keratoacanthomas and grade I and II SCCs showed variable p63 reactivity in a basal layer‐like distribution, whereas undifferentiated cells of grade III SCCs showed ++ to +++ positivity. A grade IV spindle SCC showed + immunoreactivity. The SCCs in situ showed remarkable expression of p63 in all cell layers. Terminally differentiated squamous cells were either negative or showed only focal immunoreactivity in the carcinomas.

Conclusions:  p63 is consistently expressed in the basal cells of epidermis and cutaneous appendages, including the basal/myoepithelial cells of sweat glands. Based on our findings, the balance of probabilities favors that p63 might play a role in the pattern of differentiation and in the oncogenesis of usual carcinomas of the skin.
Abundance of interstitial heparan sulfate in granuloma annulare but not in other mucinous skin diseases
Authors: Bandel Christopher , DePrisco Gregorio , Cockerell Clay J. , Ehrig Torsten
Published: March 2003

Background:  Heparan sulfate (HS), unlike other glycosaminoglycans, is mainly located on cell surfaces but can be shed into the interstitium by a regulated process. It has been found in interstitial fluid drained from cutaneous wounds, but otherwise the conditions under which the release of HS from the cell surface occurs are unknown. To better characterize this process, we have investigated the presence of interstitial HS in various skin diseases with glycosaminoglycan accumulation.

Methods:  Histologic routine material was stained immunohistochemically using an antibody recognizing HS.

Results:  Heparan sulfate immunoreactivity is present in the interstitium of young cutaneous scars and in the interstitium of the inflammatory infiltrate of granuloma annulare. No reactivity was found in a number of non‐inflammatory skin diseases with mucin deposition.

Conclusions:  The selective presence of interstitial HS in only two of the investigated skin conditions supports the existence of a regulated mechanism to release HS from the surface of cells into the interstitium. It is suggested that HS modulates the biologic actions of growth factors and cytokines not only during wound repair but possibly also in inflammatory skin diseases such as granuloma annulare.
Desmoplastic and spindle cell melanomas express protein markers of the neural crest but not of later committed stages of Schwann cell differentiation
Authors: Huttenbach Yve , Prieto Victor G. , Reed Jon A.
Published: March 2003

Background:  The rare desmoplastic and spindle cell variants of malignant melanoma exhibit histological and biochemical features suggestive of early Schwann cell differentiation. These features include a spindle‐shaped morphology, neurotropism, and the expression of the low affinity nerve growth factor receptor (p75NGFR).

Methods: We evaluated by immunohistochemistry (using formalin‐fixed, paraffin‐embedded tissues) nine desmoplastic and three spindle cell melanomas for the expression of peripherin, p75NGFR, neural cell adhesion molecule (CD56/N‐CAM), and growth‐associated phosphoprotein‐43 (GAP‐43). Peripherin is expressed in the neural crest and in neurons, but not in cells committed to the Schwann cell lineage. p75NGFR and CD56/N‐CAM also are expressed in early neural crest cells, but persist in unmyelinated and early premyelinating Schwann cells. GAP‐43 is expressed in unmyelinated Schwann cells, but is downregulated in the later premyelinating to promyelinating stages of cells committed to the Schwann cell lineage.

Results: Peripherin was expressed in 7/12 (58%), p75NGFR in 4/12 (33%), and CD56/N‐CAM in 6/12 (50%) of the desmoplastic and spindle cell melanomas. GAP‐43 was not expressed (0%) in any of the 12 melanomas (χ2, p = 0.05).

Conclusions: Desmoplastic and spindle cell melanomas express protein markers common to cells of the neural crest and to neurons similar to the immunophenotype previously reported for epithelioid cell melanomas. The expression of peripherin and the lack of expression of GAP‐43 further define that these rare subtypes of melanoma do not recapitulate the later committed stages of Schwann cell differentiation.
Merkel cell (primary neuroendocrine) carcinoma of the skin with nodal metastasis showing rhabdomyosarcomatous differentiation
Authors: Fernández‐Figueras María‐Teresa , Puig Lluís , Gilaberte Montserrat , Del Carmen Gómez‐Plaza María , Rex Jordi , Ferrándiz Carlos , Ariza Aurelio
Published: March 2003

Background:  We describe a unique case of Merkel cell (primary neuroendocrine) carcinoma of the skin with a lymph node metastasis showing rhabdomyosarcomatous differentiation. Skeletal muscle differentiation has occasionally been described in primary small cell neuroendocrine carcinomas and considered a form of dual differentiation rather than a collision tumor. In the present case, capacity for divergent differentiation appeared late in the course of the tumor, which suggests a clonal origin for both components of the neoplasm.

Conclusions:  The coexistence of neural and rhabdomyoblastic types of differentiation, best epitomized by the Triton tumor, has been construed as the product of dual differentiation of cells originated from neural crest‐derived ectomesenchyme. Since Merkel cells seem to originate from a pluripotential primitive keratinocyte and not from the neural crest, rhabdomyoblastic differentiation in a metastasis of primary neuroendocrine carcinoma of the skin probably reflects the close proximity between the programs of neural and skeletal muscle differentiation, which would have been sequentially activated in the case we are reporting.
Initial Practice Locations of International Medical Graduates
Authors: Polsky Daniel , Kletke Philip R. , Wozniak Gregory D. , Escarce José J.
Published: March 2003

Objective. To examine the influence of place of graduate medical education (GME), state licensure requirements, presence of established international medical graduates (IMGs), and ethnic communities on the initial practice location choices of new IMGs.

Data Sources. The annual Graduate Medical Education (GME) Survey of the American Medical Association (AMA) and the AMA Physician Masterfile.

Study Design. We identified 19,940 IMGs who completed GME in the United States between 1989 and 1994 and who were in patient care practice 4.5 years later. We used conditional logit regression analysis to assess the effect of market area characteristics on the choice of practice location. The key explanatory variables in the regression models were whether the market area was in the state of GME, the years of GME required for state licensure, the proportion of IMGs among established physicians, and the ethnic composition of the market area.

Principal Findings. The IMGs tended to locate in the same state as their GME training. Foreign‐born IMGs were less likely to locate in markets with more stringent licensure requirements, and were more likely to locate in markets with higher proportions of established IMG physicians. The IMGs born in Hispanic or Asian countries were more likely to locate in markets with higher proportions of the corresponding ethnic group.

Conclusions. Policymakers may influence the flow of new IMGs into states by changing the availability of GME positions. IMGs tend to favor the same markets over time, suggesting that networks among established IMGs play a role in attracting new IMGs. Further, IMGs choose their practice locations based on ethnic matching.
Effects of CAHPS Health Plan Performance Information on Plan Choices by New Jersey Medicaid Beneficiaries
Authors: Farley Donna O. , Short Pamela Farley , Elliott Marc N. , Kanouse David E. , Brown Julie A. , Hays Ron D.
Published: March 2003

Objective. To assess the effects of CAHPS health plan performance information on plan choices and decision processes by New Jersey Medicaid beneficiaries.

Data Sources/Study Setting. The study sample was a statewide sample of all new Medicaid cases that chose Medicaid health plans during April 1998. The study used state data on health maintenance organization (HMO) enrollments and survey data for a subset of these cases.

Study Design. An experimental design was used, with new Medicaid cases randomly assigned to experimental or control groups. The experimental group received a CAHPS report along with the standard enrollment materials, and the control group did not.

Data Collection. The HMO enrollment data were obtained from the state in June 1998, and evaluation survey data were collected from July to October 1998.

Principal Findings. No effects of CAHPS information on HMO choices were found for the total sample. Further examination revealed that only about half the Medicaid cases said they received and read the plan report and there was an HMO with dominant Medicaid market share but low CAHPS performance scores. The subset of cases who read the report and did not choose this dominant HMO chose HMOs with higher CAHPS scores, on average, than did those in an equivalent control group.

Conclusions. Health plan performance information can influence plan choices by Medicaid beneficiaries, but will do so only if they actually read it. These findings suggest a need for enhancing dissemination of the information as well as further education to encourage informed choices.
Effects of additional teaching of final‐year dental students on their radiographic diagnosis of caries
Authors: Wrbas K.‐TH. , Kielbassa A. M. , Schulte‐Mönting J. , Hellwig E.
Published: March 2003

The aim of this study was to evaluate whether the skills of final‐year dental students in the diagnostic interpretation of bitewing radiographs could be improved by additional didactic instruction. 6 consecutive classes of students in the same stage of education (last semester in the Department of Operative Dentistry) took part in the investigation from 1995 to 1998. At the beginning of each semester, the same in vivo made bitewing radiograph was demonstrated in a separate radiology revison lecture and interpreted with the students. The intensification of the training in the diagnosis of bitewing radiographs was made when the 4th class of students started. At the end of each semester, each student of the 6 consecutive classes was asked to evaluate the same bitewing radiograph, which had been demonstrated at the start of the semester. The students were not told that they had already diagnosed from this radiograph before. The results of the radiographic diagnosis were then analyzed using an evaluation system paying special attention to the treatment decision. True positive and true negative diagnoses were scored as correct and false positives and false negatives as incorrect. There was no significant difference (ANOVA) in the ability to diagnose from bitewing radiographs between the groups of students who received, and those who did not receive, additional training. The benefits of this type of additional instruction in the last semester in the Department of Operative Dentistry seem only to be important in some individual cases.
Student learning and the teaching‐research nexus in oral biology
Authors: Kieser Jules , Herbison Peter
Published: March 2003

Although frequently coexistent, we know little about the interactions among research, teaching and learning in higher education. This study examines the preferences of second and third year dental students for questions that require a research‐based deep approach or questions that require a straightforward didactic approach. A questionnaire was designed to evaluate the opinion of 114 students who took part in the Oral Biology course. 56 second year students (75%) responded while 58 (84%) of third year students responded. Questions that required an interpretive approach were found to be most appealing by 70.2% of all students. Questions which required a regurgitative approach were favoured by 11.6% of students. No significant differences were found when the sample was broken down by country of origin, year of study or gender, suggesting that dental students preferred research‐based learning rather than superficial didactic learning.
Are Polish and Swedish dental graduates adequately prepared for dental practice in the UK? A discussion of the transferability of general dental practitioners in Europe
Authors: Bullock Alison , Frame John , Holmlund Anders , Limanowska‐Shaw Honorata , Shaw Geoffrey
Published: March 2003

In the context of European Union harmonization, this article compares the systems of training for general dental practice in three European countries, the UK, Sweden and Poland. A UK perspective is adopted and the question as to whether dentists who have qualified in Poland or Sweden are adequately prepared for practice in the UK is explored. The paper is a result of discussion between providers of dental training in the three study countries. Key similarities, strengths and weaknesses are identified and issues pertinent to the transferability of general dental practitioners within Europe are raised.
The use of the Internet within a dental school
Authors: Walmsley A. D. , White D. A. , Eynon R. , Somerfield L.
Published: March 2003

The Internet is an increasingly popular medium for delivering educational material. The aim of this study was to determine the attitudes of students and their clinical teachers to the use of the Internet within a dental school in the UK. Questionnaires were distributed to undergraduate dental students in the three clinical years and to all their clinical academic teachers. All students and staff have access to computers and Internet at the university. The majority (72%) of students have access to a computer and 53% also have access to the Internet at home. Of the academic staff, 91% have a computer and 68% have access to the Internet at home. The reasons for use of the Internet differed between staff and students. Whilst equal proportions of students used the Internet for dentistry (38%) and for pleasure (35%), a higher proportion of staff used the Internet more for dentistry (36%) than for pleasure (14%). Students highlighted cost and time as barriers to Internet use, whereas staff lacked confidence in their ability to use the Internet. Less than half (44%) of the students are confident in the accuracy of information from the Internet compared to almost two‐thirds (64%) of staff. This study revealed differences in the attitudes of staff and students to the use of Internet as a resource for dentistry. Students are positive to the suggestion that lectures should be presented on the web. Most students (74%) did not see that this would influence attendance at lectures whilst 91% of staff stated that it would decrease lecture attendance. In conclusion, this study revealed differences in the attitudes of staff and students to the use of Internet as a resource for dentistry.
4.2 Clinical records and global diagnostic codes
Authors: Phantumvanit Prathip , Monteil Roger A. , Walsh Trevor Frank , Miotti Francesca Ada , Carlsson Peter , Doukoudakis Asterios , Fox Christopher , Harzer Winfried
Published: March 2003

A clinical record should include the personal demographic details of the patient, health status, diagnostic information and management/treatment options. However, clinical records are of little use without effective filing and retrieving systems. Coding is therefore necessary to deal with large amounts of differing data and a global coding system could be effectively developed through the use of information technology. The aim of this section was to review the main existing vocabularies and coding systems and to examine ways of improving their global application. It was concluded that global diagnostic codes would be beneficial to the patient, to the profession and to those responsible for strategic decisions concerning the delivery of health care. Extant dental clinical codes are not accepted widely or applied universally. There is an urgent need to identify existing coding systems and to assess their utility and potential for global application. Every effort should be made to include existing codes in the development of a global coding system on which all specialist areas would need to agree. This would require the provision of an overarching interdisciplinary focus and funding should be made available for this development and its implementation.
5.2 Ethics, equity and global responsibilities in oral health and disease
Authors: Hobdell Martin , Sinkford Jeanne , Alexander Charles , Alexander David , Corbet Esmonde , Douglas Chester , Katrova Lydia , Littleton Preston , MacCarthy Denise , Cherrett Helen McK. , Schou Lone , Wen Fan Ming , Zhuan Bian
Published: March 2003

The charge of this Section is ethics and global responsibilities in oral health and disease. Oral health is determined by the same factors as those for general health. To a limited extent, the level of oral health care and dental education. The philosophy and organization of the health care system and dental education, therefore, are key determinants of oral health. Dental education has expanded in many countries where there has been an increase in wealth. Unfortunately, there has been no concomitant increase in the number of dental educators. This is a problem throughout the world. This present situation raises certain ethical issues with regard to professional responsibilities. It also raises some important questions for dental education. This Section has chosen to focus its efforts on examining two issues:

•  What can be done within dental schools?

•  What can be done external to dental schools – either individually or collectively?

The best practices identified are more akin to goals, as it is recognized that, in a world in which there are enormous variations in economic, environmental, social, and cultural features, a single uniform set of practices is impracticable. The central core value identified is the realization by students, and faculty/teaching staff of the quest of life‐long learning against a background of the social and ethical responsibilities of health professionals. The conclusion of the group is that biology is not the sole determinant of health. Understanding the role of social, economic, environmental and other factors in determining health status is critical if greater equity in dental education and care are to be achieved.