bluuebunny/crossref_metadata_2025 huggingface dataset:
Infection by Borrelia burgdorferi and cutaneous B‐cell lymphoma
Authors: Cerroni Lorenzo , Zöchling Natalie , Pütz Barbara , Kerl Helmut
Published: April 2006

In past years, association of primary cutaneous B‐cell lymphoma (CBCL) with infection by Borrelia burgdorferi has been reported in a few patients. The evidence for a pathogenetic role was based on clinical grounds or raised titre of antibodies in serum. Both methods, however, do not prove the association between the micro‐organism and the CBCL, especially in countries where infection by Borrelia burgdorferi is endemic. Moreover, the exact percentage of Borrelia burgdorferi‐positive CBCL is not known. We retrieved from our files 50 cases of CBCL to perform PCR analysis of Borrelia burgdorferi DNA on paraffin‐embedded tissue sections. Only patients with primary CBCL were selected. In all cases, monoclonality of the infiltrate was confirmed by immunohistological pattern of immunoglobulin light chains or molecular analysis of Jh gene rearrangement, or both. Specific DNA sequences of Borrelia burgdorferi‐were identified in cutaneous lesions from 9 patients (follicle center lymphoma: 3/20; immunocytoma: 3/4; marginal zone B‐cell lymphoma: 2/20; diffuse large B‐cell lymphoma: 1/6). Specificity was confirmed by Southern blot hybridisation in all positive cases. We could show that Borrelia burgdorferi, DNA is present in skin lesions from a small proportion of patients (18%) with various types of CBCL. Our results may have therapeutic implications. In analogy to Helicobacter pylori‐associated MALT‐lymphomas, which in some cases can be cured by eradication of Helicobacter pylori infection, a proportion of CBCL may be cured with antibiotic therapy against Borrelia burgdorferi. Although yet speculative, adequate antibiotic treatment for patients with primary CBCL should be considered before more aggressive therapeutic options are applied, particularly in countries where infection by Borrelia burgdorferi is endemic. PCR analysis of Borrelia burgdorferi DNA is a fast test that should be performed in all patients with CBCL to identify those who more likely could benefit from an early antibiotic treatment.
p53 and bcl‐2 expression do not correlate with prognosis in primary cutaneous large T‐cell lymphomas
Authors: van Haselen Christian W. , Vermeer Maarten H. , Toonstra Johan , van der Putte Sebastian C. J. , Mulder P G. H. , van Vloten Willem A. , Willemze Rein
Published: April 2006

Overexpression of p53 protein in cutaneous T‐cell lymphoma (CTCL) has been reported in primary cutaneous large T‐cell lymphomas (PCLTCL) and has been associated with tumor progression and transformation in mycosis fungoides. However, the prognostic significance of p53 expression has not been studied thus far. In the present study we investigated the expression of p53 as well as bcl‐2 protein in 27 PCLTCL, including 19 CD30‐positive and 8 CD30‐negative lymphomas, retrieved from the registry of the Dutch Cutaneous Lymphoma Working Group.

The results were correlated with follow‐up data and proliferative activity, as assessed by the percentage of MIB‐1 positive tumor cells.

Overexpression of p53 protein, defined as nuclear staining of more than 5% of the tumor cells, was found in 10 of 27 cases (37%), including 6 of 19 (32%) CD30+lymphomas and 4 of 8 (50%) CD30–PCLTCL. bcl‐2 protein was expressed in 6 of 19 (32%) CD30+lymphomas and in only 1 of 8 (12%) CD30–PCLTCL. However, no significant correlation between p53 or bcl‐2 expression and prognosis was found, neither in the whole group, nor within the CD30+ or CD30– group. In addition, no relationship between p53 expression and proliferative activity was found. The results confirm that p53 expression is more common in PCLTCL than in mycosis fungoides and Sézary syndrome. However, neither p53 nor bcl‐2 expression correlated with survival or proliferative activity.
CD56‐positive (nasal‐type T/NK cell) lymphoma arising on the skin
Authors: Ansai Shin‐ichi , Maeda Kunihiko , Yamakawa Mitsunori , Matsuda Mikio , Saitoh Souichi , Suwa Shinobu , Saitoh Hiroki , Ohtsuka Mikio , Iwatsuki Keiji
Published: April 2006

Several authors have reported cases of patients with malignant lymphoma with unique characteristics, designated nasal‐type T/NK cell lymphoma, which expresses the natural killer (NK) cell marker and shows frequent extra‐nodal involvement and poor prognosis. We report 2 cases of this type of lymphoma which were CD56‐positive and showed a histopathologically angiocentric pattern with cutaneous and subcutaneous tumorous lesions. Patient 1 had extensive invasion of skin, underlying skeletal muscle, spleen and bone marrow, and died of sepsis 34 months after onset. Patient 2 had multiple subcutaneous nodules and invasion to mammary gland, lung, lymph node and spleen at the time of her first visit. She died of a rapid invasion of lymphoma cells to the liver 5 months after onset. Both patients showed similar immunophenotypes of tumor cells (CD2+, CD3−, CD4−, CD8−, CD20−, CD56+) and germ line configuration of the heavy chain of immunoglobulin (JH), T‐cell receptor C beta‐1 subunit DNA and T‐cell receptor J gamma subunit DNA. Epstein‐Barr virus early regions RNA was demonstrated in the nuclei of tumor cells of both patients with in situ hybridization. The histopathological examination of the skin lesions of both patients revealed the features of angiocentric lymphoma. The detection of CD56 in the tumor cells of cutaneous lymphomas should be routinely performed for the early diagnosis of this type of lymphoma with extremely poor prognosis.
Merkel cell hyperplasia in chronic radiation‐damaged skin: its possible relationship to fibroepithelioma of Pinkus
Authors: Hartschuh Wolfgang , Schulz Tilman
Published: April 2006

Moderate hyperplasia of Merkel cells (MC) in chronic sun‐damaged skin and hypertrophic actinic keratoses is well known. In the present study we investigated the number of MC in 24 samples of chronic radiation dermatitis and 19 cases of fibroepithelioma of Pinkus (FP), which is known to arise preferably in radiation‐damaged skin. Using antibodies against the low molecular weight cytokeratins 8, 18, and 20 and chromogranin A to visualize MC, we found hyperplasia of MC in chronic radiation dermatitis. Additionally, in all FPs we could detect many MC, especially in areas with a pronounced fenestrated pattern. Recently, regulative functions of MC on the growth of follicular epithelium under various conditions were discussed. Thus, MC hyperplasia suggests a causal role also in the development of FP. In this context, hyperplasia of MC in chronic radiation dermatitis could explain the frequent occurrence of FP due to radiation exposure. As we recently found MC also in trichoblastomas but not in basal‐cell carcinomas, the MC in FP may indicate its relationship to the benign trichoblastoma rather than to the basal‐cell carcinoma. It is possible that regulative influences of the MC are important for the clinically rather benign course of FP.
The Muir‐Torre syndrome in a black patient with AIDS: histopathology and molecular genetic studies
Authors: Warschaw Karen E. , Eble John N. , Hood Antoinette F. , Wolverton Stephen E. , Halling Kevin C.
Published: April 2006

In 1981, a black man had adenocarcinoma of the colon. In 1986, he had a sebaceous adenoma and the diagnosis of the Muir‐Torre syndrome was established. The patient was found to be HIV seropositive in 1986, and 8 years later fulfilled the CDC criteria for AIDS. During 1989 to 1993 the CD4 count was >200 cells/ml and the patient had 2 sebaceous tumors, 1 basal cell carcinoma and 1 keratoacanthoma. In 1994 to 1996, the CD4 count was <200 cells/ml and the patient developed 18 sebaceous tumors and a poorly differentiated adenocarcinoma of the finger which metastasized to axillary lymph nodes. Microsatellite analysis of tumor DNA from a sebaceous adenoma and adenocarcinoma of the finger revealed widespread microsatellite instability. The interaction of AIDS with the behavior of the tumors in the Muir‐Torre syndrome has not previously been reported. Although our patient had an increase in the number of new sebaceous tumors at the same time he experienced deterioration of the immune system, he is doing well 15 years after resection of adenocarcinoma of the colon and 16 months after metastatic poorly differentiated adenocarcinoma of the skin. This follows the previously observed tendency for cancers of the Muir‐Torre syndrome, especially those displaying widespread microsatellite instability, to be less lethal than their histologically similar counterparts in people without Muir‐Torre syndrome.
Altered distribution and expression of protein tyrosine phosphatases in normal human skin as compared to squamous cell carcinomas
Authors: Nanney Lillian B. , Davidson Mari K. , Gates Ronald E. , Kano Mio , King Lloyd E.
Published: April 2006

Amounts and subcellular localizations of 4 protein tyrosine phosphatases (PTPs) were compared in cultured normal human keratinocytes, an immortalized keratinocyte cell line, and 2 squamous cell carcinoma (SCC) lines. Cellular localizations for PTPs were determined in biopsies of normal human skin and SCCs. Compared to normal keratinocytes, SCC cell lines had higher levels of PTP‐1B and T‐cell PTP and comparable levels of PTP‐1C or PTP‐1D. The subcellular localization of each PTP was similar in the 3 types of keratinocytes with PTP‐1B localizing to the endoplasmic reticulum, T‐cell PTP exclusively found in the nucleus, PTP‐1C localized to the plasma membrane, cytosol and nucleus, and PTP‐1D present in both cytosol and nucleus. Compared to normal skin, immunoreactive PTP‐1B was markedly increased in the invasive margins of SCCs while T‐cell PTP was generally increased in tumors. PTP‐1C immunostaining varied between cells with no obvious difference between normal and neoplastic tissues. The intensity and distribution of immunoreactive PTP‐1D varied greatly between cells within tumors. These differences in amounts and in cellular and subcellular localization of these PTPs, especially those differences in invasive margins of SCCs, may reflect the diverse roles these PTPs play in the proliferation and invasive potential of neoplastic keratinocytes.
Differential expression of metallopanstimulin/S27 ribosomal protein in melanocytic lesions of the skin
Authors: Santa Cruz Daniel J. , Hamilton Paul D. , Klos Dennis J. , Fernandez‐Pol J. Albert
Published: April 2006

We have previously shown that human metallopanstimulin (MPS‐1) is a ubiquitous 9.4‐kDa multifunctional ribosomal S27/nuclear “zinc finger” protein which is expressed at high levels in a wide variety of cultured proliferating cells and tumor tissues, including melanoma. In the present study, we have examined the expression of the MPS‐1 protein in various types of human benign and malignant melanocytic lesions of the skin. The expression of the MPS‐1 protein was studied by immunohistochemistry using specific anti‐MPS‐1 antibodies. We found that in benign nevi, the staining is weak and in a gradient; most often, only type A melanocytes stain positive. The B and particularly the C types are negative. Remarkably, congenital nevi show a similar gradient staining of regular benign nevi, but in addition one example showed intensely positive dermal nodules adjacent to areas of negative melanocytes. In melanomas, the staining patterns for MPS‐1 are more complex. While some melanomas stain evenly and intensely positive, others have remarkably variable expression of MPS‐1. The scattered melanocytes migrating to the upper layers of the epidermis are usually intensely positive. In summary, benign lesions stain in an orderly pattern with staining gradients that correlate with the cellular differentiation of the nevi. Malignant melanomas have an erratic, often intense staining that also correlates with the disorderly growth of these neoplasms. These differential results indicate that the MPS‐1 antigen is a useful marker for melanocytic lesions at the immunohistochemical level.
The immunofluorescent profile of dermatomyositis: a comparative study with lupus erythematosus
Authors: Magro C.M. , Crowson A. N.
Published: April 2006

We have demonstrated a role for microvascular injury mediated by the membrane attack complex of complement (Cr5b−9) in the genesis of cutaneous lesions of dermatomyositis (DM) (1). The purpose of this study is to revisit the immunofluorescent (IF) profile of DM, to further investigate the role of C5b−9 in the pathogenesis of cutaneous lesions, and to see if any features of the IF profile reliably distinguish DM from LE. Lesional skin biopsies from 24 patients with clinical findings characteristic of DM were received in formalin and in Michel's transport medium. Conventional light microscopy, and IF studies with antibodies monospecific for IgG, IgA, IgM, C3, fibrin and C5b−9 were performed. The control group comprised biopsies from 31 patients with well‐documented LE. A positive lupus band test (LET) correlated highly with a diagnosis of LE, with a sensitivity of 64.5% and a specificity of 95.6% (p=0.001). The LET was most sensitive in the setting of DLE and SLE and was least sensitive in the setting of SCLE. The finding of vascular C5b−9 deposition correlated with a diagnosis of DM versus LE(P=0.001) although the false positive rate was 21.4%. The false negative rate was reduced when vascular C5b−9 was seen in the absence of antibodies to Ro, La, or RNP. While a negative LBT correlated with a diagnosis of DM (p=0.001), the specificity was only 64.5%. However, when it was seen in concert with C5b−9 along the DEJ, specificity was increased to 80.6% (p=0.001). The presence of C5b−9 in vessels and along the DEJ in conceit with a negative LBT was predictive of DM (p=0.001) with a specificity of 93.5%, sensitivity of 78.3%, a false positive rate of 10% and a false negative rate of 14.7%. The combination of a negative LBT, vascular C5b−9 deposition and negative serology for Ro, La, and RNP was a predictor of DM versus LE with a sensitivity of 90.5%, a specificity of 96.8%, a false positive rate of 5% and a false negative rate of 6.2% (p=0.001). The IF profile of DM in lesional skin comprises a negative LBT, deposition of c5b−9 within vessels and along the DEJ, and variable keratinocyte decoration for IgG and C5b−9. The most statistically powerful predictor of DM is the combination of a negative LBT with vascular C5b−9 deposition and negative serology for antibodies to Ro, La, Sm, and RNP. Demonstration of a negative LBT in all but 1 case of DM suggests that the DEJ is not a primary site for antigen‐antibody interaction. We postulate that the aforementioned IF findings reflect humorally mediated injury of enclothelium and keratinocytes, effected by C5b−9.
Cutaneous lupus mucinosis: a review of our cases and the possible pathogenesis
Authors: Kanda Naoko , Tsuchida Tetsuya , Watanabe Takahiro , Tamaki Kunihiko
Published: April 2006

Cutaneous lupus mucinosis (CLM) is a rare variant of lupus erythematosus eruptions. Our 5 cases with CLM were reviewed. All were men with systemic lupus erythematosus (SLE). CLM occurred as asymptomatic cutaneous papules, nodules, or plaques on the trunk, upper and lower extremities, and face. Histopathology of CLM mainly revealed abundant mucin deposits among splayed collagen bundles throughout the dermis. However, some CLM lesions showed discoid lupus erythematosus‐like epidermal and dermal changes and/or lupus profundus. Vasculitis was also revealed in the CLM lesions of 2 cases. The pathogenesis of CLM may be closely related to its two important features, the male preponderance and the association with SLE. Vasculopathy may also be involved in the development of CLM.
Absence of human herpesvirus 8 and Epstein‐Barr virus genome sequences in cutaneous epithelial neoplasms arising in immunosuppressed organ‐transplant patients
Authors: Kohler Sabine , Kamel Onsi W. , Chang Pearl P. , Smoller Bruce R.
Published: April 2006

Recent studies have implicated herpesvirus 8 and Epstein‐Barr virus in the development of cutaneous malignancies in immunosuppressed patients. In order to examine the strength of this association, we examined 37 malignant, pre‐malignant and benign cutaneous epithelial neoplasms removed from immunosuppressed organ recipients for the presence of human herpesvirus 8 and Epstein‐Barr viral genome sequences using polymerase chain reaction (PCR) and in situ hybridization. We examined 2 actinic keratoses, 1 benign keratosis, 11 invasive squamous cell carcinomas, 17 squamous cell carcinomas in situ and 6 basal cell carcinomas. We also examined 4 basal cell carcinomas, 1 invasive squamous cell carcinoma and 3 squamous cell carcinomas in immunocompetent hosts. In contrast to findings reported by other investigators, we were unable to detect viral genome sequences in any of the biopsies examined. Our findings suggest that human herpesvirus 8 and Epstein‐Barr virus likely do not play an etiologic cogenesis in immunocompromised patients.
Glomangiosarcoma of the lower limb: a case report with a literature review
Authors: López‐Ríos Fernando , Rodríguez‐Peralto José Luis , Castaño Esther , Ballestín Claudio
Published: April 2006

Glomangiosarcoma (GS) is a very unusual but morphologically distinctive tumor of soft tissue. We report a case of GS which occurred in the subcutaneous tissue of a 56‐year‐old man. Microscopically, a typical glomus tumor surrounded a central area of sarcoma. Immunohistochemical stains were performed, and there was a strong positive reaction for vimentin, muscle‐specific actin and smoth muscle actin.

We also review the clinicopathologic findings of the 9 GS that have previously been reported.
Immunohistochemical localization of muscarinic acetylcholine receptors in primary and metastatic malignant melanomas
Authors: Lammerding‐Köppel M. , Noda S. , Blum A. , Schaumburg‐Lever G. , Rassner G. , Drews U.
Published: April 2006

In embryos morphogenetically active cells transiently express the cholinergic system comprising cholinesterase activity and muscarinic acetylcholine receptors. Malignant melanomas develop from melanocytes, which are derived from the neural crest. Neural crest cells express the embryonic muscarinic system during migration. Using the monoclonal antibody M35, we now show that normal melanocytes carry no muscarinic receptors, whereas malignant melanoma cells express them again. In primary melanomas and metastatic melanomas, we identified muscarinic receptors in solid strands or groups of atypical cells. In all primary malignant melanomas studied we found inhomogeneous distributions of M35‐inimunoreactivity subdividing the tumors into three different zones. In the tumor center, groups or single cells often showed only little or even no immunofluorescence. In contrast, pericentrally we detected strong immunostaining in the conglomerations of atypical melanocytes. In the peripheral infiltration zone, intensely fluorescent cells in clusters or single, were spreading into the normal tissue, leading to a more patchy staining pattern. Melanocytes of nevi also possess muscarinic receptors, showing similar distribution patterns as in the melanoma. We suggest that in malignant melanomas muscarinic receptors might play a regulative role in infiltrative growth and metastasis.
Distinctive clinicopathologic features associated with regressive primary CD30 positive cutaneous lymphomas: analysis of 6 cases
Authors: Bernier Michèle , Bagot Marline , Broyer Murielle , Farcet Jean‐Pierre , Gaulard Philippe , Wechsler Janine
Published: April 2006

A distinct group of cutaneous lymphomas has been described on the basis of CD30 antigen expression by at least 75% of the tumoral cells. When confined to the skin, these CD30 positive cutaneous lymphomas seem to be associated with a better prognosis than CD30 negative counterparts and spontaneous regression may even occur.

We observed a spontaneously regressive evolution in 6 out of 9 CD30 positive primary cutaneous large cell‐lymphomas diagnosed during a 5‐year period. Clinicopathological data of regressive cases were analysed. The mean age of patients was 56.5 years. They were 3 males and 3 females. Skin lesions were solitary nodule or plaque measuring from 1.5 cm to 11 cm in diameter. Histologically, the lesions were classified as pleomorphic, medium and large cell (5 cases) or large cell anaplastic lymphoma (1 case) according to the updated Kiel classification. Delay for spontaneous regression varied from 1 to 6 months. Three of the 6 patients had cutaneous relapses, followed by a spontaneous regression. All patients remained disease‐free with an overall median follow‐up of 30 months. Histologically, some distinctive signs such as epidermal pseudoepitheliomatous hyperplasia, epidermotropism, edema, dermal vascular hyperplasia, seemed to be more frequently associated with spontaneously regressive evolution.
Alopecia areata but not androgenetic alopecia is characterized by a restricted and oligoclonal T‐cell receptor‐repertoire among infiltrating lymphocytes
Authors: Dressel Daniela , Brütt Cord Henrik , Manfras Burkhard , Zollner Thomas Matthias , Wunderlich Antje , Böhm Bernhard Otto , Boehncke Wolf‐Henning
Published: April 2006

Although the etiology of alopecia areata is still unknown, evidence has accumulated to support an autoimmune pathogenesis for this disease. To evaluate the role of T cells in alopecia areata the T‐cell receptor VB‐repertoire was investigated in lesional skin and blood of 5 patients by means of a semiquantitative technique based on the reverse transcriptase polymerase chain reaction. Three patients with androgenetic alopecia served as controls. Amplification products were screened for clonality by temperature gradient gel electrophoresis. Four of 5 patients with alopecia areata exhibited a lesional T‐cell receptor‐repertoire characterized by an almost exclusive utilization of variable regions beta2, 4, and 13. Temperature gradient gel electrophoresis revealed the oligoclonal constitution of the infiltrate. The restricted nature of the lesional T‐lymphocytic infiltrate in alopecia areata strongly suggests that an antigen‐specific T‐cell response plays an important role in the pathogenesis of this disease.
Folliculotropic mycosis fungoides with large‐cell transformation presenting as dissecting cellulitis of the scalp
Authors: Gilliam Anita C. , Lessin Stuart R. , Wilson Darren M. , Salhany Kevin E.
Published: April 2006

Follicular mycosis fungoides (MF) is a rare variant of cutaneous T‐cell lymphoma (CTCL) in which malignant lymphocytes preferentially infiltrate hair follicles. This report describes a patient with follicular mycosis fungoides presenting in a manner similar to dissecting cellulitis of the scalp with nonhealing, draining nodular lesions. Follicular mucinosis associated with folliculotropic mycosis fungoides resulted in follicular disruption and deep dissecting cellulitis. Large‐cell transformation of CTCL was present in the initial diagnostic scalp and axillary lymph node specimens. The patient died from progressive CTCL 9 months following initial diagnosis despite electron beam radiation, topical mechlorethamine, interferon‐α, and systemic chemotherapy. This case indicates that large‐cell transformation of folliculotropic mycosis fungoides is an aggressive form of CTCL, and that folliculotropic mycosis fungoides can give rise to lesions which resemble dissecting cellulitis of the scalp. Upregulation of intercellular adhesion molecule‐1 (ICAM‐1) on follicular epithelium adjacent to lymphocyte function‐associated antigen‐1 (LFA‐1)‐positive folliculotropic lymphoma cells in this report provides insight into lymphocyte homing mechanisms in folliculotropic MF.
Clear‐cell atypical fibroxanthoma: an uncommon histopathologic variant of atypical fibroxanthoma
Authors: Requena Luis , Sangueza Omar P. , Yus Evaristo Sánchez , Furio Vicente
Published: April 2006

Atypical fibroxanthoma is a superficial variant of pleomorphic malignant fibrous histiocytoma. Histopathologically, it is characterized by a dermal nodule composed of bizarre cells arranged in a haphazard‐to‐fascicular pattern. These cells are spindle or rounded, pleomorphic and with numerous atypical mitotic figures. Some cells appear polygonal with ample and foamy cytoplasm. We recently encountered two elderly patients with atypical fibroxanthoma on their face. Histopathologically, one of the lesions was composed, almost entirely, of clear cells, whereas in the other one aggregations of clear cells constituted a half of the neoplasm. Atypical multinucleated cells with a Touton‐like appearance were present. In addition to clear cells, areas of more conventional atypical spindle cells arranged in fascicles were seen, supporting the diagnosis of atypical fibroxanthoma. PAS staining failed to demonstrate glycogen in neoplastic cells. Immunohistochemistry revealed that neoplastic cells expressed positivity for vimentin, muscle‐specific actin, and alpha smooth muscle actin, whereas cytokeratin, S‐100 protein, EMA, CEA, and clesmin were negative. Ultrastructural studies showed that neoplastic cells contained abundant rough endoplasmic reticulum, mitochondria, and numerous lipid vacuoles within the cytoplasm. Clear‐cell atypical fibroxanthoma is a rare variant of atypical fibroxanthoma that should be differentiated from other clear‐cell neoplasms of the skin.
The onychomatricoma: an electron microscopic study
Authors: Kint A. , Baran R. , Geerts M.L.
Published: April 2006

The electron microscopic findings in the onychomatricoma are described. In the proximal zone of the onychomatricoma, basal cells have various aspects, some being lacunar while others have only a limited cytoplasmic rim containing mitochondria and tonofilaments. In the parakeratotic cell columns the cells elongate and homogenized tonofilaments appear. Around the lacunae the cells are poorly differentiated and their cytoplasm is granular. It can be concluded that in an onychomatricoma the basal cells have a decreased amount of tonofilaments and desmosomes and that their evolution is not uniform. The tumour can be considered as being the result of a disturbed differentiation of nail matrix cells.
Encapsulated fat necrosis in a patient with Ehlers‐Danlos syndrome
Authors: Ohtake Naoki , Gushi Akira , Matsushita Shigeto , Kanzaki Tamotsu
Published: April 2006

Mobile encapsulated lipoma, first described by Sahl in 1978 (1), is characterized by its great mobility within subcutaneous adipose tissue and presentation with or without tenderness when the nodules are manipulated. This lipoma's histopathology is very characteristic; i.e., it consists of mature viable or degenerative lipocytes encapsulated by fibrous tissue. We report a case of this so‐called mobile encapsulated lipoma involving a patient with Ehlers‐Danlos syndrome. This case is the first report of mobile encapsulated lipoma in a patient with a disease of this type. We discuss its pathogenesis and the nomenclature for these lesions.
Detection of numerical chromosomal aberrations in malignant melanomas using fluorescence in situ hybridization
Authors: Matsuta Mayumi , Imamura Yuko , Matsuta Morimasa , Sasaki Kohsuke , Kon Saiichi
Published: April 2006

To evaluate the numerical chromosomal aberration i malignant melanoma, we have applied fluorescence in situ hybridization (FISH) with repetitive DNA probes specific for chromosomes 1, 6, 7, 9, 10, and 17 on 24 fresh malignant melanomas (primary: 14, metastatic: 8).

We defined a tumor that had copies with more than 3 spots as chromosomal gain. Chromosomal copy number gain was found in 40.9% of the cases for chromosome 7, 27.2% for chromosome 6, 27.2% for chromosome 17, 22.7% for chromosome 9 and 10, and 4.5% for chromosome I. Monosomy was found in 54.5% of the cases for chromosome 10, 36.5% for chromosome 9, 27.2% for chromosome 6, 22.7% for chromosome17, and 18.1% for chromosome 1 and 7 The most frequent numerical alterations were seen in chromosomes 6, 7, 9 and 10.

Gain of chromosome 6 and 7 and/or losses of chromosome 9 and 10 may play an important role in the tumorigenesis and development of malignant melanomas.
Expression of CD44 isoforms and β1,6‐branched oligosaccharides in human malignant melanoma is correlated with tumor progression but not with mettastatisc potential
Authors: Seelentag Walter K.F. , Böni Roland , Günthet Ursuls , Futo Eva , Burg Günther , Heitz Philippu U. , Roth Jürgen
Published: April 2006

CD44, a family of closely related glycoproteins generated by alternative splicing, as well as the increased β1,6‐branching of Asn‐linked oligosaccharides (β1,6‐branches), have been implicated in tumor progression and metastasis. We have investigated the expression of CD44 standard (CD44s), various CD44 splice variants (CD44v3,‐ v4,‐ v5,‐ v6 and‐ v9), and of β1,6‐branches in a total of 37 paraffin‐embedded human primary melanomas and metastases.

Out of the 28 studied primary melanomas, 27 were positive for CD44s, 21 for CD44v5 (cytoplasmic staining) and 26 for β1,6 branches. Furthermore, superficial spreading melanomas showed a significant (p=0.004) stronger staining for CD44s than the thick (> 1.5 mm) nodular melanomas, whereas no significant difference was found with regard to staining for CD44v5 and β1,6‐branches. Eight of the 9 studied melanoma metastases were positive for CD44s, 6 for CD44v5 (cytoplasmic staining) and 7 for β1,6‐branches. No CD44v3, ‐v4, ‐v6 and ‐v9 could be detected in any of the tumors. On average, metastases as compared to primary tumors, exhibited a significant (p=0.002) weaker staining for CD44s. However, metastasizing melanomas could not be distinguished from non‐metastasizing ones based on CD44 immunostaining.
Cutaneous leiomyomas lack estrogen and progesterone receptor immunoreactivity
Authors: McGinley Kent M. , Bryant Susan , Kattine Anthony A. , Fitzgibbon James F. , Googe Paul B.
Published: April 2006

Gonadotropin‐releasing hormone analog therapy is useful in treating uterine and some extrauterine smooth muscle tumors. These smooth muscle tumors have been demonstrated to have estrogen receptor and progesterone receptor immunoreactivity. The estrogen receptor and progesterone receptor immunoreactivity of smooth muscle tumors of the skin has not been reported. We evaluated 15 examples of cutaneous leiomyomas for estrogen receptor and progesterone receptor with ER‐1D5 antibody and PGR‐1A6 antibody. None of the 15 cutaneous leiomyomas demonstrated positive staining by this method. The tumorigenesis of cutaneous leiomyomas does not appear to be related to estrogen or progesterone receptor‐mediated effects.
I‐J as an Inducible T Cell Receptor for Self
Authors: Tada Tomio , Uracz Wojciech , Abe Ryo , Asano Yoshihiro
Published: April 2006

“Jedenfalls, wenn man davorsteht, dann sieht man sich selbstaber eben nicht wie in einem gewöhnlichen Spiegel, versteht sich. Man sieht nicht sein Äusseres, sondern man sieht sein wahres inneres Wesen. so wie es in Wirklichkeit beschaffen ist. Wer da durch will, der muß ‐ um es mal so auszudrücken ‐in sich selbst hineingehen.”

Die undendliche Geschichte, bei Michael Ende, K. Thiehemanns Verlag, Stuttgart, 1979.
Distinctive Developmental Origins and Specificities of Murine CD5+ B Cells
Authors: Hardy Richard R. , Carmack Condie E. , LI YUE Sheng , Hayakawa Kyoko
Published: April 2006

CD5+ B cells constitute a small fraction of cells in the spleen of adult mice that exhibit numerous features serving to distinguish them from the bulk of IgD++CD5−“conventional” B cells. In this review we focus on two major questions relating to this population: 1) the relationship of CD5+ B cells to other B cells; and 2) the distinctive enrichment of particular autoreactive specificities in this subset. The nature of their origins is clarified by a thorough analysis of intermediate stages of early B‐cell development in both fetal and adult tissues. The reactivity to bromeliad‐treated mouse red blood cells serves as a prototype system for the investigation of biased specificities in CD5+ B cells. These lines of investigation lead us to propose that CD5+ B cells in the adult are the remnant of a distinct fetal B‐cell differentiation pathway wherein selection of cells from this fetal/neonatal population into the adult long‐lived pool results in the over‐expression of certain germline‐encoded autoreactivities.
The Potential Roles of Endogenous Retroviruses in Autoimmunity
Authors: Nakagawa Kaku , Harrison Leonard C.
Published: April 2006

Endogenous retroviruses (ERVs) are estimated to comprise up to 1% of human DNA. While the genome of many ERVs is interrupted by termination codons, deletions or frame shift mutations, some ERVs are transcriptionally active and recent studies reveal protein expression or particle formation by human ERVs.

ERVs have been implicated as aetiological agents of autoimmune disease, because of their structural and sequence similarities to exogenous retroviruses associated with immune dysregulation and their tissue‐specific or differentiation‐dependent expression. In fact, retrovirus‐like particles distinct from those of known exogenous retroviruses and immune responses to ERV proteins have been observed in autoimmune disease. Quantitatively or structurally aberrant expression of normally cryptic ERVs, induced by environmental or endogenous factors, could initiate autoimmunity through direct or indirect mechanisms.

ERVs may lead to immune dysregulation as insertional mutagens or cis‐regulatory elements of cellular genes involved in immune function. ERVs may also encode elements like tax in human T‐lymphotrophic virus type I (HTLV‐I) or tat in human immunodeficiency virus‐I (HIV‐I) that are capable of transactivating cellular genes. More directly, human ERV gene products themselves may be immunologically active, by analogy with the superantigen activity in the long terminal repeat (LTR) of mouse mammary tumour viruses (MMTV) and the non‐specific immunosnppressive activity in mammalian type C retrovirus env protein. Alternatively, increased expression of an ERV protein, or expression of a novel ERV pro‐tissue the result could be autoimmune disease. The adjective, paraneoplastic, would only seem appropriate if autoimmunity and tumour were temporally associated. Thus, ERVs could be viewed as being at the interface between tumour immunity and autoimmunity, the pivotal balance depending on the prevailing overlap between 'self and‘non‐self. Although pure speculation, this hypothesis is consistent with the emerging body of molecular evidence that ERVs play a key role in regulating immune functions in health and disease.
Human NK cells: their ligands, receptors and functions
Authors: Reyburn Hugh , Mandelboim Ofer , Valés‐Goméz Mar , Sheu Eric G. , Pazmany Laszio , Davis Daniel M. , Strominger Jack L.
Published: April 2006

Summary: The expression, or lack thereof, of class I MHC glycoproteins has a marked influence on natural killer cell function. Cells which do not express class I MHC molecules are susceptible to lysis by NK cells, and transfection of these targets with class I MHC genes can render these cells resistant to NK attack. This inhibition of NK‐killing is mediated by a novel family of receptors expressed mainly on NK cells, but also found on some T‐cells. The function of these class I MHC binding receptors when expressed on T‐cells is discussed also and a novel co‐stimulatory activity of NKAR described. Lastly, a novel mechanism by which human cytomegalovirus evades immune surveillance by NK cells is documented.
Signal transduction by human NK cell MHC‐recognizing receptors
Authors: Binstadt Bryce A. , Brumbaugh Kathryn M. , Leibson Paul J.
Published: April 2006

Summary: Cells may be protected from natural killer (NK)‐cell‐mediated killing by the expression of specific MHC class I complexes. This protective effect is due to the expression on NK cells of MHC class I‐recognizing receptors which, upon ligation, transduce potent inhibitory signals into the NK cells. The molecular signalling mechanisms employed by the human NK‐cell MHC‐recognizing killer cell inhibitory receptors (KIR) and CD94 are the focus of this review, A sequential model of KIR signalling involving lck‐dependent tyrosine phosphorylation of KIR and subsequent association of KIR with the SH2 ‐containing tyrosine phosphatase, SHP‐1, is presented. We explore how engagement of either KIR m CD94 modulates the protein tyrosine kinase‐dependent biochemical signals responsible for activation of NK‐ceil cytotoxic function. Additionally, we discuss models of inhibitory signalling proposed for each of the lymphocyte lineages, emphasizing that disparate molecular mechanisms may be utilized by ceils to produce similar biological responses.
Cords, channels, corridors and conduits: critical architectural elements facilitating cell interactions in the lymph node cortex
Authors: Gretz J. Elizabeth , Anderson Arthur O. , Shaw Stephen
Published: April 2006

: The lymph node cortex is a critical site for encounter between recirculating T cells and their specific antigens. Due to its extreme plasticity, little is understood of the underlying functional unit of the lymph node cortex, the paracortical cord. The idealized paracortical cord (approximately 100 nm by 1000 μm) stretches from a medullary cord to the base of a B‐cell follicle. In cross‐section, a cord can be visualized as a set of nested cylinders consisting of spaces bounded by cells. The spaces are: i) the lumen of the high endothelial venule (HEV), ii) perivenular channels ‐ narrow potential spaces (0.1 μm) tightly encircling the HEV, iii) corridors – broad spaces (10–15 μm) constituting the majority of the parenchyma, and iv) the cortical sinus. In addition to these spaces for cell traffic, the conduit (fifth space) is a special delivery system for the transit of soluble factors to the HEV and emigrating lymphocytes. The cellular barriers between these spaces are high endothelium, tibroblastic reticular cells, or sinus‐lining cells. This review describes the spaces of the paracortical cord and their cellular boundaries, outlines the movement of cells and fluids through these spaces, and discusses how this anatomy affects the efficiency of surveillance by T cells.
Dendritic cells in the T‐cell areas of lymphoid organs
Authors: Steinman Ralph M. , Pack Maggie , Inaba Kato
Published: April 2006

Summary: Substantial numbers of dendritic cells (DCs) are found in the T‐cell areas of peripheral lymphoid organs such as the spleen, lymph node and Peyer's patch. By electron microscopy these DCs (also called interdigitating cells) form a network through which T cells continually recirculate. The cytological features of DCs in the T‐cell areas, as well as a number of markers detected with monoclonal antibodies, are similar to mature DCs that develop from other sites such as skin and bone marrow. Some markers that are expressed in abundance are: MHC II and the associated invariant chain, accessory molecules such as CD40 and CD86, a multilectin receptor for antigen presentation called DEC‐205, the integrin CD11c, several antigens within the endocytic system that are detected by monoclonal anti‐bodies but are as yet uncharacterized at the molecular level, and, in the human system, molecules termed Sl00b, CD83 and p55. DCs in the periphery can pick up antigens and migrate to the T‐cell areas to initiate immunity However, there are new observations that DCs within the T‐cell areas also express high levels of self‐antigens and functional fas‐ligand capable of Inducing CD4+ T‐cell death. We speculate that there are at least 2 sets of DCs in the T‐cell areas, a migratory myeloid pathway that brings in antigens from the periphery and induces immunity, and a more resident lymphoid pathway that presents self‐antigens and maintains tolerance.
The changing preference of T and B cells for partners as T‐dependent antibody responses develop
Authors: MacLennan Ian C. M. , Gulbranson‐Judge Adam , Toellner Kai‐Michael , Casamayor‐Palleja Montserrat , Sze Daniel M ‐Y. , Chan Eric Y‐T , Luther Sanjiv A. , Orbea Hans Acha
Published: April 2006

Summary: Recirculating virgin CD4+ T cells spend their life migrating between the T zones of secondary lymphoid tissues where they screen the surface of interdigitating dendritic cells. T‐cell priming starts when processed of interdigitating dendritic cells. T‐cell priming starts when processed peptides or superantigen associated with class II MHC molecules are recognised. Those primed T cells that remain within the lymphoid tissue move of the outer T zone, where they interact with B cells that have taken up and processed antigen. Cognate interaction between these cells initiates immunoglobulin (Ig) class swith‐recombination and proliferation of both B and T cells; much of this growth occurs outside the T zones. B cells both B and T cells; much of this growth occurs outside the T zones. B cells migrate to follicles. Where they form germinal centres, and to extrafollicular sites of B‐cell growth, where they differentiate into mainly short‐lived plasma cells. T cells do not move to the extrafollicular foci but to the follicles; there they proliferate and are subsequently involved in the selection of B cell that have mutated their Ig variable‐region genes. During primary antibody responses T‐cell proliferation in follicles produces many times the peak number of T cell found in that site; a substantial proportion of the CD4+ memory T‐cell pool may originate from growth in follicles.
Unique site of IgG2a and rheumatoid factor production in MRL/lpr mice
Authors: Jacobson Bruce A. , Rothstein Thomas L , Marshak‐Rothstein Ann
Published: April 2006

Summary: MRL/lpr (Fas‐deficient) mice develop an autoimmune syndrome associated with excessive production of autoantibodies. A significant portion of these autoantibodies are IgG2a molecules specific for many of the autoantigens recognized by the sera of patients with systemic lupus erythematosus. In addition, MRL/lpr mice make exceedingly high titers of IgG or IgA rheumatoid factors (RF) specific for autologous IgG2a, The microenvironment of the IgG2a‐producing B cells as well as the prototypic RF autoantibodies was determined by a combination of immunohistochemical and m situ hybridization techniques. In contrast to the anti body‐producing cells present in mice responding to conventional foreign antigens, both IgG2a+ and RF+ B cells were found to be densely clustered in the T‐cell‐rich inner periarteriolar lymphatic sheath of the spleen. These results suggest that conventional antibody and autoantibody production in MRL/lpr mice may be mechanistically distinct processes.
Germinal center development
Authors: Liu Yong‐Jun , Arpin Christophe
Published: April 2006

Summary: Using a set of surface markers Including igD and CD38, human tonsillar B cells were classified into discrete subpopulations. Molecular and functional analysis allowed us to identify: i) two sets of naive B cells (Bml and Bm2); ii) germinal center founder cells (Bm2′); iii) an obscure population of germinal center B cells, displaying a high load of somatic mutations in IgV genes, Cμ to Cδ switch and preferential Igλ light chain usage: these cells may represent the precursors of normal and malignant IgD‐secreting plasma cells; iv) the centroblasis (Bm3) in which somatic mutation machinery is activated; v) the centrocytes (Bm4) in which isotype switch occurs; vi) the memory B cells. The characterization of these sub‐populations showed that: i) programmed ceil death is set before somatic mutations, possibly providing an efficient way for affinity maturation; ii) only high affinity centrocytes are allowed to switch isotype; iii) CD40‐hgation inhibits plasmacytic differentation of mature B lymphocytes; Iv) memory B cells preferentially differentiate into plasma cells; v) IgD isotype switch occurs in normal B cells; vi) receptor editing may be induced by somatic mutations in germinal centers. We also characterized two types of antigen ‐presenting cells in germinal centers: follicular dendritic cells that select high affinity B cells, and a new subset of germinal center dendritic cells that activate germinal center T cells.
The anatomical basis of intestinal immunity
Authors: Mowat Allan McI. , Viney Joanne L.
Published: April 2006

Summary: The lymphoid tissues associated with the intestine are exposed continuously to antigen and are the largest part of the immune system. Many lymphocytes are found in organised tissues such as the Peyer's patches and mesenteric lymph nodes, as well as scattered throughout the lamina propria and epithelium of the mucosa itself. These lymphocyte populations have several unusual characteristics and the intestinal immune system is functionally and anatomically distinct from other, peripheral compartments of the immune system. This review explores the anatomical and molecular basis of these differences, with particular emphasis on the factors which determine how the intestinal lymphoid tissues discriminate between harmful pathogens and antigens which are beneficial, such as food proteins or commensal bacteria. These latter antigens normally provoke Immunological tolerance, and inappropriate responses to them are responsible for immunopathologies such as food hypersensitivity and inflammatory bowel disease. We describe how interactions between local immune cells, epithelial tissues and antigen‐presenting cells may he critical for the induction of tolerance and the expression of active mucosal immunity In addition, the possibility that the intestine may act as an extrathymic site for T‐cell differentiation is discussed. Finally, we propose that, under physiological conditions, immune responses to food antigens and commensal bacteria are prevented by common regulatory mechanisms, in which transforming growth factor p plays a critical role.
Verrucous carcinoma of the mouth
Authors: Jacobson Selwyn , Shear Mervyn
Published: April 2006

This paper describes a survey of 198 cases of oral verrucous carcinoma reported in the literature and a study of a further 15 personally‐observed cases. Elderly Caucasoid males are most frequently affected, although in the South African group there were 10 females and 5 males. The lesion, which classically has a verrucous surface, may be small or more extensive. The cheek mucosa and the alveolar mucosa/gingiva are the sites most commonly involved. Sometimes more than one area is affected in the same patient and the tumor may be associated with other lesions such as leukoplakia, pseudo‐epitheliomatous hyperplasia and frank carcinoma. The etiology is uncertain but tobacco usage in any form appears to be implicated. The tumor is locally invasive and 6 of our series of 15 recurred after surgical removal. It does not metastasize unless it undergoes anaplastic transformation, which it frequently does if treated with radiotherapy. The correct treatment is therefore wide surgical excision. Histologically, there is a typical abrupt margin. The tumor has surface papillary projections and infiltrating broad, blunt rete pegs which form a “pushing margin”. The epithelium is generally well‐differentiated but there may be a high mitotic index and there may be an appearance of epithelial atypia if the epithelium is inflamed. Keratin is usually present on the surface and in the crevices of the deep invaginations but may be absent from tumors involving non‐keratinizing surfaces.
Familial gingival fibromatosis: An unusual pathology
Authors: Farrer‐brown G. , Lucas R. B. , Winstock D.
Published: April 2006

Unusual histological appearances of the gingival tissue of a father and three daughters with familial gingival fibromatosis are described. The gingival lesions of all the patients were similar and showed a marked fibroblastic activity, with scattered small calcified particles and irregular trabeculae of bone, and ulceration and inflammation of the overlying epithelium. The appearances resembled those of the common non‐familial fibrous epulis and contrasted strikingly with the dense, mature, relatively acellular bundles of collagen more usually encountered in familial gingival fibromatosis.