[Epstein-Barr virus-associated cutaneous plasmacytoma post-solid organ transplantation]. / Plasmocytomes cutanés associés au virus Epstein-Barr chez les transplantés d'organes.

BACKGROUND: Post-transplantation lymphoproliferative disorders develop in 1 to 10p. 100 of organ transplant recipients and are frequently associated with Epstein-Barr virus (EBV). Among post-transplantation lymphoproliferative disorders, plasmacytoma with cutaneous involvement is exceptional. Association with EBV has been rarely reported in post-transplantation plasmacytomas and the latency type of EBV has never been characterized. We report 2 new cases of cutaneous monotype EBV-related plasmacytomas. CASE-REPORTS: Clinical presentation was a sub-cutaneous tumor on the thigh in the first case and an ulcerated nodule of the leg in the second case, occurring respectively 7 and 8 years after organ transplantation (liver transplantation and heart transplantation). In both lesions, tumor cells exhibited lambda light chain restriction and the association with EBV was confirmed using immunohistochemistry and in situ hybridization. The expression of EBV genes in tumor cells demonstrated type III latency. DISCUSSION: The classification of post-transplantation lymphoproliferative disorders is not well defined and some authors retain 3 categories. Among the latter, plasmacytomas have been rarely described. Cutaneous involvement is reported in 4 cases and an association with EBV in only 2 cases without description of viral latency. Clinical and histological features of post-transplantation plasmacytomas appear polymorphic. We report EBV-association in both cases, with a type III latency clearly demonstrated in one case, as has been reported in other lymphoproliferative diseases in patients with congenital or acquired immunodeficiency. We also discuss various possible therapeutic strategies for post-transplantation lymphoproliferative disorders.

[Cranial fasciitis of childhood]. / Fasciite du cuir chevelu (cranial fasciitis) de l'enfant.

INTRODUCTION: A nodule of the scalp in a child of less than eleven years should evoke a cranial fasciitis among other serious diagnoses. OBSERVATION: A four-month old infant had a firm and pink nodule at the left parietal level, exhibiting a slow growth since two months. It was excised. The pathologic sample showed spindle-shaped cells within a myxoïde matrix, with a strong reactivity for smooth muscle actin (immunohistochemical analysis). Diagnosis of cranial fasciitis was made. Due to the results of pathology, it was possible to rule out the diagnosis of sarcoma, therefore, no complementary work-up was performed. Evolution was favorable. DISCUSSION: Cranial fasciitis is a diagnosis to be considered when confronted with a firm nodule of the scalp in a infant or a young child, with or without bone involvement. This is a benign lesion but worrying pathological signs may exist, making diagnosis of benignity difficult. Exeresis of the lesion, even incomplete, protects the child from possible recurrence. Evolution is always good.

Dioxins in adipose tissue of non-occupationally exposed persons in France: correlation with individual food exposure.

We evaluated individual adipose tissue (subcutaneous lipomas) dioxin contamination in non-occupationally exposed persons living in France (adult patients undergoing a surgical ablation of benign lipomas), in relation to the corresponding individually evaluated mean daily dietary dioxin intake (DDDI). The diet survey (questionnaire) included information on consumption of meat, fish, milk and dairy products, from which the individual DDDI was calculated. Sixteen subjects participated in this study. DDDI ranged between 1.06 and 3.31 pg I-TEQ/kg body weight, bw (mean value: 2.05+/-0.72). Adipose tissue polychlorinated dibenzo-p-dioxins (PCDD)/polychlorinated dibenzofurans (PCDF) levels ranged between 18.5 and 76.9 pg I-TEQ/g lipids (mean value: 35.6+/-14.8). No relation was found between the DDDI and adipose tissue PCDD/PCDF concentrations. The mean DDDI in France does not fundamentally differ from those found in other industrialised countries, is within the range of 1-4 pg I-TEQ/kg/day recently suggested by WHO-ECEH/ICPS for the tolerable daily intake of dioxins. Adipose tissue PCDD/PCDFs levels are similar to levels in other European countries and USA without relation to sex or age, and can be considered representative European background concentrations. Globalisation of alimentary production leads to a similar food exposure in Western European countries, in spite of dioxins accidental selective contaminations that are epiphenomenon and thus do not have any impact in human dioxin background levels.

[Androgenic alopecia revealing an androgen secreting ovarian tumor]. / Alopécie androgénétique révélant une tumeur ovarienne androgéno-secrétante.

INTRODUCTION: Androgen-producing tumors of the ovary are rare in postmenopausal women and are revealed by severe virilization. Leydig hilus cell tumors are the most frequent postmenopausal virilizing tumors. In this report, an unusual and rare cause of alopecia due to Leydig cell hyperplasia within the wall of a simple cyst and in the ovarian hilus is described. OBSERVATION: An 80 year-old woman complained of a 10-year history of severe androgenic alopecia associated with very mild facial hirsutism, without others signs of virilization. Hormonal blood levels showed markedly elevated testosterone. Computed tomographic scan of the adrenals and the ovaries revealed an enormous left ovarian cystic mass. Bilateral hystero-ophorectomy was performed. Histological examination demonstrated bilateral Leydig cell hyperplasia within the wall of the cyst and in the right ovarian hilus. Two months postoperative hormonal evaluation demonstrated dramatically decreased plasma levels of testosterone. COMMENTARY: The clinical, X ray and histologic aspects of this case, although rare, show that the presence of virilization should lead to a search for an androgen-secreting ovarian or adrenal tumor.

The influence of highly active antiretroviral therapy on AIDS-associated Kaposi's sarcoma.

To assess the clinical and biological benefit of highly active antiretroviral therapy on AIDS-associated Kaposi's sarcoma (KS), 13 patients with AIDS-associated Kaposi's sarcoma (five pulmonary KS and eight cutaneous KS) were prospectively followed for a mean duration of 12 months. Six patients were treated with specific anti-KS chemotherapy before or simultaneously with the introduction of antiretroviral therapy. Clinical response was assessed according to the AIDS Clinical Trial Group (ACTG) criteria. CD4 cell counts, plasma HIV-1 RNA and human herpesvirus 8 (HHV-8) viraemia were measured at baseline and at different points. Among patients with pulmonary KS, we observed three complete responses (CR), one partial response (PR) and one progression. The median survival time after the diagnosis of pulmonary KS was 15 months with a median duration of the response after the discontinuation of specific chemotherapy for KS of 8 months. Among patients with cutaneous KS, we observed four CR, three PR and one stable response. A complete response was significantly associated with a reversal in HHV-8 viraemia (five of six vs. one of six; P = 0.02, Mann-Whitney test).

Distribution of human herpesvirus-8 latently infected cells in Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma.

Human herpesvirus 8 (HHV-8, also called KSHV) is linked to the etiopathogenesis of Kaposi's sarcoma (KS), multicentric Castleman's disease (MCD), and primary effusion lymphoma (PEL). The universal presence of HHV-8 in early KS has not yet been shown. We used a mAb (LN53) against latent nuclear antigen-1 (LNA-1) of HHV-8 encoded by ORF73 to study the distribution of the cell types latently infected by HHV-8 in patch, plaque, and nodular KS, MCD, and PEL. In early KS, HHV-8 is present in <10% of cells forming the walls of ectatic vessels. In nodular KS, HHV-8 is present in cells surrounding slit-like vessels and in >90% of spindle cells, but not in normal vascular endothelium. In addition, HHV-8 colocalizes with vascular endothelial growth factor receptor-3 (VEGFR-3), a marker of lymphatic and precursor endothelium. In early KS lesions, VEGFR-3 is more extensively expressed than LNA-1, indicating that HHV-8 is not inducing the proliferation of VEGFR-3-positive endothelium directly. In MCD, HHV-8 is present in mantle zone large immunoblastic B cells. No staining for LNA-1 is seen in samples from multiple myeloma, prostate cancer, and angiosarcoma, supporting the absence of any etiological link between these diseases and HHV-8.

Ultrastructural and immunohistochemical studies of the periendothelial matrix in human melanoma: evidence for an amorphous matrix containing laminin.

Angiogenesis and the extracellular matrix are fundamental to tumor progression from in situ to invasive and metastatic disease. Laminin, a major glycoprotein integrated into basement membranes, is observed in angiogenesis and tumorigenesis. A recent study described an association between melanoma cells and endothelial cells via an amorphous matrix containing laminin. In the current study, we have examined 45 cases of human primary and metastatic melanomas by electron microscopy for the presence of an amorphous matrix. We observed an amorphous matrix without a clearly delineated lamina or basement membrane in 41 of the 45 melanomas studied. 28 cases with tissue blocks available for study were examined by immunohistochemistry for the expression of laminin and type IV collagen. We observed the presence of an angiocentric matrix containing laminin in 24 of the 28 melanomas studied. Since laminin is involved in tumor migration, the presence of laminin between melanoma cells and small vessels suggests a role for this material in periendothelial tumor migration. However, further study is required to characterize the nature of this material and the mechanisms involved.

[Absence of HHV-8 virus detected in immature hemangiomas in infants]. / Absence de détection du virus HHV-8 dans les hémangiomes immatures du nourrisson.

INTRODUCTION: The aim of our study was to search for the presence of HHV-8 DNA sequences in Biopsy specimens from hemangioma of the infancy. MATERIAL AND METHODS: The study included 9 biopsies from hemangioma. DNA of human beta-globin gene and HHV-8 were searched for by PCR using specific primers. Amplified products were revealed after an hybridization with an internal probe digoxigenin-labelled. RESULTS: Human beta-globin gene could be detected in all samples illustrating the absence of PCR inhibitor. HHV-8 could never be detected in samples analyzed. DISCUSSION: Our study does not imply any causative role of HHV-8 in the pathogenesis of hemangioma. This result must be confirmed by serologic studies.

[Kasabach-Merritt syndrome on a congenital tufted angioma]. / Syndrome de Kasabach-Merritt sur angiome en touffes congénital.

INTRODUCTION: Kasabach-Merritt syndrome is a very rare disease of infancy, with profound thrombocytopenia and a mild to severe consumption coagulopathy; this biological phenomenon is difficult to control. CASE REPORT: A 1-month old boy had a congenital plaque-like lesion in the calf. It was a biopsy-proven tufted angioma. Five weeks later, Kasabach-Merritt syndrome developed. After failure of ticlopidine + aspirin, and oral betamethasone treatment, thrombocytopenia was cured with vincristine treatment, then the leg lesion slowly continued to shrink after cessation of the treatment. It had disappeared before the age of 1 year. DISCUSSION: We highlighted two points: 1) Kasabach Merritt does not appear as a complication of a classic hemangioma (infantile, "cellular", "capillary", involuting-type), as it has long been thought. In our experience, it develops on a different endothelial cell proliferation, in this case a congenital tufted angioma, but it can also engraft on a kaposiform hemangioendothelioma. 2) These patients are difficult to treat because, up to now, no single treatment has given constant by good results. Vincristine was recently introduced in the treatment of Kasabach-Merritt syndrome, with excellent, rapid outcome. CONCLUSION: What seems a therapeutic progress in a difficult field needs further control.

[Cutaneous malacoplakia: a pediatric case]. / Malakoplakie cutanée: un cas pédiatrique.

INTRODUCTION: Cutaneous malakoplakia is an inflammatory disease characterized by granulomatous accumulation of distinctive phagocytic macrophages. It occurs mainly in visceral or orificial areas; the condition is rarely purely cutaneous, and appears to be extremely rare in childhood. CASE REPORT: A facial cutaneous crusted lesion was diagnosed as cutaneous malakoplakia in an immunocompetent child. The lesion had been excised twice and it had recurred, and the diagnosis was made possible only with a third biopsy, after a 2-year chronic expansion. This third biopsy revealed a dense granulomatous inflammation with numerous phagocytic histiocytes containing abundant fine granules and round Michaelis-Gutmann bodies, both staining with PAS, Perls and von Kossa. Biopsy cultures revealed only growth of two different streptococcus (group B) strains. The lesion resolved after a 4-month period of antibiotic therapy, including roxithromycin, ampicillin and trimethoprim-sulfamethoxasole. DISCUSSION: Diagnosis of malakoplakia is mainly made by histopathologic examination of tissue excision or biopsies. There are no specific clinical features. Most reported cases of this uncommon phagocytic reaction to common bacteria have developed in the genitourinary areas (71 p. 100); purely cutaneous localisation, as in our patient, are rare (4 p. 100). Intracytoplasmic granules may result from phagolysosomes and incomplete bacterial killing, with subsequent deposit of iron and calcium in the phagocytic macrophages. A number of reported cases have affected immunocompromised patients with either congenital immunodeficiency or secondary immunodeficiency. The most effective treatment option is based on a protracted antibiotherapy, using drugs that easily permeate the macrophages, e.g. quinolones and trimethoprim-sulfamethoxasole. Lesion may recur after surgical excision.

Angio-tumoral laminin in murine tumors derived from human melanoma cell lines. Immunohistochemical and ultrastructural observations.

Cells in tissues interact with each other and with the extracellular matrix as part of a structural and informational unit. During cancer progression, tumor cells participate in the formation of a neotissue involving other cells and matrix. We recently observed in melanoma an association between tumor and endothelial cells via an amorphous matrix containing free laminin. The pericytic location of melanoma cells in this angio-tumoral complex raised the question of an intramesenchymal migration of metastatic melanoma cells promoted by free laminin along the endothelium. However the respective roles of melanoma cells and endothelial cells in laminin secretion were not clear. In an attempt to clarify the latter issue, we injected into mice three human melanoma cells lines, one secreting laminin and two that did not, in order to identify the source of laminin secretion in the subsequent interactions between tumor cells and vascular endothelium. Using immunohistochemistry and electron microscopy we observed in all three cases an amorphous matrix containing laminin between tumor and endothelial cells. The fact that two cell lines did not secrete laminin suggests that the periendothelial/peritumoral laminin could be of endothelial origin. Given the presence of laminin alone during intramesenchymal angiogenesis and embryogenesis, we propose an analogous role for endothelial laminin in facilitating the migration of melanoma cells along the abluminal surface of the endothelium.

Prevalence of human herpesvirus 8 infection measured by antibodies to a latent nuclear antigen in patients with various dermatologic diseases.

BACKGROUND: Human herpesvirus 8 (HHV-8) has been detected in all epidemiological forms of Kaposi sarcoma (KS). The role of HHV-8 in dermatologic diseases other than KS is controversial. Some studies based on polymerase chain reaction findings suggest an association between HHV-8 and epithelial tumors of the skin, lymphoproliferative disorders, or pemphigus. OBJECTIVE: To assess the prevalence of antibodies against a latent nuclear antigen of HHV-8 in patients with various dermatologic diseases. DESIGN: An indirect immunofluorescence assay was used to search for HHV-8 antibodies. SETTING: Ambulatory or hospitalized patients from a university hospital associated with a research laboratory. PATIENTS: Eighty-three patients with various non-KS dermatologic diseases and 16 patients with KS who were seronegative for the human immunodeficiency virus. Controls were 100 healthy subjects living in the same area. RESULTS: Antibodies to HHV-8 were found in 100% (16/16) of the patients with KS and 3.6% (3/83) of the patients with non-KS dermatologic diseases: 1 patient with pemphigus vulgaris, 1 with discoid lupus erythematosus, and 1 with bullous pemphigoid. The prevalence of antibodies to HHV-8 in controls was 2% (2/100) and was not significantly different than the prevalence in patients with dermatologic diseases other than KS (P =.28). CONCLUSIONS: Our serologic study confirms the higher prevalence of HHV-8 antibodies in patients with KS and demonstrates that contrary to other human herpesviruses, HHV-8 is not a ubiquitous virus in France. We could not determine any causal association between HHV-8 and pemphigus or lymphoproliferative disorders of the skin.

Ultrastructural and immunohistochemical observations concerning laminin in B16 melanoma. Is an amorphous form of laminin promoting a non hematogenous migration of tumor cells?

The gravity of cancer is related to the propensity of tumor cells to migrate from a primary site to distant organs. It is generally accepted that tumor migration occurs in the vascular stream, via the endothelial basement membrane or lamina. A recent study identified in human malignant melanomas an angio-tumoral association (termed the angio-tumoral complex) characterized by an amorphous material juxtaposed between endothelial cells and tumor cells that contained laminin. The absence of any sign of intravasation and the pericytic location of tumor cells in this typical image raised the question of the role of these complexes in promoting tumorigenesis. Using the mouse B16 melanoma model, we observed an increase of angio-tumoral complexes with tumor progression, again without any evidence of intravasation. Given the role of laminin in migration and metastasis, we discuss a non hematogenous mechanism of tumor migration along the abluminal surface of endothelium.

Lack of evidence of human herpesvirus 8 DNA sequences in HIV-negative patients with various lymphoproliferative disorders of the skin.

Human herpesvirus 8 (HHV-8) is a new virus which has been reported in Kaposi's sarcoma and some lymphoproliferative disorders such as Castleman's disease and body-cavity-based lymphoma. Because HHV-8 shares homology with Epstein-Barr virus (EBV), we searched for the presence of HHV-8 DNA sequences in various cutaneous T- and B-cell lymphoma by the polymerase chain reaction (PCR). Forty-seven HIV-negative patients with cutaneous lymphoma or large plaque parapsoriasis were enrolled in the study. For the detection of HHV-8 DNA sequences we used PCR followed by a hybridization with a digoxigenin-labelled probe and nested-PCR. HHV-8 DNA sequences could only be detected in a patient with large plaque parapsoriasis. Our study does not suggest any direct implication of HHV-8 in the pathogenesis of most cutaneous lymphoma. Serological studies will be helpful to appreciate if there is an epidemiological link between HHV-8 and cutaneous lymphomas.