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Biomedical subjects

T Simonart

Publications and source records attributed to T Simonart.

At least 55 records · Page 3Linked to original sources

Langerhans' cell histiocytosis arising at the site of basal cell carcinoma excision.

Langerhans' cell histiocytosis (LCH) may be associated with a wide range of neoplastic disorders. However, the combination of a LCH and a basal cell carcinoma (BCC) of the skin still represents a highly unusual condition. In this publication, we report the case of a 48-year-old woman who developed a localized LCH involving the area of a previously excised BCC. Although the exact pathogenesis of this peculiar association remains yet to be elucidated, the hypothesis of an exaggerated Langerhans' cell reaction in response to the underlying BCC appears to be attractive.

Basal Cell Carcinoma↗

Iron chelators inhibit the growth and induce the apoptosis of Kaposi's sarcoma cells and of their putative endothelial precursors.

Iron is suspected to be involved in the induction and/or progression of various human tumors. More particularly, iron may be involved in the pathogenesis of Kaposi's sarcoma, a tumor of probable vascular origin. This study was designed to investigate the effect of iron deprivation on Kaposi's sarcoma. The effects of iron chelators and iron deprivation associated with serum withdrawal were investigated on Kaposi's sarcoma-derived spindle cells, on a transformed Kaposi's sarcoma cell line (Kaposi's sarcoma Y-1) and on endothelial cells, which are the probable progenitors of Kaposi's sarcoma cells. Desferrioxamine and deferiprone, two chemically unrelated iron chelators, induced a time- and concentration-dependent inhibition of endothelial and Kaposi's sarcoma cell growth. The inhibition of cell growth was associated with a decrease in Ki-67 and in both stable and total proliferating cell nuclear antigen expression. Inhibition of the progression through the G1-phase of the cell cycle was further evidenced by decreased expression of cyclin D1 and of p34 cyclin-dependent kinase 4. Terminal deoxynucleotidyl transferase-mediated desoxyuridinetriphosphate nick end labeling assay, flow cytometry with annexin-V-fluorescein and morphologic analysis indicated that iron chelation also induced a time- and concentration-dependent apoptosis. This apoptotic effect was prevented by the addition of exogenous iron. Induction of iron deprivation in the culture medium by serum withdrawal led to similar cell cycle effects, which, however, could only be partly reverted by the addition of exogenous iron. In conclusion, these results show that iron deprivation inhibits the growth and induces the apoptosis of Kaposi's sarcoma cells and of their putative endothelial precursors. This suggests that iron chelators may represent a potential therapeutic approach for the treatment of Kaposi's sarcoma.

Apoptosis↗

Relationship between endometriotic foci and nerves in rectovaginal endometriotic nodules.

The histological relationships between fibrotic tissue, endometriotic foci and nerves in the rectovaginal septum endometriotic or adenomyotic nodule were studied. This is considered to be one of the most severe forms of deep endometriosis. Masson's trichrome staining for fibrosis detection and immunohistochemistry with the S100 monoclonal antibody for nerve detection were performed in 28 rectovaginal endometriotic nodules from patients presenting with severe dysmenorrhoea and deep dyspareunia (23 patients with no other endometriotic location or potential cause of pain at laparoscopy and ultrasonography; five patients with multiple pelvic endometriotic localizations and other potential causes of pain at laparoscopy). Patients were allocated to two groups on the basis of their preoperative pain scores for pelvic pain, dysmenorrhoea and deep dyspareunia (group 1, score >7; group 2, score < or =7). For each symptom, the mean number of nerves and endometriotic lesions per high-power field and the mean largest diameter of the lesions were not statistically different in groups 1 and 2. The mean percentages of nerves located within the fibrosis of the nodule and within endometriotic lesions were significantly higher in group 1 than in group 2. Among nerves located within endometriotic lesions, there was a significantly higher proportion showing intraneurial and perineurial invasion by endometriosis in group 1 than in group 2. In rectovaginal endometriotic nodules, there was a close histological relationship between nerves and endometriotic foci, and between nerves and the fibrotic component of the nodule. We postulate that such topographical relationships could at least partially explain the strong association between this lesion and pain.

Adult↗

Phenotypic characteristics of Kaposi's sarcoma tumour cells derived from patch-, plaque- and nodular-stage lesions: analysis of cell cultures isolated from AIDS and non-AIDS patients and review of the literature.

BACKGROUND: Kaposi's sarcoma (KS) is commonly thought to be derived from endothelial cells because of the predominant expression of endothelial markers in KS lesions. However, the heterogeneity of the spindle-cell compartment makes the precise lineage relationship of KS tumour cells unclear. Cultured KS-derived spindle cells constitutively overexpress antiapoptotic proteins and exhibit invasive properties, which suggests that they may adequately represent the tumour cells of KS. OBJECTIVES: We aimed to investigate the expression of a wide variety of immunohistochemical markers by spindle cells derived from patch-, plaque- and nodular-stage lesions from patients with iatrogenic, sporadic and acquired immune deficiency syndrome-related KS, and to review the data reported by other laboratories. METHODS: Cells from six KS cell cultures derived from four subjects were examined by immunostaining. RESULTS: Comparison of these data indicates that KS-derived spindle cells generally express myofibroblast antigens but lack endothelial and/or leucocyte markers. CONCLUSIONS: As the myofibroblast phenotype is not the predominant feature of KS tissues, our findings further substantiate the view that the in vivo dominant endothelial population represents a reactive hyperplasia rather than the true KS tumour process.

Acquired Immunodeficiency Syndrome↗

Role of iron in dermatology.

Iron is involved in several biological reactions and is essential to almost all forms of life. In contrast, iron is potentially toxic. It may participate in many dermatological disorders, including pigmentation changes, inflammation, porphyrias, infections and cancers. The involvement of iron in these disorders entails a variety of mechanisms, including among others simple deposition processes, activation or inactivation of enzymatic systems, impairment of phagocyte functions and interference with apoptosis. A better understanding of the role of iron might provide novel therapeutic strategies based on iron-chelating and/or anti-oxidant agents.

Humans↗

[Primary and isolated cutaneous lymphomatoid granulomatosis following heart-lung transplantation].

BACKGROUND: Lymphomatoid granulomatosis is an Epstein-Barr virus-associated B-cell lymphoproliferative disease. It is angiocentric and angiodestructive and involves the lungs, central nervous system and skin. Exclusive cutaneous involvement is rare and may be associated with a better outcome. Contrarily to the extra-cutaneous forms of lymphomatoid granulomatosis, it is difficult or impossible to detect Epstein-Barr virus DNA sequences in primary and isolated cutaneous lymphomatoid granulomatosis. CASE REPORT: A 54-year-old woman developed erythemato-violaceous lesions on both legs 3 years after a heart-lung transplantation. The diagnosis of erythema multiforme and of drug-induced vasculitis were first made. Because of fever and of the rapid extension of the lesions, the patient was hospitalized. The histologic examination of the first lesions showed a perivascular infiltrate, without epidermotropism, composed of histiocytes, lymphocytes and plasma cells. Immunohistochemistry revealed the presence of a predominantly T-cell infiltrate with some large B cells. Subsequent biopsies were diagnosed as high grade B-cell lymphoma. Polymerase chain reaction analysis as well as in situ hybridation study showed the presence of Epstein-Barr virus load in the lesions. There was however no serologic evidence of viral reactivation. Extensive systemic evaluation revealed no visceral or bone marrow involvement. Despite antiviral treatment and CHOP polychemotherapy, the patient died 3 months after her admission. DISCUSSION: This observation of lymphomatoid granulomatosis is particular because of its exclusive cutaneous involvement associated with a fulminant evolution to high grade B lymphoma. The presence of a context of iatrogenic immunosuppression underlies the role of altered immune cellular functions in the initiation and/or progression of lymphomatoid granulomatosis and strengthens the role of a viral agent in its pathogenesis. We suggest that the presence of Epstein-Barr virus, which is generally not associated with the isolated cutaneous forms of lymphomatoid granulomatosis, may have played a role in this fulminant evolution to high grade B lymphoma.

Diagnosis, Differential↗

Early- and late-stage Kaposi's sarcoma lesions exhibit similar proliferation fraction.

There are few studies on the proliferative activity of cells in Kaposi's sarcoma. It remains unclear whether the different progressive histologic stages of Kaposi's sarcoma correlate with the proliferative activity of the tumor. To clarify this issue, we studied the Ki-67 proliferation index in 40 specimens of acquired immune deficiency syndrome-related Kaposi's sarcoma in correlation with the histologic stage of the lesions. The mean proliferation index in our combined material was rather low (8%, range 1-20%) and there was no significant difference among the different stages of the disease. Contrary to a common and probably misleading concept, our results suggest that the histologic progression of the Kaposi's sarcoma is not related to an increase of the proliferative compartment.

Acquired Immunodeficiency Syndrome↗

Penile intraepithelial neoplasia overlying Kaposi's sarcoma lesions: role of viral synergy?

Several viral agents have been detected in the lesional tissue of Kaposi's sarcoma (KS). Their precise oncogenic role remains to be determined. A 32-year-old heterosexual man with acquired immunodeficiency syndrome (AIDS) who had penile lesions of KS with overlying epithelial changes characteristic of intraepithelial neoplasia associated with concurrent infection by human papillomavirus (HPV) and human herpesvirus 8 (HHV-8) is reported. The absence of viral DNA from uninvolved skin suggests that this coinfection is more than coincidental and may involve synergy between these viruses, as has already been suggested for HPV and herpes simplex 2 virus.

Acquired Immunodeficiency Syndrome↗

In vitro sensitivity of Kaposi's sarcoma cells to various chemotherapeutic agents including acyclic nucleoside phosphonates.

The involvement of a viral agent in the pathogenesis of Kaposi's sarcoma (KS) points to antiviral agents as possible therapeutic and/or prophylactic options in the management of the disease. In the present study we investigated the antiproliferative effects of various chemotherapeutic agents, including acyclic nucleoside phosphonates, on the growth of KS-derived cells. Nested PCR amplification demonstrated that these cells do not contain human herpesvirus 8 (HHV-8) DNA sequences. The cytotoxicity of the chemotherapeutic compounds was less pronounced in KS cells than in human dermal microvascular endothelial cells, which are considered to be the normal counterpart of KS cells. Stimulation of KS cells with basic fibroblast growth factor (bFGF) and correction of the IC50 values by the doubling times revealed that the apparent chemotherapeutic resistance of KS cells could mainly be attributed to the long doubling times of these cells. bFGF-stimulated KS cells still exhibited no particular sensitivity to the acyclic nucleoside phosphonates whose activity extends to HHV-8, which is consistent with the absence of linear HHV-8 DNA synthesis in these cells. Our data suggest that neither anti-cancer agents nor antiviral agents such as the acyclic nucleoside phosphonates can discriminate efficiently between KS cells and normal endothelial cells.

Antineoplastic Agents↗

Pre-Kaposi's sarcoma: an expansion of the spectrum of Kaposi's sarcoma lesions.

We report on a lymphoedematous form of classic Kaposi's sarcoma (KS) in which characteristic purplish lesions were surrounded by atypical oedematous, flesh-coloured papules. Histological examination of these papular lesions revealed a proliferation of grouped, rather thick-walled capillaries with inflammatory infiltrates. Hot-start PCR amplification with KS 330-233 primer sequences demonstrated the presence of human herpesvirus 8 (HHV-8) sequences. In addition, cells isolated from these oedematous papules showed morphological and immunohistochemical features similar to those reported for KS-derived spindle cells. As a whole, these results suggest that these oedematous papular lesions represent pre-KS lesions and may expand the clinico-pathological spectrum of KS. The role of oedema in their induction is discussed.

Aged↗