Summary Although frequently linked clinically with autoimmune disease, no immunogenetic basis for lichen sclerosus has ever been established. In this study, we examined in detail the HLA antigens of 84 patients with histologically proven disease, compared with 357 controls. Patients with lichen sclerosus did not have the expected HLA A1, B8, DR3, DQ2 autoimmune profile. Instead, DQ7 was present in 39 of 78 (50%) of patients compared with 89 (25%) controls (P <0.001). In addition, 61 of 78 patients (78%) had either DQ7, DQ8 or DQ9 antigens, or a combination of these, compared with 142 (40%) controls (P < 0.01). Raised levels of DQ7 correspond to a glutamic acid residue at position 45 of the DQB1 locus. Proline amino acids at position 55 of this DQB1 locus could explain the raised levels of DQ7, 8 and 9, and exert a secondary effect. There is preliminary evidence that the immunogenetic profile of patients with this disease may affect disease expression with regard to site and extent of involvement.
Inhibin is a polypeptide hormone produced by the granulosa cells of the ovary, and is present in body as dimers of vanous sies each compnsng an a-and a-subunit. Free forms of the a-subunit also circulate, and the presently available radioimmunoassay (Monash asy) cannot distinguish these from biologicaly active dimeric inhibin. Recently we described a new two-site enzyme immunoassay able for the first time to measure the kvels of dimeric inhibin throughout the human menstrual cycle. The sensitivity limit of this assay is 2 pg ml-' in human serum with cross-reactivity against activin of 0.05%. The normal range of inhibin in post-menopausal women is <5 pg mll, in pre-menopausal women 2 -80 pg ml (2 -10 pg ml iin the follicular phase, 40 -80 pg ml-' in the luteal phase). This assay was used to determine inhibin levels in sera from 15 (five pre-menopausal and ten post-menopausal) patients with granulosa cell tumours of the ovary. It was raised in a pre-menopausal patient preoperatively (261 pg ml -), in six post-menopausal patients (32, 43, 54, 66, 24
The increased staining for IFN-gamma, TNF-alpha, IL-1alpha, IFN-gamma receptor, CD25, CD11a and ICAM-1 suggest that the cytokine response in lichen sclerosus shares characteristics of the cytokine response in lichen planus and chronic wounds.
Background The clinical features of lichen sclerosus, which include atrophy, scarring, fragility and tendency to form ecchymoses with only slight trauma, suggest that there is an alteration in the extracellular matrix fibres that are responsible for the tensile strength of the dermis. However, the precise nature of these changes is poorly understood. Methods Biopsies from 16 patients with untreated, histologically confirmed, vulval lichen sclerosus were examined immunohistochemically using polyclonal antibodies to collagens I and III and a monoclonal antibody to elastin. Twelve of the lichen sclerosus specimens were also stained with a monoclonal antibody to fibrillin. Normal vulva tissue and patients’ uninvolved thigh were used as controls. Results In the lichen sclerosus specimens, collagens I and III stained with a more homogeneous pattern than in the control tissues. Reduced numbers of elastin fibres were seen in the zone of sclerosus in 15 of the 16 lichen sclerosus specimens. In the control tissue fibrillin fibres were seen as a fine network of fibres in the upper dermis arranged at right angles to and inserting into the basement membrane and forming a fine network throughout the dermis. In the lichen sclerosus specimens, although fibrillin microfibrils were still seen inserting at right angles into the basement membrane, below this the fibrillin staining was reduced in the upper dermis in 11 of the 12 lichen sclerosus specimens. The zone of reduced fibrillin staining was greatest in those specimens where the band of inflammation was deep in the dermis. Conclusions The distribution of collagens I and III, elastin and fibrillin are altered in lichen sclerosus and this is likely to contribute to the fragility, scarring and atrophy seen clinically in lichen sclerosus.
Summary The role of human papillomavirus (HPV) detection in the management of patients with persistent low-grade (mild dyskaryosis or less) cervical cytological abnormalities is unclear. We have analysed cytological matenal from 167 such patients both cytologically and by non-isotopic in situ hybridisation (NISH) for HPV 16. 18. 31 and 33 and consensus primer polymerase chain reaction (PCR) amplification followed by both generic and specific typing for these HPV types. Cervical intraepithelial neoplasia (CIN) 2 or 3 was present in 40 of 167 patients (23.9%), and the positive predictive values (PPVs) for the presence of CIN 2 or 3, of moderate or severe dyskaryosis at repeat cytology and an HPV-positive NISH and genenrc PCR signal were 100%, 66% and 42% respectively. The corresponding sensitivities were 48%, 68% and 87%. Addition of cytology to molecular analysis improved both PPV and sensitivity, the best combination being NISH and cytopathology (PPV 71%, sensitivity 87%). These data demonstrate that the presence of CIN 2 or 3 in patients with mild cytological abnormalities can be predicted by molecular detection of HPV in some cases, particularly when combined with cytological analysis. However, the magnitude of this prediction is dependent on the population of patients studied, and the clinical role of this approach therefore remains to be defined.Keywords: human papillomavirus; cervix, neoplasia; cytology Human papillomaviruses are present in a wide variety of intraepithelial lesions of squamous epithelium (de Villiers, 1989;Chang, 1990;Munoz et al., 1992;Schiffman. 1992), including those of the cervix uteri. The presence of certain HPV types (16, 18, 31, 33, 35 and others) is associated with high-grade lesions namely CIN 2 and 3 and invasive cervical carcinoma but these types are found less frequently in lowgrade lesions (CIN 1 and wart virus change only) and in patients with negative cervical biopsies (Munoz et al., 1992;Schiffman, 1992;Lorincz et al., 1993;Schiffman et al., 1993).This association suggests that the detection of these viral types in an individual patient might be predictive of the presence of a high-grade lesion or a high-risk of progression of a low-grade lesion. The morphology of signal produced by in situ hybridisation correlates with the presence of viral integration (Cooper et al., 1991a;Kristiansen et al., 1994), and in studies of CIN and invasive carcinoma this punctate pattern was found in all HPV-positive cervical carcinomas and 69% of HPV-positive CIN 3 lesions (Cooper et al., 1991 b,c). Moreover, it has been suggested that it is not merely the presence of high-risk HPV types but the amount of viral DNA which is predictive of a high-grade lesion (Cuzick et al., 1992), although the strength of this prediction varies between studies (Cuzick et al., 1992Herrington et al., 1992a;Bavin et al., 1993).The recommended management of patients with moderately and severely dyskaryotic cells present in a cervical smear is immediate referral for colposcopy and possible treatment (National Co...
Background: The pathophysiology of lichen sclerosus remains uncertain. The clinical features, including increased fragility and scarring, and the histology suggest that significant reorganisation of the extracellular matrix is occurring. Tenascin, fibrinogen and fibronectin are extracellular matrix components that play a significant role in tissue remodelling, for example during wound repair. Aim: To examine the distribution of tenascin, fibrinogen and fibronectin in vulval lichen sclerosus. Materials and Methods: Immunohistochemical staining was performed to study the distribution of tenascin, fibronectin and fibrinogen in 16 specimens of untreated vulval lichen sclerosus and 1 specimen of extragenital lichen sclerosus. Haematoxylin and eosin staining of the specimens was also performed to identify the position of the pale staining homogenous zone/zone of sclerosis and the inflammatory infiltrate below this. The control tissues studied included biopsies taken from the uninvolved thigh of 13 of the lichen sclerosus patients and 6 samples of normal vulva tissue obtained during gynaecological procedures from women of similar age to the lichen sclerosus women. Results: All the lichen sclerosus specimens demonstrated increased immunostaining of tenascin in the upper dermis and comparing this with the haematoxylin and eosin staining this corresponded to the zone of sclerosis with relatively little tenascin staining associated with the inflammatory band. In 14 out of the 16 vulval lichen sclerosus specimens and the extragenital lichen sclerosus specimen fibrinogen immunostaining was increased in the upper dermis which corresponded – in haematoxylin and eosin staining – to the zone of sclerosis. There was also slightly increased fibrinogen staining in the mid dermis which corresponded to the inflammatory band. Fibronectin staining was reduced in the upper dermis of 12 of the vulval lichen sclerosus specimens and the extragenital lichen sclerosus specimen which corresponded to the zone of sclerosis. However, in 14 of the vulval lichen sclerosus specimens and the extragenital lichen sclerosus specimen, fibronectin was slightly increased in the mid and deeper dermis which corresponded to the zone of inflammatory cells and the area below this. There was also increased fibronectin staining around blood vessel walls both in the mid dermis and within the zone of sclerosis. Conclusion: The distribution of tenascin, fibrinogen and fibronectin is altered in lichen sclerosus and the alteration in these extracellular matrix components may be relevant to the initiation of scarring in lichen sclerosus and the associated increased skin fragility.
Aim-To assess the diagnostic performance of human papillomavirus (HPV) analysis in predicting cervical intraepithelial neoplasia (CIN) grades 2 and 3 in patients with persistent low grade cervical cytological abnormalities. Methods-Cervical smears from 167 women referred for colposcopy with persistent borderline, wart virus or mildly dyskaryotic changes on cervical screening were analysed by Papanicolaou staining, non-isotopic in situ hybridisation and generic and type specific polymerase chain reaction (PCR) amplification of HPV sequences. Follow up was by cytological and, where appropriate, histological analysis. Results-CIN grade 2 or 3 was identified in 46 patients after a median follow up of 27 months. HPV positivity by both techniques was associated with high grade CIN and with age less than 30 years (median age 33 years). Non-isotopic in situ hybridisation was more predictive but less sensitive than either generic or type specific PCR, but prediction was greater using either molecular technique in women over 30 years of age. Conclusions-Although the degree of prediction found is of only limited clinical value, the strong association of HPV positivity with both high grade CIN and patient age suggests that further studies of HPV testing in this patient group are warranted. (3 Clin Pathol 1996;49:493-496)
EDITORIAL COMMENT: We accepted this case report for publication since it addresses the important problem of whether hormone replacement therapy should be withheld after bilateral oophorectomy (usually associated with hysterectomy) in the premenopausal woman who had extensive endometriosis. Our endocrinologist reviewer withholds oestrogen for 6 months in such women and prescribes medroxyprogesterone acetate 10 mg BD continuously i f they have flushes or associated symptoms; he is especially unwilling to prescribe oestrogen i f removal of endometriotic deposits is deemed by the surgeon to be incomplete. Our editorial panel consensus is that it is cruel to withhold oral hormone replacement therapy from these women but that the regimen should include a progestogen as well as oestrogen as in women who still have a uterus. We agree with the authors that we need data telling us how often hormone replacement therapy is associated with return of symptoms due to endometriotic depositsin the editor's experience the problem is uncommon. Our Senior Gynaecologist Chairman states that in the few patients he has managed in whom endometriosis has been reactivated by hormone replacement therapy after pelvic clearance, the problem has been controlled by low-dose X-ray therapy in his experience this has not resulted in ureteric obstruction although he has seen 2 women present with unilateral ureteric obstruction from previously untreated endometriosis involving the lateral pelvic wall.
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