Raman spectroscopy and multivariate analysis for the non invasive diagnosis of clinically inconclusive vulval lichen sclerosus.

Vulval lichen sclerosus (LS) is a common inflammatory condition associated with an increased risk of developing vulval carcinoma. Diagnosis is usually clinical although biopsy is necessary if the diagnosis is uncertain or if there is a failure to respond to adequate initial treatment. Raman spectroscopy has the potential to be applied in vivo for near real time objective non-invasive optical diagnosis, avoiding the need for invasive tissue biopsies. The aim of this study was to evaluate the diagnostic performance of Raman spectroscopy for differentiating LS from other vulval conditions in fresh vulval biopsies. Biopsies were analysed from 27 women with suspected LS in whom the attending gynaecologist could not establish the diagnosis on clinical presentation alone. Spectral variance was explored using principal component analysis and in conjunction with the histological diagnoses was used to develop and test a multivariate linear discriminant classification model. This model was validated with leave one sample out cross validation and the diagnostic performance of the technique assessed in comparison with the pathology gold standard. After cross validation the technique was able to correctly differentiate LS from other inflammatory vulval conditions with a sensitivity of 91% and specificity of 80%. This study demonstrates Raman spectroscopy has potential as a technique for in vivo non-invasive diagnosis of vulval skin conditions. Applied in the clinical setting this technique may reduce the need for invasive tissue biopsy. Further in vivo study is needed to assess the ability of Raman spectroscopy to diagnose other vulval conditions before clinical application.

Should grade 3 endometrioid endometrial carcinoma be considered a type 2 cancer-a clinical and pathological evaluation.

OBJECTIVE: Endometrial cancer is classified into: Type I estrogen-dependent endometrioid adenocarcinoma, with good prognosis and type 2 non-estrogen-dependent cancer with serous or clear cell histology and poor prognosis. Grade 3 endometrioid cancers (G3 EEC), share features of type 1 and type 2 cancer and have not been classified as either. This study compares immunohistochemistry and survival in G3 EEC and type 2 cancers. METHODS: Clinicopathological data compared with immunohistochemistry and survival in 156 consecutive patients with poor prognosis cancer-G3 EEC, uterine papillary serous (UPSC) and clear cell carcinoma (CC), sarcoma, carcinosarcoma and endometrial tumors of mixed histology. 131 (84%) datasets were complete, 25 tumors comprising sarcoma, carcinosarcoma or mixed histologies were excluded. Tissue microarray constructed and tested for estrogen receptor (ER), progesterone receptor (PR), p53 and human epidermal growth factor receptor-2 (Her-2). RESULTS: There was no significant difference in the mean age for G3 EEC (n=68) and USPC + CC (n=38), (68.01 and 67.08 respectively, p=0.697) or stage at diagnosis (p=0.384). For ER, PR, p53 and Her-2, there was no significant difference in marker positivity between G3 EEC and UPSC + CC (p=0.612, 0.132, 0.16 and 0.132 respectively). With a mean follow-up time 148 months Disease specific and recurrence-free survival between G3 EEC and USPC + CC was similar (p=0.842 and 0.863). CONCLUSION: G3 EEC and UPSC + CC share similar clinical, immunohistochemistry and poor survival. G3 EEC is better characterised as type 2 cancer and should be treated with similar adjuvant therapy to UPSC/CC.

Endogenous control genes in prostate cells: evaluation of gene expression using 'real-time' quantitative polymerase chain reaction.

OBJECTIVE: Our aims were to measure the level of expression of Abelson (ABL1), ß-glucuronidase (GUS) and glucose-6-phosphate dehydrogenase (G6PD) genes in exfoliated urine cells from healthy and transrectal ultrasound biopsy patients with elevated prostate-specific antigen levels and/or abnormal digital rectal examinations or urinary symptoms indicative of prostate problems, as well as in archived formalin-fixed paraffin-embedded prostate materials. MATERIALS AND METHODS: Real-time quantitative polymerase chain reaction (RQ-PCR) was used to evaluate the suitability of the 3 control genes, i.e. ABL1, GUS and G6PD, as control genes for prostate cancer cells. Exfoliated urine cells from 30 healthy males, 53 male patients, 138 cases of archived paraffin-embedded prostate tissues and 3 prostate cell lines were sampled. All cells were lysed in guanidine isothiocyanate buffer from which RNA was extracted and converted to cDNA by random hexamer priming. RQ-PCR was performed using TaqMan chemistries. RESULTS: There was no significant difference in the level of expression for each of the 3 control genes in the cell lines. There was a significant difference in GUS transcript level between patients and healthy controls in both urine and prostate tissue sections (p < 0.05). G6PD transcript numbers also differed significantly from those of GUS in the prostate cell lines and tissue sections (p < 0.05). The transcript numbers of all the control genes were significantly reduced in aged samples (p < 0.001). CONCLUSION: The ABL1 gene was the most stable control gene in both clinical specimens and cell lines. Therefore, we recommend its use to enable standardization and interlaboratory comparisons for the RQ-PCR of prostatic tumour markers.

The pathology of diverticular disease.

Diverticular disease is common in the elderly Western population and its complications are frequent clinical presentations. Despite this, the pathogenesis of the condition remains relatively poorly understood. Several theories have been developed, the most acceptable suggesting elastosis of the taeniae coli as the primary event, causing shortening of the sigmoid colon, with relative mucosal excess and subsequent mucosal herniations. A Western-type diet is implicated in the increased uptake of proline from the gut, leading to elastosis of the sigmoid colon. For pathologists, in clinical practice, the disease is most commonly seen in sigmoid colonic resection specimens, usually performed for complications of the disease. It is now realised that mucosal biopsies of the luminal mucosa, in the sigmoid colon affected by diverticular disease, can produce perplexing pathological changes. In particular diverticular colitis can mimic both ulcerative colitis and Crohn's disease: care should be taken when diagnosing chronic inflammatory bowel disease on a background of diverticular disease. For pathologists, diverticular disease remains something of an enigma: although common, its pathogenesis remains ill-defined and its complications can provide diagnostic difficulties, which require precise clinical and radiological correlation.

Renal cell carcinoma presenting as AA amyloidosis: a case report and review of the literature.

A 47-year-old Caucasian man developed mild diarrhoea associated with more than 10 kg weight loss, severe fatigue and anaemia. Endoscopy demonstrated deposits of AA amyloid within the gastrointestinal tract. He had heavy proteinuria with a serum albumin of 15 g/L consistent with systemic AA amyloidosis. He had no symptoms to suggest an underlying chronic inflammatory condition but had CRP 130 mg/L and SAA 474 mg/L. In an attempt to identify the source of his inflammatory response, he underwent a contrast-enhanced whole-body computed tomography scan, which revealed a necrotising mass lesion in the right kidney consistent with a renal cell carcinoma. It also showed non-mechanical obstruction of the small bowel and, immediately post-imaging, the patient developed intractable vomiting followed by oliguric renal failure requiring haemodialysis. Despite his renal and gut failure, he underwent right radical nephrectomy without further complications. Histology showed complete resection of a clear cell renal cell carcinoma and renal amyloid deposits. Post-surgery, his acute-phase response decreased to normal, consistent with the renal cell carcinoma acting as the inflammatory stimulus. Although he remains dialysis dependent, his gut function improved and he has regained both normal weight and serum albumin. Our case demonstrates partial resolution of AA amyloidosis with removal of the inflammatory source.

Henoch-Schönlein purpura with intracerebral haemorrhage in an adult patient: a case report.

INTRODUCTION: Henoch-Schönlein purpura is a small vessel vasculitis that affects mainly the skin, joints, gastrointestinal tract and kidneys. The central nervous system is also occasionally affected, although the majority of patients experience only mild symptoms such as headaches and behavioural changes. Intracerebral haemorrhage is a rare complication of Henoch-Schönlein purpura that so far has mainly been described in children and young adolescence. CASE PRESENTATION: We describe a 42-year-old man with Henoch-Schönlein purpura who developed an acute intracerebral haemorrhage that coincided with a reactivation of his vasculitis and the development of renal failure following discontinuation of steroids. In this patient, both the Henoch-Schönlein purpura and his neurological symptoms were successfully treated with intravenous cyclophosphamide and methylprednisolone, followed by a short course of oral cyclophosphamide and long-term oral prednisolone. His renal function also recovered sufficiently not to require renal replacement therapy. CONCLUSION: The management of Henoch-Schönlein nephritis remains unclear, especially in the presence of severe complications such as intracerebral haemorrhage. We describe a successful outcome in such a patient.