Acute syphilitic interstitial orchitis mimicking testicular malignancy in an HIV-1 infected man diagnosed by Treponema pallidum polymerase chain reaction.

We report a case of acute epididymo-orchitis due to early infectious syphilis, mimicking as testicular malignancy in an undiagnosed HIV-positive individual. He presented with a mass on his testicle and simultaneously had serology consistent with early syphilis. It could not be distinguished from a malignancy, which necessitated urgent orchidectomy. Histology showed endarteritis but no evidence of gummatous involvement. Although treponemes were not detected by staining, the diagnosis was confirmed by the first reported use of Treponema pallidum polymerase chain reaction in a testicular specimen in the UK.

Autopsy pathology of cocaine users from the Eastern district of London: a retrospective cohort study.

AIM: To establish the most frequent pathological findings encountered at postmortem examination during the investigation of a fatality with a history of cocaine abuse. METHODS: Autopsied deaths investigated by the coroner for the Eastern district of London, between 2004 and 2007, in which the decedent had positive toxicology for cocaine were identified (n = 28). The autopsy records and histology of tissue taken at autopsy were retrieved and reviewed. Pathological findings (gross and microscopic, including cardiac, pulmonary, gastrointestinal, hepatobiliary, renal and neurological) were collated. RESULTS: The main pathological findings at autopsy occurring in this cohort (comprising predominantly men, mean age 31 years), were cardiovascular: left ventricular hypertrophy (46%), multifocal myocardial fibrosis (21%), coronary artery disease (29%), cerebrovascular disease (36%) and pulmonary oedema (71%). Hepatic steatosis (29%) and gastrointestinal haemorrhage (18%), due mostly to gastric erosions/ulceration, were also frequent findings. CONCLUSIONS: During a coroner's autopsy of a cocaine user, a thorough cardiac examination combined with cardiac tissue sampling for histology, are valuable investigations, which are most likely to help show pathology relevant to the cause of death.

Human papillomavirus-associated increase in p16INK4A expression in penile lichen sclerosus and squamous cell carcinoma.

BACKGROUND: Human papillomaviruses (HPVs) are sexually transmitted human carcinogens that may play a role in the oncogenesis of penile cancer. OBJECTIVES: To investigate the role of HPV infection and expression of the tumour suppressor protein p16INK4A in the pathogenesis of penile cancer. METHODS: By means of polymerase chain reaction amplification and reverse hybridization line probe assay to detect HPV infection, and immunohistochemical staining for p16INK4A and Ki67, we analysed 26 penile squamous cell carcinomas (SCCs) and 20 independent penile lichen sclerosus (LS) lesions from 46 patients. RESULTS: HPV DNA was found in 54% of penile SCCs and 33% of penile LS cases in single and multiple infections. High-risk HPV 16 was the predominant HPV type detected. No relationship between Ki67 expression and HPV infection was observed. Strong immunostaining for p16INK4A correlated with HPV 16/18 infection in both penile LS and penile SCC. In our penile SCC series the cancer margins were also associated with penile LS in 13 of 26 lesions, and HPV was detected in seven of the 13 SCC cases associated with LS and in six of the 11 SCC lesions not involving LS. CONCLUSIONS: Our study shows a high prevalence of HPV 16 and p16INK4A expression in penile lesions, consistent with an active role for HPV in interfering with the retinoblastoma pathway. High-risk HPV infection could be involved in the tumorigenic process in 50% of penile cancers, and the use of prophylactic HPV vaccines has the potential to prevent these cancers.

Fatal biliary peritonitis due to postinsertion migration of a Robinson drain tip, with erosion into the liver parenchyma.

Iatrogenic injury due to incorrectly sited drains and tubes is a rare but recognized complication and can occur at many different sites. Migration of correctly sited drains and tubes is rarer still. A handful of rare cases involving longstanding ventriculoperitoneal and lumboperitoneal shunts migrating and causing perforation of the bowel exist, often complicated by central nervous system sepsis. We present a previously unreported complication of a Robinson drain, one of 2 abdominal drains inserted under direct vision during a subtotal gastrectomy for carcinoma, in a frail 78-year-old woman. Twenty-four days postoperatively, after a period of predictably slow but steady recovery, bile-stained fluid was noted in the drain. Unfortunately, the patient rapidly deteriorated and died. Autopsy revealed multiorgan failure due to peritonitis. Both drains were noted to be correctly and firmly sutured to the skin. The tip of the right-sided Robinson drain was found to have migrated, eroding into the liver parenchyma, resulting in biliary peritonitis. The left-sided Robinson drain was correctly sited in the peritoneal cavity. We present the postmortem findings and a review of the literature.

TB-related sudden death (TBRSD) due to myocarditis complicating miliary TB: a case report and review of the literature.

TB-related sudden death (TBRSD) is rarely reported in the literature and in the majority of cases is due to bronchopneumonia and hemoptysis. Cardiac complications of tuberculosis causing sudden death can take many forms and are rarer still, with only a handful of cases reported. We describe a case of a previously fit and healthy 20-year-old Asian female who, after returning from a holiday in India, collapsed while getting off a bus. At postmortem, the only macroscopic finding of note was a localized area of fibrosis on the anterior wall of the left ventricle. Microscopic examination of this area showed Langhans giant cells; noncaseating epithelioid granulomas and acid-fast bacilli were demonstrated on Ziehl Nielsen staining. In addition, the lungs, liver, and kidneys contained multiple noncaseating granulomas. The case serves to highlight the protean nature in the presentation of this disease and the importance of postmortem histology in autopsy work.

Detection of human chorionic gonadotrophin-beta in serum or urine of prostate cancer patients is of no clinical significance.

The aim of this study was to prospectively evaluate the potential role of elevated urinary/serum human chorionic gonadotrophin-beta (hCGbeta) in prostate cancer prognosis. 104 patients with newly diagnosed prostate cancers were included; 68 patients had organ-confined, 18 had locally advanced and 18 had metastatic disease. A control group consisted of 115 patients presenting with benign prostatic disease. Serum and urinary total hCGbeta was measured prior to treatment and serum PSA was measured at diagnosis. The patients were treated along conventional lines and progression-free survival was assessed. Four patients had elevated serum and 10 had elevated urinary, total hCGbeta. There were no significant correlations between serum/urinary levels of hCGbeta and tumour stage, Gleason score or PSA. In contrast, serum PSA had significant linear correlations with both clinical tumour stage and Gleason score (p = 0.0001). At a median follow-up of 36 months, 22 (21.2%) patients had died while 17 (16.3%) others had progressed. Kaplan-Meier plots and log-rank test revealed no significant difference in progression-free survival between patients with elevated or normal levels of serum and/or urinary total hCGbeta. Clinical tumour stage, grade and PSA were statistically significant prognostic variables. Immunoassay measurement of serum or urinary hCGbeta has no significant role in the clinical management of prostate cancer.

Seasonal variation in mortality from myocardial infarction and haemopericardium. A postmortem study.

BACKGROUND: Seasonal variation in the incidence of and mortality from myocardial infarction (MI) has been well recognised for many years. Haemopericardium (HP) is usually a fatal complication of MI. No data exist in the literature with regard to the seasonal variation in mortality from HP. AIMS: To perform a necropsy based study to confirm seasonal variation in mortality from MI in a London population and to determine whether seasonal variation in mortality from HP can be established. METHODS: Postmortem causes of death issued by several pathologists, working in two public London mortuaries over a five year period from 1999 to 2004 were analysed. Deaths caused by HP secondary to traumatic or iatrogenic causes were specifically excluded, as were deaths caused by HP secondary to bicuspid aortic valve and aortic dissection. The results were subdivided into winter (1 November to 31 March) and summer (1 April to 31 October). RESULTS: In total, there were 2266 cases of MI and 135 cases of HP. Significantly more deaths from HP (83 of 135; 61.5%; p = 0.004) and MI (1051 of 2266; 46.4%; p = 0.016) occurred in the five month winter period. Furthermore, there was a significantly higher incidence of HP compared with MI during the winter (83/1051; 7.9%) than the summer (52/1215; 4.3%; p<0.001). There was no significant difference in the age or sex of patients dying in either the winter or summer. CONCLUSION: There is seasonal variation in mortality from both MI and HP in the London population, as confirmed by a postmortem study.

Does human papillomavirus play a role in the development of bladder transitional cell carcinoma? A comparison of PCR and immunohistochemical analysis.

AIM: To investigate the role of human papillomavirus (HPV) in the development of bladder transitional cell carcinoma (TCC). METHODS: Seventy eight paraffin wax embedded TCC samples were tested for the presence of HPV by two methods. First, immunohistochemistry was carried out using a polyclonal antibody capable of detecting the capsid protein of all known papillomaviruses. The second method was a consensus GP5+/6+ primer mediated polymerase chain reaction (PCR) technique, with the products analysed by both agarose gel electrophoresis and an enzyme immunoassay using type specific oligonucleotide probes for 10 different mucosal genotypes. To exclude false negative results because of the poor quality of DNA extracted from paraffin wax embedded samples, the series was extended to include 20 further blocks for which the corresponding snap frozen unfixed tissue was available. RESULTS: The two methods produced contrasting results, with 47 of the 78 samples positive for HPV antigen and none positive for HPV DNA. HPV DNA was not detected in the 20 additional paraffin wax embedded TCCs or in the 20 paired unfixed samples. In contrast, HPV DNA was amplified by PCR from all six of the paraffin wax embedded cervical carcinoma and anogenital wart control samples. CONCLUSION: The disparity between the two sets of results is probably caused by false positives resulting from the non-specificity of the polyclonal antibody used for immunohistochemistry. These results suggest that HPV is unlikely to play an aetiological role in the development of bladder TCC.

The significance of secondary neoplasms of the urinary and male genital tract.

Secondary neoplasms account for some 1.6-3.0% of solid malignancies encountered in surgical specimens from the genitourinary tract. At autopsy the proportion is higher, largely due to sampling bias. The peak incidence occurs around the seventh decade, and male and female incidences are approximately equal at all sites except the kidney, which shows a male preponderance owing to an excess of metastatic lung cancer. Adenocarcinomas are the most common histological type of secondary neoplasm and may be histologically and immunohistochemically indistinguishable from primary neoplasms arising from colonic-type epithelial metaplasia. Seeding of tumour along the urinary passages does not appear to be a significant mechanism of metastasis, and spread from one part of the genitourinary tract to another is uncommon. Clinical information and ancillary investigations are more helpful than special histological techniques in differential diagnosis.

Secondary solid neoplasms of the prostate: a clinico-pathological series of 51 cases.

The incidence, presentation, and macroscopic and histological features of secondary solid neoplasms of the prostate gland are described with reference to their differential diagnoses. A continuous series of autopsy and surgical cases from the Royal London Hospital from 1907 to the present yielded a total of 51 secondary neoplasms involving the prostate: 24 at post-mortem examination and 27 surgical specimens. The histology of these specimens was re-examined. In 34 cases, tumour reached the prostate by direct spread: 29 from the bladder and 5 from the rectum. The most common primary sites of metastases to the prostate were lung (eight cases) and pancreas (two cases). There were isolated examples of metastases from the bladder, rectum, skin (malignant melanoma), breast, eye (malignant melanoma), adrenal cortex and gallbladder. Secondary neoplasms represented 2.1% of all neoplasms in surgical specimens, a similar proportion of the total number of malignant solid neoplasms as secondary tumours at other sites in the genitourinary tract. The patients were usually symptomatic, presenting with prostatism, haematuria or pelvic pain, almost always in those with widely disseminated disease.

Molecular and kinetic features of transitional cell carcinomas of the bladder: biological and clinical implications.

Molecular and kinetic analyses have contributed to our understanding of the biology of transitional cell carcinomas (TCC) of the bladder. The concordant pattern of X-chromosome inactivation of multiple TCCs appearing at different times and at different sites and concordant genetic abnormalities in a subset of muscle-invasive TCC strongly support a monoclonal origin and a homogeneous tumor cell selection throughout the neoplasm. However, topographic intratumor heterogeneity results from the accumulation of genetic lesions in tumor suppressor genes, predominantly neurofibromatosis (NF)-1-defective in the superficial compartment and tumor protein p53 (TP53)-defective in the deep one, with lower proliferation and down-regulation of apoptosis in the latter. TCCs follow the general concept of multistep carcinogenesis and proceed through two distinct genetic pathways responsible for generating different TCC morphologies. These are the inactivation of cyclin-dependent kinase inhibitors (p15, p16, and p21WAF/CIP1) in low-grade TCC and early TP53-mediated abnormalities in high-grade TCC. TCC progression correlates with genetic instability and accumulation of collaborative genetic lesions mainly involving TP53, retinoblastoma (RB)-1, and growth factors. Distinctive genetic (low incidence of RB-1 and NF-1 abnormalities) and kinetic (slower cell turnover) profiles also correlate with a "single-file" infiltration pattern and poor survival in muscle-invasive TCCs. The underlying molecular changes of carcinoma in situ involve multiple and more extensive deletions (normally TP53-defective) than coexistent invasive TCC, suggesting an independent genetic evolution, while low-grade dysplasia is mainly polyclonal and shows a low rate of gene deletions.

Secondary neoplasms of the male genital tract with different patterns of involvement in adults and children.

AIMS: The incidence, presentation and macroscopic and histological features of secondary neoplasms of the male genital tract are described with reference to their differential diagnosis. METHODS AND RESULTS: A retrospective study of cases from the Royal London Hospital yielded a total of 31 secondary neoplasms involving the testis: 14 at postmortem examination and 17 surgical specimens. Nine cases were leukaemias: six acute lymphoblastic and two acute myeloid leukaemias in children, and one chronic lymphocytic leukaemia in an adult. The commonest primary sites of metastases to the testis were prostate (six cases), stomach (five cases) and lung (three cases). There were two malignant melanomas and isolated examples of metastases from the adrenal gland (neuroblastoma), cerebellum (medulloblastoma), soft tissue (alveolar rhabdomyosarcoma), pancreas and rectum. Of the metastases from solid tumours, 12 involved the right testis only, three involved the left and four were bilateral. In seven of these cases there were multiple testicular nodules, in seven there was a single mass, and in the rest there was diffuse involvement. Secondary neoplasms represented 4.6% of all testicular neoplasms at autopsy, and 1.6% in surgical specimens. There were five secondary penile neoplasms: two each from the pancreas and prostate and one from the bladder. Two neoplasms metastatic to the spermatic cord, both from a gastric primary, were included in the series. CONCLUSIONS: Secondary neoplasms of the testis occur with a frequency comparable to other sites in the genitourinary tract, and metastases to the spermatic cord, epididymis, and penis, are rare in comparison. Disseminated neoplasms rarely present initially at this site and are histologically distinctive in adults, but in children they must be distinguished from primary small round blue cell tumours.

Malignant lymphoma of the urinary bladder: a clinicopathological study of 11 cases.

AIM: To report the clinical and histological features and outcome of primary and secondary malignant lymphomas of the urinary bladder. METHODS: Eleven cases of malignant lymphoma of the urinary bladder were obtained from the registry of cases at St Bartholomews and the Royal London Hospitals. The lymphomas were classified on the basis of their morphology and immunophenotype, and the clinical records were reviewed. RESULTS: There were six primary lymphomas: three extranodal marginal zone lymphomas of mucosa associated lymphoid tissue (MALT) type and three diffuse large B cell lymphomas. Of the five secondary cases, four were diffuse large B cell lymphomas, one secondary to a systemic follicular follicle centre lymphoma, and one nodular sclerosis Hodgkins disease. Four patients with secondary lymphoma for whom follow up was available had died of disease within 13 months of diagnosis. Primary lymphomas followed a more indolent course. In one case, there was evidence of transformation from low grade MALT-type to diffuse large B cell lymphoma. The most common presenting symptom was haematuria. Cystoscopic appearances were of solid, sometimes necrotic tumours resembling transitional cell carcinoma, and in one case the tumours were multiple. These cases represented 0.2% of all bladder neoplasms. CONCLUSIONS: Diffuse large B cell lymphoma and MALT-type lymphoma are the most common primary malignant lymphomas of the bladder. Lymphoepithelial lesions in MALT-type lymphoma involve transitional epithelium, and their presence in high grade lymphoma suggests a primary origin owing to transformation of low grade MALT-type lymphoma. Primary and secondary diffuse large B cell lymphomas of the bladder are histologically similar, but the prognosis of the former is favourable.

DNA copy number changes in Schistosoma-associated and non-Schistosoma-associated bladder cancer.

DNA copy number changes were investigated in 69 samples of schistosoma-associated (SA) and non-schistosoma-associated (NSA) squamous cell carcinoma (SCC) and transitional cell carcinoma (TCC) of the bladder by comparative genomic hybridization (CGH). DNA copy number changes were detected in 47 tumors. SA tumors had more changes than NSA tumors (mean, 7 vs. 4), whereas the number of changes in SCC and TCC tumors was similar. SA tumors displayed more gains than losses (1.7:1), whereas NSA tumors showed an equal number of gains and losses. Changes that were observed at similar frequencies in SCC and TCC, irrespective of the schistosomal status, included gains and high-level amplifications at 1q, 8q, and 20q and losses in 9p and 13q. These changes may be involved in a common pathway for bladder tumor development and progression independent of schistosomal status or histological subtype. Losses in 3p and gains at 5p were seen only in SCC (P < 0.01) and losses in 5q were more frequent in SA-SCC than in other tumors (P < 0.05). However, changes that were more frequent in TCC than those in SCC included gains at 17q (P < 0.01) and losses in 4q (P < 0.05) and 6q (P < 0.01). Gains and high-level amplifications at 5p were seen only in SA-SCC (P < 0. 01), whereas gains and high-level amplifications with minimal common overlapping regions at 11q13 were more frequently seen both in SA-SCC and SA-TCC tumors (P < 0.01). In addition to the above mentioned alterations, several other changes were also seen at lower frequencies. The variations in the DNA copy number changes observed in TCC, SCC, SA, and NSA bladder carcinomas suggest that these tumors have different genetic pathways.

Secondary neoplasms of the bladder are histological mimics of nontransitional cell primary tumours: clinicopathological and histological features of 282 cases.

AIMS: The incidence, anatomical localization and histological appearances of secondary neoplasms of the urinary bladder are described, with emphasis on the points of distinction from primary tumours. METHODS AND RESULTS: A retrospective study of cases at the Royal Hospitals Trust yielded a total of 282 secondary bladder neoplasms, representing 2.3% of all malignant bladder tumours in surgical specimens. The commonest primary sites were the colon (21% of secondary neoplasms), prostate (19%), rectum (12%) and cervix (11%). Most tumours from these sites reached the bladder by direct spread. The most common sites of origin of tumours metastatic to the bladder were stomach (4.3% of all secondary bladder neoplasms), skin (3.9%), lung (2.8%), and breast (2.5%). Secondary tumour deposits were almost always solitary (96.7%), and 54% were located in the bladder neck or trigone. Histologically, 54% of secondary tumours were adenocarcinomas. Immunohistochemical staining patterns with prostate-specific acid phosphatase, prostate-specific antigen, carcinoembryonic antigen, chromogranin and neurone-specific enolase were similar in primary vesical and urachal adenocarcinomas and secondary adenocarcinomas from the gastrointestinal tract. CONCLUSIONS: The incidence of secondary bladder tumours is comparable to that of nontransitional cell primary tumours. Few secondary tumours have distinctive histological features, hence knowledge of the history and clinical investigations are particularly important in their diagnosis.

Ethnic factors in the pathology of the uterine cervix cervical screening: a population at variance with national targets.

In recent years, it has been noted that the rate of detection of high-grade uterine cervical abnormalities by screening in the Newham and Tower Hamlets districts have been much lower than the national average. Whilst the national average for the detection rate of moderate and severe dyskaryosis has been around 1.6%, the detection rate in Newham and Tower Hamlets has consistently been substantially lower, at 0.6-1.0%. This discrepancy may be explained on demographic grounds. The ethnic make up of the two districts differs from the national average. Newham has a mixed ethnic structure: Moslem (11%). Asian non-Moslem (12%) and other groups (77%). The population of Tower Hamlets is made up of Moslem (23%), Asian non-Moslem ( 11%) and other groups (66%). In both districts, the rate of detection of moderate and severe dyskaryosis in these population subgroups between 1997 and 1999 was 0.57% for Moslem women, 0.52% for Asian non-Moslem women and 1.18% for other women. This study attempts to confirm the effects of social factors in the differences in rates of detection of cervical intraepithelial neoplasia (CIN) in Newham and Tower Hamlets.

Xanthogranulomatous cystitis associated with malignant neoplasms of the bladder.

AIMS: Two cases of xanthogranulomatous cystitis in conjunction with malignant neoplasms of the bladder are described. METHODS AND RESULTS: A partial cystectomy [corrected] specimen from a 55-year-old man showed a urachal adenocarcinoma partly surrounded by a large xanthogranulomatous inflammatory mass. Multiple resections of the locally recurring tumour over the subsequent 10 years did not show further xanthogranulomatous changes. In the second case, a 76-year-old woman, a focus of xanthogranulomatous cystitis was present near a moderately differentiated transitional-cell carcinoma of the vesico-ureteric junction. CONCLUSIONS: Xanthogranulomatous inflammation is associated with malignant neoplasms in the bladder as it is in the kidney and extra-urinary sites, as well as with benign neoplasms and non-neoplastic conditions such as urachal diverticula. The presence of a concomitant neoplasm should therefore be considered when the diagnosis of xanthogranulomatous cystitis is made.