Hodgkin lymphoma in a patient with chronic lymphocytic leukaemia--a rare presentation of Richter's transformation.

Richter's transformation of chronic lymphocytic leukaemia (CLL) to high-grade B-cell Non-Hodgkin lymphoma occurs in < 5% of CLL cases. Transformation of CLL to Hodgkin Lymphoma is a much rarer event and here we describe a patient who developed Richter's transformation into a Hodgkin Lymphoma presenting as rapidly progressive hepatosplenomegaly.

Juxta-articular myxoma: an unusual benign mesenchymal lesion, readily mistaken for malignancy.

Myxomas are benign tumours of mesenchymal origin. We describe the first reported case of paraspinal juxta-articular myxoma. Juxta-articular myxomas show increased cellularity and distinction from cellular myxoma is required. The differential also includes malignant myxofibrosarcoma. For patient prognosis and management it is essential to separate these entities. Complete surgical excision is the mainstay of treatment as local recurrences may occur.

Apoplexia uteri: a rarely described post-mortem finding.

We present a case of apoplexia uteri, a rarely described condition of haemorrhagic necrosis in an atrophic endometrium and myometrium associated with terminal stress. This entity is well recognised in older literature but few recent publications have addressed this condition. It is thought to occur in association with hypoperfusion with passive hyperaemia and reperfusion injury. This case serves to highlight this rarely encountered entity as a possible cause of haemorrhage in an atrophic endometrium in the 'perimortem' period. Incidental findings are occasionally observed in the course of forensic autopsy practice and knowledge of rarely encountered entities, such as that described in this case, is essential to prevent diagnostic uncertainty and misdiagnosis.

Quality of colonoscopy performance among gastroenterology and surgical trainees: a need for common training standards for all trainees?

BACKGROUND AND STUDY AIM: Cecal intubation and polyp detection rates are objective measures of colonoscopy performance. Minimum cecal intubation rates greater than 90% have been endorsed by the American Society for Gastrointestinal Endoscopy (ASGE) and the Joint Advisory Group (JAG) UK. Performance data for medical and surgical trainee endoscopists are limited, and we used endoscopy quality parameters to compare these two groups. METHODS: Retrospective review of all single-endoscopist colonoscopies done by gastroenterology and surgical trainees ("registrars," equivalent to fellows, postgraduate year 5) with more than two years' endoscopy experience, in 2006 and 2007 at a single academic medical center. Completion rates and polyp detection rates for endoscopists performing more than 50 colonoscopies during the study period were audited. Colonoscopy withdrawal time was prospectively observed in a representative subset of 140 patients. RESULTS: Among 3079 audited single-endoscopist colonoscopies, seven gastroenterology trainees performed 1998 procedures and six surgery trainees performed 1081. The crude completion rate was 82%, 84% for gastroenterology trainees and 78% for surgery trainees (P < 0.0001). Adjusted for poor bowel preparation quality and obstructing lesions, the completion rate was 89%; 93% for gastroenterology trainees, and 84% for surgical trainees (P < 0.0001). The polyp detection rate was 19% overall, with 21% and 14% for gastroenterology and surgical trainees, respectively (P < 0.0001). The adenoma detection rate in patients over 50 was 12%; gastroenterology trainees 14% and surgical trainees 9% (P = 0.0065). In the prospectively audited procedures, median withdrawal time was greater in the gastroenterology trainee group and polyp detection rates correlated closely with withdrawal time (r = 0.99). CONCLUSION: The observed disparity in endoscopic performance between surgical and gastroenterology trainees suggests the need for a combined or unitary approach to endoscopy training for specialist medical and surgical trainees.

Profile of sudden death in an adult population (1999-2008).

Sudden death is the sudden and unexpected death of an individual within 24 hours of symptom onset. The vast majority of these cases are found, at autopsy, to be due to underlying ischaemic cardiac disease. We retrospectively reviewed all adult post mortems performed at Beaumont Hospital over a decade (1999-2008). Our aim was to identify all sudden death cases (natural and accidental) and subclassify them according to age profile and organ system involved. We identified 1230 sudden death cases in the review period with 775 (63%) deaths attributable to ischaemic heart disease. The rate of sudden death remained constant over the decade with 663 (54%) deaths occurring in the first five years. Our negative autopsy rate was 2.8% corresponding to 35 cases. This is the first Irish study to retrospectively review all adult sudden deaths within a defined catchment area and analyse them as outlined above.

Emergency appendicectomy in the era of laparoscopy: a one-year audit.

BACKGROUND: Appendicectomy for acute appendicitis is the commonest emergency surgical operation. With widespread acceptance of minimal access surgery most appendicectomies are now performed laparoscopically. AIMS: The aim of this study was to assess whether the rate of normal appendicectomy has changed following the introduction of laparoscopic techniques in our institution. METHODS: A retrospective study of patients having emergency appendicectomies over a 1-year period (2005) in a large teaching hospital was undertaken. RESULTS: A comparison of data was made from a prior study performed at the same hospital in 1988. 196 adult patients underwent appendectomies during this period. The normal appendectomy rate was 10.2% compared to 22.8% in the previous study. This rate was twice as high in women of reproductive age as compared to men. CONCLUSION: There has been widespread uptake of laparoscopic appendectomy in our hospital. This technique has reduced the rate of histologically normal appendicectomies due to intra-operative visualization of the appendix.

Has the ThinPrep method of cervical screening maintained its improvement over conventional smears in terms of specimen adequacy?

UNLABELLED: Liquid-based cytology (LBC) has replaced conventional smear assessment in many centers over recent years. In our laboratory this transfer took place in 1999. At that time we performed a split sample study comparing the conventional method of cervical smear evaluation with the ThinPrep system. This split sample study identified a dramatic improvement in specimen adequacy with LBC. While 11% of conventional preparations were reported as unsatisfactory and almost 9% were reported as suboptimal, evaluation of the same cases using LBC saw this combined figure reduced to 2.3%. AIM: To evaluate whether this dramatic fall in unsatisfactory smears has been maintained with the use of LBC. The database for all smears reported for 2005 (100% LBC) was interrogated. The number of unsatisfactory reports was calculated. The reason for an unsatisfactory report was recorded for each case. The overall unsatisfactory rate was compared with that reported in the 1999 split sample study. A total of 41,312 smear tests were reported in 2005. 1,342 (3.25%) were reported as unsatisfactory. Our findings support the ongoing value of LBC in a routine cervical screening laboratory in terms of continuing to maintain a low rate of unsatisfactory smears.

The difficulty with audit of high grade cervical cytology in the absence of a national screening programme.

Audit is an essential requirement of a cervical screening programme to ensure that laboratories are practising to agreed standards, and to ensure high quality patient care. The aim of this study was to assess the ability to audit high-grade cytology smear reports in a large cervical cytology laboratory in Ireland, where a nationally organised screening programme does not exist. Seven hundred and five questionnaires were forwarded to smear takers requesting follow-up data regarding high grade smear results from 2003. Seventy-four percent of the questionnaires were returned containing insufficient data, with a "don't know result" rate of >50%. This attempt at detailed audit took place 5 years ago. Annual internal audit continues to the best of the laboratory's ability but the situation, in terms of a centralised database in the context of a national screening programme, remains unchanged. A National Cervical Cytology Screening Programme is essential to centralise patient data, to allow for improved patient care, patient follow-up and audit.

Differential expression of matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in non-melanoma skin cancer: implications for tumour progression.

AIMS: To investigate the expression of matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in non-melanoma skin cancer (NMSC) and to compare their expression between different tumour types and with clinicopathological factors. METHODS AND RESULTS: A study of 11 normal skin, 29 Bowen's disease (BD), 40 squamous cell carcinoma (SCC) and 38 basal cell carcinoma (BCC) samples for MMP-2, MMP-9, TIMP-1 and TIMP-2 expression was carried out using immunohistochemistry and in situ hybridization. The expression of all metalloproteinases was greater in tumours than in normal skin. MMP-2 and MMP-9 expression was more extensive in the stroma of SCC than of BCC or BD. TIMP-1 expression was greater in the stroma of BCC than of SCC or BD and TIMP-2 expression was greater in the stroma of SCC than of BD. There was a correlation between increased metalloproteinase expression and depth of lesion (MMP-2 and TIMP-2), inflammation (MMP-2, MMP-9, TIMP-1 and TIMP-2) and microvessel density (MMP-2, MMP-9 and TIMP-2). CONCLUSIONS: MMP-2, MMP-9, TIMP-1 and TIMP-2 play an important role in the pathogenesis of non-melanoma skin cancer, but differ significantly in their expression levels between the tumour types examined. The immunoexpression of these proteins may be useful indicators of cutaneous cancer invasion and progression.

Plasmablastic lymphoma presenting as a paravertebral mass in a patient with Crohn's disease after immunosuppressive therapy.

The case of a 32-year-old man with a paravertebral mass and skin nodules, occurring against a background of immunosuppressive therapy for Crohn's disease, is presented. The tumours showed morphological and immunophenotypical features of plasmablastic lymphoma. To our knowledge, this is the first reported case of plasmablastic lymphoma presenting in this location, and also after immunosuppression with infliximab treatment for Crohn's disease.

Telomerase activity in proximal and distal gastric neoplastic and preneoplastic lesions using immunohistochemical detection of hTERT.

BACKGROUND: The incidence of distal (corpus and antrum) gastric adenocarcinoma is decreasing with a simultaneous increase in incidence of proximal (cardia) adenocarcinoma. Epidemiological studies suggest that they may represent different diseases but corroborative molecular data are scarce. Intestinal metaplasia may have a lower malignant potential in the proximal stomach but regardless of the locations, its specificity as a predictor of carcinoma is low. AIMS: The aim of this study was to establish whether human telomerase reverse transcriptase expression differs at various points in proximal versus distal gastric carcinogenesis and to test the utility of human telomerase reverse transcriptase expression as a marker of cancer risk in intestinal metaplasia. MATERIAL AND METHODS: Wax-embedded tissue from proximal and distal stomach including normal mucosa (n=86), intestinal metaplasia (n=83) and carcinoma (n=101) were used and slides were immunostained for human telomerase reverse transcriptase and pRb and scored semi-quantitatively. RESULTS: The results showed that in both proximal and distal stomach, human telomerase reverse transcriptase expression rates increased from normal mucosa to cancer. High rates of human telomerase reverse transcriptase expression were seen in the proliferative zones of glands in intestinal metaplasia. In both the locations, loss of pRb expression correlated with higher human telomerase reverse transcriptase expression. CONCLUSIONS: In conclusion, telomerase activity appears to be an early event in both proximal and distal gastric carcinogenesis and human telomerase reverse transcriptase is expressed in intestinal metaplasia. Telomerase re-expression may be facilitated by pRb inactivation.

Association between cyclooxygenase-2-expressing macrophages, ulceration and microvessel density in colorectal cancer.

AIM: In colorectal carcinomas, cyclooxygenase-2 (COX-2) is expressed predominantly by epithelial cells and is implicated in tumour progression. Tumour-associated macrophages may influence tumour growth, proliferative rate and angiogenesis and also express COX-2 when activated. Thus they may play an important stromal-epithelial role in carcinogenesis. Tauhe aim of this study was to define the relationship between microvessel density (MVD), tumour COX-2 and macrophage COX-2 expression. METHODS AND RESULTS: Sixty-five cases of formalin-fixed paraffin-embedded colorectal cancer were included in the study. Tissues were immunostained for COX-2, CD68 (macrophage marker) and CD34 (endothelial marker to assess MVD). Thirty-six cases were grossly ulcerated cancers and 29 cases showed focal/microscopic ulceration. Macrophages were in high concentration at the base of ulcerated areas, and were also diffusely dispersed within tumoral stroma. However, the pattern of macrophage COX-2 expression revealed two populations of macrophages--those deep within the tumour (negative for COX-2) and those at the base of ulcers (positive for COX-2). In all cases, the tumour epithelial cells expressed COX-2. MVD was higher at the base of ulcers, adjacent to COX-2+ macrophages, and was lower deep within the tumour. CONCLUSIONS: In colorectal cancers, macrophages may have a dual role. Those concentrated at the base of the ulcers, where there is an associated high MVD, may induce angiogenesis, but their function may be in a healing/repair process. The lack of COX-2+ macrophages and lower MVD deep within the tumour suggests that it may be the epithelial COX-2 component that is important in tumour progression.

Recurrent aneurysmal fibrous histiocytoma.

Aneurysmal fibrous histiocytoma is a rare variant of cutaneous fibrous histiocytoma that results from blood vessel proliferation and haemorrhage into a fibrous histiocytoma. The resulting lesion has a very different clinical appearance, hence the potential confusion with other skin lesions. This report describes the case of a 48 year old woman with a recurrent fibrous histiocytoma with prominent vasculature, which over a three year period recurred on two occasions, showing more progressive features of the aneurysmal variant. In addition, squamous lined cysts were present within this tumour, a finding that has not been described previously. The histological features of this rare lesion and the importance of the differential diagnosis from other similar appearing malignant lesions will be discussed.

Cytokeratin 7/20 and mucin expression patterns in oesophageal, cardia and distal gastric adenocarcinomas.

AIMS: The current study examined cytokeratin (CK)7 and 20 as well as MUC1-6 immunoprofiles in oesophageal, gastric and gastro-oesophageal junction (GOJ) adenocarcinomas. The aim was to compare expression patterns in these locations as aids to accurate classification of these morphologically similar carcinomas which all may involve the GOJ. METHODS AND RESULTS: Tissue microarrays were constructed using tissue from 14 oesophageal, 78 gastric and 39 GOJ adenocarcinomas. Sections were immunostained with CK7, CK20, MUC1, MUC2, MUC5AC and MUC6. The results of this study showed no differences in CK7 and CK20 expression patterns in the three locations. MUC2 expression was higher proximally (43% of oesophageal, 28% of GOJ and 17% of gastric carcinomas) and MUC6 expression was higher distally (7% of oesophageal, 28% of GOJ and 15% of gastric carcinomas). MUC1 expression was associated with higher pTNM-stage. CONCLUSIONS: CK 7/20 profiles have no role in distinguishing tumours of the three locations. Mucin expression patterns differed in oesophageal and gastric adenocarcinomas, although not sufficiently to classify individual cases. GOJ adenocarcinomas showed a mucin expression pattern that was partly 'gastric', and partly 'oesophageal'. MUC1 expression was associated with a higher pTNM stage.

Borderline nuclear change in cervical smears: five-year follow-up.

Borderline nuclear changes (BNC) account for 5-20% of cervical smears, and their outcome is unpredictable. Current management involves repeat smears at 6-mo intervals, for a further 12 mo with referral for colposcopy, if the changes persist. Given the uncertainty surrounding the natural history of BNC and the claim that many patients are further investigated unnecessarily and potentially "overtreated," the aim of this study was to determine the outcome for patients with a diagnosis of BNC to define whether the management protocol is appropriate for this patient group in our laboratory. A total of 808 patients with BNC were followed up. There was a 4.05% progression to high-grade dyskaryosis, and most of these were detected within the first year of follow-up. This at least justifies the early and intense follow-up of this patient group until a reliable "triage tool" is adopted to pre-select those patients with BNC who will progress or revert to negative.

Chronic osteomyelitis mimicking sarcoma.

This report describes a rare case of chronic osteomyelitis in a 60 year old man mimicking a soft tissue sarcoma. Chronic osteomyelitis is an infrequent cause of a soft tissue mass and is usually diagnosed clinically by a combination of radiology and microbiology. Rarely, COM can mimic a primary bony neoplasm, but this is the first reported case where it mimicked a soft tissue sarcoma. The clinical, radiological, and histological appearances of this case will be discussed.

Biopsy of a biopsy: validation of immunoprofiling in gastric cancer biopsy tissue microarrays.

AIMS: Tissue microarrays offer an efficient way of examining a large number of tumour cases on a single glass slide. A major concern, however, is tumour heterogeneity. Also, the use of tissue microarrays in biopsy material is unexplored. The purpose of the present study was to assess the possibility and validity of arraying three 0.6-mm cores per case in endoscopic gastric cancer biopsies for immunophenotyping. METHODS AND RESULTS: Thirty-eight cases were studied with immunohistochemical staining for p53, CD44v6 and vascular endothelial growth factor. Full tissue sections were compared with triple core-tissue microarrays. Thirty-six cases contained three cores with tumour, one case contained two cores with tumour and one case contained only a single core with viable tumour and was excluded. Three further cores had been lost from three separate cases on the sections for immunohistochemistry. kappa values for whole-sections versus tissue microarrays ranged between 0.77 and 0.94. p53 immunohistochemical staining (interpretation as + or -) yielded the best result with only 1/37 mismatches, whereas CD44v6 (graded both for intensity and extent) showed 3/37 mismatches. The small depth of tissue in cores from biopsies necessitates all cores being arrayed flush with the face of the recipient wax block for maximizing the number of sections available. Compared with the first section over 30 additional 4- micro m sections were available before the first case (with one core left) had to be excluded and 80 sections before half the tissue cores were lost. CONCLUSIONS: It is impracticable to array more than 120-150 cores per block. Tissue microarray with three cores per case is feasible and valid for studying biopsy material.

Comparison of the expression of p53, p21, Bax and the induction of apoptosis between patients with basal cell carcinoma and normal controls in response to ultraviolet irradiation.

AIM: Ultraviolet light (UV) is known to cause DNA damage in the epidermis. The damaged DNA is repaired or deleted by apoptosis to prevent the generation of cancer. It has been suggested that a deficient apoptotic mechanism may predispose individuals to skin cancer. Therefore, the response of normal controls and patients with basal cell carcinoma (BCC) to UV irradiation was investigated. METHODS: The buttock skin from normal volunteers and patients with BCC was irradiated using solar simulated radiation (SSR). SSR mimics the effect of natural sunlight. Skin biopsies were excised and examined for p53, p21, and Bax protein expression and for the induction of apoptosis. RESULTS: At 33 hours after UV irradiation, the induction of apoptosis was significantly higher (p = 0.04) in patients with BCC than in normal volunteers (Mann Whitney test). A trend towards higher p21 expression was found at 33 hours in patients with BCC (mean, 18.69 positive cells/field) than in normal volunteers (mean, 9.89), although this difference was not significant (p = 0.05 positive cells/field). CONCLUSION: These results may imply that patients with BCC have enhanced sensitivity to UV irradiation or that there is some defect in the cell arrest or repair pathways, which results in damaged cells been pushed into apoptosis rather than repair.