The histopathological mimics of inflammatory bowel disease: a critical appraisal.

The pathological diagnosis of inflammatory bowel disease (IBD) is often difficult because biopsy material may not contain pathognomonic features, making distinction between Crohn's disease, ulcerative colitis and other forms of colitides a truly challenging exercise. The problem is further complicated as several diseases frequently mimic the histological changes seen in IBD. Successful diagnosis is reliant on careful clinicopathological correlation and recognising potential pitfalls. This is best achieved in a multidisciplinary team setting when the full clinical history, endoscopic findings, radiology and relevant serology and microbiology are available. In this review, we present an up-to-date evaluation of the histopathological mimics of IBD.

A novel imaging approach to periocular basal cell carcinoma: in vivo optical coherence tomography and histological correlates.

PURPOSE: Optical coherence tomography (OCT) is a non-invasive imaging method widely used in ophthalmology. Recent developments have produced OCT devices for imaging the skin. The purpose of this study was to investigate Fourier Domain OCT morphological features of periocular basal cell carcinoma (BCC) in correlation with conventional histopathology. METHODS: Consecutive patients with periocular nodular BCC were prospectively examined with VivoSight OCT (Michelson Ltd) prior to surgical excision. OCT slice mode images were analysed using criteria defined for conventional and HD-OCT; the images were correlated to haematoxylin and eosin stained histology sections. RESULTS: A total of 15 patients with periocular BCC were recruited. Three categories of BCC morphological features were identified from slice mode OCT images: (1) Epidermal changes included epidermal thinning (15/15; 100%), ulceration and crusting (5/15, 33.3%) and decreased density of hair follicles (8/15; 53.3%); (2) Intralesional features included hyporeflective nodules (15/15; 100%), hyper-reflective edges (15/15; 100%) and hyporeflective central necrosis (3/15; 20%) (3) Perilesional features included hyporeflective borders (11/15; 73%), hypereflective margins (15/15; 100%) and dilated blood vessels (5/15; 33%). CONCLUSIONS: This study demonstrated that Fourier Domain OCT imaging offers additional information in the identification of morphological features of nodular BCC compared to conventional OCT diagnostic criteria. VivoSight produced fast, non-invasive imaging of skin lesions in the periocular region and high correlation with histology. Further studies are necessary to investigate OCT features of different histological subtypes of BCC.

Imaging of periocular basal cell carcinoma using en face optical coherence tomography: a pilot study.

AIM: To use en face optical coherence tomographic (OCT) imaging to identify features of tumour tissue and their correlation with histopathologic findings and to assess the effect of different wavelengths and resolutions of OCT in identifying tumour boundaries and features. METHODS: Excision specimens of consecutive biopsy-proven periocular basal cell carcinomas (BCCs) (n=8) were assessed by OCT, performing in vitro cross-section and en face scans of the tissues. Images were collected from three different machines: systems 1 and 2 had a wavelength of 1300 nm, and system 3 had a wavelength of 840 nm. System 2 used high numerical aperture interface optics that determines higher magnification and hence allows higher transversal resolution. All the eight specimens subsequently underwent routine histopathologic examination. RESULTS: Three common features of tumour tissue were observed in all the three systems: (1) lobular pattern of abnormal architecture, (2) dilated blood vessels and (3) high reflective margins. We compared the three systems based on their ability to pick up the three above-mentioned tumour features. In this respect, system 2 had the highest capability in picking up feature 1, followed by systems 1 and 3. In feature 2, similar results were obtained with all the three systems. System 3 was unable to pick up feature 3, whereas systems 1 and 2 performed equally. CONCLUSION: En face OCT imaging has the potential to identify tumour tissue from healthy tissue. It also showed correlation with corresponding histopathologic findings. Non-contact OCT imaging of the skin is a non-invasive and convenient method and can be useful for demarcating BCCs on the face and eyelids. Future larger studies on in vivo BCCs using en face ultra-high-resolution OCT should provide information on subtyping BCCs.

Rectosigmoid tumours: should we continue sitting on the fence?

Rectal cancers are currently defined as tumours below 15 cm from the anal verge on rigid sigmoidoscopy. Clinical trials have used this criterion to select patients for neoadjuvant chemoradiotherapy, but several authors have shown that the distance between the fully peritonealized sigmoid colon and the anal canal varies significantly between individuals. A fixed anatomical landmark would be a more reliable and reproducible method of demarcating the junction between the colon and the rectum. The distinction between rectal and sigmoid colon cancers is of particular importance as treatment protocols for rectal cancer management often involve neoadjuvant treatment in contrast to colonic cancers, so it is vital to get the anatomy right. As all rectal cancers are now assessed preoperatively by MRI, the use of a bony landmark is possible. We postulate that the fixed landmark to define the upper limit of the rectum should be the sacral promontory.

The importance of accurate pathological assessment of lymph node involvement in colorectal cancer.

This review presents an up-to-date analysis of the importance of accurate pathological lymph node staging in colorectal cancer. Lymph node staging is reliant on the technique of the surgeon and the pathologist as well as methods employed in the histopathology laboratory, and is vital for determining appropriate therapy. The significance of micrometastatic nodal disease is evaluated and new techniques for pathological evaluation are discussed. Recommendations for evaluation of lymph node status in colorectal cancer are provided based on current scientific evidence, and standardization of pathological dissection and laboratory handling is advocated.

Anorectal manifestations of sexually transmitted infections.

Sexually transmitted infections have a wide range of clinical presentations, including involvement of the anal verge, anal canal and rectum. This review focuses on anorectal sexually transmitted infections which may cause diagnostic difficulty when encountered by the coloproctologist. An approach to the diagnosis of a variety of sexually transmitted infections is set out, with a discussion of the role of biopsy and a summary of relevant histopathological findings. The value of early antibiotic treatment is discussed. Problems related to HIV/AIDS are highlighted, as clinical presentation may be atypical in immunosuppressed individuals. Sexually transmitted oncogenic viruses and their role in anal neoplasia are also briefly summarized.

Rapidly invading sebaceous carcinoma of the external auditory canal.

A very rare case of a sebaceous carcinoma of the external auditory canal with basal cell differentiation is presented. Fewer than 400 cases affecting any part of the body have so far been reported and of that only seven cases have been known to involve the external auditory canal. The clinical features, pathology and treatment are described and the relevant literature has been reviewed.

Adjuvant radiotherapy for primary mucosal malignant melanoma of the larynx.

Primary mucosal malignant melanoma (PMML) of the larynx continues to be a rare entity. To date, there are few cases reported in the world literature consisting of mainly isolated case reports and literature reviews. Traditionally believed to be radioresistant, we present a case of PMML of the right vocal fold managed with right cordectomy and adjuvant radiotherapy. The patient is well without any evidence of local recurrence or metastasis three years and four months from presentation.

An unusual cutaneous presentation of Hodgkin's disease.

Hodgkin's disease is a neoplasm of lymphoid tissue defined histopathologically by the presence of Reed-Sternberg cells in an appropriate cellular background. Hodgkin's disease extends only rarely into the skin. Sinus and fistula formation has been reported in very occasional cases. We now report a case of a 34-year-old woman presenting with a cutaneous lesion surrounding a discharging blind-ending sinus in the neck, subsequently diagnosed as Hodgkin's disease. To our knowledge this form of presentation of Hodgkin's disease has not been reported in the English literature before, and at the same time we would like to outline the difficulties in diagnosis encountered with these cutaneous lymphoid lesions.

Pulmonary fibrosis correlates with duration of tissue neutrophil activation.

The role of inflammatory cells such as neutrophil granulocytes in the pathogenesis of pulmonary scarring is unclear. We determined the metabolic activity of neutrophils with positron emission tomography (PET) to measure regional uptake of (18F)-2-fluoro-2-deoxy-D-glucose (18FDG) following its intravenous injection. Fibrogenic or nonfibrogenic substances were instilled into the right upper lobe of rabbit lungs. Time course and intensity of the 18FDG signal in the affected region varied markedly, depending on the stimulus. Time to peak signal (Tmax) and rate constant for its decline (k) for the test substances were, respectively: C5a 10 h (Tmax), 0.045 +/- 0.030 h-1 (k); Streptococcus pneumoniae 15 h, 0.068 +/- 0.012 h-1; bleomycin 28 h, 0.002 +/- 0.001 h-1; microcrystalline silica (microXSiO2), 90 h, 0.0012 +/- 0.0007 h-1; amorphous silica (aSiO2), no response. Response to the nonfibrogenic agents C5a, S. pneumoniae and aSiO2 was brief or nonexistent, falling to baseline values within 3 d, whereas that to the fibrogenic agents bleomycin and microXSiO2 persisted for up to 4 wk. Neutrophil numbers in the lung were proportional to the 18FDG signal following C5a and S. pneumoniae, but not bleomycin and microXSiO2. Autoradiography of lungs following administration of (3H)-deoxyglucose [(3H)-DG] showed specific localization to neutrophils in all models. Thus, 18FDG uptake provides a remarkably specific measure of neutrophil activity in situ, and the development of pulmonary fibrosis may be related to persistence of this activity.

Pericardial substitution after cardiopulmonary bypass surgery: a trial of an absorbable patch.

Primary closure of the pericardium affords some protection against adhesion formation and the consequent hazards of resternotomy. However, its completion may be impractical and hazardous, and therefore the pursuit of an ideal pericardial substitute has prompted much research. Twenty calves were divided into 3 groups for the study. All animals underwent right posterolateral thoracotomy. The test group (group X), consisting of 6 animals, received a poly-beta-hydroxybutyrate patch (PHB) to close the pericardium following cardiopulmonary bypass (CPB). In group Y (9 animals) the pericardium was left open following CPB. Group Z (5 animals) also had their pericardium left open but did not undergo CPB (non-CPB). The plasminogen activating activity (PAA) of homogenates of pericardial tissue samples were measured in 5 animals in group X, and 5 in group Z. Samples were taken at three time points from the time of pericardiotomy, and at reoperation 4 weeks later. In group X (CPB) there was a significant reduction in the PAA during the operation with some recovery at reoperation. The reduction in the pericardial PAA of group Z (non-CPB) animals did not reach significance. For both group X and group Z the progress of mesothelial damage, compared with that at zero time, showed a significant increase. In addition, their pericardial inflammatory features became more apparent in the later samples but more significantly in group Z. This study demonstrated no significant short-term differences in adhesion formation or postoperative coronary anatomy visibility between any of the groups. At reoperation the patch material contained pronounced macrophage activity but no regenerative mesothelium. There were no infective episodes in any of the animals studied. Furthermore, this study suggests that CPB in comparison to non-CPB has a significant affect on pericardial PAA.

Actinomycosis of the posterior triangle: a case report and review of the literature.

Actinomycosis presents acutely as an abscess, or as a chronic lesion mimicking malignancy, tuberculosis, or aspergillosis. Most disease involves the mouth and its immediate site of lymphatic drainage, the anterior triangle of the neck. We present a case of actinomycosis at the apex of the posterior triangle, suspected of being a malignancy, and discuss the importance of being aware of this as a cause of neck lumps. The diagnosis is usually made late because of the difficulties in culturing the organism, or in identifying characteristic 'sulphur granules' in pus or biopsy specimens. For these reasons, the disease is underdiagnosed. When acute or chronic neck lesions prove difficult to diagnose, microscopy and prolonged anaerobic culture of pus and biopsy specimens should be performed in addition in Ziehl-Neelsen staining, tuberculosis and fungal cultures. The tests should be repeated if negative. Specific treatment requires prolonged courses of antibiotics, despite adequate surgical excision, to prevent relapse.

Characterization of E-selectin expression, leucocyte traffic and clinical sequelae in urate crystal-induced inflammation: an insight into gout.

The self-limiting response to urate crystals allows the exploration of events involved in both the onset and resolution of gout. Using i.v. injected radiolabelled anti-E-selectin monoclonal antibody 1.2b6 together with differentially radiolabelled neutrophils, mononuclear cells and albumin, we have characterized the expression of E-selectin in relation to leucocyte traffic, microvascular permeability and clinical sequelae following intracutaneous injection of monosodium urate crystals. We found that the inflammatory response in this model involved several distinct phases. First, E-selectin expression increased over 2-6 h in the context of increases in neutrophil and mononuclear cell accumulation, and albumin leakage. Secondly, leucocyte accumulation rapidly declined despite persisting E-selectin expression. Thirdly, E-selectin expression peaked at approximately 8 h and then fell despite an increase in clinically detectable erythema and induration. Lastly, these clinical manifestations of inflammation resolved despite the continued presence of urate crystals in the tissues. The further dissection of mechanisms regulating these phases will lead to a better understanding of events in both the pathogenesis and resolution of gout. Of broader significance, this inflammatory model may yield information about the protective events that underly resolution of inflammation, and provide insights into factors which determine chronicity.

Pericardial trauma and adhesions in relation to reoperative cardiac surgery.

In an attempt to appreciate the changes that favour adhesion formation we compared the morphological and fibrinolytic changes that occur in human primary and reoperative pericardium. Ten patients undergoing primary elective open heart surgery and ten undergoing first time reoperative open heart surgery were studied. Pericardial samples were taken at four time points. At 0 (time A) and 30 (time B) minutes from the time of pericardiotomy (before the commencement of CPB), 30-50 minutes (time C) after the commencement of CPB, and then finally 10 minutes (time D) after the patient had been rewarmed. The fibrinolytic activity, as measured by the plasminogen activating activity (PAA), in the pericardial samples of the ten primary cases was compared with that in 5 of the reoperative cases. For the primary group, the PAA after 30 minutes of exposure (median 6.65 IU/cm2, range 3.85-11.89 IU/cm2, p = 0.14, n = 10) was not significantly reduced when compared to the initial activity (median 8.74 IU/cm2, range 2.22-17.68 IU/cm2, n = 10). After 30-50 minutes CPB the PAA was significantly reduced (median 3.93 IU/cm2, range 1.5-13.24 IU/cm2, p = 0.028, n = 10) and still reduced after rewarming for 10 minutes (median 3.12 IU/cm2, range 0.88-19.93 IU/cm2, p = 0.047, n = 10). The simultaneous plasma tissue-type plasminogen activator activity showed a significant (p < 0.05) increase after 30-50 minutes bypass with a later decline. The changes in the reoperative pericardial PAA were similar. In addition, the degree of PAA in reoperative pericardium was consistently lower than that observed in primary tissue. The extent of primary pericardial mesothelial damage at times B, C, and D compared with that at time A showed a significant (p < 0.01 for times B, C, and D) increase. Similarly there was a significant worsening of the degree of inflammation. Compared with primary pericardium, the reoperative samples showed a significant (p < 0.01 for times A, B, and C) preponderance of damaged mesothelium at the earlier stages of the operation. It appears that, following the initial bypass surgery, the processes that cause pericardial and mesothelial healing with recovery of PAA compete with those leading to pericardial adhesions and fibrosis. The histological and biochemical outcome seen in reoperative pericardium is the result of these competitive actions.

A rare mediastinal tumour presenting with systemic effects due to IL-6 and tumour necrosis factor (TNF) production.

Patients presenting with prolonged systemic illnesses with no specific clinical or serological defining features may be diagnosed as having atypical systemic vasculitides, but often turn out to have occult malignancies. Cytokines have been implicated in causing many of the systemic effects in such cases. In this study we describe a patient presenting after 2 years of a severe systemic illness with a marked acute phase response, due to an occult mediastinal angiomatoid malignant fibrous histiocytoma. Tumour resection was curative. We evaluated in detail the local and systemic production of cytokines induced by this tumour. Blood samples were taken pre- and post-operatively for cytokine studies. In vitro production of IL-2, IL-2R, IL-1 beta, IL-6 and TNF-alpha by cultured monocytes from the patient, as well as plasma cytokine levels, were measured by ELISA. Tumour cytokine production was also evaluated immunocytochemically, and by in situ hybridization with specific cDNA probes. Plasma IL-2R and IL-6, and IL-6 and TNF-alpha production by peripheral blood monocytes were markedly elevated before tumour resection, normalizing post-operatively. Most tumour cells and infiltrating lymphocytes stained with antibodies to IL-6, IL-6R and TNF-alpha, and expressed HLA class II. IL-6 and TNF-alpha mRNA production in the tumour was confirmed by in situ hybridization studies. We have described the first case of an occult angiomatoid malignant fibrous histiocytoma in the mediastinum. Studies of cytokine expression suggested that chronic TNF, IL-6, and IL-2 production by leucocytes and tumour cells in this patient was responsible for the severe systemic illness with which she presented.

Carcinoid heart disease: early failure of an allograft valve replacement.

A woman who had carcinoid syndrome and carcinoid heart disease underwent tricuspid and pulmonary valve replacements with a xenograft and a cryopreserved allograft, respectively. Within 3 months of the operation severe pulmonary regurgitation and pulmonary hypertension refractory to medical therapy developed. Autopsy found the biomechanical tricuspid valve to be free of disease but the allograft in the pulmonary position was involved by carcinoid heart disease in a fashion similar to the excised native pulmonary valve.

Perioperative histologic and ultrastructural changes in the pericardium and adhesions.

The presence of pericardial adhesions prolongs the operation time and increases the risk of serious damage to the heart and other major vascular structures during resternotomy. The reported incidence of such damage is 2% to 6%. Pericardial mesothelial cells exhibit fibrinolytic activity, and therefore have an actual or potential role in the breakdown of the fibrinous adhesions that serve as the initial scaffolding for the firm collagenous adhesions seen at reoperation. Ten patients undergoing primary cardiac procedures were studied to assess the morphologic changes that take place within the pericardium and to relate these to accompanying changes in the pericardial plasminogen activating activity. Samples were taken at 0, 75, and 135 minutes after pericardiotomy. Compared with samples obtained at the time of pericardiotomy, those taken at 75 and 135 minutes demonstrated a significant progression in the mesothelial cell damage (p < 0.01), together with increasing evidence of pericardial inflammation (p < 0.01). The findings from electron microscope studies confirmed and supplemented these findings. Furthermore, compared with its initial levels (median, 2.06 IU/cm2; range, 1.28 to 6.48 IU/cm2), the plasminogen activating activity of pericardial biopsy specimens was significantly reduced at 75 minutes (median, 0.64 IU/cm2; range, 0.12 to 2.44 IU/cm2; P < 0.05), with some recovery at 135 minutes (median, 1.45 IU/cm2; range, 0.12 to 4.39 IU/cm2; p = 0.059). This study has revealed that, during cardiac procedures, the pericardium undergoes inflammatory changes with concomitant damage to its mesothelium, together with a reduction in the pericardial mesothelial fibrinolytic potential.(ABSTRACT TRUNCATED AT 250 WORDS)

Familial polyarteritis nodosa.

Familial polyarteritis nodosa (PAN) is rare. We describe here two siblings who developed PAN 8 years apart. HLA typing showed that the affected family members shared a common haplotype with their unaffected mothers. Further study of the family history suggested the possibility of an inherited disorder of connective tissue predisposing to autoimmunity and aneurysm formation.