Inflammatory Reaction Pattern Research Articles

Characteristics and significance of colorectal cancer associated lymphoid reaction

A subset of colorectal cancers (CRCs) exhibits so-called Crohn's like lymphoid reaction (CLR), an inflammatory reaction pattern that consists of numerous transmural lymphoid aggregates. However, the composition of these aggregates, their biological mechanisms and their prognostic significance are not well-defined. We analyzed two CRC cohorts (418 and 149 patients) and determined clinicopathological features including survival. A new method for evaluating CLR based on counting the areal density of the lymphoid follicles (CLR density) was adopted. Immune cell densities at intratumoral and peritumoral regions, as well as the composition of the lymphoid follicles, were studied by immunohistochemistry. We found that CLR comprised of lymphoid aggregates with no evidence of granuloma formation. High CLR density associated with lower tumor stage, lack of preoperative radiotherapy or chemoradiotherapy and deficient mismatch repair enzyme expression. CLR density had positive correlations with peritumoral and intratumoral densities of CD83(+) mature dendritic cells and T cells. High CLR density associated with better survival and had prognostic value that was independent of stage, Klintrup-Mäkinen score for peritumoral inflammation and the numbers of tumor infiltrating T cells. CLR density evaluation had excellent intraobserver and interobserver agreement. In conclusion, the results suggest that CLR contributes to the adaptive antitumor immunity. Quantitative evaluation of CLR density is a relevant prognostic indicator in CRC.

High-definition optical coherence tomography: adapted algorithmic method for pattern analysis of inflammatory skin diseases: a pilot study

High-definition optical coherence tomography (HD-OCT) is a non-invasive technique for morphological investigation of tissue with cellular resolution filling the imaging gap between reflectance confocal microscopy and conventional optical coherence tomography. The aim of this study is first to correlate dermatopathologic descriptors of inflammatory skin conditions with epidermal alteration to features observed by HD-OCT. Secondly, to assess the discriminative accuracy of common inflammatory reaction patterns with epidermal alteration using HD-OCT by applying Ackerman’s algorithmic method of pattern recognition. The generated HD-OCT images of 160 patients presenting an inflammatory skin disease were analyzed with respect to the following criteria: visualization of individual cells in the epidermis and dermis and morphology of dermo-epidermal junction, papillary dermis and reticular dermis. A set of morphological features corresponding to dermatopathological descriptors are obtained and the discriminative accuracy of HD-OCT of inflammatory reaction patterns could be demonstrated. These patterns are spongiotic dermatitis, psoriasiform dermatitis, interface dermatitis and ballooning dermatitis. Additional studies to test the sensitivity and specificity of the proposed algorithm for pattern analysis are essential. The other categories of Ackerman’s pattern recognition need to be evaluated. This study provides a set of morphological features generated by HD-OCT imaging very similar to those described for reflectance confocal microscopy but with the advantages not only to visualize individual cells up to a depth of 570 μm but also in both slice and en face mode. An adapted algorithmic method for pattern analysis of common inflammatory skin diseases could be proposed. This new technique appears to be a promising method for non-invasive diagnosis, evaluation and management of common inflammatory skin diseases.

25. Histological features as predictor of aetiology in lymphocytic gastritis

Aims Lymphocytic gastritis (LG) is a gastric inflammatory reaction pattern characterised by >25 lymphocytes per 100 epithelial cells identified in 1–4% of all patients undergoing upper endosco-py. The two well established associations are gluten sensitive en-teropathy (GSE) and H. pylori (HP) infection. Many cases remain idiopathic. This study aims to determine if there are any histologi-cal differences among cases of GSE-associated LG, HP associated LG and apparent idiopathic LG. Methods All cases with a complete topographic series of gastric biopsies and an accompanying duodenal biopsy were selected from a database of 279 consecutive LG cases. Comparison was made between three groups: (1) GSE associated LG, (2) HP associated LG, and (3) idiopathic LG. Clinical features were age at presentation and gender. Histological features were site of mucosal inflammation, extent of intra-epithelial lymphocytosis (IEL), IEL density, IEL pattern (surface versus crypt), the presence of erosion, neutrophil infiltration, lymphoid follicles and intestinal metaplasia. Results No age or gender differences were observed. The GSE-associated LP cohort differed significantly from the HP-associated LP cohort in displaying antral predominant inflammation and infrequently exhibiting surface erosion or active inflammation. Idio-pathic LG showed similarities with HP-associated LG. Discussion This study has shown reproducible morphologic differences between gluten sensitive enteropathy associated and H. pylori associated lymphocytic gastritis. It also identified that idio-pathic lymphocytic gastritis shows similarities to H.pylori associated lymphocytic gastritis. The clinical implications of these findings are two-fold. Firstly, the aetiology of the lymphocytosis may be inferred from the associated morphologic features and appropriate follow up investigations can be suggested. Secondly, given the histological similarities, many cases of apparent ‘idiopathic’ lymphocytic gastritis may actually represent H. pylori associated lymphocytic gastritis. Further investigation for H. pylori or presumptive treatment may be appropriate in this cohort of patients.

Optical coherence tomography for biofilm detection in chronic rhinosinusitis with nasal polyposis

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a multifactorial disease that seems to be associated with the presence of microbial biofilms and corresponding subepithelial inflammatory reactions. Optical coherence tomography (OCT) might be applied to detect bacterial and fungal biofilms in patients with CRSwNP. A total of 27 patients with CRSwNP undergoing endoscopic sinus surgery (ESS) were analyzed. The negative control group consisted of six patients undergoing septoplasty for nasal obstruction without CRSwNP. The nasal polyps and inferior turbinate mucosa specimens applied as negative controls were processed to OCT analysis and H.E. and Gram staining. Biofilm was detected in 22 of 27 patients (81.5 %) with CRSwNP and in none of six negative controls. In our series, OCT scan showed an obvious association with the findings of H.E. and Gram staining and was allocated to be a good predictor of biofilm existence. On OCT images, biofilms were displayed as distinct superficial layers with high optical density. It was found that microscopic architecture of biofilms was strongly associated with the integrity of nasal mucosa and to the cellular pattern of subepithelial inflammatory reaction. This study confirmed the presence of microbial biofilms in patients with CRSwNP according to OCT scans and histological analysis. Since biofilms may affect the severity and recurrence rate of CRS treated by ESS they should be detected preoperatively. In conclusion, single application of OCT analysis or combination with conventional histological protocols provides a robust and reliable method for the detection of bacterial and fungal biofilms in CRSwNP. Level of evidence 3b, individual case-control study.

New insights in to the treatment of myocardial infarction.

This study investigated the effects of the L-17 compound of the group of substituted 5R1, 6H2-1,3,4-thiadiazine-2-amines on the inflammatory cellular infiltration and myocardial remodelling which occurs after acute myocardial infarction (MI) in rats. The study is based upon recent clinical and experimental work which demonstrated the role of local and systemic inflammatory reactions in postinfarction remodelling. Acute MI in rats was induced by left coronary artery coagulation. Animals were sacrificed on day one, five and seven after MI induction. The myocardiumal samples were taken from all parts of the heart and examined by histology. This included areas of infarction, infraction and areas that were peri-infarctiom and left ventricular areas distant from the damaged tissues. Serum activity of creatine phosphokinase (CPK), aspartate aminotransferase (AST), isoenzymes 1 and 2 and lactate dehydrogenase (LDH1-2) were investigated on the same three days, before and in the process of MI development was investigated (at days 1, 5 and 7). The L-17 compound to not only decreased the area of initial infarction but also changed the pattern of inflammatory reaction in the affected myocardium fundamentally. Laboratory studies of effects of L-17 compound on the development and course of experimental MI showed that administration decreased blood AST and CPK levels significantly and provided useful the data about the correlation between the activity of these enzymes and the dimensions of the significantly necrotic area. In this model of experimental MI the use of the L-17 compound induced led to the replacement of the exudative destructive inflammation that is seen under standard conditions with a more cellular "productive" pattern of inflammation, with associated reduction in initial necrosis area and the, decrease in myocardial ischaemia and reperfusion injury may account for the accelerated repair process.

Safety distance in the resection of colorectal lung metastases: A prospective evaluation of satellite tumor cells with immunohistochemistry

After complete pulmonary metastasectomy of colorectal lung metastases, tumor recurrence at the site of former resection develops in some patients. Well-described risk factors for local recurrence in the lung include incomplete resection and aerogenous spread of floating cancer cell clusters. The aim of this study was to describe the distribution and frequency of satellite cancer cells or clusters in resected tissue to deduce recommendations for safety margins in the future. Seventeen colorectal metastases from 10 patients were processed. Evaluation for pattern of growth, satellite cancer cells, and inflammatory reaction at the surface of the metastases was performed on 102 sections with CDX2 and cytokeratin 20 stains. The distance between the surface of the nodule and the satellite cancer cell was measured for each satellite and statistically evaluated. As a pattern of growth, interstitial spread, inflammatory reaction, and lymphangitic spread were observed in 41.2%, 35.3%, and 23.5%, respectively. A total of 205 satellite cancer cells were identified in 16 of 17 metastases with a mean distance to the nodule of 0.99 ± 0.85 mm (range, 0.06-6.43 mm). The percentages of satellite tumor cells that are likely to be found within 1.59 mm, 3.43 mm, and 7.4 mm around the nodule are 68.27%, 95.5%, and 99.73%, respectively. Satellite tumor cells, a potential source for local recurrence, are found in a high number around colorectal lung metastases. As a standard of care, a safety distance of 3 mm for small metastases and 8 to 10 mm for larger metastases must be maintained around the lesion to prevent local recurrence.

Primary bovine synoviocyte cultures: A useful tool for in vitro drug testing?

The aim of the study was to evaluate bovine synoviocyte culture as an in vitro model to test new intra-articular drugs. The inflammatory reaction pattern of synoviocytes as compared to fibroblasts was studied over nine passages. Expression of pro-inflammatory cytokines was assessed after stimulation with lipopolysaccharide. Immunohistochemical markers were used to identify synoviocyte populations. Primary synoviocytes expressed markedly higher amounts of interleukin-1β mRNA and tumour necrosis factor-α mRNA than fibroblasts after stimulation. This difference was lost over two passages. CD68-positive macrophage-like synoviocytes diminished over three passages, which may explain the reduced pro-inflammatory cytokine response. Primary bovine synoviocytes appear to be an appropriate and optimised model for testing novel drugs for cattle, because their response may more closely reflect in vivo tissue responses compared to cultured cell lines.

Juvenile polymyositis or paediatric muscular dystrophy: a detailed reanalysis of 13 cases

There has been much debate about the existence of juvenile polymyositis (JPM) as an entity distinct from muscular dystrophy (MD). Recent advances in techniques allow for more accurate identification of muscle disorders. <h3>Aim</h3> To re-analyse the clinical features and muscle tissue of biopsy specimens from 13 children initially given a diagnosis of JPM, to determine whether an underlying dystrophy is present. <h3>Methods</h3> Thirteen cases previously diagnosed with JPM were re-analysed using morphology, immunoperoxidase studies, Western blotting and molecular genetic analysis and compared with cases of adult polymyositis (<i>n</i>=8) and Duchenne muscular dystrophy (<i>n</i>=4). <h3>Results</h3> All 13 cases had clinical outcomes consistent with a MD. Endomysial inflammatory infiltrates, predominantly CD68+ macrophages, CD3+ and CD4+ T cells, were present in muscle from all cases. Invasion of intact myofibres by CD8+ lymphocytes was absent (<i>p</i>=0.02). Subsarcolemmal blebbing of non-necrotic fibres was obsereved in JPM (<i>p</i><0.01). The MHC-I expression pattern differed from that seen in polymyositis. Eleven JPM cases had an abnormality in sarcolemmal protein expression. <h3>Discussion</h3> All 13 cases initially diagnosed with JPM clinically and pathologically had a MD. The inflammatory reaction pattern in JPM is distinct from that seen in adult polymyositis and should abrogate the use of long-term prednisolone in this young cohort.

P.349 Surgical treatment for stages I and II tongue carcinoma

To evaluate the pattern of recanalization and specific inflammatory reaction after superselective embolization with four commercially available spherical embolic agents of different sizes in the mini pig kidney model.In 40 mini pigs, the lower poles of both kidneys were superselectively embolized with Embozene, Embosphere, Bead Block, and Contour SE particles in sizes of 40–120 μm (Embozene, Embosphere) and 100–300 μm, 500–700 μm, and 700–900 μm (Embozene, Embosphere, Bead Block, Contour SE). After a follow-up time of 4 or 12 weeks, recanalization was determined with angiography. Pathologic and histologic evaluation of the kidneys was performed, and the Banff 97 classification was used to evaluate the extent of vessel wall inflammation. Macroscopically visible ischemic changes were evaluated by using a specific ischemia score.After embolization with Embozene microspheres, larger Embosphere particles, and Bead Block and Contour SE particles, the absence of inflammation or a low inflammation score was observed. Significantly elevated inflammation scores were evident with small Embosphere particles after 4 weeks (mean score, 1.21 ± 1.0). Distinct recanalization occurred with Contour SE particles (100% recanalization with 100–300-μm particles at 12 weeks, 500–700-μm particles at 4 and 12 weeks, and 700–900-μm particles at 4 weeks). Ischemia scores were highest in the target area in all specimens. Mildly elevated ischemia scores in nontarget tissue areas were indicative of minor nontarget embolization.Except for small Embosphere particles at 4 weeks, the absence of inflammatory reaction to the embolization procedure or only low inflammatory changes were observed with all embolic agents, particle sizes, and follow-up intervals. Recanalization was evident with all embolic agents; however, it was pronounced with Contour SE particles.

The significance of histopathologic patterns in positive tuberculin skin test site

The histologic features of tuberculin skin test site is not uniform. It may be related to status of tuberculosis. Forty-eight purified protein derivative (PPD) positive-cases were chosen for the study. Thirty of the subjects had active tuberculosis. As previously reported, the histologic pattern of inflammatory reaction seen in the test site classified into three type: (a) Perivascular (PV)-type, (b) Basal spongiotic dermatitis (BSD)-type and (c) Erythema multiforme (EM)-type. The frequencies of histological patterns in active tuberculosis and latent tuberculosis were statistically analyzed. In active tuberculosis group including 30 patient, 17 (56.7%) EM-type, 9 (30%) BSD-type and 4(13.3%) PV-type inflammation were seen. Among 18 latent tuberculosis, there were 2 (11.1%) EM-type, 7 (38 8%) BSD-type and 9 (50%) PV-type inflammatory reactions. The EM-type inflammation was more common in active tuberculosis group. Bulla formation was seen in seven subjects with active tuberculosis. The histological pattern of PPD reaction site may be an important sign reflecting the nature of the tuberculosis, which may be either latent or active. The bulla formation is an important sign for active pulmonary tuberculosis. Further, detailed immunohistopathologic studies of PPD reaction with large number of cases may give important clues about tuberculosis immunology.

Inflammation and Recanalization of Four Different Spherical Embolization Agents in the Porcine Kidney Model

To evaluate the pattern of recanalization and specific inflammatory reaction after superselective embolization with four commercially available spherical embolic agents of different sizes in the mini pig kidney model. In 40 mini pigs, the lower poles of both kidneys were superselectively embolized with Embozene, Embosphere, Bead Block, and Contour SE particles in sizes of 40-120 mircom (Embozene, Embosphere) and 100-300 microm, 500-700 microm, and 700-900 microm (Embozene, Embosphere, Bead Block, Contour SE). After a follow-up time of 4 or 12 weeks, recanalization was determined with angiography. Pathologic and histologic evaluation of the kidneys was performed, and the Banff 97 classification was used to evaluate the extent of vessel wall inflammation. Macroscopically visible ischemic changes were evaluated by using a specific ischemia score. After embolization with Embozene microspheres, larger Embosphere particles, and Bead Block and Contour SE particles, the absence of inflammation or a low inflammation score was observed. Significantly elevated inflammation scores were evident with small Embosphere particles after 4 weeks (mean score, 1.21 +/- 1.0). Distinct recanalization occurred with Contour SE particles (100% recanalization with 100-300-microm particles at 12 weeks, 500-700-microm particles at 4 and 12 weeks, and 700-900-microm particles at 4 weeks). Ischemia scores were highest in the target area in all specimens. Mildly elevated ischemia scores in nontarget tissue areas were indicative of minor nontarget embolization. Except for small Embosphere particles at 4 weeks, the absence of inflammatory reaction to the embolization procedure or only low inflammatory changes were observed with all embolic agents, particle sizes, and follow-up intervals. Recanalization was evident with all embolic agents; however, it was pronounced with Contour SE particles.

Safety and Tolerability of Adjuvant Topical Tacrolimus Treatment in Boys with Lichen Sclerosus: A Prospective Phase 2 Study

BackgroundManagement of lichen sclerosus (LS) in boys is still controversial. Although in most cases only the prepuce is affected, meatal and urethral involvement may require major surgical reconstruction with substantial morbidity. ObjectiveBecause the frequency of such complicated courses is still unclear, an adjuvant postoperative treatment is highly desirable. Therefore, we addressed safety and tolerability of tacrolimus 0.1% ointment in the postoperative period. Design, Setting, and ParticipantsAmong 222 penile surgeries, in 25 cases LS was confirmed histologically and 20 of those patients participated in the adjuvant treatment study. Moreover, 18 patients of the same cohort showed a lichenoid inflammatory reaction pattern suggestive of early but not fully established LS. Interventions and MeasurementsSubsequent to the operation and after explicit information about off-label use, parents applied tacrolimus 0.1% ointment twice daily to the glans and the meatus for 3 wk in cases of proven LS. The 18 patients with possible early LS were followed up only without any treatment. Clinical follow-up was performed up to 13 mo (median). Results and LimitationsAll 20 LS patients completed the topical treatment without any relevant side-effects. Two relapses occurred in the treatment group and were clinically cured with an additional 3-wk cycle of topical tacrolimus 0.1% ointment. None of the 18 early LS cases progressed to full-scale LS. ConclusionsThis is the first study showing that tacrolimus 0.1% ointment applied immediately after surgery of fully established LS is a tolerable and most probably safe adjuvant novel treatment option. Because the therapy led to disease control in all treated individuals for >1 yr (median), this study establishes the groundwork for future trials with expanded treatment and follow-up periods to verify the true clinical benefit of tacrolimus in patients after LS surgery. Lichenoid tissue reactions suggestive of early LS seem to require no adjuvant treatment.

Prognostic value of differential expression of Laminin-5 γ2 in oral squamous cell carcinomas: Correlation with survival

In oral squamous cell carcinomas of the head and neck, Laminin-5 gamma2 has been associated with tissue invasion, lymph node metastasis and histopathological grading. In the present study, we compared the expression of the subunit gamma2 of Laminin-5 under normal, dysplastic and invading epithelia in 65 biopsies previously diagnosed for oral squamous cell carcinoma. The number of gamma2-positive cells were analyzed in relation to patients' survival, tumor grading, size of the lesion, TNM stage, histopathological pattern of invasion and inflammatory reaction. Biopsies of oral squamous cell carcinomas were deparaffinised, processed for antigen unmasking procedures and stained with antibody anti-Laminin-5 gamma2. By light microscopy, 4 optical fields of x200 were selected in three different areas including normal, dysplastic and invading epithelia. Positive cells were counted and divided into three categories, which included <20 cells, between 21 and 50 cells and >50 stained cells. Patient survival was analyzed by Kaplan-Mayer curves. gamma2-positive cells were found in the basal layer of dysplastic epithelium, within inflammatory infiltrate, at the margins of differentiated invading islands and at the forefront of undifferentiated invading nests. Observations showed that an increased number of gamma2-positive cells correlated significantly with a shorter life expectancy under invading epithelia (log-rank test p<0.05), not when a count was performed under normal or dysplastic epithelia of the same patient. The number of gamma2-positive cells also correlated with the histopathological pattern of invasion. Our results show that gamma2 may be a reliable prognostic tool for oral squamous cell carcinomas.

Clinical and histological characteristics of renal AA amyloidosis: a retrospective study of 68 cases with a special interest to amyloid-associated inflammatory response

We retrospectively reviewed the clinicopathological features of a series of 68 renal AA amyloidosis observations collected between 1990 and 2005. The amyloidogenic disease was a chronic infection (40.8%), a chronic inflammation (38%), a tumor (9.9%), a hereditary disease (9.9%), or was undetermined in 1.4% of cases. Nephrotic syndrome and renal insufficiency were noted in 63.1% and 75% of patients, respectively. The distribution pattern of glomerular amyloid deposits was mesangial segmental (14.7%), mesangial nodular (26.5%), mesangiocapillary (32.3%), and hilar (26.5%). Glomerular form was observed in 80.9% of cases and vascular form in 19.1%. AA amyloidosis-related inflammation was noted in 30 patients (44.1%) and appeared as a multinucleated giant cell reaction (27.9%) or a glomerular inflammatory infiltrate (25%), including glomerular crescents (17.6%). At the end of follow-up, 26 patients (38.2%) showed end-stage renal disease. The clinical presentation of glomerular and vascular forms was distinct with a clear predominance of proteinuria in glomerular form. Inflammatory reaction was preferentially observed in biopsies with a codeposition of immunoglobulin chains and/or complement factors in AA amyloid deposits. The distribution pattern of glomerular amyloid deposits and glomerular inflammatory reaction were independent factors influencing proteinuria level. Tubular atrophy, abundance, and distribution pattern of glomerular amyloid deposits at the time of biopsy were independent predictors of renal outcome. In conclusion, the glomerular involvement appeared as the determining histological factor for clinical manifestations and outcome of renal AA amyloidosis. AA amyloidosis-related inflammation could partly result from an immune response directed against AA fibrils and could induce amyloid resolution and crescents.

Chronic cutaneous lesions of sarcoidosis

Sarcoidosis involvement of the skin is common. The skin lesions of sarcoidosis may be nonspecific, showing a nondiagnostic inflammatory reaction pattern on histologic evaluation. Nonspecific skin lesions are often associated with an acute presentation of sarcoidosis and, in general, portend a good prognosis. Specific sarcoidosis skin lesions reveal typical sarcoid granulomas on histologic examination. These lesions tend to be chronic and require therapy for resolution. This article will review the epidemiology, diagnostic evaluation, and description of the various chronic skin lesions of sarcoidosis. Various images of these skin lesions will be demonstrated.

The inflammatory reaction pattern distinguishes primary dysferlinopathies from idiopathic inflammatory myopathies: an important role for the membrane attack complex

Degenerative muscle changes in dysferlinopathies are often accompanied by inflammatory infiltrates and may even mimic primary idiopathic inflammatory myopathies. In the present study, the inflammatory reaction pattern with respect to the cellular composition of the infiltrates and the expression of potent cytokines was characterized in dysferlinopathies and in idiopathic inflammatory myopathies. Cellular infiltrates in dysferlinopathies mainly consisted of CD4+CD25- T cells and macrophages. We noted a prominent expression of interferon-gamma which may contribute to the marked upregulation of MHC class I antigen observed on the vast majority of muscle fibres. Furthermore, membrane attack complex positive deposits were found on intact as well as necrotic muscle fibres. Collectively, our study indicates that the inflammatory reaction pattern in dysferlinopathies is distinct from the one in idiopathic inflammatory myopathies. In particular, membrane attack complex deposits and a pro-inflammatory milieu in the absence of interleukin-10 expression may contribute to progressive muscle damage in dysferlinopathies.

The inflammatory reaction pattern distinguishes dysferlinopathies from idiopathic inflammatory myopathies

Dysferlinopathies are often accompanied by inflammatory infiltrates and may even mimic idiopathic inflammatory myopathies. In the present study, the inflammatory reaction profile with respect to the cellular composition of the infiltrates and the expression of major cytokines was characterized by immunofluorescence in dysferlinopathies and compared to idiopathic inflammatory myopathies. Infiltrates consisted mainly of CD4+ CD25- T cells and macrophages. The prominent expression of interferon-gamma may underlie the marked upregulation of MHC class I antigen on the vast majority of muscle fibres. Remarkably, these data indicate that membrane attack complex was deposited on intact and necrotic muscle fibres. Collectively, these data indicate that membrane attack complex deposits and a pro-inflammatory milieu without interleukin-10 expression may contribute to pathology of dysferlinopathies.

Inflammation and prognosis in colorectal cancer

Aim of the study Previous work has indicated that quantification of inflammatory cell reaction is of prognostic value in colorectal cancer. We evaluated the prognostic significance of inflammatory cell reaction patterns in colorectal cancer and developed a grading method which could be used in the routine assessment of tumours. Methods The intensity of overall inflammatory cell reaction, numbers of neutrophilic and eosinophilic granulocytes, lymphoid cells and macrophages in both the central region and the invasive margin were estimated in 386 colorectal cancer patients. Prognostic significance was analysed by uni- and multivariate analysis. Results Our method for classification of inflammatory reaction was reliable. High-grade inflammation at the invasive margin in Dukes’ stage A and B cancers (pT1-2N0 and pT3N0, respectively) was associated with better 5-year-survival (87.6%) than low-grade inflammation (47.0%). Conclusions Inflammatory cell response at the invasive border is a relevant prognostic indicator and could be easily incorporated into the routine evaluation of histopathological specimens.

Cutaneous granulomatous inflammation

Summary A granulomatous inflammatory reaction pattern in the skin is common. There can be diverse morphological appearances histologically and numerous aetiologies. The principal reaction patterns are those of epithelioid (sarcoidal and tuberculoid) granulomas, palisaded granulomas, suppurative granulomas, xanthogranulomas, foreign body granulomas and miscellaneous granulomatous conditions. Traditionally, the granulomatous reaction pattern is considered to be a benign/reactive phenomenon. However, a number of malignancies can mimic benign granulomatous inflammation. Rational classification of cutaneous granulomatous inflammation is therefore difficult and at best imperfect since there is an overlap between the histological patterns. As with all inflammatory dermatoses, clinicopathological correlation is essential. Additionally, special techniques and molecular pathology may be required. However in a minority of cases it will not be possible to make a definitive diagnosis, even with all the clinical information available.

Polymorphisms in the interleukin-1 alpha and beta genes and the risk for Parkinson's disease

Several lines of evidence indicate that immune mechanisms are involved in the pathogenesis of neurodegenerative disorders. Activated immunocompetent cells and inflammatory cytokines are present in affected brain regions in patients with Alzheimer's (AD) and Parkinson's disease (PD). For AD biochemical and pathological data are supported by genetic studies identifying risk alleles for polymorphisms in regulatory regions of the interleukin-1 alpha (IL-1α-889) and interleukin-1 beta (IL-1β-511) gene, respectively. The partially overlapping pathology and inflammatory reaction pattern between AD and PD led us to investigate these polymorphisms in a large sample of 295 German PD patients and 270 healthy controls. We found T in position −511 in the IL-1β gene more frequent in patients compared to controls (χ 2=4.44, P=0.034). For the IL-1α-889 polymorphism no significant difference between patients and controls was observed.