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Objectives: An increased risk of haematological malignancies (HM) has been reported in GCA patients. Our study aimed to investigate the incidence and the type of HM occurring in GCA., Methods: All patients with GCA and HM living in Côte d'Or (France) were identified by crossing data from the RHEMCO (Registre des Hémopathies Malignes de Côte d'Or) and those having a positive temporal artery biopsy between 1 January 2001 and 31 December 2018., Results: Among 276 biopsy-proven GCA patients, 14 HM were identified in 12 patients (4.3%). In comparison with the general population aged >50 y, the incidence of myeloid HM and myeloproliferative syndromes were increased in GCA patients [standardized incidence ratios (SIR) = 2.71 and 5.16, respectively], with a specific increase in men with GCA (SIR = 4.82 and 9.04, respectively) but not in women. In addition, the study of SIR depending on the chronology between GCA and HM diagnoses suggests that there was an increased risk of developing GCA in men but not in women, after a diagnosis of myeloid HM (SIR = 9.56), especially if it was a MPS (SIR = 17.56)., Conclusions: Our study shows a particular epidemiology of HM in GCA patients, which is characterized by an increased incidence of myeloid HM, especially MPS, in male GCA patients. The chronology of the diagnoses of GCA and HM raises the hypothesis that clonal hematopoiesis may be implicated in some cases of GCA., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Cardiovascular risk is increased in giant cell arteritis (GCA). We aimed to characterize myocardial infarction (MI) in a GCA cohort, and to compare the GCA and non-GCA population affected by MI., Methods: In patients with a biopsy-proven diagnosis of GCA between 1 January 2001 and 31 December 2016 in Côte D'Or (France), we identified patients with MI by crossing data from the territorial myocardial infarction registry (Observatoire des Infarctus de Côte d'Or) database. Five controls (non-GCA + MI) were paired with one case (GCA + MI) after matching for age, sex, cardiovascular risk factors and prior cardiovascular disease. MI were characterized as type 1 MI (T1MI), resulting from thrombus formation due to atherothrombotic disease, or type 2 MI (T2MI), due to a myocardial supply/demand mismatch. GCA-related MI was defined as MI occurring within 3 months of a GCA flare (before or after)., Results: Among 251 biopsy-proven GCA patients, 13 MI cases were identified and paired with 65 controls. MI was GCA-related in 6/13 cases, accounting for 2.4% (6/251) of our cohort. T2MI was more frequently GCA-related than GCA-unrelated (80% vs. 16.7%, p = 0.080), and GCA diagnosis was the only identified triggering factor in 75% of GCA-related T2MI. GCA-unrelated MI were more frequently T1MI and occurred in patients who had received a higher cumulative dose of prednisone (p = 0.032). GCA was not associated with poorer one-year survival., Conclusions: GCA-related MI are mainly T2MI probably caused by systemic inflammation rather than coronaritis. GCA-unrelated MI are predominantly T1MI associated with atherothrombotic coronary artery disease., (Copyright © 2021. Published by Elsevier B.V.)

Introduction: Malakoplakia is a granulomatosis of infectious origin in reaction to a chronic bacterial infection (most commonly urinary Escherichiacoli) related to an acquired phagocytosis impairment., Patients and Methods: We report a case of penile malakoplakia in a 69-year-old man with lichen sclerosis and stenosis of the urinary meatus leading to recurrent urinary tract infections. The clinical aspect was suggestive of squamous cell carcinoma of the glans developing on lichen sclerosus, but histological examination revealed penile malakoplakia., Discussion: Malakoplakia of the genital mucosa is rare, with only one case of involvement of the glans being reported in the literature. The association with lichen sclerosus is probably not fortuitous but could in fact be due to chronic urinary tract infection favored by stenosis of the urethral meatus and possible local immunodepression following prolonged application of clobetasol., Conclusion: We report a case of penile malakoplakia associated with chronic E. coli urinary tract infection, due originally to associated genital lichen sclerosus., (Copyright © 2019. Published by Elsevier Masson SAS.)

We aim to determine whether differences in survival exist between two populations of women with metastatic breast cancer (MBC) and to identify prognostic factors of survival after metastasis diagnosis. Data on women with MBC diagnosed between 2000 and 2011 were provided by the Côte d'Or Breast cancer registry. Survival rates and median overall survival (OS) after metastasis diagnosis were determined using the Kaplan-Meier method and prognostic factors were determined in a Cox proportional hazard model. Overall, 282 women with primary MBC and 340 with secondary MBC were included. A 2-year survival rate was significantly better in women with primary MBC (50.8% [95% CI: 47.8-53.8%] versus 44.5% [95% CI: 41.8-47.2%]). However, median OS did not differ between the two groups (p = 0.1). The prognostic factors associated with worst survival were a triple-negative tumor type (p < 10 -4 ), multiple metastases sites (p < 10 -4 ), an older age at metastasis (p < 10 -4 ), and a SBR grade G3 (p = 0.007). OS between women with primary MBC and women with secondary MBC does not seem to differ significantly. This population-based study provides original epidemiological data on French women without any selection bias inherent to hospital cohorts., (© 2016 Wiley Periodicals, Inc.)

We aim to describe trends in net survival (NS) and to assess the prognostic factors among women with de novo metastatic breast cancer (MBC) according to human epidermal growth factor receptor 2 (HER2) and hormone receptor (HR) status. Data on women suffering from de novo MBC and diagnosed from 1998 to 2009 were provided by the Côte-d'Or breast cancer registry. NS was described using the Pohar Perme estimator and prognostic factors were investigated in a generalised linear model. We identified 232 patients (mean age = 64.7). Median NS was 29.2 months, 1- and 5-year NS were 76% and 26% respectively. The survival trend in patients with HER2-positive tumours who did not receive trastuzumab was similar to that in women with triple-negative tumours. A higher relative excess risk of death by cancer was observed for high-grade tumours [RER, relative excess rates = 1.76 (95% CI, confidence intervals: 1.17-2.62) for Scarff Bloom Richardson grade 3 vs. 1 + 2], while a lower risk was observed for luminal tumours [RER = 0.49 (95% CI: 0.27-0.89)] and HER2-positive tumours treated with trastuzumab [RER = 0.28 (95% CI: 0.14-0.59)], both compared with triple-negative tumours. Surgery of the primary tumour was associated with better survival [RER = 0.43 (95% CI: 0.28-0.68)]. With half of the women dead before 29 months, stage IV breast cancer still has a bleak outlook. Progress should continue with new target therapies for both HR and HER2 receptors., (© 2015 John Wiley & Sons Ltd.)

Introduction: Pyoderma gangrenosum is the ulcerative form of neutrophilic dermatoses. The most frequent extracutaneous localizations are the lungs, joints, and digestive tract., Case Record: We report a case of Pyoderma gangrenosum, which presented first as an aseptic lung abscess. The first cutaneous lesions occurred 9 months later, with skin ulcerations on the thorax and on surgical scars. The histological diagnosis was made on skin biopsies. There was no associated abnormality except for IgA monoclonal gammapathy. Clinical improvement was noted with immunosuppressive treatment., Discussion: This infrequent case report underlines that lung abscesses may be of non-infectious origin, that in Pyoderma gangrenosum, skin lesions may be come several months after extracutaneous manifestations, among which lungs abcesses are the most frequent.

Purpose: The present study was designed to determine whether the nuclear or cytoplasmic expression of survivin, was related to clinicopathological parameters and survival in sporadic colon carcinomas., Methods: Western blotting of cell fractions and immunocytochemical methodology were used in five human colon cancer cell lines. Immunohistochemical study was performed in formalin-fixed paraffin-embedded section from 46 patients with sporadic colorectal adenocarcinomas with a polyclonal antibody directed against survivin. Apoptotic index was evaluated by using the M30 antibody. Survival rates were estimated by the Kaplan-Meier method and compared using the log-rank test. Multivariate survival analysis was performed by the Cox proportional hazards model., Results: Western blotting and immunocytochemistry analyses confirmed that survivin could be detected both in the nucleus and the cytoplasm. Immunohistochemical analysis demonstrated that 39% of tumours expressed survivin in the nucleus and 41% in the cytoplasm. No relationship was observed between survivin expression and clinicopathological features. Unexpectedly, the apoptotic index appeared to be linked with high survivin nuclear expression. Overall, 3-year observed survival rate was 73% in patients with cytoplasmic survivin expression versus 48% for negative expression (P = 0.14). Survival was 72% versus 50% for positive nuclear survivin expression versus negative (P = 0.16). After adjustment for age and stage, cytoplasmic survivin expression was a significant prognostic factor. A high level of expression was associated to a better survival: RR = 0.35 [0.13-0.98], P = 0.045., Conclusion: These results indicate that the analysis of the subcellular expression of survivin is a determining factor to define the prognostic value. Its evaluation, using a polyclonal antibody, might help clinicians in the stratification of patients with colorectal cancer.

The authors report the case of a patient followed for renal angiomyolipoma. On CT surveillance, this lesion developed features of a malignant tumour with loss of the fatty component and the patient was treated by nephrectomy. Histological examination demonstrated renal angiomyolipoma with an epithelioid contingent. The various aspects of this histological and radiological variant are discussed.

The assessment of the microsatellite instability (MSI) status in colorectal cancers is presently warranted for three reasons: 1) as a screening tool for hereditary nonpolyposis colorectal cancer, 2) as a prognostic marker, and 3) as a potential predictive factor of chemotherapy response. The aim of this study was to evaluate, on a large scale with tissue samples coming from a number of different sources, the difficulties met with routine use of immunohistochemistry (IHC) and to determine if it really does offer an accurate alternative to PCR genotyping. Colorectal carcinomas from 462 consecutive patients resected in public or private hospitals were assessed for MSI status by two methods: MSI testing (with BAT-26 microsatellite) and IHC detection of hMLH1, hMSH2, and hMSH6 proteins. Of the 398 cancers tested, immunohistochemistry was noncontributory in 42 (10.5%), focal in 9 (2.3%), and discordant with the PCR results in 36 (9%). For these 87 cases, complementary analyses were performed to explain discrepancy. After additional IHC assay with modified processing protocols, 8 cases remained noncontributory, 2 focal, and 28 discordant: 18 microsatellite stability IHC/MSI PCR and 10 MSI IHC/microsatellite stability PCR. For these discordant cases, we performed a multiplex PCR assay on DNA extracted from the frozen sample and BAT-26 was amplified from DNA extracted from the paraffin blocks used for IHC. Four discordant cases were reclassified after PCR multiplex assay (3 as MSI and 1 as microsatellite stability). Five other cases displayed intratumoral heterogeneity and 19 remained discordant. The discrepancy could be partly explained by variable technical protocols of fixation in the different laboratories, leading to variations in staining quality and difficulties in IHC interpretation. This population-based study is the first one to show that IHC is not sensitive and specific enough to be used routinely. Immunohistochemistry analysis of MMR proteins must be performed in standardized conditions and interpreted by confirmed pathologists. It cannot replace PCR as long as protocols are not optimized and harmonized.

The caspase inhibitor and RING finger-containing protein cellular inhibitor of apoptosis protein 1 (c-IAP1) has been shown to be involved in both apoptosis inhibition and signaling by members of the tumor necrosis factor (TNF) receptor family. The protein is regulated transcriptionally (eg, is a target for nuclear factor-kappaB [NF-kappaB]) and can be inhibited by mitochondrial proteins released in the cytoplasm upon apoptotic stimuli. The present study indicates that an additional level of regulation of c-IAP1 may be cell compartmentalization. The protein is present in the nucleus of undifferentiated U937 and THP1 monocytic cell lines. When these cells undergo differentiation under phorbol ester exposure, c-IAP1 translocates to the cytoplasmic side of the Golgi apparatus. This redistribution involves a nuclear export signal (NES)-mediated, leptomycin B-sensitive mechanism. Using site-directed mutagenesis, we localized the functional NES motif in the caspase recruitment domain (CARD) of c-IAP1. A nucleocytoplasmic redistribution of the protein was also observed in human monocytes as well as in tumor cells from epithelial origin when undergoing differentiation. c-IAP1 does not translocate from the nucleus of cells whose differentiation is blocked (ie, in cell lines and monocytes from transgenic mice overexpressing B-cell lymphoma 2 [Bcl-2] and in monocytes from patients with chronic myelomonocytic leukemia). Altogether, these observations associate c-IAP1 cellular location with cell differentiation, which opens new perspectives on the functions of the protein.

Purpose: To determine the nature of the changes of the vascular wall after intravascular brachytherapy in stented arteries leading to incomplete stent apposition., Methods and Materials: Stents were implanted in the infrarenal aortas of rabbits, and gamma-intravascular brachytherapy (18 Gy) or a sham radiation procedure was immediately implemented. The arteries were harvested at 6 months for histologic analyses., Results: The external elastic lamina area, as well as the vascular wall area behind the stent, were significantly greater in irradiated vs. control arteries (8.94 +/- 0.68 mm2 vs. 6.87 +/- 0.40 mm2 [p <0.001] and 1.56 +/- 0.13 mm2 vs. 0.72 +/- 0.07 mm2 [p <0.001], respectively). The ratio of the intimal area behind the stent related to the total intimal area was greater in the irradiated segments (control vs. irradiated: 9.0% +/- 5.9% vs. 55.3% +/- 15.5%, p <0.05). Neointimal growth of the irradiated vessels outside the stent was characterized by marked fibrin depositions and an inflammatory response around the stent struts., Conclusion: Our study revealed the presence of a neointimal layer specifically located behind the stent, which represented the result of an unhealed fibrin-rich tissue growth process 6 months after intravascular brachytherapy.

Introduction: Imatinib (Glivec) is a new molecule that specifically inhibits tyrosine-kinase activity and is used in the treatment of chronic myeloid leukemia. Cutaneous side effects with imatinib are frequent. We report the first case of purpuric vasculitis probably due to this drug., Observation: A 65 year-old man was treated for chronic myeloid leukemia with imatinib. After two months of treatment, he developed an erythematous and squamatous on the trunk, which regressed spontaneously one week after suspension of the product. Imatinib was reintroduced two months later. The patient immediately developed a painful, infiltrated, purpuric eruption on the legs. Histological examination revealed vasculitis compatible with the diagnosis of toxiderma. Since treatment could not be suspended, oral corticosteroids were introduced and the lesions cleared within three weeks., Discussion: Adverse cutaneous reactions to imatinib are frequent. Their physiopathological mechanism is unknown.

Aims: The aim of this study was to assess the independent value of pathological criteria in the diagnosis of mismatch repair (MMR)-defective sporadic colorectal cancers., Methods and Results: Resected colorectal adenocarcinomas (n = 273) were reviewed in order to identify a number of specific morphological features of MMR-defective carcinomas. Of the 273 cases, 35.2% were right-sided and 5.9% were poorly differentiated. Focal extracellular mucin secretion was seen in 5.1% of cases and a stromal follicular reaction in 4.6%. The expression of the two major MMR proteins hMLH1 and hMSH2 was studied by immunohistochemistry. Carcinomas were considered deficient in the MMR system when a loss of nuclear signal in neoplastic cells was observed for one of the proteins. Such an extinction was seen in 37 of the cases (13.6%). The hMLH1 protein was the one most frequently altered (86.5%). After multivariate analysis, three independent factors were significantly associated with MMR deficiency: proximal location [odds ratio (OR) = 9.30; 95% confidence interval (CI) 2.79, 30.98], the presence of a true stromal follicular reaction (OR = 13.60; 95% CI 2.98, 62.00) and poor differentiation (OR = 8.33; 95% CI 1.63, 40.32)., Conclusions: These results confirm that sporadic colorectal MMR-defective adenocarcinomas display certain specific morphological characteristics. However, these pathological features are not sufficiently predictive and immunohistochemistry is needed to identify such tumours accurately.

The Inhibitor of Apoptosis Protein (IAP) family includes several critical cell death inhibitors, the expression of which could be involved in colorectal carcinogenesis. Among them, c-IAP1 and c-IAP2 expression has never been investigated in colorectal cancer. The present study was designed to determine whether expression of both IAPs was related to pathological parameters and survival in sporadic colon carcinomas. Analysis of five human colon cancer cell lines by both western blotting of cell fractions and immunocytochemistry showed that the two IAPs could be expressed both in the nucleus and in the cytoplasm. Immunohistochemical analysis of a series of 46 sporadic colorectal adenocarcinomas demonstrated that c-IAP1 expression was more frequent in the nucleus (85%), and that c-IAP2 was more often expressed in the cytoplasm (82%). A significant association was identified between a strong lymphoid infiltrate in the stroma and the nuclear expression of c-IAP2 (p = 0.02). No other relationship was observed between IAP expression and pathological features. After adjusting by age and stage, the relative risk of death was lower for cytoplasmic c-IAP1, cytoplasmic c-IAP2, and nuclear c-IAP2 expression. It was higher for nuclear c-IAP1 expression. These associations were not statistically significant, but this work underlines the importance of taking into account the subcellular location of the IAP family members in the evaluation of their prognostic significance.

A case of a chondroblastoma of the skull-base associated with a persistent hypoglossal artery (PHA) is presented. Neuroradiological findings of the PHA and the tumour are reported. The existence of a carotico-basilar communication such as a PHA should be recognized prior to skull base surgery because of the potential risk of cerebral ischemia.

Molecular biology studies have led to the identification of two different types of colorectal carcinomas. The first group, called LOH (for loss of heterozygosity), represents 80% of colorectal cancers and is characterised by aneuploidy, allelic losses and a location in the distal colon. The second group displays phenotypic microsatellite instability (MSI-positive tumours), has a near-diploid karyotype and a relatively low frequency of allelic losses. It accounts for 15% of all colorectal cancers and for about 30% of right-sided cancers. Four different pathways have been identified as responsible for tumour progression: the WNT/Wingless, the K-ras, the Transforming growth factor (TGF) and the P53 pathways. The involvement of these pathways depends on the tumour type. In LOH-positive tumours, the WNT/Wingless pathway is activated through an APC mutation, whereas MSI+ tumours do so through a catenin stabilising mutation. The TGFb growth inhibitory pathway is altered either by mutations in the signal transduction molecules SMAD2 and SMAD4 in LOH positive tumours or by mutations of TGFbRII in MSI+ tumours. In the p53 pathway, mutations in BAX may contribute to the adenoma-carcinoma transition just as p53 mutations may do in LOH positive tumours. Until now, cancer phenotype determination has had no clinical implications. However, the predictive value of the MSI status was recently stressed as a predictive factor for response to chemotherapy. Immunohistochemistry could represent a complementary strategy to molecular biology in assessing MSI status. This simple test would allow to screen all colorectal carcinomas for MSI status, which would provide valuable management information in addition to the histological assessment for tumour stage and grade.

Microsatellite instability has been proposed as an alternative pathway of colorectal carcinogenesis. The aim of this study was to evaluate the interest of immunohistochemistry as a new tool for highlighting mismatch repair deficiency and to compare the results with a PCR-based microsatellite assay. A total of 100 sporadic proximal colon adenocarcinomas were analysed. The expression of hMLH1, hMSH2 and hMSH6 proteins evaluated by immunohistochemistry was altered in 39% of the cancers, whereas microsatellite instability assessed by PCR was detected in 43%. There was discordance between the two methods in eight cases. After further analyses performed on other tumoural areas for these eight cases, total concordance between the two techniques was observed (Kappa=100%). Our results demonstrate that immunohistochemistry may be as efficient as microsatellite amplification in the detection of unstable phenotype provided that at least two samples of each carcinoma are screened, because of intratumoural heterogeneity.

Over the last 20 years, our understanding of cutaneous adverse drug reactions has improved, especially with regard to the management of affected patients. The pathophysiological mechanisms have been studied to improve our understanding. We report different clinical and histological features of cutaneous drug reactions to distinguish a non drug-induced rash from a cutaneous adverse drug reaction.

A 37-year-old woman had a histologically documented occipitovertebral metastasis from an invasive epidermoid carcinoma of the uterine cervix. The metastasis was found 3 months after the primary and was treated by local radiation therapy followed by systemic chemotherapy. Radiation therapy was highly effective in relieving the pain but was not associated with changes in magnetic resonance imaging findings. Lymph node involvement and local extension occurred. The patient died 1 year after the diagnosis of the metastasis. Involvement of the occipitovertebral junction by uterine cervix carcinoma metastasis is exceedingly rare. The relevant literature is reviewed.

Background: Hemolytic uremic syndrome (HUS) is a rare complication in solid organ transplantation. It can be associated with severe hypertension. Several risk factors have been identified including immunosuppressive drugs such as cyclosporin A and, more recently, tacrolimus., Methods: Here we report a case of tacrolimus-induced HUS in a 61-yr-old woman after liver transplantation. Hypertension, microangiopathic anemia and end-stage renal failure occurred 2 yr after liver transplantation., Results: At admission, she had malignant hypertension with a severe hypertensive retinopathy, renal failure (creatininemia: 800 micromol/L) and microangiopathic anemia (Hb: 7.3 g/dL, a low platelet count and elevated lactate dehydrogenase). At renal biopsy, histologic findings were ischemic and sclerotic glomeruli with hyaline thrombi, severe mesangiolysis and interstitial fibrosis., Conclusion: Despite steroid treatment, antihypertensive agents and fresh frozen plasma therapy, end-stage renal failure was observed and chronic hemodialysis treatment was required.

Glomus tumor is a neuro-myo-arterial benign tumor accounting for 1 to 5% of hand tumors which occurs principally in young adult females. It may be unique or multiple. Acute, focalized, pain is the main sign, the pressure of a small trigger zone induces a syncopal pain and immediate hand withdrawal. Differential diagnoses includes neurinoma, melanoma, hematoma, osteoid osteoma, fibrokeratoma, mucoid cyst, angioma, and exostosis. The diagnosis is suspected on clinical grounds, and X rays exhibits a bone erosion in one third of the cases. Magnetic resonance angiography is now the first line non invasive tool for both diagnosis and precise localization. Treatment consists in complete surgical tumor resection (J Mal Vasc 1999; 24: 364-367).