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Background: Tissue expression of endothelial cell markers of microcirculatory changes in chronic spontaneous urticaria (CSU) is poorly understood., Objectives: To explore the expression of specific endothelial cell markers [stem cell factor (SCF), vascular endothelial growth factor (VEGF) and membrane attack complex (MAC)] in lesional and nonlesional CSU skin through immunohistochemistry (IHC) and in serum., Methods: Lesional and nonlesional skin biopsies from patients with CSU (n = 23) and healthy controls (n = 9) were studied by IHC for expression of SCF, VEGF and MAC. In this population, we also investigated blood levels of VEGF and SCF. Patients were also assessed for clinical characteristics, disease activity and markers of autoimmune CSU. The study was registered at ClinicalTrials.gov (NCT03443362)., Results: Epidermal SCF reactivity was significantly higher in CSU lesional skin than in healthy skin (P = 0.026). In the dermis, SCF immunoreactivity was seen particularly in endothelial, perivascular and epithelial cells. In CSU lesional skin, the mean perivascular SCF staining was significantly more intense than in healthy controls (P < 0.001). Furthermore, CSU nonlesional skin also showed significantly higher SCF staining in dermal perivascular cells than in healthy controls (P < 0.001). Patients with CSU had the highest SCF immunoreactivity scores in the epidermis and/or on dermal endothelial cells. These patients did not have significantly higher SCF serum levels., Conclusions: To our knowledge, this is the first study to show elevated cutaneous expression of SCF in CSU. These findings underline the potential therapeutic possibilities of anti-Kit antibodies in CSU treatment., Competing Interests: Conflicts of interest Y.M. reports a grant from Fondation Brugmann for scientific research in chronic urticaria., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Abstract: Melanocytic matricoma is a rare benign pilar tumor characterized by matrical differentiation and interspersed dendritic melanocytes. It may show cellular atypia and brisk mitotic activity. Histological characterization of some lesions may be difficult. In addition, because the reported cases are few and have limited follow-up, there is insufficient experience to define outcome-based criteria for malignancy. Some cases of melanocytic matricoma with more prominent atypia have been reported as malignant, but their clinical behavior is uncertain. We present a melanocytic matricoma with interspersed benign dendritic melanocytes, but moderate basaloid atypia, focally brisk mitotic activity, and atypical mitoses. Despite the apparently good delimitation of this tumor, higher magnification revealed a slightly irregular border. However, overt malignant features such as necrosis, frank asymmetry, deep infiltration, and ulceration were not present. This tumor showed a complex aberrant genomic profile with multiple whole chromosomes or chromosomal arms, losses, and duplications. The tumor mutational burden was high. A loss-of-function alteration in CDKN2A and a loss-of-function mutation in TP53 were also present. This unexpected molecular profile contrasts with the relatively bland histology of the tumor and is in line with the difficulties in microscopic differential diagnosis between melanocytic matricoma and an indolent malignant pilomatrical tumor. We suggest that molecular studies and longer follow-up periods may help to further understand and more precisely categorize borderline pilomatrical tumors with melanocytic hyperplasia., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The abundance of publications of COVID-19-induced chilblains has resulted in a confusing situation., Methods: This is a prospective single-institution study from 15 March to 13 May 2020. Thirty-two patients received PCR nasopharyngeal swabs. Of these, 28 patients had a thoracic CT-scan, 31 patients had blood and urine examinations, 24 patients had skin biopsies including immunohistochemical and direct immunofluorescence studies, and four patients had electron microscopy., Results: COVID-19-induced chilblains are clinically and histopathologically identical to chilblains from other causes. Although intravascular thrombi are sometimes observed, no patient had a systemic coagulopathy or severe clinical course. The exhaustive clinical, radiological, and laboratory work-up in this study ruled-out other primary and secondary causes. Electron microscopy revealed rare, probable viral particles whose core and spikes measured from 120 to 133 nm within endothelium and eccrine glands in two cases., Conclusion: This study provides further clinicopathologic evidence of COVID-19-related chilblains. Negative PCR and antibody tests do not rule-out infection. Chilblains represent a good prognosis, occurring later in the disease course. No systemic coagulopathy was identified in any patient. Patients presenting with acral lesions should be isolated, and chilblains should be distinguished from thrombotic lesions (livedo racemosa, retiform purpura, or ischemic acral necrosis)., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Over the last few decades, incidence of anal cancer among HIV-positive men has been on the rise. In this context, programmes of screening and treatment of anal dysplasia which is a precursor of anal cancer have been developed. The aim of our study was to describe the efficiency, side effects and outcome of anal dysplasia treatment in a population of HIV-positive men who have sex with men (MSM)., Methods: We performed a retrospective study of HIV-positive MSM who received treatment for anal dysplasia between May 2010 and February 2014 in the Saint-Pierre University Hospital, Brussels. The different treatments used were electrocautery (ECA), infrared coagulation (IRC), surgical treatment and imiquimod., Results: Seventy-three HIV-infected MSM were included in the study, counting 62% of HGAIN. Median age was 41 years. Eighty-one per cent were on HAART. Median CD4 cell count was 525 cell/mm³, and 65% had undetectable viral loads. A total of 139 therapeutic interventions were recorded during the study period, and two-thirds of the enrolled patients received more than one treatment. At 540 days of follow-up, the rate of treatment response was 62%. Fifty per cent of the persistent HGAIN were metachronous lesions. No severe adverse events were recorded but frequent treatment-associated discomfort was reported, such as pain, self-limited bleeding, infection and anal irritation., Conclusion: Treatment of anal dysplasia appears to be safe and to offer short-term efficiency. However, its long-term efficiency remains unknown, especially in the HIV-positive population in which spontaneous clearance is lower and rate of recurrence higher.

Objective: HIV-positive men who have sex with men (MSM) are at increased risk of anal cancer. We evaluate the risk factors for anal high-grade squamous intraepithelial lesion (HSIL) (the precursor of anal cancer) in HIV-positive MSM., Methods: In this cross-sectional study within a cohort, 320 HIV-positive MSM were screened by anal cytology followed by high-resolution anoscopy (HRA) in case of abnormal cytology. Risk factors for anal HSIL were analysed., Results: Men were mostly middle-aged Caucasians with median CD4+ T lymphocytes of 638 cells/µL, 87% on combined antiretroviral therapy (cART) for a median of 5 years. 198 anal cytology samples were normal. In the 122 patients with abnormal cytology, HRA with biopsies were performed: 12% (n=15) normal, 36% (n=44) anal low-grade squamous intraepithelial lesion (LSIL) and 51% (n=63) anal HSIL. Comparing patients with or without anal HSIL (normal cytology or normal biopsy or LSIL), we found in multivariate analysis significantly fewer anal HSIL in patients with cART ≥24 months (OR 0.32 CI 95% 0.162 to 0.631, p=0.001)., Conclusions: Prolonged cART (≥24 months) is associated with fewer anal HSIL., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Confocal laser endomicroscopy (CLE) enables in-vivo, real-time, imaging of tissues with a micron-scale resolution through a fiber optic probe. CLE could be a valuable tool for the detection and characterization of suspicious (dysplastic) areas on the uterine cervix in a minimally invasive manner. This study evaluates the technical feasibility and safety of CLE on the cervix. The study also aims to create a preliminary iconography of normal and dysplastic squamous and columnar cervical epithelium. In-vivo CLE was performed on nine patients scheduled for a cervical loop electric excision procedure for high-grade superficial intraepithelial lesions. The CLE images were compared with standard hematoxylin and eosin analysis of loop electric excision procedure specimens. The histopathological diagnosis on the surgical specimen was established as per standard of care. CLE images were then reviewed by pathologists to point out specific histopathological features. pCLE of the exocervix and the transformation zone was performed successfully on seven out of nine patients. Uninterpretable images were obtained in two other cases: one using the AlveoFlex and one using the GastroFlex UHD after the application of acetic acid 2%. A total of 82.5% of the sequences recorded with the GastroFlex were suitable for interpretation. No adverse event or complications occurred. CLE enables proper in-vivo imaging of healthy and dysplastic cervical tissue. Images correlate well with the histopathological features established through traditional histology. Future blinded prospective analysis will determine the reliability of the real-time diagnosis and its potential use in the assessment and treatment of cervical lesions.

Background: Worldwide, human papillomavirus (HPV) 16 and 18 represents 70% of high-risk (HR) HPV found in cervical cancer. However HIV-positive women are more frequently infected by HRHPV other than HPV 16 or 18 (OHR). We aimed to analyse the HRHPV genotype distribution in a cohort of HIV-positive women and to estimate the potential protection offered by the different HPV vaccines., Methods: HRHPV genotypes by PCR and cytology were assessed in cervical samples from 508 HIV-positive women prospectively followed in Brussels., Results: Women characteristics were as follows: African origin (84%), median age 42 years, median CD4 T 555/μl, 89% under combined antiretroviral therapy and 73% with HIVRNA less than 20 copies/ml. HRHPV prevalence was 23% (116/508): 38% had abnormal cytology, 76% carried OHR without HPV 16 or 18 and 11% had concomitant infection by OHR and HPV 16 or 18. The most frequent HRHPV were HPV52 (19.8%), HPV18 (14.6%), HPV31/35/51/58 (12.1% each), HPV56 (9.9%) and HPV16 (9.5%). Less than 30% of women had their HRHPV genotypes included in the bivalent or quadrivalent vaccines against HRHPV 16 and 18; however, 79% had their HRHPV covered by the ninevalent vaccine against HRHPV 16/18/31/33/45/52/58., Conclusion: The HRHPV genotypes distribution found in these women living in Europe with a successfully treated HIV is similar to the one found in Central Africa with HRHPV other than HPV16 or 18 retrieved in 87%. In this population, the bivalent or quadrivalent vaccines could offer protection in only 30% of women; however this protection could be extended up to 80% with the ninevalent vaccine.

Objectives: We aimed to analyze the false-negative (FN) liquid-based cytology diagnoses from the 5 years preceding all the 2013 histologically proven cervical intraepithelial neoplasia (CIN)2-3 and squamous cell carcinoma (SCC) and to propose corrective actions., Study Design: This was a retrospective, blinded rescreening ('5-year look-back') of liquid-based cytology samples with negative categorizations, which occurred before histologically proven CIN2-3 and SCC., Results: The FN rate was 7.8% (21/256 samples preceding CIN2-3 and 0/13 samples preceding SCC). Slides confirmed as 'negative', 'interpretation error' and 'screening error', respectively, were 3.3% (9/269), 2.6% (7/269) and 1.9% (5/269). In 9/12 cases, error was associated with small atypical cells. In 7/12 cases, these diagnostic cells were less than 5/10 HPF. Inflammation and prominent reactive changes were present in 5/12 cases. Five patients had a positive clinical history. In 2 cases, there were multiple-cell-layer artifacts. Dense groups of small blue atypical cells were missed in 2 other cases. Dotting was imprecise in 6/7 samples., Conclusion: Considering the above results, we specifically reoriented our continuous education activities, focusing rapid rescreening on scanty, isolated, small, atypical cells and dense cell groups. Prior to final diagnosis, pathologists should systematically review the entire surface of the dotted slides, with special attention being devoted to slides with multiple cell layers and tridimensional groups., (© 2015 S. Karger AG, Basel.)

Currently, adenocarcinoma represents 41 % of primary lung cancers in women and 34 % in men. Thyroid metastases of lung cancer are rare and usually asymptomatic. We report the case of a patient presenting with stridor secondary to an enlarged multiple nodular thyroid accompanied by cervical lymphadenopathies accompanied by an enlarged and multiple nodular thyroid and by stridor. The final diagnosis was thyroid metastases of primary lung adenocarcinoma.

Introduction: Cervical infection with high-risk human papillomavirus (HRHPV) induces cervical cancer and is present in 14% of women in Europe. We assessed the prevalence and incidence of cervical HRHPV in a cohort of HIV-positive women living in Belgium., Methods: Prospective observational program of screening and follow up of HRHPV cervical infection performed by Hybrid Capture in 825 HIV-positive women between 2002 and 2011. Women without normal cervix at baseline were excluded., Results: The final analysis included 652 women: median age 38 years, African origin (81%), median HIV follow-up (66 months), median CD4 count (426 cells/μL) and 79% on antiretroviral therapy (cART). At baseline, HRHPV prevalence was 43% and decreased significantly as both age and CD4 cell count increased: highest prevalence (100%) in women <30 years and <200 CD4/μL and lowest (19%) in women >40 years and >500 CD4/μL (p<0.0001, multivariate analysis). The relative risk (RR) to carry HRHPV at baseline decreases proportionally by 11% for each 5 years-age increase and by 11% for each 100 CD4 cells/μL rise (RR=0.89, 95% CI: 0.85-0.93; p<0.0001, Poisson regression for both). During follow-up, incidence rate of HRHPV was 13.4 per 100 women-years., Conclusion: We found a high HRHPV prevalence of 43% and an incidence rate of 13 per 100 women-years in this cohort of HIV-positive women living in Europe and on cART. Women under 40 years-age had the highest prevalence even with CD4 count >350 cells/μL. The magnitude of HRHPV epidemiology should prompt to evaluate the clinical efficacy of vaccines against HPV in HIV-infected women.

Objectives: To describe the pitfalls encountered in switching over from conventional smears (CSm) to liquid-based cytology (LBC). To explore modifications of our usual diagnostic criteria., Study Design: 190 ThinPrep breast samples with paired biopsies were retrospectively evaluated by two breast cytopathologists experienced only in CSm. They were again studied after LBC training. The diagnostic performances were compared. In additional calculations we included those C4/suspicious samples containing 70% high-grade nuclei and up to 30% nonmalignant cells in the C5/positive category, simulating that they harbored a malignant one-cell population. We prospectively validated this modification of our diagnostic criteria., Results: Training resulted in higher complete sensitivity: 94 versus 86% (p value 0.003) and lower false negative ratio: 4 versus 12% (p value 0.003). Training generated higher complete sensitivity than collaboration without training: 94 versus 89% (p value 0.008). In the simulation, the modified criteria increased absolute sensitivity to 74% with a 0.6% false positive rate. In the validation series, they generated up to 91% absolute sensitivity, 12% suspicious rate and no false negative and false positive diagnoses., Conclusion: Training in breast LBC may increase diagnostic performance. Samples containing 70% high-grade nuclei or more can be categorized as malignant., (Copyright © 2013 S. Karger AG, Basel.)

We report a case of a 50-year old post-menopausal woman who was admitted because of a lump in the upper external quadrant of her left breast. The definitive diagnosis of periductal stromal tumor was retained after histopathological examination. Periductal stromal tumor is a rare tumor with distinct morphological features. The clinical evolution and the prognosis are relatively similar to the phyllodes tumor., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Background: The accuracy of a molecular reverse transcriptase-polymerase chain reaction (RT-PCR)-based assay for metastases detection in axillary sentinel lymph nodes (SLNs) has recently been validated in our institution and adopted as an intraoperative test for breast cancer patient management., Methods: Molecular assay performance was compared to standard postoperative histology in 253 consecutive patients with clinically node-negative T1 early breast cancer (<2 cm)., Results: The molecular assay correctly identified 26/27 macrometastases and 11/15 micrometastases. Overall concordance with histopathology was 93%, with 87% sensitivity, 94% specificity, and 75% positive and 97% negative predictive values. The molecular assay was positive in 13/14 patients with SLNs and nonsentinel lymph node (axillary lymph node [ALN])-positive histology. Notably, 2/12 patients with assay-positive/histology-negative SLNs exhibited ALN positivity., Conclusions: This molecular assay can raise the standard of care for patient management as its accuracy is similar to that of standard postoperative histology with the advantage of being standardized, objective, and fast enough for intraoperative use.

Despite the number of publications which have dealt with posterior cruciate ligament (PCL) retaining total knee arthroplasty, few studies have addressed the histology of the PCL. Based on these, the use of some predictive factors for lesions of the PCL has been suggested, as a decisive argument to substitute the ligament or not. The objective of this study was to assess the value of some predictive factors, based on objective findings. We performed histological analysis of 434 PCLs removed during total knee arthroplasty for osteoarthritis. Fifty-eight percent of these ligaments presented histological lesions. The degree of preoperative knee deformity, the intra-operative appearance of both cruciate ligaments, and gender were found to correlate with the severity of the microscopic lesions of the PCL. No such correlation was found with age nor with the type of knee deformity. Calcium pyrophosphate deposits were a frequent and potentially pejorative finding in the PCLs from osteoarthritic knees. Due to their poor sensitivity and specificity, the criteria suggested in previous studies to decide on preserving or substituting the PCL appeared fairly unreliable.

Objective: To evaluate the impact of experience on the accuracy of breast fine needle aspiration cytology (FNAC) using standardized microscopic criteria and review the possible complementarities between FNAC and core biopsy (CB)., Study Design: We studied 292 breast FNAC samples and their subsequent biopsies. The cytologic samples were blindly reevaluated 4-7 years later, when we had gained more experience and refined our diagnostic criteria. The accuracy of the first reading was compared to that obtained at the second reading. Inadequate smears were included in the accuracy calculations., Results: In the second reading, the identification of carcinomas and of benign lesions became more accurate. The improvement was statistically significant. Absolute sensitivity passed from 59.9% to 67.7%. Specificity increased from 52.0% to 56.0%. The inadequacy rate varied from 12.7% to 14.0% and complete sensitivity from 92.2% to 91.7%. The majority of inadequate smears were associated with benign lesions., Conclusion: Significant improvements are associated with increased experience. A more detailed evaluation of nuclear atypia and the use of Papanicolaou-stained material were also important. Accurate selection of patients may improve specificity. FNAC could be used in a complementary way with CB.

A 64-year-olf woman has been treated by chemotherapy for a uterine cervical carcinoma with known pathological lymph nodes in the abdomen and in the thorax. She is admitted in our Intensive Care Unit for fever and cardiac tamponade attributed to a large pericardial effusion. No diagnostic could be concluded from the analysis of the liquid or the pericardial biopsy. Complementary investigations are performed and the differential diagnosis of pericardial effusion is discussed in the context of a neoplastic disease.

Background: The relationships between EGF-R and c-erbB-2 with other factors involved in tumour regulation are not well understood. The aim of this study was to correlate the expression of these markers with tumour proliferation., Materials and Methods: The presence of EGF-R, c-erbB-2 and Ki-67 was evaluated by immunohistochemistry in non-small cell lung cancer (NSCLC) and preneoplastic lesions., Results: Forty-two percent of the tumours were positive for EGF-R, 22% for c-erbB-2 and 97% for Ki-67. No statistically significant correlation was found between EGF-R and Ki-67, EGF-R and c-erbB-2 or between c-erbB-2 and Ki-67. With regards to Ki-67, a significant difference in survival was noted in favour of patients who did not express the marker. In preneoplastic lesions, most of the low-grade lesions showed neither EGF-R nor Ki-67 staining. In contrast, most of the high-grade lesions stained positively for these proteins., Conclusion: EGF-R and c-erbB-2 do not seem to be correlated with Ki-67 in NSCLC.

We report the case of a 79-year-old woman with a longstanding lymphedema of the right arm who developed a skin lymphoma involving the right wrist area. Microscopically, the lesion was composed of numerous centroblasts infiltrating both the dermis and the subcutaneous tissue. Phenotypic investigations showed expression of CD20, CD79a, and bcl-2 protein by neoplastic cells. In addition, these cells were CD5 positive. No expression of anaplastic large cell lymphoma kinase (ALK), CD10, CD23, CD30, CD43, bcl-6, cyclin D1, p53 or p16INK4a could be seen. Polymerase chain reaction (PCR) analysis demonstrated a clonal rearrangement of the genes coding for the kappa light chain of the immunoglobulin (Ig). No rearrangement of the genes coding for the Ig heavy chain, t(14;18) or t(11;14) chromosome translocations, or Epstein-Barr virus (EBV) genomic sequences could be found. The tumor was classified as stage IE and was first cured by complete surgical excision. Nineteen months later, a recurrence was noted in the right elbow area. This study further illustrates that lymphoma of the skin may complicate chronic limb lymphedema. Like most of the previously reported cases, this neoplasm belonged to the category of diffuse large B-cell lymphoma. However, it showed CD5 expression as a singular feature.

An asymptomatic patient presented a pulmonary metastatis of a synovial sarcoma 15 years after resection of the primary tumor localized in the right groin area. The pathology findings demonstrated the non-specific variable nature of the biphasic epithelial and mesenchymatous feature of such tumors. No treatment was initiated and the patient has remained asymptomatic after five years follow-up. Lack of change in the radiological images led us to re-examine the prognosis and treatment in light of data in the literature.

Langerhans' cell histiocytosis (LCH) may be associated with a wide range of neoplastic disorders. However, the combination of a LCH and a basal cell carcinoma (BCC) of the skin still represents a highly unusual condition. In this publication, we report the case of a 48-year-old woman who developed a localized LCH involving the area of a previously excised BCC. Although the exact pathogenesis of this peculiar association remains yet to be elucidated, the hypothesis of an exaggerated Langerhans' cell reaction in response to the underlying BCC appears to be attractive.

Two experiences of peroperative diagnosis in thyroid surgery are reported. In Bordeaux (France), frozen sections are supplemented by touch smears. Imprints alone give results similar to frozen but are not suitable in differentiating follicular adenoma from carcinoma; they appear more accurate for recognising the follicular presentation of papillary carcinoma. Touch smear is a rapid cost-effective alternative to frozen section. In Brussels (Belgium), a more conventional attitude results in 185 frozen. A false negative ends in a follicular carcinoma. Eleven follicular proliferations will be signed out adenoma (8 cases) or carcinoma (3 cases) and three papillary carcinomas will only be detected after embedding. Six false negative derive from frozen section, no false positive is noted. An immediate change in the surgical procedure is justified twice. These observations argue for the free choice by the pathologist of the best technical procedure in peroperative diagnosis.

Digestive metastases of breast cancer are well documented (1-4). We report a patient with metastatic breast cancer presenting as a 5 mm polypoid benign looking lesion. The diagnosis was confirmed by histopathology and immunostaining.