Evaluation of the routine use of E-cadherin immunohistochemistry in the typing of breast carcinomas: results of a randomized diagnostic study.

AIMS: Invasive lobular carcinoma (ILC) has distinct morphology and association with loss of E-cadherin function. It has special clinical and imaging features, and its proper recognition is important. Following a recent proposal, we tested the value of the routine use of E-cadherin immunohistochemistry (IHC) in recognizing ILC. METHODS AND RESULTS: Five pathologists with experience in breast pathology from four Hungarian institutions histotyped 1001 breast cancers from diagnostic core biopsies or excision specimens randomly assigned to haematoxylin and eosin (HE) diagnosis first, followed by E-cadherin IHC; or to immediate HE and E-cadherin-based diagnosis. Of 524 cases with HE diagnosis, 73(14%) were deemed uncertain. E-cadherin made the initial histological type change in 14/524 cases (2.7%), including three with confident HE-based type allocation. Use of E-cadherin immunostaining was considered useful in 88/477 cases (18%) with immediate dual assessment, and typing uncertainty went down to 5% (25/477 cases), but was not zero. Collective assessment of 171 uncertain, difficult, nonclassical cases resulted in consensus diagnosis in most cases, but 15 cases were still doubtful as concerns their proper histological type. CDH1 gene sequencing was attempted and successful in 13; pathogenic genetic alterations were identified in seven cases. CONCLUSIONS: The routine use of E-cadherin IHC decreases the uncertainty in typing and improves the typing accuracy at the cost of potentially redundant additional immunostains. Furthermore, this procedure does not exclude uncertainty due to E-cadherin-positive ILCs, which are occasionally difficult to confidently label as ILC, especially when the growth pattern is not classic.

Screening for the presence of scleroedema adultorum of Buschke in patients with diabetes mellitus: newly diagnosed patients had a high prevalence of dyslipidaemia.

BACKGROUND: Scleroedema adultorum of Buschke is a rare disorder characterized by fibromucinous thickening of the dermis that manifests mainly at the nape of the neck and on the upper back and shoulders. This study screened patients with diabetes mellitus for skin hardening caused by scleroedema adultorum of Buschke and characterized the clinical and laboratory findings in patients with newly identified cases, with a focus on lipid metabolism abnormalities and vascular complications. METHODS: Out of 113 consecutive patients with diabetes, 11 (9.7%) new scleroedema patients, all with type 2 diabetes, were found. Their clinical and laboratory data were compared to those of the rest of the screened patients and to those of a cohort of 15 patients with scleroedema and diabetes who were already being treated in a tertiary clinical centre at the University of Pécs. RESULTS: Higher proportions of patients with dyslipidaemia, hypertriglyceridemia (P < 0.05) and increased mean levels of non-high-density lipoprotein cholesterol (non-HDL-C) were found (P < 0.01) in both scleroedema groups than in the group without scleroedema. Stroke and venous thromboembolism (VTE) were more frequently found in the histories of both the newly identified scleroedema group (each 3/11; 27.3%) and the treated cohort (each 6/15; 40.0%) than in the group without scleroedema (6/102; 5.9% in cases of stroke P = 0.021, P < 0.001; and 14/102; 13.7%; P < 0.05 in cases of VTE, respectively). Based on binary logistic regression, a high non-HDL-C level (odds ratio (OD): 3.338, confidence interval (CI): 1.77-6.28; P < 0.001) and insulin treatment (OR 7.64, CI 1.9-29.3; P = 0.003) were independent predictors of scleroedema in patients with diabetes mellitus. CONCLUSIONS: Diabetes patients with scleroedema had more severe dyslipidaemia and higher occurrence of vascular complications compared to those without scleroedema. In addition to poorly controlled type 2 diabetes mellitus requiring insulin treatment, high non-HDL-C levels may be another contributing factor to the development of scleroedema. TRIAL REGISTRATION: NCT04335396 .

In vivo detection of hyperacute neuronal compaction and recovery by MRI following electric trauma in rats.

PURPOSE: To verify the following phenomenon in vivo using quantitative magnetic resonance imaging (MRI). Neuronal compression may occur following brain injuries in the cortex and hippocampus. As well being characterized by previous histological studies in rats, the majority of these neurons undergo hyperacute recovery rather than apoptotic death. MATERIALS AND METHODS: Twenty male Wistar rats were assigned into injured or sham-injured groups (n = 10). The injured group underwent an electric trauma model to provoke compacted neuron formation. A T1 map was acquired prior to the injury and 10 T1 maps were acquired consecutively over a period of 2.5 hours after the injury, using a 3.0T scanner. Voxelwise statistical analyses were performed between timepoints. To enable comparison with the histological appearance of the compacted neurons, silver staining was performed on a sham-injured rat and five injured rats, 10, 40, 90, 150, and 300 minutes after the injury. RESULTS: A significant (corrected P < 0.05) increase in average T1 from the preinjury (895.24 msec) to the first postinjury timepoint (T1 = 951.37 msec) was followed by a significant (corrected P < 0.05) decrease (return) up to the last postinjury timepoint (T1 = 913.16 msec) in the voxels of the cortex and hippocampus. No significant (corrected P < 0.05) change in T1 was found in the sham-injured group. CONCLUSION: The spatial and temporal linkages between the MRI T1 changes and the histological findings suggest that neuronal compaction and recovery is associated with T1 alterations. MRI therefore offers the possibility of in vivo investigations of neuronal compaction and recovery. J. MAGN. RESON. IMAGING 2016;44:814-822.

Four cases of GABAB receptor encephalitis.

GABAB receptor (gamma-aminobutyric acid type B receptors - GABABR) encephalitis is a rare manifestation of autoimmune encephalitides. We report four cases - including the first two Hungarian patients - with some peculiar features. One patient developed subacute disorientation and almost complete loss of short-term memory, but no epilepsy. Without immunotherapy, his memory spontaneously improved up to mild cognitive impairment in six weeks. GABABR antibodies persisted in his serum, and 18 months later, FDG-PET detected abnormal mediastinal lymph nodes and small cell lung cancer (SCLC). Another patient had persistently decreased sodium content in the peripheral blood. In those three patients who died, CSF was abnormal, but CSF was not pathological in the patient, who spontaneously improved. Brain MRI indicated signal intensity changes in the medial temporal areas in three cases. SCLC was found in three patients. Only the patient, who spontaneously improved, survived for more than 24 months. In summary, our cases show that (i) GABABR encephalitis may develop without epilepsy; (ii) the severe short-term memory loss can spontaneously improve; (iii) persistent hyponatremia can be present in the blood; (iv) the patient with benign course without epilepsy and CSF abnormality survived; (v) spontaneously remitting encephalitis can precede SCLC by 1.5 year, which emphasizes that repeated search for cancer is of paramount importance even in cases with spontaneous improvement.

[Pathological diagnosis, work-up and reporting of breast cancer. Recommendations of the 3rd Hungarian Consensus Conference on Breast Cancer]. / Az emlõrák patológiai diagnosztikája, feldolgozása és kórszövettani leletezése. Szakmai útmutatás a III. Emlõrák Konszenzus Konferencia alapján.

There have been relevant changes in the diagnosis and treatment of breast cancer to implement the updating of the 2010 recommendations made during the 2nd national consensus conference on the disease. Following a wide interdisciplinary consultation, the present recommendations have been finalized after their public discussion at the 3rd Hungarian Consensus Conference on Breast Cancer. The recommendations cover non-operative and intraoperative diagnostics, the work-up of operative specimens, the determination of prognostic and predictive markers and the content of the cytology and histology reports. Furthermore, it touches some special issues such as the current status of multigene molecular markers, the role of pathologists in clinical trials and prerequisites for their involvement, some relevant points about the future.

A case study on the potential angiogenic effect of human chorionic gonadotropin hormone in rapid progression and spontaneous regression of metastatic renal cell carcinoma during pregnancy and after surgical abortion.

BACKGROUND: Treatment possibilities of metastatic renal cell carcinoma (mRCC) have recently changed dramatically prolonging the overall survival of the patients. This kind of development brings new challenges for the care of mRCC. CASE PRESENTATION: A 22 year-old female patient with translocation type mRCC, who previously had been treated for nearly 5 years, became pregnant during the treatment break period. Follow-up examinations revealed a dramatic clinical and radiological progression of mRCC in a few weeks therefore the pregnancy was terminated. A few days after surgical abortion, CT examination showed a significant spontaneous regression of the pulmonary metastases, and the volume of the largest manifestation decreased from ca. 30 to 3.5 cm(3) in a week. To understand the possible mechanism of this spectacular regression, estrogen, progesterone and luteinizing hormone receptors (ER, PGR and LHR, respectively) immuno-histochemistry assays were performed on the original surgery samples. Immuno-histochemistry showed negative ER, PGR and positive LHR status suggesting the possible angiogenic effect of human chorionic gonadotropin hormone (hCG) in the background. CONCLUSION: We hypothesize that pregnancy may play a causal role in the progression of mRCC via the excess amount of hCG, however, more data are necessary to validate the present notions and the predictive role of LHR overexpression.

TRPS1 expression in breast angiosarcoma.

Angiosarcoma (AS) of the breast, a rare mesenchymal neoplasm, exhibits distinct forms based on etiological and genetic features. While cases with typical clinical presentation and morphology allow for a straightforward diagnosis, challenges arise when clinical data are scarce, diagnostic material is limited, or morphological characteristics overlap with other tumors, including undifferentiated carcinomas. The trichorhinophalangeal syndrome protein 1 (TRPS1), once regarded as highly specific for breast carcinomas, now faces doubts regarding its reliability. This study explores TRPS1 expression in breast AS. Our investigation revealed that 60% of AS cases displayed TRPS1 labeling, contrasting with the 40% lacking expression. Scoring by four independent readers established a consensus, designating 12/35 ASs as unequivocally TRPS1-positive. However, uncertainty surrounded nine further cases due to a lack of reader agreement (being substantial as reflected by a kappa value of 0.76). These findings challenge the perceived specificity of TRPS1, shedding light on its presence in a noteworthy proportion of breast ASs. Consequently, the study underscores the importance of a comprehensive approach in evaluating breast ASs and expands the range of entities within the differential diagnosis associated with TRPS1 labeling.

Assessment of cells in the ascitic fluid of women with ovarian hyperstimulation syndrome: the clinical implications for subsequent ovarian malignancy.

BACKGROUND: Although some studies have reported a potential connection between ovulation induction therapy (OIT) and malignant ovarian diseases, the results have been inconclusive. In the present study, we sought to determine whether women undergoing OIT at our in vitro fertilization (IVF) clinic, especially those with severe ovarian hyperstimulation syndrome (OHSS) and suspicious cytologic findings, were at risk for developing malignant ovarian tumours after treatment. METHODS: Patients who underwent OIT at our IVF clinic were enrolled in this study and assessed for any evidence of malignant ovarian tumours. Patients who developed severe OHSS as a result of OIT were treated with a culdocentesis. Cells from the ascitic fluid were cytologically scored for abnormality and malignancy. Peripheral blood samples were obtained from patients with severe OHSS to determine serum levels of the tumour markers (CA-125 and HE4) that were used to calculate the Risk for Ovarian Malignancy Algorithm (ROMA) index. RESULTS: Follow-up data were available for 1,353 of the 1,587 patients (85%) who underwent OIT at our IVF clinic between January 2006 and December 2012. Twenty-three patients (1.4%) were hospitalized with OHSS. Culdocentesis was performed 16 times in nine patients with severe OHSS (age range, 23-34 years; mean, 27.1 years). Although cytological examination of the ascitic cells of these patients suggested malignant ovarian neoplasia, over the course of the observation period, the ovarian volume gradually decreased and became normal. Subsequent cytological and histological examinations failed to find evidence of any malignant tumours in these nine patients. None of the 1,353 participants who underwent OIT developed any malignant ovarian tumours during the study period. Moreover, none of the 462 patients who were in our ovarian tumour registry were also participants in the IVF program. CONCLUSIONS: The presence of atypical cells in the ascitic fluid of women with severe OHSS does not likely indicate malignancy; therefore, radical surgical intervention is not justified. The risk of malignancy is minimal shortly after OIT. At our centre, OIT has not been associated with any cases of ovarian tumour.

[A probable etiological role of Merkel cell polyomavirus in the development of Merkel cell carcinoma]. / Merkel-sejtes polyomavírus mint a Merkel-sejtes carcinoma valószínu kóroka.

Approximately 20% of the tumours in humans are associated with contagious viral agents. Merkel cell carcinoma is a rare and highly aggressive tumour which may originate from the epidermal stratum basale, although the origin is still controversial. This tumour is most commonly found in elderly and immunocompromised patients in sun exposed areas, especially in the head and neck regions. Merkel cell carcinoma often causes a diagnostic challenge with a dramatically increasing incidence. In 2008, a DNA tumour virus, a polyomavirus (Merkel cell polyomavirus) was detected in Merkel cell carcinomas, and this finding helped to understand the etiological background of the disease. The infectious - probably viral - etiology resulted in a paradigm shift in pathogenesis and, hopefully, in therapy as well. This review summarizes the current knowledge related to Merkel cell carcinoma and the first oncogenic human polyomavirus, the Merkel cell polyomavirus, to promote the clinical adaptation of the information.

Comparative analysis of EZH2, p16 and p53 expression in uterine carcinosarcomas.

Introduction: The role of p16 and p53 immunohistochemistry in the diagnosis of rare and aggressive uterine carcinosarcoma (UCS) has been well established. However, enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and a member of the polycomb group family is a relatively new biomarker, with limited published data on its significance in this tumor type. The goal of this study was to examine EZH2 expression in UCS and its components, in correlation with morphological features, and p16 and p53 staining patterns. Methods: Twenty-eight UCSs were included in the study. EZH2, p16 and p53 immunoreactivity were assessed independently by two pathologists in both tumor components (epithelial and mesenchymal). EZH2 and p16 immunostains were scored semiquantitatively: based on the percentage and intensity of tumor cell staining a binary staining index ("high- or low-expressing") was calculated. The p53 staining pattern was evaluated as wild-type or aberrant (diffuse nuclear, null, or cytoplasmic expression). Statistical tests were used to evaluate the correlation between staining patterns for all three markers and the different tumor components and histotypes. Results: High EZH2 and p16 expression and aberrant p53 patterns were present in 89.3% 78.6% and 85.7% of the epithelial component and in 78.6%, 62.5% and 82.1% of the mesenchymal component, respectively. Differences among these expression rates were not found to be significant (p > 0.05). Regarding the epithelial component, aberrant p53 pattern was found to be significantly (p = 0.0474) more frequent in the serous (100%) than in endometrioid (66.6%) histotypes. Within the mesenchymal component, p53 null expression pattern occurred significantly (p = 0.0257) more frequently in heterologous sarcoma components (71.4%) compared to the homologous histotype (18.8%). Conclusion: In conclusion, EZH2, p16 and p53 seem to play a universal role in the pathogenesis of UCS; however, a distinctive pattern of p53 expression appears to exist between the serous and endometrioid carcinoma components and also between the homologous and heterologous sarcoma components.

[Differential scanning calorimetry of blood plasma in breast cancer patients]. / Emlodaganatos betegek vérplazmájának differenciál pásztázó kalorimetriás vizsgálata.

Breast cancer is the commonest cause of cancer death in women worldwide. Its incidence has been increasing for many years in economically developed countries. Differential scanning calorimetry (DSC) is a thermoanalytical technique which monitors small heat changes between sample and reference materials. This examination is a validly efficient method for the demonstration of structural changes not only in the physical sciences, but in numerous human oncological diseases. The goal of this study was to measure DSC thermogram of blood plasma in breast cancer patients with different stages. Nineteen women with different tumor diameter (0.5-7.5 mm) and with or without regional lymph node metastases were involved in the study. Preoperatively peripheral blood samples were collected from the patients and from healthy controls, and plasma components were analysed by SETARAM micro DSC-II calorimeter. The diameter of the tumor tissue and the number of metastatic lymph nodes were evaluated on the basis of postoperative histological results. In the current study we found difference in changes of the thermal parameters (transition temperature, calorimetric enthalpy) of breast cancer patients' plasma components. Moreover, a tendency has been found for association of these results with tumor size and with the degree of regional lymph node involvement. Preliminary study of the clinical utility of DSC technology arises, even though there is no data in the literature. In cases of breast cancer the blood plasma may be suitable for DSC analysis for diagnosis or staging as well. In order to clarify the relationships we are planning further studies.

High Prevalence of Non-Vaccinated Oncogenic Human Papillomavirus Genotypes in High-Grade Squamous Intraepithelial Lesions of the Cervix: Thought-Provoking Results of a Detailed HPV Genotype Analysis.

Identification of HPV infection is usually performed on cytological specimens, despite the often transient virus types. HPV profile analysis of pathologically confirmed lesions can also be performed on formalin-fixed paraffin-embedded (FFPE) cone samples and should be taken as standard during follow-up. We compared HPV profiles of cytological and FFPE specimens of women diagnosed with HSIL. Archived PAP smears and FFPE cones from 49 patients were processed. For genotyping, the HPV Direct Flow CHIP test was used. All samples were positive. HPV profile agreement of the two sample types was 84.16-100%. Mono-infections occurred in 12.24% and 61.22% in PAP smears and FFPE specimens, respectively; while multi-infections were detected in 87.76% and 38.78%, respectively. The most abundant genotypes were HPVs 16, 31, and 51/33. Of all infections, 56.25% and 64.93% were caused by nonavalent vaccinated type (VT) HPVs; while 50.69% and 38.96% belonged to non-nonavalent VT HPVs, in PAP smears and FFPE specimens, respectively. Our results confirmed the importance of HPV genotyping of FFPE cone samples. We also confirmed a remarkable presence of non-vaccinated HPV types in HSIL cases indicating the importance of vaccine development.

Detection of SARS-CoV-2 proteins by immunohistochemistry in human tissues Pathology collaborative analysis / SARS-CoV-2-fehérjék kimutatása immunhisztokémiai módszerrel emberi szövetekben

Introduction: The COVID-19 (coronavirus disease 2019) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is associated with high mortality rates worldwide. Polymerase chain reaction (PCR) is extensively used for virus detection in both infected patients and deceased persons. PCR, however, gives no information about the localization of the virus in cells and tissues. Detection of spike and nucleocapsid proteins and viral ribonucleic acid (RNA) of the SARS-CoV-2 in situ might provide more information and aid in the discovery of the pathomechanism of cellular damage. There are several commercially available anti-spike and anti-nucleocapsid antibodies used to detect immunohistochemical reactions, though each gives different results. Objective: The goal of the present study was to compare the intensity and specificity of several anti-spike and antinucleocapsid antibodies in different dilutions in four Hungarian university departments. Method: Immunohistochemical reactions were performed on coded slides taken from infected lungs of 3 deceased and placenta samples with appropriate negative controls of formalin-fixed paraffin-embedded tissues, scanned, evaluated unanimously and analysed statistically by the assessors. Results: By comparing the intensity, dilution, background and reproducibility of the different primary antibodies, it was possible to select the antibodies with the best results. Conclusion: The antibodies selected with established dilutions can be used in further studies to detect SARS-CoV-2 proteins in surgical materials and in samples obtained during autopsy.

Diagnostic difficulties and therapeutic options of a giant chest paraganglioma / Óriás mellkasi paraganglioma diagnosztikai nehézségei és terápiás lehetoségei

Paragangliomas are mostly benign tumors originating from the sympathetic or parasympathetic ganglions, but malignant forms are also known. They are in the region of the head and neck, in the glomus caroticum, intra-abdominally as well as in the thorax. The investigation of the 39-year-old male patient began due to extremely high blood pressure, night sweats and a 10 kg weight loss. Chest CT scan described a huge mass in the right hilum, bronchoscopic sampling was inconclusive. Tumor biopsy was performed through right thoracotomy, but complete resection was not possible due to tissue adhesions and cardiac involvement. Histological examination verified paraganglioma, which was also confirmed by laboratory tests. Accordingly, somatostatin analog therapy was initiated, followed by I-131-MIBG treatment with good clinical effect. Coronary angiography confirmed that the right coronary artery contributed with two marginal branches to the blood supply of the thoracic mass. The tumor was successfully removed and after the cardio-thoracic surgery, the patient's antihypertensive therapy was stopped. There was no sign of relapse during follow-ups. During the medical investigation of severe blood pressure elevations, the possibility of paraganglioma should be considered. In these cases, invasive procedures, if not preceded by proper medication, can be fatal. By taking advantage of the ever-expanding therapeutic options and the cooperation between institutions, even patients with a giant paraganglioma can become tumor-free.

Pathological Diagnosis, Work-Up and Reporting of Breast Cancer 1st Central-Eastern European Professional Consensus Statement on Breast Cancer.

This text is based on the recommendations accepted by the 4th Hungarian Consensus Conference on Breast Cancer, modified on the basis of the international consultation and conference within the frames of the Central-Eastern European Academy of Oncology. The recommendations cover non-operative, intraoperative and postoperative diagnostics, determination of prognostic and predictive markers and the content of cytology and histology reports. Furthermore, they address some specific issues such as the current status of multigene molecular markers, the role of pathologists in clinical trials and prerequisites for their involvement, and some remarks about the future.

[Primary systemic therapy in breast cancer patients (2007-2010)]. / Emlodaganatos betegek primer szisztémás terápiája során elért eredményeink (2007-2010).

INTRODUCTION/AIM: The importance of preoperative neoadjuvant (NA) systemic treatment in operable breast cancer has significantly increased in the last few years. The aim of our retrospective study was to determine the effect of NA therapy in breast cancer patients treated in our unit and analyze radiological and pathological response rates in the context of surgical treatment. MATERIALS AND METHODS: One hundred and fourteen cases of breast cancer with NA therapy were analyzed and clinical data were collected from March 2007 to December 2010. Twenty-two patients received NA treatment for inoperable tumours. As far as operable cancers (92 patients), the indications for NA treatment were high tumour grade, presence of axillary metastasis and relatively young age. 5-Fluorouracil-Epirubicin-Cyclophosphamid or Taxotere-Epirubicin regimens were administered in 6 cycles followed by radiological evaluation and surgery. Herein, we compared the preoperative staging with the pathological results after surgery. RESULTS: NA therapy resulted in complete regression in 17% of patients, significant regression in 21%, while moderate regression was achieved in 43% of patients. No regression was detected in 19%. The decrease in T stage was not followed by decrease in N stage in significant number of cases. Moreover, in some cases NA therapy caused complete radiological regression, while histologically it still remained positive. In certain cases, breast conserving surgery was feasible due to down-staging caused by NA therapy. CONCLUSION: NA therapy was effective primarily in decreasing tumour size; however, it was less effective on axillary lymph node metastases. Due to the presence of the residual DCIS component, the volume of resection could not be decreased as much as down-staging of the invasive cancer would have permitted.

Wide Spectrum Analysis of Human Papillomavirus Genotypes in External Anogenital Warts.

External anogenital warts (EGW) are primarily associated with the low-risk human papillomavirus (HPV) genotypes 6 and 11, though coinfection with other low-risk and oncogenic high-risk HPV genotypes also occurs. Although there have been many studies on HPV-associated disease, the prevalence of HPV genotypes associated with EGW is not well characterized. The objective of our retrospective study was to determine the prevalence of HPV genotypes among patients diagnosed with EGW in the south-west of Hungary. Archived formalin-fixed paraffin-embedded tissues from 94 patients were processed in our study. HPV genotypes were determined, applying HPV Direct Flow CHIP test. The overall prevalence of HPV DNA in the EGW samples was 100%, yielding 131 infections among the 94 samples. Of these cases, 72.3% were mono while 27.6% were multi-infections. Out of the 131 infections, the cumulative prevalence of HPV 6 and 11 was 71%. A total of 98.9% of the samples were carrying at least one of these genotypes, while 19.1% of the cases occurred with at least one high-risk genotype. Data from our study could provide invaluable information concerning the prevalence of HPV types among patients with EGW, enabling improved assessment of the actual and future efficacy of vaccination programs, vaccine development, and forecast changes in infection patterns.

Clinical, Laboratory and Histological Features of Dipeptidyl Peptidase-4 Inhibitor Related Noninflammatory Bullous Pemphigoid.

Bullous pemphigoid (BP) is an autoimmune blistering disease of elderly patients that has shown increasing incidence in the last decades. Higher prevalence of BP may be due to more frequent use of provoking agents, such as antidiabetic dipeptidyl peptidase-4 inhibitor (DPP4i) drugs. Our aim was to assess DPP4i-induced bullous pemphigoid among our BP patients and characterize the clinical, laboratory and histological features of this drug-induced disease form. In our patient cohort, out of 127 BP patients (79 females (62.2%), 48 males (37.7%)), 14 (9 females and 5 males) were treated with DPP4i at the time of BP diagnosis. The Bullous Pemphigoid Disease Area Index (BPDAI) urticaria/erythema score was significantly lower, and the BPDAI damage score was significantly higher in DPP4i-BP patients compared to the nonDPP4i group. Both the mean absolute eosinophil number and the mean periblister eosinophil number was significantly lower in DPP4i-BP patients than in nonDPP4i cases (317.7 ± 0.204 vs. 894.0 ± 1.171 cells/µL, p < 0.0001; 6.75 ± 1.72 vs. 19.09 ± 3.1, p = 0.0012, respectively). Our results provide further evidence that DPP4i-associated BP differs significantly from classical BP, and presents with less distributed skin symptoms, mild erythema, normal or slightly elevated peripheral eosinophil count, and lower titers of BP180 autoantibodies. To our knowledge, this is the first case series of DPP4i-related BP with a non-inflammatory phenotype in European patients.

Histology, 12p status, and IMP3 expression separate subtypes in testicular teratomas.

INTRODUCTION: Two types of testicular teratomas are distinguished by the current WHO classification. Prepubertal-type teratomas are benign, while postpubertal-type teratomas are considered malignant with metastatic potential, and are associated with germ cell neoplasia in situ. Prepubertal-type cases have been reported in the adult testis potentially causing confusion and overtreatment. Demonstration of the absence of 12p abnormalities with fluorescence in situ hybridization may facilitate diagnosis. Recently, IMP3 has emerged as a potential marker of malignancy in this context. AIMS: The aim of this study was to assess histological characteristics, IMP3 expression and the presence of 12p abnormalities of pure testicular teratomas. RESULTS: Thirty-seven cases were studied, 7 patients were children and 30 were adults. Six out of 7 pediatric cases showed no 12p abnormality and were IMP3 positive. Seventy-four percent and 79% of adult cases showed 12p abnormalities and IMP3 expression, respectively. Negative cases were not associated with in situ neoplasia or metastasis, they were smaller (mean, 14 vs 39 mm), showed less histological diversity (2.4 vs 4.0 types of tissues on average) compared to positive cases. CONCLUSION: Our study provides further evidence that prepubertal-type (type I) teratomas may appear in adult testes, thus teratomas in adults may be either benign (type I) or malignant (type II). IMP3 expression may aid the distinction between type I and type II teratomas of the postpubertal testis even when GCNIS and 12p status cannot be assessed.

False-Positive Malignant Diagnosis of Nodule Mimicking Lesions by Computer-Aided Thyroid Nodule Analysis in Clinical Ultrasonography Practice.

This study aims to test computer-aided diagnosis (CAD) for thyroid nodules in clinical ultrasonography (US) practice with a focus towards identifying thyroid entities associated with CAD system misdiagnoses. Two-hundred patients referred to thyroid US were prospectively enrolled. An experienced radiologist evaluated the thyroid nodules and saved axial images for further offline blinded analysis using a commercially available CAD system. To represent clinical practice, not only true nodules, but mimicking lesions were also included. Fine needle aspiration biopsy (FNAB) was performed according to present guidelines. US features and thyroid entities significantly associated with CAD system misdiagnosis were identified along with the diagnostic accuracy of the radiologist and the CAD system. Diagnostic specificity regarding the radiologist was significantly (p < 0.05) higher than when compared with the CAD system (88.1% vs. 40.5%) while no significant difference was found in the sensitivity (88.6% vs. 80%). Focal inhomogeneities and true nodules in thyroiditis, nodules with coarse calcification and inspissated colloid cystic nodules were significantly (p < 0.05) associated with CAD system misdiagnosis as false-positives. The commercially available CAD system is promising when used to exclude thyroid malignancies, however, it currently may not be able to reduce unnecessary FNABs, mainly due to the false-positive diagnoses of nodule mimicking lesions.