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Összefoglaló. Bevezetés: Az állcsonti cysták helytálló diagnosztikája a klinikai, radiológiai és patológiai leletek együttes értékelésével lehetséges. Korábbi munkánk során többször tapasztaltuk a klinikoradiopatológiai kommunikáció és korreláció hiányát, és ez olykor inadekvát diagnózisok felállításához vezetett. Célkitűzés: Célunk ezen kommunikációs probléma mértékének becslése és annak bemutatása, hogy ez a hiányosság hogyan befolyásolhatja a diagnosztikát. Módszer: Korábbi, más célú retrospektív elemzés újraértékelése történt a klinikai (radiológiai) adatközlés, a revízió kapcsán módosuló diagnózisok számszerűsítése céljából, valamint további 3 egyetemi patológiai intézet 10-10 anonimizált leletének vizsgálata az adatközlések vonatkozásában. Eredmények: 2 intézményben 85 odontogen cysta diagnózisakor csupán a betegek életkora, neme volt 100%-osan ismert. A lokalizációra vonatkozó adekvát információ 62%-ban, a méretre vonatkozó csupán 29%-ban fordult elő a szövettani kérőlapokon. Összességében a diagnózist segítő releváns információt csak 52%-ban adtak meg. Az utólagos klinikoradiopatológiai korrelációra törekvő revízió során 38/85 esetben (45%) módosult a végső diagnózis kisebb vagy nagyobb mértékben. A megküldött leletek alapján a klinikai/radiológiai adatok közlése50% és 100% közöttinek becsülhető más intézetekben is. Az 5 intézmény közül csak az egyikben utalt specializációra az, hogy minden leletet egy patológus véleményezett, általában sok patológus (n = 25) valamelyike véleményezte a kevés tömlőt (n = 105). A diagnózis kommunikáció hiányán alapuló kisiklásának lehetőségét 5 példával illusztráljuk: cysta radicularisként leletezett paradentalis, lobos follicularis és lateralis periodontalis cysta, ductus nasopalatinus cysta és radicularis cysta differenciáldiagnosztikáját példázó tömlő, valamint botryoid odontogen cysta kerül bemutatásra. Következtetés: Az odontogen tömlők precíz diagnosztikája mind a klinikai, mind a patológiai oldalról javítást igényel, amelynek egyik része az ilyen irányú képzés lehet. Orv Hetil. 2021; 162(12): 458-467. Summary. Introduction: Proper diagnosis of jaw cysts requires the parallel evaluation of clinical, radiological and histopathological findings. Lack of clinico-radio-pathological correlation can lead to inconsistent diagnoses. Objective: To evaluate the rate of lacking clinico-pathological communication and demonstrate how this may influence diagnostics. Method: Data of a former retrospective analysis were re-evaluated to quantify the lack of clinical data communicated to pathologists and estimate the rate of final diagnoses requiring alteration after review of all available clinical data. 10 anonymized reports on odontogenic cysts from 3 university pathology departments each were analysed for the lack of relevant clinical information. Results: Only the age and gender of patients were documented in 100% for 85 jaw cysts diagnosed in 2 departments of pathology. Adequate information about cyst localization and size were communicated in 62% and 29%, respectively. Overall, information relevant to the diagnosis was given in 52% of the cases. Revision based on clinico-radio-pathological correlation led to alterations of the diagnosis in 38/85 cases (45%). Based on reports from other institutions, the communication of clinical data is estimated to be between50% and 100%. 25 pathologists were involved in reporting 105 cysts. 5 cases illustrate how diagnosis may fail without good communication: a paradental, an inflamed dentigerous and a lateral periodontal cyst, each misdiagnosed as radicular cyst; a cyst raising the differential diagnosis of nasopalatine duct versus radicular cyst; a botryoid odontogenic cyst. Conclusion: Proper diagnosis of jaw cysts requires improvements from both pathological and clinical sides, and could probably be improved through education. Orv Hetil. 2021; 162(12): 458-467.

Sentinel lymph node biopsy (SLNB) has become the preferred method of surgical pathological nodal staging of early breast cancer by the end of the nineties. As the most likely sites of metastasis, the SLNs allow a more precise staging, and indeed gross sectioning, step sectioning, immunohistochemistry, and molecular staging methods have been used to disclose metastatic involvement of these lymph nodes. This review summarizes the backgrounds of SLNB, trends in related surgery and pathology. It also gives an insight into European National recommendations related to SLN and divergent daily practices in European pathology departments, on the basis of replies to questionnaires from 84 pathologists from 38 European countries. The questionnaires revealed the post-neoadjuvant setting as an area where a significant minority of pathologists report less confidence in classifying residual nodal involvement into TNM categories. The review also summarizes the neoadjuvant therapy-related aspects of SLNB.

Simple Summary Breast cancers that lack expression of the predictive markers oestrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 are known as triple-negative breast cancers (TNBCs) and are generally considered to have a poor prognosis. As available targeted treatments are not effective, aggressive chemotherapy is frequently advocated for patients with TNBC. It is now becoming apparent that TNBC is not one entity but constitutes a range of malignancies with different clinical behaviour. This paper reviews 7 distinct histological subtypes of TNBC where the overall prognosis is favourable, and aggressive systemic treatment is generally not indicated. Their recognition and separation from the larger group of no special type TNBC are important. The members of the European Working Group for Breast Screening Pathology review the morphology, known molecular features and reported outcomes, and formulate a consensus statement regarding the approach to the subtypes that are associated with a favourable prognosis. Abstract Triple-negative breast cancers (TNBC), as a group of tumours, have a worse prognosis than stage-matched non-TNBC and lack the benefits of routinely available targeted therapy. However, TNBC is a heterogeneous group of neoplasms, which includes some special type carcinomas with a relatively indolent course. This review on behalf of the European Working Group for Breast Screening Pathology reviews the literature on the special histological types of BC that are reported to have a triple negative phenotype and indolent behaviour. These include adenoid cystic carcinoma of classical type, low-grade adenosquamous carcinoma, fibromatosis-like metaplastic carcinoma, low-grade mucoepidermoid carcinoma, secretory carcinoma, acinic cell carcinoma, and tall cell carcinoma with reversed polarity. The pathological and known molecular features as well as clinical data including treatment and prognosis of these special TNBC subtypes are summarised and it is concluded that many patients with these rare TNBC pure subtypes are unlikely to benefit from systemic chemotherapy. A consensus statement of the working group relating to the multidisciplinary approach and treatment of these rare tumour types concludes the review.

Purpose For optimal management of ductal carcinoma in situ (DCIS), reproducible histopathological assessment is essential to distinguish low-risk from high-risk DCIS. Therefore, we analyzed interrater reliability of histopathological DCIS features and assessed their associations with subsequent ipsilateral invasive breast cancer (iIBC) risk. Methods Using a case-cohort design, reliability was assessed in a population-based, nationwide cohort of 2767 women with screen-detected DCIS diagnosed between 1993 and 2004, treated by breast-conserving surgery with/without radiotherapy (BCS ± RT) using Krippendorff’s alpha (KA) and Gwet’s AC2 (GAC2). Thirty-eight raters scored histopathological DCIS features including grade (2-tiered and 3-tiered), growth pattern, mitotic activity, periductal fibrosis, and lymphocytic infiltrate in 342 women. Using majority opinion-based scores for each feature, their association with subsequent iIBC risk was assessed using Cox regression. Results Interrater reliability of grade using various classifications was fair to moderate, and only substantial for grade 1 versus 2 + 3 when using GAC2 (0.78). Reliability for growth pattern (KA 0.44, GAC2 0.78), calcifications (KA 0.49, GAC2 0.70) and necrosis (KA 0.47, GAC2 0.70) was moderate using KA and substantial using GAC2; for (type of) periductal fibrosis and lymphocytic infiltrate fair to moderate estimates were found and for mitotic activity reliability was substantial using GAC2 (0.70). Only in patients treated with BCS-RT, high mitotic activity was associated with a higher iIBC risk in univariable analysis (Hazard Ratio (HR) 2.53, 95% Confidence Interval (95% CI) 1.05–6.11); grade 3 versus 1 + 2 (HR 2.64, 95% CI 1.35–5.14) and a cribriform/solid versus flat epithelial atypia/clinging/(micro)papillary growth pattern (HR 3.70, 95% CI 1.34–10.23) were independently associated with a higher iIBC risk. Conclusions Using majority opinion-based scores, DCIS grade, growth pattern, and mitotic activity are associated with iIBC risk in patients treated with BCS-RT, but interrater variability is substantial. Semi-quantitative grading, incorporating and separately evaluating nuclear pleomorphism, growth pattern, and mitotic activity, may improve the reliability and prognostic value of these features.

Pure invasive papillary carcinoma (IPC) is a rare subtype of breast carcinoma with good prognosis compared with classical invasive breast carcinoma (IBC) of no special type. The majority of IPC are estrogen receptor and progesterone receptor (ER/PR) positive and HER2 negative (luminal A-like). We report the case of a 72-year-old women who was referred to the Senology Clinic for a routine workup following surgery for an intraductal papilloma. The core needle biopsy (CNB) showed a lesion mainly composed of irregular papillae and micropapillae with apocrine epithelial cells of low-to-intermediate nuclear grade, without a myoepithelial cell layer within the papillae and at the periphery, as demonstrated with multiple immunostains. The diagnosis of apocrine papillary lesion of uncertain malignant potential was made. The subsequent lumpectomy showed an IBC with the same cyto-architectural features as the CNB. In addition, lymphovascular invasion and papillary/micropapillary apocrine in situ lesion were noted. Notably, the tumor was ER/PR and HER2 negative and strongly positive for androgen receptor. A final diagnosis of mixed apocrine papillary/micropapillary carcinoma with triple-negative status was made. To the best of our knowledge, this is the first report of an IBC with these features. Breast pathologists should be aware of this entity when dealing with CNB samples characterized by a complex papillary lesion with apocrine atypia that lacks a myoepithelial cell layer on multiple immunostains. These lesions should be classified at least as of uncertain malignant potential based on the cyto-architectural features prompting a surgery for removal.

There have been some relevant changes in the diagnosis and treatment of breast cancer to implement the updating of the 2016 recommendations made during the 3rd national consensus conference on the disease. Following a wide interdisciplinary consultation, the present recommendations have been finalized after their public discussion at the 4th Hungarian Breast Cancer Consensus Conference. The recommendations cover non-operative, intraoperative and postoperative diagnostics, 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. The most important changes include the integration of the TNM 8th edition, the WHO classification of breast tumors 5th edition, the ASCO/CAP HER2 assessment guidelines from 2018, and the Yokohama terminology for cytology reporting; a more detailed text on tumor-infiltrating lymphocytes and size determination after neoadjuvant therapy and a broader discussion of molecular tests.

Összefoglaló. Bevezetés: Napjainkban az őrszemnyirokcsomó felkeresésének legelterjedtebb módszere a radioizotópos és kék festékes kettős jelölés, emellett azonban több más jelölés is alkalmazható. Az indociánzöld-fluoreszcencia ígéretes nyirokút-térképezési módszer, mely a találati arányát tekintve - irodalmi adatok alapján - összevethető a radioizotópos módszerrel. Módszer: Osztályunkon 2020. 03. 31. és 2020. 04. 15. között 10, emlőrák miatt operált betegünknél alkalmaztuk az indociánzöld és a kék festékes kettős jelölés módszerét az őrszemnyirokcsomó felkeresésére. Eredmények: A 10 operált betegünknél összesen 17 őrszemnyirokcsomót azonosítottunk és távolítottunk el. 16 őrszemnyirokcsomó jól festődött indociánzölddel (találati arány: 0,94; 95%-os konfidenciaintervallum [CI ]: 0,73-0,99), míg kék festékkel 9 jelölődött (találati arány: 0,53; 95%-os CI: 0,31-0,74). A szövettani feldolgozás során összesen 2 őrszemnyirokcsomó bizonyult áttétesnek, ezek közül 1 kék és fluoreszcens volt, 1 pedig csak kék festékkel jelölődött. Következtetés: Kezdeti, kis esetszámnál nyert tapasztalataink alapján az indociánzöld jelölés emlőrák során végzett őrszemnyirokcsomó-biopszia esetén jól használható kettős jelölési módszer részeként, kék festékkel kiegészítve. A módszer találati aránya, valamint fals negatív aránya irodalmi adatok alapján nem különbözik szignifikánsan a radioizotópos jelölés módszerétől. Orv Hetil. 2021; 162(8): 293-297.The current practice in sentinel lymph node biopsy for breast cancer is the radioisotope and blue dye dual labelling technique, however, other mapping methods are also available. Indocyanine green fluorescence is one of the best alternatives of the standard technique, with detection rates comparable to those of the radioisotope method.Between 31. 03. 2020 and 15. 04. 2020, a total of 10 sentinel lymph node biopsies for breast cancer were performed using the indocyanine green fluorescence and blue dye dual technique.17 sentinel lymph nodes were detected and removed in total, from which 16 showed explicit fluorescence activity (detection rate: 0.94; 95% confidence interval [CI]: 0.73-0.99), whilst 9 where blue (detection rate: 0.53; 95% CI: 0.31-0.74). During histopathological examination, 2 sentinel lymph nodes proved to be metastatic, from which 1 was fluorescent and blue, the other was blue only.Regarding our early experience based on a small number of patients, indocyanine green fluorescence, used together with blue dye as part of a dual technique, is a usable method for sentinel lymph node mapping. Based on data from the literature, the detection rate and the false-negative rate of the indocyanine green fluorescence method shows no significant difference from the radioisotope mapping technique. Orv Hetil. 2021; 162(8): 293-297.

Neoadjuvant therapy is a common form of treatment in locally advanced breast cancer (LABC) patients. Besides some guidelines for grading regression, a standardized general scheme is not yet available. The aim of our study was to compare the prognostic impact of different regression grading systems, namely the TR/NR, Chevallier, Sataloff, Denkert-Sinn, Miller-Payne, NSABP-B18, Residual Disease in Breast and Nodes and Residual Cancer Burden (RCB) on disease-free (DFS) and overall survival (OS). Data of 746 breast cancer patients treated in neoadjuvant setting between 1999 and 2019 have been included. The different regression grades and follow-up data were collected from medical charts. Statistical analysis included the Kaplan-Meier method, log-rank test and multivariate Cox regression. The average patient age was 55 years. The DFS and OS estimates of patients with complete pathological regression and residual in situ carcinoma have been significantly more favorable than those having partial regression or no signs of regression (pDFS

Introduction: The introduction of sentinel node biopsy (SNB) has led to a significant decrease of axillary lymph node dissections (ALND). The importance of the extracapsular extension (ECE) in the sentinel lymph node (SN) remains unclear. Method: The data of 635 patients with T1-T2N0M0 invasive breast cancer who underwent SNB between 2014 and 2018 were retrospectively analysed. 25% of the SNB patients (158) had metastasis in the SNs. These patients were grouped based on the presence or absence of ECE. The main objective of our study was to analyse the occurrence of massive (3) node metastasis in the case of ECE negative and ECE positive patients, where ALND was performed. Results: There were 91/158 patients (58%) in the ECE negative group and 67/158 patients (42%) in the ECE positive group. ALND was performed in 42% of the ECE negative and in 69% of the ECE positive patients. There were no significant differences in the mean age of the patients; size, histological type and grade of the tumours, presence of lymphovascular invasion and proportion of hormone and HER2 receptor positivities. In the ECE negative ALND group, pN1 involvement was 82%, pN2+pN3 involvement represented 18% of cases. In the ECE positive ALND group, pN1 involvement was 60%, pN2+pN3 involvement was found in 40% of cases. The presence of ECE was associated with greater axillary disease burden. These results show a significant difference (Absztrakt

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Small-cell lung carcinoma (SCLC) and the rare large-cell neuroendocrine carcinoma belong to the high grade pulmonary neuroendocrine carcinomas. Making the correct diagnosis and selection of treatment modalities require multidisciplinary meetings due to the morphological overlaps, aggressive behaviour and debated therapeutic guidelines of these entities. A 52-year-old woman was admitted to the hospital because of headache, nausea and tenebrous vision. The CT revealed metastatic tumour mass in the occipital lobe and in the cerebellum. Both tumours were removed and resulted in histological diagnosis of metastatic neuroendocrine carcinoma. Chest X-ray established contrast-enhancing lesion in the left lung. Bronchoscopy was performed and histological examination revealed large-cell neuroendocrine carcinoma. Postoperative skull irradiation and small-cell lung cancer chemotherapy protocol were utilized. Due to atelectasis and progression, chest irradiation was initiated, which was interrupted because of novel brain metastases. Further chemotherapy followed the non-small-cell lung cancer protocol. After 3 months, thoracic progression, brain and disseminated bone metastases were diagnosed. After a 14-month-long therapy, the patient deceased. Large-cell neuroendocrine carcinoma has a poor prognosis, the incidence of brain metastasis is 25-50%. In early stage large-cell neuroendocrine carcinoma, lobectomy is the standard treatment and adjuvant chemotherapy should also be considered. Although the non-small-cell lung cancer chemotherapy protocol is approved widely in the treatment of large-cell neuroendocrine carcinoma, the utility of SCLC scheme has also been suggested. Orv Hetil. 2020; 161(8): 313-319.Absztrakt: A rosszul differenciált neuroendocrin tumorok közé tartozik a jól ismert kissejtes carcinoma, valamint a ritka nagysejtes neuroendocrin carcinoma. A két daganat hasonló morfológiai képe, a betegség agresszív viselkedése, illetve a vitatott kezelési ajánlások miatt a diagnózis felállítása és a terápia megválasztása multidiszciplináris megközelítést igényel. Bal oldali fejfájás, hányinger, homályos látás miatt került felvételre az 52 éves nőbeteg. A képalkotó vizsgálat bal occipitalisan, illetve a kisagyban metasztázisra gyanús képletet ábrázolt. Az idegsebészeten mindkét tumort eltávolították. A szövettani vizsgálat neuroendocrin carcinoma agyi áttétét igazolta. A mellkas CT-vizsgálata a bal tüdőben kontrasztanyagot halmozó képletet igazolt. A bronchoszkópos biopsziás minta nagysejtes neuroendocrin carcinomát kórismézett. Posztoperatív koponyabesugárzást és a kissejtes tüdőrák protokollja szerinti kemoterápiát alkalmaztak. Rövidesen progresszió és atelectasia miatt mellkasbesugárzás kezdődött, amelyet ismételt agyi áttétek miatt meg kellett szakítani. A kemoterápiát a nem kissejtes tüdőrák protokollja alapján folytatták. Három hónap után mellkasi progresszió, kisagyi és csontáttétek jelentkeztek. A beteg 14 hónap kezelés után elhunyt. A nagysejtes neuroendocrin carcinoma rossz prognózisú, az esetek 25–50%-ában agyi áttétet adó tüdődaganat. A korai stádiumú nagysejtes neuroendocrin carcinoma esetében a sebészeti kezelés szerepe elsődleges, az adjuváns kemoterápia mérlegelendő. A kemoterápia során a nem kissejtes tüdőrák protokollja az elfogadott, de az irodalmi adatok alapján a kissejtes carcinoma kezelési sémája is mérlegelhető. Orv Hetil. 2020; 161(8): 313–319.

Summary The World Health Organization’s new classification of breast tumors has just been published. This review aims to examine the morphological categorization of breast carcinomas which is still principally based on histological features and follows the traditions of histological typing. It gives a subjective and critical view on the WHO classifications and their changes over time, and describes the changes related to some of the most common or challenging breast carcinomas: in situ carcinomas, invasive breast carcinomas of no special type, lobular, cribriform, tubular, mucinous, papillary, metaplastic carcinomas and carcinomas with medullary pattern and those with apocrine differentiation are discussed in more details. Although the 5th edition of the classification is not perfect, it has advantages which are mentioned along with problematic issues of classifications.

Despite national guidelines, the evaluation of effects of primary systemic treatment (PST) in breast cancer is a complex challenge. Our aims were to evaluate the response patterns focusing on correlations of radiological and pathological tumor size, regression heterogeneity in different molecular subtypes, cellularity changes and the incidence of enlarged, multinucleated neoplastic cells related to therapy. Slides of pretreatment biopsies and resection specimens of consecutive cases were reevaluated focusing on heterogeneity of regression per whole slide, and 40x or 100x magnification fields. Alteration in cellularity and the presence of multinucleated tumor giant cells were noted. The correlation of pathological and radiological sizes and their alterations were analyzed by Spearman rank correlation. The present study included 106 tumors. A decrease in size (84.9%) and cellularity (76.4%) was noted in all molecular subtypes. Inhomogeneous regression was found in 45.3%, with minor inhomogeneity in the majority. Scatter pattern regression was seen only in 8 cases (7.5%). Significant correlations were found between the pathological and radiological sizes (p = 0.02), and between the alterations of cellularity and pathological and radiological size (p = 0.04; p = 0.03, respectively). Multinucleated tumor giant cells were noted in 17.9% (n = 19), nearly exclusively in cases treated with PST including taxanes. Regression inhomogeneity following PST is present in about half of the cases, and is not related to molecular subtypes. The evaluation of the maximum area of the tumor bed is recommended for the proper evaluation of regression. Multinucleated tumor giant cells are related to PST including taxane derivate, and may cause upgrading.

Background Based on its mechanism of action, PARP inhibitor therapy is expected to benefit mainly tumor cases with homologous recombination deficiency (HRD). Therefore, identification of tumor types with increased HRD is important for the optimal use of this class of therapeutic agents. HRD levels can be estimated using various mutational signatures from next generation sequencing data and we used this approach to determine whether breast cancer brain metastases show altered levels of HRD scores relative to their corresponding primary tumor. Patients and methods We used a previously published next generation sequencing dataset of 21 matched primary breast cancer/brain metastasis pairs to derive the various mutational signatures/HRD scores strongly associated with HRD. We also carried out the myChoice HRD analysis on an independent cohort of 17 breast cancer patients with matched primary/brain metastasis pairs. Results All of the mutational signatures indicative of HRD showed a significant increase in the brain metastases relative to their matched primary tumor in the previously published whole exome sequencing dataset. In the independent validation cohort, the myChoice HRD assay showed an increased level in 87.5% of the brain metastases relative to the primary tumor, with 56% of brain metastases being HRD positive according to the myChoice criteria. Conclusions The consistent observation that brain metastases of breast cancer tend to have higher HRD measures may raise the possibility that brain metastases may be more sensitive to PARP inhibitor treatment. This observation warrants further investigation to assess whether this increase is common to other metastatic sites as well, and whether clinical trials should adjust their strategy in the application of HRD measures for the prioritization of patients for PARP inhibitor therapy.

The Breast Surgery theoretical and practical knowledge curriculum comprehensively describes the knowledge and skills expected of a fully trained breast surgeon practicing in the European Union and European Economic Area (EEA). It forms part of a range of factors that contribute to the delivery of high quality cancer care. It has been developed by a panel of experts from across Europe and has been validated by professional breast surgery societies in Europe. The curriculum maps closely to the syllabus of the Union of European Medical Specialists (UEMS) Breast Surgery Exam, the UK FRCS (breast specialist interest) curriculum and other professional standards across Europe and globally (USA Society of Surgical Oncology, SSO). It is envisioned that this will serve as the basis for breast surgery training, examination and accreditation across Europe to harmonise and raise standards as breast surgery develops as a separate discipline from its parent specialties (general surgery, gynaecology, surgical oncology and plastic surgery). The curriculum is not static but will be revised and updated by the curriculum development group of the European Breast Surgical Oncology Certification group (BRESO) every 2 years.

Breast cancer can occur in either gender; however, it is rare in men, accounting for

Apocrine encapsulated papillary carcinoma (EPC) of the breast is a rare neoplasm, and only 10 cases have been reported in the literature to date. Although EPC by definition lacks a peripheral myoepithelial layer, all previously published apocrine EPC cases were clinically indolent and lacked a conventional invasive component. Herein, we report the 11th case of apocrine EPC, which had a conventional invasive carcinoma component and provides evidence of the malignant potential of this entity. We postulate that apocrine EPC is most likely a morphological variant of conventional EPC, with the same unpredictable malignant potential as non-apocrine cases.

Membranous Ki-67 staining with the MIB-1 antibody has been described in hyalinising trabecular adenomas of the thyroid and sclerosing haemangiomas of the lung. Its relatively rare occurrence in breast tumours has also been documented. The aim of the present study was to assess the rate of any membranous MIB-1 staining in breast specimens. The staining was performed at room temperature with 1:100 dilution of the antibody. One hundred four core needle biopsies and 41 operative specimens were analysed. Membranous staining was noted in 36/144 invasive carcinomas, 20/42 in situ carcinomas and 46/99 cases of peritumoural benign/normal breast epithelium. Most often, it presented as focal and partial polarised luminal membranous staining although complete circumferential staining also occurred, and membranous labelling was sometimes accompanied by cytoplasmic staining, too. In a few cases tested, greater dilution of the primary antibody did not abolish the membranous staining, which was absent with the SP6 monoclonal Ki-67 antibody. The membranous staining of invasive tumours showed no association with histological grade, lumen formation, oestrogen or progesterone receptor status or the Ki-67 nuclear labelling. In contrast, it was associated with a HER2-positive status, although it occurred in all molecular subtypes approached by immunohistochemistry. The background of this membranous staining remains elusive. It is unlikely to represent an artefact. At least partial sharing of an epitope of the nuclear Ki-67 protein with an unidentified membranous protein and some functional differences between membranous staining producing tumours and tumours lacking this pattern of staining may both contribute to some extent.

Encouraged by our previous finding of growth hormone-releasing hormone receptor (GHRH-R) expression in metaplastic and neoplastic apocrine breast epithelium, we examined a small series of skin adnexal tumours with various degrees of apocrine (oxyphilic) differentiation, as well as normal axillary and anogenital apocrine sweat glands, for the expression of GHRH-R. Sections of formalin-fixed paraffin-embedded tissue blocks were immunostained for gross cystic disease fluid protein-15 (GCDFP-15) and androgen receptor (AR), to prove apocrine differentiation and correlate it with areas of GHRH-R expression. All but one of 19 tumours with apocrine epithelium and all five benign apocrine glands stained with both anti-GHRH-R antibodies used, each labelling a different domain of the receptor. Non-apocrine areas of the tumours and four eccrine tumours without oxyphilic features did not stain, but most sebaceous glands and some eccrine glands were labelled. Our data suggest that anti-GHRH-R antibodies highlight apocrine differentiation at extramammary sites also. Although GHRH-R seems to have a sensitivity comparable to classic apocrine markers such as AR and GCDFP-15, it seems to be inferior in specificity. The GHRH-R labelling of apocrine glands and neoplastic epithelium might also interfere with the emerging anti-GHRH targeted treatment of some malignancies acting on these receptors.

Introduction In the recent past, both clinically node-positive and node-negative but sentinel node-positive patients underwent axillary lymph node dissection (ALND), although the two groups seem to have substantially different degree of nodal involvement. Methods Data on consecutive primary breast cancer patients with documented axillary ultrasound (AXUS) results who underwent ALND between January 2003 and December 2015 either because of AXUS-guided fine needle aspiration (A-FNAC) results or because of a positive sentinel lymph node were retrospectively analysed. Results After exclusions, 316 patients staged by SNB and ALND with negative AXUS or A-FNAC (group A) were compared with 159 patients having positive A-FNAC results (group B). Tumour size and the proportion of mastectomies were greater, histological grade higher and lymphovascular invasion more frequent in Group B, where palpable lymph nodes were also more common. The proportion of cases with extensive nodal involvement (pN2 and pN3 cases) was about 3 times as much in Group B (63%) than in Group A (18%). Removal of the 50 patients with palpable lymph nodes from the analysis did not greatly influence these proportions: 60% and 19% extensive nodal involvements were noted, respectively. In this series, patients with suspicious AXUS and negative A-FNAC had more often extensive nodal involvement (25%) than AXUS negative patients (17%). Conclusions Patients in whom axillary metastases are detected by ultrasound-guided biopsy have significantly more involved nodes than SLNB-positive patients, and therefore are likely to benefit from axillary treatment.

Abstract: Introduction: The 8th edition of the Tumor-Node-Metastasis (TNM) based staging of breast cancer introduces a prognostic stage influenced by biomarkers along the traditional T, N and M categories. Aim: To retrospectively assess stage influencing prognostic variables; and the anatomic and prognostic stages on the basis of the overall survival (OS) of a cohort of deceased patients once diagnosed with breast cancer. Method: We included patients with known causes of death certified at the Bács-Kiskun County Teaching Hospital and having a history of breast cancer diagnosed on a resection specimen at the same institution. Prognostic factors were obtained from the histopathological reports. Statistics included one-way ANOVA, Dunn’s post hoc test and Kaplan-Meier curve analyses. Results: The 303 patients grouped as breast cancer related death (n = 168) or unrelated (n = 135) showed significant differences in most stage defining prognostic factors and the anatomic and prognostic stages. Significant differences in 5-year OS were observed between pT and pN categories, histological grades and estrogen receptor statuses. Except for stages I and II, significant differences were found between both different anatomic and prognostic stages (p

Abstract: Sarcoidosis is a systemic granulomatous disease of unknown aetiology, which is characterized by bilateral hilar lymphadenopathy and pulmonary disease. Clinically detected cardiac involvement occurs in 5% of sarcoid patients, although cardiac manifestations are discovered in 25% of the cases at autopsy. Sarcoid heart disease frequently causes atrioventricular block. The authors present the case of a 44-year-old man with bradycardia. On admission, second degree Mobitz II, then third degree atrioventricular block was diagnosed. Coronarography showed normal coronary arteries. 2.5 years following artificial Biotronik Entovis DR type pacemaker implantation, sudden cardiac death occurred. Autopsy revealed sarcoidosis with cardiac, pulmonary, splenic, renal and lymph node involvement. In case of young or middle-aged patients with atrioventricular block, it is best to search for other causes if the most common coronary origin can be excluded. Orv Hetil. 2017; 158(27): 1067–1070.

Apocrine breast carcinomas were evaluated for the expression of components of the growth hormone-releasing hormone (GHRH) autocrine/paracrine pathway: GHRH and its receptors (GHRH-R), as mammary apocrine carcinomas and epithelium seemed to be uniformly positive for GHRH-R in a pilot study. The apocrine phenotype was determined on the basis of hematoxylin-eosin morphology and a congruent immunohistochemical profile (estrogen receptor negativity, androgen receptor and gross cystic disease fluid protein-15 positivity). Thirty-five formalin-fixed, paraffin-embedded apocrine breast cancers in tissue microarrays and 24 cases using whole-tissue sections were evaluated for GHRH-R and GHRH expression by immunohistochemistry using polyclonal antibodies raised against various domains of GHRH-R and one polyclonal antibody specific for GHRH. GHRH-R positivity was detected in the overwhelming majority (ranging from 90% to 100%) of apocrine breast carcinomas with all but one of the antibodies applied. The expression was usually diffuse with only isolated cases showing positivity in less than 50% of tumor cells. With the PA5-33583 antibody, GHRH-R positivity was seen only in 73% of the cases in at least 50% of the tumor cells. GHRH expression was also present in all but one case tested, with more than 50% of the cells expressing it in 30/34 cases. These results support a high rate of GHRH-R and GHRH expression in apocrine breast carcinomas. Whether these findings can be exploited for the targeted treatment of apocrine breast carcinomas with GHRH antagonists requires further study.

Odontogenic keratocysts (OKCs) have a diagnostic thin epithelial lining characterised by a linear epithelial connective tissue interface generally lacking inflammatory changes, basal palisading of the nuclei and a wavy parakeratotic layer on the surface. This typical epithelium may convert to a thicker non-keratinizing one with rete pegs and a relatively flat surface after operative decompression. The aim was to characterize this type of epithelial change by immunohistochemistry for bcl2, keratin17, 10 and 19. Eleven out of 33 archived OKCs demonstrated an altered epithelium related to previous biopsy, decompressing drainage or inflammation. The typical basal bcl2 staining was lost in 10/11 cases; transepithelial CK17 was lost or markedly reduced in 9/11 cases. CK10 displayed a segmental upper layer staining in OKCs, and its loss or partial loss in the altered epithelium did not differ from negative areas of OKCs. CK19 displayed various staining patterns in the altered epithelium from lost to maintained in a patchy transepithelial distribution, the latter of which did not differ from the typical OKC staining pattern. Three of four non-keratinizing epithelial linings with basal palisading displayed immunostaining reminiscent of typical OKC epithelium. The lack of a typical epithelium is not sufficient to exclude the diagnosis of OKC if the sampling is not generous (e.g. biopsy), and the presence of non-keratinizing epithelium with basal palisading and an immunophenotype characteristic of OKC (basal bcl2, patchy or diffuse CK17 and upper layer CK10 positivity) may be consistent with the OKC diagnosis even in the absence of typical epithelial lining.

Background: A deleterious, late-onset side effect of thoracic radiotherapy is the development of radiation-induced heart disease (RIHD). It covers a spectrum of cardiac pathology including also heart failure with preserved ejection fraction (HFpEF) characterized by left ventricular hypertrophy (LVH) and diastolic dysfunction. MicroRNA-212 (miR-212) is a crucial regulator of pathologic LVH via FOXO3-mediated pathways in pressure-overload-induced heart failure. We aimed to investigate whether miR-212 and its selected hypertrophy-associated targets play a role in the development of RIHD. Methods: RIHD was induced by selective heart irradiation (50 Gy) in a clinically relevant rat model. One, three, and nineteen weeks after selective heart irradiation, transthoracic echocardiography was performed to monitor cardiac morphology and function. Cardiomyocyte hypertrophy and fibrosis were assessed by histology at week 19. qRT-PCR was performed to measure the gene expression changes of miR-212 and forkhead box O3 (FOXO3) in all follow-up time points. The cardiac transcript level of other selected hypertrophy-associated targets of miR-212 including extracellular signal-regulated kinase 2 (ERK2), myocyte enhancer factor 2a (MEF2a), AMP-activated protein kinase, (AMPK), heat shock protein 40 (HSP40), sirtuin 1, (SIRT1), calcineurin A-alpha and phosphatase and tensin homolog (PTEN) were also measured at week 19. Cardiac expression of FOXO3 and phospho-FOXO3 were investigated at the protein level by Western blot at week 19. Results: In RIHD, diastolic dysfunction was present at every time point. Septal hypertrophy developed at week 3 and a marked LVH with interstitial fibrosis developed at week 19 in the irradiated hearts. In RIHD, cardiac miR-212 was overexpressed at week 3 and 19, and FOXO3 was repressed at the mRNA level only at week 19. In contrast, the total FOXO3 protein level failed to decrease in response to heart irradiation at week 19. Other selected hypertrophy-associated target genes failed to change at the mRNA level in RIHD at week 19. Conclusions: LVH in RIHD was associated with cardiac overexpression of miR-212. However, miR-212 seems to play a role in the development of LVH via FOXO3-independent mechanisms in RIHD. As a central regulator of pathologic remodeling, miR-212 might become a novel target for RIHD-induced LVH and heart failure.

Background Pleomorphic and Florid Lobular carcinoma in situ (P/F LCIS) are rare variants of LCIS, the exact nature of which is still debated. Aim To collect a large series of P/F LCIS diagnosed on preoperative biopsies and evaluate their association with invasive carcinoma and high grade duct carcinoma in situ (DCIS). Data obtained were compared with those reported in the literature. Methods A multi-institutional series of P/F LCIS was retrieved. All cases were diagnosed on pre-operative biopsies, which was followed by an open surgical excision. Data on post-operative histopathology were available. A literature review was performed. Results A total of 117 cases were collected; invasive carcinoma and/or DCIS was present in 78/117 cases (66.7%). Seventy cases of P/F LCIS were pure on biopsy and 31 of these showed pathological upgrade in post-surgical specimens. Pre-operative biopsy accuracy was 47/78 (60.3%); pre-operative biopsy underestimation of cancer was 31/78 (39,7.%). In the literature review papers, invasive carcinoma or DCIS was associated with 274 of 418 (65.5%) cases of P/F LCIS. Pre-operative biopsy accuracy was 66% (181/274) whereas pre-operative biopsy underestimation of cancer was 33.9% (93/274). Conclusions The data presented here indicate that P/F LCIS is frequently associated with invasive carcinoma or high grade DCIS and that pre-operative biopsy is associated with an underestimation of malignancy. Open surgery is indicated when P/F LCIS is diagnosed pre-operatively.

Ipsilateral breast recurrence or second primary breast cancer can develop in patients who have undergone breast conserving surgery (BCS) and axillary surgery. The purpose of this study was to examine the feasibility of a reoperative sentinel lymph node biopsy (SLNB) as a repeated axillary staging procedure.From August 2014 through January 2017 patients with locally recurrent breast cancer or with BRCA mutation requiring risk reduction mastectomy as a second surgical procedure, underwent repeat SLNB in three Hungarian Breast Units with a radiocolloid (and blue dye) technique.Hundred and sixty repeat SLNBs were analysed, 80 after previous SLNB and 80 after previous total or partial axillary lymph node dissection (ALND). SLN identification was successful in 106 patients (66%); 77/80 (77.5%) and 44/80 (55%) in the SLNB and ALND groups, respectively. (p 0.003). Extra-axillary lymph drainage was more frequent in the ALND group (19/44, 43,2% versus 7/62, 11,3%; p 0.001). Lymphatic drainage to the contralateral axilla was observed in 14 patients (11 in the ALND group, p = 0.025), isolated parasternal drainage was detected in 4 patients (p = 0.31). Only 9/106 patients with successful repeat SLNB (8,8%, all with 1 SLN removed) had SLN metastases CONCLUSIONS: Repeat SLNB is feasible in patients with ipsilateral breast tumor recurrence or new ipsilateral primary tumor after previous BCS and axillary staging. Repeat SLNB should replace routine ALND as the standard axillary restaging procedure in recurrent disease with a clinically negative axilla. Preoperative lymphoscintigraphy is important to explore extra-axillary lymphatic drainage in this restaging setting.

Absztrakt Az őrszemnyirokcsomó-biopszia bevezetése lényegesen megváltoztatta az emlőrákos betegek axillájának hagyományos, hónalji blokkdissectióval történő kezelését, és napjainkra sokkal árnyaltabbá tette azt. Azt, hogy a korai emlőrákos betegek közül kinél kell őrszemnyirokcsomó-biopsziát végezni és kinél kell e helyett vagy ez után hónalji blokkdissectiót alkalmazni, több paraméter befolyásolja. A lehetséges opciókat a közlemény egy algoritmus formájában foglalja össze, és ennek az algoritmusnak az egyes elemeit magyarázza, az ezzel kapcsolatos legfontosabb ismeretanyagot foglalja össze.

A prognostic index (Petersen index, PI) was created for patients with pT3-4 pN0 M0 (Stage II, Dukes' B) colon cancers to distinguish between patients with better and worse outcome, and to help in recommending adjuvant chemotherapy for high risk patients in this stage. The prognostic value of the PI was evaluated in two independent retrospective series of stage II (Dukes' B) colon cancer patients. The parameters defining the PI (venous invasion, peritoneal involvement, circumferential margin involvement, perforation through the tumour) and performance of the PI were compared in two institutions. The two series of patients consisted of 127 and 87 patients. Venous invasion was more frequently detected at one of the centres (p

Microinvasion is the smallest morphologically identifiable stage of invasion. Its presence and distinction from in situ carcinoma may have therapeutic implications, and clinical staging also requires the recognition of this phenomenon. Microinvasion is established on the basis of several morphological criteria, which may be difficult and not perfectly reproducible among pathologists. The aim of this study was to assess the consistency of diagnosing microinvasion in the breast on traditional haematoxylin and eosin (HE) stained slides and to evaluate whether immunohistochemistry (IHC) for myoepithelial markers could improve this. Digital images were generated from representative areas of 50 cases stained with HE and IHC for myoepithelial markers. Cases were specifically selected from the spectrum of in situ to microinvasive cancers. Twenty-eight dedicated breast pathologists assessed these cases at different magnifications through a web-based platform in two rounds: first HE only and after a washout period by both HE and IHC. Consistency in the recognition of microinvasion significantly improved with the use of IHC. Concordance rates increased from 0.85 to 0.96, kappa from 0.5 to 0.85, the number of cases with 100 % agreement rose from 9/50 to 25/50 with IHC and the certainty of diagnosis also increased. The use of IHC markedly improves the consistency of identifying microinvasion. This corroborates previous recommendations to use IHC for myoepithelial markers to clarify cases where uncertainty exists about the presence of microinvasion. Microinvasive carcinoma is a rare entity, and seeking a second opinion may avoid overdiagnosis.

e12554 Background: ER negative (-)/PgR positive (+) breast cancer (BC) is very uncommon and questioned by many experts. We comprehensively reevaluated ER-/PgR+ BCs in the large cohort from Polish and Hungarian centers. Methods: FFPE blocks from 105 ER-/PgR+ tumors (45 breast biopsies and 64 post-operative samples from tumors not exposed to systemic therapy) were collected from 10 Polish and 3 Hungarian centers. In 60 cases available original slides with ER/PgR staining underwent reevaluation by 3 pathologists (MK, RP, WB) for ER and PgR expression by ASCO/CAP criteria. Subsequently, all samples were stained with 3 antibodies against ER (Dako monoclonal (MC) mouse anti-ERα, clone 1D5; Dako MC rabbit anti-ERα, clone EP1; VENTANA Roche MC rabbit anti-ERα, clone SP1), and PgR (Dako MC mouse anti-PgR, clone 636). If available, > 1 tissue block was used (av. 2.04 blocks/case, range 1-6). In 5 cases ESR1/PGR/ERBB2/MKi67 mRNA was measured by the Xpert® Breast Cancer STRAT4 (Cepheid, Sunnyvale, CA, USA). Results: 13 cases were excluded from immunohistochemical steps of the study due to insufficient amount of tissue and 8 - due to misdiagnosis after ER/PgR reevaluation of original slides. After re-staining, 42 cases (41.5%) retained the original phenotype, in 34 (33.67%) the ER status was corrected to ER+, and 16 (15.84%) tumors were ER/PgR-double-negative. The general agreement between anti-ER clones was moderate (Fleiss’ κ = 0.54). There were 56 ER- and 16 ER+ cases across all three assays. Five cases showed ER positivity with 2 antibodies (either SP1/EP1 or SP1/1D5), 5 tumors reacted exclusively with SP1 clone, and 2 - with 1D5 clone. Xpert Breast Cancer STRAT4 confirmed the ER-/PgR+ phenotype in 4 of 5 analyzed cases. The confirmed ER-/PgR+ BCs were characterized by lower percentage of PgR+ cells (median 5%) than BCs reclassified to ER+ (median 70%) (p = 0.022) and higher Ki67 expression than ER+ cases (median 54.5% vs 25%, respectively; p = 0.003). 39 (92.85%) ER-/PgR+ BCs presented with grade 3. Besides “conventional” high-grade cancers, we identified two distinct morphologies of ER-/PgR+ BC: resembling apocrine carcinoma (n = 5, 11.9%) and carcinoma with central acellular zone (n = 4, 9.5%). Conclusions: ER-/PgR+ BCs confirmed in the current study were defined by high-grade histology, high proliferation index and low percentage of PgR+ cells. We postulate ER-/PgR+ BC is a real albeit rare entity, and its diagnosis should be made cautiously, utilizing retesting with an alternative tissue block and anti-ER antibody.

BackgroundChemotherapeutic agents are often mutagenic. Induction of mutation associated neo-epitopes is one of the mechanisms by which chemotherapy is thought to increase the number of tumor-infiltrating lymphocytes, but the clinical relevance of this triggered immune response is not known.We decided to investigate, whether treatment with various chemotherapeutic agents with significantly different mutagenic capacity induce a significantly different number of stromal tumor-infiltrating lymphocytes (StrTIL) in the clinical setting.Methods112 breast carcinoma cases treated with pre-operative chemotherapy were selected for the study. According to chemotherapy regimen 28/112 patients received platinum-based, 42/112 cyclophosphamide-based and 42/112 anthracycline-based chemotherapy. The percentage of stromal tumor-infiltrating lymphocytes (StrTIL) was evaluated on hematoxylineosin stained slides of pre-treatment core biopsy (pre-StrTIL) and post-treatment surgical tumor samples (post-StrTIL), according to the most recent recommendation of International TILs Working Group. In survival analyses, TIL changes (ΔStrTIL) were calculated from the difference between post-StrTIL and pre-StrTIL.ResultsOf the 112 cases, 58.0% (n=65) were hormone receptor (HR) positive and 42.0% (n=47) were HR negative. There was a trend of higher post-StrTIL compared to pre-StrTIL (median 6.25% vs. 3.00%; pConclusionsStrTIL expression might be stimulated by highly (platinum), moderately (cyclophosphamide) and marginally (taxane, anthracycline) mutagenic chemotherapeutic agents. Increase in StrTIL in residual cancer compared to pre-treatment tumor tissue is associated with improved distant metastasis-free survival in cases with HR negative breast carcinoma.

BACKGROUND: Several studies have demonstrated a prognostic role for stromal tumour infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC). The reproducibility of scoring sTILs is variable with potentially excellent concordance being achievable using a software tool. We examined agreement between breast pathologists across Europe scoring sTILs on H&E-stained sections without software, an approach that is easily applied in clinical practice. The association between sTILs and response to anthracycline-taxane NACT was also examined. METHODOLOGY: Pathologists from the European Working Group for Breast Screening Pathology scored sTILs in 84 slides from 75 TNBCs using the immune-oncology biomarker working group guidance in two circulations. There were 16 participants in the first and 19 in the second circulation. RESULTS: Moderate agreement was achieved for absolute sTILs scores (intraclass correlation coefficient (ICC) = 0.683, 95% CI 0.601-0.767, p-value

Chronic kidney disease (CKD) is a public health problem that increases the risk of cardiovascular morbidity and mortality. Heart failure with preserved ejection fraction (HFpEF) characterized by left ventricular hypertrophy (LVH) and diastolic dysfunction is a common cardiovascular complication of CKD. MicroRNA-212 (miR-212) has been demonstrated previously to be a crucial regulator of pathologic LVH in pressure-overload-induced heart failure via regulating the forkhead box O3 (FOXO3)/calcineurin/nuclear factor of activated T-cells (NFAT) pathway. Here we aimed to investigate whether miR-212 and its hypertrophy-associated targets including FOXO3, extracellular signal-regulated kinase 2 (ERK2), and AMP-activated protein kinase (AMPK) play a role in the development of HFpEF in CKD. CKD was induced by 5/6 nephrectomy in male Wistar rats. Echocardiography and histology revealed LVH, fibrosis, preserved systolic function, and diastolic dysfunction in the CKD group as compared to sham-operated animals eight and/or nine weeks later. Left ventricular miR-212 was significantly overexpressed in CKD. However, expressions of FOXO3, AMPK, and ERK2 failed to change significantly at the mRNA or protein level. The protein kinase B (AKT)/FOXO3 and AKT/mammalian target of rapamycin (mTOR) pathways are also proposed regulators of LVH induced by pressure-overload. Interestingly, phospho-AKT/total-AKT ratio was increased in CKD without significantly affecting phosphorylation of FOXO3 or mTOR. In summary, cardiac overexpression of miR-212 in CKD failed to affect its previously implicated hypertrophy-associated downstream targets. Thus, the molecular mechanism of the development of LVH in CKD seems to be independent of the FOXO3, ERK1/2, AMPK, and AKT/mTOR-mediated pathways indicating unique features in this form of LVH.

Due to its mechanism of action, PARP inhibitor therapy is expected to benefit mainly tumor cases with homologous recombination deficiency (HRD). Various measures of genomic scarring based HRD scores were developed as a companion diagnostic in order to correlate it with PARP inhibitor sensitivity. We compared a variety of HRD scores in primary tumors and their corresponding brain metastases and found a significant increase in this measure in brain metastases for all measures of HRD that were tested. This discrepancy warrants further investigation to assess whether this observation is common to other metastatic sites, and potentially a significant adjustment of strategy in the application of HRD measures in clinical trials for the prioritization of patients for PARP inhibitor therapy.Key messageWe quantified homologous recombination deficiency (HRD) in paired primary breast cancer and brain metastases samples based on a previously published data set. We showed that HRD significantly increases in the brain metastases relative to its paired primary tumor. An independent validation was also performed on another set of primary breast cancer and brain metastasis pairs using the “my choice” HRD score in collaboration with Myriad Genetics.These confirmatory results suggest that brain metastases of breast cancer tend to have significantly higher HRD scores, which would prioritize those patients for PARP inhibitor therapy with those agents that cross the blood brain barrier such as veliparib and niraparib.

Inflammatory breast cancer (IBC) is a clinico-pathological entity, which has specific features of inflammation and pathological evidence of cancer, most often involving dermal lymphatics. This review looks at IBC from the pathologists point of view. The diagnostic criteria and differential diagnosis are summarized first. The staging implications are described next. Despite the overall poor prognosis of IBC, it is heterogeneous in terms of most prognostic and predictive factors (such as histological type, grade, receptor status, intrinsic subtype, inflammatory infiltrate). It seems that some molecular features (genes expressed) are unique to IBC, and this may help to identify them as IBC at the molecular level. The key carcinogenetic pathways activated in IBC, the inflammatory pathways present in the disease as well as the relation of IBC to cancer stem cells are also briefly covered. Due to the relative rarity of IBC, preclinical trials are very important in the study of this entity, and models with stromal and microenvironmental elements are expected to outperform the traditional models without these features, as the microenvironment seems to be a key component of IBC. (C) 2018 Elsevier Ltd, BASO - The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Aims Solid papillary breast carcinoma resembling the tall cell variant of papillary thyroid neoplasms (BPTC), also known as solid papillary carcinoma with reverse polarity, is a rare histological type of breast cancer that resembles morphologically the tall cell variant of papillary thyroid carcinoma. BPTCs are characterised by IDH2 R172 hotspot somatic mutations or mutually exclusive TET2 somatic mutations, concurrently with mutations affecting PI3K pathway-related genes. We sought to characterise their histology and investigate the frequency of IDH2 and PIK3CA mutations in an independent cohort of BPTCs, as well as in conventional solid papillary carcinomas (SPCs). Methods and results Six BPTCs, not previously analysed molecularly, and 10 SPCs were reviewed centrally. Tumour DNA was extracted from microdissected histological sections and subjected to Sanger sequencing of the IDH2 R172 hotspot locus and exons 9 and 20 of PIK3CA. All six BPTCs were characterised by solid, papillary and follicular architecture with circumscribed, invasive tumour nodules composed of epithelial cells with reverse polarity. IDH2 mutations were identified in all six BPTCs (three R172S, two R172T and one R172G), four of which also harboured PIK3CA mutations (two H1047R, one Q546K and one Q546R). By contrast, all SPCs lacked IDH2 mutations, while one of 10 harboured a PIK3CA mutation (H1047R). Conclusion We validated the presence of IDH2 R172 hotspot mutations and PIK3CA hotspot mutations in 100% and 67% BPTCs tested, respectively, and documented absence of IDH2 R172 mutations in SPCs. These findings confirm the genotypical-phenotypical correlation reported previously in BPTC, which constitutes an entity distinct from conventional SPC.

Although the majority of lung adenocarcinomas show mixed pattern, only the predominant component is taken into account according to the novel classification. We evaluated the proportion of different patterns and their impact on overall survival (OS) and disease-free survival (DFS). Patterns were recorded according to predominance and their proportions were rated and calculated by objective area measuring on digitalized, annotated slides of resected stage I lung adenocarcinomas. Spearman's rank correlation, Kaplan-Meier models and the log rank test were used for statistical evaluation. Two hundred forty-three stage I adenocarcinoma were included. Lepidic pattern is more frequent in tumours without recurrence (20 vs. 8%), and lepidic predominant tumours have favourable prognosis (OS 90.5%, DFS 89.4%), but proportions above 25% are not associated with improving outcome. Solid and micropapillary patterns are more frequent in patients with recurrence (48 vs. 5% and 13 vs. 4%) and predominance of each one is associated with unfavourable prognosis (OS 64.1%, DFS 56.3% and OS 28.1%, DFS 28.1%, respectively). Above 25%, a growing proportion of solid or micropapillary pattern is not associated with worsening prognosis. In contrast, tumours having micropapillary pattern as secondly predominant form a different intermediate group (OS 51.1%, DFS 57.8%). Our study was based on measured area of each growth pattern on all available slides digitalized. This is the most precise way of determining the size of each component from the material available. We propose using predominant and secondly predominant patterns for prognostic purposes, particularly in tumours having solid or micropapillary patterns.

Objective: In the breast, CD10 is expressed by myoepithelial cells (MECs), and apocrine metaplasia has also been mentioned as being positive with this marker. Apocrine lesions have been explored for the expression of CD10. Methods: The apocrine lesions studied included 11 cysts, 6 cases of apocrine adenosis, 2 of apocrine metaplasia or hyperplasia in papilloma, 13 ductal carcinomas in situ (DCIS) and invasive carcinomas (14 ductal and 4 lobular). Results: Benign apocrine lesions showed complete or partial luminal CD10 staining, although most cases included parts without staining, and 2 lesions were completely negative. The MECs were often but not always positive. Nine of the 13 cases of apocrine DCIS displayed no luminal staining, but 4 demonstrated very focal luminal positivity. The MECs around the DCIS showed a spectrum of staining from nil to strong and complete. Only 4 invasive carcinomas demonstrated luminal/membranous staining. Cytoplasmic CD10 positivity was seen focally in 4 invasive cancers and in 3 DCIS. Conclusion: CD10 positivity is luminal/membranous in most benign apocrine lesions, the staining being nonuniversal and sometimes focal. Analogous staining in apocrine malignancies seems rarer in DCIS and even rarer in invasive apocrine carcinomas, but atypical cytoplasmic positivity may also occur. CD10 is not an ideal myoepithelial marker in apocrine lesions.

In polymorbid or anaemic patients who receive preoperative radiotherapy or undergo long duration surgery involving potentially infectious sites, perioperative antibiotic prophylaxis (PAP) that is effective against normal oral bacterial flora is mandatory and plays an important role in preventing postoperative infection. In a four-year retrospective analysis, the incidence, outcome, and the efficacy of PAP were evaluated in patients treated at the Department of Oral and Maxillofacial Surgery and Otorhinolaryngology at Kecskemét Hospital. The results were compared with data from the literature to determine if the use of PAP was adequate at the Department.During the study period (between 01/09/2007 and 31/01/2011) 108 patients were evaluated. The mean duration of prophylactic antibiotic treatment was 8.3 ± 5.2 days, with cefotaxime+metronidazole being the most commonly used combination. Surgical site infection occurred in 8 patients (7.5%) in the clean-contaminated category.Our results showed that the perioperative antibiotic prophylaxis administered at our Department was efficient and effective against the oral bacterial flora of patients. Its use is recommended in head and neck microsurgery. To avoid development of antibiotic resistance and to reduce costs, it seems that the duration of antibiotic regimen for primary surgery can be reduced from 8.3 ± 5.2 days to 3 days.

The aim of the present study was to determine the benefit of orcein elastic staining of primary cutaneous melanoma specimens in detecting venous invasion. Primary cutaneous melanomas in vertical growth phase were assessed for vascular invasion. All tumour blocks were stained with haematoxylin and eosin (H&E) and orcein. The cases were reviewed by two pathologists. Vascular invasion was not identified more frequently on orcein stained slides than on H&E stained ones. Elastosis and periappendiceal elastic fibres interfered with vascular invasion detection with elastic staining. Based on our study, we conclude that elastic stains such as orcein do not improve the detection rate of venous invasion in primary cutaneous melanomas.

This review describes the changes that have been implemented in the Tumor-Node-Metastasis (TNM)-based staging of breast cancers by the new, 8th editions of the relevant Union for International Cancer Control (UICC) and American Joint Committee on Cancer (AJCC) publications. After giving a background for TNM being the common language of cancer staging and related activities like cancer treatment and registration, it summarizes not only the changes but reviews some highlights important for pathologists, and lists and comments on the differences between the publications and diagnostic practices based on them. A section is dedicated to the prognostic stages of breast carcinomas introduced in the AJCC Cancer Staging Manual, but not mentioned in the UICC TNM classification of malignant tumors. A few issues that are not appropriately covered by TNM according to the authors' view (e.g., multifocal tumors, larger lymph node metastases identified by molecular methods, the heterogeneous prognosis of M1-defined stage IV disease) close the review with the final thoughts raising the vision of a potential loss of the common staging language.

Background Postanalytic issues of Ki67 assessment in breast cancers like counting method standardisation and interrater bias have been subject of various studies, but little is known about analytic variability of Ki67 staining between pathology labs. Our aim was to study interlaboratory variability of Ki67 staining in breast cancer using tissue microarrays (TMAs) and central assessment to minimise preanalytic and postanalytic influences. Methods Thirty European pathology labs stained serial slides of a TMA set of breast cancer tissues with Ki67 according to their routine in-house protocol. The Ki67-labelling index (Ki67-LI) of 70 matched samples was centrally assessed by one observer who counted all cancer cells per sample. We then tested for differences between the labs in Ki67-LI medians by analysing variance on ranks and in proportions of tumours classified as luminal A after dichotomising oestrogen receptor–positive cancers into cancers showing low (

As concerns the microscopic morphology of ductal carcinoma in situ (DCIS), neoplastic cells are surrounded by both a myoepithelial cell layer and a basement membrane as expected from the outer structure of ducts and lobules. However, in some cases, it is impossible to state whether the structures involved by the disease are ducts or lobules. Altogether 1220 anatomic structures involved by DCIS displaying comedo necrosis from 27 slides of 21 patients (seen on both haematoxylin and eosin-stained and orcein-stained slides) were identified as representing ducts, likely ducts, unclassifiable structures, likely acini or acini on the basis of their distribution and resemblance to normal anatomic structures. All structures were then rated as having a circumferential elastic layer (as normal ducts), a partial elastic layer around more or less than half of the periphery or having no peripheral elastic layer at all (as normal acini). Structures classified as ducts or likely ducts were likely to have an elastic coating, whereas acini and likely acini had no such coating. Unclassifiable structures were generally devoid of an elastic layer. Structures (and cases) that were likely to represent neoductgenesis as proposed by Zhou et al. (Int J Breast Cancer 2014;2014:581706) were generally unclassifiable and devoid of outer elastic layer. Many duct-like structures in DCIS with comedo necrosis are devoid of elastic layer typical of normal ducts, suggesting that these structures are abnormal despite conservation of the myoepithelium and the basement membrane.

The 8th edition of the Tumor-Node-Metastasis (TNM) based staging of breast cancer introduces a prognostic stage influenced by biomarkers along the traditional T, N and M categories.To retrospectively assess stage influencing prognostic variables; and the anatomic and prognostic stages on the basis of the overall survival (OS) of a cohort of deceased patients once diagnosed with breast cancer.We included patients with known causes of death certified at the Bács-Kiskun County Teaching Hospital and having a history of breast cancer diagnosed on a resection specimen at the same institution. Prognostic factors were obtained from the histopathological reports. Statistics included one-way ANOVA, Dunn's post hoc test and Kaplan-Meier curve analyses.The 303 patients grouped as breast cancer related death (n = 168) or unrelated (n = 135) showed significant differences in most stage defining prognostic factors and the anatomic and prognostic stages. Significant differences in 5-year OS were observed between pT and pN categories, histological grades and estrogen receptor statuses. Except for stages I and II, significant differences were found between both different anatomic and prognostic stages (p0.001). Stage IV is by definition uniform, but we identified survival differences between biomarker based subgroups: triple negative carcinomas had worse OS than estrogen receptor positive and HER2 negative carcinomas.Our analysis based on real survival data suggests that the prognostic stages separate patients according to OS similarly to the anatomic stages. The results validate the prognostic stages, but also suggest that separating stage IV disease according to biomarkers makes sense. Orv Hetil. 2017; 158(35): 1373-1381.