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.

Retrospective analysis of low-risk differentiated thyroid tumours: is lobectomy the adequate approach? / Kis rizikójú differenciált pajzsmirigydaganatok retrospektív analízise: lobectomia a megfelelo választás?

Introduction: According to the recommendation of the American Thyroid Association 2015 guideline, the treatment of 1-4 cm (T1b-2) low-risk differentiated thyroid cancer (DTC) is lobectomy without radioiodine therapy. Objective: Retrospective analysis of multifocality in surgical and histological data of T1-2 patients living on moderate iodine intake. Methods: Analysis of the pathological characterisation of 81 low-risk (T1-2) DTC patients who underwent total thy-roidectomy. Patients were treated at Flor Ferenc Hospital, Kistarcsa, Hungary, between 2013 and 2019. Results: 64 patients had T1, while 17 patients had T2 status. 65/81 (80.2%) patients had papillary, and 16/81 (19.8%) had follicular subtype. Lymph node metastasis was detected up to 18.4% in papillary and 18% in follicular patients. Multifocal tumours were detected in 25% (16/64) of T1 patients, of these 10.9% (7/64) was unilateral and 14.1% (9/64) was bilateral. Multifocal tumours were detected in 11.7% (2/17) of T2 patients; both were bilateral. Distribution of T1-2 bilateral multifocal patients (11/81; 13.5%) was n = 3 T1a-, n = 6 T1b and n = 2 T2 stadium, from these 10 patients received radioiodine treatment. The sizes of contralateral tumours were <5 mm in 9 patients, and >5 mm in 2 patients. Conclusions: Due to the frequent (13.5%) bilateral multifocality in T1-2 DTC patients, we suggest total thyroidec-tomy instead of lobectomy. After lobectomy, the follow-up of the contralateral tumours is almost impossible by ul-trasonography due to the small tumour size (on average 2.8 mm) and frequently detected benign nodules; therefore the multifocality might remain undetected, which can distort the plan for adjuvant treatment.

[Pathological diagnosis, work-up and reporting of breast cancer. Recommendations from the 4th Breast Cancer Consensus Conference]. / Az emlorák patológiai diagnosztikája, feldolgozása és kórszövettani leletezése. Szakmai útmutatás a IV. Emlorák Konszenzus Konferencia alapján.

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.

[Molecular diagnostics of lung cancer and its clinical relevance]. / A tüdorák molekuláris diagnosztikájának modern szemlélete és klinikai jelentosége.

Molecular classification of lung cancer developed in the past decades to the level where even the rare genetic alterations are included. Unfortunately, adenocarcinoma benefited from this development almost exclusively. Furthermore, the tumor-agnostic novel therapy indications influence the molecular diagnostics of lung cancer including microsatellite status, tumor mutation burden or NTRK fusion gene determinations. On the other hand, the still low resection rate of lung cancer and limited availability of tumor tissue for diagnosis opened the way of routine use of liquid biopsy technologies. The routine use of target therapies triggered the development of various genetic resistance mechanisms, the monitoring of which gradually became a standard of monitoring of the disease. Beside the "targeted" diagnostics, multigene panel testing or whole exome sequencing are more frequent, resulting in a more complex genetic picture of lung cancer. This requires the categorization of genetic alterations into predictive levels for standard, investigational or hypothetic target therapies in the molecular pathology reports.

[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.

Expression of miRNAs in adenoid cystic carcinomas of the breast and salivary glands.

Despite their similar histomorphologic appearance, adenoid cystic carcinomas of the breast and salivary glands (bACCs and sACCs, respectively) are clinically and pathologically diverse. We studied the expression levels of 18 microRNAs (miRNAs) in bACCs and sACCs and control normal breast and salivary gland tissues (bNs and sNs, respectively) by quantitative real-time polymerase chain reaction on formalin-fixed paraffin embedded tissues. miRNAs showing significant differences between the study groups were selected for target prediction. Increased expression of miR-17 and miR-20a was found in bACCs compared with bNs (p(miR-17) = 0.017 and p(miR-20a) = 0.024, respectively), while the expression level of let-7b and miR-193b was lower in sACCs compared with normal sNs (p let-7b = 0.032 and p(miR-193b) = 0.023, respectively). Expression of miR-23b and miR-27b differed between normal breast and normal salivary gland tissue (p(miR-23b) = 0.007 and p(miR-27b) = 0.024, respectively), but not between bACCs and sACCs. The potential target mRNAs CCND1 and BCL2 were identified as reported targets of let-7b, miR-193b, miR-17, and miR-20a. Expression of their corresponding proteins cyclin D1 and Bcl-2 was studied by immunohistochemistry. We found both proteins overexpressed in bACCs as well as sACCs in comparison with corresponding normal tissues. However, expression of cyclin D1 and Bcl-2 proteins was not significantly different between bACCs and sACCs or between bNs and sNs. Although no differences in miRNA levels were found between bACCs and sACCs, in both organs, miRNA expression level was highly different between tumor tissue and control tissue.

Estrogen receptor negative and progesterone receptor positive breast carcinomas-how frequent are they?

Estrogen receptor (ER) testing has become an important part of breast cancer reporting as the ER status is a predictor of hormonal treatment efficacy. Progesteron receptors (PR) are often tested in parallel, and the best response to hormonal manipulations can be expected in tumors positive for both receptors. The existence of breast cancers with an ER negative and PR positive phenotype is controversial. A series of cases with this phenotype were reevaluated to clarify the existence and the frequency of this entity. A total of 205/6587 (3.1%; range of the rate per department: 0.3-7.1%.) cases reported to have the ER-negative and PR-positive status by immunohistochemistry were collected from 9 Hungarian departments. After careful reevaluation of the tumor slides and control tissues with a 1% cut-off for positivity and restaining of the questionable cases, all but 1 of the reevaluable 182 cases changed their original phenotype. Most cases converted to dual positives (n = 124) or dual negatives (n = 31) or unassessable / questionable. ER-negative and PR-positive breast cancers are very rare if existing. Such a phenotype should prompt reassessment.

Cervical cancer screening policies and coverage in Europe.

The aim of the study was to compare current policy, organisation and coverage of cervical cancer screening programmes in the European Union (EU) member states with European and other international recommendations. According to the questionnaire-based survey, there are large variations in cervical cancer screening policies and inadequacies in the key organisational elements of the programme such as registration and monitoring required for quality-assurance and fail-safe mechanisms. Based on data from available screening registers, coverage of the screening test taken within the population-based programme was below 80% in all programmes, ranging from 10% to 79%. The screening capacity is satisfactory in most EU member states, however, and there is even over-capacity in several countries. There are also countries which do not have an acceptable capacity yet. Control of proper capacity along with education, training and communication among women, medical professionals and authorities are required, accordingly. The study indicates that, despite substantial efforts, the recommendations of the Council of the EU on organised population-based screening for cervical cancer are not yet fulfilled. Decision-makers and health service providers should consider stronger measures or incentives in order to improve cervical cancer control in Europe.

Breast pathology guideline implementation in low- and middle-income countries.

The quality of breast healthcare delivery and the ultimate clinical outcome for patients with breast cancer are directly related to the quality of breast pathology practices within the healthcare system. The Breast Health Global Initiative (BHGI) held its third Global Summit in Budapest, Hungary from October 1 to 4, 2007, bringing together internationally recognized experts to address the implementation of breast healthcare guidelines for the early detection, diagnosis, and treatment in low-income and middle-income countries (LMCs). From this group, a subgroup of experts met to address the specific needs and concerns related to breast pathology program implementation in LMCs. Specific recommendations were made by the group and process indicators identified in the areas of personnel and training, cytology and histopathology interpretation, accuracy of pathology interpretation, pathology reporting, tumor staging, causes of diagnostic errors, use of immunohistochemical markers, and special requirements to facilitate breast conservation therapy. The group agreed that the financial burden of establishing and maintaining breast pathology services is counterbalanced by the cost savings from decreased adverse effects and excessive use of treatment resources that result from incorrect or incomplete pathologic diagnosis. Proper training in breast pathology for pathologists and laboratory technicians is critical and provides the underpinnings of programmatic success for any country at any level of economic wealth.

Diagnosis of myiasis by fine needle aspiration cytology: a case report.

BACKGROUND: Myiasis is the infestation of tissues and organs by dipteran larvae and is endemic in tropical areas. Diagnosis usually is made by demonstration of a larva or larvae in infected tissue, generally recognizable to the naked eye. In our case, diagnosis was based on fine needle aspiration cytology (FNAC). CASE: A 59-year-old female patient with a painful neck mass was examined at an otorhinolaryngologic department after symptoms for several weeks. The lesion was found to be an absceding lymphadenitis, based on clinical symptoms, palpation and imaging (ultrasound and computed tomography). The lesion did not improve with repeated courses of antibiotics, so surgery was performed. Pus cultures collected after incision were negative, leaving origin of the inflammation undetermined. Smears from FNA of the residual mass demonstrated a worm-like pathogen alien to most European pathologists' experience. The pathogen was identified as a dipteran larva, leading to accurate etiologic diagnosis of myiasis. More scrupulous examination of the patient's history revealed she had spent her vacation in Australia, where she probably acquired the infection. CONCLUSION: Our case demonstrates the growing importance of the pathology of infectious diseases. One reason for this may be the ever-increasing possibility, frequency and distance of travel.

Breast cancer in limited-resource countries: diagnosis and pathology.

In 2002 the Breast Health Global Initiative (BHGI) convened a panel of breast cancer experts and patient advocates to develop consensus recommendations for diagnosing breast cancer in countries with limited resources. The panel agreed on the need for a pathologic diagnosis, based on microscopic evaluation of tissue specimens, before initiating breast cancer treatment. The panel discussed options for pathologic diagnosis (fine-needle aspiration biopsy, core needle biopsy, and surgical biopsy) and concluded that the choice among these methods should be based on available tools and expertise. Correlation of pathology, clinical, and imaging findings was emphasized. A 2005 BHGI panel reaffirmed these recommendations and additionally stratified diagnostic and pathology methods into four levels--basic, limited, enhanced, and maximal--from lowest to highest resources. The minimal requirements (basic level) include a history, clinical breast examination, tissue diagnosis, and medical record keeping. Fine-needle aspiration biopsy was recognized as the least expensive reliable method of tissue sampling, and the need for comparing its clinical usefulness with that of core needle biopsy in the limited-resource setting was emphasized. Increasing resources (limited level) may enable diagnostic breast imaging (ultrasound +/- mammography), use of tests to evaluate for metastases, limited image-guided sampling, and hormone receptor testing. With more resources (enhanced level), diagnostic mammography, bone scanning, and an onsite cytologist may be possible. Mass screening mammography is introduced at the maximal-resource level. At all levels, increasing breast cancer awareness, diagnosing breast cancer at an early stage, training individuals to perform and interpret breast biopsies, and collecting statistics about breast cancer, resources, and competing priorities may improve breast cancer outcomes in countries with limited resources. Expertise in pathology was reaffirmed to be a key requirement for ensuring reliable diagnostic findings. Several approaches were again proposed for improving breast pathology, including training pathologists, establishing pathology services in centralized facilities, and organizing international pathology services.

Diagnosis of breast cancer in countries with limited resources.

Accurate diagnosis is a necessary step in the management of breast cancer. In women with breast cancer, diagnosis can confirm the presence of the disease, reduce treatment delays, and clarify the predictive and prognostic features of the cancer, which help in planning treatment and counseling women. In women with benign breast conditions, accurate diagnosis avoids erroneous treatment for breast cancer, which can have devastating consequences for the woman and unnecessarily consumes resources. The panel distinguishes between a "clinical diagnosis" of breast cancer (one based on signs and symptoms and imaging findings) and a "pathologic diagnosis" of breast cancer (one based on microscopic examination of cellular or tissue samples). The panel agrees that all women should have a pathologic diagnosis of breast cancer before they are given definitive treatment for the disease, no matter how strongly their clinical findings suggest cancer. The tools for clinical diagnosis include history, clinical breast examination, ultrasound, and diagnostic mammography; these tools provide valuable information and play important supplemental roles in ascertaining the presence of breast cancer. Mammography and ultrasound also help determine the extent of disease within the breast, which is essential when breast-conserving therapy can be offered to women. The tools for pathologic diagnosis include fine-needle aspiration biopsy, core needle biopsy, and standard surgical biopsy. The panel noted that each of these tools has potential benefits and limitations in the limited-resource setting, and concluded that the choice among them must be based on the available tools and expertise. The triple test-checking for correlation of pathology findings, imaging findings, and clinical findings-was identified as a critical practice in diagnosing breast cancer. Panelists uniformly agreed that mastectomy should not be used to diagnose breast cancer, noting that accurate diagnosis can be made by less invasive means. Expertise in pathology was identified as a key requirement for ensuring reliable diagnostic findings. Several approaches were proposed for improving breast pathology, including training pathologists, establishing pathology services in centralized facilities, and organizing international pathology services.

Apoptosis in Untreated and Hormone-Treated Prostate Cancer of Various Histological Types.

A total of 102 (66 untreated and 36 hormone-treated) prostate cancers were examined histologically in order to determine their histological grade and the percentage of apoptotic tumor cells. The less differentiated the tumors were, the higher the spontaneous apoptotic activity was. Hormone therapy increased the apoptotic index in the prostate cancers. The increase was of greater significance in grade I than in grade II and grade III tumors. The therapeutic consequences of these findings and the possibility of different oncogene-expressions in various histological types of prostate cancer are discussed.