Breast cancer (BC) is the most prevalent cancer in the world among women and there are nearly 1.7 million new cases worldwide each year. Due to a number of remarkable advances made in both diagnosis and therapy, the survival rates for BC patients have increased in those regions with adequate medical facilities. According to contemporary recommendations, any pathological diagnosis of breast lesions, before any treatment, should be based on a Core Needle Biopsy (CNB), or on a Fine Needle Aspiration Cytology (FNAC), if CNB is not available. The prognosis of the newly diagnosed breast cancer patient depends on a number of factors, among which the most important is the extent of the spread of the disease to the axillary lymph nodes. Because any further treatment is influenced by the presence and number of axillary lymph nodes involved, a complete evaluation of the axillary lymph nodes is performed on every patient that is able to tolerate it, after a formal diagnosis of invasive carcinoma. At the very least an ultrasound with guided fine needle aspiration or core biopsy of suspicious lymph nodes should be undertaken.Although CNB is the main method employed in breast lesions diagnostics, FNAC still plays a significant role in the evaluation of pathological processes in the breast, a fact that has been well documented in the relevant literature in the last 20 years. The advantages of FNAC are: the sampling is quicker; the sampling technique usually does not require the use of anaesthetics; the trauma is small, and therefore more convenient for women using anticoagulant therapy; complications are rare; the availability of the results is within a few hours; skilled operators and pathologists regard this method as being highly sensitive in the detection of any malignant cells and the equipment is less expensive. The United Kingdom National Health Service Breast Screening Program (UK NHSBSP), began in 1988. Its guidelines have been published with regards to the mode of categorizing cell changes that may be seen in cytological samples obtained by needle aspiration. Five categories have been identified: C1 (unsatisfactory specimen - non-representative), C2 (benign), C3 (atypical - most likely benign), C4 (suspected - most likely malignant) and C5 (malignant). In 1996, the American National Cancer Institute (NCI) also suggested 5 categories for cytological diagnostics of breast lesions: benign, atypical, suspected, malignant and unsatisfactory. Patients with C3 and C4 categories, namely, atypical and suspected, which carry the risk of a malignant tumour, need to undergo further examination. C1 and C2 categories have to be correlated with the results of clinical and radiological examinations. C3 and C4 categories should not be represented in more than 5% of all analyzed aspirates. Currently, there is no individual morphological criterion that cytological diagnostics of malignant breast tumours could be based on. The most important cytological criteria that indicate whether it is a benign pathological process or a malignant tumor are: cellularity of the sample (a very important criterion, but it should be carefully interpreted), loss of cell cohesiveness (characteristic of malignant tumors), cellular arrangements, cell size, biphasicity in smear, the characteristics of the nucleus (size, contour, the appearance of chromatin, the appearance of nucleolus), characteristics of cytoplasm, nuclear-cytoplasmic ratio, APSTRAKTI 93 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. mitotic figures, background appearance (necrosis, peripheral blood cells, mucus…) and the presence of inflammatory cells. It is also possible to perform immuno-histochemical staining on cytological samples, flow cytometry and molecular analyses. The FNAC treatment is characterised by solid sensitivity, specificity and predictive value. The sensitivity of FNAC ranges from 89% to 98% and the specificity is between 98% and 100%. Major shortcomings of this method are the impossibility of diagnosing in situ carcinoma and lesions followed by any abundant production of connective tissue. The CNB treatment has gained remarkable popularity since the 1980s and in many institutions has replaced FNAC. The limitations of both methods are; atypical ductal hyperplasia, fibroepithelial tumours, radial scarring and papillary lesions. In the diagnosis of breast lesions apart from aspiration cytology, other sampling techniques for cytological analysis are also applied. In the era of breast conservation therapy, breast tissue is most commonly sent for intraoperative consultation. A frozen section analysis is performed through freezing and sectioning the surgical specimen with subsequent staining, in order to obtain an extemporaneous assessment of the margins. Although this technique is extensively used by many surgeons to avoid the need for a postponed rescission, some pitfalls have been reported, such as the occurrence of artefacts due to the freezing and thawing of the adipose tissue in the specimen. A different intraoperative method for margins evaluation is imprint cytology, which consists of pressing each of the 6 faces of the specimen on 6 different slides, so that any malignant cell on any involved margin is theoretically present on the cytology of the respective slide, because of the tendency of tumour cells to adhere to glass as compared to adipocytes. Imprint cytology can also be used in assessing the representational value of the CNB samples. A significant number of authors suggest that the application of the imprint of cytology reduces the number of inadequate samples obtained by CNB and can also provide a preliminary diagnosis, especially in cases of adequately sampled malignant tumours. Nipple discharge (ND) accounts for approximately 5% of the breast-related symptoms and is the third most common reason women seek medical attention. Approximately 7% to 15% of unilateral NDs are caused by malignant lesions, primarily ductal carcinoma in-situ (DCIS). A cytological examination of the obtained content is significant in the final treatment decision. Cytological analysis, in particular FNAC, continues to play an important role in the diagnoses of breast cancer. Skilled professionals can determine breast cancer through an analysis of the cytological sample as a reliable and accurate method.

Aim: To review current terminology of mixed exocrine and endocrine tumors of the large intestine. Introduction: Previous classification of colorectal tumors contained category called “mixed adenoneuroendocrine carcinoma” (MANEC) which encompassed neoplasms of the large intestine with features of both adenocarcinoma and a neuroendocrine carcinoma. Indeed, the vast majority of the mixed colorectal tumors have these two malignant components. However, this designation is no more suitable as other combinations of neuroendocrine and non-neuroendocrine tumors are recognised. Material and Metods: A detailed review of the literature on classification of mixed neuroendocrine-nonneuroendocrine tumors has been done. Results: The nonneuroendocrine component in a mixed colorectal tumor can be either exocrine or squamous and can be either benign or malignant. The histological grade of the nonneuroendocrine component may also vary. Therefore in several recent papers a new term has been coined “mixed neuroendocrine-nonneuroendocrine neoplasms” (MiNENs) in order to convey all possible combinations of the two components. According to the histologically estimated malignant potential, MiNENs are further subdivided into three categories low grade, intermediate grade and high grade. Conclusion: The new terminology is much more comprehensible than the previous ones and ensures a more accurate assessment of biological behaviour of the mixed colorectal tumors thus avoiding overtreatment of clinically innocent lesions.

The Norvegian University of Science and Technology is the largest educational institution in Norway. It was founded in 1760 as the Trondheim Academy. The Faculty of Medicine and Health Sciences is part of the St Olav’s Hospital in Trondheim, and being there, as participant of the Annual Cytology Tutorial of the European Federation of Cytology Societies, was an outstanding experience. Colleagues from all over the world had the opportunity to meet and learn from experts in various fields of cytology. Particularly, differences between conventional and Thin Prep Pap smears, as well as immunocytochemistry of air-dried smears were thoroughly discussed.

The presentation will reflect on a one-month period of education that the author spent with the Cleveland Clinic soft tissue pathology team. Cleveland is a US city in the state of Ohio. One of its nicknames is
“The Rock and Roll Capital of the world”, due to the fact that the term R’n’R was coined in the 1950s by
a Cleveland-based disc jockey Alan Freed. The city hosts the Rock and Roll Hall of Fame, established in
1983. It is also home to the Cleveland Clinic, a multispecialty academic hospital currently ranked as the
#2 hospital by U.S. News & World Report1. In 2014, Cleveland Clinic had a total revenue of $11.63 billion, making it the #2 hospital in US on the Becker’s Hospital Review revenue list2. The author spent one
month on a UICC ICRETT fellowship in November 2016 with the Cleveland Clinic soft tissue pathology
team. The main strength of the soft tissue team is the presence of several internationally known experts
with diverse interests within the field of soft tissue and beyond, with team philosophy highlighting the
synergy of team work and individual reputation. Among various topics that were covered during the
one-month fellowship, certainly one of the most interesting was differentiation among different fibrohistiocytic neoplasms. Fibrohistiocytic tumors are among the most frequent soft tissue tumors and they
are most commonly encountered in the skin. “Fibrohistiocytic” is in fact a merely descriptive term for
cells that resemble both normal fibroblasts and histiocytes, and not a true line of differentiation3. Like
other soft tissue tumors, fibrohistiocytic neoplasms are divided into benign, intermediate and malignant
categories. In presentation, the author will reflect on the key points in the pathology diagnosis within this
category of tumors, and these are:
- being able to give a common denominator to numerous variants of benign fibrous histiocytoma
- awareness of the pitfalls in the diagnosis of dermatofibrosarcoma protuberans
- discrimination of malignant fibrohistiocytic skin-based tumors from other, more adverse cutaneous
malignancies.

Lung transplantation remains the definitive treatment for end-stage lung diseases and an option when
medical and surgical care has been exhausted. The first human single lung transplant was performed in
1963, and the patient, survived for 18 days. From 1963 to 1978, multiple attempts at lung transplantation
failed because of rejection and problems with anastomotic bronchial healing. It was only after the invention of the heart-lung machine, coupled with the development of immunosuppressive drugs, that organs
such as the lungs could be transplanted with a reasonable chance of patient recovery. The first clinically
successful long-term single lung transplant was performed in 1983, and since then over 25,000 lung transplants performed worldwide.

Adnexal tumors of the skin comprise heterogenous group with over 40 defined entities, classified by predominant differentiation into lesions with apocrine and eccrine, follicular, sebaceous, or multilineage differentiation. Some, but not all these entities are represented by benign and malignant counterparts. Their occurrence may be sporadic or as a part of inherited syndromes (e.g. Muir-Torre syndrome, Brooke-Spiegler Syndrome, or Cowden’s syndrome). Adnexal tumors may arise de novo or within hamartomatous lesions such as nevus sebaceous of Jadassohn. Adnexal carcinomas are very rare tumors (the incidence is less than 0.001%), with variable local recurrence, metastatic potential, and survival. Porocarcinoma, hidradenocarcinoma and sebaceous carcinoma (especially ocular type) are considered to have a poor prognosis, with the highest risk of local recurrence and distant metastases. Mortality of the patients with porocarcinoma is very high (65-80%) if regional or distant metastases are present. The treatment of malignant adnexal tumors is usually surgical or less frequently with radiation therapy. Patients with metastases are usually treated with chemotherapy, mostly with cytotoxic reagents, and rarely with estrogen receptor antagonists. The detailed knowledge of genetic features of adnexal tumors is still lacking. Most of the studies examined only few of the genes using low throughput techniques. Development of new generations of genome sequencing methods led to better understanding of tumors with apocrine and eccrine differentiation. For many of their subtypes, it is still unknown whether there are specific genetic changes, that could even be of diagnostic significance. Hotspot mutations in HRAS (p.G13X and p.Q61X) were found in a subset of eccrine poromas and porocarcinomas. These mutations were found in tumors with other lines of differentiation and suggesting overlapping genetical characteristics among adnexal tumors. Due to their similar histological features, cylindroma and spiradenoma are usually considered as phenotypic variations of the same entity. Their histological features can be mixed, in which case a diagnosis of spiradenocylindroma is made. In cylindroma, MYB is upregulated either by mutations in CYLD gene (syndromic cases) or due to a rearrangement of MYB gene (sporadic cases). Genetic characteristics of spiradenomas, including the status of CYLD and MYB genes, are largely unknown. It is still unclear if these two are both histological and genetical “relatives” and what is the level of heterogeneity among tumors arising sporadically or within syndromes. The presence of chromosomal rearrangements in adnexal tumors is also unexplored. TORC1-MAML2 and EWSR1-POU5F1 fusions were found in significant number of hidradenomas. Initially it was thought these fusions could be characteristic for clear cell variant of hidradenomas, but no true correlation with histology was found. Molecular alterations that differ between benign and malignant counterparts and could enable targeted therapy of adnexal carcinomas are unknown. Mutations in TP53, often UV-associated, are frequent in malignant tumors with eccrine and apocrine differentiation and can drive malignant transformation in such tumors. Porocarcinomas and ABSTRACTS 96 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. hidradenocarcinomas harbor various molecular alterations affecting PI3K-AKT or MAPK pathways that could enable targeted therapy in the future. Actionable mutations in EGFR were not found in carcinomas with eccrine and apocrine differentiation thus far. Her2 amplifications are rarely found, mostly in hidradenocarcinomas, but its therapeutic potential has only been utilized only once.16,25 Mutations of PTCH1 and TCF7L1 in hidradenocarcinomas could also enable the treatment with the inhibitors of Hedgehog and WNT/Hippo signaling pathways. It seems that current knowledge gained from genomic studies of adnexal tumors is only a scratch on the surface. In addition, there is no data on epigenetic characteristics or transcriptome of adnexal skin tumors. Taken altogether, further and detailed investigation of genome, epigenome and transcriptome of adnexal tumors is necessary. Such integrated knowledge could explain mechanisms of their development, malignant alteration and progression, so the treatment of patients with metastatic adnexal carcinomas could be changed toward targeted therapy.

Aim and introduction: Pediatric nodal marginal zone lymphoma (NMZL) is a rare, but distinct subtype of NMZL with characteristic clinical presentation, pathohistological and molecular features, therapy and prognosis. Results: We report the case of a 15-year-old boy with no remarkable past history, presented with painless enlargement of left submandibular lymph node (LN) for three months. He was admitted to the University Children’s Hospital in Belgrade in May 2016. The cervical ultrasound demonstrated moderate left submandibular lymphadenopathy, but also mild enlargement of two right submandibular LNs (17x7mm, 14x7mm). Physical examination, chest radiography and abdominal ultrasound revealed no hepatosplenomegaly and lymphadenopathy elsewhere. The result of blood count test was normal. Biochemistry showed elevated uric acid 499 umol/l, AST 45U/l, ALT 98U/l, and sedimentation rate (65mm/h). Urea, creatinine, alkaline phosphatase, LDH and CRP were normal. The patient underwent left submandibular LN excisional biopsy. The size of the LN was 47x37x20mm. The histopathological examination revealed partial architectural effacement: follicular hyperplasia and nodular B-cell infiltration with features of progressive transformation of germinal centers (PTGC) in the form of fragmentation of follicles. A CD20 immunostain shows an abnormal expansion of the marginal zone with infiltration of interfollicular space. These B-cells were negative for CD3, CD5, CD23, EBV-LMP1, bcl-6, CD10, EMA, CD30, CD15, MUM-1, and positive for bcl-2 and IgD. A CD21/ CD23/ fascin immunostain showed an expanded and disrupted follicular dendritic cell meshwork. Ki-67 highlighted residual follicular polarisation and a low proliferation rate in the interfollicular areas. Based on these pathohistological findings it was concluded that LN likely represent reactive follicular hyperplasia with atypical marginal zone hyperplasia or possible PNMZL, with APSTRAKTI 95 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. recommendation of polymerase chain reaction (PCR) analysis of clonality. Additional IGH PCR analysis demonstrated biclonal heavy chain gene rearrangement. These findings were consistent with PNMZL. After consultation with members of International BFM study group for non-Hodgkin lymphomas, followup was recommended without any treatment. The patient has remained disease free for 22 months since diagnosis. Conclusion: We presented a rare case of PNMZL with morphological features of PTGC, but immunohistochemistry and additional PCR clonality analysis were crucial for final diagnosis. This case represents a diagnostic and therapeutic challenge because of their rarity in the pediatric population.

The incidence of diabetes is on a boom in the world. Coronary heart disease is the most common macrovascular complications of diabetes. Strict control of blood glucose levels contribute to the betterment of the patient and reduce the cost of treatment. The aim is to show the influence and significance of diabetes in the five-year outcomes in patients who underwent percutaneous coronary intervention Initially in the study included 800 patients who underwent percutaneous coronary angioplasty index. After the indexing procedure clinical monitoring is completed for 720 patients (90%) whose data after the completion of the follow-up period subjected to statistical analysis, which included descriptive statistics, a mutual comparison of the examined groups were used methods for testing the significance of differences numeric-factor analysis of variance (ANOVA) student’s t test, rank sum test (Mann-Whitney U test) hi-square test. They were monitored and analyzed the parameters of cardiac status obtained on outpatient examinations, and data obtained by telephone contact with the patient. Patients involved in the study had a very good glycoregulation, therefore there were no statistically significant differences in the five-year outcomes after percutaneous coronary intervention. The study showed approximately equal distribution of the sexes patients who are suffering from diabetes, those with diabetes mellitus type 1 patients with type 2 diabetes. There is no significance in survival, no matter what the patient is suffering from diabetes, has no significance because of the small number of deaths. It is similar to myocardial infarction, no statistically significant differences between patients with diabetes and patients who do not suffer from diabetes in terms of myocardial infarction.

Penile tumors are rare neoplasms of the male urogenital tract and represent approximately 1% of all urogenital cancers in men. Squamous cell carcinoma is the most common histological type of these tumors, and is seen in about 95% of the cases. We report a case of a 66 years old male patient presented with large, neglected cancer of the penis, which grew about 6 months, but patient was not motivated for treatment until tumor began to bleed. Patient was operated and tumor was completely removed. The early postoperative course was uneventful and the patient was discharged from hospital Since penile cancers are rare entity, there are counted controversy about the best method of treatment. We believe that the individual approach to each patient relying on existing good clinical practice guidelines is currently the best therapeutic approach.