Aim Lung adenocarcinoma (ADC) is a leading subtype of lung cancer, histologically defined with five different architectural growth patterns: lepidic, acinar, papillary, solid and micropapillary. The aim of this study was to explore the prevalence of epidermal growth factor receptor (EGFR) mutation and a relationship between the specific histological patterns of lung ADC in the population of Bosnia and Herzegovina. Methods The study included tumour tissue from 102 patients with completely resected lung ADC from 2015 to 2020. Molecular testing for the presence of EGFR mutations was performed by real-time PCR method. The relationship between EGFR mutation status and clinicopathological parameters was analysed. Results The EGFR mutation was detected in 12 (11.8%) cases of ADC, more often in non-smokers (p=0.007). A higher percentage of solid growth pattern presented in ADC may be an indicator of EGFR negativity (p=0.039), while a higher percentage of micropapillary growth pattern more common in the presence of EGFR mutation (p=0.047). Conclusion The prevalence of EGFR mutation is in accordance with the expected prevalence considering our studied population, Caucasians from South Europe. Better understanding of the relationship between histological patterns and molecular characteristics of lung ADC will enable earlier diagnosis and optimal treatment for patients.

Background: Cervical cancer is a cancer that occurs in the cells of the cervix–the lower part of the uterus that connects it to the vagina and represents a global public health problem. In 2008, 530,000 new cases and 275,000 deaths from cervical cancer were recorded worldwide, and in 2018, an increase to 570,000 new cases and 311,000 deaths was recorded. For many years, it has been known that the main cause of preinvasive lesions and cervical cancer is the human papillomavirus–HPV. The total prevalence of HPV in the cervix in the general population of women is 10%. In developing countries, this prevalence is higher and describe most frequent clinical manifestations in the praxis. Objective: The aim of this study was to analyze and describe molecular genetic basis of cervical cancer and the most frequent clinical manifestations in the praxis. Methods: This is cross-sectional study based on meta-analysis of the facts published in scientific literature stored in indexed databases Medline, PubMed Central, Scopus, Hinari, etc., about molecular genetic basis of the cervical cancer with description of clinical manifestations and its consequences describing morbidity and mortality rate in the population worldwide. Results and Discussion:  In 2008, 530,000 new cases and 275,000 deaths from cervical cancer were recorded worldwide, and in 2018, an increase to 570,000 new cases and 311,000 deaths was recorded. The main cause of preinvasive lesions and cervical cancer is the human papillomavirus–HPV. HPV infection is most common in young, sexually active women under the age of 25, but cervical cancer is more common in older women. Oncogenic types of human papillomavirus 16 and 18 together with HPV 45 and 31 are the causative agents of 80% of cervical cancer cases. HPV 16 has the highest oncogenic potential. Epigenetic changes include DNA methylation and post-translational modifications of histones, such as: methylation, acetylation, phosphorylation, ubiquitination and sumoylation. Cervical intraepithelial (CIN / SIL) lesion is a premalignant change of the cervix that occurs due to chronic infection with high-risk types of HPV. Persistent infection with oncogenic types of HPV causes almost all cases of cancer. HPV DNA was detected in 99.7% of cancer samples. Conclusion: There are four main steps in the development of cervical cancer: infection of the metaplastic epithelium of the transformation zone, viral persistence, progression towards precancerous lesions and invasion of the basement membrane. Histologically, in about 80% of cases, squamous cell carcinomas arise from preexisting dysplasias. Adenocarcinoma accounts for about 15-20% of cancer cases. HPV 16 is the main cause of squamous cell carcinoma, unlike HPV 18 which is typically associated with adenocarcinoma.

Background: Lymphadenopathy is a common finding in clinical practice. The cause of enlarged nodes on clinical examination alone is challenging and there may be multiple reasons for this enlargement. It may become enlarged due to stimulation by infectious agents or the involvement of metastasis or malignant diseases, such as lymphoma. Objective: The aim of the study was to investigate the diagnostic role of fine needle aspiration cytology of lymph nodes in metastatic cancer and lymphoma. Methods: A total of 48 FNAC lymph nodes suspicious for malignancy were sampled with follow-up biopsy in Clinical Center of University of Sarajevo from 2017 to 2023. Lymph nodes were aspirated using 20-22 G needle with minimally 2 passes, spread on slides, air-dried, stained with May-Grünwald-Giemsa or Papanikolaou and residual material sent for cytoblock. Results: Out of 48 cytological samples, 30 (62.5%) revealed metastatic epithelial cells and 12 (25%) lymphoproliferative neoplasm. Three samples were suspected for malignancies, one sample was unrepresentative, one inconclusive and one falsely negative. Histopathological confirmation had 35 patients, while others were confirmed based on clinical presentation and radiological techniques. Compared to histopathological diagnosis, cytology had a sensitivity of 89.47%, specificity of 93.33%, positive predictive value (PPV) 95.04% and negative predictive values (NPV) 86.13% for epithelial metastatic cancer. The overall diagnostic test accuracy was 91.06%. For lymphoproliferative neoplasms cytology in comparison to histopathology had sensitivity 85.71%, specificity 91.18%, PPV 76.4% and NPV 95.04%. The overall diagnostic test accuracy was 89.81%. In both ways cytology is showing significant possibility to be used as a primary tool in detecting cancers. Conclusion: FNAC is a fast, reliable, and efficient method for diagnosing malignant lymphadenopathy. The cytological diagnosis can sometimes be accepted as the definitive diagnosis without further correlation with histopathology, especially in advanced malignancies and known primary malignancies.

Abstract Objective of this study was to identify the histopathological patterns and their frequency in testicular biopsy specimens from azoospermic patients and to categorize it according to Modified Johnsen scoring system. Methods: Testicular biopsies from male patients with clinical diagnosis of azoospermia were included in this study. All tissue samples were fixed in buffered 10% formalin, routinely processed and stained with Hematoxylin and Eosin. All cases were examined microscopically and categorized according to the histopathological patterns and Modified Johnsen scoring system. Results: Total 219 cases of testicular biopsies from 125 azoospermic male patients were evaluated, with 94 cases of bilateral testicular biopsy. The most prevalent age group was of 30-39 years (66.2%). The most common histological pattern was of Sertoli cell only syndrome (58.4%) while the least represented pattern was germ cell maturation arrest, seen in 4.6% cases. The most common Modified Johnsen score was 2 (66.7%). There was discordance in histologic pattern in both testes in 12.76% of patients who had bilateral testicular biopsy. Conclusion: Our study gives an insight on the most common histopathological patterns of azoospermic patients and emphasizes the need for a better national statistics and epidemiological studies of this entity. It also points out the significance of the bilateral testicular biopsy, as both, diagnostic and therapeutic procedure.

Abstract Introduction: Bones, lungs, brain and liver are the most common metastatic sites of breast carcinoma, although invasive lobular carcinoma can give metastases to less common sites, such as the gastrointestinal tract and the female genital tract. Case presentation: We present the case of a 57-year-old female with colic abdominal pain that was sent to surgery for cholecystectomy. Histopathology revealed a poorly cohesive individual or in single file neoplastic cells infiltrating all layers of the gallbladder. Immunohistochemistry revealed these cells to be CK 116, CK7, GCDFP-15, ER and PR positive, and CK20, HER-2, S-100 and E-cadherin negative. PET/CT showed numerous lytic bone lesions, but ultrasound, mammography, MRI and PET/CT revealed no breast mass. Conclusion: Although rare and poorly understood, metastases of invasive lobular carcinoma to gallbladder do exist in a minor percentage of patients, presenting usually as exacerbated cholecystitis. The problem are silent cases and patients with no history of breast carcinoma. This case is unique in that even after the diagnosis of metastatic lobular breast carcinoma to the gallbladder, the primary tumour of the breast was not detected.

Introduction: Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common skin malignancies in the heterogeneous group of non-melanoma skin cancer (NMSC). Due to increasing incidence these tumours remain significant health problem worldwide. Methods: We conducted retrospective analysis to evaluate the incidence of primary BCCs and SCCs in our institution from 2003 to 2022, and to correlate it with available clinical data. Results: We noticed that the incidence of NMSC increased between 2018 and 2022 (p<0.01). Among 1570 patients diagnosed with NMSC, BCC represented 77.9% of cases. BCC was constantly more common type of NMSC with statistically significant difference in the period from 2003-2005 and in the period from 2017- 2022 (p<0.01). Nodular subtype of the BCC was the most common, affecting primarily face. Superficial BCC occurred most commonly on trunk (p<0.01), affecting younger patients than the other histological subtypes (mean age 61.29±13.47 years (p<0.01). High-risk BCCs in men were more common on face and scalp (p<0.05). BCCs were predominantly smaller tumours (<2 cm) in contrast to SCCs with highest incidence in pT2-pT4 group (p<0.01). SCC patients were older (mean age 72.89±9.7) than BCC patients (mean age 65.15±12.80) (p<0.01). Conclusion: In order to improve prevention strategies and prevent further increase in incidence, there is need to develop current and exact registries of these malignancies, especially separately BCC and SCC.

Ankylosing spondylitis is a serious ailment that affects people, and the first signs or symptoms usually occurr between the ages of 15 and 45. While the condition is mostly prevalent in men, women are not immune to this disease. This problem is diagnosed with a combination of clinical history and X-rays, pathology and HLAB27 test. The aim of this case study is to demonstrate how macroscopic and microscopic analysis can be used for identification of the disease from a forensic point of view. In April 2018, we exhumed 11 remains near the city Višegrad, twenty-five years after the last war. All the remains were completely skeletonized. The skeleton of a female was specific and shaped like a bamboo branch, with a partial knitting of vertebral bodies in the lumbar region of spine and with total knitting in the thoracic part. The spinous processes were completely knitted. Her son gave informations for verbal autopsy that she had trouble walking and doing normal activities during life. Samples for analysis and pathological diagnostics were used to determine the real bone condition for forensic purposes. To our best knowledge our case is first one in the literature which combines macroscopic and microscopic analysis of AK in exhumed skeletal remains after 25 years of death in modern era of Europe.

Background: Bone morphogenetic protein -4 (BMP-4) plays important role in many aspects of carcinogenesis but is also involved in progression and metastasis of breast cancer where its precise role is yet to be elucidated. Objective: Since the majority of studies related to BMP-4 expression in breast cancer were conducted on cell lines of mouse models, we aimed to investigate BMP-4 tissue expression in primary human breast cancer and to correlate it with standard pathological factors for breast cancer, progression and survival. Methods: We analyzed immunohistochemical expression of BMP-4 in primary breast cancer tissue of 97 patients, correlated it with standard pathological factors for breast cancer and investigated its impact on progression and survival. Results: BMP-4 expression was positive in 74.23% breast cancer tissue specimens. We found that hormone positive breast tumors are more likely to show BMP-4 strong granular staining pattern (p<0.01; p=0.029, respectively). There was significant association between stage group and BMP-4 expression in order that stage III breast cancer group were predominantly BMP-4 positive tumors (p=0.046). Although the most common site of distant metastases in patients with BMP-4 positive tumors were bones, we found no significant association (p>0.05). Patients with BMP-4 positive breast cancer showed longer overall and progression-free survival, but the results did not reach statistical significance (p>0.05). Conclusion: The results of our study in some extent can confirm the current available data and suggest that the role of BMP-4 in breast cancer is ambiguous, acting both as tumor suppressor and tumor promoter in breast cancer. For final elucidation of its impact on survival and progression in breast cancer, multicentric studies on larger sample size are required.

Introduction: Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common skin malignancies in the heterogeneous group of non-melanoma skin cancers (NMSC). Due to their increasing incidence, these tumors remain a significant health problem worldwide. The aim is to analyze the relative frequency of primary cutaneous BCC and SCC and to correlate it with the available pathological and clinical features. Methods: We conducted a retrospective analysis to evaluate the incidence of NMSCs in our institution from 2003 to 2022 and to correlate it with patient’s age and sex, together with available pathological and clinical features: Anatomical location, histopathological subtypes of prognostic implications, and size (local stage) of the tumor. Results: We noticed that the incidence of NMSC increased between 2018 and 2022 ( p < 0.01). Among 1570 patients diagnosed with NMSC, BCC represented 77.9% of cases. BCC was a constantly more common type of NMSC, with a statistically significant difference in the period from 2003 to 2005 and in the period from 2017 to 2022 ( p < 0.01). Nodular subtype of the BCC was the most common, affecting primarily face. Superficial BCC occurred most commonly on trunk ( p < 0.01), affecting younger patients than the other histological subtypes (61.29 ± 13.47 years), p < 0.01. BCCs were predominantly smaller tumors (<2 cm) in contrast to SCCs, with the highest incidence in the pT2-pT4 group ( p < 0.01). SCC patients were older (mean age 72.89 ± 9.7) than BCC patients (mean age 65.15 ± 12.80), p < 0.01. Conclusion: To improve prevention strategies and prevent further increases in the incidence of NMSCs, there is a need to develop current and exact registries of these malignancies, especially separately for the most common types – BCC and SCC.