Background: Accurate delineation of ductal carcinoma in situ (DCIS) remains a key challenge in surgical planning. Although contrast-enhanced mammography (CEM) improves lesion detection, its clinical role in informing individualized surgical strategies remains unclear. This study evaluated the impact of CEM on preoperative assessment and surgical planning, with particular emphasis on whether its effect varies across patient subgroups. Methods: This multicentre pilot observational cohort study included 102 patients: 51 prospective patients undergoing preoperative CEM and mammography (MMG) and 51 retrospective controls assessed with MMG alone. Imaging-derived lesion size and planned resection volume were compared with pathological size using correlation analysis, intraclass correlation coefficient (ICC), and Bland-Altman methods. Surgical outcomes were assessed, and subgroup analyses explored differences according to CEM enhancement status. Results: CEM showed improved correlation with pathological DCIS size compared with MMG (ρ = 0.54 vs. 0.37), with the strongest agreement in CEM-positive lesions (ρ = 0.67; ICC 0.745). However, its clinical impact was not uniform. At the population level, CEM did not significantly change planned resection volume or surgical thresholds. In contrast, in CEM-positive patients, CEM was associated with larger planned resections, proportional to pathological tumor burden. Reoperation rates were lower in the CEM cohort (5.9% vs. 17.6%), without statistical significance, and margin status was comparable. Conclusions: The impact of CEM on surgical planning in DCIS is heterogeneous and largely confined to patients with enhancing lesions. These findings suggest that the value of CEM may lie in its selective use, where it can refine assessment of disease extent in specific subgroups rather than in routine application. Further studies incorporating predictive approaches are needed to support risk-adapted imaging strategies.

Objective: Breast lesions of uncertain malignant potential (B3) pose a diagnostic and management challenge. Surgical excision (SE) has traditionally been the standard for definitive diagnosis, but it may represent overtreatment. Percutaneous vacuum-assisted excision (VAE) offers a minimally invasive alternative. This study aimed to evaluate the safety and efficacy of VAE compared with SE for the management of B3 breast lesions, with the aim of reducing overtreatment. Materials and Methods: This retrospective single-center study included 64 patients with histologically confirmed B3 lesions diagnosed by tomosynthesis-guided vacuum-assisted breast biopsy between January 2018 and January 2024. Patients were managed by SE, VAE, or imaging follow-up, based on multidisciplinary team recommendations. Imaging characteristics, histopathology, upgrade rates, and follow-up outcomes were analyzed. Results: Most lesions presented as microcalcifications (92%). The most common histological subtypes were atypical intraductal epithelial proliferation (37.5%) and lobular neoplasia (25%). SE was performed in 26 patients (40%), VAE in 22 (34%), and 16 (25%) underwent follow-up. Malignant upgrades occurred in 8 of 26 SE-treated lesions (30.8%), predominantly atypical intraductal epithelial proliferation, while no upgrades were observed in the VAE group (p = 0.007). Mean follow-up was longer for SE (42 months) than VAE (21 months, p = 0.036). One SE patient developed invasive carcinoma at 48 months; no malignant progression occurred after VAE. Conclusion: VAE is a safe, minimally invasive and effective alternative to SE for carefully selected B3 lesions, particularly those without atypia and with imaging-pathology concordance, potentially reducing overtreatment. Multidisciplinary evaluation remains essential.

Metallothioneins (MTs) and heat shock protein 70 (HSP70) are key regulators of cellular stress response and metal homeostasis and play important roles in tumor biology. The aim of this study was to examine their expression patterns and potential prognostic significance in different molecular subtypes of breast cancer (BC), with special emphasis on triple-negative breast cancer (TNBC) and the Luminal A subtype, compared with benign breast lesions (fibroadenomas). A total of 90 tissue samples were included, and the expression of MTs in the cytoplasm and nucleus and HSP70 in the nucleus of tumor cells was analyzed immunohistochemically and correlated with clinicopathological features and treatment outcomes. Distinct expression patterns of HSP70 and MTs were observed between malignant and benign samples, as well as among the analyzed molecular subtypes of BC, suggesting their involvement in cellular adaptive mechanisms associated with malignant transformation. TNBC was characterized by less favorable clinicopathological features compared to the Luminal A subtype, including higher histological grade, increased proliferative activity, and a higher incidence of recurrence and metastatic disease. Survival analyses confirmed a worse outcome for patients with TNBC, while HSP70 and MTs expression did not show independent prognostic value in multivariate models. In conclusion, although HSP70 and MTs play important biological roles in the cellular response to stress and tumor adaptation, their expression in this study does not represent an independent prognostic indicator of clinical outcome. Nevertheless, the observed expression patterns provide insight into the complex mechanisms of tumor adaptation and emphasize the need for integrative approaches in BC biomarker research.

Cilj: Prikazati atipičnu kliničku i radiološku sliku spondilodiscitisa izazvanog meticilin-senzitivnim sojem bakterije Staphylococcus aureus (MSSA) te ukazati na važnost ranog postavljanja dijagnoze zbog pravovremenog ciljanog terapijskog pristupa i izbjegavanja komplikacija, prvenstveno epiduralnih i paravertebralnih apscesnih kolekcija. Prikaz slučaja: Prikazujemo slučaj pacijenta (77. g.) koji se na objedinjeni hitni bolnički prijam javio s nespecifičnom kliničkom slikom oštre boli u abdomenu sa širenjem prema leđima u trajanju 7-8 dana, uz nagli nastup oduzetosti obiju nogu. Kliničkim pregledom utvrđen je ispad osjeta od razine devetog torakalnog kralješka na niže uz gubitak kontrole sfinktera. S obzirom na podatak o operaciji aneurizme abdominalne aorte, učinjena je CT aortografija koja je ukazala na patološki proces na sedmom (Th7) i osmom (Th8) torakalnom segmentu, uz potpuno očuvanu koštanu strukturu kralježaka te opsežan mekotkivan supstrat paravertebralno. Indicira se hitni MR torakalne kralježnice na kojem se prikazao opsežan edem koštane srži kralježaka Th7 i Th8, prvenstveno upalnih karakteristika uz nalaz velike epiduralne kolekcije koja uvjetuje kompresivnu mijelopatiju. S obzirom na opisano pristupilo se operativnom zahvatu i dekompresiji spinalnog kanala na kojem izostaju tipični makroskopski markeri upale te se postavila sumnja na tumorski proces. Iz tkivnih uzoraka za patohistološku i mikrobiološku analizu ne potvrđuju se elementi maligne tumorske infiltracije. Iz hemokulture je izoliran MSSA. Daljnji klinički tijek kod pacijenta komplicira se razvojem pneumonije i, nažalost, smrtnim ishodom nakon šest tjedana od početka liječenja. Zaključci: Postavljanje dijagnoze spondilodiscitisa često je izazovno zbog širokog raspona kliničke i morfološke prezentacije te zahtijeva visok indeks sumnje, posebice kod starijih pacijenata s komorbiditetima zbog rizika razvoja komplikacija i fulminantnog tijeka bolesti.

Luminal B breast cancer (LBBC) represents an aggressive, high-grade ER+ disease, associated with a high proliferation rate, higher mutation burden, and higher probability of eliciting the immune response. Clinical and pathological data from 89 patients of stage II-III, triple-negative (TN), and luminal B-like BC (LB-like BC) were included in the analysis. All patients were submitted to neoadjuvant chemotherapy (NACT). Quantitative and qualitative evaluations of TILs (Tumor-Infiltrating Lymphocytes) were performed on tissue microarrays constructed from pretreatment core-needle biopsy tumor specimens. The proportion of stromal TILs, CD8, CD4, and PD-L1 positive (+) immune cells (IC), as well as the number of FOXP3, CTLA4, and HSP-70+ IC, was observed concerning tumor immunophenotype, traditional clinicopathological prognostic factors, and tumor response to NACT. There was no statistically significant difference in the proportion of stromal TILs between the LB-like and TNBC (p = 0.344) cohorts. However, a higher CD4/CD8 ratio was associated with the TNBC biology (p = 0.018) and within the LB-like BC cohort with a high proliferation index and metastatic nodal involvement (p = 0.045, p = 0.015). Within the LB-like BC cohort, a higher expression of PD-L1 and HSP70+ IC was associated with a high proliferation index of tumor cells (p = 0.018, p = 0.040), massive metastatic nodal involvement (p = 0.002, p = 0.026), and higher stages of disease (p = 0.004, p = 0.042). Better response to NACT was associated with higher numbers of HSP70+ IC and higher proportions of CD8+ cells within the LB-like BC cohort (p = 0.045, p = 0.012). Routine evaluation of immune markers and HSP70 may help identify high-risk patients of LB-like breast cancer who would have a better response to NACT.

The results from DESTINY-Breast 04 and the subsequent introduction of trastuzumab-deruxtecan as a potential treatement for HER2-low breast cancer necessitated the reevaluation of HER2 scoring. The discordance in HER2 scoring reported in previous studies led us to initiate a regional ring study and to assess our data. This ring study involved 61 breast pathology experts from four countries across the Balkans region. The research comprised 20 samples, including biopsies and surgical specimens, sourced from the archives of one institution. We amassed a total of 1220 scores. The findings indicate a significant degree of interobserver agreement among pathologists in scoring individual categories (scores 0, 1+, 2+, and 3+), with even higher agreement observed when scores 1 + and 2 + were combined into a single, HER2-low category. The findings of this study indicate that adequate education, awareness regarding the therapeutic significance of the HER2-low category, and expertise in breast pathology facilitate the accurate identification of HER2-low breast cancers. These findings will promote ongoing training in breast pathology within the region and will provide a reference for subsequent research efforts.

Background Papillary carcinoma is the most frequent type of thyroid carcinoma, while primary thyroid lymphoma is uncommon disease. The coexistence of these entities has already been described, and the common risk factor is considered Hashimoto thyroiditis. The two most frequent histotypes of primary thyroid lymphoma are diffuse large B-cell and mucosa-associated lymphoid tissue lymphoma, but the coexistence of both with papillary carcinoma is rarely reported. Methods We present a case of a previously healthy 57-years old male with rapidly growing lump on the right side of the neck. Ultrasonography revealed nodules in both thyroid lobes. Fine needle aspiration cytology and pertechnetate scintigraphy were performed. Due to the Bethesda T-5 in the “cold” nodule of the right lobe, surgery with histopathological and immunohistochemistry analysis was indicated. Results Histopathological and immunohistochemistry methods confirmed concomitant malignancies in the thyroid gland: diffuse large B-cell lymphoma and papillary carcinoma in the right, and mucosa-associated lymphoid tissue lymphoma in the left lobe with Hashimoto thyroiditis in the remaining tissue. Patient underwent therapy procedures and was without signs of local recurrence or metastatic spread on subsequent follow-up. Conclusions Sudden appearance of the neck mass in patients with Hashimoto thyroiditis should raise suspicion on primary thyroid lymphoma and be promptly taken in the diagnostic workup, including fine needle aspiration cytology. Pathology with immunohistochemistry is crucial for further clinical decision making. Since the standardized protocol in management of these complex patients is missing, personal approach and close collaboration between cytologist, pathologist, surgeon, haematologist and nuclear medicine specialist is essential.

Objectives: In this paper, we investigate the association of glycoprotein 96 (GP96) and androgen receptor (AR) expression with clinicopathological factors, additional axillary lymph node burden, and their potential role in predicting 5-year overall survival (OS) and disease-free survival (DFS) in breast cancer (BC) patients with sentinel lymph node (SLN) involvement. We also explore the prognostic value of the presence of extranodal extension (ENE) in SLN. Methods: We retrospectively enrolled 107 female patients with cT1-T2 invasive BC and positive SLN biopsy. GP96 and AR expression were immunohistochemically evaluated on tissue microarrays constructed from two 2 mm diameter cores of formalin-fixed paraffin-embedded tumor tissues from each patient. ENE in SLN was measured in the highest (HD-ENE) and widest diameter (WD-ENE). Relative GP96 gene expression was determined using real-time quantitative PCR. Results: The analysis revealed ENE in SLN as the strongest predictive factor for non-SLN metastases. Patients with WD-ENE > HD-ENE had a higher risk of non-SLN metastases and worse DFS compared to those with WD-ENE ≤ HD-ENE. High GP96 expression was associated with a greater relative risk for locoregional recurrence but showed no significant impact on OS or DFS. Histological grade 3, extensive intraductal component (EIC), higher lymph node ratio (LNR), and negative AR were associated with worse DFS, while age, histological grade 3, EIC, and higher LNR were independent predictors of OS. GP96 mRNA levels were elevated in BC tissue compared to normal breast tissue. Conclusions: ENE in SLN is the strongest predictor of non-SLN involvement and could also have prognostic significance. While GP96 expression does not influence survival outcomes, AR expression could be used as a valuable biomarker in the follow-up of BC patients.

Contrast-enhanced mammography (CEM) is a relatively new imaging technique that allows morphologic, anatomic and functional imaging of the breast. The aim of our study was to validate contrast-enhanced mammography (CEM) compared to mammography (MMG) and digital breast tomosynthesis (DBT) in daily clinical practice. This retrospective study included 316 consecutive patients who underwent MMG, DBT and CEM at the Centre for Prevention and Diagnosis of Chronic Diseases of Primorsko-goranska County. Two breast radiologists independently analyzed the image data, without available anamnestic information and without the possibility of comparison with previous images, to determine the presence of suspicious lesions and their morphological features according to the established criteria of the Breast Imaging Reporting and Data System (BI-RADS) lexicon. The diagnostic value of MMG, DBT and CEM was assessed by ROC analysis. The interobserver agreement was excellent. CEM showed higher diagnostic accuracy in terms of sensitivity and specificity compared to MMG and DBT, the reporting time for CEM was significantly shorter, and CEM findings resulted in a significantly lower proportion of equivocal findings (BI-RADS 0), suggesting fewer additional procedures. In conclusion, CEM achieves high diagnostic accuracy while maintaining simplicity, reproducibility and applicability in complex clinical settings.

Ranom dijagnozom raka dojke postiže se bolje preživljavanje i manje agresivno liječenje. Slikovne metode poput ultrazvuka, mamografije i magnetske rezonancije osnovne su metode oslikavanja dojki kojima se mogu detektirati lezije u vrlo ranoj, neinvazivnoj fazi. Kao zlatni standard u postavljanju dijagnoze koristi se patohistološka analiza tkiva, stoga su biopsije sumnjivih lezija u dojci neizostavni dio obrade. Općenito, slikovno navođena biopsija dojke potrebna je za nepalpabilne lezije, ali se preporučuje i za palpabilne lezije jer poboljšava točnost dijagnoze. Intervencije u dojci navođene ultrazvukom, mamografijom ili magnetskom rezonancijom pouzdane su metode, a postavljanje tkivnog markera nakon biopsija znak je dobre prakse. Poglavito je važno markirati lezije nakon mamografski navođene biopsije, kao i lezije manje od 5 mm jer se lezije mogu potpuno ukloniti te je tada prijeoperacijska markacija znatno otežana. Isti je princip kod neoadjuvantog liječenja kada tumorski proces može u potpunosti regredirati, stoga tkivni marker omogućuje precizno izvođenje kirurškog zahvata. Za markaciju patoloških limfnih čvorova uputno je korištenje specijalno izrađenih markera, dobre vidljivosti pod svim modalitetima oslikavanja, koji omogućuju preciznu markaciju limfnog čvora nakon provedenog neoadjuvantnog liječenja. Prijeoperacijska lokalizacija nepalpabilnih lezija koristi se za optimizaciju kirurške ekscizije radi očuvanja negativnih rubova bez žrtvovanja normalnog tkiva. Ovaj pregledni rad opisuje i minimalno invazivne tehnike, kao što su termalne ablacije, krioablacija i visokofrekventni fokusirani ultrazvuk kao alternativa kirurškoj eksciziji, s ciljem smanjenja broja komplikacija, boljeg kozmetičkog rezultata i skraćenog boravka u bolnici. Ovaj pregledni rad opisuje spektar slikovno navođenih intervencija koje se izvode u Kliničkom bolničkom centru u Rijeci.

Due to the elusive nature of invasive lobular carcinoma, mammography, ultrasound, and magnetic resonance imaging have their limitations in early detection. A 67-year-old woman presented for mammography and found retraction of breast parenchyma of the right breast. Magnetic resonance imaging and contrast mammography showed no contrast uptake in the region in question. Magnetic resonance imaging and ultrasound were found to be superior for the detection of invasive lobular carcinoma, with a sensitivity of more than 90%. On ultrasound examination, invasive lobular carcinoma may occur only with posterior acoustic shadowing. On breast magnetic resonance imaging, it is commonly described as an irregular mass and less commonly as non-mass enhancement. An additional advantage of magnetic resonance imaging is the higher detection rate of multifocal, multicentric, and contralateral breast lesions. The reason for no contrast enhancement in this particular tumor before neoadjuvant chemotherapy followed by enhancement after neoadjuvant chemotherapy is most likely at the molecular and histologic level and requires further investigation in similar cases.

BACKGROUND:Due to recent changes in breast cancer treatment strategy, significantly more patients are treated with neoadjuvant systemic therapy (NST). Radiological methods do not precisely determine axillary lymph node status, with up to 30% of patients being misdiagnosed. Hence, supplementary methods for lymph node status assessment are needed. This study aimed to apply and evaluate machine learning models on clinicopathological data, with a focus on patients meeting NST criteria, for lymph node metastasis prediction.METHODS:From the total breast cancer patient data (n = 8381), 719 patients were identified as eligible for NST. Machine learning models were applied for the NST-criteria group and the total study population. Model explainability was obtained by calculating Shapley values.RESULTS:In the NST-criteria group, random forest achieved the highest performance (AUC: 0.793 [0.713, 0.865]), while in the total study population, XGBoost performed the best (AUC: 0.762 [0.726, 0.795]). Shapley values identified tumor size, Ki-67, and patient age as the most important predictors.CONCLUSION:Tree-based models achieve a good performance in assessing lymph node status. Such models can lead to more accurate disease stage prediction and consecutively better treatment selection, especially for NST patients where radiological and clinical findings are often the only way of lymph node assessment.

Background: Although response-adjusted surgery is a highly recommended strategy following neoadjuvant systemic treatment (NAST), consensus on axillary management in cN+/ycN0 breast cancer patients is still lacking. In this setting, clinical significance of the higher false negative rate of sentinel lymph node biopsy (SLNB) procedure is unknown. The present analysis aims to evaluate the long-term safety of the SLNB in ycN0 patients. Methods: In this study, 60 patients with the operable breast cancer, undergoing surgery after NAST in Clinical Hospital Centre Rijeka, Croatia, from May 2016 to May 2018, were included in the analysis. Following a preliminary retrospective analysis in 2019, follow-up (FU) was extended, and all outcomes were re-evaluated in December 2022. Results: The median FU time was 65 months and 98% of patients had complete FU data. In the ypN0 group, ALND was performed for 15 and SLNB for 20 patients. The median number of LN retrieved in ALND and SLNB was 15 and 3, respectively. The method of surgical axillary staging had no impact on oncological outcomes; Regional Recurrence Free Survival Chi-square=0.5789, P=0.4467; Distant Recurrence Free Survival Chi-square=1.3658, p=0.2425; Breast Cancer Specific Survival Chi-square=0.9755, P=0.3233. Conclusion: Irrespective of a higher FNR following NAST, as compared to the upfront surgery setting, SLNB is a safe procedure and should be considered for all ycN0 patients, regardless of pre-treatment cN status.

Results: Of 4010 breast cancer patients, 215 (5.3%) had BBC.Of these, 106 (49%) were classified as having MBBC and 109 (51%) as SBBC.The median follow-up time for MBBC and SBBC groups was 117 and 43 months, respectively.SBBC patients were older than MBBC patients at the time of their first cancer detection by 4.4 years on average ( p = 0.007).SBBC patients also had a significantly higher cancer stage at first detection as compared with MBBC patients, but without a clear difference in cancer subtype.Under the hypothesis that MBBC and SBBC were the same cancer, lead time bias was defined as the time to second cancer in the MBBC group, which was 7.2 years on average.After adjusting for lead time bias, there was no significant difference at the 5% level in terms of overall survival distant diseasefree survival between the 2 groups, based on both the log-rank test and Cox's proportional hazards model.Conclusion(s): Clinical differences (and similarities) between synchronous and metachronous BBC can be largely explained by leadtime bias and late detection under the hypothesis that they are similar types of cancer.

Background: Triple-negative breast cancer (TNBC) has the worst prognosis and the highest immunogenic po-tential of all breast cancer subtypes. It is characterized by a lack of estrogen and progesterone receptors as well as HER2. A major component of the tumor microenvironment (TME) of TNBC is tumor-infiltrating lymphocytes (TILs). A chaperone heat shock protein 70 (HSP70) is involved in several pathways that enable tumour growth and progression, as well as in immune modulation.Methods: Immunohistochemical analysis of HSP70 expression in immune cells, as well as expression of immu-nosuppressive markers CTLA4 and PD-L1 and major TILs components: CD8, CD4 and Tregs were analyzed in the superficial and deep tumor layer of primary TNBC and compared with established clinicopathological parame-ters. Clinical data and surgical tissue samples from 68 TNBC patients who underwent initial surgery were included in the analysis and 36 control samples from benign breast tissue biopsies. Results: A higher expression of TILs, CD4, CD8 and PD-L1 was found in the invasive tumor front (ITF), as compared to the tumor center (TC) (p < 0001). HSP70 positive immune cells (HSP70(+) IC) in TC were asso-ciated with adverse clinical and pathological markers: higher stage of disease (P = 0.013), higher grade (P = 0.05) and a higher pN status (P < 0.001). In addition, higher expression of HSP70(+) IC from TC was correlated with the higher expression of FOXP3(+)T cells both in ITF (N = 61, rho=0.42, p < 0.001) and in metastatic tissue from the draining lymph nodes (N = 13, rho=0.61, P = 0.026).Conclusion: Correlations between HSP70 immune cells expression and individual TILs components support the hypothesis of its active role in inducing immunosuppression and tumor progression. Routine determination of HSP70 expression, in immune cells of TC, may be of added value in the clinical decision-making process con-cerning axillary surgery.

Background: The high mutation burden of triple-negative breast cancer (TNBC) is related to its immunogenic potential. The presence of tumour infiltrating lymphocytes (TILs) in the preclinical stage of disease reflects a proinflammatory immune response against cancer cells. However, cancer cells may modulate it to support tumour growth and progression. A chaperone HSP70 molecule expression, upregulated by oncogenic signalling, supports the formation of early-stage breast cancer (BC) as well. Moreover, in the later course of the disease, HSP70 is actively released by the cancer cells and can induce the termination of the specific immune response. The aim of this study was to explore the role and possible predictive value of the HSP70(+) immune cells in a deep layer (HSP70-IC-DL) of TNBC.

Background: In modern breast cancer (BC) management, ALND has been rarely performed procedure in the upfront surgery setting for the early-stage BC. SLNB is a standard of care for all patients presenting with clinically negative axilla (cN0), despite the 30% false-negative rate (FNR) of axillary ultrasound (AUS). Moreover, even in the case of higher-risk patients, ALND can be safely omitted, however respecting the Z0011 and AMAROS trials criteria. Although SLNB is accepted as a valid option of axillary staging following primary systemic treatment (PST), ALND is still considered a mandatory procedure for any metastasis detected in the sentinel node, regardless of its size and the pretreatment cN0 status.