OBJECTIVE To report two additional cases of glycogen-rich clear cell carcinoma (GRCC) of the breast - detailing their clinicopathologic features, immunophenotypes, and follow-up - and to provide an updated literature review since 2020. CASE REPORTS Two patients (66 and 52 years old) had GRCC confirmed morphologically and histochemically. Case 1 was ER-positive/HER2- positive (luminal B/HER2-positive) and was managed with surgery, followed by adjuvant chemotherapy, endocrine therapy, and anti-HER2 therapy (trastuzumab). Case 2 was triple-negative and received neoadjuvant chemoimmunotherapy (pembrolizumab- based) with marked pathologic tumor regression at resection. Both patients were disease-free at one and 12 months, respectively. CONCLUSIONS GRCC is heterogeneous and should not be regarded as a single clinicopathologic entity within invasive breast carcinoma of no special type or assumed to have a uniform prognosis. Management should be biomarker-guided, as illustrated by these cases. The role of targeted and immune therapies in GRCC warrants multi-institutional studies.

ABSTRACT Purpose Acinic cell carcinoma (ACC) of the breast is a very rare, primary salivary gland‐type breast malignancy, with ~100 reported cases in the literature. Limited information about the clinical features and outcomes of patients with ACC is available. Methods We utilized the Surveillance, Epidemiology, and End Results (SEER) database to identify ACC patients. For comparison, we also examined a cohort of invasive breast carcinomas of no special type (NST). Results Thirty ACC patients were identified among the more than 248 000 invasive breast carcinoma NST patients. ACCs were predominantly grade 3 carcinomas (44%) and were diagnosed at an earlier stage (67%). Hormone receptor (HR) and HER2 status data were available for only 13 patients, revealing molecular heterogeneity: HR−/HER2− (four patients), HR−/HER2+ (two patients), HR+/HER2− (four patients), and HR+/HER2+ (three patients). The median survival time for ACC patients was 19 months vs. 48 months for NST patients (p < 0.001). A complete‐case approach was utilized for the adjusted analyses, restricting the sample to 46 257 patients without missing data on all relevant covariates. The adjusted Kaplan–Meier analysis indicated a more pronounced decline in survival probabilities among patients with ACC compared to those with NST, with the number at risk in the ACC group diminishing to four patients by the 30‐month mark. In contrast, NST patients exhibited a more gradual decrease. In the multivariable Cox regression, which adjusted for age, TNM stage, HR/HER2, and chemotherapy, ACC histology was correlated with a 1.69‐fold increase in the hazard of death (HR: 1.69; 95% CI: 0.63–4.56), although this result was not statistically significant. Age and advanced stage continued to be strong predictors of poor survival, and the inclusion of an age–time interaction enhanced the model fit. Conclusion Acinic cell carcinoma of the breast is a very rare primary breast malignancy. Our study indicates potentially aggressive clinical behavior in mammary ACC; however, findings must be interpreted cautiously given inherent SEER limitations, especially regarding histologic and molecular subtyping accuracy. Further centralized studies are urgently needed for the accurate characterization of this rare entity.

A systematic review with meta-analysis (SRMA) represents the pinnacle of evidence, but its validity depends on methodological rigor. This narrative review synthesizes recommendations from major reporting frameworks—Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA-2020), Meta-Analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Overviews of Reviews (PRIOR)—into a concise checklist for peer reviewers. The checklist addresses common sources of bias that often escape editorial assessment. Initially, it outlines how reviewers should assess the rationale for an SRMA by identifying existing syntheses on the same topic and determining whether the new work provides substantive novelty or a significant update. Best practices are summarized for protocol registration, comprehensive search strategies, study selection and data extraction, risk-of-bias evaluation, and context-appropriate statistical modeling, with a specific focus on heterogeneity, small-study effects, and data transparency. Case examples highlight frequent pitfalls, such as unjustified pooling of heterogeneous designs and selective outcome reporting. Guidance is also provided for formulating balanced, actionable review comments that enhance methodological integrity without extending editorial timelines. This checklist equips editors and reviewers with a structured tool for systematic appraisal across clinical disciplines, ultimately improving the reliability, reproducibility, and clinical utility of future SRMAs.

The scientific community is continually evolving, driven by advancements, shifting priorities, and growing demands for global dissemination of knowledge. A clear example of successfully adapting to these demands is the transition from the Bosnian Journal of Basic Medical Sciences (BJBMS) to Biomolecules and Biomedicine (BB) in 2023. This strategic move symbolizes a significant step forward, expanding the journal's global reach and scientific scope.

Introduction: Tumor-infiltrating lymphocytes (TIL) are linked to responses to chemotherapy and immunotherapy and clinical outcomes, especially in high-risk breast carcinomas. MammaPrint® (MP) and BluePrint® (BP) are genomic tests designed to provide risk stratification and molecular classification for early-stage hormone receptor (HR)-positive breast carcinomas, which could include tumors with HER2-low expression. We investigated correlations between TIL measurements, HER2 status, and MP/BP assays in early-stage HR-positive breast carcinomas. Materials and Methods: 167 early-stage HR-positive breast carcinomas with known MP/BP risk categorization were evaluated for TIL using whole slide scanned images according to the International TILs Working Group 2014 guidelines. HER2-low breast cancers were identified by IHC scores of 1+ and 2+ without HER2 amplification. A subset of high-TIL, high-risk cases underwent TSO500 (Illumina) next-generation sequencing (NGS). Results: The patients had a mean age of 51 years, ranging from 26 to 75 years. Among the profiled cases, 97% were either luminal A (96/167) or luminal B (66/167) breast carcinomas, with only five cases classified as HER2-enriched (n = 2) or basal-like (n = 3) carcinomas. Tumor grade was strongly associated with recurrence risk (p<0.001). The prevalence of the HER2-low phenotype was 65%, including 46/69 (67%) high-risk cases. TIL levels ranged from 0 to 70% and were low (≤10%) in the majority (75%) of cases in the cohort. However, high TIL levels were more frequently observed in cases with high recurrence risk (56% vs. 39%, p = 0.03). Additionally, TIL-enriched high-recurrence risk carcinomas contained targetable genomic alterations, including PIK3CA, BRCA1, BRCA2, and HER2 mutations. Conclusions: TIL levels are higher in early-stage HR-positive breast carcinomas with a high recurrence risk. These tumors also harbor targetable genomic alterations, suggesting that TIL measurement and genomic profiling could enhance risk stratification and identify patients who might benefit from targeted therapies. Her-2 low expression in high-risk patients provides a consideration for including novel ADC therapies in this subset of patients. Citation Format: Zoran Gatalica, Inga Rose, Faruk Skenderi, Nataliya Kuzmova, Semir Beslija, Timur Ceric, Inga Marijanovic, Ilir Kurtishi, Semir Vranic. High Tumor-Infiltrating Lymphocyte Levels Correlate with High MammaPrint® Recurrence Risk in Early-Stage Breast Carcinomas [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-11-17.

In the current study, we assessed the prevalence and molecular features of HER2-low phenotype in the apocrine carcinomas of the breast (ApoCa) and its relationship with tumor-infiltrating lymphocytes (TILs). A cohort of 64 well-characterized therapy-naïve ApoCa was used. The TIL distribution was assessed using the hematoxylin and eosin whole slide/scanned images following the international TILs working group recommendations. Next-generation sequencing (NGS) was performed in a subset of HER2-low ApoCa. All patients were women, with a mean age of 62 years. Forty-three carcinomas were pure apocrine carcinoma (PAC; ER−/AR+), and the remaining 21 were classified as apocrine-like carcinomas (ALCs; ER+/−, AR+/−). HER2/neu was positive (score 3+ by IHC and/or amplified by FISH) in 20/43 (47%) PAC and 4/21 (19%) ALC. The prevalence of HER2-low expression (scores 1+ or 2+ without HER2 amplification) in ApoCa was 39% without significant differences between PAC and ALC (P ═ 0.14); however, the HER2-low phenotype was more prevalent in triple-negative PAC than in ALC (P < 0.001). Levels of TILs were low (≤10%) in 74% of ApoCa (median: 5%, range 0%–50%). TIL levels were significantly higher in ALC than in PAC (P ═ 0.02). HER2 status had no impact on TIL distribution (P ═ 0.45). The genomic profile of HER2-low ApoCa was similar to other subtypes of ApoCa. ApoCa has predominantly low TIL, particularly PAC. The prevalence of the HER2-low phenotype in ApoCa is high, which should have therapeutic and clinical implications given the recently approved therapies with antibody–drug conjugates (ADCs) for HER2-low breast cancers.

From February 2023 (Volume 23, Issue 1), the title of the Bosnian Journal of Basic Medical Sciences will be changed to Biomolecules and Biomedicine. The new title reflects the increasing number of published research done on subcellular/molecular level as well as translational and clinical research contained in the term Biomedicine. Biomolecules and Biomedicine will continue to be published by the Association of Basic Medical Sciences of the Federation of Bosnia and Herzegovina. Read more in the PDF.

SUMMARY In prostate adenocarcinoma, both tumorous stroma and epithelium have important role in tumor progression. Transforming growth factor beta (TGF- β) is a promotor in advanced stages of prostate cancer. Matrix Metalloproteinase 2 (MMP2), the endopeptidase that degrades extracellular matrix is considered to be overexpressed in prostatic carcinoma related to its growth and aggressiveness. Therefore, the aim was to analyze the expression of proteins TGF- β and MMP2 between both epithelium and stroma of prostatic adenocarcinoma and adjacent unaffected parenchyma. The intensity of TGF- β and MMP2 expression in epithelium, tumorous stroma and adjacent unaffected parenchyma was analyzed in 62 specimens of prostatic adenocarcinoma by microarray-based immunohistochemistry. TGF- β was more expressed in tumorous than in prostate stroma (p =0.000), while no statistical significance in case of MMP2 (p = 0.097) was found. MMP2 was more expressed in tumorous than in prostate epithelium (p =0.000), while no statistical significance in case of TGF- β (p = 0.096) was observed. The study results indicate that both tumorous stroma and epithelium have a role in tumor progression and support potential role of TGF- β and MMP2 in prostatic adenocarcinoma progression.

Purpose Apocrine carcinoma of the breast (APO) expresses HER2 in 30–50% of cases. This study explored the clinicopathological features and outcome of HER2+/APO and matched HER2+/NST cohort. Methods We used the SEER database to explore the cohorts. Univariate and multivariate analyses were used to assess the survival. Based on ER and PR [steroid receptors/SR/] and HER2 status, we divided the cohorts to match the intrinsic molecular subtypes for comparisons. Results We retrieved 259 cases of HER2+/APO. Most HER2+/APO were SR negative (65%). HER2+/APO were more prevalent in the 80+ age group (24.7% vs. 15.7%, p  < 0.001). HER2+/SR−/APO had a significantly lower histological grade than the HER2+/SR−/NST ( p  < 0.001). Breast cancer-related deaths were more prevalent in HER2+/NST (7.8% vs. 3.9%, p  = 0.019). This was particularly evident between SR− subgroups (10.4% in HER2+/SR−/NST vs. 4.2% in HER2+/SR−/APO, p  = 0.008) and was reaffirmed in breast cancer-specific survival in univariate analysis ( p  = 0.03). Other than race and SR status, HER2+/APO subgroups did not differ in clinicopathological parameters. Conclusions Our study confirms the rarity of the APO and reveals that SR status in APO does not affect these patients' prognosis. HER2+/APO tumors tend to have a less aggressive phenotype and a more favorable outcome despite a markedly lower ER/PR positivity.

A 65-year-old woman with a negative family history of breast cancer presented with a palpable mass in the left breast’s central portion. Mammography revealed an oval heteroechogenic, partly solid, partly cystic, sharply demarcated mass, measuring 100×90 mm in greatest diameter, classified as BI-RADS 4c, according to ACR BI-RADS Atlas Fifth Edition (Figure 1A-B). Breast MRI showed a lobulated mass with smooth margins appearing hypointense on T1WI and high signal intensity on T2WI (Figure 1C-D). A core needle biopsy revealed a cellular neoplasm, composed of small, closely packed tubules with spindle cell intervening stroma without prominent atypia and mitotic activity, classified as B3 category according to the UK National Coordinating Committee for Breast Screening Pathology (Figure 2A). The multidisciplinary tumor board discussed the case and recommended a wide surgical excision. With the patient’s approval, a left mastectomy was recommended and performed. The axillary clearance was not performed. The 100×90 mm tumor was grossly well-circumscribed, grayish-white, and predominantly solid, with a smaller cystic component, without necrosis and hemorrhage (Figure 2B). Histopathologic examination revealed a well-circumscribed tumor with two distinct components (tubular adenoma and phyllodes tumor) with the transition to one another (Figure 2C). The larger portion of the tumor was composed of closely packed small round to oval tubules with little intervening spindle cell stroma consistent with tubular adenoma. The smaller component showed a biphasic fibroepithelial tumor with leaf-like projections with moderately cellular stroma (Figure 2D-E). The stromal cells exhibited mild to moderate atypia, and their mitotic activity was up to six mitoses/10 hpf (Figure 2F). Stromal overgrowth was absent, while the malignant heterologous elements were not observed despite the exhaustive tumor sampling (25 paraffin blocks). The final diagnosis was a complex fibroepithelial tumor composed of borderline phyllodes and tubular adenoma. Clinical Science