Department of Biochemistry

Background and Objectives: Current guidelines recommend contrast-enhanced CT/MRI as confirmatory imaging tests for diagnosing hepatocellular carcinoma (HCC). However, these modalities are not always able to differentiate HCC from benign/dysplastic nodules that are commonly observed in cirrhotic livers. Consequently, many lesions require either pathological confirmation via invasive biopsy or surveillance imaging after 3–6 months, which results in delayed diagnosis and treatment. We aimed to develop noninvasive imaging biomarkers of liver cell size and cellularity, using magnetic resonance imaging (MRI), and to assess their utility in identifying HCC. Methods: MR cytometry combines measurements of water diffusion rates over different times corresponding to probing cellular microstructure at different spatial scales. Maps of microstructural properties, such as cell size and cellularity, are derived by fitting voxel values in multiple diffusion-weighted images to a three-compartment (blood, intra-, and extracellular water) model of the MRI signal. This method was validated in two phases: (1) histology-driven simulations, utilizing segmented histological images of different liver pathologies, and (2) ex vivo MR cytometry performed on fixed human liver specimens. Results: Both simulations and ex vivo MR cytometry of fixed human liver specimens demonstrated that HCC exhibits significantly smaller cell sizes and higher cellularities compared to normal liver and cirrhotic regenerative nodules. Conclusion: This study highlights the potential of MR cytometry to differentiate HCC from non-HCC lesions by quantifying cell size and cellularity in liver tissues. Our findings provide a strong foundation for further research into the role of MR cytometry in the noninvasive early diagnosis of HCC.

Background/Objectives: Despite conventional cytotoxic chemotherapy treatments, soft tissue sarcoma continues to remain a terminal diagnosis for most patients. Numerous chemotherapeutic agents have been trialed in soft tissue sarcoma, with marginal improvement in overall survival. Novel therapeutic approaches are needed to improve outcomes for this entity. Methods: the literature was reviewed, including a summary of pertinent adjuvant/neoadjuvant clinical trials and trials for metastatic disease. Results: Chemotherapeutic agent use in adjuvant/neoadjuvant trials provided limited if any evidence of the benefit of chemotherapy in this space. Despite multiple trials in the metastatic space, novel chemotherapeutic agents appear to have limited long-term benefits for the management of soft tissue sarcoma. Suggestions for further research, particularly with neoadjuvant clinical trials, were made. Conclusions: Chemotherapy remains an inadequate treatment option for soft tissue sarcoma, and novel therapies are needed. The neoadjuvant space provides an excellent opportunity to study the effects of innovative treatments in soft tissue sarcoma.

Background/Objectives: Primary cutaneous B-cell lymphomas (PCBCL) are a rare and heterogeneous group of non-Hodgkin lymphomas that are confined to the skin at diagnosis and exhibit a tendency for cutaneous recurrence. The 5th edition of the World Health Organization and the 2022 International Consensus Classification recognize three main subtypes: primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous marginal zone lymphoma/lymphoproliferative disorder (PCMZL/LPD), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL,LT). These subtypes differ in clinical behavior, histopathologic features, immunophenotype, and molecular alterations. Diagnosis and management remain challenging for clinicians. This review aims to provide a comprehensive overview of the defining features and current treatment strategies for PCBCL. Methods: This narrative review synthesizes current literature on the clinical, morphologic, immunohistochemical, and molecular characteristics of PCBCL. It also evaluates the diagnostic utility of immunohistochemistry, gene expression profiling, and molecular assays, particularly in distinguishing primary cutaneous disease from secondary cutaneous involvement by systemic lymphomas. Results: PCFCL arises from germinal center B-cells and must be differentiated from nodal follicular lymphoma. PCMZL/LPD is derived from post-germinal center B-cells and is often linked to chronic antigenic stimulation. Both PCFCL and PCMZL/LPD are indolent and associated with favorable outcomes. By contrast, PCDLBCL,LT is an aggressive lymphoma characterized by genetic alterations activating the NF-κB pathway, commonly including mutations to MYD88 and CD79B. Treatment strategies vary by subtype, ranging from localized therapies for indolent lymphomas to systemic chemoimmunotherapy for aggressive PCBCL. Emerging therapies, such as Bruton tyrosine kinase inhibitors and immunoregulatory agents, are being investigated for relapsed/refractory disease. Conclusions: PCBCL encompass distinct clinicopathologic entities with subtype-specific diagnostic and therapeutic considerations. While current management is guided by clinical behavior, significant knowledge gaps remain regarding the molecular mechanisms underlying skin tropism, immune evasion, and disease progression. Future research could focus on improving molecular characterization and developing personalized and immune-based therapies to enhance outcomes. This review consolidates current knowledge and highlights innovations aimed at advancing the diagnosis and treatment of PCBCL in clinical practice.