Eleftheria Lakiotaki

Renal cell carcinoma (RCC) is a common tumor that heavily depends on extracellular matrix (ECM) remodeling, an essential process involved not only in normal tissue homeostasis but also in malignant growth. This article reviews the role of matrix metalloproteinases (MMPs, zinc-dependent endopeptidases) in matrix degradation and ECM reorganization in the setting of RCC. We focus on the specific role of MMP2, MMP7, and MMP9 in clear cell renal cell carcinoma (ccRCC) and major subtypes of RCC. Higher levels of these MMPs are associated with high-grade tumors, increased risk of metastasis, and poorer patient survival rates, indicating that they may have value as prognostic markers. This review also discusses how ECM composition and structure are altered in the tumor microenvironment (TME), thereby preventing cell interactions and promoting cancer growth. Finally, it compiles the existing studies to anticipate a future era in which MMPs could serve as effective prognostic biomarkers and potential treatment targets for RCC, with implications for improving diagnostic and therapeutic interventions targeting ECM remodeling to suppress cancer progression.

Dysplasia Epiphysealis Hemimelica (DEH), or Trevor’s disease, is a rare, nonhereditary skeletal disorder involving abnormal cartilaginous overgrowth of the epiphysis. To our knowledge, malignant transformation has not been previously documented. We report a unique case of chondrosarcoma arising from a DEH lesion in the proximal humerus nearly 30 years after the initial diagnosis. The patient was treated with wide resection and reconstruction using a proximal humeral replacement with a reverse-constrained total shoulder arthroplasty. This case highlights the need for long-term follow-up in patients with DEH, especially when new symptoms suggest possible malignant transformation.

Non-Hodgkin lymphoma’s (NHL) incidence is rising over time, and B cell lymphomas comprise the majority of lymphomas. The phosphoinositide 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homologue 1 (Akt)/mammalian target of the rapamycin (mTOR) signaling pathway plays a critical role in a variety of cellular processes, such as cell proliferation and survival. Its role in lymphomagenesis is confirmed in many different types of B cell lymphomas. This review is mainly focused on the PI3K/v-akt/mTOR pathway-related oncogenic mechanisms in B cell NHLs with an emphasis on common B cell lymphoma types [diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL)]. Furthermore, it summarizes the literature regarding the clinical applications of the mTOR inhibitors temsirolimus and everolimus in B cell NHLs, which have been tested in a range of clinical trials enrolling patients with B cell malignancies, either as monotherapy or in combination with other agents or regimens.

Chronic myelogenous leukemia at blast crisis with a T-cell phenotype (T-ALL CML-BC) at diagnosis, without any prior history of CML is extremely rare. After the introduction of tyrosine kinase inhibitors (TKIs), CML patients have a median survival comparable to general population and accelerated/blast crisis are rarely encountered. Most CML patients (80%) transform into acute myeloid leukemia and the rest into B-ALL. Anecdotal cases of Ph+ T-ALL, either de novo or in the context of CML-BC have been reported. Left shift in the blood, the presence of splenomegaly/extramedullary infiltration and the occurrence of BCR::ABL1 rearrangement in both the blastic population, as well as in the myeloid cell compartment are key points in differentiating de novo Ph+ T-ALL from T-ALL CML-BC. The latter is a rare entity, characterized by extramedullary disease, p210 transcript and clonal evolution. Lack of preceding CML does not rule out the diagnosis of T-ALL CML-BC. Prompt TKI treatment with ALL-directed therapy followed by allogeneic stem cell transplantation may offer long-term survival in this otherwise poor prognosis entity. In this paper, we describe a patient with T-ALL CML-BC at presentation, still alive 51 months after diagnosis and we offer a review of the literature on this rare subject. All clinical and laboratory features are provided in order to distinguish de novo Ph+ T-ALL from T-ALL CML-BC, underscoring the prognostic and therapeutic significance of such a differentiation.

Multiple myeloma (MM) is the most common primary bone-originating tumor, whereas extramedullary plasmacytoma (EMP) is a plasma cell tumor that arises outside the bone and is most commonly found in the head and neck area. Gastrointestinal and particularly gallbladder involvement is exceedingly rare, and symptoms, if any are present, are usually similar to those seen with cholelithiasis. Treatment options usually include surgical resection and/or chemotherapy. In this report, we present a rare case of a clinically unexpected plasmablastic extramedullary plasmacytoma that was found on abdominal ultrasound (US) and magnetic resonance imaging (MRI) in a 61-year-old asymptomatic patient and led him to undergo cholecystectomy. A fluorodeoxyglucose positron emission computed tomography (FDG PET-CT) that was performed due to the onset of left thigh pain also demonstrated concurrent bone plasmacytoma. The patient is currently receiving chemotherapy and is also being prepared for autologous stem cell transplantation. In this context, we further present the diagnostic, therapeutic and prognostic challenges of EMPs. Lastly, we point out the distinct features of the plasmablastic subtype and analyze its differences compared to other histologic subtypes in achieving a successful diagnosis and management.

Hyperlactemia is a rare and potentially fatal complication of hematologic malignancies, as well as an oncological emergency, which requires a fast diagnosis and early therapeutic management, as these interventions may alter disease prognosis. Herein, we present a case of secondary liver-biopsy-confirmed diffuse large B-cell lymphoma (DLBCL), presented with elevated liver enzymes and lactic acidosis, without depicted hepatic lesions, hepatosplenomegaly, or enlarged lymph nodes on computed tomography. This case confirms the poor prognosis of cases with delayed diagnostic intervention and highlights the importance of early clinical suspicion, liver biopsy, and prompt treatment initiation.

Zinc fingers consist of one of the most abundant motifs in transcription factors and DNA-binding proteins. Recent studies provide evidence on the pathological implication of zinc finger proteins in various neurodevelopmental disorders and malignancies but their role in pediatric brain tumors is largely unexplored. To this end, we investigated the differential expression of zinc finger-containing genes along with relevant biological processes and pathways among four main brain tumor categories (pilocytic astrocytomas, ependymomas, medulloblastomas and glioblastomas). By employing an extended bioinformatic toolset, we performed a preliminary in silico study in order to identify the expression of zinc finger-containing genes and associated functions in pediatric brain tumors. Our data analysis reveals the prominent role of C₂H₂-type zinc finger-containing genes in the molecular mechanisms underlying pediatric brain tumors followed by the Ring and PHD finger types. Significant dysregulation of ABLIM2 and UHFR1 genes was detected in all tumor types drawing attention to the dysregulation of cell polarization process and Ubiquitin-Proteasome System (UPS) in the pathogenesis of pediatric brain tumors. Moreover, significant gene clustering was observed in multiple locations with two highly visible clusters revealing a contrast in gene regulation between medulloblastomas and the other three brain tumor types, indicating a promising area of future research.