Bilateral orbital plasmacytomas as first sign of extramedullary progression post CAR-T therapy: case report and literature review.

Background: Plasma cell leukemia (PCL) is an aggressive and rare form of plasma cell dyscrasia characterized by peripheral blood expression, poor prognosis, and high relapse rates. Extramedullary plasmacytomas are common in this entity and can affect various organs and soft tissues. Chimeric antigen receptor-T-cell (CAR-T) therapy is a novel immunotherapy for hematological malignancies with promising results. However, it is not indicated for PCL, and experience in this condition is limited. This case is a rare presentation of bilateral orbital plasmacytomas after CAR-T therapy in a patient with PCL history. Case presentation: We present the case of a 51-year-old female patient with a history of previous primary PCL treated with CAR-T therapy achieving complete response and without evidence of systemic progression. Six months after the treatment, she developed subacute proptosis and ptosis on the left eye.An orbital CT scan was performed and showed an orbital tumor in both eyes. A surgical biopsy with histological examination revealed plasma cells, consistent with a plasmacytoma. PET-CT and MRI confirmed the presence of tumors in both orbits. The patient was treated with dexamethasone and chemotherapy along with palliative radiation therapy to the left orbit which had a good response. Conclusion: Orbital involvement in multiple myeloma and PCL is rare, with plasmacytomas being more common in other parts of the body. In this report, we present a case of a patient with PCL history, treated with multiple therapeutic lines including CAR-T therapy, who presented bilateral orbital plasmacytomas as the first sign of extramedullary progression after the treatment. This case should be considered by specialist to be aware that the orbits are a possible location of extramedullary progression.

The molecular background of aggressive B cell lymphomas as a basis for targeted therapy.

In contrast to classifications for the majority of solid tumours, non-Hodgkin's lymphomas have been defined on the basis of their genetic alterations for many years, providing a biologically highly relevant classification. However, for aggressive B cell lymphomas, which unfortunately is the most prevalent group of lymphomas in adults, the stratification is less optimal. Gene expression profiling, analyses of chromosomal alterations and functional assays have been instrumental in dissecting these tumours to support the distinction of essentially different diseases, such as diffuse large B cell lymphoma and Burkitt's lymphoma, and now start to identify the dominant driving oncogenetic pathways that may serve as rational therapeutic targets in this essentially heterogeneous group. In this review, the molecular background and the consequences of the molecular alterations in the context of the consequences for treatment in aggressive B cell lymphoma are discussed.

Commentary on the WHO classification of tumors of lymphoid tissues (2008): "Gray zone" lymphomas overlapping with Burkitt lymphoma or classical Hodgkin lymphoma.

The 2008 WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues has introduced two new categories of high-grade B-cell lymphomas: entities in which features of diffuse large B-cell lymphoma (DLBCL) overlap with Burkitt lymphoma (DLBCL/BL) or classical Hodgkin lymphoma (DLBCL/HL). The DLBCL/BL category encompasses cases that resemble Burkitt lymphoma morphologically, but have one or more immunophenotypic or molecular genetic deviations that would exclude it from the BL category; conversely, some cases have immunophenotypic and/or genetic features of BL, but display cytologic variability unacceptable for BL. Many of the cases in the DLBCL/BL category contain a translocation of MYC as well as either BCL2 or BCL6 (so-called double-hit lymphomas) and have a very aggressive clinical behavior. The DLBCL/HL category encompasses lymphomas that exhibit the morphology of classical Hodgkin lymphoma but the immunophenotype of DLBCL, or vice versa. Most DLBCL/HL cases described present as mediastinal masses, but this category is not limited to mediastinal lymphomas. These new categories acknowledge the increasing recognition of cases that display mixed features of two well-established diseases. Whether the existence of such cases reflects shortcomings of our current diagnostic armamentarium or a true disease continuum in which such hybrid or intermediate neoplasms actually exist remains to be determined.

Commentary on the WHO classification of tumors of lymphoid tissues (2008): aggressive B-cell lymphomas.

In the novel WHO classification 2008, the classification of aggressive B-cell lymphoma has been revised for several categories with the aim to define "clean" entities. Within large B-cell lymphoma, a few distinct clinico-pathological entities have been recognized with more clinically defined entities than pathologically defined ones. The majority of known morphological variations were not considered to merit more than classification as a variant of DLBCL, not otherwise specified. Specifically, a biological subgrouping of DLBCL on the basis of molecular (activated B-cell versus germinal center B-cell) or immunophenotypic (CD5+) features was felt to be too immature to include at this stage. The role of EBV in aggressive B-cell lymphoma has been explored in more depth with the recognition of several novel and re-defined clinico-pathological entities. Also, in these diseases, clinical definitions play a very dominant role in the WHO classification 2008.

Commentary on the WHO classification of tumors of lymphoid tissues (2008): indolent B cell lymphomas.

The 4th edition of the World Health Organization classification of tumors of hematopoietic and lymphoid tissues introduces many new items to the classification scheme of the so-called indolent B cell lymphomas. New proposed entities, such as splenic B cell lymphoma/leukemia, unclassifiable, splenic diffuse red pulp small B cell lymphoma, hairy cell leukemia variant, pediatric follicular lymphoma, and pediatric marginal zone lymphoma have been coined, and some definitions of established diseases, such as chronic lymphocytic leukemia or Waldenström's macroglobulinemia have been revised. One aspect of major importance is the recent description of small clonal B cell populations, in part with a CLL phenotype, and their relationship to B-CLL. Some new subtypes or variants of follicular lymphoma with distinct clinicopathologic and/or molecular genetic characteristics have been described, including primary follicular lymphomas of the duodenum and pediatric follicular lymphomas. Furthermore, the impact of some probably early, or precursor lesions, such as follicular lymphoma in situ is discussed. Overall, we succinctly discuss the essential elements of the revisions made in the updated classification, and we identify potential opportunities for refinement of new or provisional categories in subsequent classifications.