Isinsu Kuzu

Extramedullary multiple myeloma (EMD), defined as the dissemination of clonal plasma cells to anatomical sites distant from the bone marrow, is observed in approximately 7–18% of patients at diagno...

Immunoglobulin heavy chain variable region (IGHV) mutational status and B-cell receptor (BCR) stereotypy are established prognostic markers in chronic lymphocytic leukemia (CLL). However, immunogenetic data from Türkiye and surrounding regions are scarce. We evaluated IGHV mutational status, BCR stereotypy including nearest subset assignment, and their clinical and cytogenetic correlates in a real-world Turkish CLL cohort. We retrospectively analyzed 145 patients with CLL at a tertiary referral center in Türkiye. IGHV mutational status was determined by next-generation sequencing (98% germline homology cutoff). BCR stereotypy was assigned using ARResT/AssignSubsets. Cytogenetic abnormalities were assessed by fluorescence in situ hybridization (FISH). Time-to-first treatment (TTFT), progression-free survival (PFS), and overall survival (OS) were analyzed by Kaplan–Meier method, with multivariate Cox regression for TTFT. Unmutated IGHV was detected in 55.2% of patients, higher than Western reports but consistent with Mediterranean and Middle Eastern cohorts. Unmutated cases showed adverse cytogenetics—del(11q) and multiple concurrent FISH abnormalities—whereas del(13q) predominated in mutated cases. At a median follow-up of 43.0 months unmutated status strongly predicted a profoundly shorter median TTFT compared to mutated cases (17.0 vs. 70.0 months; p < 0.0001). Notably, while an unmutated IGHV status strongly predicted a significantly shorter TTFT, it did not translate into worse PFS or OS compared to mutated cases, reflecting the transformative real-world impact and rescue capacity of modern targeted therapies utilized upon disease progression. Major stereotyped subsets were present in 15.9% of patients; subset #2 was absent, while subset #1 was predominant (39.1%). Subsets #1 and #64B were overrepresented among relapsed cases. Nearest subset #77 showed rapid progression despite mutated IGHV. CLL in Türkiye demonstrates region-specific immunogenetic features while preserving established clinico-biological correlations. Integration of IGHV status, cytogenetics, and BCR stereotypy may improve risk stratification in underrepresented populations.

Erdheim–Chester disease (ECD) is a rare, systemic, and potentially malignant non‐Langerhans cell histiocytosis characterized by the infiltration of foamy histiocytes into multiple organ systems. The diagnosis of ECD is often complicated and time‐consuming due to its rarity and heterogeneous presentation. A 39‐year‐old female presented with a progressively enlarging yellowish plaque measuring 5 × 2 cm on left periorbital skin over the past 2 years. Besides, the patient had bilateral lower extremity pain persisting for 1.5 years, significantly affecting her mobility and quality of life. Histological examination of skin biopsies revealed frequent Touton giant cells, bland‐appearing histiocytes characterized by abundant foamy (xanthomatous) cytoplasm in the dermis, which were positive for CD68, Factor XIIIa, and BRAF; negative for CD1a and S100. In bone marrow biopsy, histiocytic cells were positively stained with CD68, Factor XIIIa, and CD14, and negatively stained for CD1a, Langerin, and S100. Positron emission tomography/computed tomography imaging revealed pathological 18‐fluoro‐2‐deoxyglucose uptake in the bone marrow and widespread sclerotic bone lesions on the bilateral lower extremity. BRAF sequencing determined a BRAFV600E mutation. The patient was diagnosed with ECD, and vemurafenib was initiated. After 6 months of treatment, significant improvements were observed in both bone pain and the size and discoloration of the yellowish plaque. In conclusion, our case highlights that the primary diagnostic clue for ECD may be a single yellowish plaque, which requires further investigation in relation to other systemic symptoms. Vemurafenib treatment may lead to regression of systemic symptoms and cutaneous yellowish plaques associated with ECD carrying a BRAF mutation.

Primary central nervous system large B-cell lymphoma (PCNS-LBCL) is a rare, aggressive lymphoma that affects immune-privileged sites. Immune checkpoint molecules have been implicated in its aggressive biology, and promising results have emerged from immune checkpoint inhibitor therapy in relapsed/refractory cases. This study evaluates the tumor microenvironment (TME), immune checkpoint molecule expression, and the relationship with 9p24.1 gene region alterations in a large cohort of PCNS-LBCL, with detailed quantitative analyses. Tissue microarrays were constructed with 57 PCNS-LBCL cases and 45 systemic non-germinal center diffuse large B-cell lymphoma (DLBCL) controls. Immunostaining for CD3, CD8, CD68, CD163, PD-1, PD-L1, PD-L2, EBER in situ hybridization (ISH), and FISH for PD-L1/PD-L2 copy number alterations and translocations were performed. Digital image analysis was used for quantitative evaluations, which were compared with clinical and pathologic parameters. PCNS-LBCL showed significantly lower T-cell and histiocyte presence in the TME compared with nodal DLBCL (PP<0.001). PD-1, PD-L1, and PD-L2 expressions in the TME of PCNS-LBCL were 89%, 96%, and 90%, respectively, and were positively correlated with TME density. Tumor cell expressions of PD-L1 and PD-L2 were 31% and 34%, respectively. FISH alterations in the 9p24.1 region were infrequent and did not consistently correlate with protein expression in either PCNS-LBCL or DLBCL. Higher CD8+ T-cell and CD68+ histiocyte counts were associated with better survival in PCNS-LBCL. Lower TME density and high expression of PD-1/PD-L1/PD-L2 in PCNS-LBCL reflect the unique CNS microanatomy and may contribute to poorer prognosis. These findings support the potential benefit of immune checkpoint inhibitors in treating PCNS-LBCL, aligning with ongoing clinical trials and current literature.

This study evaluated the demographic data, clinical characteristics, treatment approaches, and treatment responses of 43 patients with primary cutaneous CD30⁺ lymphoproliferative disorders. Lymphomatoid papulosis (LyP) was characterized by predominantly papular (94.1%) and generalized (70.6%) lesions, while primary cutaneous anaplastic large-cell lymphoma (pcALCL) presented with tumoral (77.8%) and solitary (77.8%) lesions (p<0.001). Common treatments for LyP included methotrexate (response rate: 78.5%), topical corticosteroids (response rate: 83.3%), and phototherapy (response rate: 85.8%), but relapse rates were high. In pcALCL, complete remission was achieved with all treatments, with no relapses after brentuximab vedotin (BV). Secondary malignancies were noted in 20.6% of LyP cases. Both LyP and pcALCL had a 100% 5-year disease-specific survival rate, although two LyP patients (5.9%) died of secondary malignancies. In conclusion, LyP and pcALCL are both indolent lymphomas, with LyP being more prone to relapse. BV is effective for resistant pcALCL. LyP patients need long-term monitoring due to the risk of secondary malignancies.