Comparative Study on the Clinicopathologic and Molecular Characteristics of Primary and Secondary Diffuse Large B-cell Lymphoma in the Central Nervous System.

BACKGROUND/AIM: Diffuse large B-cell lymphoma of the central nervous system (CNS-DLBCL) is an aggressive B-cell lymphoma with clinical and molecular heterogeneity. Primary CNS-DLBCL (PCNSL) affects the brain, eyes, leptomeninges, or spinal cord without systemic involvement. Secondary CNS-DLBCL (SCNSL) manifests concurrently with systemic lymphoma or as an isolated CNS relapse with poor prognosis. MATERIALS AND METHODS: Next-generation sequencing (NGS) was used to identify genomic alterations in 32 PCNSL and 9 SCNSL cases. Single nucleotide variants and copy number variations in addition to the clinicopathologic data and proposed risk predictive values were compared to aid in diagnostic differentiation between the two types of lymphomas. RESULTS: The MCD genotype, characterized by mutations in MYD88 and CD79B, is the most common alteration in PCNSL and is associated with lower survival rates. The frequency of MYD88 mutation was significantly higher in PCNSL compared to SCNSL (75.0% vs. 33.3%; p=0.042). Recurrent copy number loss of 6p21 occurred in 56.1% of cases, more often in PCNSL (65.6%) than in SCNSL (22.2%) (p=0.028). Diagnostic positive predictive values (PPV) of MYD88 mutation and 6p21 loss for PCNSL were 89% and 91%, respectively. PPV of both alterations was 93% for the diagnosis of PCNSL. CONCLUSION: MYD88 mutation and 6p21 loss were significantly higher in PCNSL than in SCNSL, and novel risk prediction models based on these distinct genomic profiles can aid in the clinical differentiation of PCNSL and SCNSL.

An isolated sacral promyelocytic sarcoma in a child: A rare case report with emphasis on cytomorphology.

Myeloid sarcoma (MS) is an uncommon localized extramedullary tumor composed of immature myeloid precursor cells that can affect any organ. Promyelocytic sarcoma (PS), an extremely rare subtype of MS, is characterized by immature myeloid cells with features of acute promyelocytic leukemia (APL). We describe a case of pediatric PS that presented as a solitary sacral mass without any evidence of systemic or bone marrow involvement. The cytopathologic evaluation using touch imprint demonstrated numerous blasts with bilobed nuclei, cytoplasmic hyper-granularity, and aggregates of Auer rods, which are typical cytomorphologic features of APL. Herein, we report an extremely rare case of isolated PS in a child, emphasizing the importance of cytomorphologic evaluation, which is complemented by the findings from a comprehensive work-up.

Next Generation Sequencing Analysis of Fibrin-associated Large B-cell Lymphoma Reveals Pathogenic Single Nucleotide Variants.

BACKGROUND/AIM: Fibrin-associated large B-cell lymphoma (FA-LBCL) is a newly identified subtype of Epstein-Barr virus (EBV)-associated lymphoma. Arising within fibrinous material in confined spaces, FA-LBCL is associated with chronic inflammation. We herein report histopathologic features and molecular alterations of three cases of FA-LBCL to refine this new disease entity. MATERIALS AND METHODS: We performed immunohistochemical staining for CD3, CD20, CD10, Bcl-2, Bcl-6, MUM-1, CD10, and c-Myc and in situ hybridization for EBV-encoded RNA. Additionally, targeted DNA sequencing was conducted using commercially available gene panels. RESULTS: Three cases of FA-LBCL developed underlying lesions of retroperitoneal cyst, cardiac myxoma, and pancreatic cyst. Histopathologic features of these lesions were characterized by aggregates of atypical large cells in a background of fibrinous cellular debris. Atypical lymphoid cells were positive for CD20, Bcl-2, MUM-1, and EBV-in situ hybridization, negative for CD10, and variably positive for Bcl-6 and c-Myc. NGS analysis revealed the presence of pathogenic mutations in BRIP1, SOCS1, and KRAS. CONCLUSION: This is the first report of NGS analysis in FA-LBCL cases. It provides precise clinicopathological and molecular traits and allows its recognition as a new entity.

Prediction of Oncotype DX Recurrence Score by Evaluating the Peritumoral Tumor Budding in Early-stage Breast Carcinoma.

BACKGROUND/AIM: The Oncotype DX Recurrence Score (ORS) predicts the likelihood of recurrence and the benefit of chemotherapy in patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast carcinoma (ESBC). Tumor budding (TB) is a poor prognostic factor in breast carcinoma. This study aimed to determine the clinicopathological significance of TB in predicting ORS in patients with ESBC. PATIENTS AND METHODS: We included 359 patients with ER-positive, HER2-negative ESBC. The number of peritumoral TB was assessed, and the cases were categorized into TB-low (<10 buds) and TB-high (≥10 buds) groups. RESULTS: Patients with TB-high ESBC (170/359; 47.4%) showed a significantly higher median ORS (15.0 vs. 13.0) than those with TB-low tumors (189/359; 52.6%). Multivariate analysis revealed that high TB level was an independent predictive factor for higher ORS in patients with ESBC. CONCLUSION: High TB in ESBC independently predicted higher ORS. TB may serve as a surrogate marker for predicting ORS in patients with ESBC.

Identification of Predictive Factors for Post-operative Recurrence and Clinical Outcomes of Primary Vulvar Extramammary Paget Disease.

BACKGROUND/AIM: Data regarding the clinicopathological factors predicting recurrence and prognosis in patients with vulvar extramammary Paget disease (VPD) are limited. Therefore, we aimed to identify predictive factors for recurrence and outcomes in patients with VPD. PATIENTS AND METHODS: Forty-five patients with VPD were included in this study. We reviewed electronic medical records and pathology slides to collect clinicopathological information. RESULTS: Eighteen cases (40.0%) had resection margin (RM) involvement. Twelve patients (26.7%) received adjuvant radiation therapy (RT). Ten patients (22.2%) experienced recurrence. The recurrence rate was higher in patients who underwent wide local excision or simple vulvectomy than in those who underwent radical vulvectomy. Positive RM involvement was a significant and independent predictive factor for worse recurrence-free survival (RFS). The overall survival rate of patients who received adjuvant RT was significantly higher than that of those who underwent surgery alone. CONCLUSION: A positive RM involvement independently predicted worse RFS. The recurrence rate was significantly associated with the type of surgical procedure performed. Additionally, adjuvant RT can improve the prognosis of patients with VPD.

Assessing Resection Margin Status in Breast-conserving Surgery Specimens: Comparison Among Gross Evaluation, Frozen Section Analysis, and Permanent Section Diagnosis in 725 Patients With Breast Cancer.

BACKGROUND/AIM: An accurate evaluation of resection margin (RM) is critical in breast-conserving surgery (BCS) as negative RM status is critical for successful local control. We compared gross and microscopic methods for RM evaluation and analyzed their concordances. PATIENTS AND METHODS: Gross evaluation (GE), frozen section analysis (FSA), and permanent section diagnosis (PSD) were compared for specimens from 725 breast cancer patients. RESULTS: The RM was grossly involved in 74 cases (10.2%). The sensitivity and specificity of GE were 22.9% and 96.1%, respectively. FSA revealed positive RM in 290 cases (40.0%), with high sensitivity (86.7%) and specificity (83.1%). With PSD, 240 cases (33.1%) showed RM involvement. Discordant results between gross and microscopic methods were observed in 104 cases (14.3%). CONCLUSION: Our observations of the low sensitivity of GE, high discordance rate between gross and microscopic methods, and high sensitivity and specificity of FSA support the necessity of intraoperative FSA for assessing RM status during BCS.