Cytogenetic and pathologic characterization of MYC-rearranged B-cell lymphomas in pediatric and young adult patients.

MYC-rearranged B-cell lymphoma (BCL) in the pediatric/young adult (YA) age group differs substantially in disease composition from adult cohorts. However, data regarding the partner genes, concurrent rearrangements, and ultimate diagnoses in these patients is scarce compared to that in adult cohorts. We aimed to characterize the spectrum of MYC-rearranged (MYC-R) mature, aggressive BCL in the pediatric/YA population.

High-grade B-cell lymphoma with a quadruple-hit genetic profile including concurrent MYC, BCL2, BCL6, and CCND1 gene rearrangements.

Several reports of concurrent MYC, BCL2, BCL6, and CCND1 rearrangements in high-grade B-cell lymphoma (HGBL) have been recently described. Herein, we aimed to delineate the scope of this entity through a review of HGBL with a "quadruple-hit" genetic profile identified at our institution. We performed a retrospective review (2015-2023) at our institution of B-cell lymphoma (BCL) cases that were evaluated with concurrent MYC, BCL2, and BCL6 break-apart and IGH::MYC and IGH::CCND1 dual-color dual-fusion fluorescence in situ hybridization studies.

Superior detection rate of plasma cell FISH using FACS-FISH.

Objectives: Fluorescence in situ hybridization (FISH) for plasma cell neoplasms (PCNs) requires plasma cell (PC) identification or purification strategies to optimize results. We compared the efficacy of cytoplasmic immunoglobulin FISH (cIg-FISH) and fluorescence-activated cell sorting FISH (FACS-FISH) in a clinical laboratory setting.

Methods: The FISH analysis results of 14,855 samples from individuals with a suspected PCN subjected to cytogenetic evaluation between 2019 and 2022 with cIg-FISH (n = 6917) or FACS-FISH (n = 7938) testing were analyzed.

Clear-cell Variant of Mucoepidermoid Carcinoma Presenting as a Palatal Mass in a 10-Year-old Boy.

Background: The clear-cell variant of mucoepidermoid carcinoma (MEC) involving minor salivary glands is extremely rare in children.

Case Report: We report a case of clear-cell variant MEC in the minor salivary gland in a 10-year-old boy who presented with a mass of the right hard palate. Fine-needle aspiration showed features suggestive of clear-cell variant of MEC.

Identification of EWSR1 rearrangements in patients with immature hematopoietic neoplasms: A case series and review of literature.

Rearrangement of the EWSR1 gene (22q12.2) is a well-recognized genetic lesion in bone and soft tissue tumors. However, few reports have suggested that EWSR1 rearrangements may also occur in the setting of hematopoietic tumors.

Identification of a Cryptic t(8;20;21)(q22;p13;q22) Resulting in RUNX1T1/RUNX1 Fusion in a Patient with Newly Diagnosed Acute Myeloid Leukemia.

The detection of recurrent genetic abnormalities in acute myeloid leukemia (AML), including RUNX1T1/RUNX1 gene fusion, is critical for optimal medical management. Herein, we report a 45 year old woman with newly diagnosed AML and conventional chromosome studies that revealed an apparently balanced t(8;20)(q22;p13) in all 20 metaphases analyzed. A RUNX1T1/RUNX1 dual-color dual-fusion fluorescence in situ hybridization (FISH) probe set was subsequently performed and revealed a RUNX1T1/RUNX1 gene fusion.

Increased complexity of t(11;14) rearrangements in plasma cell neoplasms compared with mantle cell lymphoma.

Plasma cell neoplasms (PCN) and mantle cell lymphoma (MCL) can both harbor t(11;14)(q13;q32) (CCND1/IGH), usually resulting in cyclin D1 overexpression. In some cases, particularly at low levels of disease, it can be morphologically challenging to distinguish between these entities in the bone marrow (BM) since PCN with t(11;14) are often CD20-positive with lymphoplasmacytic cytology, while MCL can rarely have plasmacytic differentiation. We compared the difference in CCND1/IGH by fluorescence in situ hybridization (FISH) in PCN and MCL to evaluate for possible differentiating characteristics.

Detailed Reanalysis of 500 Breast Cancers With Equivocal HER2 Immunohistochemistry and Borderline ERBB2 Fluorescence In Situ Hybridization Results.

Objectives: We investigated the impact of our laboratory's reflex testing process for resolving ERBB2 (HER2) status on breast cancer samples that require additional workup after fluorescence in situ hybridization (FISH), per guideline recommendations published in 2018 by the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP).

Methods: In total, 500 breast cancer specimens with ERBB2 FISH results in groups 2 through 4 (all reported as immunohistochemistry [IHC] equivocal [2+] at external laboratories) were resubmitted for IHC testing in our laboratory. Per the ASCO/CAP guideline, FISH was rescored when internal IHC was also equivocal (2+), targeted to tumor areas demonstrating more intense IHC staining, if observed.

HER2 Testing for Breast Cancer in the Genomics Laboratory: A Sea Change for Fluorescence In Situ Hybridization.

Context.—: Guidelines for HER2 testing in breast cancer have changed over time, from the US Food and Drug Administration guideline to the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines published in 2007, 2013, and 2018.

Objective.

High level MYC amplification in B-cell lymphomas: is it a marker of aggressive disease?

While MYC translocations in B-cell lymphoma (BCL) have been extensively studied, the significance of MYC amplification (MYC amp) is poorly understood. This study characterizes BCL showing MYC amp, defined as uncountable FISH signals. Retrospective analysis of all BCL FISH for MYC aberrations performed at our institution (1/2010-2/2018) identified 44/9715 (0.

Fluorescence in-situ hybridisation for TP63 rearrangements in T cell lymphomas: single-site experience of 470 patients and implications for clinical testing.

Aims: The aims of this study were to review our 5-year experience with clinical FISH testing for TP63 rearrangements using both TP63 break-apart (BAP) and TBL1XR1/TP63 dual-fusion (D-FISH) probes to evaluate the frequency of TP63 rearrangements and the distribution of TBL1XR1 vs. alternate partner loci, and to assess whether both probe sets are necessary in all cases undergoing FISH testing.

Methods And Results: A retrospective review of the Mayo Clinic cytogenetic database identified 470 patients evaluated by FISH testing for TP63 rearrangements in formalin-fixed paraffin-embedded (FFPE) tissue using both BAP and D-FISH probes.

Warthin-like Mucoepidermoid Carcinoma of the Parotid Gland: Unusual Morphology and Diagnostic Pitfalls.

Background: Warthin-like mucoepidermoid carcinoma is a newly recognized rare entity and could be misdiagnosed as a benign Warthin tumor. We report such a case of a 36-year-old male who presented with a left parotid gland mass.

Case Report: Fine-needle aspiration showed features suggestive of Warthin tumor.

Acute leukemias harboring KMT2A/MLLT10 fusion: a 10-year experience from a single genomics laboratory.

The MLLT10 (formerly AF10) gene is the fourth most common KMT2A fusion partner across all acute leukemias and requires at least 3 breaks to form an in-frame KMT2A/MLLT10 fusion due to the opposite orientation of each gene. A 10-year retrospective review was performed to identify individuals from all age groups that harbor KMT2A/MLLT10 fusion obtained by our KMT2A/MLLT10 dual-color dual-fusion fluorescence in situ hybridization (D-FISH) assay. Of the 60 unique individuals identified, 31 were male and 29 were female (M:F ratio, 1.

Analysis of Common Abnormalities Seen in Chronic Lymphocytic Leukemia Using Fluorescence In Situ Hybridization.

Since fluorescence in situ hybridization (FISH) was used to define a prognostic heierarchy for chronic lymphocytic leukemia (CLL) in 2000, the method has been employed widely in cytogenetics laboratories worldwide. This chapter describes techniques and trouble-shooting to maximize the efficiency of microscope slide preparation for FISH analysis in CLL.

KMT2A (MLL) rearrangements observed in pediatric/young adult T-lymphoblastic leukemia/lymphoma: A 10-year review from a single cytogenetic laboratory.

T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) accounts for approximately 15% of pediatric and 25% of adult ALL. While the underlying frequency of KMT2A (MLL) gene rearrangements has been identified in approximately 4-8% of T-ALL/LBL cases, a paucity of literature is available to characterize further the KMT2A rearrangements in pediatric/young adult T-ALL/LBL. A 10-year retrospective review was performed to identify KMT2A rearrangements in specimens sent for T-ALL/LBL fluorescence in situ hybridization studies in patients under the age of 30 years.

Integrated Analysis of HER2 Copy Number by Cytogenomic Microarray in Breast Cancers With Nonclassical In Situ Hybridization Results.

Objectives: To develop and test an integrated approach to human epidermal growth factor receptor 2 (HER2) copy number analysis in breast cancer using in situ hybridization (ISH) and cytogenomic microarray (CMA).

Methods: CMA was performed on four clinical breast cancer samples with nonclassical patterns of HER2 ISH results. Integrated analysis was performed by correlating the data from pathology review, ISH, and CMA.

Change in Pattern of HER2 Fluorescent in Situ Hybridization (FISH) Results in Breast Cancers Submitted for FISH Testing: Experience of a Reference Laboratory Using US Food and Drug Administration Criteria and American Society of Clinical Oncology and College of American Pathologists Guidelines.

Purpose In 1998, the US Food and Drug Administration (FDA) approved human epidermal growth factor receptor 2 (HER2) testing guidelines to determine eligibility for HER2-directed therapy (HDT) in breast cancer. ASCO and the College of American Pathologists published immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) HER2 testing guidelines in 2007 (AC2007) and updated these guidelines in 2013 (AC2013). We compared the HER2 FISH amplification frequency using these three guidelines.

A Rare Pediatric Example of Subcutaneous Extraskeletal Osteosarcoma: A Case Report and Review of the Morphologic Differential Diagnosis.

Primary extraskeletal osteosarcoma is an exceedingly rare malignant neoplasm that accounts for approximately 1% of soft tissue sarcomas and most often occurs in the deep soft tissues of adults. Extraskeletal osteosarcoma is characterized by the production of osteoid, bone, and/or chondroid matrix. The diagnosis of extraskeletal osteosarcoma requires careful radiologic and clinical correlation to ensure that the patient does not have an underlying bone primary.

Automated cellular imaging system III for assessing HER2 status in breast cancer specimens: development of a standardized scoring method that correlates with FISH.

The goal of this study was to assess the performance characteristics of the Automated Cellular Imaging System (ACIS III) for HER2 immunohistochemical analysis. The study was performed on 187 biopsy slides from patients who underwent HER2 testing between January and February 2008. Three scoring methods by the ACIS III were compared with the manual score and fluorescence in situ hybridization (FISH) results for HER2 amplification.