Journal of Hematopathology最新文献

Morphologic features of aggressive/ "accelerated" chronic lymphocytic leukemia/small lymphocytic lymphoma (aCLL/SLL) have been described. Richter transformation (RT) also occurs in a subset of CLL/SLL cases. This case series examined inter-observer variability when assessing for aCLL/SLL and RT, with attention to how immunohistochemical (IHC) markers may assist in this evaluation. Twelve cases of CLL/SLL with available FFPE tissue were identified. H&E staining and IHC (CD3, CD20, CD5, CD23, LEF1, LAG3, C-MYC, PD-1, MUM1, Cyclin D1, BCL-6, p53, and Ki-67) were performed. Three hematopathologists reviewed each case. The pathologists provided a final interpretation of (1) CLL/SLL, (2) CLL/SLL with expanded and/or confluent proliferation centers or increased Ki-67 (aCLL/SLL), or (3) large cell transformation/DLBCL. The pathologists lacked consensus in the diagnosis in 6/12 cases (50%). The reviewers disagreed on the presence of expanded/confluent proliferation centers in 8/12 cases (67%). With the exception of Ki-67, no IHC marker showed a difference in the staining profile in aCLL/SLL or RT compared to low-grade cases. This series showed inter-observer variability in the evaluation for aCLL/SLL and RT. A study that serially examines genetic alterations in FFPE tissue and correlates the features with histology and IHC, at diagnosis and throughout the disease course, may help refine indicators of aggressive disease.

Quadruple-hit lymphomas are extremely rare non-Hodgkin lymphomas with a reported dismal prognosis in the few reported cases. A "quadruple hit" has been defined by the presence of concurrent MYC, BCL2, BCL6, and CCND1 chromosomal rearrangements. We report a new case of a quadruple hit lymphoma in a 73-year-old Hispanic man who presented with an enlarging left-sided neck mass. Computed tomography showed a 1.9-cm mass in left the tonsil with bulky cervical lymphadenopathy. The presence of all four chromosomal rearrangements can reportedly occur with disease progression in both diffuse large B-cell lymphomas and mantle cell lymphomas. Further characterization of the tumor by next-generation sequencing may be of benefit to delineate between these two possibilities. Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next-generation sequencing were used to confirm and classify the diagnosis. Histologic sections of the cervical lymph node demonstrated an atypical lymphoid infiltrate with large and pleomorphic cells, which were positive for CD20, CD10, BCL1 (Cyclin D1), BCL2, BCL6, and cMYC and negative for CD5 and SOX11 on immunohistochemistry with a Ki-67 proliferative index of 70%. FISH demonstrated MYC, BCL2, BCL6, and CCND1 rearrangements and the diagnosis of high-grade B-cell lymphoma with MYC, BCL2, BCL6, and CCND1 was rendered. Our patient was treated with dose adjusted etoposide, doxorubicin, cyclophosphamide, prednisone, and rituximab chemotherapy and has been in remission for 20 months.

The assessment of bone marrow iron stores is typically performed on an aspirate smear slide that has been manually stained by a technologist using a commercially available kit. This approach can contribute to inconsistent results and limit the broad use of iron staining in bone marrow specimens, particularly when laboratories have low staffing and/or high specimen volumes. Here, we describe the adaptation and validation of the Ventana Benchmark automated stainer and iron stain kit for routine clinical use of staining iron in bone marrow aspirate smear slides. We assessed accuracy and precision of the Ventana automated iron staining protocol compared to the Perls Prussian blue manual iron staining index method. Hematopathologists assigned Gale scores and enumerated the percentages of erythroid sideroblasts on paired patient bone marrow aspirate smear slides stained by the automated method and the manual iron staining method. We found a similar level of performance of the Ventana automated iron stain relative to the index manual method (as assessed by Pearson correlation and Bland-Altman analyses). In addition, there was low imprecision between replicates performed via the automated iron stain protocol. We also report superior qualitative findings of the automated method in ease of localization of iron storage, visualization of sideroblasts, and counterstain consistency. Automated iron staining of bone marrow aspirate smear slides performed similarly to the manual method and may allow for accurate routine evaluation of bone marrow iron stores as part of bone marrow analysis.

Pure erythroid leukemia (PEL) is an extremely rare subtype of acute myeloid leukemia (AML). Although not specific, PEL is almost uniformly associated with complex karyotype and TP53 mutations. Given the rarity of the disease, our understanding of its cytogenetic and molecular features deems incomplete. We aim to complement existing literature by presenting an unusual case of PEL. The case is comprehensively worked up with multiple modalities. We present for the first time a case of PEL with unusual cytogenetic and molecular features: normal karyotype with absence of TP53 mutations and presence of NPM1 and NRAS mutations. This is a valuable addition to literature, expanding our understanding of molecular and cytogenetic spectra of PEL.

Epstein-Barr virus (EBV) typically infects B cells in infectious mononucleosis (IM), but a rare case shows EBV infection in T cells. Seven cases of lymphoproliferative disorder caused by EBV-positive cytotoxic T/natural killer (NK) cell proliferation in the lymph nodes, termed IM with transient EBV infection of T and NK cells (EBV + T/NK cells in IM), are reported here. The purpose of the study is to describe clinicopathological features of EBV + T/natural killer (NK) cells in IM of the lymph node. We retrospectively analysed seven cases of Chinese children and young people adults with EBV + T/NK cells in IM. We used morphological observation, immunohistochemical staining, EB virus in situ hybridisation detection, and analysis of T-cell receptor gene rearrangement. The patients were healthy prior to illness, experiencing sudden onset occurring in all the patients, with high fever as the first symptom, followed by lymphadenopathy and hepatosplenomegaly. Diagnosis occurred < 1.5 months of symptom onset. Most lymphocytes in lesions expressed CD3 and Granzyme B or TIA-1 and lacked CD5. CD56 was expressed in numerous cells in 5 of the 7 cases. EBV-encoded RNA (EBER) was detected in medium-to-large-sized cells (50-100 cells per cell/high-power field). T-cell receptor (TCR) gene rearrangement was seen in six cases, with monoclonal rearrangement in four cases. Treatment was conservative treatment but not chemotherapy. Four received anti-HLH therapy and others anti-inflammatory treatment. All patients survived with relapse after long-term clinical observation and follow-up. EBV + T/NK cells in IM can elicit malignant features that mimic T/NK-cell lymphoma pathologically and benign features mimicking IM clinically. These findings indicate that EBV + T/NK cells in IM could serve as valuable diagnosis. Additional clinical information, including age of onset (children and young people), nature of onset (sudden), disease course (short), symptoms (systemic), EBV infection status (acute), and lymph node involvement, is crucial for accurate diagnosis and prognostic evaluation.

Chimeric antigen receptor T-cell (CAR-T) therapy is a recent advancement in precision medicine with promising results for patients with relapsed or refractory B-cell malignancies. However, rare post-therapy morphologic, immunophenotypic, and genomic alterations can occur. This study is to present a case of a patient with diffuse large B-cell lymphoma (DLBCL) who underwent anti-CD19 CAR-T therapy with disease in the uterus that showed transdifferentiation to a poorly differentiated malignant neoplasm that failed to express any lineage specific markers. In immunohistochemistry, fluorescence in situ hybridization (FISH) and targeted next-generation sequencing (NGS) were utilized to fully characterize the diagnostic DLBCL sample in comparison to the poorly differentiated neoplasm of the uterus. Analysis of the diagnostic DLBCL and the poorly differentiated neoplasm demonstrated evidence of a clonal relationship as well as revealing acquisition of mutations associated with CAR-T resistance. Furthermore, downregulation of B-cell associated antigens was observed, underscoring a mechanistic link to CAR-T evasion as well as demonstrating diagnostic confusion. This case illustrates the utility of employing multiple diagnostic modalities in elucidating a pathologic link between a B-cell lymphoma and poorly differentiated neoplasm following targeted therapy.

A 51-year-old female with menorrhagia was found to have a cervical polyp. Polypectomy and endometrial curettage showed an atypical lymphoid infiltrate. Hysterectomy was performed, showing extensive myometrial infiltration by small, cytologically bland CD3-positive αβ T cells with a non-activated cytotoxic phenotype and a low proliferative rate. PCR showed clonal TCR-β gene rearrangement. Lymph nodes were uninvolved. PET-CT was negative. A diagnosis of CD8-positive T-cell lymphoproliferative disorder (T-LPD) was made. At 6 months, the patient was asymptomatic with a negative repeat PET-CT. A critical recent advance in the classification of lymphoid neoplasms is the recognition of indolent extranodal T-LPDs, including those of the gastrointestinal tract (T-cell and NK-cell types) and skin (small/medium CD4-positive and acral CD8-positive). However, T-LPDs of the uterus are rare. Two indolent T-LPDs of the uterus have been reported, both showing a CD8-positive, nonactivated cytotoxic phenotype, low proliferative rate, and clonal TCR rearrangement. Neither developed systemic disease nor recurrence. The etiology of indolent T-LPDs and their relationship to overt T-cell lymphomas remain poorly understood. T-LPDs of the uterus may arise from effector memory T-cells that establish long-term, tissueresident immunologic memory following exposure to fetal extravillous trophoblastic cell alloantigens during a previous pregnancy. Neither our patient nor the 2 previously reported had a current pregnancy or a known recent infection or toxic exposure, and the event(s) triggering evolution into T-LPD are unknown. Indolent T-LPDs can be encountered at new and unusual extranodal sites; knowledge of their clinicopathological features will help avoid unnecessary cytotoxic chemotherapy and improve understanding of this group of disorders.