Prognostic significance of cytogenetic abnormalities in T-cell prolymphocytic leukemia.

T-cell prolymphocytic leukemia (T-PLL) is an aggressive mature T-cell neoplasm. The most common cytogenetic abnormality associated with T-PLL is inv(14)(q11.2q32) involving TCL1, but other abnormalities also have been reported. In this study, we correlated cytogenetic abnormalities with clinical outcome in 97 T-PLL patients, including 66 men and 31 women with a median age of 63 years (range, 34-81). Twenty-seven patients had a normal karyotype (NK), one had two chromosomal aberrations, and 69 had a complex karyotype (CK). Patients with a CK had poorer overall survival (OS) than patients with a NK (P = .0016). In the CK group, the most common aberrations involved 14q (n = 45) and 8q (n = 38). Additional deletions of chromosomes 17p, 11q, 6q, 12p, 13q were observed frequently. No individual cytogenetic abnormality impacted OS. Patients with ≥5 aberrations had an OS of 11 months versus 22 months in patients with <5 aberrations (P = 0.0132). Fluorescence in situ hybridization for TCL1 successfully performed in 27 cases showed rearrangement in 8/10 (80%) NK versus 16/17 (94%) CK cases. OS of patients with TCL1 rearrangement and/or 14q aberrations was not significantly different from patients without TCL1 rearrangement and 14q aberrations (P = .3467). Patients with refractory disease showed worse OS in both the NK and CK groups (P = .0014 and P < .0001, respectively), compared with patients who achieved remission but then relapsed. Stem cell transplantation did not appear to improve OS regardless of karyotype complexity. In conclusion, patients with T-PLL often have a CK which is a poor prognostic factor, particularly in patients with ≥5 cytogenetic aberrations.

Composite mantle cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma.

BACKGROUND: Composite mantle cell lymphoma (MCL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is rare, as less than 20 cases have been reported so far. However, this entity may be under-diagnosed because the two lymphomas are very similar in morphology and immunophenotype. Previous cases were mostly diagnosed with immunohistochemistry, but flow cytometry may play an important role in the detection of two tumors in the same specimen, thus achieving an accurate diagnosis. By definition, a composite lymphoma is two demarcated lymphomas occurring at the same anatomic site. Therefore, immunohistochemistry is still needed to identify the topographic relation of these two tumors. Our reported case illustrates the pitfalls in the diagnostic process and we recommend two standard panels with new markers for an accurate diagnosis of this composite lymphoma. METHOD: FACSCanto II is used with antibodies, including CD5, CD10, CD19, CD20, CD22, CD23, CD43, CD79b, CD200, kappa, and lambda. Immunohistochemical stains include PAX-5/CD5 dual stain, Cyclin D1, SOX11, and LEF-1. RESULTS: CLL/SLL is positive for CD5, CD19, CD23, CD43, and CD200, with dim expression of CD20, CD22, CD79b, and kappa. MCL is positive for CD5, CD19, CD20, CD22, CD79b, kappa, and negative for CD23, CD43, and CD200. Immunohistochemical stains show that PAX-5/CD5 stains the entire tumor population. Cyclin D1 and SOX11 only stain the central portion that represents MCL and LEF-1 stains the periphery that represents CLL/SLL. CONCLUSIONS: We recommend the use of the above panels for flow cytometry and immunohistochemistry, respectively. LEF-1 is specific for CLL/SLL; and CD200 is helpful to distinguish CLL/SLL from MCL. © 2017 International Clinical Cytometry Society.

TCL-1-positive hematogones in a patient with T-cell prolymphocytic leukemia after therapy.

T-prolymphocytic leukemia (T-PLL) is a rare mature T-cell neoplasm characterized by proliferation of prolymphocytes. Most cases involve the T-cell leukemia-1 (TCL1) gene at 14q11.2 resulting in overexpression of TCL-1, which is helpful for distinguishing T-PLL from other T-cell neoplasms. We report a patient with T-PLL whose leukemic cells were positive for TCL-1 by immunohistochemistry but with a normal karyotype. The patient had anti-CD52 antibody therapy for 12 weeks. In a follow-up bone marrow biopsy specimen, numerous TCL-1-positive cells were present, which raised the differential diagnosis of residual T-PLL. However, further immunophenotypic studies confirmed that these cells were hematogones. Therefore a diagnosis of recovering bone marrow was established. The patient underwent stem cell transplant and is now in complete remission. This case demonstrates that hematogones can express TCL-1, and this knowledge is very important for the differential diagnosis in the follow-up marrow of T-PLL patients.

Detection of BCR/ABL fusion product in normoblasts in a case of chronic myelogenous leukemia.

Erythroblast phase of chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute erythroid leukemia are rare events. The distinction between these two entities is poorly defined. The World Health Organization (WHO) classification requires the presence of more than 50% of erythroblasts in the bone marrow for the diagnosis of both the erythroid/myeloid or pure erythroid subtypes of acute erythroid leukemia. However, in previous studies of erythroblast crisis CML, the percentage of erythroid series in the bone marrow is seldom mentioned and the direct relationship of the erythroblasts and the Philadelphia chromosome has never been established. We report a well-documented case of acute erythroid leukemia transformed from CML. The studies in morphology, immunohistochemistry, and flow cytometry fulfill the WHO criteria for the diagnosis of acute erythroid leukemia, and yet the complex karyotype containing Philadelphia chromosome indicates genetic evolution. Finally, the direct demonstration of the BCR/ABL fusion product by fluorescence in situ hybridization in the erythroblasts provides concrete evidence that the erythroblasts are part of the leukemic process and not an innocent bystander.

Transformation of hairy cell leukemia to high-grade lymphoma: a case report and review of the literature.

The coexistence of hairy cell leukemia (HCL) and non-Hodgkin's lymphoma is extremely rare. In the few reports demonstrating such coexistence, the relationship between the 2 entities was mostly inconclusive. We report a case of HCL that transformed to large cell lymphoma. This case has been followed for more than 4 years with immunohistochemical, flow cytometric, and molecular genetic studies on multiple bone marrow biopsy specimens, a splenectomy specimen, and a lymph node biopsy. In our case, the immunophenotype and tartrate-resistant acid phosphatase stain confirmed that the large cell lymphoma was of HCL origin. The markedly increased Ki-67 staining (proliferation fraction) in the lymph node biopsy specimen compared to the earlier splenectomy specimen indicated the transformation of a low-grade leukemia to a high-grade lymphoma. The overexpression of p53 in the lymph node implies that p53 mutation was probably involved in the pathogenesis of HCL transformation.

A hybrid form of myeloid/NK-cell acute leukemia and myeloid/NK-cell precursor acute leukemia.

Natural killer (NK)-cell leukemia/lymphoma is a rare entity that has been defined only in recent years. In the Revised European-American Lymphoma and World Health Organization classifications, only the mature NK-cell malignancies are included. However, at least 3 types of precursor NK-cell neoplasms have been reported in the literature. These include myeloid/NK-cell acute leukemia, myeloid/NK-cell precursor acute leukemia, and blastic NK-cell lymphoma/leukemia. These leukemias are characterized by the presence of blasts, which express CD56, in the peripheral blood, bone marrow, lymph nodes, and/or extranodal tissues. We report a case that is morphologically consistent with myeloid/NK-cell acute leukemia but immunologically is myeloid/NK-cell precursor acute leukemia. This case is unique in its cutaneous presentation without involvement of the peripheral blood. Extensive flow cytometric studies were performed on the skin biopsy and bone marrow aspirate specimens, which included many markers that had not been tested before in these entities. The clinical implications of these findings are discussed.

Extranodal NK/T-cell lymphoma mimicking cellulitis.

NK/T-cell lymphoma is difficult to diagnose because there is no characteristic cytology to help the diagnosis in tissue sections, particularly when there is polymorphic cellular infiltration in the early stage of the disease. However, the nasal type of extranodal NK/T-cell lymphoma has a characteristic histologic pattern, which is angiocentric, angioinvasive and angiodestructive. Therefore, many cases of this tumor may show extensive necrosis that mimics infectious process. Furthermore, because the immunosuppressive status of these patients, they may, in fact, have superimposed infections. We are reporting a case that presented as cellulitis and only after careful examination with immunohistochemistry that a correct diagnosis of extranodal NK/T-cell lymphoma, nasal type, was established. Since this lymphoma is incurable and immunophenotyping is instrumental for the diagnosis and prediction of the prognosis, a high index of suspicion for this tumor is needed when an angiocentric lesion is found in the midline of the head and neck region, and a thorough immunohistological study should always be conducted in these cases.

Primary intestinal intraepithelial natural killer-like T-cell lymphoma: case report of a distinct clinicopathologic entity.

Intestinal T-cell lymphoma is a heterogenous group. These tumors differ in their association with enteropathy, intraepithelial or nonintraepithelial origin, primary or secondary involvement, and T-cell or natural killer-like T-cell immunophenotype. There are also nonneoplastic conditions, such as celiac disease, refractory sprue, and reactive T-cell infiltration that mimic intestinal T-cell lymphoma. Therefore, the differential diagnosis requires extensive morphologic, immunophenotypic, and molecular genetic studies. A subset of primary intestinal intraepithelial T-cell lymphoma has emerged in recent years that is distinguished from enteropathy-type T-cell lymphoma in terms of clinical presentation (nonenteropathic), morphology (monomorphic small to medium-sized cells), immunophenotype (CD3(-)CD8(+)CD56(+)), and cytogenetics. We report such a case with a unique immunophenotype (CD3(-), cytoplasmic CD3(+), CD4(-), CD8(+), CD5(-), CD7(+), CD16(-), CD56(+), CD57(-), CD103(+), T-cell intracellular antigen 1(+), and betaF1(+)) that is comparable to that of a newly identified subset of intraepithelial T cells. The tumor progressed rapidly and the patient died within 6 months after the onset of the disease. We recommend a large monoclonal antibody panel for the differential diagnosis of this heterogeneous group of T-cell lymphoma.

An unusual case of peripheral T-cell lymphoma with CD56 positivity and angiocentric, angiodestructive morphology arising in the ileum.

Natural killer cell and cytotoxic T-cell lymphomas are frequently difficult to distinguish because they share many common features, and yet it is important to make an accurate diagnosis because their prognoses differ. We report an unusual case of a white man with a CD56-positive T-cell lymphoma in the ileum. The histologic pattern was characterized by angioinvasion and angiodestruction. Immunohistochemical staining showed positive reactions to CD3, CD8, CD43, CD45RO, CD56, and T-cell intracellular antigen-1, but negative reactions to CD4, CD5, CD20, CD23, and CD57. Epstein-Barr virus (EBV) was not detected by EBV-latent membrane protein staining and EBV polymerase chain reaction technique. The T-cell receptor gamma chain gene was rearranged. According to the World Health Organization classification, the absence of EBV excludes the diagnosis of extranodal natural killer/T-cell lymphoma, nasal type. However, the association of EBV with this lymphoma in white patients is not clear. Therefore, absence of EBV alone does not necessarily exclude nasal-type natural killer/T-cell lymphoma, particularly because the histologic pattern in this case is highly characteristic of this tumor.

Chronic myelomonocytic leukemia with abnormal bone marrow eosinophils.

Chronic myelomonocytic leukemia with eosinophilia is a recently defined rare entity frequently associated with t(5;12)(q33;p13) translocation. It usually shows a peripheral eosinophil count greater than 1500/microL. However, the literature contains a small subset of cases in which the major manifestation is bone marrow eosinophilia. We report a case similar to that subset and discuss our finding that the immature eosinophils are identical to those seen in acute myelomonocytic leukemia with abnormal bone marrow eosinophils.

Fluorescence in situ hybridization: method of choice for a definitive diagnosis of mantle cell lymphoma.

Fluorescence in situ hybridization (FISH) using IGH/CCND1 probes was used to analyze 35 specimens including 27 paraffin sections, 3 bone marrow aspirates, and 5 peripheral blood smears. The 27 paraffin sections included 7 bone marrows, 10 lymph nodes, 3 spleens, 3 tonsils, 3 gastrointestinal biopsies, and 1 skin biopsy. Among these cases, 23 specimens were from 20 patients with mantle cell lymphoma (MCL) and 12 specimens were from 12 patients with non-MCL lymphomas/lymphoid hyperplasia. Specimens from all MCL patients showed positive results with FISH. In one patient, the archived paraffin sections were negative with FISH, but a fresh peripheral blood specimen showed a positive result. Negative results were obtained in all specimens from non-MCL cases. Flow cytometric analysis revealed that all cases of MCL showed CD19/CD5 staining, but the percentages of cells positive for CD23 and FMC-7 were variable, thus they cannot be depended upon for a definitive diagnosis of MCL. Immunohistochemical stains demonstrated positive staining for CD5 and CD20 and negative staining for CD23 in MCL cases but cyclin D1 was positive in only 10 of 13 MCL cases studied. Therefore, it appears that immunophenotyping alone is not sufficient to establish a definitive diagnosis of MCL. FISH should be routinely used when the diagnosis needs confirmation. FISH can be performed in a routine clinical laboratory, and it is applicable to archived material for retrospective studies. Other molecular cytogenetic techniques in comparison with FISH are discussed.