T-cell Rich Large B-cell Lymphoma Research Articles

T-cell-rich, large B-cell lymphoma in the brain of a horse.

T-cell-rich, large B-cell lymphoma (TCRLBCL) is the most commonly diagnosed type of lymphoma in horses. Here we describe the clinical signs, neuropathology, immunohistochemistry (IHC), and PCR for antigen receptor rearrangement (PARR) analysis results of a TCRLBCL in the brain of an 8-y-old male Quarter Horse that was euthanized after acute anorexia, tremors, head pressing, falling, blindness, incoordination, and seizures. Autopsy revealed a firm, smooth, pale-yellow mass that expanded both lateral ventricles and the adjacent subcortical white matter. Histologically, the mass consisted of a densely cellular neoplasm composed of large, CD79+ neoplastic B-lymphocytes admixed with sheets of small, CD3+ reactive T-lymphocytes, Iba1+ histiocytes, MUM1+ plasma cells, and rare eosinophils supported by a fine fibrovascular stroma. Formalin-fixed, paraffin-embedded tissue scrolls were retrieved and subjected to PARR analysis, which revealed a clonal reaction in the immunoglobulin gene and a polyclonal reaction for the T-lymphocyte receptor gene, consistent with a neoplastic B-lymphocyte and reactive T-lymphocyte proliferation. The diagnosis of TCRLBCL was suspected histologically and confirmed based on IHC and PARR analysis.

Cytological and immunological characteristics of a rarely occurring t-cell rich large b-cell lymphoma in a rottweiler dog

Cytological and immunological characteristics of a rarely occurring t-cell rich large b-cell lymphoma in a rottweiler dog

A Molecular Classifier Increased the Accuracy of Lymphoma Diagnosis By Expert Pathologists in the Diffuse Large B-Cell Lymphoma Gained Trial from the Lysa

A Molecular Classifier Increased the Accuracy of Lymphoma Diagnosis By Expert Pathologists in the Diffuse Large B-Cell Lymphoma Gained Trial from the Lysa

European Task Force on Lymphoma project on lymphocyte predominance Hodgkin disease: histologic and immunohistologic analysis of submitted cases reveals 2 types of Hodgkin disease with a nodular growth pattern and abundant lymphocytes

AbstractParaffin blocks and clinical data from 521 patients with lymphocyte predominance Hodgkin disease (LPHD) diagnosed between 1970 and 1994 were collected from 16 European and United States oncological centers to establish the pathologic and clinical characteristics of a large patient cohort, to determine how frequent T-cell–rich large B-cell lymphoma (TCRLBCL) is among LPHD, and to find differential diagnostic criteria distinguishing between the 2 lymphoma categories. For this purpose, conventionally and immunohistologically stained sections were reviewed by a panel of hematopathologists. The diagnosis of LPHD was confirmed in only 219 of the 388 assessable cases (56.5%). This low confirmation rate was due mainly to the presence of a new variant of classical Hodgkin disease (CHD), which resembled, in terms of nodular growth and lymphocyte-richness, nodular LPHD and, in terms of the immunophenotype of the tumor cells, CHD and was designated nodular lymphocyte-rich CHD (NLRCHD). The nodules of LRCHD consisted—as in nodular LPHD—predominantly of B cells but differed from those present in LPHD in that they represented expanded mantle zones with atrophic germinal centers. Clinically, patients with LPHD and NLRCHD showed similar disease characteristics at presentation but differed in the frequency of multiple relapses and prognosis after relapse. Patients with LPHD and NLRCHD clearly differed from patients with CHD with nodular sclerosis or mixed cellularity, as they presented with an earlier disease stage and infrequent mediastinal involvement. As 97% of the LPHD cases showed a complete or partial nodular growth pattern, their differentiation from TCRLBCL was a rare problem in the present series.

Epstein-Barr virus-positive diffuse large B-cell lymphoma, not otherwise specified: A diagnostic challenge

Epstein-Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) is an entity included in the 2016 World Health Organization classification of lymphoid neoplasms. EBV+DLBCL, NOS, is an aggressive B-cell lymphoma associated with chronic EBV infection and poor prognosis with standard chemotherapeutic approaches. We present the case of a 71-year-old male hospitalized for generalized lymphadenopathy, unexplained weight loss, and intermittent fever with pancytopenia and a very high EBV viral load. An inguinal lymph node was biopsied and reported at two different centers as Classic Hodgkin lymphoma and EBV associated lymphoproliferative, respectively. The patient was subsequently rebiopsied and a cervical lymph node was subjected to detail histopathologic and immunohistochemical evaluation by clonality studies resulting in a final diagnosis of EBV positive DLBCL, NOS. This case highlights the potential diagnostic pitfalls due to the morphologic heterogeneity of this entity and immunohistochemical overlap with Hodgkin lymphoma, T-cell rich large B-cell Lymphoma, and diffuse large B-cell lymphoma (DLBCL, NOS).

Equine Intestinal Lymphoma: Clinical-Pathological Features, Immunophenotype, and Survival

Lymphoma is the most common intestinal neoplasm in horses, but its clinical-pathological features are poorly characterized. Primary intestinal lymphoma was diagnosed in 20 horses on biopsy samples and further confirmed by postmortem examination in 16 cases. Lymphoma was found in the small intestine in 12 of 20 (60%), in the colon in 5 of 20 (25%), and in both small and large intestines in 3 of 20 (15%) cases. Gross findings included thickening of the intestinal wall (45%), mural nodules or masses (30%), and both thickening and nodules (10%). Cases were classified according to the human World Health Organization classification as enteropathy-associated T-cell lymphoma (EATL) type 1 (40%), EATL type 2 (45%), and T-cell-rich large B-cell lymphoma (TCRLBCL) (15%). With respect to histologic grade, 70% of cases were grade 1 and 30% were grade 2. Of EATLs, the infiltrate was mucosal only (12%), mucosal and submucosal (53%), or transmural (35%). EATL1 was submucosal to transmural (2/8 and 6/8), EATL2 was mucosal to submucosal (3/9 and 6/9), and TCRLBCL was always transmural. Epitheliotropism was present in most EATLs and characterized by single-cell infiltrates within the epithelium in EATL1 and intraepithelial clusters or plaques in EATL2. Median survival was 25 days for EATL1, 90 days for EATL2, and 187.5 days for TCRLBCL; differences were not statistically significant. Of the EATLs, grade 1 had a median survival of 60 days and grade 2 had a median survival of 25 days; differences were not statistically significant.

CD30 Cross-Reactivity and Expression in Feline Normal Tissues and Lymphomas.

CD30 is a transmembrane glycoprotein of the tumor necrosis factor receptor superfamily included in the diagnostic algorithm of human cutaneous, anaplastic large cell and Hodgkin lymphomas and represents an optimal therapeutic target for CD30+ tumors. Similar diagnostic and therapeutic approaches are largely missing for feline lymphomas. Cross-reactivity of the antihuman CD30 receptor clone Ber-H2 was investigated in feline lymphomas. Comparative analysis of feline and human CD30 identified 61% identity of the amino acid sequence, with 100% identity of the main sequence of the epitope targeted by the antibody (RKQCEPDYYL). CD30 expression in normal feline tissues was restricted to rare lymphoid cells in perifollicular and interfollicular lymph node areas and in the thymic medulla. In feline lymphoma, CD30 was expressed in 4 of 33 (13%) T-cell lymphomas, 3 of 22 (14%) B-cell lymphomas, and 5 of 7 (71%) mixed-cell lymphomas, showing diffuse (1/5) or multifocal (4/5) positivity restricted to neoplastic multinucleated lymphoid cells and binucleated cells consistent with Reed-Sternberg-like cells. Based on the human classification system, cell morphology, expression of multiple markers (mixed cell components), and CD30 positivity, these cases were considered most consistent with classical Hodgkin-like lymphoma (HLL). The other 2 mixed-cell lymphomas were CD30 negative and thus most consistent with either T-cell-rich large B-cell lymphoma (TCRLBCL) or nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). These findings provide multiple data supporting the cross-reactivity of the Ber-H2 anti-CD30 clone in feline tissues and give evidence of the usefulness of CD30 in the diagnostic evaluation of feline lymphoma.

Experience and Outcome of Patients with Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) over 8 Years

Introduction: NLPHL is an uncommon variant of Hodgkin lymphoma (HL) accounting for 5% incidence of all HL diagnoses. NLPHL represents a more indolent disease than classical HL, and is therefore managed uniquely. Unlike classical Hodgkin lymphoma (cHL), NLPHL shows CD20 immunoreactivity. Given the rarity of the disease, optimal management is unclear.Here we present our retrospective clinical experience of nine cases of NLPHL diagnosed over the last 8 years at our institution.Results: The median age at diagnosis was 45 years. Eight of the nine patients were males. The youngest patient was 21 years old and the oldest patient at diagnosis was 58 years old. One patient had Stage I, six had stage II and two patients had Stage-III disease. No patient had bone marrow involvement and only two patients had B symptoms. Interestingly, two sets of brothers diagnosed at different intervals were identified among this group of patients.Three out of seven patients with Stage I/II disease received radiation as the primary modality of treatment. Four patients received chemotherapy only and two patients received combined modality treatment( chemotherapy followed by radiation). Only the youngest patient received R-CVP (rituximab, cyclophosphamide, vincristine, and prednisone) to avoid anthracycline related long term toxicity. A total of four patient received R-CHOP, two of these also received involved site radiation therapy (ISRT).One patient received six cycles of AVD (doxorubicin, vincristine and dacarbazine).All the patients achieved complete response (CR) and durable remission except one patient. That particular patient had stage III NLPHL at diagnosis and was treated with R-CHOP initially. Three years later on relapse, he had T-cell rich large B cell lymphoma (TCRBCL) and is currently on a clinical trial with pembrolizumab and remains in complete remission.Conclusions: As has been the experience with other institutions, the majority of the cases of NLPHL at our institution have presented with early stage disease. Treatments have included R-CHOP regimens in most of the cases with durable remission in the majority. Although R-CVP is not the standard regimen for NLPHL, the one young patient who had stage III disease at diagnosis and received R-CVP, achieved CR and remains disease free five years later. This highlights the importance of non-anthracycline chemotherapy regimens as an option for particularly young or older frail patients.NLPHL occurs with higher than expected frequency among first-degree family members of patients with NLPHL as demonstrated in the Finnish Cancer Registry study reported in JCO 2013. Interestingly, in our small cohort, there were two sets of brothers identified with NLPHL, diagnosed metachronously. Unlike cHL, late relapse can occur as well as a propensity to transform to an aggressive B-cell Non-Hodgkin lymphoma. DisclosuresNo relevant conflicts of interest to declare.

Classification and clinical features in 88 cases of equine cutaneous lymphoma.

Equine cutaneous lymphoma is an uncommon disease that can present with variable clinical signs, immunosuppression, and rapid systemic disease progression. Various subtypes of equine lymphoma have been described and classified according to a veterinary adaptation of the World Health Organization classification system, but little data is available regarding the association between lymphoma subtypes and epidemiological criteria and/or clinical outcome. The objective of the current study was to classify previously diagnosed cases of equine cutaneous lymphoma and correlate subtypes with clinical data to investigate epidemiological trends and prognostic implications. Results from the study confirm T-cell-rich, large B-cell lymphoma (TCRLBCL) as the predominant subtype in equine cutaneous lymphoma. Cutaneous T-cell lymphoma (CTCL) was the second most common phenotype in the current study. To the authors' knowledge, a description of the morphological and immunohistochemical features of CTCL in horses, an epitheliotropic neoplasm similar to the cutaneous epitheliotropic lymphoma variant (mycosis fungoides) observed in human beings and canids, has not been previously described. Less common lymphoma subtypes identified in the study include diffuse large B-cell lymphoma and anaplastic large T-cell lymphoma. Quarter Horses almost exclusively developed TCRLBCL, while the frequency of CTCL was increased significantly in Thoroughbreds compared with other breeds. TCRLBCLs more frequently presented as multiple masses while CTCLs were more often solitary nodules. When multiple regions of the body were affected, 100% of cases were TCRBCL. Finally, there was an observable trend for longer survival in cases of TCRLBCL without local recurrence, suggesting adequate surgical excision may be an effective treatment modality.

Vanishing Bile Duct Syndrome Arising in a Patient With T-Cell–Rich Large B-Cell Lymphoma

Vanishing Bile Duct Syndrome Arising in a Patient With T-Cell–Rich Large B-Cell Lymphoma

HAEMACARE Project: Reclassifing Hematologic Neoplasias According Morphological Data.

Aims: The European Project HAEMACARE (VI Frame Research Program), is working in the reclassification of hematological neoplasias included in population based Cancer Registries of 13 European countries with the objective to improve and standardize morphological data validation.Patients and methods: a multidisciplinary research group of the I+CS integrated by epidemiologists, hematologists, pathologists is working in the reclassification of Hodgkin disease (HD) included in the population based Cancer Registry of Zaragoza (CRZ) in order to reclassify according to WHO and ICD-O classifications and identify the non other specification (NOS) cases. From January 1995 to December 2000, a total of 141 patients diagnosed as Hodgkin disease are included. The sources of data were: Zaragoza population based Cancer Registry, Aragon hematological malignancies Registry (FEHHA) and from the records of public Hospitals and the National Deaths Index. All cases were identified from the CRZ and 35 cases (24.8%) NOS were re-studied by the hematologists and pathologists and reclassified according histological and morphological subtypes of WHO classification. Diagnostic criteria were set for LRCHD: scattered Hodgkin-Reed-Sternberg cells with a classical immunophenotype in a background of small lymphocytes without admixture of eosinophils and neutrophils and without sclerosis nodular lymphocyte predominant HD (NLPHD), mixed cellular (MCD) and lymphocyte-rich classical HD (LRCHD). In 24.8% of cases were necessary to process the samples again or review smears and applied immunochemistry techniques in order to establish accurate diagnosis according the new sub-classification in NLPHD or CHD and distinguish some cases of T-cell rich large B-cell lymphoma. In addition we have calculated the estimated survival according specific morphological subtypes.Results:Hodgkin Disease. Histological distributionICD-0-3No%malesfemalesmean age(y)mean surv(y)No deaths (%)NOS*3524.8152043.75.813 (34.3)CHD6445.4392539.37.619 (29.7)MCD2114.915646.37.74 (19.0)LRCHD117.89251.16.75 (45.5)NLPHD107.06451.28.32 (20.0)Total141845743.27.143 (30.5)*non other specificationThe estimated survival analysis showed a mean of 7.6 years (95% CI: 6.7–8.4) for all cases, median not reached.Comments: In our study has been necessary to reclassify the 24.8% of cases according WHO criteria. The incidence peaks are classical. The overall survival is similar to describe previously.

Primary Intraocular T-Cell–Rich Large B-Cell Lymphoma

We report a primary intraocular T-cell-rich large B-cell lymphoma in a 57-year-old woman who underwent 3 diagnostic vitrectomies for a presumed diagnosis of panuveitis. She developed no light perception in the left eye and underwent enucleation. Histopathologic and immunohistochemical studies on the enucleated globe disclosed a primary intraocular large B-cell lymphoma involving the choroid, vitreous, and retina. A large population of T cells was identified among the neoplastic B-cell population. B-cell immunoglobulin gene rearrangement and T-cell receptor gene rearrangement studies using the polymerase chain reaction method indicated that a monoclonal immunoglobulin kappa light chain population was present and that the T-cell population was not monoclonal. This case highlights the importance of interpreting cytologic features in vitreous aspirates in the context of the clinical situation.

Primary intraocular T-cell-rich large B-cell lymphoma

Abstract We report a primary intraocular T-cell–rich large B-cell lymphoma in a 57-year-old woman who underwent 3 diagnostic vitrectomies for a presumed diagnosis of panuveitis. She developed no li...

Favorable Response to Treatment of a Child With T-Cell-Rich Large B-Cell Lymphoma Presenting With Liver Failure

The authors describe the successful management of a child with T-cell-rich large B-cell lymphoma (TCRBCL) involving the lymph nodes and liver, causing severe hepatic dysfunction. After immunohistochemical confirmation of the diagnosis, the patient was treated initially with low-dose, non-hepatotoxic chemotherapy and irradiation to the porta hepatis. Chemotherapy was gradually escalated to intensified B cell-lymphoma treatment regimens (CHOP, CYVE, COPAdM) as liver function improved. Despite prompt and notable response in the lymph nodes, the intrahepatic nodular lesions persisted radiologically. Liver function tests normalized during the course of treatment. However, radiologic studies of the liver showed abnormal regeneration with a predominant left lobe overshadowing a tiny right lobe. The patient remains in remission more than a year after completion of treatment. Judicious use of chemotherapeutic agents with or without local radiotherapy may influence the outcome and survival in children with TCRBCL involving the liver and causing abnormal hepatic function.

Transformation of Hodgkin’s disease to high-grade B-cell lymphoma: Remission after Rituximab monotherapy

We demonstrate the usefulness of immunotherapy with the CD20 antibody Rituximab in a case of transformation of Hodgkin's disease (HD) to high-grade non-Hodgkin's lymphoma (NHL). A 45-year-old women suffering from lymphocyte predominant HD of paragranuloma type (stage IVb) since 1995 showed mediastinal relapse despite of 6 cycles of chemotherapy following the COPP/ABVD-protocol in 1998. Again complete remission could be achieved after escalated BEA-COPP II therapy in May 1998. Six months later chest radiograph and CT depicted pulmonary nodules. The non-typical resection of the lung revealed pulmonary involvement of a high-grade T-cell rich large B-cell lymphoma with 100% of the tumoral cells CD20 positive. Since the symptoms occurred shortly after the BEA-COPP-escalated protocol chemotherapy resistance had to be assumed. Because of this problems and supported by the refusal of a high-dose chemotherapy with stem-cell transplantation by the patient we decided to perform a mono-immunotherapy with the monoclonal CD20 antibody Rituximab. Today, 14 months later, the patient is still in complete remission including the absence of B symptoms. Immunotherapy against CD20 positive cells in cases of sequential HD and NHL seems to be an effective therapy in chemotherapy resistant cases because of the suspected clonally relation of both diseases.

T-cell-rich large B-cell lymphoma in children and adolescents: a clinicopathologic report of six cases from the Children's Cancer Group Study CCG-5961.

T-cell-rich large B-cell lymphoma (TCRLBCL) is a morphologic subset of diffuse large B-cell lymphoma that has been confused with Hodgkin disease and reactive lymphadenopathies. To the authors' knowledge the majority of reports of TCRLBCL are from adults, and it is not widely recognized as occurring in the pediatric population. The current study reports a cohort of six cases of TCRLBCL from the Children's Cancer Group CCG-5961 study. Biopsies from patients entered on CCG-5961 were submitted for central pathology review and immunophenotyping. Six cases of TCRLBCL were identified and correlated with clinical characteristics. Of 86 cases centrally reviewed to date on CCG-5961, 20 (23%) were diagnosed as diffuse large B-cell lymphomas. Of these, 6 cases (7% of total cases and 30% of large B-cell cases) were TCRLBCL, based on a diffuse growth pattern with a minor population of neoplastic large B cells and an associated extensive reactive T-cell infiltrate. All patients with TCRLBCL were males ages 12-16 years. Three patients with TCRLBCL had advanced stage disease. No bone marrow or central nervous system involvement was detected in any case. TCRLBCL is a morphologic subtype of diffuse large B-cell lymphoma that may be difficult to recognize due to the extensive infiltrate of reactive T cells. This entity is not well recognized in pediatric patients, but in the current study represented 7% of all cases and 30% of large B-cell lymphomas received for central review from the ongoing CCG-5961 protocol. Because TCRLBCL may be confused with Hodgkin disease and reactive lymphadenopathies, it is essential that this entity be recognized in the pediatric age group.