Search

Objective: To investigate the clinicopathologic features of progressively transformed germinal center-like follicular T-cell lymphoma (PTGC-like FTCL). Methods: The clinicopathologic data of 14 PTGC-like FTCL cases that were diagnosed at the Beijing Friendship Hospital Affiliated to the Capital Medical University from January 2017 to January 2022 were retrospectively collected. Clinicopathological features, immunophenotype, and Epstein-Barr virus (EBV) infection status were analyzed in these cases. Polymerase chain reaction (PCR) was performed to detect the clonal gene rearrangements of T cell receptor (TCR) and the immunoglobulin (Ig) in 10 and 8 cases, respectively. Results: The male to female ratio was 5∶2. The median age was 61 years (range 32-70 years). All patients had lymphadenopathy at the time of diagnosis. By using the Ann Arbor system staging, seven cases were classified as stage Ⅰ-Ⅱ, and seven cases as stage Ⅲ-Ⅳ. Seven cases had B symptoms, four cases had splenomegaly, and two cases had skin rash and pruritus. Previously, three cases were diagnosed as classic Hodgkin's lymphoma, three cases as small B-cell lymphoma, two cases as atypical lymphoid hyperplasia unable to exclude angioimmunoblastic T-cell lymphoma (AITL), one case as EBV-associated lymphoproliferative disorder, and one case as peripheral T-cell lymphoma (PTCL) associated with the proliferation of B cells. All the 14 cases showed that the large nodules were composed of mature CD20+, IgD+B lymphocytes admixed with small aggregates of neoplastic cells with pale to clear cytoplasm. Moreover, hyperplastic germinal centers (GCs) and Hodgkin/Reed-Sternberg-like (HRS-like) cells were seen within these nodules in two and five cases, respectively. The neoplastic cells expressed CD3 (14/14), CD4 (14/14), PD1 (14/14), ICOS (14/14), CD10 (9/14), bcl-6 (12/14), CXCL13 (10/14), and CD30 (10/14). The HRS-like cells in five cases expressed CD20 (2/5), PAX5 (5/5), CD30 (5/5), CD15 (2/5), LCA (0/5), OCT2 (5/5) and BOB1 (2/5). Moreover, neoplastic T cells formed rosettes around HRS-like cells. EBV-encoded RNA (EBER) in situ hybridization showed scattered, small, positive bystander B lymphocytes in 8/14 cases, including 3/5 cases containing HRS-like cells. All tested cases (including five with HRS-like cells) showed monoclonal TCR gene rearrangement and polyclonal Ig gene rearrangement. Conclusions: PTGC-like FTCL is a rare tumor originated from T-follicular helper cells. It could be distinguished from angioimmunoblastic T-cell lymphoma by the formation of follicular structure, and lack of follicular dendritic cell proliferation outside the follicles and the polymorphous inflammatory background. In addition, it should be differentiated from lymphocyte-rich classical Hodgkin's lymphoma and low-grade B cell lymphoma.

Objective: To investigate the clinical, pathological and immunophenotypic features, molecular biology and prognosis of fibrin-associated large B-cell lymphoma (LBCL-FA) in various sites. Methods: Six cases of LBCL-FA diagnosed from April 2016 to November 2021 at the Beijing Friendship Hospital, Capital Medical University, Beijing, China and the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China were collected. The cases were divided into atrial myxoma and cyst-related groups. Clinical characteristics, pathological morphology, immunophenotype, Epstein Barr virus infection status, B-cell gene rearrangement and fluorescence in situ hybridization of MYC, bcl-2, bcl-6 were summarized. Results: The patients' mean age was 60 years. All of them were male. Three cases occurred in atrial myxoma background, while the others were in cyst-related background, including adrenal gland, abdominal cavity and subdura. All cases showed tumor cells located in pink fibrin clot. However, three cyst-related cases showed the cyst wall with obviously fibrosis and inflammatory cells. All cases tested were non germinal center B cell origin, positive for PD-L1, EBER and EBNA2, and were negative for MYC, bcl-2 and bcl-6 rearrangements, except one case with MYC, bcl-2 and bcl-6 amplification. All of the 5 cases showed monoclonal rearrangement of the Ig gene using PCR based analysis. The patients had detailed follow-ups of 9-120 months, were treated surgically without radiotherapy or chemotherapy, and had long-term disease-free survivals. Conclusions: LBCL-FA is a group of rare diseases occurring in various sites, with predilection in the context of atrial myxoma and cyst-related lesions. Cyst-related lesions with obvious chronic inflammatory background show more scarcity of lymphoid cells and obvious degeneration, which are easy to be missed or misdiagnosed. LBCL-FA overall has a good prognosis with the potential for cure by surgery alone and postoperative chemotherapy may not be necessary.

Objective: To investigate the clinicopathological features of angioimmunoblastic T-cell lymphoma pattern Ⅰ (AITL Pattern Ⅰ). Methods: The clinicopathological data of 11 AITL Pattern Ⅰ cases that were diagnosed at the Beijing Friendship Hospital Affiliated to Capital Medical University (10 cases) and Beijing Lu Daopei Hospital (1 cases) from January 2019 to October 2021 were retrospectively collected. Immunophenotype, Epstein-Barr virus infection status and T cell receptor (TCR) clonality of the tumor cells were tested, and clinicopathological features of cases were analyzed. Results: Among the 11 AITL Pattern Ⅰ cases, the male to female ratio was 1.2∶1.0. The median age was 59 years (range 47-78 years). Seven cases had B symptoms, while eleven cases presented with systemic lymphadenopathy. According to Ann Arbor system staging, two cases were classified as stage Ⅰ-Ⅱ, and 9 cases as stage Ⅲ-Ⅳ. Hepatosplenomegaly was present in two cases (2/11), three cases (3/11) had skin rash and pruritus, and two cases (2/11) had pleural effusion. Previously, 6 cases (6/11) were diagnosed as reactive hyperplasia, 1 case (1/11) as EBV-associated lymphoproliferative disorder, and 4 cases (4/11) as hyperplasia of lymphoid tissue, which was unable to exclude lymphoma. Histologically, all the 11 cases showed hyperplastic follicles in the paracortical regions with well-formed germinal centers. The hyperplastic follicles showed ill-defined borders and attenuated mantle zones in 7 cases. Mantle zones completely disappeared in 4 cases. The follicles were surrounded by a thin layer of atypical lymphocytes with bright or faintly stained cytoplasm. In 2 cases, the clear cells were located between the germinal centers and the thin residual mantle cell layers, showing a circular growth pattern. The cells were medium in size, with irregular karyotype, coarse chromatin and indistinct nucleoli. Immunohistochemically, CD21 staining showed that the meshworks of follicular dendritic cells(FDC)were mainly confined to the follicles. There was a subtle expansion of the meshworks of FDC in 4 cases with ill-defined borders. The atypical cells surrounding the follicles expressed CD3 (11/11), CD4 (11/11), PD-1 (11/11), CXCL13 (6/11), ICOS (10/11) and CD10 (7/11). PD-1 staining showed a strong perifollicular pattern, and a small number of positive cells were scattered around the high endothelial veins in the interfollicular region. CXCL13, ICOS and CD10 showed similar distribution patterns. EBV-encoded small RNA probe (EBER) in situ hybridization showed that EBER positive B lymphocytes were scattered in the interfollicular region (5-20/HPF) in all cases. T cell receptor gene rearrangement was monoclonal in all cases. Conclusions: Diagnosing AITL Pattern Ⅰ may be challenging and requires comprehensive analysis of clinical manifestations, histological morphology, immunophenotype and gene rearrangement results.

Objective: To investigate the clinicopathological features and prognosis of cytotoxic T-cell lymphoma (CTL). Methods: The clinicopathological data of 134 CTL patients in Beijing Friendship Hospital Affiliated to Capital Medical University, the 989 Hospital of PLA Joint Logistics Support force (formerly the 152 Hospital) and the Fourth Hospital of Hebei Medical University from 2008 to 2020 were retrospectively collected. Immunophenotype, Epstein-Barr virus infection status and T cell receptor (TCR) clonality of tumor cells were assessed, and clinicopathological features and prognosis of patients were analyzed. Results: Among the 134 CTL patients, the male to female ratio was 1.7∶1.0, the median age was 49.5 years (range 3-83 years), and 100 cases (74.6%) were under 60 years old. Forty-six point nine percent of the patients (53/113) had B symptoms. Most of the patients presented with systemic superficial lymphadenopathy. According to the Ann Arbor staging system, 36.8% (39/106) of the patients were in stage Ⅰ-Ⅱ, and 63.2% (67/106) in stage Ⅲ-Ⅳ. The rate of extranodal involvement was 51.6% (66/128). Spleen was involved in 24.2% (31/128) of the cases. Morphology showed diffuse growth of abnormal lymphocytes, infiltrating and destroying normal tissue structure. Immunohistochemical staining showed that tumor cells expressed T cell antigens (CD2, CD3, CD5, and CD7), and 72.0% (77/107) of them had decreased or lost expression of one or more antigens. According to the numbers of CD4 and CD8 expression in tumor cells, 70 cases (52.2%) were grouped into CD8 + >CD4 + group. The expression rates of TIA-1 and granzyme B were 99.2% (119/120) and 79.8% (95/119), respectively. CD20 abnormal expression rate was 27.6% (37/134) and CD56 was negative in all cases. The median Ki-67 proliferative index was 45.0% (range 5%-80%). In situ hybridization of small RNA encoded by Epstein-Barr virus was negative. Clonal TCR gene rearrangement analysis was performed on 49 cases and was positive in all cases. Ninety-one patients were followed up for a median of 36 months (range, 1 to 240 months), and 40 of the 91 patients (44.0%) died. The twenty-three patients were in complete remission (including 13 cases with localized single extranodal mass). The 3-year and 5-year overall survival rates were 53.5% and 49.4%, respectively. Univariate analysis showed that B symptom, spleen involvement, extranodal involvement, clinical stage, CD8 + >CD4 + phenotype, abnormal expression of CD20 and Ki-67 proliferation index (>60%) were associated with overall survival ( P <0.05). The multivariate Cox regression analyses showed that spleen involvement and CD8 + >CD4 + phenotype were independent prognostic factors for overall survival in CTL patients. Conclusions: CTL are more commonly found in adult males under 60 years old, often accompanied by B symptom, with a high proportion of extranodal involvement and more CD8 positive phenotypes. Spleen involvement and CD8 + >CD4 + phenotype are independent predictors of CTL overall survival. Some patients with localized extranodal CTL may have a good prognosis.

Objective: To investigate the translocations of MYC, bcl-2 and bcl-6 genes, the Epstein-Barr virus (EBV) status and the clinicopathological features of primary cardiac large B cell lymphoma (LBCL). Methods: Seven cases of primary cardiac LBCL were collected at Beijing Friendship Hospital, Capital Medical University, China from February 2013 to May 2019. The clinical feature, pathological morphology and immunophenotype were analyzed. The detections of EBV and gene rearrangements of MYC, bcl-2 and bcl-6 were conducted. The 2017 WHO classification of tumors of haematopoietic and lymphoid tissues was used to classify the tumors. Results: Four patients with right atrial lesions showed diffuse infiltration of medium size lymphoid cells with small vascular hyperplasia, without evidence of EBV infection. Without detectable gene rearrangements of MYC and bcl-2, 2 of the patients showed bcl-6 gene break-apart. The diagnosis was revised from diffuse LBCL to high-grade B-cell lymphoma, not otherwise specified (HGBL-NOS). There was a case of CD5 + diffuse LBCL involving the right atrium and ventricle and 2 cases of fibrin-associated diffuse LBCL located at left atrium without gene rearrangements of MYC, bcl-2 and bcl-6. However, EBER and EBNA2 were highly expressed in fibrin-associated diffuse LBCL. The patients were followed up for 10-71 months. Four cases of HGBL-NOS and a case of CD5 + diffuse LBCL received R-CHOP with/without autologous stem cell transplantation. All but two patients survived. Two cases of fibrin-associated diffuse LBCL were disease free without adjuvant chemotherapy and radiotherapy. Conclusions: Primary cardiac LBCL is heterogeneous, including at least HGBL-NOS. Primary cardiac HGBL-NOS most frequently occurs in the right atrium. Tumor cells of primary cardiac LBCL have the morphological characteristics similar to Burkitt lymphoma, lacking MYC and bcl-2 gene rearrangements, but usually show bcl-6 gene disruption. Fibrin-associated diffuse LBCL has a good prognosis and postoperative chemotherapy seems unnecessary.

Objective: To investigate the clinicopathological features of EBV-positive T/NK cell lymphoproliferative diseases (EBV(+) T/NK-LPD). Methods: The clinical characteristics of 156 cases of EBV(+) T/NK-LPD were collected from August 2002 to March 2015 at Beijing Friendship Hospital, Capital Medical University. Immunohistochemical staining, EBER in situ hybridization and clonal analysis of TCR gene were performed. All patients were followed up. Results: There were 106 male and 50 female patients; patients' age ranged from 1 to 75 years (median 20 years). The course of the diseases before diagnosis ranged from 2 to 540 months (median 20 months). Fever was noted in 122 patients (78.2%), 108 patients had lymphadenopathy (69.2%), and 75 patients had hepatosplenomegaly (48.1%). Thirty-three cases were grade 1, 68 cases were grade 2, and 55 cases were grade 3. TCR gene arrangement analysis was performed in 45 cases, and 33 cases (73.3%) showed clonal rearrangement. The follow-up period ranged from 1-134 months, and 44 patients (28.2%) died. There was a trend of increased death rate associated with increasing grade ( P >0.05). Conclusions: There are many types of EBV(+) T/NK-LPD, and they can be classified as systemic, relatively localized and localized. The prognosis should be based on a comprehensive analysis of pathology and clinical data. There is no significant correlation between morphological grade and mortality. An important goal of therapy is to prevent serious complications.

In recent years, there are increasing articles concerning Epstein-Barr virus associated lymphoproliferative disorder (EBV+ LPD), and the name of EBV+ LPD is used widely. However, the meaning of EBV+ LPD used is not the same, which triggered confusion of the understanding and obstacles of the communication. In order to solve this problem. Literature was reviewed with combination of our cases to clarify the concept of EBV+ LPD and to expound our understanding about it. In general, it is currently accepted that EBV+ LPD refers to a spectrum of lymphoid tissue diseases with EBV infection, including hyperplasia, borderline lesions, and neoplastic diseases. According to this concept, EBV+ LPD should not include infectious mononucleosis (IM) and severe acute EBV infection (EBV+ hemophagocytic lymphohistiocytosis, fatal IM, fulminant IM, fulminant T-cell LPD), and should not include the explicitly named EBV+ lymphomas (such as extranodal NK/T cell lymphoma, aggressive NK cell leukemia, Burkitt lymphoma, and Hodgkin lymphoma, etc.) either. EBV+ LPD should currently include: (1) EBV+ B cell-LPD: lymphomatoid granulomatosis, EBV + immunodeficiency related LPD, chronic active EBV infection-B cell type, senile EBV+ LPD, etc. (2) EBV+ T/NK cell-LPD: CAEBV-T/NK cell type, hydroa vacciniforme, hypersensitivity of mosquito bite, etc. In addition, EBV+ LPD is classified, based on the disease process, pathological and molecular data, as 3 grades: grade1, hyperplasia (polymorphic lesions with polyclonal cells); grade 2, borderline (polymorphic lesions with clonality); grade 3, neoplasm (monomorphic lesions with clonality). There are overlaps between EBV+ LPD and typical hyperplasia, as well as EBV+ LPD and typical lymphomas. However, the most important tasks are clinical vigilance, early identification of potential severe complications, and treating the patients in a timely manner to avoid serious complications, as well as the active treatment to save lives when the complications happened.

Objective: To study the clinicopathologic features, immunophenotype, clonality and Epstein-Barr virus (EBV) status of systemic EBV-positive T/NK-cell lymphoproliferative disease in adults (ASEBV(+)T/NK-LPD)., Methods: Twenty cases of ASEBV(+)T/NK-LPD were analyzed retrospectively with histopathologic review, immunohistochemistry and in-situ hybridization for EBV-encoded RNA (EBER). The follow-up data were collected., Results: There were altogether 15 males and 5 females. The median age of the patients was 34 years. The average duration from onset of symptoms to diagnosis was 8.7 months. Fever (18/20), hepatosplenomegaly (18/20) and lymphadenopathy (17/20) were the main clinical manifestations. Eleven of the 17 patients died during follow-up, with a mean survival of 2.9 months. Histologically, there was obvious expansion of T zone of the involved lymph nodes, associated with diminished lymphoid follicles. The interfollicular areas were widened and infiltrated by small to median-sized lymphoid cells which showed only mild atypia. Scattered large lymphoid cells were not uncommon. The nodal capsule was thickened in 6 cases. Focal necrosis was seen in 9 cases. Sinus histiocytic proliferation with erythrophagocytosis was observed in 3 cases. In addition, there were mild atypical lymphoid cells infiltrate into the liver, spleen, intestinal mucosa and bone marrow. Immunohistochemical study and in-situ hybridization showed that the EBER-positive cells were of T-cell lineage, with CD3 expression. They were also positive for cytotoxic molecules (granzyme B or TIA-1). Only 1 case was CD56 positive. A predominance of CD8-positive cells was demonstrated in 8 of the 14 cases studied, while CD4-positive cells predominated in the remaining 5 cases. One case showed similar proportion of CD8 and CD4-positive cells. The number of EBER-positive cells ranged from 30 to more than 300 per high-power fields. These EBER-positive cells were of small to large size and located mainly in the expanded T zone and occasionally in the germinal centers. Three of the 7 cases exhibited clonal rearrangement of T-cell receptor gamma gene, while the other 4 cases exhibited polyclonal rearrangement of T-cell receptor gamma gene., Conclusions: ASEBV(+)T/NK-LPD is a systemic disease with a subacute or chronic clinical course. Most patients suffer from relapsing fever, lymphadenopathy and hepatosplenomegaly. The disease is characterized by proliferation of EBV-infected cytotoxic T cells. The T zone of the involved lymph nodes shows expansion by mildly atypical lymphoid cells. The disease is associated with poor clinical outcome and can be life-threatening. The patients often die of multiorgan failure and bleeding.

Objective: To study the clinicopathologic features, diagnosis and differential diagnosis of systemic Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disease of childhood (CSEBV(+)T-LPD)., Methods: Thirty cases of CSEBV(+)T-LPD were retrospectively studied by light microscopy, immunohistochemistry and in-situ hybridization for EBV-encoded RNA (EBER). The clinical information and follow-up data were analyzed., Results: Nineteen of the 30 patients were males and 11 females. The median age of disease onset was 9 years (range = 1.5 to 32 years). The average duration between disease onset and diagnosis was 14 months. The major clinical manifestations were fever (96.7%), lymphadenopathy (83.3%) and hepatosplenomegaly (66.7%). Cutaneous manifestations were not uncommon, which included hypersensitivity to mosquito bite (13.3%) and skin rash (20.0%). Six of the 20 patients died on follow up. Histologically, the lymph nodes showed expansion of T zone, with diminished or effaced lymphoid follicles. The lymphoid cells were of small to medium size. Scattered large lymphoid cells were also identified in the expanded T zone. Furthermore, the liver and spleen showed mild to marked sinusoidal infiltration. In some cases, various degrees of sinus histiocytosis with erythrophagocytosis were present. Skin biopsies showed mild to marked degree of lymphocytes infiltration in dermis. Immunohistochemical study and in-situ hybridization showed that the EBER-positive cells were of T lineage and CD3 positive. They also expressed cytotoxic molecules granzyme B and TIA-1. Seven of the 8 cases examined were CD8 positive, while the remaining case was mainly CD4 positive. Thirteen of 15 cases were shown to be CD56 negative. The number of EBER-positive cells ranged from 5 to more than 500 per high-power field. These cells included small to large lymphoid cells located mostly in the expanded T zone and sometimes in the germinal centers. Nine of the 30 cases, which consisted mainly of medium to large-sized lymphoid cells, were also EBER positive., Conclusions: Systemic EBV-positive T-cell lymphoproliferative disease of childhood occurs most often in children and young adults, with a median age of 9 years. It has a subacute or chronic clinical course. Most of the patients have evidence of systemic disease, often with lymph node, liver, spleen and skin involvement. It carries a poor clinical outcome and can be life-threatening. The disease is characterized by a clonal proliferation of EBV-infected T cells with cytotoxic immunophenotype. Definitive diagnosis requires correlation between clinical, pathologic and ancillary investigation findings.