Qunpei Yang

Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells

Lymphomas arising from NK or γδ-T cells are very aggressive diseases and little is known regarding their pathogenesis. Here we report frequent activating mutations of STAT3 and STAT5B in NK/T-cell lymphomas (n=51), γδ-T-cell lymphomas (n=43) and their cell lines (n=9) through next generation and/or Sanger sequencing. STAT5B N642H is particularly frequent in all forms of γδ-T-cell lymphomas. STAT3 and STAT5B mutations are associated with increased phosphorylated protein and a growth advantage to transduced cell lines or normal NK cells. Growth-promoting activity of the mutants can be partially inhibited by a JAK1/2 inhibitor. Molecular modelling and surface plasmon resonance measurements of the N642H mutant indicate a marked increase in binding affinity of the phosphotyrosine-Y699 with the mutant histidine. This is associated with the prolonged persistence of the mutant phosphoSTAT5B and marked increase of binding to target sites. Our findings suggest that JAK-STAT pathway inhibition may represent a therapeutic strategy.

Subtype distribution of lymphomas in Southwest China: Analysis of 6,382 cases using WHO classification in a single institution

BackgroundThe subtype distribution of lymphoid neoplasms in Southwest China was analyzed according to WHO classifications. This study aims to analyze subtype distribution of lymphomas in southwest China.MethodsLymphoid neoplasms diagnosed within 9 years in a single institution in Southwest China were analyzed according to the WHO classification.ResultsFrom January 2000 to December 2008, a total number of 6,382 patients with lymphoma were established, of which mature B-cell neoplasms accounted for 56%, mature T- and NK-cell neoplasms occupied 26%, and precursor lymphoid neoplasms and Hodgkin lymphomas were 5% and 13%, respectively. Mixed cellularity (76%) was the major subtype of classical Hodgkin lymphoma; and the bimodal age distribution was not observed. The top six subtypes of non-Hodgkin lymphoma were as follows: diffuse large B-cell lymphoma, extranodal NK/T-cell lymphoma, nasal type, extranodal marginal zone lymphoma of mucosa associated lymphoid tissue, follicular lymphoma, precursor lymphoid neoplasms, and chronic lymphocytic leukemia/small lymphocytic lymphoma. Extranodal lymphomas comprised about half of all cases, and most frequently involved Waldeyers ring, gastrointestinal tract, sinonasal region and skin.ConclusionsThe lymphoid neoplasms of Southwest China displayed some epidemiologic features similar to those reported in literature from western and Asian countries, as well as other regions of China, whereas some subtypes showed distinct features. The high frequency of mature T/NK cell neoplasms and extranodal lymphomas, especially for extranodal NK/T-cell lymphoma, nasal type, is the most outstanding characteristic of this series.

Distribution of Lymphoid Neoplasms in China Analysis of 4,638 Cases According to the World Health Organization Classification

To estimate the distribution of lymphoid neoplasms in China, we conducted a comprehensive analysis, based on subtype, age, sex, and lesion, of primary and resected biopsy specimens of 4,638 lymphoid neoplasms diagnosed from 2004 to 2008 at 5 large hospitals. Of the 4,638 patients, mature B-cell neoplasms accounted for 64.3% of all lymphoid neoplasms, mature T/NK-cell neoplasms for 23.3%, and Hodgkin lymphoma for 8.6%. The most common subtype was diffuse large B-cell lymphoma (36.2%), followed by extranodal NK/T-cell lymphoma, nasal type (11.0%), classic Hodgkin lymphoma (8.4%), extranodal marginal zone B-cell lymphoma (7.7%), plasmacytic neoplasm (5.0%), and peripheral T-cell lymphoma, not otherwise specified (3.9%). For most lymphoid neoplasm subtypes, male subjects showed higher rates than female subjects. In summary, our study showed that the epidemiologic features of lymphoid neoplasms in China are distinct from those in Western countries and similar in many ways to those in other countries of the Far East.

Phase 2 trial of "sandwich" L-asparaginase, vincristine, and prednisone chemotherapy with radiotherapy in newly diagnosed, stage IE to IIE, nasal type, extranodal natural killer/T-cell lymphoma.

Extranodal natural killer/T‐cell lymphoma (ENKTL), nasal‐type, is a distinct entity of lymphoid tissue. ENKTL is sensitive to radiotherapy (RT), but the prognosis is poorer than for other types of early lymphoma. The treatment schedule is controversial.

Hepatosplenic T-cell lymphoma: clinicopathologic, immunophenotypic, and molecular characterization of17 Chinese cases

Hepatosplenic T-cell lymphoma is a highly aggressive tumor with a poor outcome. About 210 cases were identified through PubMed, of which fewer than 20 originated in Asia. We reviewed 17 Chinese cases of hepatosplenic T-cell lymphoma, including an unusual one with cutaneous pink papules, for clinicopathologic, immunophenotypic, and genotypic features; Epstein-Barr virus status; treatment; and outcome. The median age of the patients was 23 years. All patients had splenomegaly, and 88.2% of them had hepatomegaly as well. Bone marrow involvement was present in 53.3%. Eleven patients underwent splenectomy for diagnosis and treatment. Twelve specimens were collected by image-guided liver core biopsy or wedge resection. Histologically, the homogeneous small- to medium-size neoplastic lymphoid cells infiltrated the sinuses or sinusoids of the spleen, bone marrow, and liver. Diagnosis was based on image-guided core-needle biopsy of the liver alone in 41.2% of the cases. Immunohistochemically, 15 of the lesions were hepatosplenic γδ T-cell lymphoma, and the remaining 2 were hepatosplenic αβ T-cell lymphoma. Epstein-Barr virus was detected in both cases of hepatosplenic αβ T-cell lymphoma and one case of hepatosplenic γδ T-cell lymphoma. Most of the patients received cyclophosphamide, doxorubicin, vincristine, and prednisone therapy or regimens similar to it. Follow-up data were available in 70.6% of the patients; half of them died of the tumor, and the median survival time was 6 months. The frequency of bone marrow involvement was lower than that reported in the literature. Image-guided core-needle biopsy of the liver is recommended for diagnosis.

Extranodal nasal type natural killer/T-cell lymphoma of testis: report of seven cases with review of literature

Abstract Seven cases of testicular extranodal natural killer (NK)/T-cell lymphoma, nasal type, are reported, with a literature review. Two patients had a testicular lesion as the initial presentation, four had a history of nasal NK/T-cell lymphoma and the remaining patient had concomitant involvement of an adrenal gland. All patients underwent orchiectomy followed by chemotherapy (CT) and/or radiotherapy (RT). Follow-up data showed that two patients with non-primary tumors died of disease within 6 and 11 months, respectively. Histologically, the tumor had a diffuse growth pattern largely replacing the interstitial tissues. Neoplastic cells showed prominent angiocentric and angioinvasive features with focal coagulative necrosis and apoptotic bodies. Immunohistochemically, all cases were positive for cytoplasmic CD3ε and CD56. Epstein–Barr virus infection was demonstrated in all cases. Testicular NK/T-cell lymphoma, whether primary or secondary, was generally very aggressive with a poor outcome despite multimodality therapy. Novel molecular therapeutic targets and more effective treatments are needed, especially for disseminated or recurrent cases.

Hydroa vacciniforme-like lymphoma of an adult: a case report with review of the literature

Hydroa vacciniforme-like lymphoma (HVL) is a rare type of Epstein-Barr virus (EBV)-positive lymphoma of cytotoxic T-cell or natural killer cell origin that mainly affect children, characterized by a vesicopapular skin eruption that clinically resemble hydroa vacciniforme (HV). In current study, we report an adult patient with the tumor. The patient presented similar morphologic, immunophenotypic and genotypic changes of the disease with that occurred in children, whereas clinically, he showed a prolonged clinical course without hepatosplenomegaly or generalized lymphadenopathy. Whether there are some differences in biologic behavior between children and adults still remains unknown and it is necessary to collect more data to observe and to investigate in the future.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7644172219178472

Extraosseous (extramedullary) plasmacytomas: a clinicopathologic and immunophenotypic study of 32 Chinese cases

BackgroundExtraosseous plasmacytoma, so called extramedullary plasmacytoma (EMP) is relatively rare in China. The aim was investigate the clinicopathologic features of EMP and the role of Immunophenotype and genotype detection in diagnosis of EMP.MethodsThirty-two cases of EMP were investigated retrospectively by histopathology, immunophenotype, genotype and survival analysis.ResultsClinically, the mean age of the patients was 53.4. Most of the patients received no treatment after the diagnosis was established, and the prognosis was relatively poor. Histologically, in 40% of the cases, the neoplastic cells were grade II or III. The neoplastic cells expressed one or more PC associated antigens. The immunophenotype of EMP and inflammation of sinonasal regions with numerous PC infiltrations were compared and showed some difference in expression of CD45, CD27, CD44v6 and Bcl-2 as well. Ig light chain restriction was detected in 87.5% of the cases.Conclusionswe described 32 Chinese cases of EMP, compare with that reported in the literature, some differences are presented, including higher percentage of grade II and III cases, clinically inconsistent treatment and management as well as poor outcome of the disease.

Five-year analysis from phase 2 trial of "sandwich" chemoradiotherapy in newly diagnosed, stage IE to IIE, nasal type, extranodal natural killer/T-cell lymphoma.

The “sandwich” protocol, was first proposed by us and comprised of l‐asparaginase, vincristine, and prednisone chemotherapy with radiotherapy, results in 2‐year overall survival and progression‐free survival rates that surpass traditional therapies for patients with newly diagnosed, stage IE‐IIE, nasal type, extranodal natural killer/T‐cell lymphoma. The results had been published by cancer. These patients were followed up over a median period of 67 months, for which updates and the results of prognostic factors analyses are presented. The 5‐year overall survival and progress‐free survival rates were both 64%. The highest rates of death occurred during the first 6 months, and between the second and third year after enrollment. The initial therapeutic response (odds ratio = 5.83; P = 0.001) and B symptoms (odds ratio = 6.13; P = 0.043) were significant prognostic factors for overall survival. However, the international prognostic index was not significant for progress‐free survival and overall survival. There were no severe long‐term side effects. These results indicate that the “sandwich” protocol may benefit the long‐term survival of patients with newly diagnosed stage IE‐IIE, nasal type, extranodal natural killer/T‐cell lymphoma. However, additional studies with larger samples are required to confirm these results. This study is registered at www.Chictr.org (ChicTR‐TNC‐09000394).

Gastrointestinal Lymphoma in Southwest China: Subtype Distribution of 1,010 Cases Using the WHO (2008) Classification in a Single Institution

The gastrointestinal tract (GIT) is the most common anatomic site of extranodal non-Hodgkin lymphoma (NHL) involvement. The classification criteria of lymphoma have changed in recent decades, and few large-sample studies regarding subtype analysis of lymphoma have been performed in this site. Aim: Therefore, the present study was conducted to analyze the histological subtype distribution of the GIT. Method: All patients in a single institution with a diagnosis of primary NHL in the GIT were enrolled between January 2007 and April 2014. The patients were categorized according to the WHO (2008) classification of tumors of hematopoietic and lymphoid tissue. Result: A total of 1,010 eligible cases diagnosed as NHL were collected in this study. The male:female ratio was 1.7:1 and the median age was 55 years. The percent of patients with lymphoma involvement in the stomach was 52% (n = 522), and the remaining 48% (n = 484) had intestinal tract involvement. Histologically, diffuse large B cell lymphoma (DLBCL) was the most common subtype in all of the GIT lymphoma cases, and was also the most common subtype in cases involving the stomach (78%) and the intestinal tract (53%). The incidence of DLBCL and mucosa-associated lymphoid tissue lymphoma in the stomach was significantly higher than the incident in the intestinal tract (p < 0.01). T and NK cell lymphoma was significantly more common in the intestinal tract than in the stomach (p < 0.01). Extranodal NK/T cell lymphoma nasal type (ENKTL-N) was the most common subtype of T and NK cell lineage lymphoma in GIT and was also the second most common intestinal tract-involved lymphoma. Conclusion: DLBCL was the most frequent lymphoma in the stomach and in the intestinal tract. T and NK cell lineage lymphoma had a higher occurrence in the intestinal tract than in the stomach. ENKTL-N was the most frequent subtype of lymphoma derived from NK/T cell lineage, and was the second most common lymphoma among all intestinal tract lymphomas.