Objective To clarify clinical and morphological features and immunophenotype and Epstain-Barr virus infection of neoplastic cell rich Hodgkin's lymphoma (NCRHL)and to further improve our knowledge and pathological diagnosis for NCRHL. Methods 10 cases of NCRHL were analyzed for clinical features, morphology, immunophenotype, Epstein-Barr virus infection using routine eosin and haematoxylin stain, immunohistochemistry, Epstain-Barr virus encoded small RNA (EBER) in situ hybridization and combining clinical data. Results (1)NCRHL were more common in young people. The median age of the patients was 25.5 years old. The ratio of male to female was 1:2.3. Superficial lymph nodes were most frequently involved. Masses of mediastinum were seen commonly. Clinical manifestation of the patients included B symptom (6 cases), pruitus (5 cases) and anemia (1 case). (2)Architecture of lymph nodes were effected. Necrosis was seen in some cases. There were more tumor cells in NCRHL than that in the classical Hodgkin's lymphoma. The tumor cells were distributed in piece or patch or diffuse. The morphology of neoplastic cells was wore variable including Hodgkin-like cells, lacunar cell-like, mummy cell-like and anaplastic large cell-like, singular nucleated cells, and multinucleated giant cell-like cells. Numerous neutrophils and eosinophils were present in a few cases. Focal sheet, necrosis granulomatosis-like and diffuse growth pattern were found in NCRHL. (3)All of the cases were positive for CD30 and PAX-5.2/10 (20%) cases were CD15 positive. LCA, CD20 and CD3 were negative. (4)EBER was not detected in all 6 tested cases. (5)Follow up data was obtained in 8/10 cases, in which one patient was dead, one case relapsed in half a year,and the other 6 cases reached complete regression. Conclusion NRCHL is characterized mainly by neoplastic cell rich morphologically and focal sheet, necrosis granulomatosis-like and diffuse growth pattern.EBER was not detected in this tumor. Some cases have aggressive clinic process with a unfavourable prognosis. New treatment regimen should be explored.

Objective: To investigate clinicopathologic features and prognostic factors of mantle cell lymphoma(MCL). Methods: The clinical data of 349 MCL patients diagnosed at Beijing Friendship Hospital from January 2004 to January 2016 were retrospectively collected. Corresponding histological sections were reviewed. Additional studies included immunohistochemical staining using the MaxVision two-step method, IgH/CCND1 fusion gene detection by fluorescent in situ hybridization (FISH), and correlative statistical analysis. Results: Of 349 patients with MCL, the median patient age was 61 years (range: 25-83 years, M∶F=2.7∶1.0) and the age of 243 patients ranged from 51 to 70 years (69.6%). Those with B symptoms accounted for 22.4% (70/313). Most of the patients presented with superficial lymphadenopathy and the clinical stage Ⅲ-Ⅳ accounted for 76.1% (235/309). Extranodal involvement was seen in 47.9% (148/309), among which the gastrointestinal tract accounted for 31.8% (47/148) and splenic involvement accounted for 15.4% (47/305). Three hundred and nine (88.5%) cases were of classical type and 40 (11.5%) cases were of aggressive variant type, and all were composed of proliferating lymphoid cells. All the tumors were positive for CD20 and cyclin D1, and 98.6% (344/349) tumors were weakly positive or positive for CD5. FISH test was positive in 12 cases that were CD5 negative and with cyclin D1 partial expression.Two hundred and forty-three (69.6%) patients had a median follow-up of 26 months (range: 3-108 months). The 3- and 5-year overall survival rates for patients were 63.0% and 34.8%, respectively. Single factor analysis showed that age of >60 years, splenic involvement, aggressive variant type, incompletely overlapping type [Based on the degree of overlap ≥90% and <90% between the follicular dendritic cell (FDC) meshwork and tumor cells, the tumors were divided into the completely overlapped type and incompletely overlapped type] and Ki-67 index >40% had poor prognosis (P<0.05). Multiple factor Cox proportional risk regression analysis after removing the aggressive variant type showed that age, splenic involvement, the degree of overlap between the FDC meshwork and tumor cells and Ki-67 index were independent prognostic factors for overall survival rate of MCL patients (P<0.05). Conclusions MCL is more commonly found among middle-aged and elderly men. Patient age, splenic involvement, degree of overlap between FDC meshwork and tumor cells and Ki-67 index are the independent prognostic indicators for MCL.

Objective: To investigate clinicopathological features and prognosis of tonsillar mantle cell lymphoma(TMCL). Methods: Clinical data of 25 patients with TMCL at Beijing Friendship Hospital, Capital Medical University from 2002 to 2016 were included. All the cases were reviewed microscopically. Various immunohistochemical stains were performed using the MaxVision two-step method. IgH/CCND1 gene fusion was detected by fluorescent in situ hybridization(FISH). Additionally, randomly selected 40 cases of non-tonsil MCL of the same period were compared. Results: Among all mantle cell lymphomas (MCL), TMCL accounted for 5.6%(25/449). The median age of the patients was 60 years(range: 44-82 years) with a M∶F ratio of 5.3 to 1.0. The main symptoms were sore throat and foreign body sensation and patients usually presented with enlargement or mass of tonsil. At the early stage of the disease, 18 cases(72.0%) were clinically misdiagnosed as tonsillitis. Lymph node involvement was present in 76.0%(19/25) of the patients. There were 4 cases(16.0%)with current splenic involvement, 11 cases(44.0%) with pharyngeal focal recidivism, and 3 cases(12.0%) with involvement of other non-lymphoid organs. Morphologically, tonsillar architectures were effaced at various degrees. Eighteen MCL cases showed classical type and 7 cases were blastoid variant. All tumors were positive for CD20 and cyclin D1. 92.0%(23/25) tumors showed weakly positive or positive expression for CD5. FISH test that IgH/CCND1 gene fusion was positive in two CD5 negative classical cases. 18 patients(72.0%) had a median follow-up time of 26 months(range: 6-81 months). The difference of survival rate between stage Ⅰ-Ⅱ and stage Ⅲ-Ⅳ patients was not statistically significant(P>0.05). Compared with NTMCL, TMCL was found to have higher proportion of stage Ⅰ-Ⅱ disease (χ²=12.789, P<0.01), lower the proportion of non-lymphatic organ involvement (χ²=8.125, P<0.01), and better prognosis (χ²=4.351, P=0.037). Conclusion The incidence of TMCL is low and prone to be misdiagnosed as tonsillitis. Patients with TMCL are more likely at stage Ⅰ-Ⅱ at presentation and the prognosis is better than that of NTMCL.

Objective: To analyze clinical, pathological, molecular and genetic characteristics of Burkitt-like lymphoma with chromosome 11q aberration. Methods: A case of Burkitt-like lymphoma with 11q aberration was presented at Beijing Friendship Hospital in November 2016 with detailed clinicopathological features, immunophenotypes, Epstein-Barr virus(EBV) status and molecular genetic characteristics. Results: The patient was a 38-year-old man presenting with the cervical lymphadenopathy. In morphology, the tumor had the similar characteristics of Burkitt lymphoma, including diffuse infiltration of medium to large lymphoid cells, and presence of"starry sky"phenomenon. Immunophenotypically, the tumor cells were positive for CD20, CD10, bcl-6, but negative for bcl-2. MUM-1 showed weak and patchy positivity. Ki-67 index was more than 95%. C-MYC expression was seen in about 50% of tumor cells. EBV in situ hybridization was negative. IgH and IgK genes were clonally rearranged.Fluorescence in situ hybrization detection using MYC break probe was negative but ATM gene amplification on chromosome 11q was detected. The patient did not receive any chemotherapy or radiotherapy and had not recurrence during the 10 months follow-up. Conclusion Burkitt-like lymphoma with chromosome 11q aberration has similar clinical, morphological and immunological characteristics to classic Burkitt′s lymphoma.

Objective: To determine the cut-off values of Ki-67 labeling index (LI) in the histological grading of follicular lymphoma (FL). Methods: Clinicopathological data of 350 FL patients diagnosed at Beijing Friendship Hospital from June 2014 to January 2016 were analyzed retrospectively by quantitative evaluation and statistical analysis of Ki-67 LI. Results: Of the 350 patients with FL, the male and female ratio was 1.1 and the average age was (50.2±14.0) years with a median age of 51 years (range 4 to 82 years). The tumors were graded as grade Ⅰ-Ⅱ in 215 cases (61.4%), grade Ⅲ A in 105 cases (30.0%), and grade Ⅲ B in 30 cases (8.6%). The average Ki-67 values were (22.8%±8.3%) for the FL low (grade Ⅰ-Ⅱ) and (50.4%±10.7%) for high grade (Ⅲ A and Ⅲ B) and were statistically significant by Mann Whitney U test (P<0.01). Receiver operated characteristic curve analysis showed that the best diagnostic cut-off value of low grade FL was 35% (sensitivity of 96.3% and specificity of 93.3%) with the largest area under curve (AUC=0.990, P<0.01, 95%CI for 0.982-0.998). According to the analysis of four lattice diagnostic tests, Ki-67 LI >40% was an important factor (χ²=230.733, P<0.01) in predicting high grade FL. When the cut-off value of Ki-67 LI was set at 40%, high grade LF could be diagnosed with the greatest sensitivity (98.1%) and specificity (87.7%). Moreover, a significant correlation between the Ki-67 LI and the pathological grade of FL (r=0.836, P<0.01) was observed. Conclusions Ki-67 LI of below a cut-off value of 35% is a reliable indicator of low grade FL.Ki-67 over 40% is consistent with high grade FL. These Ki-67 cut-off values may serveas an important auxiliary indicator in the grading of FL.

Objective: To investigate the clinicopathologic features and prognosis of gastrointestinal mantle cell lymphoma (GI-MCL). Methods: Clinical data of 38 GI-MCL patients diagnosed at Beijing Friendship Hospital from January 2002 to January 2016 were retrospectively reviewed morphologically and immunophenotypically. IgH/CCND1 gene fusion was assessed by fluorescent in situ hybridization (FISH). For comparison, 60 cases of non-GI-MCL were randomly selected to extract the differences inclinicopathological features and patient survival between the two groups. Results: Of 38 patients with GI-MCL, the median age was 62 years (range: 35-78 years, 23 males and 15 females), of which patients of 60 years of age or older accounted for 55.3%. Patients with clinical course of less than 6 months accounted for 81.1%(30/37). The main symptoms included abdominal pain, diarrhea, anorexia and hematochezia. Those with B symptoms accounted for 32.4%(12/37). The tumor most often involved lleocecal region (57.9%, 22/38), followed by rectum (36.8%, 14/38) and sigmoid colon (28.9%, 11/37), and the stomach accounted for 18.4%(14/38). Endoscopic polypoid lesions were found in 33 cases (86.8%, 33/38), of which 22 cases (66.7%, 22/33) were multiple. Five cases (13.2%, 5/38) presented with local protuberant neoplasm. According to Ann Arbor staging, 3 cases (7.9%, 3/38) were at stage Ⅰ, 4 cases (10.5%, 4/38) were at stage Ⅱ, and 31 cases (81.6%, 31/38) were at stage Ⅳ. The number of patients with tumor involvement of abdominal and retroperitoneal lymph nodes accounted for 45.7%(16/35), including 41.7%(15/36) involving the superficial lymph node, 17.1%(6/35) involving extranodal sites, and 23.5%(8/34) having splenomegaly. All of the 38 cases were classic MCL, and the tumor was composed of uniform lymphoid cells and effacing normal mucosal structure. All tumors were positive for CD20 and CD5. 97.4% (37/38) tumors were positive for cyclin D1, and 92.0% (23/25) tumors were positive for SOX11. FISH test was positive in 1 case of cyclin D1 negative tumor. Twenty-eight patients (73.7%) had a median follow-up of 25.0 months (range: 3-79 months). The 3-year survival rate for stage Ⅰ-Ⅱ and stage Ⅲ-Ⅳ of patients were 80.0% and 69.1%, respectively (P> 0.05). The 3-year survival rate for GI-MCL and non-GI-MCL patients were 71.7% and 72.5%, respectively (P>0.05). Single factor analysis showed that age of >60 years and splenomegaly were correlated with a worse overall survival rate (P<0.05). Conclusions Gastrointestinal malaise is the most common presenting symptom in GI-MCL patients. GI-MCL more commonly involves colorectum with more frequent multiple polypoid lesions. Patients of age >60 years and with splenomegaly have poor prognosis. There is no difference in the prognosis between GI-MCL and non-GI-MCL patients.

Objective:To study the clinicopathologic features, immunophenotype and prognosis of pediatric-type follicular lymphoma (PTFL).Methods:Thirty-seven cases of PTFL at the Beijing Friendship Hospital, Capital Medical University, from January 2012 to March 2018 were analyzed using light microscopy, immunohistochemistry, and polymerase chain reaction (PCR), and 13 cases were also examined using fluorescence in situ hybridization (FISH).Results:The male to female ratio was 35∶2. The median age was 16 years. Thirty-one patients were clinical stage Ⅰ and 6 were stage Ⅱ, displaying enlargement of lymph node in the head and neck regions. Follow-up information was available in 32 patients. Only two patients received low-dose chemotherapy, and none of these patients had relapse or disease progression at the latest follow-up (ranging from 16 to 79 months; median, 37 months). Morphologically, the lymph node architecture was partially or totally effaced by expansile follicles lacking polarization, with a prominent "starry sky" appearance. The cytologic composition was dominated by monotonous medium to large-sized blastoid cells with round to oval nuclei, finely clumped chromatin, small nucleoli, and scant cytoplasm. Immunophenotypically, all cases were positive for CD20, CD10, and bcl-6, but negative for bcl-2, MUM1 and C-MYC. Tumor cells were restricted to the follicles. The Ki-67 immunohistochemistry demonstrated a high proliferation (50% to 90%). Moreover, the tumor cells in the examined 28 cases were negative for CD43, CD5 and CD23. PCR analysis revealed monoclonal Ig gene rearrangements in all specimens. Thirteen cases being subjected to the FISH testing lacked bcl-2 and bcl-6 translocations.Conclusion:PTFL is different from conventional follicular lymphoma in their distinct morphology, immunophenotypic and molecular features, and behaves like an highly indolent or benign tumor.

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.

Objective: To investigate the clinicopathologic characteristics of neoplastic cell-rich mixed cellularity classical Hodgkin lymphoma(MCCHL-R) and to compare the prognosis with typical mixed cellularity classic Hodgkin lymphoma(MCCHL). Methods: Fifty-four patients with MCCHL-R(the tumor cells >10%) and 65 patients with typical MCCHL identified from 1 721 Hodgkin lymphomas were reviewed to compare the clinicopathological characteristics including morphologic and immunophenotypic features, EBV infection status, clinical therapy and overall survival. Results: The median age of the patients of MCCHL-R was 28.5 years(range: 9-76 years, male∶female=1.6∶1.0). Twenty-seven patients(50.0%) had B symptoms. Most patients had cervical lymph node involvement(81.5%, 44/54). Mediastinum and spleen involvement were seen in 69.2%(36/54) and 24.1%(13/54), respectively. Extranodal non-lymphoid organ involvement was seen in 41.3%(19/46) cases. Morphologically, lymph node architectures were effaced at various degree with large neoplastic cells of variable morphology, including Hodgkin/Reed-Sternberg(H/RS) cells and anaplastic large cells. There were abundant background heterogeneous admixtures of non-neoplastic inflammatory and accessory cells that were predominant mature small lymphocytes. All tumors were positive for CD30 and weakly positive for PAX5. Epstein-Barr encoded RNA(EBER)detectable by in situ hybridization was seen in 39.0% cases. Forty-six patients had a median follow-up time of 32.5 months(range: 5-128 months) and the 5-year survival rate for stage Ⅰ-Ⅱ and stage Ⅲ-Ⅳ patients were 91.7% and 50.1%, respectively(P<0.05). The 5-year survival rate for MCCHL-R was lower than typical MCCHL patients. Single factor analysis showed that age of >45 years, extranodal involvement and stage Ⅲ-Ⅳ were correlated with poorer 5-year survival rate(P<0.05). Multiple factors Cox proportional hazards regression showed that extranodal involvement was the independent prognostic factor(RR: 4.352, 95%CI: 1.122-16.879, P<0.05). Conclusions MCCHL-R is more common in young people. The tumor has pathological features of classic Hodgkin lymphoma enriched with the tumor cells(>10%) and similar immunophenotype to classical Hodgkin lymphoma. Compared with typical MCCHL, extranodal disease is an independent prognostic factor of MCCHL-R.