Purpose To investigate the clinicopathological features,molecular genetics and prognosis of high grade B cell lymphoma with concurrent MYC rearrangement and 11q aberra-tions(HGBCL-MYC-11q).MethodsThree cases of HGBCL-MYC-11q were reviewed and analyzed using hematoxylin-eosin staining,immunohistochemistry,EBER in situ hybridization and fluorescence in situ hybridization.Clinical data were collected with follow-up.Results All three patients were male,age was 10,61,and 74 years,respectively.All patients had Ann Arbor stage Ⅳ disease.All three cases were biopsies occurring in the nasopharynx,upper pharynx and ileocecus,respectively.Three cases were morphologically similar to diffuse infiltrative growth of tumor cells,moderate or moderately large cells,round to slightly irregular nuclei and easily visible mitotic figures.Focal necrosis was noted in one case.One case exhibited the distinct"starry sky"pattern.All cases expressed CD20,BCL6 and MUM1 and high Ki67 index,two cases expressed CD10 and two cases ex-pressed BCL2.CD3,CD30 and TDT were all negative.EBER in situ hybridization was all negative.FISH analyses using C-MYC break-apart probes were all positive and all cases had 11q aberrations.One case only had the 11q23.3 amplification;and one case only had the 11q24.3 loss.After a follow-up for 1-18 months,one patient died and two patients survived with disease.ConclusionHGBCL-MYC-11q is rare,morphologically similar to BL/HGBCL,with MYC rearrangement and 11q abnormali-ties.We should enhance awareness of the disease and improve more accurate diagnosis and differential diagnosis of the disease.

Objective:To study the clinicopathologic features and MYD88 L265P mutation status of intravascular large B cell lymphoma (IVLBCL).Methods:Fourteen cases of IVLBCLs were diagnosed from March 2014 to December 2019 at the First Affiliated Hospital of Zhengzhou University. The clinicopathologic features and prognosis were analyzed. Epstein-Barr virus encoded RNAs and MYD88 L265P mutation status were detected using in situ hybridization and Sanger sequencing, respectively. The follow-up data were obtained by telephone interview.Results:There were 6 males and 8 females with a median age of 62 years (range: 48-73 years). The involved anatomic locations were demonstrated by positron emission tomography-computed tomography, including adrenal gland (7/14), bone (6/14), central nerve system (4/14), skin (3/14), female reproductive system (3/14), local lymph nodes (3/14), prostate (2/14), liver and spleen (2/14), sphenoid sinus (1/14), penis (1/14), bladder (1/14), and right lung (1/14). Fever was the most common symptom (7/14), followed by neurologic symptoms and lower abdominal pain (2/14 each). The reminder symptoms included rash with edema, legs weakness and numbness, or postmenopausal bleeding (1/14 each). Eleven cases were at Lugano stage Ⅳ. Four cases were associated with the hemophagocytic syndrome, while 6 cases with bone marrow involved. Microscopically, the tumor cells were generally concentrated within the small-to-medium vascular lumens or sinusoids; they had centroblast-like appearance and showed large round or oval nuclei with slightly irregularities, coarse chromatin and 1-3 distinct nucleoli. One exception was the one case with an embryoid nuclei, reminiscent of anaplastic large cell lymphoma. The mitosis was not uncommon. Extravascular neoplastic cells were seen in two cases. The neutrophils could be appreciable in most of the cases (10/14). Immunophenotyping showed that CD20 and CD79α were diffusely and strongly positive in 14 cases; 12 cases were classified as the non-GCB subtype; 6 out of the 11 cases were double expressor lymphoma; 7 out of the 12 cases were CD5-positive. Twelve cases were EBER negative. The MYD88 L265P mutation was detected in 1 case (1/10). The duration of the follow-up ranged from 0.5 to 24.0 months, and 11 patients survived and 3 died.Conclusions:IVLBCL is rare. The most common type of IVLBCL in China is Asian type with scant tumor cells. Combination of clinical and immunohistochemical features can avoid most, if not all, misdiagnoses and missed diagnoses. Some IVLBCL cases may harbor the MYD88 L265P mutation, but the prevalence of MYD88 L265P mutation in the population still warrants additional studies.

Objective:To study the clinicopathological features and prognosis of nodal lymphoplasmacytic lymphoma/Waldenstrom′s macroglobulinemia (n-LPL/WM).Methods:A total of 19 cases of n-LPL/WM were collected from May 2009 to January 2020 at First Affiliated Hospital of Zhengzhou University. The clinicopathologic features, immunophenotype, Ig gene rearrangement (BIOMED-2), MYD88 L265P mutation status (by Sanger sequencing) and follow-up data (by telephone) were analyzed.Results:There were 15 males and 4 females with a median age of 61 years (range 43 to 82 years). There were 14 WM and five LPL. The most common symptoms were weakness, fatigue (9/19) and B symptoms (11/19). Majority of the patients (16/18) presented with systemic multiple lymphadenopathies. Eighteen patients presented at advanced stages (Ⅲ/Ⅳ stage). Serum M protein status was IgM (15 cases), IgG (1 case), IgA (1 case) and no-secretory type (2 cases). Seventeen patients had bone marrow involvement. Morphologically, all 19 cases were divided into two groups: typical group (9 cases) or atypical group (10 cases). In the typical group, the structures of the lymph nodes were preserved; the neoplastic cells were predominantly plasmacytoid lymphocytes or mixed small lymphocytes, plasmacytoid lymphocytes and plasma cells, without proliferation of FDC network and follicular implantation. In the atypical group, the tumor showed effaced nodal architecture (5 cases), mainly proliferation of small lymphocytes (6 cases), FDC proliferation and/or follicular implantation (6 cases), marginal zone B cell differentiation (4 cases) and diffuse amyloidosis (1 case). Hemosiderin deposition (19 cases), infiltration of fatty tissue (19 cases) and interstitial sclerosis (9 cases) were commonly seen in both groups. Immunohistochemically, the neoplastic B cells expressed CD20 and CD79α, and the neoplastic plasma cells were positive for CD38, CD138 and MUM-1; eight cases showed light chain restriction; of the seven detected cases, five expressed IgM and the other two expressed IgG and IgA respectively; four cases expressed CD23 weakly, Ki-67 index was 10%-30%. MYD88 L265P mutation was seen in 18/18 cases. There was no significant difference in clinicopathologic features and prognosis between the two groups ( P>0.05). The median follow-up time was 61 months, 11 patients were alive, while eight died; the 5-year survival rate was 21.1%. Conclusions:n-LPL/WM is rare, but patients usually present in advanced stages. It is easily confused with other small B-cell lymphomas with plasma cell differentiation, especially basing on morphologic features alone; thus the accurate diagnosis of n-LPL/WM requires a combination of clinical features, serum M protein, immunohistochemistry, bone marrow morphology,flow cytometry and MYD88 L265P mutation status etc. The prognosis of n-LPL/WM may be not very good, and further studies with more cases are needed.

Objective:To investigate the clinicopathological features, molecular genetics, treatment and prognosis of Burkitt-like lymphoma with 11q aberration (BLL-11q).Methods:Six cases of BLL-11q diagnosed at the First Affiliated Hospital of Zhengzhou University, from January 2016 to January 2020 were reviewed and analyzed using hematoxylin-eosin staining, immunohistochemistry, EBER in situ hybridization and fluorescence in situ hybridization. Clinical information including follow-up data was collected and analyzed.Results:The median age of the six immunocompetent patients was 29 years (range 20-38 years) and the male to female ratio was 5∶1. All patients had nodal disease in the head and neck region. Five patients had Ann Arbor stage Ⅰ-Ⅱ disease, while one patient had stage Ⅳ disease. Lymph nodes showed partial or total architectural effacement by a diffuse proliferation of monomorphic lymphocytes. Four cases were morphologically similar to Burkitt lymphoma, and two cases were unclassified with histological features between Burkitt lymphoma and diffuse large B-cell lymphoma. Mitotic figures, apoptosis and necrosis were conspicuous. Five cases exhibited the"starry sky"pattern. CD20, CD10 and bcl-6 were diffusely and strongly positive. The Ki-67 index was more than 95%. The follicular-dendritic-cell meshwork was noted in one case using CD21 stain. C-MYC was expressed variably. CD3, bcl-2, MUM-1, CD30 and TDT were negative in all cases. EBER in situ hybridization was also all negative. FISH analyses using C-MYC, bcl-2 and bcl-6 break-apart probes were all negative. All cases had the 11q23.3 gain/11q24.3 loss pattern, and 11q23.3 amplification was found in one case. IgH and IRF4 break-apart probes analysis was also negative. All patients were alive with no disease after a follow-up of 4 to 19 months.Conclusion:BLL-11q is a rare lymphoma that resembles Burkitt lymphoma morphologically and phenotypically, but lacks C-MYC gene rearrangements. Instead, it has a chromosome-11q alteration characterized by proximal gains and telomeric losses. It′s necessary to improve our understanding of BLL-11q to avoid misdiagnosis and missed diagnosis.

Objective:To investigate the clinicopathological features and differential diagnosis of primary cutaneous nasal extranodal NK/T cell lymphoma (pcENKTCL-NT).Methods:Fifteen cases of pcENKTCL-NT were collected at the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2019. The clinical characteristics, morphological features, immunophenotypes, and results of in situ hybridization and gene detection were analyzed.Results:Among the 15 patients, 7 were male and 8 were female, with a male to female ratio of 1.0∶1.1. Their ages ranged from 29 to 86 years, and the median age was 59.3 years. All patients were hospitalized for skin lesions, including skin ulcers, scattered patchy red papules, and local blisters. The skin lesion might be a hard nodular mass, and part of it was a confluent patchy erythema; it could be manifested as multiple scattered nodules of different sizes, and some lesions were like round ulceration. There were 8 cases of lower limbs, 4 cases of chest (1 case with upper limb lesions), 2 cases of trunk and 1 case of neck. Most of the patients were sensitive to GGDP regimen (cisplatin, dexamethasone, gemcitabine and pemostatin). Histologically, most lesions showed tumor cells invading the epidermis and skin appendages, dermal infiltration, diffuse distribution, vascular and peritubular destruction, and some subcutaneous adipose tissue involvement. Morphologically, most of the tumor cells were mixed with small-to medium-size lymphocytes, and some were large cells, mixed cells or small cells. Immunohistochemistry showed that CD3, CD3 ε and TIA-1 were expressed in all cases, but not CD20 and CD8. CD56 and granzyme B were expressed in most of the cases, and CD5 was not expressed. Ki-67 positive index was about 50%-90%. EBV in situ hybridization was positive in all cases. The clonal rearrangement of T cell receptor gene was found in some CD56 negative cases. The 15 patients were followed up for 5-45 months, and one of them was lost to follow-up. Five patients died within 5-13 months after the diagnosis, accounting for 35.7% (5/14) of the 14 patients. The average survival time of the deceased patients was 8.6 months.Conclusions:The incidence rate of pcENKTCL-NT is relatively low, but its biological behavior is aggressive and its prognosis is overall poor. Its skin lesions and histopathological features are relatively diverse. The diagnosis should be determined with using clinical data, histological morphology, immunophenotype and EB virus in situ hybridization. At the same time, attention should be paid to differential diagnosis from other cutaneous lymphoma with cytotoxic phenotype to avoid missed diagnosis and misdiagnosis.

Objective:To study the clinicopathologic and genetic features of Waldeyer′s ring peripheral T-cell lymphoma with follicular helper T cell immunophenotypes (wPTCL-TFH), with comparison to the nodal peripheral T-cell lymphoma with TFH immunophenotypes (nPTCL-TFH) and angioimmunoblastic T-cell lymphoma (AITL), as to know this rare tumor better.Methods:The clinical data, histopathology features, EBV positivity, T cell clonality and IDH2 R172 gene mutation in 8 cases of wPTCL-TFH were collected at the First Affiliated Hospital of Zhengzhou University from December 2015 to April 2019, and analyzed by immunohistochemistry, in situ hybridization, TCR gene rearrangement (BIOMED-2) and Sanger sequencing.Follow-up data were obtained by telephone. Results:There were 6 males and 2 females with a median age of 62.5 years (age ranging from 30 to 75 years). All patients had neither fever nor skin manifestations, but were all found mucosa thickened or mass of waldeyer′s ring with multiple lymph nodes enlarged by PET-CT/CT scans. Five of the 7 patients were at advanced stages (Ⅲ/Ⅳ stage). Microscopically, the mucosa was infiltrated diffusely and characteristically by numerous small-medium sized lymphocytes, lacking polymorphous inflammatory background and extra-follicular expansion of follicular dendritic cell networks (FDC networks). The clear T cells presented in 5 cases. Ulcers on mucosal surfaces (6 cases) and local-extensive loss of intramucosal glands (7 cases) were commonly noted. Granulomas composed of epithelioid histiocytes were observed in 2 cases. Immunohistochemically, all the tumor cells expressed CD4 and at least 2 types of follicular helper of T cell (TFH) markers: PD-1 (8/8), bcl-6 (8/8), CXCL13 (7/8) and CD10 (1/8). Most of the cases (6 cases) expressed CD30. EBV positive appeared in 4 cases. All 8 cases were T cell monoclonal. IDH2 R172 were wild-type in 6 cases. One patient died at the follow-up time on 18 months; the other 7 survived (the follow-up time varied from 3 to 10 months). Conclusions:wPTCL-TFH is rare, and its clinicopathological features are similar to nPTCL-TFH which may be the manifestation of the same disease at different stage, and partly overlapped with AITL. The differential diagnosis from PTCL-NOS is necessary and comprehensive analyses of clinical, morphological, immunohistochemical and genetic features can help make a correct diagnosis.

Objective:To investigate the clinicopathological features of primary Epstein-Barrvirus (EBV) positive nodal T/NK-cell lymphomas (EBV+nodal TNKL).Methods:The clinicopathological features of 7 cases of EBV+nodal TNKL diagnosed between November 2015 and May 2019 at the First Affiliated Hospital of Zhengzhou University were analyzed using immunohistochemistry, PCR gene rearrangement and in situ hybridization.Follow-up data were also collected.Results:There were 5 males and 2 females with a median age of 54 years (ranged from 41 to 75 years). All patients presented with multiple lymphadenopathies and common B symptoms (5/7) and at an advanced Ann Arbor stage Ⅲ/Ⅳ(6/7). Bone marrow involvementwas detected in 1 patient.Six cases of T-cell origin had monomorphic patterns, and the tumor cells showed CD56 negativity and TCRαβ +/TCRγδ － with T-cell clonality. One case of NK-cell origin had polymorphic pattern, and the tumor cells showed CD56 positivity and TCRαβ -/TCRγδ -without T-cell clonality. All cases were positive for the cytotoxic markers, but showed various CD4/CD8 expression. All 7 cases were diffusely positive for EBV (>100 cell/high power field). Six of the patients received chemotherapy, and 1 patient declined the treatments. During the follow-up period ranging from 3 to 48 months, 5 of the 7 patients died of the disease. Conclusions:EBV+nodal TNKL is a rare entity and is characterized by cytotoxic molecule expression, T/NK-cell derivation, and a predominance of nodal involvement at an advanced stage. It should be differentiated from other EBV+T/NK cell lymphoproliferative disorders, especially extranodal NK/T cell lymphoma.

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of pulmonary extranodal NK/T-cell lymphoma, nasal type (ENKTL-NT). Methods: Eleven cases of newly diagnosed (10 puncture biopsies and 1 transbronchial biopsy), previously untreated pulmonary ENKTL-NT were collected at the First Affiliated Hospital of Zhengzhou University, from August 2013 to November 2018. The clinicopathological features including histomorphology, immunohistochemistry and in situ hybridization were collected and analyzed. Results: Among the 11 cases, 8 were males and 3 were females, with a male to female ratio of 8∶3.The age range was from 30 to 74 years, with an average of 48 years and a median of 43 years. Tumors involved bilateral lung lobes in 8 cases, the upper left lobe in 1 case, lower left lobe in 1 case, and upper right lobe in 1 case. Main clinical symptoms included fever, often accompanied by cough, and bloody sputum in most cases. All cases were stage Ⅳ E. Histological features included scattered or focal aggregates of marked pleomorphic tumor lymphocytes, accompanied by necrosis and heavy admixture of inflammatory cells. In a few cases, diffuse neoplastic lymphocytes or vascular central and destructive infiltrations were seen. Tumor cells in most cases expressed CD3ε, CD3, CD43, CD56, TIA-1, granzyme B, but did not express CD20, CD79a, and CD5. Ki-67 index ranged from 40%to 90%.All cases were positive for EBER by in situ hybridization. Four of five patients died during follow-up with a survival period of only 1 week to 13 months. Conclusions Pulmonary ENKTL-NT is rare, high grade malignancy with a poor prognosis. Misdiagnosis is common due to lesional necrosis and heterogeneous cell components. Immunohistochemistry and EBER in situ hybridization are essential for accurate diagnosis.

Objective To investigate the clinicopathological features, diagnosis and differential diagnosis of pulmonary extranodal NK/T‐cell lymphoma,nasal type (ENKTL‐NT).Methods Eleven cases of newly diagnosed (10 puncture biopsies and 1 transbronchial biopsy), previously untreated pulmonary ENKTL‐NT were collected at the First Affiliated Hospital of Zhengzhou University, from August 2013 to November 2018. The clinicopathological features including histomorphology, immunohistochemistry and in situ hybridization were collected and analyzed. Results Among the 11 cases, 8 were males and 3 were females, with a male to female ratio of 8∶3.The age range was from 30 to 74 years, with an average of 48 years and a median of 43 years. Tumors involved bilateral lung lobes in 8 cases, the upper left lobe in 1 case, lower left lobe in 1 case, and upper right lobe in 1 case. Main clinical symptoms included fever, often accompanied by cough, and bloody sputum in most cases. All cases were stage ⅣE. Histological features included scattered or focal aggregates of marked pleomorphic tumor lymphocytes, accompanied by necrosis and heavy admixture of inflammatory cells. In a few cases, diffuse neoplastic lymphocytes or vascular central and destructive infiltrations were seen. Tumor cells in most cases expressed CD3ε, CD3, CD43, CD56, TIA‐1, granzyme B, but did not express CD20, CD79a, and CD5. Ki‐67 index ranged from 40%to 90%.All cases were positive for EBER by in situ hybridization. Four of five patients died during follow‐up with a survival period of only 1 week to 13 months. Conclusions Pulmonary ENKTL‐NT is rare, high grade malignancy with a poor prognosis. Misdiagnosis is common due to lesional necrosis and heterogeneous cell components. Immunohistochemistry and EBER in situ hybridization are essential for accurate diagnosis.

Objective: To explore the characteristics of clinical pathology, diagnosis, and prognosis of primary renal lymphoma (PRL).Methods: The clinical features, pathological features, immune phenotypes, treatment, and prognosis of 22 patients were retrospectively analyzed. Results: The PRL patients' ages ranged from 2 to 72 years (mean, 54.3 years), of which 13 patients were older than 50 years (59.1%). All of the 22 patients were diagnosed with non-Hodgkin's lymphoma (NHL), including 20 cases of B-cell lymphoma and 2 cases of T-cell lymphoma. Seven patients were still alive and survived for 6-50 months, but the other 15 were dead and survived for only 5-35 months. Conclusion: PRL is uncommon. Clinical manifestations and imaging performance specificity are not obvious. and easily misdiagnosed. Histopathology is still the golden standard for the final diagnosis of this entity. The kidney is most easily involved followed by the bladder. B-cell NHL is the common subtype, and the most common type is the diffuse large B-cell lymphoma. Up to now,no standard regime could be performed for PRL patients. At present, comprehensive therapy, including surgery and chemotherapy, is recommended. For patients with locally advanced or highly aggressive status, therapeutic effect with chemotherapy alone is usually satisfied.