Objective:To investigate the clinical and pathologic features and diagnosis of follicular lymphoma (FL) with a predominantly diffuse growth pattern (DFL) with 1p36 deletion.Methods:Eight cases of DFL with 1p36 deletion diagnosed at Department of Pathology, Beijing Friendship Hospital, Capital Medical University ( n=5) and the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital ( n=3) from January 2017 to January 2023 were included. Their clinicopathologic features and follow-up data were analyzed. Immunohistochemistry and fluorescence in situ hybridization (FISH) were performed. Results:There were five males and three females, with a median age of 67 years, and inguinal lymphadenopathy was found as the main symptom. Histologically, similar morphologic features were sheared among all cases, with effaced nodal structure and characterized by proliferation of centrocytes in a diffuse pattern, with or without follicular components. The germinal center-related markers such as CD10 and/or bcl-6 were expressed in the tumor cells, and 1p36 deletion but not bcl-2 translocation was appreciable in these cases.Conclusions:DFL with 1p36 deletion is a rare subtype of FL, with some overlaps with other types of FL or indolent B-cell lymphomas in their pathologic features. An accurate diagnosis requires comprehensive considerations based on their clinical, pathologic, immunohistochemical, and molecular features.

Objective:To investigate the clinicopathological features and differential diagnosis of primary mucosal CD30-positive T-cell lymphoproliferative disorders (pmCD30 +TLPD). Methods:Eight cases of pmCD30 +TLPD diagnosed from 2013 to 2023 at the Department of Pathology, Beijing Friendship Hospital Affiliated to Capital Medical University and Beijing Ludaopei Hospital were retrospectively collected. The immunophenotype, EBV infection status and T-cell receptor (TCR) clonability of tumor cells were examined. The clinicopathological features were analyzed and related literatures were reviewed. Results:There were 5 females and 3 males, aged 28 to 73 years, without B symptoms, lack of trauma and autoimmune diseases. Seven cases occurred in oral mucosa and one in anal canal mucosa. Submucosal nodules with ulcerations were presented in all cases except one, which only submucosal nodule. Morphologically, there was different distribution of allotypic lymphocytes in inflammatory background. Four cases showed “kidney-shaped”, “embryonic” and “horseshoe-shaped” cells, and one case resembled Hodgkin and Reed/Sternberg (HRS) cells. Allotypic lymphocytes expressed CD3 (7/8), CD4+/CD8-(7/8) and CD4-/CD8-(1/8). CD30 was uniformly strongly positive while ALK and CD56 were negative. In situ hybridization of EBER was negative in five cases (5/5). Clonal TCR gene rearrangement was positive in two cases. Four patients did not receive radiotherapy or chemotherapy. All the seven patients survived without disease except one died due to concurrent leukopenia.Conclusions:pmCD30 +TLPD had a broad morphological spectrum and could be easily confused with primary cutaneous CD30 +TLPD and systemic ALK-negative anaplastic large cell lymphoma involving mucosa, which may lead to misdiagnosis. Although the majority of the cases had a favorable prognosis, a few cases relapsed or progressed to lymphoma.

Purpose To investigate the expression of Che-mokine(C-X-C Motif)receptor 5(CXCR5)and its clinico-pathological significance in classic Hodgkin lymphoma(CHL).Methods The expression of CXCR5 was assessed in 33 pa-tients by immunohistochemistry(IHC),and retrospectively ana-lyzed the expression and clinical significance of CXCR5 in the four subtypes of CHL.Meanwhile,10 cases of ALK-positive an-aplastic large cell lymphoma(ALCL)and 10 cases of ALK-neg-ative ALCL were collected as the control group.ResultsThere were 31 cases with CXCR5-positive in all 33 cases(93.94％),including 15/16(93.75％)in nodular sclerosis CHL,12/13(92.31％)in mixed cellularity CHL,2/2 in lymphocyte-rich CHL,and 2/2 in lymphocyte-depleted CHL.The positive ex-pressions of CXCR5 in different immunophenotypes of CHL were as follow,31/33(93.94％)in CD30 positive and PAX5 weakly positive CHL.12/14(85.71％)in CD15 negative CHL,24/26(92.31％)in CD20 negative CHL,10/11(90.91％)in EBER-negative CHL and 5/6 in LMP1-negative CHL.CXCR5 were not expressed in all 20 cases of ALCL.Conclusion The positive expression rate of CXCR5 in CHL is high.When the tumor cells are negative for CD15,LMP1 and CD20 or EBER,CXCR5 also has a high positive expression rate,which is helpful for the diagnosis of CHL.CXCR5 can be used to differentiate CHL from ALCL,especially the cases lacking typical morpholo-gy and immunohistochemistry.

Plant-derived nanovesicles have gained attention given their similarity to mammalian exosomes and advantages such as low cost, sustainability, and tissue targeting. Thus, they hold promise for disease treatment and drug delivery. In this study, we proposed a time-efficient method, PEG 8000 combined with sucrose density gradient centrifugation to prepare ginger-derived nanovesicles (GDNVs). Subsequently, curcumin (CUR) was loaded onto GDNV by ultrasonic incubation. The optimum conditions for ginger-derived nanovesicles loaded with curcumin (CG) were ultrasound time of 3 min, a carrier-to-drug ratio (GDNV:CUR) of 1:1. The study achieved a high loading capacity (94.027% ± 0.094%) and encapsulation efficiency (89.300% ± 0.344%). Finally, the drugs' in vivo distribution and anti-colitis activity were investigated in mice. CG was primarily distributed in the colon after oral administration. Compared to CUR and GDNV, CG was superior in improving disease activity, colon length, liver and spleen coefficients, myeloperoxidase activity, and biochemical factor levels in ulcerative colitis (UC) mice. In addition, CG plays a protective role against UC by modulating serum metabolite levels and gut flora. In summary, our study demonstrated that GDNV can be used for CUR delivery with enhanced therapeutic potential.

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 and prognosis of skeletal-muscle cytotoxic T-cell lymphoma (CTL).Methods:The clinical data of 14 cases of skeletal muscle CTL and 47 cases of non-skeletal muscle extranodal CTL patients in Beijing Friendship Hospital Affiliated to Capital Medical University and the 989 Hospital of the joint logistics support force of the people′s Liberation Army (the former 152 hospital) from 2008 to 2019 were collected retrospectively. Immunophenotype, EBV infection status and T-cell receptor (TCR) clonality of tumor cells were evaluated. The clinicopathological features and prognosis of the two groups were compared.Results:Skeletal-muscle CTL accounted for 23.0% (14/61) of extranodal CTL in the same period. The median age of the patients was 42.3 years (range 11-76 years), including six males and eight females. The main clinical manifestations were painless masses. Two patients (2/14) had B symptoms. The tumors occurred in the cheek (7 cases), the tongue (4 cases), the lower lip (3 cases) and the left upper arm (2 cases), and in two cases had two sites. Ten cases were of stage ⅠE and four cases stage ⅡE. Compared with non-skeletal-muscle extranodal CTL, many patients of skeletal-muscle CTL did not have B symptoms, the clinical stage was lower, and the tumor mainly involved the oral cavity (cheek, tongue and lip, P<0.05). Morphologically, the tumor showed diffuse infiltration of heterotypic lymphocytes in skeletal muscle. Immunohistochemistry showed that in 11/14 cases, there were reduced or loss of expression of some the T cell antigens (CD2, CD3, CD5, CD7). TIA-1, Gr B and CD8 (CD8 +>CD4 +) were expressed in all cases, and CD56 was negative. The median Ki-67 proliferation index was 35.0% (range 5%-60%). EBER in situ hybridization was negative in all cases. The results of TCR clonality analysis showed clonal TCR gene rearrangement were detected in eight cases. The median follow-up time was 40 months (range 10-67 months). Ten patients were tumor free; the 5-year survival rate of skeletal-muscle CTL was 100%. Compared with non-skeletal-muscle extranodal CTL (5-year overall survival rate was 35.9%), the difference was statistically significant (χ2=8.277, P=0.004). Conclusions:Skeletal-muscle CTL mostly occurs in the skeletal muscle of cheek and mouth. Tumor cells show morphologic characteristics of muscle invasion and myositis-like feature. It also shows CD8 +>CD4 +immunophenotype, cytotoxic molecular pattern and is associated with low clinical stage and good prognosis.

Objective: To investigate the clinicopathological features, immunophenotypes, genetics and prognosis of T-lymphocyte lymphoma/myeloid sarcoma combined with Langerhans cell histiocytyosis (coexistence of T-LBL/MS and LCH). Methods: Clinical and pathological data of the 6 patients with coexistence of T-LBL/MS and LCH were analyzed, who were diagnosed at the Foshan Hospital of Sun Yat-sen University and the Friendship Hospital of Capital Medical University, from December 2013 to April 2019. The hematoxylin and eosin stain, immunohitochemistry (EnVision) and in situ hybridization were used. Related literatures were reviewed. Results: Four patients were T-LBL combined with LCH, 1 was T-LBL/MS combined with LCH, and 1 was MS combined with LCH. There were 2 male and 4 female patients, with age ranged from 5 to 77 years old (median, 59 years old). Three patients represented with only multiple lymph node swelling. The other 3 displayed both multiple lymph node swelling, and skin/liver or spleen lesions. Lymph node structure was destroyed in 5 cases, while 3 cases had several residual atrophic follicles. Histologically, there were two types of tumor cells: one type of the abnormal lymphoid-cells exhibited small to medium-sized blast cells, typically showing a nested distribution, and these cells were mainly identified in residual follicles and paracortical areas; the other type of histiocytoid cells had a large cell size and abundant pale or dichromatic cytoplasm. Their nuclei were irregularly shaped, showing folded appearance and nuclear grooves. These cells were mainly present in marginal sinus, medullary sinus and interstitial area between follicles. Eosinophil infiltration in the background was not evident in any of the cases. The lymphoid-cells of medium size showed TdT+/CD99+/CD7+, with variable expression of CD34/MPO/CD2/CD3. Ki-67 index was mostly 30%-50%. However, the histiocytoid cells showed phenotype of CD1a+/S-100+/Langerin+/-, while CD163/CD68 were positive in some degree. These cells did not express any T or B cell markers. The Ki-67 index mostly ranged between 10%-20%. None of the cases had Epstin-Barr viral infection. Among the 6 patients, 4 patients were followed up (6-63 months, median time, 18.5 months), of whom 1 patient died of the disease and 3 patients were alive at the end of follow-up. Conclusions T-LBL/MS combined with LCH is a rare mixed type of immature hematopoietic disease, and mainly occurs in lymph node and skin. The clinical course is overall aggressive. Therefore, it is helpful to recognize and identify the two pathologic components in the same tissue for accurate diagnosis and proper treatment.

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 clinicopathologic features of follicular lymphoma (FL) in children. Methods: One female and one male patients with FL diagnosed in the First College of Clinical Medical Science, China Three Gorges University and Beijing Friendship Hospital of the Capital University of Medical Science in February 2016 and June 2015 were studied by HE immunohistochemistry, EBER in situ hybridization, IgH and IgK gene rearrangement analysis and IRF4 fusion gene detection. Results: The two patients′ age were 6.3 and 12 years, respectively. The lesions involved head and neck lymph nodes with duration of more than 2 months. Histopathologically, the lesions consisted of nodular proliferation of lymphoid follicles with diffuse distribution of large cells. Starry sky phenomenon was seen in one of the two cases. Immunohistochemistry showed that one case was positive for bcl-2 and MUM1, but negative for bcl-6 and CD10. Ki-67 index was>50% and oligoclonal IgK rearrangement was observed. The second case showed positivity for bcl-6, and CD10 but negative for bcl-2. Ki-67 index was>50% and clonal IgH FR1-JH and IgH FR2-JH rearrangements were detected. Both cases showed no evidence of IRF4 gene fusion. Conclusions Childhood FL is a rare B-cell lymphoma with characteristic features and high-grade histomorphology. However, its immunophenotype and molecular genetic characteristics are divergent.

Objective: To investigate the clinicopathological features of long-term tumor-free survival in patients with untreated primary diffuse large B-cell lymphoma (DLBCL) of the tonsil. Methods: The study included 80 consultation cases of primary tonsillar DLBCL from April 2006 to July 2017 in the Department of Pathology, Beijing Friendship Hospital, Capital Medical University. The patients were divided into two groups: experimental groups of 10 untreated patients with long-term tumor-free survival, and 70 patients who had been treated (control group). The clinical data, histopathological features, immunohistochemical staining, and molecular biology test results of the patients were analyzed retrospectively. Results: Patients who had long-term tumor-free survival with untreated primary diffuse large B-cell lymphoma had the disease mostly confined to the tonsil. Biopsy showed that the tonsil structure was only partially effaced and the lesions were relatively "fresh". EBER and FISH test for t (14;18) results were negative. Gene rearrangement detection showed monoclonality. There was statistically significant difference between the age, bcl-2 expression, CMYC protein expression and co-expression of CMYC and bcl-2 between the untreated group and the treated group(P<0.05). Patient gender, tumor site, histological type and clinical stage showed no difference between the untreated group and the treated group (P>0.05); The median overall survival of the untreated group and treated group was 81 months and 20 months, respectively, and the difference was not statistically significant (P>0.05).In patients younger than 40 years of age, the untreated group had a statistically significant difference in primary site and CMYC protein expression compared with the treated group (P<0.05), and there was no statistical significance in other aspects. Conclusions Long-term tumor-free survival patients with untreated tonsillar primary DLBCL have relatively unique clinical characteristics. There is no significant difference in the prognosis between the untreated and treated groups, indicating radiotherapy and chemotherapy may not be required and therefore, avoiding related side effects.