Age-related EBV-associated B-cell lymphoproliferative disorders and other EBV + lymphoproliferative diseases: New insights into immune escape and immunodeficiency through staining with anti-PD-L1 antibody clone SP142.

Epstein-Barr virus (EBV) is prevalent among healthy individuals, and is implicated in numerous reactive and neoplastic processes in the immune system. The authors originally identified a series of senile or age-related EBV-associated B-cell lymphoproliferative disorders (LPD) bearing a resemblance to immunodeficiency-associated ones. These LPDs may be associated with immune senescence and are now incorporated into the revised 4th edition of 2017 WHO lymphoma classification as EBV-positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS). These EBV+ B-cells often have a Hodgkin/Reed-Sternberg (HRS)-like appearance and are shared beyond the diagnostic categories of mature B-cell neoplasms, mature T-cell neoplasms, classic Hodgkin lymphoma, and immunodeficiency-associated LPD. In addition, peculiar new diseases, such as EBV+ mucocutaneous ulcer and EBV+ DLBCL affecting the young, were recognized. On the other hand, lymphoma classification is now evolving in accord with deeper understanding of the biology of programmed death ligand 1 (PD-L1). Assessing PD-L1 positivity by staining with the anti-PD-L1 monoclonal antibody SP142 provides new insight by discriminating between immune evasion and senescence or immunodeficiency. The aim of the present review is to briefly summarize the diagnostic use of immunostaining with SP142 in malignant lymphomas and/or LPDs that feature tumor and nonmalignant large B-cells harboring EBV.

Anaplastic variant of diffuse large B-cell lymphoma: Reappraisal as a nodal disease with sinusoidal involvement.

Anaplastic variant (av) of diffuse large B-cell lymphoma (DLBCL) is morphologically defined in the 2017 World Health Organization classification, but still an enigmatic disease in its clinicopathologic distinctiveness, posing the differential diagnostic problem from gray zone lymphoma (GZL) and classic Hodgkin lymphoma (cHL). Thirty-one cases previously diagnosed as avDLBCL were reassessed. Of these, 27 (87%) and 4 (13%) were node-based and extranodal diseases, respectively. They were further reclassified into nodal avDLBCL (n = 18), nodal CD30+ DLBCL with T-cell/histiocyte-rich large B-cell lymphoma-like features (CD30+ DLBCL-THRLBCL) (n = 6), GZL with features intermediate between DLBCL and cHL (n = 3) and CD30+ extranodal DLBCL, NOS (n = 4). The nodal avDLBCL cases had a sheet-like proliferation of large cells and/or Hodgkin/Reed-Sternberg (HRS)-like cells in 12 (67%) notably with a sinusoidal pattern in 16 (89%). They showed an expression of CD20 and/or CD79a in all and CD30 in 15 of 18. All of them were negative for PD-L1 on tumor cells, although HRS-like cells showed negativity or partial loss of other B-cell markers to varying degrees. The present study highlighted the distinctiveness of the nodal avDLBCL with sinusoidal pattern, but without neoplastic PD-L1 expression, which provide refined diagnostic criteria for a more precise pathologic and clinical characterization of this disease.

Immunohistochemical assessment of the diagnostic utility of PD-L1: a preliminary analysis of anti-PD-L1 antibody (SP142) for lymphoproliferative diseases with tumour and non-malignant Hodgkin-Reed-Sternberg (HRS)-like cells.

AIMS: The programmed death 1 (PD1)/PD1 ligand (PD-L1) axis plays an important role in tumour cells escape from immune control. PD-L1 immunohistochemistry is a useful predictor of immunotherapy response, but is still not used widely in the diagnostic setting. Here we describe results using PD-L1 immunohistochemistry during routine diagnostics in lymphoma. METHODS AND RESULTS: Ninety-one lymphoproliferative disease cases sharing tumour and non-malignant Hodgkin-Reed-Sternberg (HRS)-like cells with and without Epstein-Barr virus (EBV) association were investigated by immunohistochemistry for PD-L1 (clone SP142). PD-L1 expression was present in more than 5% of tumour or non-malignant HRS-like cells in 100% of EBV+ classical (C) Hodgkin lymphoma (HL) (n = 10) and EBV-negative nodular sclerosis CHL (n = 8); 40% of EBV+ diffuse large B cell lymphoma, not otherwise specified (DLBCL-NOS) (n = 20); and 4% of nodal peripheral T cell lymphoma of follicular helper T cell type (PTCL-TFH) (n = 22). In contrast, nodular lymphocyte-predominant HL (n = 4), lymphocyte-rich CHL (n = 6), EBV+ hyperplasia (n = 8), plasmablastic lymphoma (n = 3) and anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (n = 5) seldom exhibited PD-L1 in their large cells. Assessing PD-L1 positivity in tumour and non-malignant large cells was helpful in differentiating between CHL versus nodal PTCL-TFH (P < 0.0001) or EBV+ DLBCL-NOS (P = 0.0052) and between EBV+ DLBCL-NOS versus nodal PTCL-TFH (P = 0.0052), with PD-L1 expression indicating the first diagnosis in each of those sets. CONCLUSION: Immunohistochemical evaluation of PD-L1 expression in tumour and non-malignant HRS-like large cells may be useful for assessing either immune escape or immunodeficiency in their pathogenesis.

Comparison of Epstein-Barr virus-positive mucocutaneous ulcer associated with treated lymphoma or methotrexate in Japan.

AIMS: The aim of the present study was to compare treated lymphoma-associated Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) and methotrexate (MTX)-associated EBVMCU. METHODS AND RESULTS: Of a series of 15 Japanese patients (11 women, four men; median age 74 years, range 35-84 years), seven received MTX for the treatment of autoimmune disease and eight developed EBVMCU after treatment of malignant lymphoma [diffuse large B-cell lymphoma (n = 4) without EBV association, adult T-cell leukaemia/lymphoma (n = 2), angioimmunoblastic T-cell lymphoma (n = 1), and follicular lymphoma (n = 1)]. Ulcers were observed in the oral cavity (n = 11), gastrointestinal tract (n = 2), and skin (n = 2). All were histologically characterised by a mixture of EBV-positive large B-cell proliferation and Hodgkin/Reed-Sternberg-like cells on a polymorphous background. A total of 46% (6/13) had monoclonal immunoglobulin heavy chain gene rearrangement, but none had clonal T-cell receptor gene rearrangement. Spontaneous regression occurred in 13 of 15 cases (87%); the other two cases (13%) achieved complete remission after treatment. Of two patients in the treated lymphoma-associated subgroup, one developed multiple new ulcerative lesions on previously unaffected skin, and the other had a relapse of EBVMCU in the oral cavity. No significant clinicopathological differences were found between the subgroups. Notably, none of the patients died from EBVMCU. However, the treated lymphoma-associated subgroup had lower overall survival (P = 0.004) and a shorter follow-up period (P = 0.003) than the MTX-associated subgroup, owing to death from non-associated causes. CONCLUSIONS: Treated lymphoma-associated EBVMCU, which is an indolent and self-limited condition, must be recognised to avoid misdiagnosing it as a relapse of malignant lymphoma during treatment.

Anaplastic variant of diffuse large B-cell lymphoma with hallmark cell appearance: Two cases highlighting a broad diversity in the diagnostics.

The anaplastic variant of diffuse large B-cell lymphoma (A-DLBCL) is morphologically defined but remains an enigmatic disease in its clinicopathologic distinctiveness. Here, we report two cases involving Japanese women aged 59 years, both with A-DLBCL with the hallmark cell appearance and both indistinguishable from common and giant cell-rich patterns, respectively, of anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma. Case 1 was immunohistochemically positive for CD20, CD79a and OCT-2 but not for the other pan-B-cell markers, CD30 and ALK. Case 2 showed CD20 and CD30 positivity for 50% and 20% of tumor cells in addition to strong expression of p53 and MYC. Both were positive for fascin without Epstein-Barr virus association. Our cases provide additional support for the earlier reports that A-DLBCL exhibits clinicopathologic features distinct from ordinal diffuse large B-cell lymphoma (DLBCL), and documented its broader morphologic diversity than previously recognized. They also shed light on the unique feature of absent expression of pan-B-cell markers except for CD20 and CD79a, suggesting that A-DLBCL may biologically mimic a gray zone or intermediate lymphoma between DLBCL and classic Hodgkin lymphoma.

Grey zone lymphoma with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma: a clinicopathological study of 14 Epstein-Barr virus-positive cases.

AIMS: To investigate the clinicopathological features of Epstein-Barr virus (EBV)-positive grey zone lymphoma (GZL) with features intermediate between diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma (CHL). METHODS AND RESULTS: We investigated the clinicopathological features of 14 cases of EBV-positive GZL in Japan. The control group included 173 cases of EBV-positive CHL and 64 cases of EBV-positive DLBCL of the elderly (polymorphous type). The patients were 10 men and four women with a median age of 62 years. Twelve patients (86%) had advanced clinical stage, 11 (79%) had B-symptoms, eight (57%) had mediastinal disease, 10 (71%) had elevated serum lactate dehydrogenase (LDH) levels, and five (36%) had thrombocytopenia. All cases had CHL-like morphology but strongly expressed at least one B-cell marker. The neoplastic cells were Hodgkin and Reed-Sternberg-like cells, but with a large number of mononuclear variants. EBV-positive GZL patients were more significantly more likely than EBV-positive CHL patients to have advanced clinical stage (P = 0.023), presence of B-symptoms (P = 0.011), elevated serum LDH levels (P = 0.047), thrombocytopenia (P = 0.042), and mediastinal involvement (P = 0.023). The progression-free survival (PFS) of EBV-positive GZL patients was significantly poorer than that of EBV-positive CHL patients (P = 0.043) but no difference from EBV-positive DLBCL patients was observed (P = 0.367). CONCLUSIONS: EBV-positive GZL patients have significantly worse PFS than EBV-positive CHL patients, and are significantly more likely to have adverse clinical parameters such as advanced clinical stage, presence of B-symptoms, and thrombocytopenia. Further studies are needed to better characterize this entity, which may require the development of innovative therapeutic strategies.

Clinicopathological analysis of 46 cases with CD4+ and/or CD56+ immature haematolymphoid malignancy: reappraisal of blastic plasmacytoid dendritic cell and related neoplasms.

AIMS: In this study, we aimed to investigate the clinicopathological features of CD4+ and/or CD56+ immature haematolymphoid malignancy (iHLM), including blastic plasmacytoid dendritic cell neoplasm (BPDCN). METHODS AND RESULTS: We analysed the clinicopathological features of 46 patients diagnosed consecutively with CD4+ /CD56+ iHLM. These cases were categorised into three groups based on their immunohistochemical expression of three plasmacytoid dendritic cell (pDC) markers [CD123, CD303 and T cell leukaemia/lymphoma (TCL1)]: cutaneous BPDCN (n = 35), non-cutaneous BPDCN (n = 6) and non-BPDCN-type CD56+ neoplasms (n = 5). Compared to non-cutaneous BPDCN, cutaneous BPDCN was associated with an older median age at onset (72 years versus 45 years, P < 0.05), and higher positivity for CD4 (P < 0.05), CD123 (P < 0.05) and 2-3 pDC markers (89% versus 50%, P = 0.05). Cutaneous BPDCN was divided into terminal deoxynucleotidyl transferase (TdT)+ and TdT- subgroups, which did not differ in prognosis, although TdT+ cases showed a lower median onset age (66 years versus 79 years, P < 0.05) and higher frequency of extracutaneous lesions (P < 0.05). Compared to the BPDCN groups, non-BPDCN-type CD56+ neoplasm cases showed higher cytoplasmic CD3 positivity (P < 0.05) and less frequent BCL-2 expression (P < 0.05), and lacked cutaneous lesions. However, the survival curves overlapped. Notably, one case involved an unusual composite neoplasm, comprising CD56+ lymphoblastic lymphoma and mature CD56+ cytotoxic T cell lymphoma. CONCLUSIONS: Our present data support the recognition of cutaneous BPDCN as a homogenous entity, in contrast to the non-cutaneous form. Additional research is warranted to characterise non-BPDCN-type CD56+ neoplasms.

Nodular lymphocyte predominant Hodgkin lymphoma: Clincopathological study of 25 cases from Japan with a reappraisal of tissue associated macrophages.

Clinicopathological features of 25 nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) patients in Japan were analysed. To investigate the clinicopathological significance of tissue associated macrophages (TAM) in NLPHL, CD68 and CD163 expression were investigated. The median age at onset was 56 years (range: 6-82 years) with male predominance (64%). All patients presented with lymph node enlargement with predilection for cervical LNs. Seven cases (28%) had mediastinal lesion and four (16%) had extranodal involvement. Most cases (76%) presented with early clinical stages. After median follow up of 44 months, both of overall and progression free survival rates were 95%. The presence of >5% CD68+ TAM in NLPHL was significantly associated with older age at diagnosis (median, 71 vs 52.5 years; P = 0.048), lower hemoglobin level (33.3% vs 0%; P = 0.037) and lower CR rate after initial treatment (42.9% vs 91.7%; P = 0.038). The presence of >5% CD163+ TAM was significantly correlated with presence of B symptoms (40% vs 0%; P = 0.036). In conclusion, NLPHL is rare among Japanese and appears to present at an older age than among Western patients. In our series, the presence of >5% CD68+ TAM in NLPHL was associated with lower CR rate, but with no impact on patients' survival.

Utility of clinical, laboratory, and lymph node MYD88 L265P mutation in risk assessment of diffuse large B-cell lymphoma patients.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma and is characterized by heterogeneity in biology and clinical behavior. Mutations in the myeloid differentiation primary response 88 (MYD88) are found in different lymphoproliferative disorders and are associated with variable clinical and prognostic impact. AIM: To investigate the frequency of MYD88 L265P mutation and its clinical impact in a cohort of Egyptian DLBCL patients. METHODS: FFPE lymph node samples from 87 DLBCL patients (46 males / 41 females; median age, 58 years) were included and analyzed for MYD88 L265P by an allele-specific PCR. RESULTS: MYD88 L265P mutations were found in 52 patients (59.8%) out of 87 DLBCL cases. Patients with L265 mutation were significantly younger than non-mutated patients (p = 0.022). None of the patients with the L265P mutation showed a significant association with the clinical parameters of DLBCL. Interestingly, MYD88 L265 mutated patients were found to be significantly correlated with HCV infection (p = 0.037). The median follow-up time across the entire cohort was 26 months. Univariate analysis showed that overall survival (OS) was affected by gender, LDH level, and CNS-IPI scoring (p = 0.048, 0.008, and 0.046, respectively), while disease-free survival (DFS) was affected by B symptoms and LDH level (p = < 0.000 and 0.02, respectively). However, the MYD88 mutation status and other prognostic factors showed no association with OS or DFS. CONCLUSIONS: Our findings indicate a high frequency of MYD88 L265P mutations in our study population and not associated with prognostic markers or the outcome of the disease.

Clinicopathological Study of PD-1/PD-L1 Expression in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) with Emphasis on Large B-Cell Richter Transformation.

OBJECTIVE: In the era of immunotherapy, inhibition of the PD-1/PD-L1 immune checkpoint pathway has changed the therapeutic landscape for many tumors. Limited studies were performed on the expression of PD-1 in chronic lymphocytic lymphoma/small lymphocytic lymphoma (CLL/SLL) and its Richter transformation into diffuse large B-cell lymphoma (DLBCL-RT). This study aims to evaluate PD-1/PD-L1 expression and their prognostic role in CLL/SLL, DLBCL-RT, and DLBCL-de novo patients. MATERIAL AND METHODS: This retrospective study was conducted on 96 cases (38 CLL/SLL, 11 DLBCL-RT and 47 DLBCL-de novo) that were retrieved from the pathologic and clinical databases at the Oncology Center, Mansoura University. Immunohistochemical evaluation of PD-1 and PD-L1 was assessed in tumor cells and the microenvironment in those patients. RESULTS: This study demonstrated positive expression of PD-1 in CLL/SLL patients, mainly in proliferation centers. Moreover, it showed a higher prevalence of PD-1 expression in DLBCL-RT (9/11 patients) than in DLBCL-de novo (5/47 patients) (P < 0.001). Tumor cells revealed positive PD-L1 expression in 5/47 DLBCL-de novo patients and negative PD-L1 expression in all CLL/SLL and DLBCL-RT patients. PD-1 was positive in reactive T-cells, and PD-L1 was positive in background histiocytes and dendritic cells in all studied cases. PD-1 positive expression in tumor cells was considered an independent poor prognostic factor for overall survival (OS) in DLBCL patients (P = 0.04). In addition, DLBCL-RT had a significantly shorter OS than DLBCL-de novo (P = 0.005). CONCLUSION: The high prevalence of PD-1 expression in DLBCL-RT patients supports the promising and potential role of anti-PD-1 immunotherapy in the treatment of DLBCL-RT patients.

A Rare Case of Huge Schistosomiasis-Associated Cecal Polyp Mimicking Colon Carcinoma.

Schistosomiasis is a parasitic infection caused by Schistosoma species, commonly found in tropical and subtropical regions. It affects millions of people worldwide and can lead to different clinical presentations like abdominal pain, weight loss, anemia, and chronic colonic schistosomiasis. In rare cases, chronic infection can result in the development of polyps, which can mimic colon carcinoma, posing a diagnostic challenge. Here, we present a rare case of a huge Schistosomiasis-associated cecal polyp in a patient initially suspected to have colon cancer. The patient's clinical history and the histopathological analysis confirmed the diagnosis, emphasizing the importance of considering parasitic infections in the differential diagnosis of gastrointestinal polyps in Schistosomiasis-endemic areas. This case report highlights the need for increased awareness among healthcare professionals of the potential for Schistosomiasis-associated polyps and the importance of multidisciplinary management in such cases.

Is it essential to remove the submandibular gland in neck dissection in tongue cancer patients?

INTRODUCTION: Submandibular sialadenectomy is a part of the classic technique of neck dissection for oral cavity cancers. However, its removal is associated with a reduction in the salivary outflow in many patients, as well as, some uncommon complications such as lingual and hypoglossal nerve injuries. Assessment of the necessity of such maneuvers should be addressed. PATIENTS AND METHODS: The data of 105 patients with tongue cancer who underwent neck dissection in the Oncology Center, Mansoura University from January 2008 to March 2019 were reviewed and analyzed retrospectively. RESULTS: In all the included patients, whether showing pathologic positive or negative lymph nodes, none showed capsular or parenchymal submandibular gland metastasis except for one patient who showed direct infiltration of the gland by the primary tumor. CONCLUSION: Submandibular sialadenectomy may not be indicated as a part of neck dissection in tongue cancer patients. Further research should be conducted to focus on the effect of its preservation on disease-free and overall survival.

Prognostic value of androgen receptor expression in different molecular types of breast cancer in women.

BACKGROUND: Breast cancer is a common women's disease. Usually, oestrogen is blamed in the aetiology and correlated with the prognosis; however, androgens are recently raising concern about its role in the breast cancer treatment and prognosis. METHODS: In this study we retrieved archival paraffin blocks of breast cancer patients and stained it for androgen. Thereafter, we compared clinico-epidemiologic parameters, histopathology, neoadjuvant response and recurrence rate and pattern among patients with and without androgen receptor (AR) expression. RESULTS: In total, 119 patients fulfilled enrolment criteria; AR expression were present in 77.3% of the patients. AR expression was associated with less grade III (6.8% versus 36.4%), and less triple negative (6.2% versus 25%), but similar overall recurrence rate (25% versus 22.2%). However, distant recurrence was significantly higher in androgen positive patients (91.3% versus 33.3% of all recurrences). CONCLUSION: Androgen expression appears to be common among breast cancer, but with no clear implication in tumour aggressiveness or effect on the rate of recurrence. However, being commonly associated with distant spread may have an impact on survival of the patients.

Nicorandil ameliorates bleomycin-induced pulmonary fibrosis in rats through modulating eNOS, iNOS, TXNIP and HIF-1α levels.

Bleomycin (BLM) is one of the most common anti-cancer drugs used to treat numerous types of tumors. However, pulmonary toxicity is considered the most dramatic effect of BLM. Therefore, BLM has been frequently used for induction of pulmonary fibrosis. This study aimed to evaluate the effect of nicorandil on BLM-induced pulmonary fibrosis and explore the possible mechanisms. BLM was instilled intratracheally into male Sprague-Dawley rats as a single dose (5 mg/kg) and oral nicorandil was given (30 mg/kg/day) for 6 weeks after BLM challenge. At the end of experimental period, rats were sacrificed, and lung histopathology and biochemical parameters were evaluated. Nicorandil therapy attenuated lung inflammation and fibrosis elicited by BLM. Nicorandil significantly reduced total protein content, lactate dehydrogenase (LDH) activity and total and differential cell counts. Moreover, nicorandil diminished lung levels of malondialdehyde and total nitrite/nitrate, in addition to increasing lung contents of reduced glutathione and superoxide dismutase activity. Nicorandil reduced lung and bronchoalveolar lavage fluid contents of hypoxia inducible factor-1α (HIF-1α) and lung content of thioredoxin-interacting protein (TXNIP). Besides, nicorandil significantly improved histological lesions and reduced collagen deposition as well as hydroxyproline content. Immunohistochemical examination revealed that nicorandil-treated rats exhibited significant diminutions in protein expression levels of transforming growth factor beta-1(TGF-ß1) and inducible nitric oxide synthase (iNOS) and enhanced pulmonary protein expression of endothelial NOS (eNOS). In conclusion, these results illustrate the possible potential effects of nicorandil for managing pulmonary fibrosis caused by BLM.

EBV status has prognostic implication among young patients with angioimmunoblastic T-cell lymphoma.

Epstein-Barr virus (EBV)-positive B cells have been detected in 66%-86% of patients with angioimmunoblastic T-cell lymphoma (AITL). However, it remains controversial whether EBV status has an impact on the survival of patients with AITL. In this study, we aimed to reevaluate the impact of EBV on the clinicopathological characteristics of AITL. In particular, we focused on the impact of EBV in younger patients with AITL. In total, 270 cases of AITL were studied. Epstein-Barr virus-positive B cells were detected in 191 (71%) cases (EBER+ group). Among the patients who received anthracycline-based therapy, the EBER status did not affect the overall survival (OS) or progression-free survival (PFS). In the younger group of AITL (≤60 years), PFS was significantly worse in the EBER- group compared to the EBER+ group (P = .0013). Furthermore, the multivariate analysis identified EBER-negative status, thrombocytopenia, and elevated serum IgA level as significant adverse prognostic factors for PFS (P < .001, P < .001, and P = .002). Based on these findings, we constructed new prognostic model for the younger group, based on three adverse factors. We classified the patients into two risk groups: low risk (no or 1 adverse factor) and high risk (2 or 3 adverse factors). This new model for younger patients with AITL showed that both OS and PFS were significantly related to the level of risk (P < .0001). In summary, this study showed that, among younger patients with AITL, an EBER+ status significantly improved prognosis compared to an EBER- status. Our new prognostic model should be applicable to younger patients with AITL.

A prognostic model, including the EBV status of tumor cells, for primary gastric diffuse large B-cell lymphoma in the rituximab era.

EBV-positive diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), often affects the gastrointestinal tract. However, the prognostic significance of EBV associated with primary gastric DLBCL (gDLBCL) has not been established. This retrospective study included 240 patients with primary gDLBCL, diagnosed between 1995 and 2015. Tumor specimens were analyzed with EBER in situ hybridization. In 25 (10%) cases, tumor cells harbored EBV. The EBV+ group more frequently exhibited programmed death-ligand 1 (PD-L1) expression in microenvironment immune cells, but not tumor cells, compared to the EBV- group (86% vs 43%, P = .006). Among 156 patients that received rituximab-containing chemotherapy, the EBV+ group had a significantly worse overall survival (OS) than the EBV- group (P = .0029). Multivariate analyses identified 3 independent adverse prognostic factors of OS: multiple gastric lesions (P = .002), EBER positivity (P = .003), and B symptoms (P = .018). These factors were combined to develop a gDLBCL prognostic (gDLP) model that significantly stratified the patients into 3 distinct risk groups (Scores: good = 0, intermediate = 1, and poor = 2/3, P < .0001) with 5-year OS rates of 100%, 81%, and 39%, respectively. Patients with EBV+ gDLBCL commonly exhibited microenvironmental PD-L1 expression and showed a significantly worse prognosis than subjects with EBV- gDLBCL. Our gDLP model, which included EBV+ tumor cells, provided good predictions of clinical outcome and may be useful for selecting patients in trials in the immune-oncology era.

Clinicopathological Study of 30 Cases of Peripheral T-cell Lymphoma with Hodgkin and Reed-Sternberg-like B-cells from Japan.

The presence of Hodgkin and Reed-Sternberg (HRS)-like B-cells in peripheral T-cell lymphoma (PTCL) is rare and its clinicopathological features still remain unclear. Here, we describe 30 cases of PTCL with HRS-like B-cells from Japan. Twenty-three cases (77%) presented evidence of follicular T-helper phenotype (TFH) derivation: 12 were angioimmunoblastic T-cell lymphoma and 11 PTCL with TFH phenotype (PTCL-TFH). The remaining seven cases were diagnosed as PTCL, not otherwise specified (PTCL-NOS). Epstein-Barr virus (EBV) reactivation was detected in 25 cases (83%), but HRS-like B-cells were EBER in only 20 cases (67%). The median age at diagnosis was 77 years (range, 39-91 y), including 24 patients (80%) were older than 60 years of age. Most of the patients presented at an advanced clinical stage and were associated with higher risk according to the International Prognostic Index. The 3-year overall and progression-free survival rates were 44% and 27%, respectively. No significant clinicopathological differences were detected between PTCL-TFH, PTCL-NOS and the angioimmunoblastic cases. Cases with EBER HRS-like B-cells were associated with inferior overall and progression-free survival compared to those with EBER HRS-like B-cells, but the difference was not significant. In conclusion, HRS-like B-cells were found in a subset of T-cell lymphomas, especially in association with the TFH phenotype and EBV reactivation. These cells have a tendency to affect elderly patients and to be associated with advanced clinical stages and dismal prognosis. The EBV status of HRS-like B-cells does not seem to affect the clinicopathological features of this group of PTCLs.

Bilharzial endocervical polyp.

Schistosomiasis still represents a major threat to women's health in many developing countries. The frequency in developed countries is increasing among immigrants and tourists who have a history of freshwater exposure in endemic areas. This is a case of 43-year-old immunocompetent Egyptian woman presented by abnormal vaginal bleeding. The gynecological examination revealed an endocervical polyp measuring 3 x 2 x 1 cm. Polypectomy was done. Histopathological examination revealed several granulomas containing viable eggs of Schistosoma hematobium. Schistosomiasis is rarely presented with endocervical polyp. In developing countries, schistosomiasis may be considered in differential diagnosis of patient with endocervical polyp.