Syncytial variant of classic Hodgkin lymphoma: Four cases diagnosed with the aid of CD274/programmed cell death ligand 1 immunohistochemistry

Although several reports have highlighted neoplastic PD‐L1 (nPD‐L1) expression in classic Hodgkin lymphoma (CHL), some have addressed associations between its expression and detailed histopathologic features. Here we describe four cases of syncytial variant of CHL (SV‐CHL), with and without Epstein–Barr virus (EBV) association, and highlight the diagnostic utility of PD‐L1 (clone SP142) immunohistochemistry. The patients were a 61‐year‐old male, 45‐year‐old male, 85‐year‐old female, and 89‐year‐old female. All presented with cervical or axillary lymphadenopathy, which on biopsy had the established histopathologic features of SV‐CHL with a biphasic pattern of cohesive sheets of large tumor cells and typically scattered distribution of Hodgkin and Reed–Stenberg (HRS) cells. These tumor cells showed identical immunophenotypic findings for CD15, CD30, Fascin, PAX5, OCT2, BOB1 and EBV harboring, regardless of location. The exception was absent or decreased expression of nPD‐L1 from tumor cells in the confluent sheets, contrasting with HRS cell positivity in typical areas of CHL. These findings offer the first suggestion of possible downregulation of nPD‐L1 expression in association with the histopathologic progression of CHL. The results may be relevant for recognizing ‘confluent’ sheets in the diagnostic workup for SV‐CHL.     

Epstein–Barr virus‐positive diffuse large B cell lymphoma arising from a chronic lymphocytic leukemia: Overlapping features with classical Hodgkin lymphoma

A small proportion of patients with chronic lymphocytic leukemia (CLL) may progress to large cell lymphoma, or Richter syndrome (RS). The large cells of RS may arise through transformation of the original CLL clone (clonally related) or represent a new neoplasm (clonally unrelated), which might be Epstein–Barr virus (EBV)‐associated. We present a 61‐year‐old male with 5‐year history of CLL who developed RS on bilateral adrenal glands. The tumor showed a vague nodular growth pattern separated by thick fibrous bands and the tumor cells were large and pleomorphic, with focal sheet‐like growth pattern, in a background of small B and T‐lymphocytes. The large tumor cells were positive for CD15, CD19, CD20 (intensely and diffusely), CD30, fascin, PAX5, MUM1, OCT2, and LMP‐1 by immunohistochemical stains, and EBV by in situ hybridization. The tumor was diagnosed as EBV‐positive diffuse large B cell lymphoma (DLBCL), with overlapping features of classic Hodgkin lymphoma (CHL). The patient received salvage chemotherapy and was free of disease 2 years after adrenalectomy. We speculated that our case was a clonally unrelated tumor with his underlying CLL and discussed the differential diagnoses between EBV‐positive DLBCL and CHL in the setting of RS.     

Prognostic significance of immunophenotypes and a nodular pattern in primary mediastinal large B‐cell lymphoma

To investigate the clinicopathological and prognostic significance of a nodular pattern and immunophenotypes in primary mediastinal large B‐cell lymphoma (PMBL), histopathological features, including a nodular pattern and immunophenotypes, were analyzed in 58 Japanese PMBL patients. The patients were 23 men and 35 women with a median age of 31 years. The 4‐year progression free survival (PFS) rate was 78%, and the 4‐year overall survival (OS) rate was 89%. Among the histopathological and immunohistochemical features, Bcl6⁺ (P = 0.013), MUM1⁺ (P = 0.091), and pale cytoplasm (P = 0.064) were favorable prognostic indicators of PFS, and Bcl6⁺ (P = 0.051) and MUM1⁺ (P = 0.07) were favorable prognostic indicators of OS. Patients with Bcl2 negativity (n = 11) had 4‐year PFS and OS rates of 100%. Histologically, a nodular pattern, resembling nodular sclerosis classical Hodgkin lymphoma (CHL), was observed in 22 patients (38%). However, this was not a significant prognostic indicator. In conclusion, Bcl6⁺, MUM1⁺, Bcl2^‐, and pale cytoplasm are candidate favorable prognostic indicators for PMBL and should be further examined in larger studies. We suggest that PMBL with a nodular pattern may belong to the same histological spectrum as nodular sclerosis CHL.     

A fulminant case of classical Hodgkin lymphoma: A diagnostic dilemma of Epstein‐Barr virus‐positive large B‐cell neoplasms

We report a fulminant case of classical Hodgkin lymphoma (CHL). The patient died only approximately 2 months after the onset of subjective symptoms. Autopsy specimens revealed atypical cells resembling Hodgkin and Reed‐Sternberg (HRS) cells in a rich inflammatory background in various organs. There were marked, characteristic angiodestructive lesions from infiltrating HRS‐like cells and numerous macrophages. The HRS‐like cells were infected with Epstein‐Barr virus (EBV), immunohistochemically positive for PAX5 and CD30, and negative for CD3, CD20, and ALK. Most B‐cell markers other than PAX5 were negative, and the HRS‐like cells also expressed cytotoxic molecules. Monoclonal rearrangement of immunoglobulin heavy chain was detected by PCR analysis. According to the 2016 WHO classification, we diagnosed mixed cellularity CHL. However, EBV‐positive diffuse large B‐cell lymphoma (DLBCL), not otherwise specified and EBV‐positive B‐cell lymphoma, unclassifiable with features intermediate between DLBCL and CHL were considered as differential diagnoses because both tumors are aggressive EBV‐positive large B‐cell neoplasms with reactive inflammatory cells and sometimes contains HRS‐like cells. The clinical condition of the current case was closer to these two entities than to CHL. A diagnosis of EBV‐positive large B‐cell neoplasms was difficult because of overlapping morphological and immunohistochemical characteristics, but should be considered for prognosis.     

The value of intramural vascular invasion in colorectal cancer – a systematic review and meta‐analysis

Extramural venous invasion (EMVI) is a well‐known prognostic factor in colorectal cancer (CRC). Vascular invasion within the bowel wall, intramural vascular invasion (IMVI), has received less attention and its incidence and prognostic importance in CRC is not completely known. A systematic literature search was performed focusing on the impact of IMVI in CRC. Data were analysed using Review Manager version 5.3 on incidence and clinical endpoints local recurrence, 5‐year cancer‐specific survival (CSS) and 5‐year overall survival (OS). Meta‐analysis was performed in terms of risk ratios (RR) and hazard ratios (HR) with 95% confidence interval (95% CI). Of the initial 1199 papers identified by our search strategy, 20 were included in this meta‐analysis. Of the 8078 included patients, 1008 patients had IMVI (12.5%). Studies that re‐examined histological slides showed a higher incidence of IMVI compared to studies extracting IMVI from pathology reports (17.6 versus 7.7%, P < 0.001). Detection of IMVI increased significantly with the use of additional staining (22.9 versus 12.3%, P < 0.001). IMVI was associated with a decreased CSS HR: 1.6, 95% CI 1.2–2.2 in multivariate analysis). A borderline significant effect was observed for IMVI on local recurrence (RR: 1.5, 95% CI: 0.98–2.3) and OS (RR: 1.2, 95% CI: 1.0–1.4). In conclusion, despite the limited number of studies, there is a clear association with outcome in the presence of IMVI. This warrants more attention to this under‐reported prognostic factor.     

Intrafollicular classical Hodgkin lymphoma mimicking nodular lymphocyte predominant Hodgkin lymphoma: A report of two cases

We here report on two rare cases of intrafollicular classical Hodgkin lymphoma (CHL). Case 1 was a 34‐year‐old man who underwent left supraclavicular lymph node biopsy. Case 2 was a 28‐year‐old woman who underwent surgical resection of an anterior mediastinal mass. The histology and microenvironment of both specimens resembled those of nodular lymphocyte predominant Hodgkin lymphoma. Nodular architecture was observed, which comprised normal‐appearing small lymphocytes and scattered lymphocyte predominant (LP)‐like cells. CD23⁺ follicular dendritic cell meshworks were present in the nodules, surrounded by a mantle zone containing IgD⁺ B cells. The LP‐like cells were ringed by CD3⁺ and PD‐1⁺ T cells, and numerous CD20⁺ B cells were present in the background. However, the immunophenotypes of the LP‐like cells resembled those of Hodgkin/Reed‐Sternberg cells of CHL; they were positive for CD15, CD30, and PAX5, and negative for CD20, Bcl6, Oct2, and Bob1. These histopathological findings indicate that CHL can be derived from the germinal center.     

FOXP3(+) regulatory and TIA-1(+) cytotoxic T lymphocytes in HIV-associated Hodgkin lymphoma

Human immunodeficiency virus (HIV) infects CD4⁺ lymphocytes, leading to a development of malignant lymphomas, such as HIV‐associated Hodgkin Lymphoma (HIV‐HL). This study aimed to assess the differences in cellular composition of the inflammatory reactive background of HIV‐HLs. We examined infiltrating T lymphocytes, specifically regulatory T cells, cytotoxic cells, Epstein‐Barr virus (EBV) related antigens and HIV‐receptor CCR5. In all HIV‐HL cases, Hodgkin and Reed‐Sternberg (HRS) cells showed EBER1 expression, LMP‐1 staining positivity and EBNA‐2 staining negativity, except for one case which showed LMP‐1 staining negativity. Our histological findings indicate the percentage of CD8⁺, TIA‐1⁺ lymphocytes was significantly higher in HIV‐HL than in non‐HIV‐HL cases (P < 0.05). On the other hand, the percentage of CD4⁺, FOXP3⁺ lymphocytes was significantly lower in HIV‐HL than in non‐HIV‐HL cases (P < 0.05) but present. The percentage of CCR5⁺ lymphocytes was significantly lower in HIV‐HL than in non‐HIV‐HL cases (P < 0.05). Usually, CD4⁺ and CCR5⁺ lymphocytes are reported to be rarely detected in HIV‐associated non‐Hodgkin lymphomas, but the presence of CD4⁺ and/or FOXP3⁺ lymphocytes may be implicated in the pathogenesis of HL. In addition, although additional CD8⁺ lymphocytes are probably not EBV‐LMP specific cytotoxic T‐cells, these lymphocytes may also well be involved in the pathogenesis of HIV‐HL.     

Prognostic value of pathological lymph node status and primary tumour regression grading following neoadjuvant chemotherapy – results from the MRC OE02 oesophageal cancer trial

Aims

Neoadjuvant chemotherapy (NAC) remains an important therapeutic option for advanced oesophageal cancer (OC). Pathological tumour regression grade (TRG) may offer additional information by directing adjuvant treatment and/or follow‐up but its clinical value remains unclear. We analysed the prognostic value of TRG and associated pathological factors in OC patients enrolled in the Medical Research Council (MRC) OE02 trial.

Methods and results

Histopathology was reviewed in 497 resections from OE02 trial participants randomised to surgery (S group; n = 244) or NAC followed by surgery [chemotherapy plus surgery (CS) group; n = 253]. The association between TRG groups [responders (TRG1–3) versus non‐responders (TRG4–5)], pathological lymph node (LN) status and overall survival (OS) was analysed. One hundred and ninety‐five of 253 (77%) CS patients were classified as ‘non‐responders’, with a significantly higher mortality risk compared to responders [hazard ratio (HR) = 1.53, 95% confidence interval (CI) = 1.05–2.24, P = 0.026]. OS was significantly better in patients without LN metastases irrespective of TRG [non‐responders HR = 1.87, 95% CI = 1.33–2.63, P < 0.001 versus responders HR = 2.21, 95% CI = 1.11–4.10, P = 0.024]. In multivariate analyses, LN status was the only independent factor predictive of OS in CS patients (HR = 1.93, 95% CI = 1.42–2.62, P < 0.001). Exploratory subgroup analyses excluding radiotherapy‐exposed patients (n = 48) showed similar prognostic outcomes.

Conclusion

Lymph node status post‐NAC is the most important prognostic factor in patients with resectable oesophageal cancer, irrespective of TRG. Potential clinical implications, e.g. adjuvant treatment or intensified follow‐up, reinforce the importance of LN dissection for staging and prognostication.     

High-level cytoplasmic cyclin D1 expression in lymph node metastases from prostate cancer independently predicts early biochemical failure and death in surgically treated patients

Fleischmann A, Rocha C, Saxer‐Sekulic N, Zlobec I, Sauter G & Thalmann G N
(2011) Histopathology 58 , 781–789
High‐level cytoplasmic cyclin D1 expression in lymph node metastases from prostate cancer independently predicts early biochemical failure and death in surgically treated patients Aims: To test the prognostic significance of cyclin D1 in nodal‐positive prostate cancer. Methods and results: Nuclear and cytoplasmic cyclin D1 expression was evaluated in 119 nodal‐positive prostate cancer patients undergoing radical prostatectomy and extended lymphadenectomy. Cyclin D1 was correlated with various tumour features and biochemical recurrence‐free survival (bRFS), disease‐specific survival (DSS) and overall survival (OS). In the metastases, high‐level cytoplasmic cyclin D1 expression independently predicted poor outcome (5‐year bRFS, 12.5% versus 26.4%, P = 0.006; 5‐year DSS, 56.3% versus 80.7%, P = 0.007; 5‐year OS, 56.3% versus 78.7%, P = 0.011). These patients had a 2.62‐fold elevated risk of dying from prostate cancer as compared with patients with low‐level cytoplasmic cyclin D1 expression (P = 0.024). All other subcellular compartments of cyclin D1 expression in primary tumours and metastases were prognostically non‐significant. Conclusions: The subcellular location of cyclin D1 expression in prostate cancer is linked to specific clinical courses. Survival stratification according to biomarker expression in metastases indicates an important role for tumour sampling from these tissues.     

FOXP3+/CD68+ ratio within the tumor microenvironment may serve as a potential prognostic factor in classical Hodgkin lymphoma

Classical Hodgkin lymphoma (CHL) is characterized by extensive inflammatory immune cells, which predict the disease prognosis. Therefore, this study aimed to explore the significance of different tumor-infiltrated immune cells and subpopulation ratios observed in the tumor microenvironment of CHL, particularly relating to the disease's prognosis-focusing on overall survival (OS) and event-free survival (EFS). Utilizing immunohistochemistry, the quantification and exploration of selected immune cells' subsets, including CD3+, CD4+, CD8+, FOXP3+, CD20+, and CD68+ were conducted on 102 histological samples with primary CHL. Eosinophils were pathologically assessed. Besides, we determined the ratios between different tumor-infiltrated immune cells for each patient. Kaplan-Meier method and Cox regression modeling were used for survival analysis. We demonstrated that among all ratios and immune cells individually, only a higher FOXP3+/CD68+ ratio (≥1.36 cutoff) displayed a tendency towards a favorable OS (p = 0.057, HR = 0.43 [0.18–1.02]) and EFS (p = 0.067, HR = 0.44 [0.18–1.06]) using Cox regression modeling. Moreover, the Kaplan-Meier method showed an association of a higher FOXP3+/CD68+ ratio with a longer 5-years OS (p = 0.037) and a tendency to a better EFS (p = 0.051); however, neither the combined FOXP3+ and CD68+ nor FOXP3+ or CD68+ separately was correlated to the CHL survival. Together, these results demonstrated that the FOXP3+/CD68+ ratio could predict the outcomes of CHL, providing more informative significance than FOXP3+ and CD68+ combined or FOXP3+ and CD68+ individually and might be a potential indicator of risk stratification, which has an important value for guiding the clinical treatment.     

Prognostic significance of circulating Epstein-Barr virus DNA in pulmonary lymphoepithelioma-like carcinoma: A meta-analysis and validation study

In small-scale studies, circulating Epstein-Barr virus (EBV) DNA levels have prognostic value in patients with pulmonary lymphoepithelioma-like carcinoma (LELC). Therefore, we performed a comprehensive meta-analysis to evaluate the prognostic significance of circulating EBV DNA levels in patients with pulmonary LELC. Studies that discussed the prognostic significance of circulating EBV DNA detection in pulmonary LELC were eligible for inclusion in this study. The overall survival (OS) and progression-free survival (PFS) were the primary outcomes. Pooled hazard ratio (HR), 95% confidence intervals (CIs), and p value were calculated to estimate the prognostic significance of EBV DNA levels. Additionally, we conducted a further observation using an independent cohort. The pooled HR and 95% CI of pretreatment EBV DNA levels for OS and PFS were 3.63 (95% CI: 2.90–4.55) and 2.88 (95% CI: 1.90–4.38), respectively. The pooled HR and 95% CI for Posttreatment EBV DNA levels for OS and PFS were 3.77 (95% CI: 2.96–4.80) and 3.52 (95% CI: 1.91–6.51, p < 0.001), respectively. The independent cohort showed similar results that patients with high pretreatment EBV DNA or positive posttreatment EBV DNA had significantly inferior PFS. Circulating EBV DNA levels provide prognostic values of survival and treatment response in pulmonary LELC patients.     

Classical Hodgkin lymphoma,lymphocyte depleted type: Clinicopathological analysis and prognostic comparison with other types of classical Hodgkin lymphoma

The lymphocyte-depleted type (LD) is a morphological subtype of classical Hodgkin lymphoma (CHL), but its rarity and heterogeneous morphological character makes a definite clinicopathological identification difficult. To characterize this disease, LD cases were compared with other types of CHL. From 1982 to 2006, we collected 310 CHL cases. Among them, 29 cases were diagnosed as LD. We could additionally analyze clinical data of 157 CHL cases (including 28 LD cases) and the immunophenotype of 150 CHL cases (including 28 LD cases). We compared clinicopathological data between LD cases and other types of CHL cases and determined prognostic factors by univariate and multivariate analysis. LD showed a more progressive disease stage (stage 3/4, 64%) than other types of CHL (stage 3/4, 30%; P < 0.001), more frequent B symptoms (89% vs. 40%; P < 0.001) and extranodal invasion (50% vs. 11%; P < 0.001), older age (median: 66 vs. 33; P < 0.001), higher serum soluble interleukin 2 receptor levels (median: 8240 U/ml vs. 1705 U/ml; P < 0.001), and much poorer prognosis regardless of the international prognostic score (IPS) (five-year overall survival: 29% vs. 86%; P < 0.001). The morphological subtype of LD represented an independent prognostic factor as did age and IPS by multivariate analysis. Immunohistochemistry showed that the characteristics of Hodgkin and Reed–Sternberg (HRS) cells of LD are basically not different from those of other types of CHL in terms of CD30, CD15, and chemokine receptors, except for high-level EB-virus infection (72% vs. 41%; P = 0.002). LD should be distinguished from other types of classical Hodgkin lymphoma because of its definitive clinicopathological characters.     

Extracapsular extension but not the tumour burden of lymph node metastases is an independent adverse risk factor in lymph node-positive bladder cancer

Seiler R, von Gunten M, Thalmann G N & Fleischmann A
(2011) Histopathology  58 , 571–578
Extracapsular extension but not the tumour burden of lymph node metastases is an independent adverse risk factor in lymph node‐positive bladder cancer Aims: To evaluate risk factors in lymph node‐positive bladder cancer. Methods and results: Lymph node‐positive bladder cancer patients (n = 162), preoperatively staged N0M0, underwent cystectomy and standardized extended lymphadenectomy. Five‐year overall survival of the cohort was 33%. In univariate analysis, tumour stage (P < 0.006), extracapsular extension of lymph node metastases (P < 0.001), total diameter of metastases (P < 0.04) and lymph node stage (P < 0.03) were significantly correlated with overall survival (OS), disease‐specific survival (DSS) and recurrence‐free survival (RFS). On multivariate analysis, only extracapsular extension (OS, P < 0.002; DSS, P < 0.02; RFS, P = 0.058) and primary tumour stage (OS, P = 0.058; DSS, P < 0.02; RFS, P < 0.02) added independent prognostic information. Extracapsular extension of lymph node metastases did not correlate with a specific recurrence pattern; patients with organ‐confined tumours (pT1/2) never had pelvic relapse. Conclusions: Extracapsular extension of lymph node metastases but not lymph node tumour burden adds independent prognostic information in lymph node‐positive bladder cancer. These biological differences in lymph node‐positive bladder cancer are not reflected in the sixth, and challenge future, TNM classification.     

Epstein-Barr virus–positive nodular lymphocyte predominant Hodgkin lymphoma

Hodgkin lymphoma (HL) is classified into 2 largely distinct subgroups, namely nodular lymphocyte predominant HL (NLPHL) and classic HL (CHL). CHL is further divided into nodular sclerosis, lymphocyte-rich, mixed cellularity (MCCHL) and lymphocyte-depleted (LDCHL) subtypes. In industrialized nations, Epstein-Barr virus (EBV) has been associated with all types of CHL, especially the MCCHL and LDCHL subtypes, but is rare in NLPHL. We report 8 cases of EBV-positive NLPHL occurring in patients in the United States. All 8 patients have no history of immunosuppression and presented with localized or systemic lymphadenopathy. Histologically, 6 cases had a vaguely nodular pattern and 2 cases had a nodular and diffuse pattern. In all cases, lymphocyte predominant (LP) cells were observed in a background of small lymphocytes and histiocytes. Immunohistochemical analysis showed that the LP cells in all cases were positive for CD20, CD79a, PAX5, OCT2, and CD45 and were negative for CD15. CD30 was expressed variably in 7 cases. EBV encoded RNA was present in all LP cells in 5 cases and in a subset of LP cells in 3 cases. One patient was treated with radiation therapy and 7 patients received chemotherapy, including 4 of 7 patients who underwent autologous stem cell transplantation. EBV infection is a rare primary or secondary event in NLPHL that correlates with poorer prognosis and often requires more aggressive therapy. The variable expression of CD30 in most of these cases could be the result of EBV infection.     

Subtle CD20 positivity in the bone marrow of a patient who has a mucosa‐associated lymphoid tissue lymphoma should not be regarded as evidence of involvement in the bone marrow

Aims: Bone marrow (BM) biopsies of some mucosa‐associated lymphoid tissue (MALT) lymphoma patients show scattered or small clusters of CD20+ cells without definite lesions (subtle CD20 positivity). The aim of this study was to evaluate the clinical significance of BM involvement and subtle CD20 positivity in 122 patients diagnosed with MALT lymphoma. Methods and results: Patients were divided into three categories: BM involvement [BM(+)], subtle CD20 positivity, and no BM involvement [BM(?)]. Eleven (9%) showed BM involvement, and 17 (14%) showed subtle CD20 positivity. BM(+) patients had significantly worse progression‐free survival (PFS) than BM(?) patients [hazard ratio (HR) 6.25, P = 0.01], but there was no significant difference between subtle CD20 positivity and BM(?) patients. Patients with >30 CD3+ cells among 100 nucleated cells in the areas with increased numbers of CD3+ cells had significantly worse PFS than those with <15 CD3+ cells (HR 5.49, P = 0.02). BM(+) patients with >30 CD3+ cells had worse PFS than those with ≤30 CD3+ cells (P = 0.029), with an extent of BM(+) involvement of >10% positively correlating with >30 CD3+ cells (P = 0.015). Conclusions: Patients with BM(+) MALT lymphoma showed significantly worse PFS than those with subtle CD20 positivity and BM(?) MALT lymphoma, but the PFS of patients with subtle CD20 positivity MALT lymphoma was not significantly different from that of those with BM(?) MALT lymphoma. Increased numbers of BM T cells in MALT lymphoma patients might be suggestive of a worse prognosis.     

Epstein-Barr virus gene expression and latent membrane protein 1 gene polymorphism in pediatric liver transplant recipients

Immunosuppressed pediatric transplant recipients are at risk of developing Epstein–Barr virus (EBV)‐associated complications (such as post‐transplant lymphoproliferative disorders). Monitoring of the EBV DNA level in blood alone has a low predictive value for the post‐transplant course of EBV infection and its complications. Therefore, additional prognostic markers are widely sought. The study aim was to analyze EBV gene expression patterns and LMP1 polymorphism in relation to EBV DNA levels in pediatric liver transplant recipients. EBV load measurement, LMP1 variant, and gene expression analysis were performed in collected prospectively multiple blood samples from 30 patients. Several distinct patterns of EBV gene expression were identified: latency 2 (71%), latency 3 (13%), latency 0 (11%), and lytic infection (5%). In most children's multiple blood samples, both EBV gene expression patterns and expression levels of individual EBV genes varied significantly over time. EBV gene expression patterns were not associated with the EBV load. However, the viral load correlated with the LMP1 and LMP2 expression (r = 0.34; P = 0.006, and r = 0.45; P = 0.001, respectively). Two variants of the LMP1 gene were detected, and they were consistent over time in individual patients. A wild type of LMP1 was associated with higher EBV‐DNA loads (P = 0.03). This indicates that EBV infection in immunosuppressed patients is a very dynamic process, but changes in the state of EBV infection do not influence significantly the viral load. The latter, however, can be associated with the activity of LMP1 and LMP2 genes, as well as polymorphism of LMP1. J. Med. Virol. 83:2182–2190, 2011. © 2011 Wiley Periodicals, Inc.     

Clinicopathological characteristics and prognostic factors of advanced colorectal mucinous adenocarcinoma

Yamaguchi T, Taniguchi H, Fujita S, Sekine S, Yamamoto S, Akasu T, Kushima R, Tani T, Moriya Y & Shimoda T
(2012) Histopathology  61, 162–169 Clinicopathological characteristics and prognostic factors of advanced colorectal mucinous adenocarcinoma Aims: Mucinous adenocarcinoma (MUC) is a histological variant of colorectal adenocarcinoma. The aim of the present study was to characterize clinicopathological features and identify prognostic factors of MUCs. Methods and results: A total of 181 patients with MUC who underwent surgery between 1975 and 2003 were reviewed. The clinicopathological features of these patients were compared with those of 4125 non‐MUC patients. Univariate and multivariate analyses were conducted to identify significant prognostic factors in 102 patients with pT3 or pT4 tumour who underwent curative surgery. Patients with MUCs tended to present with more advanced clinical stages. The overall 5‐year survival rate of MUC patients was lower than that of non‐MUC patients; however, no prognostic difference was found when patients with the same clinical stages were compared. Multivariate analysis revealed male sex, bowel obstruction and infiltrating growth type as independent prognostic factors. Five‐year cancer‐specific survival rates for MUC patients with ≤1, 2 and 3 risk factors identified by multivariate analysis were 95.5%, 52.1% and 0.0%, respectively (P < 0.001). Conclusions: Mucinous adenocarcinoma represents a distinct clinicopathological entity. Sex, bowel obstruction and growth patterns might be useful prognostic factors to identify patients with a high risk of recurrence after curative resection of advanced MUCs.     

Epstein-Barr virus-associated lymphoproliferative disorder presenting with classical Hodgkin lymphoma and developing as peripheral T-cell lymphoma 9 years later: a case report of composite lymphoma

We describe a patient who was diagnosed with classical Hodgkin lymphoma (CHL) at 67-years-old and peripheral T-cell lymphoma, not otherwise specified (PTCL) at 76-years-old, and died 5 months later. Both tumors showed prominent epithelioid cell reaction admixed with neoplastic cells. Hodgkin and Reed-Sternberg cells in the swollen lymph node were positive for CD30 and EBV-encoded RNA (EBER). PTCL cells in the skin tumor were positive for cytoplasmic CD3ε, CD4 and EBER. A rearrangement band of the T-cell receptor gene was detected in the skin tumor. This case is the first documented EBV-associated composite lymphoma composed of CHL and PTCL. The patient may show the possibility that both EBV infection and/or immunodeficiency induce the development of CHL and PTCL.     

Age‐related EBV‐associated B‐cell lymphoproliferative disorders: Diagnostic approach to a newly recognized clinicopathological entity

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, which may be associated with immune senescence in the elderly and which are now incorporated into the 2008 World Health Organization lymphoma classification as EBV‐positive diffuse large B‐cell lymphoma (DLBCL) of the elderly. This newly described disease is pathologically characterized by a proliferation of atypical large B cells including Reed–Sternberg‐like cells with reactive components, which pose a diagnostic problem for pathologists. Clinically, this disease may present with lymphadenopathy, and is often extranodal, frequently involving the skin, gastrointestinal tract, or lung. Onset is usually after the age of 50; the median patient age is 70–79 years, and incidence continues to increase with age, providing additional support to the nosological term of EBV+ DLBCL of the elderly. These patients have a worse prognosis than those with EBV‐negative DLBCL or EBV+ classical Hodgkin lymphoma (CHL). The aim of the present review was to summarize the clinicopathological profile of age‐related EBV+ LPD and EBV+ Hodgkin lymphoma to facilitate diagnostic approach.