Pay attention to the detection and evaluation of CD30 in pathological diagnosis of lymphoma / 中华病理学杂志

CD30 is a transmembrane glycoprotein of tumor necrosis factor receptor family, which is expressed differently in various lymphomas. It has specific effects on the proliferation and function of tumor cells. However, the significance of CD30 expression has not been fully recognized by clinicians and pathologists, and the detection and evaluation of CD30 have not been standardized. The role of CD30 in the diagnosis of lymphoma, detection methods and reporting standards are summarized in the paper to improve the understanding of CD30.

Linfoma anaplásico de células T grandes primario cutáneo CD30+. Serie de nueve casos / Primary cutaneous CD30+ anaplastic large T-cell lymphoma. Series of nine cases

Resumen Introducción: El linfoma anaplásico de células T grandes CD30+ es un linfoma primario cutáneo en el cual no hay evidencia de enfermedad sistémica; para su diagnóstico es necesario el estudio histopatológico. Objetivo: Presentar los casos diagnosticados en el Departamento de Dermatología del Hospital General "Dr. Manuel Gea González" con linfomas anaplásicos de células T grandes primarios cutáneos CD30+ durante un periodo de 24 años. Método: Estudio retrospectivo en el que realizó estadística descriptiva. Se recopiló información de sexo, edad, características clínicas, resultados de pruebas complementarias, tratamientos previos y actuales, reportes de los estudios histopatológicos y de inmunohistoquímica. Resultados: Entre 29 309 expedientes, se encontraron nueve casos (0.000034 %) con diagnóstico de linfoma anaplásico de células T CD30+. Se hizo la confirmación del diagnóstico histopatológico e inmunohistoquímico por dos dermatopatólogos certificados. La edad promedio fue de 61.2 años, hubo predominio del sexo femenino y de lesión papular o nodular y topografía variada como presentación clínica inicial. Conclusiones: El pronóstico del linfoma anaplásico de células T grandes CD30+ en la población estudiada fue dependiente del estadio clínico. El tratamiento en etapas tempranas tiene resultados favorables.

Abstract Introduction: CD30+ anaplastic large T cell lymphoma is a cutaneous primary lymphoma in which there is no evidence of systemic disease; histopathological study is required for its diagnosis. Objective: To present the cases diagnosed with primary cutaneous CD30+ anaplastic large T-cell lymphoma over a 24-year period in Hospital General "Dr. Manuel Gea González" Department of Dermatology. Method: Retrospective study. Descriptive statistics was carried out. Information was collected on gender, age, clinical characteristics, complementary test results, previous and current treatments, histopathological studies reports and immunohistochemistry test results. Results: Of 29 309 records, nine patients (0.000034%) with a diagnosis of CD30+ anaplastic T cell lymphoma were found. Histopathological and immunohistochemical diagnosis was confirmed by two certified dermatopathologists. Average age was 61.2 years, and there was a predominance of the female gender, with initial clinical presentation as a papular or nodular lesion and varied topography. Conclusions: The prognosis of CD30+ anaplastic large T cell lymphoma in the studied population was dependent on clinical stage. The treatment at early stages has favorable results.

Treatment of primary cutaneous anaplastic large cell lymphoma

Primary cutaneous anaplastic large cell lymphoma (C-ALCL) is a rare subtype of primary cutaneous lymphoma with a favorable prognosis. Primary cutaneous CD30+ lymphoproliferative disorders, which include C-ALCL and lymphomatoid papulosis, are the second most common group of cutaneous T-cell lymphomas. C-ALCL is comprised of large cells with anaplastic, pleomorphic, or immunoblastic cytomorphology, and indeed, more than 75% of the tumor cells express the CD30 antigen. C-ALCL clinically presents with solitary or localized reddish-brown nodules or tumors, and sometimes indurated papules, and they may be with ulceration covering with dark eschar. Multifocal lesions are seen in 20% of the patients. Extracutaneous dissemination, which mainly involves the regional lymph nodes, occurs in 10% of patients. A 69-year-old man noticed a mild elevated cutaneous lesion containing central ulceration covering with brownish black necrotic tissue on the right lower lip, and the lesion was surgically removed. After the first operation, another skin lesion was developed and the histological examination confirmed the diagnosis, C-ALCL. Eight specimens were excised during the 7-month follow-up period. The patient started the treatment with low-dose oral methotrexate (15 mg/wk) and there was no recurrence for 11 months.

A Case of Primary Cutaneous Anaplastic Large Cell Lymphoma on Palm / 대한피부과학회지

Primary cutaneous anaplastic large cell lymphoma (PCALCL) is a rare primary cutaneous lymphoma that is predominantly composed of large lymphoid cells that express the CD30 antigen. The skin lesion of PCALCL is usually single, ulcerative, and located on the trunk or extremities and rarely the palm. A 25-year-old woman presented with a plaque on the left palm for 20 days. The plaque was walnut-sized and purple to gray colored with erosion in the center. Histopathologic examination showed infiltration of large atypical cells in the dermis. The large tumor cells showed positivity for CD3, CD4, and CD30 and negativity for CD8, CD20, epithelial membrane antigen, and anaplastic lymphoma kinase. PET-CT showed no other hypermetabolic lesion except that on the left palm, and we finally arrived at a diagnosis of PCALCL. The patient was treated with an intralesional injection of methotrexate (25 mg/mL, 0.45 cc). After 3 months of treatment, the walnut-sized plaque had disappeared and a peripheral hyperpigmented patch remained.

Brentuximab vedotin: clinical updates and practical guidance

Brentuximab vedotin (BV), a potent antibody-drug conjugate, targets the CD30 antigen. Owing to the remarkable efficacy shown in CD30-positive lymphomas, such as Hodgkin's lymphoma and systemic anaplastic large-cell lymphoma, BV was granted accelerated approval in 2011 by the US Food and Drug Administration. Thereafter, many large-scale trials in various situations have been performed, which led to extensions of the original indication. The aim of this review was to describe the latest updates on clinical trials of BV and the in-practice guidance for the use of BV.

Expression of CD30 in Diffuse Large B Cell Lymphoma and Its Clinical Significance / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To evaluate the expression and clinical significance of tumor necrosis factor receptor (TNFR) superfamily protein CD30 in diffuse large B cell lymhoma (DLBCL).</p><p><b>METHODS</b>The CD30 expression, clinical characteristics and prognosis of 63 patients with DLBCL, NOS out of 149 patients with DLBCL admitted in our hospital between January 2008 and December 2012 were analyzed retrospectively.</p><p><b>RESULTS</b>no significant relationship existed between CD30 expression and clinical features, such as age, sex, B symptoms, staging, ECOG PS, LDH level, extranodal site involvement, IPI, GCB or non GCB type, bone marrow involvement. By univariate analysis, the clinical factors associated with general OS and EFS, included CD30, ECOG PS, B symptoms, extranodal site involvement, LDH level, IPI, bone marrow involvement and rituximab. Univariate analysis in GCB DLBCL indicated that CD30 had no significant effect on OS and EFS. However, univariate analysis in non-GCB DLBCL indicated CD30 was associated with longer OS (P=0.037) and showed a tendency of better EFS (P=0.067). In multivariate analysis, IPI and CD30 were independent prognostic factors for OS (IPI: P=0.000, 95%CI 0.042-0.374, CD30: P=0.044, 95%CI 1.055-60.613), and IPI also was independent prognostic factors for EFS (P=0.000, 95%CI 0.040-0.360). CD30+ and DLBCL have a tendency of better EFS (P=0.050, 95%CI 0.996-56.501).</p><p><b>CONCLUSION</b>CD30 expression level correlates with the prognosis of DLBCL and has a certain clinical value, which may be a new prognostic index of DLBCL.</p>

Expression of microRNA in ALK-negative anaplastic large cell lymphoma and CD30-positive peripheral T cell lymphoma, not otherwise specified / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the role of microRNAs (miRNAs) in ALK-negative anaplastic large cell lymphoma and CD30 positive peripheral T cell lymphoma (not otherwise specified), and discuss the pathogenesis of miRNAs in ALK-negative anaplastic large cell lymphoma.</p><p><b>METHODS</b>Three cases of ALK-negative anaplastic large cell lymphoma of lymph node, 3 cases of CD30-positive peripheral T cell lymphoma (not otherwise specified) of lymph node and 3 cases of reactive hyperplasia of lymph node were detected by high flow microarray of miRNAs. The method of real-time quantitative polymerase chain reaction was further applied for 7 miRNAs in 15 cases of ALK-negatie anaplastic large cell lymphomas of lymph node and 15 cases of CD30-positive peripheral T cell lymphoma (not otherwise specified) of lymph node.</p><p><b>RESULTS</b>The significant difference of 13 miRNAs was found between ALK-negative anaplastic large cell lymphoma and CD30 positive peripheral T cell lymphoma (not otherwise specified) (P < 0.05), of which the result of 5 miRNAs was consistent with miRNAs expression spectrum: miR-664b-5p, miR-1275, miR-4739, miR-4736 and miR-504-5p, the difference was statistically significant (P < 0.05). Compared with reactive hyperplasia of lymph nodes, miR-664b-5p, miR-1275 and miR-4739 were significantly under-expressed (P = 0.004, P = 0.021, P = 0.031) and miR-4736 and miR-504-5p were significantly over-expressed (P = 0.009, P = 0.007) in ALK negative anaplastic large cell lymphoma.</p><p><b>CONCLUSIONS</b>MiR-664b-5p, miR-1275, miR-4739, miR-4736 and miR-504-5p may become an important indicator in the differentiation ALK-negative anaplastic large cell lymphoma from CD30-positive peripheral T cell lymphoma (not otherwise specified). MiR-4739, miR-4736 and miR-1275 may play important role in pathogenesis of negative-anaplastic large cell lymphoma by target genes: TNFRSF8 and TMOD1.</p>

Grey zone lymphoma with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma: clinicopathologic characterization of 16 cases showing different patterns / 中华病理学杂志

<p><b>OBJECTIVE</b>To profile the clinicopathologic features of a series of grey zone lymphoma (GZL) cases with hybrid features of diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma (CHL), with a purpose to gain an in-depth understanding of the borderline B-cell neoplasm.</p><p><b>METHODS</b>The clinical, morphologic and immunophenotyical characteristics of 16 cases were retrospectively analyzed.</p><p><b>RESULTS</b>The patients were mostly male adults, with a male to female ratio of 1.7: 1.0 and a mean age of 40.2 years. Eight patients presented with peripheral nodal lesions and five cases with mediastinal involvement. Histologically and immunophenotypically, the 16 cases were classified into three sub-categories. In 4 cases, the morphologic features resembled CHL more closely, but the neoplastic cells showed uniform and intense positive staining of CD20 (pattern 1). Although the initial impression of the other 8 cases was that of DLBCL, the expression levels of CD20 and PAX5 were variable, and CD30 or CD15 was positive (pattern 2). A characteristic feature of pattern 3, observed in the remaining 4 cases, demonstrated a broad spectrum of morphology with hybrid features of both CHL and DLBCL. The neoplastic cells in pattern 3 were positive for CD20, CD30 and CD15. EBV-LMP1 was detected in 6 of the 11 tested cases. Clinically, most patients with GZL seemed insensitive to immuno-chemotherapy of the R-CHOP regimen.</p><p><b>CONCLUSIONS</b>The diagnostic criteria for GZL with features intermediate between DLBCL and CHL is proposed by the three histologic patterns commonly seen in these lesions. Cases presented with peripheral lesions might differ from those with mediastinal presentation pathologically. At current time, there is no effective treatment for these borderline B-cell lymphomas and the prognosis is poor.</p>

A Chinese patient with relapsed and refractory Hodgkin lymphoma treated with brentuximab vedotin / 癌症

At present, approximately 20% of Hodgkin lymphomas (HL) are relapsed and refractory, and therapeutic methods including chemotherapy, radiotherapy, and even stem cell transplantation are unsatisfactory. Brentuximab vedotin, composed of CD30 antibody and a chemotherapeutic agent, is a new targeted drug that eradicates tumor cells by binding to the CD30 antigen on their surface. In clinical trials, the response rate and complete remission rate of this drug were 73% and 40%, respectively, for relapsed and refractory HL. Here we report a case of CD30-positive relapsed and refractory HL that was treated with brentuximab. Before the treatment with brentuximab, the patient underwent chemotherapy, radiotherapy, and autologous stem cell transplantation. However, the disease continued to progress, affecting multiple organs and prompting symptoms such as persistent fever. After the treatment with brentuximab, the patient's condition improved. Body temperature returned to normal after 4 days. Lung nodules were reduced in size and number after a single course of treatment, and PET/CT showed partial remission and complete remission after 3 and 6 courses of treatment, respectively. The entire treatment process progressed smoothly, though the patient experienced some symptoms due to chemotherapy, including peripheral neuritis of the limbs, irritating dry cough, and mild increase in aminotransferase. No serious adverse effects were observed. The current general condition of the patient is good; the continuous complete remission has amounted to 6 months.

A Case of Lymphomatoid Papulosis of the Eyelid

PURPOSE: Lymphomatoid papulosis (LyP) is one of the primary cutaneous CD30-positive lymphoproliferative disorders. LyP of the eyelid has rarely been reported. Herein, a case of typical LyP of the medial canthal area is reported. In addition, a literature review was performed. CASE SUMMARY: A 40-year-old female presented with a skin mass in the medial canthal area of the left eye that developed 2 months earlier. Initially, a focal skin lesion developed, and even with conservative treatment at a local clinic, progressed to a mass lesion having a central ulceration and adjacent edema. After 6 weeks, the adjacent edema had gradually decreased. On ophthalmic examination, the left medial canthal lesion was a 6 x 6 mm sized elevated mass with a central crater covered by crust. The clinical impression was keratoacanthoma. The lesion was widely excised and reconstructed by a full-thickness skin graft after an incisional biopsy. Histopathologic findings showed dermal infiltration of various inflammatory cells with atypical lymphocytes showing positivity to the CD30 antigen, and LyP was diagnosed. Systemic evaluation showed no evidence of systemic lymphoma and the patient has remained free of recurrence or systemic disease after a 1-year follow-up.

Clinicopathologic study of 40 cases of mediastinal tumours of haematopoietic and lymphoid tissues / 中华病理学杂志

<p><b>OBJECTIVE</b>To study clinical and histopathological features, and diagnosis of mediastinal tumours of haematopoietic and lymphoid tissues (MTHL).</p><p><b>METHODS</b>Forty cases of MTHL were analyzed for clinicopathology by microscopy and immunohistochemical staining and in situ hybridization, according to the updated 2008 WHO classification of tumours of haematopoietic and lymphoid tissues.</p><p><b>RESULTS</b>In 40 cases of MTHL, there were 20 males and 20 females. The ratio of male/female was 1:1. The mean age was 31.8 years and median age was 29 years (range, 12 - 70 years).Superior vena cava syndrome was observed in 28 cases. The specimens of 4 cases were obtained by lumpectomy, whereas 36 cases by biopsy (25 cases by thoracoscopy, 1 by core needle aspiration). Twenty cases lay in anterior mediastinum, and 2 in posterior, 1 in superior, 8 in anterior and superior, 2 in posterior and superior, 2 in anterior and middle, 1 in middle and anterior mediastinum.Frozen section were performed in 28 cases, and 17 cases were diagnosed as tumours of haematopoietic and lymphoid tissues (consistency ratio was 60.7%). Twelve cases were classical Hodgkin lymphomas (cHL) (8 were nodular sclerosis subtype, and 3 were mixed cellarity, 1 was lymphocyte-rich subtype), and 10 were primary mediastinal (thymic) large B cell lymphoma (PMBCL), 10 were precursor lymphocyte neoplasm [8 were T lymphoblastic leukemia/lymphomas (T-LBL), 2 were B-LBL], 1 was MALT lymphoma, 1 was composite lymphoma (PMBCL and cHL), 2 were myeloid sarcomas, 4 were gray zone lymphomas (GZL) (3 had morphology reminiscent of cHL, and 1 of DLBCL, all cases were positive for CD20, PAX5, CD30 and CD15).EBER were detected in 11 cases by in situ hybridization, 2 of which were positive (18.2%), and the 2 positive cases were cHL.</p><p><b>CONCLUSIONS</b>MTHLs occur predominantly in adolescents and young adults, mainly present as superior vena cava syndrome and anterior mediasinal masses. cHL, PMBCL, T-LBL were the most common MTHLs.GZLs mainly occur in young adults, those whose morphology reminiscent of cHL, immunohistochemistry reminiscent of PMBCL, and vice versa. Thoracoscopy, frozen section and a suitable panel of antibodies were practical approaches to MTHL.</p>

Post-transplant lymphoproliferative disorder: a clinicopathologic study of 15 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinical and histopathologic features, diagnosis, pathogenesis and therapy of post-transplant lymphoproliferative disorders (PTLD).</p><p><b>METHODS</b>The clinical and pathologic features of 15 cases of PTLD were retrospectively analyzed by light microscopy, immunohistochemistry and in-situ hybridization, according to the updated 2008 WHO classification of tumors of hematopoietic and lymphoid tissues.</p><p><b>RESULTS</b>Amongst the 15 cases studied, 14 cases had received allogenic hematopoietic stem cell transplantation (AHSCT) and 1 case had received renal transplantation. There were altogether 12 males and 3 females. The male-to-female ratio was 4:1. The mean age was 30.4 years and the median age was 31 years (range from 9 to 60 years). PTLD developed 1.5 to 132 months after transplantation (median 13.0 months). The mean age of the 14 patients with AHSCT was 28.3 years (range from 9 to 45 years) and PTLD developed 1.5 to 19 months after transplantation (mean 4.5 months). Major clinical presentation included fever and lymphadenopathy. Twelve cases involved mainly lymph nodes and the remaining 3 cases involved tonsils, stomach and small intestine, respectively. The histologic types in 4 cases represented early lesions, including plasmacytic hyperplasia (n = 1) and infectious mononucleosis-like PTLD (n = 3). Seven cases were polymorphic PTLD, with 4 cases containing a predominance of large cells. Graft-versus-host disease was also seen in the case of small intestinal involvement. Four cases were monomorphic PTLD, 3 of which were diffuse large B-cell lymphoma, 1 was plasmablastic lymphoma and 1 was a mixture of monomorphic and polymorphic PTLD. Foci of necrosis were seen in 5 cases. The proliferating index of Ki-67 was high. The positive rate of EBV-encoded RNA in AHSCT was 92.9%. The duration of PTLD onset was shorter in EBV-positive cases (range from 1.5 to 7 months) than EBV-negative cases (range from 19 and 132 months). Some cases were treated by reduction of immunosuppression, antiviral agents or anti-CD20 monoclonal antibody Rituximab. The duration of follow-up in 14 patients ranged from 0 to 8 months. Five of the patients died of the disease.</p><p><b>CONCLUSIONS</b>The diagnosis of PTLD relies on morphologic examination and immunohistochemistry. Most of them are of B-cell origin. EBV plays an important role in the pathogenesis of PTLD. The duration of disease onset is shorter in EBV-positive cases. PTLD in AHSCT cases occurs in younger age group, with shorter duration of onset, as compared to solid organ transplantation. The prognosis of PTLD is poor. The modalities of treatment include reduction of immunosuppression, antiviral agents or anti-CD20 monoclonal antibody Rituximab.</p>

Clinicopathologic features of gastrointestinal tract involvement of anaplastic large cell lymphoma / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the clinicopathological characteristics of gastrointestinal tract involvement of anaplastic large cell lymphoma (ALCL).</p><p><b>METHODS</b>The clinicopathological features of four patients with ALCL that involved gastrointestinal tract were retrospectively analyzed using immunohistochemical study, T-cell receptor gene rearrangement analysis, and evaluation for Epstein Barr virus infection status.</p><p><b>RESULTS</b>Most tumor cells in all these four cases are large and highly pleomorphic, and all four cases were classified as the common pattern ALCL. Tumor cells in all four tumors expressed CD30, and expressed at least one cytotoxic maker. Two patients were confirmed to be with anaplastic lymphoma kinase (ALK)-positive ALCL, and four patients were negative during in situ hybridization for Epstein-Barr virus-encoded RNA but showed clonal T-cell receptor gene rearrangement.</p><p><b>CONCLUSION</b>Gastrointestinal tract involvement of ALCL has the unique clinicopathological features.</p>

Primary gastric Hodgkin's lymphoma / 대한외과학회지

Gastric Hodgkin's lymphoma is extremely rare. We present a case of primary Hodgkin's lymphoma arising in the stomach of a 65-year-old woman. The patient complained of epigastric discomfort and reflux for one month. Endoscopic examination revealed a protruding lesion characterized by a smooth surface at the antrum. An abdominal computed tomography uncovered a 2.5 x 2.0 cm, exophytic submucosal mass. After the tentative preoperative diagnosis of a gastrointestinal stromal tumor, a gastric wedge resection was performed. Microscopic examination of the mass demonstrated a diffuse proliferation of large atypical lymphoid cells with mono- and binucleated pleomorphic nuclei and prominent nucleoli. Immunohistochemically, the tumor cells were positive for CD30, CD20, and CD79a, whereas they were negative for cytokeratin, carcinoembryonic antigen, CD3, CD15, epithelial membrane antigen, and anaplastic lymphoma kinase-1. Based on the morphological features and immunohistochemical results, in addition to the clinical findings, a diagnosis of primary gastric Hodgkin's lymphoma was established.

Diffuse skin hyperpigmentation in CD30+ lymphoproliferation

CD30+ T-cell lymphoproliferative disorders [LD] comprise two main groups of diseases: CD30+ LD of the skin and systemic anaplastic large cell lymphoma [ALCL]. The main feature of these disorders is the expression of CD30. We present a patient with an unusual clinical presentation of CD30+ lymphoproliferative disease in a 54-year old Caucasian male who presented with generalized lymphadenopathy and pronounced skin hyperpigmentation. In the lymph nodes and skin, CD30+ lymphoproliferation [ALCL] was diagnosed. The Prussian blue staining identified that the pigment responsible for the skin color was hemosiderin. Chemotherapy was started but the patient's condition progressively worsened and he died a week after the first cycle. The complete color transformation of the entire skin due to hemosiderin accumulation is, to the best of our knowledge, the first reported observation in a CD30+ lymphoproliferation/ALCL patient. We speculate that hemosiderin-loaded macrophages resulted from the paraneoplastic process by some still unknown mechanism

Leukemic phase of anaplastic lymphoma kinase positive, anaplastic large cell lymphoma.

Anaplastic large cell lymphoma (ALCL) is a distinct type of CD30+ T/null-cell non-Hodgkin's lymphoma that frequently involves nodal and extranodal sites. The presence of leukemic phase in ALCL is extremely rare and occurs exclusively with ALK1-positive ALCL. We describe two patients with ALK1-positive ALCL who developed a leukemic phase with rapid progression of the disease. Immunophenotypic pattern assessed on peripheral blood by flow cytometry revealed CD45, CD30, and CD25 positivity in both cases but NPM-ALK1 was expressed in only one case. Both patients developed leukemic phase as a terminal event of the disease and we share the immunophenotypic features of both cases.

Research progresses in the pathogenesis of anaplastic large cell lymphoma / 癌症

Anaplastic large cell lymphoma (ALCL) is a distinct subset of T-cell non-Hodgkin's lymphoma. As a consequence of its low incidence, general pathogenic consideration of ALCL is lacking. In this review, we summarize the pathogenesis, epidemiology, clinical manifestations, and treatment of ALCL, so as to better understand key stages of the development of this disease and provide valuable information for future treatment.

Clinicopathological features of Epstein-Barr virus-positive diffuse large B-cell lymphoma in elderly / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological features of EB virus positive diffuse large B-cell lymphomas (EBV + DLBCL) of the elderly.</p><p><b>METHODS</b>Four hundred and ninety-six cases of DLBCLs were retrospectively studied by in situ hybridization (ISH) to detect the EBV in tumor cells, and by immunohistochemistry to evaluate the expression of CD10, CD20, CD30, CD79a, bcl-6, bcl-2, MUM-1, CD5, CD3, TIA-1 and Ki-67 protein. Their clinicopathological correlations were analyzed.</p><p><b>RESULTS</b>Of the 59 cases of EBV + DLBCL, 48 cases were EBV positive. The median age of these EBV + DLBCLs was 73 years with male predominance (1.4:1). There were 11 cases with nodal presentation only, 18 cases with extra-nodal presentation and 19 cases with both lymph nodal and extra-nodal involvements, whereas about one third cases with more than one extra-nodal involvement. Thirty-five patients presented with advanced disease (Ann Arbor stage III/IV). A performance status was available in 36 cases and 5 cases had performance status of more than 1. Seven of 30 patients were found with high lactate dehydrogenase value (more than twice of the normal). An IPI-score was calculated in 30 cases and 18 cases had an intermediate/high IPI-score (3-5). The median survival for these patients was 35 months. Morphologically, EBV + DLBCLs of the elderly generally showed a diffuse and polymorphic proliferation of large lymphoid cells with varying degrees of reactive components including small lymphocytes, plasma cells, histiocytes, and epithelioid cells. These tumor cells were frequently characterized by a broad range of B-cell maturation, containing centroblasts, immunoblasts, and Hodgkin- and Reed-Sternberg (HRS)-like giant cells. The study cohort was further morphologically divided into large cell lymphoma subtypes (n = 33) and polymorphic lymphoma subtypes (n = 14) and one case with mixed subtype. Immunohistochemical studies showed that tumor cells were positive for CD20 (47/48) and/or CD79a (45/45) in almost cases. Tumor cells were MUM-1-positive in the majority of the cases (44/47) and were stained for CD10 or bcl-6 in a few cases. Expression of bcl-2 and CD30 was observed in 80.0% (28/35) and 28.9% (11/38) cases, respectively, and most of the cases (33/39) had a high proliferative index (by Ki-67 with a 50% cut-off point). Compared with other EBV + DLBCLs, except the older age and low frequency of bcl-6 staining, no other significant differences were observed in EBV + DLBCLs of the elderly.</p><p><b>CONCLUSIONS</b>EBV + DLBCLs of the elderly constitute a distinct clinicopathologic subtype of DLBCL, although many clinical and histological features with EBV + lymphomas are similar with that of younger ages. Differential diagnosis from other types of lymphomas should also be considered.</p>