[Diffuse large B-cell lymphoma of testis: a clinicopathologic and immunophenotypic study of 58 cases].

OBJECTIVE: To investigate the clinicopathologic features, immunophenotype, diagnosis and differential diagnosis, and prognostic factors of testicular diffuse large B-cell lymphoma (DLBCL). METHODS: The clinical and pathologic profiles of 58 cases of testicular DLBCL were investigated.Immunohistochemical stainings and EBER1/2 in situ hybridization were performed on formalin fixed tissues. RESULTS: The average age of the patients was 62.1 years, and the median age was 65 years. The course of disease was short in most of the cases. Clinical stages at diagnosis were mainly stage I or II (87.9%, 51/58). Forty eight patients (82.8%) had unilateral testis involvement. Inguinal lymphadenopathy was observed in 12 (20.7%) patients and the other organs were seldom involved. Morphologically, centroblast-like neoplastic cells infiltrated interstitial tissue of testis diffusely and invaded into seminiferous tubules. Tunica albuginea and vessels were involved in 14 (24.1%) and 10 (17.2%) patients, respectively. Immunophenotype analysis showed predominant non-GCB type of DLBCL (48/58, 82.8%) by Hans classification. No EBV infection was detected. Follow-up data were available in 48 (82.8%) patients. Twenty eight patients (58.3%) died of the disease. One-year, 3-year, and 5-year overall survivals were 55.7%, 31.6% and 27.6%, respectively. Age (older than 60 years), B-symptoms, high serum level of LDH, advanced Ann Arbor stage as well as lack of combination of therapy were associated with a poor prognosis. CONCLUSIONS: This large series of testicular DLBCL mainly present with local disease at diagnosis. Most cases show non-GCB immunophenotype. Despite early clinical stage at presentation, the prognosis is poor. Combined chemotherapy postoperation may prolong survival of the patients.

[Analysis of the immunohistochemical subtypes and prognosis of primary diffuse large B cell lymphoma of the central nervous system].

OBJECTIVE: To analyze the subtypes of primary diffuse large B cell lymphoma of the central nervous system (CNS DLBCL) and to explore the relationship between the subtype classification and prognosis. METHODS: Immunohistochemical staining was used to determine the expression of CD20, CD3, CD10, Bcl-6, Mum-1, CD5, Bcl-2, Ki-67, FOXP-1, GCET-1, BLIMP-1 and LMO-2 antigens on paraffin-embedded sections of 47 cases. Hans, Choi and Tally subtypes were classified, and univariate and multivariate analyses were used to elucidate the relationship between the subtypes and prognosis. RESULTS: In the 47 cases, the expression of Bcl-2 in the tumor cells was 46.8%, CD10 4.3%, Bcl-6 70.2%, Mum-1 53.2%, GCET-1 36.2%, BLIMP-1 4.3%, FOXP-1 63.8% and LMO-2 19.2%. The positive rate of Ki-67 was 30% to 95%, with a median of 80%, of which 12 cases (25.5%) was > or = 90%. The Hans subtype classification showed 16 cases (34.0%) were of GCB type and 31 cases (66.0%) of non-GCB type. The Choi subtype classification showed 16 cases (34.0%) were of GCB type and 31 cases (66.0%) of ABC type. The Tally subtype classification showed 6 cases (12.8%) were of GCB type and 41 cases (87.2%) of non-GCB type. CONCLUSIONS: The results of this study show that there is no significant correlation between the three subtypes and prognosis. The prognosis is correated with post-operative radiotherapy, chemotherapy and MTX therapy.

Sporadic Burkitt lymphomas of children and adolescents in Chinese: a clinicopathological study of 43 cases.

BACKGROUND: To investigate the clinical and pathologic features as well as the MYC translocations of childhood Burkitt lymphoma (BL) from China. METHODS: Fourty-three cases of childhood BL were retrospectively investigated in morphology, immunophenotype, genotype, treatments and survival analysis. RESULTS: Clinically, there was a marked male predominance in sex distribution (M: F=9.75:1); abdomen was the most frequent extranodal sites of involvement (46.5%), followed by jaws and facial bones (16.3%). Two third of the patients were in stageI ~ II. Morphologically, 69.76% of the cases showed classical histologic features, while 30.24% of them showed greater nuclear pleomorphism in size and shape. Five cases (11.6%) were positive for EBER1/2. Thirty-one of the 40 cases (77.5%) had the aberration of IGH/MYC translocation while 7 (17.5%) had non-IGH/MYC translocation. Thirty patients (69.7%) received operation and/or chemotherapy while 13 patients (30.3%) received no treatment. Twenty-seven patients (62.8%) died of the tumor, 16 alive, with the average survival time 4.9 and 48.7 months respectively. High IPI, advanced clinical stage, increased serum level of LDH and no chemotherapy received as well as tumor size≥10 cm were related to the lower survival rates of the tumor. CONCLUSIONS: Several differences were showed in this group of BL, including a much higher ratio of male patients, more cases in stageII, clinically inconsistent treatment and a very poor outcome. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here http://www.diagnosticpathology.diagnomx.eu/vs/1552295877710135.

[Langerhans cell histiocytosis: a clinicopathologic and immunohistochemical analysis of 258 cases].

OBJECTIVES: To observe the clinicopathologic features of Langerhans cell histiocytosis (LCH), and to evaluate the values of langerin, CD1a and S-100 protein expression in diagnosis of the tumor. METHODS: Total 258 cases of Langerhans cell histiocytosis in the past 18 years (from 1992 to 2008) were collected, morphologic review and immunohistochemical staining were performed. RESULTS: In all 258 cases, the ages of patients older than 16 years or younger than 2 years were 126 (48.8%) and 37 (14.3%), respectively, in the remaining 95 (36.8%) of the cases, the age of the patients ranged from 2 to 16 years. For all of 258 cases, there were 364 diseased sites. Bony lesions accounted for 77.2% (281 cases), especially the skull (112 cases, 39.9%), followed by lymph node (25 cases, 6.9%) and skin (14 cases, 3.8%). Clinically, unisystem or unifocal disease was predominant (201 cases, 77.9%), followed by unisystem and multifocal disease (21 cases, 8.1%), multi-system disease (26 cases, 10.1%), isolated pulmonary LCH (2 cases, 0.8%), and unclassified (8 cases, 3.1%). Histologically, variable number of Langerhans cells was present in 265 samples of 258 cases. Multinucleated giant cells were found in 166 (62.6%) of the samples. Eosinophils were the major infiltrating non-neoplastic cells, and eosinophilic abscess was seen in 57 cases (21.5%). Coagulative necrosis and dead bone were detected in 29 (10.9%) and 124 (46.8%) of the cases, respectively. Immunohistochemically, the expression of S-100 protein, CD1a and langerin was 99.1% (209/211), 100% (206/206) and 98.5% (193/196), respectively, and the sensitivity of them had no statistical difference. CONCLUSIONS: In this group of LCH cases, the ratio of adult patients is high, but the proportion of multi-organ lesion is low. No significant difference of the sensitivity is found among langerin, CD1a and S-100 expression in diagnosis of LCH.

Extranodal nasal type natural killer/T-cell lymphoma of testis: report of seven cases with review of literature.

Seven cases of testicular extranodal natural killer (NK)/T-cell lymphoma, nasal type, are reported, with a literature review. Two patients had a testicular lesion as the initial presentation, four had a history of nasal NK/T-cell lymphoma and the remaining patient had concomitant involvement of an adrenal gland. All patients underwent orchiectomy followed by chemotherapy (CT) and/or radiotherapy (RT). Follow-up data showed that two patients with non-primary tumors died of disease within 6 and 11 months, respectively. Histologically, the tumor had a diffuse growth pattern largely replacing the interstitial tissues. Neoplastic cells showed prominent angiocentric and angioinvasive features with focal coagulative necrosis and apoptotic bodies. Immunohistochemically, all cases were positive for cytoplasmic CD3ε and CD56. Epstein-Barr virus infection was demonstrated in all cases. Testicular NK/T-cell lymphoma, whether primary or secondary, was generally very aggressive with a poor outcome despite multimodality therapy. Novel molecular therapeutic targets and more effective treatments are needed, especially for disseminated or recurrent cases.

Extraosseous (extramedullary) plasmacytomas: a clinicopathologic and immunophenotypic study of 32 Chinese cases.

BACKGROUND: Extraosseous plasmacytoma, so called extramedullary plasmacytoma (EMP) is relatively rare in China. The aim was investigate the clinicopathologic features of EMP and the role of Immunophenotype and genotype detection in diagnosis of EMP. METHODS: Thirty-two cases of EMP were investigated retrospectively by histopathology, immunophenotype, genotype and survival analysis. RESULTS: Clinically, the mean age of the patients was 53.4. Most of the patients received no treatment after the diagnosis was established, and the prognosis was relatively poor. Histologically, in 40% of the cases, the neoplastic cells were grade II or III. The neoplastic cells expressed one or more PC associated antigens. The immunophenotype of EMP and inflammation of sinonasal regions with numerous PC infiltrations were compared and showed some difference in expression of CD45, CD27, CD44v6 and Bcl-2 as well. Ig light chain restriction was detected in 87.5% of the cases. CONCLUSIONS: we described 32 Chinese cases of EMP, compare with that reported in the literature, some differences are presented, including higher percentage of grade II and III cases, clinically inconsistent treatment and management as well as poor outcome of the disease.

Subtype distribution of lymphomas in Southwest China: analysis of 6,382 cases using WHO classification in a single institution.

BACKGROUND: The subtype distribution of lymphoid neoplasms in Southwest China was analyzed according to WHO classifications. This study aims to analyze subtype distribution of lymphomas in southwest China. METHODS: Lymphoid neoplasms diagnosed within 9 years in a single institution in Southwest China were analyzed according to the WHO classification. RESULTS: From January 2000 to December 2008, a total number of 6,382 patients with lymphoma were established, of which mature B-cell neoplasms accounted for 56%, mature T- and NK-cell neoplasms occupied 26%, and precursor lymphoid neoplasms and Hodgkin lymphomas were 5% and 13%, respectively. Mixed cellularity (76%) was the major subtype of classical Hodgkin lymphoma; and the bimodal age distribution was not observed. The top six subtypes of non-Hodgkin lymphoma were as follows: diffuse large B-cell lymphoma, extranodal NK/T-cell lymphoma, nasal type, extranodal marginal zone lymphoma of mucosa associated lymphoid tissue, follicular lymphoma, precursor lymphoid neoplasms, and chronic lymphocytic leukemia/small lymphocytic lymphoma. Extranodal lymphomas comprised about half of all cases, and most frequently involved Waldeyer's ring, gastrointestinal tract, sinonasal region and skin. CONCLUSIONS: The lymphoid neoplasms of Southwest China displayed some epidemiologic features similar to those reported in literature from western and Asian countries, as well as other regions of China, whereas some subtypes showed distinct features. The high frequency of mature T/NK cell neoplasms and extranodal lymphomas, especially for extranodal NK/T-cell lymphoma, nasal type, is the most outstanding characteristic of this series.

Hepatosplenic T-cell lymphoma: clinicopathologic, immunophenotypic, and molecular characterization of 17 Chinese cases.

Hepatosplenic T-cell lymphoma is a highly aggressive tumor with a poor outcome. About 210 cases were identified through PubMed, of which fewer than 20 originated in Asia. We reviewed 17 Chinese cases of hepatosplenic T-cell lymphoma, including an unusual one with cutaneous pink papules, for clinicopathologic, immunophenotypic, and genotypic features; Epstein-Barr virus status; treatment; and outcome. The median age of the patients was 23 years. All patients had splenomegaly, and 88.2% of them had hepatomegaly as well. Bone marrow involvement was present in 53.3%. Eleven patients underwent splenectomy for diagnosis and treatment. Twelve specimens were collected by image-guided liver core biopsy or wedge resection. Histologically, the homogeneous small- to medium-size neoplastic lymphoid cells infiltrated the sinuses or sinusoids of the spleen, bone marrow, and liver. Diagnosis was based on image-guided core-needle biopsy of the liver alone in 41.2% of the cases. Immunohistochemically, 15 of the lesions were hepatosplenic γδ T-cell lymphoma, and the remaining 2 were hepatosplenic αß T-cell lymphoma. Epstein-Barr virus was detected in both cases of hepatosplenic αß T-cell lymphoma and one case of hepatosplenic γδ T-cell lymphoma. Most of the patients received cyclophosphamide, doxorubicin, vincristine, and prednisone therapy or regimens similar to it. Follow-up data were available in 70.6% of the patients; half of them died of the tumor, and the median survival time was 6 months. The frequency of bone marrow involvement was lower than that reported in the literature. Image-guided core-needle biopsy of the liver is recommended for diagnosis.

[Primary gastrointestinal diffuse large B-cell lymphoma: an immunohistochemical and prognostic study of 90 cases].

OBJECTIVE: To study the immunophenotype and prognostic significance of primary gastrointestinal diffuse large B-cell lymphoma, with reference to Hans, Choi and Tally algorithms. METHODS: The clinicopathologic features and follow-up data in 90 cases of primary gastrointestinal diffuse large B-cell lymphoma were analyzed by Kaplan-Meier method, Log-rank test and Cox regression model. Immunohistochemistry was carried out using EliVision and EnVision methods for CD20, CD3ε, CD10, bcl-6, MUM-1, CD5, bcl-2, GCET1, FOXP1, LMO2, BLIMP1 and Ki-67. RESULTS: The age of patients ranged from 27 to 83 years (mean = 58 years). The male-to-female ratio was 1.31:1. Amongst the 90 cases studied, 64.4% (58/90) involved the stomach and 35.6% (32/90) involved the intestine. The immunohistochemical findings were as follows: 100% positivity for CD20, 0% for CD3ε and CD5, 17.8% (16/90) for CD10, 75.6% (68/90) for bcl-6, 52.2% (47/90) for MUM-1 (cut off was 30%), 43.3% (39/90) for MUM-1 (cut off was 80%), 50.0% (45/90) for GCET1, 45.6% (41/90) for FOXP1, 23.3% (21/90) for LMO2, 42.2% (38/90) for bcl-2 and 8.9% (8/90) for BLIMP1. The Ki-67 index ranged from 20% to 95% (median = 80%). According to Hans algorithm, 51.1% of the cases belonged to germinal center B-cell (GCB) subtype and 48.9% belonged to non-GCB subtype. In contrast, Choi algorithm classified 55.6% cases as GCB subtype and 44.4% as activated B-cell (ABC) subtype. According to Tally algorithm, 34.4% were of GCB subtype and 65.6% of non-GCB subtype. Most of the patients (67.8%, 61/90) received chemotherapy and 68.9% (62/90) underwent surgical resection. The overall 2, 3 and 5-year survival rates were 58.5%, 52.8% and 49.8%, respectively. The overall 2, 3 and 5-year survival rates in the CHOP therapy group were 68.5%, 61.2% and 52.9%, respectively. CONCLUSIONS: There is no significant difference in ratio between the GCB and non-GCB/ABC subtypes by Hans and Choi algorithms. The non-GCB subtype seems to be more prevalent according to Tally algorithm. Although there is no significant difference in survival between GCB and non-GCB/ABC subtypes by the 3 algorithms, GCB subtype tends to show a better survival. In univariate analysis, LDH level, international prognostic index, chemotherapy, surgical resection, B symptoms, number of involved sites and clinical stage are found to have prognostic significance. In multivariate analysis, Choi algorithm, Tally algorithm, chemotherapy, surgical resection, LDH level and clinical stage are independent prognostic factors.

[Primary lymphoma of breast: a clinicopathologic, immunophenotypic and prognostic study of 21 cases].

OBJECTIVE: To investigate the clinicopathologic and immunophenotypic features of primary breast lymphoma (PBL) and to discuss the diagnosis of the tumor. METHODS: Twenty-one cases of PBL with follow up data were clinically reviewed. The histologic diagnosis of the tumor was based on the updated WHO Classification of tumors of hematopoietic and lymphoid tissues (2008). Immunohistochemistry was performed by SP method and antibodies selected were as follows: CD20, CD3epsilon, CD10, Bcl-6, MUM-1, CD5, Bcl-2, CD23, CD10, cyclin D1, CD43 and Ki67. RESULTS: (1) All 21 patients were female and the median age of patients was 48 years. The right and the left breasts were involved in 11 (52.4%) and 10 patients (47.6%), respectively. According to Ann Arbor staging system, 20 cases were stage I-II (95.2%), and the remaining case was stage IV (4.8%). For the international prognostic index (IPI), 19 cases were score 0-1, and 2 cases were score 2-3. For ECOG score, 19 cases were 0, and the remaining 2 cases were 1. (2) Histologically, all 21 cases (100%) were DLBCL. Immunohistochemically, the frequency of antigen expression was as follows: CD20 (100%), MUM-1 (14/21, 66.7%), bcl-6 (5/21, 23.8%), CD10 (0), bcl-2 (13/21, 61.9%), CD5 (1/21, 4.8%); Ki-67 index: 10 cases (47.6%) were less than 59%, with the expression of seven cases (33.3%) being 60% - 89%, and more than 90% in the remaining four cases (19.1%). The median Ki-67 index was 60%. All the cases were considered non germinal center B-cell-like type of DLBCL. (3) Follow-up data was available in 64% of the cases. One, two and five-year survival rates were 11 cases, 7 cases and 3 cases, respectively. CONCLUSION: All the cases of PBL in the current study were DLBCL, non germinal center B-cell-like type, and a diagnosis of PBL can only be established after excluding breast involvement in systemic lymphoma.

[Solitary plasmacytoma of bone: a clinicopathologic, immunohistochemical and immunoglobulin gene rearrangement study].

OBJECTIVE: To investigate clinicopathologic features of solitary plasmacytoma of bone (SPB) and the role of immuno-phenotype and immunoglobulin gene rearrangement detection in the diagnosis and differential diagnosis of SPB. METHODS: A total of 21 cases of SPB were selected during a period from 1990 to 2008. A retrospective clinicopathologic study and immunohistochemistry (EnVision or EliVision methods) of 17 antigens were performed. In addition, universal IgH (FR3A/LJH/VLJH) primers and BIOMED-2 PCR multiplex tubes were used for IgK and IgL rearrangement analysis. RESULTS: The age of patients ranged from 36 to 72 years with a media of 50 years. Axial skeleton was the most common site of involvement, accounting for 66.7% of the cases (14 of 21), followed by the extremities of 33.3% (7 cases). Low serum level of M-components was found in 5 cases, including two of IgG type (21.4 g/L) and three of IgA type. Clinical manifestations were closely related to the anatomic sites involved, such as pain due to bone destruction, symptoms and signs caused by compression of spinal cord or nerve root, and pathological fracture. All cases presented as a solitary osteolytic lesion. According to the histological grading criteria, grade I tumor was seen in 12 of 21 cases (57.1%). The remaining were grade II (5 cases, 23.8%) and grade III (4 cases, 19.0%). Immunohistochemically, the neoplastic cells expressed two or more plasma cell antigens, including CD138, CD38 and PC, but no CD19 and CD20. CD79a expression detected in 23.8%(5/21) of the cases. Expression of CD56, CD27 and CD44v6 were 57.1% (12/21), 15.0% (3/20) and 23.8% (5/21), respectively. Follow-up data were available in 12 of the 21 patients (57.1%). Five patients were alive and 7 died. Three patients developed multiple myeloma (MM) and died of the tumor. CONCLUSIONS: SPB is a rare tumor with bone pain as the most common presenting symptom due to bone destruction. The diagnosis of EMP can only be established after exclusion of an extramedullay invasion by MM. Immunophenotype and IgH gene rearrangement analysis play important roles in the diagnosis of SPB.

Extranodal nasal-type natural killer/T-cell lymphoma of the skin: a clinicopathologic study of 16 cases in China.

Extranodal nasal-type natural killer/T-cell lymphoma presenting in skin, either primary or secondary, is relatively rare in China, accounting for about 4.1% of tumors. The clinicopathologic features of the neoplasm are still poorly understood. Sixteen Chinese cases of cutaneous natural killer/T-cell lymphomas were investigated retrospectively by pathology, immunophenotype, genotype, Epstein-Barr virus status, and survival analysis. The mean age of the patients was 36.3 years; 81% of the patients presented with multiple cutaneous lesions. Angiocentricity and epidermotropism were observed in 43.7% and 25%, respectively; the average number of mitoses was 12 per 10 high-power fields. The neoplastic cells of all 16 cases were positive for CD3varepsilon/CD45RO and granzyme B and negative for CD4, CD5, CD8, and CD20; 87.5% of the tumors expressed CD56. Signals for EBER were detected in 81.3% of cases. No clonal TCRgamma/TCRbeta gene rearrangement was demonstrated. Thirteen of 15 patients received chemotherapy; a partial response was achieved in 10 patients; 10 (66.7%) of 15 patients died of the disease, and the average survival time was 6.6 months. In conclusion, both primary and secondary cutaneous natural killer/T-cell lymphomas are highly aggressive. The outcome is closely related to the number and distribution of the lesions as well as the stage. In patients with generalized skin lesions and extracutaneous involvement, the prognosis usually is poor.

[Splenic T-cell and NK-cell lymphomas: a clinicopathologic and immunophenotypic analysis of 9 cases].

OBJECTIVE: To explore the clinicopathologic features and diagnosis of splenic T-cell and NK-cell neoplasms. METHODS: Nine cases of splenic T-cell and NK-cell neoplasms were collected and studied by morphology, immunophenotyping, EBER in situ hybridization and TCR-gamma gene rearrangement. Antibodies used were as follows: CD45RO, CD3epsilon, CD3, CD4, CD8, CD56, TIA-1, GranzymeB, CD30, Ki-67 and CD20. RESULTS: Among the 9 cases, hepatosplenic T-cell lymphoma (HSTCL) and extranodal nasal type NK/T-cell lymphoma (NK/TCL) were both of 4 cases, and the remaining one was peripheral T-cell lymphoma, unspecified (PTL, unspecified). Follow up data were available for 7 cases. Five patients including 2 with HSTCL, 2 with extranodal nasal type NK/TCL and one with PTL, unspecified died, with survival times ranged from 1 to 10 months. The other two patients are still alive, one with NK/TCL (two months+) and one with HSTCL (14+ months). CONCLUSION: Splenic T-cell and NK-cell neoplasms are a group of uncommon lymphomas with heterogeneous clinicopathologic features and poor prognosis. A definite diagnosis must depend on clinical manifestations, histopathology, immunophenotype and TCR gene rearrangement analysis.

[Littoral cell angioma of spleen: a clinicopathologic study of 17 cases].

OBJECTIVE: To study the clinicopathologic features and immunophenotype of splenic littoral cell angioma. METHODS: The clinical features, radiologic findings and histopathology of 17 cases of splenic littoral cell angioma were retrospectively reviewed. Immunohistochemical study was carried out on paraffin-embedded tissues, using normal spleen, cases of congestive splenomegaly and cavernous hemangioma as controls. RESULTS: All the 17 cases had similar clinical manifestations and radiologic findings. There was mild to moderate splenomegaly, with solitary or multifocal space-occupying lesions. Hepatic cysts were observed in 5 of the 17 cases. One case was also accompanied by serous cystadenoma of ovary. Gross examination revealed enlarged spleen containing single or multiple tan-colored nodules which ranged from 0.2 cm to 6.0 cm in diameter. Histologically, the lesions consisted of anastomosing vascular channels, sometimes with papillary or cavernous appearance. Two types of component cells were identified. A population of smaller cells lined the vascular channels, while another population of larger cells often floated in the vascular lumen. Both cell populations showed little cytologic atypia. Immunohistochemical study demonstrated that the smaller cells of all cases were positive for CD31 and polyclonal factor VIII-related antigen. They were negative for CD34, histiocytic markers and S-100 protein. CD8 and CD21 were expressed in 1 and 1 of the 17 cases respectively. On the other hand, the larger cells expressed histiocytic markers, including CD68 (KP1 and PG-M1), CD163 and lysozyme. There was also focal positivity for CD31. The staining for CD34, monocolonal factor VIII-related antigen and S-100 protein was negative. The immunophenotype of splenic littoral cell angioma was different from that of the controls. CONCLUSIONS: Littoral cell angioma is a benign condition, likely secondary to hemodynamic disturbance in spleen. The littoral cells become hyperplastic and anastomose, resulting in a hemangioma-like growth associated with histiocytic reaction. Attention to the characteristic histopathologic findings and immunophenotype are crucial for diagnosis.