Sinonasal haemangiopericytoma: histomorphology and differential diagnoses.

A 39-year-old female presented with a fleshy nasal polyp occluding the left nasal cavity, associated with haemopurulent discharge. Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) scans of the paranasal cavities revealed a large polypoid tumour arising from the left middle turbinate and obstructing the left maxillary sinus ostium. However, no bony or intracranial involvement was identified. A biopsy revealed a tumour with small blue round cell morphology. The tumour cells showed diffuse strong membranous CD99 positivity and patchy CD34 positivity. Ancillary cytogenetic tests for the EWSR1 and SS18/SYT gene translocations were negative. In view of the non-invasive nature of the tumour and the low cell proliferative index (Ki-67) of 5%, a medial maxillectomy resection was performed. The resection revealed additional areas with spindle-cell morphology and focal haemangiopericytic vasculature. The tumour continued to show immunoreactivity to CD99 and CD34, as well as Smooth Muscle Actin (SMA) and Muscle Specific Actin (MSA). The overall findings are in keeping with a sinonasal haemangiopericytoma. With clear surgical resection margins, the patient is on routine follow-up and is currently disease-free.

Molecular signatures to improve diagnosis in peripheral T-cell lymphoma and prognostication in angioimmunoblastic T-cell lymphoma.

Peripheral T-cell lymphoma (PTCL) is often challenging to diagnose and classify. Gene expression profiling was performed on 144 cases of PTCL and natural killer cell lymphoma and robust molecular classifiers were constructed for angioimmunoblastic T-cell lymphoma (AITL), anaplastic lymphoma kinase-positive (ALK(+)) anaplastic large-cell lymphoma (ALCL), and adult T-cell leukemia/lymphoma. PTCL-unclassifiable was molecularly heterogeneous, but we were able to identify a molecular subgroup with features of cytotoxic T lymphocytes and a poor survival compared with the remaining PTCL-not otherwise specified cases. Many of the pathologic features and substantial components of the molecular signature of AITL are contributed by the follicular dendritic cells, B-cell, and other stromal components. The expression of Th17-associated molecules in ALK(+) ALCL was noted and may represent aberrant activation of Th17-cell differentiation by abnormal cytokine secretion. Adult T-cell leukemia/lymphoma has a homogeneous molecular signature demonstrating high expression of human T-lymphotropic virus type 1-induced genes. These classifiers reflect the biology of the tumor cells as well as their microenvironment. We also constructed a molecular prognosticator for AITL that appears to be largely related to the microenvironmental signature, and the high expression of 2 immunosuppressive signatures are associated with poor outcome. Oncogenic pathways and tumor-host interactions also were identified, and these findings may lead to better therapies and outcome in the future.

Clinical differences between nasal and extranasal natural killer/T-cell lymphoma: a study of 136 cases from the International Peripheral T-Cell Lymphoma Project.

Among 1153 new adult cases of peripheral/T-cell lymphoma from 1990-2002 at 22 centers in 13 countries, 136 cases (11.8%) of extranodal natural killer (NK)/T-cell lymphoma were identified (nasal 68%, extranasal 26%, aggressive/unclassifiable 6%). The disease frequency was higher in Asian than in Western countries and in Continental Asia than in Japan. There were no differences in age, sex, ethnicity, or immunophenotypic profile between the nasal and extranasal cases, but the latter had more adverse clinical features. The median overall survival (OS) was better in nasal compared with the extranasal cases in early- (2.96 vs 0.36 years, P < .001) and late-stage disease (0.8 vs 0.28 years, P = .031). The addition of radiotherapy for early-stage nasal cases yielded survival benefit (P = .045). Among nasal cases, both the International Prognostic Index (P = .006) and Korean NK/T-cell Prognostic Index (P < .001) were prognostic. In addition, Ki67 proliferation greater than 50%, transformed tumor cells greater than 40%, elevated C-reactive protein level (CRP), anemia (< 11 g/dL) and thrombocytopenia (< 150 x 10(9)/L) predicts poorer OS for nasal disease. No histologic or clinical feature was predictive in extranasal disease. We conclude that the clinical features and treatment response of extranasal NK/T-cell lymphoma are different from of those of nasal lymphoma. However, the underlying features responsible for these differences remain to be defined.

Comparative analysis of extra-nodal NK/T-cell lymphoma and peripheral T-cell lymphoma: significant differences in clinical characteristics and prognosis.

AIM: We aimed to compare the frequencies, clinical characteristics, and prognostic factors of peripheral T-cell lymphoma (PTCL) vs. extra-nodal natural killer (NK)/T-cell lymphoma and to characterize the subtypes of extra-nodal NK/T-cell lymphoma. METHODS: We reviewed 97 consecutive patients with PTCL and extra-nodal NKT lymphoma from 2000 to 2006. During this period, a total of 780 patients with malignant lymphomas were treated in our center. The diagnostic criteria used were based on the WHO classification system of malignant lymphomas. RESULTS: Extra-nodal-NK/T-cell lymphoma and PTCL comprised 5.0% (39/780) and 7.4% (58/780) of all cases. Of the PTCL cases, histology was PTCL-NOS in 25, anaplastic large cell in 11, angioimmunoblastic T cell in 18 and other subtypes in four patients. Compared with PTCL, extra-nodal NK/T-cell lymphoma was associated with a significantly inferior rates of complete remission (33% vs. 53%, P = 0.05) and 3 yr overall survival (29.5% vs. 47.5%, P = 0.003). On multivariate analysis, extra-nodal NK/T-cell histology was independently associated with decreased survival. Further analysis into this subtype showed the nasal variant (n = 25) differed significantly from extra-nasal variant (n = 14) in terms of stage at presentation (stages III/IV, 36% vs. 79%), international prognostic index scores (high intermediate or high IPI scores, 24% vs. 64%), complete remission rates (48% vs. 7%), and median survival (10 months vs. 1 month, P < 0.0001). CONCLUSIONS: Extra-nodal NK/T-cell lymphoma was associated with a poorer prognosis compared with PTCL and is likely to comprise two distinct variants with different clinical behavior and prognosis.

Immunopathology of progressive subretinal fibrosis: a variant of sympathetic ophthalmia.

PURPOSE: We report the immunopathology of progressive subretinal fibrosis, a variant of sympathetic ophthalmia. DESIGN: Brief case report. METHOD: Review of medical record and immunopathology of a chorioretinal biopsy of a 40-year-old man who presented with left total retinal detachment (RD) following multiple vitrectomies in the right eye for RD. Small peripherally retinal holes, snow banks, and inflammatory nodules along the ora serrata were observed during left vitrectomy. Both eyes deteriorated rapidly to blindness with progressive subretinal fibrosis and inflammation over 3 months, and the patient was unresponsive to systemic prednisolone and azathioprine. RESULT: Immunopathology of the chorioretinal biopsy of the right eye revealed aggregates of CD20+ B cells, surrounded by CD3+ T cells. CD68+ macrophages were scattered throughout. CONCLUSION: The rapid clinical course described in this case may be related to the unique immunopathology of rapidly forming peudogerminal centers in the choroids and retina.

A case of sudden death from primary intracranial germinoma complicated by microvascular disease of the heart.

A coroner's autopsy conducted on an 11.5-year-old girl, with a history of hypopituitarism, manifesting as growth hormone deficiency associated with short stature, demonstrated the presence of an undiagnosed hypothalamic intracranial germinoma, showing hypophyseal and mesencephalic invasion, together with histological evidence of microvascular (small coronary artery) disease of the heart. The substantive, or primary, cause of her sudden death was clearly the intracranial germinoma, which was acutely haemorrhagic and necrotic. However, it is postulated that there might be an, as yet, undescribed association between this malignancy and the pathogenesis of the coronary microvascular disease; the latter being deemed, in this instance, to be a contributory cause of death.

Prognostic factors in patients with diffuse large B cell lymphoma: Before and after the introduction of rituximab.

This study attempted to evaluate the usefulness of the International Prognostic Index (IPI) as a prognostic model in patients treated with R-CHOP (rituximab, cyclophosphamide, vincristine, adriamycin and prednisolone) chemotherapy. We compared 279 patients with DLBCL. Among them, 183 received CHOP while 96 received R-CHOP. Results showed that there were no statistically significant differences between the two groups of patients in terms of both the patient and the lymphoma characteristics. The estimated 2-year survival was significantly higher among patients treated with R-CHOP compared to CHOP alone (85.6% vs. 64.7%, P = 0.004). Both the IPI and age-adjusted IPI were less useful as prognostic models in patients receiving R-CHOP compared to CHOP. In the multivariate analysis, age >or= 60, elevated serum LDH, low serum albumin and advanced stages of disease were each independently associated with decreased survival in patients treated with CHOP. In contrast, among those treated with R-CHOP, only male sex and advanced stage of disease were each independently associated with decreased survival. Using these two factors, patients treated with R-CHOP could be separated into three prognostic groups with 5-year estimated survival ranging from 47% to 100% (P < 0.0001). In summary, we can conclude that with the significant improvement in survival following the use of rituximab, the relevance of previously recognized prognostic factors has to be reassessed and re-evaluated.

Primary central nervous system lymphoma in an Asian population: a 15-year experience.

BACKGROUND: The aim of this study was to characterize primary central nervous system lymphoma (PCNSL) among Asian patients and to determine their outcomes with different therapeutic modalities. PATIENTS AND METHODS: Between 1990 and 2005, 37 patients with PCNSL were analyzed within 5 different treatment groups: radiotherapy alone (arm A), combined chemoradiation (arm B), chemotherapy alone with methotrexate (MTX) > or = 1 g/m2 (arm C), miscellaneous therapy (arm D), and best supportive care (arm E). RESULTS: The median age at presentation was 59 years, and the majority of patients were male (68%). All patients had aggressive diffuse large B-cell lymphoma. The number of patients in arms A to E were 6, 16, 3, 8 and 4, respectively. The overall median survival was 7.4 months, 54.1 months, not reached, 8.9 months and 0.9 months, respectively. Use of MTX 1-2.5 g/m2 per cycle and an ECOG performance status of 0-2 were each associated with improved survival on univariate analysis (p = 0.022 and p = 0.049, respectively). Compared to radiotherapy alone, use of combined chemo-radiation was associated with a trend towards improved overall median survival (7.4 vs. 54.1 months, p = 0.058). CONCLUSION: The clinical characteristics and treatment outcomes in our Asian patients were comparable to those reported in Western series. Use of MTX 1-2.5 g/m2 per cycle and an ECOG performance status of 0-2 were associated with improved survival.

Nasal-type extranodal natural killer/T-cell lymphomas: a clinicopathologic and genotypic study of 42 cases in Singapore.

We studied the clinicopathologic features of 42 cases of nasal-type extranodal natural killer (NK)/T-cell lymphoma in Singapore and compared our findings with other series reported in the Asian and Western populations. A panel of immunohistochemical stains, which included CD2, CD3, CD4, CD8, CD56, T-cell intracellular Antigen-1 and granzyme B, and in situ hybridization for Epstein-Barr virus encoded RNA (EBER) were performed. Polymerase chain reaction for T-cell receptor-gamma gene rearrangement using both gel and capillary electrophoresis were evaluated to determine the proportion of tumors which are of true T-cell lineage. We also studied the functional status of the overexpressed p53 protein in these lymphomas by correlating p53 expression with its downstream target protein, p21. In all, 31 out of 42 cases presented in the upper aerodigestive tract. The other sites of involvement included gastrointestinal tract, skin, soft tissue, testis, liver, spleen, bone marrow and brain. The tumors displayed characteristic morphologic features. In situ hybridization for EBER was detected in 41 out of 42 cases (97.6%). The only significant adverse prognostic factor identified was an International Prognostic Index of two or more. A significantly higher proportion of the tumors (27%), compared to previous studies, demonstrated monoclonal T-cell receptor-gamma gene rearrangement. There was, however, no difference in survival or clinicopathologic features between the true NK-cell tumors and their T-cell counterparts. Overexpression of p53 was present in 40% of the cases, but no significant difference in survival rate was detected in patients with p53 overexpression and there was no association between p53 overexpression with large cell morphology, and advanced stage of disease. These findings suggest that molecular aberrations other than those of the p53 pathway may be operative in the pathogenesis of this malignancy.

Population-based survival for cervical cancer in Singapore, 1968-1992.

OBJECTIVE: The aim of this study was to describe the cervical cancer survival rates in Singapore during the period of 1968 through 1992 using population-based data. STUDY DESIGN: A review of cases with cervical cancer diagnosed between 1968 and 1992 from Singapore Cancer Registry was conducted. Information on vital status at December 31, 1997, was available for 3531 cases. Cumulative observed and relative survival rates were computed by using Hakulinen's method. RESULTS: Survival in cervical cancer in Singapore has improved over the 25-year period. The overall 5-year age-standardized relative survival (ASRS) for all patients increased from 45% in 1968-1972 to 65% in 1988-92. Poorer survival rates were observed in elderly patients and Malays. CONCLUSION: The improvement in survival of cervical cancer is likely to be attributed to the rapid national development of Singapore, resulting in the improvements in health services infrastructure and accessibility, as well as to the impact of widely available cytology-based screening resulting in early detection.