Low-grade Malignant Group Research Articles

Angioimmunoblastic T-cell lymphoma: histopathological grading and prognosis

Objective: To investigate the histological features and prognostic factors of angioimmunoblastic T-cell lymphoma (AITL). Methods: The pathological data of 62 patients with AITL with complete follow-up information were retrospectively collected and analyzed from Changhai Hospital during September 2012 and September 2017. Histological and immunohistochemical (IHC) examination, in situ hybridization (ISH), and single nucleotide polymorphisms (SNP) gene mutation analysis were done. Subgroup evaluation with histology, IHC, ISH, SNP gene mutation, and association with clinical progression were performed. Results: The cohort included 62 cases of AITL, including 46 males and 16 females patients, with a median age of 64 years. Follicular dendritic cells (FDC) area showed significantly expansion (≥30%) in 40 cases; increased plasma cells (≥10%) was seen in 37 cases; B cells were distributed around blood vessels in 37 cases; and increased p53 mutation positive cells (≥40%) were seen in 39 cases; high Ki-67 index (≥40%) was seen in 39 cases; RHOA mutation was seen in 19 cases; TET2 mutation was seen in 9 cases. Overall survival analysis showed these factors were significantly correlated with tumor prognosis (P<0.05). Multivariate analysis showed that CD38 positive cells<10%, Ki-67≥40%, RHOA and TET2 mutations were risk factors associated with overall survival. Conclusions: AITL could be divided into two different prognostic groups, low-grade and high-grade, with statistically significance outcome, based on the FDC area expansion, degree of plasma cell proliferation, B cells distribution pattern combined with gene mutations and clinical progression. Low-grade malignant group progresses slowly, and high-grade malignant group is highly invasive.

Application values of 99mTc-methoxyisobutylisonitrile imaging for differentiating benign and malignant thymic masses.

The aim of the present study was to investigate the application value of 99mTc-methoxyisobutylisonitrile (MIBI) imaging to differentiate between benign and malignant thymic masses. A total of 32 patients with space-occupying mediastinal masses were enrolled and early and delayed-phase images were collected following injection with the imaging agent. The tumor to background ratio (T/N) values at the different phases were also recorded. The sensitivity of the qualitative analysis to distinguish between benign and malignant thymic masses was 95.24%, with specificity as 90.91%. The T/N values in the early and delayed phases were not significantly different in the group with benign thymic masses, but demonstrated statistical significant differences in the groups with low- and intermediate-grade malignant thymic masses. The T/N values at the above early and delayed phase were significantly different between the benign and low-grade malignancy groups, as well as between low- and moderate-grade malignancy groups. Those between the benign and moderate-grade malignancy groups demonstrated no significant difference. 99mTc-MIBI imaging was able to differentiate between benign and malignant thymic masses, and the simultaneous semi-quantitative analysis of the T/N values of the tumors may be able to initially determine the degree of malignancy of thymoma.

耳下腺癌４８例の臨床統計

We clinically analyzed 48 consecutive retrospective cases of parotid carcinoma initially treated between 1988 and 2007. Subjects were 30 males and 18 females ranging from 5 to 85 years old (average: 57.9 years). Of the 12 histological types seen, the most common was mucoepidermoid carcinoma, seen in 12 subjects (25.0%). We studied their survival based on 5 potential prognostic factors-stage, T stage, neck metastasis, facial nerve palsy, and malignancy grade-together with features of mortality and recurrence. Overall 5-year disease-specific survival was 71.2% and 10-year survival 54.9%. Survival rates were significantly lower in stage IV and high-grade malignancy groups than in stage I-III and low-grade malignancy groups. T stage, neck metastasis, and facial nerve palsy tended to compromise survival. Recurrence developed in 2 subjects, in whom significant recurrence risk factors were stage III-IV (particularly, stage IV), T3-4, and high-grade malignancy. Of 18 deaths, causes were distant failure in 11 and local failure in 5. None died of nodal failure. Analysis of these prognostic factors is important in selecting appropriate surgery and in determining indications for postoperative radiotherapy and chemotherapy, leading to better treatment outcome in those with parotid carcinoma.

Quantitative study of KI-67 antibody staining in 46 T-cell malignant lymphomas using image analysis

Image analysis with a SAMBA 2005 (ALCATEL-TITN, Co) was used to quantify the Ki-67 stained area percentage in 46 T-cell malignant lymphomas (T-ML), classified according to the updated Kiel classification. This parameter demonstrated correlation with the number of Ki-67-positive cellular profiles (r = 0.88, P less than 0.001) and was more reproducible than cell counting. A significant difference was found between low and high grade T-ML (mean values +/- SEM respectively of 10.20 +/- 1.82 per cent and 25.63 +/- 3.15 per cent). The most interesting findings were that: (1) AILD-type T-ML showed an intermediate proliferation rate (15.55 +/- 2.72 per cent) between pleomorphic T-ML with medium and with large cells (respectively 12.53 +/- 3.64 per cent and 22.43 +/- 3.46 per cent), both of which belong to the high grade malignancy group. This finding is in accordance with the poor prognosis of this subtype despite its classification in the low grade malignancy group. (2) Subclassification of the pleomorphic MLs according to the predominance of small, medium or large cells, demonstrated significant differences between these three subtypes. However, the great overlap of values between pleomorphic T-ML with medium and with large cells, seems to indicate that the subclassification of these two subtypes is less valid. (3) A wide range of values with overlap was observed in AILD-type ML, in pleomorphic with medium or large cells and in lymphoblastic T-ML: for these T-ML with variable survival courses, the Ki-67 area percentage, one parameter of proliferative activity, appears worth studying as a prognostic factor.

Surgical outcomes of spinal cord astrocytomas

Retrospective case series. To analyze prognostic factors for patients with spinal cord astrocytomas. Department of Orthopaedic Surgery, Keio University, Japan. Seven patients received total excisions (group T), eight underwent partial excisions (group P), and 15 had excisional biopsies (group B). Impacts of the tumor histological grade, the level of the tumor, the types of surgical interventions, and the use of adjuvant radiotherapies on the survival and functional outcomes of 30 patients (18 in low-grade and 12 high-grade malignancy tumors) were analyzed. The survival rate of the low-grade malignancy group was significantly higher than that of the high-grade group. The survival rate of the patients with thoracic astrocytomas was significantly higher than those with cervical astrocytomas. In both the low- and high-grade groups, the survival rates in groups P/T were significantly higher than those in group B. In the low-grade group, five patients, whose preoperative functional statuses were classified as 'fair' or better, remained 'fair' or better after surgery. In the high-grade group, the postoperative functional statuses were classified as 'no change' or 'aggravated' in all except two patients. No significant difference in the survival rates was detected between patients with and without adjuvant radiotherapy. The tumor grade and the extent of tumor resection were significant prognostic factors for survival rate. In low-grade malignancy group, good motor function was retained when surgeries were performed before substantial neurological deterioration. The efficacy of postoperative radiotherapy has yet to be determined and needs further study.

Evaluation of the malignant grade of thymic epithelial tumors according to the epithelial subclassification.

We investigated the clinicopathological correlations among 49 surgically resected thymic epithelial tumors (TET), which were subclassified according to the six subtypes established by the Marino, Kirchner, and Müller-Hermelink system, which were renamed as follows: spindle cell type (medullary thymoma), mixed spindle and polygonal cell type (mixed medullary and cortical thymoma), small polygonal cell type (predominantly cortical thymoma), large polygonal cell type (cortical thymoma), atypical type (well differentiated thymic carcinoma), and cytologically malignant type (high-grade thymic carcinoma). The related categories were grouped for statistical analysis as follows: group 1, spindle cell type and mixed type; group 2, small polygonal cell type and large polygonal cell type; group 3, atypical type; group 4, cytologically malignant type. The association of each group with the presence of myasthenia gravis, tumor stage, and the length of survival was studied. Myasthenia gravis was significantly present in patients with small polygonal type, large polygonal type, and atypical type tumors (groups 2 and 3) (P = 0.003). The tumors in group 1 showed the lowest tumor stage while those of group 4 had the most advanced tumor stage (P = 0.002). The patients in group 4 had the worst prognosis, followed by those in group 3, 2, and 1, in that order. The differences among these groups were statistically significant (P = 0.0003). From our results, we determined that TET can be separated into an extremely low-grade malignancy group (group 1), a low-grade malignancy group (group 2), an intermediate malignancy group (group 3), and a high-grade malignancy group (group 4).

Engraftment of human non-hodgkin lymphomas in mice with severe combined immunodeficiency

Malignant non-Hodgkin lymphoma (NHL) is one of the most difficult neoplasms to transplant into nude mice. Mice with severe combined immunodeficiency (SCID) accept various human cancers much more efficiently than do nude mice. The authors investigated whether SCID mice could be used as convenient hosts in which to grow human NHL in vivo. Fifty NHL specimens were engrafted into SCID mice. The original specimens and the tumors that developed in SCID mice were studied immunohistologically and by Southern blot analysis to clarify their clonal identity and to determine if they were Epstein-Barr virus (EBV)-transformed B cell proliferations. SCID tumors developed from 23 of 50 NHL specimens. Ten tumors were identical immunophenotypically and, partly, genotypically to the original NHL, showing that the original NHL grew in the SCID mice. B-cell NHL rather than T-cell NHL and high-grade rather than low-grade malignancy groups were much more easily heterotransplanted. Most of the heterotransplanted NHL were maintained by successive transplantation. In two other SCID tumors, the original NHL clones and a newly developed B-cell clone coexisted. The remaining 11 SCID tumors were composed of newly developed clones. The latter 13 tumors were shown to be human cells of B-cell lineage bearing EBV latent proteins--latent membrane protein 1 and EB nuclear antigen 2--suggesting that they originated from EBV-infected B-cells that were present in the original tumor tissues. SCID mice accept human NHL far more efficiently than do nude mice. However, frequent occurrence of spontaneous EBV-associated B-cell proliferation must be kept in mind.

Primary orbital malignant lymphoma: a clinicopathology study of 17 cases

We investigated the clinicopathologic characteristics of 17 patients (13 men and 4 women) with primary orbital malignant lymphoma using the Working Formulation. Most of the cases belonged to the low-grade malignancy group, and more women than men were in the histologically high-grade malignancy group. The phenotype of the tumor cells was investigated immunohistochemically. All cases showed the monoclonal feature of a B-cell lineage. All patients received chemotherapy with or without radiotherapy. Of 16 subjects, 15 achieved a complete remission; none of these patients has had a recurrence since the completion of the initial therapy (range of follow-up from 16 months to 10 years). One patient died.

Ki67 and 4F2 antigen expression as well as DNA synthesis predict survival at relapse/tumour progression in low-grade B-cell lymphoma.

Previous work has shown that parameters of cell activation studied on lymphoma biopsies can be used to discriminate between low-grade and high-grade non-Hodgkin's lymphomas and to predict prognosis in the low-grade malignancy group alone. We have now examined expression of several activation antigens and indicators of DNA synthesis in 29 patients with low-grade malignant B-cell lymphomas at the time of primary diagnosis and later at relapse and/or tumour progression. At both times, the level of 4F2 antigen expression examined by flow cytometry on cells in suspension as well as the number of Ki67 antigen-positive cells examined by immunohistochemistry were predictive of patient survival. DNA synthesis estimated by (3H-TdR) thymidine incorporation was of prognostic value at the second biopsy only. These parameters were more sensitive than histological demonstration of morphological transformation in secondary high-grade lymphomas in identifying high-risk patients at repeated biopsy. We propose that Ki67 or 4F2 expression or a marker of DNA synthesis (such as 3H-TdR incorporation or labelling index) should be evaluated when repeated biopsies are performed, in order to select patients for whom aggressive chemotherapy may be considered.

Flow cytometric light chain analysis of peripheral blood lymphocytes in patients with non-Hodgkin's lymphoma.

Peripheral blood lymphocytes from 96 patients with non-Hodgkin's lymphoma were studied, either at primary staging, during treatment or in follow up. The amount of surface immunoglobulin light chain per cell was determined by direct immunofluorescence staining analysed by flow cytometry. Discrepancy between kappa and lambda fluorescence profiles in the sample was considered to indicate the presence of monoclonal cells i.e., circulating lymphoma cells. The results were correlated with routine haematological findings, histopathology of the lymphoma and tumour burden. Using routine haematological methods leukaemic spread was evident in 24% of the patients in our study. Using kappa/lambda distribution analysis evidence of circulating lymphoma cells was found in an additional 27%. As expected, the major diagnostic gain was in the low grade malignant group, where 30% of the patients with normal peripheral blood according to standard procedures showed evidence of circulating lymphoma cells in the kappa/lambda distribution analysis. The corresponding gain in the high grade malignant group was 19%. In patients with active disease but without morphological evidence of leukaemia, 37% showed abnormal kappa/lambda distributions. In patients in complete remission the corresponding figure was 18%. The clinical significance of small numbers of circulating lymphoma cells is not yet understood, but a possible outlook is to use kappa/lambda distribution analysis to increase staging precision and in the early detection of relapse.

DISTRIBUTION OF HNK‐1+ CELLS IN MALIGNANT LYMPHOMAS

HNK-1, a murine monoclonal antibody, is known to react with most of the natural killer (NK) and killer (K) cells in peripheral blood. Cells reacting with this antibody (HNK-1+ cells) were studied on tissue sections of ninety two cases of malignant lymphomas (MLs) by using immunoperoxidase technique, in an attempt to elucidate the role of this type of cells in MLs. Follicular lymphomas were found to be highly infiltrated with HNK-1+ cells. The mode of infiltration in follicular lymphomas is just like in normal germinal centers. Many cases of diffuse lymphomas with cleaved nuclei, indicative of diffuse B-cell lymphomas of follicular center cell origin, as well as diffuse ML with heavy fibrosis (sclerosis) or histiocytic reaction, were also found to be infiltrated with abundant HNK-1+ cells. Meanwhile, other types of B-cell ML and all types of T-cell ML, as well as Hodgkin's disease, were shown to be very poor in HNK-1+ cell reaction. From a prognostic viewpoint, the low grade malignancy group in the NCI Working Formulation or Kiel Classification was found to be infiltrated with significantly much more HNK-1+ cells as compared to the high grade malignancy group. The significance of these findings are discussed, with the stress on the possible suppressive function of HNK-1+ cells on proliferation and differentiation of follicular center cell type B-cell MLs.

Primäres kutanes Zentrozytom: Diagnose, Verlauf und Therapie

A primary B-cell lymphoma of the skin is described, showing the clinical picture of a lymphadenosis cutis circumscripta. According to the Kiel classification, it has been classified as a centrocytic lymphoma (centrocytoma) belonging to the low-grade malignancy group. The centrocytoma is a newly defined type of lymphoma which is not identical with any earlier entity of lymphoreticular neoplasia. Although the centrocytoma is said to occur relatively often in the skin, the present case report seems to be the first clinical description of this variant. In our patient a solitary tumor of the face was found, which had slowly enlarged since 3 1/2 years. No lymph node and no systemic involvement were detectable. With a telecobalt-60 treatment up to a total of 40 Gy (= 4,000 rad) a complete involution could be achieved without recurrence 6 months after radiotherapy had been finished. In contrast to the centrocytoma of lymphonodal origin, the primary cutaneous type may obviously remain localized for a long time with low tendency to progression.