Histologic subtypes and survival of Chinese patients with non-Hodgkin's lymphomas

The histologic subtypes and survival of 840 Chinese patients with non-Hodgkin's lymphoma (NHL) were reviewed. All cases were classified according to the Rappaport and Kiel systems and the Working Formulation (WF). A low incidence of nodular/follicular lymphomas (12%) was observed. The most common histologic subtypes were diffuse histiocytic, diffuse centroblastic, and diffuse large cell lymphomas, according to Rappaport, Kiel, and the WF, respectively. A high proportion (24%) of the cases were unclassifiable, according to Kiel, because of the precise terms of the classification. The "favorable"-prognosis NHL, according to Rappaport, or the low-grade NHL, according to Kiel and the WF, had a more indolent clinical course. However, except for the nodular mixed (Rappaport) or follicular mixed (WF) lymphomas which appeared to behave like the more aggressive NHL, a plateau was not seen in the survival curves of our patients with other kinds of favorable-prognosis or low-grade NHL, indicating the lack of curative potential of these tumors. The lymphoplasmacytoid lymphoma, according to Kiel, also appeared to have a more aggressive clinical course. A plateau was seen in most of the other survival curves of patients with the more aggressive tumors, indicating the prospect of cure. However, the prognosis of the very aggressive tumors such as the diffuse lymphoblastic and diffuse small noncleaved cell lymphomas, according to the WF, remains very poor with a median survival of less than 10 months.     

Clinical and prognostic relevance of the Kiel classification of non-Hodgkin lymphomas results of a prospective multicenter study by the Kiel Lymphoma Study Group

Clinical and prognostic relevance of the Kiel classification of non-Hodgkin lymphomas (NHL) was investigated in 1127 patients entering a prospective multicenter observation study. Survival of the 782 (69–4 per cent) patients with low-grade malignant NHL (lymphocytic lymphomas, predominantly B-CLL, LP immunocytoma, centrocytic lymphoma, centroblastic-centrocytic lymphoma) exceeded that of the 341 patients (30–2 per cent) with high-grade malignant NHL (centroblastic, immunoblastic, lymphoblastic lymphomas). Prognosis was best in centroblastic-centrocytic lymphoma and in B-CLL and least favorable in immunoblastic and lymphoblastic lymphomas. Survival of LP immunocytoma and centrocytic lymphoma patients was intermediate after 2 to 2·5 years of follow-up. Corresponding to histopathology, pattern of survival curves of low-grade malignant NHL (slow decline, no plateauing) differed from that of high-grade malignant NHL (rapid decline, subsequent plateauing). Prognosis of B-CLL was superior to that of LP immunocytoma. Stages I and II were more frequent in centroblastic-centrocytic lymphoma (21 per cent) than in LP immunocytoma (2·5 per cent) and centrocytic lymphoma (11 per cent). Ability of radiotherapy to induce stable complete remissions in stage III of centroblastic-centrocytic lymphoma indicates prolonged restriction of lymphoma to the lymphatic system. In immunoblastic and centroblastic lymphomas, stages I and II were diagnosed in 34 and 38 per cent of cases, respectively, but only in stage I/I_E of centroblastic lymphoma prolonged remissions were achieved by radiotherapy. In advanced high-grade malignant NHL marked improvement of prognosis was solely possible by induction of complete remissions whereas in corresponding low-grade malignant lymphomas also partial remissions were prognostically relevant.     

Non-Hodgkin's lymphoma of the thyroid: A retrospective review of all patients diagnosed in Nottinghamshire from 1973 to 1992

The pathological and clinical features were reviewed of all primary non-Hodgkin's lymphomas (NHL) of the thyroid gland diagnosed between 1973 and 1992 in the population (1.1 million) served by the Nottingham and North Nottinghamshire Health Authorities. Of the 43 patients with histologically proven NHL, three had low grade mucosa associated lymphoid tissue (MALT) lymphomas (Stage I_eA, 2; Stage II_eA, 1), 35 had intermediate or high grade lymphomas, Stage I_ea or II_eA (intermediate MALT, 2; high grade MALT, 14; B-cell diffuse centroblastic, 17; anaplastic large cell (Ki-1) of null cell type, 1; high grade unclassifiable, 1), and one had unclassifiable NHL Stage II_eA. One patient had Stage III_eA disease (high grade MALT) and three had stage IVA disease (high grade MALT, 2; B-cell diffuse centroblastic, 1). The median age was 68 years (range 45–86) with a female : male ratio of 6:1. For the 35 patients with intermediate or high grade thyroid NHL (Stages I_eA and II_eA) the 5- and 10-year cause specific survival was 60%. The 21 patients treated between 1985 and 1992 initially with chemotherapy (except stage I_eA (<5 cm diameter) had a 5-year cause specific survival of 69% (95% CI 48–90) compared with 46% (95% CI 19–73) for the 14 patients treated between 1973 and 1984 with initial radiotherapy (χ² = 1.62). The survival of those patients with intermediate or high grade MALT lymphomas was not significantly greater than of those patients with B-cell diffuse centroblastic NHL.     

Diffuse large B-cell non-Hodgkin lymphomas: the clinical relevance of histological subclassification

In the REAL classification the diffuse large B-cell non-Hodgkin lymphomas (NHL) are grouped together, because subclassifications are considered to lack both reproducibility and clinical significance. Others, however, claim that patients with an immunoblastic NHL have a worse prognosis than patients with other types of diffuse large B-cell NHL. Therefore, we investigated the prognostic and clinical significance of histological subclassification of diffuse large B-cell NHL in a uniformly treated series of patients. For this retrospective study, all patients diagnosed as having an immunoblastic (IB) B-cell NHL by the Lymphoma Review Panel of the Comprehensive Cancer Center Amsterdam (CCCA) between 1984 and 1994, and treated according to the guidelines of the CCCA, were analysed. Patients with a centroblastic polymorphic subtype (CB-Poly) or centroblastic (CB) NHL by the Lymphoma Review Panel who were treated in the Netherlands Cancer Institute during the same period according to CCCA guidelines were used as reference groups. All patients' records were reviewed. Clinical parameters at presentation, kind of therapy and clinical outcome were recorded. All available histological slides were separately reviewed by two haemato-pathologists. One hundred and seventy-seven patients were included in the study: 36 patients (20.3%) with an IB NHL, 69 patients (39%) with a CB-Poly NHL and 72 patients (40.7%) with a CB NHL. The patients with an IB NHL tended to be older and presented more often with stage I or II and one extranodal site than patients with a CB and CB-Poly NHL. None of the subtypes showed a clear preference for localization in a particular site. The patients with IB or CB-Poly NHL showed a significantly worse prognosis than patients with CB NHL, with a 5-year overall survival for patients with CB NHL of 56.3% and for patients with IB or CB-Poly NHL 39.1% and 41.6% respectively. The 5-year disease free survival was 53.2% for the patients with CB, 32% for the patients with CB-Poly and 26.9% for the patients with IB NHL. A multivariate analysis showed that histological subtyping was of prognostic significance independent of the International Prognostic Index. This finding merits further exploration in prospective studies in order to judge the value of subclassification of large B-cell NHL as a guideline in therapy choice.     

Clinico-pathological features of malignant lymphomas in 294 Hong Kong Chinese patients, retrospective study covering an eight-year period

The clinical records and histological material from 294 adult Chinese patients with malignant lymphoma were examined. These patients were first seen at the Queen Mary Hospital, Hong Kong, during the 8-year period 1975-82. There were 27 patients (9.2%) with Hodgkin's disease (HD) and 267 with non-Hodgkin's lymphoma (NHL). The median age at presentation was younger for HD (45 years) and the male: female ratio was higher (2:1) than the corresponding figures for NHL of 51 years and 1.4:1. In 76 patients (28.5% of NHL), the disease was thought to have originated in an extra-nodal site, 48 of these cases being gastrointestinal lymphomas. It was possible to reclassify 234 NHL according to the Rappaport and Kiel classifications, and the Working Formulation (WF) proposed by the US National Cancer Institute Study; for HD, the Rye classification was used in 26 cases where suitable material was available. Nodular/follicular lymphomas made up 17.1% of nodal NHL and 5.3% of extra-nodal NHL. The "histiocytic" (Rappaport) or large-cell (WF) subtype was the commonest amongst diffuse NHL. There were only four cases of Burkitt's lymphoma. For HD, the nodular sclerosing subtype was commonest in females (5 out of 8 cases) and for males, the commonest was mixed cellularity (10 out of 18 cases). Of patients with nodal NHL 64.7%, presented with Stage IV disease. For HD, there were about equal numbers of patients presenting with Stage II and Stage IV disease (10 and 9 respectively). The low incidence of Hodgkin's disease and of follicular lymphomas is comparable to figures from other "oriental" countries such as Japan.     

Non-Hodgkin's lymphoma in the elderly. I. Pathologic features at presentation

The pathologic findings of 118 patients aged 70 years or older with non-Hodgkin's lymphoma (NHL) are reported. These patients formed 27.2% of 433 consecutive cases of NHL seen in a single institution over a 5-year period. Thirty-one of 433 NHL cases were histologically not classified, whereas the remaining 402 could be classified according to the International Working Formulation (WF) of NHL for clinical usage. Immunophenotypic analyses were carried out in 112 NHL cases; of this group 28 were NHL in elderly patients. Of the 95 elderly NHL that could be classified in the histologic categories of the WF 28 cases were in the low-grade, 41 in the intermediate-grade, and 26 in the high-grade categories. Eighty-one cases had diffuse histologic types and 14 had follicular/nodular histologic types. Thirty-five cases were of the G (diffuse large cell) + H (large cell, immunoblastic) categories. No significant differences in the prevalence of the different subtypes were observed among patients younger or older than 70 years. Immunohistologically, most NHL cases in the elderly expressed B-cell phenotype. Sixty-two NHL in the elderly were extranodal at presentation. The results of this study indicate that elderly patients form a relevant proportion of patients developing NHL and thereby present a very difficult management problem. The pathologic features of NHL in the elderly does not differ significantly from those of their younger counterparts, although an increase in diffuse versus follicular histologic patterns, and in extranodal versus nodal disease was observed with advancing age.     

Modification of Kiel and working formulation classifications for improved survival prediction in non-Hodgkin's lymphoma

The total survival of 203 patients with non-Hodgkin's lymphoma (NHL) was analyzed according to the working formulation (WF) and "expanded" Kiel classifications. The original Kiel classification consisting of low grade (LG) and high grade (HG) forms corresponded well to the LG and HG forms of the WF. When an expanded Kiel containing an intermediate grade (IG) composed of the original LG diffuse group was devised, this gave a much better separation of survival of the three grades as compared with the WF where the survival of IG and HG forms were nonsignificantly different. The main reason for this difference was the inclusion of the so-called centroblastic diffuse form in the HG Kiel, but in the IG according to the WF. In a "modified" WF analysis where this histologic entity was placed in the HG subgroup, the three survival curves then gave excellent separation like the expanded Kiel classification. Since the centroblastic diffuse form (and its analogous forms according to other classifications) has a poor prognosis, it is important that it be so recognized and treated accordingly with aggressive therapy. We propose either our expanded Kiel or modified WF classification of the three grade forms as an excellent predictor of survival.     

Salvage extended-field irradiation in follicular non-Hodgkin's lymphoma after failure of chemotherapy

PURPOSE: To evaluate the efficacy of total abdominopelvic (TAI) and total body irradiation (TBI) in heavily pretreated follicular non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: From 1983 to 1998, 34 patients received TAI (n = 22) or TBI (n = 12). All had Stage III or IV, Class B, C, D NHL in the working formulation and failed after receiving 1-5 regimens of chemotherapy. TAI was given at 20 Gy over a 3-week period. TBI was delivered in two successive half-body irradiations of 15 Gy over a 2-week period with a 4-week interval between each. RESULTS: Mean follow-up from TAI or TBI was 120 months (range, 6-180). Seventy-six percent of patients achieved complete response and 24% partial response. Median survival was 62 months, 5-year and 10-year overall survival was 59% and 41%, and disease-free survival was 56% and 30%, respectively. Grade III or IV toxicity was gastrointestinal in 38% of patients and hematologic in 30%. No toxic death or delayed complications were observed. CONCLUSION: Extended-field irradiation is feasible and efficient after failure of chemotherapy in follicular NHL.     

Childhood malignant non-Hodgkin lymphomas of uncommon histology.

Uncommon histologies were identified in 36 of 1336 cases (2.7%) of newly diagnosed childhood non-Hodgkin lymphoma (NHL). Seventeen cases were classified as follicular (six cases as mixed small and large cell, nine as large cell, and two as small non-cleaved cell) and 19 cases as diffuse (18 cases as mixed small and large cell, and one as small cell lymphocytic). The follicular pattern group included a preponderance of male patients; the median age at diagnosis was 11.7 years. These children presented primarily with low-stage disease involving lymph nodes or tonsils. All patients except one achieved complete remission and remain disease-free for 11 months to 18.8 years (actuarial 5-year event-free survival, 94%). The group with diffuse histologies was similar in sex ratio, age at diagnosis (median = 12.1 years), and nodal involvement, but tended to have more advanced-stage disease. Moreover, only 14 of 19 (74%) children with diffuse intermediate-grade histologies are alive in continuous complete remission (actuarial 5-year event-free survival, 70%). These results suggest that follicular pattern childhood NHL has an excellent prognosis, whereas cases with diffuse intermediate-grade histology are prognostically similar to those with diffuse high-grade histologies.     

Mitotic activity in non-Hodgkin's lymphoma. Relation to the Kiel classification and to prognosis

At histopathological diagnosis of non-Hodgkin's lymphoma (NHL) the mean number of mitoses in 10 high power fields (X 40) was determined in thin sections (2 micron) and designated 'mitotic index' (MI). In 38 patients the thymidine labelling index (LI) of the lymphoma cells was also determined. There was a close correlation between MIs and LIs (r = 0.81, P less than 0.001) indicating that MI reflects the proliferative activity in NHL. Among 101 patients with NHL classified according to the Kiel nomenclature MIs were generally lower in lymphomas of low grade malignant type than in the high grade malignant lymphomas. The variation of MIs within morphological subgroups was especially pronounced in high grade lymphomas. Only 18 of 49 patients (37%) with MI greater than or equal to 2 have survived for 2 years in contrast to 37 of 52 patients (77%) with MI less than 2 (P = 0.001). For patients with histologically low grade lymphomas and MI greater than or equal to 2.0 the median survival was 23 months and for those with MI less than 2.0 58 months (P = 0.09). Patients with high grade lymphomas and MI greater than or equal to 2.0 had a median survival of 15 months compared to 57 months for those with MI less than 2.0 (P = 0.04). In a multivariate analysis of 50 patients with centroblastic-centrocytic (CB-CC) or centroblastic (CB) lymphomas the importance of different prognostic factors was analysed. Among the variables age, MI, growth pattern (follicular vs. diffuse), cell type (CB-CC vs. CB), clinical stage (I vs. II-IV), initial chemotherapy (active vs. less active) only age and MI gave significant prognostic information. It is concluded that the assessment of mitoses in NHL gives prognostic information in addition to histopathologic classification. The method is simple and the proliferative activity and histopathological diagnosis can be ascertained routinely on the same occasion.     

Clinicopathological Features, Survival And Prognostic Factors Of Primary Central Nervous System Lymphomas: Trends in Incidence of Primary Central Nervous System Lymphomas and Primary Malignant Brain Tumors in A Well-Defined Geographical Area; Population-Based Data from the Danish Lymphoma Registry, Lyfo, And the Danish Cancer Reistry

It has been claimed that Primary Central Nervous System Lymphoma! (PCNSL), a rare neoplasm accounting for only a small fraction of malignant brain tumors and extrancdal non-Hcdgkin lymphomas (NHL), occur with increasing frequency in immunologically normal as well as in immunocompromised individuals. In an attempt to characterize the clinicopathological features, outcome and prognostic factors of PCNSL we here report our experience in a large unselected series of patients from a well-defined region. In addition, we present data on trends in incidence of PCNSL and primary malignant brain tumors in a well-defined geographical area. In a Danish population-based NHL registry (LYFO) representing a population of 2.7 million all new cases of NHL were registered during the approximate I I-year period from 1st January 1983 to 3 1st May 1994. Incidence data of primary malignant tumors of the brain and central nervous system in western Denmark for the period 1971-1990 have been obtained from the Danish Cancer Registry. During the approximate I I-year period 3 124 new cases of NHL were registered. Of these, I 152 (37%) were extranodal and 48 were non-AIDS related PCNSL accounting for4.2% ofextranodal NHL and 1.5% of all NHL, respectively. The average annual incidence rate of non-AIDS related PCNSL during the period was I .56 cases per million population (age range: 15-85 yrs, median: 62 yrs, MIF ratio: I).In a 23-year period there was no trend towards an increasing incidence of non-AIDS related PCNSL in a well-defined population. PCNSL accounted for 1.7% of all primary malignant brain tumors. Incidence of primary malignant brain tumors was stable, except for age ranges over 70 years. However, diagnostic artifacts might be responsible for this apparent increase. Histologically, 85% were high grade. Using the Kiel classification centroblastic diffuse (60%) and immunoblastic lymphoma (13%) were the most common subtypes. Forty-three patients had 6-cell lymphoma and no T-cell lymphoma was detected. Forty-seven cases were diagnosed pre mortem. Treatment included surgical resection (26 patients), whole brain irradiation (WBRT) (43 patients) and chemotherapy (28 patients). Median survival for those receiving either WBRT or WkRT and chemotherapy was 8 months and 20 months, respectively (p = 0.78). Overall survival was 53%. 38% and 26% at I, 2 and 5 years. Cox-regression analysis identified only one factor having independent impact on survival in PCNSL performance score 2 2 (pc 0.001. RR = 5.8     

Primary gastrointestinal non-Hodgkin's lymphomas. A retrospective clinicopathologic study of 150 cases

The records of 150 primary gastrointestinal (GI) lymphomas in adults collected from 1974 to 1982 at the Department of Pathology, University of Vienna, were reviewed. One hundred thirty-three cases of malignant lymphomas (ML) were analyzed with respect to histologic type, presenting tumor stage, and clinical course, as well as for factors influencing prognosis. The histologic type of ML as assessed by the Working Formulation and the Kiel, the Lukes and Collins, and the Rappaport classifications showed only a minor influence on prognosis. MLs of follicular center cell origin prevailed in the stomach and large cell, immunoblastic MLs prevailed in the bowel. Immunoperoxidase studies indicated a B-cell nature of GI MLs and demonstrated intracytoplasmic IgM kappa or lambda in most of the MLs of the small lymphocytic, plasmacytoid, and immunoblastic type, respectively. The 105 cases of gastric MLs represented 3.6% of all malignancies of the stomach collected during the study period. Clinical symptoms preceded the diagnosis by 4.4 months on average, and endoscopic biopsy specimens indicated malignancy in 78%. Presenting tumor stages of gastric MLs according to the Ann Arbor staging system were Stage I in 20%, Stage II in 76.2%, and Stage IV in 3.8%. The 28 cases of intestinal ML localized in the small and large bowel without any site prevalence presented with Stage I in 14%, Stage II in 82%, and Stage III in 4%. Tumor resection was performed in 90% of all cases and was followed by multiagent therapy in 53%. Radical tumor resection was obtained in 58% of the gastric MLs and only 28.6% of the intestinal MLs and was closely related to tumor stage. Statistical analysis demonstrated a significant influence of the presenting tumor stage on prognosis as expressed by the overall 2-year survival rate of 70% for Stage I versus 39% for Stage II ML. In addition, Stage II1 according to Musshoff et al. run a better course than II2 as shown by the disease-free 2-year survival rate of 49% versus 15%, respectively. Radical tumor resection was a major determinant of survival and cure of disease as exhibited by the disease-free 2-year survival rate of 57% after radical resection versus 8% after nonradical resection of ML. Finally, diffuse tumor growth and tumor penetration of the gastric wall beyond serosa decreased the survival rates.     

Relationship between clinical stage, histopathology and antibody titers against the second Epstein-Barr virus nuclear antigen (EBNA-2) in non-Hodgkin's lymphoma patients

Non-Hodgkin lymphoma (NHL) patients with centroblastic (Cb) or centroblastic-centrocytic (Cb/Cc)-diffuse lymphomas, immunocytoma (IC) and chronic lymphocytic leukemia (CLL) in clinical stages III-IV and with active disease (highly malignant group) were compared to NHL patients with CLL, IC, and centrocytic (Cc) or centroblastic-centrocytic (Cb-Cc)-diffuse/follicular lymphomas, in clinical stages I-II and with inactive disease (low malignant group) based on the presence of antibodies to Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1) and 2 (EBNA-2). In the highly malignant group, anti-EBNA-1 geometric mean titers (GMT) were 13.2 (range less than 2-80) and anti-EBNA-2 60.6 (range: 20-320). The ratio between the logarithms of anti-EBNA-1 and anti-EBNA-2 antibody titers was less than 1.0 (mean: 0.32) in all the patients examined. In 6 out of 8 patients of the low malignant group, anti-EBNA-1 titers were higher (mean: 30.1; range 10-160) than anti-EBNA-2 titers (mean: 4.3; range less than 2-80) and the EBNA 1/2 ratio was greater than 1.0. In healthy EBV-seropositive individuals, anti-EBNA-1 GMT were 49 (range: 10-320) and only 5 out of 17 individuals had detectable anti-EBNA-2 titers (GMT: 3; range less than 5-20). The EBNA-1/2 ratio was in all cases greater than 1. Among patients of the highly and low malignant groups, patients with follicular-cell-derived lymphomas had elevated antibody titers against the restricted component of early antigens (EA-R), whereas all patients with IC and 2 out of 4 CLL patients had elevated antibody titers against the diffuse component of early antigens (EA-D). The results indicate that the ratio between anti-EBNA-1 and anti-EBNA-2 antibody titers may be of diagnostic importance in patients with immunodeficiencies.     

Primary non-Hodgkin's lymphoma of bone: a clinicopathological investigation of 60 cases.

A retrospective analysis of patients presenting with primary lymphoma of bone (PLB) was performed to determine clinical factors affecting prognosis in relation to histological subtype and treatment outcome. Data from 106 patients, presenting with a PLB between 1943 and 1996, were retrieved from the files of the Netherlands Committee on Bone Tumours and Leiden University Medical Centre. The lymphomas were reclassified according to the REAL and updated Kiel classification. The clinical presentation, survival and prognostic factors were investigated. Sixty patients had sufficient clinical information and adequate follow-up to be included in the study. All 33 PLB that could be immunophenotyped were of B cell origin. According to the REAL classification, most PLB were large (B) cell lymphomas (92%) and according to the Kiel classification 45% of the tumours were centroblastic multilobated. PLB presented most often in the long bones (48%), with Ann Arbor stage I (46%), II (16%), IV (16%) and unknown (20%). Stage IV disease was exclusively caused by the presence of multiple bone lesions. Notwithstanding the heterogeneous treatment, the 5-year overall survival was 61%; 46% of patients were progression free at 5 years. Patients at presentation older than 60 had a worse overall survival (76% vs 37%, P = 0.0002) and a worse progression-free period (58% vs 28%, P = 0.0073). Patients with the immunoblastic subtype had a worse survival than the centroblastic mono/polymorphic subtype or the centroblastic multilobated subtype (P = 0.015). Primary lymphoma of bone represents an uncommon bone tumour with a relatively homogeneous morphology and clinical behaviour. Compared to other aggressive lymphomas, PLB have a favourable prognosis.     

Distinguishing features of primary hyperparathyroidism in patients with breast cancer

Thirty-five women with breast cancer and primary hyperparathyroidism (1 degree HPT) were admitted to Memorial Hospital during a 25-year period. The incidence of primary hyperparathyroidism in the breast cancer patients was similar to the incidence in the total patient population at Memorial Sloan-Kettering Cancer Center (0.15% and 0.14%, respectively). The patients with 1 degree HPT disease had clinical findings which distinguished them from those patients with cancer-related hypercalcemia. Eighty percent of the breast cancer patients with primary hyperparathyroidism had earlier stage disease (Stage 0, Stage 1, Stage 2); whereas 97% of the patients with breast cancer and hypercalcemia (not due to 1 degree HPT) had advanced disease. There appeared to be a trend towards improved survival in the breast cancer patients with primary hyperparathyroidism when compared to patients of similar stage of disease who did not have parathyroid disease.     

Centroblastic and centrocytic centroblastic malignant lymphomas, predominantly splenic (or primary of the spleen). Anatomo-clinical study of 17 cases

Seventeen cases of splenic centroblastic-centrocytic or centroblastic lymphoma are reported. A large splenomegaly is discovered in all these cases as the prominent symptom. For this reason, all these cases can be considered as primary lymphoma of the spleen. Splenectomy is done in 7 cases for diagnosis a period of 2 to 8 months after the discovery of the splenomegaly. In these patients, no bone marrow biopsy was performed before splenectomy. In 8 other cases, the diagnosis of follicular lymphoma is proposed on a bone marrow biopsy performed with the aim to disclose an etiology for the splenomegaly. In 3 of these cases, a lymph node (2 cases) or a tonsil biopsy (1 case) discover a tumoral localization before the splenectomy. In the 2 last cases, the diagnosis is recognized on a lymph node biopsy. The most important clinical and biological data are compared for these 17 patients. The anatomopathological data are described. In 15 cases, a multimicronodular pattern is recognized on the spleen section. The 2 other cases express a multimacronodular pattern. The weight of the spleen is comprised between 450 and 3,350 g, with only 6 spleens weighing less than 1,000 g. The spleens with multimicronodular pattern correspond to a follicular centroblastic centrocytic lymphoma of low grade of malignancy in the Kiel-Lennert classification. The 2 multimacronodular spleens exhibit the histological aspect of a polymorphous centroblastic lymphoma of a high grade of malignancy. The equivalent of these histological types are given in the Working Formulation. The diagnosis with others diseases of the spleen is discussed. For fourteen patients, the follow-up is available. Six patients are alive, with an evolution of many years. Because of the few number of cases, it is not possible to correlate the histological subtypes according to Kiel or to the WF, and the clinical stage with the evolution. To perform such correlation, a multicentric study should be organized.     

Prognostic value of the Kiel classification of malignant non-Hodgkin's lymphomas.

The aim of the present research was to evaluate the prognostic value of the Kiel classification of malignant non-Hodgkin's lymphomas. For this purpose a series of 100 consecutive, previously untreated adults with advanced malignant non-Hodgkin's lymphomas was analyzed. The median age of the patients was 54 years; 61 patients were males. Although the number of the various groups considered was limited, a statistically significant difference (p less than 0.001) was found in the median survival of patients with lymphomas of low-grade malignancy (lymphocytic, lymphoplasmacytoid, centrocytic, centroblastic-centrocytic lymphoma) and lymphomas of high-grade malignancy (centroblastic, lymphoblastic, immunoblastic lymphoma). A difference in survival (p less than 0.001) was also observed among the patients with lymphocytic lymphoma and those with centroblastic-centrocytic lymphoma, whereas no significant difference in survival was found between the histological subtypes of high-grade malignant lymphomas. Our observations support the opinion that the Kiel classification is useful in clinical practice to distinguish the histological types with a better prognosis from those with a worse one; in addition this classification appears to be of conceptual value.     

Non-Hodgkin's lymphoma in the elderly. A study of 602 patients aged 70 or older from a Danish population-based registry. The Danish LYEO-Study Group.

Within a 7-year period 1,597 newly diagnosed cases of non-Hodgkin's lymphoma (NHL) were included in a Danish population-based NHL registry. Of these, 602 (38%) were aged 70 years or older (age range 70-94, median: 76.8). They represent the population defined as 'elderly' patients in the present study. The average annual incidence rate for this elderly patient population was 35.7/10(5), as compared with 6.6/10(5) for patients aged less than 70 (overall annual incidence: 9.5/10(5)). Localised cases (stage I and II) and extranodal manifestations were found more frequently among elderly patients. The most common sites of extranodal involvement were the stomach (21% of all extranodal cases) and the bone marrow (16%). Histologically, follicular centroblastic/centrocytic cases were found to be less frequent (p less than 0.01) in elderly patients as compared to their younger counterparts (less than 70 years), who in contrast had a lower occurrence of diffuse centroblastic cases (p less than 0.01). Overall 7-year survival for the elderly patient population was 35% (median 1.7 years), and for patients aged less than 70 it was 57%. This difference persisted after correction for apparently NHL-unrelated deaths (52% vs. 66%, respectively, p less than 0.0001). Elderly patients with poor prognosis were characterised by the following features identified in a Cox-regression model: hepatic involvement, presence of B-symptoms, high-grade histology and elevated s-LDH. The corresponding relative risk values were in the order 2.4, 2.2, 1.9 and 1.6.     

Malignant lymphomas of the thyroid gland. Analysis of 79 patients with emphasis on histologic prognostic factors

Prognostic factors in 79 patients with malignant lymphomas involving the thyroid gland were analyzed. These patients suffered from progressively enlarging goiter with over 6 months duration in 60% of patients. The age at operation ranged from 16 to 80 years (median, 58 years). Male to female ratio was 1:1.8. Serum tests for antithyroid antibodies were positive in 83% of the patients, who also showed histologic evidence of chronic lymphocytic thyroiditis. Histologically, 52 cases (66%) were germinal center cell tumors with follicular or follicular and diffuse pattern in 9 cases. By the Working Formulation, 5-year survival rate of immunoblastic type (IBL) (13%) was much poorer than those of intermediate (79%) and low grade cases (92%) (P less than 0.001). The cases of IBL usually had a goiter of short duration, and frequently presented as advanced disease.     

Primary non-Hodgkin lymphoma of the breast: The Mayo Clinic Experience

BACKGROUND AND OBJECTIVES: To retrospectively evaluate the characteristics, natural history, results of treatment, and prognostic factors for patients diagnosed with primary breast lymphoma. METHODS: Between 1973 and 1998, 25 women and 1 man with the diagnosis of primary breast non-Hodgkin lymphoma (PNHLB) were seen at Mayo Clinic Rochester and Mayo Clinic Scottsdale. Patient characteristics, treatment methods, and outcome were analyzed. RESULTS: The median follow-up for surviving patients was 6.6 years (range: 1.8-22.1 years). There were 11 low-grade NHL, 13 intermediate-grade NHL, and 2 high-grade NHL. Three patients underwent mastectomy while 23 had local excision. The Ann Arbor stage of disease included: Stage I-21 patients, Stage II-5 patients. Sixteen patients received radiation after surgery (15 after biopsy, 1 after mastectomy). Chemotherapy was given to 10 patients as part of the initial treatment. Four patients with low-grade disease were treated with excision only. The 5-year overall survival rate was 70% and relapse-free survival rate 42%, while local control rate was 75% and distant control rate 51%. Five-year survival and relapse-free survival rates for patients with low-grade disease were 91 and 61%, respectively. Three of four patients with low-grade disease treated with excision alone were free of local recurrence. For intermediate- and high-grade PNHLB, 5-year survival rate was 61% for those treated with chemotherapy, compared to 31% for those without chemotherapy (P = 0.35), and the 5-year relapse-free survival rates were 49%, compared to 0%, respectively (P = 0.0017). Three patients with intermediate- or high-grade disease developed central nervous system (CNS) dissemination. On univariate analysis, Ann Arbor stage was the only significant prognostic factor for survival (P = 0.0021). CONCLUSIONS: The management of PNHLB should be based on histologic grade. Patients with low-grade disease may be managed with local therapy alone. The role of chemotherapy in this group is unclear. Patients with intermediate- or high-grade disease have better outcome if chemotherapy is included. An unusual site of distant dissemination for these patients is the CNS. The only significant prognostic factor for survival is Ann Arbor stage.