Niels Tinggaard Pedersen

Clinicopathological features and prognostic factors in extranodal non-Hodgkin lymphomas

Abstract In a Danish population-based non-Hodgkin lymphoma (NHL) registry, 1257 newly diagnosed NHL cases were registered over a 5-year period. Of these, 463 (37%) were extranodal. The gastrointestinal tract was the most common site of extranodal involvement (30% of the cases). Histologically, 44% of all extranodal NHL cases had high-grade, 17% intermediate and 27% low-grade features, while 12% were unclassified. The most common histological subtype (Kiel) was the centroblastic diffuse (23% of cases). 50% of all extranodal NHL were localised (stage I E or II E ) and 27% had B symptoms. Site-specific features included a strong age-correlation for thyroid and testes lymphoma (>50 years) and a high prevalence of female cases in thyroid and salivary glands lymphomas (M/F 0.14 and 0.30, respectively). Overall 7-year survival for extranodal NHL was 46% (median 4.9 years). Poor prognosis patients could be identified by the presence of one or more of the following presentation characteristics: age >65 years, B symptoms, high-grade histology, disseminated disease, elevated s-IgA and hyperuricaemia. Relative risk values ranged from 2.1 for age and B symptoms to 1.7 for hyperuricaemia.

Increasing incidence of ophthalmic lymphoma in Denmark from 1980 to 2005

PURPOSE To evaluate patient characteristics and incidence of ophthalmic lymphoma in Denmark during the period 1980 to 2005. METHODS All patients in Denmark with a diagnosis of ophthalmic lymphoma during the period 1980 to 2005 were retrieved from three different population-based registries. Specimens from all patients were collected and reclassified according to the World Health Organization (WHO) classification system. Incidence rates were calculated by using Poisson regression models. RESULTS A total of 228 patients with a histologically verified diagnosis of ophthalmic lymphoma were included. There was an equal distribution of males and females. The most frequent lymphoma subtype was extranodal marginal zone B-cell lymphoma (MALT [mucosa-associated lymphoid tissue] lymphoma, 55.5%) and most cases were located in the orbit (56.8%). High-grade lymphoma subtypes were found more frequently in males than in females. Incidence rates were highly dependent on the patients age. For all ages, a statistically significant annual average increase of 3.4% during the 26-year period was found. This increase was primarily due to a rise in the incidence of MALT lymphoma. CONCLUSIONS In the Danish population ophthalmic lymphoma consists primarily of orbital MALT lymphoma. Although it is a rare disease in mostly elderly patients, the incidence of ophthalmic lymphoma is increasing at a rapid pace.

Immunohistologic separation of B-cell-positive granulomas from B-cell-negative granulomas in paraffin-embedded tissues with special reference to tumor-related sarcoid reactions

Frozen and formalin‐fixed paraffin‐embedded tissue sections were studied concurrently in 17 cases of granulomatous lesions of different etiologies using antibodies recognizing either fixation‐sensitive or fixation‐resistant antigens. In fixed tissues, the antibodies 4KB5 and L26 for B cells and UCHL1 and MT1 for T cells gave results similar to those obtained in frozen tissues with anti‐leu‐12/leu‐14 for B cells and T‐3 for T cells. Paraffin‐embedded sections from 35 additional cases of granulomatous lesions were studied retrospectively using the same markers. The combined results from all 52 cases show that granulomas can be divided into two main “families” according to the presence or absence of B cells within the granulomas: one is a B‐cell‐negative family of lesions to which sarcoidosis and mycobacterial infection belong; the other is a B‐cell‐positive family of lesions to which toxoplasmosis, granulomatous lesions of unknown significance and tumor‐related sarcoid reactions belong.

Primary malignant lymphoma of the central nervous system

The occurrence of primary malignant lymphomas of the central nervous system in a population of approximately 1 million people has been analyzed retrospectively. Over a 12-year period, about 1000 tumors of the central nervous system were registered. Among these, 22 were primary malignant lymphomas; incidence, 1.83 per million per year. Thirteen of these tumors were of high-grade malignancy and nine were of low-grade malignancy (Kiel classification of non-Hodgkin lymphomas). The majority of the tumors were B-cell lymphomas, and there were no Hodgkin lymphomas. Neither spinal nor meningeal lymphomas occurred. Nine patients were treated only surgically, whereas 11 received postoperative irradiation or chemotherapy, or both. Of the latter patients, six are alive and well at the time of writing. The importance of making a correct diagnosis preoperatively is stressed, inasmuch as radical operation is unfavorable for these patients. A better prognosis is obtained with combinations of irradiation and chemotherapy.

Non-Hodgkin's Lymphoma Subtypes over Time in an Unselected Population of 646 Patients: A Study of Clinico-Pathological Data and Incidence Based on a Review Using the REAL-Classification

Biopsies from 646 consecutive unselected cases of non-Hodgkins lymphoma from a Danish population-based registry were reclassified according to the REAL classification 1) to study the distribution of subtypes over time. and 2) to correlate a number of clinical parameters with the various subtypes. Two cohorts from 1986 and 1992, of 292 and 354 cases, respectively, were studied. From 1986 to 1992 (diffuse large B-cell lymphoma showed a change in incidence of + 43.1%, as opposed + 2.5% for all other subtypes combined (p = 0.05). suggesting that the increasing general incidence of non-Hodgkins lymphoma is due primarily to an increasing incidence of diffuse large B-cell lymphoma. A higher rate of cell proliferation was associated with an increasing chance of having extranodal disease. For the various subgroups there was good agreement between survival and the international prognostic index.

Chromosome Aberrations in Adult Hodgkin Disease in a Danish Population-Based Study

During a 6-year period, 31 patients with Hodgkin disease (HD) were analyzed for chromosome aberrations on lymphoid tissue. We obtained metaphases in 87% (27/31). The number of cells analyzed per case ranged from 17 to 31 (median 25), and the number of abnormal mitoses was between 1 and 17 (median 6). Chromosome aberrations were found in 59% (16/27). Numerical aberrations involved all chromosomes. The most frequently gained chromosomes were numbers 2 and 9, and the most frequently lost were numbers 10, 16, 21, 22, and X. Chromosomes most frequently involved in structural aberrations were numbers 1 and 6. The most frequent subgroups were nodular sclerosis (NS) (n = 16) and mixed cellularity (MC) (n = 10). Six NS patients and 8 patients with MC showed an abnormal clone. For the NS patients with an abnormal karyotype, 4 of 6 had a gain of chromosome 2, and all had structural aberrations of chromosome 1. Of the 6 MC patients, where a partial analysis was possible, 4 had a gain of chromosome 9, 2 had structural aberrations involving chromosome 6 and 2 of chromosome 14. In 1 case a translocation normally associated with non-Hodgkin lymphoma (NHL) was found (t[11;14]), whereas other translocations characteristic of NHL, such as t(8;14), t(14;18), and t(2;5) were not observed. A review of the literature on cytogenetic investigations in HD performed on lymphoid tissue showed that the most frequently gained or lost chromosomes were 1, 2, 5, 9, and 12 for NS and 2, 5, and 9 for MC. The most frequently affected chromosomes in structural aberrations were 1 and 6 for NS, and 1, 7, and 14 for MC. Involvement of chromosome 1, 6, and 14 in structural aberrations is characteristic of lymphoid neoplasms, as are the most frequently involved bands (1p36, 6q21-q26, 14q11, and 14q32) further supporting a B- or T-cell origin of the neoplastic cell in HD. The high hyperploidy seen in HD is not a frequent observation in NHL. Although certain chromosome aberrations seem to be characteristic of HD as opposed to NHL, specific nonrandom aberrations have yet to be identified. The rather low number of abnormal mitoses found in most HD cases underlies the importance of analyzing a large number of metaphases.

Primary non-Hodgkin's lymphoma of the breast (PLB): a clinicopathological study of seven cases

Seven cases of PLB in females were reviewed. Six cases involved the breast alone (stage 1E), whereas one case also involved the ipsilateral lymph nodes (stage 2E). None had B symptoms. The age range was 37–70 years (mean 52 years). The clinical course was indistinguishable from that of breast carcinomas, though the tumors were relatively large and the duration of symptoms was relatively short. Histologically, all cases were non‐Hodgkins B‐cell lymphomas, comprising five cases of diffuse centroblastic type, one case of diffuse centroblastic‐centrocytoid type and one case of follicular centroblastic‐centrocytic type, according to the updated Kiel classification, corresponding to six cases of the diffuse large cell type and one case of the follicular mixed, small cleaved and large cell type, according to the modified International Working Formulation (IWF). None of the cases was a lymphoma of mucosa‐associated lymphoid tissue (MALT). The mammary glandular tissue outside the tumor showed ductectasia in four cases. Changes resembling fibrous disease of the breast were seen in four cases, too. The inflammatory infiltration in all these cases was mainly composed of T cells. At the time of diagnosis, all patients were receiving cytoreductive treatment. The mean followup time was 34 months (range 5–79 months). At present, six of the patients are alive and well.