Node Registry Research Articles

Lymphomas and other hematological neoplasms in the testicles

The testis may be infiltrated by hematological neoplasias. However, only few entities present as primary testicular diseases. To present hematological neoplasias in the testis, especially primary testicular hematological diseases. Selective literature research ( http://www.ncbi.nlm.nih.gov ) was combined with the clinico-pathological experience of the authors. We present the experience of the lymph node registry Kiel with hematological neoplasias of the testis and develop astaining recommendation. According to our data, the testis is mainly involved by diffuse large B‑cell lymphomas (~70% of cases) followed by precursor cell neoplasias (~20%). Most precursor cell neoplasias are disseminated diseases involving the testis. Primary testicular lymphomas are nearly exclusively diffuse large B‑cell lymphomas that show specific clinical, pathological, and molecular features discriminating them from nodal/disseminated lymphomas. Primary testicular follicular lymphomas, which have been described in the literature, seem to be extremely rare. Primary testicular lymphomas are predominantly diffuse large B‑cell lymphomas. The diagnosis is possible with few immunohistochemical stainings. However, histology cannot replace clinical staging to discriminate primary testicular lymphoma from secondary infiltration by anodal/disseminated disease.

The Mutational Landscape and Immune Microenvironment of Primary Intestinal Follicular Lymphoma (PIFL)

Introduction: Follicular lymphoma (FL) comprises a heterogeneous group of diseases. Typical FL (TFL) most commonly presents with advanced stage (AS), has a variable clinical course, and is incurable. A small subset of TFL cases present with limited stage (LS) disease, and may be cured with radiotherapy. Primary cutaneous follicular lymphoma and pediatric-type follicular lymphoma (PTFL) are non-typical FL subtypes with localized presentation and invariably benign behavior. In contrast to ASTFL, these subtypes lack BCL2 -rearrangements. We recently discovered that, in contrast to typical FLs, the majority of PTFL cases are driven by mutations activating the MAP kinase pathway and lack mutations in epigenetic modifier genes (Louissaint, Blood 2016; Schmidt, Blood 2017).Primary intestinal FL (PIFL) is another non-typical variant of FL, characterized by its distinctive restriction to the intestine (most commonly the duodenum). Despite this striking behavior, PIFL is indistinguishable from ASTFL and LSTFL by routine histology and immunohistochemistry (IHC) alone, and has a remarkably low tendency to progress or disseminate. The cell-intrinsic alterations (e.g. mutations) and cell-extrinsic factors (microenvironment) underlying the distinctive clinical behavior of PIFL are unknown.Patients and Methods: A total of 38 PIFL cases were available through the Kiel Lymph Node Registry and the Dana-Farber Cancer Institute (DFCI) / Massachusetts General Hospital (MGH), with clinical follow-up for 19 cases. We excluded cases of intestinal FL with evidence of mesenteric lymph node involvement or extra-intestinal manifestation. A total of 17 LSTFL cases were available from DFCI / MGH. We used 241 ASTFL cases from our previous study (Pastore, Lancet Oncology 2015) as a reference cohort.The targeted mutational landscape was determined by customized hybrid-capture targeted sequencing of 104 genes. In addition, we performed whole-exome-sequencing (WES) on 11 PIFL. The FL immune microenvironment was assessed on 8 PIFL and 7 LSTFL cases, respectively, by digital multiplexed gene expression profiling using the nCounter PanCancer Immune Profiling Panel (NanoString).Results: PIFL patients had a median age of 57 years (range 22-84) and a male-to-female ratio of 2:3. Most cases were restricted to the duodenum (22/38, 58%). BCL2 -rearrangements and BCL2 expression by IHC was detected in 91% (20/23) and 95% (32/33) of evaluable cases, respectively. The 10-year overall survival was 100% (median follow-up of 9.1 years), and significantly superior to LSTFL and ASFL (p <0.01, respectively).31/38 PIFL (82%) and all LSTFL (100%) cases were successfully sequenced. The mutation frequencies of the majority of recurrently mutated genes were not different between PIFL, LSTFL and ASTFL (Figure A), including CREBBP (65% vs 76% vs 70%), TNFRSF14 / HVEM (35% vs 35% vs 35%), and EZH2 (16% vs 29% vs 23%), respectively.However, the mutation frequency of the histone lysine methyltransferase KMT2D was lower in PIFL (45%, p=0.35) and LSTFL (24%, p=0.001) compared to ASTFL (77%). Approximately one-half of KMT2D- mutated ASTFL harbored multiple, potentially biallelic mutations in this gene (86/185, 47%). In contrast, biallelic mutations were present in only 12% of LSTFL (p=0.06) and 0% of PIFL (p <0.0001; Figure B).WES of 11 PIFL identified novel gene mutations in EEF1A1 and FLG in 2 cases, respectively. Furthermore, 4 cases harbored mutations in HVCN1 ,which have recently been associated with favorable clinical course (Krysiak, Blood 2017).Profiling of the immune microenvironment revealed significant differences between PIFL and LSTFL. Chemokines and cytokines including CCL21, TNFSF15, CCL11, CXCL1, CXCL6 and CCL20 were strongly enriched among the top differentially expressed genes (p=0.03). Unsupervised, hierarchical clustering by expression levels of 147 chemokines and cytokines clearly separated PIFL and LSTFL into two distinct groups (Figure C).Summary: The mutational landscape of PIFL is highly related to typical FL, both LSTFL and ASTFL. However, the lower frequency of biallelic mutations in KMT2D in PIFL and LSTFL indicates an increasing selection pressure for complete KMT2D loss during the development of, or the progression to advanced-stage FL. The highly dissimilar immune microenvironment of PIFL implies biological and clinical relevance. [Display omitted] DisclosuresDreyling:Janssen: Consultancy, Research Funding, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Sandoz: Consultancy; Gilead: Consultancy, Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; MorphoSys AG: Consultancy; Mundipharma: Consultancy, Research Funding.

Recovery of paraffin blocks and central archiving : Experiences of the Kiel lymph node registry and the German study group for Hodgkin lymphoma

Central collection of tissue blocks for pathological and translational research is particularly important in rare diseases. Transfer of tissue blocks from primary to central pathology is of crucial importance. We aimed to answer the following questions: Has the transfer of tissue blocks sent for consultation or within clinical trials changed over the last 20 years? What are the reasons for reclaiming tissue blocks by the primary pathology and what actions would convince primary pathologists to leave the blocks in the reference pathology? The first 100 biopsies of each year between 1995 and 2015 (n= 2100), as well as all tissue transfers within therapeutic studies (n= 1405, German Hodgkin Study Group, GHSG) between 1998 and 2015, were analyzed separately for block reclaims using the Department of Pathology database. Aquestionnaire evaluated the reasons for block reclaiming by the peripheral pathologists. There is asignificant increase in block reclaims during the period analyzed among submissions for consultation as well as in clinical trials (linear regression, p= 0.0195 and p= 0.0107). The percentage of block reclaims does not differ between consultations and cases submitted upon request within clinical trials (p= 0.2404, t-test). Asurvey among pathologies that reclaim the block showed that their willingness to leave the block at the reference center would increase if the compatibility with accreditation guidelines (39.3%), apositive statement from professional associations (25%), or aformal confirmation of availability (53.6%) is provided. In particular, to improve research on rare diseases, it is desirable to point out the compatibility of central archiving in adesignated center with accreditation guidelines.

Core needle biopsies and surgical excision biopsies in the diagnosis of lymphoma-experience at the Lymph Node Registry Kiel.

Current guidelines of the European Society of Medical Oncology recommend surgical excision biopsies of lymph nodes for the diagnosis of lymphoma whenever possible. However, core needle biopsies are increasingly used. We aimed to understand the common practice to choose the method of biopsy in Germany. Furthermore, we wanted to understand performance of surgical excision and core needle biopsies of lymph nodes in the diagnosis of lymphoma. The files of 1510 unselected, consecutive lymph node specimens from a consultation center for lymphoma diagnosis were analyzed. Core needle biopsies were obtained frequently from lymph nodes localized in mediastinal, abdominal, retroperitoneal, or thoracic regions. Patients undergoing core needle biopsies were significantly older and suffered significantly more often from lymphoma than patients undergoing surgical excision biopsies. Although more immunohistochemical tests were ordered by the pathologist for core needle biopsies specimens than for surgical excision biopsies specimens, core needle biopsies did not yield a definite diagnosis in 8.3% of cases, compared to 2.8% for SEB (p = 0.0003). Restricting the analysis to cases with a final diagnosis of follicular lymphoma or diffuse large B-cell lymphoma, core needle biopsies identified a simultaneous low- and high-grade lymphoma (transformation) in 3.3% of cases, compared to 7.6% for surgical excision biopsies (p = 0.2317). In Germany, core needle biopsies are preferentially used in elderly patients with a high likelihood of suffering from lymphoma. Core needle appeared inferior to surgical excision biopsies at providing a definite diagnosis and at identifying multiple lymphoma differentiations and transformation.

Skin Involvement of Mantle Cell Lymphoma May Mimic Primary Cutaneous Diffuse Large B-cell Lymphoma, Leg Type.

Mantle cell lymphoma (MCL) is a B-cell neoplasm with a variable and generally aggressive clinical course. So far our knowledge of skin involvement of MCL is limited. To understand the clinical and histopathologic features of MCL with skin involvement, the files of the Lymph Node Registry Kiel were screened for MCL diagnosed in the skin. Over a period of 13 years, 1321 biopsy specimens were diagnosed as MCL; among them, 14 patients (1%) showed skin involvement. Of these, skin was the initial site of manifestation in 6/11 (55%) cases. One patient presented with a skin-limited lymphoma. Furthermore, 7/12 (58%) patients presented with lesions on the leg. The lymphomas were highly proliferative with blastoid cytology in 12/14 (86%) cases. Moreover, the immunophenotype with expression of BCL2 (100%), MUM-1/IRF4 (83%), and IgM (82%) and lack of CD10 (25%) and BCL6 (0%) closely resembled the features of primary cutaneous diffuse large B-cell lymphoma, leg type. Solely the expression of cyclin D1 (100%) and the presence of t(11;14) (100%) allowed a distinction from cases of primary cutaneous diffuse large B-cell lymphoma, leg type. Only 2 MCL cases with skin involvement presented with classical cytology. Interestingly, in these 2 cases skin involvement occurred simultaneously in a lesion of coexisting primary cutaneous marginal zone lymphoma. Our data suggest that clinical presentation on the leg and blastoid cytology along with high proliferation and expression of Bcl2, Mum-1/IRF4, and IgM are typical for MCL involving the skin. Lymphomas with these features might be erroneously diagnosed as diffuse large B-cell lymphoma, leg type, if cyclin D1 staining is not performed.

Revising the historical collection of epithelioid cell-rich lymphomas of the Kiel Lymph Node Registry: what is Lennert’s lymphoma nowadays?

Lennert's lymphoma is a rare variant of peripheral T-cell lymphoma (PTCL) not otherwise specified (NOS). The aim of this study was to further characterize this tumour. Historical material of 97 lymphomas with a high content of epithelioid cells, collected at the Kiel Lymph Node Registry were reviewed, by applying immunohistochemistry and current diagnostic criteria. Among all cases revised, various B-cell lymphoma entities (25 cases), Hodgkin lymphomas (21 cases) and PTCL subtypes (48 cases) could be identified. A distinctive subgroup of eight PTCLs was found that were regarded as genuine Lennert's lymphomas. These cases were characterized by mild atypia, a non-activated cytotoxic phenotype [TIA1 cytotoxic granule-associated RNA binding protein (TIA1)-positive(+) and granzyme B-negative], and a substantial lack of follicular T-helper (T(FH) ) cell markers. Among the other PTCLs, including angioimmunoblastic T-cell lymphoma and PTCL NOS, many cases with positivity for more than three T(FH) cell-associated molecules were recorded. Our study shows that, according to current criteria, Lennert's lymphoma is a rare but distinctive entity among epithelioid cell-rich lymphomas, differing on grounds of morphology and immunophenotype from other PTCL subtypes. An additional finding is the broad morphological spectrum of epithelioid-cell rich PTCLs showing a T(FH) cell phenotype.

The Impact of Lymphovascular Invasion on Lymph Node Status in Patients with Breast Cancer

Lymphovascular invasion (LVI) is not uniformly found or reported in breast cancer tumor reports. We sought to determine the impact of the finding of LVI on various parameters of lymph node status in patients with breast cancer. A chart review was performed of 400 node-positive patients from a cohort of patients in a prospective multicenter national sentinel node registry. The finding of LVI was then correlated to number of positive sentinel nodes, the number of positive nonsentinel nodes, the lymph node ratio, and the size of the largest metastatic deposit. Of the 400 patients, data regarding LVI were missing in 98 (24.5%) cases. Although all of these patients were node-positive, LVI was noted to be present in 155 patients (38.8%) and absent in 147 (36.8%). LVI was found to correlate with more positive sentinel nodes (mean, 1.72 vs 1.35; P < 0.001), more positive nonsentinel nodes (mean, 2.16 vs 0.54; P < 0.001), and a higher lymph node ratio (0.29 vs 0.16; P < 0.001). LVI also correlated with size of largest metastatic deposit (P = 0.002). Although LVI is known to be associated with lymph node status, it is not frequently noted on pathology reports. Given its prognostic value, LVI should be carefully evaluated and reported.

A New Collaborative Trust Enhanced Security Model For Distributed System

Designing a distributed system with the characteristics of reliability and trustworthiness is an important issue. Yet another important issue in the distributed system is the access to remote system which can be achieved on the basis of certain access rights, policies or authorization semantics. The aim of this paper is to establish a collaborative trust enhanced security model for distributed system in which a node either local or remote is trustworthy. This paper also provides a promising solution with trust policies as authorization semantics. While designing a new secure distributed system, it has been observed that mostly the new nodes joining the system are insecure. If these perfidious nodes are provided full authorization, they can perform malicious activities in the system. In the proposed solution, node registry and service level agreements are used to ensure the trust for a new client node. Kerberos, a network authentication protocol is also used to ensure the security aspect when a client requests for certain services. In the proposed solution, we have also considered the issue of performance bottlenecks. A Reactive agent system is proposed to balance the load of service providers with the aim of enhancing the performance of the distributed system.

Germline variations of the MALT1 gene as risk factors in the development of primary gastric B-cell lymphoma

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a histologically distinct tumour derived from MALT acquired as a result of Helicobacter pylori infection. The genetic susceptibility to develop primary gastric B-cell lymphoma in patients with chronic H. pylori infection is unknown. MALT1 plays a key role in malignant B-cell transformation and lymphoma progression. Thus, we investigated germline variations of MALT1 as risk factors for gastric lymphoma in a large cohort from a European multicentre study and in total 214 lymphoma patients, 593 H. pylori infected controls and 348 healthy blood donors were genotyped for four single nucleotide polymorphisms (SNPs) covering the MALT1 locus by Taqman technology. Haplotype and single marker analyses were conducted for association testing in a case-control setting. A distinct haplotype was identified that showed a trend towards protection from high-grade and low-grade lymphomas. In single marker analysis individuals homozygous for the rare allele G of SNP3 (rs12969413) were significantly protected only from gastric high-grade lymphoma compared with controls ( p = 0.002, odds ratio (OR): 0.2, Wald 95% confidence interval (CI): 0.1 < OR < 0.6). This association could not be confirmed in a second independent cohort of high-grade lymphoma patients from the Lymph node registry in Kiel ( p = 0.531, OR: 0.8, Wald 95% CI: 0.4 < OR < 1.5). Due to the fact that SNPs 2, 3 and 4 are arranged in one LD block exhibiting nearly complete linkage disequilibrium it is rather unlikely that germline variations of MALT1 might be involved in the pathogenesis of gastric lymphoma. This is the first genetic association study that investigated polymorphisms of MALT1 as genetic risk factors in the development of primary gastric lymphoma.

Frequent occurrence of B‐cell lymphomas in angioimmunoblastic T‐cell lymphoma and proliferation of Epstein–Barr virus‐infected cells in early cases

Secondary lymphomas occurring in the setting of angioimmunoblastic T-cell lymphoma (AILT) are considered to be rare. Their occurrence has been attributed to Epstein-Barr virus (EBV)-associated lymphoproliferations. A previous study detected a dysregulated hypermutation process in B-cells of AILT. The present study aimed at estimating the frequency of B-cell lymphomas in AILT. By studying the expression of EBV and activation-induced cytidine deaminase (AID) as an indicator of hypermutating cells, we assessed whether B-cell lymphoproliferations in AILT were strictly associated with EBV and whether hypermutation might contribute to lymphomagenesis. Among 161 cases of AILT, diagnosed between 1996 and 2005 at the lymph node registry, Frankfurt, Germany, 19 cases were detected that also had B-cell non-Hodgkin lymphoma (NHL) and two cases had classical Hodgkin lymphoma (HL). EBV was detected in tumour cells of 7/18 NHL and both HL, suggesting that factors other than EBV contribute to lymphomagenesis. AID was expressed in AILT in large cells disseminated in the tissue, implying that the process of somatic hypermutation is ongoing in AILT, although the GC architecture is disrupted. This might be relevant in the development of secondary lymphomas.

Ki-Mcm6, a New Monoclonal Antibody Specific to Mcm6: Comparison of the Distribution Profile of Mcm6 and the Ki-67 Antigen

Ki-Mcm6, a New Monoclonal Antibody Specific to Mcm6: Comparison of the Distribution Profile of Mcm6 and the Ki-67 Antigen

Angioimmunoblastic lymphadenopathy (AILD)-type T-cell lymphoma: Prognostic impact of clinical observations and laboratory findings at presentation

In order to establish the clinico-pathological properties of angioimmunoblastic lymphadenopathy (AILD)-type T-cell lymphoma, we evaluated the type, incidence and prognostic significance of clinical and laboratory symptoms. Sixty-two consecutive patients diagnosed at the Kiel lymph node registry participated in the study. The median patient age was 64 years (range 21-87 years) and the female to male ratio was 1:1.4. Ninety percent of the patients were in stage III and IV and B-symptoms were observed in 68%. At diagnosis patients presented with skin rash (49%), pruritus (32%), edema (38%), pleural effusion (37%), arthritis (18%) and ascites (23%). Furthermore, they exhibited autoimmune phenomena such as cold agglutinines, circulating immune complexes, a positive Coombs test, smooth muscle antibodies, rheumatoid factors, immune hemolysis, a paraprotein, antinuclear antibodies and cryoglobulins. In univariate analysis, survival was significantly related to age (p=0.032), stage (p=0.037), B symptoms (p=0.007), rash/pruritus (p=0.038), edema (p=0.030), ascites (p=0.013), number of clinical symptoms including B symptoms (p=0.004) and excluding B symptoms (p=0.017), lactate dehydrogenase (p=0.007) and hemoglobin (p=0.020). AILD type T-cell lymphoma characteristically differs from other non-Hodgkin's lymphomas in its clinical signs and laboratory symptoms.

Malignant lymphomas of the nasal cavity and paranasal sinuses

The incidence of malignant lymphomas in the nasal cavity and paranasal sinuses was found to be 0.17% of all malignant lymphomas and 0.44% of all extranodal malignant lymphomas registered in the Kiel Lymph Node Registry from 1972 to 1987. Fifty-nine cases of malignant lymphoma presenting in the nasal cavity and paranasal sinuses were investigated with morphological and immunological methods. The median age of the patients was 64.5 years, with a female predominance (m:f = 0.87:1). In the 59 cases a marked preponderance of B-cell lymphomas was found (centroblastic n = 15, immunoblastic n = 8, Burkitt's lymphoma n = 6, Immunocytoma n = 3, centrocytic n = 1, centroblastic/centrocytic n = 1, plasmacytic n = 11); only a small number (n = 5) was of T-cell lineage (pleomorphic types). Nine further cases could not be assigned with certainty to either the T or B cell system. Angiocentricity with infiltration and destruction of vessel walls by tumour cells was demonstrated only in the T-cell lymphomas; the B-cell lymphomas, in contrast, often surrounded and compressed blood vessels with intact endothelium. No similarity to malignant lymphomas of mucosa associated lymphoid tissue, such as those in the gastrointestinal tract, was detected.

Histological, epidemiological and clinical aspects of centroblastic-centrocytic lymphomas subdivided according to the "working formulation".

A group of 424 lymphomas diagnosed as centroblastic-centrocytic lymphomas at the Lymph Node Registry in Kiel was subdivided into small (S), mixed (M) and large (L) cell groups, according to the "working formulation" proposed in a National Cancer Institute sponsored study. Histological epidemiological and clinical parameters were studied. It was found that in group S a follicular growth pattern was most frequent and in group L a follicular and diffuse growth, while group M took an intermediate position. No statistically significant differences were found in respect to epidemiological factors or overall survival. However, in the first 6 years after the diagnosis the survival in group S was better than in group M, but thereafter a reversal occurred. Group L appeared to have the worst survival throughout. Growth pattern and sclerosis were found to be of limited influence on survival within the cytological groups.

Non-Hodgkin's lymphomas in the oropharynx in children - a histological study in 11 patients

In the period from 1965 to 1979 biopsies from the oropharynx of 11 children with non-Hodgkin's lymphoma were collected at the Lymph Node Registry in Kiel. Palatine tonsil tissue was examined in all cases and, in addition, specimens from the retrolingual region of one child and the epipharynx of two patients. All biopsies showed infiltration with lymphoblastic lymphoma (LB). LB of Burkitt type was diagnosed in eight cases, T-LB (convoluted-cell type, acid phosphatase positive) in one, and unclassified LB in two. Thus, there was a strong predominance of B-cell-lymphomas.

Mesenteric lymphadenitis due to Yersinia enterocolitica.

The histopathological diagnosis of Yersinia enterocolitica infections in mesenteric lymph nodes is described on the basis of biopsy material from 14 cases collected at the Lymph Node Registry in Kiel. In all cases, the aetiological diagnosis was verified by demonstrating significant antibody titres in serological tests and, in two cases, by isolating Yersinia enterocolitica from faeces. The mesenteric lymph nodes showed a rather specific histological picture. In all cases, the capsule was thickened by oedema and stained metachromatically. The cortical and paracortical pulp was always hyperplastic owing to an increase in the number of immunoblasts, plasmablasts, and plasma cells. The sinuses were dilated and filled with intensely basophilic cells that varied in size from small to large (plasmacytoid cells and precursors). Small, or relatively large accumulations of "immature histiocytes" (transformed lymphocytes) were seen in the sinuses in about two thirds of the cases. Occasionally, there were small foci of small histiocytes (emigrated monocytes) in the cortical pulp. An abscess similar to the abscesses found in abscess-forming reticulocytic lymphadenitis due to Yersinia pseudotuberculosis was evident in only one case. The differential diagnosis is also discussed. The diseases to be considered are mesenteric lymphadenitis due to Yersinia pseudotuberculosis or salmonella infection, and nonspecific mesenteric lymphadenitis.

Eosinophilic granuloma of lymph nodes--a variant of histiocytosis X.

A clinicopathologic study of histiocytosis X in lymph nodes disclosed a special variant: primary eosinophilic granuloma of lymph nodes. This variant involves one or more lymph nodes, but does not infiltrate any other organs. Histologically, the infiltration of lymph nodes by histiocytosis X cells and eosinophils is similar to that seen in disseminated or metastatic histiocytosis X. Most cases of eosinophilic granuloma of lymph nodes are recognizable as primary, however, by the heavy infiltration of the surrounding tissue. The predominant proliferating cells are histiocytosis X cells ('Langerhans cells'), which contain Birbeck granules on electron microscopy and are lysozyme-negative. The disease was found in 30 patients among a total of 64 cases of histiocytosis X collected at the Lymph Node Registry in Kiel. Primary eosinophilic granuloma of lymph nodes occurs predominantly in children and young adults and shows a slight preponderance of males. Clinically, the patients present with mostly afebrile and sometimes painful lymphadenopathy, which is more often solitary (in the cervical or inguinal region) than widespread. The erythrocyte sedimentation rate and/or serum alpha 2-globulin level are elevated in many patients. There may also be an increase in the number of leucocytes, especially eosinophils, in the blood. The prognosis is favourable: the lymphadenopathy disappeared spontaneously in most patients and only one patient developed two recurrences. Thus, primary eosophilic granuloma of lymph nodes is interpreted as a benign lesion. It might be a special reaction of the T cell system.

Malignant and benign lymphomas of the eye, eyelid, and orbit (author's transl)

Twenty-three lymphomas of the eye, eyelid, and orbit were chosen study from biopsy material of the Department of Pathology, University of Kiel, and the Lymph Node Registry in Kiel. There were 12 malignant non-Hodgkin's lymphomas and 11 benign lymphomas. Catamnestic examination confirmed the histologic diagnosis in all 11 cases of benign lymphoma. Eleven of the malignant lymphomas represented immunocytomas and were therefore a low-grade malignancy. In contrast, there was only one case of malignant lymphoma of high-grade malignancy, which was diagnosed as centroblastic lymphoma. The immunocytoma was retrobulbar in one third of our cases and conjuctival in only 2 cases, whereas benign lymphoma had developed in the conjunctiva in 7 of 11 cases. Immunocytoma represents a tumor composed of lymphocytes and plasma cells or plasmacytoid cells. PAS-positive globular inclusions are usually found in the nucleus and/or cytoplasm of the plasma cells or plasmacytoid cells.