Reduced phagocytosis of apoptotic cells in malignant lymphoma

Efficient removal of lymphocytes undergoing programmed cell death (apoptosis) by macrophages plays an important role for the proper function of normal immune system. Furthermore, in malignant lymphoma, elimination of apoptotic tumor cells by phagocytes contributes to the anti-tumor immune response. It is unknown, however, whether macrophages in normal and malignant lymphoid tissues differ in their ability to recognize and remove apoptotic cells. Our present results demonstrate that normal and malignant lymphoid tissues differ according to the extent of the infiltration by macrophages. The highest densities of macrophages (p < 0.0001) were detected in diffuse large B-cell lymphoma, centroblastic (DLBCL-CB) and immunoblastic variants and Burkitt's lymphoma. The grade of the macrophage infiltration correlated with the proliferation rates of the tumors (p < 0.0001). Compared with normal lymphoid organs, malignant lymphoma contained lower percentages of apoptotic cells phagocytosed by tissue macrophages (p < 0.001). Of all lymphomas tested, mantle cell lymphoma and DLBCL-CB expressed the lowest percentages of phagocytosed apoptotic cells (p < 0.0001).     

Food contact substances and the need for food safety reform

A 66-year-old male presented with dyspnea and cough for 1 month. Fiberoptic bronchoscopy disclosed a huge tumor over the posterior wall of the trachea 1 cm below the vocal cord and biopsy pathology was diffuse, small cleaved lymphoma. Primary malignant lymphoma of the trachea is extremely rare. Its clinical course varies widely, and has no accepted standard of management. We describe herein the whole clinical course of this patient, which is not similar to previous reports. The relation of primary tracheal lymphoma to mucosa-associated lymphoid tissue (MALT) is also discussed.     

Analysis of ploidy and proliferative activity in childhood non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD)

We have performed DNA analysis by means of fluorescence-activated cell cytometry on paraffin-embedded tissue from the diagnostic biopsy specimens in 40 cases of non-Hodgkin's lymphoma (NHL) and 25 of Hodgkin's disease (HD) and from 50 normal tonsils as controls. For HD cases, aneuploidy was found in 7 of 25 (28%), a higher proportion than in two previous studies of mainly adult patients. Diploid tumors showed S-phase fractions (SPFs) similar to those of controls. In the NHL cases aneuploidy was found in 12 of 40 (30%) with no significant association with site, stage, histopathology, immunophenotype, or prognosis. SPFs were highest in abdominal and chest primary sites but were not related to stage. Burkitt's lymphomas had the highest SPFs relative to lymphoblastic (P < .01) and centroblastic lymphomas (P < .05). Significantly higher SPFs were found in B cell than in T cell tumors (P < .001). There was considerable heterogeneity for SPFs within each NHL subgroup. Survival was worse at 5 years for those with high SPFs compared with those with normal SPFs (P = .04). These results suggest that tumor DNA analysis may be useful in the evaluation of children with NHL. Larger studies are needed to define its role as an independent prognostic variable.     

Aluminium and injection site reactions

AIMS: To alert pathologists to the spectrum of histological appearances that may be seen in injection site reactions related to aluminium. METHODS: Four cases of injection site reaction were examined microscopically using routine staining with haematoxylin and eosin, electron microscopy and by electron probe microanalysis. RESULTS: As in previous reports, all four cases included collections of histiocytes which contained faint granular brownish refractile material within their cytoplasm; ultrastructural examination showed this to be aluminium. Two cases showed a prominent inflammatory reaction with numerous lymphoid follicles and a notable eosinophilic infiltrate. Two cases showed unusual features not described previously. In one, there was a sclerosing lipogranuloma-like reaction with unlined cystic spaces containing crystalline material. The other case presented as a large symptomatic subcutaneous swelling which microscopically showed diffuse and wide-spread involvement of the subcutis by a lymphoid infiltrate with prominent lymphoid follicles. CONCLUSIONS: This report highlights the changes encountered in aluminium injection site reactions and emphasises that the lesions have a wider range of histological appearances than described previously.     

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 IEA, 2; Stage IIEA, 1), 35 had intermediate or high grade lymphomas, Stage IEA or IIEA (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 IIEA. One patient had Stage IIIEA 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 IEA and IIEA) the 5- and 10-year cause specific survival was 60%. The 21 patients treated between 1985 and 1992 initially with chemotherapy (except stage IEA (< 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 (Chi 2 = 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.     

Seasonal rhythm of red pigment concentrating hormone in the crayfish

To evaluate the significance of microsatellite instability (MI) and loss of heterozygosity (LOH) in the development of gastric lymphoma, we examined 33 tissue-samples of 20 primary gastric B-cell lymphomas (6 low-grade lymphomas of mucosa-associated lymphoid tissue [MALT; 10 samples] and 14 diffuse large B-cell lymphomas [23 samples]). MI and LOH were evaluated at 13 microsatellite loci. In MALT lymphoma, four of six cases showed MI at one to two microsatellite loci (average 1.0 per case, 0.8 per sample), whereas in diffuse B-cell lymphoma, all samples showed MI at one to five microsatellite loci (average 2.4 per case, 2.7 per sample) (p < 0.05 and p = 0.0001). MI at the c-myc gene locus was most frequent in both types of gastric lymphomas (3 of 6 and 11 of 14 cases, respectively). Regional heterogeneity of the MI pattern was observed in two of four cases of MALT lymphoma and in four of five cases of diffuse B-cell lymphoma. On the other hand, LOH was observed only in one MALT lymphoma and in three diffuse B-cell lymphomas. Genetic instability may be an important mechanism for the development and progression of gastric lymphoma. Frequent MI at the c-myc locus might reflect an activated state and the importance of this gene in mucosal lymphocytes of chronic gastritis.     

Testicular lymphoma: a population-based study of incidence, clinicopathological correlations and prognosis. The Danish Lymphoma Study Group, LYFO

In a Danish population-based non-Hodgkin's lymphoma registry, 2687 newly diagnosed patients were registered from 1983 to 1992. 39 had testicular involvement (TL) (incidence 0.26/10(5)/year). Median age was 71 years. 24 cases had localised and 15 had disseminated disease. Histologically, all cases were diffuse (65% diffuse centroblastic type). Of the 27 tested, 11% were of T- and 89% of B-immunophenotype. In localised cases, where surgery was supplemented by combination chemotherapy (CCT), the relapse rate was 15.4%. The relapse rate for cases with localised disease treated with other regimens (orchiectomy and/or radiotherapy) was 63.6% (P < 0.05). Median relapse-free survival was 28 and 14 months, respectively. Overall 5-year survival for all cases was 17%. Adverse prognostic factors at the univariate level were stage IV, constitutional symptoms, serum lactic dehydrogenase elevation and performance score (WHO 3-4). It is suggested that the treatment of stage IE/IIE TL should include early CCT and CNS prophylaxis.     

Petrous bone tumors: primary non-Hodgkin lymphoma of the inner ear canal and cerebellopontile angle

BACKGROUND: We report about a primary Non-Hodgkin Lymphoma (NHL) of the internal auditory canal. The only previously known manifestations of a NHL in the temporal bone have been infiltrations or hemorrhagic complications due to a late manifestation or advanced systemic disease. Involvement of both temporal bones is typical. CLINICAL CASE: The 60-year-old female patient complained of an acute one-sided deafness, accompanied by a high-pitched tinnitus, rotating vertigo, and paralysis of the left half of the face. RESULTS: We found a deafness in the left ear, spontaneous nystaxis, which was interpreted as a deficiency in excitement of the vestibular organ, and a complete peripheral facial paralysis. Diagnostic imaging studies revealed a large, intrameatal solid mass in the temporal bone, measuring 1.2 x 0.8 cm. Histologic examination after translabyrinthine tumor removal demonstrated a centroblastic Non-Hodgkin Lymphoma. The following extensive interdisciplinary staging examination showed no other tumor manifestations; the CSF analysis was negative. CONCLUSIONS: The uniqueness of this case lies in the detection of a primary nongeneralized centroblastic lymphoma of the internal auditory canal. In contrast to infiltrations of systemic NHL in the same location, in which the advanced disease is responsible for the bad prognosis, this isolated lymphoma of the internal auditory canal seems analogous to extranodal MALT Lymphomas with a better prognosis. The primary extranodal NHL of the temporal bone, not reported in previous studies, is discussed with regard to clinical symptoms, differential diagnoses, and therapeutic strategies.     

Gastrointestinal lymphomas: an overview with emphasis on new findings and diagnostic problems

The first section of this article summarizes the salient clinicopathologic features of the more common types of primary gastrointestinal lymphomas, the recent explosion of information on the low grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), and new findings on multiple lymphomatous polyposis and ulcerative jejunitis. The second section discusses the practical problems that may be encountered in the diagnosis of gastrointestinal lymphomas, including diagnosis of large cell malignancies, distinction between lymphoma and reactive lymphoid hyperplasia, classification of diffuse small B-cell lymphomas (including the potential pitfall of mistaking Burkitt's lymphoma for small B-cell lymphoma), recognition of large cell transformation in low-grade B-cell MALT lymphoma, assessment of gastric biopsies from MALT lymphoma patients after anti-Helicobacter therapy, and assessment of nodal or splenic involvement in low-grade MALT lymphoma.     

Analysis of the ntp1+ gene, encoding neutral trehalase in the fission yeast Schizosaccharomyces pombe

We report a clinicopathologic feature of primary cutaneous T-cell lymphoma (CTCL) in a five-year-old boy with increasing swelling of his cheek since two years of age. Histologically, an infiltrate of atypical lymphoid cells with mature T-cell phenotype and clonality was prominent from the dermis to the subcutaneous tissue of the cheek. Although little effect was seen with aggressive multidrug-combined chemotherapy, therapy with interferon-alpha and steroids achieved a prolonged remission. This patient may provide important clues to understanding the clinicopathologic feature of rare primary CTCL in young children.     

Lymphocyte-rich well-differentiated liposarcoma: report of nine cases

Nine well-differentiated liposarcomas with foci simulating the appearance of malignant lymphoma and other lymphoid disorders are reported. Their clinical presentation and evolution were not significantly different from those of their conventional counterparts lacking a lymphoid infiltrate. Microscopically, these tumors were characterized by areas of ordinary well-differentiated liposarcoma, admixed with discrete nodules comprised of small germinal centers, and separated by an admixture of lymphocytes, spindled stromal cells, collagen, and blood vessels, in which highly atypical tumor cells were embedded. The differential diagnosis included Hodgkin's disease, Castleman's disease, and inflammatory pseudotumor. Immunohistochemical evaluation revealed a pre-dominance of T cells in the lymphocytic population. Molecular genetic studies revealed no evidence of clonal rearrangement of the T cell receptor gene, supporting the interpretation of these lymphocytes as reactive. Awareness of the existence of this variant of inflammatory liposarcoma should prevent its misinterpretation as a primary lymphoproliferative process.     

Screening times with image intensifier in orthopaedic trauma surgery

Primary lymphoma of the bladder is rare. Of the very few cases reported, most appear to be of low grade with a generally good prognosis. Since the concept of low grade lymphoma of mucosa associated lymphoid tissue (also known as marginal zone lymphoma in the REAL classification) was introduced, only six examples of this entity have been recorded at this site. We present a further case and describe its phenotypic characterization.     

Gastric malt lymphoma with crystalline immunoglobulin inclusions and secondary immunoblastic lymphoma in a cervical lymph node

A case of gastric B cell lymphoma of the mucosa-associated lymphoid tissue (MALT) with crystalline immunoglobulin inclusions in monotypic plasma cells is reported, which initially presented as a secondary immunoblastic lymphoma in a cervical lymph node. The low-grade MALT lymphoma was diagnosed 14 months after detection of the nodal high-grade lymphoma, but rare crystal-containing plasma cells of identical immunoglobulin isotype found in the immunoblastic lymphoma retrospectively confirmed a common clonal origin. The diagnostic significance of crystalline immunoglobulin inclusions and the unusual initial presentation of MALT lymphoma as a secondary high-grade lymphoma at a distant nodal site are discussed.     

Gastric syphilis: polymerase chain reaction detection of treponemal DNA in pseudolymphomatous lesions

Syphilis is an unexpected diagnosis in the stomach. To establish the diagnosis, evidence of Treponema pallidum in the gastric lesion is necessary. However, it is sometimes difficult to prove the presence of the organisms by conventional methods. The authors describe two cases of early gastric syphilis with pseudolymphomatous histology in which T pallidum gene was detected by the polymerase chain reaction (PCR) using paraffin biopsy sections. The gastric lesion of each case endoscopically and histologically simulated that of malignant lymphoma. However, no clonality was proved by immunohistochemistry or PCR gene rearrangement analysis. No spirochetal organisms were detected with certainty by Warthin-Starry silver stain, whereas the organisms were shown by immunofluorescent stain in one patient. A PCR study showed the treponemal DNA in both patients, and its validity was supported by a direct sequencing and a restriction enzyme digestion. Positive results of serological tests for syphilis and regression of the lesions after antisyphilitic treatment were confirmatory of the diagnosis. Gastric syphilis should be considered as a differential diagnosis when an atypical lymphoid infiltrate fails to show monoclonality. The present PCR method would be helpful in showing T pallidum using routinely processed small biopsy specimens as the tissue source.     

DNA methylation in mycobacteria: absence of methylation at GATC (Dam) and CCA/TGG (Dcm) sequences

The histopathology of low-grade primary gastric lymphoma re-capitulates the structure of Peyer's patches (mucosa-associated lymphoid tissue--MALT) rather than lymph nodes, characterised by an increased frequency of trisomy 3. Gastric B-cell lymphoma shows a favourable clinical behaviour, possibly as its growth appears to be influenced by a local antigen in the form of Helicobacter pylori. There is no lymphoid tissue in the normal stomach, but lymphoid tissue accumulates in gastric mucosa almost exclusively as a consequence of H. pylori infection, which has MALT characteristics, and H. pylori is found in over 90% of cases of gastric MALT lymphoma. Laboratory studies have shown that the growth of tumour cells from low-grade gastric lymphomas can be stimulated by H. pylori, and that the effect is strain-specific and mediated by contact-dependent help from H. pylori-specific T-cells. Cases of low-grade gastric lymphoma, when confined to the mucosa, may regress following eradication of H. pylori from the patient's stomach. It remains to be shown whether deeply penetrating or high-grade tumours will respond in the same way. Other outstanding questions relate to the optimum interval between eradication of H. pylori and final evaluation and expected duration of the response. Based on these laboratory and clinical findings it is possible to suggest a scheme for the pathogenesis of gastric MALT lymphoma.     

Modeling social influences on public drinking

To evaluate the potential value of endoscopic ultrasonography in primary gastric lymphoma, we compared endoscopic ultrasonography findings with endoscopic and histologic findings in 15 patients in whom the diagnosis had been established by radiography and endoscopy, including forceps biopsy. The patients were divided into four groups according to the endoscopic ultrasonography findings. The groups included the following: superficially spreading type (six patients), diffusely infiltrating type (three patients), mass-forming type (four patients), and mixed type (two patients). The endoscopic ultrasonography findings correlated well with the endoscopic, macroscopic, and histologic findings. The histologic findings in nine patients with the endoscopic ultrasonography superficially spreading type or diffusely infiltrating type revealed B-cell lymphoma arising from mucosa-associated lymphoid tissue, which shows slowly infiltrative growth. In four patients with the endoscopic ultrasonography mass-forming type, on the other hand, the tumor histologic finding consisted of diffuse large-cell or diffuse mixed-cell type. Our results indicate that endoscopic ultrasonography may provide information helpful for the management of primary gastric lymphoma.     

Misleading leads. Thallium-201 uptake in rebound thymic hyperplasia

A review was made of the six cases of primary thyroid lymphoma diagnosed at our institution. An increase in the incidence was observed of this disease in the last two years, with no evidence of lower diagnosis of anaplastic thyroid carcinoma. The presenting symptom was compression in all cases. The interval time from symptoms to diagnosis ranged from 5 to 150 days. The centroblastic pattern was the most common histologic type, with a relevant role of MALT lymphoma in the last few years. Therapy included surgical exeresis in two cases on account of compressive symptoms and radiotherapy and/or chemotherapy was always preferred on account of the stage.     

Loss of p16/INK4A protein expression in non-Hodgkin's lymphomas is a frequent finding associated with tumor progression

The CDKN2A gene located on chromosome region 9p21 encodes the cyclin-dependent kinase-4 inhibitor p16/INK4A, a negative cell cycle regulator. We analyzed p16/INK4A expression in different types of non-Hodgkin's lymphoma to determine whether the absence of this protein is involved in lymphomagenesis, while also trying to characterize the genetic events underlying this p16/INK4A loss. To this end, we investigated the levels of p16/INK4A protein using immunohistochemical techniques in 153 cases of non-Hodgkin's lymphoma, using as reference the levels found in reactive lymphoid tissue. The existence of gene mutation, CpG island methylation, and allelic loss were investigated in a subset of 26 cases, using single-strand conformational polymorphism and direct sequencing, Southern Blot, polymerase chain reaction, and microsatellite analysis, respectively. Loss of p16/INK4A expression was detected in 41 of the 112 non-Hodgkin's lymphomas studied (37%), all of which corresponded to high-grade tumors. This loss of p16/INK4A was found more frequently in cases showing tumor progression from mucosa-associated lymphoid tissue low-grade lymphomas (31 of 37) or follicular lymphomas (4 of 4) into diffuse large B-cell lymphomas. Analysis of the status of the p16/INK4A gene showed different genetic alterations (methylation of the 5'-CpG island of the p16/INK4A gene, 6 of 23 cases; allelic loss at 9p21, 3 of 16 cases; and nonsense mutation, 1 of 26 cases). In all cases, these events were associated with loss of the p16/INK4A protein. No case that preserved protein expression contained any genetic change. Our results demonstrate that p16/INK4A loss of expression contributes to tumor progression in lymphomas. The most frequent genetic alterations found were 5'-CpG island methylation and allelic loss.