The effects of guided tissue regeneration and fixation technique on osseous wound healing in rabbit zygomatic arch osteotomies

So called lethal midline granuloma is of great clinical and theoretical interest. Recent evidence has shown that most lethal midline granulomas are associated with a T-cell phenotype and they are therefore referred to as nasal T-cell lymphomas (NTCL). Immunohistochemical studies, however, have shown peculiar phenotypic features such as expression of natural killer (NK)-cell-related markers and extensive T-cell antigen loss including absence of expression of alpha beta T-cell receptor (TCR). In this study, we reported genotypic and immunohistochemical features in two cases of lethal midline granuloma. The histopathological diagnosis of the biopsy specimens was polymorphic reticulosis/midline malignant reticulosis. Both cases displayed a CD2+, CD3-, CD3 epsilon+, CD4-, CD8-, CD16-, CD56+ phenotype, suggesting that these tumors may be peripheral T-cell lymphomas with extensive loss of T-cell antigens and expression of NK cell antigen (CD56), or, alternatively, NK cell neoplasias. No TCR beta gene rearrangement was detected in these cases. Monoclonal Epstein-Barr virus (EBV) genome was detected in each specimen by Southern blot hybridization. The tumor cells in one of the two cases expressed latent membrane protein (LMP). These findings support the concept that lethal midline granuloma constitutes a distinct group of lymphomas that, in addition to their peculiar clinical features, exhibits the phenotype of extensive loss of T-cell antigens and expression of the NK cell antigen, as well as harbors the EBV. In view of the LMP-transforming potential, these data suggest that EBV may play a role in the pathogenesis of lethal midline granuloma.     

Autocrine and paracrine functions of cytokines in malignant lymphomas

Cytokines play important roles in the pathogenesis of lymphomas via an autocrine or a paracrine mechanism, or both. The characteristic clinical and histopathological features of malignant lymphomas may be due in part to elevated serum or tissue levels of cytokines. Determination of the effects of cytokines on the growth or differentiation of lymphoma cells is often complicated by the fact that more than one cytokine is responsible, and by the failure of anti-cytokine antibodies or antisense oligonucleotides to block the proliferation in vitro of lymphoma cells. However, it appears that IL-6 and/or IL-9 may play a prominent role in the tumor cell proliferation of Hodgkin's disease (HD), anaplastic large-cell lymphoma, or immunoblastic lymphoma. IL-6 may also be responsible for the plasmacytoid differentiation of lymphoma cells in polymorphic immunocytoma. The histopathological changes as a result of paracrine effects are most noticeable in HD. The malignant (H-RS) cells of HD have been shown to express IL-1, IL-5, IL-6, IL-9, TNF-alpha, M-CSF, TGF-beta, and CD80, and, less frequently, IL-4 and G-CSF. These cytokines may be responsible for the increased cellular reaction and fibrosis observed in tissues involved by HD and for the immunosuppression found in patients with HD. In contrast to H-RS cells, most non-HD lymphoma cells do not produce cytokines in excess amounts and reveal only a minimal cellular reaction. Exceptions include T-cell-rich B-cell lymphoma, angiocentric T-cell lymphoma, and angio-immunoblastic lymphadenopathy (AILD-like T-cell lymphoma. IL-4 is responsible for the T-cell reaction in T-cell-rich B-cell lymphoma, whereas IL-6 accounts for the plasma cell reaction in AILD-type T-cell lymphoma. The authors extensively review the role of cytokines in lymphomas because this may lead to major advances in the understanding of the molecular processes involved in the histopathogenesis of lymphomas.     

Primary cardiac lymphoma. No evidence for an etiologic association with Epstein-Barr virus

OBJECTIVES: To report two cases of primary cardiac lymphoma, a rare extranodal lymphoma with an unknown pathogenesis, and to compare them to secondary B-cell cardiac lymphoma. DESIGN: Clinicopathologic features are described, using histologic and immunophenotypic examinations. The Epstein-Barr virus genome is detected by in situ hybridization. PATIENTS: Of 80 autopsied cases of malignant lymphoma identified at Nagoya (Japan) University Hospital, two patients with primary cardiac lymphoma and five patients with secondary cardiac B-cell lymphoma were selected. RESULTS: None of the seven selected cases showed immunodeficiency, autoimmune disorders, or chronic inflammatory processes. Primary cardiac lymphomas had B-cell phenotypes with mu and lambda chain monoclonality. Immunostaining for Epstein-Barr virus (latent membrane protein-1) and Epstein-Barr virus-encoded RNA-1 in situ hybridization did not demonstrate an association of these lymphoma with Epstein-Barr virus infection. The majority of secondary cardiac B-cell lymphomas were extranodal lymphomas and extranodal or serosal involvement was more prominent than nodal involvement. CONCLUSION: These findings suggest that primary cardiac lymphoma, unlike pyothorax-associated pleural lymphoma, appears to have no association with chronic inflammation or Epstein-Barr virus infection.     

Femur head necrosis and bone marrow edema syndrome in pregnancy

Patients with angioimmunoblastic lymphadenopathy (AILD)-type T-cell lymphoma may develop hypergammaglobulinemia. Among four cases of AILD-type T-cell lymphoma that we have studied, we detected a correlation between the number of plasma cells in tissue and the extent of interleukin-6 (IL-6) expression in lymphoma cells. We did not detect IL-6 in three patients who had no hypergammaglobulinemia and whose tissues showed only minimal plasma cell infiltration. In the fourth patient we observed an abundant IL-6 production by lymphoma cells, which accounted for a B-cell plasmacytic tissue response and for hypergammaglobulinemia. The pathogenic significance of IL-6 was substantiated by a concomitant decrease in the serum IL-6 level, measurable tumor mass, and immunoglobulin levels, as well as by a decline in the proportion of plasmacytoid cells in peripheral blood promptly on administration of chemotherapy. Plasmacytoid B cells could be maintained in culture in the presence of IL-6, but viability was lost on co-incubation with anti-IL-6. Interleukin-1 and tumor necrosis factor were not produced by T lymphoma cells and were incapable of sustaining plasmacytoid B-cell viability in vitro. Small amounts of IL-4 were noted in T lymphoma cells. Thus, in this case of AILD-type T-cell lymphoma, tumor cells with a T-cell phenotype produced IL-6 in large quantities, explaining the accompanying B-cell and plasmacytic histologic changes and humoral disease manifestations, including marked hypergammaglobulinemia. Although not all cases of AILD-type T-cell lymphoma have an accompanying plasma cell proliferation and hypergammaglobulinemia, and although the cytokine network in these patients may be more complex than has been recognized, this case with IL-6 expression serves to illustrate the utility of cytokine assays in the analysis of the histopathologic and clinical heterogeneities of peripheral T-cell lymphomas.     

On classification of changes in necrotizing lesions of the midface

Lethal midline granuloma syndrome (LMG) describes lesions of the midface and is characterized by a progressive and often fatal ulceration and destruction of the upper air way involving the nose, the paranasal sinuses, the palate and the soft tissues of the face. Under the term LMG we distinguish four entities: idiopathic midline destructive disease (IMDD), polymorphic reticulosis (PR), non Hodkin's lymphoma and Wegener's granulomatosis (WG). Review of the literature allows to present the differential diagnosis making use of latest technological achievements in clinical immunology and immunohistochemistry. First of all the LMG must be discriminated from localized WG occurring in the midface. The clinical, serological and histopathological findings in WG are described. Literature review is carried out and recent concepts of it's etiology and pathogenesis are presented. Autoantibodies directed against cytoplasmic antigens of neutrophils (ANCA) with specificity for proteinase 3 (PR 3) are valuable marker for differential diagnosis and specificity are discussed. We make a comparison between the "limited" or "non renal" WG and "classical" or "renal" form of the disease.     

Intramedullary localization of a primary cerebral lymphoma in AIDS

A 36 years-old male with AIDS, presented with left hemiparesis revealing a right parietal tumour. Stereotactic biopsy demonstrated a malignant non-Hodgkin's lymphoma. His condition partially improved following radiotherapy and chemotherapy. Three months later he was re-admitted with progressive bilateral root pain and urinary incontinence resulting in paraplegia with sensory loss below T10. He died one month later from generalized sepsis. Neuropathology confirmed an immunoblastic B-cell malignant non-Hodgkin's lymphoma in the white matter of the right parietal lobe and revealed a centrospinal localisation of the lymphoma in the thoracic cord at T10. There was no visceral localisation of the tumour. Secondary spread to the spinal cord of malignant non Hodgkin's lymphomas, usually causes meningo-myelo-radiculitis. Intraspinal deposits of primary cerebral lymphomas are uncommon and have never been previously described in AIDS, to our knowledge. Their pathogenesis is unclear. In our case, neuropathological findings are consistent with diffusion of the primary tumour to leptomeninges and secondary infiltration of the spinal cord along the perivascular spaces.     

Cerebellopontine angle lymphoma: a case report and review of the literature

BACKGROUND: Although malignant lymphomas of the central nervous system have been reported to be increasing in frequency, cerebellopontine (CP) angle lymphoma is rare and only 13 cases have been reported previously in the literature. CASE PRESENTATION: A 63-year-old woman had progressive dizziness and nausea for 2 months. Computed tomography scanning and magnetic resonance imaging (MRI) revealed a mass lesion in the left CP angle, that was compressing the lateral-dorsal aspect of the pons and the fourth ventricle. This tumor was avascular on angiography. The tumor was surgically removed through a left lateral suboccipital approach. It was considered to arise from the subarachnoid space of the CP angle cistern. For some reason, the histologic diagnosis was not definitively made, and therefore radiation therapy was not planned. The tumor recurred within 50 days after the tumor excision. Surgical excision of the recurrent tumor was performed again. The histologic diagnosis was B-cell type malignant lymphoma. Radiation therapy was performed. In the 27 months since irradiation, a recurrent tumor has not been detected on MRI. CONCLUSIONS: Although erosion and expansion of the internal auditory canal suggest an acoustic neurinoma, CP angle lymphoma can, in rare circumstances, erode the internal auditory canal. There are three distinct patterns in which malignant lymphomas occupy the CP angle: (1) an extra-axial CP angle lymphoma, (2) an intra-axial lymphoma extending to the CP angle, and (3) a leptomeningeal lymphoma presenting as a CP angle lesion. Although malignant lymphomas rarely occupy the CP angle, it should be considered in the differential diagnosis of CP angle tumors. It is desirable to obtain a frozen section in all CP angle tumors during surgery to identify the tumor, because aggressive removal is not necessary, but radiation therapy should additionally be performed for malignant lymphomas.     

Prognosis of the skin UV-incidence increase in Poland

We studied the morphologic and immunohistochemical features of 10 peripheral T-cell lymphomas of a cytotoxic phenotype (CD3+/CD4-/CD8+), encountered among 98 peripheral T-cell lymphomas (PTCLs). Nine tumors were positive for both cytotoxic molecules, namely perforin (Pf) and granzyme B (GrB), and strong positivity was seen in the majority of the malignant cells. We also studied the expression of these molecules in 92 other cases of T-cell and natural killer (NK) cell neoplasms; 18 anaplastic large cell lymphomas (ALCLs); 63 CD4+ PTCLs; 10 CD56+ nasal lymphomas; and 1 NK-cell leukemia. Most of the CD4+ PTCLs (62 of 63) were negative for GrB, but all of the nasal lymphomas and the NK cell leukemia were positive for both Pf and GrB. Variable expression was seen among the 18 ALCLs. Within the 10 CD8+ PTCLs, 4 involved the skin, 3 of which were diagnosed as primary cutaneous lymphomas. Five patients died within 1 year of diagnosis. According to the Revised European-American Classification of Lymphoid Neoplasms, seven cases were categorized as "PTCL, unspecified," and three as "angioimmunoblastic T-cell lymphoma," "adult T-cell lymphoma/leukemia," or "small cell lymphoma," respectively. Three cases had characteristic morphologic features consisting of large lymphomatous cells with massive necrosis and nuclear fragmentation. Epstein-Barr virus mRNA was detected by in situ hybridization in three cases. Although the degree of apoptosis varied, apoptotic cells were detected in all cases by terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate-biotin nick end labeling. We conclude that CD8+ PTCLs are relatively rare, often involve extranodal sites, have an aggressive clinical course, and are often associated with Epstein-Barr virus. Compared with ALCLs, which have recently been considered as neoplasms of cytotoxic T-cells, we think that CD8+ PTCLs are more lineage-specific neoplasms of mature, cytotoxic, T lymphocytes.     

AIDS lymphoma

Most AIDS-related non-Hodgkin's lymphomas can be categorized into one of three histologic subtypes: large-cell immunoblastic, small non-cleaved cell (Burkitt's or Burkitt's-like) and diffuse large cell. Rare histologies include Ki-1 anaplastic large cell lymphoma, angiotropic large cell lymphoma, mucosa-associated lymphoid tissue, primary pulmonary T-cell lymphoma, and Sézary syndrome. Although the role of Epstein-Barr virus remains uncertain, a new herpes virus, human herpes virus 8, has been identified in the rare subset of effusion-based lymphomas. Overexpression of the cytokines interleukin-6 and interleukin-10 may have a role in pathogenesis, and they may serve as potential therapeutic targets. In addition, chronic antigenic stimulation may correlate with elevated serum CD22 levels and may serve as a tool for early detection. Novel investigational therapies in clinical development include new chemotherapy-based regimens, immune modulators, antibody therapy, as well as cellular therapy.     

Cranial cystic epidermoid: report of two cases and review of the literature

Among non-Hodgkin's lymphomas occurring in childhood two major histologic subgroups can be identified: (1) Burkitt's lymphoma and (2) T-cell lymphoblastic lymphoma, an uncommon high-grade malignant non-Hodgkin's lymphoma. Although Burkitt's lymphoma with maxillofacial involvement is a well-documented disease, T-cell lymphoblastic lymphoma in the perioral region is rare. An unusual case of T-cell lymphoblastic lymphoma with initial oral manifestation in an 18-month-old child is presented.     

Restriction fragment length polymorphism analysis of Mycobacterium bovis isolates from captive and free-ranging animals

c-myc gene abnormalities associated with lymphomagenesis, including rearrangements and mutations in the regulatory region between exon I and intron I, have been studied in 54 MALT lymphomas (43 low and 11 high grade) and 36 nodal lymphomas (27 low and 9 high grade). By Southern blot analysis, none of the 54 MALT lymphomas but 2 of 36 nodal lymphomas had c-myc gene rearrangements. Defined tumour cell populations from all MALT lymphoma cases were isolated by microdissection from frozen tissue sections and analysed by polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) and direct sequencing for somatic mutations in the exon I/intron I region of the gene. Point mutations in this region were identified in nine cases of MALT lymphomas (7/43 = 16.2 per cent of low grade; 2/11 = 18.1 per cent of high grade). These mutations were located at either the exon I/intron I border of myc intron factor (MIF) binding sites, which are critical in the negative regulation of c-myc expression. Of the nodal lymphomas, only the two cases (5-6 per cent) with c-myc gene rearrangement showed scattered or clustered mutations. These results suggest that c-myc mutations in MALT lymphomas are unlikely to be associated with chromosome translocation, which is the main cause of somatic mutations observed in other types of lymphomas. The mutations involving the c-myc regulatory regions may play a pathogenetic role in at least a proportion of MALT lymphomas.     

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.     

Gastric MALT lymphoma of low-grade malignancy. Apropos of 4 surgically treated cases

From 1990 to 1993, programmed surgery was performed in four patients with histologically low grade malignant gastric lymphomas of mucosa-associated lymphoid tissue (MALT) (partial gastrectomy = 1, total gastrectomy = 3). These small cell lymphomas have the B phenotype and are uncommon. The clinical course is usually slow and classically limited to the stomach. As for other gastric lymphomas, there is still a certain amount of discussion as to the best therapeutic choice between surgery, chemotherapy and radiotherapy. Certain elements in the literature can help in managing these low grade gastric lymphomas. Recent publications report on a prospective study on primary lymphomas of the digestive tract, a clinical trial on single drug chemotherapy alone and the relationships between Helicobacter pylori and MALT lymphoma.     

Study of malignant lymphoma in the parotid gland region

Malignant lymphomas arising in the salivary glands are very uncommon. The vast majority of these lesions are classified as extranodal non-Hodgkin's lymphoma. Clinical presentation, management, histopathology, and outcome in 11 cases of non-Hodgkin's lymphomas of the parotid gland region were reviewed. The ages of the patients ranged from 25 to 80 years (average 56.0 years) and the male to female ratio was 5:6. Presenting symptoms were painless masses (10 cases) and a painful mass (1 case) in the parotid gland region. None of the patients had facial nerve paralysis. It seems to be difficult to diagnose malignant lymphomas of the salivary glands preoperatively, because an open biopsy of the salivary glands is generally contraindicated. We failed to diagnose malignant lymphoma in the parotid gland preoperatively. The clinical stages were stage I in 5 cases, stage II in 5 cases, and stage III in 1 case. There was no patient with stage IV. Three of the stage I tumors were diagnosed as MALT (mucosa-associated lymphoid tissue) lymphomas. Eight of the tumors were treated surgically and an open biopsy of the parotid gland tumor was performed in 1 case and open biopsy of a neck lymph node in 2 cases for the purpose of diagnosis. After the diagnosis, these cases were followed up with or without radiotherapy and chemotherapy. Follow-up ranged from 6 to 109 months. The 5-year-survival rate was 60%. The outcome for this group was found to be as good as that reported by others.     

A continuous colorimetric assay for rhinovirus-14 3C protease using peptide p-nitroanilides as substrates

Primary salivary gland lymphomas are almost always of B lineage, with most being represented by low grade B-cell lymphoma of mucosa-associated lymphoid tissue. This study characterizes the rare non-B-cell lymphomas of the salivary gland based on an analysis of six cases. All patients were men, with a mean age of 53.5 years. They presented with submandibular or parotid mass, which on histological examination showed extensive interstitial infiltration by small, medium-sized, or large lymphoid cells. There was prominent invasion and expansion of the ducts and acini in five cases. Angioinvasion was evident in two cases. Three cases were of T lineage and were CD56 negative; one of these cases expressed CD30. Three cases showed an immunophenotype of CD2+ CD3(f)- CD3(p)+ CD56+, consistent with T/natural killer (NK) cell lymphoma. In situ hybridization for Epstein-Barr virus (EBV)-encoded early nuclear RNA (EBER) showed positive reaction exclusively in the three CD56+ cases. Clonal T-cell populations were shown in two CD56-negative cases by polymerase chain reaction on paraffin sections using primers for the T-cell-receptor (TCR) gamma-chain gene, but not in the other four cases (the three CD56+ cases and one CD56- case). Four patients (two CD56+ and two CD56-) died within 3 years, and two were disease free at 4 and 1.5 years, respectively. This study shows that salivary gland T- or T/NK-cell lymphomas cannot be reliably distinguished from B-cell lymphomas on morphological grounds alone, because both can show prominent lymphoepithelial lesions. It appears that T/NK-cell lymphomas, which are often extranodal in localization and strongly associated with Epstein-Barr virus (EBV), show a predilection to involve the salivary glands as well.     

Diagnostic and prognostic value of interleukin-6 in malignant non-Hodgkin's lymphomas

Sixty six patients with non-Hodgkin's lymphomas (NHL) were studied, interleukin-6 (IL-6) was revealed in the blood sera of 33 patients. IL-6 was revealed more frequently in patients with high-grade malignant (p < 0.05) than in those with low-grade malignancy. The largest group of IL-6 positive patients included NHL patients with diffuse large B-cell lymphoma and angioimmunoblastic lymphoma. The marked relationship was found between the serum IL-6 levels and the stage of disease: the serum IL-6 level was significantly lower in untreated patients with Stages II and III disease than in those with end-stage (IV) NHL. IL-6 significantly decreased upon remission, comparable with its level before the initiation of treatment. Analysing the association of prognosis of disease with the serum IL-6 showed that in the group of patients with good (The SNLG index < 2) and intermediate (2 < SNLG index < by 2.6) prognosis, the concentration of this cytokine was significantly lower than in those with poor prognosis (SNLG index > 2.6). There was a significant decrease of the total survival rates of NHL with serum IL-6 found. Therefore, IL-6 is a good prognostic marker in NHL and associated with the activity of a malignant process. Additionally, the increased serum IL-6 levels correlated with NK activities positively and with serum IL-4 levels negatively.