Histological Type Of Lymphoma Research Articles

B-cell lymphomas associated with breast implants: Report of three cases and review of the literature

Since the first reported case in 1997, over 600 women with breast implant-associated anaplastic large cell lymphoma (BI ALCL) have been reported. BI ALCL is a CD30-positive T-cell lymphoma that carries clonal T-cell receptor gene rearrangements, and a subset of cases harbors mutations in the JAK-STAT signaling pathway. Rarely, other histologic types of lymphoma have been reported in association with breast implants, including fewer than 10 cases of B-cell origin. Here, we describe three additional patients with B-cell lymphoma occurring around breast implants. Two of these patients developed extranodal marginal zone lymphoma in the peri-implant capsule, one of which had a concurrent ALCL within the superficial lining of the capsule. The third patient presented with diffuse large B-cell lymphoma inside the breast parenchyma surrounding her implant. Determining the etiology and risk factors for the development of B-cell lymphomas associated with breast implants remains challenging, given the wide spectrum of histologic features and the rarity of these neoplasms. Ultimately, we document three new cases of B-cell lymphoma arising around breast implants and highlight their clinical and pathologic features in order to expand our understanding of this rare disease presentation.

Prevalence of a Histologic Change of Ocular Adnexal Lymphoma in Patients With a History of Lymphoma.

The authors examined the prevalence of a histologic change of ocular adnexal lymphoma (OAL) grade in patients with a history of lymphoma in nonocular sites. In this retrospective study, the authors reviewed the clinical and pathological data of 209 patients with OAL treated by the senior author during 2000 to 2017. Of 209 patients with OAL, 65 (31%) had a history of lymphoma. In 54 of the 65 patients (83%), the original lymphoma and OAL were of the same histologic type. In 8 of the 65 patients (12.3%), the OAL was more indolent than the original lymphoma: 6 patients with a history of diffuse large B-cell lymphoma, one of mantle cell lymphoma, and one of grade 3 follicular lymphoma had biopsy-proven extranodal marginal-zone lymphoma in the orbital area. Two additional patients (3%) with a history of chronic lymphocytic leukemia developed OAL: diffuse large B-cell lymphoma in one patient and extranodal marginal-zone lymphoma in the other. One patient (1.5%) with a history of a low-grade follicular lymphoma relapsed as a different low-grade histology of extranodal marginal-zone lymphoma. Lower-grade OAL than the original lymphoma was more common than higher-grade OAL than the original lymphoma (p = 0.048). In this cohort of 209 patients with OAL, the authors found that nearly one third had a history of lymphoma, 17% of whom had a different histologic type of lymphoma in the orbit, more commonly a more indolent type. This underscores the importance of biopsy of OAL even in patients with a known history of lymphoma to determine the histologic subtype of orbital lymphoma and to help guide appropriate treatment.

Toxoplasma gondii infection in children with lymphoma in Eastern China: seroprevalence, risk factors and case-control studies.

Epidemiological data for Toxoplasma gondii regarding malignancy have gained increasing attention; however, the information about T. gondii infection among children with malignant lymphoma (ML) in China is unclear. Therefore, 314 children with lymphoma and 314 healthy children, age- and gender-matched, were recruited to estimate the seroprevalence of T. gondii in the participants and identify the risk factors of infection. Blood samples from all participants were collected and examined for T. gondii IgG and IgM antibodies using ELISA. The results showed that the overall seroprevalence of T. gondii antibodies (including IgG and/or IgM) in ML patients and healthy controls was 19.8% and 9.9%, respectively. Contact with the cats, consumption of oysters and history of chemotherapy were estimated to be the risk factors for T. gondii infection in children with lymphoma by multivariable logistic regression analysis, whereas in healthy children, contact with cats and consumption of oysters were the risk factors. Moreover, among various histological types of lymphoma, individuals with NK/T-cell lymphoma, B-small lymphocytic lymphoma, marginal zone B-lymphoma and Hodgkin's lymphoma had a higher seroprevalence than healthy controls (P < 0.05). These findings indicated the high prevalence of T. gondii infection in children with lymphoma, and hence, efforts should be performed to evaluate the effect of the infection further in lymphoma patients.

Immunohistochemical Profile of Hodgkin and Non-Hodgkin Lymphoma.

To analyze the frequencies of histological types of lymphoma, diagnosed with complete immunohistochemical profile in younger and older age group. Cross-sectional analytical study. Dow Diagnostic Research and Reference Laboratory, Dow University of Health Sciences, Karachi, from January 2009 to September 2013. Consecutive cases of lymphomas, which were diagnosed using immunohistochemistry, were analyzed according to WHO classification. Frequency and percentages for different types of lymphomas were calculated. Hodgkin and non-Hodgkin lymphomas characteristics in two age groups of less than and more than 40 years were compared, applying chi-square test. Out of the 318 cases, 79 (25%) were Hodgkin Lymphomas (HL) and 239 (75%) were Non-Hodgkin Lymphomas (NHL). Mixed Cellularity Hodgkin Lymphoma (MCHL) was the commonest (n=48). Amongst the NHL, 215 (89.95%) were B cell lymphomas and 24 (10.05%) were T-cell lymphomas. Diffuse Large B-Cell Lymphoma (DLBCL) was the commonest lymphoma (n=165, 69.95% of NHL). Anaplastic T-Cell Lymphoma (ALCL, n=10) was the commonest T-cell lymphoma. The frequency of HLwas significantly higher in the younger age group and that of NHLwas higher in the older age group (p < 0.001). Primary lymph node involvement was reported in 175 (55%) and cervical lymph node was the most frequent site. Extra nodal involvement was seen in 93 (29%) of all cases and was reported in 87 (36.4%) of NHLand 6 (7.5%) of HL. The most common extra nodal site was the gastrointestinal tract. Hodgkin lymphoma comprises 25% and non-Hodgkin lymphoma comprises 75% of all lymphomas. Both occur in younger age groups than reported in the West. B-cell NHLis three times more common than T-cell lymphoma. DLBCLis the most frequent lymphoma. ALCLis the most common T-cell, and mixed cellularity is the most common Hodgkin lymphoma.

Defining the Incidence and Clinical Impact of Genomic Alterations Across Different Histologic Types of Lymphoma Using a Clinically Validated Comprehensive Targeted Sequencing Assay

Background:Lymphoma is a clinically and molecularly heterogenous disease. Next generation sequencing of primary lymphoma samples has identified common recurring genomic alterations (GAs). The distribution and frequency of recurring GAs across lymphoma subtypes remains unknown because prior studies vary in sequencing methods, depth of coverage, and specimen source. In this study, we benchmark the distribution of GAs across different lymphoma subtypes by prospectively analyzing lymphoma cases and performing comprehensive DNA/RNA targeted sequencing of genes commonly found in hematologic malignancies using the Foundation One Heme (F1H) clinical assay.Methods:After obtaining proper consent, archived specimens from 183 samples [formalin fixed paraffin embedded (FFPE) N=141, peripheral blood N=28, BM aspirate N=14] distributed across lymphoma subtypes (including 62 DLBCL, 38 T cell lymphoma, 32 FL, 17 CLL, 13 MCL) were sequenced to high, uniform coverage averaging >600x for DNA, >20 million pairs for RNA. GAs were determined, including base substitutions, small insertions and deletions, rearrangements, and copy number alterations. Significant non-synonymous variants were identified as mutations from the COSMIC database, amplifications of established oncogenes, or homozygous deletions and/or clear loss-of-function mutations of known tumor suppressors. Fisher's exact test with Monte Carlo estimation corrected by false discovery rate was used for associations.Results:Samples from prospectively consented patients were banked for a median of 30 days prior to genomic analysis, range 1 day to 6.5 yr. Sequencing data was reported a median of 16 days from sample date receipt. GAs were identified in 95% of samples, with a median of 4 GAs/sample. The most common GAs were TP53 (29%), MLL2 (27%), BCL2 (25%), CDKN2A/B (17%) and CREBBP (14%). Alterations of chromatic modifiers (80%), BCR/NFkB components (51%), and cell cycle pathway (44%) were most common. In our group of unpaired follicular lymphoma samples (N=7 treatment naïve, N=25 treatment exposed), the number of GAs increased with treatment exposure. We found similar gene and biological signatures regardless of prior therapy; however differences emerge in genes of potential clinical relevance. Sequencing profiles augmented or altered the pathologic diagnosis in 11 of 183 (6%) of the cases. Importantly we were able to classify the GAs as actionable, potentially actionable and variants of unclear significance to better define the clinical relevance of targeted genomic sequencing.Conclusions:Integration of comprehensive next generation targeted genomic sequencing and clinical analysis in lymphoma provides an opportunity to describe the spectrum and incidence of GAs across different lymphoma subtypes and provide guidance on application of genomic profiling. This work serves to benchmark GAs across all lymphoma subtypes in a clinically relevant population and enables design of basket trials selecting patients based on shared genomic and biologic similarity instead of lymphoma subtype. To our knowledge, this is the largest repository of clinically annotated genomic sequencing in lymphoma.Table 1Total SpecimensN = 183Median Age at Diagnosis57Range 21 - 84Median Age at Biopsy61Range 21 - 91Sex • Male • Female113 7062% 38%Biospecimen source • Paraffin embedded • Peripheral blood • Marrow aspirate141 28 1477% 15% 8%Patient consent • Prospective consent • Retrospective consent145 3879% 21%Prospectively consented patients (N=145) Median Days to Result Median Age of Sample16 30 days8 - 81 1 day - 6.5 yr DisclosuresPalomba:Janssen: Consultancy. Gerecitano:Genentech: Consultancy, Other: Advisory Board; AbbVie: Consultancy, Other: Advisory Board. Matasar:Spectrum: Consultancy; Genentech: Consultancy. Straus:Millenium Pharmaceuticals: Research Funding. He:Foundation Medicine, Inc.: Employment, Equity Ownership. Balasubramanian:Foundation Medicine: Employment, Equity Ownership. Stephens:Foundation Medicine, Inc.: Employment, Equity Ownership. Miller:Foundation Medicine: Employment. Levine:Loxo Oncology: Membership on an entity's Board of Directors or advisory committees; CTI BioPharma: Membership on an entity's Board of Directors or advisory committees; Foundation Medicine: Consultancy. Younes:Celgene: Honoraria; Johnson and Johnson: Research Funding; Novartis: Research Funding; Bayer: Honoraria; Bristol Meyer Squibb: Honoraria; Sanofi-Aventis: Honoraria; Seattle Genetics: Honoraria, Research Funding; Curis: Research Funding; Janssen: Honoraria; Takeda Millenium: Honoraria; Incyte: Honoraria.

À propos d’un cas de lymphome anaplasique à grandes cellules diagnostiqué après explantation de prothèse mammaire

There has recently been a new controversy about the appearance of a particular histological type of lymphoma, anaplasic large cell lymphoma, in patients carriers of breast implants, with no causal link has been established for the moment. We report the case of a patient of 67 years old with recurrent effusion breast after explantation of breast prosthesis. The diagnosis of anaplasic large cell lymphoma was made after histological examination of the entire peri-prosthetic capsule after removal of most common diagnoses such as infection. Taking in hematological load was then established with the administration of chemotherapy to complete remission. All peri-prosthetic recurrent effusion should suggest the diagnosis of anaplasic large cell lymphoma, the definitive diagnosis requires the completion of a total capsulectomy with histological examination of the entire capsule.

Orbital lymphomas: Clinical and radiological features

The purpose of this prospective study was to evaluate the clinical and radiological features of a consecutive series of orbital lymphomas in two Institutions in the North West of Italy.A prospective study was performed of all cases of diagnosed orbital lymphomas. Data on patient demographics, symptoms and clinical findings, histological type of lymphoma, site of lesion, imaging, and systemic involvement were recorded in each case. The mean age of the enrolled 20 patients was 63.65 years. Most orbital lymphomas were located in the superior-lateral quadrant. Superior rectus muscle was the most frequently involved orbital structure. Most patients were affected by extranodal marginal-zone lymphomas. The diagnosis of orbital lymphomas may be challenging, because these neoplasms present few specific features. Although not typically performed by the maxillofacial surgeon, an understanding of the staging process is crucial for multidisciplinary management of orbital lymphomas.

Pediatric Gastrointestinal Diseases in Nigeria: Histopathologic Analysis of 74 Cases

BACKGROUND: Children are vulnerable to a vast number of diseases including gastrointestinal disorders, which may be associated with life threatening complications that sometimes result in mortality especially if left untreated. OBJECTIVE: To establish the age and sex distribution of children in the study population as well as the histopathological characteristics of gastrointestinal diseases that occurred in those children who were aged 14years and below in Sagamu, Southwestern Nigeria. MATERIALS AND METHODS: Demographic data such as age, sex, and clinical summary of children in the study population were extracted from the medical records of Olabisi Onabanjo University Teaching Hospital, Sagamu, Ogun State from January 2003 to December 2009. Based on this information, a review of paraffin embedded blocks and slides as well as histopathological reports of gastrointestinal diseases that occurred in those children aged 14years and below was undertaken at the Morbid Anatomy Department of the hospital. RESULTS: Seventy–four cases of gastrointestinal diseases were seen in children aged 14years and below. The majority (39.2%) of gastrointestinal diseases were accounted for by appendiceal lesions. Hirschsprung’s disease, intussusceptions, enterocolitis and jejunal atresia accounted for 29.7%, 10.8%, 6.8% and 4.1% of cases respectively. Adenocarcinoma of the intestine was the predominant gastrointestinal tumour, occurring in 5 out of 7 children. Two cases of non-Hodgkin lymphoma were also seen. The ages of the children ranged from 2 to 14 years, with a mean age of 8.6years and a peak age incidence of gastrointestinal disease in the 10-14year age group. Male children were more commonly affected with the exception of appendiceal lesions, which occurred more in females (M:F ratio= 1.6:1.0). Acute suppurative appendicitis was the most prevalent lesion of the appendix, occurring in 13 out of 29 appendiceal lesions. Moderately differentiated to poorly differentiated histological types were seen in the tumours- 3 adenocarcinomas and 2 mucinous carcinomas. Burkitt’s and Mucosal-associated types of non– Hodgkin lymphomas were the two histological types of lymphoma seen primarily in the stomach and small intestine respectively. CONCLUSION: Appendiceal lesion was the predominant paediatric gastrointestinal disease found in the study population with preponderance for female children. Adenocarcinoma was the most common gastrointestinal tumour found, while, Hirschsprung’s disease, intussusception, enterocolitis, jejunal atresia and non-Hodgkin lymphoma contributed to only a minority of the gastrointestinal diseases found in the study population.

Clinicopathological analysis of mediastinal large B-cell lymphoma and classical Hodgkin lymphoma of the mediastinum

Primary mediastinal (thymic) large B-cell lymphoma (PMLBCL) and nodular sclerosing classical Hodgkin lymphoma (NSCHL) are the major histological types of lymphoma affecting the mediastinum. We reviewed 27 patients with PMLBCL and 14 patients with NSCHL. A poor performance status, high serum lactate dehydrogenase level and strong positivity for PAX5 were all significantly more common in patients with PMLBCL than in those with NSCHL. Severe fibrosis was frequent in NSCHL, but not in PMLBCL. PDL1 was expressed by 11/25 PMLBCLs (44.0%) vs. 1/9 NSCHLs (11.1%). Expression of BCL6 was significantly more frequent in PDL1-positive PMLBCL than in PDL1-negative PMLBCL, but there were no clinical differences between these two groups. Two patients with PMLBCL with a poor prognosis had CD20(−), CD79a(+), CD15(−), and CD30(−), possibly representing a subtype of mediastinal gray zone lymphoma.

Nonmyeloablative Allogeneic Stem Cell Transplantation for Non-Hodgkin Lymphoma

Non-Hodgkin lymphomas constitute a heterogeneous group of hematologic malignancies with varying aggressiveness and many therapeutic options. Nonmyeloablative (NMA) conditioning has been the cornerstone of allogeneic adoptive immunotherapy for these diseases. This approach utilizes a reduced intensity preparative regimen to achieve engraftment with little toxicity. This allows for development of the immune graft-versus-lymphoma effect. Results depend on the histologic type of lymphoma, prognostic factors, patient characteristics, and chemosensitivity. For follicular lymphomas, NMA transplants are highly effective in patients with refractory or recurrent disease after the best chemoimmunotherapy available and who have a matched sibling or unrelated donor. In mantle cell lymphoma, autologous stem cell transplants are generally ineffective for patients with recurrent disease; we reported 6-year actuarial progression-free survival rate of 46%, using NMA allogeneic transplants. The indications of NMA transplants for diffuse large B-cell lymphoma and T-cell lymphomas are controversial; success has been reported in selected high-risk patients and those relapsing after an autologous transplantation who have chemosensitive disease. Considerations for the conditioning regimen, donor source, graft-versus-host disease prophylaxis, donor lymphocyte infusion, and relapse prevention methods are reviewed.

Coexistencia de dos tipos de linfomas en una paciente con síndrome de Sjögren. Utilidad de la PET-TAC

Sjögren syndrome is a chronic systemic autoimmune disease in which there is an increased risk of developing non-Hodgkin's lymphoma. Neoplastic lung involvement and the coexistence of different histological types of lymphoma are uncommon in these patients. These patients frequently have associated infectious processes, most of them due to oral candidiasis. When there is immunodeficiency, the hematogenous spread of the fungus may affect the lungs. We present the case of a female patient diagnosed with follicular non- Hodgkin lymphoma within the context of long-term Sjögren syndrome. In addition to the neoplastic nodal and splenic disease, the PET-CT study showed extensive lung involvement. Due to suspicion of a false positive result for pulmonary Candida infection, antifungal treatment was initiated, with no response. A further histological study showed the presence of a second and different type of lymphoma.

Coexistence of Two Different Types of Lymphoma in a Patient with Sjögren's Syndrome. The Usefulness of the PET-CT

Sjögren syndrome is a chronic systemic autoimmune disease in which there is an increased risk of developing non-Hodgkin's lymphoma. Neoplastic lung involvement and the coexistence of different histological types of lymphoma are uncommon in these patients. These patients frequently have associated infectious processes, most of them due to oral candidiasis. When there is immunodeficiency, the hematogenous spread of the fungus may affect the lungs. We present the case of a female patient diagnosed with follicular non-Hodgkin lymphoma within the context of long-term Sjögren syndrome. In addition to the neoplastic nodal and splenic disease, the PET-CT study showed extensive lung involvement. Due to suspicion of a false positive result for pulmonary Candida infection, antifungal treatment was initiated, with no response. A further histological study showed the presence of a second and different type of lymphoma.

Treatment of NonHodgkin’s lymphomas with rituximab in Slovene patients

The introduction of rituximab into the treatment of patients with NonHodgkin's lymphomas has changed the long-term prognosis of patients with CD20 positive B cell lymphomas, especially follicular and diffuse large B-cell lymphomas (DLBCLs). The addition of rituximab to chemotherapy improves the overall response rate, prolongs the response duration and the overall survival both in patients with follicular and other indolent CD20 positive lymphomas, and DLBCLs. Maintenance treatment with rituximab in patients with indolent lymphomas further prolongs the remission duration, and some of the studies have also shown survival benefit. However, the maintenance therapy in aggressive lymphomas most probably gives no further improvement in patients, who have received rituximab already in the induction treatment. Rituximab has been used at the Institute of Oncology Ljubljana since 1998. In the period from 2004 to 2006, we have treated 340 patients with rituximab either as a single agent or in combination with chemotherapy. Our treatment group included 46.8% of patients with DLBCLs and 19.4% with follicular lymphomas. In majority of the patients, rituximab was given as the first-line treatment (54.4%), while 26.2% of patients received it as the second-line treatment and 19.4% of patients as the third or subsequent line of treatment. Among patients with indolent lymphomas, just 15% received rituximab as the first-line treatment. On the other hand, 75.9% of patients with aggressive lymphomas were treated with rituximab for newly diagnosed disease. About 67.4% of patients were treated with R-CHOP combination, while the others received different rituximab-chemotherapy combinations. The overall response rate regardless of the histological type of lymphoma was 78.8%, and the highest response rate was achieved in patients with aggressive follicular lymphomas (91.7%). The highest overall response rate was observed when rituximab was given as the first-line treatment in all lymphoma types except the mantle cell lymphoma (66.6% overall response rate for the first-line treatment versus 73.7% overall response rate for the second-line treatment). In 75% of patients regardless of the histological type of lymphoma, the response lasted more than 12 months; the median response duration has not been reached yet. In patients receiving rituximab as the first-line treatment, the median response duration also has not been reached yet, while for the second-line treatment, it was 25 months and for the third or subsequent line, 24 months. The longest disease-free survival was observed in patients with DLBCLs. The overall survival rate of all patients regardless of the type of lymphoma was 75% 26 months after the beginning of the treatment, and the median overall survival has not been reached yet. When analyzed by the lines of treatment-the median overall survival has not been reached in any line. The longest overall survival was observed in patients with indolent follicular lymphomas. The treatment results with rituximab at the Institute of Oncology Ljubljana are comparable to the results of larger randomized trials. According to the beneficial influence of rituximab on the long-term prognosis of patients with CD20 positive lymphomas, it became the standard of treatment in these patients.

Non Hodgkin's Lymphoma (NHL) and Deep Vein Thrombosis (DVT): A Dangerous Liaison Still Unexplored.

Introduction DVT incidence ranges from 3 to 15% in cancer patient. Nevertheless there are only few data about DVT in lymphoma. Aim of our study is to define the real DVT risk and incidence in lymphoma patients.Patients and Methods Our study is a retrospective study including patients of two haematology centers. We considered the age of the patients, sex, histological type of lymphoma (indolent -IL- vs aggressive -AL), localization over or under diaphragm, extranodal localizations, vascular compression, stage of disease, IPI, LDH level, chemotherapy type and timing of administration (weekly vs every 2wks or 3 weeks), the use of chemotherapy regimen containing methotrexate as potential risk factors in DVT onset. Data regarding 567 NHL patients, observed from 2001 to 2006, were collected. 400 patients had indolent NHL (IL) and 167 Aggressive NHL (AL). Median age was 59 years (R 13–94), M/F ratio was 300/267. DVT was diagnosed by ultrasound or CT scan. The statistical analysis was conducted with Yates corrected chi square test, Odds Ratio (OR), Log-rank test (to compare Kaplan-Meier curves).Results 87 patients (15%) showed DVT. Of these, 37(43%) were localized at legs and 19(22%) involved abdominal veins (especially iliac veins, 10% of total). DVT onset median time was 3 months from NHL diagnosis (Range 0–156 months). Sex, histological type of lymphoma (IL vs AL), localization over or under diaphragm, extranodal localization, stage of disease, IPI, LDH level, and use of chemotherapy regimen containing methotrexate were not related to an increased risk to develop DVT. Vascular compression was the most significant risk factor for DVT development with OR 3.1 (CI95%:1.9–5), Chi Square22.7(p< 0.0001). Patients receiving weekly chemotherapy showed an increased risk to develop DVT (OR 1.8; CI95%:1.1–2.8), Chi Square5.1, p0.024. Patients aged ≥60 presented increased risk of DVT with OR 1.7(CI95%: 1–2.7), Chi Square 4.28 (p 0.04). Patients with DVT within 3 months from NHL diagnosis had an higher risk of disease relapse or non response at first line chemotherapy: OR 3.7 (CI95%: 1.8–7.3), Chi Square 13.4 (p < 0.0001), positive predictive value 0.71(CI95%: 0.57–0.82), specificity 0.95(CI95%: 0.93–0.97). However DVT had no impact on mortality and survival, also in the subgroup of patients with DLBCL. Discussion In our study vascular compression by enlarged lymphonodes, patient age ≥60 y.o., and weekly administration of chemotherapy seem to be the main risk factors to develop DVT in NHL patients. Further studies, concerning genetic conditions and other disease-related parameters, are ongoing to individuate other risk factors for thrombosis in NHL patients. The DVT development within 3 months from NHL diagnosis seems to be a risk factor for non response/relapse. An antithrombotic prophylaxis could be considered in the patients with higher thrombotic risk.

A single-center study of treatment outcomes and survival in patients with primary gastric lymphomas between 1990 and 2003

Primary gastric lymphomas are the most common extranodal non-Hodgkin's lymphomas and are divided into indolent (low grade) and aggressive (high grade) types. They are mainly the disease of middle age, with a male predominance reported by most of the studies. For several years, surgery played a central role in diagnosis, staging, and treatment of this entity, yet recently there has been a move away from a surgical approach to conservative treatment. To determine the role of surgery as the initial treatment modality, we performed this retrospective single-center research on 245 patients with primary gastric lymphoma who were treated according to our protocol between 1990 and 2003. The patients' characteristics, distribution of histological types, treatment results, and disease-specific survival were followed. According to the histology, 59.2% had diffuse large B-cell lymphoma (DLCL), 26.1% MALT lymphoma, 9.8% mixed lymphoma (indolent and aggressive at the same time), while other types were infrequent. In total, 161 patients (65.7%) were treated with surgical resection as the initial treatment, which was then followed or not by additional therapy (chemotherapy, chemotherapy and radiotherapy, radiotherapy) depending on the histological type of lymphoma and the extent of residual disease after surgery. In 84 patients (34.3%), the treatment approach was conservative. The selection of treatment (chemotherapy, chemotherapy and radiotherapy, radiotherapy or Helicobacter pylori eradication only) was based on the histological type of lymphoma, considering also the patients' physical condition. The disease-specific survival in the group of patients who underwent surgery was statistically significantly better than in patients who were treated conservatively (p=0.049). At 5 years, it was 96.9% for the group treated with surgery and 89.8% in patients treated conservatively. However, the results were biased, as the patients who were treated conservatively were either in a worse performance status or presented with a more extensive disease. Similarly, in the DLCL type the disease-specific survival was better in the surgically treated group (97.2%) than in the conservatively treated patients (89.2%). The difference was barely significant (p=0.046) and again the results have to be considered with caution due to the selection of patients in a worse performance status or with a more extensive disease for conservative treatment. In the MALT lymphoma and mixed lymphoma types, there were no differences in the disease-specific survival between both treatment groups. Regarding the statement that for conservative treatment patients were selected who were unsuitable for the resection on account of concomitant diseases or due to the fact that the process was inoperable, we believe that the conservative approach gives comparable outcomes to the approach including initial surgery. The existing evidence thus no longer justifies surgery as the standard initial treatment and preference should be given to conservative treatment approaches.

Ocular adnexal lymphoproliferative disease: a series of 73 cases.

This study involved 73 patients with lymphoproliferative lesions of the ocular adnexa. The lesions were categorized using the Revised European American Lymphoma classification of lymphoid tissues and analysed to determine the frequency and prognostic impact of tumour type, location, stage and patient's age and sex. The clinical, histopathological, immunohistochemical and phenotypic analysis by flow cytometry and follow-up data were studied. The ocular adnexal lymphoproliferative lesions included 70 lymphomas and six reactive lymphoid hyperplasia. Seventy-nine per cent had stage IE disease, 4% stage II, 1.5% stage III and 15.5% stage IV. Five patients (7%) had a past history of systemic lymphoma. Major histological types were extranodal marginal zone lymphoma (MZL) in 44 (63%), follicular (FL) in 12 (17%), diffuse large B-cell (DLBCL) in eight (11%), mantle cell (MCL) in two (3%), B-cell chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma in two (3%), peripheral T-cell lymphoma (PTCL) one (1.5%) and natural killer cell lymphoma (NKCL) in one (1.5%). Longest survival was seen in those with low-grade lymphomas (MZL and FL) and worst in PTCL and NKCL. Lymphoma-related mortality was 2% for MZL, 33% for FL, 38% for DLBCL, and 100% for MCL, PTCL and NKCL. Systemic lymphoma was present prior to, at presentation or at subsequent follow up in 26/68 (39%) of all lymphoma patients, 17% for MZL, 38% for DLBCL, 83% for FL, and 100% for MCL, CLL, PTCL and NKCL. The majority of ocular adnexal lymphomas were low-grade B-cell lymphomas (MZL). Multivariate analysis showed that the only significant independent predictors of all causes of mortality were the histological type of lymphoma and the stage of disease at presentation.

Association between hepatitis C virus and non-hodgkin’s lymphoma, and effects of viral infection on histologic subtype and clinical course

PURPOSE: Because an etiologic role for hepatitis C virus in non-Hodgkin’s B-cell lymphoma has been suggested by several reports, we assessed the prevalence of hepatitis C virus infection in patients with non-Hodgkin’s B lymphoma and in controls, and evaluated the influence of viral infection on histologic and clinical features of the lymphoma patients. PATIENTS AND METHODS: We prospectively investigated 175 consecutive patients with non-Hodgkin’s lymphoma and 350 controls for serologic and molecular markers of hepatitis C virus infection. Controls were selected from inpatients (n = 175) and outpatients (n = 175) cared for at our hospital. Patients with lymphoma who had hepatitis C virus infection were tested for mixed cryoglobulinemia. Aminotransferase levels were measured in all lymphoma patients at baseline and during and after chemotherapy. RESULTS: Hepatitis C virus prevalence in patients with non-Hodgkin’s lymphoma was significantly greater than in control subjects (37% vs 9%, P = 0.0001). Among patients with lymphoma, viral infection was associated with older mean (±standard deviation) age (67 ± 14 vs 61 ± 8 years, P = 0.001), and women (41 of 87, 47%) were more likely than men (24 of 88, 27%) to have evidence of hepatitis C infection ( P = 0.006). Thirteen of the 20 cases of immunocytoma were associated with hepatitis C virus infection, which was also more common in patients with orbital and conjunctival localization of lymphoma. Patients with mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach were less likely to have evidence of hepatitis C infection. Mixed cryoglobulinemia was much more common in patients with hepatitis C virus infection (14 of 65 vs 1 of 110, P = 0.0001); it was not associated with the histologic type of lymphoma. Patients with and without hepatitis C virus infection underwent similar chemotherapy regimens and had no differences in response to chemotherapy or in overall and disease-free survival. Hepatic toxicity from chemotherapy was seen only in patients with hepatitis C virus infection, although all but one of these patients were able to complete their planned treatment. CONCLUSION: These findings suggest that the hepatitis C virus may have a role as an etiologic agent in non-Hodgkin’s B-cell lymphoma. Some clinical and pathologic features of the disease are associated with hepatitis C virus infection, but the virus does not seem to affect prognosis.

Malignant tumors of the eyelid: a population-based study of non-basal cell and non-squamous cell malignant neoplasms.

To determine the relative frequencies, average annual incidences, and patient characteristics of non-basal cell and non-squamous cell malignant neoplasms of the eyelid in a defined geographic population. A retrospective study using the Florida Cancer Data System to identify malignant tumors of the eyelid, except for basal cell and squamous cell carcinomas, from 1981 through 1994. Cases were limited to persons who resided within Florida. Incidence of histologically confirmed malignant eyelid tumors. Two hundred six primary malignant eyelid tumors were identified. The 3 most common, in order of frequency, were melanoma, sebaceous carcinoma, and lymphoma. The median age at diagnosis for all patients was 73 years. Only 3 of the 206 malignant neoplasms occurred in blacks. The annual incidence of eyelid melanoma and sebaceous carcinoma in whites older than 20 years was 0.6 and 0.5 per million, respectively. Kaposi sarcoma was the most common type of mesenchymal tumor. Eleven different histologic types of lymphoma were found in the eyelid. Only 2 of 27 lymphomas had T-cell lineage. Malignant tumors of the eyelid other than basal cell and squamous cell carcinoma are uncommon and usually occur in elderly white persons. Primary eyelid tumors of any type are rare in blacks. The risk of a non-basal cell and non-squamous cell malignant neoplasm of the eyelid in Florida is 6.4 times greater for whites than for blacks (95% confidence interval [CI], 2.1-20.2). A variety of B-cell lymphomas can be manifested as primary eyelid tumors.

Cytokine (Interleukin-1 alpha, Interleukin-1 beta, Tumor Necrosis Factor alpha, and Interleukin-6)-Possessing Cells in Lymph Nodes of Malignant Lymphoma

Interleukin (IL)-1 alpha, IL-1 beta, tumor necrosis factor (TNF) alpha, and IL-6 are the most important triggers in the response of the immune system to infection and neoplasia. We examined the histochemical distribution of cytokine-possessing cells in neoplastic lymph nodes of 68 malignant lymphomas. The HLA-DR positive interdigitating reticulum cells (IRCs), histiocytes/macrophages (H/Ms) and epithelioid histiocytes with these cytokines were frequently encountered in Hodgkin's disease, B cell lymphoma of lymphoplasmacytic/cytoid, centroblastic and immunoblastic types, and T cell lymphoma of Lennert's and anaplastic large cell types. In almost all cases of B cell lymphoma of chronic lymphocytic leukemia, centrocytic, follicular centroblastic/centrocytic, Burkitt's types and T cell lymphoma of lymphoblastic, angioimmunoblastic lymphadenopathy and pleomorphic types, the cytokine-possessing cells were rarely or occasionally present. These lymphomas with less cytokines had also few or occasionally encountered IRCs, while H/Ms were frequently or occasionally present. Well-developed dendritic reticulum cells in some types of lymphoma had few cytokines. The population of cytokine-possessing cells was related with histologic type of lymphoma and the volume of IRCs. The IRCs might act as an important initiator of reactive cells against tumor cells. In addition, neoplastic T cells influenced the cytokines' possession of IRCs and H/Ms. Although lacunar, Hodgkin's and Reed-Sternberg cells in Hodgkin's disease and the neoplastic cells in peripheral T cell lymphoma showed weak positive reaction of TNF alpha in one third of the cases, lymphoma cells in the majority might have few cytokines, especially IL-1s and IL-6.

Superoxide dismutase, glutathione peroxidase and catalase in the red cells of patients with malignant lymphoma.

Erythrocyte superoxide dismutase, glutathione peroxidase and catalase activities have been measured in patients with untreated malignant lymphomas. Marked deficiencies of superoxide dismutase (P less than 0.001) and glutathione peroxidase (P less than 0.001) were found, whereas catalase levels were normal. There was no apparent difference in enzyme activities between the different histological types of lymphoma.