Localised non-Hodgkin lymphoma of the testis: the Sheffield Lymphoma Group experience

We evaluated clinical features, management and survival of patients with localised (stage 1E or 2E) testicular non-Hodgkin lymphoma (NHL) presenting to the Sheffield Lymphoma Group between 1972 and 2002. Thirty consecutive eligible patients were identified from the lymphoma database and clinical records of all were reviewed. Survival data were statistically analysed. The median age of patients was 74 years (range 38-87). Sixty-three percent were >70 years of age. The median duration of follow-up was 15 months (range 2.1-211). All patients had orchidectomy. Eleven (37%) had orchidectomy alone. Twelve (40%) had orchidectomy and chemotherapy, 4 (13%) had orchidectomy and radiotherapy. Three (10%) had orchidectomy, chemotherapy and radio-therapy. Five (17%) had immediate disease progression following orchidectomy or whilst on treatment. A complete response was seen in the remaining 25 (84%) irrespective of treatment modality. Seven (23%) of patients remain alive, with a median follow-up of 73 months (range 9.9-211). Six (20%) died of causes not related to their lymphoma. Twelve (40%) relapsed following a complete response and median time to relapse was 9 months. Only 1 of these relapses was in the central nervous system; 1 in bone, 1 in skin, 2 in the contralateral testis. The majority of relapses (58%) occurred in the lymph nodes. Primary testicular lymphoma is an uncommon and poor prognosis disease usually affecting older men. The data and experience available to guide the treatment strategies for testicular lymphoma are limited. However, the evidence points to a combined modality approach being the most likely effective treatment, comprising surgery, anthracycline-containing combination chemotherapy with or without prophylactic contralateral testis and regional lymph node irradiation.     

Peripheral T cell lymphoma: The Sheffield Lymphoma Group experience (1977-2001)

Peripheral T-cell lymphomas (PTCL) account for approximately 10% of all non-Hodgkin's lymphomas. The aim of this retrospective study was to analyse the presentation, management, outcome and significant prognostic factors in a large series of patients with PTCL. It includes 104 consecutive patients who presented to the Sheffield Lymphoma Group between 1977 and 2001. Clinical parameters were recorded for each subgroup. End points were response to treatment and survival. Survival analysis was used to assess the prognostic value of the variables. PTCL not otherwise specified contributed 52% of cases followed by anaplastic large cell lymphoma with 17% and angiocentric type with 13% of cases. The overall complete remission (CR) of the series was 59%. Stage at diagnosis affected response to treatment with 81% of cases in stage 1 and 2 achieving CR compared to 43% in stages 3 and 4 (p60 years (p<0.05), high grade histology (p<0.001), presence of B symptoms (p<0.005), nodal presentation (p<0.005) and advanced stage at diagnosis (p<0.001). Histological sub-type did not significantly correlate to outcome. In conclusion whilst a number of prognostic indicators can assist in determining the outcome in PTCL, these lymphomas are complex and often follow an unpredictable course. In order to make the best clinical decisions in individual cases, more clinical study is required.     

Non-Hodgkin's lymphoma presenting with spinal involvement: the Sheffield Lymphoma Group experience (1970-2000).

Spinal non-Hodgkin's lymphoma is rare. We retrospectively reviewed the clinical and histopathologic records of 39 consecutive patients referred to the Sheffield Lymphoma Group from 1970 to 2000 and analysed the prognostic differences between localised (stage IE and IIE) and secondary (stage III and IV) spinal non-Hodgkin's lymphoma (S-NHL) patients. Forty-five percent of all patients were over 60 years old. More patients were male (58%); presented with stage IE and IIE (63%), mostly of intermediate/high grade histology (74%); over a third had symptoms; nearly a third (11 patients) were paraplegic and 14 had sphincter dysfunction at diagnosis. The overall survival of all patients was 39% at 5 years (median 24.7 months), whilst that of localised S-NHL was 51% (median 89.7 months). Univariate analysis showed better survival for patients with good mobility status at presentation (p < 0.0l) and complete response to initial treatment (p < 0.00l). In primary S-NHL, histology (p < 0.05) significantly influenced overall survival. In conclusion, disease is frequently locally advanced at presentation with aggressive histologic grade: thorough staging should always be performed to exclude widespread disease. Good mobility status predicts for good survival outcome. Optimal treatment is still uncertain.     

Primary B-cell lymphoma of the skin: the Sheffield Lymphoma Group Experience (1984-2003)

The clinical presentation, treatment and outcome were retrospectively evaluated in a series of 66 patients with primary B-cell lymphoma of the skin, referred to the Sheffield lymphoma group (SLG) between 1984 and 2003. This is the largest series reported from the UK. The lymphoma database was searched and clinical records were reviewed. Absence of any detectable extracutaneous lesion and the expression of B-cell restricted antigens by neoplastic cells were the essential criteria for selection of cases. The cohort included 37 (56%) males and 29 (44%) females with a mean age of 59 years. The most commonly involved site was the trunk and the disorder typically showed non-aggressive clinical behaviour; the majority of the patients presented with stage I (82%) disease with a tendency to remain localised to a limited area of the skin. Follicular lymphoma was the most common histologic subtype (35%), the next most frequent was the diffuse large cell lymphoma (32%) whereas marginal zone lymphoma constituted 15%. The majority (47%) of patients were treated with radiotherapy for localised disease whereas chemotherapy was given in 20% of patients, with single agent chlorambucil being most frequently used. Surgical excision as the sole modality of treatment was adequate in 33%. Disease-free survival (DFS) was 91% at 1 year, 82% at 2 years and 60% at 5 years. DFS was significantly lower with older age (>45 years), leg lesions, generalised and multiple lesions, and for those treated with chemotherapy. The survival at 5 and 10 years was 80%. The histologic grade, leg involvement and the number of lesions were the most significant variables affecting overall survival. Only 7 patients died of lymphoma. In conclusion, primary cutaneous B-cell lymphoma represents a specific entity concerning clinical behaviour, response to treatment, and overall prognosis.     

Limited stage I and II follicular non-Hodgkin's lymphoma: the Nebraska Lymphoma Study Group experience

The purpose of this study was to evaluate the outcome and prognostic factors of patients with limited stage follicular non-Hodgkin's lymphoma treated prospectively by the Nebraska Lymphoma Study Group (NLSG). Forty previously untreated patients, median age 64 years, with limited stage follicular lymphoma were prospectively treated according to the protocols of the NLSG between January 1980 and December 1990. The follicular large cell type represents 75% of the cases, and 14 of the biopsies also had a diffuse component (composite lymphoma). The initial treatment was radiation therapy (RT) to the involved field in 15 patients, anthracycline-containing combination chemotherapy (CT) in 20, and combined RT and CT in 5. Thirty-seven patients (92.5%) achieved a complete remission (CR). The median follow-up is 120 months (range, 20 to 214). Of the 37 patients achieving a CR, 7 patients are alive in first CR, one died due to sepsis, another because of a myeloproliferative disorder at 77 months following chemotherapy, 6 died because of unrelated causes in first CR. Twenty-two patients relapsed between 1 to 128 months following a CR. The estimated 10-year event-free survival is 21% (95% CI: 7 to 35). Two patients received no or palliative therapy after relapse and both died of progressive disease. Nineteen patients received salvage therapy and 15 achieved a second remission. The median survival after first relapse is 55 months. The estimated 10-year overall survival is 44% (95% CI: 28 to 60). Various factors including sex, histologic subtype, stage, and degree of follicularity do not influence the overall survival or event-free survival. CT with or without RT resulted in a better trend for 10-year event-free survival in stage IA patients compared to RT alone but estimated 10-year overall survival is no different. The overall survival is worse in the > or = 60 age group but this difference is not evident if data is adjusted for cause specific death. In conclusion, limited stage follicular lymphoma has an excellent initial response to radiation therapy or chemotherapy; however the recurrence rate is high and cure is limited.     

Results of radiation therapy of extranodal non-Hodgkin's lymphoma of the head and neck--a study of the Japan Lymphoma Radiation Therapy Study Group

During the years 1972-81, 168 patients with extranodal Non-Hodgkin's lymphoma localized in the head and neck were treated with radiation. Five-year survival rates were 62% in stage I, 56% in stage II, and 91% in diffuse well-differentiated lymphocytic, 77% in diffuse mixed, 52% in diffuse poorly-differentiated lymphocytic and diffuse histiocytic each. Marginal relapse was rare after radiation therapy, but relapses were not infrequently noticed in distant extranodal sites. Bone and/or soft tissue relapses were frequently noticed in patients with lesions initially located in the nasal cavity, paranasal sinus and oral cavity.     

Results of radiation therapy in extranodal non-Hodgkin's lymphoma of the head and neck--a study of the Japan Lymphoma Radiation Therapy Study Group

Extranodal non-Hodgkin's lymphoma (NHL) in the head and neck except Waldeyer's ring treated with radiation were analyzed. No definite difference was observed both in actuarial and relapse-free five-year survival rate between stage I and II. There was a high survival rate with orbital NHL in which most of the patients occupied with favorable histology. Prognosis of the disease was highly influenced by the histologic subtype; five-year survival was 91.4% in DWDL, 77.2% in the DM, 52.0% in DPDL and 51.7% in DH. Application of histologic classification with the Working Formulation was also recommended. There was a high incidence of extranodal relapses to bone and/or soft tissue from the lesions with nasal cavity, paranasal sinus and oral cavity.     

UCHL1-positive extranodal lymphoma resembling multiple lymphomatous polyposis of the gastrointestinal tract

Histopathologic and immunohistochemical studies were done on paraffin sections from a patient with alimentary tract lymphoma resembling multiple lymphomatous polyposis of the gastrointestinal tract (MLP). Diffuse, but not follicular, proliferation of medium-sized lymphoid cells was noted in the polypoid lesions of the alimentary tract, peripancreatic lymph nodes, spleen, liver, and bone marrow. These cells possessed a T-cell-related antigen (UCHL1), but were negative for the B-cell-related and myeloid cell-related antigens examined. Because neoplastic cells in MLP are usually of B-cell origin, the current case will provide important information on the relation between phenotypes and morphologic patterns of proliferation.     

A radiotherapeutic experience for localized extranodal non-Hodgkin's lymphoma: prognostic factors and re-evaluation of treatment modality

Between 1966 and 1988, 149 patients were treated with radiotherapy for localized extranodal lymphoma. The average total dose given was 39.8 Gy for low grade disease and 48.7 Gy for all other disease. Of the 149 patients, 60 also received adjuvant chemotherapy. Twenty-four had low grade lymphoma, 109 had intermediate grade disease, and 16 had high grade disease, histologically. The distribution of histological grade and T/B phenotype varied with the primary site. Low grade lymphomas were found mainly in the orbit, and T-cell lymphomas were found in the nasal cavity and nasopharynx. The 5-year survival rates according to tumor location were 89% for oral cavity, 86% for paranasal sinus, 83% for thyroid, 69% for orbit, 47% for Waldeyer's ring (WAR), 44% for testis, 23% for CNS, 21% for nasal cavity and 60% for other sites. Histological grade and T/B phenotype both had prognostic importance. Combined chemotherapy significantly improved the survival rate only for disease with intermediate or high grade histology. Other prognostic factors according to the primary site were the bulk of lymph node for WAR disease, the radiation dose for CNS disease, bone erosion for orbital disease, stridor for disease of the thyroid, and the tumor stage for disease of both the testis and the thyroid.     

Intestinal non-Hodgkin's lymphoma: a multicenter prospective clinical study from the German Study Group on Intestinal non-Hodgkin's Lymphoma.

PURPOSE: Intestinal non-Hodgkin's lymphomas are not well characterized. We therefore studied prospectively their clinical features and response to standardized therapy. PATIENTS AND METHODS: Fifty-six patients with primary intestinal lymphoma were included in a prospective, nonrandomized multicenter study. Lymphoma resection was recommended and staging was performed according to the Ann Arbor classification. Patients were scheduled to receive six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) chemotherapy, and at stages EIII to EIV, they received additional involved-field radiotherapy. Corticosteroids were used in patients who could not receive chemotherapy. RESULTS: Thirty-five patients had intestinal T-cell lymphoma (ITCL), 21 patients had intestinal B-cell lymphoma (IBCL; 18 diffuse large-cell lymphomas, two marginal-cell lymphomas, and one follicle-center lymphoma). Thirty-four patients at stages EI to EII (14 ITCL and 20 IBCL) and nine patients at stages EIII to EIV (all ITCL) received chemotherapy. No patient in stages EIII to EIV received radiotherapy, because death occurred in 12 of 14 patients. Two-year cumulative survival in patients with IBCL was 94% (95% CI, 82% to 100%) and higher than in patients with ITCL (28% [95% CI, 13% to 43%]; P <.0001), even when only stages EI to EII were considered (ITCL, 37.5% [95% CI, 16.5% to 58.5%]; P <.0001). IBCL patients compared with ITCL patients were at lower lymphoma stages (P <.01), had higher Karnofsky status (P <.005), had intestinal perforation less often (P <.05), required emergency operation less often (P <.05), received CHOP (P <.05) more often, and reached complete remission (P <.0005) more frequently. CONCLUSION: IBCL patients at stages EI and EII respond well to chemotherapy, but the prognosis and treatment of ITCL patients is unsatisfactory.     

A retrospective international study on primary extranodal marginal zone lymphoma of the lung (BALT lymphoma) on behalf of International Extranodal Lymphoma Study Group (IELSG)

Primary lymphoma of the lung is a rare entity. Clinical features, optimal treatment, role of surgery and outcomes are not well defined, and the follow‐up is variable in published data. Clinical data of 205 patients who were confirmed to have bronchus mucosa‐associated lymphoid tissue lymphoma from December 1986 to December 2011 in 17 different centres worldwide were evaluated. Fifty‐five per cent of the patients were female. The median age at diagnosis was 62 (range 28–88) years. Only 9% had a history of exposure to toxic substances, while about 45% of the patients had a history of smoking. Ten per cent of the patients had autoimmune disease at presentation, and 19% patients had a reported preexisting lung disease. Treatment modalities included surgery alone in 63 patients (30%), radiotherapy in 3 (2%), antibiotics in 1 (1%) and systemic treatment in 128 (62%). Patients receiving a local approach, mainly surgical resection, experienced significantly improved progression‐free survival (p = 0.003) versus those receiving a systemic treatment. There were no other significant differences among treatment modalities. The survival data confirm the indolent nature of the disease. Local therapy (surgery or radiotherapy) results in long‐term disease‐free survival for patients with localized disease. Systemic treatment, including alkylating‐containing regimens, can be reserved to patients in relapse after incomplete surgical excision or for patients with advanced disease. Copyright © 2015 John Wiley & Sons, Ltd.     

Primary gastrointestinal non-Hodgkin's lymphoma: a review of 175 British National Lymphoma Investigation cases.

A retrospective analysis was performed upon 175 patients with Non-Hodgkin''s Lymphoma involving the gastrointestinal tract and entered into BNLI trials and studies between 1974-1988. Malignant histiocytosis of the intestine (MHI), which was present in 16 patients, was associated with a survival of less than 25% at 18 months, and probably accounted for the poor survival of patients with jejunal involvement. Histopathological evidence of tumour origin from mucosa-associated lymphoid tissue (MALT) was found in 50% of patients with gastric involvement and in 27% of those with intestinal involvement. The overall survival of the series as a whole was 44% at 10 years. Multivariate analysis identified evidence of tumour origin from MALT as the only factor to attain prognostic significance in patients with gastric involvement, and clinical stage and the presence of MHI as the only factors to attain prognostic significance in patients with intestinal involvement. It is suggested that there is a need for a large multicentre prospective study of GIT lymphoma.     

Low-grade non-Hodgkin's lymphomas--report of the Japanese Lymphoma Radiation Therapy Group (JLRTG)

The clinical features of 102 patients with low grade non-Hodgkin's lymphomas treated from 1972 to 1981 among the hospitals belonging to the JLRTG were retrospectively reviewed. According to the Rappaport classification, there were 29 cases of NPDL, 26 of NM and 47 of DWDL. The survival rate and relapse-free survival rate for all patients at 10 years were 49% and 41%, respectively. No obvious difference in survival rate was seen by histologic type, but patients with DWDL had a better relapse-free survival rate than those with NM (P less than 0.01). This study also suggested that patients with stages I and II low grade lymphomas might be treated by irradiation alone, if they are staged properly.     

Primary extranodal non-Hodgkin's lymphoma of the head and neck.

Among 387 cases of non-Hodgkin's lymphoma (NHL) treated in our units between January 1977 and December 1990, 52 (13.4%) had primary extranodal (PE) NHL of the head and neck. The median age was 55 years with a M:F ratio of 1.9:1. The most frequent primary site was the tonsil (28 cases), followed by oral cavity, parotid gland, orbit and other sites. The aggressive histological subtypes predominate. 55.2% of the patients were in stage I and 44.8% in stage II of disease. The CR rate was high (94.2%). The 5 years' overall survival rate was 65% and it was influenced mainly by stage (stage I 82.5% vs. 48.7% in stage II). Sex, age and histology did not significantly affect survival rate. Patients with primary Waldeyer's ring involvement (WR group) did not differ significantly from the other primary sites analyzed as a group (non-WR group) in respect to median age, sex distribution, histology and CR rates. They differed, however, in: (1) stage distribution with stage II disease more frequent in the WR group; (2) overall survival and disease-free survival both of which were significantly better in the non-WR group; and (3) the high incidence of GI tract involvement as initial manifestation of relapse in the WR group. It is concluded that the behaviour of the Waldeyer's ring PE-NHL is rather distinctive and should be considered separately from the other PE-NHL of the head and neck.     

Lymphoma of the gastrointestinal tract.

Non-Hodgkin's lymphoma (NHL) of the gastrointestinal (GI) tract accounts for 4% to 20% of all NHLs and is the most common extranodal site of presentation. The stomach is the major organ involved by GI lymphoma. Helicobacter pylori infection, immunosuppression after solid-organ transplantation, celiac disease, inflammatory bowel disease, and human immunodeficiency virus (HIV) infection may be risk factors for GI lymphoma. A significant proportion of gastric lymphomas are of low-grade histology and arise from mucosal-associated lymphoid tissue (MALT). Such MALT lymphomas may be associated with H. pylori infection and may undergo complete regression following eradication of H. pylori. Lymphoma of the small bowel, colon, and rectum may also occur, but are less common than gastric lymphoma. Distinct clinicopathologic entities, such as primary intestinal T-cell lymphoma, immunoproliferative small intestinal disease, and multiple lymphomatous polyposis have been described. Surgery, radiation therapy, and chemotherapy have been used in the treatment of GI lymphomas. However, the optimal management of these lymphomas has never been determined by prospective randomized clinical trials. Such trials by cooperative groups are needed to answer many of the vital unanswered questions concerning extranodal lymphomas of the GI tract.     

Localised lymphoma of bone: prognostic factors and treatment recommendations. The Princess Margaret Hospital Lymphoma Group.

Twenty seven adult patients with newly diagnosed non-Hodgkin's lymphoma localised to either bone (Stage IE) or bone and regional lymph nodes (Stage IIE) were treated between 1967 and 1988. Median age was 53 years and the commonest histology (21 patients) was diffuse histiocytic lymphoma. Twenty-four patients were treated radically: 15 with radiation therapy (XRT) alone and nine with chemotherapy plus radiation therapy (CMT). The cause specific survival for these patients was 56% at 5 years and 40% at 10 years. Survival was significantly better for patients treated by CMT (88% at 5 years) as compared to XRT alone (40% at 5 years, P = 0.03) and for age less than 60 (72% at 5 years) compared to greater than or equal to 60 (30% at 5 years, P = 0.018). Relapse-free rate was 27% at 5 years with XRT alone and 89% with CMT (P = 0.01). Risk factors for loco-regional relapse (seven cases) included: large tumour bulk, treatment by XRT alone and use of 'limited' radiation fields. No radiation dose-response relationship could be identified in this study. Long term local control and survival for localised lymphoma of bone were excellent after treatment by CMT but XRT alone was associated with unacceptably high local and distant failure rates.     

Chemotherapy following surgery for stages IE and IIE non-Hodgkin's lymphoma of the gastrointestinal tract

Twenty-six patients were treated with chemotherapy following surgery for gastrointestinal non-Hodgkin's lymphoma (GI-NHL). The median age was 50 years (range, 20 to 76). The primary site included stomach (16 patients), small bowel (seven), large bowel (two), and mesenteric nodes (one). Following surgery, nine patients had macroscopic and four patients had microscopic residual disease, and 13 were felt to have had complete surgical resection. Thirteen patients were stage I and 13 were stage II. Sixteen patients were treated with COPP (cyclophosphamide, vincristine, procarbazine, prednisone), nine with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), and one with CVP (cyclophosphamide, vincristine, prednisone). At a median follow-up of 50 months (8+ to 178+ months) ten of 12 stage I patients and nine of 14 stage II patients remain alive. Of the nine patients with macroscopic residual disease, four died of disease 6.5 to 11.0 months after diagnosis, and five are alive 8+ to 178+ months from diagnosis. Fourteen of the remaining 17 patients who had complete surgical resection are alive without disease. Death in the other three patients was due to multiple abdominal abscesses at 12 months, adenocarcinoma of the colon at 57 months, and dementia and progressive neurologic dysfunction at 65 months. No patient who had complete resection has relapsed or developed systemic disease after chemotherapy. These results suggest that complete surgical resection is an important prognostic factor and that chemotherapy without irradiation in completely resected localized GI-NHL can prevent local and systemic relapse resulting in long-term disease-free survival.     

The significance of bone marrow involvement in non-Hodgkin's lymphoma: the Eastern Cooperative Oncology Group experience

Data from four clinical trials conducted by the Eastern Cooperative Oncology Group (ECOG) were used to investigate the importance of bone marrow involvement as a prognostic factor in patients with non-Hodgkin's lymphoma (NHL). A total of 502 patients, 275 with nodular, poorly differentiated lymphocytic lymphoma (NLPD) and 227 with diffuse histiocytic lymphoma (DHL) or diffuse mixed-cell lymphoma (DML), were included in this analysis. Patients were separated into four categories: stage III, stage IV with bone marrow involvement (stage IV-M), stage IV without marrow involvement (stage IV-O), and stage IV with bone marrow and other organ involvement (stage IV-OM). Among the DHL and DML patients, the incidence of marrow involvement was 23%. However, stage IV-M patients had a prognosis that is similar to stage IV-O and stage IV-OM and worse than stage III patients. In contrast, the incidence of involvement with NLPD was 59% and patients with stage IV-M had a survival not different than stage III and not worse than stage IV-O and stage IV-OM. The results suggest that the current emphasis on bone marrow biopsy(s) as a routine diagnostic staging procedure for patients with NHL should be reevaluated. The necessity for this procedure in stage III patients with NLPD is not apparent from our data. One can still justify a bone marrow biopsy in stage I and II patients and can confirm the complete clinical response when all nodes have regressed in more advanced disease.