Extranodal Presentation Research Articles

Aggressive T/Natural killer cell lymphoma presenting as testicular tumor

BACKGROUND Nonnasal CD56+ T/natural killer (NK) cell lymphomas with morphologic and immunogenetic features similar to those of the distinctive nasal T/NK cell lymphoma are uncommon and have been characterized only recently. They show predominantly extranodal presentation, high stage disease, a highly aggressive course, strong association with Epstein–Barr virus (EBV), and lack of T cell receptor gene rearrangement. Only one previously reported case had a testicular presentation, although the testis is not uncommonly involved during the course of disease in both nasal and nonnasal T/NK cell lymphomas. METHODS Three patients with T/NK cell lymphoma who presented initially with a testicular mass are reported. RESULTS The three patients underwent orchidectomy for testicular tumor. Histologically, the testes showed diffuse dense infiltration of medium-sized or large lymphoma cells. Angiocentric growth and necrosis were prominent in two cases. The lymphoma had the following immunophenotype: CD2+ CD3ϵ+ CD56+ compatible with T/NK cell lymphoma; two lacked staining with Leu4 (CD3), and one had weak staining. With immunohistochemical preparations, it was noted that the rete testis stained consistently for CD56, and the Leydig cells and Sertoli cells showed patchy staining. The neoplastic cells harbored EBV, as demonstrated by in-situ hybridization. Additional sites of disease were detected at the time of the diagnosis in one patient (nose) or appeared soon afterwards in all three patients (skin or gastrointestinal tract). All three patients died within 5 months. CONCLUSIONS This study confirms that testicular CD56+ T/NK cell lymphoma tends to disseminate early, pursues an aggressive course, and is strongly associated with EBV. CD56 recognizes the neural cell adhesion molecule (NCAM), which exhibits homophilic binding properties. The expression of CD56 in the normal testicular constituents can perhaps explain the tendency for T/NK cell lymphoma to localize in this organ. Cancer 1996;77:1198-205.

Aggressive T/Natural killer cell lymphoma presenting as testicular tumor

Nonnasal CD56+ T/natural killer (NK) cell lymphomas with morphologic and immunogenetic features similar to those of the distinctive nasal T/NK cell lymphoma are uncommon and have been characterized only recently. They show predominantly extranodal presentation, high stage disease, a highly aggressive course, strong association with Epstein-Barr virus (EBV), and lack of T cell receptor gene rearrangement. Only one previously reported case had a testicular presentation, although the testis is not uncommonly involved during the course of disease in both nasal and nonnasal T/NK cell lymphomas. Three patients with T/NK cell lymphoma who presented initially with a testicular mass are reported. The three patients underwent orchidectomy for testicular tumor. Histologically, the testes showed diffuse dense infiltration of medium-sized or large lymphoma cells. Antiocentric growth and necrosis were prominent in two cases. The lymphoma had the following immunophenotype: CD2+ CD3 epsilon+ CD56+ compatible with T/NK cell lymphoma; two lacked staining with Leu4 (CD3), and one had weak staining. With immunohistochemical preparations, it was noted that the rete testis stained consistently for CD56, and the Leydig cells and Sertoli cells showed patchy staining. The neoplastic cells harbored EBV, as demonstrated by in-situ hybridization. Additional sites of disease were detected at the time of the diagnosis in one patient (nose) or appeared soon afterwards in all three patients (skin or gastrointestinal tract). All three patients died within 5 months. This study confirms that testicular CD56+ T/NK cell lymphoma tends to disseminate early, pursues an aggressive course, and is strongly associated with EBV. CD56 recognizes the neural cell adhesion molecule (NCAM), which exhibits homophilic binding properties. The expression of CD56 in the normal testicular constituents can perhaps explain the tendency for T/NK cell lymphoma to localize in this organ.

Non‐Hodgkin's Lymphomas in Turkey: Eighteen Years’Experience at the Hacettepe University

In this retrospective study, 470 patients with non‐Hodgkin's lymphoma (NHL) who had been followed in the Hacettepe University Medical Oncology Department between 1973 and 1990, were evaluated to establish their epidemiologic, clinical and therapeutic characteristics. Out of 470 patients, 302 (62.2%) were male and 168 (37.8%) were female. The ages ranged from 16 to 85, with a median of 44 years. Constitutional symptoms were present in 46.4% of the patients. According to the Working Formulation, low, intermediate, and high‐grade lymphomas comprised 33.4%, 54.9%, and 12.7%, respectively. The most common extranodal presentation was gastrointestinal. The chemotherapy regimens most commonly used were CVP (cyclophosphamide, vincristine, prednisone), BCNOP (bleomycin, cyclophosphamide, mitoxantrone, vincristine, prednisone), CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and CHOP‐Bleo (cyclophosphamide, doxorubicin, vincristine, prednisone, bleomycin). The response rates and the survival figures attained with these regimens were not statistically significantly different (P > 0.05). In the Cox multivariate model, pathologic grade, leukopenia, responsiveness to chemotherapy, bone marrow involvement and age were the important factors influencing the disease‐free survival, while responsiveness to chemotherapy, age, presence of constitutional symptoms, pathologic grade, extranodal presentation and stage were the important factors influencing the overall survival. The distribution of NHL according to grade and stage was similar to that in western societies, while constitutional symptoms and lymphomas of the small intestine including immunoproliferative small intestinal disease were more common in Turkey.

Clinical significance of bcl-2-MBR gene rearrangement and protein expression in diffuse large-cell non-Hodgkin's lymphoma: an analysis of 83 cases.

The goal of this study was to assess the prognostic significance of a rearrangement of the major breakpoint region of the bcl-2 gene and/or expression of bcl-2 protein in diffuse large-cell lymphomas of B-cell origin. All 83 patients diagnosed at the Cross Cancer Institute between 1987 and 1992 with malignant lymphoma (ML), diffuse large-cell ML non-cleaved-cell ML or cleaved-cell ML, or with diffuse large-cell immunoblastic ML were studied. bcl-2 rearrangement was identified by a polymerase chain reaction technique. This technique detects the approximately 60% of rearrangements involving the major breakpoint region bcl-2 gene (bcl-2-MBR). bcl-2 protein expression was studied by immunohistochemistry. More than 66% of the cases expressed bcl-2 protein, whereas 18% had a detectable bcl-2-MBR gene rearrangement. Overall, cases with bcl-2-MBR rearrangement had shorter disease-free periods. Cases with nodal and extranodal presentation had a similar frequencies of bcl-2-MBR rearrangement; however, the disease-free period of patients with extranodal presentation and bcl-2-MBR rearrangement was significantly shorter than that of those without rearrangement. bcl-2 protein is frequently expressed in diffuse large-cell lymphomas, but does not influence prognosis. The bcl-2-MBR gene rearrangement may possibly be associated with a shorter disease-free period, particularly in the specific setting of a lymphoma with extranodal presentation.

Non-hodgkin's lymphoma of the thyroid gland: Prognostic factors and treatment outcome

Purpose : Non-Hodgkin's lymphoma presenting in the thyroid gland is uncommon. A review of the Princess Margaret Hospital experience was performed to assess treatment outcome and prognostic factors in this rare extranodal presentation of localized lymphoma. Methods and Materials : Fifty-two patients treated at the PMH between 1978 and 1986 were identified and their records reviewed retrospectively. Staging procedures revealed 16 patients with Stage I, 28 with Stage II, and eight with Stages III or IV disease. Five patients were treated on a protocol designed for anaplastic carcinoma of thyroid and they were excluded from detailed analysis. Of 39 patients with Stages I and II disease, 18 were treated with radiotherapy alone, three chemotherapy alone, and 18 combined modality therapy. Combined modality therapy was used mainly in patients with large tumor bulk. Results : The overall 5-year actuarial survival and cause-specific survival were 56% and 64%, respectively. The overall relapse-free rate was 61% at 5 years. Among the 39 patients with Stages I and II disease, the 5-year actuarial survival, cause-specific survival, and relapse-free rate were 64%, 73%, and 66%, respectively. There were no significant differences in outcome between those treated with radiotherapy alone and those treated with combined modality therapy (cause-specific survival: p = 0.25, relapse: p = 0.06). A univariate analysis showed that the only variable to reach statistical significance was tumor bulk. Age was marginally significant while stage and histology were not statistically significant, possibly due to the fairly homogeneous distribution of patients in each of these variables. Patients with progression or relapse of lymphoma after initial treatment frequently died of disease. Isolated gastrointestinal relapses occurred in three cases, representing 27% of all relapses. Conclusion : Based on the above results, we recognize that the majority of patients with localized thyroid lymphoma require combined modality therapy and we recommend radiotherapy alone only for a small, select group of patients with Stage I disease and small tumor bulk.

CD5 Expression in B-Cell Small Lymphocytic Malignancies

The authors examined the relationship between CD5 antigen expression and a nodal or extranodal presentation for three subtypes of low-grade non-Hodgkin's lymphoma: small lymphocytic (23 cases), small lymphocytic with plasmacytoid differentiation (10 cases), and lymphocytic lymphoma of intermediate differentiation (IDL) (29 cases). Antigen expression was studied by the avidin-biotin complex immunoperoxidase technique in frozen sections and correlated with expression of other B- and T-cell markers. Lack of CD5 expression was significantly associated with extranodal presentation among the over-all study group (p less than 0.001), as well as for those with small lymphocytic lymphoma and IDL, but not for those presenting with small lymphocytic lymphomas with plasmacytoid differentiation (p less than 0.21). Eleven patients presented exclusively with extranodal disease involving lung and respiratory tract, skin and subcutaneous tissue, salivary gland, stomach, conjunctiva, and uterus. All such lesions were CD5 negative and had been classified as small lymphocytic (four cases), small lymphocytic-plasmacytoid (four cases), and IDL (three cases). Retrospective review of these 11 cases demonstrated common histologic features described as characteristic of lymphomas of mucosa-associated lymphoid tissue (MALT). Two additional patients presented with disseminated nodal disease and involvement of gastrointestinal tract and oropharynx; both were CD5 positive. These findings support the concept that at least two antigenically distinct B-cell subpopulations may be involved in pathogenesis of low-grade small lymphocytic malignancies.

Clinical and biological analysis of peripheral T-cell lymphomas: a single institution study.

Peripheral T-cell lymphoma (PTCL) accounts for 15-20% of non-Hodgkin's lymphoma in the Western World. Clinical, histopathologic, phenotypic and genotypic data were received from 33 cases of PTCL referred to our institution. The median age order was 50 years, 78% were males, and 18% had a history of a preceding disorder of the lymphoid system. 60% had stage 4 at diagnosis and B symptoms were also present in 60%. The most frequent sites of extranodal involvement were bone marrow (54%), liver (45%) and skin (33%). Twenty-eight of 33 cases were histologically classified according to the Working Formulation (most in the diffuse mixed and large-cell subgroups) and the Kiel updated system. Phenotypic and genotypic studies of malignant cells showed a considerable heterogeneity with respect to the expression of either T-cell receptor (TCR) alpha beta and gamma delta and pan-T differentiation molecules. Of the studied cases 63% expressed TCR-alpha beta. All five patients with PTCL of the TCR-gamma delta subtype had a peculiar extra-nodal presentation. The vast majority of cases expressed an abnormal T-cell phenotype with respect to the expression of pan-T antigens, including the lack of expression of the TCR-associated CD3 molecule in 2 cases. Rearrangements of the TCR beta and/or delta-chain genes showed clonality in 21 of the 23 studied cases. Twenty-five patients were treated with a multiagent chemotherapy regimen with curative intent and the remainder received a less intensive palliative regimen. Only 9 patients achieved CR (8 of whom had received an anthracycline-containing regimen) and the 4-year survival rate was 25%.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary small intestinal lymphoma.

Gastro-intestinal tract is the most common site of extranodal presentation in non-Hodgkin's lymphoma. Among the subsites the small intestine predominates. This paper presents a review of 21 cases of primary gastro-intestinal lymphoma seen at the Department of Radiation Oncology, Christian Medical College, Vellore, during the period 1979-1986. All patients had laparotomy, and biopsy from the primary site. Histopathological subtypes were done in the International Working Formulation. Stage groupings were done applying the Crowther and Blackledge staging system. Post-laparotomy treatment decision was made depending on the patient's general condition, completeness of surgery and histological subtype. The overall survival rate was 31.5% at 5 years. Early stage disease and high-grade lymphomas have a better prognosis if treated adequately.

Rosai-Dorfman Disease Involving the Premaxilla

Sinus histiocytosis with massive lymphadenopathy (SHML), introduced in 1969 by Rosai and Dorfman, is a benign and self-limited (albeit often relapsing) pseudolymphomatous entity with characteristic histopathologic features. Although the presence of massive cervical lymphadenopathy often aids in the diagnosis of SHML, the disease may present in the absence of detectable nodal involvement (Rosai-Dorfman disease). Therefore, the physician must be aware of such extranodal presentations. A recent review of the 365 cases in the SHML registry has revealed a preponderance of eyelid and/or orbital involvement; only 26 cases were found with subcutaneous or soft tissue involvement in areas other than the eyelid and/or orbit. This is a case report of one such atypical presentation of SHML without clinically apparent lymphadenopathy or eyelid or orbital involvement.

Primary Lymphoma of Bone: Long Term Results in Patients Treated with Vincristine - Adriamycin - Cyclophosphamide and Local Radiation

Primary lymphoma of bone (PLB) is an unusual but well-recognized extranodal presentation of non-Hodgkin's lymphoma. In most series treatment with radiotherapy alone results in a cure rate of approximately 40%. Between January 1972 and December 1982, 26 patients with biopsy proven PLB were treated at the Rizzoli Institute with radiotherapy (4000-5,500 rad) and chemotherapy (vincristine, cyclophosphamide and adriamycin). The minimal clinical staging included complete blood cell counts and serum chemistries, bone radiography, full lung tomography, isotope bone scan, bone marrow biopsy and bipedal lymphoangiograms. At a median follow-up of 13 years (8.5-18.5) there were only three relapses (2 cases of meningeal involvement and 1 recurrence in another bone). No local recurrences nor second tumor in the irradiated field were observed. We conclude that the addition of chemotherapy to radiotherapy results in an excellent cure rate for patients with PLB.

The molecular biology of B-cell lymphoma: Clinicopathologic implications

Nonrandom chromosomal translocations like the t(14;18), t(8;14), and t(11;14) are found in distinct types of B-cell malignancies. Recent molecular studies concerning their structure and origin showed that many translocations occur in early precursor B cells and may be interpreted as aberrant immunoglobulin gene rearrangements. The available data from in vitro experiments, transgenic mice, and normal human individuals indicate that these translocations are essential but insufficient for full tumorigenesis. The consequent "multi-hit" concept might have important implications for the detection of minimal residual disease using the polymerase chain reaction for these translocations. The strong associations with specific types of lymphomas underline their differences in histogenetic origin. Thus, based on differences in bcl-1 and bcl-2 rearrangements, molecular analysis may help to distinguish follicular lymphoma from diffuse centrocytic lymphoma and chronic lymphocytic leukemia. Furthermore, based on differences in bcl-2 and c-myc rearrangements, subtypes of de novo centroblastic lymphoma can be distinguished that have striking differences in biological behavior, especially nodal versus extranodal presentation. Therefore, future studies will show an increasing clinical relevance of molecular analysis in B-cell neoplasia.

HIV-associated non-Hodgkin's lymphomas: Clinical characteristics and outcome. The experience of the French Registry of HIV-associated Tumors*

From 1/87 to 12/89, the French Registry of HIV-associated tumors recorded 131 cases of intermediate- and high-grade non-Hodgkin's lymphomas (NHL). There were 47 small non-cleaved Burkitt-type lymphomas (SNCL), 32 immunoblastic lymphomas (IL) and 52 diffuse large-cell or predominantly large-cell lymphomas (LCL). There were differences in the clinical patterns of the histological subtypes. Isolated extranodal presentation was less frequent in SNCL (2/47) than in IL (13/32) and LCL (17/49) (p less than 0.0001). In the latter two groups, the central nervous system was the principal site of extranodal involvement (16/30), 87% of SNCL, patients had no previous manifestations of AIDS whereas 40% of IL and LCL patients presented full-blown AIDS (p less than 0.01). At the time of NHL diagnosis, the median blood CD4 lymphocyte count was higher in SNCL (266/microL) than in LCL (125/microL, p less than 0.05) and IL (80/microL, p less than 0.01), 69% of stages I/II patients, 31% of stages III/IV, and 33% of stage ie patients achieved complete remission (CR), p less than 0.05. Overall median survival time was 5 months. There was no statistical difference in CR and survival rates among histological types. The two-year actuarial survival rate was 25% (median 8 months) for initially asymptomatic patients or those with persistent generalized lymphadenopathy (PGL) and 9% (median 3 months) for those previously with AIDS-related complex (ARC) and AIDS patients (p less than 0.001). Response to treatment was the other predictor factor. The two-year survival rate was 42% (median 16 months) for patients who achieved CR, and 5% (median 3 months) for those who did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Lymphocytic Lymphoma of Intermediate Differentiation

All cases of lymphocytic lymphoma of intermediate differentiation (IDL) referred to the National Cancer Institute were reviewed in order to define the histopathologic spectrum of the disease and to investigate morphologic and immunophenotypic features with potential prognostic relevance. Thirty-three cases were classified as IDL according to histologic criteria. Immunophenotypic analysis was performed in 27 cases, and clinical records were available for 22 patients. The median age was 58 years, and the male-to-female ratio, 3.4:1. All patients presented with stage III or IV disease, and five had extranodal presentations. Median survival was 56.3 months, with only three patients having a prolonged relapse-free survival (greater than 2 years). Morphologically, 14 cases were diffuse or only vaguely nodular; 18 cases showed a mantle zone pattern with naked germinal centers. There was a trend toward prolonged median survival for patients with the mantle zone (77.4 months, p = 0.098). The neoplastic population was composed of irregular or cleaved small lymphoid cells with a mitotic rate ranging from 5 to 62 per 20 high-power fields (hpf). A histologically distinctive variant with blastic cytologic features was identified (seven cases). The blastic variant was associated with a higher mitotic index (51.3 versus 19.0) and shortened survival (24.9 months). In contrast to the histologic progression often observed in follicular lymphomas, in no case was transformation to a large-cell or small noncleaved lymphoma observed. All cases had a mature B-cell phenotype demonstrating monoclonal Ig and B-cell surface antigens. Seventy-eight percent were CD5 positive; three of six CD5-negative cases presented in mucosal-associated extranodal sites. CD10 and CD25 were expressed in 52% and 44%, respectively, but did not show clinical correlations. The proliferative rate measured by Ki-67 positivity correlated with the mitotic index, but neither of these parameters had a statistically significant influence on survival.

Non-Hodgkin's lymphoma: a histopathologic and immunohistochemical study of 79 cases

Recently immunophenotyping has become a valuable tool in the diagnostic workup of malignant lymphoma. We classified 79 consecutive cases of non-Hodgkin's lymphoma experienced at our hospital during the last two years according to the Working Formulation and immunologically using MT1, UCHL1 and MB2 monoclonal antibodies. The results of this study are as follows: 1) four cases (5.1%) were low grade, 54 cases (68.4%) were intermediate grade, and 21 cases (23.3%) were high grade. The most common subtype was 'diffuse, mixed' type, 2) fifty cases (63.3%) showed T-cell phenotype and 14 cases (17.7%) showed B-cell phenotype. Immunophenotyping was impossible in 15 cases due to either double staining or negative staining. 3) the incidence of extranodal presentation was high (65.8%) and the most common extranodal site was the upper aerodigestive tract (29.1%) followed by the gastrointestinal tract (16.4%), and 4) MT1, UCHL1 and MB2 monoclonal antibodies are valuable markers of T- and B-cells in paraffin embedded tissue, enabling retrospective study. However, because these antibodies are not lineage specific, the results of immunostaining should be interpreted with caution.

DIFFUSE LARGE CELL LYMPHOMA: A TEACHING HOSPITAL EXPERIENCE

Improvement in the treatment of diffuse large cell lymphoma (DLCL) over the last 15 years has been one of the notable successes of modern chemotherapy. This paper reports a three year experience (1985–87) of 46 unselected consecutive patients with DLCL in a single teaching hospital. A striking finding was that visceral, extranodal presentations were disproportionately common. The excellent response of stage I patients to chemotherapy alone is emphasised as is the role of immunophenotyping in diagnosis.

Peripheral T-cell lymphoma in childhood. A clinicopathological study of six cases.

A review of the pathological material from 42 children with non-Hodgkin's lymphoma seen over a 44 month period revealed 10 large cell tumours. Of these, six were classified as peripheral T-cell lymphoma, an entity rarely reported in childhood. Three patients were boys and three girls (median age 9.5 years), and extranodal presentation was a feature of two patients. Five had high-grade tumours; of these, three were classified as large cell anaplastic, Ki-1 positive and two as pleomorphic large cell. The remaining patient had a low-grade tumour of angioimmunoblastic type. T-cell subsets were examined in three cases and showed the following phenotypes: CD4-, CD8-; CD4+, CD8-; CD4-, CD8+. Three of the patients with high-grade tumours died, with a mean survival of 22 weeks. The remaining patients are alive and clinically disease-free for between 10 and 24 months after treatment.

Primary prostatic involvement in non-hodgkin lymphoma

We report 3 cases of primary extranodal lymphoma of the prostate, an unusual extranodal presentation rarely diagnosed antemortem. Symptoms of prostatism associated with an enlarged hard prostate with pyuria and hematuria in younger patients should suggest the diagnosis. Urine cytologic examination should aid in the diagnosis of this condition.

Non-Hodgkin's lymphoma: A case involving four third molar extraction sites

M alignant lymphomas are neoplasms of the lymphopoietic portion of the reticuloendothelial system.’ Lymphomas are the third most common malignant lesions of the oral region, fillowing squamous cell carcinoma and salivary gland neoplasms.2-4 NonHodgkin’s lymphomas (NHL) encompass a separate group of diseases that differ from Hodgkin’s lymphomas in cytologic characteristics, natural history, response to therapy, and prognosis.5 NHL can occur in all age groups and can affect either gender. While the initial lesion usually presents in the lymph nodes, extranodal presentations of NHL are common, with occurrence in the central nervous system, the gastrointestinal tract, the kidneys, the testes, the bone, and the skin6 The incidence of extranodal NHL in the oral region, however, is less common. A study of 1467 cases of extranodal NHL by Freeman and coworkers7 reported 417 of these cases as having been initially seen in the head and neck region; of those, 9.5% involved the oral cavity. NHL has occurred in almost every soft and hard tissue of the oral region, but no predominant site in the mouth has been determined.’ A case of extranodal NHL involving four third molar extraction sites is presented. A review of the literature failed to reveal any other such case.

Primary lymphoma of bone in children: analysis of treatment results with adriamycin, prednisone, Oncovin (APO), and local radiation therapy.

Primary lymphoma of bone is an unusual extranodal presentation of pediatric non-Hodgkin's lymphoma (NHL). Treatment with radiotherapy alone has resulted in a disease-free survival rate of approximately 50% in most adult series. Between January 1973 and April 1985, 11 children with biopsy-proven NHL of bone were seen and treated at our institutions. The minimal clinical staging included chest and bone radiographs, a radionuclide bone scan, complete blood cell counts and serum chemistries, and a bone marrow aspirate and biopsy. The age range was 9 to 17 years with a median age of 14 years. Histology included diffuse lymphoblastic lymphoma in four patients and diffuse histiocytic lymphoma in seven. Each patient was treated with the Adriamycin/prednisone/Oncovin (APO) protocol and ten patients received concomitant radiation to the whole bone when possible and a boost to the primary lesion(s). The median tumor dose was 5,000 rad (range, 3,600 to 5,600). The median follow-up was 8 years. There have been no relapses, but two patients have developed second bone tumors 5 and 7 1/2 years after beginning therapy. Each second tumor arose directly in the radiation field. The overall 8-year actuarial survival is 83%. We conclude that APO and local radiation results in excellent overall survival for children with primary NHL of bone. The occurrence of two second bone tumors, however, raises questions regarding dose and/or the role of radiation for this disease.

Stages I and II non-Hodgkin's lymphomas of Waldeyer's ring and the neck.

In a previous communication we reported our results for patients with localized extranodal presentations of non-Hodgkin's lymphomas of the head and neck who were admitted between 1961-1969. This review describes our larger experience from 1947-1982 in treating 137 Stages I and II Waldeyer's ring patients whose slides were available for reclassification according to the modified Rappaport System. All of these patients were treated definitively as follows: radiotherapy only, 113 patients; radiotherapy and combination chemotherapy, 17 patients; chemotherapy only, seven patients. The overall 5-year survival was 50%. Significant differences were determined for specific subgroups. For patients staged after lymphangiography, the 5-year survival was 67% as compared with 32% for non-lymphangiogram staged patients (p = 0.002). Stage (Ann Arbor) also influenced results. The 5-year survival figure for Stage I was 70% as compared with 42% for Stage II (p = 0.002). The combination of extent of disease in Waldeyer's ring and the status of the neck had a major impact on survival. When the disease was staged according to the TNMAJCC System, the 5-year survivals were: 75% for T1-T2-TX N0; 53% for T1-T2-TX N+; 54% for T3-T4 N0; and 36% for T3-T4 N+. Also, results for tonsil (52%) and base of tongue (66%) disease were better than for disease involving the nasopharynx (39%) or multiple sites (25%). Treatment also influenced survivals and disease-free survivals. The best results were obtained in patients who were treated with radiotherapy and combination chemotherapy. The 5-year survival and disease-free survival figures were 78% and 69%, respectively.