Extranodal non-Hodgkin's lymphoma of the head and neck

Forty-six patients referred to our department between 1970 and 1982 with biopsy proven extranodal non-Hodgkin's lymphoma (NHL) of the head and neck were analysed. The median follow-up was 78 months. As a result of histological revision, six cases were excluded. By retrospective staging, 10 patients were found to have advanced disease (stage IV) at the moment of presentation, and three showed infradiaphragmatical nodes (stage III). All stage I-II patients except one were treated with radiotherapy. The 5-year actuarial relapse-free survival was 50% for the whole group, and 77% for the 26 patients who achieved complete remission after initial treatment. All stage IV patients died from lymphoma. Initial response and localised disease were the most significant prognostic features.     

Extranodal lymphoma of the head and neck area

Records of 64 patients with extranodal lymphoma of the head and neck area treated at this institution between 1965 and 1982 have been reviewed. Of these cases, 78% had Stage I-EA disease, 20% had Stage II-EA disease, and 2% had Stage III-EA disease. Excluded from this study were patients of the pediatric age, patients with previous chemotherapy and surgery, patients in whom extranodal involvement has been a terminal manifestation of wide-spread disease, and patients with nodal involvement with extension of disease outside the lymph nodes. Patients with a histiocytic histology accounted for 63%, 28% were of lymphocytic histologies, 4.5% were of mixed histologies, and in 4.5% a diagnosis of lymphoma or benign lymphocytic proliferation had been made. The paranasal sinuses, nasal cavity, and oral cavity were the most frequent sites of involvement, making up 39% of the cases--with the orbit, central nervous system, nasopharynx, salivary glands, thyroid, skin, and larynx following in that order of frequency. All patients received a definitive course of radiotherapy, except patients with CNS involvement. In no case was chemotherapy given concomitantly with the radiation therapy. One-third of the patients did require chemotherapy at a later time for progression of disease. No patients were lost to follow-up. Seven patients with primaries of the brain were inevaluable for response; however, all patients having visible or palpable tumors achieved a complete response (100%), and there was no recurrence or persistent disease in the field of therapy. The next area of disease involvement depended on the site of the primary. Nodal involvement following extranodal disease carried a poor prognosis.     

Extranodal head and neck non-Hodgkin's lymphomas in children in Finland

During the 20-year period from 1961 to 1980, 17 cases of extranodal head and neck non-Hodgkin's lymphoma in children under 15 years of age were diagnosed in Finland. Eight cases had tumours in tonsils or nasopharyngeal adenoids and 9 cases lymphomas of other sites of the head and neck. The age-adjusted annual incidence rate for all cases was 0.69 and for tumours of the pharyngeal lymphatic tissue 0.35 per 10(6) children. Seven of the 17 tumours were undifferentiated lymphomas (Burkitt's and non-Burkitt's types) and 5 lymphoblastic lymphomas. The overall 5-year disease-free survival rate was 37%. Five of the 9 patients with tonsillar or adenoid lymphomas were disease-free more than 5 years.     

A clinicopathologic study of orbital and adnexal non-Hodgkin's lymphoma.

An analysis of non-Hodgkin's lymphoma involving the orbital structures was performed at the University of Iowa between 1937 and 1975. Sixteen cases of primary orbital lymphoma were diagnosed. Histopathologic reclassification according to the Rappaport scheme and the clinical course of each histologic sub-category was described. There were 5 patients with reactive hyperplasia, 2 patients with well-differentiated lymphoid proliferation with Dutcher bodies which were also felt to be reactive, 3 patients with diffuse poorly differentiated lymphocytic lymphoma, 4 patients with nodular poorly differentiated lymphocytic lymphoma, and 2 patients with diffuse histiocytic lymphoma. It was concluded that the Rappaport classification is applicable to orbital lymphoid tumors and that those lymphomas which do present as primary tumors should be staged as one would stage the same histologic category of lymphoma presenting in other sites. Radiation therapy appears to be an effective treatment for local control; however, patients with primary orbital lymphoma should undergo observation for systemic disease similar to patients with lymphoma presenting in other sites. Excisional biopsy is recommended to facilitate precise classification.     

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.     

Multilobated non-Hodgkin's lymphoma. A clinicopathologic entity

Multilobated non-Hodgkin's lymphomas (NHL) have recently been recognized as an NHL variant. During a period of 10 years we observed 30 individuals with NHL in which more than 30% of the malignant cells had a characteristic multilobation. The immunologic phenotype was determined in 14 of these cases. One was of T-cell lineage, and the others exhibited B-lymphoid markers. Sixty-eight percent of the patients presented with extranodal localizations. In the clinical follow-up a complete remission was observed in 78% of patients with a mean duration of 37 months (range, 5 to 120 months). The actuarial survival after 5 years was 45%. From these data we conclude that multilobated NHL are comparable to diffuse, large cleaved-cell NHL of an intermediate grade malignancy according to the Working Formulation or are comparable to the diffuse centrocytic-centroblastic NHL according to the Kiel classification. The neoplastic cells are to be considered as variants of follicle center cells, but the clinicopathologic correlation indicates that multilobated NHL represent a distinct nosologic entity.     

An unusual presentation of non-Hodgkin's lymphoma in the head and neck

The lymphomas are a group of lymphoproliferative disorders that can be divided histologically in the two main groups of Hodgkin's and non-Hodgkin's lymphoma. They sometimes present in the head and neck, and the diagnosis and management require a multidisciplinary approach. An unusual case is described presenting at an advanced stage because of patient delay in seeking medical help.     

Extranodal primary tumor site indicates poor prognosis in childhood head and neck non-Hodgkin's lymphomas

As a result of the diversity of lymphoid structures in the head and neck, we analyzed clinical characteristics and outcomes of 87 consecutive children with non-Hodgkin's lymphoma (NHL) arising in this region to determine if the nodal versus extranodal primary site influences prognosis. Thirty-one children had primary nodal NHL whereas 56 had extranodal NHL. The two groups were similar in the distribution of age, gender, race, serum lactic dehydrogenase levels, and disease stage. However, extranodal tumors were slightly more likely to have small non-cleaved cell histology (32/56 versus 11/31, p = 0.07) than nodal tumors. In a multivariate analysis, extranodal involvement (p = 0.017), advanced stage disease (p = 0.054) and treatment era (p = 0.056) were each significantly associated with a shorter time of event-free survival. Children with extranodal and extralymphatic NHL had an even worse treatment outcome than did others (p = 0.006). The poor prognosis of extranodal involvement was also evident among children with stage I or II NHL. We conclude that extranodal involvement has an adverse influence on treatment outcome in children with NHL arising in the head and neck region.     

Radiation therapy for primary non-Hodgkin's lymphoma of the head and neck

Thirty-seven previously untreated cases of primary non-Hodgkin's lymphoma in the head and neck were treated at our department from September 1977 through January 1983. The survival rate at three years by stage was 84% in stage I, 44% in stage II and 0% in stage III and IV. Stage, T- and B-cell markers, initial primary site, the level of lymph node involvement (UICC, 1978) and number were important prognostic factors. Chemotherapy in the pre- or post-radiation period was essential, especially in stage II. It was proved that adequacy of radiation portals with special reference to anatomical considerations was necessary.     

Recent progress in non-Hodgkin's lymphoma study in Japan

Great progress has been made in clinical research on non-Hodgkin's lymphoma during the last 15 years. Surface marker and DNA analyses of immunoglobulin and T-cell receptor genes are essential for new classification of the disease according to the cellular origin of tumor cells. This approach resulted in the establishment of new disease entities such as adult T-cell leukemia/lymphoma(ATL), immunoblastic lymphoadenopathy (IBL)-like T-cell lymphoma, and the pleural B-lymphoma occurring in long-standing pyothorax. New retrovirus, HTLV-I, was found during studies on ATL. Prevention of HTLV-I infection is an important project. HTLV-I negative ATL was also found and is of particular interest in understanding leukemogenesis of ATL. An oncogen such as bcl-2 is important for characterization of follicular lymphoma. Prognostic factors of patients with T-lymphoma are completely different from those of B-lymphoma. Risk grouping by combination of major prognostic factors is useful for the selection of the best treatment modality and the accurate estimation of prognosis of patients at initial presentation. The effect of combination chemotherapy should be evaluated separately between T- and B-lymphomas because of the difference in response rate and prognostic factors.     

Early stage head and neck non-Hodgkin's lymphoma. The effect of tumor burden on prognosis

Treatment results were investigated in 113 previously untreated patients with clinical Stage I and II (Ann Arbor) non-Hodgkin's lymphoma of the head and neck. Fifty-six Waldeyer's ring, 34 other extranodal sites, and 23 cervical nodal lesions were included. The overall relapse-free survival at 5 years was 41%. Age and Ann Arbor stage influenced relapse-free survival. The results suggested that the tumor cell burden is a fundamental prognostic factor for patients with Waldeyer's ring disease and for patients with only cervical nodal disease. Abdominal relapse was most frequent, followed by generalized relapse. From 1981, patients were randomized in a clinical trial to receive either chemotherapy (cyclophosphamide, vincristine, and prednisone [CVP], five courses) or whole-abdominal irradiation (25 Gy/20 Fr) as an adjuvant therapy. Patients could not tolerate the whole-abdominal irradiation well. A significant improvement in survival has been obtained by adjuvant chemotherapy.     

Pilot study of modified version of CHOP plus radiotherapy for early-stage aggressive non-Hodgkin's lymphoma of the head and neck

PURPOSE: To evaluate the safety and efficacy of a modified version of cyclophosphamide, doxorubicin, vincristine, prednisone (pirarubicin, cyclophosphamide, vincristine, and prednisone [THP-COP]) plus radiotherapy for early-stage aggressive non-Hodgkin's lymphoma of the head and neck. METHODS AND MATERIALS: Between December 1993 and December 1999, 41 patients with early-stage non-Hodgkin's lymphoma with intermediate-grade histologic features were enrolled in our study. The mean patient age was 51 years. Of the 41 patients, 27 had Stage I and 14 Stage II disease. The primary site was Waldeyer's ring, a neck node, or an extranodal site in 14, 11, and 16 patients, respectively. The immunophenotype was B cell in 29 and T cell in 12 patients. All patients were in the low-risk category according to the International Prognostic Index. Chemotherapy consisted of 40 mg/m(2) i.v. pirarubicin (THP-Adriamycin), 750 mg/m(2) i.v. cyclophosphamide, and 1.0 mg/m(2) i.v. vincristine, on Day 1 and 40 mg/m(2) p.o. prednisone on Days 1-5. The combination chemotherapy was given twice at a 14-day interval. Radiotherapy was given to involved areas at a fraction size of 2.0-2.5 Gy up to a total of 40 Gy within 4-5 weeks. The mean follow-up period was 63 months. RESULTS: The 5-year overall survival rate was 89%. The 5-year cause-specific survival and progression-free survival rate was 90% and 81%, respectively. The 5-year progression-free survival rate for patients with Waldeyer's ring primaries was 93%. Patients with tumor <5 cm in size had greater 5-year progression-free survival than those with tumor >5 cm in size (85% vs. 33%, p <0.05, log-rank test). Grade 4 neutropenia was seen in 12% of patients; however, 93% of patients (38 of 41) received chemotherapy as scheduled with the support of granulocyte colony-stimulating factor. CONCLUSION: Biweekly THP-COP plus radiotherapy is feasible and effective for Stage I-II low-risk non-Hodgkin's lymphoma.     

Extranodal non-Hodgkin's lymphoma presenting as an abdominal wall mass. A case report and review of the literature

Soft tissue lymphoma is a very rare clinical entity with varying presentation characteristics and atypical clinical and imaging features. The present report describes a patient who presented with a painless soft tissue mass on the posterolateral surface of the abdominal wall, simulating a neoplasm of mesenchymal origin. After complete surgical excision, the tumor was diagnosed as a diffuse large B-cell lymphoma. No B-symptoms were present and clinical staging did not reveal other sites of disease (stage I EA). The International Prognostic Index score was equal to 1 and classified the patient to the good risk group. Post-operatively the patient was treated with immuno-chemotherapy consisting of rituximab plus cyclophosphamide, epirubicin, vincristine and prednisolone and is currently free of disease for 10 months. The case is discussed with a brief review of the literature on the diagnosis, treatment and outcome of soft tissue lymphomas.     

Radiation therapy treatment of stage I and II extranodal non-Hodgkin's lymphoma of the head and neck

We have reviewed the records of 76 patients with Stage I or II extranodal non-Hodgkin's lymphoma who were referred to the Division of Radiation Oncology, Mallinckrodt Institute of Radiology, during the years 1964 through 1974. The histologic slides were reviewed in the 67 cases in which they were available. Forty-three percent of Ann Arbor Stage I and II patients relapsed after primary radiation treatment.Seventy-three percent of these failed in sites distant from the irradiated volume. Failures in the treated volume were infrequent (7%) except in those patients presenting with primary lesions of the brain (4/5). Those patients presenting with lesions of Waldeyer's ring experienced a decrease in survival with increasing tumor size. Because of the high rate of failure in distant sites with tumors in the lingual and palatine tonsils, we are recommending the study of adjuvant chemotherapy in these cases, after primary radiation treatment.     

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue of the head and neck area: high rate of disease recurrence following local therapy

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphoma is a distinct entity with specific clinical and pathologic features that may affect diverse organs. MALT-lymphomas remain localized within their original environment for a long period of time. As recent data have demonstrated a relatively high rate of multiorgan involvement at diagnosis, the authors have retrospectively evaluated 36 patients presenting with MALT-lymphoma in the head and neck area. The authors focused on patients' disease localization, initial treatment, clinical course, and follow-up. METHODS: Thirty-six patients with a histologically verified diagnosis of an extranodal marginal zone B-cell MALT-lymphoma arising in the head and neck area were included in this retrospective analysis. RESULTS: Treatment consisted of surgical resection as the sole treatment in 4 patients (11%), surgical resection with consecutive radiotherapy in 13 patients (36%), radiotherapy alone in 11 patients (31%), chemotherapy in 2 patients (6%), surgical resection plus radiotherapy and chemotherapy in 4 patients (11%), and combined radiation and chemotherapy in 1 patient (3%). Complete and partial disease remissions after initial treatment were achieved in 22 (61%) and 13 patients (36%), respectively, whereas one patient refused any therapy. Four patients (11%) were lost to follow-up and 15 patients (43%) have had disease recurrence after a median time of 11 months (range, 3-80 months). CONCLUSIONS: These data suggest that MALT-lymphomas of the head and neck area are preferentially treated using local modalities such as radiation and/or resection. This practice, however, is associated with an unexpectedly high rate of dissemination or disease recurrence. Obtaining an initial complete response is crucial in these patients. According to previous data, the possibility of understaging in such patients cannot be ruled out. Clinical trials with application of systemic treatment are warranted for these patients.     

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.     

Biologic progression in non-Hodgkin's lymphoma. A flow cytometric study

The nuclear DNA content of 37 primary non-Hodgkin's lymphomas both at presentation and at relapse was determined by flow cytometric analysis from paraffin-embedded tissue to investigate changes in DNA ploidy and S-phase fraction (SPF) during the course of the disease, and their association with survival. The repeat biopsies were done from 5 months to 15 years after the diagnosis. Four low-grade lymphomas according to the Working Formulation transformed into intermediate-grade lymphomas (four of 11, 36%), and four intermediate-grade lymphomas into high-grade lymphomas during the follow-up (four of 16, 25%), and five of these eight transformed lymphomas were fatal within 18 months after relapse. The SPF correlated strongly with poor prognosis if measured either from the primary biopsy (P = 0.008), the first (P = 0.009), or the latest repeat biopsy (P = 0.006). If SPF was greater than or equal to 6% larger in a repeat biopsy than at presentation prognosis was poor; six of nine such patients died from lymphoma within 11 months from recurrence. An increase of greater than or equal to 6% in the SPF was more common in high-grade (four of nine, 44%) and intermediate-grade (four of 16, 25%) lymphomas than in low-grade lymphomas (one of 11, 9%), and it was occasionally (three of nine) associated with a morphologic change. In a few cases a repeat biopsy was diploid despite DNA aneuploidy at presentation. In conclusion, the study provides evidence that not only may low-grade lymphomas transform into higher grade lymphomas, but high-grade lymphomas may also frequently transform into more malignant forms during the course of the disease. The SPF is useful in monitoring the biological behavior of non-Hodgkin's lymphoma, and it appears to give information not obtained by histologic study alone.     

Primary gastric non-Hodgkin's lymphoma. A retrospective clinico-pathological study.

Prognostic factors and treatment results were analysed in 72 consecutive patients with primary gastric lymphoma treated between 1970 and 1985. There were 37 patients in stage IE, 17 in IIE, 3 in IIES and 15 in stage IV. Histopathological re-evaluation and classification according to the TNM system were performed. We found that disseminated disease (stage IV), serosal penetration (T3), involvement of adjacent organs (T4) and extensive abdominal lymph node involvement (N3) were poor prognostic factors. Neither histological malignancy grading, nor the appearance of lympho-epithelial lesions were significantly associated with relapse-free survival. Forty-six patients with 'limited localized' disease (stage IE, IIE, N3 excluded) received potentially curative treatment (surgery, radiotherapy, chemotherapy or combinations thereof), of whom 85% remained relapse-free. Thirty-four patients did only get local treatment (surgery and/or radiotherapy) with curative potential, the relapse-free survival rate was 85%. We conclude that primary gastric lymphoma stage IE and IIE (N3 excluded) is often a truly localized disease that can be cured with local therapy.