|Primary (extranodal) lymphoma arising in the
paranasal sinus (e.g. the maxilla) is quite rare and there is a minimal amount of
information available. The survival statistics vary widely as noted below. In general
these patients are treated with combine modality therapy (CMT) generally chemotherapy
(e.g. R-CHOP) followed by involved field irradiation
From Cancer. 1997 Aug 1;80(3):477-88. below: In Western populations, lymphomas of the nasal cavity and paranasal sinuses rank among the uncommon extranodal lymphomas, accounting for 0.17% of all lymphomas in the Kiel Lymph Node Registry The limited clinical experience with these lesions has resulted in controversies regarding pathologic classification, natural history, and optimal management.Historically, an ambiguous nomenclature has been applied to lesions in this region. Terms have included polymorphic reticulosis, pseudolymphoma, midline granuloma syndrome, lethal midline granuloma, nonhealing midline granuloma, necrosis with atypical cellular exudate, midline destructive granuloma, and idiopathic midline destructive disease. Over the past decade, it has become appreciated that these lesions are lymphomas of the sinonasal tract, rendering this previously used nomenclature obsolete.
Geographic differences in the frequency and histologic subtype of these tumors have become more apparent. In Asian populations and in Peru, nasal lymphomas are more common and are predominantly T-cell lymphomas with angiocentric features, whereas B-cell subtypes are typically more common among the sinonasal lymphomas observed in Western populations. Although pathologic classification of these lesions has become more clear, controversies regarding clinical behavior remain. This retrospective review of 70 cases of lymphoma of the nasal cavity and paranasal sinuses in a Western population was undertaken to further define the natural history of these lesions and to evaluate the treatment results and prognostic factors for two sequentially treated groups of patients.
In this update of the authors' experience with sinonasal lymphomas, the clinical presentation was similar to that previously reported from MDACC as well as others in Western countries. Patients tend to be elderly males with locally advanced tumors. Maxillary sinus tumors are more common than nasal cavity primaries. Cervical lymph node metastases are present in approximately 25% of patients with localized disease, and the histology of > 90% of the lesions is intermediate grade. Reports concerning the immunophenotype of sinonasal lymphomas in Western populations have been mixed, with some finding B-cell lesions to be much more common,whereas others note a greater frequency of T-cell lesions. In this series, immunophenotype was available for 19 tumors. In agreement with a large series recently reported by Abbondanzo a slight predominance of B-cell lesions was observed.
The above clinical picture is in contrast to that observed in Asian populations. Asian patients tend to be male but younger than those observed in Western populations, with a median age near 50 years. The nasal cavity, the second most frequent site of extranodal lymphomas after the gastrointestinal tract, is more common as a primary site than the maxillary sinus in Asia. Although most lesions are classified as intermediate grade in the Working Formulation, they are predominantly T-cell lymphomas with angiocentric features, also termed angiocentric immunoproliferative lesions (AILs)
The use of chemotherapy in patients with sinonasal lymphoma has been standard treatment at many institutions for years. This practice has been based on the high rates of distant recurrence after XRT in all but those patients with small Stage IE disease and on the general efficacy of chemotherapy in treating intermediate grade lymphomas. The report by Liang et al. from China of 100 primary nasal T-cell lymphomas found no improvement in outcome with the addition of chemotherapy.In contrast, the results of the current study demonstrate a statistically significant improvement in FFP with CMT for patients with paranasal sinus and nasal cavity lymphomas. The explanation for the discrepancy between the two series is unclear, but the high percentage of AILs in the Hong Kong experience is one possible explanation. When compared with B-cell lymphomas, T-cell lymphomas have been reported to have a significantly worse recurrence free survival and OS when treated with combination chemotherapy. In addition, Aviles et al. reported that the presence of angiocentric features in sinonasal lymphomas predict for lower recurrence free survival when treated by XRT alone as well as an inferior salvage rate with combination chemotherapy.
Variable patterns of failure after treatment have been reported. In this report, only 4 patients (6%) experienced local failure. However, local failure appears to be more common in nasal T-cell lymphoma. In the series by Liang et al., local failure occurred in 15% of patients and accounted for 71% of all recurrences after complete response.Again, the high proportion of angiocentric lesions may explain this discrepancy, but technical XRT considerations cannot be excluded.
Several institutions have reported a high incidence of CNS relapse for patients with sinonasal lymphoma. Along with others, the authors have not observed this predilection for CNS spread. The reasons for this difference are not known. Cooper et al. have suggested that as in other lymphomas, the development of CNS disease may be a reflection of systemic lymphoma progression. The authors of the current study have observed cases that support this explanation. One of the 12 patients who presented with Stage IV disease had widespread lymphoma with CNS involvement, and another patient had CNS failure after salvage chemotherapy as one manifestation of widely disseminated lymphoma. However, the authors have also found CNS failure to be associated with local failure, again suggesting technical explanations for failure pattern. The single CNS failure after initial therapy that they observed was secondary to a radiotherapy marginal miss. In addition, two of the five patients excluded from the study because they received XRT outside MDACC developed local recurrence, and one presented with CNS failure at the time of an otherwise isolated local failure. Local failure at the base of the skull can remain unrecognized clinically and can provide access to the CNS. This issue of CNS failure is reminiscent of a similar one involving parameningeal rhabdomyosarcoma. Early reports of high rates of CNS failure led to children with parameningeal primaries receiving whole brain or craniospinal irradiation. With improvement in diagnostic imaging allowing better tumor definition and increased recognition of the need for generous base of skull coverage, CNS failures have become less common. Based on more recent treatment results, XRT to the CNS is currently recommended only for patients with documented CNS disease at diagnosis. Consistent with the parameningeal rhabdomyosarcoma experience, each of the series reporting high CNS failure rates in paranasal sinus lymphomas included patients treated prior to the development of high quality CT imaging and MRI. In addition, in one of these series, all primary lymphomas in the anatomic vicinity of the maxillary sinus (including the orbit, palate, and nasopharynx) were associated with high CNS recurrence rates. Local failure may be a more common cause of CNS failure than previously believed for these lymphomas. Lumbar puncture and MRI of the brain appear to be indicated for patients with base of skull involvement.
Significant treatment-related morbidity occurred in this series of patients. This reflects the long period of time that the study spans. Fewer complications have occurred in patients treated more recently. With improved dental prophylaxis, treatment of all radiotherapy fields daily, and lower radiation doses, osteonecrosis has become very rare in this patient group. Radiation-induced visual complications have been carefully analyzed in two recent reports. At the authors' currently recommended dose of 39.6 Gy in 22 fractions, damage to the optic nerve is not observed. Corneal damage and resultant loss of vision are a function of the structures being irradiated and the dose they receive. If the cornea and lacrimal gland can both be spared, damage is not observed. If only one of these structures can be blocked, the complication rate historically has been 15-25%. Newer methylcellulose and/or polyvinyl alcohol-based eye lubricants may decrease complications in this group of patients, but data are not yet available. If neither the cornea nor the lacrimal gland can be blocked, loss of vision approaches 100%. Unfortunately, patients with lesions large enough to warrant such extensive radiation fields are the ones who are at greatest risk for local recurrence with its attendant morbidity and mortality. Omitting XRT to spare morbidity can be considered, but in the only data available for treatment of these lesions with chemotherapy alone, local recurrence occurred in 4 of 16 patients. Furthermore, the local recurrence rate in the report by Liang et al. supports the need for local treatment in addition to chemotherapy for patients with AILs.
Reported 5-year survival rates for sinonasal lymphomas have ranged from 12-86%. The combination of a broad distribution of survival rates and variable patterns of recurrence has resulted in diverse therapy recommendations. These have included whole brain XRT, intrathecal chemotherapy, or both. It has also been suggested that these patients should be considered for experimental consolidation therapy such as autologous bone marrow transplantation. The authors' results with CMT (and no CNS treatment) in a Western population yielded 5-year FFP rates of 87% and 70% for patients with Stage IE and IIE lymphoma, respectively. Two recent randomized studies also favor CMT over chemotherapy alone for patients with early stage intermediate and high grade non-Hodgkin's lymphoma. Therefore, the authors continue to recommend combination chemotherapy with involved field XRT for these patients. Currently, their preference for chemotherapy is a doxorubicin-containing regimen such as CHOP. Although the median number of cycles of chemotherapy in this series was eight, there are now data indicating that three cycles of CHOP may be sufficient when compared with XRT. Currently, different numbers of chemotherapy cycles are being tested in a prospective trial at MDACC. When chemotherapy is medically contraindicated, XRT is a reasonable alternative for patients with Stage IE(T1-3) disease but is insufficient for patients with more advanced disease (Stage IE(T4), II-IV).
|Sinonasal lymphoma: a clinicopathologic
analysis of 58 cases from the Massachusetts General Hospital.
Cuadra-Garcia I, .Am J Surg Pathol. 1999 Nov;23(11):1356-69.
Departamento de Patologia, Hospital de Oncologia, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Segura Social, Mexico City.
Few large series compare lymphomas of the nasal cavity with those of the paranasal sinuses. We studied the cases of 58 patients, 34 males and 24 females, aged 7 to 92 years (mean, 57 years), who had lymphoma involving the nasal cavity or paranasal sinuses. Thirty-three patients had diffuse large B-cell lymphoma (DLBCL). Twenty-three were male and 10 were female, with an age range of 7 to 91 years (mean, 63 years); two were HIV-positive. Only 2 of 11 cases tested (one in an HIV-positive patient and one of lymphomatoid granulomatosis type) were Epstein-Barr virus (EBV)-positive. Thirty (91%) involved paranasal sinuses, 10 with nasal involvement, whereas three cases had nasal, but not sinus, involvement. At last follow-up, 16 (67%) were free of disease 7 to 169 months later (mean, 65 months), and 8 (33%) had died of disease 2 to 166 months later (mean, 45 months). Seventeen patients had nasal-type natural killer (NK)/T-cell lymphoma. There were 10 women and 7 men, aged 27 to 78 years (mean, 48 years). Thirteen of 14 were EBV-positive. Sixteen patients had nasal involvement, eight with sinus involvement. Eleven (73%) of 15 were alive and well 6 to 321 months later (mean, 139 months), three (20%) died of lymphoma 1, 11, and 12 months later, and one (7%) is alive with disease. There was one case each of marginal zone B-cell lymphoma, Burkitt's lymphoma, Burkitt-like lymphoma, peripheral T-cell lymphoma of unspecified type, and adult T-cell lymphoma/leukemia. In an additional three cases, the lymphomas were composed predominantly of large cells, but no immunophenotyping could be performed for subclassification. In 19 cases (17 DLBCLs, 1 Burkitt-like lymphoma, and 1 lymphoma of uncertain lineage), presenting symptoms included complaints related to the eyes. In 16 cases (13 DLBCLs, 1 Burkitt-like lymphoma, 1 nasal NK/T-cell lymphoma, and 1 lymphoma of uncertain lineage), the orbit was invaded by lymphoma. In our series, the most common lymphoma to arise in the sinonasal area is DLBCL, followed by nasal NK/T-cell lymphoma. Comparison of these two types of lymphoma showed that lymphomas involving sinuses without nasal involvement were predominantly DLBCLs (20 of 21), whereas nasal cavity lymphomas without sinus involvement were usually NK/T-cell type (8 of 11) (p = 0.000125). Compared with patients with DLBCL, patients with nasal NK/T-cell lymphoma were overall younger, with a lower male-to-female ratio. Lymphomas of B-cell lineage were more likely to be associated with symptoms related to the eyes (p < 0.0005) and to have extension to the orbit (p < 0.01) than were lymphomas of T- or NK-cell lineage. In contrast to results of Asian studies in which nasal NK/T-cell lymphoma has a very poor prognosis, our nasal NK/T-cell lymphomas had an outcome similar to that of DLBCL.
malignant lymphoma of the sinonasal tract--treatment outcome for 53 patients according to
Non-Hodgkin's lymphoma of the paranasal sinuses: clinical and
pathological features, and response to combined-modality therapy.
Lymphoma of the nasal cavity and paranasal sinuses: improved outcome
and altered prognostic factors with combined modality therapy.
Lymphoma of the nasal cavity and paranasal sinuses: treatment and
outcome of early-stage disease.
Non-Hodgkin's lymphoma of the sinonasal tract.
Primary non-Hodgkin's lymphomas of the paranasal sinuses and nasal
cavity. A report of 18 cases with stage IE disease.