(J. Cancer Res. Pract.

) 28(4),183-188, 2012
journal homepage:www.cos.org.tw/web/index.asp

Case Report Sinonasal Diffuse Large B Cell Lymphoma

Weng-Chi Lei1, Ruey-Long Hong2*
1 2

Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan

Abstract.
Non-Hodgkin lymphoma arising from the sinonasal tract is rare. We present hereby a 71 year-old man with the chief complaints of a left nasal mass, nasal obstruction, bleeding and anosmia. Functional endoscopic sinus surgery and biopsy yielded diffuse large B cell lymphoma. The patient remained disease-free for about 6 years after 4 courses of CHOP (Cyclophosphamide, doxorubicin, vincristine, prednisolone) and consolidative involved field radiotherapy, and then the lymphoma recurred in the right nasal cavity. Lymphoblasts were present in the peripheral blood, which turned out to have originated from lymphoma with bone marrow involvement. A cerebrospinal fluid study was also positive for lymphoblasts. The patient died 3 months after the disease recurrence despite salvage chemotherapy. The clinical characteristic of sinonasal diffuse large B cell lymphoma is distinct, and there is no consensus regarding standard treatment in this rare group of patients. Keywords : sinonasal lymphoma, diffuse large B cell lymphoma

B
1
1 2

2*

71 B CHOP 6 B

: B

INTRODUCTION
Diffuse large B cell lymphoma (DLBCL) occurs in

about 40% of newly diagnosed cases of non-Hodgkin lymphoma. It is a heterogeneous disease and its clas-

184

W. C. Lei et al./JCRP 28(2012) 183-18

sification, according to the 2008 WHO classification of hematologic malignancies, depends mainly on the primary site of involvement. Lymphomas arising from the sinonasal site comprise mostly of natural killer (NK)/T-cell origin [1,2], while reports regarding sinonasal DLBCL are rare. Here we report a case of sinonasal DLBCL, initially presented as stage IIE disease. The lymphoma relapsed as stage IV disease after remaining disease-free for about 6 years. Clinical characteristics and prognosis of this rare group of DLBCL will also be discussed.

CASE REPORT
A 71 year-old man had a history of hypertension and herniated intervertebral disc. He used to smoke one pack per day for over 40 years. He suffered from left nasal obstruction, bleeding and anosmia in February 2005. No headache, blurred vision, diplopia, ear fullness, otalgia, local swelling or numbness was complained of. Besides, there was no fever, weight loss or night sweats. He visited an ENT clinic at a local hospital, and a functional endoscopic sinus surgery and biopsy was performed, which yielded a left nasal mass. Pathology showed medium to large-sized mononuclear cells with a pleomorphic nucleus containing a prominent nucleolus (Figure 1A). These large cells were stained positive to CD20, which was compatible with the diagnosis of diffuse large B cell lymphoma. He later visited our hospital for a second opinion. On admission, necrotic tissue and debris were found in the left nasal cavity. No other lesion was noted at the ENT field and no neck lymph node was palpable. A PET scan (Figure 2) showed abnormal focal areas of increased activity due to hypermetabolism at the left

B
Figure 1. A) Pathology of left nasal mass in February 2005 (H&E stain, x400); B) Pathology of recurrent tumor in right nasal cavity in September 2011 (Left: H&E stain, x400;

*Corresponding author: Ruey-Long Hong M.D. * Tel: +886-2-23123456 ext.67510 Fax: +886-2-23711174 E-mail: rlhong@ntu.edu.tw

right: IHC stain for CD20)

ethmoid and maxillary sinus, which was compatible with malignancy. Besides, lymph node metastasis to

W. C. Lei et al./JCRP 28(2012) 183-188

185

resonance imaging (MRI) in October 2005 showed complete remission (CR). In addition, a PET scan in December 2009 and head and neck and brain MRI in March 2011 all showed no evidence of recurrence. The patient remained event-free until September 2011, when diplopia developed. A mass in the right nasal cavity was found by ENT endoscopy. Recurrence of lymphoma was suspected. Biopsy of the right nasal mass showed large-sized cells with pleomorphic nuclei, and some of them contained a prominent nucleolus. These large cells were diffusely stained positive for CD20 (Figure 1B), which confirmed recurrent disease. Besides, a hemogram showed anemia and left-shifted white blood cells. Lymphoblasts with a high nucleus-cytoplasmic ratio in the peripheral blood were also found (Figure 3A). A bone marrow study showed lymphoma cell infiltrations (Figure 3B). These cells were positive for CD20 and negative for CD3 by flow cytometry. Therefore, recurrent diffuse large B cell lymphoma, stage IV with IPI 4 points was diagnosed. Salvage chemotherapy with CEOP (Cyclophosphamide, epirubicin, vincristine, prednisolone) was administered thereafter. However, he suffered from progressive weakness and remained bed-ridden despite salvage chemotherapy. Cytology of CSF yielded presence of lymphoma cells (Figure 4). A diFigure 2. PET scan showing left ethmoid, maxillary sinus mass with bone destruction and left thoracic inlet lymph node agnostic impression of lymphoma with central nervous system (CNS) involvement was made, and intrathecal chemotherapy (methotrexate, Ara-C and steroid) was given then. Whole brain radiotherapy was also carried out. Because of deteriorating clinical condition the left thoracic inlet region was also found. Laboratory data showed leukocytosis (16000/L) with normal WBC differentiation. Elevated LDH (481U/L), ALT (122U/L) and ALP (283U/L) levels were found. Staging workup concluded the disease stage as IIE, with the international prognostic index (IPI) as 2 points. The patient later received four courses of CHOP (Cyclophosphamide, doxorubicin, vincristine, prednisolone) plus consolidative involved field radiotherapy (50Gy/25 fractions). A follow-up magnetic and progressively poor performance status, palliative oral chemotherapy with cyclophosphamide was given to this patient. He later died of septicemia in January 2012.

DISCUSSION
Although extranodal NK/T cell lymphoma, nasal type has already been included as a distinct entity in the 2008 WHO classification of hematologic malignancies, the clinical characteristics and prognosis of

186

W. C. Lei et al./JCRP 28(2012) 183-188

both B and T cells. The 5-year overall survival for B and T or NK/T cell lymphomas were 66% and 41%, respectively (p=0.042). Patients with an elevated LDH level had a worse outcome, and LDH was the only

independent poor prognostic factor for DLBCL patients in the multivariate analysis in this study. Another study from Korea, using immunophenotypic analysis with CD20, CD45RO, CD3, CD56 as differentiating markers [1], identified B cell in 25%, T cell in 33%, and NK/T cell in 42% of lymphoma primarily arising from the sinonasal region. The majority (63%) of B cell lymphoma involved the paranasal sinuses while most of the T cell (67%) and NK/T cell (68%) lymphoma involved the nasal cavity. The pattern of treatment failure was similar between B cell and NK/T cell lymphomas. As compared to NK/T cell lymphoma, patients with sinonasal B cell lymphoma had a longer overall survival and disease-free survival. The five year survival rates for B cell and NK/T cell lymphomas were 57% and 37%, respectively. Another study from China focused on 25 patients with primary nasal DLBCL [5]. The median age was 48 years with male predominance (72%). Most of the patients had stage I disease (72%) with paranasal extension (84%). B symptoms (weight loss, night sweats, and fever) (4%) and an elevated LDH level (20%) were infrequent and over three-fourths of them were stain, x1000); B) bone marrow infiltrated with lymphoma cells (Liu stain, x1000)

B
Figure 3. A) Lymphoblasts in peripheral blood (Liu

Figure 4. Lymphoma cells in CSF (Liu stain, x1000)

of low risk (IPI 0-1 point). Median overall survival was 35 months, and 3-yr overall survival rate was 51%. Patients with an ECOG performance score of

diffuse large B cell lymphoma arising from this anatomic site is not well defined. Noses and sinuses account for about 20% of all extranodal sites involved in non-Hodgkin lymphoma and are the third most common site of all [3]. In addition, a recent study [4] from Tainan, Taiwan, showed that among 76 patients with lymphomas arising from the upper aerodigestive tract, 18 (27%) of them were of the sinonasal region. B cell accounted for 16.7% (3 of 18) and NK/T cell accounted for 83.3% (15 of 18) of these 18 patients. Stage I/II disease accounted for over 90% of cases for

0-1 had a better outcome than patients with a score of 2-3 (3-yr OS: 51% vs 20%, p=0.025). Patients with low risk also had longer survival than those with higher risks (3-yr OS: 54% vs 17%, p=0.033). In addition, patients achieving CR after therapy also fared better than non-CR patients (3-yr OS: 67% vs 13%, p=0.008). In this study, 7 of 8 patients with sufficient data evaluable for the pattern of failure had extranodal failures. One had local recurrence. Among the 7 extranodal sites involved, only one (14%) was CNS involved in recurrence.

W. C. Lei et al./JCRP 28(2012) 183-188

187

Four of 14 patients (29%) suffered from CNS relapse in another case series of primary paranasal sinus DLBCL [6]. Two of the 4 patients were in CR and 2 were in PR after CHOP or CHOP-like regimen. None of these 4 patients achieved second CR after salvage intrathecal and systemic chemotherapy and all of them died of their disease 2 to 11 months after CNS relapse. CNS prophylaxis was suggested in addition to systemic chemotherapy by the authors because of the high rate of CNS relapse. Rituximab plus anthracycline-based chemotherapy became the standard treatment of DLBCL in the past decade[7,8]. In the prospectively randomized study by Feugier et al. [9] adding rituximab to CHOP did not influence the risk of CNS occurrence in elderly DLBCL patients compared to CHOP alone. Low rituximab diffusion across the bloodbrain barrier was proposed as the mechanism of the lack of influence of rituximab. Age-adjusted IPI was the only identified risk factor that influenced relapse of CNS disease. Although a few reports discussed the role of rituximab in treating sinonasal DLBCL, concerning its high rate of CNS relapse, CNS prophylaxis has nevertheless been proposed by some authors [6]. Guirguis et al. [10] retrospectively reviewed the impact of CNS prophylaxis and outcome of DLBCL patients treated with R-CHOP. Patients receiving CNS prophylaxis tended to be more advanced in the disease, and had more severe extranodal disease and a higher IPI score. Patients who did not receive CNS prophylaxis had lower events (2.7%) than those who did (11.1%). Testicular involvement was the only significant prognostic factor for CNS relapse (HR: 33.5, p<0.001). They concluded that R-CHOP may negate the need of CNS prophylaxis except for patients with testicular lymphoma. There seems to be some differences regarding the clinical manifestations and outcome of patients with lymphomas from the sinonasal region between the West and the East. Fifty-eight patients presenting with lymphoma from the nasal cavity or paranasal sinuses were reported from Massachusetts General Hospital

[11]. In this report, DLBCL was more frequent than NK/T cell lymphoma (57% vs. 29%). Besides, there were more female patients with NK/T cell lymphoma while there were more male patients with DLBCL. At last follow-up, 73% of NK/T cell lymphoma patients had no evidence of disease, in contrast to 67% of DLBCL patients remaining disease-free. Furthermore, more continuous complete remission was noted in NK/T cell lymphoma patients (73% vs. 58% of DLBCL).

CONCLUSIONS
In conclusion, DLBCL is a rare presentation of malignancy in the sinonasal region. In most of cases DLBCL presents as stage I or II disease. There are some discrepancies regarding clinical characteristics and treatment outcome between Eastern and Western sinonasal lymphomas, with NK/T cell more prevalent in the East and DLBCL more prevalent in the West. Besides, NK/T cell lymphoma confers a worse outcome in the East, while it is similar to DLBCL in the West. Until now, there is no consensus regarding standard treatment in this rare group of patients. CNS prophylaxis may be needed on account of the high rate of CNS relapse. More studies are needed to better understand the biologic nature of DLBCL and define its proper treatment.

REFERENCES
1. Kim GE, Koom WS, Yang WI, et al. Clinical relevance of three subtypes of primary sinonasal lymphoma characterized by immunophenotypic analysis. Head Neck 26: 584-93, 2004. 2. Li YX, Coucke PA, Li JY, et al. Primary non-Hodgkin's lymphoma of the nasal cavity: prognostic significance of paranasal extension and the role of radiotherapy and chemotherapy. Cancer 83: 449-56, 1998. 3. Yang QP, Zhang WY, Yu JB, et al. Subtype distribution of lymphomas in Southwest China: analysis of 6,382 cases using WHO classification

188

W. C. Lei et al./JCRP 28(2012) 183-188

in a single institution. Diagn Pathology 6: 77, 2011. 4. Chen SW, Chang ST, Lu CL, et al. Upper aerodigestive tract lymphoma in Taiwan. J Clin Pathol 63: 888-93, 2010. 5. Lu NN, Li YX, Wang WH, et al. Clinical behavior and treatment outcome of primary nasal diffuse large B-cell lymphoma. Cancer 118: 1593-8, 2012. 6. Oprea C, Cainap C, Azoulay R, et al. Primary diffuse large B-cell non-Hodgkin lymphoma of the paranasal sinuses: a report of 14 cases. Br J Haematol 131: 468-71, 2005. 7. Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 346: 235-42, 2002. 8. Pfreundschuh M, Trumper L, Osterborg A, et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients

with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol 7: 379-91, 2006. 9. Feugier P, Virion JM, Tilly H, et al. Incidence and risk factors for central nervous system occurrence in elderly patients with diffuse large-B-cell lymphoma: influence of rituximab. Ann Oncol 15: 129-33, 2004. 10. Guirguis HR, Cheung MC, Mahrous M, et al. Impact of central nervous system (CNS) prophylaxis on the incidence and risk factors for CNS relapse in patients with diffuse large B-cell lymphoma treated in the rituximab era: a single centre experience and review of the literature. Br J Haematol 159: 39-49, 2012. 11. Cuadra-Garcia I, Proulx GM, Wu CL, et al. Sinonasal lymphoma: a clinicopathologic analysis of 58 cases from the Massachusetts General Hospital. Am J Surg Pathol 23: 1356-69, 1999.