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Year : 2021  |  Volume : 6  |  Issue : 1  |  Page : 1-6

Extranodal non-Hodgkin's lymphoma of the sinonasal tract: A review

Department of Otorhinolaryngology, IMS and SUM Hospital, Siksha “O” Anusandhan University (Deemed to be), Bhubaneswar, Odisha, India

Date of Submission04-Jul-2020
Date of Decision12-Sep-2020
Date of Acceptance29-Sep-2020
Date of Web Publication08-Apr-2021

Correspondence Address:
Prof. Santosh Kumar Swain
Department of Otorhinolaryngology, IMS and SUM Hospital, Siksha “O” Anusandhan University (Deemed to be), Bhubaneswar - 751 003, Odisha
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/bjhs.bjhs_63_20

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Lymphoma is classified into Hodgkin's lymphoma (HL) or non-HL (NHL). NHL is more commonly found in the head-and-neck region. Majority of the extra-nodal location for NHL is the Waldeyer's ring. These NHLs are rarely found in the sinonasal tract. The clinical presentations of the extra-nodal sinonasal NHL are usually nonspecific. Computed tomography scan of the head-and-neck region usually reveals the extent of the neoplasm. However, the confirmatory diagnosis is done by the tissue biopsy and study of the immunohistochemistry. The treatment modality is controversial in regards to the best therapeutic option. Chemotherapy or concomitant chemoradiation is an important treatment option. Surgery has a limited role for the treatment of the sinonasal NHL. The increasing prevalence and the significant morbidity of the sinonasal NHL are often critical to do early diagnosis and treatment. Early diagnosis along with continuous monitoring and close follow-up are recommended for the early diagnosis and effective treatment. Clinicians should have knowledge regarding the clinical presentations of the extranodal NHL. Correct and timely diagnosis is helpful for effective treatment of the sinonasal NHL. The aim of this review article is to discuss about the etiopathology, clinical presentations, investigations, and current treatment of the sinonasal NHL.

Keywords: Large B-cell lymphoma, non-Hodgkin's lymphoma, sinonasal tract

How to cite this article:
Swain SK, Acharya S. Extranodal non-Hodgkin's lymphoma of the sinonasal tract: A review. BLDE Univ J Health Sci 2021;6:1-6

How to cite this URL:
Swain SK, Acharya S. Extranodal non-Hodgkin's lymphoma of the sinonasal tract: A review. BLDE Univ J Health Sci [serial online] 2021 [cited 2022 Jul 2];6:1-6. Available from: https://www.bldeujournalhs.in/text.asp?2021/6/1/1/313359

Lymphomas are important clinical entity in the modern medicine and often create challenge to the clinicians. Malignancy of the head-and-neck region accounts for 3% of all the cancers where lymphoma occupies the second place in terms of frequency.[1] Lymphoma is the second most common neoplasm found in the head and neck region after squamous cell carcinoma.[2] Lymphomas are group of malignant tumors arising from the lymphoreticular system, which is divided into Hodgkin's disease and non-Hodgkin's lymphomas (NHLs). Lymphomas constitute 3%–5% of all the malignancies with NHL account to 60% of the cases.[3] These may appear in the lymph nodes in the head-and-neck region or as extra-nodal tumors. The NHL at the sinonasal tract is considered as extra-nodal lymphoma and rarely found in the clinical practice. The sites for extranodal lymphomas are found in the oral cavity, pharynx, Waldeyer's ring, sinonasal tract, larynx, and trachea. In these extra-nodal sites, the mucosa-associated lymphoid tissue is richly present and can give rise to several lymphoproliferative disorders. The sinonasal tract such as nasal cavity and paranasal sinuses are rarely affected by the primary NHL.[4] Primary NHL of the sinonasal tract is uncommon, and majority of these cases are primarily found in maxillary sinus followed by the ethmoid sinuses and the nasal cavity.[5] In the medical literature, NHL in the sinonasal tract has been known as monoclonal B-cell neoplasia, polymorphic reticulosis, lethal granuloma, and pseudolymphoma.[6] According to the Revised European-American Lymphoma (REAL) classification, NHL is a heterogeneous group of the disease with morphological, peculiar, phenotypic, and molecular features (B-cell, T-cell, and putative natural-killer [NK] cell neoplasm).[7] REAL classification does not differentiate these neoplasms as high or low grade unlike other classification. The aim of this review article is to discuss about the etiopathology, clinical presentations, and current management of the sinonasal NHL.

  Methods for Literature Search Top

For searching the published research articles, we conducted an electronic survey and 156 abstracts were identified through PubMed, SCOPUS, Medline and Google Scholar database with word extranodal NHL and sinonasal tract. A search strategy using Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines was developed. Randomized controlled studies, observational studies, comparative studies, case series, and case reports were evaluated for the eligibility. This article focuses only on the extranodal NHL of the sinonasal tract. The search articles with nonsinonasal NHL and NHL of the lymph nodes were excluded. Review articles with no primary research data were also excluded. The search terms in the database included NHL, sinonasal tract, and extra-nodal lymphoma. The abstracts of the published articles were identified by this search method, and other articles were identified manually from citations. This manuscript reviews the etiopathology, epidemiology, clinical presentations, investigation, and current treatment of the sinonasal NHL. This review article presents a baseline from where further prospective studies for sinonasal NHL could be designed and also helps as a spur for further research in this rarely encountered clinical entity.

  Epidemiology Top

The head-and-neck region of the human body accounts for more than one-third of extranodal lymphomas. The sinonasal tract is rarely affected in the Caucasian population which constitutes 0.2%–2% of the head-and-neck lymphomas.[8] Lymphoma accounts for 11% of the sinonasal cancers.[9] Sinonasal NHL is uncommon in the Caucasian population unlike in South American and Asian populations where it is second place after the digestive tract.[10] Diffuse large B-cell lymphoma (DLBCL) is prevalent among the Caucasian population, whereas NK/T lymphoma is predominates in Asia and South America.[8] DLBCL involves more to the paranasal sinuses and NK/T lymphoma involves more to the nasal cavities.[11] In West, isolated sinonasal lymphoma is commonly seen among elderly male and found in the paranasal sinuses, whereas in the far East, the lesions are more in the nasal cavity and found among younger age group.[8],[12] Globally, there is a clear racial and regional variation of the incidence of NHL. DLBCL is more common in Western population, whereas NK T-cell lymphoma (NKTCL) is common among Asian and Latin American population.[13]

  Etiopathology Top

Lymphomas are the malignancies that arise in the lymphoreticular system and classified into the Hodgkin's lymphoma (HL) and NHL which are described by Dr. Thomas Hodgkin's in 1832.[14] In the head and neck region, NHL represents 60% of all the types of the lymphoma and consists of B-cell, T-cell, and NKTCL on the basis of the histological classification. The DLBCL accounts for the highest frequency among NHL.[15] The exact etiology of the lymphoma is unknown, but the exposure of the virus is often associated with Burkitt's lymphoma, and there is also threefold increase of HL among adults those exposed to Epstein–Barr virus.[16] The NHL has been incidence of 4%–10% among patients with AIDS.[17] However, the common sites for NHL are digestive tract, central nervous system, and bone marrow. There are the several types of the genetic mutation found in the NHLs. In sinonasal NHL, the chance of the mutations in p53, K-ras, c-kit, beta-catenin, and BAK gene is more in B-cell lymphoma, whereas EBV infection and genetic mutations lead to NK/T-cell lymphoma.[18] In the head and neck region, extra-nodal lymphomas most commonly arise in the Waldeyer's ring such as adenoids, tubal tonsils, palatine tonsils, and lingual tonsils.[19] Other sites involved are sinonasal tract (nasal cavity and paranasal sinuses), orbit, thyroid gland, and salivary glands.[20] NHLs are commonly diagnosed as nonepithelial tumor at the nasal cavity and paranasal sinuses such as the maxillary sinus and ethmoid sinuses. The sinonasal NHL often present aggressive progression and lead to local extension.

  Clinical Presentations Top

The clinical presentations and thorough history taking are helpful toward the diagnosis of the sinonasal NHL. The NHL of the sinonasal tract is not easily differentiated and diagnosed as the histopathological pictures and clinical presentations may be similar to inflammatory diseases in its early stages. These malignancies are common in males than females and usually found in the fifth and sixth decades of life. The mean age for the diagnosis of the sinonasal NHL ranges from 45 to 75 years.[8] The clinical presentations are usually nonspecific and vague in nature such as nasal obstruction, nasal congestion, rhinorrhea, headache, and facial swelling with or without pain.[21] Within the paranasal sinuses and nasal cavity, NHL often presents with epistaxis, nasal blockage, with or without blood stained nasal discharge, vision disturbance, hearing impairment, facial swelling, weight loss, and fever.[22] Anterior rhinoscopic examination often show a polypoidal mass and associated with ulceration and necrosis in the early stage of the disease. Endoscopic nasal examination with a zero degree rigid nasal endoscope shows mass in the nasal cavity [Figure 1] with hemorrhagic and friable in nature which often blocks the nasal cavity or sometimes extends to the contralateral side after eroding the nasal septum and bony wall of the nose and sinuses. The endoscopic examination can assess the origin of the tumor from the maxillary sinus, ethmoidal sinus, frontal sinus, and sphenoid sinuses. Clinical examination of the patients may show an irregular mass in the nasal pyramid. The clinical presentations of the sinonasal NHL vary as per the type of the histological pattern of the tumor and staging [Table 1].[23] Majority of the low-grade lymphomas present with sinonasal mass and nasal obstruction.[24] The high-grade variety present with aggressive clinical symptoms such as nonhealing ulcerative lesions, involvement of the cranial nerves, swelling of the face, nasal bleeding, naso-facial pain, sinonasal bony erosion, and proptosis. NK/T cell lymphomas are associated with perforation of the nasal septum with or without destruction. NK/T cell lymphoma often presents with nasal obstruction and nasal discharge, deceased vision, and proptosis. The systemic clinical presentations such as fever of unknown origin, night sweating, and inexplicable loss of weight are often described in patients of HL than with NHL.[25] The staging of the sinonasal NHL is usually based on the Ann–Arbor classification [Table 2]. This pathology may confuse with granulomatous disease of the nasal cavity such as Wegner's granulomatosis.
Figure 1: Diagnostic nasal endoscopy showing polypoidal appearance of the sinonasal non-Hodgkin's lymphoma

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Table 1: Clinical profile of the patients with extra-nodal non-Hodgkin's lymphoma of the sinonasal tract (Shohat et al.[23])

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Table 2: Ann arbor staging of lymphoma

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  Investigations Top

The confirmatory diagnosis of the extranodal NHL at the sinonasal tract is done by the tissue biopsy and study of the immunohistochemistry. Imaging includes contrast-enhanced computed tomography (CT) and MRI which are helpful to assess the extent of the neoplasm, bone destruction, staging of the tumor and also helpful for choosing the suitable site for the biopsy. The imaging pattern of the bulky tumor, particularly with infiltrating growth leads to bony erosion of the sinus walls.[12] High-grade B-cell lymphoma may cause invasion of the orbital soft tissue and bony destruction more associated with high-grade T-cell lymphoma.[26] Radiograph shows a definite mass with less commonly cloudy or opaque paranasal sinuses. CT scans [Figure 2] are helpful for evaluating the extent of the destruction and involvement of the paranasal sinuses and orbits and so considered as the gold standard for evaluation of the tumor. Radiographically, NHL is seen as area of radiolucency lytic lesions and small percentage cases exhibit radio-opaque appearance. This radiolucent pathology may mimic to common odontogenic lesions such as chronic apical periodontitis and chronic periodontitis.[27] However, the radiological findings are not specific to the NHL, so the clinicians consider that approximately 80% of the lesion show osteolytic pattern and remaining 20% show a sclerotic lesions.[28] The diagnosis of the NHL cannot be established on the basis of the imaging criteria. Positron emission tomography (PET) with 18F-fluorodeoxyglucose and PET/CT is helpful for staging of the tumor and evaluating the therapeutic response. The histopathological findings are required for confirmation of the diagnosis and for starting of the oncological treatment. Correct diagnosis is done from the tissue biopsy. Diagnostic nasal endoscopy under local anesthesia is done for obtaining the tissue sample and its histopathological examination. The histopathological analysis is done with hematoxylin and eosin stain which show atypical and large sized lymphocytes [Figure 3]. Immunohistochemical staining shows positive for CD20 [Figure 4], CD79a, bcl-6, and MUM-1. Careful immunohistochemical assessment is important for differentiating the lymphomas from other types of the malignancies as well as the exact types of the lymphoma. Positive staining for leukocyte common antigen from histopathological specimen differentiates the lymphomas from the nonlymphoid tumors.[29] Early diagnosis and staging are required for effective treatment.
Figure 2: Computed tomography scan of the nose and paranasal sinus with coronal view showing sinonasal non-Hodgkin's lymphoma mass with bone erosion in left nasal cavity, maxillary and ethmoid sinuses

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Figure 3: Histopathological picture showing neoplastic cells arranged uniformly with large and round nuclei with little cytoplasm and dispersed coarse to fine nuclear chromatic and inconspicuous nucleoli (HXE, ×400)

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Figure 4: Immunohistochemical staining of tumor cells showing positive for CD20 (×400)

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  Treatment Top

The clinical, histological, and evolutional heterogeneity of the malignant lymphoma creates problems from the treatment point of view and the therapeutic options of these malignancies are significantly changes over the period of time. Before treatment, clinician should know the exact site of the lesion and its spread from the clinical presentations and imaging. The sinonasal NHL often presents with peri-orbital edema, facial swelling, and changes in the mucosal lining of the nasal cavity which are not found in the NHL of other sites. The other nonspecific symptoms such as nasal block, rhinorrhea, rhinitis, and sinusitis are found in sinonasal NHL, and these features are not seen in NHL at the sites other than sinonasal tract. The treatment modality is controversial in regard to the best therapeutic option for the patient. In spite of tumoral dimensions, the medical treatment such as chemotherapy is effective, whereas the surgical treatment is not useful. The objective of the surgical treatment is essentially a diagnostic requirement both for extra-nodal and lymph node sites. The primary modality of the treatment for NHL is cytostatic chemotherapy. The treatment of the sinonasal NHL involves a multidisciplinary team consisting otorhinolaryngologists, pathologists, radiologists, and oncologist. After proper evaluation, the patient should be staged and recommended for the treatment. The treatment options include radiotherapy, chemotherapy alone or in combination as first line or second line of treatment. Patients with Stage I EA disease with diameter up to 5 cm are often treated with radiotherapy, whereas the bulky tumors or Stage III or IV disease are treated with combined chemotherapy and radiotherapy. The treatment of sinonasal NHL is exclusively medical treatment which is based on chemotherapy and/or except external radiation.[30] Combination chemoradiation is the mainstay of the treatment in sinonasal DLBCL.[31] Most commonly used treatment regimen is traditionally cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP).[31] The chemotherapy and immunotherapy are rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (i.e., R-CHOP regimen) in the standard dose are given as per weight of the patient. Other chemotherapy regimens such as bleomycin, doxorubicin, cyclophosphamide, vincristine, and prednisolone, and cyclophosphamide, epidoxorubicin, vincristine, and prednisone have been used with some success.[32] Only radiation therapy is argued to be effective for early stage of the disease.[33] There is still debate on combination chemoradiation is more effective in sinonasal NHL.[33] Surgery has a limited role in the treatment of the sinonasal NHL. The mutilating surgical option must be avoided in these cases. The role of the surgery is usually limited to the biopsy only. The surgical removal of the NHL in the sinonasal tract does not show a good therapeutic response and often limited to the biopsy for the diagnosis.[34] Although otolaryngologist often encounters sinonasal NHL during their practice, a definite treatment is usually done by medical and radiation oncologists. Surgical treatment is only useful if the lesion is focal and reasonable expectation with clear margin or the burden of the tumor is so great that the patient would improve clinically by reducing the morbidity.

  Prognosis Top

Patients of sinonasal lymphoma have a better prognosis than lymphoma in the lymph nodes with similar histologic grading.[12] In one study of the sinonasal lymphoma, 5-year survival was 52% and 5-year freedom from the progression was 57%.[35] This study documented that stage of the disease and patient ages were the independent factors for the prognosis of the disease.[35] The prognosis of the sinonasal NHL depends on the type and stage of the tumor, spreading to vital structures such as central nervous system and the general conditions of the patients.[36] NHL at the nose and paranasal sinuses may mimic to the benign pathological lesions and may manifest either as an isolated pattern or in combination with systemic disease. The B-cell lymphoma has a favorable prognosis in majority of the cases, whereas T-cell and extra-nodal NK cell lymphomas are often associated with the rapid progression of the disease and death.[37] However, histopathologically, the high-grade NHL of the sinonasal tract has a worst prognosis.

  Conclusion Top

Primary sinonasal NHLs are uncommon lesions. Early diagnosis and staging of the tumor are essential for the appropriate and effective treatment. It is usually thought that the differential diagnosis of the sinonasal NHL include sinonasal polyposis or chronic sinusitis. Hence, the clinician or otolaryngologist should keep in the mind the existence of the primary sinonasal NHL to avoid delayed diagnosis and treatment. The diagnosis is based on the histopathological examination and immunochemistry study. Chemoradiation therapy significantly improves the survival of the patients with sinonasal NHL. It is very important for a clinician and otolaryngologists to be familiar with this clinical entity and its management. Delayed diagnosis and treatment will lead to high morbidity and mortality of the patient. Although sinonasal NHL has nonspecific clinical presentations, it is very important to have a high index of suspiciousness to rule out NHL in the sinonasal tract as this disease is a curable lesion with better prognosis in the early stage.

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2]


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