Nasal NK/T-cell Lymphoma Presenting as Acute Inflammation of Nasal Vestibule

Abstract

Extra nodal nasal NK/T cell lymphoma is relatively a rare type of non-Hodgkin lymphoma. Variable clinical presentation with rapidly progressive necrosis of the cartilaginous and bony wall of the nose and upper respiratory passages leads to delayed diagnosis and treatment. A 43-years-old patient presented with right nasal pain and furuncle-like swelling. The swelling progressed rapidly to cellulitis to the face up to the right eye. Within 2 months, it had advanced to necrosis of the lateral vestibular cartilage, medial maxillary wall, turbinate and nasal septal cartilage. Biopsy reported as non-Hodgkin diffuse T cell (angiocentric T cell) lymphoma.

Introduction

Extra nodal NK/T cell lymphoma is aggressive. Rapid necrosis can be seen in extra nodal regions particularly nasal and paranasal sinuses. Three quarter of the extranodal nasal lymphomas are T cell related and the rest being B-cell lymphomas. Extra nodal lymphomas can develop in either T cells or natural killer (NK) cells, which attack foreign cells. Sometimes it is difficult to identify the cells from T cells or NK cells [1]. The term NK/T-cell lymphoma is preferred for the classification. NK/T cell lymphoma is seen usually in the nose and paranasal sinuses and are associated with Epstein-Barr virus (EBV) infection [2]. Sinonasal tract lymphomas may be difficult to define correctly because of the inadequate biopsy material, compared with nodal lymphomas. The majority of the patients often experience localized and aggressive clinical course. Although radiotherapy has been proved beneficial for early stage disease but irradiation followed by course of chemotherapy reported 70% outcome [3].

Case Presentation

A 43-year-old male presented with pain and swelling over the right side nose which was associated with nasal block and discharge for 2 weeks. There was no cough, chest pain, difficulty in breathing, sore throat, odynophagia or dysphagia. There was no history of otalgia, otorrhoea or hearing impairment. On examination, diffuse right nasal vestibular swelling with inflammation and tenderness was noted which was extending to the cheek as well as the infraorbital margin. Inferior turbinate was not visualized on anterior rhinoscopy because of edema and congested nasal mucosa. At first, it was diagnosed as right nasal furuncle and treated with antibiotics. The patient defaulted for 2 months. Later, he developed extensive cellulitis extending from the nasal vestibule to the medial canthus with ulceration. The necrotic ulcer was covered with slough and foul smell. Wound debridement was done leaving the anterior right nasal perforation (Fig. 1).

Fig. 1.

Right vestibular and nasal necrotic mass

Endoscopic nasal examination revealed necrotic ulcerated mass involving the lateral nasal wall occupying the nasal cavity and eroding the cartilaginous septum as well as inferior turbinate. Biopsy was taken from the mass and sent for histopathological review. CT scan of the paranasal sinuses was done and showed a mass which eroded the right lateral bony wall extended to anterior and middle ethmoidal air cells occupying the nasal cavity (Fig. 2a) with erosion of septum cartilage (Fig. 2b).

Fig. 2.

a CT scan showing mass occupying the nasal passage. b CT scan showing loss of nasal septum

Histopathology was reported as inflammatory granulomatous disease. The patient was advised for second biopsy with deeper and viable tissue. A second histopathological examination showed features suggestive of non-Hodgkin’s diffuse T cell lymphoma (angiocentric T cell lymphoma) (Fig. 3b). Immunohistochemistry showed positive for T cell markers (CD30) and negative for CD20. CD56 (Fig. 3a) was positive with brown tinge similar in biological behavior of tumor noted and diagnosed as NK/T cell lymphoma. In due course, the patient was referred to the hematologist for further management.

Fig. 3.

a Immunohistochemical study, neoplastic cells to be positive for the pan T-cell antigen CD30 (positive cells have a brown tinge). b Histopathology, Infiltrated large neoplastic cells with moderate amount of cytoplasm and Histiocytic resembling cells

Discussion

Malignant lymphomas involving nasal cavity, paranasal sinuses and hard palate are uncommon and difficult to diagnose. Lymphomas account for 3–5% amongst all head and neck malignant tumors. Non-Hodgkin’s lymphomas (NHL) account for 80–85%. NK/T cell neoplasms are rare and subtype aggressive and destructive lymphoma of the aero digestive tract, midfacial, nose and paranasal sinuses. This tumor was first described by McBride in 1897 [4–7]. In 1922, Stewart et al. reported 10 cases of a chronic destructive midfacial process known as Stewart’s syndrome or Stewart’s granuloma [8]. Later, Williams popularized the term lethal midline granuloma, describing a destructive process of the nasal cavity of unknown etiology. NK/T cell lymphoma is the most frequently used term to designate a lesion previously known as mid-facial granuloma which is classified by WHO as NK/T cell lymphoma of the nasal type, confirmed by modern cytogenetic, immunologic and molecular studies [9]. Geographically, NK/T cell lymphoma is more frequent in Asian and Latin American countries than in Western countries in male in elderly population. It is universally associated with EBV infection [1].

The diagnosis of NK/T cell lymphoma should be considered in cases which present with a small cutaneous ulcerative lesion with thickened underlying mucosa in the nasal cavity. The current case was presented with nasal discharge, bleeding, obstruction, and pain. The patient usually develops extensive midfacial destruction, perforated nasal septum and erosion of the lateral nasal wall which may result in loss of nasal support leading to cosmetic and functional deformity. A similar presentation was appreciated in our patient with extensive destruction of the lateral nasal wall and septum which was revealed in a CT scan of the paranasal sinuses.

The histopathological examination in our case had a diffuse lymphomatous infiltrate with an angiocentric and angiodestructive pattern with extensive areas of necrosis destroying the hair follicles. Plasma cells, histiocytes and eosinophils were laden with atypical lymphocytes. In the REAL Classification, this type of nasal lymphoma was considered an angiocentric lymphoma, together with pulmonary lymphomatous granulomatosis of B-cell origin, based on morphological features [8]. Until recently, however, it has remained obscure whether angiocentric lymphoma with the NK cell profile is a true NK cell neoplasm or a bonafide T cell neoplasm with aberrant expression of NK cell markers; hence, a few investigators have preferred the noncommittal lineage designation NK/T cell lymphoma rather than putative NK cell lymphoma [10, 11].

The most common immunophenotype of this disease are positivity for CD56, CD2, and CD30 as well as surface CD20 [12, 13]. Immunohistochemistry was performed and confirmed in our patient to be positive for LCA, CD56 and cytoplasmic CD30, thus confirming the diagnosis. Ishii et al. first recognized the presence of tumor cells expressing CD3 in this lesion and termed this disease nasal T-cell lymphoma [14]. However, Suzumiya et al. demonstrated that tumor cells of this nasal lymphoma express cytoplasmic CD3 and CD56, but not T-cell receptors, suggesting their NK-cell origin [15].

Analyses of gene mutations, especially p53 and c-kit, have been reported and identified the genetic abnormalities [16, 17]. Unfortunately, it was not done in our case. Further studies including HLA antigen typing of patients is necessary to further clarify the disease mechanisms [18]. A correlation of exposure to certain pesticides and organochlorines with increased titers of antibodies to EBV was reported in NK/T cell lymphoma [17].

Radiotherapy alone has been used for limited stage of ENKL with 5-year overall survival approximately 50%. Multidrug chemotherapy combined with external beam radiation therapy is beneficial for prolonged survival [18]. Our patient was referred to hematologist and treatment plan followed. It has been noted that despite intensive combined radiation and chemotherapy, disease free and overall survival time is only 9–12 months and none of the patients with disseminated disease survived beyond a few years. Although, the mortality rates are very high in untreated cases.

Conclusion

Nasal NK/T cell lymphoma is a rare but aggressive neoplasm. The ambiguous nature of these symptoms can impose dilemma in diagnosis. It should be considered for differential diagnosis in a patient with a furuncle like lesion in the nose with rapid destructive progression. Initial histopathology results may be inconclusive or misleading and a repeat deeper biopsy may be indicated. Representative biopsy material and good interaction with the pathologist is vital. Early diagnosis and multimodal therapy is also desirable. However, prognosis remains poor in most cases.