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Table of Contents
ORIGINAL ARTICLE
Year : 2018  |  Volume : 15  |  Issue : 2  |  Page : 88-93

Extranodal nasofacial natural Killer/T-cell lymphoma: Our experiences at a tertiary care hospital of Eastern India


1 Department of Otorhinolaryngology, IMS and SUM Hospital, Siksha ‘O’ Anusandhan University, Bhubaneswar, Odisha, India
2 Directorate of Medical Research, IMS and SUM Hospital, Siksha ‘O’ Anusandhan University, Bhubaneswar, Odisha, India
3 Department of Pathology, Apollo Hospital, Bhubaneswar, Odisha, India

Date of Web Publication5-Jul-2018

Correspondence Address:
Santosh Kumar Swain
Department of Otorhinolaryngology, IMS and SUM Hospital, Bhubaneswar - 751 003, Odisha
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/am.am_10_18

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  Abstract 

Background: Natural killer (NK)/T-cell lymphoma is a rare nonHodgkin's lymphoma originating in the nasofacial area including nasal cavity and paranasal sinuses. NK/T-cell lymphoma has an aggressive clinical course with unfavorable prognosis. Objective: Analysis of the etiopathogenesis, clinical profile, diagnostic difficulties, treatment options, and outcome in patients with NK/T-cell lymphoma of the sinonasal area. Materials and Methods: This is a retrospective observational study conducted over the period January 2012–December 2017. Age, gender, clinical presentation, histological diagnosis, radiological presentations, and immunophenotype characteristics were taken into consideration. Results: There were six patients, i.e., four males and two females with the common symptom were nasal obstruction (78%), nasal discharge (68%), and nasal bleeding (58%). The diagnosis was established by histopathological examination and immunohistochemistry. Computed tomography scan was done in all patients. Five patients were treated with chemoradiation one patient died after 6 months of treatment. Conclusion: Nasofacial NK/T-cell lymphoma is a rare clinical entity. Diagnosis is based on histopathological examination, immunophenotype, and molecular characteristics. It is an aggressive lymphoma which needs multidisciplinary approach. Its prognosis is poor. Optimal management of NK/T-cell lymphoma in the nasofacial area should be based on multidisciplinary approach among best outcome. Practicing physicians need to be aware of this nonspecific presentation of this lesion.

Keywords: Chemotherapy, natural killer/T-cell lymphoma, nasofacial, radiotherapy, sinonasal area


How to cite this article:
Swain SK, Sahu MC, Baisakh MR. Extranodal nasofacial natural Killer/T-cell lymphoma: Our experiences at a tertiary care hospital of Eastern India. Apollo Med 2018;15:88-93

How to cite this URL:
Swain SK, Sahu MC, Baisakh MR. Extranodal nasofacial natural Killer/T-cell lymphoma: Our experiences at a tertiary care hospital of Eastern India. Apollo Med [serial online] 2018 [cited 2021 Dec 2];15:88-93. Available from: https://www.apollomedicine.org/text.asp?2018/15/2/88/235989


  Introduction Top


Nasofacial natural killer (NK)/T-cell lymphoma is a midfacial necrotizing lesion, characterized by granulomatous lesions with destruction of the mucosa of the upper aerodigestive tract. Nasofacial NK/T-cell lymphoma is newly recognized clinical entity of nonHodgkin's lymphoma. This lesion is now definitively categorized in the World Health Organization lymphoma classification system as nasal or sinonasal type extranodal NK/T-cell lymphoma. It is common in those of Asian origin, whereas rare in the western population.[1] Extranodal NK/T-cell lymphoma of nasofacial area cause necrosis with the involvement of midfacial bone causing the centrifugal destruction of facial bone with no tendency to the healing of lesions. The etiopathogenesis is unknown, but it is related to Epstein-Barr virus infection, which is often associated with poor prognosis.[2] It is difficult to diagnose due to the wide array of similar pathology and nonspecific symptoms. The different terminology used for this diseases are Stewart's granuloma, lethal midline granuloma, idiopathic midline granuloma, idiopathic midline destructive disease, midline nonhealing granuloma, polymorphic reticulosis, and lymphomatoid granulomatosis.[3] It occurs around the 4th decade and male-to-female ratio is 8:1–2:1.[2],[3] Common sites for sinonasal NK/T-cell lymphomas are the maxillary sinus, nasopharynx, oropharynx, palate, oral cavity, tonsils, and hypopharynx.[4] Clinical manifestations vary according to the site being affected. The common clinical findings to all such lesions are the progression of ulceration or vegetative process to the destruction of the nasofacial region, resulting in functional and cosmetic deformity.[5] Nasofacial NK/T-Cell lymphoma is aggressive, locally destructive and necrotic lesion of the midfacial area. The differential diagnosis of this NK/T-cell lymphoma of the nasofacial region is Wegener's granuloma and epidermoid carcinoma. Here, we are presenting six cases of extranodal nasofacial NK/T-cell lymphoma causing progressive midfacial destruction with its comparison with different clinical parameters, diagnosis, and treatment.


  Materials and Methods Top


All patients with sinonasal NK/T-cell lymphomas were retrospectively analyzed between January 2012 to December 2017 at our tertiary care teaching hospital. All six cases of sinonasal NK/T-cell lymphoma were managed at our institution. Detail clinical profiles of each patient are given below.

Case 1

A 56-year-old male patient presented with a small ulcerative lesion over the dorsum of nose 3 months back. The lesion progressively increased its dimension with dry and necrotic appearance to present one [Figure 1]. On examination, a crust covered mass seen over the midline nasofacial area. There was no lymphadenopathy. There was no history of nasal bleeding, hyposmia, post-nasal drip or a cough. The routine blood test did not reveal any relevant findings, and fine-needle aspiration cytology was inconclusive. Urine analysis, liver function tests, and renal function test were normal except raised erythrocyte sedimentation rate (ESR). HIV-enzyme-linked immunosorbent assay (ELISA) and HbsAg tests had negative reports. Computed tomography (CT scan) of nose and sinus revealed the presence of extensive destruction of soft tissue and nasal septum [Figure 2]. A biopsy was taken from the lesion and sent for histopathological examination. The histopathological examination was showing a diffuse lymphomatous infiltrates with angiocentric and angiodestructive pattern [Figure 3]. An extensive area of necrosis with infiltration of plasma cells, histiocytes, and eosinophils are present along with atypical lymphocytes. Immunohistochemistry study showed abnormal lymphocytes of CD56, CD3, and CD4 [Figure 4]. The patient is referred to Hemato-Oncology department for further treatment.
Figure 1: Patient showing necrotic lesions over nasofacial area

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Figure 2: Computed tomography scan of paranasal sinus with coronal cut showing destruction of dorsum of nose along with mucosal hypertrophy in maxillary sinus and ethmoidal sinus

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Figure 3: (a) Photomicrograph showing extensive necrosis (H and E, ×100) and (b) showing atypical lymphocytes, plasma cells, histiocytes, and eosinophils (H and E, ×400)

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Figure 4: Immunohistochemistry lymphocytes positive for CD56 and CD3 (H and E, ×100)

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Case 2

A 38-year-old female patient presented with an ulcerative lesion over the left nasofacial area for the past 6 months. The lesion progressively increased its dimension with dry and necrotic appearance. On examination, a crust covered mass seen over the left side nasofacial area [Figure 5]. There was no lymphadenopathy. She had no history of nasal bleeding, hyposmia, post-nasal drip or cough. The routine blood test did not reveal any relevant findings, and fine-needle aspiration cytology was inconclusive. Urine analysis, liver function tests, and renal function test were normal except raised ESR. HIV-ELISA and HbsAg tests had negative reports. CT scan of nose and paranasal sinus revealed the presence of extensive destruction of soft tissue and left maxillary sinus. A biopsy was taken from the lesion and sent for histopathological examination, which was showing a diffuse lymphomatous infiltrates with the angiocentric and angiodestructive pattern. An extensive area of necrosis with infiltration of plasma cells, histiocytes, and eosinophils are present along with atypical lymphocytes. Immunohistochemistry study showed abnormal lymphocytes of CD56 and CD3. The patient is referred to Haemato-Oncology department for further treatment
Figure 5: Patient showing a crust covered lesion seen over the left side nasofacial area

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Case 3

A 63-year-old male came to outpatient department of otolaryngology with complaints of left sided nasal obstruction and epistaxis on and off for 3 months and nasal mass for 2 months. On anterior rhinoscopy, a reddish mass was coming out of the left nasal cavity. The sthe urface of the mass was covered with crusts. On probing, the mass was firm in consistency and noncompressible. Biopsy from the mass and immunohistochemistry confirmed the diagnosis of NK/T-cell lymphoma. The patient was referred to Oncology department for radiotherapy and chemotherapy.

Case 4

A 43-year-old male presented with bilateral nasal obstruction, with foul-smelling bilateral purulent nasal discharge for 5 months. He had associated weight loss of 5 kg over 4 months. On examination there is a fleshy, polypoidal mass, bleeding on touch and filling the entire right nasal cavity, pushing back the ipsilateral middle turbinate and nasal septum. Diagnostic nasal endoscopy was impossible due to the size of the mass. Oral cavity examination showing hard palate ulceration. Histopathological analysis of biopsy samples from the right nasal cavity and hard palate, taken under local anesthesia, found friable tissue with necrotic areas, suggestive of infectious or tumoral pathology, without being able to decide between the two. Immunohistochemistry diagnosed sinonasal NK/T-cell lymphoma. The lymphoid elements were positive for cytoplasmic CD3 and CD56. The patient was referred to the department of Oncology for chemoradiation.

Case 5

A 72-year-old male referred to our hospital for midline facial destructive lesion. The patient had a small growth on the nose 1 year back, become ulcerated and enlarged to present size. He has nasal obstruction with discharge and headache. Biopsy of the mass showed dense polymorphic cell infiltrates with the presence of histiocytes, eosinophils, and number of atypical lymphoid cells in an angiocentric distribution. There was area of necrosis also seen. Immunophenotypically, the tumor cells were positive for CD3 and CD56 but negative for CD20. Few large atypical lymphocytes were positive for CD30. CT scan showed radio-opacity of the nasal cavity, both maxillary sinuses, ethmoidal, frontal, and sphenoid sinuses. Patient referred to oncology department for treatment.

Case 6

A 66-year-old female presented with 2 months history of enlarging ulceration over the nose, despite adequate antibiotics treatment for suspecting infection. She had no history of trauma. She had complained of nasal pain, nasal crusting, nasal obstruction, epistaxis, and cosmetic deformity. After taking a biopsy, the histopathological picture showed a mixture of a large number of atypical lymphoid cells along with plasma cells, histiocytes, and occasionally eosinophils. Vascular invasion with occlusion of the lumen by lymphoid cells (angiodestructive) with varying degrees of cellular atypia was seen. Immunohistochemical analysis showed tumor cells positive for leukocyte common antigen and negative for CD20 and CD30. Patient referred to Oncology department for further treatment.

Treatment

All patients received multidrug chemotherapy of four cycles (CHOP regimen). Then, he got external beam irradiation (36 Gy). The patient got symptomatically improvement after 3 months of treatment.


  Results Top


The study comprises six patients with NK/T-cell lymphoma in the nasofacial area. Six patients were diagnosed with nasofacial NK/T-cell lymphoma at during 2010–2016 on the basis of pathological and immunophenotypical criteria. Age of the patients, sex, locations of the lesions, histological diagnosis, immunohistochemical type, the time interval between the clinical onset and diagnosis and known risk factors were recorded. The mean age of the patients is 56 years (range 38–72 years) and mean time to the first consultation was 4 months. Out of six patients, five were male and one was female. All the patients were in the age group of 38–72 years. The major clinical manifestations were necrosis over the nose, nasal obstruction, nasal discharge, nasal bleeding, and recurrent fever. Cervical lymphadenopathy was seen in one out of six patients. Nasal endoscopy was done in all patients, showing necrotic and friable mass at nasal cavity. One patient died due to suicidal attempt. Biopsies were done in all patients and histopathological examination with immunohistochemistry study confirmed the diagnosis. Histopathological examination showed a diffuse lymphomatous infiltrates with the angiocentric and angiodestructive pattern. An extensive area of necrosis with infiltration of plasma cells, histiocytes, and eosinophils are present along with atypical lymphocytes. Immunohistochemistry study showed abnormal lymphocytes of CD56, CD3, and CD4. After confirmed diagnosis, all patients were sent to thr Oncology department for treatment. Details of patient's profile are given in [Table 1] and [Table 2].
Table 1: Details patient's profile

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Table 2: Detail clinical profile of the patients

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  Discussion Top


Nasofacial NK/T cell lymphomas are aggressive, locally destructive lesion of the midfacial area. It is a rare clinicopathological entity characterized by necrotic process arising in the sinonasal cavity and extending to the midfacial area with the centrifugal destruction of the nasal bone. It is also called as polymorphic reticulosis, midline malignant reticulosis, Stewart's granuloma and NK/T-cell lymphoma.[6] Sinonasal NK/T cell lymphoma is a rare clinical entity, but often seen in Asia, Mexico and South America than North America and Europe.[7] The onset of this disease is usually 5th decade of life in western country,[8] whereas in Asia, patients are young with mean age of 40 years and male predominance.[2] The nonspecific clinical symptom is a major obstacle in early diagnosis and management of this lesion. Mature or peripheral NK/T cell lymphomas constitute 10%–15% of all nonHodgkin's lymphoma and out of them, natural type NK/T cell lymphoma is the most common type. Now, this variety is referred to as angiocentric lymphoma in the Revised European American Lymphoma classification or as nasal NK/T cell lymphoma by the World Health organization-European organization for research and treatment of cancer classification.[9] Some suggest Epstein Barr virus (EBV) may play a role in the development of NK/T-Cell lymphoma.[10] The surface of the affected site is associated with crusting and necrotic tissue, and hence, the diagnosis of NK/T-cell lymphoma is extremely difficult by taking only punch biopsy. This difficulty may explain why some clinician misses the diagnosis. Excisional biopsy or deep biopsy is often essential for the diagnosis of this disease. The diagnosis of mid-facial NK/T-cell lymphoma is based on the histopathological picture, immunophenotype of the atypical cells, and the analysis of T-cell receptor genes.[11] The characteristic histopathological picture in NK/T cell lymphoma shows angiocentric and angiodestructive growth pattern with zonal necrosis. The immunohistochemical study shows positive CD3, CD43, CD45RO, CD20, and CD57 reveals the atypical lymphoid cells have T-cell phenotype.[12] Nasal variety of NK/T cell lymphoma reveal specific characteristics of NK cells. NK cells are cytolytic cells, act against tumor cells and cell affected by bacteria and viruses without prior sensitization. Bipotential progenitor cells in the bone marrow differentiate into T and NK cells. NK cells commonly appear as small lymphocytes with azurophilic granules and immunophenotypically express the characteristic CD56 marker. As a common ontogeny with T cells, NK cells express some T cell markers. Nasal NK/T cell lymphomas have a predilection for nasal cavity and upper part of the aerodigestive tract. They also affect the skin and soft tissue in the nasofacial area. Elderly males with age group of above 50 years are usually affected. The clinical presentation varies according to the location and histopathological type. The most common clinical presentation is chronic nasal obstruction or purulent nasal discharge.[11] The necrotic lesion mimic to other granulomatous lesions and often difficult to diagnose due to the nonspecific symptoms and often require multiple biopsies for the confirmed diagnosis. Nasal NK/T cell lymphoma is an aggressive lesion with rapid downhill progression. If it is untreated, it can cause high mortality if not treated timely. The high mortality is due to septicemia, invasion into blood vessels or into brain leading to abscess formation. Combined chemotherapy followed by external beam radiation is beneficial in patients and good survival rate.[13] Gross appearance of the lesion is usually looking like necrotic granuloma with ulcerations and destruction of nose and sinuses with the destruction of soft tissue, cartilage, and bone. There is usually aggressive and lethal progression with rapid destruction of the nasofacial area. Nasal septal perforation with mutilation of the surrounding tissues often occurs.[14] The most common symptoms are nasal stuffiness with or without nasal discharge. Ulcerations at nasal cavity or oral cavity along with conjunctivitis may occur. Radiological findings in CT scan and magnetic resonance imaging are not distinctive for other malignant lesions, typically showing irregular margins, bone destruction, and heterogeneous contrast enhancement. Histopathological examination revealed tissue necrosis infiltration with a mixture of small, medium, and large size lymphoid cells. Immunohistochemical study revealed that these abnormal lymphoid cells are CD2+, CD3, CD4, CD4−, CD5−, CD15−, and CD56+. The most common immunophenotype are CD56+, CD2+ and surface CD2−.[15] The diagnosis of NK cell lymphoma was confirmed. EBV RNA is seen in 80%–100% of cases of NK/T cell lymphoma whereas less often (15%–40%) present in the nasal type of NK/T cell lymphoma cases.[16]

Treatment of NK/T-cell lymphoma in the sinonasal area is not well codified, and it depends on the stage of the disease. Some suggest the use of anthracylcine-based polychemotherapy followed by external radiation for patients younger than 60 years of age, whereas the same association but without anthracycline in older patients.[7] Other still advice radiotherapy alone in the less advanced stage of the disease as failure rate with chemotherapy alone is around 40%. Radiotherapy after failure cases of chemotherapy cause improvement of prognosis.[17] Overall survival of patients with all treatment is around 37%.[18] Localized extranodal NK/T-cell lymphoma of nasofacial area responds well to radiotherapy. Radiotherapy has the greatest benefit if given early and disease is localized.[19] About 20%–30% of patients treated with radiotherapy alone has chance of failure in extranodal site,[20] and local recurrence rate ranges from 31% to 67%.[21] Chemotherapy in local disease reduces the chances of recurrence and systemic dissemination. Current chemotherapeutic regimes are reserved for control of micrometastases following radiotherapy.[8] When this tumor invading the surroundings and bony part, Radiotherapy should be added with chemotherapy. As in other tumor, the clinical outcome is achieved with early treatment. Treatment of sinonasal NK/T-cell lymphoma is done by the CHOP (Cyclophosphamide, Doxorubicin hydrochloride, Vinicristine sulfate) chemotherapy and radiotherapy.[12] Hemato-oncologist arranged six course of chemotherapy followed by he had undertaken radiotherapy in our case except in case-4 who had taken the only radiotherapy. This disease has a poor outcome. One patient died out of six in our series. This patient died (Case-5) during radiotherapy. The prognosis of NK/T-cell lymphoma is extremely poor if it is associated with systemic involvement. Better prognosis is expected with an early and accurate diagnosis along with aggressive treatment with chemotherapy and radiotherapy.


  Conclusion Top


Nasofacial location of NK/T-cell lymphoma is a rarely seen. The confusing clinical profile of this disease often creates suspicion for exact diagnosis. Diagnosis is based on the biopsy and immunohistochemistry. Immunohistochemistry is always mandatory to diagnose this disease and its treatment. Early diagnosis and intervention prolongs the survival of the patients. Treatment needs combined chemotherapy and radiotherapy. This disease carries an overall poor prognosis; although in our case, the lesion is localized with midline destruction of soft tissue at nasofacial area but has a very aggressive pattern. Optimal management of NK/T-cell lymphoma in sinonasal area should be based on multidisciplinary approach among Otorhinolaryngologists, medical oncologist, and radiation oncologist for best outcome. Practicing physicians need to be aware of this nonspecific presentation of lesion and to prevent delay in diagnosis.

Study limitations

This study has a relatively small sample size and may limit the outcome of above clinical interpretation. However, this study will definitely add the clinical acumen to NK/T-cell lymphoma in our region.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

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