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 Table of Contents  
Year : 2015  |  Volume : 40  |  Issue : 1  |  Page : 44-48

Nasal extranodal T/NK-cell lymphoma presenting as a palatal lesion: an uncommon clinical presentation of a rare disease

1 Center of Hematology and Hemotherapy of Ceara, Fortaleza, Brazil
2 Department of Pathology, Faculty of Medicine, Federal University of Ceara, Fortaleza, Brazil

Date of Submission23-Nov-2014
Date of Acceptance18-Dec-2014
Date of Web Publication24-Apr-2015

Correspondence Address:
F da Silva Herivaldo
Centro de Hematologia e Hemoterapia do Ceara - HEMOCE, Av. José Bastos, 3390, 60435-160 Fortaleza, Ceara
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1110-1067.155798

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A 27-year-old woman presented with a 6-month history of a painful and erosive lesion in the hard palate with a progressive increase in size. Examination indicated two ulcerated lesions in the hard palate. Histopathology showed dense exudation of atypical mononuclear leukocytes composed of small and medium lymphoid cells with round or oval nuclei. Immunohistochemistry showed abnormal T-cell population with strong expression for CD45RO and CD7 with negativity for CD20 and certain T antigenic loss, suggesting T-cell lymphoma. Serology for the Epstein-Barr virus was positive. This is the second case of nasal extranodal T/NK-cell lymphoma presenting as a palatal ulcer reported to date.

Keywords: Epstein-Barr virus, immunohistochemistry, nasal extranodal T/NK lymphoma

How to cite this article:
Amarante M, Rocha Filho F D, Castro A, Silva Junior G B, Herivaldo F d. Nasal extranodal T/NK-cell lymphoma presenting as a palatal lesion: an uncommon clinical presentation of a rare disease. Egypt J Haematol 2015;40:44-8

How to cite this URL:
Amarante M, Rocha Filho F D, Castro A, Silva Junior G B, Herivaldo F d. Nasal extranodal T/NK-cell lymphoma presenting as a palatal lesion: an uncommon clinical presentation of a rare disease. Egypt J Haematol [serial online] 2015 [cited 2021 Sep 22];40:44-8. Available from: http://www.ehj.eg.net/text.asp?2015/40/1/44/155798

  Introduction Top

Nasal extranodal T/natural killer (NK)-cell lymphoma is an uncommon clinicopathologic entity of non-Hodgkin's lymphomas (NHLs) that is associated closely with Epstein-Barr virus (EBV) infection [1],[2],[3],[4],[5] . It usually affects adults, with a median age of 50 years. It is much more common in East Asian and Latin American countries than in westerns countries [6] , suggesting that ethnic factors influence the pathogenesis of these lymphomas.

The most common clinical presentation is a facial midline lesion or nasal destruction, and a distant metastasis is infrequent [7] .

The extranodal T/NK-cell lymphoma is characterized by a wide cytological spectrum and angiocentricity is frequent. The diagnosis is made on the basis of immunohistochemistry (IHC), which defines the cellular immunophenotype as T/NK.

The clinical course is usually highly aggressive. Localized disease has a relatively good prognosis with radiotherapy [8],[9] . However, advanced disease is often refractory to radiation and chemotherapies, and remission is transient even if achieved, and thus the prognosis is very poor [10],[11] .

  Case report Top

A 27-year-old Brazilian woman was admitted to our hospital with a 6-month history of a painful and erosive lesion in the hard palate with a progressive increase in size. The patient complained of chronic sinusopathy and gradually worsening nasal obstruction.

About 1 month after the appearance of the lesion, the patient observed the emergence of a pustule in the left nasal wing that progressively grew and developed into necrosis, nasal stuffiness, periorbital swelling, and fever. After treatment of the infection, the patient was started on 60 mg of prednisone daily for Wagner Granulomatosis (WG) and soon after, the emergence of acneiform lesions was observed in the face and the trunk.

The patient presented later with worsening of the periorbital swelling, watering, and elimination of purulent and fetid secretion, and was referred to our hospital with probable cellulitis. She was started on clindamycin and ceftriaxone.

On hospital admission, the patient was afebrile, normotensive, and was not in respiratory distress. A physical examination indicated multiple coalescent acneiform lesions in the face and the trunk and two ulcerated lesions in the hard palate besides necrosis areas. The largest lesion was situated in the central line and was more anterior than the other. The left nasal wing presented almost total occlusion of the left nostril and a large ulcerated lesion with a necrosis component ([Figure 1]). The left orbit presented with swelling. There were no palpable lymph nodes in the head and neck. The cardiac examination indicated no abnormalities, and the lungs had normal vesicular breath sounds without adventitious sounds. No hepatosplenomegaly was noted on abdominal examination. Extremities and neurological examinations were normal.
Figure 1 (a) A large ulcerated lesion in the left nasal wing with necrosis. (b) An extended palatal lesion in the midline with ulceration.

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The initial laboratory examination showed hemoglobin 11.2 g/dl, hematocrit (Ht) 33.6%, mean corpuscular volume (MCV) 81.9 fl, and mean corpuscular hemoglobin (MHC) 27.4 pg/dl, the white blood cell count was 5.87 × 10 9 /l (polymorphs 83%, lymphocytes 13%, monocytes 3%, eosinophils1%, basophiles 0%), and the platelet count was 1.75 × 10 11 /l. Serum chemistries showed a creatinine level of 0.5 mg/dl, blood urea nitrogen of 33.6 mg/dl, aspartate aminotransferase of 32 IU/l, alanine aminotransferase of 35 IU/l, alkaline phosphatase (ALP) of 43 UI/l, γ-glutamyl transferase of 15 UI/l, uric acid of 2.8 mg/dl, and albumin of 3.2 mg/dl; serum lactate dehydrogenase was elevated to 589 IU/l (normal range 240-480 IU/l). The results of coagulation tests were as follows: prothrombin time (PT) 10.6 s (92%), international normalization ratio (INR) 1.06, activated partial thromboplastin time (APTT) 25.6 s. Erythrocyte sedimentation rate was 18 mm. Serologies for syphilis (VDRL), HIV, and hepatitis type B and C were negative, but serology for EBV was positive.

The computed tomography (CT) scans showed a lesion of irregular contours, in the projection of the subcutaneous cellular tissue in the anterior part of the face, extending from the level of the superior lip to the glabella. The subcutaneous cellular tissue of the anterior wall of the left maxillary sinus and preseptal tissue of the left orbit were also affected. The bony skeleton was intact. There was also mucous thickening of the sphenoid sinus and ethmoidal air cells, the maxillary sinuses were filled with a material with an attenuation coefficient of soft tissue, and there was pneumatization of the middle left nasal concha. These findings could be interpreted as an expansible lesion of soft tissue in the anterior part of the face of unspecified aspect ([Figure 2]).
Figure 2 Computed tomography scans showing a lesion of the subcutaneous cellular tissue in the anterior part of the face, the anterior wall of the left maxillary sinus, and preseptal tissue of the left orbit.

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The previous biopsy showed microsections represented by an ulcerated mucous membrane with a dense mixed exudation of leukocytes in the core, constituted by small and medium lymphocytes, among which there were macrophages, a few neutrophils, and eosinophils. Some cells had vesiculous nuclei, evident nucleoli, and scarce cytoplasm that could correspond to immunoblasts. Atypical cells besides a vasoproliferative reaction and necrosis focuses were also observed. The mitotic figures were few and the sections were negative for acid fast bacilli and fungi by Wade and Grocott.

The new histopathologic study showed microsections represented by an ulcerated mucous membrane partially covered by a fibrinogranulocytic cover. The core showed dense exudation of mononuclear leukocytes composed of small and medium lymphoid cells with round or oval nuclei and, sometimes, irregular contour. The cytoplasm was scarce and clear, and, although diffusely distributed, there was clear angiocentricity. Such cells were also observed among the cells of the scaly epithelium that covered the sample, favoring the diagnosis of extranodal lymphoma.

The new IHC showed diffuse, strong, and homogeneous expression for CD45, CD45RO, and CD7, with negativity for CD20 (B antigen) and certain T antigenic loss (negative CD3) ([Figure 3]). The NK-cell marker CD56 was unavailable. On the basis of the clinical picture and histopathology, such findings led us to the diagnosis of non-Hodgkin's T/NK-cell lymphoma, nasal type, described by the WHO classification. Other IHC markers were used ([Table 1]).
Table 1 Immunohistochemistry markers used

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CT scans of the chest, abdomen, and pelvis showed no distant metastasis sites.
Figure 3 (a) HE staining with dense exudation of mononuclear leukocytes (×40). (b) Negativity for CD20. (c, d) Strong positivity for CD45RO and CD45 (brown). (e) Negativity for CD3. (f) Positivity for CD7 with an angiotropism pattern (brown).

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The patient was started on multidrug chemotherapy - that is, the CHOP-14 (cyclophosphamide, adriblastine, vincristine, prednisone) regimen consisting of intravenous cyclophosphamide (750 mg/m 2 ), adriblastine (50 mg/m 2 ), vincristine (1.5 mg/m 2 ), and oral prednisone (100 mg/day for 5 days) administered every 2 weeks for four cycles, besides four doses of intrathecal chemotherapy with methotrexate (12 mg) and cytarabine (40 mg). Granulocyte colony-stimulating factor was used from day 2.

The patient presented with succeeding episodes of febrile neutropenia, the first being on day 12 of the first cycle, and was started on vancomycin and piperacillin with tazobactam.

After the fourth cycle of chemotherapy, new CT scans of the face sinuses were performed, which showed regression of the lesion and of the inflammatory process. Four other cycles were programmed. The patient remains alive after the seventh cycle of chemotherapy and will start radiotherapy.

  Discussion Top

The NHLs correspond to a heterogeneous group of tumoral entities of lymphoid origin. These lymphoproliferative syndromes encompass a large number of different morphologic entities, with variable clinical presentations and prognostics, responding differently to the treatment.

The association between virus and lymphomas is known, particularly with the EBV [12] . EBV is associated with many different types of NHL in immunocompetent as well as immunocompromised patients.

This virus was originally discovered because of its association with Burkitt's lymphoma [13] . It is also associated with the development of various malignant neoplasms such as primary immunodeficiency-related lymphomas, Hodgkin disease, post-transplantation lymphoproliferative disorders, rheumatoid arthritis-related lymphomas, some cases of AIDS-related lymphoma, angiocentric lymphomas, lymphomatoid granulomatosis, aggressive NK-cell lymphomas, and many other cases of T-cell lymphoma [14] .

EBV involves two types of interaction with host cells: a productive, cytolytic infection characterized by a high copy number of the EBV genome and the release of viral particles, and a nonproductive, latent infection [15],[16] .

The lymphotropism and integration into the cellular genome are essential characteristics to the lymphomagenesis. The lymphoma arises from clonal expansion of lymphoid cells that are transformed by the accumulation of genetic lesions affecting oncogenes and tumor-suppressor genes. EBV infects the cell before the malignant transformation and actively participates in the development of the tumoral process. In these cases, the proliferating cells frequently express the encoded proteins, latent membrane protein (LMP1) and EBNA-2. The infected patients usually present a high blood titer of antibodies to EBV.

In immunocompetents, EBV was more frequently associated with T than B lymphomas. A study of T lymphomas of extranodal location showed that the detection of EBV varies according to the primitive site and the geographic or ethnic factors [17] . In a series of primitive T intestinal lymphomas registered in Mexico and in Europe, the research of EBV was frequently positive in the Mexican patients, but not in the Europeans [12] .

In a Korean study, T and NK-cell lymphoproliferative diseases accounted for 64% of EBV-associated disease and 47.5% of T or NK-cell lymphomas were associated with EBV [18] . Although the disease can present at any age, found predominantly in men, the same study showed that the incidence of NK/T-cell lymphoma began to increase from the twenties onward, supporting the idea that adult-onset nasal NK/T-cell lymphoma may develop with a background of chronic latent EBV infection. In the case described here, the patient was a 27-year-old woman and she presented serology reagent only for EBV.

T/NK-cell lymphoma is the most frequently used term to designate a non-Hodgkin's aggressive and destructive lymphoma of the aerodigestive tract, or facial midline tissue, previously known as mid-facial granuloma. This lymphoma is classified by WHO as T/NK extraganglionar lymphoma of the nasal type [19] . The T/NK-cell lymphomas have also been described in other extranodal sites such as skin, soft tissues, testis, respiratory, and gastrointestinal tract, liver, and spleen [20] .

Histopathology usually shows a mixed cellular infiltrate of atypical lymphocytes, plasma cells, eosinophils, histiocytes, and acute inflammatory cells [21] . The cellular proliferation is pleomorphic and is frequently accompanied by invasion of small blood vessels (angiocentricity). Large, hyperchromatic, and atypical cells can predominate or they may be mixed. If the small cells are more prevalent, the disease can be difficult to distinguish from an inflammatory process [22] . Similar findings were observed in our case.

IHC usually indicates the presence of antigens associated with the T cell such as CD2, CD7, CD45RO, and CD43 [23] ; however, very commonly, CD2 and other markers of T cells, such as surface CD3, are absent. The cells frequently express the NK-cell marker CD56, but not CD16 or CD57. Cytotoxic markers such as granzyme B and TIA-1 are also present. Monoclonal rearrangement of the T-cell receptor genes is seldom found, despite the clonality shown by other methods [24],[25] . In our case, IHC could confirm the T-cell origin of the tumor and, although the NK-cell marker CD56 was unavailable, the biological behavior of NK-positive and T-positive nasal extranodal lymphomas is similar [26] and CD56 is not specific only to NK cells [27],[28] .

Patients can present a variety of clinical signs and symptoms. Nasal obstruction, nasal purulent secretion, epistaxis, sinusitis, odontogenic pain, visual disturbances, syndrome of the cavernous sinus, facial pain, syndrome of the insensitive mentus, sinusocutaneous fistulae, necrosis, ulceration, and septal perforation may be present, sometimes accompanied by fever and weight loss in advanced cases. Our patient presented preferential involvement at the level of the mid-facial area, destruction of the palate, increase in the size of the orbit, and prominent edema with necrosis and no destruction of bony tissue.

Because of the nonspecific clinical manifestations, the diagnosis is frequently delayed, with worsening of the prognosis and reduced patient survival.

The principal differential diagnoses of the nasal T/NK-cell lymphomas include B NHL, carcinomas, granulomatous diseases such as WG, and infectious diseases such as New World cutaneous leishmaniasis, mucormycosis, syphilis, aspergillosis, and paracoccidioidomycosis.

WG is usually characterized by generalized necrotizing vasculitis involving both arteries and veins and the presence of glomerulitis [28] . A Turkish study reported a typical WG with isolated sinonasal tract involvement with a final diagnosis of NK/T-cell angiocentric lymphoma by repeated biopsies [29] .

In the literature, there are reports of a hemophagocytic syndrome occurring in patients with these lymphomas, and this is frequently fatal. In patients with lymphoma-associated hemophagocytic syndrome from Japan, the EBV genome was only rarely found in patients with B-cell lymphoma, but was present in more than 80% of patients with T/NK-cell lymphoma [30] .

This case represents an uncommon presentation of a rare disease that presented initially with innocuous symptoms and was misdiagnosed as Wegner's granulomatosis. Despite the delay in diagnosis, the patient showed satisfactory response to chemotherapy. Only one other case of nasal extranodal T/NK-cell lymphoma presenting as a palatal ulcer has been reported [31] .

  Acknowledgements Top

Conflicts of interest

There are no conflicts of interest.

  References Top

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  [Figure 1], [Figure 2], [Figure 3]

  [Table 1]


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