Extranodal NK/T-Cell Lymphoma,Nasal Type—Case Report of 2 Cases

Clinic Cases

Case 1

A 17-year-old male was admitted to hospital for fever, right periorbital edema, purulent rhinorrhea, and nasal obstruction for 3 days (Figure 1A). He had been under treatment with antibiotic and corticoid for rhinosinusitis, with no improvement. Previous surgery was performed 6 months before for “nasal polyposis.” The anatomopathological (AP) highlighted polypoid inflammatory mucosa.

Figure 1.

A, Periorbital edema on the right eye during hospital admission. B, Axial contrast computerized tomography of sinuses revealing complete obliteration of the maxillary and sphenoid sinus, ethmoidal cells, and frontal sinus on the right, as well as of the nasolacrimal duct, and infiltration of the skin and subcutaneous on the right. C, Axial contrast computerized tomography of sinuses revealing extraconal infiltrating and expanding injury compromising eye socket and right periorbital region, with proptosis of the eyeball.

Upon examination, he presented with peripalpebral edema on the right, conjunctival hyperemia with preserved ocular mobility and visual acuity and painless subcutaneous nodules on the right hemiface. Nasoendoscopy showed no changes in the left or nasopharynx; in the right, edema and mucosa hyperemia obstructing the upper airway and purulent rhinorrhea.

Contrast computerized tomography (CT) of sinuses and orbit revealed extraconal infiltrating and expanding injury compromising orbit and right periorbit, with eyeball proptosis; maxillary, sphenoid sinus, ethmoidal cells, frontal sinus, and nasolacrimal duct were obliterated; and infiltration of the skin and subcutaneous on the right was identified (Figure 1B and C).

Abdomen CT revealed splenomegaly (15.5 cm). Pelvis and chest CT were normal. Serologies, rheumatic tests, hemoculture, uroculture, and Mantoux were negative. During admission, cefepime was commenced for febrile neutropenia. Biopsy of the lesion via nasal endoscopy in the right nasal cavity was performed with Epstein-Barr virus (EBV) checking positive. There was not enough material for diagnosis through immunohistochemistry due to the large amount of necrotic material.

There was a gradual worsening of pancytopenia, increase in lactate dehydronagenase (LDH), and episode of right severe epistaxis, which was controlled with nasal packing. Bone marrow biopsy was carried out due to the suspicion of lymphoma, with negative result. Prednisone was initiated in lower doses, and new biopsy of the lesion in the right nasal cavity was performed through lateral rhinotomy, anatomopathology examination identified lymphoma. Extranodal natural killer /T-cell lymphoma, nasal type (ENKL) was confirmed by immunohistochemistry. Treatment with radiotherapy and outpatient chemotherapy was commenced.

After 2 months, the patient was admitted to hospital with fever and pancytopenia. A treatment with piperacillin and tazobactam was commenced. As no response was observed, antibiotic treatment was changed to cefepime. Fever persisted, general condition worsening progressed, liver and renal failure occurred. Nephrotoxic and hepatotoxic drugs were suspended, with no improvement in the condition. A new abdominal CT was requested for investigation of the clinical worsening, which suggested lymphoma progression with renal and hepatic infiltration. There was no response to new pushes of corticosteroid therapy. Patient died on the 17th day of admission.

Case 2

An 86-year-old female, healthy, was referred to otorhinolaryngologist after 3 months of admission at another hospital due to acute rhinosinusitis with no response to clinical treatment. She reported nasal obstruction, pain, and facial pressure on the left side, and pyrexias. Computerized tomography (Figure 2A) showed complete opacification of the sinuses on the left with eye globe deviation and partial destruction of the ipsilateral lamina papyracea. Upon examination, she presented hyperemia, peripalpebral edema, and deviated left eye; otoscopy, oral assessment, and cervical palpation without abnormalities; rhinoscopy, granulomatous infiltrated lesion with irregular mucosa was identified, obstructing the left nasal cavity. Right videonasofibroscopy had no abnormalities. Biopsy from the left nasal cavity revealed inflammation and the presence of fungi. Patient experienced clinical worsening and progression of the lesion with crusts in the nasal dorsum and increase in the edema and periocular hyperemia. Rheumatoid factor, antineutrophil cytoplasmic antibody, complement, anti-HIV, and syphilis workup was normal. Cultures showed Candida sp. and Aspergillus sp. A treatment for aspergillosis was initiated. However, the case progressed to worsening of the lesion, necrosis of the nasal dorsum, and palate infiltration. Debridement of the lesion and biopsy was performed (Figure 2B). The immunohistochemistry confirmed T/NK cells lymphoma of the nasal type. On the 45th day of chemotherapy, the patient presented partial response to the treatment but died after 5 months of admission.

Figure 2.

A, Coronal contrast computerized tomography of nose and sinuses demonstrating complete opacification of the sinuses on the left side with eye globe deviation and partial destruction of the ipsilateral lamina papyracea. B, Pre- and postdebridement of the lesion and removal of fragments for biopsy.

Discussion

Lymphoma is a lymphatic system neoplasia arising from the clonal proliferation of B or T cells, which is subdivided in 2 groups: Hodgkin lymphomas and non-Hodgkin lymphomas. The non-Hodgkin lymphomas are divided into B and T cells and NK cells. The primary nasal lymphoma is rare and represents 0.44% of the extranodal lymphomas of the nasal–sinusal region. It is an extranodal tumor of the T cells and non-Hodgkin natural killer—T/NK type. About 75% of the primary nasal lymphomas arise from the T-lineage cells. ¹

Extranodal natural killer/T-cell lymphoma, nasal type, previously known as lethal midline granuloma, received different denominations due to the difficulty to determine its physiopathologic mechanism. The present denomination “extranodal NK/T-cell lymphoma of the nasal type” was adopted by the REAL rating (Revised European American Lymphoma Classification), proposed by World Health Organization. ² It is more frequent in Eastern countries, especially in males, and there is no age predilection. Some authors report that ENKL represents 40% to 74% of the sinonasal lymphomas in these places. ³ The physiopathology is unknown. However, the relation to immunodepression, autoimmune disorders, and infections agents is known. ¹

Unspecific symptoms such as nasal obstruction, rhinorrhea, and epistaxis normally comprise the initial condition. Initially, the symptoms may suggest sinusopathy; however, the disease progresses. ^1,3,4,5

Extranodal natural killer /T-cell lymphoma, nasal type is characterized by the destruction of soft parts involving structures of the upper respiratory tract: nose, sinuses, palate, and facial soft tissues. ¹ The histopathological and immunophenotypic characteristics include angiocentric features, angiodestruction with a changeable level of atypia, infiltrated polymorph with normal, and atypical lymphocytes of different sizes with plasmocytes, eosinophils, and histiocytes. The neoplastic cells usually express CD2, CD56, and CD3 epsilon range in the cytoplasm, are CD3 negative surface (−), and CD3 positive cytoplasmic (+). They are typically CD4—and CD8—but can express CD4, CD8, and/or CD7. ^4,6

The presence of the EBV by in situ hybridization reinforces the diagnostic. Studies suggest that the EBV viral load may have a prognostic impact besides being useful in the follow-up of the therapeutic response. ^4,6,7

Therapeutic schemes of radiotherapy and chemotherapy, associated or not, have been proposed for ENKL. ⁸ However, similarly, there are still few randomized prospective studies which corroborate a better treatment. Studies with small number of patients suggest that transplant with hematopoietic stem cells might be promising. ⁹