Deceptive nasal NK/T-cell lymphoma

Introduction

Nasal NK/T cell lymphoma (NKTL), also known as lethal midline granuloma, rarely manifests in the nose and paranasal sinus. It is very aggressive and carries a very poor prognosis; hence, early diagnosis and treatment determine the outcome of this disease. Clinical features of NKTL overlap with atrophic, chronic and granulomatous rhinosinusitis. NKTL is diagnosed mainly by exclusion as the clinical course and histopathology are often misleading and even the latest radiological investigations provide little help in making the diagnosis. We present a case of NKTL that masqueraded as fungal rhinosinusitis.

Case report

A 30-year-old man presented with facial swelling and fever for the previous 2 months. He also gave a history of nasal obstruction with foul-smelling nasal discharge for 1 month. Subsequently, he developed difficulty in opening his eyes and loss of vision in the left eye. He was a motor mechanic working in a hot humid geographical location. On examination (Figure 1), there was facial oedema extending from the infra-orbital margin up to the nasofacial grooves bilaterally. The left nasal ala and its adjoining skin were covered with crusts. The nasal cavity was filled with yellow-greenish crusts producing a foul nasal discharge. There was an anterior septal perforation. The soft palate contained multiple superficial ulcers. OPEN IN VIEWER

Investigations revealed a mild anaemia (Hb: 100 g/L), mild thrombocytopenia (platelets: 140 × 10³/mm³), a raised ESR (56 mm/h), mildly deranged liver function tests, a negative syphilis, HIV and hepatitis screen, and normal chest radiography. High-resolution computed tomography (CT) of the paranasal sinuses showed non-enhancing soft tissue in the nasal cavity itself and all the paranasal sinuses except the right frontal (Figures 2 and 3). The osteomeatal complex was wide with a nasal septal perforation. OPEN IN VIEWER

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Figure 3.

Coronal section of nasal and paranasal sinus high-resolution CT showing necrotic soft tissue in maxillary and ethmoidal sinuses and the nasal cavity bilaterally.

On the basis of this, a probable diagnosis of invasive fungal rhinosinusitis was entertained. Sinus endoscopy revealed extensive crusts and polypoidal mucosa in all the sinuses. The latter was debrided and sent for histopathological examination, which demonstrated predominantly necrotic tissue, scattered inflammatory cells, with hyperchromatic irregular nuclei, but no fungal elements seen on PAS stain. However, fungal culture indicated an acremonium species. There was some improvement with lipoidal amphotercin B treatment in the first week, but following this the patient’s facial and neck oedema worsened. A second scan was performed that showed pansinusitis, diffuse oedema in the naso- and laryngo-pharynx, and facial subcutaneous tissues. Cervical lymphadenopathy at levels III–V was noted. Despite antibiotics and antifungal therapy, the patient’s condition failed to improve. He was, therefore, again subjected to sinus endoscopy and further debridement. This time abundant necrotic tissue, markedly transformed cells, histocytosis and angioinvasion were found. These features are suggestive of NKTL, which was confirmed by positive immunohistochemistry (CD2, CD3 and CD56). However, after a single cycle of chemotherapy, the patient died.

Discussion

Fungal rhinosinusitis has been recognised over the last two decades. Although it is more common in immunocompromised patients, it may also be seen in immunocompetent individuals as a chronic or indolent invasive fungal sinusitis, an allergic fungal sinusitis or a fungus ball. Clinical presentation depends upon the immune status and common symptoms include nasal congestion, periorbital discomfort, polyps, proptosis, bony erosion and rapidly progressive cranial nerve deficits. Although the clinical history and associated radiology may help, microbiology and histopathology are necessary to reach a diagnosis. Surgical debridement, antifungal therapy and immune support direct the clinical outcome.

Our case showed unexpected rapid deterioration, forcing us to revise our diagnosis to extranodal NKTL, which is rare in the sinonasal region and is mainly found in Asia and Latin America. ¹ It presents with aggressive destruction of the midline structures, typically in adults but also in children. It is predominantly found in men (male:female ratio, 2:1) and associations exists with the Epstein–Barr virus (EBV), genetics, geography, lifestyle and environmental factors. ¹ While NKTL is most common in the nasal cavity, other sites where it can be found include the skin, gastro-intestinal tract, testis, kidney, upper respiratory tract and rarely the eye and orbit. It is locally destructive and nasal septal perforation has been reported in 40% of cases. ² Clinical features usually mimic chronic rhinosinusitis and CT scan shows homogenous and non-enhancing tumour without central necrosis which in early cases may be confined to the nasal cavity. ³

A good amount of viable tissue is a prerequisite for satisfactory histopathological examination of biopsy specimens, otherwise necrotic tissue will mislead the management as occurred in our case.^2,4,5 On histopathology, angioinvasion and necrosis is always seen; transformed cells and reactive histiocytes with erythrophagocytosis are confirmatory features.^2,6 However, these features are also found in other types of lymphoma, requiring immunohistochemistry to make a precise estimation. Positive cytoplasmic CD2, CD3 and CD56 with negative surface CD3 and cytotoxic markers (TIA-1 and granzyme B) are usually seen in NKTL. An association with EBV, validated by in situ hybridization of EBV of early RNA, is found with NKTL but EBV is also associated with other lymphomas found, especially in HIV-positive patients.^2,6–11 Treatment consists of chemoradiation, depending upon the stage of the disease. However, it has a very poor prognosis, with an average survival rate of only 6–25 months, though Vazquez et al. ¹² found better results in extranodal NKTL.

Another differential is Wegener’s granulomatosis, but this needs immunofluorescence studies for confirmation. In our case, the fungal elements found in the debrided tissue led us to presume a fungal rhinosinusitis. However, in our case, fungi were secondary to NTKL, which was missed owing to inadequate biopsy specimens.

Conclusion

NKTL can easily masquerade as chronic or fungal rhinosinusitis and we should keep a suspicion of an underlying leukaemia or lymphoma in resistant fungal or chronic rhinosinusitis showing atrophic changes. Histological diagnosis in NKTL is difficult and adequate biopsy should be supplied to the pathologist who should always perform immunohistochemistry analysis for its exact diagnosis to avoid delay in management.