Nasal-type extranodal NK/T-cell lymphoma presenting as recurrent periorbital cellulitis

Abstract

Nasal-type extranodal natural killer/T-cell lymphoma (ENKTCL) is a rare disease with a poor prognosis. It has features similar to other granulomatous and infectious diseases of the nose and paranasal sinuses, which can make diagnosis challenging and delayed. We present a case of 38-year-old man who was admitted to the hospital on three occasions over a 3-month period for right periorbital erythema, nasal congestion and discharge. Following two separate surgical debridement and biopsies, ENKTCL was diagnosed and the patient was commenced on chemoradiotherapy. The case highlights the atypical nature of his presentation and the high degree of suspicion for a pathological process that must be maintained to formulate the diagnosis.

Background

Sinonasal lymphomas are rare in Western populations, occurring at a higher incidence in Asia and South America, and account for 2.6%–6.7% of all non-Hodgkin lymphomas (NHLs).¹ Nasal T-cell lymphomas differ phenotypically from lymphomas of the paranasal sinuses and Waldeyer’s ring, which tend to be of B-cell origin.²

Known previously as midline malignant reticulosis or polymorphic reticulosis, extranodal natural killer/T-cell lymphoma (ENKTCL) is a rare disease and constitutes as much as 3% of all NHLs.³ Often proving challenging to diagnose, it is associated with a 50% mortality rate from extranodal spread or relapse.⁴ It is closely associated with Epstein–Barr virus (EBV) infection.¹

We present the case of a 38-year-old man who presented on three occasions with right periorbital cellulitis and oedema. Initially thought to be infectious in nature, he was diagnosed with sinonasal-type ENKTCL following two subsequent surgical debridement and biopsies. Mori et al in 2018 presented a case of nasal-type ENKTCL that took time to make a final pathological diagnosis.⁵ Similarly, the Gomes et al case report took 5 months from initial complaint to diagnosis.⁶ We agree with Gomes et al that multiple deep-tissue biopsies are usually required.

Case presentation

A 38-year-old Polish man presented to the emergency department with right periorbital swelling and nasal congestion associated with a right frontal headache/periorbital pain. The patient has no other comorbidities that could be linked to immunosuppression; history was notable for intranasal cocaine and nicotine use for 3 years. Examination demonstrated an erythematous ‘swollen inflamed orbit’ with mild proptosis of the right eye, eye movement was intact. Endonasally, the nasal mucosa of the right nasal cavity was inflamed, swollen with purulent drainage and necrotic debris, while the mucosa of the left nasal cavity was normal. CT imaging demonstrated opacification of the right ethmoid and maxillary sinuses with an erosion of lamina papyracia (figures 1 and 2); he was treated for a periorbital cellulitis, and his clinical picture improved with intravenous antibiotics, nasal decongestants and steroids without surgical intervention.

Figure 1.

Preoperative axial paranasal sinus CT scan illustrating right ethomid opacification and partial erosion of the lamina paparicia.

Figure 2.

Coronal paranasal sinus CT scan on third presentation demonstrating a right intraorbital soft tissue mass with globe displacement.

Six weeks later, he represented with similar symptoms and signs. CT imaging demonstrated similar findings with additional findings of an extraconal intraorbital inflammatory mass (figure 2). In addition to medical treatment, he underwent exploratory endoscopic sinus surgery. The mucosa of the ethmoids and maxillary and frontal sinuses was highly atypical, replaced by white, poorly vascularised necrotic tissue, with frank pus released from the maxillary and frontal sinuses. Workup for granulomatous autoimmune disorders was negative. Multiple biopsies confirmed necrotic tissue with inflammation and vancomycin-resistant enterococci were grown from the pus released intraoperatively. With assistance from clinical microbiology, he was treated with linezolid.

Nevertheless, 3 weeks later, he again developed right periorbital swelling and erythema. Following further biopsies and debridement, histopathological and immunohistochemistry examination of tissue taken from the medial orbital wall and the lateral maxillary sinus wall confirmed ENKTCL (figure 3). Full-body CT scan and bone marrow aspirate revealed the disease was confined to the paranasal sinuses.

Figure 3.

(A–D) Lateral maxillary sinus wall. H&E-stained sections at ×40 (A) and ×100 (B) magnification showing infiltrate of intermediate and large atypical lymphocytes, with extensive necrosis. The cells express CD3 (C) and EBER-ish (D) is strongly positive. EBER-ish, EBV-encoded RNA in-situ hybridisation.

This patient was referred to haematology for workup. Positron emission tomography–CT imaging confirmed disease confined to the nose and paranasal sinuses.

Following multidisciplinary discussion, the patient was treated with four cycles of steroid, methotrexate, ifosfamide, L-asparaginase and etopside (SMILE) chemotherapy, in addition to radiation therapy.

The patient provided informed consent before he was taken into consideration as a case study for possible journal publication.

Outcome and follow-up

After receiving four cycles of (SMILE) chemotherapy and radiation, the patient is currently in remission and under regular follow-up by the haematology and otolaryngology teams.

Discussion

Extranodal NK/T-cell lymphoma is a rare malignancy in the USA and Europe, being far more common among Asians and individuals of native American descent in Mexico, Central America and South America.⁴ Previously, many cases were defined as polymorphic reticulosis or lethal midline granuloma. It is currently recognised as a subtype of lymphoma. In most cases, this is of NK-cell lineage; less frequently, it is composed of cytotoxic T cells.¹ The pathogenesis of this type of lymphoma is strongly linked to the EBV.¹ However, the prognostic value of EBV DNA in ENKTCL remains unclear.⁷

Several cases of ENKTCL within the nose and paranasal sinuses have been described in the literature. Bhatt et al reports a case presenting with palatal performation and naso-oral fistula.⁸ A total of 138 cases of the NK cell worldwide between 2006 and 2016 according to The International Peripheral T-cell Lymphoma Project.⁹ Diagnosis is typically challenging, with symptoms often mimicking chronic rhinosinusitis. A low index of suspicion for possible malignancy with repeated and multiple biopsies is critical for an early diagnosis. This is not the first Irish case of ENKTCL causing orbital complications. Hughes et al describes uveitis and recurrent retinal detachment.¹⁰

Pathological evaluation demonstrated fibroconnective tissue with extensive necrosis and an infiltrate of dense lymphoid infiltrate composed predominantly of intermediate sized atypical lymphoid cells, with scattered larger cells. Areas of angiocentric/angiodestructive growth were also present. The atypical lymphoid infiltrate expressed CD2, CD3, CD56 and granzyme B. EBV-encoded RNA in-situ hybridisation (EBER-ish) was strongly positive (figure 3). Bone marrow biopsy showed scattered EBV-encoded RNA-positive cells (EBV-encoded small RNAs). The B-cell CD20 marker was negative in the atypical cells. A clonal T-cell population was demonstrated by multiplex PCR. A clonal population favours a cytotoxic T-cell origin rather than natural killer-cell origin.

Steroids preoperatively are to be avoided when faced with a suspected lymphoma diagnosis. They may distort cellular morphology and compromise the accuracy and timeliness of a histological diagnosis; this can influence both the choice of treatment and the patient’s response.

ENKTCLs are relatively resistant to CHOP chemotherapy (it includes the drugs cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate (Oncovin) and prednisone).⁴ Radiation has been shown to improve survival in some series.¹¹

High dose of cyclophosphamide, BiCNU (carmustine) and etopside with bone marrow transplantation may also have a role in the treatment of recurrences.¹² The rate of long-term remission is low in patients with this disease, and 50% will die from distant extranodal spread or from relapses outside the treatment field.¹¹

In summary, this patient with ENKTCL presented with features of recurrent orbital cellulitis, highlighting many of the diagnostic difficulties that can arise in such cases, and the patient’s subsequent management.

Learning points.

• The diagnosis of nasal-type extranodal natural killer/T-cell lymphoma can be difficult and delayed due to similarity of presenting symptoms with acute sinusitis.

• Steroid usage may make the diagnosis of lymphoma more difficult.

• Multiple biopsies are often required to assist diagnosis.

• Non-infectious causes of periorbital cellulitis and oedema should always be considered when patients fail to demonstrate a complete response to extensive medical/surgical treatment of acute rhinosinusitis.