Man With a Progressive Nasal Wound
A previously healthy 35-year-old man presented with a progressively worsening right nasal wound. The wound had appeared 10 months earlier as a small hyperkeratotic and painful nodule that rapidly expanded, destroying part of his right nasal bones as well as the right maxillary sinus In addition, the patient had noted intermittent fever, diaphoresis, and weight loss.
On admission, the patient appeared cachectic but in no acute distress. His temperature was 37.3°C (99.1°F); heart rate, 89 beats per minute; blood pressure, 105/60 mm Hg; and oxygen saturation on room air, 94%. Pertinent findings on physilymph nodes and generalized muscle wasting. No organomegaly was noted.
The patient was anemic (hemoglobin level, 10 g/dL and hematocrit, 29%) as well as thrombocytopenic (platelet count, 129,000/μL). His white blood cell count was 4000/μL with 91% neutrophils, 7% lymphocytes, 2% monocytes, and 0% atypical lymphocytes. Blood urea nitrogen level was 22 mg/dL and creatine level was 1.7 mg/dL. His liver function was abnormal with an alkaline phosphatase level of 307 IU/L, aspartate aminotransferase of 168 IU/L, alanine aminotransferase of 67 IU/L, and total bilirubin of 0.9 mg/dL. Erythrocyte sedimentation rate was 20 mm/h. Other laboratory values were normal. A chest radiograph showed no acute abnormality.
After the patient was admitted, a facial-maxillary CT scan revealed destruction of the osseous structures of the right nasal and maxillary regions with thickening of bilateral paranasal soft tissues as well as the right medial canthus in close proximity to the right orbital globe (Figure 2). A biopsy of the right nasal tissue showed abnormal infil- tration of pleomorphic lymphoid-like cells (Figure 3). Immunophenotyping per flow cytometry revealed these cells to be CD45+, CD2+, CD7+, CD56+, CD3−, CD5−, and CD57−. In-situ hybridization for Epstein-Barr virus (EBV) encoded RNA (EBER-1) was positive in these cells (Figure 4). Chest, abdominal, and pelvic CT scans showed only mild splenomegaly without lymphadenopathy.
The patient was given one whole-brain prophylactic radiation therapy session with 10 courses of localized facial radiation therapy and chemotherapy with the ESHAP regimen. Nevertheless, his clinical condition deteriorated; pancytopenia, multiple systemic infections, and renal and liver failure developed. The patient died shortly after while he was receiving hospice care.
NASAL NK-T CELL LYMPHOMA: AN OVERVIEW
Nasal NK-T cell lymphoma belongs to a family of peripheral T cell lymphoma (PTCL) called extra-nodal NK-T cell lymphoma. PTCL are a heterogeneous group of generally aggressive neoplasms that account for only 10% to 15% of all non-Hodgkin lymphoma.1 The classification of PTCL is controversial; the modified WHO classification has currently been adopted. Staging of PTCL is based on the Ann-Arbor system for Hodgkin and non-Hodgkin lymphoma.
Extra-nodal NK-T cell lymphoma is a subtype of PTCL. There are three major prototypes within this subgroup: nasal type, intestinal type, and subcutaneous panniculitis type. This patient had the nasal type.
Nasal NK-T cell lymphoma was formerly known as angiocentric lymphoma.2 It is the most common cause associated with the syndrome of lethal mid-line granuloma. Nasal NK-T cell lymphoma is most often seen in Southeast Asia. Some clusters have been reported in Central and South America; however, it remains extremely rare in North America and Europe. The age of onset ranges from 13 to 88, with a higher incidence in males than in females. Nasal NK-T cell lymphoma is highly associated with EBV infection and HLA A11 type. Although the underlying genetic alteration of nasal NK-T cell lymphoma is currently unclear, many studies have reported an association with chromosomal loss and/or deletion.1,3
CLINICAL MANIFESTATIONS
Nasal NK-T cell lymphoma typically presents with a mid-facial or nasal lesion that may be mistaken for other diagnoses. Particular attention should be paid to associated signs and symptoms such as head and neck lymphadenopathy, weight loss, nasal obstruction, epistaxis, nasal pain, and orbital swelling.
Laboratory studies may show cytopenia (anemia, neutropenia, thrombocytopenia, or pancytopenia) and abnormal liver function if there is hepatic involvement; however, test results are normal in most patients who present early.
WORKUP
Diagnosis of nasal NK-T cell lymphoma is based on tissue biopsy and immunophenotype with flow cytometry or immunohistochemistry. The malignant infiltrate is usually diffuse and shows an angiocentric and/or angiodestructive pattern. The cells are usually pleomorphic with irregular nuclei, and mitotic figures are easily found. The most typical immunophenotype of nasal NK-T cell lymphoma is CD2+, CD7+, and CD56+. Other T and NK-cell associated antigens are usually negative, including CD3, CD4, CD5, and CD57. As mentioned earlier, nasal NK-T cell lymphoma is almost always associated with EBV; therefore, in situ hybridization for EBV-encoded RNA (EBER-1) is almost always positive in patients with nasal NK-T cell lymphoma.
MANAGEMENT
The treatment of nasal NK-T cell lymphoma remains a challenge. Sobrevilla-Calvo and colleagues4 showed that radiation therapy was superior to chemotherapy in achieving complete remission and improving 5-year survival rate. A more recent report from Rodriguez and associates5 found that a combination of radiation therapy and chemotherapy resulted in a higher percentage of patients who achieved complete and partial remission.
PROGNOSIS
Nasal NK-T cell lymphoma may disseminate rapidly to various sites, including skin, testes, gastrointestinal tract, and lymph nodes. Despite a good initial response to therapy, the relapse rate is high and the prognosis remains extremely poor.6
This case illustrates the potential of non-infectious diseases to masquerade as infectious and the importance of recognizing a rare entity with common clinical presentations. Although nasal NK-T cell lymphoma is extremely rare in the western hemisphere, prompt diagnosis can lead to early and appropriate treatment to prevent mortality in this aggressive malignancy.
1. Jaffe ES, Krenacs L, Kumar S, Kingman DW, and Raffeld M. Extranodal peripheral T-cell and NK-cell neoplasms. Am J Clin Pathol. 1999;111(suppl 1): S46-S55.
2. Yih WY, Stewart JCB, Kratochvil FJ, et al. Angio- centric T-cell lymphoma presenting as midface destructive lesion: case report and literature review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2002;94:353-360.
3. Porcu P, Baiocchi RA, Magro C. Recent develop- ments in the biology and therapy of T-cell and natural killer-cell lymphomas. Curr Opin Oncol. 2003;15:353-362.
4. Sobrevilla-Calvo P, Meneses A, Alfaro P, et al. Radiotherapy compared to chemotherapy as initial treatment of angiocentric centrofacial lymphoma (polymorphic reticulosis). Acta Oncologica. 1993; 32(1):69-72.
5. Rodriguez J, Romaguera JE, Manning J, et al. Nasal-type T/NK lymphomas: a clinicopathologic study of 13 cases. Leukemia Lymphoma. 2000;39 (1-2):139-144.
6. Koom WS, Chung EJ, Yang WI, et al. Angiocentric T-cell and NK/T-cell lymphomas: radiotherapeutic viewpoints. Int J Radiation Oncology Biol Phys. 2004;59:1127-1137.
