Extranodal NK/T-cell lymphoma, nasal type

Definition

An extranodal lymph showing a wide morphological spectrum. There is commonly angiocentricity, vascular destruction and necrosis. While most cases are of NK-cell type, some appear to be composed of cytotoxic g/d T-cells.

Synonyms

Epidemiology

The median patient age is about fifty years^2,4. Most common in Asia (Japan⁴, Korea and China), it is also relatively common in Mexico, South and Central America², where it occurs in adults with a male predominance. It has also been reported in immunosuppressed and post-transplantation patients. EBV is probably pathogenic. Cases complicating transplantation have been reported.

Clinical features

Involvement is most commonly of the nasal cavity, nasopharynx and palate, also of skin, soft tissues, gastrointestinal tract and testes. There may be secondary lymph node involvement. Marrow involvement is uncommon, but there may be overlap with aggressive NK leukaemia.

Patients present with nasal obstruction, epistaxis or midfacial destructive lesions. Rapid dissemination may occur. There may be a haemophagocytic syndrome, which is often a late clinical complication associated with a rapidly fatal outcome².

Cutaneous cases may be solitary but are usually generalised, consisting of tumours, ulcer, or vasculitis/panniculitis. There is commonly a haemophagocytic syndrome¹.

Histopathology

At all sites, there is mucosal ulceration. There is a diffuse lymphomatous infiltrate with angiocentricity and angiodestruction. Fibrinoid necrosis of vessel walls may be seen. Massive coagulative necrosis is common⁴ and there is often marked apoptosis⁴. The neoplastic cells vary from small to large and anaplastic. The nuclei tend to be somewhat elongated, so-called cleaved-like cells, admixed with large blastic cells with round nuclei⁴. An abundant admixture of small lymphocytes, plasma cells, histiocytes and eosinophils may be present, mimicking an inflammatory process.

Cutaneous disease is often "bottom-heavy" with extension into subcutaneous fat. Epidermotropism is rare but an overlying florid pseudoepitheliomatous hyperplasia may mimic carcinoma.

Immunohistochemistry

CD2	positive2, 9/20 (in frozen tissue sections)4
CD3	surface-negative but cytoplasmic e-positive2, 31/31 (polyclonal: monoclonal CD3 (Leu4) on frozen sections is negative)4
CD4	usually negative, 0/314
CD5	usually negative, 0/304
CD7	occasionally positive, 7/20 (in frozen tissue sections)4
CD8	usually negative, 3/31 (cases of positivity may be cytotoxic T-cell lymphomas)4
CD11b	may be positive
CD16	usually negative2, 0/20 (in frozen tissue sections)4
CD20	0/314
CD30	occasionally positive
CD43	usually positive, 23/314
CD45RO	usually positive, 24/314
CD56	positive2 (unless cytotoxic T-cell type), 29/314
CD57	usually negative2
CD94	20/20 (in frozen tissue sections)4
TCR	usually negative, 0/20 (in frozen tissue sections)4
granzyme B	usually positive2, 30/314
TIA-1	usually positive2, 30/304
perforin	usually positive2
TCR	usually negative, unless composed of NK-like T-cells
EBV	positive, 12/314

Cytogenetics

6q deletions are common². T-cell gene rearrangements are lacking.

Molecular studies

• 31/31 positive for EBER-1 (by in-situ hybridisation)⁴

• T-cell receptor b gene rearrangement: 0/7⁴

• T-cell receptor g gene rearrangement: 1/7⁴

Differential diagnosis

Small cell type may be difficult to distinguish from an inflammatory infiltrate (previously referred to as polymorphic reticulosis). This is also the case when there are numerous admixed inflammatory cells. In situ hybridisation for EBER is very helpful.

Herpes simplex infection in the nasal area may produce extensive lymphoid proliferation and necrosis: the lymphocytes are predominantly CD56 positive. However, they lack cytotoxic markers and there is an absence of EBV by in situ hybridisation².

if cutaneous, see cutaneous T-cell lymphoproliferative disorders

lymphomatoid granulomatosis

• blastic or monomorphic NK cell lymphoma/leukemia

• CD56-positive peripheral T-cell lymphoma

• enteropathy-associated T-cell lymphoma

  An overlying florid pseudoepitheliomatous hyperplasia may mimic carcinoma

• While lymphomas of the nasal cavity are of NK type, those in the paranasal sinuses are more often of B-cell origin⁴.

Management

Radiotherapy may be effective for localised disease, but is usually combined with chemotherapy². Expression of high levels of multidrug resistance gene confers resistance to chemotherapy².

Prognosis

Nasal disease is of very variable prognosis with a reported 5-year survival of 58%⁴. Stage I disease has a favourable prognosis⁴. Extra-nasal disease is highly aggressive. There is frequently deletion or mutation of p53, but this does not appear to be of prognostic significance². Expression of CD94 may be associated with a better prognosis³.

References

World Health Organization Classification of Tumours, Tumours of the haematopoietic and lymphoid tissues, IARC Press 2001.

¹ Liu, V. and McKee, P.H. Cutaneous T-cell lymphoproliferative disorders: approach for the surgical pathologist: recent advances and clarification of confused issues. Adv Anat Pathol 2002;9:79-100.

² VE Nava and ES Jaffe. The pathology of NK-cell lymphomas and leukamias. Adv Anat Pathol 2005;12:27-34.

³Lin CW, Chen YH, Chuang YC, et al. CD94 transcripts imply a better prognosis in nasal-type extranodal NK/T-cell lymphoma. Blood 2003; 102:2623-31

⁴ Kitamura A, Yamashita Y, Hasegawa Y, et al. Primary lymphoma arising in the nasal cavity among Japanese. Histopathology 2005; 47:523-32

This page last revised 19.12.2005.

©SMUHT/PW Bishop