Peripheral T-cell lymphoma expressing the gamma/delta (γδ) T-cell receptor (TCR) is a recently characterized aggressive neoplasm.¹ They are unusual lymphomas described initially to involve only the liver and spleen (hepatosplenic γδ T-cell lymphoma),² but later they were found in other extranodal sites.³ The intestine, however, is rarely involved.

A 51-year-old man with fever, abdominal pain, diarrhea, and weight loss of 6 kg over a 2-week period presented with acute peritonitis. There was no history of gluten sensitivity. Emergency laparotomy showed two perforated jejunal tumors measuring 8 and 12 cm, which were surgically resected. Another jejunal tumor adherent to the colon could not be removed. Pathologic examination showed sheets of medium-sized lymphomatous cells under the ulcerated epithelium infiltrating the mucosa and submucosa (Fig 1A, CD3 staining). Mitosis was frequent, but no angiocentric lesions were identified. No enteropathy (villous atrophy, crypt hyperplasia, and increase in intraepithelial lymphocytes)⁴ was identified in the nontumorous intestinal mucosa. Immunohistochemical studies showed that the lymphoma cells expressed cytoplasmic CD3, CD8, and CD56 (Fig 1B, CD56 staining), but not CD5 and other B-cell markers. In situ hybridization for Epstein-Barr virus–encoded RNA was negative. A postoperative abdominal computed tomography (CT) scan showed a heterogeneous, circumferential small bowel lymphoma measuring 17 cm × 9 cm. Infiltration of the peritoneal fat (Fig 2, arrows) was noted around the matted bowels (Fig 2, marked B), which showed a central lumen containing air and contrast material. The marrow was not involved. Two courses of cyclophosphamide, epirubicin, vincristine, and prednisolone (CEOP) were administered, which resulted in a minimal response.

Before the third course of CEOP, the patient developed generalized convulsion. A CT scan of the brain showed two minimally enhancing hyperdense nodules with surrounding edema in the right high parietal lobe (Fig 3, arrows) and the left frontal lobe (Fig 3 inset, arrows). Lumbar puncture showed lymphoma cells with abundant pale cytoplasm containing azurophilic granules (Fig 4A) that were CD2⁺, CD3⁺, CD4⁻, CD8⁺, and CD56⁺ and expressed the γδ TCR (Fig 4B). Polymerase chain reaction for the TCR-γ gene showed a monoclonal band. The features were consistent with metastatic T-cell lymphoma from the gut primary tumor. He became comatose and died soon afterward.

The differential diagnoses in this case included enteropathy-associated T-cell lymphoma, natural killer (NK) cell lymphoma, and γδ T-cell lymphoma.⁵ Enteropathy-associated T-cell lymphoma, particularly in patients with celiac disease, is extremely rare in the Chinese.⁴ Furthermore, pathologic changes of enteropathy were absent in our case. The expression of the NK cell antigen CD56 makes NK cell lymphoma another possibility. NK cell lymphomas are extranodal lymphomas that may present in the bowel.^6,7 Histologically, the tumor is characterized by angiocentricity, angiodestruction, and zonal necrosis.¹ They express cytoplasmic CD3ε and may thus be confused with peripheral T-cell lymphomas, if immunohistochemical studies of the tumors by polyclonal anti-CD3 antibodies are used.^1,6,7 However, surface CD3 and TCR are not expressed in NK cell lymphomas, and the TCR gene is not rearranged.¹ The absence of histologic features of NK cell lymphomas, the expression of surface CD3 and TCR, the absence of Epstein-Barr virus in the tumor cells, and the presence of clonal TCR gene rearrangement excluded the diagnosis of NK cell lymphoma in our patient.

The diagnosis is therefore consistent with primary intestinal γδ T-cell lymphoma. γδ T-cell lymphoma was first described as a distinct entity, hepatosplenic γδ T-cell lymphoma, that preferentially affected the liver and spleen without nodal involvement. The neoplastic cells are typically CD2⁺CD3⁺CD4⁻CD5⁻CD8⁻, with variable expression of CD56 and other cytotoxic markers, eg, TIA-1, granzyme B, and perforin.^2,3 The disease is aggressive and has a poor survival rate. Nonhepatosplenic γδ T-cell lymphomas have since been reported.³

To date, only three cases of primary intestinal γδ T-cell lymphoma have been described.^3,8 Our case illustrates some interesting features. First, extensive multifocal intestinal infiltration with bowel perforation is a common mode of presentation.^3,4,8 Enteropathy and gluten sensitivity are typically absent. Interestingly, the tumor cells in our case were apparently derived from CD8⁺ γδ T cells, normally a rare subpopulation of circulating γδ T cells.⁹ This is in contrast to nearly all the reported cases of γδ T-cell lymphoma whether or not they are hepatosplenic, in which the tumor cells were CD4⁻CD8⁻, reflecting derivation from the commonest circulating CD4⁻CD8⁻ γδ T cells.^2,3 Therefore, without an analysis of the TCR, our case may be confused with other intestinal αβ T-cell lymphomas, which are commonly CD3⁺CD4⁻CD5⁻CD8⁺ and which may present with similar clinical features.⁴

Finally, CNS dissemination is rarely reported in intestinal γδ T-cell lymphomas. CNS involvement may be related to CD56 expression in our case. Known as neural cell adhesion molecule, CD56 engages in homophilic binding with itself physiologically,¹⁰ so that preferential metastasis of CD56⁺ lymphomas to CD56-expressing sites has been reported.^6,7 Thus, the peculiar CNS dissemination in our case may be attributable to the expression of CD56. Accordingly, further studies are needed to define the risk of CNS involvement in CD56⁺ γδ T-cell lymphomas.