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Unusual Hematologic Malignancies

Case 3. CNS Involvement in CD56-Positive Intestinal Gamma/Delta T-Cell Lymphoma

Queen Mary Hospital, Hong Kong

Peripheral T-cell lymphoma expressing the gamma/delta () 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 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 x 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.

View larger version (87K): [in this window] [in a new window]   Fig 1.

The differential diagnoses in this case included enteropathy-associated T-cell lymphoma, natural killer (NK) cell lymphoma, and 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 CD3 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 T-cell lymphoma. T-cell lymphoma was first described as a distinct entity, hepatosplenic 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 T-cell lymphomas have since been reported.³

To date, only three cases of primary intestinal 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⁺ T cells, normally a rare subpopulation of circulating T cells.⁹ This is in contrast to nearly all the reported cases of 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^- T cells.^2,3 Therefore, without an analysis of the TCR, our case may be confused with other intestinal ß 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 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⁺ T-cell lymphomas.

NOTES

Copyright © 2002 American Society of Clinical Oncology

REFERENCES

1. Harris NL, Jaffe ES, Diebold J, et al: World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: Report of the clinical advisory committee meeting, Airlie House, Virginia, November 1997. J Clin Oncol 17: 3835-3849, 1999[Abstract/Free Full Text]

2. Farcet JP, Gaulard P, Marolleau JP, et al: Hepatosplenic T-cell lymphoma: Sinusal/sinusoidal localization of malignant cells expressing the T-cell receptor gamma delta. Blood 75: 2213-2219, 1990[Abstract/Free Full Text]

3. Arnulf B, Copie-Bergman C, Delfau-Larue MH, et al: Nonhepatosplenic gamma delta T-cell lymphoma: A subset of cytotoxic lymphomas with mucosal or skin localization. Blood 91: 1723-1731, 1998[Abstract/Free Full Text]

4. Chott A, Haedicke W, Mosberger I, et al: Most CD56+ intestinal lymphomas are CD8+CD5- T-cell lymphomas of monomorphic small to medium size histology. Am J Pathol 153: 1483-1490, 1998[Abstract/Free Full Text]

5. de Wolf-Peeters C, Achten R: Gamma delta T-cell lymphoma: A homogeneous entity? Histopathology 36: 294-305, 2000[CrossRef][Medline]

6. Chan JKC, Sin VC, Wong KF, et al: Nonnasal lymphoma expressing the natural killer cell marker CD 56: A clinicopathologic study of 49 cases of an uncommon aggressive neoplasm. Blood 89: 4501-4513, 1997[Abstract/Free Full Text]

7. Kwong YL, Chan ACL, Liang R, et al: CD 56⁺ NK lymphomas: Clinicopathological features and prognosis. Br J Haematol 97: 821-829, 1997[CrossRef][Medline]

8. Katoh A, Ohshima K, Kanda M, et al: Gastrointestinal T cell lymphoma: Predominant cytotoxic phenotypes, including alpha/beta, gamma/delta T cell and natural killer cells. Leuk Lymphoma 39: 97-111, 2000[Medline]

9. Bucy RP, Chen CL, Cooper M: Tissue localization and CD8 accessory molecule expression of T gamma/delta cells in humans. J Immunol 142: 3045-3049, 1989[Abstract]

10. Lanier LL, Chang C, Azuma M, et al: Molecular and functional analysis of human natural killer cell-associated neural cell adhesion molecule (N-CAM/CD56). J Immunol 146: 4421-4426, 1991[Abstract]

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Chim, C.S. Articles by Kwong, Y.L. Search for Related Content PubMed PubMed Citation Articles by Chim, C.S. Articles by Kwong, Y.L. Social Bookmarking                            What's this?