TEACHING CASE 5

Relevant clinical history:
A 68 year old man with a ten year history of celiac disease presented with a 1-2 month onset of fevers, sweats, weight loss, and abdominal pain. At surgery, the patient was found to have numerous small bowel mucosal ulcerations, masses, and strictures.

H & E images:

Low power	Medium power
High power	Hematoxylin and eosin stained sections of the tumor show a malignant tumor eroding through the mucosal surface (left), composed of sheets of cells with enlarged nuclei and some nucleoli (center, right)

The process appears to be a malignant tumor, with immunohistochemical studies revealing the following immunophenotype:

	Cytokeratin (antibody OSCAR): Negative The tumor cells are negative.
	CD45: Positive CD30: Negative CD20: Negative
	CD3: Positive The tumor cells are uniformly positive; note that, as found not infrequently in T cell malignancies, the antibody yields both a membranous as well as cytoplasmic immunostaining pattern.
	CD5: Negative The tumor cells are negative, but some non-neoplastic T cells are identified within the tumor.
	CD56: Negative Anti-CD56 The tumor cells are negative, but the antibody does identify some nerve twiglets that are trapped within this tumor.
	Ki67-antigen (antibody MIB-): Very high The Ki67-defined cell proliferation index of this tumor is very high, in excess of 90%.
	TIA-1: Positive The presence of this cytotoxic granule protein is confirmed, showing a characteristic coarse, cytoplasmic granular pattern.

FINAL DIAGNOSIS: Enteropathy type T cell lymphoma

DISCUSSION:
The majority of primary intestinal lymphomas are of B-cell lineage; furthermore, most of these are high-grade tumors (e.g., diffuse large B cell lymphoma, Burkitt-type lymphoma). Low grade B cell lymphomas are less common, and include extra-nodal marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT) type and, less frequently, follicular center-cell lymphomas. Primary intestinal mantle-cell lymphoma often presents as multiple lymphomatous polyposis and similarly to its lymph node-based counterpart, has an unfavorable prognosis.

The case at hand clearly marks as a T cell lymphoma (i.e., CD3-positive). While NK-T cell lymphomas, with the identical CD56+/EB virus+ immunophenotype as their more common nasal counterparts have been described (1), most primary intestinal T-cell lymphomas are characterized as enteropathy-type T cell lymphoma in the new W.H.O. classification (2). In the older REAL classification this was referred to as 'intestinal T cell lymphoma', and it did not have a real counterpart in the Working formulation. It most commonly occurs in the jejunum or ileum, and most patients, as in the case at hand, present with celiac disease (although the 10 year history as in this case is unusually long). Enteropathy-type T cell lymphoma typically forms an ulcerating mucosal mass, with the tumor composed histologically of medium- to large cells with round or angulated nuclei and prominent nucleoli. Admixture with non-neoplastic inflammatory cells, including histiocytes and eosinophils, is common, and may obscure the tumor.

As in the case at hand, the tumor cells generally show an abnormal T cell pheontype: CD3+/CD5-/CD7+/CD8+ or -/CD4-, and also express the cytotoxic granule associated proteins TIA-1, granzyme B, and perforin.

Clinically, these are aggressive diseases with a high mortality rate. Death often results from abdominal complications in patients weakened by uncontrolled malabsorption. A useful recent review of intestinal T cell lymphomas was written by Chott et al. (3).

References:

1. Chim CS, Au WY, Shek TW, Ho J, Choy C, Ma SK, et al. Primary CD56 positive lymphomas of the gastrointestinal tract. Cancer 2001;91(3):525-33.
2. Jaffe ES, Harris NL, Stein H, Vardiman JW, editors. Pathology and genetics of tumours of the hematopoietic and lymphoid tissues. Lyon: IARC Press; 2001.
3. Chott A, Vesely M, Simonitsch I, Mosberger I, Hanak H. Classification of intestinal T-cell neoplasms and their differential diagnosis. Am J Clin Pathol 1999;111(1 Suppl 1):S68-74.
   
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