—  SHORT COURSE #63  —

A Practical Approach to the Diagnosis of Common Hematopoietic and Solid Tumors of Childhood

Case 9 - Diffuse Large B-Cell Lymphoma

D. Ashley Hill, M.D.
Mihaela Onciu M.D.


Case History:
17-year-old previously healthy boy presenting with small bowel obstruction. An abdominal CT showed a terminal ileal mass. The patient underwent terminal ileal resection. The resected mass measured 8 cm in greatest dimension and was situated 13-14 cm proximal to the ileal-cecal valve. The margins of resection were grossly clear of tumor. No additional sites of involvement were found at staging work-up.

Microscopic Findings:
Histologic sections showed an infiltrative malignant lymphoid neoplasm with diffuse growth pattern involving all layers of the small intestinal wall with ulceration of the overlying mucosa. Focally (<10% of the tumor) a nodular architecture was noted. Within the diffuse and focal areas the infiltrate was composed of relatively uniform large lymphoid cells with irregular nuclear outlines, coarsely clumped chromatin and variably prominent peripherally-located nucleoli. Frequent mitotic figures were noted. The sampled regional mesenteric lymph nodes showed no evidence of lymphoma.

Differential Diagnosis:
  1. Diffuse large B-cell lymphoma

  2. Burkitt lymphoma, atypical variant

  3. Enteropathy-associated T-cell lymphoma.

Immunophenotypic Findings:
By flow cytometry, the tumor contained a population of large lymphoid cells that expressed CD10, CD19, CD20, CD23, and lambda light chain restricted surface immunoglobulin, and were negative for CD34 and Tdt. Immunohistochemical staining showed the tumor cells to strongly express CD45 and CD20, with weak expression of CD10, BCL-2 and BCL-6. Staining for Ki-67 highlighted a proliferation fraction of ~80%. Tumor cells were negative for CD3. The latter stain was positive in the numerous mature T-lymphocytes infiltrating the tumor.

Molecular/Cytogenetic Analysis:
Cytogenetic analysis revealed complex clonal abnormalities as follows: 45,X,-Y,del(6)(q14),del(17)(p13)[13]/57,idemx2,+1,+3,+5,+9,+10,+15,+16,+20,+20, +22[1]/46,XY[6]. There was no evidence of a Burkitt-type translocation. Molecular analysis was not performed.

Diagnosis:
Diffuse large B-cell lymphoma, centroblastic variant. The expression of CD10, BCL-6, and BCL-2, as well as the focal nodular architecture suggest follicular center cell differentiation in this lymphoma.