pathtalk.org is a weblog about pathology and laboratory medicine.

B-cell clonality: Recurrent lymphoma?

Clinical History and Pathological Findings
An elderly woman presented with mild anemia and was found to have a positive fecal occult blood test and a positive serum anti-H. pylori IgG antibody test. Endoscopy was performed, and several superficial gastric and duodenal ulcers were biopsied.

B-cell IgH PCR revealed a clonal B-cell population, and the diagnosis of extranodal marginal-zone lymphoma was made. After treatment with antibiotics, repeat biopsy showed persistent lymphoma, and she underwent radiation therapy. After radiation, further biopsies demonstrated complete histological remission of the lymphoma.

Follow Up
After an interval of twenty months, she was found to have an incidental parathyroid adenoma, for which she underwent a parathyroidectomy and partial thyroidectomy.

The morphological and immnuohistochemical findings in the thyroid seemed more consistent with Hashimoto thyroiditis than with lymphoma. However, given her history, B-cell IgH PCR was performed on the thyroid tissue. A clonal B-cell population was detected, with the same immunoglobulin gene rearrangement size as the previous clonal population detected in the patient’s gastric MALToma. FISH for t(11;18) showed that the translocation was present in both the gastric and thyroid samples.

Discussion
This case raises some interesting questions about the significance of clonality in lymphomagenesis. Though clonality is usually strong evidence for hematopoietic malignancy, a growing body of literature shows that clonality may be found in various benign hematopoietic cell populations.¹ In gastric MALT lymphoma, the malignant behavior of the B-cell clone is believed to be driven by continual antigenic stimulation by H. pylori antigens, which is why antibiotic treatment is frequently curative, and why persistent clonal B-cell populations can sometimes be found in cases of complete histological lymphoma regression.^2-3 There is also evidence that patients with autoimmune disease have a decreased response to H. pylori eradication therapy.⁴ The presence of t(11;18) typically indicates a more aggressive course with a diminished response to antibiotic treatment, which also raises questions about prognosis and about the significance of the possible autoimmune stimulus in the thyroid. To date, this patient has no clinical evidence of further malignant behavior of the B-cell clone, in the thyroid or elsewhere. What do you think? Could the clonal cells in the thyroid be thyroid benign, or will her lymphoma progress?

1. Torlakovic E, Cherwitz DL, Jessurun J, Scholes J, McGlennen R. B-cell gene rearrangement in benign and malignant lymphoid proliferations of mucosa-associated lymphoid tissue and lymph nodes. Human pathology. 1997 Feb;28(2):166-73.
2. Hussell T, Isaacson PG, Crabtree JE, Spencer J. The response of cells from low-grade B-cell gastric lymphomas of mucosa-associated lymphoid tissue to Helicobacter pylori. Lancet. 1993 Sep 4;342(8871):571-4.
3. Fishleder A, Tubbs R, Hesse B, Levine H. Uniform detection of immunoglobulin-gene rearrangement in benign lymphoepithelial lesions. The New England journal of medicine. 1987 Apr 30;316(18):1118-21.
4. Raderer M, Osterreicher C, Machold K, Formanek M, Fiebiger W, Penz M, et al. Impaired response of gastric MALT-lymphoma to Helicobacter pylori eradication in patients with autoimmune disease. Ann Oncol. 2001 Jul;12(7):937-9.