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Follicular Lymphoma (Grade 3) Arising within Hashimoto's Thyroiditis |
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Autoimmune inflammatory conditions, including lymphocytic (Hashimoto's) thyroiditis and Sjögren's syndrome, are notorious for harboring reactive B-cell subclones that should not be over-interpreted to represent malignant lymphoma in FNA specimens. Depending on clinical and radiographic findings, detection of suspicious B-cell subclones in FNA specimens by flow cytometry and /or by PCR warrants serious consideration of surgical excision. |
Primary follicular lymphomas of the thyroid gland are rare and much less common than primary marginal zone or large cell lymphomas. In contrast to the majority of nodal-based follicular lymphomas, many extranodal follicular lymphomas arising in thyroid, salivary gland, skin, testis and other sites are BCL2 negative. In a highly relevant 2009 report, half of primary follicular lymphomas of the thyroid gland were BCL2 negative. BCL2 negative cases presented at stage IE and achieved complete remission with multimodality therapy.
A 68 year-old female with a known history of Hashimoto's thyroiditis underwent (A) fine needle aspiration. Based upon FNA findings, she subsequently underwent (B) subtotal thyroidectomy.
- FNA smears consist overwhelmingly of polymorphous lymphoid tissue with frequent tingible body macrophages, suggestive of follicular lymphoid hyperplasia. However, increased large, suspicious lymphocytes are also present. There are relatively few scattered groups of follicular epithelium, including Hurthle cell metaplasia.
- Thyroidectomy reveals a predominant background of typical lymphocytic thyroiditis. In addition, there are discrete macronodules of more densely packed, atypical follicular lymphoid proliferation comprised of admixed small and large centrocytes, lacking frequent tingible bodies, lacking follicle polarization, and lacking frequent mitotic figures. By conventional morphologic criteria, macronodules very much resemble grade 3 follicular lymphoma.
Atypical Follicular Macronodule Images
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low power
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high power
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CD20+
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BCL2-negative
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- FNA flow cytometry reveals a minor 7% population of atypical large B-cells that are CD19+ CD20 (bright)+ CD5- CD10+ and surface lambda light chain-restricted. PCR testing is positive for clonal IgH gene rearrangement but negative for BCL2 gene rearrangement.
- By paraffin immunohistochemistry, suspicious macronodules within the thyroidectomy specimen contain CD20+ BCL2- follicle center B-cells. Of note, there are a large number of CD3+ BCL2+ follicular T-cells within atypical macronodules as well as areas of typical, benign lymphocytic thyroiditis. Paraffin FISH testing is negative for BCL2 gene rearrangement.
Lymphocytic (Hashimoto’s) thyroiditis harboring reactive B-cell subclones versus follicular lymphoma arising within Hashimoto’s thyroiditis.
In the current case, the combination of classic morphologic features and B-cell clonality (confirmed by both flow cytometry and PCR IgH gene rearrangement) is diagnostic of malignant follicular lymphoma despite negativity for BCL2 abnormalities.
Graff-Baker A et al. (2009). Primary thyroid lymphoma: a review of recent developments in diagnosis and histology-driven treatment. Am J Surg Pathol 33:22.
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