Australian Society of Cytology - Pursuit of Excellence
Australian Society of Cytology

Case of the Month

November 2004 - Answer and Discussion

Non Hodgkin's Lymphoma

Answer

Cytology:

DIAGNOSTIC CRITERIA

  • The smears were highly cellular

  • Numerous single cells were seen

  • Some areas showed a mixed population of mature and immature lymphocytes. Occasional tingible body macrophages were noted (Figure 1).

  • Eosinophils were present, however no plasma cells were seen.

  • Scant residual thyroid epithelium showing oncocytic change and a microfollicular pattern was present. Lymphoid cells were admixed with the oncocytic groups (Figure 2).

  • Lymphoid tangles were seen

  • In a few areas the lymphoid population was not so polymorphous, and approximately 60% of the cells were intermediate to large immature lymphocytes. These cells had irregular nuclear membranes and nucleoli. Occasional mitotic figures were seen (Figure 3).

DIFFERENTIAL DIAGNOSIS
Non Hodgkin’s Lymphoma (NHL) arising on the basis of a Hashimoto’s thyroiditis, or a chronic lymphocytic thyroiditis/Hashimoto’s thyroiditis

ANCILLARY TESTS
Anti-thyroid antibody testing was suggested. The patients titre was >2500, indicating she had a raging Hashimoto’s thyroiditis.
Flow cytometry showed a predominant population of B- lymphoid cells. There were no definite light chain restrictions. A kappa lambda ratio of 6:1 (which is often seen in lymphomas) was not demonstrated. Flow cytometry concluded that although monoclonality could not be established, the possibility of a B-cell lymphoproliferative disorder should be considered

FINAL CYTOLOGY REPORT
Atypical lymphocytosis suspicious of a NHL arising on the basis of a Hashimoto’s thyroiditis.
Further investigation was recommended

Histology:

A right thyroid lobectomy was performed. Three surrounding lymph nodes were also excised. The thyroid showed extensive involvement by an atypical lymphoid infiltrate (Figures 4&5). The lymph nodes showed a similar atypical lymphoid proliferation.
Cell phenotyping showed the material was CD 20, CD19 & CD10 positive and CD5 and Bcl-2 negative.

FINAL DIAGNOSIS
Non Hodgkin's Lymphoma, Follicular centre cell origin
Flow cytometry analysis- CD 20, CD19 and CD10 positive
Bcl-2 negative

Microfollicles of oncocytes with admixed lymphocytes (20x H&E) Atypical lymphocytes similar to those seen in the FNA (40x H&E)
Figure 4 Figure 5

Discussion

Thyroid Lymphomas represent approximately 1-5% of all thyroid malignancies. They usually present as a rapidly growing nodule, and occur mostly in middle aged or older patients. Women are more commonly affected. Most are B-cell type (CK20 +ve)1. NHL subtypes seen in the thyroid include FCC (Follicular Centre Cell), MALT (Mucosa- Associated Lymphoid Tissue) and DCBC (Diffuse Large B-Cell). The cytodiagnosis of MALT-type lymphomas may be difficult, as the population is often more heterogeneous 1. Approximately 75% of thyroid lymphomas arise on the basis of Hashimoto’s thyroiditis. It is believed that prolonged immunologic stimulation causes impairment of cell control mechanisms. Other autoimmune diseases (SLE, Sjogren’s syndrome, immunoblastic lymphadenopathy) have also been linked to development of B-cell lymphomas 2
Cdc25A and cdc25B phosphatases are possible oncogenes involved in the development of thyroid lymphomas. They are expressed in chronic thyroiditis and lymphomas, but not in normal follicular cells. These oncogenes are thought to stimulate cell cycle progression, playing a role in the malignant transformation of chronic thyroiditis and the progression of lymphomas3.

Misdiagnosis of NHL arising on the basis of a Hashimoto’s thyroiditis or a chronic lymphocytic thyroiditis can be minimised by:

  • Adequate sampling of multiple sites within a thyroid nodule

  • Being clinically suspicious of any rapidly growing nodule

  • Carefully ruling out NHL in highly cellular aspirates with increased lymphocytes and scant thyroid epithelium, particularly in patients >40 years of age

References:

  1. SANGALLI G. SERIO G. ZAMPATTI C. LOMBUSICO G. COLOMBO L. (2001).
    Fine Needle aspiration cytology of primary lymphoma of the thyroid: a report of 17 cases. Cytopathology 12(257-263)
  2. AOZASA K.(1990) Hashimoto’s thyroiditis as a risk factor for thyroid lymphoma. Acta Pathol Jpn. 40(7): 459-68
  3. ITO Y. YOSHIDA H. MATSUZUKA N. NAKAMURA Y. NAKAMINE H. KAKUDO K. KUMA K. MIYAUCHI A. (2004). Cdc25A and cdc25B expression in malignant lymphoma of the thyroid: correlation with histologic subtypes and cell proliferation. Int J Mol Med. 13(3):431-5

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