Not All Rheumatoid Factor-Positive Tests Mean RA
Immunohistochemistry staining demonstrated a diffuse predominance of CD3 positive T cells (see Figure 2C, p. 28). Flow cytometry was notable for an expanded population of CD3-positive T cells.
The patient was evaluated by oncology and treated with CHOEP (cyclophosphamide, doxorubicin, etoposide, vincristine and prednisone). Despite treatment, he experienced a rapid decline in his health, with cutaneous metastases developing in late 2018 and recurrent hypercalcemia in early to mid-2019. He succumbed to his AITL in mid-2019.
Discussion
AITL is a rare disease that accounts for 1–2% of all non-Hodgkin’s lymphomas and about one in five cases of peripheral T cell lymphomas.4 First described in 1974, the disease was named angioimmunoblastic lymphadenopathy with dysproteinemia.2,4,5 Patients classically presents with B symptoms, as described above, or with a rash (observed in 20–50%), which may include urticarial lesions and nodular tumors.4
AITL leads to three pathologically characteristic histological and architectural changes in lymph nodes: extensive alteration of the nodal architecture, abundance of small vessels and polyclonal proliferation of immune reactive cells.6
Once considered an aggressive neoplasia that derived from an abnormal immune reaction, genomic studies have since demonstrated AITL to be a clonal rearrangement of T cell receptor genes due to acquired driver genes.2,7 Follicular T helper cells are the main subset implicated in the pathogenesis of AITL. This subset of T cells resides within the follicles, and their main role is to support B cell survival, proliferation, maturation and migration.3
Several genetic changes have been implicated in the neoplastic transition of T follicular helper cells, such as the G17V mutation of Ras homolog family member A.3 Although this mutation has also been identified in other malignancies, such as diffuse gastric carcinoma and Burkitt lymphoma, it may serve as a non-invasive diagnostic test for AITL in the future.1,3
Given the immune-activating effects of AITL, the production of detectable levels of rheumatoid factor and the anti-smooth muscle antibody may result in positive autoantibody tests.3