How I Diagnose Angioimmunoblastic T-Cell Lymphoma

Yi Xie, MD, PhD; Elaine S. Jaffe, MD


Am J Clin Pathol. 2021;156(1):1-14. 

In This Article

Case Presentations

Case 1

The patient is a 71-year-old woman with generalized lymphadenopathy. She had a history of polymyalgia rheumatica and had been treated with low-dose steroids for 2 years. A biopsy of an axillary lymph node was performed. Flow cytometry disclosed an atypical T-cell population that was positive for CD2, CD4, CD5, and CD7, with loss of surface CD3, and negative for CD8. Forty-five percent of the T cells were positive for CD10. H&E-stained sections showed a diffuse infiltrate of atypical lymphoid cells, effacing nodal architecture Figure 1. Focal follicles with regressive changes were present. The paracortex showed prominent vascularity, with high endothelial venules exhibiting an arborizing pattern. While some cells resembling Hodgkin/Reed-Sternberg (HRS) cells were present, the atypia in the background lymphocytes argued against a diagnosis of classic Hodgkin lymphoma (CHL). As noted, flow cytometry suggested an abnormal phenotype with loss of surface CD3 and expression of CD10. The atypical lymphocytes were also positive for PD1 and ICOS, confirming a TFH phenotype. The HRS-like cells were positive for Epstein-Barr virus (EBV) and were rosetted by the atypical TFH population. A diagnosis of T-cell lymphoma was confirmed by clonal rearrangement of T-cell receptor genes by polymerase chain reaction (PCR). In this case, the differential diagnosis would include nodal PTCL with TFH phenotype vs AITL. Two features favor AITL in the pres-ent case: the marked expansion of CD21 dendritic cells enveloping clusters of the atypical lymphocytes and the presence of EBV-positive B cells.

Figure 1.

Angioimmunoblastic T-cell lymphoma with Epstein-Barr virus (EBV)–positive Hodgkin/Reed-Sternberg (HRS)–like cells. A, H&E shows a diffuse infiltrate of small- to medium-sized lymphoid cells with scattered admixed plasma cells. Prominent high endothelial venules were present. Scattered cells resembling HRS-like cells are present (×400). B, CD21 shows expanded dendritic cells that envelope clusters of atypical lymphoid cells (×200). The lymphoid cells are positive for CD4 (C, x400) and CD10 (D, x400). CD30 is positive in the HRS-like cells, (E, x400) many of which are also positive for CD15. (F, x400), CD30 staining also highlights a subset of atypical lymphoid cells. The HRS-like cells are positive for EBV by EBER in situ hybridization (G, x400) and PAX5 (H, x200) and exhibit variation in morphology.

Case 2

The patient is a 63-year-old woman with a several-month history of cervical and submandibular lymphadenopathy with night sweats and fever. The patient had anemia (hematocrit, 22%; hemoglobin, 71 g/L) with normal WBC count and normal platelets. She exhibited polyclonal hypergammaglobulinemia (85 U/L) and moderately elevated lactic dehydrogenase (LDH) (326 U/L). EBV viral load was detected at 420 copies/mL. Chest computed tomography showed bilateral pleural effusions and widespread lymphadenopathy affecting axillary, paratracheal, and para-aortic lymph nodes, as well as hepatosplenomegaly. A cervical lymph node biopsy was performed.

H&E sections of the lymph node Figure 2 showed numerous follicles with germinal centers displaying a starry sky pattern. The reactive germinal centers appeared to lack well-formed mantle cuffs and instead were surrounded by medium-sized to larger lymphoid cells with clear cytoplasm and vesicular nuclei. Admixed plasma cells were present in the interfollicular region. Increased vascularity was noted in the paracortex. Immunohistochemical stains were performed for CD20, CD79a, CD3, CD4, CD8, CD10, PD1, ICOS, CD21, and IgD. Epstein-Barr virus-encoded small RNAs (EBER) in situ hybridization for EBV was performed. The IgD stain confirmed the absence of a normal mantle cuff. Instead, the germinal centers were encircled by an atypical T-cell population that was positive for PD1, ICOS, and CD10. The atypical T cells were positive for CD3 and CD4. CD21 showed follicular dendritic cell (FDC) meshworks largely confined to the follicles. EBER was positive in scattered cells in the interfollicular region (10–20/high-power field). PCR studies were performed. These confirmed a clonal rearrangement pattern for T-cell receptor γ genes and a polyclonal IG rearrangement pattern.

Figure 2.

Angioimmunoblastic T-cell lymphoma pattern I. A, Reactive germinal center is surrounded by atypical cells with clear cytoplasm and immunoblastic features. High endothelial venules surround the atypical follicular structure (×100). B, The perifollicular cells have clear cytoplasm; admixed plasma cells are present (×400). C, CD20 highlights the germinal centers and scattered interfollicular B cells (×40). D, PD1 is strongly positive in the perifollicular T cells (×40). Perifollicular T cells show cytologic atypia seen with CD3. (E, x400) F, A CD21 stain shows well-formed follicular dendritic cell meshworks within the follicles but no expansion in the paracortex (×400).

A diagnosis of AITL pattern I was made based on these findings. AITL pattern I can be mistaken for atypical follicular hyperplasia. A clue in the current case on H&E was the absence of well-formed mantle cuffs. Cytologic atypia was readily seen on immunohistochemical stains. AITL pattern I often lacks the FDC expansion seen in more advanced cases. Evolution of AITL pattern I to patterns II to III has been shown in patients with sequential biopsies.[15]