A 74-year-old female presented for enlarged right axillary lymph node measuring 2.6 cm in the greatest dimensions, detected on routing screening mammogram. Needle core biopsy was performed, HE slides showed focal sinusoidal pattern of medium to large sized tumor cells. The large, atypical cells had round to oval nuclei, distinct nucleoli, and abundant cytoplasm and were slightly cohesive. (A, HE 40X) This morphological picture prompted work up for metastatic neoplasms, especially breast lobular carcinoma. The initial immunohistochemical (IHC) stains showed that tumor cells were negative for AE1/3, ER-Dx, P40, CK7 and S100, while positive for PAX8 (B, 40x). PAX8 positivity further prompted the workup towards endocrine, gynecologic and genitourinary primary neoplasms and the second round of work up included CAM5.2, TTF1, GATA3, WT1, CK20, SALL4 and PLAP IHC stains. Albeit, all these stains were negative, but CD45 was diffusely positive in neoplastic cells (C, 40X).  On additional stains, the neoplastic cells were positive for CD19, CD20, CD22, PAX5 (D, 40X), MUM-1, C-MYC, BCL-6, partially positive for CD30, while they were negative for CD3, ALK-1, BCL-1, BCL-2, P53 and CD10.  Ki-67 proliferation index was about 80-90%.

Overall, these findings were consistent with, large B cell lymphoma, focally involving this needle core. The final diagnosis was then rendered as with large B cell lymphoma, non- germinal center B phenotype, most compatible with diffuse large B cell lymphoma, activated B cell type. This case raises the awareness of important pitfall of large B cell lymphoma mimicking metastatic carcinoma and cross reactivity of PAX8 with PAX5. PAX8 stain highlights thyroid, gynecologic and occasional genitourinary neoplasms and normal tissues. But PAX8 also cross reacts with PAX5, which can occasionally stain B cell neoplasms and normal B cells, as PAX5. By highlighting this case, we also want to highlight an important unusual pattern of large B cell lymphoma mimicking metastatic neoplasms, including breast, gynecologic and genitourinary primary.