Nodal T Follicular Helper Lymphomas (nTFHL) are a recently defined category of mature T-cell neoplasms, which includes the prototypic angioimmunoblastic-type. Here, we present two cases, illustrating hallmark diagnostic features and key management issues. In Case 1, a 43-year-old female presented with right neck swelling, which spontaneously resolved after a non-diagnostic needle biopsy. She later developed progressive multi-site lymphadenopathy. An excisional biopsy confirmed PTCL with TFH phenotype. She achieved a complete remission (CR) with CHOEP followed by consolidative autologous stem cell transplant (ASCT) but relapsed after one year. She attained a 2nd CR with salvage therapy (brentuximab, then duvelisib) and underwent consolidative allogeneic SCT. She remains in remission for over 2 years. In Case 2, a 60-year-old female with no contributory medical history presented with progressive lymphadenopathy, diffuse erythematous rash, B-symptoms, dactylitis, and arthralgias. She was positive for anti-CCP and treated for a presumed rheumatologic condition with a prolonged steroid taper. Her B-symptoms improved though she had persistent lymphadenopathy and new splenomegaly. An excisional lymph node biopsy was consistent with AITL with mutations in RHOA, TET2, and IDH2. She was treated with CHOEP and consolidative ASCT but relapsed after 10 months. She received salvage treatment with romidepsin/azacitidine followed by valemetostat on clinical trial, then a consolidative allogeneic SCT. She has remained in remission for over 3 years despite graft failure. Together, these cases highlight 1) common clinical features in disease presentation, 2) epigenetic modifiers as key molecular findings, and 3) the potential curative role of allogeneic SCT in the salvage setting.
