Lymphomatoid Papulosis Revealing Occult Peripheral T-Cell Lymphoma with a T-Follicular Helper Phenotype

Lymphomatoid papulosis (LyP) is a rare indolent lymphoproliferative disorder characterized by recurrent papules and nodules due to abnormal CD30+ T-cell aggregates in the skin. Although LyP generally follows an indolent clinical course, approximately 20-50% of patients develop a secondary associated cutaneous or nodal lymphoid malignancy. Here, we present an unusual case in which LyP was the initial manifestation of an otherwise occult peripheral T-cell lymphoma (PTCL) with a T-follicular helper (TFH) phenotype.

A 58-year-old woman with no significant past medical history presented with a six-month history of persistent scattered erythematous papules involving the trunk and extremities. Skin biopsy of a right upper arm lesion demonstrated an epidermotropic T-cell infiltrate composed of scattered enlarged CD30+/CD4+/CD8− lymphocytes with a clonal T-cell receptor gamma gene rearrangement, consistent with LyP. In the absence of clinical evidence of mycosis fungoides or systemic lymphoma, observation was initially recommended.

During a follow-up evaluation, routine screening mammography unexpectedly revealed right axillary lymphadenopathy. Excisional lymph node biopsy demonstrated an atypical CD30-positive T-cell infiltrate with clonal rearrangements involving the B-cell gene, T-cell receptor gamma gene, and T-cell receptor beta gene, consistent with PTCL with a TFH phenotype. Staging PET/CT demonstrated hypermetabolic lymphadenopathy above and below the diaphragm with extranodal involvement of the left knee soft tissue and multiple osseous lesions.

The patient received six cycles of brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone (BV-CHP). End-of-treatment PET/CT demonstrated improvement in disease burden but persistent uptake within the left knee and new hypermetabolic lesions involving the right knee, prompting evaluation for allogeneic hematopoietic stem cell transplantation. Following completion of chemotherapy, her LyP lesions paradoxically flared with increased body surface area involvement and ulceration, leading to the initiation of weekly low-dose methotrexate.

Although LyP can be histologically malignant-appearing, it is typically an indolent disorder managed conservatively or with skin-directed therapy.¹ However, its well-recognized association with secondary lymphoid malignancies underscores the importance of ongoing clinical surveillance. The presence of clonal T-cell receptor rearrangements has been associated with an increased likelihood of an accompanying lymphoid neoplasm and may warrant heightened clinical vigilance.² Most malignancies linked to LyP include mycosis fungoides, primary cutaneous anaplastic large cell lymphoma, and classical Hodgkin lymphoma. In contrast, systemic PTCL with a TFH phenotype appears to be a considerably less common association. This case illustrates that LyP may serve as a sentinel manifestation of an otherwise clinically occult aggressive T-cell lymphoma, even in the absence of constitutional symptoms.

Our case highlights the importance of recognizing the possibility of underlying lymphoma in patients with LyP. Although routine extensive screening is not indicated for all patients with LyP, additional clues such as persistent lymphadenopathy, atypical clinical features, or concerning imaging findings should prompt further evaluation for an associated hematologic malignancy.