Loss of CD30 Expression in Anaplastic Large Cell Lymphoma Following Brentuximab Therapy
July 2016 | Volume 15 | Issue 7 | Case Reports | 894 | Copyright © July 2016
Colton Nielson BS,b Ryan Fischer MD,a Garth Fraga MD,a and Daniel Aires MDa
aUniversity of Kansas Medical Center, Kansas City, KS
bUniversity of Kansas School of Medicine, Kansas City, KS
Monoclonal antibody therapy is a new innovation in cancer therapy. Binding of monoclonal antibodies to tumor cells facilitates their destruction by the immune system. Tumor cells with mutated target antigens may escape detection by monoclonal antibodies and exhibit a selective growth advantage. This phenomenon was first recognized in CD20-negative B-cell lymphomas in patients previously treated with the anti-CD20 monoclonal antibody rituximab. We report a cutaneous recurrence of systemic ALCL with an anomalous CD30-negative immunophenotype. The patient had been previously treated with the anti-CD30 monoclonal antibody brentuximab. To our knowledge, we present the first reported case of a cutaneous recurrence of systemic ALCL with an anomalous CD30-negative immunophenotype following chronic brentuximab therapy. J Drugs Dermatol.
A 74-year-old male with peripheral T-cell non-Hodgkin’s Lymphoma (NHL) s/p stem cell transplant in November 2010 and recurrent CD30+ T-cell lymphoproliferative disorder/anaplastic large cell lymphoma (ALCL) treated with brentuximab since 2013, presented to the outpatient clinic complaining of a new lesion on his left medial thigh. The lesion had been present for one week prior to appointment. The patient reported spontaneous crusting similar to that in a prior focus of ALCL. Review of systems was negative. Physical exam revealed two central eschar-like lesions within a 1.2 cm erythematous plaque on his left medial thigh.
Clinical differential diagnosis included recurrent CD30+ lymphoma vs arthropod bite vs a novel neoplasm. Punch biopsy demonstrated ulcerated skin with eschar (Figure 1). The surrounding skin demonstrated signs of ischemic necrosis. There was a dense angio-invasive and angio-destructive infiltrate of medium and large CD3(+) T-cells in the subjacent dermis. Lesional T-cells possessed irregular nuclei with finely dispersed chromatin and formed occasional mitoses (Figure 2). They were associated with signs of vascular injury including perivascular fibrin deposits, endothelial cell swelling and vascular destruction. The lesional T-cells were almost all non-reactive for CD30 (<1% positive). They were non-reactive for Epstein-Barr virus by in situ hybridization. We diagnosed recurrent ALCL with anomalous loss of CD30 expression due to chronic brentuximab therapy.
Anaplastic large cell lymphoma (ALCL) is one of the more common subtypes of T-cell lymphoma.1 ALCL was first recognized
based on characteristic histopathologic features (sinusoidal invasion) and strong expression of CD30.1,2 However, neither sinusoidal invasion nor CD30-positivity proved to be specific.2 Molecular studies have found ALCL to be of T-cell origin.2 Tumor cells exhibit aberrant loss of expression of many T-cell associated antigens.2 CD3 and CD45RO are negative in greater than 50% of cases.2
ALCL can present in the skin, lymph nodes, or visceral organs.2 Primary cutaneous ALCL has a much better prognosis than systemic ALCL.2,3 Primary cutaneous anaplastic large cell lymphoma (PCALCL) must be distinguished from other cutaneous T cell lymphomas such as mycosis fungoides and from systemic ALCL.3 PCALCL is negative for anaplastic lymphoma kinase and manifests as solitary or multiple raised erythematous persistent tumors.1 Cutaneous tumors of ALCL often ulcerate and may itch.1
CD30 is a member of the tumor necrosis factor receptor superfamily. It is expressed on the cell surfaces of lymphocytes activated by mitogens or viral infection. Stimulation of CD30 causes cell cycle arrest and induces apoptotic cell death in ALCL cells.3,4 Brentuximab vedotin is a conjugate of an anti-CD30 antibody and monomethylauristatin E, which inhibits the polymerization of microtubule.3,5 Brentuximab has recently been approved for the treatment of relapsed Hodgkin lymphoma (HL) and systemic anaplstic large-cell lymphoma (ALCL).5 A meta-analysis of 21 studies on the efficacy of brentuximab treatment for ALCL by Zinzani et al. revealed a response and remission rates of 75% and 74% in 28 patients with ALCL.6 The role of brentuximab in PCALCL has yet to be determined. Two