Anaplastic lymphoma kinase (ALK)‐negative anaplastic large cell lymphoma with MYC rearrangement

Abstract

Anaplastic large-cell lymphoma (ALCL) can be further classified into anaplastic lymphoma kinase-positive (ALK +) and ALK-negative types. ALK-negative ALCL is indistinguishable from ALK + ALCL by morphology, but lacks ALK translocation or protein expression. Patients with ALK + ALCL have an overall better prognosis than patients with ALK-negative ALCL, in part because they are younger, but also likely due to biological factors because ALK-negative ALCL is a molecularly heterogeneous entity. 1,2 MYC is altered in many malignancies including lymphomas and some solid tumours. 3 Although the role of MYC dysregulation has been studied extensively in B-cell lymphomas, 4-8 studies of MYC aberrations in T-cell lymphomas are very limited. A few reports suggest that T-cell lymphomas often have increased MYC copy number, but rarely carry MYC rearrangement (MYC-R). 9-12 To date, only three cases of T-cell lymphoma harbouring MYC-R have been reported in the literature. All three cases were ALK + ALCL and these neoplasms arose in children who had an aggressive clinical course. 13-15 The presence or importance of MYC-R in ALK-negative ALCL has not been reported. Here, we describe two patients with MYC-R ALK-negative ALCL, one of whom also had concurrent dual specificity phosphatase 22 (DUSP22) rearrangement (DUSP22-R). Patient 1, a 58-year-old woman presented to another hospital with a neck mass and B symptoms (fever, night sweats and weight loss). Full blood count (FBC) data were not available. Computerised tomography (CT) showed multiple large lymph nodes involving the cervical, axillary, mediastinal, iliac, inguinal regions and subcutaneous nodules. Excisional biopsy of a neck lymph node revealed ALK-negative ALCL (Fig 1). Using immunohistochemistry and flow cytometry immunophenotyping, the lymphoma cells were positive for CD2, CD3, CD4, CD7 (subset), CD8 (dim), CD30 (uniform and strong), T-cell receptor (TCR) alpha/beta, MYC

Central nervous system ALK-negative anaplastic large cell lymphoma with IRF4/DUSP22 rearrangement

“…Other IRF4 alterations, most commonly extra copies of IRF4, were seen in a wide variety of T-cell lymphoproliferative disorders, including cutaneous ALCL, and were mutually exclusive with cases harboring IRF4/DUSP22 translocations [10]. The effects of additional cytogenetic alterations on prognosis are unknown; rare cases of DUSP22 rearranged ALCLs demonstrating other alterations, one with concurrent TP63 rearrangement and another with concurrent MYC rearrangement, showed complete remission after chemotherapy although the patient with DUSP22 and MYC rearrangements died 53 months after diagnosis from an unknown cause [8,12]. There is no consensus on the optimal therapy for PCNSL, but treatment most often consists of high-dose methotrexate as part of multiagent chemotherapy, with or without radiation [41].…”

“…Alterations in TP63 are associated with a poor prognosis and lack of any of these rearrangements with an intermediate prognosis, with 5-year OS of 0–17% and 33–42%, respectively [ 1 , 11 ]. MYC rearrangement has been rarely reported in ALK-negative ALCL with 2 patients recently described by Khanlari et al both of whom had aggressive disease although one demonstrated a concurrent DUSP22 rearrangement and had longer survival compared to the patient without the alteration [ 12 ].…”