Leukaemic variants of cutaneous t-cell lymphoma: Erythrodermic mycosis fungoides and Sézary syndrome
Publication date: Available online 6 June 2019Source: Best Practice &Research Clinical HaematologyAuthor(s): Xochiquetzal U. Martinez, Cosimo Di Raimondo, Farah R. Abdulla, Jasmine Zain, Steven T. Rosen, Christiane QuerfeldAbstractMycosis fungoides (MF) and Sézary syndrome (SS) are the most common types of cutaneous lymphoma, accounting for approximately 60% of cutaneous T-cell lymphomas. Diagnosis requires correlation of clinical, histologic, and molecular features. A multitude of factors have been linked to the aetiopathogenesis, however, none have been definitively proven. Erythrodermic MF (E-MF) and SS share overlapping clinical features, such as erythroderma, but are differentiated on the degree of malignant blood involvement. While related, they are considered to be two distinct entities originating from different memory T cell subsets. Differential expression of PD-1 and KIR3DL2 may represent a tool for distinguishing MF and SS, as well as a means of monitoring treatment response. Treatment of E-MF/SS is guided by disease burden, patients’ ages and comorbidities, and effect on quality of life. Current treatment options include biologic, targeted, immunologic, and investigational therapies that can provide long term response with minimal side effects. Currently, allogeneic stem cell transplantation is the only potential curative treatment.
Mycosis fungoides (MF) and Sezary syndrome (SS) are subtypes of extranodal T cell nonHodgkin lymphoma, and are the most common forms of cutaneous T cell lymphoma (CTCL). Although both subtypes involve the skin, SS is characterized by leukemic involvement of malignant T cells that typically match the clone found in the skin. MF has a plethora of clinicopathological variants, one of which is the pigmented purpuric dermatosis (PPD)-like MF. Although the PPD-like MF is rarely reported, it has been previously described as either preceding MF or appearing as the initial presentation of MF.
CONCLUSIONS: Our results show that STAT3 is activated in advanced cases and associated with large-cell transformation, while the activation of NFAT and NFκB is maintained throughout the disease. These findings could have important diagnostic and therapeutic implications. This article is protected by copyright. All rights reserved. PMID: 31049933 [PubMed - as supplied by publisher]
Conclusion: CCL21 induced mTOR activation in MyLa cells, followed by expression of MALAT1, causing cell migration. MALAT1 and mTOR are potential therapeutic targets for MF.
Conclusions Epidemiological studies have repeatedly helped identify definitive triggers for several diseases. As highlighted in this perspective report, previous studies strongly argue for the interplay between intrinsic factors and putative preventable extrinsic triggers/promoters for CTCL. Given the evidence of geographical regional clustering of CTCL patients, CTCL occurrence in unrelated family members and recent evidence implicating S. aureus in the pathogenesis/progression of CTCL, more research is needed to decipher the precise mechanism by which specific environmental exposures may be driving the pathogenesis of t...
Conclusions The major challenges in the development of adoptive cell therapy for T cell tumors, as mentioned above, remain fratricide, T cell aplasia and the potential for leukemic transduction or poor T cell function if used in the autologous setting. Approaches to overcome fratricide include the genetic modification and deletion of the T cell antigen in the case of long-term CAR-T cell persistence or regulated CAR-T expression. To ensure restoration of T cell immunity, transient CAR expression can be achieved incorporation of a CAR suicide gene, transient CAR expression using mRNA electroporation, or short-lived NK cell...
CONCLUSIONS: These findings can be explained by a model where malignant transformation takes place during early T-cell development giving rise to circulating pre-malignant clones which home to the skin producing clinically apparent lesions of cutaneous lymphoma. Therapeutic strategies in T-cell lymphoma should therefore target those early lymphoma precursor cells. PMID: 30808775 [PubMed - as supplied by publisher]
ConclusionThe reason for the association between the high serum copper levels and adverse prognosis is unknown. We hypothesized that interleukin-6 is secreted primarily by non-neoplastic cells at MF skin sites, leading to release of copper by the liver. Local production of interleukin-6 at the lesion sites might conceivably also promote neoplastic cell progression by stimulation of the STAT3 pathway. Further studies on the relationship between activated tumor-associated macrophages, serum copper levels, interleukin-6, or C-reactive protein and prognosis might be informative.
ConclusionThe reason for the association between high serum copper and adverse prognosis is unknown. We hypothesize that IL-6 is secreted primarily by non-neoplastic cells at MF skin sites, leading to release of copper by the liver. Local production of IL-6 at lesion sites conceivably might also promote neoplastic cell progression via stimulation of the STAT3 pathway. Further studies on the relationship between activated tumor-associated macrophages, serum copper, IL-6 or C-reactive protein and prognosis might be informative.
Greater than normal serum copper levels in a subset of patients with early mycosis fungoides lymphoma correlated with a worse prognosis compared with that of patients with normal copper levels. The reason for this association is unknown. We hypothesized that inflammatory cytokines such as interleukin-6 secreted by inflammatory cells in skin lesions might play a role in disease progression.
An above normal serum copper level in a subset of patients with early mycosis fungoides lymphoma correlated with a worse prognosis compared to patients with normal copper levels. The reason for this association is unknown. We hypothesize that inflammatory cytokines such as interleukin-6 secreted by inflammatory cells in skin lesions may play a role in disease progression.