BACKGROUND:Mycosis fungoides (MF) is the most prevalent subtype of primary cutaneous T-cell lymphoma. Large cell transformation of MF (LCTMF) is rare and confers a poor prognosis. Radiotherapy (RT) is an effective local treatment for LCTMF; however, dose-response data are limited. METHODS:Eligibility for this retrospective study required biopsy-proven LCTMF with clinico-pathological correlation, diagnosed 1/1/1990-1/10/2021, and managed at Peter MacCallum Cancer Centre. RESULTS:83 patients were eligible. Median age was 68 years, 63 (76 %) patients had cutaneous-only LCTMF at time of diagnosis. Median follow-up was 8.0 (95 % CI: 6-11) years. Details of 155 irradiated LCTMF lesions (from 49 patients) were available: 150 cutaneous, 5 extra-cutaneous. For cutaneous LCTMF, median equivalent dose in 2.0 Gy per fraction (EQD2, α/β of 10) was 30.6 (range, 4.7-46.3) Gy. Dose-response data were available for 141 cutaneous LCTMF lesions. Overall response rate (ORR) was 94 % (60 % complete response (CR), 35 % partial response). For cutaneous lesions treated with >12.0 Gy, ORR was 100 %. Increasing doses of RT were associated with greater CR rates: doses >36.0 Gy achieved 100 % CR rate. 22 (27 %) patients had unifocal cutaneous-only LCTMF and were treated with local RT-alone, median EQD2 36.0 Gy (range, 17.3-46.3 Gy). CR rate was 100 %. 9 (41 %) patients remained relapse-free (median follow-up, 3.2 years). Only 1 patient experienced infield-only recurrence at first relapse. CONCLUSION:LCTMF is radio-responsive, with EQD2 >12.0 Gy associated with 100 % ORR. Dose-response was observed, with EQD2 >36.0 Gy achieving 100 % CR rate. For unifocal cutaneous LCTMF, RT-alone achieved excellent infield control with possible curative potential in a proportion of patients.

Primary cutaneous T-cell lymphomas (CTCL) are a rare and heterogeneous group, associated with significant morbidity and mortality. Mycosis fungoides (MF), the most common subtype, typically follows an indolent course, whereas Sézary syndrome (SS) is a leukemic and aggressive variant. Treatment strategies for MF are diverse, stage-dependent, and individualized to the patient. While early-stage disease can be effectively managed with skin-directed therapies, advanced or relapsed/refractory disease is associated with a poorer prognosis and frequently necessitates multiple sequential therapies. Current systemic therapeutic options include immunomodulatory drugs, targeted therapies, and chemotherapy, and are aimed at achieving disease control rather than disease cure. Presently, the only potentially curative treatment option is allogeneic stem-cell transplantation. Regional variation in drug access impacts treatment decisions, whilst the evolving landscape of novel agents continues to challenge current paradigms. This review discusses the underlying biology, clinical features, current and emerging therapeutic strategies for relapsed or refractory MF/SS.

INTRODUCTION:Primary cutaneous T cell lymphomas (CTCL) comprise a diverse group of malignancies with distinct and variable treatment options and prognoses. Differentiating between subtypes can be challenging due to overlapping heterogeneous clinical and histopathologic features, mandating careful clinicopathologic correlation for diagnosis. Mycosis fungoides (MF) is the most common subtype, whereas the less frequent Sézary syndrome (SS) is viewed at the more aggressive end of the MF/SS spectrum. Large cell transformation (LCT) is a rare phenomenon associated with poor prognosis, arising in a subset of patients with MF/SS, although the exact etiology and molecular pathogenesis remains unclear. AREAS COVERED:Progression of these diseases is influenced by a variety of immunologic factors. Our advancing understanding of immune pathways and tumor microenvironment may accelerate the development of targeted therapies. This review examines the immune-modulating effects of current and emerging therapeutic drugs for MF/SS. It encompasses both established clinical guidelines and emerging targeted agents currently under investigation in clinical trials. EXPERT OPINION:The treatment landscape for CTCL, especially advanced disease, is becoming increasingly focused on immunotherapies and biologic agents. These treatments have the potential to provide patients with more effective clinical outcomes. The development of synergistic combination therapy will also be important expanding therapeutic options in patients with advanced CTCL.

Lentigo maligna (LM), a type of in situ melanoma, has a high rate of local recurrence after surgical resection. Although recurrences might represent inadequately excised incident LMs, apparent recurrences could be new primary LMs developing from distinct melanocytic clones in the same UVR-damaged anatomical region. Because distinguishing these possibilities has implications for patient management, we tested genetic relationships between incident and recurrent LMs. Incident LMs with histologically clear margins and their recurrent LMs and invasive LM melanomas were laser microdissected for DNA extraction. Tumor and matched germline DNA underwent whole-exome sequencing. Clonal relationships between incident and recurrent LMs were tested by elucidating and tracking clones within and across samples. Seven incident LMs with recurrent LM and 4 with recurrent LM melanoma were sequenced. LM/LM melanomas had a high mutational burden, a predominant UVR signature, copy number alterations, and defects in DNA repair and cell-cycle checkpoint regulator genes. All incident LMs were clonally related to their postoperative local recurrences. We therefore found that local recurrences of LM commonly arise from subclinical residual disease after surgery. The mutational landscape of recurrent LM/LM melanoma was typical of melanomas arising from chronic sun exposure but also displayed features described in late-stage melanomas.

BACKGROUND/OBJECTIVES:Cutaneous manifestations of Waldenstrom's macroglobulinaemia (WM), a rare B-cell lymphoproliferative disorder, present a diagnostic challenge. The intent of this article is to raise awareness to clinicians of a potentially overlooked condition, particularly in the context of patients with a monoclonal IgM paraproteinaemia, but also to describe the diagnostic complexity of the disease from a clinicopathological perspective. METHODS:We describe the clinical presentation and histopathological findings of two patients with cutaneous involvement of WM. RESULTS:Cutaneous presentations included erythematous and salmon pink plaques, which were either tender or non-tender. Histopathology analysis in both cases demonstrated direct lymphocytic infiltration by malignant lymphocytes of WM, with case 1 demonstrating aberrant CD10 expression. CONCLUSION:The broad cutaneous signs of WM are sparsely described in the literature, and these can even precede formal diagnosis. Ongoing clinical suspicion is warranted from both a clinical and histopathological perspective where patients present with a monoclonal IgM paraproteinemia.

Cancer systemic therapeutics and radiotherapy are often associated with dermatological toxicities that may reduce patients’ quality of life and impact their course of cancer treatment. These toxicities cover a wide range of conditions that can be complex to manage with increasing severity. This review provides details on twelve common dermatological toxicities encountered during cancer treatment and offers measures for their prevention and management, particularly in the Australian/New Zealand context where skincare requirements may differ to other regions due to higher cumulative sun damage caused by high ambient ultraviolet (UV) light exposure. Given the frequency of these dermatological toxicities, a proactive phase is envisaged where patients can actively try to prevent skin toxicities.

Sneddon-Wilkinson (SW) disease is rare condition which typically occurs in the context of a monoclonal immunoglobulin and treatment options have not been well studied. Here we present a case of a 65-year-old female with SW with underlying, otherwise indolent, lymphoplasmacytic lymphoma (LPL) with an IgA paraprotein, who achieved a complete skin remission with the administration of the Bruton Tyrosine Kinase inhibitor (BTKi), acalabrutinib.

Traditionally, Sezary syndrome (SS) has been associated with few therapeutic options and poor prognosis, with 5-year disease-specific survival (DSS) less than one-third in historical cohorts. However, newer therapies and combinations are associated with impressive time-to-next-treatment (TTNT), particularly allogeneic stem-cell transplantation (AlloSCT) and combination therapies notably those including extracorporeal photopheresis. In this multicentre, international study, we explored the prognostic outcomes of 178 patients exclusively managed for SS, diagnosed between 2012 and 2020, and treated in the modern therapeutic era. In this cohort, 58 different therapies were delivered, with 13.5% of patients receiving AlloSCT. Long-term survival exceeded historical reports with 5-year DSS and OS of 56.4% and 53.4% respectively. In those receiving AlloSCT, prognosis was excellent: 5-year DSS and OS were 90.5% and 78.0% respectively. Confirming the results from the Cutaneous Lymphoma International Consortium (CLIC), LDH and LCT had significant prognostic impact. Unlike earlier studies, stage did not have prognostic impact; we speculate that greater relative benefit favours patients with extensive lymphomatous nodal disease (Stage IVA2) compared to historical reports. For patients ineligible for AlloSCT, the prognosis remains relatively poor (5-year DSS 51.4% and OS 49.6%), representing ongoing unmet needs for more effective novel agents and investigation of improved therapeutic combinations.

The CD30-postive lymphoproliferative disorders, including lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma, account for up to 30% of all cutaneous T-cell lymphomas (CTCLs) and are the second most common form of CTCLs after mycosis fungoides. Both conditions differ in their clinical presentations; however, they share the expression of the CD30 antigen as a common immunophenotypic hallmark. There is a wide spectrum of management options depending on factors such as extent of disease, staging and treatment tolerability. This Clinical Practice Statement is reflective of the current clinical practice in Australia.

Background and Purpose: Primary cutaneous CD4 + small/medium T-cell lymphoproliferative disorder (PCSMLPD) is a benign behaving condition, typically manifesting as solitary head or neck papules, frequently creating cosmetic concerns. Optimal management of this rare disease is unclear. Herein, patterns of care and treatment outcomes are described, with particular focus on low-dose RT. Materials and Methods: Eligibility required biopsy-proven PCSMLPD on central review, diagnosed between 2007-2022. Patterns of care, treatment responses and relapse patterns were assessed. Freedom-from-progression (FFP) was compared between RT and surgery. Results: 41 patients were eligible. First-line treatments were: RT, 19 (46.3 %); surgery, 17 (41.5 %) (3 received adjuvant RT); watchful waiting, 5 (12.2 %). Median follow-up was 37.7 months. Overall, 24 patients received RT (19 definitive first-line, 3 adjuvant, 2 second-line). 10 (42 %) received 4 Gy in 2 fractions (with no acute toxicities); 14 (58 %) received 20-40 Gy. Complete response rate was 100 %. No post-RT relapses observed. After first-line surgery alone (n = 14, 3 with positive margins), 4 (28.5 %) experienced relapse (2 local, 2 distant). Watchful-waiting (n = 5) led to partial resolution post-biopsy in 4 patients; no complete resolution seen. 3-year FFP for RT alone was 100 % vs 61 % for surgery alone (p = 0.12). Conclusion: RT is a successful, non-invasive option for PCSMLPD: 100 % achieved complete response, with no relapses, and FFP appearing numerically superior to surgery in this cohort. In this first series of lowdose RT for PCSMLPD, 4 Gy in 2 fractions appears an excellent treatment option, offering durable disease control, no acute toxicities and convenient treatment time of only 2 days. Crown Copyright (c) 2022 Published by Elsevier B.V. All rights reserved. Radiotherapy and Oncology 178 (2022) 1-6

Key Points • For patients with Sezary syndrome (SS), first-line combination therapies have greater time-to-next-treatment (TTNT) than monotherapies.• Extracorporeal photopheresis is associated with good TTNT benefit, particularly when delivered in the first line.

Supplementary Tables 1-3 from Histone Deacetylase Inhibitor Panobinostat Induces Clinical Responses with Associated Alterations in Gene Expression Profiles in Cutaneous T-Cell Lymphoma

SummaryWith new, effective treatments for chronic lymphocytic leukaemia (CLL) the impact of second malignancies is increasingly important. We performed a retrospective case‐controlled study examining the effect of CLL and its treatment on melanoma‐specific survival and recurrence. A total of 56 patients with melanoma with CLL were matched 1:1 to patients without CLL for age, date of diagnosis, gender and melanoma tumour, node, metastasis (TNM) stage. Multivariate analysis found CLL was associated with significantly worse melanoma‐specific mortality (hazard ratio [HR] 2.46, 95% confidence interval [CI] 1.27–4.74, p = 0.007) and recurrence (HR 3.44, 95% CI 1.79–6.63, p < 0.001). Patients with CLL had poor immunotherapy tolerance and prior CLL treatment was not associated with melanoma outcomes.

Since the concurrence of bullous pemphigoid (BP) and psoriasis was first reported in 1929, an increasing number of studies has been published to analyse their relationship in recent years. However, the pathogenesis of the concurrence is not yet well understood, and the coexistence of the two conditions imposes a difficult therapeutic challenge. This case report demonstrates the first case of secukinumab achieving a dramatic clinical improvement of both chronic psoriasis and active BP.