Cutaneous Lymphoma Research Articles

More than Skin Deep: Imaging of Dermatologic Disease in the Head and Neck.

Evaluation, staging, and treatment of skin cancers involve a multidisciplinary team, with radiology playing an integral role. Imaging evaluation of dermatologic disease that involves the head and neck is especially important due to the proximity of important structures such as nerves, bone, muscle, and lymph nodes. The authors review the pathophysiology of the most common types of skin cancer, as well as cutaneous lymphoma, and the available treatment modalities and algorithms. Emphasis is placed on pretreatment evaluation and posttreatment surveillance. In the pretreatment setting, a checklist of key radiologic features that are important in the staging of dermatologic disease is discussed, namely superficial and dermal lymphatic spread, perineural tumor invasion and spread, osseous invasion, and metastatic nodal disease. In the setting of high-risk or metastatic disease, a contrast-enhanced CT scan of the neck or a PET/CT scan is typically obtained approximately 12 weeks after treatment; imaging may be used first to detect residual or recurrent disease, metastatic nodal disease, or unexpected complications such as osteoradionecrosis. The authors highlight the radiologist's role in the care of patients with dermatologic disease, which can be more than skin deep. ©RSNA, 2024.

Clinical features, treatment options and outcomes in primary cutaneous B-cell lymphomas: a real-world, multicenter, retrospective study.

Primary cutaneous B-cell lymphomas (PCBCLs) are rare cutaneous neoplasms with limited literature regarding treatment options and associated treatment outcomes. This study aimed to investigate and present real-world treatment outcomes in patients with PCBCLs. All patients with PCBCL who were treated in five major referral centers for cutaneous lymphoma in Greece over 10 years were retrospectively included with their baseline characteristics and treatment-associated outcomes collected and analyzed. In total, 235 PCBCL patients, of whom 125 (53.2%) were females, were included. The median age at diagnosis was 60 years (IQR 47-72), and the median follow-up duration was 3 years (IQR 1.3-6.4). The most common subtype was primary cutaneous marginal zone lymphoma (PCMZL) (52.3%), followed by primary cutaneous follicle center lymphoma (PCFCL) (40.9%), and primary cutaneous large B-cell lymphoma, leg type (PCDLBCL, LT) with 16 (6.8%) cases. Complete responses (CRs) were observed in 77.3% after first-line treatment. Both radiotherapy (RT) and surgical excision (SE) achieved superior outcomes, with 88.9% and 89% achieving CR, respectively. Relapses occurred in 22.6% of initial complete responders. The median time to the next treatment (TTNT) for the PCMZL and PCFCL was 349 days. RT and topical/intralesional steroids demonstrated longer TTNT compared to SE (445 and 359 vs. 154 days). For PCMZL and PCFCL, the 1-year progression-free survival (PFS) was 84.2% (75.7-89.9) and 85% (75.1-91.2), and the 5-year PFS was 66.5% (55.2-75.5) and 58.8% (44.4-70.7), respectively. PCBCLs have favorable outcomes. RT demonstrates significantly increased TTNT compared to SE, suggesting RT as the preferable option. After careful evaluation, "watch and wait" may be a reasonable option for asymptomatic patients.

Increasing the effectiveness of total-skin electron beam therapy by reducing the manifestations of radiation dermatitis in patients with primary lymphomas. A comparative randomized prospective study

Background. One of the main adverse events that significantly reduce the quality of life of patients and limit the total focal dose is radiation-induced skin reactions (RISR). Their timely diagnosis, prevention, and treatment remain urgent tasks of modern radiotherapy. Aim. To improve the effectiveness of total skin irradiation (TSI) in patients with primary skin lymphomas by reducing the clinical manifestations of RISR by using additional therapy with a hydrogel containing active components with vasoprotective and anti-inflammatory action. Materials and methods. A comparative randomized prospective study was conducted, including data from 52 patients who received electron TSI by conventional fractionation at a total focal dose of 14 to 30 Gy for primary cutaneous lymphomas at the Granov Russian Research Center of Radiology and Surgical Technologies from September 2021 to January 2024. Before the first TSI session, during treatment and 2 weeks after the end of radiation therapy, all patients underwent assessment for RISR, quantitative assessment of various degrees of severity of radiodermatitis using instrumental methods and assessment scales; for the observation group, a therapeutic regimen for the prevention and treatment of RISR was used, including a hydrogel with troxerutin (2%) and trolamine (0.07%), and in the control group, basic skin care using moisturizers. Results. Analysis of the physiological parameters of the skin showed statistically significant differences between the study groups: patients of the study group (group I; 30 subjects receiving the above-mentioned therapeutic regimen) compared with the control group (group II; 28 subjects who did not receive specific treatment for radiodermatitis) reported significantly lower rates of erythema (386±12.3 and 572±14.4; p=0.005), transepidermal water loss (25±0.3 and 38±0.4 g/m2/h; p0.001) and a decrease in peak endothelial-dependent vasodilation of microvasculature and blood flow in the skin. A lower proportion of severe radiodermatitis (86.3 and 73.3%; p0.05) and a statistically significant difference in the subjective quality of life scores by the 29-point Skindex-29 scale by an average of 22.2% were also found. Conclusion. A comparative analysis of the quantitative indicators of radiodermatitis in the study group and the control group showed that the topical application of the hydrocolloid gel containing troxerutin and trolamine reduces the clinical manifestations of RISR concerning objectively measured physiological parameters of the skin and blood flow parameters of the microvasculature measured by high-frequency ultrasound, thus improving the quality of life of patients during and after the course of radiation therapy.

An update on EBV-related cutaneous lymphoproliferative disorders: a systematic review.

Epstein Barr virus (EBV) positive B lymphoproliferative disorders (LPD) with cutaneous involvement include a series of rare entities that go from indolent processes to aggressive lymphomas. Since the latest WHO-EORTC classification of cutaneous lymphomas in 2018, significant changes have been included in the new classifications of hematological malignancies. B-cell EBV+ LPD mainly affect immunocompromised patients while T-cell EBV+ LPD are more prevalent in specific geographic regions such as Asia, Central America, and South America. This systematic review summarizes the main clinical, histological, immunophenotypic and molecular characteristics of B- and T-cell EBV+ LPD that may compromise the skin at diagnosis. B-cell EBV+ LPD include primary cutaneous lymphomas such as EBV-MCU, as well as cutaneous systemic lymphomas that may present such as lymphomatoid granulomatosis (LG), EBV+ diffuse large B cell lymphoma, NOS, plasmablastic lymphoma (PBL), and extracavitary primary effusion lymphoma (EC-PEL). EBV+, EBV-positive polymorphic B cell LPD, or post-transplant lymphoproliferative disorders (PTLD). Regarding T-cell EBV+ LPD, most of these entities are categorized within T/NK-cell lymphoproliferative processes and lymphomas of childhood, including extranodal T/NK lymphoma, and even more exceptional forms such as EBV-positive T-cell centrofollicular lymphoma and intravascular T/NK-cell lymphoma. Diagnosis is based on integrating the clinical, histological, immunohistochemical, and genetic criteria discussed throughout this article. Management is multidisciplinary, posing a challenge for dermatologists and hematologists involved in the management of these patients. Having scientific evidence available in this field is of paramount importance because overtreatment must be carefully avoided.

Real-world Pattern-of-Care Analysis of Cutaneous Lymphomas Radiotherapy Among EORTC Members.

We aim to determine the current treatment patterns and recommendations among physicians for cutaneous lymphomas and to identify the types of skin lymphomas for which existing radiation regimens need improvement. A questionnaire from the European Organisation for Research and Treatment of Cancer (EORTC) was distributed to all members of the Cutaneous Lymphoma Tumour Group and radiation oncology scintific council. This online survey included 13 questions regarding treatment practices for patients with cutaneous lymphoma. The survey was conducted from August 21 to December 18, 2023. Frequency distributions and subgroup comparisons were calculated and analyzed. We collected 51 completed questionnaires from investigators from 19 countries specializing in cutaneous lymphoma treatment. Radiation doses varied significantly (range, 4-60 Gy). Based on the histologic entity, up to one-third of the investigators delivered hypofractionated regimens (range, 14% - 35%). Reduced-dose radiotherapy was considered by 27% to 63% of investigators. Meanwhile, 18 (35%) investigators considered adapting the radiation dose to the response to immunochemotherapy when treating primary cutaneous diffuse large B-cell lymphomal-leg type. Regarding total skin electron beam therapy, 91% of centres delivered reduced-dose regimens, and 18% of investigators applied ultra-hypofractionated protocols. Radiotherapy of cutaneous lymphoma patients is highly heterogeneous among EORTC centres. Development of evidence-based recommendations for radiotherapy dose, fractionation, and technique for cutaneous lymphomas is required for optimization and standardization of treatment.

Integrative epidemiology and immuno-transcriptomics uncover a risk and potential mechanism for cutaneous lymphoma unmasking or progression with dupilumab therapy

There have been multiple reports of the anti-IL4Rα agent, dupilumab, as associated with the onset and/or progression of cutaneous T-cell lymphoma (CTCL). We sought to evaluate safety signals associated with dupilumab, with a focus on CTCL, and to evaluate possible underlying mechanism(s) for the potential association. First, we used the FDA pharmacovigilance database, FAERS, to evaluate if dupilumab was associated with CTCL including both positive controls (conjunctivitis, eosinophilia, and arthralgia) and exposure controls (other medications with similar indications including JAK-inhibitors and the anti-IL13, tralokinumab,) to reduce and evaluate confounding bias. Thereafter, we used publicly available bulk and single cell-RNA seq datasets to probe possible underlying mechanisms through which dupilumab might be associated with CTCL. Between January 2019 and Q2 of 2023, there were 181,575 unique reports of dupilumab related adverse events (AE) in FAERS with 606 of these being for a neoplasm. Dupilumab had 30.0 times the proportional reporting ratio (PRR) (95% CI: 25.0 - 35.9) for CTCL compared to all other medications in FAERS. The risk was highest in males aged 45-65. The PRR for conjunctivitis, eosinophilia, and arthralgia, known side effects of dupilumab, were 35.6 (34.4 - 36.8), 2.15 (2.00 - 2.31), and 2.14 (2.07 - 2.18) respectively. Using the log-count normalized PRR (AE score) to account for PRR inflation when reports were small, the top safety signals included conjunctivitis (AEscore 8.3) and CTCL (AEscore 4.9). Bulk RNA sequencing data showed changes in IL4RA and IL13RA1 expression in CTCL and in epidermal layers of atopic dermatitis (AD) biopsies. Single-cell transcriptomic studies revealed that this change was similar in AD and CTCL, and that keratinocytes seemed to be the most divergent cell type with regards to IL4R and IL13RA1. An effect on keratinocyte specific gene expression was also independently observed in available bulk RNA sequencing data. These data suggest that dupilumab might be causing an unmasking or progression of CTCL via the same mechanism through which it improves atopic dermatitis: IL13 receptor blockade, which leads to increased IL13 in the local milieu, driving CTCL stimulation and progression. However, these associations need further evaluation given the inherent limitations of the FAERS database and our non-experimental approach.

Treatment of atopic dermatitis with abrocitinib in real practice in Spain: efficacy and safety results from a 24-week multicenter study.

Abrocitinib, a selective JAK 1 inhibitor, was recently approved in Europe. Despite its approval, real-world data on its efficacy and safety in treating moderate-to-severe atopic dermatitis (AD) remains limited. This study aimed to evaluate the short-term effectiveness and safety of abrocitinib in a real-life setting for patients with moderate-to-severe AD. We conducted a retrospective multicenter study involving adult patients with moderate-to-severe AD who started abrocitinib treatment between May 1, 2023, and September 30, 2023, in 15 Spanish hospitals. Treatment doses were 100 or 200 mg daily, based on clinical assessment. Data collection included patient demographics, AD history, comorbidities, previous treatments, and disease severity indicators such as SCORing atopic dermatitis (SCORAD), Eczema Area and Severity Index (EASI), body surface area, and Peak Pruritus NRS scores at baseline, 4, 12, and 24 weeks. Quality of life was measured using the Dermatology Life Quality Index (DLQI), and safety was assessed by monitoring adverse reactions and various biochemical parameters. The cohort comprised 76 patients with an average age of 33.93 years; 57.89% were male. Before abrocitinib, 36.84% were naïve to advanced therapies. The baseline mean scores were SCORAD 47.04, EASI 21.79, and DLQI 15.01. At Week 24, there were significant improvements: EASI was reduced to 2.81, and 70.58% of the patients achieved EASI 75. However, 18.42% discontinued treatment mainly due to inefficacy or adverse effects. The safety profile was favorable, with 22.37% reporting mild adverse events (AEs) and one serious case of cutaneous lymphoma. This first Spanish series assessing abrocitinib in real-world conditions reveals a significant improvement in AD symptoms and quality of life in a range of severity and prior treatment failures. Abrocitinib was well-tolerated, with few serious AEs, highlighting its potential as an effective treatment option for AD.

Non-Invasive Imaging Including Line-Field Confocal Optical Coherence Tomography (LC-OCT) for Diagnosis of Cutaneous Lymphomas.

Background/Objectives: Primary cutaneous lymphomas (PCL) are a heterogeneous group of non-Hodgkin lymphomas arising from malignant T (CTCL) or B (CBCL) cells, often mimicking other skin conditions. Recently, non-invasive diagnostic imaging modalities, including dermoscopy, Reflectance Confocal Microscopy (RCM), and Line-field Optical Coherence Tomography (LC-OCT), have become increasingly important, supporting clinicians in clinical practice. Hence, our study aimed to describe dermoscopic, RCM, and LC-OCT features of PCL and to explore their role in PCL management. Methods: Between December 2022 and January 2024, 40 lesions of 25 patients with PCL were retrospectively analyzed at the Dermatologic Unit of the University of Siena, Italy. Predefined dermoscopic, LC-OCT, and RCM criteria were assessed and their frequencies were calculated. Results: At dermoscopy, CTCL lesions were characterized by pinkish structureless areas (58,6%) and homogeneous distributed dotted vessels (35,7%), whereas 57.1% of CBCL presented with orange-yellow structureless areas. Considering CTCL, lymphocytes in the epidermis, dermal-epidermal junction, and dermis were detected by LC-OCT in 73.1%, 66.7%, and 51.9% and by RCM in 72.2%, 55.6%, and 61.1% of cases, respectively. The detection of lymphocytes was more precise using RCM than LC-OCT in CTCL (p < 0.001). Dermal infiltration of medium-reflective cells was visible in 80% and 40% of CBCL cases by LC-OCT and RCM, respectively. Conclusions: Non-invasive imaging techniques may support clinicians in managing PCL; however, further studies are mandatory in this field.

Primary cutaneous T-cell lymphoma not otherwise specified (NOS) uncovering a novel RAB27A variant in Griscelli syndrome type 2.

Griscelli syndrome type 2 (GS2) is a rare, autosomal recessive disorder that typically emerges during childhood. It manifests with partial albinism, silvery hair, immunodeficiency and hemophagocytic lymphohistiocytosis predisposition (HLH). Our findings suggest that lymphoproliferative disorders, including cutaneous lymphomas, should be considered part of the dermatological spectrum of GS2. While GS2 has previously been diagnosed in adults presenting with HLH, our observations indicate that HLH is not an inevitable outcome, even in patients who survive into their fifth decade of life.

Evaluation of clinical and follow-up outcomes in primary cutaneous B-cell lymphomas: A single-center retrospective study from 2006 to 2022

Evaluation of clinical and follow-up outcomes in primary cutaneous B-cell lymphomas: A single-center retrospective study from 2006 to 2022

A-179 The Cutaneous Lymphoma International DIgital PAthology (CLIDIPA) Registry - a multi-center, collaborative initiative to facilitate Artificial Intelligence-driven research within Cutaneous Lymphomas

A-179 The Cutaneous Lymphoma International DIgital PAthology (CLIDIPA) Registry - a multi-center, collaborative initiative to facilitate Artificial Intelligence-driven research within Cutaneous Lymphomas

A-194 Primary cutaneous anaplastic large cell lymphoma with locorregional lymph node involvement in a pregnant woman

A-194 Primary cutaneous anaplastic large cell lymphoma with locorregional lymph node involvement in a pregnant woman

A-234 CD30+ Primary Cutaneous Follicle Center Lymphoma: an atypical immunohistochemical profile

A-234 CD30+ Primary Cutaneous Follicle Center Lymphoma: an atypical immunohistochemical profile

A-184 Primary cutaneous marginal zone Lymphoma or Lymphoproliferative disorder?Comparison of initial tumor, recurrence and outcome in 61 patients

A-184 Primary cutaneous marginal zone Lymphoma or Lymphoproliferative disorder?Comparison of initial tumor, recurrence and outcome in 61 patients

A-166 Health-related quality of life in primary cutaneous B-cell lymphoma following local radiotherapy

A-166 Health-related quality of life in primary cutaneous B-cell lymphoma following local radiotherapy

A-185 Primary cutaneous follicule center lymphoma- differential diagnostic and prognostic aspects

A-185 Primary cutaneous follicule center lymphoma- differential diagnostic and prognostic aspects

A-274 Indolent primary cutaneous B-cell lymphomas resemble persistent antigen reactions without signs of dedifferentiation

A-274 Indolent primary cutaneous B-cell lymphomas resemble persistent antigen reactions without signs of dedifferentiation

A-255 Spontaneously regressive primary cutaneous diffuse large B-cell lymphoma, leg-type: a single-center retrospective study

A-255 Spontaneously regressive primary cutaneous diffuse large B-cell lymphoma, leg-type: a single-center retrospective study

A-295 Radiotherapy Dose for Primary Cutaneous Anaplastic Large Cell Lymphoma

A-295 Radiotherapy Dose for Primary Cutaneous Anaplastic Large Cell Lymphoma

A-202 Validation Of Next Generation Sequencing Using EuroClonality-NDC Panel In Primary Cutaneous Lymphomas and comparison with Traditional PCR Techniques

A-202 Validation Of Next Generation Sequencing Using EuroClonality-NDC Panel In Primary Cutaneous Lymphomas and comparison with Traditional PCR Techniques