Paediatric onset lymphomatoid papulosis: results of a multicentre retrospective cohort study, on behalf of the EORTC Cutaneous Lymphoma Tumours Group (CLTG).

BACKGROUND: Lymphomatoid Papulosis (LyP) is a rare cutaneous T-cell lymphoproliferative disorder. Comprehensive data on LyP in the paediatric population is scarce. OBJECTIVES: To characterize epidemiological, clinical, histopathological, and prognostic features of paediatric LyP. METHODS: This was a retrospective, multicentre international cohort study including 87 cases of children and adolescents with LyP diagnosed between 1998 and 2022. Patients aged ≤ 18 years old at disease onset were included. Diagnosis was made in each centre based on clinical-pathological correlation. RESULTS: Eighty-seven patients from 12 centres were included. The mean age at onset was 7.0 years (range 3 months-18 years) with a male to female ratio of 2:1. The mean time between onset of first cutaneous lesions and diagnosis was 1.3 years (range 0-14 years). Initial misdiagnosis concerned 26.4% of patients. Initially, LyP was most often misdiagnosed as Pityriasis lichenoides et varioliformis acuta (PLEVA), insect bites, or mollusca contagiosa. Erythematous papules or papulonodules were the most frequent clinical presentation. Pruritus was specifically mentioned for 20.7% of patients. The main histological subtype was type A in 55.1% of the cases. If analysed, monoclonal TCR rearrangement was found in 76.5% of the skin biopsies. The overall survival rate was 100% with follow up at 5 years available for 33 patients and at 15 years for 8 patients. A development of associated haematological malignancy (HM) occurred in 9.6% of the cases (7/73), including four mycosis fungoides (MF) cases, one primary cutaneous anaplastic large cell lymphoma (pc-ALCL), one systemic ALCL and one case of acute myeloid leukaemia. If we compare incidence rates of cancer with the world 0-19 years old population from 2001-2010, we estimate a significantly higher risk of associated malignancy in general, occurring before the age of 19 years old with incidence rate ratio of 87.49 (CI 86.01-88.99). CONCLUSIONS: We report epidemiological data from a large international cohort of children and adolescents with LyP. Overall the prognosis of the disease is good, with excellent survival rates for all patients. Due to increased risk of associated HM, a long-term follow-up should be recommended for LyP patients.

Psychological Distress and Treatment Outcome in Patients With Early-Stage Mycosis Fungoides.

BACKGROUND: Skin diseases have been shown to worsen psychological distress, which, in turn, may be detrimental to treatment outcomes. Both the impact of psychological distress on response to treatment in mycosis fungoides (MF) and the effect of treatments on psychological well-being are unclear. OBJECTIVES: To evaluate (1) the association between pretreatment psychological morbidity and treatment outcome in early-stage MF and (2) the impact of response to treatment on psychological well-being. METHODS: This was a prospective cohort study of patients with early-stage MF who started a new stage-directed treatment for their disease. The response was determined using the modified severity-weighted assessment tool, and psychological distress was assessed using the 12-item General Health Questionnaire (GHQ-12) and Penn State Worry Questionnaire (PSWQ). Participants were followed for 1 year. RESULTS: In all, 24 consecutive patients were recruited. Objective response rate was 71% (17/24), consistent with existing literature. Prior to treatment, 9 patients (38%) had clinically significant psychological distress on the GHQ-12, while 8 (33%) demonstrated high-level worry on the PSWQ. Of these patients, 6 had pathologic scores on both instruments. Patients with significantly less baseline anxiety/depression on the GHQ-12 responded better to treatment than patients with higher levels (P = .004). In addition, responders' mean GHQ-12 scores decreased by 39% and their PSWQ scores by 17%, whereas nonresponders' GHQ-12 scores increased by 93% (P = .042) and their PSWQ scores by 11% (P = .019). CONCLUSIONS: These findings suggest that (1) baseline psychological distress is associated with worse outcomes in patients with early-stage MF and that (2) effective treatment improves psychological morbidity.

Boost of innate immunity cytokines as biomarkers of response to extracorporeal photopheresis in patients with leukaemic cutaneous T-cell lymphoma.

BACKGROUND: Extracorporeal photopheresis (ECP) has emerged as a systemic first-line immunomodulatory therapy in leukaemic cutaneous T-cell lymphoma (L-CTCL) and is now beginning to be utilized in other T-cell-mediated diseases. Although ECP has been used for nearly 30 years, its mechanisms of action are not sufficiently understood, and biomarkers for response are scarce. OBJECTIVES: We aimed to investigate the immunomodulatory effects of ECP on cytokine secretion patterns in patients with L-CTCL, to help elucidate its mechanism of action. METHODS: A total of 25 patients with L-CTCL and 15 healthy donors (HDs) were enrolled in this retrospective cohort study. Concentrations of 22 cytokines were simultaneously quantified by using multiplex bead-based immunoassays. Neoplastic cells in patients' blood were evaluated by flow cytometry. RESULTS: Firstly, we observed a distinct cytokine profile pattern difference between L-CTCLs and HDs. There was a significant loss of tumour necrosis factor (TNF)-α, and significant increase of interleukins (IL)-9, IL-12 and IL-13 in the sera of patients with L-CTCL compared with HDs. Secondly, patients with L-CTCL who received ECP were classified as treatment responders and nonresponders according to the quantitative reduction of malignant burden in their blood. We evaluated cytokine levels in culture supernatants from patients' peripheral blood mononuclear cells (PBMCs) at baseline and 27 weeks after ECP initiation. Strikingly, PBMCs purified from ECP responders released statistically higher concentrations of innate immune cytokines IL-1α, IL-1ß, granulocyte-macrophage colony-stimulating factor (GM-CSF) and TNF-α in comparison with ECP nonresponders. In parallel, responders showed clearance of erythema, reduction of malignant clonal T cells in the blood, and a potent boost of relevant innate immune cytokines in individual patients with L-CTCL. CONCLUSIONS: Taken together, our results demonstrate that ECP stimulates the innate immune network, and facilitates redirection of the tumour-biased immunosuppressive microenvironment towards proactive antitumour immune responses. The alterations of IL-1α, IL-1ß, GM-CSF and TNF-α can be used as biomarkers of response to ECP in patients with L-CTCL.

An Analysis of Risk Factors for the Development of Acneiform Eruptions in Patients on Monoclonal Antibody Epidermal Growth Factor Receptor Inhibitors.

Acneiform eruptions occur frequently and early in patients on epidermal growth factor receptor inhibitors (EGFRi). Identification of baseline patient risk factors would prompt earlier referral to dermatology to optimize prevention and management. The primary objective of this retrospective study is to determine the association between clinical and demographic characteristics and the development of acneiform eruptions. A retrospective chart review was conducted on patients diagnosed with colon and head and neck cancers who started EGFRi between January 2017 and December 2021. Patients were followed until death or September 2022. Baseline demographic and clinical parameters were documented and patients were followed from the time of diagnosis to most recent visit for the development and management of an acneiform eruption. Regression analyses were performed to determine the association between baseline characteristics and the development of acneiform eruptions. A total of 66 patients were treated with cetuximab or panitumumab between 2017-2021 were included in the analysis. Forty-seven of the sixty-six patients developed an acneiform eruption while on EGFRi therapy (71.2%). Combination cancer therapy with another chemotherapeutic agent was associated with a lower risk of acneiform eruption (OR 0.03, P = .027). No other baseline features were statistically associated with a lower risk of acneiform eruption. Acneiform eruptions are a common cutaneous adverse event of EGFRi therapy. Ongoing research is required to elucidate risk factors for the development of acneiform eruptions, to improve the quality of life of oncology patients.

A systematic review of oral retinoids for treatment of acneiform eruptions induced by epidermal growth factor receptor inhibitors.

Epidermal growth factor receptor inhibitors (EGFRi) are now standard of care in patients with EGFR mutations in non-small cell lung cancer (NSCLC) and are increasingly being used in other EGFR mutated cancers, including gastrointestinal, and head and neck. However, EGFRi are well known to cause acneiform eruptions, which are shown to positively correlate with tumor response to treatment, but may be severe enough to cause interruption of their treatment. Although most guidelines call for the use of tetracyclines to treat these acneiform eruptions, there is mounting evidence for the use of systemic retinoids instead. The objective of this review is to summarize available data on the use of systemic retinoids for management of acneiform eruptions on EGFRi. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE and EMBASE were searched from database inception until December 10th, 2021. All articles were screened and relevant data extracted independently in duplicate by two reviewers. In total, 16 case reports, case series and retrospective reviews were included. Forty-three patients were treated with retinoids for their acneiform eruption due to EGFRi. The majority (77%) noted moderate to significant improvement after treatment initiation with minimal adverse events (16%). The findings of this systematic review suggest that systemic retinoids are a safe and effective therapy for the management of acneiform eruptions induced by EGFRi.

Electrodessication Matricectomy With Modified Hyfrecator Tip: Case Series and Literature Review.

Nail matricectomy is indicated in the management of painful onychodystrophies, including recalcitrant onychocryptosis, onychogryphosis, onychauxis, and refractory onychomycosis. Although many matricectomy methods have been described, with phenolization being the best studied, no one method has clearly emerged as superior. We present a series of 14 patients who underwent a total of 18 matricectomies with either phenolization or electrodessication (ED) in a private dermatology office, and describe a simple and effective variation of the ED technique using a modified hyfrecator tip. A video demonstration of this technique is included. We also describe ED matricectomy in the context of a review of the literature, ascertaining recurrence rates, complication rates, healing time, and patient satisfaction. The nuances of technique specifics (such as the use of adjunct methods and antibiotics), as well as outcome predictors and measurements have been highlighted. We found ED to be comparable to other forms of matricectomy, with the advantages of ease of use, minimal complications, and good satisfaction rates.

Apremilast in dermatology: A review of literature.

Apremilast is an orally administered small molecule that specifically inhibits the phosphodiesterase-4 enzyme and modulates the immune system by increasing the levels of intracellular cyclic adenosine monophosphate (cAMP) and inhibiting IL-2 & 8, interferon-γ and tumor necrosis factor (TNF) production. It is FDA approved for the treatment of psoriasis, psoriatic arthritis, and oral ulcers of Behcet's disease. More recently, apremilast has been used off-label to treat varied dermatological diseases where systemic corticosteroids or immunosuppressive agents were not effective. We review the efficacy and safety of apremilast in the treatment of aphthous stomatitis, Behçet's disease, chronic actinic dermatitis, atopic dermatitis, cutaneous sarcoidosis, hidradenitis suppurativa, lichen planus, and discoid lupus erythematosus in cases where standard treatment has failed.

Impact of the New McGill Undergraduate Medical Curriculum on Medical Students' Diagnostic Accuracy of Common Dermatoses Encountered in Primary Care.

BACKGROUND: The McGill Faculty of Medicine implemented a new undergraduate medical curriculum in 2013 with additional preclinical lectures in dermatology. At the time of writing, no Canadian prospective study has been published on undergraduate dermatology training in the context of a complete curricular renewal. OBJECTIVES: Our study was designed to determine the impact of increasing preclinical teaching in dermatology on medical students' diagnostic accuracy and learning retention of common dermatoses encountered in primary care. METHODS: A standardized questionnaire was administered to the Classes of 2015, 2016, 2017, and 2018 in 6 versions for a total of 6 times over their 4 years of training. Each version featured 10 photographs of common dermatoses encountered in primary care. Students were invited to participate anonymously and on a voluntary basis. RESULTS: A small absolute, but statistically significant difference, of 3% was detected in the fourth and final year of training between the old curriculum (average score = 70%, standard deviation = 15%) and the new curriculum (average score = 73%, standard deviation = 15%), P = .03. Furthermore, the Class of 2018's performance improved year by year over the entire 4 years of the new curriculum. CONCLUSIONS: Additional preclinical lectures in dermatology do improve medical students' diagnostic accuracy of common dermatoses encountered in primary care. Furthermore, they do retain their learning throughout the preclinical and clerkship years.

Distribution and Clustering of Cutaneous T-Cell Lymphoma (CTCL) Cases in Canada During 1992 to 2010.

BACKGROUND: Clustering of patients with cutaneous T-cell lymphoma (CTCL) was reported in several jurisdictions around the world. This rare cancer is known to affect spouses and in some cases multiple members of the same family. These combined results suggest the existence of external disease triggers/promoters. We recently conducted the first comprehensive analysis of CTCL incidence and mortality in Canada, which revealed case clustering in several regions. OBJECTIVES: To extend our previous analysis on CTCL incidence across Canada and to provide all the collected data on CTCL patient incidence in Canada during the period of 1992 to 2010. METHODS: Clinical parameters for patients with CTCL in Canada were analyzed using 2 independent population-based cancer registries: Canadian Cancer Registry and Le Registre Québécois du Cancer. The CTCL incidence rates were examined on different geographical levels, including provinces/territories, cities, and forward sortation areas. RESULTS: Our findings further corroborate our earlier observations of higher CTCL incidence in Newfoundland and Labrador, maritime provinces (Nova Scotia and New Brunswick), and prairie provinces (Manitoba and Saskatchewan). Also, most cities with high CTCL incidence were located in these provinces. Extensive mapping of high-incidence postal codes supports case clustering in a number of communities that are located in the proximity of industrial centres and seaports. CONCLUSIONS: Detailed analysis of CTCL incidence in Canada is critical to fully understand the burden of this disease in our country, to begin the search for a possible external trigger for this lymphoma, and to reform how health care resources are distributed throughout the country to better serve Canadian patients with CTCL.

Comprehensive analysis of cutaneous T-cell lymphoma (CTCL) incidence and mortality in Canada reveals changing trends and geographic clustering for this malignancy.

BACKGROUND: Previous reports of geographic clustering of cutaneous T-cell lymphoma (CTCL) in Texas, Pittsburgh, and Sweden as well as the occurrence of CTCL in married couples and family members raise a possibility of the existence of an external and potentially preventable trigger(s) for this rare skin cancer. METHODS: The authors studied CTCL incidence and mortality in Canada using 3 distinct population-based cancer databases. Data on patients' sex, age at the time of diagnosis, subtype of CTCL malignancy, reporting province, city, and postal code were analyzed. CTCL cases were mapped across Canada using geographic information systems software. RESULTS: In total, 6685 patients with CTCL were identified in Canada during 1992 through 2010 (CTCL incidence rate, 11.32 cases per million individuals per year), of which 58% were males. The mean age at diagnosis was 59.4 ± 21.5 years. Geographic analysis of patients revealed increased CTCL incidence on the provincial and city levels in several eastern provinces and in Manitoba. An analysis according to postal codes (Forward Sortation Area [FSA]) identified select communities in which several high-incidence FSAs were contiguous or adjacent. Several of these FSAs were located in industrial regions of Canadian cities. Conversely, 3 of 8 low-incidence FSAs were clustered in Ottawa, Ontario, which has very little industrial presence. An analysis of CTCL mortality in Canada corroborated the current incidence findings. CONCLUSIONS: The current results provide a comprehensive analysis of CTCL burden in Canada and highlight several important areas of geographic case clustering. These findings argue that industrial exposures may play an important role in promoting CTCL pathogenesis. Cancer 2017;123:3550-67. © 2017 American Cancer Society.

Primary Cutaneous B-Cell Lymphoma in Young Monozygotic Twins: A Case Report.

Although familial aggregation of lymphoproliferative disorders has been described, heredity has not been implicated in the etiology of primary cutaneous B-cell lymphomas (PCBCL). We report herein the first case of 2 young monozygotic twins with PCBCL. The first twin was an 18-year-old woman when she presented with multiple skin nodules on the thorax and head. Histology showed an atypical small B-cell proliferation, consistent with primary cutaneous marginal zone lymphoma (PCMZL). Molecular genetics studies demonstrated B-cell clonality. Seven years later, the second twin developed her first lesion that was histologically similar to that of her twin. She subsequently developed other clinically similar lesions. Histology was consistent with PCMZL and showed B-cell clonality. Occurrence of PCBCL in these monozygotic twins raises the possibility of a genetic risk factor. Further study of such rare cases may offer valuable insights into the molecular basis of the etiology and pathogenesis of this unusual disorder.

Tazarotene 0.1% Cream as Monotherapy for Early-Stage Cutaneous T-Cell Lymphoma.

BACKGROUND: Numerous treatments are available for cutaneous T-cell lymphoma (CTCL), including systemic retinoids. Very few data are available on topical retinoids. OBJECTIVES: The aim of this study was to evaluate the safety and efficiency of tazarotene as monotherapy for early-stage CTCL. METHODS: An open-label, prospective study of tazarotene as monotherapy for stages IA to IIA CTCL was conducted. Index lesions on 10 patients were followed for 6 months on treatment, plus at least 6 months off treatment. RESULTS: Six patients (60%) showed complete response (CR). Erythema, scaling, thickness, and lesion area decreased progressively throughout treatment. The mean time to CR was 3.8 months; CR was durable for at least 6 months in 83%. Of the 4 patients (40%) without CR, 2 (20%) had stable disease and 2 (20%) stopped the medication because of local side effects; none showed progression. CONCLUSIONS: This is the first Canadian trial providing evidence that topical tazarotene has excellent potential as a monotherapy agent for stages I to IIA CTCL.

Identification of geographic clustering and regions spared by cutaneous T-cell lymphoma in Texas using 2 distinct cancer registries.

BACKGROUND: Cutaneous T-cell lymphomas (CTCLs) (mycosis fungoides and its leukemic variant, Sezary syndrome) are rare malignancies. Reports of the occurrence of mycosis fungoides in married couples and families raise the possibility of an environmental trigger for this cancer. Although it has been suggested that CTCL arises from inappropriate T-cell stimulation, to the authors' knowledge no preventable trigger has been identified to date. METHODS: Using region, zip code, age, sex, and ethnicity, the authors analyzed the demographic data of 1047 patients from Texas who were seen in a CTCL clinic at The University of Texas MD Anderson Cancer Center during 2000 through 2012 (the MDACC database) and 1990 patients who were recorded in the population-based Texas Cancer Registry between 1996 and 2010. Subsequently, data from both databases were cross-analyzed and compared. RESULTS: The current study findings, based on the MDACC database, documented geographic clustering of patients in 3 communities within the Houston metropolitan area, in which CTCL incidence rates were 5 to 20 times higher than the expected population rate. Analysis of the Texas Cancer Registry database defined the CTCL population rate for the state to be 5.8 cases per million individuals per year (95% confidence interval, 5.5-6.0 per million individuals per year), thus confirming the observations from the MDACC database and further highlighting additional areas of geographic clustering and regions spared from CTCL in Texas. CONCLUSIONS: The current study documented geographic clustering of CTCL cases in Texas and argued for the existence of yet unknown external causes/triggers for this rare malignancy.

Primary Cutaneous Multifocal Indolent CD8+ T-Cell Lymphoma: A Novel Primary Cutaneous CD8+ T-Cell Lymphoma.

We report the case of a patient who was referred to our institution with a diagnosis of CD4+ small/medium-sized pleomorphic lymphoma. At the time, the patient showed a plethora of lesions mainly localizing to the legs; thus, we undertook studies to investigate the lineage and immunophenotype of the neoplastic clone. Immunohistochemistry (IHC) showed marked CD4 and CD8 positivity. Flow cytometry (FCM) showed two distinct T-cell populations, CD4+ and CD8+ (+/- PD1), with no CD4/CD8 co-expression and no loss of panT-cell markers in either T-cell subset. FCM, accompanied by cell-sorting (CS), permitted the physical separation of four populations, as follows: CD4+/PD1-, CD4+/PD1+, CD8+/PD1- and CD8+/PD1+. TCR gene rearrangement studies on each of the four populations (by next generation sequencing, NGS) showed that the neoplastic population was of T-cytotoxic cell lineage. IHC showed the CD8+ population to be TIA-1+, but perforin- and granzyme-negative. Moreover, histiocytic markers did not render the peculiar staining pattern, which is characteristic of acral CD8+ T-cell lymphoma (PCACD8). Compared to the entities described in the 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas, we found that the indolent lymphoma described herein differed from all of them. We submit that this case represents a hitherto-undescribed type of CTCL.