Reflectance confocal microscopy as a new diagnostic tool in transformed mycosis fungoides.

Patients with mycosis fungoides typically experience an indolent disease. In some cases, the disease undergoes a process of large cell transformation which often heralds a more aggressive course with shortened overall survival. In order to rule out large cell transformation, biopsy specimens are often collected from patients with established disease who develop new papules, plaques or tumours. In some cases, multiple biopsies are needed and scar, infection and sampling error can occur. Our aim was to evaluate lesions suggestive of large cell transformation using in vivo reflectance confocal microscopy and to correlate confocal features with histopathologic findings in three patients with biopsy-proven mycosis fungoides who developed new lesions during follow-up. A total of six lesions, two lesions per patient, were examined. Reflectance confocal microscopy demonstrated large bright roundish pleomorphic cells in the epidermis, dermoepidermal junction, dermis and hair follicle in 5 of 6 lesions. The same 5 lesions were confirmed as large cell transformation by histopathology. Dermoepidermal junction obscuration, Pautrier microabscesses, epidermal disarray, spongiosis and dendritic cells were also detected by reflectance confocal microscopy and correlated to histopathology. In conclusion, reflectance confocal microscopy is useful in identifying large cell transformation within mycosis fungoides lesions. Reflectance confocal microscopy can therefore be of value in targeting the biopsy site, thereby reducing the chance of a false-negative histopathological finding.

Systematic review and proposal of an in vivo reflectance confocal microscopy assessment tool for cutaneous lymphoma.

BACKGROUND: Reflectance confocal microscopy (RCM) is a non-invasive imaging technique that provides dynamic information and allows in vivo monitoring, with excellent histologic correlation. In the last decade, the use of RCM for cutaneous T-cell lymphomas (CTCL) has been reported. CTCL may require multiple biopsies for diagnosis due to its equivocal clinical presentation. RCM was described as a possible tool to help determine the best site for skin biopsy. This study aims to systematically review all RCM features reported in literature for CTCL. METHOD: A systematic literature search concerning CTCL evaluated by RCM was performed in eight electronic databases until May 2019 following PRISMA-DTA quality assessment. RESULTS: Eighteen RCM features were described in patients with CTCL. The most frequent were: interface dermatitis (89%), epidermal lymphocytes (82%), epidermal architectural disarray (81%), and vesicle-like structure (Pautrier microabscess) (51%). CONCLUSION: In order to establish comparable parameters among the studies identified, we proposed descriptors for CTCL features and a grading system to quantify them. This will facilitate to define the role of RCM in the diagnosis and monitoring of CTCL patients.

Management of cutaneous T-cell lymphomas: Established and emergent therapies.

Cutaneous T-cell lymphoma is an uncommon group of non-Hodgkin's lymphoma primarily affecting the skin. It is comprised of a variety of entities with different clinical behaviours and prognosis. Mycosis fungoides is the commonest subtype, and Sézary syndrome is a much rarer form of cutaneous T-cell lymphoma. At this stage, control rather than cure is the goal of therapy, with particular emphasis placed on preserving quality of life. Our review of the efficacy, safety profile and accessibility of treatment modalities for mycosis fungoides/Sézary syndrome is a tailored guide for the clinician treating these rare conditions.

Anti-programmed cell death-1 therapy-associated bullous disorders: a systematic review of the literature.

Bullous disorders are rare adverse events associated with anti-programmed cell death-1 (anti-PD1) therapy. This paper presents two new cases of bullous disorders under anti-PD1 therapy and systematically reviewed the literature to foster a better understanding of the presentation and pathogenesis of bullous disorders under anti-PD1. A systematic review of the literature was completed using MEDLINE, Embase, PubMed and LILACS databases. We identified 29 cases of bullous disorders under anti-PD1 therapy, including our two new cases. This includes 18 cases of bullous pemphigoid (BP), five cases of toxic epidermal necrolysis (TEN)/Stevens-Johnson syndrome (SJS) spectrum, one case of erythema multiforme (EM), four cases of bullous lichenoid reactions and one case of vesiculobullous eczema. In BP, blistering occurred by a median of 23 weeks after anti-PD1 therapy initiation and is often preceded by a prodrome, which lasts for a median of 9.5 weeks. Limbs and trunk were the most frequently involved body sites. Most cases (76%) achieved remission. In TEN/SJS/EM, blistering was usually preceded by a prodrome of interface dermatitis that lasted for a median of 1.5 weeks. Most cases (80%) died from either TEN/SJS or disease progression. Bullous disorders under anti-PD1 may be classified clinically as BP, SJS/TEN/EM, bullous lichenoid reactions and vesiculobullous eczema and histologically by intraepidermal splitting and subepidermal splitting. BP is usually preceded by a pruritic eruption and has a relatively good prognosis. SJS/TEN is usually preceded by a maculopapular eruption and has a very poor prognosis.

Intracorneal pustular drug eruption, a novel cutaneous adverse event in anti-programmed cell death-1 patients that highlights the effect of anti-programmed cell death-1 in neutrophils.

The introduction of anti-programmed cell death-1 (anti-PD1) monoclonal antibodies has revolutionized the treatment of various advanced malignancies. Despite its efficacy, anti-PD1 therapy is accompanied by a variety of cutaneous adverse events. A 79-year-old man developed erythematous scaly plaques and pustules of the forehead, legs and arms after four cycles of nivolumab infusions every 2 weeks. Histology showed intracorneal pustules with dermal neutrophils and eosinophils. He was treated successfully with topical corticosteroids without discontinuation of nivolumab. We report subcorneal pustular eruption as a novel cutaneous adverse event in patients on anti-PD1 therapy. Other neutrophilic eruptions (psoriasis, Sweet's syndrome, acute generalized pustulosis) have been reported in patients on anti-PD1 treatments, suggesting the neutrophil as another cell type modulated by anti-PD1 antibodies.

Management of the cutaneous adverse effects of antimelanoma therapy.

The advent of targeted therapy and immunotherapy has revolutionized the management of advanced melanoma. However, these novel therapies are associated with adverse effects (AEs), of which cutaneous toxicities are the most frequently observed. These cutaneous AEs can exert significant morbidity and impact on patient quality of life, hence the recognition and management of AEs is fundamental in preventing interruption or cessation of survival-prolonging treatments. Additionally, knowledge of these AEs are necessary in order for healthcare professionals to counsel patients when starting treatment and in the initiation of AE prophylaxis. The incidence and clinical presentation of the cutaneous toxicities of novel melanoma therapies will be discussed, and treatment guidelines provided.

Coexistence of Hidradenitis Suppurativa with Autoimmune Thyroiditis: Report of Three Cases.

Hidradenitis suppurativa (HS) is a chronic, relapsing inflammatory skin disease affecting terminal hair follicles in apocrine-gland-bearing skin. The pathogenesis of HS is still unknown, although increasing evidence suggests that the immune system plays an important role. Herein we describe 3 patients with HS coexisting with autoimmune (Hashimoto's) thyroiditis (AT). To our knowledge, the co-occurrence of these two diseases has not previously been described. The coexistence of HS with autoimmune disorders, such as AT, may support the hypothesis on dysregulation of the immune system's function as implicated in the pathogenesis of HS. Based on our findings, we feel that an assessment of thyroid function and antithyroid antibodies should be performed in patients with HS.