Causes of Death in Cutaneous T-Cell Lymphoma Patients.

BACKGROUND: The advancing evolution toward a Th2 immune environment confers a progressive immunosuppression in patients with longstanding cutaneous T-cell lymphoma (CTCL). The conjunction of the disease-related immunosuppression as well as the immunosuppressive character of some CTCL treatments increase the risk of infectious and neoplastic diseases, sometimes with fatal outcomes. OBJECTIVES: The aim of the study was to prospectively study the causes of death in a cohort of CTCL patients, in a tertiary university skin cancer center. METHODS: All CTCL patients who died between 2008 and 2020 were included. The cause of the death was classified as directly or indirectly related or unrelated to CTCL. RESULTS: Over the study period, 31 (13F/18m) patients with CTCL died (mean age: 75.2 years), mean delay between diagnosis and death: 3.2 years (min: 1, max: 12 years), 58.1% of death causes were classified as indirect (infection), 12.9% directly related (blastic transformation), 22.5% unrelated, and 6.5% of unknown cause. 51.6% of mycosis fungoides (MF) patients who died had early-stage disease (1A-2A) or were on remission. 45.2% of dead patients had advanced-stage MF (2B-4B). Mean CRP level is increased in patients who died from infection whereas LDH level increased in patients with blastosis. A tertiary center is expected to manage of a higher proportion of CTCL patients with advanced-stage disease. CONCLUSIONS: As infection represented more than 50% of the causes of death in CTCL patients, particular attention should be given to preventive measures such as anti-infective vaccination. Regular surveillance of CRP and LDH levels could be helpful for follow-up of MF patients, respectively, with regards to infection and blastosis.

Risk Factors for Skin Infections in Mycosis Fungoides.

BACKGROUND: Mycosis fungoides (MF) is the most frequent type of primary cutaneous natural killer and T-cell lymphoma. MF-required immunosuppressive therapies and MF-related immunosuppressive characteristics render patients with MF more prone to infections. AIM: To describe the clinical features of cutaneous infections observed in MF patients. MATERIALS AND METHODS: A series of 56 MF patients were followed prospectively over 3 years and screened for cutaneous infections. TYPE OF STUDY: Prospective observational study. RESULTS: Four herpes simplex virus type-I (HSV-I), 2 staphylococcal (S. aureus) impetiginizations and 2 Malassezia infections were detected in single isolated plaque/patch stage MF as well as 1 varicella zoster virus infection (herpes zoster, HZ) and 2 cases of cellulitis in 10 patients. All patients presented advanced MF. All the diagnoses were delayed due to atypical clinical presentations. CONCLUSIONS: Patients with advanced MF should be particularly monitored for skin infections, especially by HSV and S. aureus. Unexplained exacerbation or the sudden appearance of oozing or ulcerations in MF lesions should initiate a search for viral or bacterial agents. Cellulitis and HZ can be severer and prolonged in MF patients.

Cemiplimab for locally advanced and metastatic basal cell carcinoma.

INTRODUCTION: Locally advanced basal cell carcinoma (laBCC) represents approximatively 1% of all BCCs. Metastatic BCC (mBCC) is even more rare. Most cases are observed in immunocompromised patients, particularly solid organ transplant recipients (OTRs). When surgery and/or radiation therapy for laBCC or mBCC is not reasonable, oral hedgehog inhibitor (HHI) therapy may be initiated. LaBCC or mBCC patients with primary or secondary resistance, progression or intolerance to HHIs could benefit from programmed cell death protein-1 (PD-1) inhibitors as this has recently been published for cemiplimab, a recombinant IgG4 human monoclonal antibody anti-PD-1 for the intravenous treatment of laBCC and mBCC. AREAS COVERED: Principal studies evaluating the efficacy and safety of cemiplimab for laBCC and mBCC are presented and discussed. EXPERT OPINION: Cemiplimab is the first FDA (2021) approved anti-PD-1 antagonist for the systemic treatment of laBCC and mBCC which had previously shown disease progression on or intolerance to HHIs. Experts currently recommend cemiplimab as a first-line systemic alternative. As cemiplimab therapy is associated with a risk of organ graft rejection, advantages and disadvantages should be evaluated for every individual OTR patient with laBCC or mBCC, eligible for cemiplimab therapy.

A Comprehensive Update of the Atypical, Rare and Mimicking Presentations of Mycosis Fungoides.

INTRODUCTION: Mycosis fungoides (MF) is the most frequent subtype of primary cutaneous T cell lymphomas (pCTCL). The diagnosis may be particularly difficult in the early stages as well as in atypical and rare clinical presentations. Furthermore, MF may simulate a large variety of common dermatologic disorders and patterns, both histopathologically and clinically. METHODS: A literature search was performed to provide a comprehensive update on the rare and atypical MF manifestations as well as the dermatoses and dermatological patterns that could be imitated by MF. RESULTS: A total of 114 publications were found describing a series of different dermatoses and dermatological patterns mimicked by MF, as well as some particular localizations of MF lesions and dermatoses that occur in preexisting MF lesions. CONCLUSIONS: The number of dermatoses that can be imitated by MF is ever-increasing. Patients with common dermatologic conditions that prove to be treatment refractory should be biopsied without delay, and sequentially as necessary, to prevent delay in diagnosis and progression of disease. Clinicopathologic correlation is the best way of diagnosis.

Cemiplimab for locally advanced cutaneous squamous cell carcinoma: safety, efficacy, and position in therapy panel.

INTRODUCTION: Locally advanced cutaneous squamous cell carcinoma (lacSCC) is rare. Approximately one-fourth of the cases are observed among immunocompromised patients, in particular in solid organ transplant recipients (OTRs). LacSCC has a very poor prognosis. Surgery with or without radiotherapy remains the golden standard of treatment for cSCC. However, in advanced cases, there is a medical need for alternative treatment options. Classic systemic treatments include chemotherapy and/or EGFR inhibitors. Recently the effectiveness of programmed cell death protein-1 (PD-1) inhibitors has been demonstrated for lacSCC. Cemiplimab is a recombinant IgG4 human monoclonal antibody against the PD-1 protein for the intravenous treatment of lacSCC. AREAS COVERED: The principal studies evaluating the efficacy and safety of cemiplimab for lacSCC are presented. EXPERT OPINION: Cemiplimab is the first anti-PD-1 antibody that was FDA (2018) and EMA (2019) approved as a systemic treatment for lacSCC and/or metastatic cSCC when curative surgery or radiotherapy is no longer amenable. For this situation, experts currently recommend cemiplimab as a first-line systemic alternative. As cemiplimab therapy is potentially associated with a risk of organ graft rejection, pros and cons should be evaluated for every individual OTR patient with lacSCC.

Biologicals for moderate-to-severe plaque type psoriasis in pediatric patients.

INTRODUCTION: Psoriasis affects around 2% of children in Europe. The majority of cases is readily managed with topical treatments using corticosteroids without or with calcipotriol. More resistant and extensive moderate-to-severe cases require UVA or UVB phototherapies or conventional systemic treatment including ciclosporin, acitretin and methotrexate. However, these therapies are associated with a low tolerability and potential cumulative long-term adverse effects and toxicities. AREAS COVERED: About 15 years ago, the first biological appeared for the treatment of moderate-to-severe plaque type psoriasis in adult patients. Several years later, the first biologic treatment to be approved in children was etanercept, a soluble receptor that binds both tumor necrosis factor (TNF)-α and ß followed by adalimumab, a monoclonal antibody against TNF-α, and currently by ustekinumab, a monoclonal IL12/23 p40 antagonist and, very recently, secukinumab and ixekizumab, both IL17 antagonists. All these biologic treatments brought significantly improved treatment results compared to light-based therapies and conventional treatments and present very good tolerance and safety profiles. EXPERT OPINION: Due to their excellent efficacy and safety profiles ustekinumab, secukinumab and ixekizumab could currently be considered as a first-line treatment options for moderate-to-severe childhood and adolescent psoriasis requiring a systemic treatment.

Exploratory Assessment of Oxygen Flow-Assisted Cutaneous Administration of Methotrexate for Superficial Basal Cell Carcinoma, Mycosis Fungoides, and Extramammary Paget Disease.

The molecular weight of methotrexate (MTX) makes cutaneous penetration difficult. Oxygen flow could enhance the skin permeation of MTX diluted in the proprietary LP3 carrier system. This pilot study aims to assess the efficacy, safety, and tolerance of oxygen flow-assisted LP3-MTX3% for treating superficial skin cancers. Patients with superficial basal cell carcinoma (n = 12), extramammary Paget disease (n = 5), classic mycosis fungoides (MF; n = 10), and folliculotropic MF (n = 6) were included in the study and were treated with four weekly applications of oxygen flow-assisted LP3-MTX3%. Photographs and biopsies were performed before and one month after treatment. At one month after treatment, the mean superficial basal cell carcinoma erythema-crusting-thickness clinical score, the extramammary Paget disease erythema-oozing-scaling/hyperkeratosis-pain/pruritus clinical score, and the modified composite assessment of index lesion severity classic MF and folliculotropic MF scores were improved by 77.5% ± 17.1% (P < 0.0001), 66.7% ± 22.9% (P = 0.011), 51.3% ± 32.2% (P = 0.0007), and 27.8% ± 32.0% (P = 0.086), respectively. At one month after treatment, histology revealed partial and total clearances for superficial basal cell carcinoma (1/12, 11/12), extramammary Paget disease (4/5, 1/5), classic MF (8/10, 2/10), and folliculotropic MF (6/6, 0/6). Tolerance was excellent and no pain was observed. MTX was never detectable in serum at baseline and 1, 2, 3, 8, 24, 48, and 72 hours post-treatment. In conclusion, the interesting therapeutic efficacy of oxygen flow-assisted LP3-MTX3% for treating superficial basal cell carcinoma, extramammary Paget disease, and MF lesions prompts further studies on a larger scale.

Cutaneous Breast Cancer Metastases Successfully Treated Using an Oxygen Flow Assisted Topical Administration of Methotrexate (OFAMTX).

INTRODUCTION: Cutaneous metastases of breast cancer remain a therapeutic challenge. Oxygen flow-assisted topical administration of methotrexate 5% (OFAMTX, 5% methotrexate in a carrier solution) has recently been proven to be an efficacious alternative treatment for extramammary Paget's disease, which is considered to be an in situ mammary adenocarcinoma of the epidermis. CASE REPORT: A 51-year-old patient with triple negative breast cancer presenting with biopsy-proven skin metastases on the chest agreed to a treatment with OFAMTX5%. The treatment duration was 2 weeks and consisted of twice-weekly sessions with OFAMTX5% applied to an area of skin of approximately 40 cm2. Skin biopsies were performed before and 2 months after procedure. The tolerance to the treatment was excellent, and no pain sensations were experienced. Two months post-procedure the treated area presented a post-inflammatory hyperpigmentation. No residual metastatic lesions were detectable on the control skin biopsy. Six months post-procedure the patient is still in clinical remission. DISCUSSION: OFAMTX5% represents an alternative skin-directed, painless, patient-friendly and efficacious adjuvant treatment for superficial metastatic lesions of breast cancer. Larger series are required to evaluate the potential of OFAMTX5% for the treatment of superficial metastatic lesions of breast cancer.

Granulomatous Reactions from Tattoos Following BRAF Inhibitor Therapy.

BRAF inhibitors may present several cutaneous adverse effects, including actinic keratosis, squamous cell carcinoma, keratoacanthoma, rashes, increased photosensitivity, panniculitis, palmoplantar and capillary involvement, pruritus and xerosis as well as granulomatous reactions. A 30-year-old patient with multiple tattoos received dabrafenib and trametinib for metastatic melanoma. After 4 months, he developed an induration and thickening strictly limited to several tattoos. Histopathology revealed nonnecrotizing granulomas in the dermis. Topical steroids relieved pruritus but not the granulomatous aspect of the tattoos. As far as we know, this is the first description of granulomatous reactions restricted to preexisting tattoos following BRAF inhibitor therapy.

Giant morphea-form basal cell carcinoma of the umbilicus: Successful debulking with vismodegib.

Basal cell carcinoma of the umbilicus is very rare. The nodular subtype is the main representative. Giant basal cell carcinomas represent around 1% of all basal cell carcinomas. The hedgehog pathway inhibitor vismodegib is indicated for advanced basal cell carcinoma and CD56-negative immunostaining seems indicative for successful treatment. A 54-year-old man presented a 10 cm × 14 cm large and 4.5 cm deep morphea-form basal cell carcinoma with faint immunohistochemical CD56 expression arising from the umbilicus. A sequential treatment was initiated with debulking using vismodegib 150 mg per day for 4 months, followed by reconstructive surgery. To the best of our knowledge, this is the first report of a giant basal cell carcinoma of the morphea-form type of the umbilicus. The sequential treatment plan reduces the duration of vismodegib inherent adverse effects and significantly reduces the tumor mass prior to surgery. Besides increasing adherence to vismodegib treatment, this approach facilitates the surgical technique and improves cosmetic outcome.

Eruptive Seborrheic Keratoses Restricted to Plaque/Patch-Stage Mycosis Fungoides.

Eruptive seborrheic keratoses (ESK) are rare in dermatology. They are usually inflammatory in nature and may be encountered as Leser-Trélat sign. ESK may also be simultaneously observed with hepatic angiomas, chemotherapy, segmental neurofibromatosis, HIV or erythrodermic pityriasis rubra pilaris, psoriasis, and drug eruption. ESK may be transient and self-healing. Others recede after successful treatment of the underlying disease. In some instances, seborrheic keratoses may follow an isotopic response and remain strictly restricted to sites of previous eczema, photo-exposition or tattoos. A patient with patch/plaque lesions of classic-type mycosis fungoides (MF) presented sudden ESK that were exclusively limited to the MF lesions. In conclusion, this patient combined an isotopic response and ESK.

Pachyderma in Primary Cutaneous NK and T-Cell Lymphoma and Leukemia Cutis.

BACKGROUND: Pachyderma is defined as severely thickened skin with deep folds and is occasionally observed with primary cutaneous NK and T-cell lymphoma (pCNKTCL), primary cutaneous B-cell lymphoma (pCBCL), and leukemia cutis (LC). AIM: To describe the clinical, histological, and therapeutic particularities of a series of pCNKTCL, pCBCL, and LC patients with pachyderma. RESULTS: In a series of pCNKTCL (n = 70), pCBCL (n = 12), and LC (n = 2) patients followed up during 9 years, 6 cases of pachyderma were observed. Pachyderma occurred on the arms (n = 2), thighs (n = 1), forehead (n = 1), and face (n = 2). The mean age of the patients was 69 years (51-82). The stages were erythrodermic (T4) mycosis fungoides (MF) (n = 1), folliculotropic MF (FMF) (n = 2), classic (T2) MF (n = 2), and chronic myeloid leukemia (n = 1). The erythrodermic MF patient with acute pachyderma on the right arm responded rapidly to oral steroids. The other cases were indolent, appeared progressively, and were highly treatment resistant. Histology revealed dense dermal neoplastic infiltration. The immunohistological profile of the pachydermic lesions was similar to common MF and LC. CONCLUSION: Pachyderma is an atypical manifestation of MF and LC and may occur on the face (FMF) or the extremities (MF). The rapidly appearing pachyderma may be transitory and responds readily to oral steroids.

Koebner Phenomenon and Mycosis Fungoides.

Mycosis fungoides (MF) is the most frequent type of primary cutaneous T-cell/NK-cell lymphoma. The Koebner phenomenon is defined as the appearance of cutaneous lesions on previously noninvolved skin following trauma and is observed in a series of cutaneous diseases including psoriasis, lichen planus, viral warts, molluscum contagiosum, etc. In this case report, 3 patients with longstanding MF are presented, the 1st with the appearance of a circumscribed early-stage type MF lesion rapidly following a surgical excision of an infundibular cyst, the 2nd with the appearance of a unique unilateral palmar tumoral MF lesion at the pressure site of a crutch, and the 3rd presented localized MF early stage lesions at the friction site of a belt. This report suggests that some MF patients may experience Koebner phenomenon-induced MF lesions and that MF should be added to the long list of skin diseases potentially exhibiting the Koebner phenomenon.