Oriol Yélamos

A comparative study of proliferative nodules and lethal melanomas in congenital nevi from children.

Differentiating proliferative nodules (PNs) from melanomas arising in congenital nevi (CN) is a considerable challenge for dermatopathologists. Most of the specimens dermatopathologists assess that deal with this differential diagnosis involve proliferations of melanocytes arising in the dermis. In this study, we compare the clinical, histologic, and molecular findings of these 2 conditions. In our database, we found 22 examples of PNs arising in the dermis of CN and 2 cases of lethal melanomas arising from the dermis/epidermis of CN of children. Importantly, we found that among dermal melanocytic proliferations arising from CN in children, PNs are far more common than lethal melanomas. Clinically, multiplicity of lesions favored a diagnosis of PNs, whereas ulceration was infrequent in PNs compared with lethal melanomas. Histologically, PNs showed several distinct patterns including expansile nodules of epithelioid melanocytes with mitotic counts lower than that seen in the melanomas (1.67 vs. 12.5 mitoses/mm2), a small round blue cell pattern often highly mitotically active, neurocristic-like, blue nevus-like, a nevoid melanoma-like pattern, or an undifferentiated spindle cell pattern. The lethal melanomas both featured expansile nodules of epithelioid melanocytes with high mitotic counts (range, 5 to 20 mitoses/mm2) and an ulcerated overlying epidermis. At the molecular level, the PNs showed mostly whole chromosomal copy number aberrations, which in some cases were accompanied by rare partial chromosomal aberrations, whereas both lethal melanomas showed highly elevated copy number aberrations involving 6p25 without gains of the long arm of chromosome 6.

Results of the 2016 International Skin Imaging Collaboration International Symposium on Biomedical Imaging challenge: Comparison of the accuracy of computer algorithms to dermatologists for the diagnosis of melanoma from dermoscopic images

Background Computer vision may aid in melanoma detection. Objective We sought to compare melanoma diagnostic accuracy of computer algorithms to dermatologists using dermoscopic images. Methods We conducted a cross‐sectional study using 100 randomly selected dermoscopic images (50 melanomas, 44 nevi, and 6 lentigines) from an international computer vision melanoma challenge dataset (n = 379), along with individual algorithm results from 25 teams. We used 5 methods (nonlearned and machine learning) to combine individual automated predictions into “fusion” algorithms. In a companion study, 8 dermatologists classified the lesions in the 100 images as either benign or malignant. Results The average sensitivity and specificity of dermatologists in classification was 82% and 59%. At 82% sensitivity, dermatologist specificity was similar to the top challenge algorithm (59% vs. 62%, P = .68) but lower than the best‐performing fusion algorithm (59% vs. 76%, P = .02). Receiver operating characteristic area of the top fusion algorithm was greater than the mean receiver operating characteristic area of dermatologists (0.86 vs. 0.71, P = .001). Limitations The dataset lacked the full spectrum of skin lesions encountered in clinical practice, particularly banal lesions. Readers and algorithms were not provided clinical data (eg, age or lesion history/symptoms). Results obtained using our study design cannot be extrapolated to clinical practice. Conclusion Deep learning computer vision systems classified melanoma dermoscopy images with accuracy that exceeded some but not all dermatologists.

Systemic methotrexate for the treatment of psoriasis.

In the era of biologic therapies, methotrexate (MTX), a classic immunomodulator, is still the cornerstone of systemic treatment of psoriasis. MTX has been used for many years, achieving good responses with a good safety profile. However, only a few randomized clinical trials have been performed involving MTX, and most of the current evidence comes from pivotal studies of biologic drugs. The aim of this article is to make an extensive review of the MTX mechanism of action, pharmacokinetics, efficacy, safety and tolerability, especially focusing on the future perspective of this old drug and recent advances in the field of pharmacogenetics.

Anti-Tumour Necrosis Factor-Induced Visceral and Cutaneous Leishmaniasis: Case Report and Review of the Literature

Background: Leishmaniasis is a chronic protozoan disease in which organisms are found within phagolysosomes of the mononuclear phagocyte system. There are three major forms: cutaneous, mucocutaneous and visceral. We report the first case of visceral leishmaniasis with cutaneous involvement in a patient with rheumatoid arthritis treated with the anti-tumour necrosis factor (anti-TNF) adalimumab. Objective: To highlight cutaneous leishmaniasis as the first indicator of a kala-azar disease in a patient treated with anti-TNF and to review the literature on leishmaniasis in the context of anti-TNF therapy. Case Report: A 59-year-old woman presented with a crusted plaque on the right elbow 34 months after the initiation of adalimumab. A cutaneous biopsy showed intracellular amastigotes. No Leishmania parasites were observed in a bone marrow aspirate, but laboratory tests showed anaemia and impaired liver function, abdominal ultrasonography showed hepatomegaly, and ELISA serology was strongly positive for Leishmania antibodies in serum and urine. Adalimumab was withdrawn and treatment combining intralesional pentavalent antimonials and liposomal amphotericin was started. Eight weeks later, the leishmaniasis had resolved. Conclusion: A skin biopsy disclosing leishmaniasis should prompt tests to rule out visceral leishmaniasis, especially in an area such as the Mediterranean where the prevalence of latent Leishmania infection is high.

Acute Severe Methotrexate Toxicity in Patients with Psoriasis: A Case Series and Discussion

Background: Methotrexate (MTX) is considered a relatively safe drug when prescribed at low-dose regimens not exceeding 25 mg/week. Severe acute toxicity is rare and presents with mucositis, cutaneous ulceration and pancytopenia. Most cases occur as the result of inadvertent overdosing due to erroneously taking the drug daily. However, concomitant factors such as older age, co-medication and renal failure may increase the drugs toxicity. Case Reports: We report four consecutive cases of acute MTX toxicity in patients with psoriasis vulgaris. In three patients, MTX was erroneously taken daily for 2-4 weeks. All three patients recovered following MTX withdrawal and intensive treatment. The fourth patient was taking 7.5 mg weekly MTX as prescribed, but had concomitant factors and died. Conclusion: Although low-dose MTX appears to be a safe medication, acute MTX toxicity can be a life-threatening emergency. Greater awareness of possible MTX toxicity is still needed for its prevention, early diagnosis and management.

Nonoverlapping Clinical and Mutational Patterns in Melanomas from the Female Genital Tract and Atypical Genital Nevi

Genital melanomas (GM) are the second most common cancer of the female external genitalia and may be confused with atypical genital nevi (AGN), which exhibit atypical histological features but have benign behavior. In this study, we compared the clinical, histological, and molecular features of 19 GM and 25 AGN. We described chromosomal copy number aberrations and the mutational status of 50 oncogenes and tumor suppressor genes in both groups. Our study showed that a pigmented lesion occurring in mucosal tissue, particularly in postmenopausal women, was more likely to be a melanoma than a nevus. GM had high levels of chromosomal instability, with many copy number aberrations. Furthermore, we found a completely nonoverlapping pattern of oncogenic mutations when comparing GM and AGN. In GM, we report somatic mutations in KIT and TP53. Conversely, AGN had frequent BRAF V600E mutations, which were not seen in any of the GM. Our results show that GM and AGN have distinct clinical and molecular changes and that GM have a different mutational pattern compared with AGN.

Multiple Cutaneous Melanomas and Clinically Atypical Moles in a Patient With a Novel Germline BAP1 Mutation

IMPORTANCE Several kindreds having germline BAP1 mutations with a propensity for uveal and cutaneous melanomas and other internal malignancies have been described in an autosomal dominant tumor predisposition syndrome. However, clinically atypical moles have not been previously recognized as a component of this syndrome, to our knowledge. We describe the first kindred to date with a germline mutation in BAP1 associated with multiple cutaneous melanomas and classic dysplastic nevus syndrome. OBSERVATIONS We describe a 53-year-old man who was initially seen in 2003 with dysplastic nevus syndrome, multiple atypical melanocytic proliferations showing loss of immunostaining for BAP1, and 7 cutaneous melanomas. Germline testing was performed in the proband, his 16-year-old son, and his 13-year-old daughter, revealing a germline mutation in the BAP1 gene (c.592G>T, p.Glu198X) in the proband and in his 16-year-old son. CDKN2A and CDK4 genes were wild type. No members of this kindred reported a history of uveal melanoma. CONCLUSIONS AND RELEVANCE To our knowledge, this is the first report of a patient with multiple melanomas, dysplastic nevus syndrome, and an inactivating germline BAP1 mutation. The coexistence of dysplastic nevus syndrome and a BAP1 germline mutation extends the spectrum of the BAP1 tumor predisposition syndrome and may confer a greater risk for cutaneous melanomas.

Handheld optical coherence tomography–reflectance confocal microscopy probe for detection of basal cell carcinoma and delineation of margins

Abstract. We present a hand-held implementation and preliminary evaluation of a combined optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) probe for detecting and delineating the margins of basal cell carcinomas (BCCs) in human skin in vivo. A standard OCT approach (spectrometer-based) with a central wavelength of 1310 nm and 0.11 numerical aperture (NA) was combined with a standard RCM approach (830-nm wavelength and 0.9 NA) into a common path hand-held probe. Cross-sectional OCT images and enface RCM images are simultaneously displayed, allowing for three-dimensional microscopic assessment of tumor morphology in real time. Depending on the subtype and depth of the BCC tumor and surrounding skin conditions, OCT and RCM imaging are able to complement each other, the strengths of each helping overcome the limitations of the other. Four representative cases are summarized, out of the 15 investigated in a preliminary pilot study, demonstrating how OCT and RCM imaging may be synergistically combined to more accurately detect BCCs and more completely delineate margins. Our preliminary results highlight the potential benefits of combining the two technologies within a single probe to potentially guide diagnosis as well as treatment of BCCs.

Primary cutaneous T-cell lymphomas: a review

Primary cutaneous T-cell lymphomas (CTCLs) represent a number of extranodal lymphomas arising from a malignant population of lymphocytes in the skin, with the most common type being mycosis fungoides (MF) representing half of all primary CTCLs. Despite advances in immunohistochemistry and molecular methodology, significant diagnostic challenges remain due to phenotypic overlap of primary CTCLs with several inflammatory dermatoses, secondary lymphomas, among other conditions. Clinical features such as presentation and morphology, staging, histology, immunophenotype and molecular features must be considered in detail before a diagnosis is made in order to minimise false-positive, false-negative and indeterminate diagnoses. Herein, we review primary CTCLs, including epidemiological data, a brief summary of clinical presentations, immunophenotype, molecular signatures and differential diagnoses.

Correlation of Handheld Reflectance Confocal Microscopy With Radial Video Mosaicing for Margin Mapping of Lentigo Maligna and Lentigo Maligna Melanoma

Importance The management of lentigo maligna (LM) and LM melanoma (LMM) is challenging because of extensive subclinical spread and its occurrence on cosmetically sensitive areas. Reflectance confocal microscopy (RCM) improves diagnostic accuracy for LM and LMM and can be used to delineate their margins. Objectives To evaluate whether handheld RCM with radial video mosaicing (HRCM-RV) offers accurate presurgical assessment of LM and LMM margins. Design, Setting, and Participants This prospective study included consecutive patients with biopsy-proven LM and LMM located on the head and neck area who sought consultation for surgical management from March 1, 2016, through March 31, 2017, at the Dermatology Service of the Memorial Sloan Kettering Cancer Center. Thirty-two patients underwent imaging using HRCM-RV, and 22 patients with 23 LM or LMM lesions underwent staged surgery and contributed to the analysis. Main Outcomes and Measures Clinical lesion size and area, LM and LMM area based on HRCM-RV findings, surgical defect area estimated by HRCM-RV, and observed surgical defect area. In addition, the margins measured in millimeters estimated for tumor clearance in each quadrant based on HRCM-RV findings were calculated and compared with the surgical margins. Results Among the 22 patients (12 men and 10 women; mean [SD] age, 69.0 [8.6] years [range, 46-83 years]) with 23 lesions included in the final analysis, the mean (SD) surgical defect area estimated with HRCM-RV was 6.34 (4.02) cm2 and the mean (SD) area of surgical excision with clear margins was 7.74 (5.28) cm2. Overall, controlling for patient age and previous surgery, surgical margins were a mean of 0.76 mm (95% CI, 0.67-0.84 mm; P < .001) larger than the HRCM-RV estimate. Conclusions and Relevance Mapping of LM and LMM with HRCM-RV estimated defects that were similar to but slightly smaller than those found in staged excision. Thus, mapping of LM using HRCM-RV can help spare healthy tissue by reducing the number of biopsies needed in clinically uncertain areas and may be used to plan treatment of LM and LMM and counsel patients appropriately.