Treatment of progressive locally advanced and metastatic basal cell carcinoma after two lines of treatment with hedgehog inhibitors and anti-PD1: The role of sonidegib rechallenge L. Ambrosio, C. Retrosi, M. Agozzino, C. Cantisani, N. Di Meo, G. Di Lella, R. Giuffrida, S. Guida, S. Lembo, C. Longo, I. Zalaudek, G. Pellacani, C. Conforti Journal of the European Academy of Dermatology and Venereology, 2025 Locally advanced basal cell carcinoma (laBCC) and metastatic basal cell carcinoma (mBCC) are often treated with Hedgehog pathway inhibitors (HHIs) like vismodegib and sonidegib, immune checkpoint inhibitors (ICIs) such as cemiplimab, chemotherapy like carboplatin and paclitaxel, and occasionally antifungal agents when standard therapies fail.1, 2 This systematic review aims to assess third-line treatments for advanced BCC (aBCC), focusing on protocols, outcomes, side effects and follow-ups. A PRISMA-based literature search of PubMed included terms such as ‘locally advanced basal cell carcinoma’, ‘metastatic basal cell carcinoma’, along with ‘vismodegib’, ‘sonidegib’, ‘rechallenge’, ‘cemiplimab’, ‘third line therapy’, ‘recurrences’ and ‘progression disease’. Studies involving laBCC or mBCC patients treated with first- and second-line therapies followed by HHI rechallenge were included. Non-responders were defined by progressive disease. Reviews, meta-analyses, cohort studies and case series were included, with only English articles selected. Additional references were identified through manual checks. Thirteen cases of HHI rechallenge in aBCC were identified, with seven males and six females averaging 65 years. Four cases were mBCC and nine laBCC. The head and neck were the most common sites, while the lungs and bones were typical metastatic locations.3, 4 Eleven patients received vismodegib as first-line therapy, and two received sonidegib, with an average therapy duration of 18.9 months and a follow-up of 19.8 months. Side effects were reported in 12 patients, including weight loss, muscle spasms, arthralgia, dysgeusia, nausea and alopecia. As second-line therapy, eight patients received cemiplimab and five pembrolizumab, with an average duration of 5.3 months and follow-up of 18.7 months. Adverse effects were minimal, occurring in three cases, and led to treatment discontinuation in only one case. Notably, eight patients did not respond to ICIs and experienced disease progression. For third-line therapy, HHI rechallenge involved sonidegib in 10 cases and vismodegib in 3, with an average duration and follow-up of 8 months. Of these, three patients progressed immediately, four achieved partial responses and six had stable disease. One patient on sonidegib maintained a complete response at 9 months of follow-up. Additionally, six patients on sonidegib exhibited sustained responses lasting 9–29 months, though four eventually relapsed. Side effects were similar to those observed in first-line therapy, with discontinuation in only two cases. Six patients remained relapse-free during follow-up. Notably, two patients underwent fourth-line therapy with cemiplimab rechallenge and were still under follow-up at the time of publication4 (Table 1). Two major studies evaluated SHI rechallenge after a complete response in BCC. Herms et al. reported an 85% objective response rate in 27 patients rechallenged with vismodegib, with 37% achieving complete responses.5 Bassompierre et al. found a 65.7% overall response rate in 35 patients, with 34.3% complete and 31.4% partial responses.6 Lower complete response rates in both studies likely stem from acquired resistance via SMO mutant clones.5, 6 It is important to highlight that, in the reported studies, none of the patients who underwent rechallenge had been a non-responder to first-line therapy. This observation could suggest that this therapeutic option may be valid for patients who discontinue the initial treatment due to side effects, complete or partial response, before the development of acquired resistance. 1L: vismodegib (6 months); PR 2L: cemiplimab (5 months); CR 3L: sonidegib + itraconazole (10 months); PR 1L: sonidegib (5 months); CR 2L: cemiplimab (4 months); PR (clinical response but progression at imaging) 3L: sonidegib (2 months); PR (ongoing at the time of publication) 1L: vismodegib (22 months); PR 2L: cemiplimab (4 months); PD 3L: sonidegib (10 months); SD 1L: vismodegib (19 months); PR 2L: cemiplimab (16 months); PD 3L: sonidegib (13 months); SD 4L: cemiplimab 1L: vismodegib (27 months); PR 2L: cemiplimab (8 months); SD; discontinuation due to side effects 3L: sonidegib (3 months; discontinuation for patient's request); SD 4L: cemiplimab, ongoing 1L: vismodegib (7 months); PR 2L: cemiplimab (1 months); PD 3L: sonidegib (3 months); SD 1L: vismodegib (25 months); PR 2L: cemiplimab (2 months); PD 3L: sonidegib (3 months); SD; ongoing 1L: sonidegib (13 months); PR 2L: cemiplimab (2 months); PD 3L: vismodegib (1 months); PD; discontinuation due to side effects 1L: vismodegib (13 months); SD 2L: pembrolizumab (4 months); PD 3L: sonidegib (9 months); CR 1L: vismodegib (22 months); SD 2L: pembrolizumab (2 months); SD (stopped for no drug approval) 3L: vismodegib (20 months); PR and afterwards progression 1L: vismodegib (64 months); SD 2L: pembrolizumab (6 months); SD (stopped for patient's request) 3L: sonidegib (29 months); PR, ongoing 1L: vismodegib (26 months); SD 2L: pembrolizumab (6 months); SD 3L: vismodegib (4 months); SD (discontinuation due to side effects) 1L: vismodegib (2 months); SD 2L: pembrolizumab (5 months); PD 3L: sonidegib (3 months); PD 1L: Weight loss 2L: — 3L: — 1L: Muscle spasm, arthralgia, dysgeusia, nausea, weight loss 2L: Fatigue (I), weakness (I), pruritus (I) 3L: — 1L: Muscle spasms (I), dysgeusia (I) 2L: — 3L: — 1L: Muscle spasms (II), dysgeusia (II), alopecia (III) 2L: Exacerbation of psoriasis 3L: — 1L: Alopecia, muscle spasms, weight loss 2L: Vasovagal presyncope, myocarditis cause of discontinuation 3L: — 1L: — 2L: — 3L: — 1L: dysgeusia, alopecia 2L: — 3L: — 1L: Muscle spasms (II), dysgeusia (III), weight loss (III) 2L: — 3L: Dysgeusia (II), weight loss (II) and discontinuation 1L: Nausea, alopecia 2L: — 3L: Nausea 1L: Alopecia, weight loss, loss of appetite, muscle pain, arthralgia 2L: — 3L: Loss of appetite, weight loss Gorlin-Goltz syndrome 1L: Alopecia, muscle spasm, depression 2L: — 3L: Muscle spasms, depression, weight gain, amenorrhea, brittle nails, fatigue 1L: Dysgeusia (I), alopecia (I), weight loss (III), muscle spasm (I) 2L: — 3L: Loss of appetite, weight loss (III) cause of discontinuation 1L: Unknown 2L: — 3L: Myalgia, diarrhoea, nausea This review highlights the potential of HHI rechallenge as a third-line therapy for aBCC after failure of first- and second-line treatments. Sustained responses observed in certain cases underscore its viability, especially for patients without prior resistance. Nevertheless, further studies are necessary to solidify its place in the therapeutic algorithm for aBCC.7, 8 Future efforts should focus on offering mutational and structural analyses to predict resistance and tailor treatment choices for optimal and sustained responses across different clinical scenarios. Unrestricted grant by Sun Pharma. None declared. The study was a retrospective evaluation conducted in accordance with the principles of the Declaration of Helsinki and the International Council for Harmonization and Good Clinical Practice guidelines. Not applicable. The data that support the findings of this study are available from the corresponding author upon reasonable request.
Discovering basal cell carcinoma cellular origin via reflectance confocal microscopy Luca Ambrosio, Vincenzo Roberti, Pablo Uribe, Camilla Chello, Miguel Villaseca, Cristian Navarrete‐Dechent, Chiara Retrosi, Claudio Conforti, Giovanni Pellacani Journal of the European Academy of Dermatology and Venereology, 2025 The data that support the findings of this study are available from the corresponding author upon reasonable request.
Evaluating the therapeutic efficacy of the 595 nm pulsed dye laser system for treating capillary malformations Domenico Piccolo, Chiara Retrosi, Irene Fusco, Tiziano Zingoni, Claudio Conforti Dermatology Reports, 2025 Capillary malformations are the most prevalent low-flow vascular abnormalities. We present the case of a 30-year-old woman with a lateral capillary malformation. Dermoscopy showed an erythematous background and rare telangiectatic vessels for less than 5-10% of the entire area examined. The patient underwent a single treatment session with a 595 nm pulsed dye laser (PDL). An excellent immediate response was observed at the end of the session, with a noticeable reduction in the capillary malformation confirmed at clinical follow-up two months later. Dermatoscopic and 3D photographic evaluation before and after laser treatment also documented the disappearance of the erythematous background and telangiectatic vessels.
Reflectance Confocal Microscopy and Dermoscopy for the Diagnosis of Solitary Hypopigmented Pink Lesions: A Narrative Review Luca Ambrosio, Anna Pogorzelska-Antkowiak, Chiara Retrosi, Giovanni Di Lella, Marco Spadafora, Iris Zalaudek, Caterina Longo, Giovanni Pellacani, Claudio Conforti Cancers, 2024 Diagnosing solitary pink skin lesions poses a significant challenge due to the scarcity of specific clinical and dermoscopic criteria. Several benign lesions, such as cherry angioma, clear cell acanthoma, dermal nevus, keloid, hypertrophic scar, and Spitz nevus, often exhibit similar clinical and dermoscopic features. This similarity extends to some malignant lesions, including basal cell carcinoma, actinic keratosis, and amelanotic melanoma, making differentiation difficult. Recent studies highlight the enhanced diagnostic accuracy of reflectance confocal microscopy (RCM), which offers increased sensitivity and specificity compared to dermoscopy alone for diagnosing skin cancer. This study aims to summarize the application of dermoscopy and RCM in distinguishing between benign and malignant pinkish–reddish skin lesions. The integration of RCM with traditional dermoscopic techniques improves the ability to accurately identify and differentiate these lesions. However, it is crucial to note that for any suspicious lesions, a final diagnosis must be confirmed through surgical excision and histopathological evaluation. This comprehensive approach ensures accurate diagnosis and appropriate treatment, highlighting the importance of combining advanced imaging techniques in clinical practice.
Unraveling the Complex Nexus of Human Papillomavirus (HPV) in Extragenital Keratinocyte Skin Tumors: A Comprehensive Analysis of Bowen’s Disease and In Situ Squamous-Cell Carcinoma Claudio Conforti, Chiara Retrosi, Marina Agozzino, Caterina Dianzani, Ermanno Nardon, Anselmo Oliveri, Eros Azzalini, Stefania Guida, Giovanni Pellacani, Giovanni Di Lella, Franco Rongioletti, Iris Zalaudek, Serena Bonin Journal of Clinical Medicine, 2024 This comprehensive study delves into the intricate landscape surrounding the role of human papillomavirus (HPV) in extragenital keratinocyte skin tumors, specifically exploring Bowen’s disease (BD) and in situ squamous-cell carcinoma (iSCC). Through a multifaceted examination, this research study elucidates the nuanced interplay of HPV, gender dynamics, anatomical site variations, and potential implications for the etiopathogenesis of these malignancies.
Clinical and Dermoscopic Diagnosis of Actinic Keratosis Claudio Conforti, Luca Ambrosio, Chiara Retrosi, Carmen Cantisani, Giovanni Di Lella, Luca Fania, Roberta Rotunno, Iris Zalaudek, Giovanni Pellacani Dermatology Practical and Conceptual, 2024 Actinic keratosis (AK) is one of the most frequent tumors of the skin; the diagnosis is basically clinical although in some cases it may be difficult to distinguish it from other keratinocytic or even melanocytic neoplasms when it presents in pigmented form. Over the years several clinical classifications and scores to objectify the burden of disease have been created. In this review the most frequent scores and classification systems are summarized along with dermoscopic criteria that allow diagnosis with greater sensitivity and specificity.
Multidisciplinary care for patients with epidermolysis bullosa from birth to adolescence: experience of one Italian reference center Chiara Retrosi, Andrea Diociaiuti, Cristiana De Ranieri, Marialuisa Corbeddu, Claudia Carnevale, Simona Giancristoforo, Maria Rosaria Marchili, Guglielmo Salvatori, Marta Luisa Ciofi degli Atti, May El Hachem, Massimiliano Raponi Italian Journal of Pediatrics, 2022 Background Epidermolysis bullosa (EB) is a disabling and chronic genodermatosis characterized by mucocutaneous fragility with blister formation after minimal trauma. Severity ranges between very mild forms to extremely severe or lethal subtypes. Depending on disease subtypes, blisters may be localized also in larynx, bladder, esophagus, and most frequent disease complications are malnutrition, chronic anemia, osteoporosis, limb contracture and early development of squamous cell carcinomas. EB is classified into four major groups: EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB) and Kindler EB (KEB). No specific treatment is available; however, a multidisciplinary management is mandatory in order to treat the lesions, to prevent complication, and to give a psychological support to the patient and family members. Objective To report the experience on a therapeutic education plan of an Italian reference center for epidermolysis bullosa in the last 30 years. Methods In our study we included all patients with EB from 1990 to the present, dividing them into three age groups (< 5 years, > 5–12 years and > 12–18 years). The therapeutic plan involved all multidisciplinary team members, since born until adolescence. The multidisciplinary team has been progressively established; the dermatologists act as patient case manager, in collaboration with the pediatrician, endocrinologist, dietician, dentist, plastic surgeon, digestive surgeon, geneticist, psychologist and a dedicated nurse. Other dedicated specialists are involved upon patient needs. Results Two hundred fifteen patients have been recruited and followed in our hospital since 1990. One hundred forty patients (65%) are on follow-up, 27 patients (13%) died and only 11 (5%) were lost to follow-up. Our patients manifested the specific complications related to their EB subtype in keeping with the data reported in the literature. Eighteen (8%) patients affected with JEB severe died within the first year of life, 9 patients (5%) died for squamous cell carcinoma in adulthood and were affected with recessive DEB; only 1 patient died for squamous cell carcinoma at the age of 16. Conclusions An adequate management of EB patients require a multidisciplinary approach with an educational plan to guarantee an appropriate treatment and to support and accompany patients and their families since birth along life. The dynamic educational plan adopted in our hospital showed good clinical and psychological outcome in our population, allowing adherence to treatment, reducing the frequency of complications and improving life expectancy and quality of life.
Giant congenital exophytic strawberry-like mass in a newborn C. Carnevale, A. Diociaiuti, C. Retrosi, G. Gualdi, A. Fabiano, A. Stracuzzi, M. El Hachem Clinical and Experimental Dermatology, 2022 A male newborn was referred at birth because of a suspected giant congenital haemangioma on his back. He had been delivered vaginally at 38 + 5 weeks after a normal pregnancy. Ultrasonography during the fifth month of pregnancy had not detected the mass; however, at birth, a purplish-red, reniform, nodular and pedunculated skin tumour measuring 80 × 50 × 35 mm was visible on the right paravertebral lumbosacral area. This strawberry-like mass had a tense consistency and a smooth surface with homogeneous, diffuse and yellowish point depressions (Fig. 1a,b). Doppler ultrasonography showed that the tumour was not vascular in nature. Complete surgical excision was performed and the tumour was sent for histology. Histological examination showed a well-circumscribed dermal lesion composed of multiple folliculosebaceous units, with frequent cystic dilated hair infundibules (Fig. 2a). The units were embedded in a loose fibromyxoid stroma with interspersed thin smooth muscle bundles, which were nicely highlighted by desmin. Small lobules of immature adipose tissue were scattered within the stroma (Fig. 2b). Small nerve trunks and ectatic vessels were also seen (Fig. 2c). No connections between the sebaceous lobules and the overlying epidermis were noted. At the periphery, a stromal cleft separated the lesion from the surrounding dermis. What is your diagnosis? Folliculosebaceous cystic hamartoma (FSCH). FSCH, first described in 1991 by Kimura et al.,1 is an uncommon benign skin lesion, with < 100 cases reported in the literature since the first description. FSCH usually manifests with a single, small (5–15 mm), flesh-coloured, sessile or pedunculated mass, frequently located on the head, in particular on the central part of the face and nose. FSCH is usually isolated, and a syndromic form has never been reported in the literature. It primarily affects middle-aged adults,1, 2 but has also been described in infancy and a very few congenital cases have been reported.3-5 Emsen and Livaoglu described a case of FSCH appearing at 6 months of age as a congenital case.6 According to previous reports, FSCH is defined ‘giant’ when the lesion ranges from 50 to 230 mm in diameter,2 and only a very small number of giant FSCH have been reported.2-6 Congenital FSCH were described as ‘giant’ in only three cases, with the patients being 6, 9 and 12 months of age; however, the lesions were smaller at birth in all three cases.3-5 To our knowledge, our patient is the first case of congenital FSCH that was giant since birth. FSCH is considered a hamartoma because of the coexistence of multiple mature ectodermal and mesodermal elements. Histological examination is necessary to define the diagnosis. Whereas the clinical aspects and the localization are characteristic in adults, there are variations in its appearance in newborns and children. CO2 laser, oral acitretin and surgery are the most useful therapeutic options.1-6 Our patient was treated with excision surgery, and has been in good health since then. To gain up-to-date knowledge on the classification of and investigations for folliculosebaceous cystic hamartoma. This learning activity is freely available online at http://www.wileyhealthlearning.com/ced Once the test is passed, you will receive a certificate and the learning activity can be added to your RCP CPD diary as a self-certified entry. This activity will be available for CPD credit for 2 years following its publication date. At that time, it will be reviewed and potentially updated and extended for an additional period.
Basal cell carcinomas are not only UV-related Nicola DI MEO, Claudio CONFORTI, Roberta VEZZONI, Chiara RETROSI, Michela LONGONE, Mattia FADEL, Iris ZALAUDEK Italian Journal of Dermatology and Venereology, 2021
Cutaneous granuloma mimicking amelanotic melanoma Claudio CONFORTI, Chiara RETROSI, Roberta VEZZONI, Paola CORNELI, Vincenzo PICCOLO, Roberta GIUFFRIDA, Nicola DI MEO, Iris ZALAUDEK Italian Journal of Dermatology and Venereology, 2021
Inverse psoriasis in patient treated with atezolizumab Paola Corneli, Nicola Meo, Serena Fagotti, Claudio Conforti, Eleonora Farinazzo, Alberto Zacchi, Chiara Retrosi, Roberta Vezzoni, Maria A. Pizzichetta, Iris Zalaudek International Journal of Dermatology, 2020
Secukinumab-induced subacute cutaneous lupus erythematosus Claudio Conforti, Chiara Retrosi, Roberta Giuffrida, Roberta Vezzoni, Damiano Currado, Luca Navarini, Eleonora Farinazzo, Carmen Dell'Aquila, Katiuscia Nan, Nicola Di Meo, Iris Zalaudek Dermatologic Therapy, 2020
Benign dermatoses of the male genital areas: A review of the literature Claudio Conforti, Roberta Giuffrida, Nicola Di Meo, Michela Longone, Silvia Vichi, Claudia Colli, Teresa Deinlein, Roberta Vezzoni, Chiara Retrosi, Enzo Errichetti, Serafinella Patrizia Cannavò, Iris Zalaudek, Caterina Dianzani Dermatologic Therapy, 2020
Is there more than one road to nevus-associated melanoma? Roberta Vezzoni, Claudio Conforti, Silvia Vichi, Roberta Giuffrida, Chiara Retrosi, Giovanni Magaton-Rizzi, Nicola Di Meo, Maria Antonietta Pizzichetta, Iris Zalaudek Dermatology Practical and Conceptual, 2020
Overview on the treatment of Lyme disease in pregnancy Claudio Conforti, Roberta Vezzoni, Chiara Retrosi, Michela Longone, Paola Corneli, Giovanni Magaton Rizzi, Katiuscia Nan, Nicola Di Meo, Iris Zalaudek Giornale Italiano Di Dermatologia E Venereologia, 2020
