AMR SeriesMetastatic Cutaneous Basal Cell Carcinoma Report of 2 Cases Preceding the Hedgehog Pathway Antagonists EraBisceglia, Michele MD*; Panniello, Gaetano MD†; Nirchio, Vincenzo MD‡; Sanguedolce, Francesca MD§; Centola, Michele MD∥; Ben-Dor, David J. MD¶Author Information *Anatomic Pathology, School of Biomedical Sciences, Etromapmax Pole, Lesina (FG) †Unit of Clinical Dermatology, Department of Internal Medicine ‡Unit of Diagnostic Cytopathology, Department of Pathology §Unit of Anatomic Pathology, Department of Pathology, Polyclinic of Foggia, Foggia ∥School of Medicine, University of Perugia, Perugia, Italy ¶Department of Pathology, The Barzilai Medical Center, Ashkelon, Israel Case 1 of this report was previously presented at the XXVII Incontro di Istopatologia Dermatologica, April 3-4, 2003, Turin, Italy, and was published in the proceedings of the Congress [G Ital Dermatol Venereol 2004; 139(suppl 1):116-117]. Case 2 of this report was previously presented in the “Dermatopathology” session at the 6th SIAPEC National Congress of the Italian Society of Anatomic Pathology, October 27-29, 2011, Palermo, Italy, and was published in abstract form in the proceedings of the Congress (Pathologica 2011; 103:177-178). M.B., G.P., and V.N.: were formerly at the “IRCCS, Casa Sollievo della Sofferenza” Hospital, San Giovanni Rotondo (FG), Italy, many years ago, when they observed the 2 cases reported herein. The authors have no funding or conflicts of interest to disclose. All figures can be viewed online in color at www.anatomicpathology.com. Reprints: Michele Bisceglia, MD, Via Santa Chiara, 9, Manfredonia 71043, Italy (e-mail: email@example.com). Online date: December 27, 2019 Advances In Anatomic Pathology: March 2020 - Volume 27 - Issue 2 - p 98-111 doi: 10.1097/PAP.0000000000000259 Buy Metrics Abstract Basal cell carcinoma (BCC) of the skin is the most common type of malignant human tumor. However, metastatic BCC is a very rare event with weakly effective therapeutic options and a poor prognosis, until a few years ago. In 2012, small-molecule therapies, capable of inactivating the hedgehog signaling pathway and thus reducing tumor growth and progression, were introduced into clinical practice for the treatment of patients with advanced BCC. We present retrospectively 2 personal cases of metastatic BCC of the skin, from the premolecular therapy era, from primary tumors that arose years before in the head and neck area. The former case occurred in a 45-year-old woman with a history of recurrent BCC of the retroauricular skin who eventually died due to diffuse metastatic spread. The latter case concerned a 70-year-old man also with a history of recurrent BCC of the nasal-perinasal skin who developed multiple subcutaneous and lymph node metastases in the neck. In both cases, the diagnoses were based on biopsies of the metastatic sites. The first patient died 5 months after the diagnosis of metastatic disease, while the second was alive and disease-free 2 years after neck lymph node dissection and external radiation therapy, and then lost to follow-up. We extensively discuss several tumor entities with basal or basaloid features that may enter the differential diagnosis with BCC in metastatic sites. In addition, we briefly summarize the advances in clinical therapeutics using small molecules, which are now an integral part of the treatment of such advanced BCC cases. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.