SummaryMerkel cell carcinoma (MCC, ICD‐O M8247/3) is a rare, malignant, primary skin tumor with epithelial and neuroendocrine differentiation. The tumor cells share many morphologic, immunohistochemical, and ultrastructural features with cutaneous Merkel cells. Nevertheless, the cell of origin of MCC is unclear. MCC appears clinically as a reddish to purple spherical tumor with a smooth, shiny surface and a soft to turgid, elastic consistency, usually showing rapid growth. Spontaneous and often complete regressions of the tumor are observed. These likely immunologically‐mediated regressions explain the cases in which only lymph node or distant metastases are found at the time of initial diagnosis and why the tumor responds very well to immunomodulatory therapies even at advanced stages. Due to its aggressiveness, the usually given indication for sentinel lymph node biopsy, the indication of adjuvant therapies to be evaluated, as well as the complexity of the necessary diagnostics, clinical management should already be determined by an interdisciplinary tumor board at the time of initial diagnosis.

ZusammenfassungDas Merkelzellkarzinom (MCC, ICD‐O M8247/3) ist ein seltener, maligner, primärer Hauttumor mit epithelialer und neuroendokriner Differenzierung. Die Tumorzellen teilen viele morphologische, immunhistochemische und ultrastrukturelle Eigenschaften mit den Merkel‐Zellen der Haut. Die Ursprungszelle (cell of origin) des MCC ist dennoch unklar. Das MCC imponiert klinisch als ein rötlich bis violett farbiger kugeliger Tumor mit glatter glänzender Oberfläche und weicher bis prall‐elastischer Konsistenz, der in der Regel ein schnelles Wachstum aufweist. Spontane, häufig auch komplette Regressionen des Tumors werden beobachtet. Diese wahrscheinlich immunologisch‐vermittelten Regressionen erklären die Fälle, bei denen zum Zeitpunkt der Erstdiagnose nur Lymphknoten‐ oder Fernmetastasen gefunden werden und warum der Tumor auch in weit fortgeschrittenen Stadien sehr gut auf immunmodulierende Therapien anspricht. Aufgrund seiner Aggressivität, der in der Regel gegebenen Indikation zur Schildwächterlymphknotenbiopsie, der zu evaluierenden Indikation adjuvanter Therapien, sowie der Komplexität der notwendigen Diagnostik sollte das Vorgehen bereits bei Erstdiagnose durch ein interdisziplinäres Tumorboard festgelegt werden.

For patients with advanced basal cell carcinoma (aBCC) first-line treatment with hedgehog inhibitors (HHIs) and second-line treatment with PD1 inhibitors (PD1i) is available, offering combination and sequencing options. Here, we focus on the efficacy and safety of HHI reinduction after PD1i failure. Retrospective data analysis was performed with 12 patients with aBCC (locally advanced (n = 8)/metastatic (n = 4)). These patients (male:female 6:6, median age 68 years) initially received HHIs, leading to complete/partial response (66%) or stable disease (33%). Median treatment duration was 20.8 (2–64.5) months until discontinuation due to progression (n = 8), adverse events (n = 3), or patient request (n = 1). Subsequent PD1 inhibition (pembrolizumab 42%, cemiplimab 58%) yielded a partial response (8%), stable disease (33%), or progression (59%). Median treatment duration was 4.1 (0.8–16.3) months until discontinuation due to progression (n = 9), adverse events (n = 1), patient request (n = 1), or missing drug approval (n = 1). HHI reinduction resulted in complete/partial response (33%), stable disease (50%), or progression (17%). Median treatment duration was 3.6 (1–29) months. Response duration in the four responding patients was 2–29+ months. Thus, a subgroup of patients with aBCC responded to reinduction of HHI following PD1i failure. Therefore, this sequential treatment represents a feasible treatment option.