Treatment options for unresectable, recurrent or metastatic salivary gland carcinomas (SGC) are scarce. Trophoblast cell surface antigen 2 (Trop-2) is a transmembrane glycoprotein that is involved in a variety of oncogenic cell signaling pathways. Its potential as a target for the antibody–drug conjugate sacituzumab govitecan has already been demonstrated in different tumor entities. The United States Food and Drug Administration approved this antibody–drug conjugate for the treatment of metastatic triple-negative breast cancer. Here, we aimed to investigate Trop-2 protein expression in different entities of SGCs. We retrospectively reviewed the medical records of all patients that underwent surgery for a primary SGC in a tertiary referral center between 1990 and 2014. Immunohistochemical (IHC) staining for Trop-2 was performed and rated as negative, weak, moderate or high using a semiquantitative score. Additionally, representative cases were analyzed using MALDI-mass spectrometry (MS) imaging to confirm the IHC results. The cohort consisted of 114 tumors of the parotid gland (90.4%) and submandibular gland (9.6%). It mainly included mucoepidermoid, salivary duct and adenoid cystic carcinomas. In IHC samples, 44% showed high, 38% moderate and 10% weak expression rates of Trop-2. MALDI-MS imaging confirmed the presence of Trop-2 protein in 80% of the tested tumor samples. This is the first study to demonstrate that several types of SGC express Trop-2 with variable intensity. Since there are currently few systemic treatment options for advanced SGCs, Trop-2 represents a promising target for further clinical studies, for instance, with sacituzumab govitecan.

Background and Objectives: The incidence of distant metastases in patients with head and neck cancer (HNC) is approximately 10%. Pulmonary metastases are the most frequent distant location, with an incidence of 70–85%. The standard treatment options are chemo-, immuno- and radiotherapy. Despite a benefit for long-term survival for patients with isolated pulmonary metastases, pulmonary metastasectomy (PM) is not the treatment of choice. Furthermore, many otorhinolaryngologists are not sufficiently familiar with the concept of PM. This work reviews the recent studies of pulmonary metastatic HNC and the results after pulmonary metastasectomy. Materials and Methods: PubMed, Medline, Embase, and the Cochrane library were checked for the case series’ of patients undergoing metastasectomy with pulmonary metastases published since 1 January 2000. Results: We included the data of 15 studies of patients undergoing PM. The 5-year survival rates varied from 21% to 59%, with median survival from 10 to 77 months after PM. We could not identify one specific prognostic factor for long-term survival after surgery. However, at least most studies stated that PM should be planned if a complete (R0) resection is possible. Conclusions: PM showed reliable results and is supposedly the treatment of choice for patients with isolated pulmonary metastases. Patients not suitable for surgery may benefit from other non-surgical therapy. Every HNC patient with pulmonary metastases should be discussed in the multidisciplinary tumor board to optimize the therapy and the outcome.

Procollagen 11A1 (COL11A1) is a central component of the extracellular matrix in many carcinomas, which is considered to be mainly produced by cancer associated fibroblasts (CAFs). As COL11A1 expression correlates with adverse prognosis and is implicated in chemoresistance, it is a promising putative target. For the first time, we used RNA in-situ hybridization to systematically identify the cells that produce COL11A1 in the ten most prevalent carcinoma types, lymphomas (n = 275) and corresponding normal tissue (n = 55; panCancer cohort). Moreover, as most salivary gland carcinomas (SGC) display distinct stromal architectures, we also analysed 110 SGC. The corresponding protein formation of COL11A1 was determined by MALDI-TOF–MS-Imaging. We report that colon, breast and salivary duct carcinomas are highly infiltrated by COL11A1 positive CAFs (CAFs_COL11A1) and might thus be promising candidates for antidesmoplastic or COL11A1-targeted therapies. The amount of CAFs_COL11A1 correlated significantly with tumour grade, tumour stage and nodal spread in the panCancer cohort. Significant associations between CAFs_COL11A1 and vascular invasion, perineural spread and nodal spread were observed in the SGC cohort. Also, we discovered that tumour cells of intercalated duct derived SGC and CAFs produce COL11A1 in a mutually exclusive manner. Our findings represent a novel mode of extracellular matrix production in carcinomas and could be highly relevant in the future. Our findings elucidate the mode of COL11A1 expression in very different carcinoma types and may aid to categorise tumours in the setting of possible future COL11A1-related therapies.

Adenoid cystic carcinoma (ACC) is a rare malignancy in the head and neck. The prognosis remains poor and late recurrences often occur after 5 years and later. To date, there are no reliable prognostic markers for ACC. In several solid tumors, tertiary lymphoid structures (TLS) are associated with improved survival. This study aims to investigate the role of distribution patterns of tumor infiltrating immune cells (TIL) in ACC. A cohort of 50 patients from three different cancer centers was available for analysis. Sections were stained for CD3, CD4, CD8 and CD20 and evaluated with regard to their distribution of TIL. Patterns were determined as infiltrated-excluded, infiltrated-inflamed and presence of tertiary lymphoid structures. About half of the cases showed an infiltrated-excluded TIL pattern and only a minority of six cases had TLS present within the tumor. Within the inflamed phenotype CD3+ cells were by far the most abundant lymphocyte subtype, and within this compartment, CD8+ T cells were predominant. There was no influence on overall or disease-free survival by any of the TIL patterns. This indicates that ACC is a tumor with very low immunogenicity and even abundance of lymphocytes does not seem to improve prognosis for this disease. Therefore, the observed lack of response towards immunotherapy is not surprising and other methods to induce recognition of ACC by the immune system must be found.