A major part of non-small cell lung cancer (NSCLC) patients treated with mono- or multimodal concept develop therapy resistance. Despite the abundance of biomarkers investigated in the past, there is still a need for valid NSCLC biomarkers. Glycodelin, an immunosuppressive endometrial protein, has been shown to be also expressed in NSCLC. Here, we investigated its potential as a biomarker in metastatic and advanced stage NSCLC. Glycodelin gene and protein expression were measured in 28 therapy-naïve resected tumors as well as in corresponding brain (n = 16) and adrenal gland (n = 12) metastasis by qPCR and IHC. Moreover, we correlated glycodelin gene expression of cryoconserved therapy-naïve biopsies (n = 55) of advanced stage patients with glycodelin serum concentrations and patient survival. Using follow-up samples of the patients, we monitored glycodelin serum concentrations during therapy. Glycodelin expression correlated between primary tumor and distant metastases within the same patients. The gene expression of glycodelin in therapy-naïve biopsies also correlated with the serum concentrations of the patients (r = 0.60). Patients with elevated serum concentrations showed a tendency in lower overall survival (p = 0.088) and measuring of glycodelin indicated a progression of the disease earlier compared to clinical diagnostic. Taken together, we demonstrate that glycodelin is a promising prognostic and follow-up biomarker for metastatic and advanced NSCLC.

Adrenocortical carcinoma (ACC) is a rare and aggressive tumor whose molecular signaling pathways are not fully understood. Using an in-silico clinical data analysis approach we retrieved human gene mutation data from the highly reputed Cancer Genome Atlas (TCGA). ACC-specific gene mutations were correlated with proliferation marker FAM72 expression and Mutsig along with the algorithmic implementation of the 20/20 rule were used to validate their oncogenic potential. The newly identified oncogenic driver gene set (ZFPM1, LRIG1, CRIPAK, ZNF517, GARS and DGKZ), specifically and most repeatedly mutated in ACC, is involved in tumor suppression and cellular proliferation and thus could be useful for the prognosis and development of therapeutic approaches for the treatment of ACC.

The last 10 years have produced an amazing number of significant discoveries in the field of adrenal endocrinology. The development of the adrenal gland was linked to specific molecules. Cortisol-producing lesions were associated mostly with defects of the cyclic AMP (cAMP) signaling pathway, whereas aldosterone-producing lesions were found to be the result of defects in aldosterone biosynthesis or the potassium channel KCNJ5 and related molecules. Macronodular adrenal hyperplasia was linked to ARMC5 defects and new genes were found to be involved in adrenocortical cancer (ACC). The succinate dehydrogenase (SDH) enzyme was proven to be the most important molecular pathway involved in pheochromocytomas, along with several other genes. Adrenomedullary tumors are now largely molecularly elucidated. Unfortunately, most of these important discoveries have yet to produce new therapeutic tools for our patients with adrenal diseases: ACC in its advanced stages remains largely an untreatable disorder and malignant pheochromocytomas are equally hard to treat. Thus, the challenge for the next 10 years is to translate the important discoveries of the previous decade into substantial advances in the treatment of adrenal disorders and tumors.

Therapeutic agents targeting the PD-1/PD-L1 axis have shown durable clinical responses in patients with various cancer types. Although objective responses are common, intrapatient heterogeneous responses have been described, and the mechanism for the different organ responses remains unknown. We present a series of patients in whom a lack of response was noted solely in the adrenal glands. This is the first case series describing 3 patients with heterogeneous patterns of response to pembrolizumab with progression of adrenal metastatic disease despite objective response (complete or partial response) in all other sites of metastatic disease. Two patients, one with melanoma and one with uterine carcinosarcoma, underwent robotic adrenalectomy for enlarging adrenal metastases. An additional patient with melanoma underwent laparotomy with attempted resection, but infiltration of the adrenal tumor into the inferior vena cava prohibited safe excision. This report provides additional insight into the heterogeneous patterns of disease response to anti-PD-1 therapy, highlighting the adrenal gland as a potential sanctuary site for this immunotherapy. These cases display the potential benefit of early surgical resection in this scenario and the pitfalls of delaying referral to a surgeon for assessment of operative intervention.

Papillary thyroid carcinoma (PTC) is considered one of the most favorable tumors, indolent, with rare distant dissemination. Lungs and bones are the most common metastatic sites. Unusual sites of PTC distant metastases are extremely rare. Brain, liver, skin, kidney, pancreas, and adrenal gland PTC metastases have been sporadically reported in the literature. An 86-year-old female patient underwent total thyroidectomy and neck dissection due to PTC. Postoperative whole body iodine-131 scintigraphy with I-131 SPECT/CT of the abdomen revealed radioiodne avid left adrenal gland metastasis together with high postoperative serum thyroglobulin (Tg) value of more than 5000 µg/L and high serum Tg antibodies. Considering the above-mentioned findings, patient's age and multiple comorbidities, radioiodine therapy was applied. PTC metastases to the adrenal gland are extremely rare, and to our knowledge, only nine cases have been reported in the literature. This case report complements rare examples of unusual PTC metastases.