Malignant mediastinal tumors are a group representing some of the most demanding oncological challenges for early, multi-level, and successful management. The timely identification of any suspicious clinical symptomatology is urgent in achieving an accurate, staged histological diagnosis, in order to follow up with an equally detailed medical therapeutic plan (interventional or not) and determine the principal goals regarding efficient overall treatment in these patients. We report a case of a 24-year-old male patient with an incident-free prior medical history. An initial chest X-ray was performed after the patient reported short-term, consistent moderate chest pain symptomatology, early work fatigue, and shortness of breath. The following imaging procedures (chest CT, PET-CT) indicated the presence of an anterior mediastinal mass (meas. ~11 cm × 10 cm × 13 cm, SUV: 8.7), applying additional pressure upon both right heart chambers. The Alpha-Fetoprotein (aFP) blood levels had exceeded at least 50 times their normal range. Two consecutive diagnostic attempts with non-specific histological results, a negative-for-malignancy fine-needle aspiration biopsy (FNA-biopsy), and an additional tumor biopsy, performed via mini anterior (R) thoracotomy with “suspicious” cellular gatherings, were performed elsewhere. After admission to our department, an (R) Video-Assisted Thoracic Surgery (VATS) was performed, along with multiple tumor biopsies and moderate pleural effusion drainage. The tumor’s measurements had increased to DMax: 16 cm × 9 cm × 13 cm, with a severe degree of atelectasis of the Right Lower Lobe parenchyma (RLL) and a pressure-displacement effect upon the Superior Vena Cava (SVC) and the (R) heart sinus, based on data from the preoperative chest MRA. The histological report indicated elements of a combined, non-seminomatous germ-cell mediastinal tumor, posthuberal-type teratoma, and embryonal carcinoma. The imminent chemotherapeutic plan included a “BEP” (Bleomycin^®/Cisplatin^®/Etoposide^®) scheme, which needed to be modified to a “VIP” (Cisplatin^®/Etoposide^®/Ifosfamide^®) scheme, due to an acute pulmonary embolism incident. While the aFP blood levels declined, even reaching normal measurements, the tumor’s size continued to increase significantly (DMax: 28 cm × 25 cm × 13 cm), with severe localized pressure effects, rapid weight loss, and a progressively worsening clinical status. Thus, an emergency surgical intervention took place via median sternotomy, extended with a complementary “T-Shaped” mini anterior (R) thoracotomy. A large, approx. 4 Kg mediastinal tumor was extracted, with additional RML and RUL “en-bloc” segmentectomy and partial mediastinal pleura decortication. The following histological results, apart from verifying the already-known posthuberal-type teratoma, indicated additional scattered small lesions of combined high-grade rabdomyosarcoma, chondrosarcoma, and osteosarcoma, as well as numerous high-grade glioblastoma cellular gatherings. No visible findings of the previously discovered non-seminomatous germ-cell and embryonal carcinoma elements were found. The patient’s postoperative status progressively improved, allowing therapeutic management to continue with six “TIP” (Cisplatin^®/Paclitaxel^®/Ifosfamide^®) sessions, currently under his regular “follow-up” from the oncological team. This report underlines the importance of early, accurate histological identification, combined with any necessary surgical intervention, diagnostic or therapeutic, as well as the appliance of any subsequent multimodality management plan. The diversity of mediastinal tumors, especially for young patients, leaves no place for complacency. Such rare examples may manifest, with equivalent, unpredictable evolution, obliging clinical physicians to stay constantly alert and not take anything for granted.

Primary chondrosarcoma of the sternum is a rare malignancy whose anatomical location can create major diagnostic, resection, and reconstruction challenges. We report a 62-year-old man with severe obesity and a heavy smoking history who presented with a progressively enlarging, painful sternal swelling. Preoperative imaging conducted via computed tomography and positron emission tomography–computed tomography demonstrated a large heterogeneous mass at the anterior thoracoabdominal junction infiltrating the xiphoid process. CT-guided biopsy established grade III chondrosarcoma. Because of the tumor’s size, location, and infiltrative features, bilateral transverse thoraco-sternotomy (“Clamshell” Procedure) was performed. “En bloc” resection included the middle and lower sternum, involved soft tissues and adjacent costal arches, followed by prosthetic synthetic polypropylene mesh reconstruction. The final pathology documented tumor-free examined margins (R₀), with an approximately 10 mm closest reported clearance. The postoperative course was prolonged and complex. The patient required 18 days of intensive care and tracheostomy on postoperative day 8 because of delayed awakening and intermittent oxygen desaturation. Wound dehiscence necessitated surgical revisions on postoperative days 29 and 44; during the second revision, the infected mesh was removed. The tracheostomy was removed on day 64, and the patient was discharged in a stable condition two days later. This case demonstrates that extensive open approaches remain indispensable for selected chest wall malignancies. It also emphasizes the importance of coordinated multidisciplinary perioperative care from diagnosis through recovery, while illustrating how reconstructive resources, patient risk, and infection can determine the procedure’s outcome.

Melanoma, an aggressive type of skin cancer, has historically posed significant therapeutic challenges when diagnosed in an advanced stage. The advent of immunotherapy over the recent decades has fundamentally transformed treatment strategies for melanoma. This chapter explores the evolution of immunotherapeutic approaches for cutaneous melanoma and their mechanism of action, focusing mainly on immune checkpoint inhibitors (ICIs), such as CTLA-4, PD-1, and PD-L1 inhibitors. Immunotherapy agents, such as ipilimumab, pembrolizumab, and nivolumab, have demonstrated substantial improvement of overall and progression-free survival in clinical trials, while their combination regimens offer enhanced efficacy at the cost of increased toxicity. Emerging modalities, such as intralesional therapies (T-VEC), personalized mRNA vaccines, and tumor-infiltrating lymphocyte (TIL) therapy, are currently being tested for their potential to overcome the resistance mechanisms of melanoma against ICIs and enhance the antitumor response. Immune-related adverse events (irAEs) remain a major concern in melanoma immunotherapy, necessitating careful patient selection as well as multidisciplinary management. The role of tumor microenvironmental (TME) factors and predictive biomarkers is also under consideration so that personalized immunotherapy may emerge in clinical practice. Despite the remarkable progress of immunotherapy agents and regimens, challenges continue to persist, including resistance, toxicity, and increased treatment cost. Thus, there is still a need for ongoing research and broader global access, along with the integration of novel combination strategies to further improve treatment outcomes. Immunotherapy for melanoma has shifted its prognosis from a fatal diagnosis to a manageable chronic condition, even in advanced cases, being one of the most important advances in modern oncology.