Case Reports in Oncological Medicine

Paragangliomas are rare neuroendocrine tumors that arise from chromaffin-containing tissue. Surgical resection and/or radiation are used for locoregional disease, and reduction of tumor burden with systemic therapy is reserved for metastatic disease. Iobenguane I-131, somatostatin analog (octreotide), and Sunitinib are noncytotoxic options for treatment, while cyclophosphamide, vincristine, and dacarbazine (CVD) and temozolomide are often used as initial chemotherapy options as studies have shown that they offer some tumor response. However, there are no randomized clinical trials demonstrating prolonged survival with the use of chemotherapeutics in metastatic cases. Investigation of alternative therapies that provide survival benefit is thus necessary. We present a case of a 69-year-old female with metastatic malignant paraganglioma presenting as a left parapharyngeal neck mass, which metastasized after surgery, requiring radiation therapy for bony metastasis who was treated with a radioisotope somatostatin analog for disease progression.

Background. The role of immunotherapy continues to evolve across both solid and hematologic malignancies. However, while use of immunotherapy has increased via the advent of checkpoint inhibition, chimeric antigen receptors, and vaccines against malignant cells, there remains uncertainty regarding the recognition and management of delayed immune-related reactions and post treatment immune-related sensitivity to subsequent medications, such as BRAF/MEK kinase inhibitors. Furthermore, it is unclear how immunotherapy may alter the adverse effect profile and efficacy of subsequent lines of treatment. Case Presentation. Discussed is a patient with stage IV metastatic melanoma who failed first-line treatment with a combination of nivolumab and ipilimumab. He was then treated with BRAF/MEK kinase inhibition via Encorafenib and Binimetinib. Shortly thereafter, the patient developed posterior reversible encephalopathy syndrome (PRES) and a generalized pruritic rash that was biopsied with consideration toward drug reaction versus drug-induced hypersensitivity syndrome (DIHS), formerly called drug reaction with eosinophilia and systemic symptoms (DRESS). The BRAF/MEK combination was held and steroid taper initiated with continued response even beyond conclusion of the steroid taper. Discussion and Conclusions. This case highlights the diagnostic challenge presented by PRES and DIHS in the setting of immunotherapy and BRAF/MEK kinase inhibition for malignant melanoma. The clinical rationale for reinitiating therapy following severe immune reactions subsequent to immunotherapy in the setting of relapsed/refractory metastatic melanoma is discussed. Additionally, the durable response our patient experienced throughout the drug hold period and steroid taper and its clinical potential etiologies and applications are reviewed. As checkpoint inhibition and tyrosine-kinase inhibitors have become cornerstones of cancer therapy, larger studies and long-term observations are needed to investigate the risks and benefits across different sequences of therapy.

Neurofibromatosis type 1 (NF-1) is known to be associated with increased risk of malignancy by at least fourfold. Malignant lymphomas are rare in adults with NF-1. Hereby, we present a 75-year-old male with NF-1 complaining of weakness, nausea, and vomiting associated with abdominal pain. Three months prior to presentation, he had suffered a motor vehicle accident (MVA) resulting in multiple rib fractures that was seen in chest X-ray. For the following three months, he had intermittent chest pain, but it was attributed to the recent rib fracture. During this admission, the severity of chest pain worsened and the associated vomiting inclined further investigation; including CT imaging and bone biopsy, it was revealed to be a rare case of diffuse B cell lymphoma in a patient with NF-1. However, we believe the recent MVA caused an anchoring bias in making a prompt diagnosis. In addition, the appearance of the neurofibroma, resulted in suboptimal physical examination, and hence, there was a delay in reaching the diagnosis. We will discuss here the presentation of this case, to highlight the rare association and to increase awareness of when encountering a challenging diagnosis.

Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are rare tumors composed of two different histological components, one of which is of a neuroendocrine origin. Given its suggested underdiagnosis and consequent low prevalence, no clear diagnostic and treatment guidelines are available, and treatment usually follows regimens similar to that of the most aggressive component. On the other hand, multiple primary tumors (MPTs) are also rare neoplastic entities that usually confer a challenge regarding treatment options, for a regimen that comprises both the primary and the synchronous/metachronous malignancy should be used. Here, we discuss the challenging diagnostic and therapeutic management of a patient with an ileocecal MiNEN that presented along with a synchronous squamous non-small-cell lung cancer (SQ-NSCLC). The patient presented with intestinal obstruction symptoms for which he underwent an emergency resection of the ileocecal MiNEN. An initial CT scan showed an additional lung mass later identified as an SQ-NSCLC after bronchoscopy biopsy analysis. Given the rapid hepatic metastatic progression, palliative platinum-based chemotherapy was initiated, with an adequate response of the local and metastatic lesions of the MiNEN, but suggested platinum resistance and progression of the pulmonary neoplasm. Second-line treatment with pembrolizumab directed for the SQ-NSCLC was initiated; however, it was stopped after immune-mediated toxicities developed. A third-line chemotherapy scheme with carboplatin/gemcitabine was initiated, but central nervous system (CNS) progression developed, with the patient dying 11 months after initial diagnosis.

Immune checkpoint inhibitors, such as nivolumab, a programmed death receptor-1 (PD-1) inhibitor, have dramatically improved the treatment of advanced melanomas. Chemosaturation with percutaneous hepatic perfusion (PHP) delivers chemotherapy in high doses directly to the liver and is a potentially effective treatment modality in metastatic uveal melanoma with liver metastases. Its safety and effectiveness have not been studied in patients also receiving immunotherapy. A 46-year-old male with a history of uveal melanoma of the right eye was found to have liver metastases. He was treated with PHP using high-dose melphalan for 6 months with a partial response followed by progression. Two months after his last PHP treatment, the patient was started on nivolumab. After two doses of nivolumab, the patient developed severe hepatitis that progressed to fulminant hepatic failure and death despite treatment with high-dose corticosteroids and mycophenolate mofetil. Nivolumab and other immune checkpoint inhibitors have been effective in treating advanced melanoma and extending life. However, there are serious immune adverse events that can occur. While hepatitis after taking nivolumab has been documented, fulminant hepatic failure is rare. We believe that prior PHP treatment contributed to the severity of the hepatitis and, ultimately, fulminant hepatic failure. To our knowledge, this is the only case of fulminant hepatic failure secondary to a checkpoint inhibitor with preceding PHP. Specific precautions should be made in patients who have been exposed to PHP in the past, and further studies should be done to assess the safety of using checkpoint inhibitors after PHP.

Langerhans cell histiocytosis (LCH) is a rare disease, afflicting approximately 4.6 and 1-2 per 1 million children and adults, respectively. While LCH can involve numerous organ systems such as the lung or bone, it is uncommon for the disease to be limited to the skin. Radiotherapy has an established role for osseous lesions. However, the efficacy and dose for nonosseous manifestations of the disease are not well described. In the current case report, we detail a 49-year-old adult male with skin-limited LCH requiring palliative radiotherapy (RT) to numerous sites for pain control. The patient was initially diagnosed and treated with single agent cytarabine for approximately 6 months. Despite treatment, he had little symptomatic response of his cutaneous lesions. We delivered a single dose of 8 Gray (Gy) to 3 separate skin lesions, including the bilateral groin, right popliteal region, and right axillary lesion, which resulted in pain reduction and partial response at four-month follow-up. Subsequently, we decided to treat the left axillary untreated lesion to a higher dose of 24 Gy in 12 fractions. At four-month follow-up, the left axilla RT resulted in complete clinical response and improved pain control compared to the right axilla. Following RT treatments, the patient was found to have a BRAF mutation, and vemurafenib was initiated. Further follow-up with positron emissions tomography demonstrated complete metabolic response in numerous disease areas, including both axillae. Based on this case report’s findings, a higher radiotherapy dose may be more effective for treating cutaneous LCH.