Aggressive PitNETs and Potential Target Therapies: A Systematic Review of Molecular and Genetic Pathways.

Recently, advances in molecular biology and bioinformatics have allowed a more thorough understanding of tumorigenesis in aggressive PitNETs (pituitary neuroendocrine tumors) through the identification of specific essential genes, crucial molecular pathways, regulators, and effects of the tumoral microenvironment. Target therapies have been developed to cure oncology patients refractory to traditional treatments, introducing the concept of precision medicine. Preliminary data on PitNETs are derived from preclinical studies conducted on cell cultures, animal models, and a few case reports or small case series. This study comprehensively reviews the principal pathways involved in aggressive PitNETs, describing the potential target therapies. A search was conducted on Pubmed, Scopus, and Web of Science for English papers published between 1 January 2004, and 15 June 2023. 254 were selected, and the topics related to aggressive PitNETs were recorded and discussed in detail: epigenetic aspects, membrane proteins and receptors, metalloprotease, molecular pathways, PPRK, and the immune microenvironment. A comprehensive comprehension of the molecular mechanisms linked to PitNETs' aggressiveness and invasiveness is crucial. Despite promising preliminary findings, additional research and clinical trials are necessary to confirm the indications and effectiveness of target therapies for PitNETs.

Treatment strategy for vertebral metastases from anal squamous cell carcinoma: a comprehensive literature review and case report.

Purpose/aim of the study: Purpose/aim of the study:Central nervous system (CNS), skull, and vertebral metastases from anal squamous cell carcinoma (SCC) are an exceedingly rare entity. We report the first case of multiple vertebral metastases from a primary anal SCC with the aim of define a target therapeutic strategy.Case presentation: We present the case of a 68-year-old male admitted to our hospital for acute exacerbation chronic low back pain and left L2 radiculopathy. His medical history included the diagnosis of a human papilloma virus related, moderately differentiated anal SCC (cT3N0M0-stage IIB), treated with standard chemoradiotherapy regimen two years earlier. Spinal magnetic resonance imaging revealed an isolated solid lesion of the L2 vertebral body. After the surgical removal, histopathological examination confirmed the diagnosis of moderately differentiated SCC. At 1-month radiological follow-up, two new lesions at the level of T7 to T11 were identified. Additional chemotherapy and radiotherapy for metastatic localization of L2, T7, and T11 were administered. Two-year follow-up demonstrated a radiologically and clinically well-controlled disease. To supplement our case, a systematic literature review on the CNS, skull, and vertebral metastases and their treatments has been performed.Conclusion: Despite several proposed guidelines for the management of vertebral metastases, at present, a universally accepted treatment strategy for vertebral metastases from anal SCC has not been defined. Based on our clinical experience and literature review, in case of vertebral metastases from anal SCC, a prompt and aggressive, local and systemic, and multimodal treatment of the vertebral lesions may be paramount to improve the patient outcomes.

Lactotroph PitNET/adenoma associated to granulomatous hypophysitis in a patient with Crohn's disease: A case report.

Granulomatous hypophysitis is a rare and poorly understood condition. Although certain cases are treated as primary pituitary autoimmune disorders, rare cases may be associated with pituitary neuroendocrine tumours (PitNETs) and systemic inflammatory diseases. Here, we report a case of a 47-year-old man that underwent endoscopic trans-sphenoidal excision of a pituitary mass diagnosed as PitNET. On histologic evaluation, the neoplasm showed an admixture of granulomas with extensive inflammatory infiltrate and lactotroph PitNET/adenoma. Careful anamnestic examination revealed a diagnosis of Crohn's disease 20 years prior. Although rarely done, both PitNET and Crohn's disease may be associated with granulomatous hypophysitis, and our patient had both conditions. During the 6-year follow-up, PitNETs and hypophysitis did not recur, while Crohn's disease was only partially controlled by medical therapy. To our knowledge, this is the first description of association of granulomatous hypophysitis, PitNET and Crohn's disease.