A primitive neuroendocrine liver tumour?

The aim of the present report is to present a possible primitive case of a neuroendocrine tumour (NET) of the liver. During a routine ultrasound examination, a 51-year-old woman was diagnosed with a lesion in the second segment of the liver, suggestive of a metastasis. A well differentiated neuroendocrine carcinoma (G2, Ki67 = 4.4%) was identified by liver biopsy, positive for chromogranin, synaptophysin and neuron specific enolase. An additional extensive examination aimed at finding the primitive lesion was unsuccessful and PET with 68Gallium revealed a single liver lesion. A left lobectomy was performed, but 15 months later a second liver lesion with the same characteristics as the previous one was observed and was surgically treated, followed by therapy with octreotide LAR 30 mg. A four-year follow-up did not show evidence of a different primitive NET: therefore, while it is improbable that a metastatic G2 primitive tumour would not have presented in the 4-year period, a diagnosis of primitive NET of the liver was made. The paper gives the opportunity of describing an unusual case of a primitive liver neuroendocrine tumour and of presenting the successful treatment of both surgery and cytoreductive pharmacological therapy

PD-L1 Expression and Immune Cell Infiltration in Gastroenteropancreatic (GEP) and Non-GEP Neuroendocrine Neoplasms With High Proliferative Activity

The potential of neuroendocrine neoplasms (NEN) to respond to checkpoint inhibitors is largely unknown and full of great expectations. Immunohistochemical (IHC) studies of programmed cell death ligand 1 (PD-L1) expression in the tumor microenvironment and its implications in predicting the response to checkpoint inhibition is a very active subject. Currently, the combined analysis of PD-L1 expression and tumor-associated immune cell (TAIC) infiltration is considered the best predictive marker of therapeutic response. Here we investigated the expression of PD-L1 on tumor cells (TC) and tumor-infiltrating immune cells (IC) by IHC in 68 NEN samples with a high proliferation rate (Ki-67 >20%) from 57 patients and in 22 samples we correlated it with TAIC density by assessing intratumoral infiltration of CD3+, CD8+, and CD68+ cells. Furthermore, the tumor microenvironment was evaluated according to the classification of Teng et al. We detected PD-L1 expression in 31.6% of NEN G3. Its expression usually was weak and more IC than TC expressed PD-L1. The proportion of tumors positive for PD-L1 was comparable in NEN from different sites of origin but varied depending on tumor differentiation and disease extension. No positive IHC staining was found in 3 well-differentiated neuroendocrine tumors (NETs) with a proliferation rate above 20% (NET G3). When analyzing TAIC, we rarely (18.2%) detected intratumoral CD8+ cells, whereas infiltration by CD3+ and CD68+ cells was more common (45.5 and 59.1%, respectively). By combining CD3+ cells and PD-L1 status, we identified the immune ignorant phenotype of tumor microenvironment as being the most common phenotype, supporting the concept of a preferably combined immunotherapeutic approach in neuroendocrine carcinoma (NEC)

MEN1 syndrome: an anusual case

Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant endocrine disorder and is characterised by the concurrent appearance of adenomas of the parathyroid glands, neuroendocrine-enteropancreatic tumours, and pituitary adenomas, as well as other types of less frequent tumours, such as adrenal cortical tumours, carcinoid tumours, lipomas, etc. Two different forms, familial and sporadic, have been described. The gene responsible, MEN1, consists of 10 exons encoding a 610-amino acid protein known as menin. The MEN1 syndrome is caused by inactivating mutations in MEN1 tumour suppressor gene. The combination of clinical and genetic investigation helps in the diagnosis. Genetic testing has been advocated to identify MEN1 carriers of the MEN1 families for the purpose of earlier detection of tumours. We present a patient with traditionally described manifestations of MEN1 (a parathyroid hyperplasia associated with a pancreatic neuroendocrine tumour and a gastrinoma), but with a negative genetic test for the MEN1 mutation