Neuroendocrine neoplasms of liver - A 5-year retrospective clinico-pathological study applying World Health Organization 2010 classification

Abstract

AIMTo study the clinicopathological characteristics of neuroendocrine neoplasms (NEN) on liver samples and apply World Health Organization (WHO) 2010 grading of gastroenteropancreatic (GEP) NEN.METHODSClinicopathological features of 79 cases of NEN of the liver diagnosed between January 2011 to December 2015 were analyzed. WHO 2010 classification of GEP NEN was applied and the tumors were graded as G1, G2 or G3. Two more categories, D1/2 (discordant 1/2) and D2/3 (discordant 2/3) were also applied. The D1/2 grade tumors had a mitotic count of G1 and Ki-67 index of G2. The D2/3 tumors had a mitotic count of G2 and Ki-67 index of G3. The follow up details which were available till the end of the study period (December 2015) were collected.RESULTSOf the 79 tumors, 16 each were G1 and G2, and 18 were G3 tumors. Of the remaining 29 tumors, 13 were assigned to D1/2 and 16 were D2/3 grade. Male preponderance was noted in all tumors except for G2 neoplasms, which showed a slight female predilection. The median age at presentation was 47 years (range 10-82 years). The most common presentation was abdominal pain (81%). Pancreas (49%) was the most common site of primary followed by gastrointestinal tract (24.4%) and lungs (18%). Radiologically, 87% of the patients had multiple liver lesions. Histopathologically, necrosis was seen in only D2/3 and G3 tumors. Microvascular invasion was seen in all grades. Metastasis occurred in all grades of primary NEN and the grades of the metastatic tumors and their corresponding primary tumors were similar in 67% of the cases. Of the 79 patients, 36 had at least one follow up visit with a median duration of follow up of 8.5 mo (range: 1-50 mo). This study did not show any impact of the grade of tumor on the short term clinical outcome of these patients.CONCLUSIONLiver biopsy is an important tool for clinicopathological characterization and grading of NEN, especially when the primary is not identified. Eighty-seven percent of the patients had multifocal liver lesions irrespective of the WHO grade, indicating a higher stage of disease at presentation. Follow up duration was inadequate to derive any meaningful conclusion on long term outcome in our study patients.

Clinical characteristics and outcome of primary hepatic neuroendocrine tumors after comprehensive therapy

“…Neuroendocrine tumors (NETs), mostly originating from bronchopulmonary and gastrointestinal sites, are uncommon low-malignancy tumors that affect 6.98/100000 individuals annually, however, the incidence rate was in upward trend from 2000 to 2014 worldwide[ 1 , 2 ]. According to the World Health Organization 2019 classification of gastroenteropancreatic NETs, NETs are divided into four grades: NET G1 (low grade), NET G2 (intermediate grade), NET G3 (high grade), and neuroendocrine carcinomas (NEC), based on mitotic count and Ki-67 index of the tumor[ 3 , 4 ]. More than 80% of hepatic NETs are metastatic for the dual blood supply to the liver provides an advantage for tumor metastasis to the liver.…”

Retrospective analysis of interventional treatment of hepatic metastasis from gastroenteropancreatic neuroendocrine tumors

“…Unfortunately, only 5%-10% of diagnosed patients are eligible for resection with a risk of extremely high recurrence rates. It was reported that 94% of patients will relapse within 5 years (6,7). Metastasis usually occurs in the prophase of NETs.…”

<p>Primary Hepatic Neuroendocrine Tumor Mimicking Ruptured Hepatocellular Carcinoma with AFP Elevation: A Case Report and Literature Review</p>

“…6,7 Immunohistochemically, most PHNET cases were reported to be strongly positive for CgA (67-100%) and Syn (92-100%). 5,[13][14][15] Several pieces of literature provided detailed serum AFP level in PHNET patients, mostly in normal range from 1.2 to 4.8 ng/mL, only one case with highly elevated AFP of 7397 IU/mL (8950 ng/mL). 7,13,15 Notably, the PHNET case with significant AFP elevation showed a high tumor grade of G3 and a poor prognosis with 0.7-month survival, but no further mechanism analysis was performed.…”

“…5,[13][14][15] Several pieces of literature provided detailed serum AFP level in PHNET patients, mostly in normal range from 1.2 to 4.8 ng/mL, only one case with highly elevated AFP of 7397 IU/mL (8950 ng/mL). 7,13,15 Notably, the PHNET case with significant AFP elevation showed a high tumor grade of G3 and a poor prognosis with 0.7-month survival, but no further mechanism analysis was performed. 15 Another differential diagnosis in this case is HCC with neuroendocrine component or mixed tumor of HCC and NEC.…”