Primary Extragastrointestinal Stromal Tumours in the Hepatobiliary Tree and Telocytes

Abstract

The first decade of the twenty-first century witnessed the presence and light microscopic, immunophenotypic, and ultrastructural characterization of interstitial Cajal-like cells (coined as 'telocytes') in virtually every extragastrointestinal site of the human body by Laurentiu M. Popescu and his co-workers. Not surprisingly, stromal tumours, immunophenotypically similar to that of telocytes [CD117 (c-KIT) +/CD34 +], have also been sporadically reported outside the tubular gut (so-called extragastrointestinal stromal tumours, EGISTs), including the gall bladder, liver, and pancreas. A meticulous literature search from January 2000 to November 2015 have found 9 such case reports of EGISTs in the gall bladder, 16 in the liver, and 31 occurring in the pancreas. The site wise mean age at presentation for these tumours were reported to be 62.2 ± 16.6, 50.9 ± 20.1, and 55.3 ± 14.3 years, respectively. Six of nine EGISTs in the gall bladder were associated with gallstones. On pathological evaluation, these tumours exhibited prominent spindled cell morphology and consistent expression of CD117/c-KIT and CD34 on immunohistochemistry and variable expression of vimentin and α-smooth muscle actin. The biological behaviour of hepatic and pancreatic lesions was favourable compared to that in the gall bladder, following definitive surgery with or without imatinib therapy. While the exact pathophysiologic role played by telocytes in various organs is yet to be fully elucidated, there seems to be a direct link between these enigmatic stromal cells and pathogenesis of gallstones and origin of EGISTs, and a hope for targeted therapies. Furthermore, the possible role of telocytes in hepatic regeneration and liver fibrosis opens a new dimension for futuristic research.

Acute Cholecystitis Reduces Interstitial Cells of Cajal in Porcine Gallbladder Through Decreased mRNA Synthesis

“…Recent studies have shown that reduced biliary system ICCs, ICC injury or loss of function, and compromises in the and c-kit/SCF pathway may play important roles in biliary system motility diseases, including cholelithiasis [16,17] and may be closely connected to malignant tumors in the biliary system. Indeed, numerous CD117-positive cells (c-kit protein) have been detected in pathological gallbladder malignant stromal tumor specimens [22].…”

Extragastrointestinal stromal tumour of the lesser omentum: A case report and literature review

“…Experimental studies have detected interstitial Cajal-like cells the so-called telocytes, in pancreatic and hepatic tissue [17], [31]. In most series of EGISTs, a female predominance, a greater size and a higher mitotic index than GISTs were observed.…”

“…Extragastrointestinal stromal tumours (EGISTs) are very uncommon compared to their gastrointestinal counterparts and typically are not connected to the walls or serosal surfaces of gastrointestinal tubular organs. Most of them originate from the intestinal mesentery and the omentum but there have been sporadic reports of EGISTs in other sites such as retroperitoneum, liver, hepatobiliary tree, pancreas, spleen, uterus, vagina, inguinal hernia sac, rectovaginal septum, ovary, pleura, pericardium, prostate, urinary bladder, scrotum, seminal vesicles and abdominal wall [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35]. Although EGISTs seem to have morphological and immunohistochemical similarities with GISTs, their pathogenesis, incidence, genetic background and prognosis are not completely known because they are extremely rare [6].…”

Recently Discovered Interstitial Cell Population of Telocytes: Distinguishing Facts from Fiction Regarding Their Role in the Pathogenesis of Diverse Diseases Called “Telocytopathies”

“…Interestingly, in the case of specific PDGFRα-mutant GISTs, preliminary results indicate that even telocytes can be a source cell population of this tumor [111]. Since telocytes, formerly known as interstitial Cajal-like cells, are routinely described within the glands associated with the digestive tube (the pancreas and liver with the gallbladder and hepatobiliary tree), they are implicated as the possible source of extragastrointestinal stromal tumors (eGISTs) localized in these organs [112]. Interestingly, eGISTs are rarely localized in organs outside of the digestive system, such as the prostate [113], the vagina [114], the uterus [115] or the inferior vena cava [116].…”