GIST Manifesting as a Retroperitoneal Tumor

Abstract

Most gastrointestinal stromal tumors (GISTs) occur in the tubular gastrointestinal tract, but some present apparently outside the GI-tract. In this study, we analyzed 112 GISTs located in the retroperitoneum. These tumors occurred in 55 women and 57 men with a median age of 65 years (range: 21-89 years). Based on clinically or histologically detected connections to GI-tract, 15 tumors were considered likely of gastric, 9 duodenal, and 13 of small intestinal origin. The remaining cases were categorized by location as peripancreatic (n = 25), pelvic (n = 11), mesenteric (n = 4), and of unspecified/miscellaneous sites (n = 35). The tumors varied in size 3-35 cm (median, 15 cm) and by mitotic rate per 5 mm2, 0- >100 (median 10). Histologically the tumors apparently arising outside the GI-tract had features of intestinal (n = 41) and gastric GISTs (n = 25); 9 cases had indeterminate histology. The histologic variants included spindled, epithelioid, vacuolated, nested and myxoid potentially simulating other tumors such as liposarcoma and solitary fibrous tumor. Most GISTs were KIT-positive (106/112 cases), and the remaining 6 tumors were Dog1/Ano1-positive. Five cases showed focal nuclear positivity for MDM2. KIT mutations were detected in 42/59 cases, and PDGFRA mutations in 4/16 KIT wild-type and 3/5 of the KIT-negative tumors analyzed. One pelvic retroperitoneal GIST was SDH-deficient. All 79 patients were dead at last follow-up with a median survival of 14 months, with few survivals > 5 years. Only operable vs. inoperable tumor was a statistically favorable factor in univariate analysis (p<0.01). In multivariate analysis, mitotic rate > 50/5 mm2 was significant for a shorter survival (HR 5.25, 95% CI 1.65-16.8., p<0.01). Histologic and clinicopathologic similarity of extragastrointestinal retroperitoneal GISTs with GISTs of GI-tract suggests their GI tract origin. Potentially overlapping features between GIST and other retroperitoneal tumors necessitate use of multiple diagnostic markers and molecular genetic studies.

<p>Retroperitoneal Extragastrointestinal Stromal Tumors Have a Poor Survival Outcome: A Multicenter Observational Study</p>

“… 25 Likewise, immunohistochemistry is essential for confirming the diagnosis of eGISTs. Findings from a retrospective analysis of a single institution 12 showed that 95% (106/112 cases), 62% (53/86 cases), and 93% (81/87 cases) of the eGIST patients were stained positive on IHC for CD117, CD34 and DOG-1, respectively. In a study, 26 the authors found that 92.2% (47/51 cases), 80.6% (25/31 cases), and 100% (13/13 cases) of the patients had positive staining with CD117, CD34 and DOG-1, respectively, on IHC from multi-institutional data collected in South Korea.…”

“…However, despite the similarities in IHC and genetic testing between eGISTs and GISTs, the prognoses of eGISTs are less favorable compared to GISTs as the former tends to have higher proliferative mitotic indices (GISTs vs eGISTs, median range, 4–8/50 HPF 36 – 38 vs 10–15/50 HPF 12 , 39 , 40 ), larger tumor size (GISTs vs eGISTs, median range, 4–7 cm 38 , 41 , 42 vs 7.5–15 cm 12 , 14 , 39 , 40 , 43 ) and greater risk to recurrence or distant metastasis. 14 , 44 Similarly, our findings showed that the median tumor size (13 cm, range, 0.4–29 cm) and mitotic value (13 HPF, range, 0–50 HPF) were in accordance with that of reported literature.…”

“…They found that the prognoses of retroperitoneal eGISTs (n = 79) were poor and had a median survival of only 14 months. 12 However, some scholars believe that the biological characteristics of eGISTs resemble that of GISTs arising from the distal digestive tract. 13 Another study showed that eGISTs derived from the omentum, whose tumor cells are rarely epithelial cells, possessed similarities to gastric GISTs and had better prognosis compared to eGISTs arising from other locations.…”

What is New in Gastrointestinal Stromal Tumor?

“…29-33 E-GISTs generally share canonical morphologic, immunohistochemical, and molecular features of conventional GISTs, and E-GISTs primarily arising in the mesentery or retroperitoneum seem to follow a more aggressive clinical course 31, 33 , compared to cases arising in the omentum. 30 Some E-GISTs arise in the tubular GI tract but have become substantially detached from the gastric or intestinal primary site, which can therefore be clinically occult.…”

“…Origin from developmental abnormalities (such as enteric duplication) has also been proposed. 33 GISTs arising primarily in visceral organs are exceedingly rare, and have not been systematically studied. 34, 35 GISTs manifesting primarily in visceral organs such as the liver or spleen most likely represent distant metastases from an occult GI tract primary GIST.…”