NTRK2 expression in gastrointestinal stromal tumors with a special emphasis on the clinicopathological and prognostic impacts

Sasa, Keita; Son, Raku; Oguchi, Akiko; Ashizawa, Karin; Hasegawa, Nobuhiko; Kubota, Daisuke; Suehara, Yoshiyuki; Takagi, Tatsuya; Okubo, Taketo; Akaike, Keisuke; Sugimoto, Kiichi; Takahashi, Makoto; Sakamoto, Kazuhiro; Hashimoto, Takashi; Mine, Shinji; Fukunaga, Tetsu; Ishijima, Muneaki; Hayashi, Takuo; Yao, Takashi; Murakawa, Yasuhiro; Saito, Tsuyoshi

doi:10.1038/s41598-024-51211-7

Cited by 3 publications

(1 citation statement)

References 39 publications

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“…Compared to FISH and NGS, IHC is a cheap and fast testing method and is available in many hospitals. IHC staining for Pan-TRK has been used to screen NTRK fusions in several cancers [31][32][33][34][35][36][37]. However, both the sensitivity (50%) and specificity (16.7%) of Pan-TRK staining are low [22], and the stain may be focal, as observed in our study.…”

Section: Discussionmentioning

confidence: 47%

ETV6::NTRK3 Fusion-Positive Wild-Type Gastrointestinal Stromal Tumor (GIST) with Abundant Lymphoid Infiltration (TILs and Tertiary Lymphoid Structures): A Report on a New Case with Therapeutic Implications and a Literature Review

Machado,

Claramunt-Alonso,

Lavernia

et al. 2024

IJMS

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Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, with proto-oncogene, receptor tyrosine kinase (c-kit), or PDGFRα mutations detected in around 85% of cases. GISTs without c-kit or platelet-derived growth factor receptor alpha (PDGFRα) mutations are considered wild-type (WT), and their diverse molecular alterations and biological behaviors remain uncertain. They are usually not sensitive to tyrosine kinase inhibitors (TKIs). Recently, some molecular alterations, including neurotrophic tyrosine receptor kinase (NTRK) fusions, have been reported in very few cases of WT GISTs. This novel finding opens the window for the use of tropomyosin receptor kinase (TRK) inhibitor therapy in these subtypes of GIST. Herein, we report a new case of NTRK-fused WT high-risk GIST in a female patient with a large pelvic mass (large dimension of 20 cm). The tumor was removed, and the histopathology displayed spindle-predominant morphology with focal epithelioid areas, myxoid stromal tissue, and notable lymphoid infiltration with tertiary lymphoid structures. Ten mitoses were quantified in 50 high-power fields without nuclear pleomorphism. DOG1 showed strong and diffuse positivity, and CD117 showed moderate positivity. Succinate dehydrogenase subunit B (SDHB) was retained, Pan-TRK was focal positive (nuclear pattern), and the proliferation index Ki-67 was 7%. Next-generation sequencing (NGS) detected an ETV6::NTRK3 fusion, and this finding was confirmed by fluorescence in situ hybridization (FISH), which showed NTRK3 rearrangement. In addition, an RB1 mutation was found by NGS. The follow-up CT scan revealed peritoneal nodules suggestive of peritoneal dissemination, and Entrectinib (a TRK inhibitor) was administered. After 3 months of follow-up, a new CT scan showed a complete response. Based on our results and the cases from the literature, GISTs with NTRK fusions are very uncommon so far; hence, further screening studies, including more WT GIST cases, may increase the possibility of finding additional cases. The present case may offer new insights into the potential introduction of TRK inhibitors as treatments for GISTs with NTRK fusions. Additionally, the presence of abundant lymphoid infiltration in the present case may prompt further research into immunotherapy as a possible additional therapeutic option.

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Section: Discussionmentioning

confidence: 47%

ETV6::NTRK3 Fusion-Positive Wild-Type Gastrointestinal Stromal Tumor (GIST) with Abundant Lymphoid Infiltration (TILs and Tertiary Lymphoid Structures): A Report on a New Case with Therapeutic Implications and a Literature Review

Machado,

Claramunt-Alonso,

Lavernia

et al. 2024

IJMS

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Differential diagnosis of gastrointestinal stromal tumors versus leiomyomas by special stains

Zhang,

Qin,

2024

BMC Gastroenterol

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The objective of the study was to investigate whether special stains can differentiate gastrointestinal stromal tumors (GISTs) and gastrointestinal leiomyomas (GILs). In this retrospective study, 39 cases of GISTs (diameter, 0.2–8.8 cm) and 75 cases of GILs (diameter, 0.2–4.5 cm) were recruited, all biopsy specimens were obtained by endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) excision, and the depth of excision included the whole mucosa, mucosal myometria, and most submucosa. GISTs and GILs were the most common types of mesenchymal tumors found anywhere along the gastrointestinal (GI) tract, from the esophagus to the rectum. GISTs were often associated with a higher risk of malignancy. In this study, the gender, age of onset, size and sites of the lesions, together with the number of mucosal or lamina propria lesions all have significant differences, nevertheless, there was no significant difference in cell morphology of GISTs and GILs tested by hematoxylin eosin (H&E) stain, and all showed low echo areas by EUS examination. In this retrospective study, the GISTs and GILs had been diagnosed by immunohistochemistry combined with clinical morphology. Subsequently, special stains including Masson’s trichrome (MT) stain, Alcian blue periodic acid-Schiff (AB-PAS) stain (pH 2.5), Wright-Giemsa (W-G) stain and periodic acid-Schiff (PAS) combined with diastase periodic acid-Schiff (D-PAS) stains were also applied in the diagnosis, the retrospective study results showed that 92.3% GISTs were stained blue with MT stain, 97.3% GILs were stained red with MT stain ( P < 0.01), almost all GISTs were PAS-negative (light purple), in contrast, all GILs were PAS-positive (rose red) ( P < 0.01), all of these experiments set control using the blood vessels stained by MT and AB-PAS stains. Nevertheless, there was no significant difference between GISTs and GILs stained by W-G stain. These obvious and meaningful differential results were also confirmed in the detection of new GISTs and GILs cases using MT and AB-PAS stains. In conclusion, MT and AB-PAS stains could also identify GISTs and GILs cases, particularly, AB-PAS was more sensitive and more specific, providing a more cost-effective, simple, and high sensitivity and specificity inspection methods, which should be noticed and widely used in the future, especially in resource-limited grass-roots testing institution or in cases with inconclusive immunostains or insufficient material. Supplementary Information The online version contains supplementary material available at 10.1186/s12876-024-03511-5.

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Differential diagnosis of gastrointestinal stromal tumors versus leiomyomas by special stains

zhang,

qin,

2024

Preprint

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The objective of the study was to investigate whether special stains can differentiate gastrointestinal stromal tumors (GISTs) and gastrointestinal leiomyomas (GILs). In this retrospective study, 39 cases of GISTs (diameter, 0.2–8.8 cm) and 75 cases of GILs (diameter, 0.2–4.5 cm) were recruited, all biopsy specimens were surgically resected under endoscopic ultrasound (EUS) guidance. GISTs and GILs were the most common types of mesenchymal tumors found anywhere along the gastrointestinal (GI) tract, from the esophagus to the rectum. GISTs were often associated with a higher risk of malignancy. In this study, the gender, age of onset, size and sites of the lesions, together with the number of mucosal or lamina propria lesionsa all have significant differences, nevertheless, there was no significant difference in cell morphology of GISTs and GILs tested by hematoxylin eosin (HE) stain, and all showed low echo areas by EUS examination. In this retrospective study, the GISTs and GILs had been diagnosed by immunohistochemistry (IHC), combined with clinical signs and symptoms. Subsequently, special stains including Masson's trichrome (MT) stain, Alcian blue periodic acid Schiff (AB-PAS) stain, Wright-Giemsa (W-G) stain and periodic acid Schiff (PAS) combined with diastase periodic acid Schiff (D-PAS) stains were also applied in the diagnosis, the retrospective study results showed that 92.3% GISTs were stained blue with MT stain, 97.3% GILs were stained red with MT stain (P < 0.01), almost all GISTs were PAS-negative (light purple), in contrast, all GILs were PAS-positive (rose red) (P < 0.01), all of these experiments set control using the blood vessels stained by MT and AB-PAS stains. Nevertheless, there was no significant difference between GISTs and GILs stained by W-G stain. These obvious and meaningful differential results were also confirmed in the detection of new GISTs and GILs cases using MT and AB-PAS stains. In conclusion, MT and AB-PAS stains could also identify GISTs and GILs cases, particularly, AB-PAS was more sensitive and more specific, providing a more cost-effective, simple, and high sensitivity and specificity inspection methods, which can instead of IHC analysis in the future, especially in resource-limited grass-roots testing institution.

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NTRK2 expression in gastrointestinal stromal tumors with a special emphasis on the clinicopathological and prognostic impacts

Cited by 3 publications

References 39 publications

ETV6::NTRK3 Fusion-Positive Wild-Type Gastrointestinal Stromal Tumor (GIST) with Abundant Lymphoid Infiltration (TILs and Tertiary Lymphoid Structures): A Report on a New Case with Therapeutic Implications and a Literature Review

ETV6::NTRK3 Fusion-Positive Wild-Type Gastrointestinal Stromal Tumor (GIST) with Abundant Lymphoid Infiltration (TILs and Tertiary Lymphoid Structures): A Report on a New Case with Therapeutic Implications and a Literature Review

Differential diagnosis of gastrointestinal stromal tumors versus leiomyomas by special stains

Differential diagnosis of gastrointestinal stromal tumors versus leiomyomas by special stains

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