Micrometastatic gastric glomus tumour confirmed by next‐generation sequencing

摘要

Sir: Glomus tumours are uncommon perivascular neoplasms.1 Derived from the glomus bodies of the dermis involved in thermoregulation, glomus tumours are found most frequently in areas of the body rich in such glomus bodies, including the subungual areas of the digits and the distal extremities in general. Although they are most common in the superficial tissues, glomus tumours may occur in visceral organs, including the liver, lung, pancreas, and gastrointestinal and genitourinary tracts.2 When glomus tumours do occur in the gastrointestinal tract, they are most often located in the stomach.3 Gastric glomus tumours present as intramural nodules, and are generally found incidentally, although they may undergo ulceration and cause haemorrhage. Histologically and immunophenotypically, gastric glomus tumours are identical to their cutaneous counterparts. Microscopically, three cell types can be detected: glomus cells, smooth muscle cells, and vasculature. Different tumour variants are characterized by varying amounts of these cellular components,1 but, to the unwary, they may be mistaken for neuroendocrine tumours (carcinoid), epithelioid gastrointestinal stromal tumours, and even malignant lymphoma. Glomus tumours are typically benign, although occasional cases have been reported to metastasize.4 Malignant glomus tumours tend to be large (>20 mm), and to show atypical mitotic figures.5 Immunohistochemical staining most frequently shows reactivity for α-smooth muscle actin, muscle-specific actin, vimentin, and calponin.6 The immunohistochemical profile of glomus tumours has been better elucidated than the molecular genomics. What commentary exists has primarily concerned paragangliomas of the head and neck, which, in past usage, were frequently (and inaccurately) referred to as glomus tumours. Specifically in true glomus tumours, a recent examination demonstrated NOTCH1-3 rearrangements, most commonly MIR143–NOTCH fusion, in more than half of a set of 33 glomus tumours arising both from the extremities and the viscera, including both benign and malignant tumours. These gene fusions were believed to lead to tumorigenesis through oncogenic activation of NOTCH, which is involved in vascular smooth muscle differentiation.7 Therefore, we report a case of a 46-year-old woman who was referred after receiving a wedge liver biopsy for abnormal liver function tests at the time of a cholecystectomy. On histopathological examination, there was an incidentally discovered 1.1-mm lesion (Figure 1). The lesion was positive for synaptophysin, but negative for other markers, including S100, CD45, cytokeratin 7, and chromogranin. The outside pathology report stated that there were no mitotic figures or necrosis, but minimal focal calcifications were present within the tumour. The report entertained several differential diagnoses, including a metastatic low-grade neuroendocrine tumour from the gut (i.e. carcinoid) or islet-cell tumour. Although synaptophysin positivity is characteristic of gastrointestinal neuroendocrine tumours, positivity can also be seen with glomus tumours, and this diagnosis was not entertained.8 A magnetic resonance imaging (MRI) study of the patient's pancreas showed no possible primary tumours. MRI enterography revealed a well-defined ovoid 14-mm mass along the gastric wall adjacent to the left hepatic lobe margin (Figure 2). An octreotide scan was negative for any tracer-avid tumour. The patient subsequently underwent a robot-assisted wedge excision of the stomach tumour, yielding a 10-mm mass. Histological evaluation established a diagnosis of glomus tumour (Figure 3). This finding prompted re-evaluation of the liver lesion, which was then reclassified as a glomus tumour. Given the surprising finding of two glomus tumours, further analysis was performed to ascertain whether these tumours represented synchronous primary tumours or metastatic disease. Genomic tumour DNA was extracted from formalin-fixed paraffin-embedded secti