A case of adrenal metastasis of hepatocellular carcinoma diagnosed by endoscopic ultrasound‐guided fine‐needle aspiration

Abstract An 82‐year‐old man had been treated for lung adenocarcinoma and hepatocellular carcinoma (HCC). Contrast‐enhanced computed tomography examination showed swelling of the left adrenal gland, suggesting metastasis of lung adenocarcinoma, HCC, or primary adrenal tumor. Endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) was performed for the pathological diagnosis, and adrenal metastasis of HCC was diagnosed. No notable complications due to EUS‐FNA were found. There have been reports of adrenal metastasis due to various cancers, but there are few reports that can confirm the diagnosis of adrenal metastasis of HCC using EUS‐FNA. Adrenal metastasis of HCC is not a rare condition, but it may be difficult to diagnose in the case of multiple cancer complications. We experienced a case in which EUS‐FNA was useful for the diagnosis of adrenal metastasis of HCC.


INTRODUCTION
Endoscopic ultrasound (EUS) is the widely used medical imaging method for viewing abdominal diseases.EUS-guided fine needle aspiration (EUS-FNA) is used for a diagnostic procedure to investigate pathological findings. 1Many tumors can develop adrenal metastasis, and lung cancer is the most common cancer.The incidence of adrenal metastasis in patients with hepatocellular carcinoma (HCC) is reportedly 6.9%-19.1%. 2 Although some cases of adrenal metastasis from lung carcinoma have been reported, there were only two F I G U R E 1 (a) Computed tomography during the arterial phase showed a tumor with 7 cm in diameter (white arrowheads) in liver segment 4. Computed tomography showed the high-density area in liver segment 7 (white arrow).(b) Computed tomography was performed after the first transcatheter arterial chemoembolization, and the tumor in liver segment 4 could not be detected.Furthermore, it revealed that a tumor with a 1 cm diameter was detected in liver segment 7 as a variable hepatocellular carcinoma (white arrow).
drinking and smoking history was 20 cigarettes per day for 60 years.
Computed tomography (CT) revealed that right upper lung cancer was stage IIIA.And a 7 cm diameter liver tumor was detected in liver segment 4. Furthermore, CT showed the high-density area in liver segment 7 (Figure 1a).He received surgery for stage IIIA right upper lobe adenocarcinoma without neoadjuvant chemotherapy.
The tumor in liver segment 4 was diagnosed with HCC of stage III by fine needle aspiration biopsy, and transcatheter arterial chemoembolization (TACE) was performed twice two months.Since the high-density area with CT in liver segment 7 was not as typical as HCC, it stayed under observation.A month after performing TACE twice, CT revealed that HCC in liver segment 4 almost disappeared, but a highdensity area in liver segment 7 was diagnosed with new HCC (Figure 1b).So, TACE was performed again for HCC in liver segment 7. Three months after performing TACE three times, CT revealed a mass lesion measuring 23 mm in diameter at the left adrenal gland, and the primary HCC was not in the liver (Figure 2a,b).It suggested the possibility of an adrenal metastasis from lung adenocarcinoma, HCC, or a primary adrenal gland tumor.Because the serum levels of tumor markers were within the normal range, we couldn't accurately diagnose the tumor.Therefore, we decided to perform EUS-FNA.A physical examination showed no abnormality on admission.According to the guidelines of pheochromocytoma, if the serum and urine levels of catecholamine were within the normal range as in this case (Table 1), 123I-metaiodobenzylguanidine (MIBG) scintigraphy was not always necessary.Therefore,MIBG scintigraphy was not performed in this case.EUS revealed a well-defined hypoechoic mass in the left adrenal gland, and the lesion displayed a poor Doppler sign.EUS-FNA was performed using a 25-gauge core needle (Acquire; Boston Scientific Co.; Figure 2c,d).The puncture was performed twice, and there were no complications associated with EUS-FNA including hemorrhage.The day after the EUS-FNA, the serum and urine levels of catecholamine were within the normal range (Table S1).Pathological findings showed that tumor cells with eosinophilic cytoplasm and circular nuclear including small nucleolus formed strands and gland-like structures.In the immunohistochemical staining, hepatocyte-paraffin-1 positive cells were observed in the tumor (Figure 3).Fine needle biopsy of the liver tumor revealed a well to moderately differentiated HCC.HCC is composed of trabecular and pseudoglandular patterns with hyperchromatic nuclei and eosinophilic granules resembling hepatocytes.These pathological findings were like that from EUS-FNA of the adrenal gland tumor.Because of these findings, we diagnosed the patients as HCC stage IVB with left adrenal metastasis.HCC was present only in the left adrenal gland, and the patient had good liver function (Child-Pugh A).Because he refused to receive the excision of the adrenal tumor, he received TACE for left adrenal metastasis from HCC.However, he had a poor therapeutic response to TACE and started treatment with lenvatinib.After treatment with lenvatinib for three months, follow-up CT revealed that the tumor size increased from 23 to 52mm in diameter at the left adrenal gland.After about two weeks, he developed hypothyroidism.He had been medicated with levothyroxine, but his general condition worsened.It was difficult to continue chemotherapy due to the decline in performance status, so palliative care was started.After about a month, he died because of deterioration of general conditions Computed tomography showed a tumor with 23 mm in diameter at the left adrenal gland, suggesting the possibility of an adrenal metastasis from lung adenocarcinoma, hepatocellular carcinoma, or a primary adrenal gland tumor (white arrow).And liver tumors were not detected in liver segments 4 and 7 on computed tomography.(c, d) Endoscopic ultrasound shows a hypoechoic mass in the left adrenal gland (white arrowheads).We performed endoscopic ultrasound-guided fine-needle aspiration of the left adrenal gland using a 25-gauge needle.

DISCUSSION
Abdominal ultrasonography, CT, and magnetic resonance imaging are indispensable for diagnosing cancer.In situations such as double cancer or the existence of inflammation, these tests alone can make it difficult to diagnose the metastasis.In addition, tissue examination is also required for definitive diagnosis of cancer, but the method of tissue examination is limited for retroperitoneal organs such as the adrenal gland.In the gastrointestinal field, EUS is a valuable method for diagnosing cancer.If it can be visualized by EUS, it is possible to perform histological examination by EUS-FNA.Since the EUS-FNA was reported by Vilmann et al. in 1992, 1 it has become possible to collect samples of deep organs such as the adrenal gland relatively safely and easily with the progress of technology.Martinez et al. performed EUS-FNA on 95 swollen adrenal tumors and reported favorable results that 92% could be achieved with a definitive diagnosis and no complications were observed. 5he probability that an adrenal tumor is a metastatic tumor is estimated at about 2% in non-cancer-bearing patients and about 30-70% in cancer-bearing patients. 6he adrenal gland has abundant blood flow and is easily metastasized by various kinds of cancers.Malignant melanoma, thyroid cancer, renal cell carcinoma, pancreatic cancer, colon cancer, and lung cancer are often the primary lesions.Of the 398 autopsy cases of HCC from 1988 to 2012,156 (39.1%) had extrahepatic metastases, 74.5% had lung metastases, 24.8% had bone metastases, 19.1% had adrenal metastases, 17.1 had local lymph nodes. 7There are few reports that adrenal metastasis of HCC compared to lung cancer.There are only two reports that diagnosed adrenal metastasis of HCC by EUS-FNA. 3,4he diagnostic accuracy of adrenal metastatic tumors by EUS-FNA has been shown in one retrospective study of 150 patients of lung cancer, in which six (4%) had CT and five (3.3%) had PET-CT showing metastases in one or both adrenal glands and EUS-FNA was performed in 11 (7.3%) patients, with a diagnosis of adrenal metastases in four patients. 8In this report, the diagnostic accuracy of adrenal metastatic tumors is 96% by CT, 97% by PET-CT, and 100% by EUS-FNA.In this case, it was difficult to distinguish whether it was a primary adrenal tumor or a metastatic tumor because of the history of treatment for lung adenocarcinoma and HCC.A left adrenal tumor could be visualized by EUS, and FNA was performed and pathological examination was performed.By comparing the histopathological findings of previous HCC diagnoses, adrenal tumors could be diagnosed as metastasis of HCC.If we did not perform EUS-FNA for a left adrenal tumor, the alternative methods of EUS-FNA were percutaneous ultrasoundguided fine-needle aspiration, and laparoscopic biopsy et al.Some reports suggest that the right adrenal gland can be sampled with EUS-FNA by a duodenal approach.However, EUS-FNA of the right adrenal gland requires us to twist the scope, and more likely to result in perforation.Therefore, the success rate of the EUS-FNA of the right adrenal gland is not high, and it is not a safe examination. 9here are reports that EUS-FNA did not cause any complications for adrenal tumors diagnosed as pheochromocytoma by pathological results, however, one study described hypertensive crisis occurred as the complication. 10Therefore, blood tests should be performed before EUS-FNA to check for pheochromocytoma comorbidity and adequate informed consent should be performed for pheochromocytomaassociated crises.It was considered that using a 25-gauge needle reduced the risk of bleeding and a potential pheochromocytoma using fine-needle biopsy needles increased the amount of tissue that could be collected.
The advantages of EUS-FNA compared to percutaneous biopsy are that there is no radiation exposure or contrast administration, and real-time echo-guided puncture is possible.It is important to perform a wholebody search in advance, not to mention drawing and puncture skills, to determine the indication and purpose of EUS-FNA, and to perform it appropriately.

R E F E R E N C E S S U P P O R T I N G I N F O R M AT I O N
Additional supporting information can be found online in the Supporting Information section at the end of this article.
Table S1.The blood test data after the endoscopic ultrasound guided-fine needle aspiration.