Primary Adrenal Lymphoma Diagnosed by Endoscopic Ultrasound Fine-Needle Aspiration Biopsy: A Case Report

Introduction

Primary adrenal lymphoma (PAL) is a rare lymphoma that occurs in both adrenal glands, as diffuse large B-cell lymphoma (DLBCL) in 92% of cases [1], leading to nonspecific symptoms, such as fatigue, loss of appetite, and weight loss for adrenal insufficiency, with elevated lactate dehydrogenase (LDH) [2]. Physical examination reveals skin/mucosal hyperpigmentation, hepatosplenomegaly, and lymphadenopathy in a few patients. For these nonspecific manifestations, it is still difficult to detect PAL in the early stage, which can lead to a poor clinical outcomes and result in a short mean survival, of approximately 7 months [1]. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) has been suggested for evaluating adrenal lymphomas and extra-adrenal extensions; however, a lack of biopsy data could affect patient prognosis. Adequate biopsies can be obtained during surgery, and lesions can be removed simultaneously. However, in multivariate logistic regression analysis, surgery did not improve survival as did chemotherapy [3]. A study including 31 patients with PAL-DLBCL reported no benefit from adrenalectomy before chemotherapy [4]. Surgery-related adrenal insufficiency, which made obtaining biopsy challenging, might be to blame. Meanwhile, with the dysfunction of blood cells, like thrombocytopenia, traditional management could be more dangerous. Here, we reported a case of PAL with low platelet counts that we diagnosed via endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) biopsy, which can support further treatment safely, without significant harm to adrenal function.

Case Report

A 72-year-old man had masses on both adrenal glands identified incidentally by ultrasound a month before presentation, without any symptoms such as fatigue, pain, or loss of appetite. Ultrasound images showed a 4.3×1.3-cm hypoechoic nodule on left adrenal gland and a 3.7×2.0-cm nodule on right adrenal gland, with a sharp and regular outer margin. Enhanced computed tomography (CT) scan showed diffuse lesions on both adrenal glands. The left nodule ranged to 6.4×3.7 cm, while the right was smaller, ranging 4.2×2.4 cm, with homogeneously enhancement. Enhanced magnetic resonance imaging (MRI) found a slightly heterogeneously enhanced mass on both adrenal glands, whose sizes were similar to that seen on CT. MRI found his spleen was a little larger, without enhanced signal (15.4×5.5 cm). No obvious enlarged lymph nodes were found in the abdominal cavity, pelvic cavity, and retroperitoneum.

The patient was a non-drinker and non-smoker, and had chronic gastritis 10 years ago, without any history of other diseases concerning gastrointestinal diseases or tumor. He denied any chronic or recent use of medications or any family history of tumors. He had not experienced any obvious weight loss on admission. The body mass index of patient was 27.68 kg/m2. Physical examination results were almost negative.

Laboratory test results revealed low platelets (44×109/L; reference range 125–350×109/L) and mild anemia for low hemoglobin (115 g/L; reference range 130–175 g/L). His LDH was slightly elevated (308 U/L; reference range 109–245 U/L). Also, his white blood cell count (3.53×109/L; reference range 3.5–9.5×109/L), hepatic and renal functions, coagulation function, and fecal tests were almost normal. No obvious abnormality was found in the morphology of peripheral blood cells. Adrenal function was normal. 18F-FDG PET-CT found high FDG uptake in both adrenal lesions. SUVmax of the left was 11.7, the right was 9.2 (Figure 1), further confirming there were no metastatic lesions in the abdominal cavity or beyond.

Because of the low platelet count, surgery and percutaneous FNA were considered dangerous. With platelet transfusion improving coagulation function (platelets; 73×109/L) and prophylactic antibiotics, the patient underwent EUS, which showed a hypoechoic mass with a little blood flow on the left adrenal gland (Figure 2A), about 3.8×2.2 cm, with moderate elasticity (Figure 2B). Several small anechoic areas were visible inside. There was a lymph node next to the abdominal aorta, measuring about 0.9×0.6 cm. The spleen was large, with a heterogeneous echo. Two FNA biopsies were performed in the left adrenal mass (needle: Echo, COOK 22G; Figure 2C). Silk thread-like puncture specimens were obtained (Figure 2D). We confirmed there was no active bleeding on gastric wall (Figure 2E) and completed the EUS. After normal postoperative treatment, no bleeding or other complications occurred.

The biopsy specimen showed clustered middle-sized oval lymphoid cells, with heterogeneity in coagulated blood. Ultrathin cell detection found atypical cells with large nuclei, rough chromatin, irregular nuclear membrane, and high nuclear-to-cytoplasmic ratio, highly suspected tumor cells, with a few normal lymphocytes and neutrophils (Figure 3A–3C). Immunohistochemistry showed CD3(−), CD20(+), PAX5(+), CD5(−), CD23(−), CD10(−), CD138(−), Bcl-6(+), Cyclin D1(−), CD30(−), CK(−), MUM1(+), C-MYC 10%+, Ki-67(90%+), and ERBR(−) (Figure 3D–3I). Final diagnosis was PAL, non-germinal center DLBCL.

After confirming the diagnosis, the patient went to the hematology clinic and subsequently underwent chemotherapy (R-CHOP) and radiation therapy. One year later, the left adrenal lesion had shrunk, and the right lesion had disappeared completely, with stable adrenal function confirmed by blood test, and no further metastases or adrenal hemorrhage were detected via PET-CT.

Discussion

With rich microvascularity, 33.3% of adrenal lesions that develop after lung cancer diagnosis are metastatic [5], which reveals that it is one of the most common metastatic sites. With respect to primary cancer diagnosis, 18F-FDG PET-CT can be used to diagnose metastasis, with high sensitivity (94%) and specificity (85%) [6]. However, adrenal glands can also develop primary lesions, including hyperplasia, adenomas, adenocarcinoma, and even lymphoma, which are difficult to diagnose without biopsy. CT-guided percutaneous FNA had complication rates of up to 8.4% decades ago [7]. The recent complication rate has decreased, but the undiagnostic rate of up to 28% cannot be ignored [8]. In 1996, Chang et al [9] first reported a patient with an adrenal mass diagnosed by EUS-FNA. After an undiagnostic CT-guided FNA, the patient had metastatic lung cancer confirmed via EUS-FNA and avoided high-risk surgical intervention, suggesting that EUS-FNA might be a better alternative for diagnosing adrenal masses. Dietrich et al [10] reported that the left adrenal gland could be more easily visualized by EUS than by transabdominal ultrasound in patients (98% vs 69%), whereas the right adrenal gland could be the opposite (30% vs 99%). In a 20-year single institution study, Novotny et al [11] reported no statistically significant difference in overall adequacy rates for adrenal cytology between CT-guided FNA and EUS-FNA (93% vs 89%). Furthermore, EUS-guided radiofrequency ablation has been reported for left adrenal lesion treatment [12]. These findings suggest that, as a minimally invasive procedure, EUS-FNA is a safe method for evaluating left adrenal lesions, with excellent diagnostic yield.

Early studies have shown that the left adrenal gland can be explored easily via EUS, whereas imaging the right adrenal gland is challenging because its location is far from the gastrointestinal tract. In 2004, Jhala et al [13] reported for the first time in selected patients that EUS-FNA of the right adrenal gland could be a feasible choice. An increasing number of clinicians have successfully completed EUS-FNA for the right adrenal gland without complications [14–18], most of which are completed via the transduodenal approach. The published visualization rate for the right adrenal gland via EUS has ranged from 30% [10] to 87.3% [19]. Given the shorter endoscopic route and higher success rates reported in prior studies, we performed EUS-FNA on the left adrenal mass, despite bilateral adrenal lesions in this case. For patients with left adrenal lesions unsuitable for FNA, EUS-guided sampling of the right adrenal gland can serve as an alternative approach.

Zhang et al [20] reported that EUS-FNA had fewer adverse events than did percutaneous FNA in a single-institution study. A meta-analysis [21] including 360 adrenal lesions revealed that EUS-FNA had 95% sensitivity and 99% specificity in detecting metastasis. Recently, in a nationwide multicenter study [22], EUS-FNA for adrenal glands had only an 8.83% undiagnostic rate. In addition to inevitable undiagnostic FNA, EUS-FNA theoretically has similar complications to those of CT-guided FNA, including hemorrhage, infection, bacteremia, and needle tract metastases. However, in the abovementioned cases and a meta-analysis [21], severe complications were seldom reported in EUS-FNA for adrenal glands, even in patients with malignant tumors. Even with anticoagulant therapy and antiplatelet therapy, no bleeding events occurred in a nationwide multicenter study [22]. Only 1 patient was reported to experience adrenal hemorrhage 1 year after EUS-FNA [18]. Pheochromocytoma poses the highest risk for triggering adrenal hypertensive crisis. Even in a few cases in which pheochromocytomas were safely diagnosed by EUS-FNA without preoperative endocrine evaluation [14,22], the use of creatinine, total catecholamines, vanillylmandelic acid, and metanephrines in 24-h urine, to exclude pheochromocytoma before FNA, was suggested [18].

Low platelet counts limit diagnostic methods for the patient. Generally, EUS-FNA requires platelet counts of 50×109/L [23], while percutaneous FNA can require the same or fewer [24,25]. In our case, different from liver biopsy or spleen biopsy, adrenal percutaneous FNA could be more complex, making it in dilemma even after platelet transfusion. Considering that surgery could be a risk, after multidisciplinary discussion, we chose EUS to access left adrenal lesions and implemented FNA successfully. Given that lymphoma is more prone to thrombocytopenia, patients with lymphoma may be more suitable for adrenal diagnosis via EUS-FNA. More clinical trials are needed to confirm its safety and damage to adrenal function.

Conclusions

EUS-FNA is a safe and effective approach for the diagnosis of primary adrenal lesions, including PAL with thrombocytopenia. By obtaining adequate biopsy samples with minimal invasiveness, EUS-FNA reduces iatrogenic adrenal injury, potentially leading to better clinical outcomes.