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A man in his 70s came to our department with jaundice. He was diagnosed with Merkel cell carcinoma in the left eyebrow area 3 years ago and was followed up after tumor resection. Endoscopic retrograde cholangiopancreatography was performed because the computed tomography and abdominal ultrasonography revealed bile duct dilatation. However, the duodenum was too narrow and deformed to reach the ventral papilla. Percutaneous transhepatic cholangiodrainage was performed, and bile cytology revealed no malignant findings; however, it did not sufficiently reduce the jaundice. Subsequently, endoscopic ultrasound-fine needle biopsy was performed on his right adrenal mass, which led to a diagnosis of the rare Merkel cell carcinoma. In summary, we report here of a case in which endoscopic ultrasound-fine needle biopsy led to the diagnosis of Merkel cell carcinoma recurrence.

Background: There are few studies on the efficacy of temozolomide (TMZ) in the treatment of Metastatic pheochromocytoma / paraganglioma (MPP) patients. And it remains unclear which MPP patients may benefit from TMZ treatment., Methods: This was a prospective study. MPP patients were enrolled. Patients were treated with TMZ until disease progression or intolerable toxicities. The primary endpoints were disease control rate (DCR) and objective response rate (ORR). Secondary endpoints included biochemical response rate progression-free survival (PFS) and safety. We compared the difference between effective and ineffective groups, to explore which patients are more suitable for TMZ treatment., Results: 62 patients with MPP were enrolled and tumor response were evaluated in 54 patients. The DCR was 83% (35/42), and the ORR was 24% (10/41) among the progressive patients. PFS was 25.2 ± 3.1 months. The most common adverse event was nausea (41/55). We found that 92.9% (13/14) of patients with MGMT methylation greater than 7% respond to treatment. For the patients with MGMT methylation less than 7%, Ki-67 index could be used to guide the use of TMZ in these patients. Among the patients with Ki-67 index less than 5%, 66% (8/12) patients showed respond to treatment, and only 33% (4/12) patients with Ki-67 index more than 5% showed respond to TMZ., Conclusions: This study indicated that TMZ is a potential choice for the treatment of MPP with the high ability on disease control and well tolerability. We recommended to MGMT methylation analysis test and Ki-67 index to guide TMZ application., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Abstract: Pheochromocytomas (PHEOs) are neural crest-derived tumors originating from the chromaffin cells of the adrenal medulla and were recognized as one of the subtypes of paragangliomas by the World Health Organization in 2022. 68 Ga-labeled somatostatin analog ( 68 Ga-DOTA-NOC, 68 Ga-DOTA-TOC, and 68 Ga-DOTA-TATE) PET imaging has shown significant performance compared with 123 MIBG scintigraphy in the diagnosis of paragangliomas. It is now known that fibroblast activation protein (FAP) is overexpressed by various cancer-associated fibroblasts, including PHEOs. We would like to present the findings of 68 Ga-DOTA-FAPI-46 PET/CT and 68 Ga-DOTA-TATE PET/CT imaging performed for restaging on a 42-year-old man diagnosed with metastatic PHEO., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Secondary adrenal tumors (SATs) are uncommon, and the benefits of adrenalectomy for SATs have not been well-established. A systematic review and meta-analysis were conducted to assess the survival benefits of adrenalectomy for SATs., Method: ology: A systematic literature search was performed (1990-2022). The inclusion criteria included a known primary tumor with confirmed adrenal metastasis in patients who underwent adrenalectomy. The primary outcome was the overall survival (OS)., Results: A total of 26 studies were included, with 2279 patients. The average age at the time of diagnosis was 61.1 years. Lung cancer was the most common primary tumor. The average time from primary tumor diagnosis to identification of adrenal metastasis was 17 months. The median OS was 35.2 months. One, three, and five-year OS were 79.7 ​%, 49.1 ​%, and 37.9 ​%, respectively., Conclusion: The results of this review provide insight into the long-term survival of patients with SATs who underwent adrenalectomy. The study highlights the need for further research to identify the risk factors that play a role in the outcome of adrenalectomy in patients with SATs., Competing Interests: Declaration of competing interest The authors declare no conflict of interest to declare. No financial support to be declared., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To provide a nationwide description of postoperative outcomes and analysis of prognostic factors following adrenalectomy for metastases., Background: Adrenal glands are a common site of metastases in many malignancies. Diagnosis of adrenal metastases is on the rise, leading to an increasing number of patient candidates for surgery without consensual management., Methods: We conducted a population-based study between January 2012 and December 2022 using the French National Health Data System (SNDS) and the Eurocrine registry (NCT03410394). The first database exhaustively covers all procedures carried out in France, while the second provides more clinical information on procedures and tumor characteristics, based on the experience of 11 specialized centers., Results: From the SNDS, we extracted 2515 patients who underwent adrenalectomy for secondary malignancy and 307 from the Eurocrine database. The most common primary malignancies were lung cancer (n=1203, 47.8%) and renal cancer (n=555, 22.1%). One-year survival was 84.3% (n=2120). Thirty-day mortality and morbidity rates were, respectively, 1.3% (n=32) and 29.9% (n=753, including planned intensive care unit - stays). Radiotherapy within the year before adrenalectomy was significantly associated with higher 30-day major complication rates ( P =0.039). In the Eurocrine database, the proportion of laparoscopic procedures reached 85.3% without impairing resection completeness (R0: 92.9%). Factors associated with poor overall survival were the presence of extra-adrenal metastases (hazard ratio =0.64; P =0.031) and incomplete resection (≥R1; hazard ratio=0.41; P =0.015)., Conclusions: The number of patients who can receive local treatment for adrenal metastases is rising, and adrenalectomy is more often minimally invasive and has a low morbidity rate. Subsequent research should evaluate which patients would benefit from adrenal surgery., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Medullary thyroid cancer (MTC) is one of the rare neuroendocrine malignancies. This cancer is hereditary in approximately 20% of cases. Although lymph node (LN) metastasis is prevalent in MTC, distant metastasis is not commonly seen in these patients. The most common locations for metastasis are the lungs, liver, and bones. This study presents an extremely rare MTC metastasis to bone marrow (BM) and adrenal gland, which has not been reported before., Case: The patient was a 50-year-old man with a diagnosis of MTC and total thyroidectomy 2 months before his presentation. He came to the emergency department (ED) complaining of dyspnea, diffuse bone pain, nonbloody diarrhea, and abdominal cramps starting in the last month before. Initial treatment with intravenous fluid infusion and loperamide, due to the provisional diagnosis of infectious diarrhea, was ineffective. Further assessments revealed severe pancytopenia and a massive tumor above the left kidney. Bone marrow aspiration (BMA) and biopsy (BMB) led to the diagnosis of invasive metastasis of the MTC to the BM and the left adrenal gland. In the initial evaluations, his COVID-19 test became positive, and despite all efforts, his condition deteriorated, and he died 5 days after admission due to respiratory distress., Conclusion: Most MTC cases present with thyroid nodules in the initial steps and are confined to the thyroid gland or the adjacent LNs. These cases are mostly cured by thyroidectomy and LN dissection. This neuroendocrine cancer infrequently becomes aggressive and involves other parts of the body. However, involving BM or adrenal gland has been scarcely reported. Due to ineffective red and white blood cell production, BM metastasis can cause pancytopenia and, consequently, pallor, fatigue, dyspnea, and susceptibility to infections. High calcitonin levels can also cause diarrhea. The initial diagnosis is mostly with neck ultrasound (US) and fine needle aspiration (FNA). Total thyroidectomy is the main therapeutic option for these patients. Calcitonin and carcinoembryonic antigen (CEA) are sensitive indicators of recurrence or remaining tumors, which might be helpful for the initial diagnosis and postoperation follow-up. Although extremely rare, invasive metastasis of MTC might involve unusual body organs such as the BM or adrenal glands. In cases of unjustifiable pancytopenia or adrenal dysfunction in MTC-positive patients, these possibilities should be considered and ruled out by some specific evaluations, such as bone marrow biopsy and contrast-enhanced imaging., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

Objective: To compare the diagnostic performance of [ 68 Ga]DOTATATE PET/CT, [ 18 F]FDG PET/CT, MRI of the spine, and whole-body CT and MRI for the detection of pheochromocytoma/paraganglioma (PPGL)-related spinal bone metastases., Materials and Methods: Between 2014 and 2020, PPGL participants with spinal bone metastases prospectively underwent [ 68 Ga]DOTATATE PET/CT, [ 18 F]FDG PET/CT, MRI of the cervical-thoracolumbar spine (MRI spine ), contrast-enhanced MRI of the neck and thoraco-abdominopelvic regions (MRI WB ), and contrast-enhanced CT of the neck and thoraco-abdominopelvic regions (CT WB ). Per-patient and per-lesion detection rates were calculated. Counting of spinal bone metastases was limited to a maximum of one lesion per vertebrae. A composite of all functional and anatomic imaging served as an imaging comparator. The McNemar test compared detection rates between the scans. Two-sided p values were reported., Results: Forty-three consecutive participants (mean age, 41.7 ± 15.7 years; females, 22) with MRI spine were included who also underwent [ 68 Ga]DOTATATE PET/CT (n = 43), [ 18 F]FDG PET/CT (n = 43), MRI WB (n = 24), and CT WB (n = 33). Forty-one of 43 participants were positive for spinal bone metastases, with 382 lesions on the imaging comparator. [ 68 Ga]DOTATATE PET/CT demonstrated a per-lesion detection rate of 377/382 (98.7%) which was superior compared to [ 18 F]FDG (72.0%, 275/382, p < 0.001), MRI spine (80.6%, 308/382, p < 0.001), MRI WB (55.3%, 136/246, p < 0.001), and CT WB (44.8%, 132/295, p < 0.001). The per-patient detection rate of [ 68 Ga]DOTATATE PET/CT was 41/41 (100%) which was higher compared to [ 18 F]FDG PET/CT (90.2%, 37/41, p = 0.13), MRI spine (97.6%, 40/41, p = 1.00), MRI WB (95.7%, 22/23, p = 1.00), and CT WB (81.8%, 27/33, p = 0.03)., Conclusions: [ 68 Ga]DOTATATE PET/CT should be the modality of choice in PPGL-related spinal bone metastases due to its superior detection rate., Clinical Relevance Statement: In a prospective study of 43 pheochromocytoma/paraganglioma participants with spinal bone metastases, [ 68 Ga]DOTATATE PET/CT had a superior per-lesion detection rate of 98.7% (377/382), compared to [ 18 F]FDG PET/CT (p < 0.001), MRI of the spine (p < 0.001), whole-body CT (p < 0.001), and whole-body MRI (p < 0.001)., Key Points: • Data regarding head-to-head comparison between functional and anatomic imaging modalities to detect spinal bone metastases in pheochromocytoma/paraganglioma are limited. • [ 68 Ga]DOTATATE PET/CT had a superior per-lesion detection rate of 98.7% in the detection of spinal bone metastases associated with pheochromocytoma/paraganglioma compared to other imaging modalities: [ 18 ]F-FDG PET/CT, MRI of the spine, whole-body CT, and whole-body MRI. • [ 68 Ga]DOTATATE PET/CT should be the modality of choice in the evaluation of spinal bone metastases associated with pheochromocytoma/paraganglioma., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Small-cell melanoma masquerading as an adrenal non-Hodgkin lymphoma. The index report illustrates the deceptive cytomorphologic features of a small cell type malignant melanoma metastatic to the adrenal gland. The diagnosis was confirmed by performing immunocytochemistry on the cell block sections. The key cytomorphologic mimics and their distinctive features have also been highlighted., (© 2024 John Wiley & Sons Ltd.)

Few reports have highlighted the rare presence of somatic ATRX variants in clinically aggressive, metastatic pheochromocytoma/paraganglioma (PCC/PGL); however, none have addressed detailed clinical presentation (including biochemistry and imaging) and management of these patients. Here, we address these clinical features and management based on four PCC patients with somatic ATRX variants from our National Institutes of Health PCC/PGL cohort. A total of 192 patients underwent exome sequencing (germline, somatic, or both), and four males were found to have somatic ATRX variants (with additional somatic VHL and FH oncogenic variants in patients 2 and 4, respectively). Per-lesion and per-patient comparisons were performed among functional imaging scans performed at the NIH. Biochemical phenotype and response to systemic treatment were evaluated. This mini-series supports prior studies showing aggressive/metastatic PCC in patients with somatic ATRX variants, as all developed widespread metastatic disease. All four PCC patients presented with noradrenergic biochemical phenotype, and some with significant elevation in 3-methoxytyramine. 18 F-FDOPA PET/CT was found to be the superior functional imaging modality, with 100% lesion detection rate when compared to that of 68 Ga-DOTATATE, 18 F-FDG, 18 F-FDA, and 123 I-MIBG scans. While patients did not respond to chemotherapy or tyrosine kinase inhibitors, they responded to targeted radiotherapy using high-specific-activity 131 I-MIBG (Azedra ® ) or 177 Lu-DOTATATE (Lutathera ® )., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Cortez, Kuo, Jha, Patel, Carrasquillo, Prodanov, Charles, Talvacchio, Derkyi, Lin, Taïeb, Del Rivero and Pacak.)

Objective: To analyze the clinical characteristics, etiological composition, imaging features, and prognosis of adrenal metastases. Methods: This study is a retrospective case series that included 96 patients with pathologically confirmed adrenal metastases who were treated at West China Hospital, Sichuan University, from 2007 to 2017. Clinical features such as sex, age, tumor size, biochemical tests, imaging characteristics, postoperative pathology, treatment methods, and prognosis were collected and analyzed. The prognosis of patients and its influencing factors were analyzed by Kaplan-Meier survival curve and single-factor Cox risk proportional model. Results: Among the 96 included patients, 64 were male and 32 were female, with a median age of 60 years. There were 89 cases of unilateral adrenal metastases, five cases of bilateral metastases, and two cases with unspecified laterality. The median diameter of the metastases was 3.5 cm×2.9 cm, with an average CT value of 31 HU. Thirty-four cases of adrenal hormones were evaluated, and no abnormality was found.The primary tumor sites were as follows: lung ( n =36), kidney ( n =19), liver ( n =12), pancreas ( n =7), rectum ( n =3), stomach ( n =2), and one case each of tumor in the esophagus, skin, thyroid, left maxillary muscle, breast, bladder, cervix, chest wall, and gastrointestinal tract. There were three cases with unknown primary tumors. The most common pathological type was lung adenocarcinoma (20.8%, 20/96), followed by hepatocellular carcinoma (9.4%, 9/96) and high-grade invasive urothelial carcinoma of the kidney (8.3%, 8/96). Thirty-nine cases were diagnosed concurrently with the primary tumor, while 37 cases were diagnosed after the primary tumor, with a median interval of 15 months (range: 2-144 months). There was no significant correlation between the death risk of adrenal metastatic tumor patients and gender, age, and the size of the metastatic tumor (all P >0.05). There were 4 patients with radiotherapy and chemotherapy alone, 19 patients with surgery alone, and 6 patients with combined radiotherapy and chemotherapy. The median overall survival was 1, 3, and 7 years, respectively. Conclusions: Adrenal metastases were mostly diagnosed at the same time as the primary tumor or within 15 months after the diagnosis of the primary tumor. Unilateral metastasis is common. The lungs are the most common primary lesion, followed by the kidney and liver. CT is the preferred method for the diagnosis of adrenal metastases, and the plain CT value is more than 30 HU. The overall prognosis of adrenal metastases is poor. The prognosis was better for patients who underwent surgery combined with radiotherapy and chemotherapy than those who received only surgery or radiotherapy and chemotherapy alone.

Objectives: Aim of this study was to assess the value of virtual non-contrast (VNC) reconstructions in differentiating between adrenal adenomas and metastases on a photon-counting detector CT (PCD-CT)., Material and Methods: Patients with adrenal masses and contrast-enhanced CT scans in portal venous phase were included. Image reconstructions were performed, including conventional VNC (VNC Conv ) and PureCalcium VNC (VNC PC ), as well as virtual monochromatic images (VMI, 40-90 keV) and iodine maps. We analyzed images using semi-automatic segmentation of adrenal lesions and extracted quantitative data. Logistic regression models, non-parametric tests, Bland-Altman plots, and a random forest classifier were used for statistical analyses., Results: The final study cohort consisted of 90 patients (36 female, mean age 67.8 years [range 39-87]) with adrenal lesions (45 adenomas, 45 metastases). Compared to metastases, adrenal adenomas showed significantly lower CT-values in VNC Conv and VNC PC (p = 0.007). Mean difference between VNC and true non-contrast (TNC) was 17.67 for VNC Conv and 14.85 for VNC PC . Random forest classifier and logistic regression models both identified VNC Conv and VNC PC as the best discriminators. When using 26 HU as the threshold in VNC Conv reconstructions, adenomas could be discriminated from metastases with a sensitivity of 86.7% and a specificity of 75.6%., Conclusion: VNC algorithms overestimate CT values compared to TNC in the assessment of adrenal lesions. However, they allow a reliable discrimination between adrenal adenomas and metastases and could be used in clinical routine in near future with an increased threshold (e.g., 26 HU). Further (multi-center) studies with larger patient cohorts and standardized protocols are required., Clinical Relevance Statement: VNC reconstructions overestimate CT values compared to TNC. Using a different threshold (e.g., 26 HU compared to the established 10 HU), VNC has a high diagnostic accuracy for the discrimination between adrenal adenomas and metastases., Key Points: • Virtual non-contrast reconstructions may be promising tools to differentiate adrenal lesions and might save further diagnostic tests. • The conventional and a new calcium-preserving virtual non-contrast algorithm tend to systematically overestimate CT-values compared to true non-contrast images. • Therefore, increasing the established threshold for true non-contrast images (e.g., 10HU) may help to differentiate between adrenal adenomas and metastases on contrast-enhanced CT., (© 2024. The Author(s).)

Metastatic pheochromocytomas and paragangliomas (PPGLs) are frequently associated with skeletal complications. Primary objective: to describe the frequency of adverse skeletal related events (SREs) in PPGL patients with bone metastases (BMs). Secondary objectives: to 1) identify predictive and prognostic factors for SREs and 2) obtain information on the effectiveness of bone resorption inhibitors in reducing SRE risk and improving outcomes in term of survival and SREs time onset. In this retrospective multicenter, multinational study, 294 PPGL patients were enrolled. SREs occurred in 90 patients (31 %). Fifty-five patients (19 %) had bone fractures, 47 (16 %) had spinal cord compression, and 11 (4 %) had hypercalcemia. Twenty-two patients (7 %) had more than one SRE. Sixty-four patients (22 %) underwent surgery, and 136 (46 %) underwent radiotherapy. SREs occurred a median of 4.4 months after diagnosis of BM (range, 0-246.6 months). Independent factors associated with reduced risk of SREs in multivariable analysis were I-131-MIBG radionuclide therapy (hazard ratio [HR], 0.536 [95 % CI, 0.309-0.932]; P = .027) and absence of liver metastases (HR, 0.638 [95 % CI, 0.410-0.992]; P = .046). The median overall survival duration was 5.3 year. In multivariable analysis, age younger than 48 years at PPGL diagnosis (HR, 0.558 [95 % CI, 0.3877-0.806]; P = .002), absence of liver metastases (HR, 0.618 [95 % CI, 0.396-0.965]; P = .034), treatment with bisphosphonates or denosumab (HR, 0.598 [95 % CI, 0.405-0.884]; P = .010), and MIBG radionuclide therapy (HR, 0.444 [95 % CI, 0.274-0.718]; P = .001) were associated with a reduced risk of death. SREs occur frequently and early in bone-metastatic PPGL patients but do not negatively impact survival. MIBG radionuclide therapy and treatment with bone resorption inhibitors are associated with favorable outcome., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Recently, the treatment landscape for metastatic pheochromocytomas and paragangliomas (MPPGL) has seen both progress and setbacks. We provide an up-to-date review of the multimodality management of MPPGL and discuss novel opportunities and current challenges in the treatment landscape. Given the unique clinical presentation of MPPGL, we discuss the management of hormone-related clinical sequelae and traditional modalities of therapy. Advances in the understanding of the molecular biology of these diverse tumors have enabled novel strategies such as augmenting DNA damage by targeted delivery of radionuclides such as 131 I and 177 Lu, abrogating tumor angiogenesis, hypoxia resistance, and DNA damage repair. Despite progress, we address the significant challenges still faced by patients and researchers engaged in efforts to improve outcomes in these rare cancers., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: V.S. reports research funding to the institution from Eli Lilly and Company and Crinetics Pharmaceuticals. He has served as a consultant to GE Oncology and has received speaking fees from Lantheus. He serves on the advisory board for Exelixis. N.P-T. has served as a consultant or advisory board member for and/or received honoraria from Actinium Pharma, Progenics, Medimmune/Astrazeneca, Illumina, and ImaginAb and conducts research institutionally supported by Y-mAbs, ImaginAb, BMS, Bayer, Clarity Pharma, Janssen, and Regeneron. C.J. reports receiving research funding to the institution from Exelixis, Lantheus Pharmaceuticals, Progenics Pharmaceuticals, and Merck Sharp and Dohme and is a scientific advisory board member for Lantheus Pharmaceuticals, Progenics Pharmaceuticals, and Merck Sharp and Dohme. K.P. was a one-time advisory board member of Exelixis, Lantheus, Ipsen, and Novartis., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Glandular metastases (GMs; adrenal gland, pancreas, thyroid, ovary, breast, or prostate) are rare in metastatic clear cell renal cell carcinoma (mccRCC). Previous studies have indicated that GM patients treated with antiangiogenic therapy experience significantly longer overall survival (OS)., Objectives: To assess outcomes for mccRCC with or without GMs treated with nivolumab., Design, Setting, and Participants: The GETUG-AFU-26 NIVOREN phase 2 trial evaluated the activity and safety of nivolumab in patients with mccRCC who experienced failure of antiangiogenic therapies (NCT03013335). In this ancillary study, patients were divided into two groups according to the presence or absence of at least one GM., Outcome Measurements and Statistical Analysis: The primary outcome was OS; secondary outcomes were progression-free survival (PFS) and the objective response rate (ORR). Survival was estimated using the Kaplan-Meier method. Univariate and multivariable Cox regression models are used to estimate the hazard ratio (HR) with 95% confidence interval (CI) for survival outcomes. Subgroup analyses were performed for patients with pancreatic metastases and patients with adrenal metastases., Results and Limitations: Among 720 patients treated with nivolumab between February 2016 and July 2017, 217 had GMs, of whom 151/217 had adrenal metastases and 86/217 had pancreatic metastasis. Patients with adrenal metastases had worse 12-mo OS (64% vs 71.1%) and 6-mo PFS (27.2% vs 36.6%) and a lower objective response rate (12.5%, 95% CI 7.6%-19.0%, vs 23.2%, 95% CI 19.8-27.0%; p = 0.005) than patients without adrenal metastases. Conversely, univariate analysis showed that patients with pancreatic metastases had significantly better 12-mo OS (82.3% vs 67.9%; HR 0.59, 95% CI 0.40-0.85) in comparison to patients with nonpancreatic GMs. On multivariable analysis, only adrenal metastasis remained associated with adverse prognosis., Conclusions: Adrenal metastasis is an independent prognostic factor for poor response and survival in the GETUG-AFU-26 NIVOREN trial. Limited activity with nivolumab was observed for patients with mccRCC with adrenal metastases. These results warrant an evaluation of the prognostic value of adrenal metastases in patients treated with immunotherapy combinations with ipilimumab or tyrosine kinase inhibitors., Patient Summary: Our study showed that metastasis in the adrenal glands could be an independent factor associated with poor response to immunotherapy and survival for patients with metastatic kidney cancer. It would be useful to evaluate the prognostic value of adrenal gland metastasis in patients treated with immunotherapy combinations or immunotherapy agents combined with drugs called tyrosine kinase inhibitors., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: Assess safety and efficacy of thermal ablation for adrenal metastases (AM) secondary to non-small cell lung cancer (NSCLC)., Materials and Methods: This retrospective study included patients with NSCLC AM treated with thermal ablation between 2/2010-11/2021. Local tumor progression free survival (LTPFS) and overall survival (OS) were calculated using Kaplan-Meier method. Adverse events were graded using Common Terminology Criteria for Adverse Events v5., Results: Seven patients (mean age ± SD, 63.9 ± 12.5 years; 6 males) with seven AM were treated in eight sessions. Retreatment was performed in one patient with residual disease. Five sessions were with microwave ablation and 3 with radiofrequency ablation. Mean tumor size was 20.1 ± 7.0 mm. Median number of ablation probes used was 1 (range, 1-5), with a median of 3 activations (range, 1-3), and average ablation time of 14.4 ± 15.0 minutes. Response based on RECIST v 1.1 or PERCIST criteria revealed stable disease in 1 tumor, progression of disease in 3 tumors (one was re-ablated), and partial response in 3 tumors. Median LTPFS was not reached (NR) [95 % CI: 1- NR]. Median OS was 47.97 months (95 % CI: 18.63- NR). Intraprocedural hypertension (blood pressure ≥180 mmHg) occurred during 5/8 (62.5 %) sessions and intraoperative tachycardia occurred during 2/8 (25 %) sessions. Complications within one month of ablation occurred in 3/8 (37.5 %) sessions: grade 2 pneumothorax, grade 1 hematuria, and grade 2 adrenal insufficiency., Conclusions: In this small series, thermal ablation for NSCLC AM resulted in prolonged local control and OS with no major complications., Competing Interests: Declaration of competing interest - Etay Ziv receives research grants from MSK, Druckenmiller, NETRF, AACR, NANETS, SIR, RSNA, Ethicon, and Novartis. - Stephen B. Solomon has received grants from GE healthcare, Elesta, and Johnson & Johnoson. He is a paid consultant for GE Healthcare, XACT, Endoways, Microbot, Varian, Merch, Orchestra Biomed, and MedX. He has stock options for Aperture Medical, Johnson & Johnson, and Lantheus. - Erica S. Alexander is a paid consultant of Boston Scientific. - The remaining authors have no conflicts to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Congenital adrenal hyperplasia (CAH) encompassed a bunch of autosomal recessive disorders characterized by impaired cortisol levels due to an enzymatic deficiency in steroid synthesis. In adult male patients with CAH, a frequent complication related to poor disease control is the development of ectopic adrenocortical tissue in the testes, named testicular adrenal rest tumors (TART). Conversely, ovarian adrenal rest tumors (OART) in females are extremely rare and adrenal rests in sites other than gonads are so uncommon to have been described only few times in literature., Case Presentation: We report a case of a male patient with untreated CAH and oncologic history of pleomorphic sarcoma who presented with massive bilateral adrenal enlargement and adrenal rest tumors in peri-lumbar and peri-cecal sites, which mimicked metastasis from sarcoma., Conclusions: The development of massive adrenal enlargement and ectopic adrenal rest tumors in sites other than gonads, even if very uncommon, should be suspected in patients with CAH and prolonged periods of undertreatment., (© 2024. The Author(s).)

Pheochromocytomas are rare tumours originating in chromaffin cells, representing 0.1%-1% of all secondary hypertension cases. The majority are benign and unilateral, characterised by the production of catecholamines and other neuropeptides. Mainly located in the adrenal gland, they are more frequent between the third and fifth decades of life. Iodine-131 metaiodobenzylguanidine ( 131 I-MIBG), a radiopharmaceutical agent used for scintigraphic localisation of pheochromocytomas, has been employed to treat malignant pheochromocytomas since 1983 in a few specialised centres around the world. We reviewed our clinical experience in one such case of a young lady who presented with history of abdominal pain, headache and lower back pain. On evaluation, ultrasonography revealed a right adrenal mass and elevated urine vanillylmandelic acid levels. Following surgical resection and histopathological confirmation of pheochromocytoma, MIBG scintigraphy revealed osseous metastases and hence, she underwent 131 I-MIBG therapy., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Abstract: Ganglioneuroma (GN) is the most differentiated and benign variant of neuroblastic tumors, most commonly located in the posterior mediastinum, followed by the retroperitoneum and adrenal gland. Children of <10 years of age are more commonly affected than adults. Though benign, GNs can very rarely metastasize to regional lymph nodes or distant sites like liver, bone, spleen, and soft tissues. Metastatic lesions are assumed to represent neuroblastomas in which the metastasis and the primary tumor, both have matured. This differentiation can occur spontaneously or after treatment. We present a primary ganglioneuroma of adrenal gland in a 4-year-old child with nodal metastasis, without any blastemal component at any site., (Copyright © 2024 Copyright: © 2024 Journal of Cancer Research and Therapeutics.)

Abstract: An 84-year-old man with prostate adenocarcinoma underwent 68 Ga-PSMA PET/CT due to PSA recurrence. Foci of 68 Ga-PSMA uptake were observed in bilateral adrenal glands. Adrenal MRI showed metastasis only in the left adrenal gland. Metastatic 68 Ga-PSMA uptake was also observed in the mediastinum and bone. Enzalutamide treatment was started. Follow-up 68 Ga-PSMA PET/CT scan showed regression in both adrenal gland metastases and other metastases., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The purpose of this paper is to summarize 3 methods for treating adrenal metastases with stereotactic body radiation therapy. This article is not meant to provide consensus guidelines but rather to present 4 practical examples of treatment techniques using different treatment platforms from 3 institutions., Competing Interests: Disclosures James B. Yu reports grant funding and speaking fees from Pfizer/Myovant, speaking fees from RefleXion, and consulting fees from Boston Scientific, outside the scope of this work. Simon S. Lo reports grants from the Kuni Foundation, travel funds from JASTRO, and leadership roles at Radiosurgery Society and ACR. Minsun Kim, Erin Sculley, and David J. Grew report no conflicts of interest. Kathryn Hitchcock reports being the local principal investigator for research sponsored by Merck, compensated for writing work for MedScape, and being compensated by NRG Oncology for a leadership role. She also reports food and lodging from Florida Society for Clinical Oncology, Florida Dental Convention, and honoraria from MSKCC Cancer Center. She reports support for meeting travel from Philips, Mvision, Colorectal Cancer Alliance, and GI ASCO. She reports 3 unrelated patents and unpaid volunteer membership in the NCI, NIH, and ASTRO committees., (Copyright © 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: To study the prevalence of primary adrenal tumors and adrenal metastases in patients with neuroendocrine neoplasms (NENs) and describe these in detail. NENs can be further divided into neuroendocrine tumor (NET) and neuroendocrine carcinoma (NEC)., Methods: A review of medical files was conducted for all patients who underwent a 68 Gallium-DOTATOC-PET/CT during 2010-2023 or adrenalectomy during 1999-2023 at the Karolinska University Hospital., Results: In total, 68 Gallium-DOTATOC-PET/CT was performed on 1750 individuals with NEN, among whom 12 (0.69%) had adrenal tumors. Of these, 9 (0.51%) were NEN metastases. Out of 1072 adrenalectomies, 4 (0.37%) showed evidence of NEN metastases. Thus, 16 patients with NEN exhibited adrenal tumors. The adrenal tumors were found on average 5 years after the NEN diagnosis and 19% of the adrenal tumors with simultaneous NEN were benign. Few had all adrenal hormones measured. None had an adrenal insufficiency nor an adrenal biopsy. Another synchronous metastasis was found in 69% at the time of the adrenal tumor discovery. During the median 2-year follow-up, 38% of the subjects had deceased (with the exclusion of individuals presenting supposedly benign adrenal tumors 31%) all due to tumor complications. A comparison between individuals identified through 68 Gallium-DOTATOC-PET/CT and those who underwent adrenalectomy revealed a higher prevalence of NETs in the former group and NECs in the latter group., Conclusion: Adrenal primary tumors and adrenal metastases are infrequent occurrences in patients with NEN. Most cases involved the presence of NEN metastasis upon the initial discovery of adrenal tumors. The overall prognosis was found to be favorable., (© 2024. The Author(s).)

Ectopic ACTH syndrome (EAS) remains one of the most demanding diagnostic and therapeutic challenges for endocrinologists. Thymic neuroendocrine tumors account for 5%-10% of all EAS cases. We report a unique case of a 31-year-old woman with severe EAS caused by primary metastatic combined large-cell neuroendocrine carcinoma and atypical carcinoid of the thymus. The patient presented with severe hypercortisolemia, which was successfully controlled with continuous etomidate infusion. Complex imaging initially failed to detect thymic lesion; however, it revealed a large, inhomogeneous, metabolically active left adrenal mass infiltrating the diaphragm, suspected of primary disease origin. The patient underwent unilateral adrenalectomy, which resulted in hypercortisolemia resolve. The pathology report showed an adenoma with adrenal infarction and necrosis. The thymic tumor was eventually revealed a few weeks later on follow-up imaging studies. Due to local invasion and rapid progression, only partial resection of the thymic tumor was possible, and the patient was started on radio- and chemotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dzialach, Wojciechowska-Luzniak, Maksymowicz and Witek.)

Competing Interests: Competing interests: None declared.

Abstract: Prostate carcinoma (PC) is the second most common malignant tumor in males globally. The metastatic spread of PC usually involves the pelvic and abdominal lymph nodes and the skeletal system. Cutaneous metastases are exceedingly uncommon and typically manifest themselves late in the disease course, considered as ominous sign with limited treatment options and a poor prognosis. We describe a patient wherein 68 Ga-PSMA-11 PET/CT detected multiple uncommon metastatic sites in the cutaneous region of the scrotum, penis, and thigh, as well as in the subcutaneous region of anterior abdominal wall, and in bilateral adrenal glands. These findings served as a theranostic tool for selecting 177 Lu-PSMA-617 treatment for these extremely rare metastatic sites., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Data regarding treatment options and their efficacy for metastatic paragangliomas (mPPGL) is limited. This study aims to report a single center experience in treating mPPGL, comparing the efficacy and safety of various treatment approaches., Methods: Retrospective analysis of patients with mPPGL treated at an Endocrinology Department of a cancer institute between January 2000 and October 2022., Results: We analyzed 25 patients with mPPGL, 8 pheochromocytomas and 20 paragangliomas (12% multifocal), followed for a median of 9 [4; 14] years. Surgical approach, aimed at the primary tumor or at debulking of metastases, was the only treatment achieving complete response: 87% in primary tumor and 87.5% with debulking of metastases. These were long-lasting results with a duration of 69 (23.8; 136.8) months in primary tumor removal and 35.1 (15.3; 41) months in metastases debulking. As for other therapeutic approaches, such as radioactive isotopes, tyrosine kinase inhibitors, chemotherapy and external beam radiotherapy, the main outcome was stable disease, with few partial responses. At the last follow-up, 66% of the patients were alive, 15.4% were in remission and 84.6% had stable disease. Median overall survival was 14 years. The 5-year and 10-year survival rates from primary tumor diagnosis were 77.9% and 66.9% respectively, and from metastasis diagnosis were 67.4% and 55.6%, respectively., Conclusion: This is the only European single center analysis addressing outcomes of different therapies in mPGL. The results support surgery as a first-line treatment, being the only approach that may achieve complete response with satisfactory and long-lasting results., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Metastatic phaeochromocytomas and paragangliomas (MPPGs) are orphan diseases. Up to 50% of MPPGs are associated with germline pathogenic variants of the SDHB gene. These tumours and many non-familial MPPGs exhibit a phenotype that is characterised by abnormal angiogenesis. We aimed to assess the activity and safety of cabozantinib, an antiangiogenic multi-tyrosine kinase inhibitor, in patients with MPPGs., Methods: The Natalie Trial is a single-arm, phase 2 clinical trial being conducted at The University of Texas MD Anderson Cancer Center (Houston, TX, USA). Patients aged 18 years or older with histologically confirmed, progressive, and unresectable MPPGs, with an Eastern Cooperative Oncology Group performance status of 0-2, were treated with oral cabozantinib 60 mg/day. The primary endpoint was the investigator-assessed overall response rate per the Response Evaluation Criteria in Solid Tumours version 1.1 criteria. All outcomes were assessed in all evaluable participants who received any amount of study treatment. The trial is registered with ClinicalTrials.gov (NCT02302833) and is active but not recruiting., Findings: From March 10, 2015, to May 11, 2021, 17 patients (13 male participants and four female participants) were enrolled. The median follow-up was 25 months (IQR 18-49). The overall response rate was 25·0% (95% CI 7·3-52·4; four of 16 patients). Seven grade 3 adverse events were reported in six patients, including single cases of hand-and-foot syndrome, hypertension, rectal fistula, QT prolongation, and asymptomatic hypomagnesaemia, and two cases of asymptomatic elevations of amylase and lipase. There were no grade 4 adverse events and no patient died on-study., Interpretation: Cabozantinib shows promising activity in patients with MPPGs., Funding: Team NAT Foundation, Margaret Cazalot, and Clarence P Cazalot., Competing Interests: Declaration of interests CJ reports receiving research funding to the institution from Exelixis, Lantheus Pharmaceuticals, Progenics Pharmaceuticals, and Merck Sharp and Dohme and is a scientific advisory board member for Lantheus Pharmaceuticals, Progenics Pharmaceuticals, and Merk Sharp and Dohme. MAH reports receiving research funding to the institution from Exelixis, Merck, and Corcept and Honoraria from HRA pharma. MC reports receiving research funding to the institution from Exelixis, SeaGen, ApricityHealth, US Department of Defense, Janssen, Pfizer, and AstraZeneca; is a scientific advisory board member for Exelixis, Eisai, and SeaGen; and is a member of the speaker's bureau for Curio Science, Dava Oncology, and MJH Life Sciences. YL reports receiving research funding to the institution from Lantheus Pharmaceuticals. All other authors declare no competing interests., (© 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objective: The existing prediction models for metastasis in pheochromocytomas/paragangliomas (PPGLs) showed high heterogeneity in different centers. Therefore, this study aimed to establish new prediction models integrating multiple variables based on different algorithms., Design and Methods: Data of patients with PPGLs undergoing surgical resection at the Peking Union Medical College Hospital from 2007 to 2022 were collected retrospectively. Patients were randomly divided into the training and testing sets in a ratio of 7:3. Subsequently, decision trees, random forest, and logistic models were constructed for metastasis prediction with the training set and Cox models for metastasis-free survival (MFS) prediction with the total population. Additionally, Ki-67 index and tumor size were transformed into categorical variables for adjusting models. The testing set was used to assess the discrimination and calibration of models and the optimal models were visualized as nomograms. Clinical characteristics and MFS were compared between patients with and without risk factors., Results: A total of 198 patients with 59 cases of metastasis were included and classified into the training set (n = 138) and testing set (n = 60). Among all models, the logistic regression model showed the best discrimination for metastasis prediction with an AUC of 0.891 (95% CI, 0.793-0.990), integrating SDHB germline mutations [OR: 96.72 (95% CI, 16.61-940.79)], S-100 (-) [OR: 11.22 (95% CI, 3.04-58.51)], ATRX (-) [OR: 8.42 (95% CI, 2.73-29.24)] and Ki-67 ≥ 3% [OR: 7.98 (95% CI, 2.27-32.24)] evaluated through immunohistochemistry (IHC), and tumor size ≥ 5 cm [OR: 4.59 (95% CI, 1.34-19.13)]. The multivariate Cox model including the above risk factors also showed a high C-index of 0.860 (95% CI, 0.810-0.911) in predicting MFS after surgery. Furthermore, patients with the above risk factors showed a significantly poorer MFS (P ≤ 0.001)., Conclusions: Models established in this study provided alternative and reliable tools for clinicians to predict PPGLs patients' metastasis and MFS. More importantly, this study revealed for the first time that IHC of ATRX could act as an independent predictor of metastasis in PPGLs., (© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Background: The decision for resection of adrenal metastasis from colorectal cancers remain controversial and there is no proposed standard treatment. The aim of the article is to review the available literature on outcomes and complications rates following adrenalectomy for adrenal metastasis from colorectal cancer., Methods: Relevant papers were identified through electronic databases. Data was extracted independently by two authors on a Microsoft Excel spreadsheet up to June 2023., Results: A total of 55 studies were included in the final analysis (145 cases). A large proportion of patients had an uneventful postoperative recovery following surgical adrenalectomy. The mean length of follow up ranged from 2 months to 9.5 years. A total of 33 (22.8%) patients were alive and well with no evidence of local or systemic recurrence; 2 (1.4%) patients had recurrence in the bed of adrenalectomy; 2 (1.4%) patients were alive with recurrence in the contralateral adrenal gland; 4 (2.8%) patients were alive with extra-adrenal metastasis, and 7 (4.8%) patients were alive and well with no comments regarding local and systemic recurrence. Post-operative mortality following adrenalectomy was uncommon: 1 patient died due to systemic sepsis following anastomotic leak. 17.2% of patients died due to disease progression., Conclusion: If complete resection can be achieved, surgical adrenalectomy in the surgically fit patient should be strongly considered, especially in patients with solitary adrenal metastasis which may translate into survival benefits and potential surgical cure., (© 2024 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Adrenocortical carcinoma (ACC) is a rare malignant tumour from the adrenal cortex. Half of the cases are functional, with ACTH-independent autonomous cortisol production being the most common. It is rare for ACC to present with markedly elevated metanephrine levels, characteristic of pheochromocytoma. We report a case of a large functioning adrenal tumour with overlapping biochemical features of ACC and pheochromocytoma. Biopsy confirmed the histopathological diagnosis of metastatic ACC., Competing Interests: The authors declared no conflict of interest., (© 2024 Journal of the ASEAN Federation of Endocrine Societies.)

A 72-year-old man was referred to our urology department due to a giant adrenal tumor detected by computed tomography( CT). Endocrine screening showed that cortisol, renin, aldosterone, adrenaline, and noradrenaline levels were all normal, and there was no evidence of adrenal hyperfunction. The adrenal tumor was so large that we suspected malignancy. Contrast-enhanced CT of the abdomen was performed for qualitative diagnostic purposes, and showed wall thickening of the sigmoid colon extending for approximately 6 cm. Lower gastrointestinal endoscopy was performed and revealed a full circumferential type 2 tumor in the sigmoid colon. Biopsy results showed intermediate differentiated ductal adenocarcinoma. Tumor markers were as follows: CEA 23.1 ng/mL, CA19-9 962 U/mL. The adrenal tumor was suspected of being malignant due to its size, but imaging examinations did not lead to a diagnosis of primary or metastatic disease. There were no tumors other than those in the sigmoid colon and adrenal glands. Since complete resection was deemed possible, sigmoid colon resection and combined left adrenalectomy were performed for both a diagnosis and treatment. A histopathological examination revealed that the histology of the adrenal tumor resembled that of colorectal cancer, leading to a diagnosis of left adrenal metastasis from sigmoid colon cancer.

Objectives: For diagnosing left adrenal gland metastasis in lung cancer, clinical guidelines recommend to perform EUS, but EUS-B (EUS using an EBUS-scope) is increasingly being used. We evaluated the diagnostic performance of both procedures., Materials and Methods: We did a systematic review (PROSPERO, CRD42023416205) and searched MEDLINE and EMBASE on 04-July-2023 for studies evaluating EUS and/or EUS-B in diagnosing left adrenal gland metastases in adults with (suspected) lung cancer. Outcomes were: (1) ability to visualize the left adrenal gland, (2) ability to sample (in those with successful visualization and in whom sampling was attempted), (3) ability to obtain adequate material (in those with successful sampling), (4) malignancy detection rate (in those with successful sampling), and (5) remaining risk of malignancy (in those with a negative EUS(-B)-FNA and undergoing a reference standard). We performed random-effects meta-analyses., Results: We included 19 studies (EUS: n = 11, EUS-B: n = 6, both: n = 2), covering 1712 patients. All studies had high (n = 18) or unclear (n = 1) risk of bias (QUADAS-2). Average ability to visualize the left adrenal gland was 0.94 (95 %CI 0.82-0.98; n = 7 studies). Average ability to sample was 1.00 (95 %CI 0.99-1.00; n = 9). Average ability to obtain adequate material was 0.96 (95 %CI 0.93-0.98; n = 18). Average malignancy detection rate was 0.42 (95 %CI 0.34-0.49; n = 18). Remaining risk of malignancy was 0.07 (95 %CI 0.04-0.12; n = 8). Ability to visualize was slightly higher for EUS (0.99; 95 %CI 0.90-1.00) than EUS-B (0.84; 95 %CI 0.70-0.92; p = 0.025), but the other performance characteristics were similar. No major complications were reported., Conclusion: Both EUS and EUS-B have good performance and are safe for left adrenal gland analysis in patients with lung cancer, but the number of high-quality studies is limited and further well-constructed prospective studies are needed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Adrenal metastasectomy has an increasing role in multimodality oncologic care for diverse primary cancer types. In this review, we discuss the epidemiology, evaluation, and contemporary best practices in the management of adrenal metastases from various primaries. Initial evaluation of suspected adrenal metastases should include diagnostic imaging to assess the extent of tumor involvement and determine surgical resectability, as well as biochemical evaluation for hormone secretion. Biopsy has a minimal role and should only be performed in tumors that are established to be non-hormone secreting and when the biopsy results would change clinical management. Adrenal metastasectomy is associated with survival benefit in selected patients. We suggest that adrenal metastasectomy has the greatest benefit in four clinical scenarios: (1) disease limited to the adrenal gland in which adrenalectomy renders the patient disease-free; (2) isolated progression in the adrenal gland in the setting of otherwise controlled metastatic extra-adrenal disease; (3) need for palliation of symptoms related to adrenal metastases; or (4) in the context of tissue-based clinical trials. Both minimally invasive and open adrenalectomy techniques are safe and appear to have equivalent oncologic outcomes. Minimally invasive approaches are favored when technically feasible while maintaining oncologic principles. A multidisciplinary evaluation including clinicians with expertise in the primary cancer type is essential to the successful management of adrenal metastases., (© 2023. Society of Surgical Oncology.)

BACKGROUND. Adrenal masses are often indeterminate on single-phase postcontrast CT. Dual-energy CT (DECT) with three-material decomposition algorithms may aid characterization. OBJECTIVE. The purpose of this study was to compare the diagnostic performance of metrics derived from portal venous phase DECT, including virtual noncontrast (VNC) attenuation, fat fraction, iodine density, and relative enhancement ratio, for characterizing adrenal masses. METHODS. This retrospective study included 128 patients (82 women, 46 men; mean age, 64.6 ± 12.7 [SD] years) who between January 2016 and December 2019 underwent portal venous phase abdominopelvic DECT that showed a total of 139 adrenal lesions with an available reference standard based on all imaging, clinical, and pathologic records (87 adenomas, 52 nonadenomas [48 metastases, two adrenal cortical carcinomas, one ganglioneuroma, one hematoma]). Two radiologists placed ROIs to determine the following characteristics of the masses: VNC attenuation, fat fraction, iodine density normalized to portal vein, and for masses with VNC greater than 10 HU, relative enhancement ratio (ratio of portal venous phase attenuation to VNC attenuation). Readers' mean measurements were used for ROC analyses, and clinically optimal thresholds were derived as thresholds yielding the highest sensitivity at 100% specificity. RESULTS. Adenomas and nonadenomas were significantly different (all p < .001) in VNC attenuation (mean ± SD, 18.5 ± 12.9 vs 34.1 ± 8.9 HU), fat fraction (mean ± SD, 24.3% ± 8.2% vs 14.2% ± 5.6%), normalized iodine density (mean ± SD, 0.34 ± 0.15 vs 0.17 ± 0.17), and relative enhancement ratio (mean ± SD, 186% ± 96% vs 58% ± 59%). AUCs for all metrics ranged from 0.81 through 0.91. The metric with highest sensitivity for adenoma at the clinically optimal threshold (i.e., 100% specificity) was fat fraction (threshold, ≥ 23.8%; sensitivity, 59% [95% CI, 48-69%]) followed by VNC attenuation (≤ 15.2 HU; sensitivity, 39% [95% CI, 29-50%]), relative enhancement ratio (≥ 214%; sensitivity, 37% [95% CI, 25-50%]), and normalized iodine density (≥ 0.90; sensitivity, 1% (95% CI, 0-60%]). VNC attenuation at the traditional true noncontrast attenuation threshold of 10 HU or lower had sensitivity of 28% (95% CI, 19-38%) and 100% specificity. Presence of fat fraction 23.8% or greater or relative enhancement ratio 214% or greater yielded sensitivity of 68% (95% CI, 57-77%) with 100% specificity. CONCLUSION. For adrenal lesions evaluated with single-phase DECT, fat fraction had higher sensitivity than VNC attenuation at both the clinically optimal threshold and the traditional threshold of 10 HU or lower. CLINICAL IMPACT. By helping to definitively diagnose adenomas, DECT-derived metrics can help avoid downstream imaging for incidental adrenal lesions.

Adrenal glands represent a common site of metastases from several primary tumors, including lung cancer, breast cancer and melanoma. Surgical resection is considered the standard of care, but surgery is not always feasible given the challenges related to anatomical site and/or due to patient and/or disease characteristics. Stereotactic body radiation therapy (SBRT) represents a promising treatment for oligometastases, though the literature on its role for adrenal metastases is still heterogeneous. Herein are summarized the most relevant published studies on the efficacy and safety of SBRT for adrenal gland metastases. The preliminary data suggests that SBRT yields high local control rates and symptom relief with a mild pattern of toxicity. Advanced radiotherapy techniques including IMRT and VMAT, a BED10 > 72 Gy and the use of 4DCT for motion control should be considered for a high quality ablative treatment of adrenal gland metastases., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: This study aimed to determine the accuracy of texture analysis in differentiating adrenal lesions on unenhanced computed tomography (CT) images., Methods: In this single-center retrospective study, 166 adrenal lesions in 140 patients (64 women, 76 men; mean age 56.58 ± 13.65 years) were evaluated between January 2015 and December 2019. The lesions consisted of 54 lipid-rich adrenal adenomas, 37 lipid-poor adrenal adenomas (LPAs), 56 adrenal metastases (ADM), and 19 adrenal pheochromocytomas (APhs). Each adrenal lesion was segmented by manually contouring the borders of the lesion on unenhanced CT images. A texture analysis of the CT images was performed using Local Image Feature Extraction software. First-order and second-order texture parameters were assessed, and 45 features were extracted from each lesion. One-Way analysis of variance with Bonferroni correction and the Mann-Whitney U test was performed to determine the relationships between the texture features and adrenal lesions. Receiver operating characteristic curves were performed for lesion discrimination based on the texture features. Logistic regression analysis was used to generate logistic models, including only the texture parameters with a high-class separation capacity (i.e., P < 0.050). SPSS software was used for all statistical analyses., Results: First-order and second-order texture parameters were identified as significant factors capable of differentiating among the four lesion types ( P < 0.050). The logistic models were evaluated to ascertain the relationships between LPA and ADM, LPA and APh, and ADM and APh. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the first model (LPA vs. ADM) were 85.7%, 70.3%, 81.3%, 76.4%, and 79.5%, respectively. The sensitivity, specificity, PPV, NPV, and accuracy of the second model (LPA vs. APh) were all 100%. The sensitivity, specificity, PPV, NPV, and accuracy of the third model (ADM vs. APh) were 87.5%, 82%, 36.8%, 98.2%, and 82.7%, respectively., Conclusion: Texture features may help in the characterization of adrenal lesions on unenhanced CT images.

Purpose: Adrenal gland metastases (AGMs) are a common manifestation of metastatic tumor spread, especially in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). In patients with a limited systemic tumor burden, effective treatments for AGMs are needed. Due to varying fractionation schemes and limited reports, short-course treatment results for stereotactic body radiotherapy (SBRT) for AGMs are lacking. This work analyzes the outcomes of short-course SBRT for AGMs., Methods: Patients who underwent robotic SBRT for AGMs with one to five fractions were eligible for analysis., Results: In total, data from 55 patients with 72 AGMs from two institutions were analyzed. Most AGMs originated from renal cell carcinoma (38%) and NSCLC (35%). The median follow-up was 16.4 months. The median prescription dose and isodose line were 24 Gy and 70%, respectively. Most patients (85%) received SBRT with just one fraction. The median biologically effective dose assuming an α/β ratio of 10 (BED 10 ) was 80.4 Gy. The local control and progression-free survival after 1 and 2 years were 92.9%, 67.8%, and 46.2%, as well as 24.3%, respectively. Thirteen patients (24%) suffered from grade 1 or 2 toxicities. The BED 10 showed a significant impact on LC (p < 0.01). Treatments with a BED 10 equal to or above the median were associated with a better LC (p < 0.01)., Conclusion: Robotic SBRT is an efficient and safe treatment modality for AGM. Treatment-associated side effects are sporadic and manageable. Results suggest short-course SBRT to be a preferable and time-saving treatment option for the management of AGMs if an adequate BED 10 can be safely applied., (© 2022. The Author(s).)

Background: While the number of adrenal biopsies has increased due to more "incidentalomas" were detected by widespread use of imaging studies, there have been very limited studies to evaluate the utility of rapid on-site evaluation (ROSE) in obtaining adequate core needle biopsy (CNB) tissue for diagnosis of adrenal lesions., Methods: We retrospectively reviewed all percutaneous adrenal CNB cases with available ROSE for a 12-year period in our institute in order to assess the usefulness of ROSE in adrenal CNB sampling., Results: A total of 83 cases were identified in our database. The majority of cases (52/83, 63%) were diagnosed as metastatic malignancies with the lung being the most common primary site. Adrenal hyperplasia/adenoma was the most common primary adrenal lesion. The concordance between the ROSE interpretations and CNB final diagnoses is 80%. The interpretation errors accounted for majority (11/17, 65%) of the discordant cases., Conclusion: ROSE assessment during adrenal CNB procedures is a helpful tool for obtaining adequate diagnostic tissue. Pathologists should be familiar with adrenal cytology in order to reduce interpretation errors at ROSE., (© 2022 Wiley Periodicals LLC.)

Regarding the prognosis of cases with advanced-stage hepatocellular carcinoma (HCC), a recent clinical study showed that the immune checkpoint inhibitors atezolizumab plus bevacizumab have superior efficacy to sorafenib. However, only a few reports have focused on their effects on extrahepatic metastases. We herein report a case of HCC in a 59-year-old man with intrahepatic lesions treated successfully by hepatic arterial chemoembolization, radiotherapy, and sorafenib; the extrahepatic lesion in the adrenal gland was treated by atezolizumab plus bevacizumab. The patient showed a tumor-free condition for one year. We have summarized the clinical course and reviewed the literature to underscore the efficacy of atezolizumab plus bevacizumab for treating extrahepatic lesions of HCC.

Aim: To assess if radiomic feature analysis could help to differentiate between the lipid-poor adenomas and metastases to the adrenal glands., Materials and Methods: Eighty-six patients (women:men 42:44; mean age 66 years) with biopsy-proven adrenal metastases and 55 patients (women:men 39:16; mean age 67 years) with lipid-poor adenomas who underwent contrast-enhanced, portal-venous phase CT of the abdomen. Radiomic features were extracted using the PyRadiomics extension for 3D Slicer. Following elastic net regularisation, seven of 1,132 extracted radiomic features were selected to build a radiomic signature. This was combined with patient demographics to create a predictive nomogram. The calibration curves in both the training and validation cohorts were assessed using a Hosmer-Lemeshow test., Results: The radiomic signature alone yielded an area under the curve of 91.7% in the training cohort (n=93) and 87.1% in the validation cohort (n=48). The predictive nomogram, which combined age, a previous history of malignancy, and the radiomic signature, had an AUC of 97.2% in the training cohort and 90.4% in the validation cohort., Conclusion: The present nomogram has the potential to differentiate between a lipid-poor adrenal adenoma and adrenal metastasis on portal-venous CT., (Copyright © 2022 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Optimal doses for the treatment of adrenal metastases with stereotactic radiotherapy (SBRT) are unknown. We aimed to identify dose-volume cut-points associated with decreased local recurrence rates (LRR). A multicenter database of patients with adrenal metastases of any histology treated with SBRT (biologically effective dose, BED10 ≥50 Gy, ≤12 fractions) was analyzed. Details on dose-volume parameters were required (planning target volume: PTV-D98%, PTV-D50%, PTV-D2%; gross tumor volume: GTV-D50%, GTV-mean). Cut-points for LRR were optimized using the R maxstat package. One hundred and ninety-six patients with 218 lesions were included, the largest histopathological subgroup was adenocarcinoma (n = 101). Cut-point optimization resulted in significant cut-points for PTV-D50% (BED10: 73.2 Gy; P = .003), GTV-D50% (BED10: 74.2 Gy; P = .006), GTV-mean (BED10: 73.0 Gy; P = .007), and PTV-D2% (BED10: 78.0 Gy; P = .02) but not for the PTV-D98% (P = .06). Differences in LRR were clinically relevant (LRR ≥ doubled for cut-points that were not achieved). Further dose-escalation was not associated with further improved LRR. PTV-D50%, GTV-D50%, and GTV-mean cut-points were also associated with significantly improved LRR in the adenocarcinoma subgroup. Separate dose optimizations indicated a lower cut-point for the PTV-D50% (BED10: 69.1 Gy) in adenocarcinoma lesions, other values were similar (<2% difference). Associations of cut-points with overall survival (OS) and progression-free survival were not significant but durable freedom from local recurrence was associated with OS in a landmark model (P < .001). To achieve a significant improvement of LRR for adrenal SBRT, a moderate escalation of PTV-D50% BED10 >73.2 Gy (adenocarcinoma: 69.1 Gy) should be considered., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Melanoma remains a large global burden with a significant proportion of patients succumbing to metastatic disease. The adrenal gland is a common area for metastasis with surgical treatment as the main modality. Radiotherapy is less utilised in this setting with uncertainty over deliverability and efficacy. Here, we present the details and outcomes of 20 patients treated with radiotherapy, with or without systemic therapy, for melanoma adrenal metastasis in a single institute. Twenty patients were identified from radiation treatment and medical records from between 2015 and 2019 at our institution. Three patients had bilateral radiotherapy treatments and therefore 23 adrenal lesions were analysed. Demographics, indications for treatment, radiotherapy methodology and outcomes were recorded. Outcomes were based on serial 18F FDG PET/computerized tomography scans reporting using the PERCIST criteria. The most common indication for radiotherapy was oligo-progressive disease (70%) followed by symptom palliation. Eight (35%) of the treatments were delivered by stereotactic ablative body radiotherapy. Twelve (60%) patients had concurrent immunotherapy. Twenty of twenty-three (87%) adrenal lesions had an initial response to treatment with 12 (60%) maintaining local control until death or end of follow-up. Median adrenal-specific progression-free survival was 13 months. Four patients (17%) required salvage adrenalectomy. Symptom palliation was achieved in the majority of patients for which it was indicated and there were no grade three toxicities. The median time from radiotherapy to change of immunotherapy treatment was 4 months. Radiotherapy for melanoma adrenal metastasis is effective and deliverable. With the majority of patients achieving a palliative and clinically relevant durable response, adrenalectomy can be reserved as a salvage option., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Hyaluronan (HA) is one of the essential elements of the extracellular matrix (ECM), involved in the onset of metastasis in various tumors. The interaction and binding of the ligand-receptor HA/cluster of differentiation-44 (CD44) regulate the physical and biochemical properties of the ECM, which correlates with an increased propensity toward metastasis and poor survival outcome. Our study aimed to explore HA for predicting metastasis and survival rate in patients with small-cell lung cancer (SCLC)., Materials and Methods: This prospective cohort study recruited 72 patients with SCLC. Plasma HA and CD44 levels were assayed by enzyme-linked immunosorbent assay (ELISA) for 72 cases before initial systematic treatment (baseline samples), and plasma HA was detected via after-2-cycle-chemotherapy (A-2-C-CT) in 48 samples. Logistic regression analysis and the Cox proportional risk model were used to determine the independent predictors of distant metastasis and survival rate of patients., Results: Baseline plasma HA was notably associated with bone metastasis (BM) [OR (95% CI = 1.015 (1.006-1.024), p = 0.001]. Multivariate logistic regression analysis showed that baseline plasma HA was chosen as an independent predictor of BM. Either baseline HA or CD44 or both were associated with BM. Dynamic alteration of HA was notably associated with A-2-C-CT clinical efficacy. Multivariate Cox regression analysis in forward likelihood ratio showed that A-2-C-CT HA was an independent predictor of progression-free survival (PFS) and overall survival (OS)., Conclusions: HA appears to be used as an independent predictive factor for BM, and the dynamic detection of HA can predict prognosis in SCLC patients. The mechanism of the HA/CD44 axis in BM of SCLC deserves further exploration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhao, Zhang, Hu, Zhang, Liu, Wang, Guo, Zhang, Li and Li.)

Introduction: Lung cancer patients (LCP) require invasive evaluation of left adrenal glands (LAG) if distant metastases (M1b/1c) are suspected in CT or PET-CT. Only few studies showed utility of endosonography and particularly EUS-b-FNA as minimally invasive endoscopic method of LAG analysis., Material and Methods: A retrospective study of consecutive LCP was conducted in two pulmonology centers between January 2010 and December 2019. Records of complete endosonographic staging with use of single ultrasound bronchoscope or two scopes were overviewed. The analysis included cases of enlarged LAG (body size or limbs > 10 mm) examined and sampled by EUS-b-FNA or EUS-FNA., Results: 142 of 2596 LCP staged by complete endosonography (M: 88, F: 54 mean age 64.7) had enlarged LAG, which were biopsied by conventional EUS-FNA (52) and/or by EUS-b-FNA (90). Strong correlation with gland diameter (P < 0.001) was observed. The incidence of LAG metastases in analyzed group was 52.1% (74/142) and regarding histology: SCLC 76.9% (10/13), adenocarcinoma 66.7% (44/66), NSCLC 56.3% (9/16) and SCC 17.5% (7/40). A specificity and PPV for both methods were 100%. A sensitivity, accuracy and NPV for EUS-FNA were 91.7%, 96.2%, 93.3% and for EUS-b-FNA 88%, 93.3% and 87%, respectively and no significant differences for both methods were noted (P = 0.62, 0.44, 0.35). No severe complications afterall biopsies were observed. A six months clinical follow up included all negative LCP with enlarged LAG., Conclusions: After our study EUS-b-FNA seems to be a reasonable method of choice for LAG assesssment in LCP.

Case Presentation: A 30-year-old man with a history of childhood asthma, a 15-pack-year smoking history, and methamphetamine abuse was intubated and started on mechanical ventilation because of acute hypoxic respiratory failure after experiencing progressive dyspnea and a nonproductive cough over the previous year. During the previous 3 months, he had multiple clinic visits, with chest radiographs showing diffuse, bilateral, reticulonodular opacities and small bilateral pleural effusions and was treated for community-acquired pneumonia. Testing for COVID pneumonia was negative, and he failed to respond to antimicrobial therapy. Physical examination on admission showed diffuse fine crackles bilaterally on lung auscultation. Admission laboratory test results were unremarkable., (Copyright © 2021. Published by Elsevier Inc.)

Adrenal metastases occur in 15-35% of oncological patients. Surgery is the first treatment option. Stereotactic body radiotherapy (SBRT) has been largely explored in oligometastatic patients unfit for surgery, representing an effective and non-invasive local treatment. The results of a multi-institutional experience of SBRT on adrenal metastases in the oligorecurrent or oligoprogressive setting are herein reported. We collected data of adrenal gland metastases treated with SBRT in three Italian centers from 2010 to 2020. End-points of the present study were: Overall survival (OS), Local control of treated metastases (LC), Progression free survival (PFS), and toxicity. 149 adrenal gland metastases were treated with SBRT in 142 patients. The most common primary tumor was lung cancer (58.4%), followed by kidney cancer (9.4%). Median lesion's volume was 28.5 cm 3 (2.5-323.4). The median SBRT dose was 40 Gy (10-60). Median follow-up was 14.4 months. One- and two-year OS were 72.3% and 53.5%. At univariate analysis performance status correlated with survival (HR 1.57, p = 0.006). One- and two-year LC were 85.4% and 79.2%, with lung primary tumor (HR 0.33, p = 0.021) and BED10 (HR 0.97, p = 0.036) significant independent factors. One- and two-year PFS were 37.7% and 24.8%. Median time to polymetastatic disease was 11.3 months. Grade 1 and 2 toxicity occurred in 21 (14.7%) and 3 (2.1%) patients. The results from this large multi-center study confirm the efficacy and safety of SBRT in the management of adrenal gland metastases, as a valid alternative to other more invasive local approaches., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)