Adrenal angiosarcoma, a rare neoplasm: a case report and a literature review
Case Report

Adrenal angiosarcoma, a rare neoplasm: a case report and a literature review

Gaia Cicioni1 ORCID logo, Immacolata Iannone1, Cristina De Padua1, Enrico Spalice1, Daniele Crocetti1, Mariarita Tarallo1, Luigi Petramala2, Claudio Letizia3, Paolo Sapienza1

1Department of Surgery, Sapienza University of Rome, Rome, Italy; 2Department of Medical and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy; 3Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

Contributions: (I) Conception and design: G Cicioni, P Sapienza, D Crocetti; (II) Administrative support: G Cicioni, P Sapienza; (III) Provision of study materials or patients: G Cicioni, I Iannone, P Sapienza; (IV) Collection and assembly of data: G Cicioni, P Sapienza; (V) Data analysis and interpretation: G Cicioni, P Sapienza; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Paolo Sapienza, MD, PhD. Professor of Surgery, Chair Department of Surgery, Chief General and Mini-Invasive Surgical Unit, Department of Surgery, Sapienza University of Rome, AOU Policlinico Umberto I, Viale del Policlinico 155, Rome 00161, Italy. Email: paolo.sapienza@uniroma1.it.

Background: Angiosarcoma (AS) is a rare malignant tumor of vascular endothelial origin, accounting for approximately 1% of soft tissue sarcomas. Primary adrenal AS represents an exceptionally rare entity, with very limited cases reported in the literature, resulting in significant diagnostic and therapeutic challenges.

Case Description: A 67-year-old male with arterial hypertension presented with an incidentally detected left adrenal mass on abdominal ultrasound. Contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) revealed a large heterogeneous lesion measuring up to 90 mm × 82 mm × 88 mm, with hemorrhagic components and progressive enlargement, raising suspicion for an aggressive malignancy. Endocrine workup was unremarkable. The patient underwent robotic left adrenalectomy with complete (R0) resection. Histological examination showed a malignant proliferation of pleomorphic epithelioid cells; immunohistochemistry confirmed positivity for CD31, CD34, and podoplanin, with a Ki-67 index of ~80%, establishing the diagnosis of adrenal AS. No adjuvant therapy was administered. At 4-month follow-up, the patient was alive and disease-free. A systematic review of the PubMed database identified 51 additional published cases, totaling 52 patients. The disease predominantly affects males (67%), mean age 58 years. Overall survival was 41% and disease-free rate 33% at 36 months; tumor size <6 cm was associated with improved survival (P=0.04).

Conclusions: Primary adrenal AS is an aggressive tumor with poor prognosis. Complete surgical resection is the cornerstone of treatment. However, since available evidence is limited, no definitive prognostic factors can be established.

Keywords: Adrenal gland; angiosarcoma (AS); epithelioid; case report

Submitted Jan 07, 2026. Accepted for publication Mar 25, 2026. Published online Jun 18, 2026.

doi: 10.21037/gs-2026-1-0012

Highlight box

Key findings

• This case report describes a primary adrenal epithelioid angiosarcoma (AS) in a 67-year-old male, managed with robotic adrenalectomy achieving complete (R0) resection, with no evidence of disease at 4-month follow-up. A systematic literature review of 52 cases confirms that primary adrenal AS is a rare and aggressive malignancy with poor overall prognosis and limited evidence to guide management.

What is known and what is new?

• Primary adrenal AS is an extremely rare vascular malignancy, with fewer than 55 cases reported since its first description in 1988. Diagnosis is exclusively histopathological, and surgical resection is the mainstay of treatment; no standardized adjuvant protocols exist.

• This manuscript adds a new documented case of primary adrenal epithelioid AS managed with minimally invasive robotic surgery and contributes an updated systematic literature analysis of 52 patients, demonstrating that tumor size <6 cm is significantly associated with improved overall survival (P=0.04).

What is the implication, and what should change now?

• Clinicians should maintain a high index of suspicion for primary adrenal AS when evaluating large, heterogeneous adrenal masses with hemorrhagic or necrotic features, even in the absence of specific radiological markers. Early surgical intervention with complete resection is critical. Given the aggressive biological behavior and poor outcomes, multidisciplinary evaluation and reporting of new cases are strongly encouraged to build evidence for future prognostic and treatment guidelines.

Introduction

Angiosarcoma (AS) originates from the vascular endothelium is a rare tumor that accounts for the 1% of soft tissue sarcomas (1). Most ASs occur in the skin, trunk, extremities, head and neck, and a few occur in the breast, liver, spleen and heart (2). Primary adrenal AS is an extremely rare malignancy (3), accounting for only a small fraction of all visceral ASs.

Since its first description by Kareti et al. (4) in 1988, 51 patients have been reported in the literature, underscoring both its rarity and the limited clinical experience available for guiding diagnosis and management. This neoplasm typically affects individuals in late adulthood and often presents with nonspecific symptoms such as abdominal discomfort, fullness, or incidental detection on imaging, making the preoperative diagnosis particularly challenging.

The deep retroperitoneal location of the adrenal glands, combined with the heterogeneous radiologic appearance of these tumors, contributes to frequent diagnostic uncertainty. Adrenal AS can mimic several more common adrenal lesions, including adrenocortical carcinoma, pheochromocytoma, and hyper-vascular metastatic disease on noninvasive diagnostic studies (1-24). The absence of specific clinical or biochemical markers further complicates early recognition, and most cases are identified only after surgical excision.

Since the rarity of this neoplasm, every new documented case might contribute to valuable information regarding its clinical behavior, radiologic characteristics, and optimal management strategies. We added to the limited body of evidence available our patient affected with primary adrenal epithelioid AS and performed an extensive literature review with the aim to enhance awareness of this uncommon adrenal malignancy. We present this article in accordance with the CARE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0012/rc).

Case presentation

A 67-year-old Caucasian man, with a medical history remarkable for arterial hypertension under antihypertensive treatment, reported no known drug allergies and denied smoking, alcohol consumption, or illicit drug abuse. He also denied any occupational or environmental exposure to known risk factors associated with AS, including vinyl chloride or arsenic. His family history was negative for endocrine, metabolic, and oncological diseases. His physiological history reported regular diet, normal bowel habits, and no sleep disturbances and no previous surgical interventions.

During a urological visit, an abdominal ultrasound was prescribed as part of the routine assessment. This exam revealed a solid, rounded, and inhomogeneous retroperitoneal mass. A contrast-enhanced computed tomography (CT) scan of the abdomen a left adrenal lesion measuring 78 mm × 84 mm × 83 mm with a density of approximately 40 Hounsfield units (HU) (Figure 1A). Five months later, an abdominal magnetic resonance imaging (MRI) was performed and confirmed the presence of the left adrenal mass, now measuring 90 mm × 82 mm × 88 mm. The lesion shows a homogeneous capsular thickness and markedly heterogeneous internal content due to the presence of septations and hypointense components on T2-weighted sequences, with an overall mild hyperintensity on T1-weighted sequences, consistent with partial internal hemorrhagic components. The lesion demonstrated marked restriction of cellular diffusivity on diffusion weighted imaging (DWI) sequences but did not exhibit any post-contrast enhancement (Figure 1B). The finding, slightly increased in size compared to the CT scan, although initially suggestive of an adrenal cystic/pseudocystic lesion, remains of uncertain interpretation and warrants surgical evaluation.

Figure 1 Preoperative imaging and pathological appearance of primary adrenal angiosarcoma. (A) Enhanced CT showed a mass on the left adrenal gland. (B) MR shows a homogeneous capsular thickness and markedly heterogeneous internal content due to the presence of septations and hypointense components. (C) Gross morphology of adrenal mass. CT, computed tomography; MR, magnetic resonance.

Routine laboratory tests were within normal limits, with a hemoglobin level of 12 g/dL. Laboratory endocrine workup included plasma metanephrines within the normal range (25.0 pg/mL; reference values <65 pg/mL), and a basal cortisol level of 1.8 µg/dL (reference values 6.2–19.4 µg/dL). No hormonal hypersecretion was documented.

Since the progressive enlargement of the mass and imaging characteristics, the patient was scheduled for surgical removal of the adrenal mass. He underwent a robotic left adrenalectomy. The left adrenal gland was found markedly enlarged (15 cm in maximum diameter) and a complete en-block resection was performed (R0 resection) (Figure 1C). No lymphadenectomy was associated. The procedure concluded without intraoperative complications. The pathological examination described a large central cavitated area containing coagulated blood and necrotic material. Microscopically, the lesion consisted of a malignant proliferation of pleomorphic cells with epithelioid features, prominent eosinophilic nucleoli, and abundant cytoplasm, arranged in cords and solid nests. A large central area of necrosis with diffuse hemorrhage was present. Residual adrenal cortical tissue surrounded the neoplasm, the analysis confirmed negative margins and absence of lymphovascular invasion. Immunohistochemistry showed positivity for melanoma antigen A (Melan-A), calretinin, CD31, CD34, and podoplanin, and negativity for cytokeratin Ae1/AE3 (CKAe1/AE3) and spinal muscular atrophy (SMA). The Ki-67 proliferation index was approximately 80%. The final diagnosis was a malignant vascular neoplasm with morphological and immunophenotypic characteristics consistent with AS. The postoperative course was uneventful, and the patient was discharged in the second postoperative day. The patient underwent an oncologic visit, and no chemo or radiotherapy was prescribed. At a follow-up of 4 months, the patient is alive and without evidence of disease recurrence.

All procedures performed in this case were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Materials and methods

Literature search

A comprehensive literature search was conducted using the PubMed database from 1951 to June 2025. Additional manual screening of the reference lists from relevant studies and previous review articles was also performed. No language restrictions were applied. The search term used was “adrenal angiosarcoma”.

Studies were considered eligible if they provided sufficient information on clinical presentation, diagnostic workup (radiological and/or pathological), and follow-up, and if histopathological confirmation of AS was clearly documented. Reports in which the adrenal involvement was not definitively of primary origin were excluded. In cases of duplicate publications, only the most recent and comprehensive version was retained.

The initial search yielded 237 records, all screened by two reviewers (G.C. and P.S.). After applying the predefined inclusion and exclusion criteria, 42 articles were selected for final analysis. No additional studies were identified through hand-searching.

Data extraction

Data extraction was performed by two reviewers (G.C. and P.S.) using a standardized predefined form. Extracted variables included authors, year of publication, patient demographics (age and sex), tumor laterality (right, left, or bilateral adrenal gland), tumor size, preoperative diagnostic procedures, histopathological features, and administration of adjuvant therapy. When available, follow-up information was collected, including duration of follow-up (converted to months), occurrence of recurrence or metastasis, and patient status (alive or deceased) at the last documented evaluation. Ambiguities or unclear data points were resolved by re-examining the original manuscripts.

Statistical analysis

Data were entered into a computer spreadsheet (Microsoft Excel for Mac version 16.104), and data analysis was performed with SPSS {version 30.0.0.0 [172] for macOS Tahoe 26.2} software. All values are expressed as mean ± standard deviation. Cumulative survival and disease-free interval rates were determined according to the Kaplan-Meier method and compared with the log-rank (Mantel-Cox) test. A P value <0.05 was utilized to determine significance.

Results

All articles published between January 1988 and June 2025 were considered for the present analysis. A total of 237 records were initially identified through the literature search. After exclusion of non-pertinent, duplicate, or incomplete reports, 49 articles were included (references listed in Table 1), yielding a total of 52 patients, including the present case, affected by pathologically confirmed primary adrenal AS. Demographic and clinical characteristics of the study population are summarized in Table 1.

Table 1

Summary of published cases of primary adrenal angiosarcoma with histological confirmation

Author Publication year Age (years) Sex Side Size (cm) Presentation Management Chemotherapy Radiotherapy Metastasis Outcome
Kareti et al. (4) 1988 54 Male Left 6 Left upper quadrant abdominal pain Left adrenalectomy + resection of lateral gastric wall, pancreatic tail, left kidney, and spleen for recurrent tumor bloc resection 7 months later None None None Alive 1 year after surgery
Livaditou et al. (5) 1991 59 Male Right 7 Right upper quadrant pain Adrenalectomy with nephrectomy None None N/A Died 8 days after operation
Bosco et al. (6) 1991 54 Female Right 6 Fatigue Right adrenalectomy N/A N/A N/A No recurrence
Fiordelise et al. (7) 1992 67 Male N/A N/A Lower back pain Adrenalectomy N/A N/A Yes Died 2 months after surgery
Ben-Izhak et al. (8) 1992 41 Male Right 10 Epigastric discomfort Laparotomy None Yes None Free of disease
Schwenk et al. (9) 1994 50 Male N/A 5.5 Nausea, vomiting and diarrhea Adrenalectomy N/A N/A Yes Died 9 months later
Sasaki et al. (10) 1995 65 Male Left 8 Nausea, fever Adrenalectomy N/A N/A Yes Died of disease 2 months later
Invitti et al. (11) 2001 34 Male Left 4.3 Cushing appearance Adrenalectomy None None None Alive 2 years after surgery
Croitoru et al. (12) 2001 63 Male Left 3 Incidental finding Left adrenalectomy None None None Not reported
Kruger et al. (13) 2001 70 Male Right 8 Abdominal pain Adrenalectomy None None None Died 3 weeks after surgery
Ferrozzi et al. (14) 2001 67 Male Left 13 Left flank pain Adrenalectomy None None Yes Died 3 months after surgery
Ferrozzi et al. (14) 2001 60 Female Right 7 Abdominal pain Adrenalectomy None None None Not reported
Pasqual et al. (15) 2002 70 Female Right 5 Abdominal pain Right adrenalectomy None N/A N/A No recurrence at 18 months
Rodríguez-Pinilla et al. (16) 2002 61 Male Right 12 Abdominal pain En bloc resection of tumor None None N/A No recurrence at 3 years
Al-Meshan et al. (17) 2004 50 Male Left 7 Left flank pain Left adrenalectomy None None None Alive 12 years after surgery
Gambino et al. (18) 2008 49 Female Right Incidental finding Right adrenalectomy None None None Alive 1 year after surgery
Schreiner et al. (19) 2012 69 Female Right 12.5 Lower back pain Adrenalectomy with nephrectomy None None None N/A
Lepoutre-Lussey et al. (20) 2012 35 Male Right 6 Polyuria and hypertension Right laparoscopic adrenalectomy Adriamycin/ifosfamide N/A N/A Alive 2 years after surgery
Derlin et al. (21) 2012 67 Male Right N/A Fatigue, weight loss Right adrenalectomy N/A N/A Yes N/A
Kędzierski et al. (22) 2013 55 Male Left 14 Lower back pain Left adrenalectomy None None None N/A
Criscuolo et al. (23) 2013 68 Male Left 7 Pain in left thorax Laparoscopic adrenalectomy Anthracycline Yes Yes Died due to cachexia 4 months later
Sung et al. (24) 2013 42 Male Right 14 Right flank pain Right adrenalectomy and right nephrectomy None Yes Yes Died of disease
Sebastiano et al. (25) 2013 72 Female Right 13.7 Lower back pain Adrenalectomy None None None N/A
Hayashi et al. (26) 2014 63 Male Right 8.3 Dyspnea and weight loss Adrenalectomy None None None N/A
Babinska et al. (27) 2014 64 Female Right 8.7 Abdominal pain Open right adrenalectomy Refused None Yes Died 2 years later with metastasis
Hendry et al. (28) 2014 60 Female Left 4.3 Incidental finding Laparoscopic adrenalectomy None None None Alive at 9 months after surgery
Cornejo et al. (29) 2015 53 Female Left 15 Adrenalectomy Yes Yes Yes Died 3 months after surgery
Cornejo et al. (29) 2015 74 Male Left 8.5 Adrenalectomy None None None Died 5 months after surgery
Cornejo et al. (29) 2015 75 Female Left 11 Adrenalectomy None None Yes Died 1.5 years after surgery
Cornejo et al. (29) 2015 75 Female Left N/A Adrenalectomy None None Yes Alive at 2 years after surgery
Gusembauer et al. (30) 2015 67 Male Right 15.8 Right upper quadrant pain Right adrenalectomy Sunitinib None No Alive 1 year after surgery
Fuletra et al. (31) 2016 59 Female Right 7 Abdominal pain Right adrenalectomy Doxorubicin, ifosfamide, and mesna Yes N/A Alive 1.5 years after surgery
Grajales-cruz et al. (32) 2017 69 Male Right 16.4 Right flank pain Right adrenalectomy Doxorubicin/ifosfamide Yes Yes Died of disease 1 year later
Takizawa et al. (33) 2017 67 Male Right 3.4 Incidental finding Right adrenalectomy Paclitaxel None Yes Died 1.5 years after surgery, penile carcinoma
Li et al. (1) 2017 59 Male Left 5.4 Left flank pain Left laparoscopic adrenalectomy N/A N/A N/A Alive at 6 months after surgery
Yang et al. (34) 2018 60 Male Left 6.5 High blood pressure Laparoscopic left adrenalectomy None None No Alive
Yang et al. (34) 2018 60 Male Left 8 Severe pain in left lumbar region Left adrenalectomy, left nephrectomy, and splenectomy None None N/A Died of disease 1 month later
Ishii et al. (35) 2018 56 Male Left 7.4 Incidental finding Adrenalectomy + splenectomy None None None Alive 1.5 years after surgery
Antao et al. (36) 2019 58 Male Left 17.5 Left-sided abdominal pain Left adrenalectomy, left nephrectomy, splenectomy, partial gastrectomy, and distal pancreatectomy Paclitaxel, doxorubicin, carboplatin, etoposide-doxorubicin, mitotane Yes None Died due to disease progression and complications
Imran et al. (37) 2020 38 Female Right 8 Hemoptysis Right adrenalectomy Paclitaxel Yes Yes Alive 6 months after surgery
Elbaset et al. (38) 2020 52 Male Left 7 Incidental finding Open adrenalectomy None None None Alive 3 years after surgery
Erickson et al. (39) 2021 60 Female N/A N/A N/A N/A N/A N/A N/A N/A
Debruyn et al. (40) 2021 63 Male Right 16 Abdominal pain Open adrenalectomy None None None N/A
Ladenheim et al. (41) 2022 44 Female Left 8.4 Abdominal pain Left adrenalectomy. nanoparticle-albumin-bound paclitaxel None No Alive 14 months after surgery
Ladenheim et al. (41) 2022 65 Male Left 7.4 Incidental finding Left adrenalectomy None None Yes Died due to disease progression
10 months later
Wei et al. (42) 2021 51 Male Left 4 Lower back pain Retroperitoneal laparoscopic resection of the left adrenal tumor Liposomal doxorubicin and paclitaxel None Yes Complete response, alive 12 months after surgery
Wannasai et al. (43) 2023 59 Male Right 8.7 Abdominal bloating Right adrenalectomy None None N/A Lost to follow-up
Alsarraj et al. (44) 2023 54 Female Right 5.7 Right flank pain Right laparoscopic adrenalectomy N/A N/A None Follow-up by oncological team
Noman et al. (45) 2023 59 Male Left 17 Left flank pain Open left adrenalectomy doxorubicin and ifosfamide → gemcitabine None Yes Alive 10 months after surgery with regression of metastasis
Feng et al. (46) 2023 41 Male Left 4.4 Abdominal pain Left adrenalectomy Paclitaxel None None Alive 1 year after surgery
Parisi et al. (47) 2023 41 Female Right 11.8 Right flank pain Right adrenalectomy Paclitaxel → pembrolizumab with doxorubicin-ifosfamide/irinotecan None Yes Died after 6 months
Cicioni et al. 2025 67 Male Left 15 Incidental finding Robotic Adrenalectomy None None None Alive 6 months after surgery

N/A, not applicable.

Primary adrenal AS affected male in 35 (67%) cases and females in 17 (33%). The mean age at presentation was 58.3±10.5 years (range 34–75 years). Tumor laterality was retrievable in 48 cases, showing a slight predominance of left adrenal involvement 25 (52%) patients when compared with the right side 24 (48%) patients.

Tumors were generally large at presentation, had a mean diameter of 8.8±3.9 cm (range 3.0–17.5 cm), most commonly (33 cases—62%) exceeding 6 cm in maximum diameter. Abdominal or flank pain was the most common presenting symptom, reported in 29 patients (54%). Incidental detection occurred in 8 (15%) cases, while general systemic symptoms, including weight loss, fatigue, or weakness, were observed in 6 (11%) patients. The tumor was predominantly not hormones secreting, but 1 (2%) patient presented with a Cushing’s syndrome and 2 (4%) patients with arterial hypertension hormone related. In 6 (14%) patients, information regarding clinical presentation was not reported.

All patients underwent an abdominal CT scan (52 patients—100%) or magnetic resonance (MR) (6 patients—12%) which revealed heterogeneous adrenal masses with areas of necrosis and hemorrhage, without pathognomonic radiological features.

Diagnosis relied exclusively on histological examination combined with immunohistochemistry, demonstrating endothelial differentiation.

Neo-adjuvant therapies were never administered. All patients underwent surgery, and no intraoperative mortality was recorded. An open surgical approach was performed in 43 (84%) patients, while laparoscopic adrenalectomy was used in 7 (14%). A robotic adrenalectomy was reported in 1 (2%) patient and in 1 (2%) was not described the surgical approach.

Metastatic disease was present at diagnosis in 4 (8%) patients or developed within 6 months of follow-up in 4 (8%) patients. Thereafter, 7 (16%) patients had metastasis at a longer follow-up (median 14 months), most frequently involving the liver, lungs, bone, and skin. In 3 (6%) patients affected with metastatic disease no data were retrievable. Adjuvant chemotherapy was administered in 14 (27%) patients but 1 (2%) declined. Radiotherapy was used in 8 (15%) patients. 27 (52%) patients did not require any systemic treatment. Adjuvant chemo- or radiotherapies were used for R1 resection, advanced local disease, or distant metastasis. The chemotherapeutic agents used included paclitaxel, doxorubicin with or without ifosfamide, and liposomal doxorubicin. Targeted therapy with sunitinib or pembrolizumab were reported in 2 (4%) patients.

All patients had an available follow-up (mean 9±10 months, median 6 months, range minimum 1–maximum 38 months), the overall survival rate at 12-, 24- and 36-month were 62%, 41% and 41% (Figure 2A) respectively, whereas the disease-free interval was 62% at 12-month, 33% at 24-month and 33% at 36-month (Figure 2B). Tumors less than 6 cm had a significative role in survival rates (P=0.04) whereas had no influence in disease-free intervals (P=0.20) (Figure 2C,2D).

Figure 2 Kaplan-Meier analysis of overall survival and disease-free survival in patients with primary adrenal angiosarcoma, according to pooled data from the literature review. (A) Short- and long-term survival rates. (B) Short- and long-term disease-free intervals. (C) Tumor size and short- and long-term survival rates. (D) Tumor size and short- and long-term disease-free intervals.

Discussion

Primary adrenal AS represents one of the rarest malignant neoplasms of the adrenal gland, characterized by aggressive biological behavior and a poorly defined clinical profile.

Since the first description in 1988 (4), describing a 54-year-old male patient successfully treated with surgical resection alone and remaining disease-free at 1 year, this entity has appeared only sporadically. The extreme rarity of this tumor has precluded the development of evidence-based diagnostic algorithms and standardized therapeutic strategies, resulting in significant challenges in early recognition, optimal surgical management, and integration of systemic therapies.

We believe that the demographic distribution of this disease may suggest a potential role for long-term environmental exposure or cumulative carcinogenic insults in tumor development. To date, the only risk factors sporadically associated with AS include chronic exposure to carcinogens such as vinyl chloride, arsenic, and thorium dioxide, as well as prior radiotherapy (1,32). However, none of these predisposing factors have been consistently documented in patients with primary adrenal AS, suggesting that its pathogenesis remains largely unknown and likely multifactorial.

Tumor size at presentation was highly variable but generally had a size exceeding 6 cm. This finding reflects the silent biological behavior of the adrenal ASs which are frequently associated with the absence of hormone-related symptoms, thus likely contributing to a delayed detection. Tumor laterality showed a slight predominance of left-sided lesions.

Patients typically present with abdominal and/or flank pain. Incidental detection on imaging studies was rare. Functional presentations were exceedingly rare, only one patient was affected with a Cushing-like syndrome and 2 were hypertensive. Systemic symptoms, including weight loss, fatigue, or weakness, were rarely described, predominantly in the setting of advanced disease.

Preoperative staging of primary adrenal AS remains particularly challenging, since pathognomonic radiological features have not been well identified. Available data indicate that imaging characteristics on CT and MR are largely non-specific (48). Like ASs arising in other solid organs, adrenal ASs frequently exhibit marked intratumoral heterogeneity, including extensive areas of necrosis—especially in larger lesions—and, occasionally, calcifications (49). On contrast-enhanced imaging, early irregular arterial enhancement may be observed in portions of the mass, with more progressive and heterogeneous enhancement on delayed phases. In larger tumors, enhancement tends to be predominantly peripheral, surrounding central necrotic areas, and prominent irregular vascular structures have also been described (50). However, most of these imaging features significantly overlap with those of more common adrenal masses, particularly metastases from hyper-vascular primary tumors, pheochromocytomas, and adrenocortical carcinoma, further complicating preoperative diagnosis.

Metastatic disease was present at diagnosis or developed early during follow-up in patients. The most common sites of metastasis included the liver, lungs, bone, and skin, reflecting a dissemination pattern like that observed in other visceral ASs. Notably, metastatic spread was also documented in tumors measuring less than 5 cm, indicating the absence of a linear correlation between primary tumor size and metastatic potential.

All patients underwent surgical treatment, most commonly through an open approach with resection of the involved adrenal gland. In several cases, particularly in advanced disease, en-bloc multivisceral resections were required due to direct infiltration of adjacent organs, most frequently involving the kidney, spleen, pancreas, and stomach. These findings further underscore the marked local aggressiveness of primary adrenal AS.

The histological evaluation combined with extensive immunohistochemistry remains the cornerstone and currently the only definitive method for the diagnosis of primary adrenal AS. Adrenal ASs have a predominantly epithelioid pattern, characterized by sheets of pleomorphic cells with eosinophilic cytoplasm and prominent nucleoli lining irregular vascular spaces. Unlike ASs at other sites, well-defined vessel formative patterns may be less evident, and cytokeratin positivity is frequently observed, potentially leading to misdiagnosis as metastatic epithelial or other mesenchymal tumors. For this reason, morphology alone is insufficient for diagnosis. A broad immunohistochemical panel demonstrating endothelial differentiation, including CD31, CD34, ETS-related gene (ERG), Friend leukemia integration 1 (FLI1), and factor VIII-related antigen, together with negativity for Melan-A, is mandatory.

Neoadjuvant therapies were never administered. Adjuvant chemo- or radiation therapies were seldom employed, reflecting the absence of standardized treatment protocols for primary adrenal AS because no clear survival or disease-free benefits were demonstrated.

Overall prognosis remains poor, half of the patients died, in fact, within the first 2 years. Tumors less than 6 cm in maximum diameter had a significant role in survival rates.

Our study has some limitations including the known problems linked to data retrieval from case report and the relatively short- and heterogeneous follow-up which precludes definitive conclusions regarding long-term oncological outcomes.

In conclusion, primary adrenal AS remains a diagnostic and therapeutic challenge due to its extreme rarity, aggressive biological behavior, and lack of specific clinical or radiological features. This neoplasm is often not initially considered in the differential diagnosis of adrenal masses. Definitive diagnosis relies exclusively on histological examination combined with comprehensive immunohistochemistry. We recommend that any non-functioning adrenal mass larger than 4–6 cm, particularly when associated with hemorrhagic, necrotic, or rapidly progressive features, should be approached with suspicion for an aggressive vascular malignancy, regardless of an apparently benign radiological appearance.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0012/rc

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0012/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0012/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this case were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

  1. Li XM, Yang H, Reng J, et al. A case report of primary adrenal angiosarcoma as depicted on magnetic resonance imaging. Medicine (Baltimore) 2017;96:e8551. [Crossref] [PubMed]
  2. Gaballah AH, Jensen CT, Palmquist S, et al. Angiosarcoma: clinical and imaging features from head to toe. Br J Radiol 2017;90:20170039. [Crossref] [PubMed]
  3. Wei H, Mao J, Wu Y, et al. Case Report: Postoperative Recurrence of Adrenal Epithelioid Angiosarcoma Achieved Complete Response by Combination Chemotherapy With Liposomal Doxorubicin and Paclitaxel. Front Oncol 2021;11:791121. [Crossref] [PubMed]
  4. Kareti LR, Katlein S, Siew S, et al. Angiosarcoma of the adrenal gland. Arch Pathol Lab Med 1988;112:1163-5.
  5. Livaditou A, Alexiou G, Floros D, et al. Epithelioid angiosarcoma of the adrenal gland associated with chronic arsenical intoxication? Pathol Res Pract 1991;187:284-9. [Crossref] [PubMed]
  6. Bosco PJ, Silverman ML, Zinman LM. Primary angiosarcoma of adrenal gland presenting as paraneoplastic syndrome: case report. J Urol 1991;146:1101-3. [Crossref] [PubMed]
  7. Fiordelise S, Zangrandi A, Tronci A, et al. Angiosarcoma of the adrenal gland. Case report. Arch Ital Urol Nefrol Androl 1992;64:341-3.
  8. Ben-Izhak O, Auslander L, Rabinson S, et al. Epithelioid angiosarcoma of the adrenal gland with cytokeratin expression. Report of a case with accompanying mesenteric fibromatosis. Cancer 1992;69:1808-12.
  9. Schwenk W, Sarbia M, Haas R, et al. Primary hemangiosarcoma as a rare form of an incidentally discovered mass of the adrenal glands. Dtsch Med Wochenschr 1994;119:217-21. [Crossref] [PubMed]
  10. Sasaki R, Tachiki Y, Tsukada T, et al. A case of adrenal angiosarcoma. Nihon Hinyokika Gakkai Zasshi 1995;86:1064-7. [Crossref] [PubMed]
  11. Invitti C, Pecori Giraldi F, Cavagnini F, et al. Unusual association of adrenal angiosarcoma and Cushing's disease. Horm Res 2001;56:124-9. [Crossref] [PubMed]
  12. Croitoru AG, Klausner AP, McWilliams G, et al. Primary epithelioid angiosarcoma of the adrenal gland. Ann Diagn Pathol 2001;5:300-3. [Crossref] [PubMed]
  13. Krüger S, Kujath P, Johannisson R, et al. Primary epithelioid angiosarcoma of the adrenal gland case report and review of the literature. Tumori 2001;87:262-5. [Crossref] [PubMed]
  14. Ferrozzi F, Tognini G, Bova D, et al. Hemangiosarcoma of the adrenal glands: CT findings in two cases. Abdom Imaging 2001;26:336-9. [Crossref] [PubMed]
  15. Pasqual E, Bacchetti S, Waclaw B, et al. Adrenal incidentalomas: indications for surgery. Chir Ital 2003;55:29-34.
  16. Rodríguez-Pinilla SM, Benito A, Ballestín C, et al. Angiosarcoma of Adrenal Gland Report of a Case and Review of the Literature. 2002. Available online: https://www.researchgate.net/publication/238692832_Angiosarcoma_of_Adrenal_Gland_Report_of_a_Case_and_Review_of_the_Literature
  17. Al-Meshan MK, Katchy KC. An unusual angiosarcoma. A case report. Med Princ Pract 2004;13:295-7.
  18. Gambino G, Mannone T, Rizzo A, et al. Adrenal epithelioid angiosarcoma: a case report. Chir Ital 2008;60:463-7.
  19. Schreiner AM, Hoda RS. Primary adrenal epithelioid angiosarcoma showing rhabdoid morphology on air-dried smears. Diagn Cytopathol 2012;40:E162-4. [Crossref] [PubMed]
  20. Lepoutre-Lussey C, Rousseau A, Al Ghuzlan A, et al. Primary adrenal angiosarcoma and functioning adrenocortical adenoma: an exceptional combined tumor. Eur J Endocrinol 2012;166:131-5. [Crossref] [PubMed]
  21. Derlin T, Clauditz TS, Habermann CR. Adrenal epithelioid angiosarcoma metastatic to the epicardium: diagnosis by 18F-FDG PET/CT. Clin Nucl Med 2012;37:914-5. [Crossref] [PubMed]
  22. Kędzierski L, Hawrot-Kawecka A, Holecki M, et al. Angiosarcoma of the adrenal gland. Pol Arch Med Wewn 2013;123:502-3.
  23. Criscuolo M, Valerio J, Gianicolo ME, et al. A vinyl chloride-exposed worker with an adrenal gland angiosarcoma: a case report. Ind Health 2014;52:66-70. [Crossref] [PubMed]
  24. Sung JY, Ahn S, Kim SJ, et al. Angiosarcoma arising within a long-standing cystic lesion of the adrenal gland: a case report. J Clin Oncol 2013;31:e132-6. [Crossref] [PubMed]
  25. Sebastiano C, Zhao X, Deng FM, et al. Cystic lesions of the adrenal gland: our experience over the last 20 years. Hum Pathol 2013;44:1797-803. [Crossref] [PubMed]
  26. Hayashi T, Gucer H, Mete O. A mimic of sarcomatoid adrenal cortical carcinoma: epithelioid angiosarcoma occurring in adrenal cortical adenoma. Endocr Pathol 2014;25:404-9. [Crossref] [PubMed]
  27. Babinska A, Peksa R, Swiątkowska-Stodulska R, et al. The collection of five interesting cases of adrenal tumors from one medical center. World J Surg Oncol 2014;12:377. [Crossref] [PubMed]
  28. Hendry S, Forrest C. Epithelioid angiosarcoma arising in an adrenal cortical adenoma: a case report and review of the literature. Int J Surg Pathol 2014;22:744-8. [Crossref] [PubMed]
  29. Cornejo KM, Hutchinson L, Cyr MS, et al. MYC Analysis by Fluorescent In Situ Hybridization and Immunohistochemistry in Primary Adrenal Angiosarcoma (PAA): a Series of Four Cases. Endocr Pathol 2015;26:334-41. [Crossref] [PubMed]
  30. Gusenbauer K, Ruzhynsky V, Kak I, et al. Angiosarcoma of the adrenal gland with concurrent contralateral advanced renal cell carcinoma: A diagnostic and management dilemma. Can Urol Assoc J 2015;9:E302-5. [Crossref] [PubMed]
  31. Fuletra JG, Ristau BT, Milestone B, et al. Angiosarcoma of the Adrenal Gland Treated Using a Multimodal Approach. Urol Case Rep 2017;10:38-41. [Crossref] [PubMed]
  32. Grajales-Cruz A, Baco-Viera F, Rive-Mora E, et al. Primary Adrenal Angiosarcoma: A Rare and Potentially Misdiagnosed Tumor. Cancer Control 2017;24:198-201. [Crossref] [PubMed]
  33. Takizawa K, Kohashi K, Negishi T, et al. A exceptional collision tumor of primary adrenal angiosarcoma and non-functioning adrenocortical adenoma. Pathol Res Pract 2017;213:702-5. [Crossref] [PubMed]
  34. Yang F, Yang Y, Yu J, et al. Primary epithelioid angiosarcoma of the adrenal gland: aggressive histological features and clinical behavior. Int J Clin Exp Pathol 2018;11:2721-7.
  35. Ishii S, Omori S, Uesugi N, et al. A case of angiosarcomas which occurred in an adrenal gland and spleen synchronously. Int Cancer Conf J 2018;7:134-6. [Crossref] [PubMed]
  36. Antao N, Ogawa M, Ahmed Z, et al. Adrenal Angiosarcoma: A Diagnostic Dilemma. Cureus 2019;11:e5370. [Crossref] [PubMed]
  37. Imran S, Allen A, Saeed DM, et al. Adrenal angiosarcoma with metastasis: Imaging and histopathology of a rare adrenal cancer. Radiol Case Rep 2020;15:460-6. [Crossref] [PubMed]
  38. Elbaset MA, Zahran MH, Badawy M, et al. Report of two rare cases of adrenal incidentalomas with different origins: revisiting pathological and radiological findings with a short review of the literature. J Egypt Natl Canc Inst 2020;32:25. [Crossref] [PubMed]
  39. Erickson LA. Angiosarcoma of the Adrenal Gland. Mayo Clin Proc 2021;96:1376-8. [Crossref] [PubMed]
  40. DeBruyn E, Hamed AB, Salloum RH, et al. Adrenal Epithelioid Angiosarcoma as a Rare Etiology of Chronic Abdominal Pain. ACS Case Rev Surg 2024;4:38-45.
  41. Ladenheim A, Tian M, Afify A, et al. Primary Angiosarcoma of the Adrenal Gland: Report of 2 Cases and Review of the Literature. Int J Surg Pathol 2022;30:76-85. [Crossref] [PubMed]
  42. Wei H, Mao J, Wu Y, et al. Case Report: Postoperative Recurrence of Adrenal Epithelioid Angiosarcoma Achieved Complete Response by Combination Chemotherapy With Liposomal Doxorubicin and Paclitaxel. Front Oncol 2021;11:791121. [Crossref] [PubMed]
  43. Wannasai K, Charoenchue P, Junrungsee S, et al. A Rare Case of Primary Adrenal Epithelioid Angiosarcoma. Am J Case Rep 2023;24:e939397. [Crossref] [PubMed]
  44. Alsarraj OM, Alqahtani A, Alswayyed M, et al. Primary Adrenal Angiosarcoma and its Management: A Case Report. Cureus 2023;15:e48762. [Crossref] [PubMed]
  45. Noman M, Zeer AMM, Zeer ZMM, et al. Epithelioid angiosarcoma of the adrenal gland with metastasis: a case report and literature review. Ann Med Surg (Lond) 2023;85:3106-12. [Crossref] [PubMed]
  46. Feng RL, Hua YF, Guo L, et al. Primary adrenal angiosarcoma: A case report. Asian J Surg 2023;46:3936-8. [Crossref] [PubMed]
  47. Parisi X, Peric M, Bennett AE, et al. Primary Adrenal Epithelioid Angiosarcoma: A Case Report. Int J Surg Pathol 2024;32:515-22. [Crossref] [PubMed]
  48. Otal P, Escourrou G, Mazerolles C, et al. Imaging features of uncommon adrenal masses with histopathologic correlation. Radiographics 1999;19:569-81. [Crossref] [PubMed]
  49. Thapar S, Rastogi A, Ahuja A, et al. Angiosarcoma of the liver: imaging of a rare salient entity. J Radiol Case Rep 2014;8:24-32. [Crossref] [PubMed]
  50. Thompson WM, Levy AD, Aguilera NS, et al. Angiosarcoma of the spleen: imaging characteristics in 12 patients. Radiology 2005;235:106-15. [Crossref] [PubMed]
Cite this article as: Cicioni G, Iannone I, De Padua C, Spalice E, Crocetti D, Tarallo M, Petramala L, Letizia C, Sapienza P. Adrenal angiosarcoma, a rare neoplasm: a case report and a literature review. Gland Surg 2026;15(6):177. doi: 10.21037/gs-2026-1-0012

Article Options

Download Citation

Share