Metastatic Alveolar Soft Part Sarcoma Presenting as an Adrenal Incidentaloma: A Case Report with Review of Literature
International Journal of Surgical Pathology 2025, Vol. 33(5) 1128-1134 @ The Author(s) 2025 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/10668969241308234 journals.sagepub.com/home/ijs
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Sonali Dixit, MD, DNB, Pathology1, Nayantrishna Nath, MD Pathology1 (D, Shipra Agarwal, MD Pathology, MNAMS1 (D , Sameer Rastogi, MD, DM Medical Oncology”, Shamim Ahmed Shamim, MD, Nuclear Medicine3, Rishi Nayyar, MS, MCh, Urology4, Devasenathipathy Kandasamy, MD, Radiology5, and Mehar Chand Sharma, MD, Pathology1
Abstract
Background. Metastasis of alveolar soft part sarcoma (ASPS) to the adrenal gland is infrequent, with only eight patients reported in the literature. Here we present an ASPS in an adolescent girl presented as a hypervascular adrenal incidentaloma along with a review of the available literature. This study aims to serve as a reference to aid in the pre- operative radiological and histopathological diagnosis of this rare entity. Case presentation. A 17-year-old adolescent girl presented to the Department of Urology after the detection of a hypervascular left adrenal incidentaloma on follow-up PET-CT, five months post-surgery for frontal bone ASPS. The radiological differential diagnoses were adrenocortical carcinoma, pheochromocytoma, and metastatic ASPS. The post-operative adrenalectomy specimen, on gross exami- nation, revealed a solid, variegated tumor replacing the entire normal adrenal parenchyma. Haematoxylin and eosin- stained sections showed a tumor with cells dispersed in nests separated by large fibrovascular septae. The tumor cells were large, polygonal with abundant clear to eosinophilic cytoplasm and prominent nucleoli. Occasional mitotic figures, foci of necrosis, dystrophic calcification, and sinusoidal and vascular invasion were noted. Histopathological dif- ferential diagnoses were metastatic ASPS, a primary adrenocortical carcinoma, and local infiltration/metastases from renal cell carcinoma. Ancillary studies including immunohistochemistry, fluorescent in situ hybridization (FISH), and ultrastructural examination helped to confirm the diagnosis of alveolar soft part sarcoma metastatic to the adrenal gland. Conclusion. ASPS presenting as a hypervascular incidentaloma is rare and is likely to be misdiagnosed, especially as adrenocortical carcinoma, pheochromocytoma, and renal cell carcinoma. The differential diagnosis is further com- plicated by an overlap of pathological features among these entities. A relevant clinical history and ancillary tests are mandatory to diagnose these tumors. Early detection can help timely therapeutic intervention that can improve patient outcome.
Keywords
alveolar soft part sarcoma, adrenal, metastatic, incidentaloma, hypervascular
Introduction
Alveolar soft part sarcoma (ASPS) is a rare malignancy of young adults, accounting for < 1% of soft tissue sarcomas. It is commonly associated with lung, bone, and brain metastases.” There are only eight published examples of ASPS metastatic to the adrenal gland.2-9 Here we discuss an ASPS in an adolescent girl presenting as a hypervascular adrenal incidentaloma, along with a discussion of the possible pitfalls in diagnosis during pre- operative radiological evaluation and histopathological examination.
1Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
2Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India
3Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
4Department of Urology, All India Institute of Medical Sciences, New Delhi, India
5Department of Radiology, All India Institute of Medical Sciences, New Delhi, India
Corresponding Author:
Shipra Agarwal, Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110029, India.
Email: drshipra0902@gmail.com
Case Presentation
A 17-year-old adolescent girl was referred to the Department of Urology after detecting a hypervascular left adrenal mass on a PET-CT examination. The latter had been performed as a work-up during the follow-up post- surgery for ASPS involving the frontal bone five months prior to the current presentation (Figure 1). The pre- operative radiological differential diagnoses were adreno- cortical carcinoma, pheochromocytoma, and metastatic ASPS. The serum hormonal profile was normal, ruling out a functional tumor. Fine needle aspiration cytology (FNAC) and core biopsy of the mass were inadequate and yielded only fibro-collagenous tissue, following which a left diagnostic and therapeutic adrenalectomy was done. On gross examination, the specimen measured 4.5× 4.1 x 1.2 cm and weighed 39 gm. The cut surface revealed a solid, variegated tumor almost entirely replacing the adrenal gland but without any capsular breach (Figure 2).
Histopathological examination revealed a tumor with cells dispersed in nests separated by large fibrovascular septae. The tumor cells were large, polygonal with abun- dant clear to eosinophilic cytoplasm and prominent nucle- oli (Figure 2). Occasional mitosis, foci of necrosis, dystrophic calcification, and sinusoidal and vascular
invasion were noted. There was microscopic infiltration of tumor into peri-adrenal fat. A histopathological differen- tial diagnosis of ASPS, adrenocortical carcinoma, pheo- chromocytoma, perivascular epithelioid cell tumor (PEComa) and local infiltration/metastases from renal cell carcinoma was considered. On immunohistochemistry, the tumor cells were negative for keratin (Bio SB, clone: AE1/AE3), melanA (Dako, clone: A 103), SF1 (Zeta corp., clone: N1665), calretinin (Bio SB, clone: EP1798), inhibin (Biocare, clone: 13CR1), synaptophysin (Bio SB, clone: EP158), and chromogranin (Thermo, clone: LK2H10), arguing against adrenocortical carcinoma, pheo- chromocytoma, and PEComa. The cells were also negative for CD10 (Biocare, clone: 56c6), and PAX8 (Cell marque, clone: 3F9), arguing against a clear cell renal cell carcinoma.
There was, however, diffuse immunopositivity for Cathepsin K (Cell marque, clone:3F9) and TFE3 (GenomeMe, clone: IHC 672), and negative reaction for vimentin (Bio SB, clone: V9), confirming the possibility of a metastatic alveolar soft part sarcoma. Ki67 prolifera- tion index was 6%-7%. Periodic Acid-Schiff with diastase stain revealed intracytoplasmic crystals and coarse gran- ules, that were confirmed to be rhomboid-shaped crystals on ultrastructural examination (Figure 2).
A
B
C
D
E
F
G
H
K
L
M
1
1
FISH assay performed using TFE3 break-apart probe (CT-PAC013-10-OG, LSP TFE3 5 CytoOrange / LSP TFE3 3 CytoGreen probe) confirmed TFE3 gene rearrangement involving 15% of the cells (Figure 2), against the suggested cut-off of %> 7.15% positive nuclei with any pattern of break-apart signals.10
Hence a final diagnosis of alveolar soft part sarcoma met- astatic to the left adrenal gland was made. The patient was referred to medical oncology, where a follow-up PET-CT scan revealed metastases to the lung, liver, and skull. An FDG-avid soft tissue density lesion was also noted in the left suprarenal region, suggestive of residual disease. MRI brain showed the metastatic diseases involving the skull vault (Figure 1).
In view of the widely metastatic and non-treatable disease, the patient’s relatives were appraised about the poor prognosis.
Literature Search Strategy
A systematic search of the literature was conducted on PubMed, PubMed Central, and Ovid Medline, with the fol- lowing restrictions: date (1 January 1957 to 31 March 2024), studies (humans), and language (no limitations). Search terms included “Alveolar soft part sarcoma meta- static to adrenal”, “metastatic alveolar soft part sarcoma”, and “Alveolar soft part sarcoma AND adrenal”.
Literature Review and Analysis
Only eight examples of ASPS with adrenal metastasis have been reported in the international literature.2-9 Of these, merely three presented as an adrenal mass, with the rest being documented at autopsy. Table 1 enlists the details of all these eight tumors and the present patient.
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TFE3, FISH
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HE,400X
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TFE3,400X
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CathepsinK,400X
F
EM
| SN | Authors (Year) | Age (years)/ Sex | Primary site of the tumor | Sites of metastasis other than the adrenal | Detection of adrenal involvement | Ancillary testing on adrenal tumor | Therapy given | Follow-up after detection of adrenal disease |
|---|---|---|---|---|---|---|---|---|
| 1 | Macfarlane et al® (1957) | 6 / Man | Left thigh | Left cerebral hemisphere, spinal cord, inguinal LN Autopsy - Liver, lung, vertebral column, skull, palate | At autopsy | None | Excision of left thigh mass | NA |
| 2 | Karnauchow Magne et al (1963) | 23 / Woman | Left forearm | Brain, heart, lungs, paratracheal lymph node, left kidney, left adrenal and left ovary | At autopsy | None | Excision of the primary tumor (left forearm) mass | NA |
| 3 | Liberman et al (1966) | 26 / Man | Left brachioradialis | Liver, brain, and skin on autopsy | At autopsy | None | Radical muscle resection of primary tumor (left brachioradialis) | NA |
| 4 | Ho et al8 (1979) | 96 / Woman | Right upper neck | Brain, liver, lung, cardiac, spleen | At autopsy | None | Partial resection of the primary tumor (right side of upper neck) followed by radiotherapy and chemotherapy | NA |
| 5 | Pak et al7 (1987) | 23 / Man | Thigh | Cerebral hemisphere, ocular, lungs, brain, kidneys, liver, spleen, pancreas, small intestine and left upper extremity | At autopsy | None | cisplatin and doxorubicin hydrochloride for primary tumor | NA |
| 6 | Selvarajah S et al3 (2014) | 41 / Woman | NA | Not mentioned | During follow-up | EM and FISH | Not available | NA |
| 7 | Niu L et al2 (2016) | 36 / Man | Right lower extremity | Lung, kidney, cardiac | During follow-up | None. Histopathological findings- not available | Resection of primary tumor (right lower extremity), Systemic chemotherapy Cyberknife treatment for adrenal and cardiac metastasis | FOD; 3 months |
(continued)
| disease of adrenal Follow-up after detection | months No follow-up AWD; 14 |
|---|---|
| given | palliative and |
| Therapy | primary masses |
| to of | |
| Referred Excision chemotherapy adrenal | |
| tumor testing on | Cathepsin- K crystals rearrangement gene 3 Positive for Intracytoplasmic |
| adrenal | TFE TFE Positive |
| Ancillary | TFE3, rhomboidal FISH: IHC: IHC: EM: |
| involvement of adrenal | systemic on adrenal with follow-up |
| Detection | non-specific incidentaloma hypervascular Presented During radiology symptoms; |
| adrenal other | liver |
| lung, | |
| the metastasis | |
| than of | vault, |
| Sites | Skull None |
| of | |
| site tumor | region bone |
| Primary the | Gluteal Frontal mass |
| Sex Age (years)/ | Woman 17 / 23 / Man |
| (Year) | (2018) M patient |
| Authors | al Goroshi Current |
| et | |
| SN | 9 8 |
ASPS- alveolar soft part sarcoma, DOD- died of disease, FOD- free of disease, AWD- alive with disease, IHC- immunohistochemistry, FISH- fluorescent in situ hybridization, EM- electron microscopy, NA- not applicable.
Discussion
ASPS is a rare sarcoma of uncertain histogenesis, espe- cially prevalent in female patients aged 15-35 years.3, It is characterized by the nonreciprocal chromosomal trans- location t(X;17) (p11.2; q25), resulting in ASPL :: TFE3 fusion.12 The most common primary sites of involvement are deep soft tissues of the thigh, buttock, and trunk (11). Distant metastases are common, particularly to the lung, bone, and brain (1). We present here a rare example of an adolescent girl who presented to the urology department with a hypervascular adrenal incidentaloma, diagnosed 5 months post-surgery for ASPS of the frontal bone. Only one other example of ASPS presenting as a hypervascular adrenal mass has been reported in the literature (4). Adrenal tumors that commonly show a heterogeneous bright enhancement on PET-CT are adrenocortical carci- noma, pheochromocytoma, metastases from renal cell car- cinoma, and hepatocellular carcinoma (4). ASPS is histopathologically characterized by the presence of large polygonal cells with abundant granular eosinophilic to clear cytoplasm arranged in a nested or pseudoalveolar growth pattern (12). Notably, all the tumors considered in the differential diagnosis of hypervascular adrenal mass show a similar morphological appearance, increasing the risk of misdiagnosis on small specimens. In the current patient, FNAC and core biopsy were attempted but were unsatisfactory for evaluation, and an accurate diagnosis could be made only on resection. Extensive ancillary testing was employed for confirmation. This included immunohistochemistry to rule out other differential diag- noses with clear cell morphology including clear cell renal cell carcinoma and adrenocortical carcinoma, molec- ular analysis demonstrating fusion involving the TFE3 gene, and ultrastructural evaluation documenting the diag- nostic intracytoplasmic rhomboid crystals.
Of the eight published ASPS metastatic to the adrenal gland, only one was subjected to ultrastructural examina- tion and FISH analysis (3). The prevalence of adrenal involvement is low. Selvarajah et al reported adrenal metastasis in one of their 17 (6%) ASPS patients (3). In another study, adrenal metastasis was noted in only one of the 53 (2%) patients with ASPS (5). A comprehensive evaluation of all such tumors including the current patient revealed that the age of presentation is wide, varying from six years to 96 years (Table 1; mean age, 32.33 ± 25.9 years; median age, 23 years). Thus, excluding our patient, to date only eight reported examples of ASPS metastatic to the adrenal exist in the literature (Table 1). The primary site has been variable and includes lower extremity (27,9), upper extremity in (5,6), upper neck (8), gluteal region (4), and frontal bone (current patient). In five of these patients, adrenal metastases were detected on autopsy. There was associated multi-organ involvement in all these patients (5-9). In the current patient and two
| TFE3 | − | − | − | − | + ± + | ||
|---|---|---|---|---|---|---|---|
| Cathepsin | K | ||||||
| − | − | + + + | |||||
| Arginase/ | HepPar1/ | Glypican | − | + | − − − | ||
| CD10 | + | + | + | − | |||
| CA9 | ± | + | − | ||||
| PAX8 | − | − | + | − − − | |||
| GATA3 | − | + | − | − | − − − | ||
| Chromogranin Synaptophysin | − | + | − | − | − − − | ||
| + | ±+ | − | − | − − − | |||
| Calre-tinin | + | ± | − | − | − − ± | ||
| MelanA | + | − | − | − | − − + | ||
| Inhibin | + | ± | |||||
| SF1 | + | − | − | ||||
| Keratin | − | K7: ± K20: - | K7: ± K20: ± | − − − | |||
| 14,15,16 | cell | 18 carcinoma | |||||
| Diagnosis | 13 carcinoma Adrenocortical | Pheochromo-cytoma | Clear cell Renal 17 carcinoma | Hepatocellular | Index patient ASPS 19,20 PEComa |
others with available details, adrenal disease was detected during follow-up radiology (2,4). Such patients have been variably managed with surgical excision (2) and palliative chemotherapy (4). A short follow-up of 3 months was available only in one published report, at the end of which the patient was free of disease (2). Our current patient is alive with widely metastatic disease, 14 months following the detection of adrenal disease.
Conclusions
Alveolar soft part sarcoma presenting as an adrenal inci- dentaloma is a typical example of ‘an uncommon disease having a common presentation. A wide age range with overlapping clinical, radiological, and histomorphological findings complicates and delays accurate diagnosis and patient management. A high index of suspicion is, hence, essential, keeping in mind that adrenal involvement usually indicates a widely metastatic disease.
Histopathological evaluation supplemented with immu- nohistochemistry (Table 2), ultrastructural, and molecular analysis is imperative for differentiating ASPS from other commoner primary and metastatic neoplasms involv- ing the adrenal gland.
The best treatment option for this entity is still unknown. Hence, we encourage clinicians to report their experience with adrenal ASPS to understand this entity better and plan appropriate management.
Abbreviations
| ASPS | Alveolar soft part sarcoma |
| FISH | Fluorescent in situ hybridization |
| PEComa | Perivascular epithelioid cell tumor |
Authors’ Contributions
SD, NN, and SA wrote the main manuscript text and prepared Figures and Table. SA, MCS did the critical review and editing of the manuscript and analysis of electron microscopy. SR, SAS, RN, and DK provided clinical and radiological inputs during manuscript preparation.
Consent for Publication
Consent for publication was given as per institutional policy.
Data Availability
Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Declarations
Ethics approval and consent to participate Informed consent was given as per institutional policy.
Ethical Approval
No data that can potentially and clearly identify the patient was included in the manuscript.
Funding
The authors received no financial support for the research, author- ship, and/or publication of this article.
Informed Consent
Not applicable, because this article does not contain any clinical trials.
Trial Registration
Not applicable, because this article does not contain any clinical trials.
ORCID iDs
Nayantrishna Nath İD https:/orcid.org/0000-0002-9594-6709 Shipra Agarwal ID https://orcid.org/0000-0001-7037-4444
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