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Urology Case Reports
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UROLOGY CASE REPORTS
Alan Partin, MD, PHD J. Wein, MD, Editors-in-Chief
Oncology
Non-functional oncocytic adrenocortical carcinoma: Case report with clinicopathologic and surgical correlation
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Induparkavi Murugesana,”(, Vikas Kailashiya a, Sahil Datab, Madan Gopal Bhardwaj b, Sameer Trivedi b
a Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
b Department of Urology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
ARTICLE INFO
Keywords:
Oncocytic adrenocortical carcinoma Incidentaloma Histopathology Adrenalectomy Immunohistochemistry Oncoytic neoplasm
ABSTRACT
Oncocytic adrenocortical carcinoma (OACC) is a rare variant of adrenocortical carcinoma composed predomi- nantly of oncocytic cells. We present the case of a 45-year-old female with a large, non-functional left adrenal mass diagnosed as OACC. Imaging revealed a well-defined, vascular, heterogeneously enhancing mass without metastasis. Histopathology showed oncocytic cells disposed in nests and sheets with capsular and venous in- vasion, with low mitotic activity. Surgical excision was curative, and the patient remains disease-free at 10 months. This case highlights the diagnostic and prognostic utility of histologic scoring systems and underlines the role of surgery as the primary treatment in localized OACC.
1. Introduction
Adrenocortical carcinoma (ACC) is a rare neoplasm with an inci- dence of 0.5-2 per million population in the United States. 1However, the epidemiology in Asia is not known. The subtypes include conven- tional, oncocytic, myxoid and sarcomatoid variants. Less than 85 cases of oncocytic ACC (OACC) have been reported in the literature.2 OACC are non-functional, most commonly seen in the left adrenal gland and are part of the spectrum of oncocytic adrenocortical neoplasms (OAN) comprising the benign oncocytoma and oncocytic neoplasm of uncertain malignant potential (OANUMP), histopathologically classified using the Lin-Weiss-Bisceglia system.2 Unlike the conventional ACC seen in women, OACC is most commonly seen in men (F:M = 1:1.1) with a mean age of 48 years.3 The oncocytic variant has a better prognosis compared to the conventional ACC - risk of recurrence, metastasis and death being 5.1 %, 3.7 % and 7.4 % based on systematic review conducted by Bot- tazz, et, al .. 2 The driver mutations include WNT pathway, chromosome remodeling genes, cell cycle regulation genes and PKA pathway. ACC maybe associated with germline mutations - TP53 p.R337H, explaining presence of geographical pockets.1 Angioinvasion is currently the best indicator of disease-free survival in low grade ACCs. A Ki67 index >15 % is associated with poor outcome. Mitosis, p53, beta-catenin IHC, high SF1 and loss of ATRX, ZNRF3, BUB1B and PINK1 have also been studied
in ACCs. When compared with ACC, OACC has lower driver mutational burden of beta catenin and cell cycle regulation genes but mitochondrial DNA deletions are more commonly associated.4 PDL1 IHC can be done for immunotherapy response prediction.1 Surgery with careful mainte- nance of capsule is considered the treatment of choice2
2. Case
A 45-year-old lady presented with dull to severe aching, non- radiating pain in the left flank for 1 year along with a diffuse swelling in the left hypochondrium, gradually increasing in size up to 10 x 10cm. On physical examination, the lump was firm to hard with a smooth surface, ballotable and moving with respiration. Finger insinuation was possible above the swelling. No history of orthopnea, fractures, deep vein thrombosis, striae, easy bruisability, proximal muscle weakness, palpitations, headache, postural dizziness or change in weight.
Ultrasonography shows a 6.6x3.8 x 10.8cm (513 cc) heteroechoic solid lesion with internal vascularity in the left suprarenal region with retained fat planes between the lesion and left kidney. The lesion abuts the kidney inferiorly and the spleen superiorly. No lymph nodes were enlarged. CT triphasic angiography revealed a 17.4x10.8 × 7.8cm well- defined heterogeneously enhancing mass in the left suprarenal region with areas of calcification and multiple non-enhancing central necrotic
* Corresponding author. 101, 36/6, Manar Merlin Apts, BTM Layout 2nd stage, 14th Main, Bangalore, 560076, India.
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areas abutting the splenic vessels but with maintained fat planes with the spleen. The mass was continuous with the left adrenal gland. Mul- tiple enhancing vascular channels are seen in the arterial phase. The attenuation of the enhancing area in the arterial phase (CT attenuation value - +60 to 100HU), extension anteriorly - abuts the splenic vessels and maintained fat planes with spleen, postero-medially - indents and compresses the kidney with maintained fat planes, posterolaterally and laterally - maintained fat planes with abdominal wall musculature. Both the kidneys appeared normal (Fig. 1). HRCT Thorax showed no evidence of metastasis. FDG PET showed lobulated heterogeneously enhancing
hypermetabolic lesion (SUVmax - 21.8) in the left adrenal region with necrotic areas and calcific foci. Overnight dexamethasone suppression test, serum cortisol, testosterone, DHEAS, metanephrines and methox- ytyramine levels were normal. Patient was diagnosed as left adrenal incidentaloma and underwent left open adrenalectomy. Intra- operatively, solid, hard mass arising from left adrenal gland, displac- ing left kidney inferomedially, bowel loops medially, spleen superiorly was noted (Fig. 2A). Patient tolerated the procedure well and post- operative recovery was uneventful. No adjuvant therapy was advised. Follow up FDG-PET scan showed no evidence of any lesions. The patient
| Parameters | Our study | N.A. et al.10 | Picut et al.11 | Bottazzi et al.2 | Santos et al.12 | Candy PA. et al.13 |
|---|---|---|---|---|---|---|
| Year | 2025 | 2025 | 2024 | 2023 | 2024 | 2025 |
| Age (years) | 45 | 45 | 60 | 88 | 65 | 54 |
| Sex | F | M | F | F | F | M |
| Symptoms | Left flank pain and swelling | Abdominal pain | Dizziness, headache, weight gain, refractory hypertension, new onset diabetes mellitus, psychosis | Abdominal swelling and | Epigastric pain with periumbilical radiation, nausea and vomiting | Incidental - work-up for spinal injury. |
| constipation | ||||||
| CECT | Multiple enhancing central necrotic areas, calcification | Well-defined -arising from right adrenal gland. | Bilobed left adrenal mass, vascularized, no calcification | Solid mass - encapsulated and not homogenous, displacing pancreas and vessels | Heterogenously enhancing lobulated mass | Left adrenal mass |
| Blood | Normal | Normal | DHEAS and urinary metanephrines - marginally increased | Normal | Normal | Normal |
| investigations | ||||||
| Procedure | Left open adrenalectomy | Right laparoscopic assisted adrenalectomy | Left laparoscopic adrenalectomy | Left open adrenalectomy | Thoracoabdominal adrenalectomy | Left laparoscopic adrenalectomy |
| Gross | Well circumscribed, tan-brown | Well-circumscribed yellow | Bilobed with positive margins | Round, encapsulated mass with | Irregular, circumscribed, tan-brown, | Solid, tan-grey |
| examination | to yellow cut surface. Necrosis | brown, homogenous cut surface, | cut surface showing yellow and | variegated appearance with necrosis | ||
| and haemorrhage. | focal haemorrhage. | brown areas. | and haemorrhage. | |||
| Size (cm) | 18 | 15 | 12 | 17 | 16 | 4.5 |
| Architecture | Diffuse, nests | Nest, sheet, singly dispersed | Trabeculae and nests | Sheets, nests | Diffuse | |
| Cells | Oncocytic cells and clear cells | Oncocytic cells and clear cells | Polygonal cells with abundant | Polygonal cells with abundant | Oncocytic cells with | |
| granular, eosinophilic cytoplasm. | eosinophilic cytoplasm | eosinophilic cytoplasm | ||||
| Mitosis | 3/50 | 6 to 8/50 | >5/50, atypical mitosis present | Low | 10-15/50 | >5/50, atypical mitosis seen. |
| Necrosis | Present | Present | Present | Present | Present | Present |
| Lympho- | Present | Absent | Present | Present | ||
| vascular | ||||||
| invasion | ||||||
| Capsular | Present | Present | Present | Absent | ||
| invasion | ||||||
| Periadrenal fat | Absent | Present | ||||
| invasion | ||||||
| Criteria used | LWB | Weiss: 5/9, LWB: 2 major +3 minor | Weiss modified criteria - Uncertain potential for malignancy | LWB, Helsinki score, Reticulin algorithm. Ki-67 = 10-15 % | LWB. Ki-67 = 10 %. Reticulin framework is disrupted. | |
| Follow-up | Doing well 10 months post- surgery | Doing well at 6 months follow up. | Improved mental health | Doing well at 2 follow op | Pulmonary and liver metastasis present at diagnosis. |
is presently doing well at 10 months after surgery.
Gross examination showed a tumour weighing 937g, measuring 18x12 × 7.5cm. Outer surface was pale brown, bosselated with areas of congestion. The cortex and medulla could not be differentiated. The tumour was capsulated, reaching up to but not involving the periadrenal fat. Cut surface was nodular with a variegated appearance ranging from tan brown to yellow. Areas of gelatinous secretions, fat, necrosis and haemorrhage were seen (Fig. 2B and C). No lymph nodes were noted. Microscopic examination shows a tumour disposed predominantly in sheets along with nests composed of both oncocytic cells and clear cells (Fig. 3A to B) which are pleomorphic, polygonal with abundant granular and eosinophilic cytoplasm - attributed to the increased number of mitochondria, containing large nuclei with prominent nucleoli consti- tuting up to 95 % of the cell population. Around 3 mitotic figures were seen in 50 high power fields (Low mitotic tumour grade) in the hot spots. No atypical mitosis was noted. Capsular invasion, venous invasion and necrosis was seen (Fig. 3C). The pathologic stage classification - pTNM, AJCC 8th edition was used to for staging as pT2 (Tumour larger than 5cm with no extradrenal invasion). The disrupted reticulin framework is shown in Fig. 3D and E. Immunohistochemistry for Melan A was positive (Fig. 3F).
3. Discussion
Oncocytic adrenocortical carcinoma (OACC) as defined by the 5th edition of WHO Classification of tumours is ACC with more than 90 % of cells composed of oncocytic cells.5 Presence of marked nuclear pleo- morphism, eosinophilic cytoplasm and solid sheet like disposition, the Lin-Weiss-Bisceglia system is used to classify them into benign (fails to satisfy any of the major or minor criteria), uncertain malignant potential (satisfies at least one minor criterion but no major criterion) and ma- lignant (at least one major criterion present), the minor criteria being 1. Size more than 10cm or weight more than 200g, 2. Necrosis, 3. Capsular invasion and 4. Sinuosoidal invasion. The major criteria are 1. More than 5 mitosis in 10mm2, counted in 50 high power fields, each field of area 0.2mm2, 2.Atypical mitosis and 3. Venous invasion. The Helsinki scoring system takes into account mitosis, necrosis and numeric value of the Ki-67 proliferation index and a score >17 is suggestive of poor prog- nosis. The reticulin algorithm is based on mitosis, vascular invasion and necrosis in the presence of altered reticulin framework.5 No single sys- tem is diagnostically accurate in all cases. Presence of bona fide vascular invasion is a criterion that can prognosticate the disease.1 Since mitosis is an important parameter, Ki67 labelling index and phosphohistone H3 must be used to assess mitotic count with >20 mitosis/10 mm2 signi- fying high grade. Higher mitotic count is used for deciding adjuvant mitotane therapy in ACC. IGF2 paranuclear IHC can be used to differ- entiate adenomas from carcinomas. For OACC, the Lin-Weiss-Bisceglia system, Helsinki score and reticulin algorithm is relied upon.1 An immunohistochemical study of four oncocytic adrenocortical carci- nomas conducted by Hoang et al., showed that the tumour cells are positive for cytokeratins, focally inhibin positive but negative for syn- aptophysin, chromogranin and S-100. Benign tumours tend to show synaptophysin positivity. One-half and on-third of the cases are respectively positive for alpha-inhibin and melan A apart from anti-mitochondrial antibodies as shown by a review.3 Electron micro- scopically, there is presence of large number of mitochondria, lipid droplets and well-formed rough endoplasmic reticulum in contrast to the conventional adrenocortical carcinoma where smooth endoplasmic reticula are characteristic.6
Thomas SS et al.7 on a study based on 44 cases of ACC in India found a male preponderance with a mean age of 38.5 years. Out of 44, 26 cases were functional, most common hormone being cortisol. Most of the patients underwent adrenalectomy. In addition, en bloc resection of extra adrenal organs, radiation therapy, chemotherapy and mitotane were administered based on extent of the disease. Aubert’s Weiss scoring system was used and a score >3 was considered malignant. Margin
status, ENSAT stage (European network for the study on adrenal tu- mours were risk factors for mortality. Being a male carried higher risk for metastasis. Tumour size, capsular invasion, vascular invasion and Weiss score did not increase the risk. Radiotherapy and chemotherapy did not reduce local recurrence. One-half of the tumours were functional with the most common presentation being associated with increased sex hormones followed by cortisol as shown by a review.3 On reviewing OAN and OANUMP patients - uncertain margin status and presence of necrosis were significant risk factors for recurrence, however, necrosis is currently not a major LWB criteria, necessitating modification to enhance discriminatory ability in light of oncocytoma and OANUMP presenting with metastatic lesions. A higher proportion of recurrence cases met the criteria: tumor ≥4 cm, pre-contrast HU > 10, and washout <60 % absolute/<40 % relative.8 Padua et al.9 performed a systematic review of 24 trials on systemic therapy in adrenocortical neoplasms and have concluded that more studies are required to frame definitive management plans. Table 1 shows a brief review. Adjuvent mitotane confers better survival in patients with early disease whereas chemo- therapy offers no survival advantage. Immunotherapy and targeted therapy also show no distinct advantage. The 5-year survival is around 47 %, with a median survival of around 5 years.3 A study on 44 patients found OACC to have smaller size, lower indeterminate margins, lym- phovascular invasion, recurrence, and longer survival than ACC. Ki-67 and ENSAT stage predict recurrence risk and guide mitotane ther- apy.14 OACCs show LRIG1 mutations-a tyrosine kinase receptor reg- ulator-also seen in ACCs, indicating a potential pathogenic pathway.15
4. Conclusion
OACCs are rare tumours with difficulty categorizing into benign and malignant on imaging because of low lipids no matter the size and contrast enhancement. OACC has better survival as compared to con- ventional ACC. Therefore, it falls on the skill of the pathologist to pru- dently use the different criteria - Weiss, Helsinki, Lin-Weiss-Bisceglia system along with reticulin stains and IHC for accurate classification into the correct variant and behaviour.
CRediT authorship contribution statement
Induparkavi Murugesan: Writing - original draft, Methodology, Data curation, Conceptualization. Vikas Kailashiya: Writing - review & editing, Supervision, Investigation, Data curation, Conceptualization. Sahil Data: Writing - original draft, Investigation, Data curation. Madan Gopal Bhardwaj: Writing - original draft, Investigation, Data curation. Sameer Trivedi: Writing - review & editing, Investigation, Conceptualization.
Acknowledgements
The authors would like to thank the patient and the laboratory technical staff for their support.
References
1. WHO Classification of Tumours Editorial Board. Urinary and Male genital tumours. Adrenal Gland Tumours. fifth ed. Lyon, France: International Agency for Research on Cancer; 2022.
2. Coppola Bottazzi E, Gambardella C, Mongardini FM, et al. Prognosis of adrenal oncocytic neoplasms (AONs): literature review of 287 cases and presentation of the oldest patient. J Clin Med. 2023;12(21):6925. https://doi.org/10.3390/ jcm12216925. PMID: 37959390; PMCID: PMC10649738.
3. Lam AKY. Adrenocortical carcinoma: updates of clinical and pathological features after renewed world health organisation classification and pathology staging. Biomedicines. 2021;10; 9(2):175. https://doi.org/10.3390/biomedicines9020175. PMID: 33578929; PMCID: PMC7916702.
4. Duregon E, Volante M, Cappia S, et al. Oncocytic adrenocortical tumors: diagnostic algorithm and mitochondrial DNA profile in 27 cases. Am J Surg Pathol. 2011;35 (12):1882-1893. https://doi.org/10.1097/PAS.Ob013e31822da401. PMID: 21989346.
5. WHO Classification of Tumours Editorial Board. Urinary and Male genital tumours. Tumours of the Testis. fifth ed. Lyon, France: International Agency for Research on Cancer; 2022.
6. Hoang MP, Ayala AG, Albores-Saavedra J. Oncocytic adrenocortical carcinoma: a morphologic, immunohistochemical and ultrastructural study of four cases. Mod Pathol. 2002;15(9):973-978. https://doi.org/10.1038/modpathol.3880638. PMID: 12218215.
7. Thomas SS, Marathe A, Cherian AJ, et al. Adrenocortical carcinoma: a therapeutic challenge - 44 cases from a single tertiary care center in India. Indian J Surg Oncol. 2022;13(2):251-259. https://doi.org/10.1007/s13193-021-01440-3. PMID: 35782795; PMCID: PMC9240166.
8. Kim BC, Han H, Kwon D, et al. Limitation of the current Lin-Weiss-Bisceglia criteria in predicting poor prognosis in oncocytic adrenocortical neoplasms of uncertain malignant potential and oncocytoma diagnosed by the Lin-Weiss-Bisceglia criteria. Ther Adv Endocrinol Metab. 2025 Apr 30;16, 20420188251328186. https://doi.org/ 10.1177/20420188251328186. PMID: 40313870.
9. Padua TC de, Marandino L, Raggi D, et al. A systematic review of published clinical trials in the systemic treatment of adrenocortical carcinoma: an initiative led on behalf of the global society of rare genitourinary tumors. Clin Genitourin Cancer. 2023;21(1):1-7. https://doi.org/10.1016/j.clgc.2022.10.011. PMID: 36376169.
10. N A, Anne D, Shetty B, Velagapudi M, Nadella N. Unraveling adrenal oncocytoma: clinical presentation, diagnosis, and surgical success. Cureus. 2025 Mar 20;17(3),
e80891. https://doi.org/10.7759/cureus.80891. PMID: 40255829; PMCID: PMC12009102.
11. Picut B, Dubuis JB, Demarchi MS, Fournier I. Atypical clinical presentation of oncocytic adrenocortical carcinoma with decompensated metabolic syndrome and psychotic outbreak. BMJ Case Rep. 2025;18(3), e262948. https://doi.org/10.1136/ bcr-2024-262948. PMID: 40032570; PMCID: PMC11880429.
12. Santos CD, Carbonell DJS. A histomorphologic and ultrastructural report of an oncocytic adrenal cortical carcinoma with clinicoradiologic correlates. Cureus. 2024 Nov 21;16(11), e74184. https://doi.org/10.7759/cureus.74184. PMID: 39712708; PMCID: PMC11663143.
13. Candy PA, Gallappatige A, Durbhakula P. Case report: high grade oncocytic adrenocortical carcinoma. Pathology. 2025;57(S54). https://doi.org/10.1016/j. pathol.2024.12.183.
14. Prinzi A, Guarnotta V, Di Dalmazi G, et al. Multicentric retrospective analysis of oncocytic adrenocortical carcinoma: insights into clinical and management strategies. Endocr Pathol. 2025 Apr 11;36(1):11. https://doi.org/10.1007/s12022- 025-09857-0. PMID: 40214939; PMCID: PMC11991974.
15. Condello V, Bongiovanni M, Juhlin CC. Oncocytic adrenal tumors: a tri-focal review with integrated cytopathological, pathological, and molecular perspectives. Acta Cytol. 2025. https://doi.org/10.1159/000545715. PMID: 40188823; PMCID: PMC12101806.