IMAGES FOR SURGEONS
Royal Australasian College of Surgeons
Diagnostic dilemma for an adrenal mass: perivascular epithelioid cell neoplasm versus adrenocortical carcinoma
A 37-year-old female was referred to the emergency department by her family doctor for ongoing epigastric abdominal pain. Prior to presentation, the patient had gone for an abdominal ultrasound organized by her family doctor. This identified a solid mass anterior to the left kidney. A follow-up computed tomography (CT) of her abdomen was organized, after which she was told to present to the emergency department. No other past medical history or family his- tory was relevant to this case.
The tri-phasic CT abdomen revealed a well-defined retroperito- neal mass, measuring 5 cm by 4.5 cm by 5 cm, anterior to the upper pole of the left kidney, separate from the adrenal gland and pan- creas, no retrocrural or para-aortic lymphadenopathy and no ascites. Differential diagnosis included a phaeochromocytoma and neurofi- broma. This was excluded when biochemistry markers, including cancer markers (CA 12-5, CA 19-1, CEA, metanephrine, normetanephrine, 3-methoxytyramine, urinary chemistry) were within normal range. A multidisciplinary meeting was conducted and surgical resection was decided.
The patient underwent laparoscopic surgery via an anterior trans- abdominal approach for the removal of the retroperitoneal mass, with no evidence of peritoneal disease or lymphadenopathy. A tumour measuring 5.7 cm by 5.3 cm by 4.5 cm, weighing 69 g was excised through an extension via the camera port. It had a largely smooth and rounded external surface with a small amount of attached fatty tissue (Fig. 1).
Histopathology of the tumour showed highly cellular, plump polygonal eosinophilic oncocytic tumour cells. Many areas showed a finely vacuolated cytoplasm, with some patchy clear cell change (Fig. 2). Nuclei were vesicular, with finely granular chromatin pat- terns, with moderate variation in sizes. A provisional diagnosis of an atypical perivascular epithelioid cell neoplasm (PEComa) was made based on the eosinophilic tumour cells, and positive Melan A stains on Immunohistorychemistry (IHC). However, as there was no staining for smooth muscle markers, this was uncertain. Further expert opinions were sought, which demonstrated that isolated mitoses had atypical morphology. One area showed attenuated nor- mal adrenal cortex at the edge of the lesion, indicating that it had arisen within the adrenal gland itself. These findings best fit with a diagnosis of an adrenocortical carcinoma (ACC).
The patient was discussed at our multidisciplinary team meeting and diagnosed with stage 2 ACC. As the tumour was fully resected, she was followed up by the medical oncology team for surveillance. Two years on, she has had no further recurrence with ongoing mon- itoring from the medical oncology team.
PEComas were first termed Zamboni in 1996, comprising a family of soft tissue tumours that share a distinctive cell type. They
are composed of perivascular epithelioid cells (with no known nor- mal counterpart), distributed as nest and sheets with clear to granu- lar eosinophilic cytoplasm and an association with blood vessel walls.1 Furthermore, PEComas stain positive for HMB45, HMSA-1, Melan A, MITF, actin and less commonly desmin.2 ACCs originate from cells of the adrenal cortex and should be diag- nosed by an experienced pathologist using the Weiss criteria for adrenocortical tumours, with local invasion or distant metastasis confirming malignancy.3 ACCs stain positive for SRC-1, Melan A, CAM5 and inhibin.4
ACCs can secrete multiple hormones concurrently (or be inter- mittently functional) such as mineralocorticoids, glucocorticoids or androgen, with majority of ACCs progressing to Cushing’s syn- drome with or without virilization.5,6 Functional assessment should
INCHES
CM
9
₽
NO
6
MEDLINE
7
3
8
9
10
P
be completed for all adrenal masses prior to resection beginning with hormonal markers (e.g. cortisol). If elevated, baseline serum dehydroepiandrosterone sulphate and overnight 1 mg dexametha- sone suppression test should be done. PEComas are non-functional tumours and do not express hormones.
On CT scan, both diseases appear solid, with an area of central necrosis and demonstrate prominent contrast enhancement.7 ACCs tend to have hypo to isotense signals on T1. Furthermore, adrenal tumours greater than 6 cm are highly suspicious for malignancy. As compared to PEComas which may be hyperintense on T1-weighted magnetic resonance imaging images because of the increase in vascularity.7
R0 surgical resection is the management of choice for isolated PEComas and ACCs.2,5 There is no standard approach to the re- section of a retroperitoneal mass. Surgical approach is dependent on the tumour location and surgeon preference. Medical manage- ment of PEComas includes mechanistic target of rapamycin (mTOR) inhibitor agents such as sirolimus or temsirolimus. For ACCs, adjuvant mitotane with resected stage I to III ACCs can be used to reduce the risk of recurrence.
This is the first case report that characterizes the differences between an adrenal PEComa and an ACC. A multidisciplinary approach should be undertaken in the diagnosis and management of rare retroperitoneal tumours.
Acknowledgement
We would like to thank Professor Christopher Fletcher, MD, FRCPath (Brigham and Woman’s Hospital, Boston) for kindly reviewing the histopathology slides and giving us his opinion.
Author contributions
Amos Nepacina Liew: Investigation; writing-original draft; writing-review & editing. John Slavin: Data curation. Niyaz
Naqash: Supervision. asiri arachchi: Supervision; writing- review & editing. Ian Simpson: Data curation.
References
1. Hornick JL, Fletcher CDM. PEComa: what do we know so far? Histopa- thology 2006; 48: 75-82.
2. Zarineh A, Silverman JF. Adrenal perivascular epithelioid cell tumor: a case report with discussion of differential diagnoses. Arch. Pathol. Lab. Med. 2011; 135: 499-502.
3. Weiss LM, Medeiros LJ, Vickery AL Jr. Pathologic features of prognos- tic significance in adrenocortical carcinoma. Am. J. Surg. Pathol. 1989; 13: 202-6.
4. Weissferdt A, Phan A, Suster S, Moran CA. Adrenocortical carcinoma: a comprehensive immunohistochemical study of 40 cases. Appl. Immunohistochem. Mol. Morphol. 2014; 22: 24-30.
5. Allolio B, Fassnacht M. Clinical review: adrenocortical carcinoma: clini- cal update. J. Clin. Endocrinol. Metab. 2006; 91: 2027-37.
6. Libe R. Adrenocortical carcinoma (ACC): diagnosis, prognosis, and treatment. Front. Cell Dev. Biol. 2015; 3: 45.
7. Rajiah P, Sinha R, Cuevas C, Dubinsky TJ, Bush WH Jr, Kolokythas O. Imaging of uncommon retroperitoneal masses. Radiographics 2011; 31: 949-76.
Amos N. Liew,* MBBS, GradDipSurgAnat ID Niyaz Naqash, ** MBBS, FRACS Asiri Arachchi, ** MBBS, FRACS Ian Simpson,¿ MBBS, FRCPA John Slavin,§ MBBS, FRCPA
*Department of Surgery, Monash Health, Melbourne, Victoria, Australia, Department of Surgery, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Victoria, Australia, ¿Department of Anatomical Pathology, Monash Health, Melbourne, Victoria, Australia and §Department of Anatomical Pathology, St Vincent’s Hospital, Melbourne, Victoria, Australia
doi: 10.1111/ans.16648