- Email: [email protected]
Unravelling Adrenal Oncocytic Neoplasm
Review
Unravelling Adrenal Oncocytic Neoplasm Mayur Virarkar, Madhavi Patnana, Raghunandan Vikram, Peeyush Bhargava, Elizabeth Birkenfeld, Tara Sagebiel Abstract Oncocytic neoplasms are rare tumors arising in the adrenal glands and usually considered as nonfunctional and benign. We report 4 cases of adrenal oncocytic neoplasm. The paucity of literature describing this entity increases the chance for misdiagnosis. Confirmatory diagnosis is by tissue sampling with adrenalectomy as the mainstay of treatment. Clinical Genitourinary Cancer, Vol. -, No. -, --- ª 2018 Elsevier Inc. All rights reserved. Keywords: Adenoma, CT, MRI, Rare, Weiss criteria
Introduction Oncocytic neoplasms are typically benign tumors, arising in the kidneys or thyroid, parathyroid, salivary, or pituitary glands, and less commonly found in the respiratory tract.1,2 Oncocytic neoplasms arising in the adrenal glands are extremely rare, nonfunctional, and mostly benign tumors.3 Radiologists and surgeons should be aware of this entity because of its common benign nature and other histopathologic variants. We report 4 cases of adrenal oncocytic neoplasm and a review of the recent literature.
Case 1 A 59-year-old female with medical history of ventricular arrhythmia and tachyarrhythmias requiring defibrillator and ablative therapy, cardiomyopathy, dyslipidemia, and hypothyroidism, was in the process of being evaluated for a heart transplant. She underwent a computed tomography (CT) of the chest, abdomen, and pelvis, demonstrating a 7.8-cm left adrenal gland mass in close proximity to the stomach (Figure 1). Her biochemical studies reported chromogranin A to be normal at 26. Her 24-hour urine collection for 5-hydroxyindoleacetic acid was normal at 2.7, and her plasma metanephrines were normal. Her outside urine catecholamines and vanillylmandelic acid were also normal. There was slight elevation in her plasma epinephrine at 104 (normal [< 95]). Her plasma norepinephrine and dopamine levels were normal. She underwent laparoscopic left adrenalectomy, with pathology revealing borderline Department of Diagnostic Radiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX Submitted: Oct 10, 2018; Accepted: Oct 21, 2018 Address for correspondence: Mayur Virarkar, MD, Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 E-mail contact: [email protected]
1558-7673/$ - see frontmatter ª 2018 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.clgc.2018.10.011
oncocytic adrenal cortical neoplasm of uncertain malignant potential. Immunohistochemical stains showed that the tumor cells are positive for calretinin and Mel A103, with patchy positivity for synaptophysin and cytokeratin cocktail; neoplastic cells are negative for inhibin, HMB-45, desmin, smooth muscle actin, chromogranin, and S-100. These results confirm an adrenocortical origin. The tumor cells exhibit a diffuse growth pattern with exclusively oncocytic cytoplasm and invasion into peri-adrenal adipose tissue. The mitotic rate is low (1 per 50 high power fields [HPFs]), with no atypical mitosis seen and no clear cut vascular invasion or tumoral necrosis. Postoperatively, she has partial adrenal insufficiency and was temporarily treated with cortisol.
Case 2 A 38-year-old female presented with migraines and several years history of dysfunctional uterine bleeding and amenorrhea for 1 year. At her subsequent endocrine evaluation, she presented with a 20-pound weight gain and found to have hirsutism and virilization. She underwent hormone evaluation including testosterone and DHEA sulfate, which were both elevated. She underwent a dexamethasone suppression test with dexamethasone every 6 hours for 48 hours. Following this test, she had a cortisol of 4.4 and an adrenocorticotropic hormone (ACTH) of less than 1.1. Predexamethasone suppression test, her ACTH was 16.2. A CT of the abdomen showed a 4.2-cm right adrenal gland nodule and a 2.7-cm left adrenal gland cyst (Figure 2). Ultrasound revealed a cystic lesion in the left adrenal gland and a solid right adrenal mass. Magnetic resonance imaging (MRI) of the abdomen demonstrated an enhancing 4-cm right adrenal mass with intermediate to high T2 signal and mild underlying heterogeneity and no invasion into the vasculature or adjacent structures. MRI also confirmed the left adrenal cyst. Subsequently, she underwent an open right adrenalectomy. The pathology reported adrenal cortical oncocytic neoplasm; hematoxylin
Clinical Genitourinary Cancer Month 2018
-1
Adrenal Oncocytic Neoplasm Table 1 Weiss Histopathologic Criteria Weiss Histopathological Criteria 1. High nuclear grade 2. Mitotic rate greater than five per 50 high power fields 3. Atypical mitotic figures 4. Eosinophilic tumor cell cytoplasm (greater than 75% tumor cells) 5. Diffuse architecture (greater than 33% of tumor) 6. Necrosis 7. Venous invasion 8. Sinusoidal invasion 9. Capsular invasion
and eosin sections showed an oncocytic neoplasm with 0 mitosis/50 HPFs, no lymphovascular or capsular invasion identified. Quantitative Ki-67 shows the proliferative index is 2.0% in average. She was given supportive medical management. No recurrent or metastatic disease was seen on postoperative follow-up MRI and CT, and she is on continued surveillance for recurrence.
Case 3 A 24-year-old female initially presented for evaluation of shortness of breath and had a CT to rule out pulmonary embolus where a 3-cm left adrenal mass was found. Endocrine evaluation was normal, and she was placed into surveillance with follow up CTs for 4 years prior to presenting to our institution. She continued to complain of intermittent shortness of breath and also complained of
fatigue, difficulty sleeping, headache, intermittent chest pain, heart palpitations, and depression. She denied family history of thyroid, parathyroid, pancreatic, and adrenal malignancy. Her past medical history includes hypertension, irregular heart rate, and urinary tract infection. A CT showed a 3.5 3-cm left adrenal mass with homogeneous enhancement measuring 40 Hounsfield units (HUs) on noncontrast examination and 120 HUs on the portal venous phase images (Figure 3). The left adrenal mass was deemed indeterminate by CT evaluation criteria. She underwent a left cortical sparing adrenalectomy. The pathology reported oncocytic adrenocortical neoplasm. The neoplasm was composed of sheets and loose clusters of cells with abundant eosinophilic cytoplasm. Features worrisome for aggressive/malignant behavior (atypical mitoses, necrosis, capsular invasion, large size, lymph-vascular space invasion) were not identified. By immunohistochemistry, the neoplastic cells show patchy positivity for MelanA and focal positivity for synaptophysin. The neoplastic cells are negative for HMB-45 and chromogranin. Both the morphologic and immunohistochemical features support the above diagnosis. Quantitative Ki-67 is 5.2% in average and 8.0% in hotspot. Based on established histologic criteria, the behavior is expected to be indolent. She is on surveillance and follow-up on biochemical profile including catecholamines, metanephrine, aldosterone, and electrolytes.
Case 4 A 43-year-old female presented to the emergency room with abnormal heavy menstrual bleeding. She was referred to a gynecologist and abnormal lab. Outside labs excluded
Figure 1 Case 1. Axial (A), Coronal (D), and Sagittal (E) Contrast Enhanced Computed Tomography Images Demonstrate a Heterogeneously Enhancing Left Adrenal Mass (Arrow). Longitudinal Ultrasound (B) and Transverse Power Doppler Ultrasound (C) Images Show a Heterogeneous Hypoechoic Left Adrenal Mass With Internal Vascularity (Arrow)
2
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Clinical Genitourinary Cancer Month 2018
Mayur Virarkar et al Figure 2 Case 2. A, Axial Contrast-Enhanced Computed Tomography Image Demonstrates an Enhancing Right Adrenal Mass (Arrow). Longitudinal (B) and Transverse (C) Ultrasound Images Show a Heterogeneous Hypoechoic Right Adrenal Mass With Internal Vascularity (Arrow). Axial T2 (D), Coronal T2 (E), T1 In-phase (F), T1 Out-phase (G), Post-contrast T1 (H), Diffusion (I), and Apparent Diffusion Coefficient (J) Images of Magnetic Resonance Imaging of the Abdomen Demonstrates a T2 Hyperintense Enhancing Right Adrenal Mass With Restrictive Diffusion and Without Internal Lipid or Macroscopic Fat (Arrow). A Left Adrenal Cyst (Thicker Short Arrow [D, F]) Is Also Noted
pheochromocytoma or excessive cortisol. She had elevated testosterone and DHEA. Patient has had some hirsutism and thinning of her hair. She had a 20-pound unintentional weight loss. The patient has had polycystic ovarian syndrome for the past 12 years and has had irregular menses during this time. She has no children. She had a 10epack-year smoking history and no oncologic history. A CT showed a right adrenal gland mass measuring 7.8 9.1 cm with invasion into the liver and the inferior vena cava (Figure 4). Subsequently she underwent a right radical adrenalectomy with partial right hepatectomy. The pathology reported oncocytic adrenal
cortical neoplasm of uncertain malignant potential. The adrenal cortical tumor had a Weiss score of 2 (clear cells < 25% of tumor cells and diffuse architecture > 33% of tumor). The tumor shows 2 mitoses per 50 HPFs. Based on the Lin-Weiss-Bisceglia criteria for oncocytic adrenal cortical neoplasms, the tumor meets one of the minor criteria (> 10 cm in size and weight > 200 grams). The computer-assisted quantitative Ki-67 staining shows an average of 3.6% (8092 total nuclei) and a hotspot of 4.4% (1562 total nuclei). Postoperatively, she is on supportive treatment and a surveillance plan.
Figure 3 Case 3. Axial Non-contrast (A), Axial (B), Coronal (C), and Sagittal (D) Contrast-Enhanced Computed Tomography Images Demonstrate a Well-Circumscribed Heterogeneously Enhancing Left Adrenal Mass (Arrow)
Clinical Genitourinary Cancer Month 2018
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Adrenal Oncocytic Neoplasm Figure 4 Case 4. Axial (A), Coronal (C), and Sagittal (D) Contrast-Enhanced Computed Tomography Images Demonstrate an Enhancing Right Adrenal Mass (Arrow). B, Axial Contrast-enhanced Computed Tomography Image Shows Focal Fatty Infiltration in Segment VII of the Liver (Thick Arrow)
Discussion We report 4 cases of rare oncocytic adrenal cortical neoplasm. The paucity of literature describing it increases the chance for misdiagnosis. Fewer than 150 cases in the English literature have been reported to our knowledge, with a lesser number including MRI, CT, ultrasound, and pathologic findings together.
Background Oncocytic neoplasms arising in the adrenal glands are extremely rare, and are usually discovered to be nonfunctional and mostly benign. The first description was in 1986 by Kakimoto et al4 and confirmed on electron microscopy by Smirnova et al.5 Few cases have been reported in the literature, most frequently described as incidental findings. In 2 of our patients, the neoplasms were reported incidentally during comorbidity workup. A different distribution pattern can be seen in the population with regards to the age, patient gender, size, and lesion location. The peak incidence is 50 to 70 years and more frequent in females. Most of them are incidentally detected. The mean age at diagnosis is 47 years (range, 27-72 years) and more common in the left gland.1 In our study, all our patients were female, with a mean age of 32.3 years (range, 24-59 years). Two masses were found on the left and 2 on the right.
The most important differential diagnosis is the adrenal adenoma. The majority of adrenal lesions can be differentiated based on lipid concentration. The majority of benign lesions are lipid-rich, with low attenuation on CT. The CT criterion used for the diagnosis of benign lipid-rich adenoma on unenhanced CT is attenuation of 10 HUs or less. In our patients, CT illustrated well-defined heterogeneous homogenous enhancing adrenal mass, with heterogeneous appearance in only 1 patient. Other differentials include pheochromocytoma, adrenal hyperplasia, adrenal cortical carcinomas,6 and metastasis with biochemical evaluation aiding in diagnosing these conditions. On MRI imaging, there was no loss of signal on T1 in-phase to out-phase chemical shift imaging, as seen in lipid-rich adrenal adenoma. There was no vascular invasion, regional lymph node involvement, or any perilesional fat stranding. No typical pattern has been described on ultrasound. Two of the 4 patients who underwent ultrasound showed heterogeneous hypoechoic adrenal masses with internal vascularity. In conclusion, CT and MRI findings can aid in detection of an adrenal oncocytic neoplasm or to differentiate between benign and malignant oncocytic neoplasms, thus narrowing the diagnosis. The diagnosis of oncocytic neoplasm can be confirmed on tissue sampling by biopsy or fine-needle aspiration cytology.6
Histopathology Imaging
4
-
In management, the tumor size usually differentiates a benign from a malignant adrenal mass. A diameter of less than 4 to 5 cm is usually considered benign. The mean size in our patients was 6 cm (range, 3.5-8.5 cm).
Clinical Genitourinary Cancer Month 2018
According to the current classification, there are 3 histologic categories: pure and benign oncocytoma, oncocytic neoplasm of uncertain malignant potential, and oncocytic carcinoma.7 Of the 4 patients in our study, histology revealed 2 oncocytic neoplasms and 2 with unknown malignant potential. A tumor is defined as an adrenocortical carcinoma
Mayur Virarkar et al when 3 or more of the following criteria are met: (1) a high nuclear grade; (2) a mitotic rate of more than 6 per 50 HPFs; (3) atypical mitosis; (4) more than 25% clear cells; (5) a diffuse architecture pattern in more than one-third of the tumor; (6) confluent necrosis; (7) venous invasion; (8) sinusoidal invasion; and (9) capsular invasion. The criteria, also known as Weiss criteria,8 are considered the standard tools for the diagnosis of adrenocortical malignancy (Table 1). This histopathologic system is the most widely used for differentiating benign from malignant adrenocortical tumors. Each Weiss criterion is scored 0 when absent and 1 when present. Thus each tumor is graded from 0 to 9 for determination of a total Weiss score. A tumor is considered malignant when it meets 4 or more of these histologic criteria.
Management Adrenalectomy is the mainstay of treatment.9-11 All of our patients underwent adrenalectomy with overall good outcomes.12 One of our patient developed partial adrenal insufficiency post adrenalectomy and was prescribed a short course of oral cortisol. It was thought to be owing to temporary suppression of the contralateral adrenal gland by the mildly functioning adrenal mass. The remaining patients were managed by supportive treatment and on surveillance with MRI or CT and regular biochemical evaluations.
Limitation Our retrospective study is limited by the number of patients; however, considering the rarity of the disease, these numbers can be considered acceptable. There are no current guidelines regarding the optimum imaging modality, time interval between imaging, or posttreatment surveillance; decisions are largely dependent on clinical and laboratory evaluations.
Conclusion Adrenal oncocytic neoplasm is a rare and usually benign condition. The diagnosis is made on the basis of histologic
examination, and adrenalectomy has been used as a successful treatment strategy.
Acknowledgments The authors would like to thank all participants for their support of this study.
Disclosure The authors have stated that they have no conflicts of interest.
References 1. Mearini L, Del Sordo R, Costantini E, Nunzi E, Porena M. Adrenal oncocytic neoplasm: a systematic review. Urol Int 2013; 91:125-33. 2. Maximo V, Rios E, Sobrinho-Simoes M. Oncocytic lesions of the thyroid, kidney, salivary glands, adrenal cortex, and parathyroid glands. Int J Surg Pathol 2014; 22: 33-6. 3. Tirkes T, Gokaslan T, McCrea J, et al. Oncocytic neoplasms of the adrenal gland. AJR Am J Roentgenol 2011; 196:592-6. 4. Kakimoto S, Yushita Y, Sanefuji T, et al. Non-hormonal adrenocortical adenoma with oncocytoma-like appearances. Hinyokika Kiyo 1986; 32:757-63. 5. Smirnova EA, Mikhailov IG. [Electron microscopic characteristics of oncocytoma of the lung, small intestine and adrenal gland]. Arkh Patol 1986; 48:79-81. 6. Khan M, Caoili EM, Davenport MS, et al. CT imaging characteristics of oncocytic adrenal neoplasms (OANs): comparison with adrenocortical carcinomas. Abdom Imaging 2014; 39:86-91. 7. Ertan Y, Argon A, Ozdemir M, Yurekli BPS, Dokumcu Z, Makay O. Oncocytic adreno cortical tumors: pathological features of 16 cases and review of the literature. J Environ Pathol Toxicol Oncol 2017; 36:237-44. 8. Papotti M, Libe R, Duregon E, Volante M, Bertherat J, Tissier F. The Weiss score and beyond–histopathology for adrenocortical carcinoma. Horm Cancer 2011; 2: 333-40. 9. Eldahshan S, Celia A, Zeccolini G, Guerini A, Breda G. Laparoscopic transperitoneal adrenalectomy for adrenocortical oncocytoma. Arch Ital Urol Androl 2008; 80:82-4. 10. Modi P, Goel R, Kadam G. Retroperitoneoscopic partial adrenalectomy for large adrenocortical oncocytoma. J Endourol 2007; 21:419-22. 11. Young JA, Chapman WH 3rd, Kim VB, et al. Robotic-assisted adrenalectomy for adrenal incidentaloma: case and review of the technique. Surg Laparosc Endosc Percutan Tech 2002; 12:126-30. 12. Lin BT, Bonsib SM, Mierau GW, Weiss LM, Medeiros LJ. Oncocytic adrenocortical neoplasms: a report of seven cases and review of the literature. Am J Surg Pathol 1998; 22:603-14.
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Unravelling Adrenal Oncocytic Neoplasm Mayur Virarkar, Madhavi Patnana, Raghunandan Vikram, Peeyush Bhargava, Elizabeth Birkenfeld, Tara Sagebiel Abstract Oncocytic neoplasms are rare tumors arising in the adrenal glands and usually considered as nonfunctional and benign. We report 4 cases of adrenal oncocytic neoplasm. The paucity of literature describing this entity increases the chance for misdiagnosis. Confirmatory diagnosis is by tissue sampling with adrenalectomy as the mainstay of treatment. Clinical Genitourinary Cancer, Vol. -, No. -, --- ª 2018 Elsevier Inc. All rights reserved. Keywords: Adenoma, CT, MRI, Rare, Weiss criteria
Introduction Oncocytic neoplasms are typically benign tumors, arising in the kidneys or thyroid, parathyroid, salivary, or pituitary glands, and less commonly found in the respiratory tract.1,2 Oncocytic neoplasms arising in the adrenal glands are extremely rare, nonfunctional, and mostly benign tumors.3 Radiologists and surgeons should be aware of this entity because of its common benign nature and other histopathologic variants. We report 4 cases of adrenal oncocytic neoplasm and a review of the recent literature.
Case 1 A 59-year-old female with medical history of ventricular arrhythmia and tachyarrhythmias requiring defibrillator and ablative therapy, cardiomyopathy, dyslipidemia, and hypothyroidism, was in the process of being evaluated for a heart transplant. She underwent a computed tomography (CT) of the chest, abdomen, and pelvis, demonstrating a 7.8-cm left adrenal gland mass in close proximity to the stomach (Figure 1). Her biochemical studies reported chromogranin A to be normal at 26. Her 24-hour urine collection for 5-hydroxyindoleacetic acid was normal at 2.7, and her plasma metanephrines were normal. Her outside urine catecholamines and vanillylmandelic acid were also normal. There was slight elevation in her plasma epinephrine at 104 (normal [< 95]). Her plasma norepinephrine and dopamine levels were normal. She underwent laparoscopic left adrenalectomy, with pathology revealing borderline Department of Diagnostic Radiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX Submitted: Oct 10, 2018; Accepted: Oct 21, 2018 Address for correspondence: Mayur Virarkar, MD, Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 E-mail contact: [email protected]
1558-7673/$ - see frontmatter ª 2018 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.clgc.2018.10.011
oncocytic adrenal cortical neoplasm of uncertain malignant potential. Immunohistochemical stains showed that the tumor cells are positive for calretinin and Mel A103, with patchy positivity for synaptophysin and cytokeratin cocktail; neoplastic cells are negative for inhibin, HMB-45, desmin, smooth muscle actin, chromogranin, and S-100. These results confirm an adrenocortical origin. The tumor cells exhibit a diffuse growth pattern with exclusively oncocytic cytoplasm and invasion into peri-adrenal adipose tissue. The mitotic rate is low (1 per 50 high power fields [HPFs]), with no atypical mitosis seen and no clear cut vascular invasion or tumoral necrosis. Postoperatively, she has partial adrenal insufficiency and was temporarily treated with cortisol.
Case 2 A 38-year-old female presented with migraines and several years history of dysfunctional uterine bleeding and amenorrhea for 1 year. At her subsequent endocrine evaluation, she presented with a 20-pound weight gain and found to have hirsutism and virilization. She underwent hormone evaluation including testosterone and DHEA sulfate, which were both elevated. She underwent a dexamethasone suppression test with dexamethasone every 6 hours for 48 hours. Following this test, she had a cortisol of 4.4 and an adrenocorticotropic hormone (ACTH) of less than 1.1. Predexamethasone suppression test, her ACTH was 16.2. A CT of the abdomen showed a 4.2-cm right adrenal gland nodule and a 2.7-cm left adrenal gland cyst (Figure 2). Ultrasound revealed a cystic lesion in the left adrenal gland and a solid right adrenal mass. Magnetic resonance imaging (MRI) of the abdomen demonstrated an enhancing 4-cm right adrenal mass with intermediate to high T2 signal and mild underlying heterogeneity and no invasion into the vasculature or adjacent structures. MRI also confirmed the left adrenal cyst. Subsequently, she underwent an open right adrenalectomy. The pathology reported adrenal cortical oncocytic neoplasm; hematoxylin
Clinical Genitourinary Cancer Month 2018
-1
Adrenal Oncocytic Neoplasm Table 1 Weiss Histopathologic Criteria Weiss Histopathological Criteria 1. High nuclear grade 2. Mitotic rate greater than five per 50 high power fields 3. Atypical mitotic figures 4. Eosinophilic tumor cell cytoplasm (greater than 75% tumor cells) 5. Diffuse architecture (greater than 33% of tumor) 6. Necrosis 7. Venous invasion 8. Sinusoidal invasion 9. Capsular invasion
and eosin sections showed an oncocytic neoplasm with 0 mitosis/50 HPFs, no lymphovascular or capsular invasion identified. Quantitative Ki-67 shows the proliferative index is 2.0% in average. She was given supportive medical management. No recurrent or metastatic disease was seen on postoperative follow-up MRI and CT, and she is on continued surveillance for recurrence.
Case 3 A 24-year-old female initially presented for evaluation of shortness of breath and had a CT to rule out pulmonary embolus where a 3-cm left adrenal mass was found. Endocrine evaluation was normal, and she was placed into surveillance with follow up CTs for 4 years prior to presenting to our institution. She continued to complain of intermittent shortness of breath and also complained of
fatigue, difficulty sleeping, headache, intermittent chest pain, heart palpitations, and depression. She denied family history of thyroid, parathyroid, pancreatic, and adrenal malignancy. Her past medical history includes hypertension, irregular heart rate, and urinary tract infection. A CT showed a 3.5 3-cm left adrenal mass with homogeneous enhancement measuring 40 Hounsfield units (HUs) on noncontrast examination and 120 HUs on the portal venous phase images (Figure 3). The left adrenal mass was deemed indeterminate by CT evaluation criteria. She underwent a left cortical sparing adrenalectomy. The pathology reported oncocytic adrenocortical neoplasm. The neoplasm was composed of sheets and loose clusters of cells with abundant eosinophilic cytoplasm. Features worrisome for aggressive/malignant behavior (atypical mitoses, necrosis, capsular invasion, large size, lymph-vascular space invasion) were not identified. By immunohistochemistry, the neoplastic cells show patchy positivity for MelanA and focal positivity for synaptophysin. The neoplastic cells are negative for HMB-45 and chromogranin. Both the morphologic and immunohistochemical features support the above diagnosis. Quantitative Ki-67 is 5.2% in average and 8.0% in hotspot. Based on established histologic criteria, the behavior is expected to be indolent. She is on surveillance and follow-up on biochemical profile including catecholamines, metanephrine, aldosterone, and electrolytes.
Case 4 A 43-year-old female presented to the emergency room with abnormal heavy menstrual bleeding. She was referred to a gynecologist and abnormal lab. Outside labs excluded
Figure 1 Case 1. Axial (A), Coronal (D), and Sagittal (E) Contrast Enhanced Computed Tomography Images Demonstrate a Heterogeneously Enhancing Left Adrenal Mass (Arrow). Longitudinal Ultrasound (B) and Transverse Power Doppler Ultrasound (C) Images Show a Heterogeneous Hypoechoic Left Adrenal Mass With Internal Vascularity (Arrow)
2
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Clinical Genitourinary Cancer Month 2018
Mayur Virarkar et al Figure 2 Case 2. A, Axial Contrast-Enhanced Computed Tomography Image Demonstrates an Enhancing Right Adrenal Mass (Arrow). Longitudinal (B) and Transverse (C) Ultrasound Images Show a Heterogeneous Hypoechoic Right Adrenal Mass With Internal Vascularity (Arrow). Axial T2 (D), Coronal T2 (E), T1 In-phase (F), T1 Out-phase (G), Post-contrast T1 (H), Diffusion (I), and Apparent Diffusion Coefficient (J) Images of Magnetic Resonance Imaging of the Abdomen Demonstrates a T2 Hyperintense Enhancing Right Adrenal Mass With Restrictive Diffusion and Without Internal Lipid or Macroscopic Fat (Arrow). A Left Adrenal Cyst (Thicker Short Arrow [D, F]) Is Also Noted
pheochromocytoma or excessive cortisol. She had elevated testosterone and DHEA. Patient has had some hirsutism and thinning of her hair. She had a 20-pound unintentional weight loss. The patient has had polycystic ovarian syndrome for the past 12 years and has had irregular menses during this time. She has no children. She had a 10epack-year smoking history and no oncologic history. A CT showed a right adrenal gland mass measuring 7.8 9.1 cm with invasion into the liver and the inferior vena cava (Figure 4). Subsequently she underwent a right radical adrenalectomy with partial right hepatectomy. The pathology reported oncocytic adrenal
cortical neoplasm of uncertain malignant potential. The adrenal cortical tumor had a Weiss score of 2 (clear cells < 25% of tumor cells and diffuse architecture > 33% of tumor). The tumor shows 2 mitoses per 50 HPFs. Based on the Lin-Weiss-Bisceglia criteria for oncocytic adrenal cortical neoplasms, the tumor meets one of the minor criteria (> 10 cm in size and weight > 200 grams). The computer-assisted quantitative Ki-67 staining shows an average of 3.6% (8092 total nuclei) and a hotspot of 4.4% (1562 total nuclei). Postoperatively, she is on supportive treatment and a surveillance plan.
Figure 3 Case 3. Axial Non-contrast (A), Axial (B), Coronal (C), and Sagittal (D) Contrast-Enhanced Computed Tomography Images Demonstrate a Well-Circumscribed Heterogeneously Enhancing Left Adrenal Mass (Arrow)
Clinical Genitourinary Cancer Month 2018
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Adrenal Oncocytic Neoplasm Figure 4 Case 4. Axial (A), Coronal (C), and Sagittal (D) Contrast-Enhanced Computed Tomography Images Demonstrate an Enhancing Right Adrenal Mass (Arrow). B, Axial Contrast-enhanced Computed Tomography Image Shows Focal Fatty Infiltration in Segment VII of the Liver (Thick Arrow)
Discussion We report 4 cases of rare oncocytic adrenal cortical neoplasm. The paucity of literature describing it increases the chance for misdiagnosis. Fewer than 150 cases in the English literature have been reported to our knowledge, with a lesser number including MRI, CT, ultrasound, and pathologic findings together.
Background Oncocytic neoplasms arising in the adrenal glands are extremely rare, and are usually discovered to be nonfunctional and mostly benign. The first description was in 1986 by Kakimoto et al4 and confirmed on electron microscopy by Smirnova et al.5 Few cases have been reported in the literature, most frequently described as incidental findings. In 2 of our patients, the neoplasms were reported incidentally during comorbidity workup. A different distribution pattern can be seen in the population with regards to the age, patient gender, size, and lesion location. The peak incidence is 50 to 70 years and more frequent in females. Most of them are incidentally detected. The mean age at diagnosis is 47 years (range, 27-72 years) and more common in the left gland.1 In our study, all our patients were female, with a mean age of 32.3 years (range, 24-59 years). Two masses were found on the left and 2 on the right.
The most important differential diagnosis is the adrenal adenoma. The majority of adrenal lesions can be differentiated based on lipid concentration. The majority of benign lesions are lipid-rich, with low attenuation on CT. The CT criterion used for the diagnosis of benign lipid-rich adenoma on unenhanced CT is attenuation of 10 HUs or less. In our patients, CT illustrated well-defined heterogeneous homogenous enhancing adrenal mass, with heterogeneous appearance in only 1 patient. Other differentials include pheochromocytoma, adrenal hyperplasia, adrenal cortical carcinomas,6 and metastasis with biochemical evaluation aiding in diagnosing these conditions. On MRI imaging, there was no loss of signal on T1 in-phase to out-phase chemical shift imaging, as seen in lipid-rich adrenal adenoma. There was no vascular invasion, regional lymph node involvement, or any perilesional fat stranding. No typical pattern has been described on ultrasound. Two of the 4 patients who underwent ultrasound showed heterogeneous hypoechoic adrenal masses with internal vascularity. In conclusion, CT and MRI findings can aid in detection of an adrenal oncocytic neoplasm or to differentiate between benign and malignant oncocytic neoplasms, thus narrowing the diagnosis. The diagnosis of oncocytic neoplasm can be confirmed on tissue sampling by biopsy or fine-needle aspiration cytology.6
Histopathology Imaging
4
-
In management, the tumor size usually differentiates a benign from a malignant adrenal mass. A diameter of less than 4 to 5 cm is usually considered benign. The mean size in our patients was 6 cm (range, 3.5-8.5 cm).
Clinical Genitourinary Cancer Month 2018
According to the current classification, there are 3 histologic categories: pure and benign oncocytoma, oncocytic neoplasm of uncertain malignant potential, and oncocytic carcinoma.7 Of the 4 patients in our study, histology revealed 2 oncocytic neoplasms and 2 with unknown malignant potential. A tumor is defined as an adrenocortical carcinoma
Mayur Virarkar et al when 3 or more of the following criteria are met: (1) a high nuclear grade; (2) a mitotic rate of more than 6 per 50 HPFs; (3) atypical mitosis; (4) more than 25% clear cells; (5) a diffuse architecture pattern in more than one-third of the tumor; (6) confluent necrosis; (7) venous invasion; (8) sinusoidal invasion; and (9) capsular invasion. The criteria, also known as Weiss criteria,8 are considered the standard tools for the diagnosis of adrenocortical malignancy (Table 1). This histopathologic system is the most widely used for differentiating benign from malignant adrenocortical tumors. Each Weiss criterion is scored 0 when absent and 1 when present. Thus each tumor is graded from 0 to 9 for determination of a total Weiss score. A tumor is considered malignant when it meets 4 or more of these histologic criteria.
Management Adrenalectomy is the mainstay of treatment.9-11 All of our patients underwent adrenalectomy with overall good outcomes.12 One of our patient developed partial adrenal insufficiency post adrenalectomy and was prescribed a short course of oral cortisol. It was thought to be owing to temporary suppression of the contralateral adrenal gland by the mildly functioning adrenal mass. The remaining patients were managed by supportive treatment and on surveillance with MRI or CT and regular biochemical evaluations.
Limitation Our retrospective study is limited by the number of patients; however, considering the rarity of the disease, these numbers can be considered acceptable. There are no current guidelines regarding the optimum imaging modality, time interval between imaging, or posttreatment surveillance; decisions are largely dependent on clinical and laboratory evaluations.
Conclusion Adrenal oncocytic neoplasm is a rare and usually benign condition. The diagnosis is made on the basis of histologic
examination, and adrenalectomy has been used as a successful treatment strategy.
Acknowledgments The authors would like to thank all participants for their support of this study.
Disclosure The authors have stated that they have no conflicts of interest.
References 1. Mearini L, Del Sordo R, Costantini E, Nunzi E, Porena M. Adrenal oncocytic neoplasm: a systematic review. Urol Int 2013; 91:125-33. 2. Maximo V, Rios E, Sobrinho-Simoes M. Oncocytic lesions of the thyroid, kidney, salivary glands, adrenal cortex, and parathyroid glands. Int J Surg Pathol 2014; 22: 33-6. 3. Tirkes T, Gokaslan T, McCrea J, et al. Oncocytic neoplasms of the adrenal gland. AJR Am J Roentgenol 2011; 196:592-6. 4. Kakimoto S, Yushita Y, Sanefuji T, et al. Non-hormonal adrenocortical adenoma with oncocytoma-like appearances. Hinyokika Kiyo 1986; 32:757-63. 5. Smirnova EA, Mikhailov IG. [Electron microscopic characteristics of oncocytoma of the lung, small intestine and adrenal gland]. Arkh Patol 1986; 48:79-81. 6. Khan M, Caoili EM, Davenport MS, et al. CT imaging characteristics of oncocytic adrenal neoplasms (OANs): comparison with adrenocortical carcinomas. Abdom Imaging 2014; 39:86-91. 7. Ertan Y, Argon A, Ozdemir M, Yurekli BPS, Dokumcu Z, Makay O. Oncocytic adreno cortical tumors: pathological features of 16 cases and review of the literature. J Environ Pathol Toxicol Oncol 2017; 36:237-44. 8. Papotti M, Libe R, Duregon E, Volante M, Bertherat J, Tissier F. The Weiss score and beyond–histopathology for adrenocortical carcinoma. Horm Cancer 2011; 2: 333-40. 9. Eldahshan S, Celia A, Zeccolini G, Guerini A, Breda G. Laparoscopic transperitoneal adrenalectomy for adrenocortical oncocytoma. Arch Ital Urol Androl 2008; 80:82-4. 10. Modi P, Goel R, Kadam G. Retroperitoneoscopic partial adrenalectomy for large adrenocortical oncocytoma. J Endourol 2007; 21:419-22. 11. Young JA, Chapman WH 3rd, Kim VB, et al. Robotic-assisted adrenalectomy for adrenal incidentaloma: case and review of the technique. Surg Laparosc Endosc Percutan Tech 2002; 12:126-30. 12. Lin BT, Bonsib SM, Mierau GW, Weiss LM, Medeiros LJ. Oncocytic adrenocortical neoplasms: a report of seven cases and review of the literature. Am J Surg Pathol 1998; 22:603-14.
Clinical Genitourinary Cancer Month 2018
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