Endocr Pathol DOI 10.1007/s12022-015-9365-8
An Unusual Adrenal Cortical Nodule: Composite Adrenal Cortical Adenoma and Adenomatoid Tumor Orhun Cig Taskin 1 & Hasan Gucer 1,2 & Ozgur Mete 1,2
# Springer Science+Business Media New York 2015
Case History A 47-year-old man was found to have an incidental 7-cm right adrenal cortical nodule during the assessment of nonspecific symptoms. The endocrine workup was consistent with a non-functioning adrenal cortical nodule. The patient underwent right adrenalectomy due to large size of the lesion. Gross examination of the right adrenal gland confirmed an encapsulated yellow to white 7.0-cm nodular lesion in the cortex.
What Is Your Diagnosis? Histopathological Diagnosis: Composite Adrenal Cortical Adenoma and Adenomatoid Tumor On histological examination, this nodule consisted of clear cell adrenal cortical adenoma admixed with canalicular (angiomatoid) and tubular (gland-like) structures (Fig. 1a–d). Focal cystic change was also noted (Fig. 1b). Tubular structures were typically characterized by flat cells (Fig. 1a, c, d).
* Ozgur Mete [email protected] 1
Department of Pathology, University Health Network, 200 Elizabeth Street, 11th floor, Toronto, Ontario M5G 2C4, Canada
2
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
Some of these cells exhibited vacuolated cytoplasm resembling signet ring cells (Fig. 1c). Canalicular regions consist of pseudovascular spaces, composed of anastomosing flattened cells with scant cytoplasm resembling endothelial cells (Fig. 1a–d). Lymphoid aggregates, fibrosis, hyalinization, and calcification were observed. There was no evidence of necrosis or invasive growth. No mitotic figures were noted. The tubular and canalicular structures were negative for SF-1 (Fig. 2a), CD31, HMB-45, melan-A (clone A103), and S100 protein and were positive for AE1/AE3 (Fig. 2b), D2-40 (Fig. 2c), calretinin (Fig. 2d), and HBME-1 (Fig. 2e), justifying a mesothelial origin. CD34 was positive only in normal vascular endothelial cells (Fig. 2f). The adrenal cortical adenoma component was positive for SF-1 (Fig. 2a), melan-A (clone A103), and calretinin (focal weak) (Fig. 2d). p53 remained negative throughout the lesion. In light of the morphologic and immunohistochemical findings, the diagnosis of composite adrenal cortical adenoma and adenomatoid tumor was rendered.
Comment Adenomatoid tumor is a benign neoplasm of mesothelial origin that is generally seen in paratesticular adnexa, uterus, and fallopian tubes [1]. This entity has also been described in other organs including the adrenal gland [2-7]. Given the close developmental relationship of adrenals with the coelomic epithelium which also gives rise to mesothelial lining, one can understand why adrenal glands may host a spectrum of mesothelial-derived lesions including mesothelial inclusions, mesothelial adrenal (epithelial) cysts, and adenomatoid tumors. While
Endocr Pathol Fig. 1 The lesion consisted of clear adrenal cortical adenoma admixed with canalicular (angiomatoid) and tubular (glandlike) structures (a–d). Focal cystic change was also noted (b). Some gland-like structures resemble signet ring cells due to the presence of round intracytoplasmic vacuole (c). Canalicular regions consist of pseudovascular spaces, composed of flattened cells with scant cytoplasm resembling endothelial cells (a–d)
adenomatoid tumors have no characteristic imaging findings, they often present as isolated lesions in the adrenal gland [2-5]. However, rare cases have been identified in association with underlying micronodular cortical hyperplasia [6] or myelolipoma [7]. To our knowledge, we present herein a unique example of adenomatoid tumor occurring within an adrenal cortical adenoma in order to discuss the diagnostic challenges associated with this unusual presentation by emphasizing the role of ancillary tools. While adenomatoid tumors tend to present with welldelineated borders, those associated with expansive growth into the periadrenal soft tissue may simulate non-functioning adrenal cortical carcinomas. As illustrated in this case, the presence of irregular tubular structures surrounded by flattened cells may be mistaken for a vascular neoplasm, particularly a lymphangioma (Fig. 1a–d). Adenomatoid tumors are positive for mesothelial markers (calretinin, HBME-1), cytokeratins (AE1/AE3, CK5/6, CK7), and thrombomodulin. Of note, adenomatoid tumors also express D2-40 similar to lymphangiomas; therefore, the use of a panel of markers including mesothelial markers, cytokeratins, and other vascular endothelial markers (CD31, CD34, ERG) is important in this distinction. Complex tubules with gland-like appearance or cell groups with round intracytoplasmic vacuole, vesicular
nucleus (Fig. 1c), and small nucleolus may simulate metastatic adenocarcinoma or signet ring cell carcinoma, respectively [5]. In the presented case, the lack of pleomorphism, mitotic figures, necrosis, and cellular atypia argue against malignancy. It is important to emphasize that adenomatoid tumors typically stain for keratins; therefore, one cannot rely on the demonstration of keratin positivity to rule out metastatic carcinoma. One has also to remember that positivity for keratins along with vascular markers can also be encountered in an epithelioid angiosarcoma occuring in adrenal cortical adenoma [8]. The application of appropriate markers to determine the cellular origin (e.g., SF-1 for adrenal cortical origin, vascular endothelial markers for angiomas, and mesothelial markers for adenomatoid tumor) is crucial to solve this quandary. The absence of epithelial mucins, negativity for CEA, low MIB-1 labeling index, and positivity for mesothelial markers helps the diagnostician in this distinction. Some adenomatoid tumors exhibit cystic change simulating epithelial or endothelial adrenal cysts [2, 9]. Both epithelial and endothelial adrenal cysts have a thin capsule with a non-infiltrating border. Rare cases of retroperitoneal mesotheliomas infiltrating the adrenal gland should also be considered in the differential diagnosis of adenomatoid tumor arising in the adrenal gland [10].
Endocr Pathol Fig. 2 The clear cell adrenal cortical adenoma component was diffusely positive for SF-1, whereas both tubular and canalicular structures were negative for SF-1 (a). Tubular and canalicular structures were positive for AE1/AE3 (b), D2-40 (c), calretinin (d), and HBME-1 (e), confirming their mesothelial origin. CD34 was positive in only normal vascular endothelial cells (f)
While rare corticomedullary tumors have been defined, composite tumors of the adrenal gland are typically restricted to those originating from the adrenal medulla. To our knowledge, the presented case is a unique example of composite adrenal cortical adenoma and adenomatoid tumor. Despite its rarity, this presentation should be added to the spectrum of unusual adrenal cortical nodules.
References 1.
2.
3. Conflict of Interest The authors declare that they have no conflict of interest. 4. Ethical Statement This case report does not contain any research studies with human participants or animals performed by any of the authors. Therefore, for this type of manuscript formal consent is not required.
Wachter DL, Wünsch PH, Hartmann A, Agaimy A (2011). Adenomatoid tumors of the female and male genital tract. A comparative clinicopathologic and immunohistochemical analysis of 47 cases emphasizing their site-specific morphologic diversity. Virchows Arch 458:593–602. Bisceglia M, Carosi I, Scillitani A, Pasquinelli G (2009). Cystic lymphangioma-like adenomatoid tumor of the adrenal gland: Case presentation and review of the literature. Adv Anat Pathol.16:424-32. Phitayakorn R, Maclennan G, Sadow P, Wilhelm S (2011). Adrenal adenomatoid tumor in a patient with human immunodeficiency virus. Rare Tumors. 3:e21. El-Daly H, Rao P, Palazzo F, Gudi M. A (2010). A rare entity of an unusual site: adenomatoid tumour of the adrenal gland: a case report and review of the literature. Patholog Res Int 2010:702472.
Endocr Pathol 5.
Isotalo PA, Keeney GL, Sebo TJ, Riehle DL, Cheville JC (2003). Adenomatoid tumor of the adrenal gland: a clinicopathologic study of five cases and review of the literature. Am J Surg Pathol 27:96977. 6. Chung-Park M, Yang JT, McHenry CR, Khiyami A (2003). Adenomatoid tumor of the adrenal gland with micronodular adrenal cortical hyperplasia. Hum Pathol. 34:818-2. 7. Timonera ER, Paiva ME, Lopes JM, Eloy C, van der Kwast T, Asa SL (2008). Composite adenomatoid tumor and myelolipoma of adrenal gland: report of 2 cases. Arch Pathol Lab Med 132:265-7.
8.
Hayashi T, Gucer H, Mete O (2014). A mimic of sarcomatoid adrenal cortical carcinoma: epithelioid angiosarcoma occurring in adrenal cortical adenoma. Endocr Pathol. 25:404-9. 9. Liu YQ, Zhang HX, Wang GL, Ma LL, Huang Y (2010). A giant cystic adenomatoid tumor of the adrenal gland: a case report. Chin Med J (Engl). 123:372-4. 10. Nomura M, Sasano H, Okada Y, Watanabe T, Sakamoto S, Sakiyama Y, Sakamoto R, Abe I, Horiuchi T, Yanase T, Takayanagi R (2009). Adrenal failure caused by a retroperitoneal malignant mesothelioma. Intern Med. 48:2109-14.
An Unusual Adrenal Cortical Nodule: Composite Adrenal Cortical Adenoma and Adenomatoid Tumor Orhun Cig Taskin 1 & Hasan Gucer 1,2 & Ozgur Mete 1,2
# Springer Science+Business Media New York 2015
Case History A 47-year-old man was found to have an incidental 7-cm right adrenal cortical nodule during the assessment of nonspecific symptoms. The endocrine workup was consistent with a non-functioning adrenal cortical nodule. The patient underwent right adrenalectomy due to large size of the lesion. Gross examination of the right adrenal gland confirmed an encapsulated yellow to white 7.0-cm nodular lesion in the cortex.
What Is Your Diagnosis? Histopathological Diagnosis: Composite Adrenal Cortical Adenoma and Adenomatoid Tumor On histological examination, this nodule consisted of clear cell adrenal cortical adenoma admixed with canalicular (angiomatoid) and tubular (gland-like) structures (Fig. 1a–d). Focal cystic change was also noted (Fig. 1b). Tubular structures were typically characterized by flat cells (Fig. 1a, c, d).
* Ozgur Mete [email protected] 1
Department of Pathology, University Health Network, 200 Elizabeth Street, 11th floor, Toronto, Ontario M5G 2C4, Canada
2
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
Some of these cells exhibited vacuolated cytoplasm resembling signet ring cells (Fig. 1c). Canalicular regions consist of pseudovascular spaces, composed of anastomosing flattened cells with scant cytoplasm resembling endothelial cells (Fig. 1a–d). Lymphoid aggregates, fibrosis, hyalinization, and calcification were observed. There was no evidence of necrosis or invasive growth. No mitotic figures were noted. The tubular and canalicular structures were negative for SF-1 (Fig. 2a), CD31, HMB-45, melan-A (clone A103), and S100 protein and were positive for AE1/AE3 (Fig. 2b), D2-40 (Fig. 2c), calretinin (Fig. 2d), and HBME-1 (Fig. 2e), justifying a mesothelial origin. CD34 was positive only in normal vascular endothelial cells (Fig. 2f). The adrenal cortical adenoma component was positive for SF-1 (Fig. 2a), melan-A (clone A103), and calretinin (focal weak) (Fig. 2d). p53 remained negative throughout the lesion. In light of the morphologic and immunohistochemical findings, the diagnosis of composite adrenal cortical adenoma and adenomatoid tumor was rendered.
Comment Adenomatoid tumor is a benign neoplasm of mesothelial origin that is generally seen in paratesticular adnexa, uterus, and fallopian tubes [1]. This entity has also been described in other organs including the adrenal gland [2-7]. Given the close developmental relationship of adrenals with the coelomic epithelium which also gives rise to mesothelial lining, one can understand why adrenal glands may host a spectrum of mesothelial-derived lesions including mesothelial inclusions, mesothelial adrenal (epithelial) cysts, and adenomatoid tumors. While
Endocr Pathol Fig. 1 The lesion consisted of clear adrenal cortical adenoma admixed with canalicular (angiomatoid) and tubular (glandlike) structures (a–d). Focal cystic change was also noted (b). Some gland-like structures resemble signet ring cells due to the presence of round intracytoplasmic vacuole (c). Canalicular regions consist of pseudovascular spaces, composed of flattened cells with scant cytoplasm resembling endothelial cells (a–d)
adenomatoid tumors have no characteristic imaging findings, they often present as isolated lesions in the adrenal gland [2-5]. However, rare cases have been identified in association with underlying micronodular cortical hyperplasia [6] or myelolipoma [7]. To our knowledge, we present herein a unique example of adenomatoid tumor occurring within an adrenal cortical adenoma in order to discuss the diagnostic challenges associated with this unusual presentation by emphasizing the role of ancillary tools. While adenomatoid tumors tend to present with welldelineated borders, those associated with expansive growth into the periadrenal soft tissue may simulate non-functioning adrenal cortical carcinomas. As illustrated in this case, the presence of irregular tubular structures surrounded by flattened cells may be mistaken for a vascular neoplasm, particularly a lymphangioma (Fig. 1a–d). Adenomatoid tumors are positive for mesothelial markers (calretinin, HBME-1), cytokeratins (AE1/AE3, CK5/6, CK7), and thrombomodulin. Of note, adenomatoid tumors also express D2-40 similar to lymphangiomas; therefore, the use of a panel of markers including mesothelial markers, cytokeratins, and other vascular endothelial markers (CD31, CD34, ERG) is important in this distinction. Complex tubules with gland-like appearance or cell groups with round intracytoplasmic vacuole, vesicular
nucleus (Fig. 1c), and small nucleolus may simulate metastatic adenocarcinoma or signet ring cell carcinoma, respectively [5]. In the presented case, the lack of pleomorphism, mitotic figures, necrosis, and cellular atypia argue against malignancy. It is important to emphasize that adenomatoid tumors typically stain for keratins; therefore, one cannot rely on the demonstration of keratin positivity to rule out metastatic carcinoma. One has also to remember that positivity for keratins along with vascular markers can also be encountered in an epithelioid angiosarcoma occuring in adrenal cortical adenoma [8]. The application of appropriate markers to determine the cellular origin (e.g., SF-1 for adrenal cortical origin, vascular endothelial markers for angiomas, and mesothelial markers for adenomatoid tumor) is crucial to solve this quandary. The absence of epithelial mucins, negativity for CEA, low MIB-1 labeling index, and positivity for mesothelial markers helps the diagnostician in this distinction. Some adenomatoid tumors exhibit cystic change simulating epithelial or endothelial adrenal cysts [2, 9]. Both epithelial and endothelial adrenal cysts have a thin capsule with a non-infiltrating border. Rare cases of retroperitoneal mesotheliomas infiltrating the adrenal gland should also be considered in the differential diagnosis of adenomatoid tumor arising in the adrenal gland [10].
Endocr Pathol Fig. 2 The clear cell adrenal cortical adenoma component was diffusely positive for SF-1, whereas both tubular and canalicular structures were negative for SF-1 (a). Tubular and canalicular structures were positive for AE1/AE3 (b), D2-40 (c), calretinin (d), and HBME-1 (e), confirming their mesothelial origin. CD34 was positive in only normal vascular endothelial cells (f)
While rare corticomedullary tumors have been defined, composite tumors of the adrenal gland are typically restricted to those originating from the adrenal medulla. To our knowledge, the presented case is a unique example of composite adrenal cortical adenoma and adenomatoid tumor. Despite its rarity, this presentation should be added to the spectrum of unusual adrenal cortical nodules.
References 1.
2.
3. Conflict of Interest The authors declare that they have no conflict of interest. 4. Ethical Statement This case report does not contain any research studies with human participants or animals performed by any of the authors. Therefore, for this type of manuscript formal consent is not required.
Wachter DL, Wünsch PH, Hartmann A, Agaimy A (2011). Adenomatoid tumors of the female and male genital tract. A comparative clinicopathologic and immunohistochemical analysis of 47 cases emphasizing their site-specific morphologic diversity. Virchows Arch 458:593–602. Bisceglia M, Carosi I, Scillitani A, Pasquinelli G (2009). Cystic lymphangioma-like adenomatoid tumor of the adrenal gland: Case presentation and review of the literature. Adv Anat Pathol.16:424-32. Phitayakorn R, Maclennan G, Sadow P, Wilhelm S (2011). Adrenal adenomatoid tumor in a patient with human immunodeficiency virus. Rare Tumors. 3:e21. El-Daly H, Rao P, Palazzo F, Gudi M. A (2010). A rare entity of an unusual site: adenomatoid tumour of the adrenal gland: a case report and review of the literature. Patholog Res Int 2010:702472.
Endocr Pathol 5.
Isotalo PA, Keeney GL, Sebo TJ, Riehle DL, Cheville JC (2003). Adenomatoid tumor of the adrenal gland: a clinicopathologic study of five cases and review of the literature. Am J Surg Pathol 27:96977. 6. Chung-Park M, Yang JT, McHenry CR, Khiyami A (2003). Adenomatoid tumor of the adrenal gland with micronodular adrenal cortical hyperplasia. Hum Pathol. 34:818-2. 7. Timonera ER, Paiva ME, Lopes JM, Eloy C, van der Kwast T, Asa SL (2008). Composite adenomatoid tumor and myelolipoma of adrenal gland: report of 2 cases. Arch Pathol Lab Med 132:265-7.
8.
Hayashi T, Gucer H, Mete O (2014). A mimic of sarcomatoid adrenal cortical carcinoma: epithelioid angiosarcoma occurring in adrenal cortical adenoma. Endocr Pathol. 25:404-9. 9. Liu YQ, Zhang HX, Wang GL, Ma LL, Huang Y (2010). A giant cystic adenomatoid tumor of the adrenal gland: a case report. Chin Med J (Engl). 123:372-4. 10. Nomura M, Sasano H, Okada Y, Watanabe T, Sakamoto S, Sakiyama Y, Sakamoto R, Abe I, Horiuchi T, Yanase T, Takayanagi R (2009). Adrenal failure caused by a retroperitoneal malignant mesothelioma. Intern Med. 48:2109-14.
