- Email: [email protected]
Adrenocortical oncocytoma: a case report and review of literature
Journal of Pediatric Surgery (2008) 43, E1–E3
www.elsevier.com/locate/jpedsurg
Adrenocortical oncocytoma: a case report and review of literature Gargah T. Tahar a,⁎, Kaabar N. Nejib b , Sayed S. Sadok b , Lakhoua M. Mohamed Rachid a a
Department of Pediatrics, Charles Nicolle Hospital, Tunis, Tunisia Department of Pediatric Surgery, Habib Thameur Hospital, Tunis, Tunisia
b
Received 22 October 2007; revised 15 December 2007; accepted 17 December 2007
Key words: Adrenal gland; Children; Oncocytoma; Precocious puberty
Abstract Oncocytic tumors of the adrenal gland are uncommon. Most of these oncocytomas are benign and nonfunctioning. We report the case of functioning adrenocortical located in the right adrenal gland in a 6-year-old girl who presented with pseudoprecocious puberty and elevation of the estradiol level. She had an adrenalectomy. The tumor was small and composed predominantly of oncocytes. No criteria of malignancy were found. A discussion of this case and a review of the literature on this entity are presented. © 2008 Elsevier Inc. All rights reserved.
Adrenocortical oncocytoma is an unusual and mostly nonsecreting adrenal neoplasm. When secretion is noted, it produces steroid excess and results in a clinical presentation such as virilization, feminization, or Cushing syndrome [1]. The authors report a 6-year-old girl with pseudoprecocious puberty induced by adrenocortical oncocytoma. We describe the clinicopathologic and immunohistochemical findings associated with this tumor.
On physical examination, results showed that Tanner stage was S2P3A1, mental and motor development were appropriate for age, weight and height were at +1DS, blood
1. Case report A 6-year-old girl with pseudoprecocious puberty was referred to our department for investigation. The parents are healthy and nonconsanguineous, and there was no family history of cancer. Four months before admission, our patient developed sexual pubic hair and breast hypertrophy. She became violent and unable to play with other children. ⁎ Corresponding author. Tel.: +1 216 23 06 15 15; fax: +1 216 71 57 82 97. E-mail address: [email protected] (G.T. Tahar). 0022-3468/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2007.12.067
Fig. 1 T2-weighted axial MRI. A focus of high-signal intensity in the right adrenal gland.
E2
G.T. Tahar et al. Table 2 Criteria of malignancy oncocytoma proposed by Bisceglia et al [16]
Fig. 2 Microscopy. Tumor cells have characteristic oncocytic aspects with abundant eosinophilic cytoplasm (H&E, original magnification ×100).
pressure was normal (110/65 mm Hg), and pulse rate was 68 beats per minute. An abdominal mass was not palpable. Neurologic, cardiac, and pulmonary examinations showed no abnormal findings. Urinalysis was unremarkable. Bone age was advanced by 18 months as compared with her chronological age. Hormonal studies showed an elevated serum estradiol level (N61 pg/mL) and decreased levels of pituitary gonadotropins (follicle-stimulating hormone, 0.28 mU/mL; luteinizing hormone, undetectable). The dehydroepiandrosterone sulfate (1.8 µmol/L), total testosterone, 17-OH-progesterone, and cortisol levels were all normal. The urinary vanillylmandelic acid level was within a reference range. Abdominal ultrasonography showed a 27 × 25-mm mass in the right suprarenal area with no calcifications (Fig. 1). Magnetic resonance imaging (MRI) confirmed the ultrasonographic findings of a very well-demarcated mass 30 × 20 × 15-mm in the right adrenal gland, which was isodense with adrenocortical gland tissue on T1-weighted and T2-weighted images (Fig. 2). After the administration of gadolinium, there was decreased enhancement as compared with the adrenocortical tissue. There were no enlarged abdominal lymph nodes observed. After these investigations, an adrenal sex steroid-secreting tumor such as adenoma or
Table 1
Major criteria
Minor criteria
Mitotic rate N5 mitoses/50 high power fields Atypical mitosis Venous invasion
Large size tumor N10 cm and/or N200g Necrosis Capsular invasion Sinusoidal invasion
carcinoma was strongly suspected. The girl underwent a laparotomy; an adrenocortical mass was noted, which was well localized. Removal of the tumor with adjacent adrenocortical gland was performed. The tumor weighed 30 g and measured 35 mm in its largest dimension. The cut surface was brown and lobulated by fibrous septa and show neither necrosis nor hemorrhage. Light microscopic examination showed no abnormalities in the adjacent adrenal gland. The tumor was surrounded by a thick fibrous capsule. It consisted predominantly of large polygonal cells containing eosinophilic granular cytoplasm arranged in a solid pattern, interspersed with capillaries (Fig. 2). Occasional cellular atypia with enlarged nuclei and prominent nucleoli were observed. No necrosis, mitosis, or vascular invasion was seen. At the periphery, there were glandular tissues and tubules. The immunohistochemical profile was typical for adrenocortical oncocytoma and was positive for mitochondrial antigen MTCO2. Vimentin was negative, and proliferative activity wasvery low. Our final diagnosis was that of pseudoprecocious puberty caused by an adrenocortical oncocytoma. Twelve months after operative resection, our patient is well with no clinical or radiologic evidence of tumor recurrence. Estradiol was suppressed within the prepubertal range. The manifestations of pseudoprecocious puberty were effectively reduced—S1P2A1.
2. Discussion Oncocytic tumors are histologically characterized by cells with eosinophilic granular cytoplasm and ultrastructurally by the presence of numerous closely packed mitochondria. These
Clinical characteristics of 7 cases of functioning adrenocortical oncocytoma
Case and reference Age (y) Sex
Presenting symptoms
1 [1] 2 [7] 3 [8] 4 [9] 5 [10] 6 [11] 7 [12] Our case
Virilization 5 Virilization 2.2 Cushing syndrome 15 Preclinical Cushing syndrome Bilateral gynecomastia 6 Bilateral gynecomastia estradiol excess 20 Virilization 5 Pseudopuberty 3
61 53 51 54 5O 50 12 6
Female Female Male Male Male Male Female Female
Size of tumor (cm) Localization of tumor Profile Left adrenal Right adrenal Right adrenal Both adrenals Left adrenal Left adrenal Left adrenal Right adrenal
Benign Benign Malignant Malignant Malignant Malignant Benign Benign
Adrenocortical oncocytoma: a case report and review of literature tumors have been reported in a variety of anatomical sites, most frequently in kidney, thyroid, parathyroid, salivary gland, and pituitary [2,3]. In children, only renal oncocytoma is commonly reported [4-6]. The adrenocortical oncocytoma is extremely rare, commonly benign, and nonfunctioning. MEDline search revealed 6 cases of functioning adrenocortical oncocytoma (Table 1). All other reported adrenocortical oncocytomas were nonfunctioning and occur predominantly in females [13]. They are encountered incidentally during investigation for an abdominal mass or unrelated symptoms. There are no pathognomonic features on radiolographic study, but MRI is essential for the detection of enlarged lymph nodes suggestive of malignancy [14]. The diagnosis of oncocytoma is established by histologic and immunohistochemical studies; oncocytic tumors are composed entirely or almost exclusively of oncocytes, which are epithelial cells with eosinophilic granular cytoplasm [2]. In immunohistochemical analysis, these tumors are usually strongly positive for antimitochondrial antibodies, and frequently, vimentin and keratin is identified [15]. In our patient, the immunohistochemical profile was typical for adrenocortical oncocytoma. Clinical and biological features confirmed its secretory capacity. The major practical problem was to differentiate benign from malignant adrenocortical oncocytoma. Several reported studies have demonstrated that a combination of clinical, biochemical, and in particular, histologic parameters can distinguish most adrenocortical adenomas from carcinoma. There was no uniform scoring system used for the pathologic classification. In 2004, Bisceglia et al [16] proposed a new criteria (major and minor in Table 2) modified from the Weiss [17] and Vargas [18] to discriminate adrenocortical adenoma and carcinoma—if none of the major or minor criteria are present, the oncocytoma can be considered as benign. When the tumor exhibits one or more minor criteria, it is considered as borderline. The presence of one or more major criteria defines the lesion as a malignant oncocytoma. Many data suggest that the oncocytoma reported here is benign. First, none of major or minor criteria are present; second, no recurrence or evidence of metastasis was observed within 12 months after surgery. In children, the treatment of secreting tumors is complete surgical excision, but the management of an incidental nonfunctioning adrenocortical oncocytoma is controversial. Any adrenal tumor greater than 6 cm should be removed [19,20].
E3
References [1] Erlandson RA, Reuter VE. Oncocytic adrenal cortical adenoma. Ultrastruct Pathol 1991;15:539-47. [2] Chang A, Harawi SJ. Oncocytes, oncocytosis, and oncocytic tumors. Pathol Annu 1992;27:263-304. [3] Tallini G. Oncocytic tumours. Virchows Arch 1998;1:5-12. [4] Chen TS, McNally M, Hulbert W, et al. Renal oncocytosis presenting in childhood. Int J Surg Pathol 2003;11:325-9. [5] Seyedzadeh A, Parashar K, Raafat F, et al. Bilateral multifocal renal oncocytoma. Pediatr Nephrol 2003;18:1286-8. [6] Ciftci AO, Talim B, Senocak ME, et al. Renal oncocytoma: diagnostic and therapeutic aspects. J Pediatr Surg 2000;35(9):1396-8. [7] Xiao GQ, Pertsemlidis DS, Unger PD. Functioning adrenocortical oncocytoma: a case report and review of the literature. Ann Diagn Pathol 2005;9:295-7. [8] Golkowski F, Buziak B, et al. The unique case of adrenocortical malignant and functioning oncocytic tumour. Exp Clin Endocrinol Diabetes 2007;115(6):401-4. [9] Midorikawa S, Hashimoto S, Kuriki M, et al. A patient with preclinical Cushing's syndrome and excessive DHEA-S secretion having unilateral adrenal carcinoma and contralateral adenoma. Endocr J 1999;46(1):59-66. [10] Kadiri A, Chraibi. Bilateral gynecomastia revealing malignant feminizing adrenocortical carcinoma. Ann Endocrinol 1994;55(1): 43-4. [11] Czajka I, Zglicznsk W, Kasperlik-Zaluska A, et al. Gynecomasty as a first sign of adrenal carcinoma: case report. Endockrynol Pol 2005;56 (6):940-4. [12] Gumy-Pause F, Bongiovanni M, Wildhaber B, et al. Adrenocortical oncocytoma in a child. Pediatr Blood Cancer 2006, doi:10.1002/ pbc.21090. [13] Sasano H, Suzuki T, Sano T. Adrenocortical oncocytoma. A true nonfunctioning adrenocortical tumor. Am J Surg Pathol 1991;15: 949-56. [14] Zderic SA. Renal and adrenal tumors in children. Urol Clin N Am 2004;31:607-17. [15] Hoang MP, Ayala AG, Albores-saavedra J. Oncocytic adrenocortical carcinoma: a morphologic, immunohistochemical and ultrastructural study of four cases. Mod Pathol 2002;15:973-8. [16] Bisceglia M, Ludovico O, Di Mattia A. Adrenocortical oncocytic tumors: report of 10 cases and review of the literature. Int J Surg Pathol 2004;12:231-4. [17] Weiss LM, Medeiros LJ, Vickery Jr AL. Pathologic features of prognostic significance in adrenocortical carcinoma. Am J Surg Pathol 1989;13:202-6. [18] Vargas MP, Vargas HI, Kleiner DE, et al. Adrenocortical neoplasms: role of prognostic markers MIB-1, P53, and RB. Am J Surg Pathol 1997;21:556-62. [19] Porcaro AB, Novella G, Ficarra V, et al. Adrenal incidentalomas: surgical treatment in 28 patients and update of the literature. Int Urol Nephrol 2001;32:295-302. [20] Sabbaga CC, Avilla SG, Schulz C, et al. Adrenocortical carcinoma in children. Clinical aspects and prognosis. J Pediatr Surg 1993;28: 841-3.
www.elsevier.com/locate/jpedsurg
Adrenocortical oncocytoma: a case report and review of literature Gargah T. Tahar a,⁎, Kaabar N. Nejib b , Sayed S. Sadok b , Lakhoua M. Mohamed Rachid a a
Department of Pediatrics, Charles Nicolle Hospital, Tunis, Tunisia Department of Pediatric Surgery, Habib Thameur Hospital, Tunis, Tunisia
b
Received 22 October 2007; revised 15 December 2007; accepted 17 December 2007
Key words: Adrenal gland; Children; Oncocytoma; Precocious puberty
Abstract Oncocytic tumors of the adrenal gland are uncommon. Most of these oncocytomas are benign and nonfunctioning. We report the case of functioning adrenocortical located in the right adrenal gland in a 6-year-old girl who presented with pseudoprecocious puberty and elevation of the estradiol level. She had an adrenalectomy. The tumor was small and composed predominantly of oncocytes. No criteria of malignancy were found. A discussion of this case and a review of the literature on this entity are presented. © 2008 Elsevier Inc. All rights reserved.
Adrenocortical oncocytoma is an unusual and mostly nonsecreting adrenal neoplasm. When secretion is noted, it produces steroid excess and results in a clinical presentation such as virilization, feminization, or Cushing syndrome [1]. The authors report a 6-year-old girl with pseudoprecocious puberty induced by adrenocortical oncocytoma. We describe the clinicopathologic and immunohistochemical findings associated with this tumor.
On physical examination, results showed that Tanner stage was S2P3A1, mental and motor development were appropriate for age, weight and height were at +1DS, blood
1. Case report A 6-year-old girl with pseudoprecocious puberty was referred to our department for investigation. The parents are healthy and nonconsanguineous, and there was no family history of cancer. Four months before admission, our patient developed sexual pubic hair and breast hypertrophy. She became violent and unable to play with other children. ⁎ Corresponding author. Tel.: +1 216 23 06 15 15; fax: +1 216 71 57 82 97. E-mail address: [email protected] (G.T. Tahar). 0022-3468/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2007.12.067
Fig. 1 T2-weighted axial MRI. A focus of high-signal intensity in the right adrenal gland.
E2
G.T. Tahar et al. Table 2 Criteria of malignancy oncocytoma proposed by Bisceglia et al [16]
Fig. 2 Microscopy. Tumor cells have characteristic oncocytic aspects with abundant eosinophilic cytoplasm (H&E, original magnification ×100).
pressure was normal (110/65 mm Hg), and pulse rate was 68 beats per minute. An abdominal mass was not palpable. Neurologic, cardiac, and pulmonary examinations showed no abnormal findings. Urinalysis was unremarkable. Bone age was advanced by 18 months as compared with her chronological age. Hormonal studies showed an elevated serum estradiol level (N61 pg/mL) and decreased levels of pituitary gonadotropins (follicle-stimulating hormone, 0.28 mU/mL; luteinizing hormone, undetectable). The dehydroepiandrosterone sulfate (1.8 µmol/L), total testosterone, 17-OH-progesterone, and cortisol levels were all normal. The urinary vanillylmandelic acid level was within a reference range. Abdominal ultrasonography showed a 27 × 25-mm mass in the right suprarenal area with no calcifications (Fig. 1). Magnetic resonance imaging (MRI) confirmed the ultrasonographic findings of a very well-demarcated mass 30 × 20 × 15-mm in the right adrenal gland, which was isodense with adrenocortical gland tissue on T1-weighted and T2-weighted images (Fig. 2). After the administration of gadolinium, there was decreased enhancement as compared with the adrenocortical tissue. There were no enlarged abdominal lymph nodes observed. After these investigations, an adrenal sex steroid-secreting tumor such as adenoma or
Table 1
Major criteria
Minor criteria
Mitotic rate N5 mitoses/50 high power fields Atypical mitosis Venous invasion
Large size tumor N10 cm and/or N200g Necrosis Capsular invasion Sinusoidal invasion
carcinoma was strongly suspected. The girl underwent a laparotomy; an adrenocortical mass was noted, which was well localized. Removal of the tumor with adjacent adrenocortical gland was performed. The tumor weighed 30 g and measured 35 mm in its largest dimension. The cut surface was brown and lobulated by fibrous septa and show neither necrosis nor hemorrhage. Light microscopic examination showed no abnormalities in the adjacent adrenal gland. The tumor was surrounded by a thick fibrous capsule. It consisted predominantly of large polygonal cells containing eosinophilic granular cytoplasm arranged in a solid pattern, interspersed with capillaries (Fig. 2). Occasional cellular atypia with enlarged nuclei and prominent nucleoli were observed. No necrosis, mitosis, or vascular invasion was seen. At the periphery, there were glandular tissues and tubules. The immunohistochemical profile was typical for adrenocortical oncocytoma and was positive for mitochondrial antigen MTCO2. Vimentin was negative, and proliferative activity wasvery low. Our final diagnosis was that of pseudoprecocious puberty caused by an adrenocortical oncocytoma. Twelve months after operative resection, our patient is well with no clinical or radiologic evidence of tumor recurrence. Estradiol was suppressed within the prepubertal range. The manifestations of pseudoprecocious puberty were effectively reduced—S1P2A1.
2. Discussion Oncocytic tumors are histologically characterized by cells with eosinophilic granular cytoplasm and ultrastructurally by the presence of numerous closely packed mitochondria. These
Clinical characteristics of 7 cases of functioning adrenocortical oncocytoma
Case and reference Age (y) Sex
Presenting symptoms
1 [1] 2 [7] 3 [8] 4 [9] 5 [10] 6 [11] 7 [12] Our case
Virilization 5 Virilization 2.2 Cushing syndrome 15 Preclinical Cushing syndrome Bilateral gynecomastia 6 Bilateral gynecomastia estradiol excess 20 Virilization 5 Pseudopuberty 3
61 53 51 54 5O 50 12 6
Female Female Male Male Male Male Female Female
Size of tumor (cm) Localization of tumor Profile Left adrenal Right adrenal Right adrenal Both adrenals Left adrenal Left adrenal Left adrenal Right adrenal
Benign Benign Malignant Malignant Malignant Malignant Benign Benign
Adrenocortical oncocytoma: a case report and review of literature tumors have been reported in a variety of anatomical sites, most frequently in kidney, thyroid, parathyroid, salivary gland, and pituitary [2,3]. In children, only renal oncocytoma is commonly reported [4-6]. The adrenocortical oncocytoma is extremely rare, commonly benign, and nonfunctioning. MEDline search revealed 6 cases of functioning adrenocortical oncocytoma (Table 1). All other reported adrenocortical oncocytomas were nonfunctioning and occur predominantly in females [13]. They are encountered incidentally during investigation for an abdominal mass or unrelated symptoms. There are no pathognomonic features on radiolographic study, but MRI is essential for the detection of enlarged lymph nodes suggestive of malignancy [14]. The diagnosis of oncocytoma is established by histologic and immunohistochemical studies; oncocytic tumors are composed entirely or almost exclusively of oncocytes, which are epithelial cells with eosinophilic granular cytoplasm [2]. In immunohistochemical analysis, these tumors are usually strongly positive for antimitochondrial antibodies, and frequently, vimentin and keratin is identified [15]. In our patient, the immunohistochemical profile was typical for adrenocortical oncocytoma. Clinical and biological features confirmed its secretory capacity. The major practical problem was to differentiate benign from malignant adrenocortical oncocytoma. Several reported studies have demonstrated that a combination of clinical, biochemical, and in particular, histologic parameters can distinguish most adrenocortical adenomas from carcinoma. There was no uniform scoring system used for the pathologic classification. In 2004, Bisceglia et al [16] proposed a new criteria (major and minor in Table 2) modified from the Weiss [17] and Vargas [18] to discriminate adrenocortical adenoma and carcinoma—if none of the major or minor criteria are present, the oncocytoma can be considered as benign. When the tumor exhibits one or more minor criteria, it is considered as borderline. The presence of one or more major criteria defines the lesion as a malignant oncocytoma. Many data suggest that the oncocytoma reported here is benign. First, none of major or minor criteria are present; second, no recurrence or evidence of metastasis was observed within 12 months after surgery. In children, the treatment of secreting tumors is complete surgical excision, but the management of an incidental nonfunctioning adrenocortical oncocytoma is controversial. Any adrenal tumor greater than 6 cm should be removed [19,20].
E3
References [1] Erlandson RA, Reuter VE. Oncocytic adrenal cortical adenoma. Ultrastruct Pathol 1991;15:539-47. [2] Chang A, Harawi SJ. Oncocytes, oncocytosis, and oncocytic tumors. Pathol Annu 1992;27:263-304. [3] Tallini G. Oncocytic tumours. Virchows Arch 1998;1:5-12. [4] Chen TS, McNally M, Hulbert W, et al. Renal oncocytosis presenting in childhood. Int J Surg Pathol 2003;11:325-9. [5] Seyedzadeh A, Parashar K, Raafat F, et al. Bilateral multifocal renal oncocytoma. Pediatr Nephrol 2003;18:1286-8. [6] Ciftci AO, Talim B, Senocak ME, et al. Renal oncocytoma: diagnostic and therapeutic aspects. J Pediatr Surg 2000;35(9):1396-8. [7] Xiao GQ, Pertsemlidis DS, Unger PD. Functioning adrenocortical oncocytoma: a case report and review of the literature. Ann Diagn Pathol 2005;9:295-7. [8] Golkowski F, Buziak B, et al. The unique case of adrenocortical malignant and functioning oncocytic tumour. Exp Clin Endocrinol Diabetes 2007;115(6):401-4. [9] Midorikawa S, Hashimoto S, Kuriki M, et al. A patient with preclinical Cushing's syndrome and excessive DHEA-S secretion having unilateral adrenal carcinoma and contralateral adenoma. Endocr J 1999;46(1):59-66. [10] Kadiri A, Chraibi. Bilateral gynecomastia revealing malignant feminizing adrenocortical carcinoma. Ann Endocrinol 1994;55(1): 43-4. [11] Czajka I, Zglicznsk W, Kasperlik-Zaluska A, et al. Gynecomasty as a first sign of adrenal carcinoma: case report. Endockrynol Pol 2005;56 (6):940-4. [12] Gumy-Pause F, Bongiovanni M, Wildhaber B, et al. Adrenocortical oncocytoma in a child. Pediatr Blood Cancer 2006, doi:10.1002/ pbc.21090. [13] Sasano H, Suzuki T, Sano T. Adrenocortical oncocytoma. A true nonfunctioning adrenocortical tumor. Am J Surg Pathol 1991;15: 949-56. [14] Zderic SA. Renal and adrenal tumors in children. Urol Clin N Am 2004;31:607-17. [15] Hoang MP, Ayala AG, Albores-saavedra J. Oncocytic adrenocortical carcinoma: a morphologic, immunohistochemical and ultrastructural study of four cases. Mod Pathol 2002;15:973-8. [16] Bisceglia M, Ludovico O, Di Mattia A. Adrenocortical oncocytic tumors: report of 10 cases and review of the literature. Int J Surg Pathol 2004;12:231-4. [17] Weiss LM, Medeiros LJ, Vickery Jr AL. Pathologic features of prognostic significance in adrenocortical carcinoma. Am J Surg Pathol 1989;13:202-6. [18] Vargas MP, Vargas HI, Kleiner DE, et al. Adrenocortical neoplasms: role of prognostic markers MIB-1, P53, and RB. Am J Surg Pathol 1997;21:556-62. [19] Porcaro AB, Novella G, Ficarra V, et al. Adrenal incidentalomas: surgical treatment in 28 patients and update of the literature. Int Urol Nephrol 2001;32:295-302. [20] Sabbaga CC, Avilla SG, Schulz C, et al. Adrenocortical carcinoma in children. Clinical aspects and prognosis. J Pediatr Surg 1993;28: 841-3.