Original Paper
Eur Surg Res 2008;40:235-238 DOI: 10.1159/000111147
Received: April 16, 2007
Accepted after revision: August 27, 2007 Published online: November 20, 2007
Malignant and Unclear Histological Findings in Incidentalomas
F. Duenschedeª F. Bittingerb A. Heintz” T. Musholtª M. Korenkova P. Kannd P. Ewalda I. Gockelª T. Jungingerª
ªDepartment of General and Abdominal Surgery, bInstitute of Pathology, Johannes Gutenberg University
Hospital Mainz, “Department of General and Visceral Surgery, Hildegardis Hospital, Mainz, dDepartment of Internal Medicine, Institute of Endocrinology, University Hospital Giessen/Marburg, Marburg, Germany
Key Words
Endoscopic surgery . Incidentaloma . Malignancy · Adenoma · Adrenal carcinoma
Abstract
Background: The management of incidentalomas with tu- mor size 3 cm and larger is still under controversial discus- sion. Study Design: Clinical charts of 65 patients who under- went adrenalectomy for an incidentaloma were reviewed. Results: Sixty-five patients were operated. There were 28 men and 37 women with a median age of 56.9 years. Median size of all resected lesions was 4.1 cm. Indications for surgery were tumor size equal and larger than 3 cm, recurrent pain, hormone status and patients’ fear of malignancy. In 45 pa- tients, the adenomas did not meet the defined criteria of malignancy. There were 9 cases of adrenal hyperplasia, and two cysts and two hematomas were found in 4 patients. Moreover, 1 schwannoma and 1 myelolipoma were removed. In 3 patients, a primary adrenocortical carcinoma of 3.4, 4.0, and 5.0 cm in diameter, respectively, was identified. In 1 pa- tient, an adrenal cortical carcinoma of 10.0 cm in diameter was operated. In 1 patient, the status (size: 4.5 cm) could not be determined conclusively. Conclusion: Hormonal activity should be determined independent of the size, and lesions with hormonal activity should be resected; in the presence of hormonally inactive masses, removal of tumors of 3 cm and larger in size is recommended.
Copyright @ 2008 S. Karger AG, Basel
Introduction
The availability of imaging diagnostic techniques has resulted in a marked improvement in the detection of ad- renal tumors (incidentalomas) [1, 2]. The hormonal activ- ity and the risk of malignancy associated with the tumor are of crucial importance in the choice of the appropriate therapeutic procedure [3]. The assessment of the malig- nancy risk is based on the size of the lesion [4]. While both the presence of hormonal activity and a tumor greater than 5-6 cm in diameter represent an indication for surgical excision, it remains an open question wheth- er patients with smaller tumors should be selected for surgery or not.
In the latter group of patients, the indication for sur- gery depends on the respective risk of malignancy as well as on the operative risk. On one hand, there is growing evidence for adrenal cortical carcinoma with a small tu- mor size of only 3 cm or larger [4] while at the same time the use of minimal invasive techniques for adrenalecto- my has led to a decrease in the operative risk. Conse- quently, this has increasingly led to the resection of hor- monally inactive incidentalomas of less than 5 cm in di- ameter [5, 6].
The present study of 65 patients was designed to deter- mine the rate of malignancy in incidentalomas, depend- ing on tumor size, especially those measuring between 3 and 5 cm. Our results may serve as a basis for decision
| KARGER | @ 2008 S. Karger AG, Basel 0014-312X/08/0402-0235$24.50/0 |
| Fax +41 61 306 12 34 | |
| E-Mail karger@karger.ch | Accessible online at: |
| www.karger.com | www.karger.com/esr |
Department of General and Abdominal Surgery
| Clinical features | Status | Weiss et al. [7] | Hough et al. [8] | van Slooten et al. [9] |
|---|---|---|---|---|
| Nuclear atypia | moderate to severe | 1 | 0.39 | 2.1 |
| Nuclear hyperchromatism | moderate to severe | 2.6 | ||
| Nucleolei | prominent | 4.1 | ||
| Atypical mitoses | identified | 1 | ||
| Xanthochromatic cells | <25% of total vol. | 1 | ||
| Architecture | diffuse growth | 1 | 0.92 | 1.6 |
| Veins | tumor invasion | 1 | 0.92 | 1.6 |
| Sinus | tumor invasion | 1 | 0.92 | 1.6 |
| Tumor capsule | tumor invasion | 1 | 0.37 | 3.3 |
| Necroses | identified | 1 | 0.69 | |
| Regressive changes | marked | 5.7 | ||
| Fibrous bands | identified | 1.00 | ||
| Mitoses | >5/50 high power field | 1 | ||
| >10/100 high power field | 0.69 | |||
| >2/10 high power field | 9.0 |
between immediate surgical management and delayed treatment of patients with incidentaloma of the adrenal gland.
Materials and Methods
From January 1994 to December 2006, 65 patients underwent adrenalectomy for incidentaloma of the adrenal gland in the De- partment of General and Abdominal Surgery of the Johannes Gutenberg University Mainz Hospital. Data collection included patient sex and age, surgical approach, postoperative hospital stay, complication rate and risk category, as well as hormonal ac- tivity and malignancy in dependence of tumor size. The endocri- nologic diagnostics was carried out by the assessment of 24-hour urinary catecholamine levels, the dexamethasone suppression test, and the measurement of serum electrolytes after detection of the adrenal mass. The diagnosis was based on imaging meth- ods including abdominal ultrasound, abdominal computed to- mography and magnetic resonance imaging. Patients were se- lected for surgery with tumors equal and larger than 3 cm in size.
The malignancy stage was determined based on the scores of Weiss, Hough, and van Slooten (table 1) [7-9]. Furthermore, a correlation between the histologic findings and tumor size was established.
We only included those patients whose adrenal lesions were discovered accidentally on abdominal imaging, performed for other reasons than suspected adrenal disease [10].
Results
A total number of 65 patients, 28 men and 37 women, underwent surgery; the mean age was 56.9 (range 23- 80) years. Median size of all resected lesions was 4.1 cm [1-10].
Patients with tumors <3 cm and >5 cm in diameter showed no features of hormonal activity, while hormonal activity was found in 8 (12.3%) patients with a tumor be- tween 3 and 5 cm in diameter. These lesions were found to be benign. Pre-Cushing’s syndrome with incompletely suppressed serum cortisol was identified in 7 patients and hyperaldosteronism was found in 1 patient.
Altogether, we operated 7 patients with tumor sizes <3 cm in diameter. In 2 of these patients, the indication for surgery was recurrent pain. In 4 patients, we found an increase in tumor size during follow-up examination and in 1 case the patient’s fear of malignancy led to the resec- tion of the lesion.
In 2 patients with cysts, adrenalectomy was performed because of recurrent pain.
Fifty-nine patients underwent surgery using laparo- scopic approach (25 retroperitoneal and 34 transperito- neal). Conversion to an open procedure was required in 1 patient with adhesion of the adrenal gland to the renal capsule. Conventional transabdominal approach was carried out in 6 patients. There were no intraoperative or postoperative complications.
| Laparoscopic adrenalectomy | 59 |
| Conversion | 1/59 |
| Conventional transabdominal approach | 6 |
| Postoperative complications | – |
| Postoperative hospital stay, median, days | 5.9±2 |
| Ade- nomas | Hyper- plasia | Hema- tomas | Cysts | Schwan- noma | Myeolo- lipoma | Carci- nomas | Incon- clusive | |
|---|---|---|---|---|---|---|---|---|
| 1-3 cm | 3 | 4 | – | – | – | – | – | – |
| 3-5 cm | 36 | 5 | 1 | 2 | – | – | 3 | 1 |
| >5 cm | 6 | – | 1 | – | 1 | 1 | 1 | – |
| Total | 45 | 9 | 2 | 2 | 1 | 1 | 4 | 1 |
The postoperative hospital stay was 5.9 ± 3 days (ta- ble 2). The ASA Classification grade II or grade III had no influence on the length of hospitalization.
Pathohistologic Findings
In 45 patients, the excised adenoma was without any of the described malignancy criteria (table 3): there were 9 cases of adrenal hyperplasia, while in 2 patients either cysts or hematomas were found. One schwannoma and one myelolipoma were also detected in 1 patient. A veri- table carcinoma was detected in 4 of the patients: in 3 cases size ranged from 3 to 5 cm in diameter (3.4, 4.0, and 5.0 cm), whereas in 1 carcinoma was 10 cm in diameter.
A comparison of the different scores showed corre- sponding results for 64 of the 65 patients. The tumor sta- tus could not be determined conclusively in 1 patient with an incidentaloma of 4.5 cm in diameter, because each of the three scores yielded a different histopatho- logic finding: according to Weiss [7] (score: 3) the mass represented an adenoma, it was inconclusive according to Hough [8] (score: 1.39), and the score of van Slooten [9] (score: 10.4) showed an adrenocortical carcinoma.
The 3 patients with histologically verified carcinoma between 3 and 5 cm in diameter have been operated lap- aroscopically and are without evidence of recurrence at a median follow-up examination of 5.8 years. The patient with the adrenocortical carcinoma of 10 cm in diameter has been operated conventionally and died 6 months af- ter surgery due to a progressive systemic disease, includ-
ing pulmonary and hepatic metastases. The patient with the inconclusive lesion has been operated laparoscopical- ly and is without evidence of recurrence until now.
Discussion
Endocrinologic diagnostics is indicated for all inci- dentalomas, regardless of their size. They are detected at a rate of 1-4% on computed tomography [11]. In the pres- ent series of patients, 8 of the 65 detected incidentalomas (12.3%) were hormonally active. This is in accordance to results reported by others [12, 13], who found hormone secretion in 5-25% of the incidentalomas in their studies. Pre-Cushing’s Syndrome was diagnosed in the majority of our patients (7/8), while other hormonal disorders were observed less frequently. With regard to tumor diameter, hormonal activity was noted to be increased particularly in tumors between 3 and 5 cm in diameter (6/11).
The indication for surgical excision of hormonally in- active incidentalomas is based on the assessment of the malignancy risk which is correlated to the size of the tu- mor [1, 4]. A number of scoring systems have been devel- oped with a view to the fact that the histologic examina- tion does not always enable the definite diagnosis of ad- renal malignoma. Three of the most widely used scoring systems were applied in the present patient population. A benign tumor was consistently identified in 60 of the 65 patients, and in 4 patients an adrenal carcinoma was also confirmed by all scoring systems. In one patient, a ma- lignoma was detected based on only one scoring system, while both of the remaining scores indicated the presence of a benign growth. The tumor status was therefore de- fined as inconclusive in this patient.
Regarding tumor size, no malignoma was detected in our patients with incidentalomas of less than 3 cm in size. Malignomas were found in 3 of 48 (6.25%) patients with tumors ranging from 3 to 5 cm in diameter. One patient of this group had an inconclusive finding. One carcinoma was found in the group of tumors >5 cm.
These results indicate that there is a substantial risk of malignoma even in the presence of relatively small le- sions. The incidence of malignancy in small tumors is closely related to patient selection. Assuming that the ma- jority of incidentalomas is not detected, the prevalence rate of malignoma can be expected to be very low in an unselected population group. The fact that patients un- dergoing surgery for incidentaloma represent a selected patient group explains the higher incidence of maligno- mas in these patients [14]. The comparatively highest
prevalence rate of malignomas was thus found in the present patient population. Favia et al. [15] report a ma- lignancy risk of 2% for tumors from 3 to 5 cm in size, and of 5.5% for lesions >5 cm. Linos et al. [16] demonstrated a similar malignancy risk of 3.5% for masses from 3 to 5 cm in diameter.
Schullick and Brennan [17] reported the most favor- able prognosis for tumors of less than 5 cm in diameter. The surgical removal of incidentalomas <5 cm is further supported by Mantero et al. [12] and Linos et al. [16], who advocate the surgical excision of lesions 4 cm in diameter. In addition Caplan et al. [18] view a tumor size of 3 cm and larger as an indication for surgical resection.
Our findings support the surgical excision of hormon- ally inactive incidentalomas smaller than 5 cm in diam- eter, in particular because the risk associated with endo- scopic adrenalectomy is low in specialized institutions. In
the 59 patients of our series there were no intraoperative or postoperative complications. Comparable results have been reported by other authors [19-21]. In addition to the low operative risk, the fact that in adrenal carcinoma the earliest possible resection of the tumor is associated with the most favorable prognosis serves as a further indica- tion for surgery [22]. Our results of follow-up examina- tion also support laparoscopic adrenalectomy for adrenal cortical neoplasms, especially for lesions equal and larger than 3 cm in size [23].
The present study suggests the following diagnostic and therapeutic procedure in the treatment of inciden- taloma: (1) hormonal activity should be determined in- dependently of tumor size; (2) surgical excision is indi- cated for lesions with confirmed hormonal activity; (3) in the presence of hormonally inactive masses, the removal of tumors 3 cm and larger in size is recommended.
References
1 Duh QY: Adrenal incidentalomas. Br J Surg 2002;89:1347-1349.
2 Prinz RA, Brooks MA, Churchill R: Inciden- tal asymptomatic adrenal masses detected by computed tomographic scanning. JAMA 1982;248:701-704.
3 Rossi R, Tauchmann L, Lombardi GD, Mar- tino M, Battista C, Del Viscovo L, Nuzzo V, Lombardi G: Subclinical Cushing’s syn- drome in patient with adrenal incidentalo- ma, clinical and biochemical features. J Clin Endocrinol Metab 2000;85:1440-1448.
4 Sturgeon C, Hen WT, Clark OH, Duh QY, Kebebew E: Risk assessment in 457 adrenal carcinomas: how much does size predict the likelihood of malignancy? J Am Coll Surg 2006;2002:423-430.
5 Heniford T, Arca MJ, Walsh RM, Gill IS: Laparoscopic adrenalectomy for cancer. Semin Surg Oncol 1997;16:293-306.
6 Junginger T, Heintz A, Beyer J, Kann P, Jaursch-Hancke C, Niemann U: Das Inzi- dentalom der Nebenniere: Erleichtert eine neue Operationstechnik die Entscheidung zur Operation? Dt Ärztebl 2001;18:1183- 1188.
7 Weiss LM, Medeiros LJ, Vickery AL: Patho- logic features of prognostic significance in adrenal cortical carcinoma. Am J Surg Pathol 1989;13:202-206.
8 Hough AJ, Hollifield JW, Page DL, Hart- mann WH: Prognostic factors in adrenal cortical tumors. A mathematical analysis of clinical and morphologic data. Am J Clin Pathol 1979;72:390-399.
9 van Slooten H, Schaberg A, Smeenk D, Moo- lenaar A: Morphologic characteristics of be- nign and malignant adrenocortical tumors. Cancer 1985;55:766-773.
10 Bülow B, Jansson S, Juhlin C, Stehen L, Tho- ren M, Wahrenberg H, Valdermarsson S, Wängberg B, Ahren B: Adrenal incidentalo- ma - follow-up results from a Swedish pro- spective study. Eur J Endocrinol 2006;154: 419-423.
11 Ross NS, Aron DC: Hormonal evaluation of the patient with incidentally discovered ad- renal mass. N Eng J Med 1990;323:1401- 1405.
12 Mantero F, Terzalo M, Arnaldi G, Osella G, Massini AM, Ali A Giovagnelli M, Opocher G, Angeli A: A survey on adrenal s of the Ital- ian society of endocrinology. J Clin Endocri- nol Metab 2000;85:637-644.
13 Cicala MV, Sartorato P, Mantero F: Inciden- tally discovered masses in hypertensive pa- tients. Best Pract Res Clin Endocrinol Metab 2006;20:451-466.
14 Terzalo M, Ali A, Osella G, Mazza E: Preva- lence of adrenal carcinoma among inciden- tally discovered adrenal masse. Arch Surg 1997;132:914-919.
15 Favia G, Lumachi F, D’Amico DF: Adreno- cortical carcinoma: is prognosis different in non-functioning tumors? Results of surgical treatment in 31 patients. World J Surg 2001; 25:735-738.
16 Linos DA, Stylopoulos N, Raptis SA: Adren- aloma: a call for more aggressive manage- ment. World J Surg 1996;20:788-793.
17 Schullick RD, Brennan MF: Long term sur- vival after complete resection and repeat re- section in patients with adrenocortical car- cinoma. Ann Surg Oncol 1999;6/83:719- 726.
18 Caplan RH, Kisken WA, Huiras CM: Inci- dentally discovered adrenal masses. Minn Med 1991;74:23-26.
19 Gagner M, Lacroix A, Bolte E: Laparoscopic adrenalectomy in Cushing’s syndrome and pheochromozytoma. N Eng J Med 1992;327: 1033-1037.
20 Gagner M, Pump A, Heniford T, Pharaud D, Lacroix A: Laparoscopic adrenalectomy. Lessons learned from 100 consecutive proce- dures. Ann Surg 1997;3:238-247.
21 Thompson GB, Grant CS, van Heerden JA, Schlinkert RT, Young WF, Farley DR, Ilstrup DM: Laparoscopic versus open posterior ad- renalectomy; a case-control study of 100 pa- tients. Surgery 1997;121:1132-1136.
22 Icard P, Goudet P, Charpenay C, Andreas- sian B, Carnaille B, Chapuis Y, Cougard P, Henry JF, Proye C: Adrenocartical carcino- mas: surgical trends and results of a 253-pa- tient series from French Association of En- docrine Surgeons study group. World J Surg 2001;25:891-897.
23 Kebebew E, Siperstein AE, Clark OH, Duh QY: Results of laparoscopic adrenalectomy for suspected and unsuspected malignant adrenal neoplasms. Arch Surg 2002;137: 948-951.
Copyright: 5. Karger AG, Basel 2008. Reproduced with the permission of 5. Karger AG, Basel. Further reproduction or distribution (electronic or otherwise) is prohibited without permission from the copyright holder.
Copyright: 5. Karger AG, Basel 2008. Reproduced with the permission of 5. Karger AG, Basel. Further reproduction or distribution (electronic or otherwise) is prohibited without permission from the copyright holder.