Malignant Adrenal Tumors Research Articles

MicroRNA era: the importance for diagnosis and prognosis of adrenocortical tumors.

MicroRNAs play an essential role in posttranscriptional regulation of gene expression. They are evolutionary conserved, small, noncoding, 19–22-nucleotide RNAs, whose abnormalities, such as up- or downregulated expression, have been associated with several neoplasms, including adrenocortical tumors. Expression levels of distinct microRNAs can distinguish benign from malignant adrenal tumors. This current review provides recent data on the miRNAs profile in benign and malignant adrenocortical tumors diagnosed in adult and pediatric patients.

Initial Experiences with a New Technique for Adrenal Surgery: Single-Port Adrenalectomy Retroperitoneoscopically (SPAR)

Introduction: Since the introduction of transperitoneal laparoscopic adrenalectomy,1 several retroperitoneal techniques have emerged. Retroperitoneoscopy can be performed with the patient in lateral or prone position.2,3 Standard three trocars are being used, but single-access retroperitoneal adrenalectomy is a new technique of which, few reports exist.4 The use of straight instruments for this procedure was reported only once.5 In our center, single-port adrenalectomy retroperitoneoscopically (SPAR) was started in 2011. Based on the literature, this retroperitoneoscopic technique was performed only in patients with small benign tumors (≤6 cm) and low body mass index (BMI) (<30).6 To our knowledge, this is the first video in urological literature showing this technique (duration 8.49 minutes). The results after seven procedures were evaluated. Materials and Methods: From May 2011 until February 2013, seven patients with either benign adrenal tumors or treatment-refractory Cushing underwent unilateral (n=5) or bilateral (n=2) SPAR, respectively, by one experienced laparoscopist. The single incision laparoscopic surgery (SILS) port (Covidien) was introduced through a 2.5–3 cm skin incision at the tip of the 12th rib with the patient in a prone position. Pneumoretroperitoneum was at constant pressure of 20 mm Hg. A 30° 5-mm laparoscope and standard instruments consisting of bipolar forceps and a Ligasure or Harmonic scalpel were used. The adrenal vein was clipped with 10-mm titanium clips. Patient characteristics, indications for surgery, perioperative outcomes, and complications were analyzed from a prospectively collected database by descriptive statistics (SPSS 20). Results: Mean age (six women and one man) was 47±5.8 years and BMI 24±1.0. In five patients, unilateral SPAR was performed for primary aldosteronism (mean tumor diameter: 1.5±0.14 cm). The mean operating time was 68±9.3 minutes and blood loss 7±1.2 mL. The mean hospital stay was 3.4±0.5 days. No conversions were indicated. One complication, that is, ureter injury (Clavien-Dindo grade IIIb), has occurred during a procedure in which the isolation cap of the Ligasure dislocated several times during introduction into the trocar opening with probable current leakage. During secondary open reconstruction, a clear thermal injury was identified at the proximal ureter. No late sequelae occurred. In the bilateral procedures, the operating times were 117 and 137 minutes, blood loss 5 mL each, and hospital stay 3 and 9 days, respectively. Depletion of excessive perioperative fluid challenge caused the extended hospital stay in one patient. Conclusions: In this video, SPAR is shown to be technically feasible for small benign adrenal tumors. Considering anatomical restrictions, retroperitoneoscopic surgery of malignant adrenal tumors is contraindicated. Initial results are encouraging with short operating times and minimal blood loss. The hospital stay is slightly longer compared to some reports in literature, but this seems a regional phenomenon in which endocrinologic reasons play a role. From a surgical point of view, most patients are able to go home on day 1 or 2 postoperatively. The serious complication that occurred indicates that close monitoring of technical problems during surgery is important. Future research should focus on the safety and advantages for cosmesis and postoperative pain. No competing financial interests exist. Runtime of video: 8 mins 49 secs

Characterization of lipid-rich adrenal tumors by FDG PET/CT: Are they hormone-secreting or not?

The purpose of this study was to evaluate the diagnostic ability of FDG PET/CT to predict the hormone-secretion status of lipid-rich adrenal tumors. This study included 29 lipid-rich (CT number <10 HU) adrenal tumors 2 cm or larger in diameter in 28 patients who underwent FDG PET/CT. The diagnoses were based on endocrine examinations, including adrenal venous sampling and subsequent surgical resection, or on the endocrinological and morphological imaging follow-up during a period of at least 6 months. The FDG uptake of the adrenal tumors was evaluated semi-quantitatively using maximum standardized uptake values (SUVmax) and a ratio of the adrenal SUVmax compared to the liver SUVmax (SUVratio) was used for comparison. The statistical significance of differences was assessed using the Mann-Whitney U test, and a p value <0.05 was considered to be statistically significant. The lipid-rich adrenal tumors were proved to be 16 non-hormone-secreting tumors (15 adenomas and one myelolipoma) and 13 hormone-secreting tumors (five subclinical cortisol-producing adenomas, six aldosterone-producing adenomas and two adenomas that produced both cortisol and aldosterone). None of the patients had pheochromocytoma or a malignant adrenal tumor. The SUVmax (median, range) of the hormone-secreting tumors (3.2, 2.0-8.3) was higher than that of the non-hormone-secreting tumors (2.4, 1.8-3.3) (p < 0.05). Similarly, the SUVratio of the hormone-secreting tumors (0.95, 0.70-3.10) was higher than that of the non-hormone-secreting tumors (0.72, 0.54-0.95) (p < 0.01). There was no significant difference in the tumor diameter between the two groups (p = 0.8). The sensitivity, specificity and accuracy of FDG PET/CT for differentiating hormone-secreting tumors from non-hormone-secreting tumors were 0.69, 0.81 and 0.76 for cutoff SUVratio of 0.8, and were 0.46, 1 and 0.76 for the cutoff SUVratio of 1.0, respectively. A lipid-rich adrenal tumor presenting increased FDG uptake compared with that of the liver is likely to be a hormone-secreting adenoma. Therefore, additional endocrinological investigations are strongly recommended when an FDG-avid lipid-rich incidentaloma is detected on FDG PET/CT.

A case of virilzing adrenocortical carcinoma diagnosed by urine steroid profiling

Childhood adrenocortical carcinoma is rare and has poor prognosis. Histopathological examination often helps in differentiating between benign versus malignant adrenal tumors. However, the diagnostic accuracy of adrenal biopsies varies and could be affected by the sampling and the quality of the specimen. Urine steroid profiling (USP) has been used to differentiate between malignant tumors from benign ones. We report a case of virilizing adrenocortical carcinoma in which the diagnosis was made with the help of the characteristic USP findings

Transperitoneal Laparoscopic Adrenalectomy for Large Right Adrenal Tumors (≥10 cm): Tips and Tricks

Abstract Introduction: To introduce some tips and tricks in transperitoneal laparoscopic adrenalectomy for large right adrenal tumors (≥10cm). Materials and Methods: Ten patients with a large right adrenal mass were operated in Changhai Hospital from January 2011 to February 2013. This population consisted of four male patients and six female patients, and the largest tumor size of 10 to 14 cm. For those adrenal mass bigger than 10 cm, we prefer the transperitoneal approach to facilitate manipulation. First, bigger space is beneficial for dissection and exposure of the big adrenal mass. Second, a clear anatomy can prevent important anatomic marks such as vena cava, renal vein, and adrenal vein from injury. We placed the first paraumbilical trocar for the camera. Under the endoscope, three more trocars were placed in the midclavicular line, parasternal line, and anterior line axillary along the costal margin. This trocar placement is the guarantee of sufficient angle and space for triangle manipulation, wi...

Minimally invasive surgery for malignant adrenal tumors

BackgroundThe increasingly widespread use of minimally invasive surgery has allowed surgeons to exploit this approach for malignant adrenal tumors, though its actual role remains debated. The purpose of this study was to ascertain whether minimally-invasive surgery is a safe and effective treatment for adrenal carcinoma and metastases. MethodsDemographic and clinical data were prospectively entered in a computerized endocrine surgery registry for all patients who underwent surgery for adrenal lesions at our institution over a 20-year period (1991–2010). For the purposes of the present study, the registry was queried to identify patients who had minimally-invasive surgery for adrenocortical carcinoma (group 1) or adrenal metastases (group 2). ResultsOut of 332 patients undergoing adrenalectomy 25 were operated on for adrenal malignancies: 9 (group 1) had primary adrenal carcinomas and 16 (group 2) had adrenal metastases. Successfully laparoscopic adrenalectomy was performed in 16.6% (1/6) and in 93.3% (14/15) of group 1 and group 2, respectively. The mean operating time was 140 min (range 70–280 min) and 80 min (range 50–180 min) for groups 1 and 2, respectively.The median survival for group 1 was 30 months and Kaplan–Meier life table analysis showed a survival rate of 89%, 25.4% and 12.7% at 1, 3 and 5 years, respectively. The median survival for group 2 was 28 months and Kaplan–Meier life table analysis identified survival rates of 94%, 20.1% and 6.7% at 1, 3 and 5 years, respectively. ConclusionsThis study shows that laparoscopic resection is inappropriate for patients with known or suspected adrenocortical carcinoma, while the laparoscopic approach can be justified and is feasible in case of adrenal metastases.

Giant Accessory Right-Sided Suprarenal Spleen in Thalassaemia

An accessory spleen is defined as ectopic splenic tissue that develops due to failure of fusion of cells during embryonic development as they migrate from the midline to the left upper quadrant. While benign, complications may arise which include trauma, torsion, or infarction of the ectopic tissue. Additionally, patients who have had a splenectomy secondary to treatment for previous pathology such as a haematological malignancy or idiopathic thrombocytopenia purpura may experience persistent symptoms due to the accessory splenic tissue. The presence of an accessory spleen is therefore of significant diagnostic and therapeutic importance. To the best of the authors' knowledge, this case is the second and largest reported case of a giant right suprarenal accessory spleen and highlights the difficulty in differentiation of these masses from malignant adrenal tumours.

Clinical characteristics and follow-up of Korean patients with adrenal incidentalomas

Background/AimsWe investigated the clinical characteristics and follow-up findings of subjects with adrenal incidentalomas in a single, tertiary-care hospital in South Korea.MethodsThe study consisted of a retrospective analysis of 282 adrenal incidentaloma patients who underwent radiographic and endocrinological evaluations at Samsung Medical Center in Seoul, South Korea, between January 2004 and July 2011.ResultsMost (86.2%) of the subjects were found to have nonfunctioning tumors. Functioning tumors were seen in 39 patients (13.8%). Among them, 28 (9.9%) had subclinical Cushing syndrome (SCS), six (2.1%) had pheochromocytoma, and five (1.8%) had primary hyperaldosteronism. Malignant adrenal tumors were discovered in three cases: two (0.7%) were primary adrenal cancers, and one (0.4%) was a secondary metastasis from a lung cancer. Significant risk factors for functional tumors were female gender (odds ratio [OR], 3.386; 95% confidence interval [CI], 1.611 to 7.117; p = 0.0013) and a noncontrast attenuation value of > 10 Hounsfield units (OR, 2.806; 95% CI, 1.231 to 6.397; p = 0.0141). During follow-up (mean, 22.5 months) of 72 of the patients, three (4.2%) developed hormonal changes due to functional tumors. One was confirmed as pheochromocytoma by histopathology, and the others were diagnosed with SCS and followed routinely without surgical intervention. No malignant transformation was found in these patients.ConclusionsBased on these findings, initial hormonal and radiographic evaluations for adrenal incidentalomas appear to be more important than follow-up tests because functional or malignant changes are rare.

Ultrasonographic appearance of adrenal glands in healthy and sick cats.

The first part of the study aimed to describe prospectively the ultrasonographic features of the adrenal glands in 94 healthy cats and 51 chronically sick cats. It confirmed the feasibility of ultrasonography of adrenal glands in healthy and chronically sick cats, which were not statistically different. The typical hypoechoic appearance of the gland surrounded by hyperechoic fat made it recognisable. A sagittal plane of the gland, not in line with the aorta, may be necessary to obtain the largest adrenal measurements. The reference intervals of adrenal measurements were inferred from the values obtained in the healthy and chronically sick cats (mean ± 0.96 SD): adrenal length was 8.9-12.5 mm; cranial height was 3.0-4.8 mm; caudal height was 3.0-4.5 mm. The second part of the study consisted of a retrospective analysis of the ultrasonographic examination of the adrenal glands in cats with adrenal diseases (six had hyperaldosteronism and four had pituitary-dependent hyperadrenocorticism) and a descriptive comparison with the reference features obtained in the control groups from the prospective study. Cats with hyperaldosteronism presented with unilateral severely enlarged adrenal glands. However, a normal contralateral gland did not preclude a contralateral infiltration in benign or malignant adrenal neoplasms. The ultrasonographic appearance of the adrenal glands could not differentiate benign and malignant lesions. The ultrasonographic appearance of pituitary-dependent hyperadrenocorticism was mainly a symmetrical adrenal enlargement; however, a substantial number of cases were within the reference intervals of adrenal size.

Study of radiofrequency ablation treatment of adrenal malignant tumors by ultrasound-guided unipolar cooling cycle

Objective To analyze the efficacy and the safety of ultrasound guided multiple-spot sector stereotaxis in unipolar cooling cycle radiofrequency ablation treatment of adrenal malignant tumors.Methods 36 adrenocortical carcinoma primary or metastatic tumors were treated with ultrasound guided percutaneous radiofrequency ablation by the multiple spot sector stereotaxis in unipolar cooling cycle.All patients were performed contrast enchanced ultrasound (CEUS) 15 minutes after treatment to determine whether the tumors were completely inactivated,if did not completely inactivated based on the imaging,the same therapy can be repeated.To evaluate response,contrast-enhanced CT scans (CECT) or CEUS were obtained 1 month after the procedure,if did not completely inactivated,the same therapy can be repeated.Before and after the procedure,the blood cortisol,adrenocorticotropic hormone (ACTH) and sugar level were detected and compared respectively.Results The efficacy:in the 36 lesions,31 lesions were inactivated and 5 lesions were residual by realtime CEUS.32 lesions were inactivated and 4 lesions were residual by CECT one month after the RFA therapy.There were no significant differences between the two groups(x2 =0.127,P =0.722).The hormone level:the blood cortisol,ACTH and sugar level were recovered normal after the therapy.The complication and adverse reaction:①Pain:all the patients felt slight pain and thermal expasion of the ablation region,among them,19 patients felt obvious pain were relieved after using analgesic.② Fluctuation of heart rate:14 patients' heart rate were slowed down,it was reached to 25-55 beats per minute,0.5mg atropine was given by intravenous injection to make the heart rate return to normal.③ Fluctuation of bloodpressure:9 patients' bloodpressure were elevated in the procedure,systolic pressure was 21-28 kPa,diastolic pressure was 13-19 kPa,5 mg nicardipine was given then relieved.There was no serious complication and dead cases in all the patients.Conclusions RFA is a safe and effective procedure for the treatment of adrenal malignant tumors and has great value in clinic applications. Key words: Ultrasonography; Microbubbles; Adrenal gland neoplasms; Catheter ablation; Contrastenhanced CT

Immunohistochemical detection of FSH receptors in pituitary adenomas and adrenal tumors

Objectives . Follicle stimulating hormone (FSH) receptors (FSHR) are physiologically expressed in the ovary and testis. It is well known that FSHR are also expressed in gonadal cancers, but the data on their incidence in extra-gonadal tumors are scarce. Recently, the expression of FSHR in the vascular endothelium within different human cancers was found, but nothing is known on FSHR appearance in non-gonadal endocrine tumors. The present paper reports on the immunohistochemical detection of FSHR in human pituitary adenomas and adrenal tumors. Materials and methods . The study included samples of 28 pituitary adenomas and 36 adrenal tumors. Moreover, 2 samples of non-tumoral adrenal glands were also studied. FSH receptor immunostaining was performed on paraffin sections using the rabbit anti-human FSH-R polyclonal antibody raised against 1-190 amino acid sequence from the human FSH-R (sc-13935). The pituitary adenomas were immunostained to reveal the pituitary hormones and the proliferation marker Ki-67. Results . In the pituitary adenomas, positive immunostaining with anti-FSHR antibody occurred in the adenoma cells cytoplasm and endothelia of the intra- and peritumoral blood vessels. The cytoplasmic immunostaining was found in the majority of investigated tumors but the intensity of staining was weak to moderate. There is some tendency towards the higher cytoplasmic FSHR score in tumors with higher Ki-67 index (atypical adenomas). In contrast to the cytoplasm, the FSHR immunostaining in blood vessels is strong and concerns all the investigated samples. Strong FSHR immunostaining is present in the endothelium of intra- and/or peritumoral blood vessels in the majority of pheochromocytomas, approximatively one half of the adrenocortical adenomas and both cases of the adrenal cancers. The immunostaining is detectable also in the tumoral cell cytoplasm in all but one examined pheochromocytomas.. All the investigated adrenocortical adenomas presented strong immunostaining of cell membranes. No immunostained cell membranes were found. in adrenal cancers. The positive immunostaining was found in glandular cells, but not in blood vessels, of non-tumoral adrenal cortex and medulla. Conclusions . Immunostaining of FSHR often occurs in the endothelium of intra- and/or peritumoral blood vessels of pituitary adenomas and benign and malignant adrenal tumors. The immunostaining may be also present in tumoral cells. A role of FSHR expression in these tumors (stimulation of angiogenesis? stimulation of cell growth?) needs further studies to be clarified.

Immunohistochemical detection of FSH receptors in pituitary adenomas and adrenal tumors

Follicle stimulating hormone (FSH) receptors (FSHR) are physiologically expressed in the ovary and testis. It is well known that FSHR are also expressed in gonadal cancers, but the data on their incidence in extra-gonadal tumors are scarce. Recently, the expression of FSHR in the vascular endothelium within different human cancers was found, but nothing is known on FSHR appearance in non-gonadal endocrine tumors. The present paper reports on the immunohistochemical detection of FSHR in human pituitary adenomas and adrenal tumors. The study included samples of 28 pituitary adenomas and 36 adrenal tumors. Moreover, 2 samples of non-tumoral adrenal glands were also studied. FSH receptor immunostaining was performed on paraffin sections using the rabbit anti-human FSH-R polyclonal antibody raised against 1-190 amino acid sequence from the human FSH-R (sc-13935). The pituitary adenomas were immunostained to reveal the pituitary hormones and the proliferation marker Ki-67. In the pituitary adenomas, positive immunostaining with anti-FSHR antibody occurred in the adenoma cells cytoplasm and endothelia of the intra- and peritumoral blood vessels. The cytoplasmic immunostaining was found in the majority of investigated tumors but the intensity of staining was weak to moderate. There is some tendency towards the higher cytoplasmic FSHR score in tumors with higher Ki-67 index (atypical adenomas). In contrast to the cytoplasm, the FSHR immunostaining in blood vessels is strong and concerns all the investigated samples. Strong FSHR immunostaining is present in the endothelium of intra- and/or peritumoral blood vessels in the majority of pheochromocytomas, approximatively one half of the adrenocortical adenomas and both cases of the adrenal cancers. The immunostaining is detectable also in the tumoral cell cytoplasm in all but one examined pheochromocytomas. All the investigated adrenocortical adenomas presented strong immunostaining of cell membranes. No immunostained cell membranes were found. in adrenal cancers. The positive immunostaining was found in glandular cells, but not in blood vessels, of non-tumoral adrenal cortex and medulla. Immunostaining of FSHR often occurs in the endothelium of intra- and/or peritumoral blood vessels of pituitary adenomas and benign and malignant adrenal tumors. The immunostaining may be also present in tumoral cells. A role of FSHR expression in these tumors (stimulation of angiogenesis? stimulation of cell growth?) needs further studies to be clarified.

Giant suprarenal tumor

Adrenal tumors evoke considerable interest and represent various diagnostic challenges. Adrenal tumors can be stratified into adrenal medullary and adrenocortical tumors. Approximately 60% of adrenocortical tumors are hormonally active and show specific signs and symptoms. Patients with a nonfunctioning adrenal tumor usually present with abdominal discomfort due to the mass effect of the tumor. An imaging feature that differentiates benign from malignant adrenal neoplasms is the tumor size. Thus, for the differential diagnosis of adrenal lesions, measurement of the Hounsfield units on an unenhanced computed tomographic scan is of great value when differentiating malignant from benign lesions. Herein, we describe a young female patient who presented with a huge left suprarenal tumor. She underwent complete resection of the adrenal tumor. The final pathological diagnosis was an adrenocortical carcinoma. There has been no evidence of recurrence for the last 4 years.

Adrenalectomía laparoscópica en patología benigna

Laparoscopic adrenalectomy in benign disease Introduction: Nowadays the laparoscopic approach is the procedure of choice in adrenal diseases, except malignant adrenal tumors. Methods: A descriptive and retrospective study of the first 55 cases of laparoscopic adrenalectomy performed in our hospital between 1998 and 2011, we reviewed the short and long term results. Results: We had one case of conversion to open surgery in a patient with accidental section of the right renal vein. One case of reoperation due to hepatic injury. One case of postoperative mortality in a 71 year old woman with high anesthetic risk operated for Cushings syndrome. Other complications were a case of hydropneumothorax and three cases of abdominal wall hematoma in site of laparoscopic trocar. In the follow up at 45 months all the patients remain asymptomatic, except one with ectopic Cushings syndro- me due to bronchial carcinoid. Conclusions: Laparoscopic adrenalectomy has good results and is an easily reproducible procedure, but must be performed by expert laparoscopic surgeons with a good knowledge of adrenal anatomy and experience in open surgery which allow them to solve the complications that may arise during the laparoscopic procedure.

Importance of the biologic effective dose in achieving local control of adrenal tumors treated with stereotactic radiosurgery.

e21114 Background: Adrenalectomy achieves long term survival in ~ 25% of patients with solitary adrenal metastasis (SAM). Stereotactic radiosurgery (SRS) represents a potential non-surgical alternative to this same endpoint, but reported local control rates vary from 45% to 96%. SRS delivers a range of biologic effective doses (BED) dependent upon fraction size, number and schedule. We herein review our experience with SRS for adrenal metastasis to evaluate the interaction between BED and local adrenal tumor control. Methods: The Winthrop SRS data base was queried to identify 14 patients undergoing SRS for malignant adrenal tumors from 2006 to 2011. Patients were characterized by their primary tumor site, stage at diagnosis and the time to adrenal involvement. BED was calculated for each patient. Local adrenal tumor control and durability of response were also recorded. Results: Calculated BEDs ranged from 4,667 cGy to13,000 cGy. Of the factors examined, BED was the single most important predictor of local adrenal tumor control. According to best adrenal tumor response, mean BEDs were: 10,053 cGy for radiographic regression of disease; 8,115 cGy for stable disease, and 6,667 cGy for progression of disease (p = 0.0465, by one-tail test). No solid tumor patient responded to SRS with BED &lt; 8,800 cGy and no patient immediately progressed through SRS with BED &gt; 6,667 cGy. Duration of adrenal tumor control also correlated with calculated mean BED which was: 9,676 cGy for never locally failing (n=6) and 7,600 cGy for ever locally failing tumors (n=5). However, eventual local treatment failure was seen in one of three patients receiving even the highest calculated BED (13,000 cGy). Conclusions: Because eventual local failures are observed with SRS even at the highest examined BED, adrenalectomy rather than SRS should remain the standard of care for patients with potentially curable SAM. SRS remains an acceptable alternative to adrenalectomy for palliation of symptomatic adrenal tumors or for the definitive treatment of SAM in non-surgical candidates. When given for these purposes, our data support the use of SRS regimens delivering a minimum BED of 8,800 cGy.

Abstract 3932: IL13Rα2 regulates cell invasion, and is a therapeutic target for adrenocortical carcinoma

Abstract Adrencortical neoplasms are one of the most common human neopolasms. Furthermore, it is difficult to distinguish localized benign from malignant adrenal tumors. Adrenocortical carcinoma (ACC) is a relatively rare but aggressive malignancy with limited therapeutic options for patients with advanced and metastatic disease. Several genome wide expression studies have shown overexpression of Interleukin-13 Receptor alpha2 (IL13Rα2) in some human malignancies but the function of this gene in cancer cells is poorly understood. We evaluated IL13Rα2 mRNA expression in normal (n=21), and in benign (n=78) and malignant (n=10) adrenocortical tumors. We found 11-fold higher expression in malignant tumors compared to benign (p&amp;lt;0.05) and absent expression in normal adrenocortical tissue. Immunohistochemistry analysis confirmed high protein expression in malignant and benign tumors and absent expression in normal adrenocortical tissues (p&amp;lt;0.05). IL13Rα2 mRNA expression level also had 90% accuracy for distinguishing benign from malignant adrenocortical tumors. We used IL13Rα2 siRNA knockdown to assess its effect on cell proliferation and cell invasion in the NCI H295R cell line, which expressed high levels of IL13Rα2. IL13Rα2 knockdown did not significantly affect cell proliferation but did decrease invasion by 60% as compared to negative control (p&amp;lt;0.05). To determine the significance of IL13Rα2 as a therapeutic target for ACC, we evaluated the sensitivity in two ACC cell lines (NCI-H295R with high IL13Rα2 expression and SW13 with low IL13Rα2 expression) to a highly specific IL-13 targeting immunotoxin (IL-13-PE). We found the IC50 for IL-13-PE was 1.3ng/ml (NCI-H295R) and 1000ng/ml (SW13) in the cell lines. Based on this observation, we then tested the efficacy of IL-13-PE therapy in an ACC xenograft model in athymic nude mice. Mice receiving either intratumoral or intraperitoneal IL-13-PE therapy as compared to control showed a significant reduction in tumor size as well as tumor necrosis (p&amp;lt;0.05), and had prolonged survival (p&amp;lt;0.05). Both routes of IL-13-PE administration were well tolerated with no significant toxicity. Our study indicates that IL13Rα2 is overexpressed in 100% of ACC, is a good diagnostic marker for ACC, regulates ACC cell invasion, and is a novel therapeutic target for the treatment of ACC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3932. doi:1538-7445.AM2012-3932

Imaging of Adrenal Masses with Emphasis on Adrenocortical Tumors

Because of the more widespread and frequent use of cross-sectional techniques, mainly computed tomography (CT), an increasing number of adrenal tumors are detected as incidental findings (“incidentalomas”). These incidentaloma patients are much more frequent than those undergoing imaging because of symptoms related to adrenal disease. CT and magnetic resonance imaging (MRI) are in most patients sufficient for characterization and follow-up of the incidentaloma. In a minor portion of patients, biochemical screening reveals a functional tumor and further diagnostic work-up and therapy need to be performed according to the type of hormonal overproduction. In oncological patients, especially when the morphological imaging criteria indicate an adrenal metastasis, biopsy of the lesion should be considered after pheochromocytoma is ruled out biochemically. In the minority of patients in whom CT and MRI fail to characterize the tumor and when time is of essence, functional imaging mainly by positron emission tomography (PET) is available using various tracers. The most used PET tracer, [18F]fluoro-deoxy-glucose (18FDG), is able to differentiate benign from malignant adrenal tumors in many patients. 11C-metomidate (11C-MTO) is a more specialized PET tracer that binds to the 11-beta-hydroxylase enzyme in the adrenal cortex and thus makes it possible to differ adrenal tumors (benign adrenocortical adenoma and adrenocortical cancer) from those of non-adrenocortical origin.

Fine Needle Aspiration Cytology of Adrenal Oncocytic Neoplasm of Uncertain Malignant Potential

Sir, Adrenocortical oncocytic neoplasms (AONs) are rare tumors with only about 55 cases reported in the English language literature [1]. Histologic features that predict the biologic behaviour of AONs appear to differ from those of conventional adrenocortical tumors. In 2004, the modified Weiss system was proposed for AONs [2]. A 72-years old male was admitted for evaluation of a palpable abdominal mass. Computer Tomography scan of the abdomen revealed a large heterogeneously enhancing mass lesion arising from the left upper retroperitoneum having clear fat planes with pancreas, spleen and left kidney [Table/Fig-1A]. Possibility of malignant adrenal neoplasm was considered. Image guided Fine Needle Aspiration [FNA] smears were cellular showing singly dispersed polygonal cells with eccentric nucleus and dense granular cytoplasm [Table/Fig-1B]. A few cells were clinging to delicate capillaries in a clean background [Table/Fig-1B] (inset) suggesting a diagnosis of adrenal oncocytic neoplasm. The left adrenalectomy specimen consisted of a 2005 gm solid, encapsulated, globular mass measuring 20 × 15 × 12 cm. Cut surface of the tumor was solid, fleshy tan brown with lobulations of haemorrhage and necrosis [Table/Fig-1C]. The tumor was encapsulated and showed neoplastic cells arranged in a diffuse, solid pattern with multiple foci of haemorrhage, microcystic degeneration and necrosis [Table/Fig-1D]. Tumor cells were uniform with abundant brightly eosinophilic granular cytoplasm, round to oval vesicular nucleus. Mitotic figures, capsular and venous invasion were absent. A final diagnosis of adrenal oncocytic tumor of uncertain potential was given based on modified Weiss Criteria. Electron Microscopy confirmed the oncocytic nature of cells. [Table/Fig-1] [Table/Fig-1]: (1A) - CT scan showing a large well defined mass with heterogenous echotexture; (1B) - Smear showing singly dispersed cells with eccentric nucleus and granular cytoplasm (PAP 40X); (1B inset) - Smear showing tumor cells attached to delicate ... AONs have the potential to behave in a benign fashion, recur or extensively infiltrate into the adjacent organs. Average age at diagnosis is 47 years (range 6-77) with a slight female predilection [3]. Size varies from 2.2 to 20 cm and weight from 8 to 1900 g [1]. In our case the tumor weighed 2005 gm which is the highest so far reported. Imaging characteristics of adrenal oncocytic tumors are described as single case reports . Fibrous encapsulation and heterogeneous areas do not differentiate between benign and malignant oncocytic tumors [4]. Cytopathologic diagnosis of AONs by FNA is described by some authors.[5] Some of the criteria of Modified Weiss system like necrosis and atypical mitosis can be evaluated on cytology. Unfortunately accurate mitotic count, venous invasion and capsular invasion can not be assessed in smears. In the absence of major criteria, it is best to designate the tumor as an oncocytic adrenal neoplasm with a note for a detailed histopathologic assessment. If any minor criteria are present, designation AON of uncertain malignant potential may be rendered. In our case there was no necrosis or atypical mitosis on smears. However due to the large size and heterogeneous areas on CT scan, possibility of malignancy was still considered preoperatively. Only after detailed histopathologic examination, it was designated AON of uncertain malignant potential. Awareness of Modified Weiss criteria will help in averting over diagnosis of malignancy while dealing with FNA of AON.

Positional statement of the European Society of Endocrine Surgeons (ESES) on malignant adrenal tumors

Malignant adrenal tumors are very rare, and in addition, the criteria determining whether an adrenal neoplasm is benign or malignant are not precise. This explains that it is difficult to give clear recommendations, and in many cases, it is easier to recommend what should not be done than to recommend what should be done. The European Society of Endocrine Surgeons organized in Lyon (May 13–14, 2011) a workshop on malignant or potentially malignant adrenal tumors. In the year prior to the workshop, three working groups reviewed the available literature on pheochromocytomas (PCCs)/paragangliomas (PGLs), adrenocortical carcinomas, and metastases, respectively. In their respective field, these three working groups tried to grade the evidence for recommendations in accordance with accepted international standards. Results of their extensive update were presented during this workshop, and recommendations were discussed in three plenary sessions with input from all the participants. Articles were amended on the basis of the discussion at the workshop. Adrenocortical carcinomas

Urine Steroid Metabolomics as a Biomarker Tool for Detecting Malignancy in Adrenal Tumors

Context:Adrenal tumors have a prevalence of around 2% in the general population. Adrenocortical carcinoma (ACC) is rare but accounts for 2–11% of incidentally discovered adrenal masses. Differentiating ACC from adrenocortical adenoma (ACA) represents a diagnostic challenge in patients with adrenal incidentalomas, with tumor size, imaging, and even histology all providing unsatisfactory predictive values.Objective:Here we developed a novel steroid metabolomic approach, mass spectrometry-based steroid profiling followed by machine learning analysis, and examined its diagnostic value for the detection of adrenal malignancy.Design:Quantification of 32 distinct adrenal derived steroids was carried out by gas chromatography/mass spectrometry in 24-h urine samples from 102 ACA patients (age range 19–84 yr) and 45 ACC patients (20–80 yr). Underlying diagnosis was ascertained by histology and metastasis in ACC and by clinical follow-up [median duration 52 (range 26–201) months] without evidence of metastasis in ACA. Steroid excretion data were subjected to generalized matrix learning vector quantization (GMLVQ) to identify the most discriminative steroids.Results:Steroid profiling revealed a pattern of predominantly immature, early-stage steroidogenesis in ACC. GMLVQ analysis identified a subset of nine steroids that performed best in differentiating ACA from ACC. Receiver-operating characteristics analysis of GMLVQ results demonstrated sensitivity = specificity = 90% (area under the curve = 0.97) employing all 32 steroids and sensitivity = specificity = 88% (area under the curve = 0.96) when using only the nine most differentiating markers.Conclusions:Urine steroid metabolomics is a novel, highly sensitive, and specific biomarker tool for discriminating benign from malignant adrenal tumors, with obvious promise for the diagnostic work-up of patients with adrenal incidentalomas.