Predicting malignancy in patients with adrenal tumors using 18 F-FDG-PET/CT SUVmax.

BACKGROUND AND OBJECTIVES: 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG-PET/CT) parameters may help distinguish malignant from benign adrenal tumors, but few have been externally validated or determined based on definitive pathological confirmation. We determined and validated a threshold for 18 F-FDG-PET/CT maximum standard uptake value (SUVmax) in patients who underwent adrenalectomy for a nonfunctional tumor. METHODS: Database review identified patients with 18 F-FDG-PET/CT images available (training cohort), or only SUVmax values (validation cohort). Discriminative accuracy was assessed by area under the curve (AUC), and the optimal cutoff value estimated by maximally selected Wilcoxon rank statistics. RESULTS: Of identified patients (n = 171), 86 had adrenal metastases, 20 adrenal cortical carcinoma, and 27 adrenal cortical adenoma. In the training cohort (n = 96), SUVmax was significantly higher in malignant versus benign tumors (median 8.3 vs. 3.0, p < .001), with an AUC of 0.857. Tumor size did not differ. The optimal cutoff SUVmax was 4.6 (p < .01). In the validation cohort (n = 75), this cutoff had a sensitivity of 75% and specificity 55%. CONCLUSIONS: 18 F-FDG-PET/CT SUVmax was associated with malignancy. Validation indicated that SUVmax ≥ 4.6 was suggestive of malignancy, while lower values did not reliably predict benign tumor.

Texture Analysis as a Radiomic Marker for Differentiating Benign From Malignant Adrenal Tumors.

OBJECTIVE: The aim of this study was to evaluate the use of texture analysis for differentiation between benign from malignant adrenal lesions on contrast-enhanced abdominal computed tomography (CT). METHODS: After institutional review board approval, a retrospective analysis was performed, including an electronic search of pathology records for all biopsied adrenal lesions. Patients were included if they also had a contrast-enhanced abdominal CT in the portal venous phase. Computed tomographic images were manually segmented, and texture analysis of the segmented tumors was performed. Texture analysis results of benign and malignant tumors were compared, and areas under the curve (AUCs) were calculated. RESULTS: One hundred twenty-five patients were included in the analysis. Excellent discriminators of benign from malignant lesions were identified, including entropy and standard deviation. These texture features demonstrated lower values for benign lesions compared with malignant lesions. Entropy values of benign lesions averaged 3.95 using a spatial scaling factor of 4 compared with an average of 5.08 for malignant lesions (P < .0001). Standard deviation values of benign lesions averaged 19.94 on the unfiltered image compared with an average of 34.32 for malignant lesions (P < .0001). Entropy demonstrated AUCs ranging from 0.95 to 0.97 for discriminating tumors, with sensitivities and specificities ranging from 81% to 95% and 88% to 100%, respectively. Standard deviation demonstrated AUCs ranging from 0.91 to 0.94 for discriminating tumors, with sensitivities and specificities ranging from 73% to 93% and 86% to 95%, respectively. CONCLUSION: Texture analysis offers a noninvasive tool for differentiating benign from malignant adrenal tumors on contrast-enhanced CT images. These results support the further development of texture analysis as a quantitative biomarker for characterizing adrenal tumors.

Comparison of Adrenal Tumor Size in Ultrasound Examinations with and without the Use of a Contrast Agent.

Background and objectives: Patients diagnosed with incidentally found adrenal tumors (incidentaloma) that do not meet the criteria for surgical treatment require follow-ups with repeated imaging. The aim of this study is to compare the accuracy of the measurements of the adrenal tumor size in ultrasound (US) with and without contrast in comparison to computed tomography (CT) or magnetic resonance (MRI). Further, this study attempts to answer the question of whether contrast-enhanced ultrasound (CEUS) can improve imaging accuracy and replace CT/MRI in the monitoring of patients with adrenal tumors. Materials and Methods: The retrospective analysis included 79 adult patients with adrenal incidentalomas not exceeding a dimension of 6 cm who underwent a CT or MRI scan, US, and CEUS with the use of SonoVue in two-dimensional (2D) and three-dimensional (3D) projections and Doppler techniques. Tumor vascularization in CEUS was classified as follows: peripheral, peripheral-central, central, or poor. Results: Of 79 adrenal tumors, 48.1% showed peripheral, 29.1% showed poor, 21.5% showed peripheral-central, and only 1.3% showed central vascularization. The median volume of tumors detected with CEUS (69.9 cm3) was significantly higher than with US (44.5 cm3) and CT or MRI (57.1 cm3). The relative error of the adrenal volume with CEUS compared with CT or MRI was significantly higher than with standard US, regardless of the type of tumor vascularization. Conclusions: CEUS does not improve the accuracy of adrenal tumor size assessment regardless of the type of vascularization.

Role of indo-cyanine green (ICG) fluorescence in laparoscopic adrenalectomy: a retrospective review of 55 Cases.

BACKGROUND: Indo-Cyanine Green Fluorescence is an emerging technology with more frequent use in laparoscopic and robotic surgery. It relies on near-infrared (NIR) fluorescence to demonstrate tissue perfusion with demarcation of tissue planes and vascular pedicles. The aim of the study is to evaluate the role of this technology in laparoscopic adrenalectomy (LA). METHODS: 55 patients underwent laparoscopic adrenalectomy using NIR Fluorescence enabled laparoscope. All cases received a standard initial dose of 5-mg dye to aid tissue visualization. Surgery proceeded with "fluorescence mode" demonstrating real-time NIR images superimposed on standard white-light imaging. The timing, number of doses were dictated by the operating surgeon, which were recorded and correlated with intra-operative fluorescence visualization. RESULTS: 54 patients underwent successful LA, with one conversion in a case of large pheochromocytoma due to difficult hemostasis. The lag between ICG administration and visualization of adrenal fluorescence varied between 30 and 75 s. The total duration of adrenal parenchymal fluorescence after a single dose did not exceed 15 min in our series. Average total administered dose was 14.4 mg. We suffered no mortality. There were no adverse effects due to the dye. 5 patients suffered Grade I complications, with one patient suffering Grade II and IV complication each, as per Clavien-Dindo Classification. Final histopathology demonstrated pheochromocytoma, adrenocortical adenoma, adrenocortical carcinoma, cushing's adenoma, aldosteronoma, and myelolipoma. CONCLUSION: We describe our initial positive experience with ICG fluorescence in LA, with a detailed description of dye administration in our study. The technology offers real-time differentiation of tissues and identification of vascular structures, providing immediate guidance during surgery. Further evaluation of its role in adrenocortical malignancy is warranted. NIR fluorescence is a safe, useful addition in laparoscopic adrenalectomy which will undergo further refinement over time.

Screening of antitumor polypeptide drug and enhanced CT imaging based on drug target analysis.

Molecular targeted antitumor drugs is a major progress in recent years, these drugs usually target specific molecules to tumor cell signaling pathways, reduce toxicity, and can achieve individualized treatment. In this study, we screened three polypeptide proteins by yeast two hybrid systems, which could inhibit tumor growth obviously. The results of this study are expected to further develop new antitumor drugs. Moreover, by using contrast-enhanced computed tomography (CECT) imaging, this study proposes an algorithm for the computer-aided diagnosis (CAD) and classification of adrenal tumors. The experimental results demonstrate an excellent classification performance of this algorithm. Therefore, the method proposed in this paper may accurately locate and qualitatively diagnose the adrenal tumor in an effective manner, thereby providing important references for treatment.

[Grading of neuroendocrine tumors]. / Grading neuroendokriner Tumoren.

The current WHO classification of neuroendocrine tumors (NET) differentiates between typical carcinoids (low grade NET), atypical carcinoids (intermediate grade NET) and small cell and large cell carcinomas (high grade NET) according to the prognosis. Neuroendocrine neoplasms (NEN) of the gastrointestinal tract and the pancreas are graded in an identical way. Together with the TNM system this enables a preoperative estimation of the prognosis in biopsies and fine needle aspirates. Well-differentiated tumors are graded into G1 tumors by the number of mitoses, <2 per 10 high-power fields (HPF) and the Ki-67 (index <3 %) and G2 tumors (2-20 mitoses/10 HPF, Ki-67 3-20 %). Discrepancies between the number of mitoses and the Ki-67 index are not uncommon and in these cases the higher value of the two should be applied. The more differentiated tumors of the G3 type have to be differentiated from undifferentiated carcinomas of the small cell type and large cell type with a much poorer prognosis. Prognosis relevant grading of thyroid cancers is achieved by special subtyping so that the G1-G3 system is not applicable. The rare cancers of the parathyroid gland and of the pituitary gland are not graded. Adrenal tumors also have no grading system. The prognosis is dependent on the Ki-67 index and with some reservations on the established scoring systems.

Adrenal Imaging Features Predict Malignancy Better than Tumor Size.

INTRODUCTION: In adrenal tumors, size ≥ 4 cm has been an indication for adrenalectomy due to concern for malignancy. We compared mass size to imaging features (ImF) for accuracy in diagnosing adrenal malignancy. METHODS: Data were retrieved for 112 consecutive patients who had adrenalectomy from January 2011 to August 2014. ImF was classified as nonbenign if HU > 10 on unenhanced CT scan or if loss of signal on out-of-phase imaging was absent on chemical-shift MRI. Indications for resection included hormonal hypersecretion, nonbenign ImF, and/or size ≥ 4 cm. RESULTS: Of 113 resected adrenals, 37 % were functional. Histologic malignancy occurred in 18 % (20/113) and included 3 adrenocortical carcinomas (ACC), 1 epithelioid liposarcoma, 1 lymphoma, 1 malignant nerve sheath tumor, and 14 adrenal metastases. Patients with malignancies were older (mean age, 60 ± 13 vs. 51 ± 14 years, p = 0.01). Malignant tumors were larger on preoperative imaging (mean 5.3 ± 3.2 vs. 3.9 ± 2.4 cm, p = 0.03). All 20 malignant masses had nonbenign ImF. In predicting malignancy, the sensitivity, specificity, NPV, and PPV of nonbenign ImF was 100, 57, 100, and 33 %, respectively. Size ≥ 4 cm was less predictive with sensitivity, specificity, NPV, and PPV of 55, 61, 86, and 23 %, respectively. If size ≥ 4 cm had been used as the sole criterion for surgery, 45 % of malignancies (9/20) would have been missed including 8 metastases and an ACC. CONCLUSIONS: In resected adrenal tumors, the presence of nonbenign ImF is more sensitive for malignancy than mass size (100 vs. 55 %) with equivalent specificity. Regardless of mass size, adrenalectomy should be strongly considered when non-benign ImF are present.

[New aspects of tumor pathology of the adrenal glands]. / Neues aus der Tumorpathologie der Nebenniere.

In daily routine pathology of the adrenal glands three tumor entities are important: adrenocortical tumors, adrenomedullary tumors and metastases. The differentiation of these three main tumor types can often be difficult structurally but immunostaining enables a definite diagnosis in nearly all cases. Adrenocortical tumors are positive for steroidogenic factor 1 and melan-A and always negative for chromogranin A whereas adrenomedullary tumors express chromogranin A but never keratin. A broad spectrum of antibodies is available for the identification of metastases and even the rare epithelioid angiosarcomas. For adrenocortical tumors, adenomas and carcinomas can be differentiated using three scoring systems and the Ki-67 index in adenomas should not exceed 3%. Using scoring systems and the Ki-67 index approximately 90% of cortical tumors can be differentiated into benign or malignant tumors. For pheochromocytomas two scoring systems are used for differentiating benign and malignant tumors but the results are less dependable.

Two cases of neuroblastoma comprising two distinct clones.

We report two cases of high-risk metastatic neuroblastoma, comprising two biologically distinct components in the adrenal primary tumor, which showed clear differences not only histologically but also in MYCN amplification and HA-RAS/TRKA immunoreactivity (Case 1), anaplastic lymphoma kinase (ALK) immunoreactivity (Case 2). These two cases with multiple separated components were similar to cases classified as ganglioneuroblastoma, nodular subtype (GNBn), in terms of composite tumor. Comparable to the GNBn category, the prognosis of the patients described here may depend on the components with unfavorable histology according to International Neuroblastoma Pathology Classification. Further analyses of such composite neuroblastoma cases are important for assessing disease prognosis.

Ultrasound imaging in the diagnosis of benign and suspicious adrenal lesions.

BACKGROUND: The purpose of this study was to define the ultrasound imaging characteristics of adrenal tumors and to assess the performance of ultrasound in differentiating benign 'leave-alone' lesions from suspicious lesions. MATERIAL AND METHODS: We enrolled 882 patients in this study. The nature of each lesion was determined by histopathology. Ultrasound finding of each lesion was compared with its corresponding histopathologic result. The final study group consisted of 911 adrenal masses in 882 patients. All images were reviewed by 2 experienced investigators in a double blind manner. RESULTS: There were 553 adenomas identified in the study, which constituted 60.70% of the lesions. There were 161 pheochromocytomas (17.67%), 49 myelolipomas (5.38%), 39 cysts (4.28%), 37 metastasis (4.06%), 35 ganglioneuromas (3.84%), 22 lymphomas (2.41%), and 15 cortical carcinomas (1.65%). The sensitivity, specificity, and accuracy of ultrasound-based diagnosis were 89%, 99%, and 93.9%, respectively. A positive predictive value of 90.9% and a negative predictive value of 94.2% were obtained in this study. CONCLUSIONS: This large-sample study showed that ultrasound was a reliable method in differentiating benign 'leave-alone' lesions from suspicious lesions.

Perioperative management of pheochromocytoma: the heart of the issue.

Pheochromocytoma is an endocrine tumor derived from the adrenal medulla and paraganglia. Pheochromocytoma presents with a wide spectrum of symptoms, from a silent adrenal mass to cardiac arrest. Perioperative management of pheochromocytoma is critical for preventing perioperative cardiovascular complications. Traditionally, perioperative management focuses on blood pressure control, which has generated considerable controversy. In this review, we suggest that perioperative management should focus more on treating subclinical and clinical pheochromocytoma-induced cardiomyopathy. We first describe the natural history of pheochromocytoma and illustrate that cardiomyopathy is present to various degrees in patients with pheochromocytoma. We then classify pheochromocytomas into 3 groups according to the risks of developing clinical cardiomyopathy. After going over perioperative physiological changes, we propose that the need for preoperative preparation depends on the risk level of the pheochromocytoma. We present the regimens for perioperative management, emphasizing that the goals of perioperative management should extend beyond blood pressure control and include improvement of cardiac function. Perioperative management in unique clinical situations is also discussed.

Histologic and immunohistochemical classification of 41 bovine adrenal gland neoplasms.

Tumors of the adrenal glands are among the most frequent tumors in cattle; however, few studies have been conducted to describe their characteristics. The aim of this study was to classify 41 bovine adrenal neoplasms from 40 animals based on macroscopic and histologic examination, including electron microscopy and immunohistochemistry for melan A, synaptophysin, chromogranin A, vimentin, pan-cytokeratin, 2',3'-cyclic nucleotide-3'-phosphohydrolase (CNPase), and Ki-67. The tumors were classified as 23 adrenocortical adenomas, 12 adrenocortical carcinomas, 2 schwannomas, 2 pheochromocytomas (1 malignant), and 1 ganglioneuroma. Five histologic features were characteristic of metastasizing adrenocortical tumors: invasion of the capsule, vascular invasion, diffuse growth pattern, spindle-cell morphology, and nuclear pleomorphism. Adrenocortical tumors with at least 3 of these features were classified as malignant. Immunohistochemically, adrenocortical tumors expressed melan A (16/19), vimentin (14/26), cytokeratin (11/26), and chromogranin A (9/27), whereas pheochromocytomas expressed chromogranin A (2/2), synaptophysin (2/2), and vimentin (1/2). Both schwannomas expressed CNPase. An immunohistochemistry panel consisting of antibodies against melan A, synaptophysin, and CNPase was considered most useful to classify bovine adrenal tumors. However, the distinction between benign and malignant adrenocortical tumors was based on histologic features as in human medicine.

Malignant pheochromocytoma: new malignancy criteria.

PURPOSE: The pathological diagnosis of malignancy in pheochromocytomas remains a controversial issue. According to the WHO, malignancy is defined in the presence of metastasis. Multiparameter scoring systems such as PASS (Pheochromocytoma of Adrenal gland Scaled Score) have been used but remain controversial. The aim of this study was to search for new immunohistologic elements allowing determination of pheochromocytoma malignancy. METHODS: Among 53 patients operated for pheochromocytoma between 1993 and 2009, we selected pheochromocytomas with proven metastasis, seven cases in group 1 (G1) and paired two others groups: group 2 (G2), patients who had "benign" pheochromocytoma with PASS ≥4 and group 3 (G3), patients who had "benign" pheochromocytoma with PASS <4. We retrospectively analysed PASS criteria, size, weight, tumour necrosis, Ki-67 and pS100 staining. RESULTS: The size and weight of the lesion were directly and significantly correlated to malignancy in all three groups: respectively 9.7 cm and 292.0 g (G1), 6.2 cm and 83.8 g (G2) and 3.8 cm and 37.1 g (G3) (p < 0.005 for both). Tumour necrosis (TN) was present in all G1 (p < 0.005) and respectively at 0% and 37.5% in G2 and G3. Ki-67 is directly correlated to presence of TN (p < 0.005) and malignancy (G1 14.1%, G2 1.8%, G3 2.6%; p < 0.001). All G1 had a Ki-67 index >4%, although one G3 presented an 11% Ki-67 index. There was an inverse statistically significant correlation between the three groups in staining using pS100 (p < 0.01). CONCLUSIONS: Size and weight of the pheochromocytoma are directly related to PASS and malignancy. The presence of tumour necrosis, Ki-67 index >4% and pS100 absence impose a close histopathological evaluation and follow-up with regard to cases presenting a high risk of malignancy/recurrence.

Adrenal cancer: relevance of different grading systems and subtypes.

PURPOSE: The subclassification of adrenal cancers according to the WHO classification in ordinary, myxoid, oncocytic, and sarcomatoid as well as pediatric types is well established, but the criteria for each subtype are not sufficiently determined and the relative frequency of the different types of adrenal cancers has not been studied in large cohorts. Therefore, our large collection of surgically removed adrenal cancers should be reviewed o establish the criteria for the subtypes and to find out the frequency of the various types. METHODS: In our series of 521 adrenal cancers the scoring systems of Weiss et al., Hough et al., van Slooten et al. and the new Helsinki score system were used for the ordinary type of cancer (97% of our series) and the myxoid type (0.8%). For oncocytic carcinomas (2%), the scoring system of Bisceglia et al. was applied. RESULTS: Discrepancies between benign and malignant diagnoses from the first thee classical scoring systems are not rare (22% in our series) and could be resolved by the Helsinki score especially by Ki-67 index (more than 8% unequivocally malignant). Since all our cancer cases are positive in the Helsinki score, this system can replace the three elder systems. For identification of sarcomatoid cancer as rarest type in our series (0.2%), the scoring systems are not practical but additional immunostainings used for soft tissue tumors and in special cases molecular pathology are necessary to differentiate these cancers from adrenal sarcomas. According to the relative frequencies of the different subtypes of adrenal cancers the main type is the far most frequent (97%) followed by the oncocytic type (2%), the myxoid type (0.8%) and the very rare sarcomatoid type (0.2%). CONCLUSIONS: The Helsinki score is the best for differentiating adrenal carcinomas of the main, the oncocytic, and the myxoid type in routine work. Additional scoring systems for these carcinomas are generally not any longer necessary. Signs of proliferation (mitoses and Ki-67 index) and necroses are the most important criteria for diagnosis of malignancy.

Molecular imaging and radionuclide therapy of pheochromocytoma and paraganglioma in the era of genomic characterization of disease subgroups.

In recent years, advancement in genetics has profoundly helped to gain a more comprehensive molecular, pathogenic, and prognostic picture of pheochromocytomas and paragangliomas (PPGLs). Newly discovered molecular targets, particularly those that target cell membranes or signaling pathways have helped move nuclear medicine in the forefront of PPGL precision medicine. This is mainly based on the introduction and increasing experience of various PET radiopharmaceuticals across PPGL genotypes quickly followed by implementation of novel radiotherapies and revised imaging algorithms. Particularly, 68Ga-labeled-SSAs have shown excellent results in the diagnosis and staging of PPGLs and in selecting patients for PRRT as a potential alternative to 123/131I-MIBG theranostics. PRRT using 90Y/177Lu-DOTA-SSAs has shown promise for treatment of PPGLs with improvement of clinical symptoms and/or disease control. However, more well-designed prospective studies are required to confirm these findings, in order to fully exploit PRRT's antitumoral properties to obtain the final FDA approval. Such an approval has recently been obtained for high-specific-activity 131I-MIBG for inoperable/metastatic PPGL. The increasing experience and encouraging preliminary results of these radiotherapeutic approaches in PPGLs now raises an important question of how to further integrate them into PPGL management (e.g. monotherapy or in combination with other systemic therapies), carefully taking into account the PPGLs locations, genotypes, and growth rate. Thus, targeted radionuclide therapy (TRT) should preferably be performed at specialized centers with an experienced interdisciplinary team. Future perspectives include the introduction of dosimetry and biomarkers for therapeutic responses for more individualized treatment plans, α-emitting isotopes, and the combination of TRT with other systemic therapies.

Defining oligometastatic non-small cell lung cancer: A simulated multidisciplinary expert opinion.

INTRODUCTION: Synchronous oligometastatic non-small cell lung cancer (NSCLC) definition varies from 1 metastasis in 1 organ (tumour-node-metastasis 8 [TNM8]), 1-3 metastases (European Society for Medical Oncology [ESMO]), ≤3 metastases (including mediastinal nodes [MLN]) after systemic treatment to 3-5 metastases in ongoing trials. A single definition is however needed to design/compare trials. To assess oligometastatic NSCLC definitions used by clinical experts in daily practice and its evolution, we redistributed a 2012 case-based survey (Dooms, the World Congress of Lung Cancer 2013). METHODS: In December 2017, 10 real-life multidisciplinary team (MDT) discussed patients (good condition, no significant comorbidities, 18F-fluorodeoxyglucose positron emission tomography/brain magnetic resonance imaging staged, all < 5 metastases, 9/10 ≤ 3 metastases, oncogene-addicted or wild-type) were distributed to 33 international NSCLC experts involved in the European Organisation for Research and Treatment of Cancer oligometastatic NSCLC consensus group, questioning is this oligometastatic disease and if oligometastatic, which treatment proposal. The answers provided in 2017 were compared with the 2012 answers; real-life treatment and survival of the patients was added. RESULTS: Twenty-six of 33 experts (24 centres) replied: 8 medical oncologists, 7 pulmonologists, 7 radiation oncologists, 4 thoracic surgeons. Sixty-two percent of respondents discussed the cases with their MDT. One case had 100% oligometastatic consensus, and 3 cases had >90% consensus; the number of treatment proposals varied between 3 and 8. Radical treatment was more often offered in case of single metastasis or N0. Compared with 2012, there was a trend towards a more conservative oligometastatic definition and chemotherapy was more frequently included in the treatment proposal. CONCLUSIONS: Oligometastatic NSCLC definition was conservative. The number of organs, MLN status and radical treatment possibility seem to be components of daily practice oligometastatic definition.

Tree-based Methods for Characterizing Tumor Density Heterogeneity.

Solid lesions emerge within diverse tissue environments making their characterization and diagnosis a challenge. With the advent of cancer radiomics, a variety of techniques have been developed to transform images into quantifiable feature sets producing summary statistics that describe the morphology and texture of solid masses. Relying on empirical distribution summaries as well as grey-level co-occurrence statistics, several approaches have been devised to characterize tissue density heterogeneity. This article proposes a novel decision-tree based approach which quantifies the tissue density heterogeneity of a given lesion through its resultant distribution of tree-structured dissimilarity metrics computed with least common ancestor trees under repeated pixel re-sampling. The methodology, based on statistics derived from Galton-Watson trees, produces metrics that are minimally correlated with existing features, adding new information to the feature space and improving quantitative characterization of the extent to which a CT image conveys heterogeneous density distribution. We demonstrate its practical application through a diagnostic study of adrenal lesions. Integrating the proposed with existing features identifies classifiers of three important lesion types; malignant from benign (AUC = 0.78), functioning from non-functioning (AUC = 0.93) and calcified from non-calcified (AUC of 1).

Genetics of adrenal tumors associated with Cushing's syndrome: a new classification for bilateral adrenocortical hyperplasias.

Adrenocortical causes of Cushing's syndrome include the following: common cortisol-producing adenomas, which are usually isolated (without associated tumors) and sporadic (without a family history); rare, but often clinically devastating, adrenocortical carcinomas; and a spectrum of adrenocorticotropin-independent, and almost always bilateral, hyperplasias, which are not rare, and are the most recently recognized cause. The majority of benign lesions of the adrenal cortex seem to be linked to abnormalities of the cyclic AMP signaling pathway, whereas cancer is linked to aberrant expression of insulin-like growth factor II, tumor protein p53 and related molecules. In this article, we propose a new clinical classification and nomenclature for the various forms of adrenocorticotropin-independent adrenocortical hyperplasias that is based on their histologic and genetic features. We also review the molecular genetics of adrenocortical tumors, including recent discoveries relating to the role of phosphodiesterase 11A. This is a timely Review because of recent advances in the clinical and molecular understanding of these diseases.

[Diagnostic difficulties in adrenal incidentaloma--analysis of 125 cases]. / Trudnosci diagnostyczne dotyczace 125 przypadkowo wykrytych guzów nadnerczy.

INTRODUCTION: Therapeutic approach to incidentaloma, in spite of existing algorithms, is not always obvious due to diagnostic difficulties. The aim of the study was to assess the validity of the initial diagnoses of incidentaloma which determined the qualification for the operation. MATERIAL AND METHODS: 125 patients hospitalised in the Endocrinology Dept. of the Medical University of Bialystok in the years 2003-2005 and in the Endocrinology dept. of Voivodeship Hospital of Bialystok. The patients were clinically and hormonally examined (metanephrines in daily urine collection, daily cortisol rhythm, short dexamethasone test, aldosterone, and renin plasma activity, Na, K levels in the serum) as well as computer tomography of the adrenal glands were performed. RESULTS: 42 patients were qualified for adrenalectomy. Adenoma was confirmed in 25 patients (in 7 subclinical Cushing syndrome was diagnosed, in 2 Conn disease, in 16 inactive changes), phaeochromocytoma in 6 patients, cysts in 3, lipoma in 2, carcinoma in one, in 4 patients metastases (in 2 of kidney carcinoma, in 1 of malignant melanoma and in 1 of planocellular carcinoma) and in one oncocytoma. Metanephrines urine measurements showed 33% of false positive results. CONCLUSIONS: Qualification for adrenalectomy requires an assessment of tumor's enlargement, its tissue density, morphology and growth dynamics. To reduce the percentage of false positive results of metanephrine measurement there is to eliminate an influence of some drugs, victuals, beverages and nicotine and eventually to carry out additional tests. The decision as to proceeding with adrenal incidentaloma should be individualized based on clinical symptoms, hormonal tests and tumor morphology.

Update on Adrenal Tumours in 2017 World Health Organization (WHO) of Endocrine Tumours.

The fourth edition of the World Health Organization (WHO) classification of endocrine tumours contains substantial new findings for the adrenal tumours. The tumours are presented in two chapters labelled as "Tumours of the adrenal cortex" and "Tumours of the adrenal medulla and extra-adrenal paraganglia." Tumours of the adrenal cortex are classified as cortical carcinoma, cortical adenoma, sex cord stromal tumours, adenomatoid tumour, mesenchymal and stromal tumours (myelolipoma and schwannoma), haematological tumours, and secondary tumours. Amongst them, schwannoma and haematological tumours are newly documented. The major updates in adrenal cortical lesions are noted in the genetics of the cortical carcinoma and cortical adenoma based on the data from The Cancer Genome Atlas (TCGA). Also, a system for differentiation of oncocytoma from oncocytic cortical carcinoma is adopted. Tumours of the adrenal medulla and extra-adrenal paraganglia comprise pheochromocytoma, paraganglioma (head and neck paraganglioma and sympathetic paraganglioma), neuroblastic tumours (neuroblastoma, nodular ganglioneuroblastoma, intermixed ganglioneuroblastoma, and ganglioneuroma), composite pheochromocytoma, and composite paraganglioma. In this group, neuroblastic tumours are newly included in the classification. The clinical features, histology, associated pathologies, genetics, and predictive factors of pheochromocytoma and paraganglioma are the main changes introduced in this chapter of WHO classification of endocrine tumours. The term "metastatic pheochromocytoma/paraganglioma" is used to replace "malignant pheochromocytoma/paraganglioma." Also, composite pheochromocytoma and composite paraganglioma are now documented in separate sections instead of one. Overall, the new classification incorporated new data on pathology, clinical behaviour, and genetics of the adrenal tumours that are important for current management of patients with these tumours.