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.

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.

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.

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.

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.

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).

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.

New Insights into the Nuclear Imaging Phenotypes of Cluster 1 Pheochromocytoma and Paraganglioma.

Pheochromocytomas and paragangliomas (PPGLs) belong to the family of neural crest cell-derived neoplasms. In up to 70% of cases they are associated with germline and somatic mutations in 15 well-characterized PPGL driver or fusion genes. PPGLs can be grouped into three main clusters, where cluster 1 includes PPGLs characterized by a pseudohypoxic signature. Although cluster 1 tumors share several common features, they exhibit unique behaviors. We present here unique insights into the imaging phenotypes of cluster 1 PPGLs based on glucose uptake, catecholamine metabolism, and somatostatin receptor expression. Recent data suggest that succinate is a major player in the imaging phenotype of succinate dehydrogenase-deficient PPGLs. This review emphasizes the emerging stromal cell-succinate interaction and highlights new perspectives in PPGL theranostics.

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.

Lipomatous tumours in adrenal gland: WHO updates and clinical implications.

Adrenal lipomatous tumour is a group of adrenal tumours with a significant component of adipose tissue. According to the current World Health Organization (WHO) classification of tumours of endocrine organs, adrenal myelolipoma is the only entity amongst the group of tumours being described. In the literature, other more recently documented adrenal lipomatous tumours included 24 lipomas, 32 teratomas and 16 angiomyolipomas. Rare fatty tumours of the adrenal gland comprised liposarcoma, hibernoma, adrenocortical tumours with fat component and rare adrenal tumours with fat component. Myelolipoma comprises approximately 3% of primary adrenal tumour. It is noted more commonly in females and in the right adrenal gland. Approximately 40 bilateral myelolipomas were reported. The tumour is most frequently recorded in patients between fifth and seventh decades of life. Adrenal lipomas are often seen in males and in the right adrenal gland. They were commonly noted in patients in the sixth decade of life. The diagnosis could only be possible on examination of the surgically removed specimen. Adrenal teratomas were more common in females and with a bimodal age distribution. Slightly over 60% of the patients with adrenal teratoma are symptomatic. Adrenal angiomyolipomas were often symptomatic, more common in females and in the fifth decades of life. To conclude, adrenal lipomatous tumour is uncommon. They are often benign and non-functional. It is important to recognize the features of this group of lipomatous tumours in the adrenal gland as they are being detected on increasing incidence as a result of the wide-spread use of modern imaging modalities.

[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.

Pheo-Type: A Diagnostic Gene-expression Assay for the Classification of Pheochromocytoma and Paraganglioma.

CONTEXT: Pheochromocytomas and paragangliomas (PPGLs) are heritable neoplasms that can be classified into gene-expression subtypes corresponding to their underlying specific genetic drivers. OBJECTIVE: This study aimed to develop a diagnostic and research tool (Pheo-type) capable of classifying PPGL tumors into gene-expression subtypes that could be used to guide and interpret genetic testing, determine surveillance programs, and aid in elucidation of PPGL biology. DESIGN: A compendium of published microarray data representing 205 PPGL tumors was used for the selection of subtype-specific genes that were then translated to the Nanostring gene-expression platform. A support vector machine was trained on the microarray dataset and then tested on an independent Nanostring dataset representing 38 familial and sporadic cases of PPGL of known genotype (RET, NF1, TMEM127, MAX, HRAS, VHL, and SDHx). Different classifier models involving between three and six subtypes were compared for their discrimination potential. RESULTS: A gene set of 46 genes and six endogenous controls was selected representing six known PPGL subtypes; RTK1-3 (RET, NF1, TMEM127, and HRAS), MAX-like, VHL, and SDHx. Of 38 test cases, 34 (90%) were correctly predicted to six subtypes based on the known genotype to gene-expression subtype association. Removal of the RTK2 subtype from training, characterized by an admixture of tumor and normal adrenal cortex, improved the classification accuracy (35/38). Consolidation of RTK and pseudohypoxic PPGL subtypes to four- and then three-class architectures improved the classification accuracy for clinical application. CONCLUSIONS: The Pheo-type gene-expression assay is a reliable method for predicting PPGL genotype using routine diagnostic tumor samples.

Update on Paragangliomas and Pheochromocytomas.

Genomic studies in the recent decades lead to the identification of new genetic mutations that have been shown to play detrimental roles in the formation of pheochromocytoma or paraganglioma. The majority of these genetic mutations detected affect two major cellular pathways - pseudo hypoxic pathway and kinase signalling pathway. Genetic mutations also resulted in syndromes related to paraganglioma/pheochromocytoma. The classical syndromes comprise - neurofibromatosis, multiple neuroendocrine neoplasia (MEN) (II and III) syndromes and von Hippel-Lindau syndrome. Also, mutations in succinate dehydrogenase genes contribute to the understanding of hereditary paragangliomapheochromocytoma syndromes, Carney's triad and Carney- Stratakis syndrome. Lesions newly known to be associated with the genetic mutations in pheochromocytoma/ paraganglioma include gastrointestinal stromal tumour and renal cell carcinoma. Pathological features, proliferative index, genetic and biochemical parameters could help to predict the malignant potential of paraganglioma and pheochromocytoma. Different predictive systems have been proposed and with the help of immunochemical studies. Pathologist should be aware of the advances in knowledge and contribute to the validation of the pathological features and markers for prediction of malignant potential of this group of tumours.

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.

Complete evaluation of adrenal tumours in a tertiary care institution in Thuringia, Germany.

INTRODUCTION AND OBJECTIVE: Adrenal tumours, mainly incidentalomas, are an increasingly common clinical and diagnostic challenge. The aim of the present study was the retrospective evaluation of all patients with adrenal tumours treated in our university department from 1.1.1999-31.12.2013 PATIENTS AND METHODS: 187 patients (108 females: 79 males, mean age 57.7 years) were found to have adrenal tumours in our institution during the study period. All patients underwent basic and, when indicated, advanced analytical testing for hormonal activity. Tumours were classified according to patients' gender, age at diagnosis, tumour localization and size, as well as benignity and malignancy when postinterventional histopathological examination was conducted. RESULTS: 134 (71.7%) patients had non-hormone secreting tumours, 17 (9.1%) pheochromocytoma, 13 (7.0%) Conn-syndrome, 13 (7.0%) adrenal Cushing's disease, 1 congenital adrenal hyperplasia and 2 sexual hormone-secreting tumours. 7 (3.7%) tumours could not be definitively classified due to unclear or marginal test-results. Cushing's disease was more prevalent in females (11 females: 2 males). 163 (87.2% of the total cohort) tumours were unilateral [95 (50.8%) left; 68 (36.4%) right] and 24 (12.8%) were bilateral. Tumour size was <3 cm in 109 (58.3%), 3-6 cm in 63 (33.7%) and >6 cm in 15 (8.0%) patients. 60 (32.1%) patients underwent adrenalectomy, thereof 88.9% of the patients with hormonally active tumours, while 8 (4.3%) were evaluated with ultrasound-guided biopsy. Malignancy was confirmed in 10 individuals (5.3%; 3 non-functioning tumours, 3 pheochromocytomas, 2 Cushing's patients and 2 sexual-hormone secreting tumours), while 2 surgical specimens with histopathological diagnosis of pheochromocytoma showed signs of malignant changes. Benignity was histopathologically confirmed in 55 patients. CONCLUSIONS: The prevalence of detected adrenal tumours is rising due to widely available and applied abdominal imaging procedures. The vast majority of them are benign, of small size (<3 cm) and hormonally inactive. Adrenalectomy is the therapeutic method of choice in big and/or confirmed hormone-secreting tumours.

[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.

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.

Accuracy of cytology in distinguishing adrenocortical tumors from pheochromocytoma in companion animals.

BACKGROUND: The distinction between adrenocortical tumors and pheochromocytoma can be challenging using clinical findings, diagnostic imaging and laboratory tests. Cytology might be a simple, minimally invasive method to reach a correct diagnosis. OBJECTIVES: The purpose of this study was to assess the accuracy of cytology in differentiating cortical from medullary tumors of the adrenal glands in dogs and cats. METHODS: Cytologic key features of adrenocortical tumors and pheochromocytoma were defined by one reference author. Cytologic specimens from primary adrenal tumors were submitted to 4 cytopathologists who were asked to classify the tumors based on the previously defined key features without knowledge of previous classification. RESULTS: Twenty specimens from histologically confirmed adrenal tumors (Group 1) and 4 specimens from adrenal tumors causing adrenal-dependent Cushing's syndrome (Group 2) were evaluated by the 4 cytopathologists. Accuracy in differentiating cortical from medullary origin ranged from 90% to 100%, with a Kappa coefficient of agreement between cytopathologists of 0.95. CONCLUSIONS: The origin of an adrenal tumor can be easily determined by cytology alone in many cases. However, cytology was not reliable in distinguishing benign from malignant neoplasia. Additional studies are needed to assess possible risks and complications associated with fine-needle biopsy of adrenal tumors in dogs and cats.