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The adrenal gland is really two glands in one.  The adrenal cortex, the outer portion of the adrenal gland is responsible for the majority of the body's steroid production. The term corticosteroids is derived from this origin.  Steroids have many functions but their main action is in form of salt retention which in turn leads to regulation of the blood pressure as well as sex steroid production.

The adrenal medulla is the central portion of the gland and is primarily responsible for the production of catecholamines (epinephrine, norepinephrine, and dopamine). 

Biopsies of the adrenal gland are uncommon but often performed to distinguish between a primary malignancy of the adrenal gland versus a metastasis, which is more common.  Frequently, a CT guided fine needle aspiration is performed by the radiologist.  The pathologist will take the aspiration specimen, smear it on a slide and stain it.  Frequently, a diagnosis can be rendered sparing the patient a very invasive surgical procedure. 

Addison's Disease
Adrenal Cortical Carcinoma
Adrenogenital Syndrome


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A method for quantifying adrenocortical nodular hyperplasia at autopsy: Some use of the method in illuminating hypertension and atherosclerosis

Richard E. Tracy, MD, PhD
Steven White, BS

Ann Diagn Pathol 6: 20-29, 2002 Abstract quote

Quantifying the severity of adrenocortical nodular hyperplasia at autopsy or surgery has much potential practical value. For instance, this inquiry explores the correlation of adrenal nodularity with features of atherosclerosis in coronary arteries and microvascular features of hypertension in the renal cortex.

Tissue retrieved from forensic autopsies in 96 men and women ages 16 to 88 years were evaluated for adrenal nodularity, coronary atheroma, and hypertensive renal microvasculopathies. Formalin-fixed adrenal glands were cut into 0.5-cm thick slices and fixed to plastic sheets with SuperGlue (Ross Products, Inc, Columbus, OH). After ranking the specimens on increasing nodularity, they were judged to fall into 10 distinguishable grades of increasing severity; photographs of a representative in each grade were arranged onto a panel. Each gland was then assigned the grade of the photograph it most resembled. Coronaries and kidneys were evaluated in paraffin sections. Weight and nodularity of adrenal glands increased with age. Men with at least one instance of atheroma in the coronary sample had heavier and more nodular glands (age-adjusted) than in men without atheroma. The differences held stronger statistical significance for nodularity than for weight because nodularity continued to show significance even within age groups sometimes represented by few cases. Hypertensive renal microvasculopathies failed to correlate with any of the adrenal features. Women were too few for the analysis.

Findings made with the panel of photographs now available for grading adrenocortical nodular hyperplasia showed interesting correlations with coronary atherosclerosis in this data set, suggesting that use of this method might offer some insight into cardiovascular disease.



Adenomatoid tumor of the adrenal gland: a clinicopathologic study of five cases and review of the literature.

Isotalo PA, Keeney GL, Sebo TJ, Riehle DL, Cheville JC.


Am J Surg Pathol. 2003 Jul;27(7):969-77 Abstract quote

We report the clinicopathologic, immunophenotypic, DNA ploidy, and MIB-1 proliferative findings of five adenomatoid tumors of the adrenal gland.

All patients were male, and tumors were incidental radiologic, surgical, or autopsy findings. Mean patient age at diagnosis was 41 years (range 31-64 years). The tumors ranged from 1.2 to 3.5 cm (mean 2.8 cm; median 3.2 cm) in greatest dimension, and all originated within the adrenal gland. The tumors were composed of anastomosing variably sized tubules lined by epithelioid as well as flattened cells. Signet-ring-like cells were present in all cases. The previously described histologic patterns of adenomatoid tumor, adenoid, angiomatoid, cystic, and solid, were observed, and each tumor contained multiple histologic patterns. In three of five cases, there was extra-adrenal extension of tumor into periadrenal adipose tissue. All adenomatoid tumors infiltrated the adrenal cortex, and in four cases the adrenal medulla was involved.

All tumors exhibited strong immunoreactivity for calretinin, cytokeratins AE1/AE3, and CAM 5.2, cytokeratin 7, and vimentin. Tumors showed weak and focal immunoreactivity for cytokeratin 5/cytokeratin 6 and were negative for CD15, CD31, CD34, cytokeratin 20, MOC31, and polyclonal carcinoembryonic antigen. Ploidy analysis using Feulgen-stained sections and image analysis showed that three tumors were diploid and two were tetraploid. Tumors exhibited low MIB-1 proliferative activity, ranging from 0.2% to 2.7% (mean 1.6%). In three cases with clinical follow-up, no recurrence or metastases occurred.

Adrenal gland adenomatoid tumors are morphologically and immunophenotypically identical to adenomatoid tumors of the genital tract and appear benign.

Adrenal Myelolipomas Show Nonrandom X-chromosome Inactivation in Hematopoietic Elements and Fat: Support for a Clonal Origin of Myelolipomas.

Bishop E, Eble JN, Cheng L, Wang M, Chase DR, Orazi A, O'malley DP.

*Department of Pathology and Laboratory Medicine, Division of Hematopathology, 702 Barnhill Drive, Riley 0969, Indianapolis, IN 46202 daggerDepartment of Pathology and Laboratory Medicine, Indiana University School of Medicine, 635 Barnhill Drive Rm. 128, Indianapolis, IN 46202-5120 double daggerDepartment of Pathology and Human Anatomy, Loma Linda University School of Medicine, 11021 Campus Avenue, AH Rm. 335, Loma Linda, CA 92350.

Am J Surg Pathol. 2006 Jul;30(7):838-843. Abstract quote  

Myelolipomas are defined as mature fat associated with hematopoietic elements, often found in the adrenal gland. The question of whether the hematopoietic cells are truly "normal" has not been evaluated extensively.

In this study, we evaluated histologic, immunohistochemical features and comparisons of X-chromosome inactivation patterns in 19 myelolipomas. Formalin-fixed, paraffin-embedded tissue from 19 myelolipomas was stained with hematoxylin and eosin and immunostained with monoclonal antibodies against CD138, CD34, CD117, CD42a, hemoglobin, myeloperoxidase, collagen IV, and nerve growth factor receptor.

Histologic evaluation included estimates of overall cellularity of hematopoietic tissue, estimates of cellularity in the areas of highest concentration of hematopoietic tissue, myeloid to erythroid ratio, and numbers of megakaryocytes. X-chromosome inactivation analysis was performed on myelolipomas from 11 female patients by polymerase chain reaction. Myelolipomas showed wide variation in cellularity within the lesion (5% to 90%) with no correlation with the patient's age. All the myelolipomas demonstrated normal trilineage hematopoiesis and cellular morphology, with few early myeloid precursors, as evidenced by negativity for CD117 and only rare positivity for CD34 antibodies. Most of the myelolipomas (14/18) had markedly increased megakaryocytes compared with normal marrows. The majority of myelolipomas also had a stromal composition and vascular patterns that were different from those of normal bone marrow. X-chromosome inactivation studies demonstrated nonrandom X-chromosome inactivation in 8/11 myelolipomas from female patients.

Myelolipomas are morphologically different from the normal bone marrow. The majority of myelolipomas also have nonrandom X-chromosome inactivation, suggesting a clonal origin for these tumors.

Incidentally detected giant oncocytoma arising in retroperitoneal heterotopic adrenal tissue.

Corsi A, Riminucci M, Petrozza V, Collins MT, Natale ME, Cancrini A, Bianco P.

Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy.

Arch Pathol Lab Med 2002 Sep;126(9):1118-22 Abstract quote

A nonfunctional retroperitoneal oncocytoma incidentally discovered in a 40-year-old woman is described. The tumor, which was 17 cm in largest dimension, was completely separated from the kidneys and adrenal glands and consisted of nests of polygonal cells with large, granular, eosinophilic cytoplasm. Significant nuclear atypia, necrosis, and mitosis were absent.

Ultrastructural analysis confirmed the oncocytic nature of the neoplastic cells. Since neoplastic cells were not immunoreactive for chromogranin and did not contain dense-core secretory granules, the diagnosis of oncocytic paraganglioma was excluded. Cells immunoreactive for 3beta-hydroxysteroid dehydrogenase, the enzyme catalyzing the conversions of pregnenolone to progesterone and dehydroepiandrosterone to androstenedione, were identified in the tumor, thus strongly indicating adrenocortical tissue origin. Multiple nests of 3beta-hydroxysteroid dehydrogenase-positive cells were detected in the loose retroperitoneal connective tissue.

These findings strongly support the origin of the tumor from heterotopic retroperitoneal rests of the adrenal gland. To our knowledge, only 1 similar case has been described in the literature to date.



High diagnostic accuracy of adrenal core biopsy: results of the German and Austrian adrenal network multicenter trial in 220 consecutive patients.

Saeger W, Fassnacht M, Chita R, Prager G, Nies C, Lorenz K, Barlehner E, Simon D, Niederle B, Beuschlein F, Allolio B, Reincke M.

Institute of Pathology, Marienkrankenhaus, Hamburg, Germany

Hum Pathol 2003 Feb;34(2):180-6 Abstract quote

Incidentally detected adrenal tumors are a common finding during abdominal ultrasonography, computed tomography, and magnetic resonance imaging. Although most of these lesions are benign adenomas, adrenocortical carcinomas and metastases constitute 5% to 10% of all tumors. Adrenal biopsy may be helpful, but its diagnostic value is controversial and disputed, and prospective studies have not yet been performed. Therefore, the diagnostic accuracy of adrenal core biopsy was evaluated in a prospective multicenter study involving 8 surgical centers in Germany and Austria.

A total of 220 biopsies from surgical specimens of the adrenal gland were punctured in an ex vivo approach and processed for pathohistologic diagnosis using paraffin sections, routine staining, and immunohistochemistry (keratin KL1, vimentin, S100 protein, chromogranin A, synaptophysin, neuron-specific enolase, D11, MiB-1, and p53 protein). The evaluating pathologist was blinded for clinical data from the patients. A total of 89 adrenal adenomas (40.5%), 22 adrenal carcinomas (10.0%), 55 pheochromocytomas (25.0%), 15 metastases (6.8%), 16 adrenal hyperplasias (7.2%), and 23 other tumors (10.5%) were studied. Nine cases were excluded due to incomplete data (n = 2) or insufficient biopsy specimen (n = 7). In the remaining 211 tumors, compared with the final diagnoses of the surgical specimen, bioptic diagnoses were absolutely correct in 76.8% of the cases, nearly correct in 13.2% of the cases, and incorrect in 10% of the cases. Pheochromocytomas were correctly diagnosed in 96% of the cases, cortical adenomas were correctly or nearly correctly reported in 91% of the cases, cortical carcinomas were correctly or nearly correctly reported in 76% of the cases, and metastases were correctly or nearly correctly reported in 77% of the cases. Of the 39 malignant lesions, only 4 were misclassified, 2 as benign and 2 as possibly malignant. This resulted in an overall sensitivity for malignancy of 94.6% and specificity of 95.3%.

Our findings suggest that adrenal core biopsy is a useful method for identifying and classifying adrenal tumorous lesions if sufficient biopsy specimens can be obtained. However, in clinical practice it remains to be shown whether the benefits of biopsy outweigh the risks of the procedure.


Adrenal pseudocyst: A unique case with adrenal renal fusion, mimicking a cystic renal mass.

Fan F, Pietrow P, Wilson LA, Romanas M, Tawfik OW.
Ann Diagn Pathol. 2004 Apr;8(2):87-90. Abstract quote

We describe an unusual adrenal pseudocyst mimicking radiologically and clinically renal mass. The cyst measured 12 cm in diameter and had a fibrotic external envelope that was fused with the renal capsule.

The possible diagnostic pitfalls encountered in this case are discussed.
Sustentaculoma: Report of a Case of a Distinctive Neoplasm of the Adrenal Medulla.

Lau SK, Romansky SG, Weiss LM.

From the *Department of Pathology, City of Hope National Medical Center, Duarte, CA; and daggerDepartment of Pathology, Long Beach Memorial Medical Center, Long Beach, CA.

Am J Surg Pathol. 2006 Feb;30(2):268-273. Abstract quote  

A case of a morphologically distinctive tumor of the adrenal medulla occurring in a 54-year-old woman is described.

On microscopic examination, the tumor was well circumscribed and characterized by the presence of ill-defined, irregular nests of spindle cells with oval to elongated nuclei, tiny nucleoli, and abundant eosinophilic cytoplasm. The tumor was associated with a moderate infiltrate of lymphocytes and plasma cells with occasional lymphoid follicles. Necrosis, marked cellular atypia, and mitoses were absent.

Immunohistochemical studies demonstrated the tumor cells to be strongly reactive for vimentin, S-100 protein, and CD56, and nonreactive for glial fibrillary acidic protein, chromogranin, synaptophysin, melanoma-associated antigens, and dendritic cell markers. Ultrastructural examination showed elongated cells with interdigitating cytoplasmic processes devoid of a basal lamina. No secretory granules were noted. The morphology, immunophenotype, and ultrastructure of this unique neoplasm suggest derivation from sustentacular cells of the adrenal medulla.

We propose the designation "sustentaculoma" for this hitherto undescribed neoplasm of the adrenal gland.



A103 Immunostaining in the Diagnosis of Adrenal Cortical Tumors
An Immunohistochemical Study of 316 Cases

Timothy S. Loy, MD, Roy W. Phillips, MD, and Chadwick L. Linder, MD

From the Department of Pathology, University of Missouri Medical School, Columbia, Mo


Arch Pathol Lab Med 2002;Vol. 126, No. 2, pp. 170–172. Abstract quote

Context.—The monoclonal antibody A103 recognizes an antigen on melanoma cells known as Melan-A or MART-1. Recent studies have shown that A103 also reacts with adrenal cortical cells and may be useful in the diagnosis of adrenal cortical tumors. However, only small numbers of some of the tumors in the differential diagnosis of adrenal cortical neoplasms have been studied.

Objective.—To study the specificity of A103 immunohistochemistry in a large number of tumors in the differential diagnosis of adrenal cortical neoplasms.

Design.—Formalin-fixed, paraffin-embedded tissue from 21 adrenal cortical tumors, 16 cases of metastatic carcinoma to the adrenal, 10 pheochromocytomas, and 269 extra-adrenal carcinomas was evaluated for A103 immunoreactivity using a commercially available antibody (Novocastra, Newcastle, UK).

Results.—Positive staining was seen in all of the adrenal cortical tumors but in none of the adrenal metastases or pheochromocytomas. In the 269 extra-adrenal carcinomas, A103 immunoreactivity was limited to a single ovarian serous carcinoma.

Conclusion.—A103 immunostaining is useful in distinguishing adrenal cortical neoplasms from other carcinomas and pheochromocytoma.



Experience gained from operation of 103 adrenal incidentalomas.

Proye C, Jafari Manjili M, Combemale F, Pattou F, Ernst O, Carnaille B, Wemeau JL.

Clinique Chirurgicale Adulte Est, Service de Chirurgie Generale et Endocrinienne, Hopital Huriez, CHU de Lille, France.

Langenbecks Arch Surg 1998 Oct;383(5):330-3 Abstract quote

BACKGROUND: Adrenal incidentaloma poses a perplexing problem for physicians. The challenge is to identify the rare functioning or malignant adrenal tumor that should be removed.

PATIENTS AND METHODS: From 1970 until December 1996, we managed 579 patients with adrenal hyperplasia or neoplasm. Of these, 110 were followed without any operation and 469 were operated on. The histology from the operated patients revealed 145 pheochromocytomas, 72 Cushing's syndrome, 98 aldosteronomas, 21 virilizing tumors, 3 feminizing tumors, 98 non-functioning adrenalomas, 17 metastases, 7 cysts, and 15 miscellaneous tumors.

RESULTS: Among the 98 non-functioning adrenal tumors, 79 were incidentalomas. Histological examination of 103 operated incidentalomas found 55 adenomas (5 functioning=aldosteronomas), 12 benign pheochromocytomas, 3 malignant or suspicious pheochromocytomas, 8 cystic lymphangiomas, 4 metastases, 4 angiomas, 3 ganglioneuromas, 4 myelolipomas, 1 hyperplasia, 2 hematomas, 2 cysts, and 5 adreno-cortical carcinomas. Among the non-operated incidentalomas, the most frequent findings were adenomas, metastases, hematomas, cysts and pseudotumoral hyperplasia; three disappeared spontaneously. No patients died of unrecognized adrenocortical carcinoma.

CONCLUSION: Our experience confirms that in case of incidentaloma, the first concern is a nonfunctional pheochromocytoma (15%), and the less common occurrence is adreno-cortical carcinoma (2%). We recommend a restrictive surgical approach in the setting of adrenal incidentalomas.

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Commonly Used Terms With Diseases of the Adrenal Glands

VMA and HVA-Vanillylmandelic acid and homovanillic acid.  These are metabolic byproducts of catecholamine production.

Basic Principles of Disease
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Last Updated July 10, 2006

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