Incidentaloma pathophysiology: Difference between revisions
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On microscopic pathology, Pheochromocytoma typically demonstrates a nesting (Zellballen) pattern on microscopy. This pattern is composed of well-defined clusters of tumor cells containing eosinophilic cytoplasm separated by fibrovascular stroma. | On microscopic pathology, Pheochromocytoma typically demonstrates a nesting (Zellballen) pattern on microscopy. This pattern is composed of well-defined clusters of tumor cells containing eosinophilic cytoplasm separated by fibrovascular stroma. | ||
[[File:Adrenal gland Conn syndrome4.jpg|center|300px|thumb|Adrenocortical adenoma gross pathology, source: By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=5938524]] | |||
[[File:Adenoma adrenal.jpg|center|300px|thumb|Adrenal adenoma microscopic picture, source: By Michael Feldman, MD, PhDUniversity of Pennsylvania School of Medicine - | |||
CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=535950]] | |||
[[File:Adrenal cortical carcinoma.JPG|300px|center|thumb|Adrenocortical carcinoma gross pathology, source: By AFIP Atlas of Tumor Pathology - [1], Public Domain, https://commons.wikimedia.org/w/index.php?curid=6719487]] | |||
[[File:Adrenal cortical carcinoma (1).jpg|300px|center|thumb|Adrenocortical carcinoma microscopic picture, source: By AFIP Atlas of Tumor Pathology - [1], Public Domain, https://commons.wikimedia.org/w/index.php?curid=6719510]] | |||
[[File:Myelolipoma.jpg|300px|center|thumb|Myelolipoma gross pathology,source: By Mattopaedia - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=5668284]] | |||
[[File:Myelolipoma histology HE.jpg|300px|center|thumb|By Mattopaedia - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=5688142]] | |||
==References== | ==References== | ||
Revision as of 15:11, 30 August 2017
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Incidentaloma Microchapters |
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Incidentaloma pathophysiology On the Web |
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Risk calculators and risk factors for Incidentaloma pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
The pathophysiology of [disease/malignancy] depends on the histological subtype.
Pathophysiology
- Incidentalomas are adrenal tumors that often discovered as an incidental finding. Most incidentalomas are nonfunctional, 9% are found to secrete low levels of cortisol, 4% are pheochromocytomas, and 1.5% are aldosteronomas [2].
- Malignancy is an uncommon cause of adrenal incidentaloma in patients without a known diagnosis of cancer. Frequency of primary adrenal carcinoma is approximately 2 to 5 percent; and 0.7 to 2.5% have nonadrenal metastases to the adrenal gland [1,5,10-12].
- Adrenal mass size is important because the smaller the adrenocortical carcinoma is at the time of diagnosis, the better the overall prognosis. A 4 cm cutoff had a 93 percent sensitivity of detecting adrenocortical carcinoma with 90% being more than 4 cm in diameter when discovered.
- Most adrenocortical carcinomas are sporadic, but some occur as a component of hereditary cancer syndromes. [49,50]
Associated Conditions
- Most adrenocortical carcinomas are sporadic, but some occur as a component of hereditary cancer syndromes. [49,50]
- Hereditary cancer syndromes
- Li-Fraumeni syndrome (breast cancer, soft tissue and bone sarcoma, brain tumors), associated with inactivating mutations of the TP53 tumor suppressor gene on chromosome 17p.
- Beckwith-Wiedemann syndrome (Wilms' tumor, neuroblastoma, hepatoblastoma), associated with abnormalities in 11p15.
- Multiple endocrine neoplasia type 1 (MEN1) (parathyroid, pituitary, and pancreatic neuroendocrine tumors and adrenal adenomas, as well as carcinomas), associated with inactivating mutations of the MEN1 gene on chromosome 11q. [51,52]
Genetics
TP53 gene, located on chromosome 17p13, is the most frequently mutated gene in human cancers. A role for the TP53 tumor suppressor gene in sporadic ACCs is suggested by the frequent finding of loss of heterozygosity (LOH) at the 17p13 locus in sporadic ACCs [56,57]. Although loss of heterozygosity at 17p13 is common, only approximately one-third of these tumors have a mutation of TP53 [58-65]. This suggests that another as yet unidentified suppressor gene is present in this locus [65].
Another chromosomal locus that is strongly implicated in the pathogenesis of ACC is 11p, the area of abnormality in Beckwith-Wiedemann syndrome [70] and the site of the insulin-like growth factor-2 (IGF-2) gene. LOH at the 11p15 locus and overexpression of IGF-2 have been associated with the malignant phenotype in sporadic ACCs [56,71,72]. However, other growth-related tumor suppressor genes at this locus may also be involved [57].
Most adrenocortical tumors are monoclonal, suggesting that they result from accumulated genetic abnormalities, such as activation of proto-oncogenes and inactivation of tumor suppressor genes.
Beta-catenin mutations (CTNNB1)
- Constitutive activation of beta-catenin in the Wnt signaling pathway has been identified as a frequent alteration in benign and malignant adrenocortical tumors [8].
- The increased occurrence of adrenal tumors in patients with mutations of adenomatous polyposis coli (APC) suggested that the Wnt/beta-catenin pathway could be involved in adrenal tumorigenesis [9].
- This pathway is essential for embryonic development of the adrenal [10], and its ectopic constitutive activation is associated with cancer development in a number of tissues [11,12].
Aberrant receptors
- Cortisol hypersecretion is the most frequent hormonal abnormality detected in patients with functioning unilateral adrenal adenomas. It had been assumed that the mechanism for this was non-ACTH-dependent autonomous cortisol secretion from the adenoma.
Somatic mutations of protein kinase A (PKA) catalytic subunit (PRKACA) were identified in patients with overt Cushing's syndrome but not in adenomas secreting less cortisol [20].
- In additional reports, the same mutation was found in over 50 percent of patients with Cushing's syndrome due to adrenal adenomas [17,19,21].
- The most frequent hotspot p.Leu206Arg mutation is located in the active cleft of the catalytic subunit, inactivating the site where the regulatory subunit RII-beta usually binds, thus causing a constitutive PKA activation.
Mutations in aldosterone-producing adenomas
- The most frequent causes of primary aldosteronism include bilateral idiopathic hyperplasia and unilateral aldosterone-producing adenoma.
- Somatic mutations in KCNJ5 have been identified in patients with primary aldosteronism due to APAs.
- These mutations are more common in women than men; APAs with KCNJ5mutations are larger than those without mutations.
- Somatic mutations in other important genes implicated in regulation of aldosterone synthesis (ATP1A1, ATP2B3, CACNA1D, CTNNB1, ARMC5) have also been identified.
Gross Pathology
Adrenocortical adenoma
On gross pathology, adrenocortical adenoma is a well circumscribed, yellow tumour in the adrenal cortex, which is usually 2–5 cm in diameter. The color oftumorr, as with adrenal cortex as a whole, is due to the stored lipid (mainly cholesterol), from which the cortical hormones are synthesized
Myelolipoma
On gross pathology, myelolipoma are usually found to occur alone in one adrenal gland, but not both. They can vary widely in size, from as small as a few millimetres to as large as 34 centimeters in diameter. The cut surface has colours varying from yellow to red to mahogany brown, depending on the distribution of fat, blood, and blood-forming cells. The cut surface of larger myelolipomas may contain haemorrhage or infarction.
Grossly, adrenocortical carcinomas are often large, with a tan-yellow cut surface, and areas of hemorrhage and necrosis.
On gross pathology, A multinodular and multicentric pattern of growth of pheochromocytoma may be seen.
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Microscopic Pathology
On microscopic examination, the tumor usually displays sheets of atypical cells with some resemblance to the cells of the normal adrenal cortex. The presence of invasion and mitotic activity help differentiate small cancers from adrenocortical adenomas.[5]
On microscopic pathology, Pheochromocytoma typically demonstrates a nesting (Zellballen) pattern on microscopy. This pattern is composed of well-defined clusters of tumor cells containing eosinophilic cytoplasm separated by fibrovascular stroma.
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