Adrenocortical carcinoma pathophysiology: Difference between revisions

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==Pathophysiology==
==Pathophysiology==
This tumor can produce the hormones [[cortisol]], [[aldosterone]], [[estrogen]], or [[testosterone]], as well as other hormones.  In women the [[tumor]] often releases these hormones, which can lead to male characteristics.
 
Mutations of the tumor suppressor genes '''''TP53''''' and '''''TP57''''' might also be possible contributing factors for  the development of [[adrenocortical carcinoma]].
===Genetics===
===Genetics===
The [[p53]] and retinoblastoma gene (RB) [[tumor suppressor gene]]s located on chromosomes 17p, 13q respectively,  may be changed. The genes h19, insulin-like growth factor II ('''''IGF-II'''''), p57<sup>kip2</sup> are important for fetal growth and development. They are located on chromosome 11p. Expression of the h19 gene is markedly reduced in both nonfunctioning and functioning adrenal cortical carcinomas, especially in tumors producing [[cortisol]] and [[aldosterone]]. There is also a loss of activity of the p57<small>kip2</small> gene product in [[virilizing]] adenomas and adrenal cortical carcinomas. In contrast, '''''IGF-II''''' gene expression has been shown to be high in adrenal cortical carcinomas.<ref>{{cite book |author=Kufe D |editor=Benedict RC, Holland JF |title=Cancer medicine |publisher=B.C. Decker |location=Hamilton, Ont |year=2000 |edition=5th |isbn=1-55009-113-1 |oclc=156944448 }}</ref>
==Gross Pathology==
===Gross Pathology===
On gross pathology, adrenocortical carcinomas are often large, with a tan-yellow cut surface and areas of [[hemorrhage]] and [[necrosis]].
On gross pathology, adrenocortical carcinomas are often large, with a tan-yellow cut surface and areas of [[hemorrhage]] and [[necrosis]].


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<sup>Shown above is a large adrenal cortical carcinoma resected from a 27-year-old woman. The tumor measured 17 cm in diameter and invaded kidney and spleen which necessitated en bloc removal of these organs with tumor. Patient had evidence of virilization.</sup>
<sup>Shown above is a large adrenal cortical carcinoma resected from a 27-year-old woman. The tumor measured 17 cm in diameter and invaded kidney and spleen which necessitated en bloc removal of these organs with tumor. Patient had evidence of virilization.</sup>
===Microscopic Pathology===
==Microscopic Pathology==
On [[histopathology|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 [[mitosis|mitotic activity]] helps differentiate small cancers from [[adrenocortical adenoma]]s.<ref name="Weidner's">{{cite book |author=Richard Cote, Saul Suster, Lawrence Weiss, Noel Weidner (Editor) |title=Modern Surgical Pathology (2 Volume Set) |publisher=W B Saunders |location=London |year= |pages= |isbn=0-7216-7253-1 |oclc= |doi=}}</ref>
On [[histopathology|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 [[mitosis|mitotic activity]] helps differentiate small cancers from [[adrenocortical adenoma]]s.<ref name="Weidner's">{{cite book |author=Richard Cote, Saul Suster, Lawrence Weiss, Noel Weidner (Editor) |title=Modern Surgical Pathology (2 Volume Set) |publisher=W B Saunders |location=London |year= |pages= |isbn=0-7216-7253-1 |oclc= |doi=}}</ref>
The Weiss criteria of adrenocortical malignancy comprise the most reliable histopathological scoring system differentiating ACC from ACA 9–11
ACC can be diagnosed by the presence of at least 3 of the 9 Weiss criteria:
* Three relate to cytological features (nuclear grade, mitoses and atypical mitoses)
* Three refer to tumor structure (clear cells, diffuse architecture, and confluent necrosis)
* Three relate to invasion (venous invasion, sinusoidal invasion, and capsular infiltration)
However, occasionally some cases such as pediatric tumors or adrenocortical oncocytomas do pose diagnostic challenges if the final diagnosis is based solely on the Weiss criteria.
In addition, as in any of the histopathological scoring systems, interobserver differences among surgical pathologists are also by no means negligible factors, particularly when the tumors are possibly low grade carcinomas.


[[Image: 800px-Adrenal_cortical_carcinoma_-_low_mag.jpg‎|400px]]
[[Image: 800px-Adrenal_cortical_carcinoma_-_low_mag.jpg‎|400px]]

Revision as of 18:45, 18 September 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2]Shivali Marketkar, M.B.B.S. [3]Ahmad Al Maradni, M.D. [4]

Overview

On gross pathology, a large tan-yellow surface with areas of hemorrhage and necrosis is a characteristic finding of adrenocortical carcinoma. On microscopic histopathological analysis, sheets of atypical cells with some resemblance to the cells of the normal adrenal cortex are a characteristic finding of adrenocortical carcinoma.

Pathophysiology

Genetics

Gross Pathology

On gross pathology, adrenocortical carcinomas are often large, with a tan-yellow cut surface and areas of hemorrhage and necrosis.

Shown above is a large adrenal cortical carcinoma resected from a 27-year-old woman. The tumor measured 17 cm in diameter and invaded kidney and spleen which necessitated en bloc removal of these organs with tumor. Patient had evidence of virilization.

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 helps differentiate small cancers from adrenocortical adenomas.[1]

The Weiss criteria of adrenocortical malignancy comprise the most reliable histopathological scoring system differentiating ACC from ACA 9–11

ACC can be diagnosed by the presence of at least 3 of the 9 Weiss criteria:

  • Three relate to cytological features (nuclear grade, mitoses and atypical mitoses)
  • Three refer to tumor structure (clear cells, diffuse architecture, and confluent necrosis)
  • Three relate to invasion (venous invasion, sinusoidal invasion, and capsular infiltration)

However, occasionally some cases such as pediatric tumors or adrenocortical oncocytomas do pose diagnostic challenges if the final diagnosis is based solely on the Weiss criteria.

In addition, as in any of the histopathological scoring systems, interobserver differences among surgical pathologists are also by no means negligible factors, particularly when the tumors are possibly low grade carcinomas.

Micrograph of an adrenocortical carcinoma (left of image - dark blue) and the adrenal cortex it arose from (right-top of image - pink/light blue). Benign adrenal medulla is present (right-middle of image - gray/blue). H&E stain.

Video

Shown below is a video explaining the histology of adrenocortical carcinoma

{{#ev:youtube|7jMFENhPaOM}}

References

  1. Richard Cote, Saul Suster, Lawrence Weiss, Noel Weidner (Editor). Modern Surgical Pathology (2 Volume Set). London: W B Saunders. ISBN 0-7216-7253-1.

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