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'''Adrenal gland''' is a little organ that hangs-out above the kidney.  Pathologists rarely see it.  It uncommonly is affected by tumours.
[[Image:Gray1183.png|thumb|400px|A drawing of the adrenal glands.]]
'''Adrenal gland''' is a little organ that hangs-out above the [[kidney]].  Pathologists rarely see it.  It uncommonly is affected by tumours.


==Anatomy & histology==
==Anatomy & histology==
:''Adrenal cortical rest'' redirects here.
===Anatomy===
*Cortex.
*Medulla.


===Histology===
Note:
Composed for ''cortex'' and medulla''.
*Adrenal tissue may be associated with gonads or between gonads and adrenal gland proper.<ref>{{Cite journal  | last1 = Barwick | first1 = TD. | last2 = Malhotra | first2 = A. | last3 = Webb | first3 = JA. | last4 = Savage | first4 = MO. | last5 = Reznek | first5 = RH. | title = Embryology of the adrenal glands and its relevance to diagnostic imaging. | journal = Clin Radiol | volume = 60 | issue = 9 | pages = 953-9 | month = Sep | year = 2005 | doi = 10.1016/j.crad.2005.04.006 | PMID = 16124976 }}</ref>
*Cortex has three layers - Mnemonic: '''GFR''' (from superficial to deep):
**Zona glomerulosa - salt (e.g. aldosterone)
***eosinophilic cytoplasm???
***Normally discontinuous layer.
**Zona fasciculata - sugar (e.g. cortisol)
***Clear cytoplasm - '''key feature'''.
***Largest part of the cortex ~ 70%.
***Cells in cords/nests???
**Zona reticularis - steroid (e.g. dehydroepiandrosterone).
***Marked eosinophilia of cytoplasm - '''key feature'''.
***Granular/reticular cytoplasm.
*Medulla - produces ''NED'': norepinephrine, epinephrine, dopamine.


==Clinical==
===Microscopic===
Patients getting a bilat. adrenalectomy get pre-treatment with steroids.
It is composed of a ''cortex'' and a ''medulla''.
http://www3.interscience.wiley.com/cgi-bin/fulltext/119909358/PDFSTART
 
====Cortex====
It has three layers - mnemonic: '''GFR''' (from superficial to deep):
#Zona glomerulosa - salt (e.g. aldosterone).
#*Eosinophilic cytoplasm. (???)
#*Layer normally discontinuous.
#Zona fasciculata - sugar (e.g. cortisol).
#*Clear cytoplasm - '''key feature'''.
#*Largest part of the cortex ~ 70%.
#*Cells in cords/nests. (???)
#Zona reticularis - steroid (e.g. dehydroepiandrosterone).
#*Marked eosinophilia of cytoplasm - '''key feature'''.
#*Granular/reticular cytoplasm.


Adrenal insuff. may be immediately post-op.
Note:
http://ats.ctsnetjournals.org/cgi/content/full/62/5/1516===
*Normal cortex may not be completely encapsulated, i.e. the adrenal capsule may have defects.<ref>{{Ref_H4P4|1236}}</ref>
**In other words: the cortex may "spill" into the surrounding fat.


==Benign==
====Medulla====
*Spironolactone bodies.<ref>{{cite journal |author=Kovacs K, Horvath E, Singer W |title=Fine structure and morphogenesis of spironolactone bodies in the zona glomerulosa of the human adrenal cortex |journal=J. Clin. Pathol. |volume=26 |issue=12 |pages=949-57 |year=1973 |month=December |pmid=4131694 |pmc=477936 |doi= |url=http://jcp.bmj.com/cgi/pmidlookup?view=long&pmid=4131694}}</ref>
It consists of two cell types:<ref name=Ref_PBoD8_1159>{{Ref PBoD8|1159}}</ref>
**Location: zona glomerulosa (where aldosterone is produced).
#Chromaffin cells.  
**Appearance: eosinophilic spherical laminated whorls.
#*Arise of neural crest.
**Etiology: long-term use of spironolactone.
#Sustentacular cells (supporting cells).


==Adenomas==
Produce ''NED'': norepinephrine, epinephrine, dopamine.
Radiology<ref>URL: [http://emedicine.medscape.com/article/376240-overview http://emedicine.medscape.com/article/376240-overview].</ref>
*Radiologists are good at identifying adenomas, as they are usually lipid rich and have a characteristic low HU signal.


Treatment is excision if...<ref name=pmid10870039>PMID 10870039.</ref><ref name=pmid19035218>PMID 19035218.</ref>
=====Images=====
*Lesions >30 mm.
<gallery>
*Hormonally active.
Image:Adrenal_gland_(medulla).JPG | Adrenal medulla. (WC)
*Non-incidental finding. (???)
Image:Adrenal_cortical_carcinoma_-_low_mag.jpg | Adrenal cortex & medulla (right of image), and tumour (left of image). (WC/Nephron)
</gallery>
<gallery>
Image:Adrenal rest - epididymis -- low mag.jpg | Adrenal rest - low mag. (WC/Nephron)
Image:Adrenal rest - epididymis -- intermed mag.jpg | Adrenal rest - intermed. mag. (WC/Nephron)
Image:Adrenal rest - epididymis -- high mag.jpg | Adrenal rest - high mag. (WC/Nephron)
</gallery>


===Hyperplasia vs. adenoma===
=====www=====
*Hyperplasia is multifocal.<ref>IAV. 18 February 09.</ref>
*[http://www.webpathology.com/image.asp?case=78&n=5 Adrenal medulla (webpathology.com)].


===IHC===
Adrenal cortex:<ref name=pmid18579979>{{Cite journal  | last1 = De Padua | first1 = M. | last2 = Rajagopal | first2 = V. | title = Myxoid adrenal adenoma with focal pseudoglandular pattern. | journal = Indian J Med Sci | volume = 62 | issue = 5 | pages = 199-203 | month = May | year = 2008 | doi =  | PMID = 18579979 }}</ref>
*Chromogranin A -ve.
*Synaptophysin +ve.
*Alpha-inhibin +ve.
*Vimentin +ve.
*Melan A +ve.
*AE1/AE3 -ve.
*RCC -ve (0 +ve of 63 cases<ref name=pmid21490444>{{Cite journal  | last1 = Sangoi | first1 = AR. | last2 = Fujiwara | first2 = M. | last3 = West | first3 = RB. | last4 = Montgomery | first4 = KD. | last5 = Bonventre | first5 = JV. | last6 = Higgins | first6 = JP. | last7 = Rouse | first7 = RV. | last8 = Gokden | first8 = N. | last9 = McKenney | first9 = JK. | title = Immunohistochemical distinction of primary adrenal cortical lesions from metastatic clear cell renal cell carcinoma: a study of 248 cases. | journal = Am J Surg Pathol | volume = 35 | issue = 5 | pages = 678-86 | month = May | year = 2011 | doi = 10.1097/PAS.0b013e3182152629 | PMID = 21490444 }}</ref>).
*EMA -ve (0 +ve of 63 cases<ref name=pmid21490444/>).


==Neoplasms==
A panel that may be useful for [[adrenal cortical adenoma|adenoma]] versus [[adrenal cortical carcinoma|carcinoma]]:<ref name=pmid26317117>{{Cite journal  | last1 = Kovach | first1 = AE. | last2 = Nucera | first2 = C. | last3 = Lam | first3 = QT. | last4 = Nguyen | first4 = A. | last5 = Dias-Santagata | first5 = D. | last6 = Sadow | first6 = PM. | title = Genomic and immunohistochemical analysis in human adrenal cortical neoplasia reveal beta-catenin mutations as potential prognostic biomarker. | journal = Discoveries (Craiova) | volume = 3 | issue = 2 | pages =  | month =  | year =  | doi = 10.15190/d.2015.32 | PMID = 26317117 }}
===Benign neoplasms===
</ref><ref name=pmid11196463>{{Cite journal  | last1 = Arola | first1 = J. | last2 = Salmenkivi | first2 = K. | last3 = Liu | first3 = J. | last4 = Kahri | first4 = AI. | last5 = Heikkilä | first5 = P. | title = p53 and Ki67 in adrenocortical tumors. | journal = Endocr Res | volume = 26 | issue = 4 | pages = 861-5 | month = Nov | year = 2000 | doi = | PMID = 11196463 }}</ref>
*Beta-catenin, p53, reticulin, inhibin, melan A, Ki-67.


==Adrenal cortical adenoma==
==Clinical==
===Epidemiology===
Patients getting a bilateral adrenalectomy get pre-treatment with steroids.<ref>URL:
*Often an incidental finding.
[http://www3.interscience.wiley.com/cgi-bin/fulltext/119909358/PDFSTART http://www3.interscience.wiley.com/cgi-bin/fulltext/119909358/PDFSTART]. Accessed on: 21 August 2010.</ref>


Pathologic/clinical:  
Adrenal insufficiency is an immediate danger post-op.<ref>URL: [http://ats.ctsnetjournals.org/cgi/content/full/62/5/1516 http://ats.ctsnetjournals.org/cgi/content/full/62/5/1516]. Accessed on: 21 August 2010.</ref>
*May be hormonally active.


===Histology===
=Benign=
Classic features:
The section covers non-neoplastic pathologies of the adrenal gland. These uncommonly come to the pathologist.
*Well-defined cell borders.
*Clear cytoplasm.
*May have foci of necrosis/degeneration and nuclear atypia.


In aldosterone producing tumours:
*Adrenal incidentalomas<ref>{{Cite journal  | last1 = Aljabri | first1 = KS. | last2 = Bokhari | first2 = SA. | last3 = Alkeraithi | first3 = M. | title = Adrenal hemangioma in a 19-year-old female. | journal = Ann Saudi Med | volume = 31 | issue = 4 | pages = 421-3 | month =  | year =  | doi = 10.4103/0256-4947.76411 | PMID = 21293064 }}</ref>
*May extend outside of the capsule (should not be diagnosed as ''adrenal cortical carcinoma''.
**Adrenal tumors
*No atrophy of non-hyperplastic cortex.
**Greater than 1 cm
**Identified on imaging performed for other indications
*Found in up to 10% of patients undergoing abdominal imaging.
*Management problematic
** Guidelines incorporate lesion size, functional status and imaging features.
**Resection is generally advocated for
***Functioning lesions.
***Radiographic features suggestive of malignancy.
***Growth during observation.
==Stress response==
*In fetuses - fat content increases due to stress<ref name=pmid964978>{{cite journal |author=Becker MJ, Becker AE |title=Fat distribution in the adrenal cortex as an indication of the mode of intrauterine death |journal=Hum. Pathol. |volume=7 |issue=5 |pages=495–504 |year=1976 |month=September |pmid=964978 |doi= |url=}}</ref> -- see: ''[[Fetal_autopsy#Adrenal_fetal_fat_pattern]]''.
*In newborns/children/adults - fat content decreases due to stress.


In cortisol producing tumours:
==Spironolactone bodies==
*Atrophy of the non-hyperplastic cortex (due to feedback inhibition from the [[pituitary gland]]).
{{Main|Spironolactone bodies}}


==Pheochromocytoma==
==Hemorrhagic adrenalitis==
*[[AKA]] ''Waterhouse-Friderichsen syndrome''.
===General===
===General===
*Considered to be a [[paraganglioma]].<ref>EP P.327.</ref>
*Classically thought to be only due to ''Neisseria meningitidis''; however, more recently also associated with ''Staphylococcus aureus'',<ref name=pmid16177250>{{cite journal |author=Adem PV, Montgomery CP, Husain AN, ''et al.'' |title=Staphylococcus aureus sepsis and the Waterhouse-Friderichsen syndrome in children |journal=N. Engl. J. Med. |volume=353 |issue=12 |pages=1245–51 |year=2005 |month=September |pmid=16177250 |doi=10.1056/NEJMoa044194 |url=}}</ref> and ''Streptococcus pneumoniae''.<ref name=pmid14747454>{{cite journal |author=Hamilton D, Harris MD, Foweraker J, Gresham GA |title=Waterhouse-Friderichsen syndrome as a result of non-meningococcal infection |journal=J. Clin. Pathol. |volume=57 |issue=2 |pages=208–9 |year=2004 |month=February |pmid=14747454 |pmc=1770213 |doi= |url=}}</ref>


===Clinical===
===Gross===
*Paroxysms (i.e. episodic) tachycardia, headache, anxiety.
Features:
*Massive haemorrhage within the substance of the adrenal gland.


===Epidemiology===
DDx (autopsy):
*Tumour arises from medulla
*Post-mortem changes.
*Literally means "dusky" (pheo) "colour" (chromo) - dull appearance on gross


===Histology===
===Microscopic===
Features:
Features:
*Architecture:
*Massive haemorrhage within the substance of the adrenal gland.
**Cell nests, ''auf deutsch'': Zellballen (literally ''Cell balls'').
***Useful for differentiating from ACC.
*Nuclei.
**+/-Pleomorphism.
**Nucleoli may be prominent (not signif. prognostically).
*Cellular morphology.
**Polygonal cells.
*Cytoplasm.
**Basophilic, granular.
*Other.
**Haemorrhagic.


==Ganglioneuroma==
Image: [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770213/figure/f1/ Haemorrhage in adrenal (nih.gov)].
Micro.<ref>[need ref]</ref>
*Disordered fibrinous material
*Ganglion cells.
**Large cells with large nucleus.
***Prominent nucleolus.


==Myelolipoma==
<gallery>
Image:Adrenal WaterhouseFriderichse EColiSepsis LP PA.JPG|Adrenal hemorrhage -low power - E. coli sepsis (SKB)
Image:Adrenal WaterhouseFriderichse EColiSepsis MP PA.JPG|thumb|Adrenal hemorrhage - medium power - E. coli sepsis (SKB)
</gallery>


==Adenomatoid tumour==
==Adrenal cytomegaly==
*[[AKA]] ''adrenocortical cytomegaly''.
*[[AKA]] ''adrenal gland with cytomegaly''.


===Malignant neoplasms===
===General===
==Adrenocortical carcinoma (ACC)==
May be associated with:<ref>URL: [http://www.humpath.com/?adrenal-cytomegaly http://www.humpath.com/?adrenal-cytomegaly]. Accessed on: 3 January 2012.</ref>
Epi.
*[[Beckwith-Wiedemann syndrome]].
*Prognosis sucks.
* Prematurity.
* Rh-incompatibility.<ref name=pmid4336262>{{Cite journal  | last1 = Aterman | first1 = K. | last2 = Kerenyi | first2 = N. | last3 = Lee | first3 = M. | title = Adrenal cytomegaly. | journal = Virchows Arch A Pathol Pathol Anat | volume = 355 | issue = 2 | pages = 105-22 | month =  | year = 1972 | doi =  | PMID = 4336262 |URL = http://www.springerlink.com/content/v06w5250415jr818/ }}</ref>


===Microscopic===
===Microscopic===
Features:
Features:
*Very pleomorphic nuclei.
*Large cells in the adrenal cortex.<ref name=pmid4336262/>
*High mitotic rate.
 
*Atypical mitoses.
==Addison disease==
*Eosinophilic cytoplasm.
===General===
*Chronic adrenocortical insufficiency.
 
Clinical:
*Brown skin - due POMC (a precursor of ACTH and melanocyte stimulating hormone (MSH)).<ref name=Ref_PBoD8_1157>{{Ref PBoD8|1157}}</ref>
**POMC presence implies the [[pituitary gland]] intact.
*Hypotension.
*Nausea and vomiting.
 
DDx:<ref name=Ref_PBoD8_1155>{{Ref PBoD8|1155}}</ref>
*Autoimmune.
*[[Tuberculosis]].
*[[HIV|AIDS]].
*Malignancy.
 
Notes:
*Secondary adrenocortical insufficiency (due to pituitary pathology):<ref name=Ref_PCPBoD8_585>{{Ref PCPBoD8|585}}</ref>
**No hyperpigmentation (as no POMC).
**Aldosterone usu. normal.


==Malignant pheochromoctyoma==
===Microscopic===
*Like the description in ''benign neoplasms''.
Features:<ref name=Ref_PBoD8_1157>{{Ref PBoD8|1157}}</ref>
*Differentiated from benign pheochromocytoma by mets - often aided by radiologic report.
*Atrophy adrenal cortex - specifically zona fasciculata and zona reticularis.
*Features useful for differentiating benign from malignant:<ref>EP P.259.</ref>
**Marked nuclear atypia.
**Invasion:
***Capsular.
***Vascular.
**Necrosis.
**Cellular monotony.
**Mitoses:
***Rate.
***Atypical mitosis.


==Neuroblastoma==
Notes:
===Epidemiology===
*There is preservation of zona glomerulosa and medulla.
*Usually paediatric population.
 
=Benign neoplasms=
 
==Adrenal hemangioma==
Radiographic incidentalomas but may be large and calcified raising a radiographic ddx of adrenal cortical carcinoma.
*Rare.
*40 and 70 years.
*2:1 female-to-male ratio
<gallery>
Image:Adrenal Hemangioma LP CTR.jpg|Adrenal hemangioma - low power (SKB)
Image:Adrenal Hemangioma MP CTR.jpg|Adrenal hemangioma - medium power (SKB)
</gallery>
 
==Adrenal cortical adenoma==
{{Main|Adrenal cortical adenoma}}
 
==Pheochromocytoma==
{{Main|Pheochromocytoma}}
 
==Adrenal ganglioneuroma==
{{Main|Ganglioneuroma}}
 
===General===
*May be retroperitoneal.
*Multiple ganglioneuromas may be due to [[multiple endocrine neoplasia IIb]].
 
===Gross===
*Solid.
*White.
*Firm.
*Well-circumscribed.
*May be nodular.
 
DDx (gross):
*[[Leiomyoma]].
 
Images:
*[http://commons.wikimedia.org/wiki/File:Adrenal_ganglioneuroma_02.JPG Adrenal ganglioneuroma (WC)].
*[http://www.webpathology.com/image.asp?n=2&Case=84 Ganglioneuroma (webpathology.com)].


===Microscopic===
===Microscopic===
*Small round cell tumour.
Features:
*Ganglion cells - '''key feature'''.
**Large cells with large nucleus.
***Prominent nucleolus.
*Disordered fibrinous material.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Ganglion_high_mag.jpg Ganglion - benign (WC)].
 
==Adrenal myelolipoma==
{{Main|Adrenal myelolipoma}}
 
==Adenomatoid tumour==
See: ''[[Uterine_tumours#Adenomatoid_tumour|Adenomatoid tumours (uterine tumours)]]''.
 
=Malignant neoplasms=
==Adrenocortical carcinoma==
*[[AKA]] ''adrenal cortical carcinoma''.
*Abbreviated ''ACC''.
{{Main|Adrenocortical carcinoma}}
 
==Neuroblastoma==
{{Main|Neuroblastoma}}


=See also=
*[[Small round cell tumours]].


==References==
=References=
{{reflist|2}}
{{reflist|2}}


[[Category:Endocrine pathology]]
[[Category:Endocrine pathology]]
[[Category:Genitourinary pathology]]
[[Category:Genitourinary pathology]]
Michael
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