Difference between revisions of "Adrenal gland"

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====Micro====
====Micro====
The sections show a lesion in the medulla of the adrenal gland that is arranged in nests (Zellballen).  The tumour cells have abundant grey/blue granular cytoplasm, and nuclei with granular chromatin (salt and pepper chromatin). The lesion is surrounded by a compressed rim of adrenal cortex and fibrosis tissue.  The core of the lesion is fibrotic and has clusters of hemosiderin-laden macrophages.
The sections shows a partially hemorrhagic lesion in the medulla of the adrenal gland that is arranged in nests (Zellballen).  The tumour cells have abundant grey/blue granular cytoplasm, and nuclei with granular chromatin (salt and pepper chromatin). The lesion is surrounded by a compressed rim of adrenal cortex and fibrosis tissue.  The core of the lesion is fibrotic and has clusters of hemosiderin-laden macrophages.


There is no capsular invasion. Vascular invasion is not identified.  There is no necrosis. Mitotic activity is not appreciated.   
There is no capsular invasion. Vascular invasion is not identified.  There is no necrosis. Mitotic activity is not appreciated.   

Revision as of 18:05, 12 November 2012

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

  • Cortex.
  • Medulla.

Histology

It is composed of a cortex and a medulla.

Cortex

It has three layers - mnemonic: GFR (from superficial to deep):

  1. Zona glomerulosa - salt (e.g. aldosterone).
    • Eosinophilic cytoplasm. (???)
    • Layer normally discontinuous.
  2. Zona fasciculata - sugar (e.g. cortisol).
    • Clear cytoplasm - key feature.
    • Largest part of the cortex ~ 70%.
    • Cells in cords/nests. (???)
  3. Zona reticularis - steroid (e.g. dehydroepiandrosterone).
    • Marked eosinophilia of cytoplasm - key feature.
    • Granular/reticular cytoplasm.

Medulla

It consists of two cell types:[1]

  1. Chromaffin cells.
    • Arise of neural crest.
  2. Sustentacular cells (supporting cells).

Produce NED: norepinephrine, epinephrine, dopamine.

IHC

Adrenal cortex:

  • Chromogranin A -ve.
  • Synaptophysin +ve.
  • Alpha-inhibin +ve.

Clinical

Patients getting a bilateral adrenalectomy get pre-treatment with steroids.[2]

Adrenal insufficiency is an immediate danger post-op.[3]

Benign

The section covers non-neoplastic pathologies of the adrenal gland. These uncommonly come to the pathologist.

Stress response

Spironolactone bodies

General

Etiology:

  • Long-term use of spironolactone.

Microscopic

Features:[5]

  • Location: zona glomerulosa (where aldosterone is produced).
  • Appearance: eosinophilic spherical laminated whorls.

Images:

Hemorrhagic adrenalitis

  • AKA Waterhouse-Friderichsen syndrome.

General

  • Classically thought to be only due to Neisseria meningitidis; however, more recently also associated with Staphylococcus aureus,[6] and Streptococcus pneumoniae.[7]

Gross

Features:

  • Massive haemorrhage within the substance of the adrenal gland.

DDx (autopsy):

  • Post-mortem changes.

Microscopic

Features:

  • Massive haemorrhage within the substance of the adrenal gland.

Image: Haemorrhage in adrenal (nih.gov).

Adrenal cytomegaly

  • AKA adrenocortical cytomegaly.
  • AKA adrenal gland with cytomegaly.

General

May be associated with:[8]

Microscopic

Features:

  • Large cells in the adrenal cortex.[9]

Addison disease

General

  • Chronic adrenocortical insufficiency.

Clinical:

  • Brown skin - due POMC (a precursor of ACTH and melanocyte stimulating hormone (MSH)).[10]
  • Hypotension.
  • Nausea and vomiting.

DDx:[11]

Notes:

  • Secondary adrenocortical insufficiency (due to pituitary pathology):[12]
    • No hyperpigmentation (as no POMC).
    • Aldosterone usu. normal.

Microscopic

Features:[10]

  • Atrophy adrenal cortex - specifically zona fasciculata and zona reticularis.

Notes:

  • There is preservation of zona glomerulosa and medulla.

Benign neoplasms

Adrenal cortical adenoma

General

Epidemiology:

  • Often an incidental finding.

Pathologic/clinical:

  • May be hormonally active.
  • Radiologists are good at identifying adenomas, as they are usually lipid rich and have a characteristic low HU signal.[13]

Indications for excision:[14][15]

  • Lesions >30 mm.
  • Hormonally active.
  • Non-incidental finding. (???)

Microscopic

Classic features:

  • Well-defined cell borders.
  • Clear cytoplasm.
  • May have foci of necrosis/degeneration and nuclear atypia.

In aldosterone producing tumours:

  • May extend outside of the capsule (should not be diagnosed as adrenal cortical carcinoma).
  • No atrophy of non-hyperplastic cortex.

In cortisol producing tumours (Cushing syndrome):

  • Atrophy of the non-hyperplastic cortex (due to feedback inhibition from the pituitary gland).

Notes:

Pheochromocytoma

General

  • Considered to be a paraganglioma.[17]
  • Literally means "dusky" (pheo) "colour" (chromo) - dull appearance on gross.
  • Tumour arises from adrenal medulla - chromaffin cells.[18]

Memory device - the rule of 10s:[18]

Clinical

  • Classic finding: hypertension.
  • Paroxysms (i.e. episodes) of tachycardia, headache, anxiety, hypertension.

Laboratory findings (urine):

  • Vanillylmandelic acid (VMA).
  • Metanephrines.

Microscopic

Features:[19]

  • Chief cells:
    • Usu. polygonal cells, may be spindled.
    • Arranged in cell nests - "Zellballen" (literally cell balls) - key feature.
    • Stippled chromatin (AKA salt and pepper chromatin) - coarsely granular chromatin.
    • Granular cytoplasm, often basophilic - important.
  • Sustentacular cells (structural support cell).
  • Often haemorrhagic - highly vascular.
  • +/-Nuclear pleomorphism.

Notes:

  • The nested architecture (Zellballen) is useful for differentiating from ACC.
  • Metastasis sole criteria of malignancy.[18]

Images:

DDx:

Pheochromocytoma versus adrenal cortical carcinoma
  • Pheochromocytoma and adrenal cortical carcinoma overlap histologically.[20]

Favour pheochromocytoma:

  • Small chickenwire-pattern blood vessels, nests, salt-and-pepper chromatin, red blood cell extravasation.

Favour adrenal cortical carcinoma:

  • Nucleolus, sheeting.

Malignant pheochromoctyoma

  1. Robbins says metastases are the sole criteria of malignancy.[18]
  2. Thompson suggests one can differentiate benign from malignant with the aid of the following:[21]
    • Marked nuclear atypia.
    • Invasion:
      • Capsular.
      • Vascular.
    • Necrosis.
    • Cellular monotony.
    • Mitoses:
      • Rate.
      • Atypical mitosis.

IHC

  • Chief cells:
    • Chromogranin A +ve.
    • Synaptophysin +ve.
  • Sustentacular cells:
    • S100 +ve.

Electron microscopy

  • Membrane-bound secretory granules.

Sign out

ADRENAL MASS, LEFT, ADRENALECTOMY:
- PHEOCHROMOCYTOMA.

Micro

The sections shows a partially hemorrhagic lesion in the medulla of the adrenal gland that is arranged in nests (Zellballen). The tumour cells have abundant grey/blue granular cytoplasm, and nuclei with granular chromatin (salt and pepper chromatin). The lesion is surrounded by a compressed rim of adrenal cortex and fibrosis tissue. The core of the lesion is fibrotic and has clusters of hemosiderin-laden macrophages.

There is no capsular invasion. Vascular invasion is not identified. There is no necrosis. Mitotic activity is not appreciated.

The adrenal cortex is unremarkable.

Adrenal ganglioneuroma

Main article: Ganglioneuroma

General

Gross

  • Solid.
  • White.
  • Firm.
  • Well-circumscribed.
  • May be nodular.

DDx (gross):

Images:

Microscopic

Features:

  • Ganglion cells - key feature.
    • Large cells with large nucleus.
      • Prominent nucleolus.
  • Disordered fibrinous material.

Images:

Adrenal myelolipoma

General

  • Benign and rare.
  • Typically asymptomatic and hormonally inactive.[22]
    • Symptoms: back or abdominal pain.
  • Diagnosis - usu. by abdominal CT.

Treatment:

  • Watchful waiting if small (<=7 cm) and asymptomatic.[22]

Microscopic

Features:[23]

  • Adipose tissue.
  • Hematopoietic elements from all three lineages:
    1. Erythroid.
    2. Myeloid.
    3. Megakaryocytic.
  • +/-Calcification.[22]

DDx:

Images:

Adenomatoid tumour

See: Adenomatoid tumours (uterine tumours).

Malignant neoplasms

Adrenocortical carcinoma

  • AKA adrenal cortical carcinoma.
  • Abbreviated ACC.

General

  • Prognosis sucks, esp. in adults.

Epidemiology:

Gross

  • +/-Encapsulated.
  • Necrotic-appearing.

Image:

Microscopic

Various criteria exist for this diagnosis. The most widely used is the Weiss criteria, which is a big long clunker.

Image:

Notes:

  • Tumour may contain fat.[24]

Adult

Weiss criteria

Three of the following:[25]

  1. High nuclear grade.
  2. High mitotic rate; >5/50 HPF (@ 40X obj.) - definition suffers from HPFitis.
  3. Atypical mitoses.
  4. Cleared cytoplasm in >= 25% of tumour cells.
  5. Sheeting (diffuse architecture) in >= 1/3 of tumour cells.
  6. Necrosis in nests.
  7. Venous invasion.
  8. Adrenal sinusoid invasion; lymphovascular space invasion within the adrenal gland.
  9. Capsular invasion.
Volante criteria

There is a simplified set of criteria by Volante et al. - that is not widely used:[26]

  • Reticular network disruption (with reticulin staining).
  • One of the three following:
    1. Abundant mitoses >5/50 high-power fields - definition suffers from HPFitis.
    2. Necrosis.
    3. Vascular invasion.

Pediatric

The criteria in the pediatric setting are somewhat different. This is discussed by Wieneke et al.[27] and Dehner and Hill.[28]

Dehner and Hill propose a very simple system:[28]

  • "Low risk" < 200 g & confined to the adrenal.
  • "Intermediate risk" 200-400 g, no mets, +/-microscopic disease outside adrenal.
  • "High risk" >400 g, or mets, or gross invasion of adjacent structures.

IHC

  • Vimentin +ve.
  • Melan A +ve.
  • Inhibin-alpha +ve.
  • Cytokeratins +ve/-ve.

Others:

Neuroblastoma

See also: olfactory neuroblastoma.

General

Epidemiology:

  • Usually paediatric population.

Laboratory findings:

  • Increased urine homovanillic acid.

Predictors of a poor prognosis:[30]

  • High mitotic-karyorrhectic index.
  • Lack of schwannian stroma.
  • >18 months.
  • Near ploidy.
  • N-MYC amplification.
  • Lymph node spread.
  • Distant spread.

Classification:

Gross

Microscopic

Features:[33]

  • Small round blue cells separated by thin (pink) fibrous septa.
  • Homer-Wright rosettes.
    • Rosette with a small (~100 micrometers - diameter) meshwork of fibers (neuropil) at the centre.[34]
  • Neuropil-like stroma = paucicellular stroma with a cotton candy-like appearance; see comparison below.
    • >50% neuropil-like stroma -- otherwise it's a ganglioneurona or ganglioblastoma.

Notes:

  • The fibrous septa are especially useful for differentiation from lymphoma.

DDx:

Images:

Schwannian vs. neuropil

Feature Schwannian Neuropil
Cellularity high ~ spacing of cells < 30 µm low ~ spacing of cells > 100 µm
Fibrillary yes, long fine strands no
Associations ganglion cells neuroblasts
Cytoplasmic vacuolation yes ?

Classification/grading

Commonly grouped by the Shimada classification, which depends on the presence a number of things including:

  • Mitoses/karyorrhectic cells.
  • Molecular abnormalities.

IHC

  • PGP 9.5 +ve.[36]
    • PGP = protein gene product.
  • NB-84 +ve.[37]
    • More sensitive that synaptophysin.
  • Synaptophysin +ve.
  • CD99 -ve.

EM

Distinctive EM appearance:[38]

  • Dendritic processes with longitudinally oriented microtubules.
  • Membrane bound electron-dense granules (contain catecholamines).
  • Desmosomes
    • Not seen in EWS, RMS, lymphomas.
  • Membrane densities.

Pertinent negative:[38]

  • No glycogen.

See also

References

  1. ↑ Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009). Robbins and Cotran pathologic basis of disease (8th ed.). Elsevier Saunders. pp. 1159. ISBN 978-1416031215.
  2. ↑ URL: http://www3.interscience.wiley.com/cgi-bin/fulltext/119909358/PDFSTART. Accessed on: 21 August 2010.
  3. ↑ URL: http://ats.ctsnetjournals.org/cgi/content/full/62/5/1516. Accessed on: 21 August 2010.
  4. ↑ Becker MJ, Becker AE (September 1976). "Fat distribution in the adrenal cortex as an indication of the mode of intrauterine death". Hum. Pathol. 7 (5): 495–504. PMID 964978.
  5. ↑ Kovacs K, Horvath E, Singer W (December 1973). "Fine structure and morphogenesis of spironolactone bodies in the zona glomerulosa of the human adrenal cortex". J. Clin. Pathol. 26 (12): 949-57. PMC 477936. PMID 4131694. http://jcp.bmj.com/cgi/pmidlookup?view=long&pmid=4131694.
  6. ↑ Adem PV, Montgomery CP, Husain AN, et al. (September 2005). "Staphylococcus aureus sepsis and the Waterhouse-Friderichsen syndrome in children". N. Engl. J. Med. 353 (12): 1245–51. doi:10.1056/NEJMoa044194. PMID 16177250.
  7. ↑ Hamilton D, Harris MD, Foweraker J, Gresham GA (February 2004). "Waterhouse-Friderichsen syndrome as a result of non-meningococcal infection". J. Clin. Pathol. 57 (2): 208–9. PMC 1770213. PMID 14747454. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770213/.
  8. ↑ URL: http://www.humpath.com/?adrenal-cytomegaly. Accessed on: 3 January 2012.
  9. ↑ 9.0 9.1 Aterman, K.; Kerenyi, N.; Lee, M. (1972). "Adrenal cytomegaly.". Virchows Arch A Pathol Pathol Anat 355 (2): 105-22. PMID 4336262.
  10. ↑ 10.0 10.1 10.2 Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009). Robbins and Cotran pathologic basis of disease (8th ed.). Elsevier Saunders. pp. 1157. ISBN 978-1416031215.
  11. ↑ Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009). Robbins and Cotran pathologic basis of disease (8th ed.). Elsevier Saunders. pp. 1155. ISBN 978-1416031215.
  12. ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 585. ISBN 978-1416054542.
  13. ↑ URL: http://emedicine.medscape.com/article/376240-overview.
  14. ↑ Luton, JP.; Martinez, M.; Coste, J.; Bertherat, J. (Jul 2000). "Outcome in patients with adrenal incidentaloma selected for surgery: an analysis of 88 cases investigated in a single clinical center.". Eur J Endocrinol 143 (1): 111-7. PMID 10870039.
  15. ↑ Liu, XK.; Liu, XJ.; Dong, X.; Kong, CZ. (Jun 2008). "[Clinical research about treatment for adrenal incidentalomas]". Zhonghua Wai Ke Za Zhi 46 (11): 832-4. PMID 19035218.
  16. ↑ IAV. 18 February 2009.
  17. ↑ Thompson, Lester D. R. (2006). Endocrine Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 327. ISBN 978-0443066856.
  18. ↑ 18.0 18.1 18.2 18.3 Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 586. ISBN 978-1416054542.
  19. ↑ Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009). Robbins and Cotran pathologic basis of disease (8th ed.). Elsevier Saunders. pp. 1161. ISBN 978-1416031215.
  20. ↑ Sangoi, AR.; McKenney, JK. (Mar 2010). "A tissue microarray-based comparative analysis of novel and traditional immunohistochemical markers in the distinction between adrenal cortical lesions and pheochromocytoma.". Am J Surg Pathol 34 (3): 423-32. doi:10.1097/PAS.0b013e3181cfb506. PMID 20154585.
  21. ↑ Thompson, Lester D. R. (2006). Endocrine Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 259. ISBN 978-0443066856.
  22. ↑ 22.0 22.1 22.2 Daneshmand, S.; Quek, ML. (2006). "Adrenal myelolipoma: diagnosis and management.". Urol J 3 (2): 71-4. PMID 17590837.
  23. ↑ 23.0 23.1 Cha, JS.; Shin, YS.; Kim, MK.; Kim, HJ. (Aug 2011). "Myelolipomas of both adrenal glands.". Korean J Urol 52 (8): 582-5. doi:10.4111/kju.2011.52.8.582. PMC 3162227. PMID 21927708. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3162227/.
  24. ↑ Heye S, Woestenborghs H, Van Kerkhove F, Oyen R (2005). "Adrenocortical carcinoma with fat inclusion: case report". Abdom Imaging 30 (5): 641–3. doi:10.1007/s00261-004-0281-5. PMID 15688105.
  25. ↑ Jain M, Kapoor S, Mishra A, Gupta S, Agarwal A (2010). "Weiss criteria in large adrenocortical tumors: a validation study". Indian J Pathol Microbiol 53 (2): 222–6. doi:10.4103/0377-4929.64325. PMID 20551521.
  26. ↑ Volante M, Bollito E, Sperone P, et al. (November 2009). "Clinicopathological study of a series of 92 adrenocortical carcinomas: from a proposal of simplified diagnostic algorithm to prognostic stratification". Histopathology 55 (5): 535–43. doi:10.1111/j.1365-2559.2009.03423.x. PMID 19912359.
  27. ↑ Wieneke JA, Thompson LD, Heffess CS (July 2003). "Adrenal cortical neoplasms in the pediatric population: a clinicopathologic and immunophenotypic analysis of 83 patients". Am. J. Surg. Pathol. 27 (7): 867–81. PMID 12826878.
  28. ↑ 28.0 28.1 Dehner LP, Hill DA (2009). "Adrenal cortical neoplasms in children: why so many carcinomas and yet so many survivors?". Pediatr. Dev. Pathol. 12 (4): 284–91. doi:10.2350/08-06-0489.1. PMID 19326954.
  29. ↑ Unger P, Hoffman K, Pertsemlidis D, Thung S, Wolfe D, Kaneko M (May 1991). "S100 protein-positive sustentacular cells in malignant and locally aggressive adrenal pheochromocytomas". Arch. Pathol. Lab. Med. 115 (5): 484–7. PMID 1673596.
  30. ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 254. ISBN 978-1416054542.
  31. ↑ Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, Roald B (July 1999). "Terminology and morphologic criteria of neuroblastic tumors: recommendations by the International Neuroblastoma Pathology Committee". Cancer 86 (2): 349–63. PMID 10421272.
  32. ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 253. ISBN 978-1416054542.
  33. ↑ Chung EM, Murphey MD, Specht CS, Cube R, Smirniotopoulos JG (2008). "From the Archives of the AFIP. Pediatric orbit tumors and tumorlike lesions: osseous lesions of the orbit". Radiographics 28 (4): 1193–214. doi:10.1148/rg.284085013. PMID 18635637.
  34. ↑ Wippold FJ, Perry A (March 2006). "Neuropathology for the neuroradiologist: rosettes and pseudorosettes". AJNR Am J Neuroradiol 27 (3): 488–92. PMID 16551982.
  35. ↑ URL: http://radiographics.rsna.org/content/28/4/1193.full. Accessed on: 12 January 2011.
  36. ↑ Ootsuka, S.; Asami, S.; Sasaki, T.; Yoshida, Y.; Nemoto, N.; Shichino, H.; Chin, M.; Mugishima, H. et al. (Jun 2008). "Useful markers for detecting minimal residual disease in cases of neuroblastoma.". Biol Pharm Bull 31 (6): 1071-4. PMID 18520032.
  37. ↑ Miettinen, M.; Chatten, J.; Paetau, A.; Stevenson, A. (Mar 1998). "Monoclonal antibody NB84 in the differential diagnosis of neuroblastoma and other small round cell tumors.". Am J Surg Pathol 22 (3): 327-32. PMID 9500774.
  38. ↑ 38.0 38.1 Mackay, B.; Masse, SR.; King, OY.; Butler, J. (Dec 1975). "Diagnosis of neuroblastoma by electron microscopy of bone marrow aspirates.". Pediatrics 56 (6): 1045-9. PMID 1196755.
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