Difference between revisions of "Adrenal gland"

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*[[AKA]] ''adrenal cortical carcinoma''.
*[[AKA]] ''adrenal cortical carcinoma''.
*Abbreviated ''ACC''.
*Abbreviated ''ACC''.
 
{{Main|Adrenocortical carcinoma}}
===General===
*Prognosis sucks, esp. in adults.
 
Epidemiology:
*May be associated with a syndrome:<ref name=Ref_PBoD8_1157>{{Ref PBoD8|1157}}</ref>
**[[Li-Fraumeni syndrome]].
**[[Beckwith-Wiedemann syndrome]].
 
===Gross===
*+/-Encapsulated.
*Necrotic-appearing.
 
Image:
<gallery>
Image:Adrenal_cortical_carcinoma.JPG | ACC - cytology (WC/AFIP)
</gallery>
 
===Microscopic===
Various criteria exist for this diagnosis.  The most widely used is the ''Weiss criteria'', which is a big long clunker.
 
Notes:
*Tumour may contain fat.<ref name=pmid15688105>{{cite journal |author=Heye S, Woestenborghs H, Van Kerkhove F, Oyen R |title=Adrenocortical carcinoma with fat inclusion: case report |journal=Abdom Imaging |volume=30 |issue=5 |pages=641–3 |year=2005 |pmid=15688105 |doi=10.1007/s00261-004-0281-5 |url=}}</ref>
 
====Images====
<gallery>
Image:Adrenal_cortical_carcinoma_-_low_mag.jpg | ACC - low mag. (WC/Nephron)
Image:Adrenal_cortical_carcinoma_-_m_-_high_mag.jpg | ACC - high mag. (WC/Nephron)
Image:Adrenal_cortical_carcinoma_-_high_mag.jpg | ACC with normal adrenal medulla - high mag. (WC/Nephron)
</gallery>
www:
*[http://path.upmc.edu/cases/case166.html ACC (upmc.edu)].
 
====Adult====
=====Weiss criteria=====
Three of the following:<ref name=pmid20551521>{{cite journal |author=Jain M, Kapoor S, Mishra A, Gupta S, Agarwal A |title=Weiss criteria in large adrenocortical tumors: a validation study |journal=Indian J Pathol Microbiol |volume=53 |issue=2 |pages=222–6 |year=2010 |pmid=20551521 |doi=10.4103/0377-4929.64325 |url=}}</ref>
#High nuclear grade.
#High mitotic rate; >5/50 HPF (@ 40X obj.) - definition suffers from [[HPFitis]].
#Atypical mitoses.
#Cleared cytoplasm in >= 25% of tumour cells.
#Sheeting (diffuse architecture) in >= 1/3 of tumour cells.
#Necrosis in nests.
#Venous invasion.
#Adrenal sinusoid invasion; lymphovascular space invasion within the adrenal gland.
#Capsular invasion.
 
=====Volante criteria=====
There is a simplified set of criteria by ''Volante et al.'' - that is not widely used:<ref name=pmid19912359>{{cite journal |author=Volante M, Bollito E, Sperone P, ''et al.'' |title=Clinicopathological study of a series of 92 adrenocortical carcinomas: from a proposal of simplified diagnostic algorithm to prognostic stratification |journal=Histopathology |volume=55 |issue=5 |pages=535–43 |year=2009 |month=November |pmid=19912359 |doi=10.1111/j.1365-2559.2009.03423.x |url=}}</ref>
*Reticular network disruption (with reticulin staining).
*One of the three following:
*#Abundant mitoses >5/50 high-power fields - definition suffers from [[HPFitis]].
*#Necrosis.
*#Vascular invasion.
 
====Pediatric====
The criteria in the pediatric setting are somewhat different.  This is discussed by Wieneke ''et al.''<ref name=pmid12826878>{{cite journal |author=Wieneke JA, Thompson LD, Heffess CS |title=Adrenal cortical neoplasms in the pediatric population: a clinicopathologic and immunophenotypic analysis of 83 patients |journal=Am. J. Surg. Pathol. |volume=27 |issue=7 |pages=867–81 |year=2003 |month=July |pmid=12826878 |doi= |url=}}</ref> and Dehner and Hill.<ref name=pmid19326954>{{cite journal |author=Dehner LP, Hill DA |title=Adrenal cortical neoplasms in children: why so many carcinomas and yet so many survivors? |journal=Pediatr. Dev. Pathol. |volume=12 |issue=4 |pages=284–91 |year=2009 |pmid=19326954 |doi=10.2350/08-06-0489.1 |url=}}</ref>
 
Dehner and Hill propose a very simple system:<ref name=pmid19326954/>
*"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:
*Synaptophysin +ve/-ve.
*Chromogranin A -ve.
**Pheochromocytoma +ve.
*[[EMA]] -ve.
**[[Renal cell carcinoma]] +ve.
*S100 -ve.
**[[Pheochromocytoma]] +ve (sustentacular cells).<ref>{{cite journal |author=Unger P, Hoffman K, Pertsemlidis D, Thung S, Wolfe D, Kaneko M |title=S100 protein-positive sustentacular cells in malignant and locally aggressive adrenal pheochromocytomas |journal=Arch. Pathol. Lab. Med. |volume=115 |issue=5 |pages=484–7 |year=1991 |month=May |pmid=1673596 |doi= |url=}}</ref>
*PAX-8 -ve.<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>
*CD10 +ve/-ve -- cannot be used to differentiate from [[RCC]].<ref name=pmid20390424>{{Cite journal  | last1 = Mete | first1 = O. | last2 = Kapran | first2 = Y. | last3 = Güllüoğlu | first3 = MG. | last4 = Kiliçaslan | first4 = I. | last5 = Erbil | first5 = Y. | last6 = Senyürek | first6 = YG. | last7 = Dizdaroğlu | first7 = F. | title = Anti-CD10 (56C6) is expressed variably in adrenocortical tumors and cannot be used to discriminate clear cell renal cell carcinomas. | journal = Virchows Arch | volume = 456 | issue = 5 | pages = 515-21 | month = May | year = 2010 | doi = 10.1007/s00428-010-0901-0 | PMID = 20390424 }}</ref>


==Neuroblastoma==
==Neuroblastoma==

Revision as of 02:24, 23 August 2014

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

Adrenal cortical rest redirects here.

Anatomy

  • Cortex.
  • Medulla.

Microscopic

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.

Note:

  • Normal cortex may not be completely encapsulated, i.e. the adrenal capsule may have defects.[1]
    • In other words: the cortex may "spill" into the surrounding fat.

Medulla

It consists of two cell types:[2]

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

Produce NED: norepinephrine, epinephrine, dopamine.

Images

  • Adrenal medulla. (WC)

  • Adrenal cortex, medulla and tumour. (WC/Nephron)

www:

IHC

Adrenal cortex:[3]

  • Chromogranin A -ve.
  • Synaptophysin +ve.
  • Alpha-inhibin +ve.
  • Vimentin +ve.
  • Melan A +ve.
  • AE1/AE3 -ve.

Clinical

Patients getting a bilateral adrenalectomy get pre-treatment with steroids.[4]

Adrenal insufficiency is an immediate danger post-op.[5]

Benign

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

Stress response

Spironolactone bodies

Main article: Spironolactone bodies

Hemorrhagic adrenalitis

  • AKA Waterhouse-Friderichsen syndrome.

General

  • Classically thought to be only due to Neisseria meningitidis; however, more recently also associated with Staphylococcus aureus,[7] and Streptococcus pneumoniae.[8]

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:[9]

Microscopic

Features:

  • Large cells in the adrenal cortex.[10]

Addison disease

General

  • Chronic adrenocortical insufficiency.

Clinical:

  • Brown skin - due POMC (a precursor of ACTH and melanocyte stimulating hormone (MSH)).[11]
  • Hypotension.
  • Nausea and vomiting.

DDx:[12]

Notes:

  • Secondary adrenocortical insufficiency (due to pituitary pathology):[13]
    • No hyperpigmentation (as no POMC).
    • Aldosterone usu. normal.

Microscopic

Features:[11]

  • 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.[14]

Indications for excision:[15][16]

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

Notes:

  • Cushing disease is due to the ACTH over-production by the pituitary.
  • In cortisol producing tumours (Cushing syndrome): atrophy of the non-hyperplastic cortex (due to feedback inhibition from the pituitary gland).

Microscopic

Classic features:

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

Note:

  • In aldosterone producing tumours:

DDx:

Pheochromocytoma

General

  • Considered to be a paraganglioma.[19]
  • Literally means "dusky" (pheo) "colour" (chromo) - dull appearance on gross.
  • Tumour arises from adrenal medulla - chromaffin cells.[20]

Memory device - the rule of 10s:[20]

Clinical

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

Laboratory findings (urine):

  • Vanillylmandelic acid (VMA).
  • Metanephrines.

Microscopic

Features:[21]

  • 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.[20]
  • Surrounding adrenal cortex is typically compressed.[22]

DDx:

Images

  • Carotid body tumour - low mag. (WC/Nephron)

  • Carotid body tumour - high mag. (WC/Nephron)

Pheochromocytoma versus adrenal cortical carcinoma
  • Pheochromocytoma and adrenal cortical carcinoma overlap histologically.[23]

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.[20]
  2. Thompson suggests one can differentiate benign from malignant with the aid of the following:[24]
    • 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, RIGHT, ADRENALECTOMY:
- PHEOCHROMOCYTOMA.
- SURGICAL MARGIN NEGATIVE FOR PHEOCHROMOCYTOMA.

COMMENT:
The tumour cells stains for chromogranin and synaptophysin. S-100 marks the sustentacular cells.
Inhibin is negative in the tumour cells. The immunostaining pattern is consistent with a 
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

Myelolipoma redirects here.

General

  • Benign and rare.
  • Typically asymptomatic and hormonally inactive.[25]
    • Symptoms: back or abdominal pain.
  • Diagnosis - usu. by abdominal CT.

Treatment:

  • Watchful waiting if small (<=7 cm) and asymptomatic.[25]

Microscopic

Features:[26]

  • Adipose tissue.
  • Hematopoietic elements from all three lineages:
    1. Erythroid.
    2. Myeloid.
    3. Megakaryocytic.
  • +/-Calcification.[25]

DDx:[27]

Images

  • Myelolipoma (WC/Mattopaedia)

www:

Adenomatoid tumour

See: Adenomatoid tumours (uterine tumours).

Malignant neoplasms

Adrenocortical carcinoma

  • AKA adrenal cortical carcinoma.
  • Abbreviated ACC.
Main article: Adrenocortical carcinoma

Neuroblastoma

See also: olfactory neuroblastoma.

General

Epidemiology:

  • Usually paediatric population.

Laboratory findings:

  • Increased urine homovanillic acid.

Predictors of a poor prognosis:[28]

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

Classification:

Gross

Microscopic

Features:[31]

  • 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.[32]
  • 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.[34]
    • PGP = protein gene product.
  • NB-84 +ve.[35]
    • More sensitive that synaptophysin.
  • Synaptophysin +ve.
  • CD99 -ve.

EM

Distinctive EM appearance:[36]

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

Pertinent negative:[36]

  • No glycogen.

See also

References

  1. ↑ Mills, Stacey E. (2012). Histology for Pathologists (4th ed.). Lippincott Williams & Wilkins. pp. 1236. ISBN 978-1451113037.
  2. ↑ 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.
  3. ↑ De Padua, M.; Rajagopal, V. (May 2008). "Myxoid adrenal adenoma with focal pseudoglandular pattern.". Indian J Med Sci 62 (5): 199-203. PMID 18579979.
  4. ↑ URL: http://www3.interscience.wiley.com/cgi-bin/fulltext/119909358/PDFSTART. Accessed on: 21 August 2010.
  5. ↑ URL: http://ats.ctsnetjournals.org/cgi/content/full/62/5/1516. Accessed on: 21 August 2010.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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/.
  9. ↑ URL: http://www.humpath.com/?adrenal-cytomegaly. Accessed on: 3 January 2012.
  10. ↑ 10.0 10.1 Aterman, K.; Kerenyi, N.; Lee, M. (1972). "Adrenal cytomegaly.". Virchows Arch A Pathol Pathol Anat 355 (2): 105-22. PMID 4336262.
  11. ↑ 11.0 11.1 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ URL: http://emedicine.medscape.com/article/376240-overview.
  15. ↑ 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.
  16. ↑ 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.
  17. ↑ Thompson, Lester D. R. (2006). Endocrine Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 200. ISBN 978-0443066856.
  18. ↑ IAV. 18 February 2009.
  19. ↑ Thompson, Lester D. R. (2006). Endocrine Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 327. ISBN 978-0443066856.
  20. ↑ 20.0 20.1 20.2 20.3 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.
  21. ↑ 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.
  22. ↑ URL: http://www.pathpedia.com/Education/eAtlas/Histopathology/Adrenal/Pheochromocytoma.aspx. Accessed on: 27 May 2013.
  23. ↑ 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.
  24. ↑ Thompson, Lester D. R. (2006). Endocrine Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 259. ISBN 978-0443066856.
  25. ↑ 25.0 25.1 25.2 Daneshmand, S.; Quek, ML. (2006). "Adrenal myelolipoma: diagnosis and management.". Urol J 3 (2): 71-4. PMID 17590837.
  26. ↑ 26.0 26.1 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/.
  27. ↑ Lam, KY.; Lo, CY. (Sep 2001). "Adrenal lipomatous tumours: a 30 year clinicopathological experience at a single institution.". J Clin Pathol 54 (9): 707-12. PMID 11533079.
  28. ↑ 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.
  29. ↑ 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.
  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. 253. ISBN 978-1416054542.
  31. ↑ 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.
  32. ↑ Wippold FJ, Perry A (March 2006). "Neuropathology for the neuroradiologist: rosettes and pseudorosettes". AJNR Am J Neuroradiol 27 (3): 488–92. PMID 16551982.
  33. ↑ URL: http://radiographics.rsna.org/content/28/4/1193.full. Accessed on: 12 January 2011.
  34. ↑ 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.
  35. ↑ 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.
  36. ↑ 36.0 36.1 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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