Pheochromocytoma

Pheochromocytoma is a tumour of the adrenal gland medulla. It may be benign or malignant.

General

Considered to be a paraganglioma.^[1]
Literally means "dusky" (pheo) "colour" (chromo) - dull appearance on gross.
Tumour arises from adrenal medulla - chromaffin cells.^[2]

Memory device - the rule of 10s:^[2]

10% extra-adrenal (e.g. carotid body, organ of Zuckerkandl (neighourhood of aortic bifuration/IMA branch point)).
10% bilateral.
10% malignant.
10% no hypertension.
25% associated within a syndrome:
1. Multiple endocrine neoplasia 2A and 2B.
2. von Hippel-Lindau syndrome.
3. Neurofibromatosis type 1.
4. Familial paraganglioma syndromes - several.

Clinical

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

Laboratory findings (urine):

Vanillylmandelic acid (VMA).
Metanephrines.

Microscopic

Features:^[3]

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.^[2]
Surrounding adrenal cortex is typically compressed.^[4]

DDx:

Adrenal cortical carcinoma - pheochromocytoma versus adrenal cortical carcinoma.

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.^[5]

Favour pheochromocytoma:

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

Favour adrenal cortical carcinoma:

Nucleolus, sheeting.

Malignant pheochromoctyoma

Robbins says metastases are the sole criteria of malignancy.^[2]
Thompson suggests one can differentiate benign from malignant with the aid of the following:^[6]
- 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.

References

↑ Thompson, Lester D. R. (2006). Endocrine Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 327. ISBN 978-0443066856.
↑ ^2.0 ^2.1 ^2.2 ^2.3 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.
↑ 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.
↑ URL: http://www.pathpedia.com/Education/eAtlas/Histopathology/Adrenal/Pheochromocytoma.aspx. Accessed on: 27 May 2013.
↑ 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.
↑ Thompson, Lester D. R. (2006). Endocrine Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 259. ISBN 978-0443066856.

[Ref_EP327-1] Thompson, Lester D. R. (2006). Endocrine Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 327. ISBN 978-0443066856.

[Ref_PCPBoD8_586-2] 2.0 ^2.1 ^2.2 ^2.3 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.

[3] 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.

[4] URL: http://www.pathpedia.com/Education/eAtlas/Histopathology/Adrenal/Pheochromocytoma.aspx. Accessed on: 27 May 2013.

[pmid20154585-5] 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.

[Ref_EP259-6] Thompson, Lester D. R. (2006). Endocrine Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 259. ISBN 978-0443066856.

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