Pheochromocytoma

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Pheochromocytoma
Diagnosis in short

Pheochromocytoma. H&E stain.

LM Zellballen (nests of cells), fibrovascular septae, salt-and-pepper nuclei, +/-hemorrhage (very common)
LM DDx adrenocortical carcinoma, paraganglioma
IHC chief cells: chromogranin A +ve, synaptophysin +ve; sustentacular cells: S-100 +ve
Site adrenal gland (same tumour arising at other sites known as paraganglioma)

Syndromes Multiple endocrine neoplasia 2A and 2B, von Hippel-Lindau syndrome,Neurofibromatosis type 1, familial paraganglioma syndromes (several)

Clinical history hypertension (classic Hx), paroxysms of tachycardia, headache, anxiety, hypertension
Prevalence uncommon
Prognosis usually benign
Clin. DDx other adrenal gland masses, renal cell carcinoma, other abdominal masses

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]

Clinical

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

Laboratory findings (urine):

  • Vanillylmandelic acid (VMA).
  • Metanephrines.

Macroscopic

  • Medullary tumour
  • Round to oval mass
  • Dusky red and possibly haemorrhagic

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.
  • Rarely pigmented [4]

Notes:

  • The nested architecture (Zellballen) is useful for differentiating from ACC.
  • Metastasis sole criteria of malignancy.[2]
  • Surrounding adrenal cortex is typically compressed.[5]

DDx:

Images

Pheochromocytoma versus adrenal cortical carcinoma

  • Pheochromocytoma and adrenal cortical carcinoma overlap histologically.[6]

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 (8th Ed.) says metastases are the sole criteria of malignancy.[2]
  2. Thompson suggests one can differentiate benign from malignant with the aid of the following:[7]
    • 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.

Pheochromocytoma versus adrenal cortical carcinoma (ACC):[6]

  • Melan A -ve.
    • Positive in ACC.
  • Inhibin -ve.
    • Positive in ACC.
  • Calretinin -ve.
    • Positive in ACC.

A panel:

  • S-100, chromogranin, calretinin, EMA, PAX8.

Electron microscopy

  • Membrane-bound secretory granules.

Sign out

Right Adrenal (Mass), Adrenalectomy:
     - Pheochromocytoma, margin clear.

Comment:
The tumour stains as follows:
POSITIVE: synaptophysin, chromogranin A, S-100 (sustentacular cells).
NEGATIVE: EMA, inhibin.
Proliferation (Ki-67): <2% of tumour cells.

The immunostaining pattern is consistent with a pheochromocytoma.


Block letters

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.

See also

References

  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.
  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. Bellezza, G.; Giansanti, M.; Cavaliere, A.; Sidoni, A. (Oct 2004). "Pigmented "black" pheochromocytoma of the adrenal gland: a case report and review of the literature.". Arch Pathol Lab Med 128 (10): e125-8. doi:10.1043/1543-2165(2004)128<e125:PBPOTA>2.0.CO;2. PMID 15387689.
  5. URL: http://www.pathpedia.com/Education/eAtlas/Histopathology/Adrenal/Pheochromocytoma.aspx. Accessed on: 27 May 2013.
  6. 6.0 6.1 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.
  7. Thompson, Lester D. R. (2006). Endocrine Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 259. ISBN 978-0443066856.