Adrenal carcinoma

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sara Mohsin, M.D.[2]

Synonyms and keywords: Adrenocortical carcinoma, Adrenal cortical carcinoma, Adrenal cortical cancer, Adrenal cortex cancer, Adrenal cancer, Adrenal tumor, Neuroblastoma, Pheochromocytoma, Ganglioneuroma, Adrenocortical adenoma, Adenomatoid tumor, Myelolipoma, Schwannoma.

Overview

Adrenal carcinoma or adrenal tumor is an aggressive disease which can originate either in the cortex (steroid hormone-producing tissue) or medulla of the adrenal gland. According to the 2017 WHO classification of adrenal tumors, adrenal cortical tumors are subclassified into cortical adenoma, cortical carcinoma, sex cord stromal tumors, adenomatoid tumor, mesenchymal and stromal tumors (myelolipoma, schwannoma), hematological tumors and secondary tumors, whereas tumors of adrenal medulla are subclassified into pheochromocytoma, paraganglioma, neuroblastic tumors, composite pheochromocytoma, and composite paraganglioma. Pathogenesis includes many genetic pathways, most prominent being Wnt-Beta catenin pathway and also association with other diseases such as multiple endocrine neoplasia (MEN1 and MEN2), familial adenomatous polyposis, Beckwith-Wiedemann syndrome, Li-Fraumeni syndrome, Lynch syndrome,von Hippel-Lindau disease, carney Complex/Syndrome, neurofibromatosis type 1 and congenital adrenal hyperplasia. Adrenocortical carcinoma is remarkable for the many hormonal syndromes which can occur in patients with steroid hormone-producing ("functional") tumors, including Cushing's syndrome, Conn syndrome, virilization, and feminization. Adrenal carcinoma can be treated with both medical therapy and surgery depending upon the stage of the tumor.

Historical perspective

Classification

Updated 2017 WHO classification of adrenal tumors
Tumors of adrenal gland
Tumors of adrenal cortex
Tumors of the adrenal medulla

and extra-adrenal paraganglia

Pathophysiology

Normal anatomy and physiology of adrenal glands

Normal anatomy and function of Adrenal glands
Adrenal gland layers Functions
Adrenal cortex (outer layer)
Adrenal medulla (Inner layer)
source: By David Richfield (User:Slashme) and Mikael Häggström. Derived from previous version by Hoffmeier and Settersr.In external use, this diagram may be cited as:Häggström M, Richfield D (2014). "Diagram of the pathways of human steroidogenesis". Wikiversity Journal of Medicine 1 (1). DOI:10.15347/wjm/2014.005. ISSN 20018762. - Self-made using bkchem and inkscape, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=6355511

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Epigenetics

VEGF signaling, source: By Mikael Häggström.When using this image in external works, it may be cited as:Häggström, Mikael (2014). "Medical gallery of Mikael Häggström 2014". WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.008. ISSN 2002-4436. Public Domain.orBy Mikael Häggström, used with permission. - [1]Interactions of VEGF ligands and VEGF receptors ResearchVEGF.com, retrieved on November, 13, 2009, Public Domain, https://commons.wikimedia.org/w/index.php?curid=3475250
WNT pathwayssource: By Fred the OysteriThe source code of this SVG is valid.This vector graphics image was created with Adobe Illustrator., GFDL, https://commons.wikimedia.org/w/index.php?curid=36340188
microRNA function, source: By Kelvinsong - Own work, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=23311105

Gross pathology

Adrenocortical carcinoma

A large adrenal cortical carcinoma resected from a 27-year-old woman. The tumor measured 17 cm in diameter and invaded kidney and spleen which necessitated en bloc removal of these organs with the tumor. - By AFIP Atlas of Tumor Pathology - [1], Domena publiczna, https://commons.wikimedia.org/w/index.php?curid=6719487

Pheochromocytoma

Bilateral pheochromocytoma in MEN2. Gross image. Source: https://upload.wikimedia.org/wikipedia/commons/5/5f/Bilateral_pheo_MEN2.jpg

Microscopic pathology

Pathologic criterias for adrenocortical carcinoma

Pathologic criteria Details Age applicability
Weiss criteria

Adrenocortical carcinoma can be diagnosed by the presence of at least 3 of the 9 Weiss criteria:

  1. High nuclear grade (III or IV)
  2. High mitotic rate i.e. presence of >5 mitotic figures/50 high-power fields, definition suffers from HPFitis (counting 10 random fields in area of greatest number of mitotic figures on 5 slides with the greatest number of mitosis)
  3. Atypical mitoses (abnormal distribution of chromosomes or excessive number of mitotic spindles)
  4. Cleared or vacuolated cytoplasm in >/= 25% of the tumor cells
  5. Sheeting (diffuse architecture of patternless sheets of cells)) in >= 1/3 of tumor cells
  6. Necrosis in nests (microscopic necrosis)
  7. Venous invasion (veins must have smooth muscles in wall; tumor cell clusters or sheets forming polypoid projections into the vessel lumen or polypoid tumor thrombi covered by endothelial layer)
  8. Adrenal sinusoid invasion (sinusoid is endothelial lined vessel in adrenal gland with little supportive tissue; consider only sinusoids within tumor)
  9. Capsular invasion (nests or cords of tumor extending into or through capsule with a stromal reaction); either incomplete or complete)

Modified Weiss criteria (score of 3 or more suggests malignancy):

Adults
Volante criteria

Simplified criteria by Volante et al (not widely used) is as follows:

Wieneke et al and Dehner & Hill

Wieneke et al and Dehner & Hill proposed the following very simple system:

Pediatrics
Micrograph of an adrenocortical carcinoma (left of image - dark blue) and the adrenal cortex it arose from (right-top of image - pink/light blue). Benign adrenal medulla is present (right-middle of image - gray/blue). H&E stain. - Source: https://librepathology.org
Micrograph of pheochromocytoma. Source: By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=5938524
Histopathology of adrenal pheochromocytoma. Adrenectomy specimen. Source: CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=535945
Micrograph of pheochromocytoma. Source: CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=535944

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Epidemiology and demographics

Risk factors

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Symptoms in children

{{#ev:youtube|https://www.youtube.com/watch?v=ea1sXgd5ui8&t=697s}}

Symptoms in adults

Presentation of non-functional adrenal carcinoma

Physical Examination

Laboratory findings

Laboratory findings of different hormonal syndromes in adrenal carcinoma
Hormonal syndrome Laboratory findings
Cushing syndrome
Virilization
Conn syndrome
Feminization

Imaging studies

Imaging studies for the diagnosis of adrenal carcinoma
Imaging study Details
CT[46]
MRI
Bone scan
PET scan[47][48][49][50][51][52]
123I-metaiodobenzylguanidine SPECT[50]
Molecular imaging[53]
Adrenal angiography
Adrenal venography
Ultrasound exam

Biopsy

Adrenalectomy

Treatment

Medical Therapy

Different types of medical therapies for treatment of adrenal carcinoma
Type of medical therapy Details
Radiation therapy There are following two types of radiation therapies that can be used for the treatment of adrenal carcinoma:
Radiofrequency ablation
Chemotherapy (chemoembolization)[55][56][57][58]
Hormonal therapy
Biological therapy (immunotherapy)
Targeted therapy
mTOR antagonists

Surgery

5-year disease-specific survival rate stratification in relation to the disease stage at the time of ACC tumor resection
Stage of the disease at the time of tumor resection 5-year disease-specific survival
Stage I 82%
Stage II 58%
Stage III 55%
Stage IV 18%
Comparison of UICC and ENSAT staging systems for adrenocortical carcinoma
Stage UICC/WHO 2004 ENSAT 2008
I
  • T1, N0, M0
  • T1, N0, M0
II
  • T2, N0, M0
  • T2, N0, M0
III
  • T1-2, N1, M0
  • T3, N0, M0
  • T1-2, N1, M0
  • T3-4, N0-1, M0
IV
  • T1–4, N0-1, M1
  • T3, N1, M0
  • T4, N0-1, M0
  • T1–4, N0-1, M1

T1: tumor  5 cm; T2: tumor  5 cm; T3: tumor infiltration in surrounding tissue; T4: tumor infiltration in adjacent organs [ENSAT additionally the presence of a tumor thrombus in the Vena Cava or Vena Renalis]; N0: absence of positive lymph nodes; N1: presence of positive lymph nodes; M0: absence of distant metastases; M1: presence of distant metastasis.

Differentiating Adrenal carcinoma from other Diseases

Bilateral

Unilateral

References

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