Adrenal gland and paraganglia
Adrenocortical adenoma
Children

Author: Carmen Perrino,, M.D. (see Authors page)

Editor: Debra Zynger, M.D.

Revised: 29 March 2016, last major update November 2013

Copyright: (c) 2003-2016, PathologyOutlines.com, Inc.

PubMed Search: Adrenal cortical adenoma children
Cite this page: Children. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/adrenalcorticalchildren.html. Accessed December 2nd, 2016.
Definition / General
  • Benign neoplasm arising from adrenal cortical cells, with variable functional activity
  • If functional, may have biochemically detectable or clinically recognizable features of an endocrine syndrome
Terminology
  • Adrenal cortical neoplasm/tumor (ACN/ACT):
    • Refers to both adrenal cortical adenoma (ACA) and adrenal cortical carcinoma (ACC)
    • Term often used because these two entities can be difficult to distinguish histologically in children (Radiographics 1999;19:989)
Epidemiology
  • Generally uncommon in children; only ~25 cases annually in U.S. in those < 20 years (Braz J Med Biol Res 2000;33:1225)
  • Bimodal age distribution; most commonly < age 5, second peak ages 9-16 years
  • Incidence higher in females, M:F ratio 1:1.6 (J Clin Oncol 2004;22:838)
  • Higher incidence in southern Brazil, associated with specific p53 mutation (R337H TP53)
  • Associated with several genetic syndromes:
    • Beckwidth-Wiedemann syndrome: hemihypertrophy, splanchnomegaly, macroglossia, intraabdominal neoplasms (i.e. adrenal cortical neoplasms, nephroblastoma, hepatoblastoma), due to alteration of 11p15 region
    • Li-Fraumeni syndrome (SBLA syndrome): sarcoma (rhabdomyosarcoma), breast/brain tumors, leukemia, laryngeal carcinoma, lung cancer, adrenal cortical carcinoma; due to alteration of p53 on chromosome 17p
    • Carney triad: malignant gastrointestinal stromal tumor, pulmonary chondroma, extra-adrenal paraganglioma, adrenal cortical adenoma
    • Adrenogenital syndrome: adrenal cortical neoplasms, congenital adrenal hypertrophy
  • No proven relationship with environmental factors
Sites
Pathophysiology
  • May arise due to defective apoptosis (J Clin Endocrinol Metab 2000;85:2048)
  • Predisposing genetic factors are present in ~50% of children with adrenal cortical tumors, most commonly Li-Fraumeni syndrome and Beckwith-Wiedemann syndrome (see above)
Clinical Features
  • ~50% present with palpable mass
  • ~90% have an associated endocrine abnormality, most frequently due to secretion of several hormones causing multiple/mixed endocrine syndromes:
    • Virilization:
      • Females: increased muscle mass (Herculean habitus), facial hair, deep voice, pubic hair, clitoromegaly
      • Males: penile enlargement, pubic hair
    • Feminization: gynecomastia
    • Cushing syndrome: obesity (generalized in pediatric patients), moon facies, plethora, striae, thin skin, easy bruising, hirsutism, telangiectasias, hyperhidrosis, see Adrenal and Chemistry chapters
    • Conn syndrome: hypertension, proximal muscle weakness, headache, polyuria, tachycardia with/without palpitation, hypokalemia, hypocalcemia, see Adrenal and Chemistry chapters
Diagnosis
  • Atypical histologic features are commonly found in children, making adrenal cortical adenomas difficult to distinguish from adrenal cortical carcinoma
Laboratory
  • Increased 24-hour urinary ketosteroid excretion (i.e. 17-ketosteroids)
  • Increased serum dehydroepiandrosterone sulfate (DHEA-S), cortisol, testosterone, androstenedione, and estradiol
Radiology Description
  • Distinction between adrenal cortical adenoma and adrenal cortical carcinoma difficult radiologically
    • Hematogenous metastases or venous spread indicate carcinoma
  • Ultrasound: good initial screening test
    • Rounded or ovoid, circumscribed mass; lobulated border; may have thin, echogeneic capsule-like rim; rarely calcification; hyperechoic renal medullary pyramids
  • Computed Tomography (CT): best technique for examination
    • Circumscribed; heterogeneous (may have central hemorrhage and necrosis); thin, capsule-like rim; high-attenuation medullary areas with associated suprarenal mass on unenhanced CT; increased retroperitoneal fat; larger lesions enhance heterogeneously with IV contrast
  • Magnetic Resonance Imaging (MRI): few described cases
    • Intermediate signal intensity on T1-weighted images; high signal intensity relative to liver on T2-weighted images
Prognostic Factors
  • Due to rarity and heterogeneity, definitive prognostic factors have been difficult to establish and multiple systems have been proposed (including Weiss and modified Weiss systems, see Adrenocortical carcinoma topic)
  • Tumor weight is most reliable adverse prognostic factor, with proposed cut-offs ranging from 100 to 500 grams
  • AFIP adverse prognostic factors in pediatric patients (0-2: benign; 3: indeterminate; 4+: malignant):
    • Tumor weight (>400 grams), tumor size (>10.5 cm), extension into periadrenal soft tissue/adjacent organs, invasion of vena cava, venous invasion, capsular invasion, necrosis, mitoses (>15/20 HPF), atypical mitotic figures (Am J Surg Pathol 2003;27:867)
Case Reports
Treatment
  • Surgical resection is only definitive management
  • Steroids given to patients with functioning tumors and suppression of contralateral adrenal gland
  • Chemotherapy not well established
Radiology Images

Images hosted on other servers:

Homogeneous left adrenal mass with distinct borders

Heterogeneous retrohepatic mass

Homogeneous, solid right suprarenal mass

Flank mass with echogenic focus

Left flank mass with calcification

Heterogeneous mass, necrosis, capsule-like rim

Clinical Images

Images hosted on other servers:

Moon facies, acne, bitemporal excess hair

Moon facies and central obesity

Facial and chest hair, absence of breasts

Back acne

Penile enlargement

Clitoromegaly and pubic hair

Gross Images

Images hosted on other servers:

External surface, during surgery

Intact capsule

Smooth, homogeneous cut surface

Micro Description
  • Resembles adrenal cortical adenoma in adults - pale, polygonal cells with vacuolated to eosinophilic cytoplasm
  • Architectural patterns: Alveolar/nesting, solid, trabecular, oncocytic, myxoid, pseudoglandular
  • May have nuclear pleomorphism, nuclear hyperchromasia, enlarged nuclei, necrosis, capsular invasion, rare mitoses
  • Intracytoplasmic hyaline globules in 10%
Micro Images

Images hosted on other servers:

Adrenal cortical neoplasm with pale vacuolated cells

Small round tumor cells

Nuclear atypia, pleomorphism, multinucleated forms

Neoplasm on right
and normal adrenal
gland

Virtual Slides

Atypical adrenal cortical adenoma

Cytology Description
  • May resemble normal adrenal cortical cells or have focal cytologic atypia
  • Cytoplasm is clear/translucent and vacuolated due to lipid
  • Small, round, uniform nuclei with granular chromatin and distinct nucleoli
  • Naked nuclei may be present in a background of small lipid droplets
Positive Stains
  • Positive (75%+ of cases): inhibin, MelanA/Mart1, NSE, CD56, vimentin (Mod Pathol 2003;16:591)
  • Usually positive (~60% of cases): synaptophysin
  • Low Ki-67 index
Negative Stains
  • Cytokeratin (positive in 10%), chromogranin
Electron Microscopy Description
  • Intracytoplasmic lipid droplets, abundant smooth endoplasmic reticulum, nuclear pseudoinclusions (due to irregularity of nuclear membrane), prominent mitochondria
Molecular / Cytogenetics Description