Background

A 51-year-old hypertensive lady with recently diagnosed Diabetes mellitus, presented with complaints of weight gain and hair loss. CT whole abdomen showed a large soft tissue lesion in right supra renal region measuring 8 x 6cm. Serum cortisol: 39.26 mcg/dl. Surgical excision was performed.

Gross specimen

Fig. 16a; Gross 1: A circumscribed bright yellow to orange coloured tumor

Fig. 16b; Gross 2: Tumor with myxoid areas

Microscopy

Fig 16c; H&E; 4x

Fig 16d; H&E; 10x

Fig 16e; H&E; 20x

Fig 16f; H&E; 40x

Fig 16g; H&E; 10x

Immunohistochemistry

Fig 16h; CK

Fig 16i; Chromogranin A

Fig 16j; PAX-8

Fig. 16k; Melan-A

Fig 16l; Synaptophysin

Questions & Answers:

1. What is your diagnosis?
   • Adrenal cortical adenoma
   • Adrenal cortical carcinoma –low grade
   • Adrenal cortical carcinoma –high grade
   • Pheochromocytoma
2. Which of the following is/are associated with this tumor?
   • Li Fraumeni syndrome
   • Beckwith-Wiedemann syndrome
   • Congenital adrenal hyperplasia
   • All of the above
3. Definitive criteria for malignancy in this tumor is:
   • Distant metastases
   • Presence of atypical mitotic figures
   • Necrosis
   • Vascular invasion
4. Which of the following IHC marker is usually not expressed in this tumor?
   • Synaptophysin
   • Chromogranin A
   • Melan A
   • Inhibin A

POINTS TO REMEMBER

• Malignant epithelial tumor of adrenal cortical cells.
• Median age of presentation: Bimodal, with peaks in 1^st  and 5^th decade of life.
• Female predilection
• Mostly involves single adrenal gland
  • If bilateral adrenal enlargement is seen :  Think of something else
• Clinical features:
  • Symptoms of steroid hormone excess
  • Abdominal pain and fullness
  • Incidental
  • Both androgen and estrogen production in an adrenal tumor:  suspicious for adrenocortical carcinoma
• Modified Weiss criteria:
  • Score:  2x mitotic rate criterion  + 2x clear cytoplasm criterion + abnormal mitosis criterion + necrosis criterion + capsular invasion criterion
  • Score ≥3-  suggests malignancy

• Histological variants:
  • Oncocytic
  • Myxoid
  • Sarcomatoid
• Differential diagnosis:
  • Adrenal cortical adenoma
  • Oncocytoma
  • Pheochromocytoma
  • Renal cell carcinoma(primary and metastatic)
  • Hepatocellular carcinoma(primary and metastatic)
  • Metastatic melanoma
• Immunohistochemistry markers :  
  • Positive markers:  SF-1, Inhibin A , Melan A, Synaptophysin,  Calretinin
  • Negative markers: CK, EMA  & CEA,  Chromogranin A(usually negative)
• Reticulin stain:  highlights loss of nested architecture
• Genetic alterations: 
  • Overexpression of IGF2,  DLGAP5 & PINK1
  • TP53 mutation
  • WNT pathway defects (CTNNB1 mutation)
• Associated hereditary syndromes:
  • Li-Fraumeni syndrome
  • Lynch syndrome
  • Multiple endocrine neoplasia type 1
  • Familial adenomatous polyposis
  • Carney complex
  • Beckwith-Wiedemann syndrome
  • Neurofibromatosis type 1
• Treatment:
  • Surgical excision
  • Locoregional lymph node dissection for localized tumor
  • Radiation therapy for metastatic tumor
• Adverse prognostic factors:
  • Hypercortisolism
  • Age>50 years
  • Ki67 index-high
  • Increased expression of SF-1

Contributed by: Dr. Sunil Pasricha

Compiled by: Dr. Vidya Menon

In case of queries, email us at: info.pathbliss@rgcirc.org

Adrenal Adrenocortical carcinoma Endocrine Neoplasms Weiss criteria

Last modified: 17/08/2021