Can adrenocortical carcinoma become renal cancer?

Adrenocortical Carcinoma Cannot Transform Into Renal Cancer

Adrenocortical carcinoma (ACC) and renal cell carcinoma are distinct malignancies with different cellular origins, and ACC does not transform into renal cancer. 1

Understanding Adrenocortical Carcinoma

Adrenocortical carcinoma is a rare but aggressive malignancy that originates from the adrenal cortex with an estimated incidence of 0.5-2 new cases per million people per year 1. Key characteristics include:

• ACC arises from the adrenal cortex and has specific histopathological and immunohistochemical features that distinguish it from other malignancies 1
• Diagnosis requires careful pathological evaluation, often using the Weiss criteria (score ≥3 suggests malignancy) and Ki-67 labeling index 1
• Immunohistochemical markers for ACC include positivity for inhibin-alpha, steroidogenic factor 1 (SF1), calretinin, melan-A, and synaptophysin 1, 2

Distinguishing ACC from Renal Cell Carcinoma

These two malignancies can be clearly differentiated through:

• Immunohistochemical staining: ACC is typically negative for epithelial membrane antigen (EMA), while renal cell carcinomas are consistently strongly positive 3
• ACC is typically positive for adrenal-specific markers like inhibin-alpha and melan-A, while renal cell carcinoma expresses markers like carbonic anhydrase IX (CAIX), PAX8, and RCC marker 4
• Molecular and genetic profiles differ significantly between these two malignancies 5

Relationship Between Adrenal and Kidney Tumors

While ACC does not transform into renal cancer, there are important relationships to understand:

• ACC can invade adjacent organs including the kidney in advanced stages, but this represents direct invasion rather than transformation 1
• For ACC tumors not invading the kidney, concomitant nephrectomy does not improve disease-free survival or overall survival 1
• In rare cases, adrenocortical tissue can be found within the kidney (adrenal rest), and ACC can arise from this ectopic tissue, termed "intrarenal adrenocortical carcinoma" - but this is still ACC, not renal cancer 2
• Renal cell carcinoma can metastasize to the adrenal gland, which should not be confused with primary ACC 3, 4

Clinical Implications

Understanding the distinction between these tumors is critical for proper management:

• Complete surgical resection (R0) remains the cornerstone of ACC treatment, with margin-free resection providing the best chance for long-term survival 1, 6
• In locally advanced ACC, resection of adjacent organs may be necessary to achieve R0 status, but kidney-sparing surgery should be performed when possible 1
• Misdiagnosis between ACC and renal cell carcinoma can lead to inappropriate treatment strategies, as highlighted in case reports where ACC was initially misdiagnosed as other entities 5
• Proper pathological evaluation with appropriate immunohistochemical staining is essential for accurate diagnosis 4

Common Pitfalls in Diagnosis

• Biopsy of adrenal masses is generally contraindicated due to risk of tumor spillage and poor diagnostic power to discriminate between benign and malignant adrenocortical tumors 1
• ACC can be misdiagnosed as other entities including pheochromocytoma or renal cell carcinoma if comprehensive immunohistochemical evaluation is not performed 5
• Adrenal metastases from renal cell carcinoma can sometimes be confused with primary adrenal tumors, requiring careful pathological evaluation 3, 4

In conclusion, while ACC can locally invade the kidney or rarely arise from adrenal rests within the kidney, it does not transform into renal cancer, as these are distinct malignancies with different cellular origins and molecular characteristics 1, 2.