1.3 Histological classification of RCC
The WHO histological classification of renal cell carcinomas (2016) is based on the morphology and architecture of tumour cells, as well as molecular and genetic characteristics. Although new subtypes have been identified, the most common are:1,2
- Clear cell RCC
- Non-clear cell
- Papillary RCC
- Chromophobic RCC
- Collecting duct RCC
- Unclassified RCC
The classification is important, as the individual subtypes show different clinical progression. Chromophobic RCC and papillary RCC type 1 are the least aggressive, whereas clear cell RCC, Collecting duct RCC and papillary RCC type 2 are the most aggressive.
A
B
C
D
A: Clear Cell-RCC (ccRCC)3-6,8
- Emanates from the proximal tubules
- It is the most common subtype (70–75%)
- Macroscopically, the tumour is golden yellow. Microscopically, the cancer cells are seen with clear cytoplasm
- Most often characterised by a defect in the von-Hipple-Lindau (VHL) gene
B: Papillary RCC (PapRCC)3,4,7
- Emanates from the proximal tubules
- Is the second most common subtype (10–15%)
- PapRCC can be subdivided into type 1 (1/3) and type 2 (2/3) based on the morphological appearance of the cells
- PapRCC is most often small tumours that may be multifocal
- They are typically well-defined, surrounded by a thick pseudocapsule. Activation of the MET pathway (most often type 1) or mutation in fumarate hydratase (type 2) can be seen
C: Chromophobic RCC3,4
- Emanates from the distal tubules
- Rare subtype (4–5%)
D: Collecting duct RCC3,4
- Emanates from the distal tubules/collector tubes
- Very rare subtype (<0.2%)
Other important pathological prognostic factors that should be included in the histology description:1,2
- Presence of rhabdoid or sarcomatoid morphology, representing an extreme form of tumour dedifferentiation
- WHO grading system (grades 1–4): In this classification, grade 1-3 is based on nucleole morphology in the tumour cells, while grade 4 is based on nuclear morphology (extreme nuclear pleomorphism, multinuclear giant cells) and/or the presence of sarcomatoid and/or rhabdoid dedifferentiation. This classification has only been validated in ccRCC and papRCC
- Presence of necrosis
- Vascular invasion
- pT, pN and possibly pM stage (See section on anatomical staging of RCC)
- Leibovich score which is a sum of 5 histological parameters.
- pT stage (0–4)
- pN stage (0–2)
- Tumour size (0–1)
- Fuhrman grading based on core morphology and separately graded from 1–4 and scores from 0–3. Fuhrman grade 1 and 2 = score 0, grade 3 = score 1 and grade 4 = score 3
- Necrosis (0–1)
The Leibovich score can be between 0 and 11. The higher the score, the greater the risk of recurrence.
References
- DaRenCa guidelines
- ESMO, The 2016 WHO classification of tumours of the urinary system and male genital organs – Part A: renal, penile and testicular tumours. Moch et al. Eur Urol 2016 (70)
- Deng FM, Melamed J. Histologic variants of renal cell carcinoma: does tumor type influence outcome? ol Clin North Am. 2012;39(2):119-132, v
- Delacroix Jr SE, Wood CG, Jonasch E. Renal neoplasia. I: Taal MW, Chertow GM, Marsden PA, Skorecki K, Yu ASL, Brenner BM, eds. Brenner & Recter’s The Kidney. 9th ed. Philadelphia, PA: Elsevier Saunders; 2012:1508-1535
- Linehan WM, Rini BI, Yang JC. Cancer of the kidney. I: DeVita VT, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2011:1161-1182
- Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015;373(19):1814-1823
- Zhou M, Hattab EM, Eble JN, Cheng L. Neoplasms of the kidney. I: Zhou M, Galluzi-Magi C, eds. Genitourinary Pathology. 2nd ed. Philadelphia, PA: Elsevier Saunders; 2015:306-377
- Lenehan & Zbar Cancer cell 2004
