Multilocular cystic renal cell carcinoma is an uncommon but diagnostically challenging variant of renal cell carcinoma that fortunately has an excellent prognosis. Histological features of this tumor include thin fibrous septa lined by clear cells with low grade nuclear atypia and small aggregates of similar cells in the septa. Strictly speaking, however, this variant does not have solid nodules in the septa, papillary projections into cystic spaces, or solid masses in an otherwise cystic tumor. Note that conventional clear cell RCC can focally show histologically similar areas. When examining a resected tumor, the recognition of this tumor is relatively straightforward (provided you take and examine multiple sections). But encountering these lesions on needle biopsy (frequently followed by cryoablation!) is not-so straight-forward but important because of the important prognostic differences between this variant and conventional clear cell RCC. A paper by Williamson, Halat, Eble et al in the October 2012 issue of American Journal of Surgical Pathology (2012;36:425-433) present the authors’ experience and data on an immunohistochemical panel that will be helpful to pathologists confronting adult cystic renal tumors.
The authors studied 24 well-characterized multilocular cystic RCCs (ML-RCC) and 24 consecutive matched conventional clear cell RCCs (CC-RCC) with an immunohistochemical panel consisting of CD10, CK7, AMACR(P504S), vimentin, EMA, CAM5.2, carbonic anhydrase IX (CA-IX), PAX-2, smooth muscle actin (SMA), ER, and PR.
Significant differences were found between ML-RCC and CC-RCC with staining for CD10 and CK7. In ML-RCC CD10 showed focal apical membranous staining in cyst-lining cells in 38% of cases, diffuse staining in both cyst-lining and septal cells in 25%, and was negative in 37%. CC-RCC, on the other hand, was positive in 96% of cases with the majority showing diffuse reactivity throughout the tumors. In contrast, CK7 was positive in 92% of ML-RCC cases, usually (63%) showing diffuse staining of the cyst-lining cells, while CK7 was negative in 62% of CC-RCC cases with 38% of these cases showing only focal reactivity (none > 25%).
Almost all cases of both types show positivity for EMA, CAM5.2, CA-IX, and PAX-2 but, notably, CA-IX most clearly highlighted individual clear cells and septal aggregates in ML-RCC and showed diffuse, strong, uniform membranous staining in the cyst-lining cells.
The authors conclude that none of the markers show sufficient positive or negative predictive value to supplant rigorous sampling and light microscopic examination. Indeed, I have discussed this very situation with Dr. John Cheville at Mayo Clinic Rochester, who has published extensively on renal pathology and has studied ML-RCC in particular, and he stressed the importance of careful microscopic examination without relying on IHC to identify or characterize clear cells, especially those in septal aggregates. The authors point out the unexpected finding of CK7 reactivity in ML-RCCs, which raises the possibility of cystic papillary RCC—a tumor that also shows prominent cystic architecture, albeit with at least focal papillary structures. This tumor, however, also typically shows a rather unique finding of solid acinar areas composed of branching ductular or tubular structures.
To me, the most useful finding is the use of CA-IX to highlight septal aggregates, which would be especially useful in CT-guided needle biopsies. It seems tempting to add CD10 and CK7 but these don’t seem hardy enough to be very helpful and might actually be confusing. Perhaps this article isn’t one that you want to rush out and read but keep it in mind next time you get one of these cystic renal tumors.