The Histologic Diversity of Chromophobe Renal Cell Carcinoma With Emphasis on Challenges Encountered in Daily Practice

Abstract

Chromophobe renal cell carcinoma (ChRCC) is the third most common renal cell carcinoma in adults. The aim of this review is to provide a comprehensive overview highlighting the broad morphologic spectrum of ChRCC, and offer a practical approach for handling cases in daily practice. For the purpose of this review, we classify ChRCC subtypes as (1) classic, (2) eosinophilic, (3) sarcomatoid, and (4) other rare patterns. The concept of eosinophilic ChRCC has significantly evolved, yet it still is one of the major diagnostic challenges pathologists face in routine practice due to its morphologic overlap with renal oncocytoma. Rare patterns of ChRCC have been described over the last few decades, showing a wide histologic spectrum including those with adenomatoid microcystic pigmented, multicystic, neuroendocrine, small cell, and papillary features. ChRCC represents a heterogenous group of neoplasms, demonstrating varied but unique morphologic and genetic profiles. Although the field of ChRCC knowledge is still evolving, rare patterns can present diagnostic challenges if they are not known to pathologists and/or clinicians. Proper and generous tumor sampling along with careful histologic examination allow for recognition of these rare morphologies. The role of routine molecular testing appears to be limited. From a clinical management standpoint, the rare patterns of ChRCC seem to have no definite clinical implications at present and likely can be managed similarly to usual ChRCC. Finally, we will discuss distinctive novel/emerging renal neoplasms previously considered under the spectrum of ChRCC, low-grade oncocytic renal tumor and eosinophilic vacuolated tumor, with regard to their current significance and implications for future classification strategies.

Renal Neoplasia Occurring in Patients With PTEN Hamartoma Tumor Syndrome

“…1A, B). 10 None of the 5 chromophobe RCCs were associated with tumor necrosis or sarcomatoid differentiation. All papillary RCCs were encapsulated and 1 of 4 tumors (patient #6) showed the historical “type 1” morphology, additionally with the architectural pattern recently described as “microcystic” (Fig.…”

“…5,6 Of note, 4 of 5 chromophobe RCCs in our study showed classic chromophobe morphology including large polygonal cells with distinct cell borders (leaf/plant-like), smaller cells with eosinophilic cytoplasm, wrinkled irregular hyperchromatic nuclei (raisinoid), and perinuclear halos. 10 The fifth was a "multicystic pigmented" chromophobe RCC, a pattern with variably cystic to cribriform architecture and both intracytoplasmic and extracellular pigment, unique histologic findings that do not impact expected clinical behavior. 10,28 The genomic landscape of chromophobe RCC is complex.…”

“…10 The fifth was a "multicystic pigmented" chromophobe RCC, a pattern with variably cystic to cribriform architecture and both intracytoplasmic and extracellular pigment, unique histologic findings that do not impact expected clinical behavior. 10,28 The genomic landscape of chromophobe RCC is complex. Whereas classic sporadic examples have losses of chromosomes 1, 2, 6, 10, 30, 70, 21, comprehensive genomic analysis has also shown a low somatic mutation rate, including TP53, PTEN, TERT promoter, FOXI1, RHCG, LINC01187, and CYCLOPS genes.…”

Kidney Tumor Friends: A 15-Year History and Legacy of Ondřej Hes, MD, PhD (1968-2022)

“…Of note, there were also a number invited review articles on various renal tumor topics by some of the speakers of the most recent 2021 KTF on various renal tumor entities. [27][28][29][30] It is worth noting that the 2 GUPS critical review articles of the recent advances in renal neoplasia, led by Ondřej and other colleagues, paved the road for the 2022 WHO blue book. 31,32 Throughout its 15-year history, Ondřej Hes personally organized both scientific and social programs and he always stated "KTF would not have been possible without the generous support of friends, colleagues, as well as the Biopticka laboratory and its staff, in particular Irena Kratochvílová and David Michal."…”

“…Of note, there were also a number invited review articles on various renal tumor topics by some of the speakers of the most recent 2021 KTF on various renal tumor entities. 27–30 It is worth noting that the 2 GUPS critical review articles of the recent advances in renal neoplasia, led by Ondřej and other colleagues, paved the road for the 2022 WHO blue book. 31,32…”