ESC, ALK, HOT and LOT: Three Letter Acronyms of Emerging Renal Entities Knocking on the Door of the WHO Classification

Abstract

Kidney neoplasms are among the most heterogeneous and diverse tumors. Continuous advancement of this field is reflected in the emergence of new tumour entities and an increased recognition of the expanding morphologic, immunohistochemical, molecular, epidemiologic and clinical spectrum of renal tumors. Most recent advances after the 2016 World Health Organization (WHO) classification of renal cell tumors have provided new evidence on some emerging entities, such as anaplastic lymphoma kinase rearrangement-associated RCC (ALK-RCC), which has already been included in the WHO 2016 classification as a provisional entity. Additionally, several previously unrecognized entities, not currently included in the WHO classification, have also been introduced, such as eosinophilic solid and cystic renal cell carcinoma (ESC RCC), low-grade oncocytic renal tumor (LOT) and high-grade oncocytic renal tumor (HOT) of kidney. Although pathologists play a crucial role in the recognition and classification of these new tumor entities and are at the forefront of the efforts to characterize them, the awareness and the acceptance of these entities among clinicians will ultimately translate into more nuanced management and improved prognostication for individual patients. In this review, we summarise the current knowledge and the novel data on these emerging renal entities, with an aim to promote their increased diagnostic recognition and better characterization, and to facilitate further studies that will hopefully lead to their formal recognition and consideration in the future classifications of kidney tumors.

Keywords: ALK; ESC; HOT; LOT; anaplastic lymphoma kinase rearrangement; emerging entity; kidney; new entity; oncocytic renal tumor; unclassified renal cell carcinoma; unclassified renal tumor.

Figure 1

Eosinophilic solid and cystic renal cell carcinoma (ESC RCC) show grossly mixed macrocystic and solid appearances (A). Solid and cystic areas can also be appreciated at low power (B). The solid areas demonstrate diffuse and compact growth with adjacent cyst trabeculae showing hobnailing (C). Eosinophilic cells exhibit voluminous cytoplasm with readily recognizable coarse cytoplasmic granules (‘stippling’); aggregates of foamy histiocytes and lymphocytes are often found (D,E). CK20 is positive in the majority of ESC RCC (F).

Figure 1

Eosinophilic solid and cystic renal cell carcinoma (ESC RCC) show grossly mixed macrocystic and solid appearances (A). Solid and cystic areas can also be appreciated at low power (B). The solid areas demonstrate diffuse and compact growth with adjacent cyst trabeculae showing hobnailing (C). Eosinophilic cells exhibit voluminous cytoplasm with readily recognizable coarse cytoplasmic granules (‘stippling’); aggregates of foamy histiocytes and lymphocytes are often found (D,E). CK20 is positive in the majority of ESC RCC (F).

Figure 2

ALK rearrangement-associated RCC (ALK-RCC) shows a variegated gross appearance (A). On microscopy, multiple growth patterns can be seen in a single tumor, including solid (B), papillary (C), tubular and tubulocystic (D). Intracytoplasmic vacuoles and individual signet ring cells can also be found (E) often with a mucinous background (D,E). There is ALK1 protein expression on immunohistochemistry (F).

Figure 3

High-grade Oncocytic Tumor (HOT) of kidney often mimics the color of the adjacent renal parenchyma (A). It demonstrates solid growth of mostly eosinophilic cells, admixed with ‘clear’ cells with intracytoplasmic vacuoles (B). The eosinophilic cells have voluminous cytoplasm with large intracytoplasmic vacuoles; the nuclei show prominent to often very large nucleoli (C,D). Cathepsin K is positive on immunohistochemistry (E). On electron microscopy, numerous intracytoplasmic mitochondria are present (F).

Figure 4

Low-grade oncocytic tumor (LOT) of kidney grossly shows tan to yellow cut surface (A). LOT is a non-encapsulated tumor showing mostly solid growth; focal tubular-tubuloreticular patterns can be present more centrally (B). There are frequent, sharply delineated edematous areas containing single cells and irregularly cell cords (C). The eosinophilic cells show ‘low-grade’, round to oval nuclei, often with delicate perinuclear clearing (D). On immunostains, CD117 is typically negative and there is diffuse reactivity for CK7 (insert) (E). Electron microscopy shows densely packed intracytoplasmic mitochondria (F).