Final Diagnosis
Low-grade oncocytic tumor (LOT)
Discussion
The field of renal neoplasia has been characterized by significant expansion in the past years, and this is particularly evident in the field of renal oncocytic tumors. The term ‘’other oncocytic tumors of the kidney’’ essentially refer to the heterogeneous group of oncocytic tumors which are not classifiable as oncocytoma, chromophobe renal cell carcinoma, or other tumor types with eosinophilic features. A recently described, currently emerging entity in the WHO 2022 classification is low-grade oncocytic tumor (LOT), which demonstrates a fairly consistent morphological, immunohistochemical, and molecular profile. These mostly occur in the sporadic setting and have very rarely been associated with tuberous sclerosis (1).
LOT usually presents as a single, small, low-stage, tan-brown tumor. LOTs are usually well-circumscribed, unencapsulated lesions showing mostly solid sheets and compact nests, with gradual transition to loosely connected strands with sharp delineation to edematous stroma (aka ‘boats in a bay’ arrangement in contrast to ‘’archipelaginous’’ morphology of oncocytoma). The cells are eosinophilic, with bland round to oval nuclei lacking prominent nucleoli or nuclear irregularity. Perinuclear ‘halos’ are frequently present (2).
LOT of kidney has a consistent immunopattern, being invariably CD117-negative and diffusely CK7-positive. Nevertheless, rare cases may show focal/weak CD117 reactivity. LOT is also positive for AE1/AE3, PAX8, E-cadherin, BerEP4 and MOC31, while fumarate hydratase is retained. In contrast, it is negative for carbonic anhydrsase IX, CK20, CK5/6, p63, CD15, HMB45, melan-A, and vimentin. CD10 and AMACR are mostly negative or only focally positive. Colloidal iron is either negative or only demonstrates luminal positivity (2).
The molecular data on these tumors are limited, with cases sometimes featuring TSC1, TSC2, or MTOR mutations (3). Generally LOTs are diploid, sometimes with deletions of chromosomes 19p, 19q, and 1p (4). To date, these neoplasms have not been found to have aggressive behavior (hence the designation “tumor” is preferred to “carcinoma”).
Key Differential Diagnosis
Oncocytoma: A wide spectrum of different growth patterns including solid, nested, and tubulocystic within abundant hyalinized and edematous stroma (‘’archipelaginous’’ morphology). Small, central round-to-oval nuclei without perinuclear halos, prominent cell membranes, coagulative necrosis and papillary formations. Immunoprofile: CD117 (+) and Cathepsin K (-), CK7 (-) or focally (+).
Eosinophilic variant of chromophobe RCC: More compact solid growth. Neoplastic cells have distinct (plant-like) cell membranes, raisinoid nuclei with irregular contours, frequent binucleation, and perinuclear halos. Immunoprofile: CD117 (+),CK7 (+) (diffuse), Cathepsin K (-).
Eosinophilic vacuolated tumor (EVT): Diffuse sheets, nests or tubulocystic growth pattern. The neoplastic cells have abundant eosinophilic cytoplasm and large intracytoplasmic vacuoles, as well as prominent nucleoli. Immunoprofile: Cathepsin K (+), CK7 (-), CD117 (+), CD10 (+).
Eosinophilic solid and cystic renal cell carcinoma (ESC RCC): Solid and cystic growth pattern with characteristic cytoplasmic coarse or fine granular stippling (reminiscent of ‘’leismaniasis’’). Immunoprofile: usually at least focally CK20 (+), CD117 (-), CK7 (-).
Other entities in the differential diagnosis include: hybrid oncocytic/chromophobe tumor (HOCT), succinate dehydrogenase-deficient renal cell carcinoma (SDH-RCC), MiT family translocation renal cell carcinoma (MiTF RCC), and epithelioid angiomyolipoma. Importantly, the combination of the morphologic features of LOT along with its rather characteristic immunohistochemical profile [c-kit (-) and CK7 (+)] are generally adequate for the diagnosis.
References
- Moch et al., editors. Chapter: Other oncocytic tumours of the kidney. In: WHO Classification of Tumours Editorial Board. Urinary and male genital tumours. Lyon (France): International Agency for Research on Cancer; 2022. . (WHO classification of tumours series, 5th ed.; vol. 8). https:// publications.iarc.fr/610.
- Siadat et al. ESC, ALK, HOT and LOT: Three Letter Acronyms of Emerging Renal Entities Knocking on the Door of the WHO Classification. Cancers (Basel). 2020 Jan 9;12(1):168. doi: 10.3390/ cancers12010168.
- Morini et al. Low-grade oncocytic renal tumor (LOT): mutations in mTOR pathway genes and low expression of FOXI1. Mod Pathol. 2022 Mar;35(3):352-360. doi: 10.1038/s41379-021-00906-7. Epub 2021 Sep 16.
- Williamson et al. Low-grade oncocytic tumour of the kidney is characterised by genetic alterations of TSC1, TSC2, MTOR or PIK3CA and consistent GATA3 positivity. Histopathology. 2023 Jan;82(2):296-304. doi: 10.1111/his.14816. Epub 2022 Oct 18.