Discussion of case

The landscape of renal neoplasia has significantly expanded in the past years, particularly in the field of renal oncocytic tumours. It is increasingly recognised that there are oncocytic tumours that do not fit into any of the traditional ‘eosinophilic chromophobe RCC’ and ‘oncocytoma’ tumour categories (1–3). A newly described, currently provisional entity is Low-grade oncocytic tumour (LOT) of the kidney, which shows a fairly consistent morphological and immunohistochemical profile. These mostly coccur in the sporadic setting and have very rarely been associated with tuberous sclerosis (3).

They present as relatively small, tan to brown tumours. LOTs are usually well circumbsribed unencapsulated lesions showing solid sheets and compact nests, with gradual transition to loosely connected strands with sharp delineation to oedematous stromal (aka ‘boats in a bay’ arrangement). The cells are eosinophilic, with bland round to ovoid (low-grade) nuclei lacking prominent nucleoli or nuclear irregularity. There often show perinuclear ‘halos’. They are characteristically diffusely positive for CK7 and negative for CD117 (1–4). The molecular data on these tumors are limited, with one study showing that LOTs are generally  diploid tumours, sometimes with deletions of chromosomes 19p, 19q, and 1p(2)  and another having identified TSC1/TSC2/mTOR mutations (5). To date, these neoplasms have not been found to have aggressive behaviour (hence the designation “tumour” is preferred to “carcinoma”) (1–5).

Key differential diagnosis

Oncocytoma: Different growth patterns including solid, nested, tubulocystic within abundant stroma (‘archipelaginous’ morphology). Small, central round to oval nuclei without perinuclear halos, prominent cell membranes, coagulative necrosis and papillary formations. CD117 (+) and Cathepsin K (-), CK7 (-) or only focally (+).

Oncocytic chromophobe RCC: More compact solid growth. The oncocytic cells have more pronounced cell membranes, raisinoid nuclei with irregular contours, binucleation, perinuclear halos. CD117 (+), MOC31 (+), diffuse CK7 (+), Cathepsin K (-).

EVT: Diffuse sheets, nests or tubulocystic growth pattern. The cells have abundant eosinophilic cytoplasm and marked intracytoplsmic vacuoles, “high-grade nuclei”, often with prominent nucleoli. Cathepsin K (+), CK7 (-), CD117 (+) , CD10 (+).

ESC RCC : Solid and cystic growth with characteristic cytoplasmic coarse or fine granular stippling (reminiscent of ‘leismaniasis’). These tumours usually show at least focally CK20 (+). CD117 (-), CK7 (-).

References

1. Trpkov K, Williamson SR, Gill AJ, Adeniran AJ, Agaimy A, Alaghehbandan R, et al. Novel, emerging and provisional renal entities: The Genitourinary Pathology Society (GUPS) update on renal neoplasia. Mod Pathol  an Off J United States Can Acad  Pathol Inc. 2021 Jun;34(6):1167–84.
2. Trpkov K, Williamson SR, Gao Y, Martinek P, Cheng L, Sangoi AR, et al. Low-grade oncocytic tumour of kidney (CD117-negative, cytokeratin 7-positive): a distinct entity? Histopathology. 2019 Aug;75(2):174–84.
3. Cancer IA for R on, Moch H, Reuter VE. WHO Classification of Tumours of the Urinary System and Male Genital Organs [Internet]. International Agency for Research on Cancer; 2016. (IARC Who Classification of Tum). Available from: https://books.google.co.uk/books?id=qxQyjgEACAAJ
4. Guo Q, Liu N, Wang F, Guo Y, Yang B, Cao Z, et al. Characterization of a distinct low-grade oncocytic renal tumor (CD117-negative and cytokeratin 7-positive) based on a tertiary oncology center experience: the new evidence from China. Virchows Arch. 2021 Mar;478(3):449–58.
5. Morini A, Drossart T, Timsit M-O, Sibony M, Vasiliu V, Gimenez-Roqueplo A-P, et al. Low-grade oncocytic renal tumor (LOT): mutations in mTOR pathway genes and low expression of FOXI1. Mod Pathol  an Off J United States Can Acad  Pathol Inc. 2022 Mar;35(3):352–60.

Summary of clinical history

62-year-old female with incidentally discovered left renal lesion on imaging underwent robotic partial nephrectomy.

Gross findings

Well defined nodule in the left kidney measuring 30 x 25 x 17 mm.  Cream-tan cut surface.

Microscopic findings

• Well circumscribed unencapsulated tumour comprising solid sheets and microcysts
• Focal sharply delineated oedematous stromal areas with thin trabeculae (aka ‘boats in a bay’ arrangement)
• The cells had abundant granular eosinophilic cytoplasm, round to oval nuclei, without irregularities or nucleoli. Often with perinuclear ‘halos’
• No evidence of increased mitotic activity, sarcomatoid change, rhabdoid change, necrosis or lymphovascular invasi