CASE OF THE WEEK
Editor: Mahmut Akgul (akgulm@amc.edu)
2022-26/July 4
Contributors: Daniel Athanazio, Maiara Ferreira de Souza
A woman in her early 60s underwent a radical nephrectomy due to a 9.0cm tumor with multi-cystic central component and solid nodular appearance at periphery at imaging studies. Thoracic imaging showed multiple small cysts in the lung suggestive of lymphangioleiomyomatosis. The gross picture shows the 9.0 cm with both multicystic appearance in central kidney and solid configuration in upper lobe. Venous invasion in renal sinus (upper third). The lower lobe shows smaller white nodules –the largest measuring 2 cm. Further sectioning showed multiple white spots within renal parenchyma. Some of them are illustrated in figure 2. Figures 3 to 5 illustrate the large tumor.
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Quiz
a) Tuberous sclerosis complex-associated papillary renal cell carcinoma
b) Epitheloid PEComa
c) Clear cell renal cell carcinoma
d) Clear cell papillary renal tumor
e) Chromophobe renal cell carcinoma
1. a
Tuberous sclerosis complex associated – papillary renal cell carcinoma
Multiple white spots in renal parenchyma were minute angiomyolipomas (both epithelioid and of classical type) as seen in Figure 2. The largest angiomyolipoma was of epithelioid type measuring 2 cm (see larger nodule in the lower lobe in Figure 1). Both imaging suggestion of lymphangioleiomyomatosis and the diagnosis of multiple angiomyolipomas were highly suggestive of tuberous sclerosis(TSC): two major criteria, thus sufficient for the diagnosis. Genetic analysis later confirmed a pathogenic mutation in TSC1 gene.
The larger tumor was a renal cell carcinoma that fits in the described category of “Tuberous Sclerosis Complex-Associated Papillary Renal Cell Carcinoma”. In 2014, Yang and colleagues described this pattern as common in epithelial renal neoplasms related to tuberous sclerosis complex (TSC): 24 out of 46 tumors(52%). Branching papillae are seen in 75% of these tumors (see Figure 3). Nested and solid growth are also described (Figure 4). Cystic changes and microcysts were common and seen in 13/24 tumors. In our case, the center of the tumor was very reminiscent of clear cell papillary renal cell tumor (Figure 5). Large clear cell cytology is the predominant cell type in these tumors (23/24) but are commonly intermixed with cells exhibiting finely granular, eosinophilic cytoplasm (14/24). Tumor cell aggregates are usually separated by stromal fibrous bands that may be prominent and may show smooth muscle differentiation (leiomyomatous stroma).
Indeed, these tumors show overlapping features with those described as renal cell carcinoma with leiomyomatous stroma (RCCLMS). Indeed, in other series of TSC-related renal cell tumors,Guo et al described RCCLMS pattern as a common among epithelial kidney tumors in these patients: 17 out of 57 (29%). Interestingly, sporadic RCCLMS commonly harbor somatic mutations in TSC1 and TSC2 genes. Tuberous sclerosis complex-associated papillary renal cell carcinomas are usually indolent as there is one case with nodal metastasis documented (1/24). Our case shows signs of aggressive behavior such as invasion of a large vein. Other specific renal cell tumors well known to be associated with TSC are Hybrid Oncocytic/Chromophobe Tumor; Chromophobe carcinoma; and eosinophilic solid and cystic renal cell carcinoma.
Guo J, Tretiakova MS, Troxell ML, Osunkoya AO, Fadare O, Sangoi AR, Shen SS, Lopez-Beltran A, Mehra R, Heider A, Higgins JP, Harik LR, Leroy X, Gill AJ, Trpkov K, Campbell SC, Przybycin C, Magi-Galluzzi C, McKenney JK. Tuberous sclerosis-associated renal cell carcinoma: a clinicopathologic study of 57 separate carcinomas in 18 patients. Am J Surg Pathol. 2014 Nov;38(11):1457-67.
Henske EP, Cornejo KM, Wu CL. Renal Cell Carcinoma in Tuberous Sclerosis Complex. Genes (Basel). 2021 Oct 8;12(10):1585.
Shah RB, Stohr BA, Tu ZJ, Gao Y, Przybycin CG, Nguyen J, Cox RM, Rashid-Kolvear F, Weindel MD, Farkas DH, Trpkov K, McKenney JK. “Renal Cell Carcinoma With Leiomyomatous Stroma” Harbor Somatic Mutations of TSC1, TSC2, MTOR, and/or ELOC (TCEB1): Clinicopathologic and Molecular Characterization of 18 Sporadic Tumors Supports a Distinct Entity. Am J Surg Pathol. 2020 May;44(5):571-581.
Yang P, Cornejo KM, Sadow PM, Cheng L, Wang M, Xiao Y, Jiang Z, Oliva E, JozwiakS, Nussbaum RL, Feldman AS, Paul E, Thiele EA, Yu JJ, Henske EP, Kwiatkowski DJ, Young RH, Wu CL. Renal cell carcinoma in tuberous sclerosis complex. Am J Surg Pathol. 2014 Jul;38(7):895-909.
Daniel Athanazio
Imagepat, Laboratory of Pathology Federal University of Bahia / Hospital Universitário Professor Edgard Santos
Salvador, Bahia, Brazil
Maiara Ferreira de Souza
Imagepat, Laboratory of Pathology
Kidney
Renal cell carcinoma; Tuberous Sclerosis; TSC1; angiomyolipoma