cow-2022-38

a) Renal neurofibroma

b) Angiomyolipoma

c) Sarcomatoid renal cell carcinoma

d) Renal leiomyoma

e) Leiomyoma

1. d

Renal leiomyoma

This 4.5 cm right upper pole renal mass was well-circumscribed and had homogenous tan-white whorled cut surfaces without necrosis (Figure 1B). Microscopic examination revealed that the lesion arose from the renal capsule (Figures 1B & 2). Spindle cells were present in an orderly fascicular growth pattern interspersed with stroma. The cytoplasm was eosinophilic and nuclei were cigar-shaped and bland, without mitoses or atypia (Figure 2 inset). On immunohistochemical evaluation, lesional cells were positive for alpha-smooth muscle actin (SMA) and desmin, and negative for cytokeratin AE1/AE3, S-100, HMB45, neurofilament protein, beta-catenin, CD34, and DOG-1. Ki-67 staining showed less than 1% proliferation and in situ hybridization (ISH) for EBER was negative (Figure 3). These findings are consistent with the diagnosis of renal leiomyoma.

Renal leiomyomas are rare benign mesenchymal tumors that usually arise in the renal capsule or renal pelvis. It is currently estimated that renal leiomyomas account for less than 1% of treated renal neoplasms. While these tumors were previously identified primarily on autopsy, more frequent medical imaging has led to increased incidental identification and treatment of these typically asymptomatic lesions. Occasionally, a large renal leiomyoma will present due to mass effect. Other symptoms may include a palpable flank mass, flank pain, or hematuria. They are found more frequently in adult women, possibly due to the expression of estrogen and progesterone receptors in a high proportion of these tumors. Despite this association, the cause of renal leiomyomas is not well understood. Previous reports have identified associations with Epstein-Barr Virus and tuberous sclerosis, but more investigation of the etiology of renal leiomyomas is needed.

While the differential diagnosis for renal leiomyoma can broadly include all benign and malignant renal spindle cell neoplasms, three important tumors to consider in the differential are leiomyosarcoma, sarcomatoid renal cell carcinoma (sRCC), and lipid-poor angiomyolipoma (AML). Leiomyosarcoma is the malignant counterpart of leiomyoma and can be distinguished by cytologic atypia (nuclear heterogeneity and abnormal mitotic figures), tumor necrosis, and increase in proliferation. It is also important to differentiate renal leiomyoma from sRCC, which is a rare dedifferentiation process that can occur in any subtype of RCC and carries a very poor prognosis. Similar to leiomyosarcoma, this lesion can often be ruled out based on the presence of residual carcinoma, tumor cellular atypia, high mitotic rate, and necrosis. Further confirmation is provided by immunohistochemistry, with sRCC typically staining positive for AE1/AE3 and negative for SMA and desmin. Lipid poor AML should also be ruled out, as renal leiomyoma has frequently been misclassified as this similar-appearing benign mesenchymal tumor. These tumors are composed of varying proportions of spindle and epithelioid smooth muscle cells, thick-walled blood vessels, and adipose tissue. Lipid-poor AMLs, particularly those that are enriched with spindle-shaped smooth muscle cells, have historically been misclassified as leiomyomas. Both AMLs and leiomyomas express smooth muscle markers; however, they can be distinguished with either HMB-45 or cathepsin K. AML should show co-expression of HMB-45 and/or cathepsin K with smooth muscle markers, while leiomyomas stain negative for HMB-45 and cathepsin K.

The prognosis of renal leiomyoma is excellent. Small leiomyomas can be treated with biopsy and surveillance. Large tumors are typically resected. Once the tumor is removed, it should not recur unless resection was incomplete.

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Patil PA, McKenney JK, Trpkov K, et al. Renal leiomyoma: A contemporary multi-institution study of an infrequent and frequently misclassified neoplasm. The American Journal of Surgical Pathology. 2015 Mar;39(3):349-356.

Romero FR, Kohanim S, Lima G, et al. Leiomyomas of the kidney: Emphasis on conservative diagnosis and treatment. Urology. 2005 Dec;66(6):1319e1-1319e3.

Shuch B, Bratslavsky G, Linehan WM, et al. Sarcomatoid renal cell carcinoma: A comprehensive review of the biology and current treatment strategies. The Oncologist. 2012 Jan;17(1):46-54.

Tsujimura A, Miki T, Takaha M, et al. Renal leiomyoma associated with tuberous sclerosis. Urologia Internationalis. 1996 Mar;57(192):192-193.

Jaime Eberle-Singh, Sherry Lee, Li Li
Thomas Jefferson University; Philadelphia, PA, USA

Kidney

Kidney, leiomyoma