November 2022 – Genitourinary Pathology

A woman in her late 20s presented with multiple slow growing renal masses measuring up to 4.2 cm in greatest dimension on CT imaging. Representative images of the masses are shown in the figures below with H/E, CA-IX, and CK7 staining.

Figure 1: 4x
Figure 2: 20x
Figure 3: Carbonic Anhydrase 9 (CA-IX), 10x
Figure 4: Cytokeratin 7 (CK7), 10x

What is the most likely diagnosis?

  • Clear cell renal cell carcinoma
  • Clear cell papillary renal cell tumor
  • Renal cell carcinoma with fibromyomatous stroma
  • Papillary renal cell carcinoma

The correct answer is ...

Renal cell carcinoma with fibromyomatous stroma.

As seen on H/E, the above mass forming lesion is comprised of cells with clear cytoplasm arranged in alveolar/ acinar patterns with intersecting bands of fibromyomatous stroma (Figure 1). Immunohistochemical stains reveal that the tumor cells, exhibit membranous carbonic anhydrase 9 (Figure 3) staining and in contrast to the majority of other clear cell renal cell carcinomas are diffusely positive for CK7 (Figure 4). Taken together, the immunohistochemical and morphologic features of this tumor are consistent with what has been described as a renal carcinoma with fibromuscular stroma.1

Dense cytoplasmic condensation is commonly seen in these tumors and may be mistakenly characterized as rhabdoid change (Figure 2). Grading these as high-grade tumors with rhabdoid change may not be accurate as these are mostly indolent tumors with rare reports of metastasis to regional lymph nodes. 

Therefore, correctly diagnosing these tumors has important implications for accurate prognostication.

It is important to note that these tumors can have significant morphologic overlap with those that have alterations of TSC1, TSC2, MTOR, and/or TCEB1 (ELOC) genes.2 Unfortunately, no immunohistochemistry based surrogate markers are available to make this distinction. Next generation sequencing of the tumor and/or germline testing may be helpful in this regard. Current NCCN guidelines recommend germline testing for patients presenting with multifocal and or bilateral tumors as well as in patients with a younger age of onset (<46 years of age). A diagnosis of renal cell carcinoma with fibromyomatous stroma in the appropriate clinical context can therefore have important implications for establishing a diagnosis of tuberous sclerosis complex.3-4 


  1. Shah RB. Renal cell carcinoma with fibromyomatous stroma-the whole story. Adv Anat Pathol. 2022; 29, 168-177.
  2. 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; 44, 571-581.
  3. Gupta S, Jimenez RE, Herrera-Hernandez L, Lohse CM, Thompson RH, Boorjian SA, Leibovich BC, Cheville JC. Renal neoplasia in tuberous sclerosis: a study of 41 patients. Mayo Clin Proc. 2021; 96, 1470-1489.
  4. Guo J, et al. 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. 

Luke Cypher, M.D., Ph.D.

Fellow, Surgical Pathology
Mayo Clinic

Sounak Gupta, M.B.B.S., Ph.D.

Consultant, Anatomic Pathology
Mayo Clinic
Associate Professor of Laboratory Medicine and Pathology
Assistant Professor of Pathology
Mayo Clinic College of Medicine and Science

MCL Education

This post was developed by our Education and Technical Publications Team.