A 71-year-old woman with a history of autosomal dominant polycystic kidney disease (ADPKD) and polycystic liver disease, status post living donor transplant two years ago, was found to have a new lesion in the medial inferior left native kidney in a recent follow-up imaging. On CT scan, the lesion was described as an indeterminant heterogeneous and soft tissue attenuating/enhancing mass measuring approximately 6 cm. This mass was FDG-avid compared to the parenchyma and with cystic change on the comparison PET/CT (Figure 1). Given the strong consideration for a primary renal neoplasm, the patient underwent bilateral native kidney nephrectomy.
Grossly, the cross section of the kidney showed a unifocal, well-circumscribed tumor with a yellow-tan, friable cut surface, in the background of polycystic parenchyma. Microscopic images and immunohistochemical staining are as shown (Figure 2,3). H&E-stained slides demonstrate tubules, microcysts, cords and papillary structures, lined by uniform cuboidal cells with conspicuous nucleoli (evident on medium-power magnification), embedded within a myxoid and focally hyalinized stroma. The tumor focally shows spindle cells morphology. The tumor cells are diffusively positive for CK7 and AMACR (p504s), but negative for c-Kit and CA-IX, with retained expression of fumarate hydratase (FH). Genetic studies revealed loss of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, 22, and X, and gain of 5q31.1q35.3.
The correct answer is ...
Mucinous tubular and spindle cell carcinoma.
Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney is a rare, usually asymptomatic renal neoplasm that can mimic more common renal neoplasms due to its heterogenous morphological features. MTSCC can occur over a wide age range and is more common in women (3-4:1). The staging category is often low (pT1, pT2) at the time of diagnosis, and the tumor is curable by partial or complete nephrectomy. The usual location of MTSCCs is renal cortex. Grossly, they can present as a white or gray to yellow, tan, or even pink mass with a solid cut surface. Typically, MTSCC presents a tubular morphology lined by bland cuboidal cells with areas of spindle cell proliferation in a mucinous background.
In some cases, MTSCC may present in a “mucin" poor form with elongated and spindled tubular structures as well as focal papillary growth pattern, resembling type 1 PRCC. Immunophenotypically, MTSCC is positive for AMACR, which is normally expressed in proximal collecting tubules of the kidney. However, AMACR is also expressed in other RCCs including PRCC, albeit less so in the sarcomatoid PRCC. Both MTSCC and PRCC also express CK7 and EMA. Additionally, RCC-Ma, high-molecular weight cytokeratin (HMWK), and c-kit are all negative in both MTSCC and papillary RCC.
Despite the similar morphology and immunophenotypic profile, recent studies have shown that at the molecular level, MTSCC and PRCC are distinct. Multiple genetic abnormalities including losses in chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22 are present in MTSCC. However, the characteristic PRCC genetic aberration including trisomy chromosome 7 and 17, and the loss of chromosome Y, have not been reported in MTSCC. Chromosomal microarray performed on our case showed multiple chromosomal losses, and in conjunction with the morphology, supported the diagnosis of MTSCC.
Due to its spindled component, MTSCC may also be misdiagnosed as sarcomatoid RCC, especially in cases with spindle cell predominance. Considering the poor prognosis of sarcomatoid RCC compared to MTSCC, it is clinically important to distinguish between these morphologically similar entities. The absence of large hyperchromatic, pleomorphic nuclei or significant mitotic activity help distinguish MTSCC from more aggressive RCCs.
On the other hand, the tubular morphology in MTSCC can be mistaken with other entities such as tubulocystic carcinoma. Microscopically, the latter features tightly packed tubules and cysts with cuboidal to columnar cell lining within a bland fibrous stroma. The cysts can measure up to a few millimeters in diameter, and along with the fibrotic stroma could help distinguish this carcinoma from MTSCC
Less commonly, MTSCC may display a clear cell pattern within its tubular component, including cytoplasmic pallor, and vacuolisation, but not to the extent that resembles a typical clear cell RCC. Clear cell RCCs may also show variable morphologic patterns (including strong circumferential membranous pattern), but, in contrast to MTSCC, they uniformly express CA-IX and are usually negative or only focally positive for CK7.
RCCs reported in the background of PCKD include CCRCC, tubulocystic RCC and PRCC. To our knowledge, this is the first report of MTSCC in this context.
Amir Nazem, M.D., Ph.D.
Resident, Anatomic Pathology and Neuropathology
Maryam Shahi, M.D.
Senior Associate Consultant, Anatomic Pathology
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science