Clear renal cell carcinoma with angioleiomyomatous stroma in a noninherited renal cancer syndrome: Is it a different entity?

Shanmugasundaram Rajaian; Karrthik Krishnamurthy; Lakshman Murugasen; Srinivas Chakravathy Narasimhachar

doi:10.4103/UROS.UROS_27_20

CASE REPORT

Year : 2020 | Volume : 31 | Issue : 4 | Page : 194-196

Clear renal cell carcinoma with angioleiomyomatous stroma in a noninherited renal cancer syndrome: Is it a different entity?

Shanmugasundaram Rajaian¹, Karrthik Krishnamurthy¹, Lakshman Murugasen¹, Srinivas Chakravathy Narasimhachar²
¹ Department of Urology, MIOT International, Chennai, Tamil Nadu, India
² Department of Pathology, MIOT International, Chennai, Tamil Nadu, India

Date of Submission	18-Mar-2020
Date of Decision	06-May-2020
Date of Acceptance	30-May-2020
Date of Web Publication	25-Jul-2020

Correspondence Address:
Shanmugasundaram Rajaian
Department of Urology, MIOT International, 4/112, Mount Poonamallee Road, Manapakkam, Chennai - 600 089, Tamil Nadu
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/UROS.UROS_27_20

Abstract

Renal cell carcinoma (RCC) comprises only 3% of adult cancer cases. In most cases, patient is asymptomatic and the tumor mass is incidentally detected during radiological imaging for other medical conditions. Only one-third of patients with RCC present with hematuria, palpable tumor mass, or flank pain. Most of the cases of RCC are with clear or papillary cells, but a small subset of cases have demonstrated clear cell RCC with leiomyomatous stroma. The World Health Organization classification of tumors of the urinary system and male genital organs 2016 and the International Society Urological Pathology 2012 Vancouver classification have identified RCC with leiomyomatous stroma (RCCLMS) as an emerging entity of RCC. RCCLMS has been seen with inherited renal cancer syndromes such as tuberous sclerosis complex and von Hippel-Lindau disease. Here, we present a rare case of RCC with morphological and histopathological findings of the RCCLMS subset but showed noninherited mutational traits.

Keywords: Leiomyomas, renal angiomyoadenomatous tumor, smooth muscles, von Hippel-Lindau disease

How to cite this article:
Rajaian S, Krishnamurthy K, Murugasen L, Narasimhachar SC. Clear renal cell carcinoma with angioleiomyomatous stroma in a noninherited renal cancer syndrome: Is it a different entity?. Urol Sci 2020;31:194-6

How to cite this URL:
Rajaian S, Krishnamurthy K, Murugasen L, Narasimhachar SC. Clear renal cell carcinoma with angioleiomyomatous stroma in a noninherited renal cancer syndrome: Is it a different entity?. Urol Sci [serial online] 2020 [cited 2023 Oct 2];31:194-6. Available from: https://www.e-urol-sci.com/text.asp?2020/31/4/194/290857

Introduction

Among malignant renal cell tumors, 65%–75% of cases are of clear renal cell carcinomas (RCCs). They are mainly seen more in males as compared to females in a ratio of 2:1.^[1] A rare type of RCC with clear cells along with leiomyomatous stroma was described in a few reports in 2006 and 2009.^[2],[3]

The World Health Organization classification of tumors of the urinary system and male genital organs 2016 and the International Society Urological Pathology 2012 Vancouver classification have recognized RCC with leiomyomatous stroma (RCCLMS) as a provisional entity subtype.^[4],[5] RCC with leiomyomatous or angioleiomyomatous-like stoma (RCCLMS) is often seen in inherited renal cancer syndromes such as tuberous sclerosis complex (TSC) and von Hippel-Lindau disease (VHL). Immunohistochemically, these tumors are positive for cytokeratin (CK) 7 and CD10 immunomarkers. Here is a case of RCCLMS in a female with noninherited renal cancer syndrome.

Case Report

A 69-year-old female presented with abdominal pain, vomiting, and fever for a week. The initial ultrasound examination revealed a hypoechoic endophytic lesion in the upper pole of the right kidney. Her renal function was normal. Contrast-enhanced computed tomography and magnetic resonance imaging [Figure 1]a, [Figure 1]b, [Figure 1]c showed a well-defined heterogeneous endophytic enhancing solid mass of 4 cm × 4 cm size in the upper pole of the right kidney.

Figure 1: (a and b) Contrast-enhanced computed tomography of the abdomen showing well-defined, completely endophytic tumor in the upper pole of the right kidney (hollow arrow), (c) magnetic resonance imaging of the abdomen confirmed the nature of tumor and noninvolvement of Pelvicalyceal System (PCS) (hollow arrow), (d) Peroperative picture showing completely covered nature of tumor by surrounding renal parenchyma (hollow arrow), (e) excised specimen after partial nephrectomy with preserved renal parenchyma margin (arrowheads)

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She had a significant medical history of multiple uterine fibroids, for which early hysterectomy was performed at the age of 35 years. She also had multiple occasions of excision of cutaneous leiomyomas. However, she had no clinical features of TSC.

Right open partial nephrectomy was performed since the tumor was endophytic in nature and close to the pelvicalyceal system. The tumor mass was excised completely with normal renal parenchymal margin [Figure 1]d and [Figure 1]e. Histopathological evaluation of the mass revealed clear RCC with prominent angioleiomyomatous stroma (RCCLMS) [Figure 2]. No lipomatous component was noted.

Figure 2: (a) Tumor showing clear cells in the tubular pattern (asterisk) separated by smooth muscle fibers and blood vessels (hollow arrows), (b) clear cells showing low-grade nuclei and smooth muscle fibers (hollow arrows). Immunohistochemistry staining: (c) positivity for smooth muscle actin in stroma (solid arrows), (d) diffuse positivity for pan cytokeratin (cytokeratin 7) in tumor cells (hollow arrows), (e) negative for CD 10 in tubular cells (asterisk), (f) negative for myogenin (asterisk)

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Her nervous system imaging was negative for any TSC features. In view of her history, hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome was considered as a probable diagnosis. However, her cytogenetic study was negative for inherited syndromes such as VHL disease, TSC1, TSC2, TCEB1, mammalian target of rapamycin (MTOR), and fumarate hydratase (FH) coding genes. Her postoperative stay was uneventful.

Discussion

Renal cancers with clear cells and the presence of smooth muscles are found in a variety of RCC (clear cell or papillary) or in Renal angiomyoadenomatous tumor (RAT). The majority of them can be differentiated on the basis of morphological appearance, the arrangement of clear cells, and the number of smooth muscles (intracapsular or intratumoral).^[5] As per the review of RCCLMS cases, it was significantly detected in the age group of 31–79 years with no prominent gender dominance and most probably affecting the right kidney.^[6] However, female gender predominance (male:female = 1:2) has been noted in a recent study of RCCLMS by Shah et al.^[7] The above case reassures these findings as the patient was a 69-year-old female with the right kidney involvement.

Leiomyomas are found in multiple numbers in the majority of cases in the skin or uterus. They are seen in patients with HLRCC and are identified at a mean age of 30 years.^[8] The above patient also had multiple fibroids, for which hysterectomy was done in her mid-thirties; the histopathology revealed uterine leiomyomas. Most of the cases with RCCLMS are clinically asymptomatic and are incidentally diagnosed during any radiological investigation.

These tumors appear well defined, noncapsulated, and on cut-section, they are homogenously white with multiple trabeculae placed in a criss-cross pattern. Microscopically, the tumor consists of small nodules of the epithelial cells surrounded by a capillary network in a stroma of intertwining bundles of spindle cells of the smooth muscles. There are no signs of tumor necrosis, and a voluminous amount of leiomyomatous component is seen. These features help in differentiating RCCLMS from clear cell RCC, which has a brown or yellowish appearance with hemorrhage and necrosis.

In a report by Shah et al. with 18 cases of RCCLMS, the microscopic features revealed elongated and branching tubules lined by clear cells that were separated by smooth muscle stroma.^[7] The molecular findings in these patients showed recurrent mutations in TSC1, TSC2, MTOR, and ELOC but intact VHL gene. The RCCLMS cases showed 100% reactivity to CK7, CAM5.2, and CD10. In our case, the medical history of uterine and cutaneous leiomyomas and the presenting signs of RCCLMS favor the diagnosis for HLRCC, as there were no genetic mutations in VHL, TSC 1, TSC2, TCEB1, MTOR, and intact FH, which rule out its hereditary trace.

The prognosis of patients with RCCLMS is good, as of the 42 cases reported by Kuhn et al.^[2] and Parilla et al.^[9] Forty-one cases were alive and 18 cases had no history of reoccurrence on follow-up till 11 years.

RCC with smooth muscle stroma can be seen in renal angiomyoadenomatous tumour (RAT), a variant with TCEB1 mutation and in another variant with CD10 positivity. Rarely it is noted in other varieties of TSC. These varieties show overlapping features. This case report highlights a rare subtype of RCC with a unique presentation of noninheritance, which makes the diagnosis of RCCLMS difficult and controversial. This also reveals the problems in differentiating RCCLMS from other similar entities as clear cell RCC, RAT, and TSC.

Conclusion

Clear cell RCC with leiomyomatous stroma is a rare subset of RCC tumors. Few cases of RCCLMS have been reported which state the inheriting, indolent, and low-grade nature of this tumor. The morphological features of RCCLMS are similar to certain varieties of RCCs, which make the accurate diagnosis a challenge. Its clinical prognosis is good with no reported reoccurrence. The above case is a rare presentation of RCCLMS with noninherited trace, thereby stating its variability for the diagnosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Acknowledgments

Authors would like to thank Dr. Triveni Bangera for her assistance in manuscript preparation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Cohen HT, McGovern FJ. Renal-cell carcinoma. N Engl J Med 2005;353:2477-90.
2.	Kuhn E, De Anda J, Manoni S, Netto G, Rosai J. Renal cell carcinoma associated with prominent angioleiomyoma-like proliferation: Report of 5 cases and review of the literature. Am J Surg Pathol 2006;30:1372-81.
3.	Shannon BA, Cohen RJ, Segal A, Baker EG, Murch AR. Clear cell renal cell carcinoma with smooth muscle stroma. Hum Pathol 2009;40:425-9.
4.	Moch H, Amin MB, Argani P, Cheville J, Delahunt B, Martignoni G, et al. WHO Classification of Tumours of the Urinary System and Male Genital Organs. 4^th ed. Lyon, France: International Agency for Research on Cancer; 2016.
5.	William MM, Grignon DJ, Perlman EJ. Kidney tumors in adults. In: Tumors of the Kidney, Bladder, and Related Urinary Structures, AFIP Atlas of Tumor Pathology Series 4. Ch. 2. Washington DC: American Registry of Pathology; 2004.
6.	Yeh YA, Constantinescu M, Chaudoir C, Tanner A, Serkin F, Yu X, et al. Renal cell carcinoma with leiomyomatous stroma: A review of an emerging entity distinct from clear cell conventional renal cell carcinoma. Am J Clin Exp Urol 2019;7:321-6.
7.	Shah RB, Stohr BA, Tu ZJ, Gao Y, Przybycin CG, Nguyen J, et al. 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 2019;44:571-81.
8.	Merino MJ, Torres-Cabala C, Pinto P, Linehan WM. The morphologic spectrum of kidney tumors in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. Am J Surg Pathol 2007;31:1578-85.
9.	Parilla M, Alikhan M, Al-Kawaaz M, Patil S, Kadri S, Ritterhouse LL, et al. Genetic underpinnings of renal cell carcinoma with Leiomyomatous Stroma. Am J Surg Pathol 2019;43:1135-44.