2021-12/ March 22
Contributor: Stephanie Conrad, Ming Zhou

A woman in her late 50s with hypertension had an incidentally discovered 1.7 cm right renal mass. She underwent a right partial nephrectomy. Presented are the histological findings.


1. What is the correct diagnosis?

a) Angiomyolipoma

b) Leiomyoma

c) Renal cell carcinoma with sarcomatous differentiation

d) Gastrointestinal stromal tumor (GIST)

e) Solitary fibrous tumor


2. Which of the following immunohistochemical assays, when positive expression is present, supports the diagnosis?

a) Desmin

b) HMB45

c) Cytokeratins

d) PAX 8

e) STAT6


3. What histological feature supports the diagnosis?

a) Vascular proliferation

b) Rare mitoses

c) Sclerotic background

d) Dysmorphic blood vessels

e) Spindle cell predominance

1. a; 2. b; 3. d

1. a. Angiomyolipoma; 2. b. HMB45; 3. d. Dysmorphic blood vessels

The lesion consists predominantly of bland spindle cells with focal areas of dysmorphic thick-walled blood vessels from which the spindle cells are emanating. There are no adipocytes. A prominent feature is the abundant sclerotic and hyalinized stroma in which spindle cells are embedded. Immunohistochemically, HMB45 demonstrates positive staining in a scattered subset of spindled cells, consistent with the staining pattern of angiomyolipoma. A lesion such as this one earns the designation of sclerosing angiomyolipoma (AML).

Sclerosing variant of AML is a recently described variant of PEComa characterized by prominent stromal fibrosis and hyalinization with at least 50% hyalinized stroma (1). To date, all cases of sclerosing PEComa have been reported in middle-aged women, including this current case. Most sclerosing PEComas arise in the retroperitoneum and are usually pararenal in location. Renal sclerosing AMLs are exceedingly rare with only 3 cases reported. Most cases behave in a benign fashion but there have been 2 reports of malignant behavior. Criteria for malignancy in PEComas include 5 histologic features: tumor size > 5 cm, infiltrative growth pattern, high nuclear grade, necrosis, and mitotic activity > 1 per 50 high-power fields. Tumors with 2 or more of these features should be considered as malignant, and tumors showing only a single feature should be considered as having “uncertain malignant potential” (2). Follow-up information of renal sclerosing AML is exceedingly scarce. Three patients were alive and free of tumor after surgery with a follow-up 4-10 months.

Lesions such as this one with scant to absent adipocytes can be challenging to diagnose as AML. The presence of dysmorphic blood vessels and positive immunohistochemistry for melanocytic markers such as HMB-45 are helpful in these circumstances. When the classic triphasic morphology of AML is absent, IHC can be used to aid in rendering a diagnosis. AML expresses melanocytic markers: HMB-45, Melan-A (Mart-1), MiTF, cathepsin K as well as smooth muscle makers and is negative for epithelial markers including cytokeratin, EMA/MUC1 and PAX8.

When faced with lesions composed of predominantly spindled cells in a sclerotic background, the differential diagnosis includes primary smooth muscle tumors such as leiomyoma, renal cell carcinoma with sarcomatous differentiation, soft tissue tumor such as solitary fibrous tumor and GIST, and lesions that may have significant fibrous components such as IgG4 sclerosing disease. A primary smooth muscle tumor is exceedingly rare in the kidney (4). As the matter of fact, a renal tumor with prominent smooth muscle component is probably an AML. Unlike AML, a smooth muscle tumor would not stain positive for melanocytic markers.

Renal cell carcinoma with sarcomatous differentiation should be considered even when there is a scant epithelial component. However, there is usually significant nuclear atypia in the spindle cells which may demonstrate positive staining with cytokeratin, CK5/6 and PAX8. An epithelial component may be identified after extensive sampling.

Exceedingly rare (58 cases reported in the literature to date) yet possible are extra-gastrointestinal stromal tumors (EGIST) originating from the retroperitoneum. EGISTs are composed of spindle cells most commonly but may consist of epithelioid cells or a mixture of spindle and epithelioid cells (6, 9). These cells may also exhibit a sclerosing morphology (9). Histologically EGIST are distinguished from AML based on the presence of clear to faintly eosinophilic cytoplasm and a well-developed capillary vasculature. Unlike AML, GIST cells will not stain positive with melanocytic markers (3). In the case of a suspected EGIST, CD117 is a highly specific immunohistochemical marker that is positive in 95% of cases (6, 9). A case demonstrating positive CD117 and negative HMB45 would favor EGIST over AML (6).

A lesion with strikingly similar histological features to sclerosing AML is solitary fibrous tumor (SFT). However unlike AML, it is an extremely rare occurrence in the kidney. Histologically SFT is composed of varying amounts of spindle cells, collagen fibers and blood vessels. The spindle cells are randomly arranged, often described as a patternless pattern. Similar to AML is the presence of vascularized stroma; however these blood vessels are thin-walled and dilated into irregular forms frequently described as staghorn or hemangiopericytoma-like. Additionally SFTs may have a fibrous background composed of thick irregular collagen. SFT cells will stain diffusely positive for CD34, STAT6 and BCL2 (7, 9).

IgG4 related kidney disease (IgG4-RKD) is a fibroinflammatory condition which commonly affects males over the age of 65 years with nearly half having a history of allergy. IgG4 disease in the kidney is characterized by dense lymphoplasmacytic infiltrates with irregularly whorled fibrosis in the background. On IHC, the presence of more than 10 IgG4 positive plasma cells per high-power (40X) field and/or ratio of IgG4-positive plasma cells/IgG-positive plasma cells >40% is consistent with IgG4 disease. Moreover, serum IgG4 levels will be elevated in cases of IgG4 disease (8).

1. Matsuyama A, Hisaoka M, Ichikawa K, Fujimori T, Udo K, Uchihashi K, Aoki S, Hashimoto H. Sclerosing variant of epithelioid angiomyolipoma. Pathol Int. 2008 May;58(5):306-10. doi: 10.1111/j.1440-1827.2008.02228.x. PMID: 18429830.

2. Hornick JL, Fletcher CD. Sclerosing PEComa: clinicopathologic analysis of a distinctive variant with a predilection for the retroperitoneum. Am J Surg Pathol. 2008 Apr;32(4):493-501. doi: 10.1097/PAS.0b013e318161dc34. PMID: 18223480.

3. Folpe AL, Mentzel T, Lehr HA, Fisher C, Balzer BL, Weiss SW. Perivascular epithelioid cell neoplasms of soft tissue and gynecologic origin: a clinicopathologic study of 26 cases and review of the literature. Am J Surg Pathol. 2005 Dec;29(12):1558-75. doi: 10.1097/01.pas.0000173232.22117.37. PMID: 16327428.

4. Demir A, Yazici CM, Eren F, Türkeri L. Case report: good prognosis in leiomyosarcoma of the kidney. Int Urol Nephrol. 2007;39(1):7-10. doi: 10.1007/s11255-005-4025-4. PMID: 17268912.

5. Zhao Y, Bui MM, Spiess PE, Dhillon J. Sclerosing PEComa of the kidney: clinicopathologic analysis of 2 cases and review of the literature. Clin Genitourin Cancer. 2014 Oct;12(5):e229-32. doi: 10.1016/j.clgc.2014.04.009. Epub 2014 Jun 12. PMID: 25044147.

6. Casella C, Villanacci V, D’Adda F, Codazzi M, Salerni B. Primary Extra-gastrointestinal Stromal Tumor of Retroperitoneum. Clin Med Insights Oncol. 2012;6:189-97. doi: 10.4137/CMO.S9180. Epub 2012 Apr 23. PMID: 22563251; PMCID: PMC3342024.

7. Xie Z, Zhu G, Cheng L, Liu J, Ye H, Wang H. Solitary fibrous tumor of the kidney: Magnetic resonance imaging characteristics in 4 patients. Medicine (Baltimore). 2018 Aug;97(34):e11911. doi: 10.1097/MD.0000000000011911. PMID: 30142798; PMCID: PMC6112982.

8. Teng F, Lu H, Zheng K, Chen G, Wen Y, Liu Z, Peng L, Huo L, Zeng X, Zhang W, Li X. Urinary System Manifestation of IgG4-Related Disease: Clinical, Laboratory, Radiological, and Pathological Spectra of a Chinese Single-Centre Study. J Immunol Res. 2020 Jul 3;2020:5851842. doi: 10.1155/2020/5851842. PMID: 32714995; PMCID: PMC7354653.

9. Zhou Ming, Netto J. Gorge, Epstein I. Jonathan. 2012 High yeild pathology: Uropathology, Elsevier.

Stephanie J Conrad
Tufts Medical Center
Boston, MA

Ming Zhou
Tufts Medical Center
Boston, MA


Kidney, Sclerosing Angiomyolipoma, PECOMA