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The renal angiomyolipoma (AML) is a benign tumor characteristically composed of fat, smooth muscle tissue, and vessels. We collected AMLs from our nephrectomy database, reclassified them according to their histological appearance, recorded the demographic, clinical, and pathological parameters, and compared them with oncocytoma (RO) and renal cell carcinoma (RCC). Immunohistochemistry was ordered in 41 cases. In 2224 nephrectomies, we found 52 AMLs with a 53 mm median size. The mean age was 52.76. Forty-eight tumors were sporadic, while four were hereditary. The revision resulted in 31 classic, 13 leiomyoma-like, five lipoma-like, two epithelioid, and one AML with epithelial cysts. SMA was diffusely positive, except for the epithelioid type, while MelanA harbored stronger expression than HMB45. AML was more frequent in females and appeared ten and 7 years earlier than RO and RCC, respectively. The follow-up time was 7.42 years, and neither tumor-related death nor relapse occurred. AML is rare in nephrectomies and develops primarily in females in their 50s with an average size of 50–60 mm at the surgery. The histological appearance in order of frequency is classic, leiomyoma-like, lipoma-like, epithelioid, and cystic. The MelanA, HMB45, and SMA immunohistochemistry can support the light-microscopic findings.
The angiomyolipoma (AML) is a benign tumor occurring mainly in the kidney and belongs to the perivascular epithelioid cell tumors (PEComa) [
AML cases were collected from the archive of the Department of Pathology, Albert Szent-Györgyi Medical School, University of Szeged. Two pathologists (AJ and LK) reviewed all hematoxylin eosin-stained slides and available immunohistochemical staining. They reclassified the cases according to the current classification scheme, and the subtypes were as follows: classic AML, AML with epithelial cysts (AMLEC), lipoma-like AML, leiomyoma-like AML, oncocytic AML, and epithelioid AML (eAML) [
All immunohistochemical stains available in 22 tumors were reviewed. By using tissue microarray technique, another 19 AMLs were stained by MelanA (Labvision, clone A103, mouse monoclonal antibody, dilution 1:200), HMB45 (Cell Marque, clone hmb-45, mouse monoclonal antibody, dilution: 1:200), and SMA (Cell Marque, clone 1a4, mouse monoclonal antibody, dilution: 1:300). Two 2-mm-thick tissue cores represented the tumors. The reactions were evaluated in a semiquantitative fashion (0% positivity = negative; 1%–50% positivity = +; 51%–100% positivity = ++). The FFPE blocks were unavailable in eleven cases; hence, no immunohistochemistry was performed for these tumors.
For parametric and non-parametric tests, the SPSS software package was applied, and the differences were deemed significant if
Fifty-two AML cases were diagnosed from 2224 nephrectomy specimens. The mean age of all patients was 52.76 years (range 27–76 years). In males, 7 tumors, while, in females, 45 AMLs occurred (female-to-male ratio: 6.42:1). Forty-eight tumors were sporadic in our data set, and four were linked to TSC. The mean ages of sporadic and TSC cases were 54.04 and 37.75, respectively. One tumor developed in polycystic kidney disease, and another one evolved in a graft kidney. Tumor rupture and hemorrhagic complications occurred in eight patients (shown in
Ruptured angiomyolipoma with hemorrhage. There is a fatty tumor on the cut surface with several foci of hemorrhage (red arrow). On the other hand, several smaller tumor nodules are present (black arrow). The renal parenchyma is hard to recognize (asterisks).
The clinical features of the cases investigated.
Case | Age | Sex | Signs/Circumstances of discovery | Tuberous sclerosis | Surgery | Additional data |
---|---|---|---|---|---|---|
1 | 52 | F | No data | No | Radical nephrectomy | - |
2 | 66 | F | Incidental finding at cholecystectomy | No | Tumor resection | - |
3 | 73 | F | Tumor rupture | No | Total nephrectomy | - |
4 | 36 | F | No data | No | Total nephrectomy | - |
5 | 46 | F | Tumor rupture | No | Total nephrectomy | - |
6 | 55 | F | Tumor rupture | No | Total nephrectomy | - |
7 | 58 | F | Retroperitoneal hemorrhage | No | Total nephrectomy | - |
8 | 33 | F | No data | Yes | Total nephrectomy | - |
9 | 26 | F | No data | No | Total nephrectomy | - |
10 | 49 | F | No data | No | Tumor resection | - |
11 | 26 | F | Surgical finding at kidney transplantation | No | Total nephrectomy | - |
12 | 45 | F | Incidental finding at SLE examination | No | Tumor resection | - |
13 | 34 | F | No data | Yes | Radical nephrectomy | - |
14 | 46 | F | No data | No | Total nephrectomy | - |
15 | 53 | F | No data | No | Radical nephrectomy | - |
16 | 47 | F | No data | No | Tumor resection | - |
17 | 62 | F | No data | No | Total nephrectomy | - |
18 | 60 | F | No data | No | Total nephrectomy | - |
19 | 52 | F | Tumor rupture | No | Radical nephrectomy | - |
20 | 49 | F | Incidental finding on abdominal US | No | Total nephrectomy | - |
21 | 49 | F | At the examination of hemorrhoids | No | Radical nephrectomy | - |
22 | 60 | F | Tumor rupture | No | Total nephrectomy | - |
23 | 57 | F | No data | No | Radical nephrectomy | - |
24 | 60 | F | Hematuria | No | Total nephrectomy | - |
25 | 67 | F | No data | No | Total nephrectomy | - |
26 | 35 | F | No data | No | Total nephrectomy | - |
27 | 56 | M | At the examination of kidney stones | No | Tumor resection | - |
28 | 31 | F | At the examination of PCOS | No | Tumor resection | - |
29* | 40 | F | Hemorrhagic shock | Yes | Total nephrectomy | - |
30 | 58 | F | Tumor rupture | No | Total nephrectomy | Evolved in horseshoe kidney |
31 | 43 | M | At the examination for kidney transplantation | No | Radical nephrectomy | Evolved in polycystic kidney |
32 | 66 | F | No data | No | Total nephrectomy | - |
33 | 73 | M | At the examination of BPH | No | Tumor resection | - |
34 | 76 | F | Incidental finding on abdominal US | No | Tumor resection | - |
35 | 54 | M | At graft kidney’s follow-up | No | Tumor resection | Evolved in graft kidney |
36 | 65 | F | No data | No | Total nephrectomy | - |
37 | 68 | M | No data | No | Total nephrectomy | - |
38 | 68 | F | No data | No | Total nephrectomy | - |
39 | 46 | M | At the examination of urethral discharge | No | Total nephrectomy | - |
40 | 75 | F | No data | No | Total nephrectomy | Ipsilateral RO is present |
41 | 69 | F | No data | No | Tumor resection | - |
42 | 56 | F | No data | No | Tumor resection | - |
43 | 74 | F | No data | No | Total nephrectomy | Ipsilateral ccRCC is present |
44* | 43 | F | Renal pain, tumor rupture | Yes | Radical nephrectomy | - |
45 | 65 | F | No data | No | Tumor resection | - |
46 | 33 | F | No data | No | Tumor resection | - |
47 | 31 | M | No data | No | Total nephrectomy | - |
48 | 57 | F | No data | No | Total nephrectomy | - |
49 | 46 | F | Renal colic | No | Total nephrectomy | Ipsilateral HOCT and ccRCC are present |
50 | 60 | F | At gastrointestinal examination | No | Tumor resection | - |
51 | 54 | F | Subcostal pain | No | Total nephrectomy | - |
52 | 41 | F | Incidental finding on abdominal US | No | Tumor resection | - |
F, Female; M, Male; SLE, Systemic lupus erythematosus; US, Ultrasound; PCOS, Polycystic ovary syndrome; BPH, Benign prostatic hyperplasia; RO, Renal oncocytoma; ccRCC, Clear cell renal cell carcinoma; RCC-U, Renal cell carcinoma unclassified. * Case #29 and #44 are from the same patient.
The median size of all tumors was 53 mm (range: 4–300 mm), but in cases with tuberous sclerosis, it was found to be 260 mm. The revision of the cases resulted in thirty-one classic, thirteen leiomyoma-like, five lipoma-like, two epithelioid, and one AMLEC. No oncocytic AML was seen. Synchronous tumors were observed in four cases (
The pathological characteristics of the cases investigated.
Case | Laterality | Focality | Size (mm) | Histological subtype | Immunohistochemistry |
---|---|---|---|---|---|
1 | Right | Unifocal | 20 | Leiomyoma-like | MelanA: ++, HMB45: +, SMA: ++ |
2 | Right | Unifocal | 6 | Leiomyoma-like | MelanA: ++, HMB45: +, SMA: ++ |
3 | Right | Unifocal | No data | Classic | MelanA: -, HMB45: +, SMA: ++ |
4 | Left | Unifocal | 40 | Classic | MelanA: +, HMB45: +, SMA: ++ |
5 | Left | Unifocal | 75 | Classic | MelanA: ++, HMB45: +, SMA: ++ |
6 | Right | Unifocal | 20 | Classic | MelanA: ++, HMB45: −, SMA: ++ |
7 | Right | Unifocal | 39 | Leiomyoma-like | MelanA: ++, HMB45: +, SMA: ++ |
8 | Left | Multifocal | No data | Classic | MelanA: ++, HMB45: ++, SMA: ++ |
9 | Right | Unifocal | 36 | Leiomyoma-like | MelanA: ++, HMB45: ++, SMA: ++ |
10 | Left | Unifocal | 70 | Lipoma-like | MelanA: +, HMB45: +, SMA: ++ |
11 | Left | Multifocal | No data | Classic | Not performed |
12 | Right | Unifocal | 22 | Classic | MelanA: +, HMB45: +, SMA: ++ |
13 | Left | Multifocal | 200 | Classic | MelanA: ++, HMB45: ++, SMA: ++ |
14 | Left | Multifocal | 25 | Classic | Not performed |
15 | Right | Unifocal | 90 | Classic | Not performed |
16 | Right | Unifocal | 20 | Classic | Not performed |
17 | Left | Unifocal | 17 | Leiomyoma-like | HMB45: +, SMA: ++ |
18 | Left | Unifocal | 25 | Classic | Not performed |
19 | Left | Unifocal | 46 | Classic | MelanA: ++, HMB45: ++, SMA: ++ |
20 | Right | Unifocal | 170 | Lipoma-like | Not performed |
21 | Left | Unifocal | 65 | Classic | Not performed |
22 | Left | Unifocal | 245 | Classic | Not performed |
23 | Left | Unifocal | 100 | Classic | MelanA: +, HMB45: +, SMA: ++ |
24 | Right | Unifocal | 30 | Leiomyoma-like | Not performed |
25 | Right | Unifocal | 40 | Classic | MelanA: +, HMB45: −, SMA: ++ |
26 | Left | Unifocal | 80 | Classic | MelanA: −, HMB45: +, SMA: ++ |
27 | Left | Unifocal | 37 | Leiomyoma-like | HMB45: +, SMA: ++ |
28 | Right | Unifocal | 40 | Classic | MelanA: ++, HMB45: ++, SMA: ++, CD1a: −, Ki67: 1% |
29 | Right | Multifocal | 300 | Classic | MelanA: +, HMB45: +, SMA: ++ |
30 | Right | Unifocal | 155 | Classic | MelanA: +, HMB45: +, SMA: ++ |
31 | Left | Multifocal | 6 | Classic | MelanA: ++, HMB45: +, SMA: ++ |
32 | Left | Unifocal | 42 | Leiomyoma-like | MelanA: +, HMB45: +, SMA: ++, h-Caldesmon: ++ |
33 | Left | Unifocal | 20 | Classic | MelanA: +, HMB45: +, SMA: ++, CathepsinK: + |
34 | Left | Unifocal | 31 | Leiomyoma-like | MelanA: ++, HMB45: ++, SMA: ++ CD1a: − |
35 | Right | Unifocal | 45 | Lipoma-like | MelanA: ++, HMB45: ++, SMA: ++ |
36 | Right | Unifocal | No data | Classic | Not performed |
37 | Left | Unifocal | 40 | Epitheloid | MelanA: +, HMB45: +, SMA: +, EMA: −, PAX2: −, S100: −, CD56: −, Ki67: 1% |
38 | Left | Unifocal | 69 | Classic | MelanA: ++, HMB45: -, SMA: ++ |
39 | Right | Unifocal | 20 | Cystic | Epithel: CK7: ++, PAX8: ++, MNF116: ++, Stroma: MelanA: +, HMB45: +, SMA: ++, ER: +, PR: +, TLE1: −, S100: −, CD34: −, Ki67: <1% |
40 | Right | Unifocal | 4 | Classic | MelanA: +, HMB45: +, SMA: ++ |
41 | Left | Unifocal | 23 | Leiomyoma-like | MelanA: +, HMB45: −, SMA: ++ |
42 | Left | Unifocal | 46 | Classic | MelanA: ++, HMB45: −, SOX10: -, SMA: ++ |
43 | Right | Unifocal | 11 | Leiomyoma-like | MelanA: +, HMB45: −, SMA: ++ |
44 | Left | Unifocal | 260 | Classic | MelanA: ++, HMB45: +, SMA: ++ |
45 | Right | Unifocal | 30 | Lipoma-like | Not performed |
46 | Graft | Unifocal | 5 | Lipoma-like | MelanA: +, HMB45: +, SMA: ++, S100: ++, CD34: -, Ki67: <1% |
47 | Left | Unifocal | 52 | Leiomyoma-like | HMB45: +, SMA: ++, CD117: +, Ki67: 1%–2% |
48 | Right | Unifocal | 28 | Classic | HMB45: +, SMA: ++ |
49 | Left | Multifocal | 4 | Classic | MelanA: −, HMB45: ++, PAX8: −, SDHB: ++, β-Catenin: ++ (membrane), SMA: ++ |
50 | Left | Unifocal | 15 | Leiomyoma-like | MelanA: ++, HMB45: +, SMA: ++, Ki67: 1%–2% |
MelanA: +, HMB45: -, SMA: +, CD68: +, CathepsinK: +, CD117: +, PAX2: − | |||||
51 | Left | Unifocal | 42 | Epitheloid | PAX8: −, FH: ++, SDHB: ++, CA9: −, CK7: −, CD10: −, TFE3: −, GATA3: − |
PBRM1: ++, BAP1: ++ | |||||
52 | Left | Unifocal | 55 | Classic | MelanA: ++, HMB45: +, SMA: ++ |
− = negative (0% positivity), + = 1%–50% positivity, ++ = 51%–100% positivity.
HMB45, Human melanoma black 45; SMA, Smooth muscle actin; CD, Cluster of differentiation; EMA, Epithelial membrane antigen; PAX, Paired-box; ER, Estrogen receptor; PR, Progesterone receptor; TLE1, Transducin-like enhancer of split 1; SOX10, SRY-related HMG-box 10; SDHB, Succinate dehydrogenase B subunit; FH, Fumarate hydratase; CA9, Carbonic anhydrase 9; CK7, Cytokeratin 7; TFE3, Transcription factor 3E; GATA3, GATA-binding factor 3; PBRM1, Polybromo 1; BAP1, BRCA1 associated protein 1.
Classic AML was the most common subtype (59.61%). Two tumors occurred in males (case #31 and #33). In case #35, the tumor developed in damaged kidney parenchyma (polycystic kidney), while, in case #33, the patient used finasteride to treat benign prostatic hyperplasia. All TSC-linked cases showed classic morphology.
Classic angiomyolipoma.
This morphology was seen in 25% of the AMLs investigated. These tumors contained only a small amount of fat tissue; therefore, macroscopically, they caused no impression of AML (shown in
Leiomyoma-like angiomyolipoma.
We registered a lipoma-like appearance in five cases, and case #35 evolved in a transplanted kidney.
Lipoma-like angiomyolipoma.
We diagnosed two tumors as eAML. This subtype required several immunohistochemical staining at the original histological diagnosis. Invasion, mitotic activity, and tumor cell necrosis were exclusively seen in these tumors (shown in
Epithelioid angiomyolipoma.
This tumor was discovered in a 46-years-old male. The relatively small lesion was accidentally noticed during a urological investigation. Histologically, the tumor shared some characteristics with metanephric stromal tumor, and the tumor cells were estrogen and progesterone receptor-positive. We have no data on any hormonal treatment.
Angiomyolipoma with epithelial cysts.
We compared the gender, age and tumor size of AML patients with those, who were operated with oncocytoma (RO) and renal cell carcinoma (RCC). The AML is more common in females (AML vs. RO;
Oncocytoma and AML are the most common benign tumors of the kidney [
68-year-old female patient’s CT scan accidentally reveals an angiomyolipoma.
AML is rare in nephrectomy specimens, and it is either sporadic or associated with TSC. It typically develops in women around 50 years, and the average size of surgically treated cases is about 50–60 mm. Histologically, the tumor may be classic, leiomyoma-like, lipoma-like, epithelioid, or cystic, in order of frequency. The eAML may be malignant, so such tumors should be treated like RCC and closely monitored. The pathological diagnosis is usually problem-free, and the light-microscopic findings may be supplemented by MelanA, HMB45, and SMA immunostaining.
The raw data supporting the conclusion of this article will be made available by the authors, without undue reservation.
The studies involving human participants were reviewed and approved by Regional and Institutional Human Medical Biological Research Ethics Committee, University of Szeged. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.
ZF prepared the figures and wrote the manuscript. IK and LV provided the patient characteristics and follow-up data. AJ and FS performed the histological analysis and immunohistochemical evaluation. LK contributed to the study concept and final supervision of the manuscript.
The University of Szeged, Faculty of Medicine Research Fund-Hetényi Géza Grant (Grant No. 5S 340 A202) and the New National Excellence Program funded this research (Grant No. UNKP-21-4-SZTE-131, UNKP-22-4-SZTE-305).
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The authors gratefully acknowledge the assistance of Vivien Sánta and Samir Martin in the language editing of the text.