Angiomyolipoma, AML

This tumour is most common in the kidney but may be seen at a variety of other sites including liver^9,10,30, sporadically in the skin²¹, bone¹⁷, mediastinum, heart¹⁸, lungs^11,12, lymph nodes, nasal cavity^19,20, oral cavity, parotid, pharynx, nasal cavity, colon^22,23,24,25, spleen, abdominal wall¹³, pelvis⁸, spermatic cord, penis, ovary¹⁵, vaginal wall, uterus¹⁴, cervix, Fallopian tube, bladder¹⁶, and adrenal⁶.

When associated with tuberous sclerosis, angiomyolipomas are more likely to be multiple. In tuberous sclerosis, there is germline mutation of either the gene for hamartin (TSC1) on chromosome 9q34 or the gene for tuberin (TSC2) on chromosome 16p13.3. In renal angiomyolipomas associated with tuberous sclerosis, there is loss of expression of one or other of these two genes, consonant with a two-hit model. In angiomyolipomas associated with sporadic lymphangioleiomyomatosis, there is loss may be loss of heterozygocity for TSC2. Tuberin is a member of the cell signalling pathway involved in RNA translation. This pathway is a target for the drug rapamycin, giving a potential mode of treatment of malignant tumours²⁸.

This tumour is thought to be one of a family of tumours arising from perivascular epithelioid cells (PEComas).

Clinical features

There is a marked female predominance in sporadic AML but an equal sex incidence when associated with tuberous sclerosis. While 80% of patients with tuberous sclerosis have AML, less than 50% with renal and only 5-10% of those with hepatic AML have tuberous sclerosis²⁹.

Histology

Angiomyolipomas are composed of an admixture of thick-walled blood vessels, smooth muscle cells and adipocytes in very variable proportions. If smooth muscle predominates, they are leiomyoma-like, if fat predominates, they are lipoma-like. The epithelioid variant of angiomyolipoma is composed predominantly or exclusively of epithelioid cells. Many hepatic cases are composed predominantly of epithelioid cells. A variant of epithelioid angiomyolipoma shows marked pleomorphism and is designated as an atypical angiomyolipoma.

Immunohistochemistry

HMB-45	12/12¹, 24/29², 0/1 (pulmonary case)¹², 21/21³⁰
Melan-A	12/12¹, 25/29², 19/21³⁰
Tyrosinase	1/12¹, 4/29²
Mitf	2/12¹, 22/29²
CD117	21/21 (14 cases staining in more than 50% of cells, 4 cases staining in 25-50% of cells and 3 cases staining in <25% of cells: staining was present in epithelioid, small intermediate round cells and spindle cells: fat cells stained focally)³⁰
SMA	17/18³⁰
S-100	10/18³⁰
epithelial markers	negative⁴
oestrogen and progesterone receptors	~25%⁶

Ultrastructure

Cells contain premelanosomes²⁹.

Cytogenetics

The tumours of sporadic AML frequently show loss of heterozygocity of chromosome 16p, the site of the TSC2 gene²⁹.

Differential diagnosis

lipoleiomyosarcoma (well differentiated liposarcoma with leiomyosarcomatous differentiation, L-LMS). In AML, the smooth muscle component shows cytoplasmic clearing and frequently epithelioid features, but less prominent eosinophilia than in L-LMS. In AML, the blood vessels lack intramural hyperchromatic cells. The adipocytes do not show the features of well differentiated liposarcoma⁷.
atypical epithelioid components may resemble renal cell carcinoma²⁷.

Prognosis

These are usually benign tumours. Rare exceptions showing malignant epithelioid foci and metastatic behavior have been reported^{3,5, 26,27}. These epithelioid variants show the same immunoreactivity as the benign type. Rarely, typical AML undergoes sarcomatous change and acquires malignant behaviour²⁹.

References

¹ Miettinen M et al. Microphthalmia transcription factor in the immunohistochemical diagnosis of metastatic melanoma: comparison with four other melanoma markers. Am J Surg Pathol 2001;25:205-211.

² Zavala-Pompa, A., Folpe, A. L., Jimenez, R. E., Lim, S. D., Cohen, C., Eble, J. N., Amin, M. B. Immunohistochemical study of microphthalmia transcription factor and tyrosinase in angiomyolipoma of the kidney, renal cell carcinoma, and renal and retroperitoneal sarcomas: comparative evaluation with traditional diagnostic markers. Am J Surg Pathol 2001;25:65-70.

³ Cibas ES et al. Malignant epithelioid angiomyolipoma ("sarcoma ex angiolipoma") of the kidney. Am J Surg Pathol 2001;25:121-126.

⁴ L'Hostis H et al. Renal angiomyolipoma. A clinicopathologic, immunohistochemical and follow-up study of 46 cases. Am J Surg Pathol 1999;23:1011-1020.

⁵ Mai KT et al. Epithelioid cell variant of renal angiomyolipoma. Histopathology 1996;28:277-280.

Diagnostic histopathology of tumors. Edited by CDM Fletcher. 2nd edition. Churchill Livingstone. Page 485.

⁶ Lam, K. Y., Lo, C. Y. Adrenal lipomatous tumours: a 30 year clinicopathological experience at a single institution. J Clin Pathol 2001;54:707-712.

⁷ Folpe, A.L. and Weiss, S.W. Lipoleiomyosarcoma (well-differentiated liposarcoma with leiomyosarcomatous differentiation): a clinicopathologic study of nine cases including one with dedifferentiation. Am J Surg Pathol 2002;26:742-9.

⁸ Gronchi, A., J. Diment, et al. (2004). "Atypical pleomorphic epithelioid angiomyolipoma localized to the pelvis: a case report and review of the literature." Histopathology 44(3): 292-5.

⁹ Goodman, Z. D. and K. G. Ishak (1984). "Angiomyolipomas of the liver." Am J Surg Pathol 8(10): 745-50.

¹⁰ Tsui, W. M., R. Colombari, et al. (1999). "Hepatic angiomyolipoma: a clinicopathologic study of 30 cases and delineation of unusual morphologic variants." Am J Surg Pathol 23(1): 34-48.