Angiomyolipoma, AML

This tumour is most common in the kidney but may be seen at a variety of other sites including liver9,10,30, sporadically in the skin21, bone17, mediastinum, heart18, lungs11,12, lymph nodes, nasal cavity19,20, oral cavity, parotid, pharynx, nasal cavity, colon22,23,24,25, 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, 0/112, 21/2130

Melan-A

12/121, 25/292, 19/2130

Tyrosinase

1/121, 4/292

Mitf

2/121, 22/292

CD117

21/2130

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

Prognosis

These are usually benign tumours. Rare exceptions showing malignant epithelioid foci and metastatic behavior have been reported3,5, 26,27. These epithelioid variants show the same immunoreactivity as the benign type. Rarely, typical AML undergoes sarcomatous change and acquires malignant behaviour29.

References

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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.

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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.

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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.

11 Guinee, D. G., Jr., D. S. Thornberry, et al. (1995). "Unique pulmonary presentation of an angiomyolipoma. Analysis of clinical, radiographic, and histopathologic features." Am J Surg Pathol 19(4): 476-80.

12 Ito, M., Y. Sugamura, et al. (1998). "Angiomyolipoma of the lung." Arch Pathol Lab Med 122(11): 1023-5.

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14 Vang, R. and R. L. Kempson (2002). "Perivascular epithelioid cell tumor ('PEComa') of the uterus: a subset of HMB-45-positive epithelioid mesenchymal neoplasms with an uncertain relationship to pure smooth muscle tumors." Am J Surg Pathol 26(1): 1-13.

15 Anderson, A. E., X. Yang, et al. (2002). "Epithelioid angiomyolipoma of the ovary: a case report and literature review." Int J Gynecol Pathol 21(1): 69-73.

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20 Banerjee, S. S., B. Eyden, et al. (2001). "Monotypic angiomyolipoma of the nasal cavity: a heretofore undescribed occurrence." Int J Surg Pathol 9(4): 309-15.

21 Val-Bernal, J. F. and C. Mira (1996). "Cutaneous angiomyolipoma." J Cutan Pathol 23(4): 364-8.

22 Hikasa, Y., T. Narabayashi, et al. (1989). "Angiomyolipoma of the colon: a new entity in colonic polypoid lesions." Gastroenterol Jpn 24(4): 407-9.

23 Maesawa, C., G. Tamura, et al. (1996). "Angiomyolipoma arising in the colon." Am J Gastroenterol 91(9): 1852-4.

24 Maluf, H. and B. Dieckgraefe (1999). "Angiomyolipoma of the large intestine: report of a case." Mod Pathol 12(12): 1132-6.

25 Chen, J. S., L. J. Kuo, et al. (2003). "Angiomyolipoma of the colon: report of a case and review of the literature." Dis Colon Rectum 46(4): 547-9.

26 Takahashi, N., R. Kitahara, et al. (2003). "Malignant transformation of renal angiomyolipoma." Int J Urol 10(5): 271-3.

27 Kawaguchi, K., Y. Oda, et al. (2002). "Malignant transformation of renal angiomyolipoma: a case report." Am J Surg Pathol 26(4): 523-9.

28 Harris, G. C., T. A. McCulloch, et al. (2004). "Malignant perivascular epithelioid cell tumour ("PEComa") of soft tissue: a unique case." Am J Surg Pathol 28(12): 1655-8.

29 Hornick JL,Fletcher CD. PEComa: what do we know so far? Histopathology 2006; 48:75-82

30 Makhlouf HR, Remotti HE,Ishak KG. Expression of KIT (CD117) in angiomyolipoma. Am J Surg Pathol 2002; 26:493-7

This page last revised 2.5.2006.