CLINICAL FEATURES

• 0.7 - 2.0% of all renal tumors; predominantly women, in a ratio of 2 to 1. average age, 41 years;

• The tumors are multiple in approximately 1/3 of the cases and bilateral in approximately 15%;

• Strong association with tuberous sclerosis (TS).  80% TS have angiomyolipomas, and 1/3 angiomyolipomas present with TS. TS is an autosomal dominant disorder caused by mutation and loss expression of either TSC1 (chromosome 9q34) or TSC2 (chromosome 16p13) genes that encodes hamartin and tuberin, respectively. Mutation of the TSC2 gene is also seen in lymphangioleiomyomatosis.

• Also associated with von Recklinghausen disease, von Hippel-Lindau syndrome, and autosomal dominant (adult) polycystic kidney disease (TSC2/PKD1 contiguous gene syndrome).

• Locations: mostly in the kidney, but also in the renal capsule (capsulomas), attached to the renal capsule but predominantly in the perirenal tissues, localized to the retroperitoneum without renal attachments, and in abdominal organs such as the liver, fallopian tubes, spleen, and regional lymph nodes. The tumors at extrarenal sites are likely multicentricity rather than metastases.

• Image studies show a fatty mass with intermixed soft tissue density.

GROSS FINDINGS

• Typically intrarenal tumor, mostly solitary but multiple tumors observed in 20% cases.

• Usually circumscribed, but no capsule. tend to enlarge at the expense of the adjacent renal parenchyma.

• Ordinarily lobular, yellow, gray, and slightly oily. Tumors consisting primarily of smooth muscle may be pale gray and firm.

• Hemorrhage seen in half of the cases, especially in symptomatic cases, and may be extensive enough to nearly replace the tumor.

MICROSCOPIC FINDINGS

• Composed of mature adipose tissue, blood vessels, and smooth muscle, characteristically admixed in a haphazard fashion.

• Mature adipose tissue with some variation in cellular size and nuclear appearance.

• The blood vessels are a striking component of the tumor and typically have very thick, abnormally formed walls. In many areas, the muscular tissue of the blood vessels is replaced by dense fibrous connective tissue of irregular thickness. The blood vessels of angiomyolipomas may be extremely tortuous and their walls focally thinned and dilated, creating small cirsoid aneurysms. The vessels lack elastic lamina.

• Smooth muscle, irregular arranged in sheets and interlacing bundles, often intimately associated with the outer layers of the muscular walls of the blood vessels. Occasionally, smooth muscle cells show a striking degree of cellular pleomorphism, with nuclear enlargement, hyperchromasia, multinucleated giant cells, scattered mitoses, focal necrosis and Intracytoplasmic granules.

• Perivascular epithelioid cells (PEC cells), clear (abundant glycogen) to eosinophilic cytoplasm, large hyperchromatic bizarre nucleus. A variation of the smooth muscle cell.

SUBTYPES

• Epithelioid Angiomyolipoma, composed either partially or completely of large epithelioid cells. The epithelioid cells range from intermediate-sized polygonal cells to giant cells with abundant acidophilic cytoplasm. The cells may be mononuclear or multinucleated and have prominent nuclei with macronucleoli. Variable degrees of nuclear pleomorphism are seen and mitotic activity may be brisk. Necrosis is often present. In some cases, the characteristic thick-walled blood vessels and adipose tissue of an angiomyolipoma are absent. Epithelioid angiomyolipomas are considered to be malignant neoplasms with the capacity to be locally aggressive and metastasize.

DIFFERENTIAL DIAGNOSES

• Leiomyoma: angiomyolipoma has characteristic blood vessels and adipose tissue;

• Leiomyosarcoma: angiomyolipoma has characteristic blood vessels and adipose tissue with a paucity of mitotic figures, despite cytological atypia.

• Sarcomatoid RCC: RCC positive for cytokeratins, and negative for CD117, muscle markers and melanocytic markers.

• Melanoma: angiomyolipoma has characteristic blood vessels and adipose tissue, and expresses muscle markers.

IMMUNOHISTOCHEMISTRY AND SPECIAL STAINS

• The smooth muscles express muscle markers (muscle-specific actin, smooth muscle actin, desmin), vimentin, CD117 and melanocytic markers (HMB-45, MART-1, tyrosinase, and microphthalmia transcription factor). They are negative for cytokeratins.

ELECTRON MICROSCOPE

• Ultrastructural studies reveal cells with typical features of smooth muscle, adipocytes, and transitional forms with features of both cell types. A spectrum of granules is present, including some with rhomboid and spherical shapes as well as typical premelanosomes.

CYTOGENETIC STUDIES

• Mutation and loss expression of either TSC1 (chromosome 9q34) or TSC2 (chromosome 16p13) genes.

TREATMENT AND PROGNOSIS

• Almost all cases are benign.

REFERENCES

• AFIP Atlas of Tumor Pathology. Fourth Series, Tumors of the Kidney, Bladder, and Related Urinary Structures.

• Enzinger and Weiss's Soft Tissue Tumors. Sharon W. Weiss, John R. Goldblum.

• Rosai and Ackerman's Surgical Pathology, 9th edition;

Summarized by: Zenggang Pan, MD, PhD