PEComas: the past, the present and the future

Abstract

The perivascular epithelioid cell (PEC) is a cell type constantly present in a group of tumors called PEComas. PEC expresses myogenic and melanocytic markers, such as HMB45 and actin. Recently, recurrent chromosomal alterations have been demonstrated in PEC. At present, PEComa is a widely accepted entity. In the past 10 years, the use of this term has allowed to report and describe numerous cases permitting to start highlighting the biology of this group of lesions. PEComas are related to the genetic alterations of tuberous sclerosis complex (TSC), an autosomal dominant genetic disease due to losses of TSC1 (9q34) or TSC2 (16p13.3) genes which seem to have a role in the regulation of the Rheb/mTOR/p70S6K pathway. There are some open questions about PEComas regarding its histogenesis, the definition of epithelioid angiomyolipoma and the identification of the histological criteria of malignancy. An innovative therapeutic trial using rapamycin is under way for tumors occurring in TSC such as renal angiomyolipoma and lymphangioleiomyomatosis. Its success could provide the rationale for the use of the same drug in other lesions composed of PECs, especially in the malignant ones.

Fig. 1

Renal angiomyolipoma: perivascular epithelioid cells arranged around a blood vessel; H&E ×20

Fig. 2

Diagram demonstrating the modulation of morphology and immunophenotye of PECs

Fig. 3

Hepatic angiomyolipoma: strong granular HMB45 immunoreactivity in perivascular epithelioid cells; HMB45 ×20

Fig. 4

Renal microhamartoma completely composed of perivascular epithelioid cells; H&E ×20

Fig. 5

Cystic angiomyolipoma: strong positivity for actin in the solid extracystic component; SM ACT ×10

Fig. 6

Prostatic PEComa composed of epithelioid cells with clear cytoplasm arranged in nests; H&E ×4

Fig. 7

Bladder PEComa composed of epithelioid cells with clear cytoplasm arranged in nests, H&E ×4

Fig. 8

Uterine PEComa composed of epithelioid cells with a clear cytoplasm and well-defined cell borders; H&E ×10

Fig. 9

Pulmonary lymphangioleiomyomatosis composed of epithelioid cells arranged around a vascular channel; H&E ×20

Fig. 10

Pulmonary clear-cell “sugar” tumor composed of epithelioid cells with a clear cytoplasm and well-defined cell borders. A prominent and vascular channel is present; H&E ×10

Fig. 11

Pulmonary clear-cell “sugar” tumor: HMB45 immunoreactivity in tumor cells; HMB45 ×20

Fig. 12

Pancreatic clear-cell “sugar” tumor: this tumor has overlapping features of the clear-cell “sugar” tumor of the lung: epithelioid cells, with a clear cytoplasm and with a nested or appearance; H&E ×4

Fig. 13

Hepatic angiomyolipoma: solid component made of large epithelioid cells; H&E ×10

Fig. 14

Hepatic angiomyolipoma: cytoplasmic signal in immunohistochemical reaction for p70S6K; p70S6K ×10