Lipofibroadenoma arising in hyperplastic thymic tissue: Possible perivascular origin of lipofibroadenoma

Abstract

To the Editor Thymic lipofibroadenoma is a benign and very rare mediastinal lesion with only eight cases reported in the literature (summarized in Supplementary Table S1 and Supplementary References). It is histologically characterized by the mixture of adipocytic, fibrotic and thymic epithelial elements, with predominance of adipocytic and fibrotic elements over the narrow strands of thymic epithelial cells. Although it is classified under the category of thymoma in the latest version of the World Health Organization (WHO) Classification of Tumors of the Thymus, it is still controversial whether this lesion is a true neoplasm or a hamartomatous lesion. Furthermore, the pathogenesis and early lesion of lipofibroadenoma is largely unknown due to its rarity. Here, we present a case of thymic lipofibroadenoma arising in hyperplastic thymic tissue. At the boundary between typical lipofibroadenoma area and hyperplastic thymic tissue element, stromal component of lipofibroadenoma was consistently observed in the perivascular spaces of hyperplastic thymic tissue, indicating the possible perivascular origin of thymic lipofibroadenoma. A 55‐year‐old female was incidentally discovered to have a mediastinal tumor in a health‐checkup PET‐CT and visited Department of Surgery, Division of Thoracic Surgery, Keio University Hospital (Tokyo, Japan). The tumor was well‐ circumscribed, 2.5 cm in diameter, and showed mild accumulation of F‐fludeoxyglucose (SUV max: 2.0). She had no symptoms and revealed no apparent physical findings at presentation. Operation was performed under the preoperative diagnosis of thymoma. Macroscopically, the tumor was thinly encapsulated, clearly demarcated from the surrounding thymic tissue, and 4.5 × 1.8 × 1.3 cm in size. The cut surface showed mixture of yellow and white areas. Lobulation was not evident within the lesion (Fig. 1a). Histologically, the lesion was composed of the mixture of areas showing the features of typical thymic lipofibroadenoma and hyperplastic thymic tissue (Fig. 1b). The lipofibroadenoma area showed narrow strands of CK19 epithelial cells compressed by the growth of stromal component containing adipocytes, fibroblasts and collagen fibers (Fig. 1c and Supplementary Fig. S1a,b). These epithelial cells did not show increased expression of PAX8 (Supplementary Fig. S1c), which is frequently observed in neoplastic epithelium of thymoma. Blood vessels were constantly observed at the center of each stromal area. Both epithelial and stromal components contained scattered CD3 T cells and CD20 B cells, and only a few TdT immature lymphocytes were observed in lipofibroadenoma area (Supplementary Fig. S1d,e). The hyperplastic thymic tissue area was composed of cortex and medulla (Fig. 1d). The medulla was found constantly among the cortex, and each medulla contained Hassall s corpuscles. There were no histological evidences of type B1 thymoma, excluding the possibility of lipofibroadenoma arising from type B1 thymoma, of which four cases have been reported previously (Supplementary Table S1). Neither epithelial nor stromal components in this lesion showed histological evidence of malignancy. Of note, at the boundaries between lipofibroadenoma area and hyperplastic thymic tissue area, stromal components of lipofibroadenoma (adipocytes, fibroblasts and collagen fibers) was consistently observed in the perivascular space of hyperplastic thymic tissue (Fig. 1e). This was followed by the expansion of the stromal component of lipofibroadenoma and compression of the hyperplastic thymic tissue (Fig. 1f). Finally, at the center of the lipofibroadenoma area, only narrow strands of CK19 epithelial cells remained and the stromal component of lipofibroadenoma became predominant, establishing the typical histology of lipofibroadenoma (Fig. 1c). These findings strongly suggest that the lipofibroadenoma element in this lesion has originated in and expanded through the perivascular spaces of hyperplastic thymic tissue, just like also suggested in the pathogenesis of thymolipoma. The same observation could be expected in the four previous cases of lipofibroadenoma arising in type B1 thymoma (Supplementary Table S1); however, detailed histopathological findings at the boundary of lipofibroadenoma and type B1 thymoma have not been provided in these cases. Interestingly, in the perivascular spaces where the stromal components of lipofibroadenoma was observed, vascular