Parosteal lipoma of the thigh with cartilaginous and osseous differentiation: an osteochondrolipoma

Parosteal lipoma of the thigh with cartilaginous and osseous differentiation: an osteochondrolipoma

Annals of Diagnostic Pathology 10 (2006) 279 – 282 Radiologic-Pathologic Correlations Parosteal lipoma of the thigh with cartilaginous and osseous d...

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Annals of Diagnostic Pathology 10 (2006) 279 – 282

Radiologic-Pathologic Correlations

Parosteal lipoma of the thigh with cartilaginous and osseous differentiation: an osteochondrolipoma Tilman Rau, MDa,4, Stephan Soeder, MDa, Alexander Olk, MDb, Thomas Aigner, MD, PhDa a

Department of Pathology, Friedrich-Alexander University of Erlangen-Nuremberg, D-91054 Erlangen, Germany b Department of Surgery, Friedrich-Alexander University of Erlangen-Nuremberg, D-91054 Erlangen, Germany

Abstract

Lipomas are very common benign soft tissue neoplasms. They are usually slow-growing and may occur anywhere in the body. Mature cartilage and bone arising in a lipoma is a rare event and is mostly associated with a parosteal localization of the neoplasm. We describe a new case of osteochondrolipoma showing not only major adipocytic differentiation but also areas of fibrocytic and cartilaginous cell differentiation and bone formation (both endochondral and membranous). The occurrence of at least 4 distinct directions of mesenchymal cell differentiation within a benign neoplasia underlines the concept of multilineage differentiation of pluripotent mesenchymal stem cells. Such a multidirectional potential was recently well established in vitro in stem cells present in adult adipocytic tissue. D 2006 Elsevier Inc. All rights reserved.

Keywords:

Parosteal lipoma; Multilineage differentiation; Chondrolipoma; Osteolipoma; Mesenchymoma

1. Introduction

2. Case report

Lipomas are very common benign soft tissue neoplasms. They are usually slow-growing and may occur anywhere in the body. Because of their localization, lipomas are distinguished into superficial and deep lipomas. The latter are further subclassified as intramuscular, intermuscular, intraosseous, or parosteal [1]. Cartilage and bone arising in a lipoma is a rare event and often, but not always, associated with a parosteal localization. Benign lipomatous lesions can be divided into different entities [1,2] with multiple mesenchymal differentiations observed (ie, angiolipomas or myolipomas). In this study, we present a case of lipoma of mature cartilage and bone formation located in the thigh, with preoperative magnet resonance tomography, gross and microscopic pathological findings, immunohistochemistry, and follow-up data. Beyond the differential diagnosis, the possible pathogenesis of such lesions is discussed.

2.1. Clinical history and radiology A 70-year-old male patient was referred to the surgical Department of the University Erlangen-Nuremberg. On physical examination, a firm mass with a diameter of 8 cm was firmly attached to the left femur. Pulse, motility, and neurological functions were normal. Magnet resonance tomography showed a well-defined lobulated lipomatous structure ventral and lateral to the left femur. The lesion showed inhomogenous areas of fibrous tissue and most likely bony structures (Fig. 1A, B). During the surgical intervention, no tight connection to bony or muscular structures was found; hence, the tumor could be removed easily. One year postoperative, no recurrence of the disease was present. There were no clinical complications typical for parosteal lipoma surgery such as nerve palsy [3], bowing deformity, and erosion of the underlying bone or impairment of movement [4,5]. 2.2. Pathological findings—gross pathology

4 Corresponding author. Tel.: +49 9131 85 25782; fax: +49 9131 85 25785. E-mail address: [email protected] (T. Rau). 1092-9134/$ – see front matter D 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.anndiagpath.2006.03.009

The gross specimen consisted of an encapsulated large mass measuring 9.0  7.5  4.0 cm with a smooth surface consisting of a thin vascularized fibrous capsule (Fig. 1C). After slicing, mainly yellowish mature adipose tissue with a

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Fig. 1. Magnet resonance tomography in transversal (A) and frontal (B) imaging. Macroscopy (C, total specimen; D, cut surface) of the osteochondrolipoma.

noticeable amount of fibrous and bony streaks and some solid whitish and translucent areas were visible (Fig. 1D). 2.3. Pathological findings—histopathology Histologically, the tumor showed univacuolated mature fat tissue with embedded strands of connective tissue. These regions had a small amount of mainly fibroblastic cells.

Woven bony structures were visible almost everywhere, including osteocytes and a small rim of osteoblasts (Fig. 2A, D). Partly cartilaginous areas were found adjacent to woven bone formations (Fig. 2C). The tumor was well vascularized and tightly attached to the periostium of the femur (Fig. 2B). The proliferation rate throughout the tumor was very low (b 1%). No mitotic figures were observed

Fig. 2. Histologic overviews of the tumor specimens with large amount of fat cells and focal areas of bone formation (A); attachment to the periostium (B); areas of endochondral (C) and desmal (D) ossification.

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Fig. 3. Comparison of endochondral (A-D) and desmal (E-H) ossification in detail (A, E) and by immunolocalization of aggrecan (B, F) collagen types II (C, G) and X (D, H).

anywhere. Only a slightly increased amount of proliferating cells was found in the fibrous septa (about 1%) as demonstrated by immunostaining for MIB1. Areas of hematopoiesis were not present. 2.4. Phenotyping of ossification The tumor showed desmal and endochondral ossification (Fig. 2C, D). Desmal ossification is the most common kind of bone formation in the human body, if apposition of bone to the metaphyse of long bones is counted. Desmal ossification is typically seen in heterotopic bone formation. Endochondral ossification is a more complex event, from a pluripotent stem cell leading to cartilage formation and afterward to bone formation. Clue cells of endochondral ossification are differentiated and finally hypertrophic chondrocytes. These cells can be detected by immunohistochemistry, showing a strong positivity for aggrecan, collagen type II, and focally collagen type X, whereas areas of desmal ossification show no such phenotype (Fig. 3). S100 protein is expressed in a similar pattern (data not shown), with S100 protein being selectively found in the chondrocytic cells of endochondral ossification but lacking in areas of desmal ossification. Protocols for immunohistochemistry were published before [6]. 3. Discussion Lipomas are the most common benign soft tissue neoplasms. They occur in elderly patients and do not show any predilection for sex and race. Normally, they are found subcutaneously at the back, the neck, the shoulders, the abdomen, or the proximal extremities [1,7,8]. Our case differed from this typical arrangement by 2 rare alterations. First, the lesion was deeply localized with attachment to the femur. Although the periostium in our case was connected to the tumor, the term periosteal lipoma is misleading because the periostium is not the origin of this neoplasm [9]. Thus, for

such a lesion with a broad attachment to the underlying bone, commonly, the term parosteal lipoma is used [5]. Parosteal lipomas are often found at the femur [10-12] and rarely elsewhere [3,5,9,13-15]. Second, the lesion showed extensive areas of cartilaginous and osseous differentiation. In fact, parosteal lipomas are prone to develop bony structures, although parosteal lipoma and osteolipoma should not be used synonymously as the first term describes the localization and the latter the composition of the tumor. Neither parosteal lipomas show always bony areas nor do all osteolipomas occur in a parosteal location. Thus, osteo- and chondrolipomas were found for example in the oral cavity [16,17], the nose [18], the breast [19], and the suprasellar region [20,21]. The differential diagnosis of osteo/chondrolipomas yields on the one hand to secondary hyperostosis of the underlying bone. Here, osseous structures are not part of the tumor itself [14], whereas in our case, the cartilage and bone structures were encapsulated within the lipoma. In addition, mature cartilaginous areas in a lipoma should be distinguished from chondroid lipoma [1,2,22]. This lesion also shows focal hyalinization of the tumor matrix but has an immature aspect with multivacuolated cells and myxoid changes [2]. As the chondroid lipoma is integrated into the newest classifications of lipomateous lesions [1,7,22], osteolipomas, chondrolipomas, and osteochondrolipomas should be included as one subvariety of lipomas as well. The nomenclature of osteochondrolipomateous lesions is controversial. As there are at least 4 cellular components of the tumor (lipocytes, fibroblasts, chondrocytes, and osteocytes), some authors regard this lesion as a benign mesenchymoma [23]. Because the predominant component is a mature fat tissue, the tumor, in our opinion, is still best considered as a lipoma with mature cartilaginous and osseous differentiation, more specifically as an osteochondrolipoma.

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Over the years, the pathogenesis of cartilage and bone formation within a lipoma was explained by 3 theories, according to which bony structures in lipomas originate from multipotent cells, different cell lines (ie, mixed lesions) [13], or the bony and cartilaginous areas are because of metaplastic changes of the neoplastic tissue itself or the tumor stroma. It is improbable that an osteochondrolipoma develop as a primary mixed mesenchymal tumor of 2 independent cell lines [9]. The latter option would exclude the osseous and cartilaginous areas from the neoplasia itself, for which a reason is not evident. Most attractively, different differentiation lines of multipotent stem cells are initiated; these cells have been shown to exist also in adult differentiated fat tissue [24,25]. In vitro and animal models showed a multidirectional differentiation capacity of adipose tissue–derived stem cells. This allows formation of bone, cartilage, fat, muscle, blood vessels, and fibrous tissue from the same precursor cells [24]. Notably, bone formation can be found in 2 ways and as firstly identified histologically and on the molecular level in this paper can be found in parallel in these tumors: directly (membranous) or indirectly via a cartilage precursor (endochondral). The fact that most lipomas are basically pure lipomas might be more surprising than lesions showing a multidirectional mesenchymal differentiation pattern. In this scenario, the most likely explanation for a more pleomorphic differentiation capacity of deeply located lipogenic neoplasm might be that in the depth of the limbs, more multipotent stem cells exist; obviously, other factors such as mechanic stimulation or microtraumata of periosseus lesions or a paracrine influence of the periosteum cannot be excluded. The latter is known to secrete chondro- and osteogenic factors, for example, during fracture healing. Acknowledgments This work was supported by a grant from the EU (EuroBoNet). References [1] Murphey MD, Carroll JF, Flemming DJ, et al. From the archives of the AFIP: benign musculoskeletal lipomatous lesions. Radiographics 2004;24:1433 - 66. [2] Meis JM, Enzinger FM. Chondroid lipoma. A unique tumor simulating liposarcoma and myxoid chondrosarcoma. Am J Surg Pathol 1993;17:1103 - 12.

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