Histol Histopathol (1999) 14: 845-860 Histology and 001: 10.14670/HH-14.845 Histopathology http://www.hh.um.es From Cell Biology to Tissue Engineering Invited Review Malignant fibrous histiocytoma (MFH). A comparison of MFH in man and animals. A critical review P. Schneiderl, U. Busch2, H. Meister3, Q. Qasem3 and P.H. Wunsch4 1Hermann-Volz-Str .77, 2Kbhlesrain 87/4, 3Practice for Pathology, District Hospital (Biberach/Riss 1, 2, 3) and 41nstitute for Pathology, Clinicum Nurnberg, Germany Summary. This review gives information about e.g., 62.3 years (aorta) or 49.9 (inferior vena cava). The localization and types of MFH in man and animals such average span of lives was 23-93 years. as mouse, rat, cat, dog, opossum, cattle, horse and birds MFH was first described as a distinct type of [e.g. mallard (a wild duck)]. Furthermore, this paper sarcoma by O'Brien and Stout (1964). The tumour is reports about cell culture dealing with MFH. called synonymously as malignant fibrous xanthoma or The aim of this publication is to show that MFH pleomorphous fibrous xanthoma according to Weiss and originates from a primitive mesenchymal stem cell, Enzinger (1978). Little and McCarthy (1993) designated fibroblastoid cell and fibroblasts. Histiocytes are, this tumour as a high-grade primary bone sarcoma. according to the literature in a small amount constituents Requena et al. (1997) emphasized that an atypical fibro­ of MFH and are reactive cells or without any meaning. xanthoma was a superficial variant of pleomorphic In our own studies using rats [strain: Chbb: THOM MFH. (SPF)] the characteristic storiform or cartwheel pattern MFH is often a consequence of therapy, mostly after of tumour cells were evident. The cells were elongated, radiotherapy or chemotherapy with doxorubicin and rich in endoplasmic reticulum and possessed no or very cyclophosphamide (Costa, 1994). This neoplasm is also few Iysosomes. The cells were predominantly fibroblasts induced by 4-hydroxyamino-quinoline-1-oxide (Mii et and fibroblastoid cells. These cells were intermingled aI., 1982), 7,12-dimethylbenz(a)anthracene (Nikitin et with giant cells. In other species mentioned above, the aL , 1993) or by a similar agent (Sakamoto, 1986) in rats. MFH showed very similar histological features. Our own Narita et al. (1997) described a family aggregation of results and findings obtained from the literature support soft tissue sarcomas which they designated in part as our concept that the MFH represents a primitive MFH. The authors concluded that the observed features phenotype or pleomorphic sarcoma which may closely resembled the Li-Fraumeni syndrome because differentiate in one or more directions. Histiocytes are they noted different neoplasms (liposarcoma and gastric not a neoplastic component. carcinoma) seen at the very same time as MFH. MFH is sometimes a consequence of primary Key words: Malignant fibrous histiocytoma, MFH, diseases e.g. fibrous dysplasia (Ruggieri et al. , 1994; Man, Animals, Electron microscopy Ohmori et aI., 1996) a benign disease which often occurs predominantly in the area of femur, tibia and face's skull (monoostotic, Morbus Jaffe-Lichtenstein; the polyostotic Introduction variant mostly found in girls is named Albright­ syndrome). After fibrous dysplasia a fibrosarcoma or The human MFH, a not uncommon type of soft osteosarcoma could also be a consequence (Ruggieri et tissue sarcoma (Zagars et aI. , 1996), is a neoplasm of aI. , 1994). According to Little and McCarthy (1993) late adult life (Kirchner et aL, 1984b; Cole et aI., 1993; MFH is sometimes the consequence of post-radio­ Fang et aL, 1996) but often found in children too (Cole therapy, Paget's disease, osteosarcoma or giant cell et al., 1993; Kodet et aL, 1993; Malone, 1993; Corpron tumour. et aL, 1996; Hari et aI. , 1996; Palmer et aI., 1997; Shah The question arises as to whether the designation as et aI. , 1996). MFH is justified. It is the aim of our review to clarify According to Burke and Virmans (1993) who this. Since the publication by Leder (1967) it is well­ studied MFH in great vessels (see below; next chapter), known, that phagocytic cells such as histiocytes, the mean age of adult patients suffering from MFH was, macrophages but also resident phagocytes like Kupffer's cells of the liver originate from monocytes. Because Offprint requests to: Dr. Peter Schneider. Hermann·Volz-Str.77, 0- malignant cells possess characteristics of stem cells the 88400 Biberach/Riss. Germany MFH must actually derive from monocytes. Mature 846 MFH in man and animals phagocytes could then form at the most benign Localization and types of MFH in man neoplasms. A very important review about human soft tissue Localization tumours has been published by Kirchner and Wunsch (1981). In this monograph, amongst other things, the MFH is mostly localized within soft tissues of the distribution and differential diagnoses are discussed. extremities, bone (Little and McCarthy, 1993; Hartmann Similar statements were given by the same authors et a\., 1997; Nishida et a\., 1997) trunk or limb girdles (Wunsch and Kirchner, 1982). Wunsch and Mulle r (Pritchard et aI., 1993) but also in other organs or (1982) emphasized that in differential diagnosis for regions of the body such as paranasal sinuses (Biiltmann hemangiopericytoma different mesenchymal neoplasms, et aI., 1981), pleura (Aozasa et aI., 1994), lung also a MFH, have to be taken into consideration. (Rosemberg et a\., 1993; Gal et a\., 1994; Halyard et a\. , The literature on MFH is extensive. About 600 1996; Suster, 1995; Shah et aI., 1996; Barbas et aI. , references are available. The papers are for the most part 1997; Hartmann et aI., 1997) - a benign fibrous those dealing with therapy (cytostatic agents, surgery hi stiocytoma must be taken into consideration in and radiation). We used only such lite rature where differential diagnosis of lung MFH (Schneider and pathology was the predominant part or where pathology Wunsch, 1980), heart (Beck et a\., 1985; Okita et aI., was integrated as an important factor into a paper. 1994; Teramoto et a\., 1995; Fang et a\., 1996), larynx We intended to use the exact morphological (Benett and McFarlane, 1993; Kuwabara et a\., 1994; definitions to describe anatomical sites and structures. Scott and Carter, 1995; Soh et a\., 1996), spleen (Lieu et Here, we orientated ourselves by Krstic (1984). aI. , 1993; Bonilla et a\., 1994), head and neck together Fig. 1. MFH , overall view, typical storiform-pleomorphic pattern or Fig. 2. MFH, magnification of a sector, pleomorphic bizarre giant cells. structure respectively, cell-dense, fusocellular, giant cell containing, The MFH includes spindle cells similar to fibroblasts and histiocytes. sarcomatous tumour. H-E, x 240 H-E, x 400 847 MFH in man and animals with larynx, tonsils and/or regional lymph nodes (30%). (Bremer et aI., 1982; Singh et aI., 1993; Zapater et aI., 1995), axilla (Fukunaka et aI., 1996), spermatic cord Types ofMFH (Glazier et aI., 1996), pancreas (Haba et aI., 1996), leptomeninges (Hari et aI., 1996) as well as peritoneum, Different authors have described the types of MFH: retroperitoneum, mesentery and intestine (Hauser et aI., histologically the MFH can be subdivided into: 1) 1993), large vessels such as aorta, inferior vena cava storiform-pleomorphic (the most common type); 2) and/or pulmonary artery (Burke and Virmani, 1993; myxoid type; 3) giant cell type; 4) inflammatory type; Khan et aI., 1997), intracranial localization (Kirchner et and 5) angiomatoid type aI., 1984b), urinary bladder (Kunze e t aI., 1994; There are only slight differences b etween the Weingartner et aI., 1995), liver (Lieu et aI., 1993), investigators who proposed and described this kidney (Lopez et aI., 1996), brain (Martinez-Salazar et nomenclature. All those who studied the types of MFH aI., 1997), oesophagus (Naganuma e t aI., 1996), considered this matter as a similarity (Weiss and mandible (Onyango and Awange, 1993; Sohail et aI., Enzinger, 1978; Biiltmann et aI., 1981; Kirchner et aI., 1995; Narvaez et aI., 1996), pleura (Rizkalla et aI., 1994) 1984a,b; Muller et aI., 1984; Wiinsch and Dubrauszky, and trachea (Sennaroglu et aI., 1996). 1987; Cole et aI., 1993; Nascimento, 1993; Kunze et aI., Biiltmann et al. (1981) stressed the fact, that more 1994; Miller et aI., 1994; Costa et aI., 1995; Meister, than 60% of the cases are found in the area of 1995; Riede and Sterry, 1995; Unnik, 1995; LeDoussal extremities. The retroperitoneum, abdominal walls and et aI., 1996; Zagars et aI., 1996). The MFH in man is chest wall are the organs closest to MFH-development illustrated by Figs. 1-4. We studied this malignant Fig. 3. MFH . magnification of a sector. mainly a picture of fibroblastic Fig. 4. MFH, magnification of a sector, beside multinucleated bizarre spindle celis together with some multinucleated giant celis. H-E, x 480 giant cells and fibroblasts ("histiocytic" cells); there are also inflammatory celis. H-E, x 480 848 MFH in man and animals tumour in approx. 250 cases. in a hind leg tissue of a ddY-mouse. Mouse uterine tumours similar to MFH were MFH in animals observed by Turusov et al. (1993). Trukhanova et al. (1998) described 1,2-dimethylhydrazine (DMH)-induced Mouse uterine sarcomas, including several MFHs. Roholl et al. (1988) registered MFH in mice of all Tillmann et al. (1997) implanted microchips in test groups including controls during a cancerogenicity CBB/y mice. Subcutaneous soft tissue tumours occurred study. There are also different data from studies in mice at the site of these microchips. Although the neoplasms which suggested that neoplasms resembling MFH may developing at the implantation site had a mixed develop from mouse bone marrow cells or peritoneal histological appearance, two main tumour types were macrophages transformed by SV 40 virus (Yumoto and identified. The majority of the neoplas ms were Morimoto, 1980). fibrosarcomas.