Hyalinising spindle cell tumour with giant rosettes: report of a case with unusual features including original histological and ultrastructural observations

Pathology (2001 ) 33, pp. 101– 107

HYALINISING SPINDLE CELL TUMOUR WITH GIANT ROSETTES: REPORT OF A CASE WITH UNUSUAL FEATURES INCLUDING ORIGINAL HISTOLOGICAL AND ULTRASTRUCTURAL OBSERVATIONS RICHARD A. SCOLYER , STANLEY W. MC CARTHY, EDWARD J. WILLS , ALLAN A. PALM ER Department of Anatomical Pathology, Royal Prince Alfred Hospital, Sydney, Australia

Summary Hyalinising spindle cell tumour with giant rosettes (HSCTGR) is an uncommon, recently described low-grade sarcoma which shares many histological features with low-grade fibromyxoid sarcoma (LGFMS). We report a case of HSCTGR occurring in the deep soft tissues of the thigh of a 46-year-old woman, that presented as a slowly growing, painless mass. Microscopically the tumour was composed of spindled stromal cells amongst which were scattered socalled collagen rosettes. The distinctive feature of this case was the previously unreported finding of lymphoid cells of T-cell phenotype admixed with fibrohistioctyic cells in the cellular cuff surrounding the collagenous core of the rosettes. The case was further unusual in that it included focal areas of increased cellularity with a mitotic count of up to three per 10 high-power fields. While the latter feature has been associated with increased recurrences and metastases in LGFMS, it is not known whether the significance is similar in HSCTGR. The spindled stromal cells showed ultrastructural features of poorly differentiated fibroblasts, while those at the edges of the rosettes showed features of altered fibroblasts, some with a fibrohistiocytic appearance. These findings support the interpretation that HSCTGR forms part of the spectrum of sarcomas showing fibroblastic differentiation. Key words: Soft tissue, hyalinising spindle cell tumour with giant rosettes, fibromyxoid sarcoma, rosette, fibrosarcoma, low-grade fibrosarcoma with palisaded granulomalike bodies, pathology. Accepted 28 July 2000

INTRODUCTION Hyalinising spindle cell tumour with giant rosettes ( HSCTGR) is an uncommon, recently described low-grade sarcoma which shares many histological features with lowgrade fibromyxoid sarcoma ( LGFMS).1 Like the latter, HSCTGR is characteristically a circumscribed, deep-seated soft tissue tumour with a deceptively bland microscopic appearance being composed of spindle-shaped cells in a fibrous and myxoid stroma. However, in addition HSCTGR also includes large hyalinised collagen rosette-like structures composed of a central collagen core surrounded by plump oval- to spindle-shaped cells. Immunohistochemical studies of HSCTGR have shown inconsistent results.1– 7 Despite the occurrence of S–100 protein, neurone-specific enolase and CD57 positivity in many of the reported cases and evidence of schwannian differentiation by electron

microscopy in one case report,5 a recent ultrastructural study of three cases showed features of fibroblastic cells.6 Local recurrence has occurred in two of the reported cases,1 and recently two cases that metastasised have been documented. 7,8 It is not known whether HSCTGR represents a distinctive low-grade soft tissue sarcoma or merely a variant of LGFMS. It is hoped that the recognition of further cases of this uncommon soft tissue tumour will help better define its histological spectrum, biological behaviour and relationship to other low-grade soft tissue sarcomas. We present another variant of this distinctive soft tissue sarcoma. It displayed the previously unreported finding of lymphoid cells of T-cell phenotype surrounding the collagen rosettes, and focal areas of hypercellularity with a mitotic count of up to three per 10 high-power fields. The stromal cells of our case showed ultrastructural features of poorly differentiated fibroblasts supporting the classification of this tumour as fibroblastic in origin.

CASE REPORT A 67-year-old Bosnian female with no significant past medical history presented with a slowly growing mass in the medial aspect of the right upper thigh. Clinically the lesion was thought to be a lipoma. A magnetic resonance imaging scan showed a well-defined 5-cm diameter tumour within the sartorius muscle. The margins of the tumour merged with the adjacent muscle but no extension into surrounding adipose tissue was identified. Core biopsies of the tumour measuring up to 15 mm in length were taken and sent for histopathological examination in consultation with two of the authors ( SWM and AAP) . The tumour was locally excised 1 month later. At operation, a 7´5´4-cm circumscribed, grey– tan mass was found within the sartorius muscle and was shelled out. Subsequently a wide local excision was performed. The patient’s post-operative course was complicated by pulmonary emboli. At 13 months follow-up she remains well with no evidence of recurrent or metastatic disease.

MATERIALS AND METHODS The specimens consisted of formalin-fixed tissue. Representative sections of the tumour were processed routinely and embedded in paraffin. Histological sections ( 5 m m) were cut and stained with haematoxylin and eosin. Formalin-fixed, paraffin-embedded tissue was also stained immunohistochemically using the avidin– biotin– alkaline phosphatase method. The antibodies used are presented in Table 1. Tissue for electron microscopy was fixed in glutaraldehyde buffered with sodium cacodylate, post-fixed with osmium tetroxide and en bloc stained with uranyl acetate. Dehydration was performed through graded solutions of alcohol with final

ISSN 0031–3025 printed/ISSN 1465– 3931 online/01/010101 – 07 © 2001 Royal College of Pathologists of Australasia DOI: 10/1080 /00313020120034984

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TABLE 1

Source and dilution of antibodies

Antibody Smooth muscle actin ( sma) Desmin CD 34 CD57 ( Leu–7) S–100 protein Epithelial membrane antigen ( EMA) Cam 5.2 AE1/AE3 Neurone specific enolase ( NSE) Vimentin Chromogranin Synaptophysin Neurofilament protein ( NFP) CD45 ( leucocyte common antigen) CD3 CD45RO ( UCHL–1) CD20 ( L26) CD79a CD68

Dilution

Source

1:100 1:100 1:50 1:50 1:500 1:100 1:100 1:100 1:200 1:100 1:200 1:250 1:100 1:100 1:100 1:100 1:100 1:100 1:200

Dako Dako Dako Novocastra Dako Dako Novocastra Dako Dako Dako Dako Dako Dako Dako Dako Dako Dako Dako Dako

embedding in Spurr’s resin. Epon sections ( 1-m m thick) were stained with toluidine blue and were examined by light microscopy. Representative areas were thin sectioned, stained with uranyl acetate and lead citrate and examined in a Philips EM 410LS electron microscope.

RESULTS Both the core biopsies and subsequent excision specimen showed similar histopathological features. No tumour was found in the wide local excision specimen. Macroscopic features Grossly, the tumour was well circumscribed and the cut surface had a vaguely whorled pale grey appearance (Fig. 1). No macroscopic areas of necrosis, haemorrhage, cystic degeneration or cartilaginous or osseous metaplasia were present. Microscopic findings A thin pseudocapsule of compressed fibrous tissue surrounded the tumour. Focally the tumour infiltrated through this pseudocapsule into a small fragment of attached adipose tissue. The tumour consisted of fibrous tissue of variable architecture and cellularity containing scattered large so-called collagen rosettes ( Fig. 2). The spindled fibrous stroma showed distinct hypercellular and hypocellular areas which tended to merge together. The hypercellular areas were composed of plump spindle-shaped cells in fascicles and vague storiform arrangements. Here the nuclei had coarse clumped chromatin with moderate hyperchromasia and mitotic figures were increased, focally numbering up to three mitoses per 10 high-power fields. These hypercellular areas merged with loose myxoid areas where mitoses were rare and the cells were more attenuated, being widely separated by pale myxoid material which included scattered wavy collagen fibres. Focal prominent stromal hyalinisation was also present. Thin walled vessels were dispersed throughout the

Fig. 1 The excision specimen showed a circumscribed tumour with a whorled pale grey cut surface reminiscent of a uterine leiomyoma. There is a thin fibrous pseudocapsule .

tumour, and in some areas had a haemangiopericytic-type pattern. There was a tendency towards perivascular hypercellularity of the tumour in the myxoid areas ( Fig. 3). The collagen rosettes were dispersed throughout the tumour but showed a tendency to cluster together. Some of the rosettes had a serpiginous outline and others coalesced. Individual rosettes were up to 800 m m in diameter and consisted of a basic structure of a central hyalinised collagenous core, in which the fibres were arranged radially, surrounded by a cuff of plump fibrohistiocytic cells and admixed mononuclear lymphoid cells. The fibrohistiocytic cells had vesicular chromatin and there were occasional intranuclear cytoplasmic pseudoinclusions, a feature also noted in occasional cells in the stromal component of the tumour. The cuffs ranged from three to seven cells in thickness and the peripheral fibrohistiocytic cells tended to merge with the surrounding fibroblastic cells of the stromal

Fig. 2 Photomicrograph showing spindled fibrous stroma within which are scattered so-called collagen rosettes. These consist of a central hyalinised collagen core which is surrounded by a more cellular mantle of cells ( H & E, original magnification, ´40).

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Fig. 3 The spindled stroma showed areas of hypo- and hypercellularit y including areas of perivascular hypercellularity as seen in low-grade fibromyxoid sarcoma ( H & E, original magnification, ´200 ).

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component. Scattered fibrohistiocytic and lymphoid cells were scattered through the collagenous cores. The rosettes appeared to have a spectrum of appearances with the central collagenous cores ranging from those with little collagen and numerous cells to others which were composed almost entirely of hyalinised collagen devoid of a significant cellular component ( Fig. 4).

Immunohistochemical findings Both the spindled cells and the cells within the collagenous rosettes were vimentin positive. In addition, some of the spindled cells expressed smooth muscle actin but were negative for desmin, CD68, CD34, S–100 protein, AE1/ AE3, Cam5.2, EMA, NSE, CD57, chromogranin, synaptophysin and NFP. Positive staining for CD68 was present in the fibrohistiocytic cells at the periphery of the rosettes. There was focal weak staining for S–100 protein, NSE and CD57 in the cells within the core and sometimes around the margin of the collagenous rosettes but all other markers tested were negative. The small mononuclear lymphoid cells within the cellular cuffs of the collagenous rosettes were positive for CD45, CD3 and CD45RO and were negative for CD20 and CD79a.

Ultrastructural features The spindled stromal areas of the tumour showed variable cellularity ranging from highly cellular intersecting fascicles of spindle cells separated by collagen fibrils (Fig. 5), to more sparsely cellular areas in an amorphous matrix containing occasional groups of collagen fibrils, myxoid substance and strands of basement membrane-like material ( Fig. 6). The fibroblastic tumour cells were mostly spindle shaped with bipolar processes which were more attenuated in the myxoid areas. The nuclei were ovoid to elongated with a relatively smooth surface contour and occasionally contained cytoplasmic pseudoinclusions. The cytoplasmic contents were often rather sparse, apart from intermediate filaments, variable amounts of branching rough-surfaced endoplasmic reticulum ( often at the cell periphery) and a moderate-sized Golgi zone. Lysosomes were rare. Occa-

( b)

( c)

Fig. 4 The collagen rosettes had a spectrum of appearances possibly related to their stage of development. Some contained numerous cells both within the hyalinised collagenous core and surrounding cuff ( a), most contained scattered cells within the cores and more cells in the cuff ( b) and others had only a few cells within the collagenous core and in the surrounding cuff ( c) ( H & E, original magnification, ´200 ).

sional cells contained membrane-bound intracytoplasmic collagen fibrils. The cores of the rosettes consisted of collagen and filamentous material in a low-density matrix which included occasional cells. In general, the collagen showed a normal banding pattern and fibril width, although so-called spiral or “frayed” collagen was seen in occasional rosettes. No

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Fig. 5 The spindled stromal cells showed ultrastructural features of fibroblasts. A rudimentary intercellular junction is present ( arrow ). Collagen fibrils are scattered between the tumour cells ( original magnification, ´12,000 ).

Fig. 6 Spindle cells with attenuated bipolar processes, widely separated by matrix containing sparse collagen fibrils and basement membrane-like material ( top of field) ( original magnification, ´6,250).

necrosis or mineralisation were seen. A mantle of plump cells, fibroblasts, scattered small lymphocytes and capillaries surrounded the cores. The nucleus of the former had an irregular surface contour with indentations, notching or occasional cytoplasmic pseudoinclusions and a small nucleolus ( Fig. 7). The bulky cytoplasm included prominent rough endoplasmic reticulum which often contained crystalline material with an average transverse periodicity of 18 nm within mildly dilated cisternae ( Fig. 8). Golgi zones were well developed. Lysosomes were mostly of primary type, but occasional angulated forms with fibrillar ( “Gaucher-like”) contents were also present (Fig. 8). Intermediate filaments formed prominent aggregates in many cells. Other organelles included moderately large mitochondria and occasional lipid droplets. Intracellular collagen was only rarely observed. Where in close contact with other cells of the same type, occasional rudimentary cell junctions were seen. No basal lamina was present around these cells.

similar case had been illustrated in a textbook of soft tumour pathology under the designation of “low grade malignant histiocytic fibrous histiocytoma”.9 Since Lane et al.’s description, a further nine cases have been documented in seven reports,2 – 8 six of which have appeared in the English language literature. The tumours have occurred about twice as frequently in males compared with females and the ages of those patients have ranged from 14 to 65 years. Most cases have involved the deep soft tissues, particularly the extremities, although single cases have involved the lungs,3 pararectal space,2 presacral area5 and lower abdomen.4 Most cases have presented as a slowly growing, painless mass. Recently the first metastasising case was reported and these authors suggested the tumour should be called “lowgrade fibrosarcoma with palisaded granulomalike bodies ( giant rosettes)”.7 Subsequently, a second metastasising case has been documented which was associated with long survival.8 In their original description Lane et al. noted that HSCTGR closely resembled low-grade fibromyxoid sarcoma, but was distinguished from the latter by the presence of rosette-like structures formed by neoplastic cells arranged circumferentially around a collagenous core.1 The spindled stromal areas of HSCTGR resemble LGFMS, being composed of spindle-shaped cells arranged in fascicles of variable thickness, ranging from broad and

DISCUSSION Hyalinising spindle cell tumour with giant rosettes is a lowgrade soft tissue sarcoma which was originally described in 1997 by Lane et al. in a report of 19 cases.1 Prior to this a

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Fig. 7 Tumour cell at the edge of a collagen rosette showing nuclear pseudoinclusions of cytoplasm ( original magnification, ´8,600).

Fig. 8 Detail of a cell at the edge of a rosette demonstrating banded inclusions within rough surfaced endoplasmic reticulum and a lysosome ( l) with fibrillary contents ( original magnification, ´45,750 ).

sweeping to thin and undulating, and are admixed with abundant collagen. These areas alternate with myxoid areas containing fewer cells and less collagen. Other features occasionally noted in LGFMS include a rich capillary network within the myxoid areas, a lymphoid infiltrate, increased perivascular cellularity and mild nuclear pleomorphism, 10,11 all of which were present in our case. However, the uncommon features of vascular invasion and ischaemic necrosis of occasional LGFMS have not been reported in HSTGR. Our finding of lymphoid cells admixed with the plumper stromal cells has not been previously reported in HSCTGR. These cells displayed a T-cell phenotype as indicated by the immunohistochemical stains. The T-cells were present at the periphery of each rosette but appeared to be more prominent in those rosettes which included more stromal cells. We suspect these rosettes are of a younger age than those with a more hypocellular appearance. The lymphoid cells may represent a reaction to the deposition of the collagen in these structures, or alternatively may be reacting to the stimulus inciting the collagenous deposition. Our case included focal areas of hypercellularity associated with an increased mitotic rate of up to three per 10 high-power fields, consistent with an intermediate grade fibrosarcoma. Although such an appearance has been associated with and noted in recurrences of LGFMS,10,11 it

is not known whether it has similar prognostic significance in HSCTGR. While one case in the original description of HSCTGR entity was associated with a similar appearance, the follow-up period was only 1 month.1 The presence of collagen rosettes has been used as the major feature distinguishing HSCTGR from LGFMS. In the series of LGFMS reported by Goodlad et al.,11 the authors commented on, but did not illustrate, a case which included amianthoid fibres. Amianthoid fibres are defined strictly as “a collagenous structure containing a few or many giant collagen fibrils”12 with normal banding periodicity, hence it is not possible to unequivocally diagnose collagen fibres as amianthoid by light microscopy alone. As ultrastructural features were not described in Goodlad et al.’s case of LGFMS with amianthoid fibres, we wondered whether it may therefore represent another case of HSTGR. However, personal communication with one of the authors ( C.D.M. Fletcher) suggests this is not the case. As stressed by Ludvikova et al.,2 the collagen fibrils of the rosettes in HSTGR have a normal width and periodicity and are therefore not amianthoid. Nielsen et al.6 confirmed this finding and, similarly, our case also demonstrated normal collagen, apart from occasional spiral fibrils. The latter are an abnormal form of collagen found in a variety of connective tissue disorders and occasional neoplasms.13

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There have been few cases of HSCTGR studied ultrastructurally.2,5– 7 Although most reports have suggested the tumour is composed of fibroblasts,2,6,7 one case has been considered to show schwannian differentiation.5 The ultrastructural features of the spindle cells in the present case were those of fibroblasts. No myofibroblastic or myoid elements were identified. The cells at the edges of the rosettes appeared to be a mixture of fibroblasts which were presumably synthesising excess collagen within the rosettes and others that had taken on fibrohistiocytic features. These latter cells may be involved in the reabsorption and breakdown of excess collagen. In their recent ultrastructural study of three cases of HSCTGR, Nielsen et al.6 illustrate material, which they term collagen fibres, within the rough endoplasmic reticulum of the plump stromal cells at the edge of the collagen rosettes. This finding was confirmed in our case, but we consider that, while this material no doubt represents crystallised secretory protein, its interpretation6 as collagen ( or, for that matter, procollagen) is uncertain. Banded material of similar appearance, mostly with a periodicity of 20– 22 nm, has been described in various other tumour and non-neoplastic cells, not all of which are involved in collagen synthesis.14 Intracellular membranebound collagen fibrils with the normal banding periodicity were identified in both the spindled stromal and rosette cells in our case but were quite rare. Whether these represent collagen that has developed within the cell or phagocytosed fibrils is a matter of conjecture. Intranuclear cytoplasmic pseudoinclusions have been noted in occasional cells at the periphery of the rosettes on light microscopic examination,1 but have not been documented as an ultrastructural finding previously; we identified pseudoinclusions both in the spindle cells within the fibrous stromal areas and in the plump rosette cells. Immunohistochemical studies on HSCTGR have yielded inconsistent results.1– 7 The most consistent findings have been vimentin positivity in both the spindle cell component and the cells within the rosettes, the latter of which have also sometimes expressed S–100, CD57 and NSE. The immunohistochemical profile of our case was similar. In addition, our case demonstrated positive staining for CD68 in the fibrohistiocytic cells at the periphery of the rosettes consistent with their ultrastructural appearance. This finding has not been previously reported in HSCTGR. Negative staining for CD68 documented in the initial description of this tumour1 may be a false negative, possibly related to the method of antigen retrieval used. In our case, some of the spindled stromal cells also expressed smooth muscle actin. The reason for the expression of sma, S–100 protein, CD57 and NSE remains unclear. We found no ultrastructural evidence of myofibroblastic or schwannian differentiation. The differential diagnosis of HSCTGR includes a number of benign and malignant soft tissue tumours. This may be a particular problem in limited biopsies such as core biopsies. As discussed above, HSCTGR is distinguished from LGFMS by the presence of giant collagen rosettes in the former. Besides lacking the signature rosettes, all variants of malignant fibrous histiocytoma are composed of cells much more pleomorphic than those present in HSTGR. Even on limited biopsy material, the low-grade myxofibrosarcoma can be distinguished from HSCTGR because the cells are more atypical and the stroma less collagenous. 15 Fibrosarcomas ( FS) are composed of

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fascicles of spindle-shaped cells typically in a herring bone pattern. The greater cellularity and mitotic activity and lack of rosettes, myxoid areas and cellular variability help distinguish these tumours from HSCTGR. Although the sclerosing epithelioid variant of FS contains areas of hyalinization, the cells are plumper and more epithelioid than HSCTGR and the rosettes and myxoid areas are lacking.16 Spindle cell liposarcoma may resemble HSCTGR but again lacks the rosettes and is more cellular with greater atypia and contains an atypical adipocytic component with lipoblasts.17 A number of tumours have occasionally been reported to contain collagen rosette-like structures and may enter the differential diagnosis of HSCTGR. These include benign and malignant peripheral nerve sheath tumours,18,19 leiomyomas, 20 osteosarcomas, 21 chondrosarcomas 2 and palisaded myofibroblastoma.22 Although the latter tumour has also been designated haemorrhagic spindle cell tumour with aminanthoid fibres,23 the collagen conforms to the width and banding pattern of normal collagen fibrils, and hence does not fulfil the ultrastructural criteria of amianthoid fibres. In most instances the differential diagnosis will be straightforward. The presence of a capsule, thick walled blood vessels, Antoni A and B areas, Verocay bodies and S–100 positivity in nerve sheath tumours, malignant osteoid production in osteosarcomas, cartilage containing atypical cells in chondrosarcomas and the typical lymph node location and admixture of spindle cells and extravasated red blood cells in palisaded myofibroblastoma are important features that help distinguish these tumours from HSCTGR. A number of other benign soft tissue tumours may also be considered in the differential diagnosis of HSCTGR. These include fibromatosis, myxoma,24 fibrous histocytoma, perineurioma,25,26 solitary fibrous tumour and the recently designated collagenous fibroma (also called desmoplastic fibroblastoma and stellate cell fibroma).27 The presence of typical areas of each of these tumours and the use of immunohistochemical stains, EMA for perineural tumours and CD34 for SFT, will aid in their distinction. The histological spectrum, biological behaviour and relationship of HSCTGR to other low-grade soft tissue sarcomas have yet to be fully defined. Suster, in a critical commentary on the report by Ludvikova et al.,28 raised the question: “Does the presence of giant rosette-like structures represent a valid basis for creation of a new entity–and, what is the biological significance, if any, of this finding?” He also raised the possibility that the positive immunohistochemical staining for S–100 protein, CD57 and NSE noted in the origin study of HSCTGR may represent an attempt at specific differentiation.28 As the ultrastructural features of these cells are basically that of altered fibroblasts and are similar to those of the stromal component, we conclude that the rosettes do not represent an attempt at specific differentiation and the expression of these immunohistochemical markers is an aberrant finding. Hopefully the documentation of further cases of HSCTGR will further clarify whether HSCTGR is a valid clinicopathological entity or simply a variant of LGFMS. AC KN OW LED GEM ENTS The authors wish to thank Dr Andrew Sanki for providing clinical and follow-up information, Dr Ian Katz who provided tissue from the excision specimen, and the staff of the immunohistochemistry laboratory of Royal Prince Alfred Hospital and the Central

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Sydney Area Health Service Electronmicroscope Unit of Concord Repatriation General Hospital for technical assistance. Address for correspondence: R.A.S., Department of Anatomical Pathology, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2050, Australia.

References 1. Lane KL, Shannon RJ, Weiss SW. Hyalinizing spindle cell tumour with giant rosettes. A distinctive tumour closely resembling low-grade fibromyxoid sarcoma. Am J Surg Pathol 1997; 21: 1481– 8. 2. Ludvikova M, Michal M, Zamecnik M. Hyalinizing spindle cell tumour with giant rosette-like structures. Pathol Res Pract 1998; 194: 577– 81. 3. Magro G, Fraggetta F, Manusia M, Mingrino A. Hyalinizing spindle cell tumour with giant rosettes: a previously undescribed lesion of the lung. ( letter to the editor). Am J Surg Pathol 1998; 22: 1431– 3. 4. Meister P, Babaryka I. Hyalinizing spindle cell tumour with giant rosettes. Case report with immunohistochemical characterization . Pathologe 1999; 20: 183– 8 ( abstract ). 5. de Pinieux G, Anract P, le Charpentier M, Carlioz A, Coindre JM, Vielh P et al. A case of hyalinizing spindle cell tumour with giant rosettes in the presacral region. Immunohistochemical and ultrastructural study. Ann Pathol 1998; 18: 488–91 ( abstract ) . 6. Nielsen GP, Selig MK, O’Connell JX, Keel SB, Dickersin GR, Rosenberg AE. Hyalinizing spindle cell tumour with giant rosettes. A report of three cases with ultrastructural analysis. Am J Surg Pathol 1999; 23: 1227– 32. 7. Woodruff JM, Antonescu CR, Erlandson RA, Boland PJ. Low-grade fibrosarcoma with palisaded granulomalike bodies ( giant rosettes). Report of a case that metastasized. Am J Surg Pathol 1999; 23: 1423– 8. 8. Farinha P, Olivereira P, Soares J. Metastasizing hyalinizing spindle cell tumour with giant rosettes: report of a case with long survival. Histopathology 2000; 36: 92–3. 9. Hajdu SI. Differential diagnosis of soft tissue and bone tumours. Philadelphia, PA: Lea & Febiger 1986: 280, 363. 10. Evans H. Low-grade fibromyxoid sarcoma. Am J Surg Pathol 1993; 17: 595– 600. 11. Goodlad JR, Mentzel T, Fletcher CDM. Low-grade fibromyxoid sarcoma: clinicopathological analysis of eleven new cases in support of a distinct entity. Histopathology 1995; 26: 229– 37. 12. Ghadially FN. As you like it, part 2: A critique and historical review of the electron microscopy literature. Ultrastruct Pathol 1999: 23: 1–17. 13. Hull MT, Warfel KA. Ultrastructure of abnormal collagen in human tumours. Ultrastruct Pathol 1986; 10: 293–301. 14. Sinclair-Smith CC, Emms M, Mills AE. Intracisternal paracrystalline serpigenous inclusions: a marker of disordered fibroblastic proliferation. Ultrastruct Pathol 1989: 13: 443–9. 15. Mentzel T, Calonje E, Wadden C, Camplejohn RS, Beham A, Smith

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ADDENDUM Flope et al.29 have recently published a large series of cases of LGFMS and HSCTGR and suggested that these two tumours are closely related entities and probably represent ends of a common spectrum rather than distinct entities. They also noted that the presence of focal areas of intermediate- to high-grade sarcoma does not portend a worse outcome in the short term.