sclerosing epithelioid fibrosarcoma
Monday 27 April 2009
Case 38 : Sclerosing epithelioid fibrosarcoma
Definition: Sclerosing epithelioid fibrosarcoma is a rare variant of fibrosarcoma. It is a mesenchymal neoplasm composed of round to oval cells dispersed in a nestlike or cordlike distribution on a highly collagenous tissue background and is now recognized as a distinct clinical entity.
Sclerosing epithelioid fibrosarcoma is a rare and poorly
recognized but distinct variant of fibrosarcoma (ICD-O
code 88 10/3).
Sclerosing epithelioid fibrosarcoma can occur from adolescence to the older years.
It is localized mainly in soft tissues, but it also can arise as a primary tumor of bone, in the neural system, or in the ovary.
This tumour type shows a wide age range.
It shows a predilection for the lower limb/limb girdle.
These are aggressive lesions with a high rate of metastasis.
It is characterized by epithelioid cells with clear cytoplasm set in a dense collagenous matrix, sometimes associated focally with a more conventional fascicular growth pattern.
SEF is characterized histopathologically by low-grade tumor features: round or oval cells typically arranged in a cord- or nest-like distribution with a collagen background almost effacing the neoplastic cells.
Mitotic figures are either scant or absent, and necrosis is uncommon.
- hyalinizing tumors
- fibrosing fibrosarcomas
Sclerosing epithelioid fibrosarcoma, together with fibromyxoid sarcoma (FMS) and hyalinizing spindle cell tumor with giant rosettes (HSCTGR), belongs to the family of "fibrosing fibrosarcomas". Some data support the hypothesis that FMS and HSCTGR may represent the same entity and should be regarded as lowgrade sarcomas.
- Fibromyxoid sarcoma initially was described by Evans in 1987 and characterized as an indolent, low-grade fibromyxoid neoplasm arising in deep soft tissue with paradoxical aggressive features.
- In FMS, the local failure rate was 33%, metastases occurred in 42%, and 18% of patients were DOD. Local recurrence rates between 30% and 75% have been observed in several small series with followups ranging from 74% to 100%. In contrast, recurrence of metastasis ranged from 0% to 58%. Died of disease rates ranged from 14% and 33%.
Hyalinizing spindle cell tumor with giant rosettes
- Hyalinizing spindle cell tumor with giant rosettes is a similarly rare low-grade fibrosarcoma variant with a very low metastatic potential.
- Hyalinizing spindle cell tumor with giant rosettes was described for the first time by Lane et al. in 1997, who reported one local recurrence and no metastases in 12 of 19 patients with available followup. To 2010, six patients with pulmonary metastases have been described.
- Hyalinizing spindle cell tumors with giant rosettes and FMS have histologic low-grade tumor features and HSCTGR often manifests by an indolent clinical behavior. Based on a series of 56 patients with a mean followup of 3 years, local failure occurred in five (9%) and metastatic disease in three patients (6%; one HSCTGR, two FMS, but no metastases at diagnosis). One patient was DOD (2%).
- Diagnostically, the most challenging problem is to distinguish SEF from undifferentiated carcinoma, which might be impossible based purely on histology.
- Therefore, immunohistochemical analysis appears mandatory. Specific protein expression or genetic changes have not been described in SEF.
- The only immunostaining marker consistently reported positive (as in our patient) was vimentin, which is a general marker for soft tissue sarcomas and therefore not specific for SEF.
- Occasional positivity of rare tumor cells for other general markers of soft tissue sarcomas like EMA, S100, or cytokeratin are not useful for diagnosis of a patient with SEF, because these also may be positive in other tumors.
In contrast to HSCTGR and FMS, local recurrence in patients with SEF was seen in 40% and distant disease in 80%, and 67% of patients with local recurrence had distant metastasis develop.
Thus, SEF bears malignant potential and therefore appears as the most malignant variant in this family of low-grade fibrosarcomas followed by FMS.
Sclerosing epithelioid fibrosarcoma is a clinically aggressive but histologically low-grade sarcoma with unsatisfactory treatment results. It typically takes 33 months from the first onset of symptoms to diagnosis.
Sclerosing epithelioid fibrosarcoma has a predisposition for local recurrence
with metastasis primarily to the lung.
The role of systemic treatment remains unclear.
Consequently, SEF may be treated preferably by resection, including reexcision after intralesional excision.
Moreover, preoperative or postoperative radiation as used in other soft tissue sarcomas also should be considered.
Nota bene: Fibrosing fibrosarcomas
Low-grade fibromyxoid sarcoma (FMS) and hyalinizing spindle cell tumor with giant rosettes (HSCTGR) and SEF belongs to the family of fibrosing fibrosarcomas. Each of these tumors has distinctive clinical features; they share in common histologic components suggesting a close relationship.
Sclerosing epithelioid fibrosarcoma is characterized by rearrangement of 10p11 and amplification of 12q13 and 12q15, including the HMGIC gene, a transcriptional activator.
FUS-positive low-grade fibromyxoid sarcoma
- fibrosing-type fibrosarcomas
- fibromyxoid sarcoma (FMS)
- hyalinizing spindle cell tumor with giant rosettes (HSTGR)
- sclerosing epithelioid fibrosarcoma (SEF)
The response of SEF to treatment has not yet been fully characterized. Furthermore, the current low-grade classification might be misleading because it disregards the full malignant potential of SEF.
The resulting lack of familiarity of treating physicians with SEF might lead to misinterpretation of this rare entity. Thus, the malignant potential of SEF might be underestimated. The potential consequence of this is inadequate therapy leading to an unfavorable treatment result.
Sclerosing Epithelioid Fibrosarcoma-A Report of Two Cases with Cytogenetic Analysis of FUS Gene Rearrangement by FISH Technique. Rekhi B, Folpe AL, Deshmukh M, Jambhekar NA. Pathol Oncol Res. 2010 May 25. PMID: 20499220
Sclerosing epithelioid fibrosarcoma of the bone: a case report of high resistance to chemotherapy and a survey of the literature. Grunewald TG, von Luettichau I, Weirich G, Wawer A, Behrends U, Prodinger PM, Jundt G, Bielack SS, Gradinger R, Burdach S. Sarcoma. 2010;2010:431627. PMID: 20396630 [Free]
A primary sclerosing epithelioid fibrosarcoma of the pubic bone, with evidence of divergent epithelial differentiation. Wang G, Eyden B. Ultrastruct Pathol. 2010 Apr;34(2):99-104. PMID: 20192707
The evolving classification of soft tissue tumours: an update based on the new WHO classification. Fletcher CD. Histopathology. 2006 Jan;48(1):3-12. PMID: 16359532
Sclerosing epithelioid fibrosarcoma of the liver infiltrating the inferior vena cava. Tomimaru Y, Nagano H, Marubashi S, Kobayashi S, Eguchi H, Takeda Y, Tanemura M, Kitagawa T, Umeshita K, Hashimoto N, Yoshikawa H, Wakasa K, Doki Y, Mori M. World J Gastroenterol. 2009 Sep 7;15(33):4204-8. PMID: 19725160 [Free]
Multiple bone metastasis of sclerosing epithelioid fibrosarcoma 12 years after initial surgery-increasing ki-67 labeling index. Kanno A, Hatori M, Hosaka M, Kishimoto KN, Watanuki M, Watanabe M, Itoi E. Sarcoma. 2009;2009:953750. Epub 2009 Mar 29. PMID: 19343182 [Free]
Sclerosing epithelioid fibrosarcoma: case presentation and a systematic review. Ossendorf C, Studer GM, Bode B, Fuchs B. Clin Orthop Relat Res. 2008 Jun;466(6):1485-91. PMID: 18340502 [Free]
Sclerosing epithelioid fibrosarcoma of the cecum: a radiation-associated tumor in a previously unreported site. Frattini JC, Sosa JA, Carmack S, Robert ME. Arch Pathol Lab Med. 2007 Dec;131(12):1825-8. PMID: 18081443
Amplification of 12q13 and 12q15 sequences in a sclerosing epithelioid fibrosarcoma. Gisselsson D, Andreasson P, Meis-Kindblom JM, Kindblom LG, Mertens F, Mandahl N. Cancer Genet Cytogenet. 1998 Dec;107(2):102-6. PMID: 9844602
Abdulkader I, Cameselle-Teijeiro J, Fraga M, Caparrini A, Forteza J. Sclerosing epithelioid fibrosarcoma primary of the bone. Int J Surg Pathol. 2002;10:227–230.
Antonescu CR, Erlandson RA. Fibrosarcoma mimicking plasmacytoma or carcinoma: an ultrastructural study of 4 cases. Ultrastruct Pathol. 2001;25:31–37.
Arnould L, Jouannelle C, Mege F, Maillefert F, Fargeot P, Devillebichot C, Collin F. [Sclerosing epithelioid fibrosarcoma: a fibrosarcoma with a very long course.]. Ann Pathol. 2000;20:154–157.
Arya M, Garcia-Montes F, Patel HR, Emberton M, Mundy AR. A rare tumour in the pelvis presenting with lower urinary symptoms: ‘sclerosing epithelioid fibrosarcoma’. Eur J Surg Oncol. 2001;27:121–122.
Battiata AP, Casler J. Sclerosing epithelioid fibrosarcoma: a case report. Ann Otol Rhinol Laryngol. 2005;114:87–89.
Bezic J, Tomic S, Glavina-Durdov M, Alfirevic D, Samija I, Krizanac S. Sclerosing epitheloid fibrosarcoma: a report of two cases. Pathologica. 2004;96:433–435.
Bhattacharya B, Dilworth HP, Iacobuzio-Donahue C, Ricci F, Weber K, Furlong MA, Fisher C, Montgomery E. Nuclear betacatenin expression distinguishes deep fibromatosis from other benign and malignant fibroblastic and myofibroblastic lesions. Am J Surg Pathol. 2005;29:653–659.
Bilsky MH, Schefler AC, Sandberg DI, Dunkel IJ, Rosenblum MK. Sclerosing epithelioid fibrosarcomas involving the neuraxis: report of three cases. Neurosurgery. 2000;47:956–959.
Choi HY, Kwon NS, Lee SJ, Lee DK, Park K, Lee CW, Jo MK. Sclerosing epithelioid fibrosarcoma of the kidney. Korean K Urol. 2007;48:986–989.
Chow LT, Lui YH, Kumta SM, Allen PW. Primary sclerosing epithelioid fibrosarcoma of the sacrum: a case report and review of the literature. J Clin Pathol. 2004;57:90–94.
Christensen DR, Ramsamooj R, Gilbert TJ. Sclerosing epithelioid fibrosarcoma: short T2 on MR imaging. Skeletal Radiol. 1997; 26:619–621.
Decroisette C, Melloni B, Moldovan D, Gazaille V, Fermeaux V, Bertin F, Bonnaud F. [Pleural metastases of sclerosing epithelioid fibrosarcoma] [in French]. Rev Pneumol Clin. 2006;62:179–182.
Donner LR, Clawson K, Dobin SM. Sclerosing epithelioid fibrosarcoma: a cytogenetic, immunohistochemical, and ultrastructural study of an unusual histological variant. Cancer Genet Cytogenet. 2000;119:127–131.
Evans HL. Low-grade fibromyxoid sarcoma: a report of two metastasizing neoplasms having a deceptively benign appearance. Am J Clin Pathol. 1987;88:615–619.
Eyden BP, Manson C, Banerjee SS, Roberts IS, Harris M. Sclerosing epithelioid fibrosarcoma: a study of five cases emphasizing diagnostic criteria. Histopathology. 1998;33:354–360.
Folpe AL, Lane KL, Paull G, Weiss SW. Low-grade fibromyxoid
sarcoma and hyalinizing spindle cell tumor with giant rosettes: a
clinicopathologic study of 73 cases supporting their identity and
assessing the impact of high-grade areas. Am J Surg Pathol.
Franchi A, Massi D, Santucci M. Hyalinizing spindle cell tumor
with giant rosettes and low-grade fibromyxoid sarcoma: an immunohistochemical and ultrastructural comparative investigation.
Ultrastruct Pathol. 2003;27:349–355.
Frattini JC, Sosa JA, Carmack S, Robert ME. Sclerosing epithelioid
fibrosarcoma of the cecum: a radiation-associated tumor
in a previously unreported site. Arch Pathol Lab Med. 2007;131:
Garcia de Leo´n MA, Torres Coscoyuela M, Herna´ndez Sa´nchez
L. Sclerosing epithelioid fibrosarcoma: a complicated diagnosis.
Rev Orthop Traumatol. 2001;45:419–422.
Genevay M, Coindre JM, Guillou L. [Recent entities in soft tissue
tumor pathology. Part 2][in French]. Ann Pathol. 2003;23:
Gisselsson D, Andreasson P, Meis-Kindblom JM, Kindblom LG,
Mertens F, Mandahl N. Amplification of 12q13 and 12q15
sequences in a sclerosing epithelioid fibrosarcoma. Cancer Genet
Goodlad JR, Mentzel T, Fletcher CD. Low grade fibromyxoid
sarcoma: clinicopathological analysis of eleven new cases in
support of a distinct entity. Histopathology. 1995;26:229–237.
Guillou L, Benhattar J, Gengler C, Gallagher G, Ranchere-Vince
D, Collin F, Terrier P, Terrier-Lacombe MJ, Leroux A, Marques
B, Aubain Somerhausen Nde S, Keslair F, Pedeutour F, Coindre
JM. Translocation-positive low-grade fibromyxoid sarcoma:
clinicopathologic and molecular analysis of a series expanding
the morphologic spectrum and suggesting potential relationship
to sclerosing epithelioid fibrosarcoma: a study from the French
Sarcoma Group. Am J Surg Pathol. 2007;31:1387–1402.
Hansen T, Katenkamp K, Brodhun M, Katenkamp D. Low-grade
fibrosarcoma: report on 39 not otherwise specified cases and
comparison with defined low-grade fibrosarcoma types. Histopathology.
Hanson IM, Pearson JM, Eyden BP, Slawik S, Harris M.
Evidence of nerve sheath differentiation and high grade morphology
in sclerosing epithelioid fibrosarcoma. J Clin Pathol.
Hindermann W, Katenkamp D. [Sclerosing epithelioid fibrosarcoma][
in German]. Pathologe. 2003;24:103–108.
Hu WW, Lai RQ, Wang J, Feng XD, Li GM. [Sclerosing epithelioid
fibrosarcoma: a clinicopathologic study of eight cases][in
Chinese]. Zhonghua Bing Li Xue Za Zhi. 2004;33:337–341.
Jiao J, Rhodes DG, Burgess DJ. Multiple emulsion stability:
pressure balance and interfacial film strength. J Colloid Interface
Karaki S, Mochida J, Lee YH, Nishimura K, Tsutsumi Y. Lowgrade
malignant perineurioma of the paravertebral column,
transforming into a high-grade malignancy. Pathol Int. 1999;
Lane KL, Shannon RJ, Weiss SW. Hyalinizing spindle cell tumor
with giant rosettes: a distinctive tumor closely resembling lowgrade
fibromyxoid sarcoma. Am J Surg Pathol. 1997;21:1481–
Magro G, Fraggetta F, Manusia M, Mingrino A. Hyalinizing
spindle cell tumor with giant rosettes: a previously undescribed
lesion of the lung. Am J Surg Pathol. 1998;22:1431–1433.
Meis-Kindblom JM, Kindblom LG, Enzinger FM. Sclerosing
epithelioid fibrosarcoma: a variant of fibrosarcoma simulating
carcinoma. Am J Surg Pathol. 1995;19:979–993.
Miettinen M. From morphological to molecular diagnosis of soft
tissue tumors. Adv Exp Med Biol. 2006;587:99–113.
O’Sullivan MJ, Sirgi KE, Dehner LP. Low-grade fibrosarcoma
(hyalinizing spindle cell tumor with giant rosettes) with pulmonary
metastases at presentation: case report and review of the
literature. Int J Surg Pathol. 2002;10:211–216.
Oda Y, Takahira T, Kawaguchi K, Yamamoto H, Tamiya S,
Matsuda S, Tanaka K, Iwamoto Y, Tsuneyoshi M. Low-grade fibromyxoid sarcoma versus low-grade myxofibrosarcoma in the
extremities and trunk: a comparison of clinicopathological and
immunohistochemical features. Histopathology. 2004;45:29–38.
Ogose A, Kawashima H, Umezu H, Hotta T, Gu W, Yamagiwa
H, Ito T, Tohyama T, Nishijima H, Endo N. Sclerosing epithelioid
fibrosarcoma with der(10)t(10;17)(p11;q11). Cancer Genet
Perigny M, Dion N, Couture C, Lagace R. [Low grade
fibromyxoid sarcoma: a clinico-pathologic analysis of 7 cases]
[in French]. Ann Pathol. 2006;26:419–425.
Reid R, Barrett A, Hamblen DL. Sclerosing epithelioid fibrosarcoma.
Watanabe K, Suzuki T. Epithelioid fibrosarcoma of the ovary.
Virchows Arch. 2004;445:410–413.
Weiss SW, Goldblum JR. Enzinger and Weiss’ Soft Tissue
Tumors. 4th ed. St Louis MO: Mosby; 2001.
Woodruff JM, Antonescu CR, Erlandson RA, Boland PJ. Lowgrade
fibrosarcoma with palisaded granulomalike bodies (giant
rosettes): report of a case that metastasized. Am J Surg Pathol.