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.
FUS rearrangements in sclerosing epithelioid fibrosarcoma (SEFS)
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.
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