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Background
This is a rare soft tissue sarcoma usually located in the deep soft tissue in the groin or lower extremities. It is important to differentiate this tumor from other soft tissue tumors. Recently it has been hypothesized that this tumor probably forms a histologic spectrum with another rare tumor known as Hyalinizing Spindle Cell Tumor with Giant Rosettes.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION INCIDENCE Rare AGE RANGE-MEDIAN 6-65 years
Mean 35 years75% males
PATHOGENESIS CHARACTERIZATION CHROMOSOMAL ALTERATIONS-FUS-CREB3L2 or FUS-CREB3L1 Am J Dermatopathol. 2011 Apr;33(2):140-3.
FUS (16p11) Gene Rearrangement as Detected by Fluorescence In-Situ Hybridization in Cutaneous Low-Grade Fibromyxoid Sarcoma: A Potential Diagnostic Tool.
Patel RM, Downs-Kelly E, Dandekar MN, Fanburg-Smith JC, Billings SD, Tubbs RR, Goldblum JR.
Source
From the *Departments of Pathology; and †Dermatology, University of Michigan, Ann Arbor, MI; ‡Departments of Anatomic Pathology; and §Molecular Pathology, Cleveland Clinic, Cleveland, OH; and ¶Department of Orthopaedic and Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC.
AbstractAm J Dermatopathol. 2011 Apr;33(2):140-3. Abstract quote
Low-grade fibromyxoid sarcoma (LGFMS) is a rare, typically deep-seated soft tissue neoplasm with deceptively bland cytology and metastatic potential. A t(7;16)(q34;p11) translocation, yielding a FUS/CREB3L2 fusion gene, has been identified in approximately 80%-90% of deep soft tissue LGFMS. Cutaneous fibromyxoid neoplasms occur not infrequently; dermatopathologists rarely consider LGFMS in the differential diagnosis, as this lesion is uncommon in the skin.
We identified a group of superficial LGFMS and a spectrum of other cutaneous fibromyxoid neoplasms and performed fluorescence in situ hybridization (FISH) to assess the frequency of FUS rearrangement. FISH for the chromosomal rearrangement of FUS (16p11), using a dual-color, break-apart probe (Abbott Molecular/Vysis, Des Plaines, IL), was performed on formalin-fixed paraffin-embedded tissue sections from superficial LGFMS (n = 6), myxomas (n = 10), and myxofibrosarcoma/myxoid malignant fibrous histiocytomas (myxoid MFH) (n = 5). One hundred nonoverlapping tumor nuclei per case were evaluated for either fused (normal) or split (translocated) signals. Of the LGFMS, 4 of 6 (67%) showed a rearrangement of FUS (range: 72%-80% positive nuclei per 100 nuclei). The other neoplasms within the differential diagnosis were devoid of any rearrangement involving FUS (range: 0%-2% positive nuclei per 100 nuclei). Our observed frequency of FUS rearrangement in superficial LGFMS is consistent with those published in the literature for more deeply seated lesions.
When applied to suspicious superficial myxoid or fibromyxoid neoplasms, the FUS FISH probe in formalin-fixed paraffin-embedded tissue can be a useful ancillary technique for diagnosis of this uncommon and deceptively bland tumor.
*University Institute of Pathology, Lausanne, Switzerland
†Léon-Bérard Cancer Center, Lyon ‡Georges-François Leclerc Cancer Center, Dijon §Gustave Roussy Institute, Villejuif ∥Alexis Vautrin Cancer Center, Nancy ¶Claudius Regaud Cancer Center, Toulouse **Genetic Laboratory of Solid Tumors, CNRS UMR 6543 and Nice University Hospital, Nice ††Bergonié Institute and University “Victor Segalen”, Bordeaux, France ♯Jules Bordet Institute, Brussels, Belgium.
Low-grade fibromyxoid sarcomas (LGFMS) bear either the t(7,16) (q32-34;p11) or t(11,16) (p11;p11) translocations, resulting in FUS-CREB3L2 or FUS-CREB3L1 fusions, respectively. Heretofore, fusion transcripts were mainly detected in frozen tissues, using reverse transcription-polymerase chain reaction.
In this study, we aimed to develop a reliable method to detect these in paraffin-embedded tissues, and to examine the clinicopathologic characteristics of a series of translocation-positive LGFMS. Sixty-three neoplasms with typical morphologic features of LGFMS and 66 non-LGFMS tumors selected for their resemblance to LGFMS (LGFMS-like tumors) were examined. RNA of sufficient quality could be extracted from 111/129 (86%) cases (59 LGFMS, 52 non-LGFMS). Of all, 48/59 (sensitivity, 81%) LGFMS contained detectable transcripts (45 FUS-CREB3L2, 3 FUS-CREB3L1).
Most relevant clinicopathologic features of fusion-positive LGFMS included predominance in lower extremities (22/48; thigh: 13/48), deep situation (46/48), and occasional presence of unusual histologic features, for example, hypercellular areas (16/48), foci of epithelioid cells (13/48), and giant rosettes (6/48). Most tumors expressed EMA (41/45), at least focally, CD99 (38/41) and bcl-2 (36/41) while being essentially negative for CD34 (2/45), mdm2 (1/41), smooth muscle actin (1/45), S100 protein (0/46), desmin (0/44), h-caldesmon (0/42), keratins (0/44), and CD117 (0/40). Eleven presumed LGFMS were fusion negative. Of all, 7/52 non-LGMFS neoplasms contained FUS-CREB3L2 transcripts, of which 4 had been diagnosed as sclerosing epithelioid fibrosarcoma. In conclusion, FUS-CREB3L1/L2 fusion transcripts can be detected in paraffin-embedded LGFMS in a sensitive manner, using reverse transcription-polymerase chain reaction. Most fusion-positive LGFMS are EMA-positive and CD34/S100/smooth muscle actin negative.
The presence of epithelioid cells and fusion transcripts in both LGFMS and a subset of sclerosing epithelioid fibrosarcoma suggest that these neoplasms might be related.
- Matsuyama A,
- Hisaoka M,
- Shimajiri S,
- Hayashi T,
- Imamura T,
- Ishida T,
- Fukunaga M,
- Fukuhara T,
- Minato H,
- Nakajima T,
- Yonezawa S,
- Kuroda M,
- Yamasaki F,
- Toyoshima S,
- Hashimoto H.
*Department of Pathology and Oncology, School of Medicine, University of Occupational and Environmental Health daggerDepartment of Pathology, Kyushu Kousei Nenkin Hospital, Kitakyushu double daggerDepartment of Pathology, Nagasaki University Hospital, Nagasaki section signDepartment of Surgical Pathology, School of Medicine, Teikyo University Hospital parallelDepartment of Pathology, NTT MC Kanto Medical Center Division of Pathology, The Jikei Third Hospital, Tokyo #Department of Clinical Research and Laboratory Medicine, Hiroshima Prefectural Hospital, Hiroshima **Pathology Section, Kanazawa University Hospital, Kanazawa daggerdagger
Department of Tumor Pathology, Gunma University Graduate School of Medicine, Gunma double daggerdouble daggerDepartment of Human Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima section sign section signDepartment of Surgical Pathology, Fujita Health University Hospital, Toyoake parallel parallelDepartment of Pathology, Saga Prefectural Hospital Koseikan, Saga paragraph sign paragraph signDepartment of Pathology, Kitakyushu Municipal Medical Center, Kitakyushu, Japan.
A diagnosis of low-grade fibromyxoid sarcoma (LGFMS) remains problematic because of its bland-looking histologic features that can be potentially confused with other benign or low-grade fibromyxoid lesions. Recent cytogenetic and molecular analyses have shown that most LGFMSs have a characteristic chromosomal abnormality, t(7;16)(q33;p11), resulting in the FUS-CREB3L2 fusion gene. However, such assays have only rarely been used to analyze formalin-fixed, paraffin-embedded tumor samples.
In the present study, we conducted a reverse transcription-polymerase chain reaction assay to detect the FUS-CREB3L2 fusion transcripts using formalin-fixed, paraffin-embedded tumor tissue specimens from 16 LGFMSs including 3 cases with giant collagen rosettes. The primers were newly designed to specifically amplify most of the junctional regions of the FUS-CREB3L2 fusion gene transcripts previously reported. The FUS-CREB3L2 fusion gene transcripts were detected in 14/16 (88%) cases of LGFMS. A nucleotide sequence analysis of the PCR products revealed that different portions of the FUS exon 6 or 7 were fused with various sites of the CREB3L2 exon 5, resulting in 12 different nucleotide sequences. We also tested a primer set to detect the FUS-CREB3L1 fusion transcript, which is a rare variant of the gene fusion in LGFMS, although no PCR products were identified in any case. The FUS-CREB3L2 fusion transcripts were not detected in any of the 123 other soft-tissue tumors, including desmoid-type fibromatoses, myxofibrosarcomas, soft-tissue perineuriomas, and congenital or adult fibrosarcomas.
These data suggest that our reverse transcription-polymerase chain reaction assay is a reliable method to detect FUS-CREB3L2, which can thus help in accurately diagnosing LGFMS.
Low-grade fibromyxoid sarcoma and hyalinizing spindle cell tumor with giant rosettes share a common t(7;16)(q34;p11) translocation.
Reid R, de Silva MV, Paterson L, Ryan E, Fisher C.
University Department of Pathology/Scottish Bone Tumour Registry Western Infirmary, Glasgow, United Kingdom.
Am J Surg Pathol. 2003 Sep;27(9):1229-36. Abstract quote
Low-grade fibromyxoid sarcoma (LGFMS) is a rare metastasizing soft tissue tumor with deceptively bland histologic features. The hyalinizing spindle cell tumor with giant rosettes (HSCT) is thought to be a closely related tumor differing only by the presence of collagen rosettes.
We report the occurrence of a common t(7;16)(q34;p11) translocation in 2 cases of HSCT and 2 cases of LGFMS, thereby providing the first cytogenetic proof that LGFMS and HSCT are variants of the same entity. The tumors occurred in the thighs of 2 females and in the buttock and supraclavicular fossa of 2 males. One HSCT had a spectrum of unusual histologic features, including the presence of plump epithelioid cells with abundant cytoplasm and strands and nests of clear epithelioid cells separated by eosinophilic hyalinized stroma. Two cases showed a hitherto unreported, focal staining with epithelial membrane antigen, thus adding to the immunohistochemical profile of these tumors. LGFMS and HSCT probably have a wider spectrum of morphologic features than previously thought, the awareness of which will help pathologists to avoid diagnostic pitfalls.
Demonstration of the t(7;16)(q34;p11) translocation will help to diagnose difficult cases with unusual histologic features.Low grade fibromyxoid sarcoma. a further low-grade soft tissue malignancy characterized by a ring chromosome.
Mezzelani A, Sozzi G, Nessling M, Riva C, Della Torre G, Testi MA, Azzarelli A, Pierotti MA, Lichter P, Pilotti S.
Department of Pathology and Cytopathology, Istituto Nazionale Tumori, Via G. Venezian 1, 20133, Milan, Italy.
Cancer Genet Cytogenet 2000 Oct 15;122(2):144-8 Abstract quote
Supernumerary rings in the context of a simple karyotype characterize several low-grade malignant tumors of soft tissue and bone. Low-grade fibromyxoid sarcoma is an uncommon low-grade sarcoma, the cytogenetics of which has not yet been reported.
Here we describe the first molecular-cytogenetic characterization of a pulmonary metastasis of low-grade fibromyxoid sarcoma. The histology of the primary and recurrent tumors was consistent with the diagnosis of low-grade fibromyxoid sarcoma of the usual type, whereas the pulmonary metastasis was of the "giant rosettes" variant.
Cytogenetic analysis revealed a ring chromosome. Because gain of material of chromosomes 7 and 16 was detected by CGH, the ring chromosome is assumed to be composed of material from these respective chromosomes.
SPECIAL STAINS/
IMMUNO-PEROXIDASECHARACTERIZATION Vimentin Positive Negative S100, SMA, CK, EMA, CD34 A case of low-grade fibromyxoid sarcoma of the thigh.
Ugai K, Kizaki T, Morimoto K, Sashikata T.
Division of Pathobiology, College of Nursing Art and Science Hyogo, Akashi, Japan.
Pathol Int 1994 Oct-Nov;44(10-11):793-9 Abstract quote
A case of low-grade fibromyxoid sarcoma in the thigh of a 21 year old female is described.
The patient had a fist-sized well-defined mass in her left thigh that enlarged over a 6 month period. Histologically, the neoplasm showed contrasting fibrous and myxoid areas with a swirling growth pattern. Cellularity was low to moderate, and the stromal cells were benign looking without mitoses or nuclear pleomorphism. The tissue was not noticeably vascular. Some stromal cells were aggregated around the blood vessels.
The stromal cells were immunoreactive to vimentin, but were negative to keratin, desmin, alpha-smooth muscle actin, actin HHF35, S-100 protein, neuron-specific enolase, and epithelial membrane antigen. Ultrastructural examinations of the stromal cells revealed well-developed rough endoplasmic reticulum, mitochondria, pinocytotic vesicles, and numerous intermediate-sized filaments in the cytoplasm. These findings seem to indicate that the stromal cells were fibroblastic in origin. The occurrence of the tumor in a young adult, its location and its large, well defined borders together with the characteristics revealed through histological investigation, indicated that it was in fact what has been termed by Evans as a low-grade fibromyxoid sarcoma.
Low-grade fibromyxoid sarcoma.
Fukunaga M, Ushigome S, Fukunaga N.
Department of Pathology, Jikei University School of Medicine, Tokyo, Japan.
Virchows Arch 1996 Nov;429(4-5):301-3 Abstract quote
A low-grade fibromyxoid sarcoma arising in the thigh of a 16-year-old Japanese girl is described. The patient had a well-circumscribed mass measuring 3.5 cm in its greatest diameter within her left vastus medialis muscle and a 6-month history of pain.
Microscopically, the tumour was not encapsulated and filtrated into adjacent skeletal muscle. The tumour was characterized by poor to moderate cellularity, a proliferation of bland-appearing spindle tumour cells, and alternating fibrous and myxoid areas with a whorled pattern of the tumour cells. Neither cellular atypia nor mitotic figures were observed. There was no tumour necrosis.
Immunohistochemically, the tumour cells were diffusely and strongly positive for vimentin and desmin. Some cells contained alpha smooth muscle actin. They were uniformly negative for CAM5.2, epithelial membrane antigen, muscle-specific actin (HHF35), factor-VIII-related antigen, S-100 protein, neurofilament, CD34, and CD31. The tumour had a diploid DNA content with S-phase fractions of 6.6% by flow cytometry. The patient was alive with no evidence of disease 11 months after excision.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES Hyalinizing spindle cell tumor with giant rosettes: a distinctive tumor closely resembling low-grade fibromyxoid sarcoma.
Lane KL, Shannon RJ, Weiss SW.
Department of Pathology, University of Michigan Hospitals, Ann Arbor 48109-0054, USA
Am J Surg Pathol 1997 Dec;21(12):1481-8 Abstract quote
We report the findings of 19 cases of a previously undescribed spindle cell tumor of soft tissues that resembles a low-grade fibromyxoid sarcoma but contains distinctive rosettelike structures.
The tumors occurred principally as a painless, slowly growing, deeply situated mass of the proximal extremities in young to middle-aged adults (age range 14-65 years; mean 38). Although grossly circumscribed, the tumors had infiltrative borders microscopically and were composed of bland spindled cells situated in a hyalinized to myxoid stroma.
The most characteristic feature of the tumor was scattered large rosettelike structures that often merged with serpinginous areas of dense hyalinization. The rosettes consisted of a central collagen core surrounded by a rim of rounded cells morphologically and immunophenotypically different from the cells of the spindled stroma. These cells expressed a number of antigens, including S-100 protein, neuron-specific enolase, and leu 22, in contrast to the stroma, which usually lacked these antigens. Of the 12 patients with available follow-up information, one patient treated with simple excision clinically developed local recurrence of the tumor 20 months after initial biopsy. No other recurrences were reported during the limited follow-up period, and no patient developed metastatic disease. However, the favorable prognosis of the patients in our series to date may relate to the limited follow-up period (approximately 3 years), as well as initial treatment by wide excision in nearly half of the patients.
We regard the hyalinizing spindle cell tumor with giant rosettes as a distinctive type of low-grade fibroblastic tumor that with time may prove to behave similar to a low-grade fibromyxoid sarcoma and, hence, to represent an unusual variant thereof.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSIS Rare with some tumors showing low grade features and others showing hyalinizing spindle cell tumor with rosettes Low-grade fibromyxoid sarcoma. A report of two metastasizing neoplasms having a deceptively benign appearance.
Evans HL.
Department of Pathology, University of Texas M.D. Anderson Hospital, Houston 77030.
Am J Clin Pathol 1987 Nov;88(5):615-9 Abstract quote
Two deceptively benign-appearing, unclassifiable but very similar fibromyxoid sarcomas characterized histologically by bland, innocuous-appearing fibroblastic cells and a swirling, whorled growth pattern are presented.
The tumors both occurred in women in their late twenties and were located in the soft tissues of the scapular area and the axillary-chest wall area, respectively. Lung metastases developed in both cases; one patient died 94 months after excision of the primary neoplasm, whereas the other was alive at 82 months.
The designation "low-grade fibromyxoid sarcoma" is suggested for these tumors.
Low-grade fibromyxoid sarcoma. A report of 12 cases.
Evans HL.
Department of Pathology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Am J Surg Pathol 1993 Jun;17(6):595-600 Abstract quote
Twelve cases of low-grade fibromyxoid sarcoma are presented.
The patients' ages ranged from 6 to 51 years; all but three were between 26 and 46 years of age. The tumor was located in the thigh or inguinal area in four patients, in the shoulder area in three patients, and in the axilla-chest wall area, the perineum, the small bowel mesentery, the neck, and the buttock in one patient each. Tumor size (maximum dimension) varied from 3.5 to 15 cm in the nine cases in which it was known (median, 9.5 cm). Histologically, the neoplasms demonstrated contrasting fibrous and myxoid areas, a swirling, whorled growth pattern (at least in part), and bland, deceptively benign-appearing fibroblastic spindle cells; cellularity was low to moderate, mitotic figures were uncommon, and nuclear pleomorphism was usually absent or slight. Focal histologic findings in a minority of the cases included increased perivascular cellularity, moderate nuclear pleomorphism (more often in recurrent tumors), and, in myxoid areas, a rich capillary vascular network (vascularity was usually not prominent).
On follow-up, nine patients experienced local recurrence (from one to numerous times); recurrence was subsequently controlled in five cases but not in the remaining four. Distant metastasis occurred in seven cases, chiefly to the lungs, but two of these patients were rendered tumor-free (to latest follow-up) by excision of metastases. At latest follow-up, four patients had died of tumor at 8, 9, 31, and 31 1/2 years, respectively, three were alive with recurrent or metastatic tumor at 6 1/2, 12 1/2, and 50 years, respectively, and five were alive and tumor-free at 5 1/2, 10 1/2, 12, 22 1/2, and 44 years, respectively. One tumor, in the patient who died at 31 years, demonstrated "dedifferentiation" at 30 years. Low-grade fibromyxoid sarcoma is a distinctive, indolent soft-tissue sarcoma.
Low-grade fibromyxoid sarcoma: clinicopathologic case report with review of the literature.
Shidham VB, Ayala GE, Lahaniatis JE, Garcia FU.
Department of Surgical Pathology, Medical College of Wisconsin, Milwaukee 53226, USA.
Am J Clin Oncol 1999 Apr;22(2):150-5 Abstract quote
Low-grade fibromyxoid sarcoma is a rare, benign-appearing soft tissue neoplasm with an aggressive clinical course characterized by multiple local recurrences over several years, with ultimate spread to lung and occasionally to bone. Thus far, a total of 24 cases of low-grade fibromyxoid sarcoma have been reported in the literature.
The authors present an additional case that grossly and microscopically emphasizes a pronounced lobular pattern of contrasting areas of cellularity showing high proliferative activity, as demonstrated by a proliferation marker, Ki 67 with MIB-1, and hypocellular areas with prominent myxoid component and abundant collagen fibrils. There was predominance of delicate capillary-sized stromal vessels with collagenized walls in both cellular and myxoid areas. The unusual features in this case were osseous metaplasia, prominent intranuclear pseudoinclusions, DNA tetraploidy, and membrane-bound intracytoplasmic fat vacuoles. The immunoprofile and cytologic and ultrastructural features are described.
After the excision of the tumor, the patient was treated with radiotherapy without chemotherapy. The patient has been observed for 26 months and is alive without the evidence of disease. The postoperative follow-up with axial computed tomography at 24 months showed no evidence of disease, except postsurgical fibrotic changes.
Low-grade fibrosarcoma with palisaded granulomalike bodies (giant rosettes): report of a case that metastasized.
Woodruff JM, Antonescu CR, Erlandson RA, Boland PJ.
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA
Am J Surg Pathol 1999 Nov;23(11):1423-8 Abstract quote
"Hyalinizing spindle cell tumor with giant rosettes" is a tumor recently described by Lane et al. and thought by them possibly to represent a form of low-grade fibromyxoid sarcoma. Proof of a metastatic potential was lacking. We report an example of this tumor on the arm of a 28-year-old woman. The ultrastructural study of the tumor confirmed the fibroblastic nature of the lesion, which subsequently metastasized to the lung. Histologically, the giant rosettes simulated palisaded granulomas.
Our findings warrant classifying the tumor as a sarcoma, and we suggest the designation low-grade fibrosarcoma with palisaded granulomalike bodies (giant rosettes).
Low-grade fibromyxoid sarcoma.
van den Bossche MR, Van Mieghem H.
Department of Abdominal Surgery, Sint-Elisabeth Hospital, Brussels, Belgium.
Oncology 2000 Apr;58(3):207-9 Abstract quote
Described is a low-grade fibromyxoid sarcoma (LGFMS) of the abdominal wall muscles in a 38-year-old black woman. There was no evidence of metastatic disease. A 5.2-kg LGFMS - the largest case ever reported - was resected. One year after surgery, the patient is alive without any sign of local recurrence or distant metastasis.
Follow-up comprises abdominal and thoracic CT scans at 6-month intervals.
TREATMENT Excision
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Last Updated April 25, 2011
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