Tumors with EWSR1-CREB1 and EWSR1-ATF1 fusions: the current status

EWSR1-CREB1 and EWSR1-ATF1 are gene fusions of which one or both have now been consistently described in 5 histopathologically and behaviorally diverse neoplasms: angiomatoid fibrous histiocytoma, conventional clear cell sarcoma (of tendons and aponeuroses), clear cell sarcoma-like tumor of the gastrointestinal tract, hyalinizing clear cell carcinoma of the salivary gland, and primary pulmonary myxoid sarcoma. Some of the tumors in this group have been described only recently, and others have been the subject of recent genetic insights contributing to their characterization. These neoplasms are all rare; yet, the increasing frequency with which EWSR1-CREB1 and EWSR1-ATF1 fusions are being described in separate entities is noteworthy. The additional molecular mechanisms by which tumors with such variable morphologic, immunohistochemical, and clinical phenotypes are generated are yet to be understood. We review the clinicopathologic and molecular features of this group of neoplasms unified by the presence of EWSR1-CREB1 and EWSR1-ATF1 genetic fusions.     

Primary pulmonary fibrous histiocytoma: report of three cases

Since 1969, fibrous histiocytoma has been recognized as a distinct entity. It occurs in benign and malignant forms. The authors describe two cases of the malignant pulmonary variety, which is considered very rare, and one case of benign pulmonary fibrous histiocytoma. All patients were treated successfully by local excision; there was no recurrence or metastases after a postoperative follow-up of 1 month, 8 years and 7 years respectively. The diagnosis is confirmed histologically according to criteria set forth by the World Health Organization. Treatment is by early complete surgical excision. Further study is needed to determine the merits of radiotherapy and chemotherapy postoperatively.     

Membranous nephropathy associated with angiomatoid fibrous histiocytoma in a pediatric patient

Background

Though membranous nephropathy is a much more common cause of nephrotic syndrome in the adult population, it accounts for only a small fraction of cases in pediatrics.

Case-Diagnosis/Treatment

We report a case of a 16-year-old boy with nephrotic syndrome due to membranous nephropathy in the setting of a rare tumor, angiomatoid fibrous histiocytoma. This patient’s nephrotic-range proteinuria completely resolved following resection of this tumor. Angiomatoid fibrous histiocytoma, while known to cause other paraneoplastic syndromes such as anemia, has never been reported to cause membranous nephropathy.

Conclusions

This case highlights a novel and treatable secondary cause of membranous nephropathy. Because secondary causes are more common in children than in adults, a high index of suspicion for other underlying pathology including malignancy should be considered. It also suggests that urinalysis may be a helpful screening tool in cases of angiomatoid fibrous histiocytoma.     

Malignant fibrous histiocytoma of the stomach: Report of two cases

(Received for publication on July 8, 1996; accepted on May 12, 1997)     

Retroperitoneal malignant fibrous histiocytoma. Report of two cases.

We present 2 cases of malignant fibrous histiocytoma (MFH) of the retroperitoneum. Only 12-14% of all MFH occur in the retroperitoneum. Both patients were operated with the diagnosis of a kidney tumor. The surgical exposure showed a tumor arising from the retroperitoneum, infiltrating or surrounding the kidney. We would like to emphasize that large tumors of the retroperitoneum which resemble kidney tumors can also arise from mesenchymal tissue.     

Evaluation of CD68 and other histiocytic antigens in angiomatoid malignant fibrous histiocytoma.

Immunohistochemistry for the histiocyte antigens CD68, L1, factor XIIIa, and S100 protein was performed on 19 cases of angiomatoid malignant fibrous histiocytoma (MFH) and for keratin, leukocyte common antigen, factor VIII-related antigen, muramidase, and desmin on six of these cases. Nine of 19 cases expressed the histiocyte differentiation antigen CD68, and in three cases expression was seen in greater than 90% of cells. Of the 19 cases studied, three contained rare S100-positive tumor cells, and two expressed factor XIIIa within tumor cells. In three of the six cases, rare desmin-positive tumor cells were identified. The neoplastic cells did not express the other antigens studied. CD68 was not detected in any of 12 cases of storiform-pleomorphic and myxoid MFH or in any of 24 cases of normal tissues or nonfibrohistiocytic mesenchymal tumors except for granular cell tumors. These results indicate that either the cells of angiomatoid MFH differentiate along lines of a tissue macrophage or alternatively, and perhaps more likely, are mesenchymal tumors with a phenotypic alteration, paralleling an enhanced capacity for phagocytosis and acquisition of lysosomes. In either event, the immunophenotype contrasts with conventional MFH and provides another independent set of observations in support of a separation of angiomatoid from conventional MFH.     

Clear Cell Carcinoma in the Oral Cavity with Three Novel Types of EWSR1-ATF1 Translocation: A Case Report

Clear cell carcinoma (CCC) is a rare epithelial malignant tumor of the salivary glands. It is characterized by tumor cells with clear cytoplasm, hyalinized stroma, and most importantly the fusion genes EWSR1-ATF1, EWSR1-CREM, and EWSR1-PLAG1. Break-apart FISH has been performed for multiple CCC cases, but direct sequencing analysis has been performed in relatively few. Herein, we report an interesting case of CCC harboring three EWSR1-ATF1 translocations: EWSR1 exon 8-ATF1 exon 4, EWSR1 exon 7-ATF1 exon 4, and EWSR1 exon 7-ATF1 exon 5. This case indicates the possibility of independent EWSR1-ATF1 gene translocations, and could provide insight into CCC tumorgenesis.     

Malignant fibrous histiocytoma of the mesentery: report of two cases and review of the literature

Malignant Fibrous Histiocytoma (MFH) rarely affects the abdomen and only a few cases arising in the mesentery have to date been discovered. In this paper, two cases of MFH of the mesentery are described and a review of the literature is reported.     

Inflammatory fibrous histiocytoma (? anthogranuloma). Report of two cases with ultrastructural observations in one.

Two cases of inflammatory fibrous histiocytoma are presented, one occupying the pleural space, and the other the retroperitoneum. One of the cases was studied with the electron microscope and confirmed the histiocytic and xanthomatous nature of the lesion. It is suggested that the term xanthogranuloma be replaced by fibrous histiocytoma, and that when a considerable inflammatory component is present in the stroma, a guarded prognosis be entertained. Ultrastructurally there are no distinctive features for the inflammatory variant of the fibrous histiocytoma.     

Malignant fibrous histiocytoma of the mediastinum and lung: a report of three cases

One case of primary malignant fibrous histiocytoma of the lung and two cases of that tumor in the mediastinum are reported. Primary malignant fibrous histiocytoma is rare in those areas, appearing more commonly in deep fascia and skeletal muscles of the extremities and torso and in the retroperitoneum. Most of the tumors contain both fibroblast-like and histiocyte-like cells; some contain pleomorphic giant cells and inflammatory cells. They are often confused with other sarcomas, and their true biologic potential is not clearly defined. Radiation appears to be a very useful adjunct to surgical therapy and was used in the cases reported here.     

A case of pulmonary metastasis of malignant fibrous histiocytoma with left atrial infiltration via the pulmonary vein

We report a case of a woman who at age 58 had an operation on the right femur for malignant fibrous histiocytoma (MFH). At age 63, a chest X-ray examination disclosed a tumor shadow, for which we suspected metastasis from the MFH. Chest computed tomography showed that the tumor had infiltrated to the left atrium via the pulmonary vein. We operated on the patient, first dividing the arterial supply to the lower lobe, and then opening the pericardium. We blocked the lower pulmonary vein and left atrium with a Cooley-Dera clamp and resected the tumor. The tumor was polypoid and had invaded the left atrium. Fifteen months after this lung surgery, the patient was diagnosed with a brain tumor, which was resected. Invasive primary lung cancer to the left atrium via the pulmonary vein is common, but metastasis from a sarcoma such as MFH to the left atrium via the pulmonary vein is extremely rare.     

Malignant fibrous histiocytoma of the perirenal tissue: report of a case--a statistical study of 58 cases of urological malignant fibrous histiocytoma in Japanese literature

A 78-year-old man was admitted in June 18, 1982 with a two-year history of general fatigue and loss of appetite. Physical examination revealed a child's head sized, firm, not tender, right upper quadrant mass which had an almost smooth surface and had respiratory displacement. Preoperative diagnosis was a hypovascular renal tumor presenting at the lower part of the right kidney. Right nephrectomy was performed on July 6, which displayed a specimen 1,300 g and 17 X 12 X 10 cm. The light yellow tumor appeared between the renal parenchyma and large fatty masses. The tumor was histologically diagnosed as storiform-pleomorphic malignant fibrous histiocytoma (MFH) and disclosed infiltration of both the fibrous renal capsule and adjacent perirenal fatty tissue. There was no invasion of the tumor into the renal parenchyma and the case was considered to arise from the fibrous renal capsule or the perirenal tissue. Although he had been treated with ifosfamide and adriamycin three times after operation and with immunotherapy of 3 g of PSK per day for about five months, he died three years and one month after operation. We reviewed 58 cases of MFH arising from the retroperitoneum and genitourinary tract (urological MFH) in the Japanese literature.     

Malignant fibrous histiocytoma. Clinicopathologic and ultrastructural study of 12 cases.

The clinical and pathologic findings of 12 cases of malignant fibrous histiocytoma of the soft tissues are presented. The mean age of the patients (eight males and four females) was 64 years, and there was a strong predilection for localization in the extremities (10 cases). The lesion is of rather low-grade malignancy, with metastases in only a minority of cases (three cases) but with nonetheless a marked tendency for local recurrence (nine cases). Histologically, the essential feature of the tumor is its biphasic composition with both histiocytic and fibroblastic components, the latter showing a characteristic storiform pattern. In addition, a variable number of xanthomatous cells and multinucleated giant cells were observed. Ultrastructural studies confirmed the presence of the aforementioned cells and in addition revealed a primitive mesenchymal cell. It is suggested that this cell may be a primitive histiocyte from which the two main cellular components of the tumor arise.