Osteogenic sarcoma. Malignant fibrous histiocytoma subtype

A distinctly different entity from the now well-delineated malignant fibrous histiocytoma (MFH) of bone is the MFH histopathologic subtype of osteogenic sarcoma. Although uncommon, recently the authors have encountered six cases of this neoplasm, in each of which the soft tissue component was devoid of bone elements and was microscopically indistinguishable from MFH of bone or soft tissue. Neoplastic osteoid and woven bone were present in the osseous component of each tumor, however. Radiologically, the lesions generally were osteoblastic but focally osteolytic with features typical of osteogenic sarcoma. Pain was the most common presenting symptom. There was no age or sex predilection. Immunocytochemical staining showed strong positivity with alpha-1-antichymotrypsin within malignant bizarre giant cells and occasional neoplastic osteoblasts in five cases. The biological behavior followed a very aggressive course. Four of the six patients developed pulmonary metastases 6 to 12 months after initial surgery; one patient presented initially with pulmonary metastases. Adequate tumor sampling as well as optimal correlation with clinical and radiographic information are required to distinguish the MFH subtype of osteogenic sarcoma from MFH of bone, both being high-grade neoplasms, however.     

Current topics in the diagnosis and treatment of malignant fibrous histiocytoma

Malignant fibrous histiocytoma (MFH) is a tumor about which much remains unknown. The cell origin, molecular mechanism of pleomophism and mechanism of pleomorphic change in a cell undergoing malignant change have not been elucidated. MFH-like histological changes are observed in many bone and cartilage sarcomas, and some renal cell carcinomas and malignant lymphomas. These changes occur in many subtypes of sarcomas such as osteogenic sarcoma, chondrosarcoma, leiomyosarcoma, rhabdomyosarcoma, and liposarcoma. MFH has been regarded as one tumor classification from its special histopathological features. In clinical pathological studies these tumors are divided into low-grade fibrous tumors and fibrous histiocytic tumors. With the establishment of molecular biological diagnostic methods, MFH-like histological features can be seen in changes in cellular differentiation of many sarcomas. Patients with MFH often have repeated recurrences before a diagnosis is made, and the tumor is partially resected. Furthermore, distance metastasis develops and the prognosis is poor. The sensitivity of MFH to radiotherapy and chemotherapy is insufficient, and evidence is lacking for adjuvant treatment. Rescue following initial treatment failure is extremely difficult. Local control of 70% to 90% can be achieved if a correct diagnosis is made, and a curative wide resection or salvage wide resection are done early. For treatment of bone and soft tissue sarcoma, a correct diagnosis and initial treatment are extremely important. MFHs are rare tumors that occur in every part of the body. Many cases need to be accumulated in joint clinical studies across fields according to organ and specialty, and effective treatment method developed. We need to advance the standardization of treatment for MFH, and eliminate wrong initial treatment through the active provision of information.     

A case of primary malignant fibrous histiocytoma of the right lung

A malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma found in adults, but a primary MFH of the lung is very rare. A chest X-ray taken of a 73-year-old man revealed a massive lesion in the right upper lobe, and a subsequent right upper lobe lobectomy uncovered a soft, light yellow tumor in the right S3 area, measuring 2.8 x 2.6 x 1.7 cm. Histologically, the tumor manifested a typical storiform pattern of spindle-sharp cells with no sign of a myosarcoma. As no abnormal lesion was detected in the abdomen and extremities, the tumor was diagnosed as a primary MFH of the lung.     

Detection of a human sarcoma-associated antigen with monoclonal antibodies

Hybridoma cells were derived from a mouse immunized with plasma membranes prepared from the fresh tumor tissues of a patient with malignant fibrous histiocytoma (MFH), a soft tissue sarcoma. Supernatants from the resultant hybridoma clones were screened for positive antibody binding to tumor membranes and negative binding to membrane preparations of normal tissues using a solid-phase radioimmunoassay. Two distinct monoclonal IgG1 (kappa) antibodies, 19-14 and 19-24, were identified that showed identical patterns of reactivity with a large panel of tissues. Both antibodies displayed high levels of binding to membranes prepared from a majority of MFH and osteogenic sarcoma tumors tested. Moderate levels of binding were obtained with melanoma, colorectal carcinoma, and first-trimester fetal membranes. Weak or no significant binding was observed with membranes from a variety of autologous and allogeneic normal adult tissues. Antibody reactivities could be specifically removed by absorption with MFH and osteosarcoma membranes but not with adult muscle membranes. An electrophoretic analysis of immunoprecipitated membrane antigens indicated that antibodies 19-14 and 19-24 reacted with the same protein, a monomer with an approximate molecular weight of 102,000. The antigen was detected in membrane preparations of MFH, osteosarcoma, and first trimester fetus, but was not present in normal adult spleen. However, a small amount of antigen of molecular weight 107,000 was precipitated from a normal adult liver preparation, which suggests that related antigens may be present in low levels in some normal tissues. Antibodies 19-14 and 19-24 also specifically bound to intact, cultured MFH cells, indicating that the relevant antigens were expressed on the outer cell surface.     

Sarcoma of the nasal cavity and paranasal sinuses

The management of sarcoma of the nasalcavity and paranasal sinuses is a challenging problem because of natural behaviour and evasive diagnosis of the tumour and the anatomic location. Sarcoma is a malignant tumour of mesenchymal or mesodermal origin, and is therefore of lymphoid, fibrous, bony or cartilaginous origin. The incidence of sarcoma in cancers of the nose and paranasal sinuses is 5% (Lewis, 1969). The present paper surveys 11 cases of sarcoma of soft part, bony and cartilaginous origin, treated in our hospital during 1978–84.     

Clinico-morphological analysis of bone fibrosarcomas (a retrospective study)

The data on 35 cases of bone fibrosarcoma treated at the Center clinic in 1955-1982 are presented. A retrospective morphological investigation left diagnosis unchanged in 17 cases (48.6%). In 9 cases diagnosis was changed to fibrous histiocytoma of the bone, in 2--parostal sarcoma and in one case--"dedifferentiated" chondrosarcoma. In 6 cases, diagnosis could not be improved and neoplasms were identified as poly-morphocellular sarcoma. Clinically, a more favorable course and prognosis are distinguishing features of fibrosarcoma as compared with osteogenic sarcoma and malignant fibrous histiocytoma.     

食管原发性恶性纤维组织细胞瘤:3例报告及文献复习

We reported three cases of polypoid tumor of the esophagus, among them one case of sarcomatous tumor partly covered with superficial squamous cell carcinoma. The sarcoma was consisted of anaplastic spindle and pleomorphic tumor cells, which was similar to malignant fibrous histiocytoma (MFH) of the soft tissue. Diagnosis of the surgery resected speci-men was confirmed by histological, immunohistochemical and electron microscopic methods. Both diagnostic and differential diagnostic problems of primary MFH of the esophagus and world medical literatures were discussed.     

Immunohistochemical study of bone GLA protein in primary bone tumors.

METHODS. The immunoreactivity of bone GLA protein (BGP) in primary bone tumors, including osteosarcoma, chondrosarcoma, malignant fibrous histiocytoma of bone (MFH), and giant cell tumor of bone (GCT), was investigated with anti-BGP rabbit serum and peroxidase-antiperoxidase complex. RESULTS. As to intracellular localization, BGP antigenicity was detected in 33 of 35 cases of osteosarcoma and 12 of 25 cases of chondrosarcoma. However, there were no positive findings in all 15 cases of MFH or 20 cases of GCT. In chondrosarcoma, the frequency of positively stained cases increased according to pathologic grading (i.e., 3 of 14 cases of Grade 1, 7 of 9 cases of Grade 2, and 2 of 2 cases of Grade 3). Although the multinucleated cells in MFH or GCT were not immunostained, BGP antigenicity was observed in the multinucleated cells of osteosarcoma (12 of 15 cases). In the matrix of osteosarcoma, BGP immunoreactivity of the tumorous osteoid was observed in 28 of 32 cases. However, in the matrices of chondrosarcoma, MFH, and GCT, BGP immunoreactivity was not observed. CONCLUSION. These results suggest that the immunohistochemical study of BGP is useful for the differential diagnosis of bone tumors.     

Polypeptide growth factors and their interrelation with hormones in the blood plasma of patients with primary bone tumors]

A relationship between blood plasma levels of polypeptide growth factors and those of peptide and sex steroid hormones, as assayed radioimmunologically, was studied in 91 patients with bone tumors of various histology and 45 healthy donors. The levels of insulin-like growth factor (IGF-1) and somatotropic hormone were significantly higher in cases of chondrosarcoma and patients suffering osteogenic sarcoma in the late puberal period as compared to controls and cases of fibrous histiocytoma, giant-cell tumor, benign tumors and tumor-like lesions of the bone. The peak levels of IGF-1, somatotropic hormone and insulin were registered in osteogenic sarcoma patients who developed pulmonary metastases either in the course or after the completion of combined treatment. Somatostatin level was significantly lower in patients with osteogenic sarcoma aged 11-20 years as compared to healthy adolescents, the lowest level being observed in adolescents suffering osteogenic sarcoma with metastases to the lungs. No relationship was established between total testosterone level, on the one hand, and those of IGF-1 and epidermal growth factor, on the other. A reverse correlation was established between concentrations of IGF-1 and total estradiol. The role of polypeptide growth factor antagonists in combined treatment of bone sarcomas is discussed.     

Chemotherapy of malignant fibrous histiocytoma of bone. A report of five cases

Five patients with evaluable malignant fibrous histiocytoma (MFH) of bone (three with primary tumor and two with primary tumor and metastatic disease) were treated with preoperative chemotherapy including high dose methotrexate (HDMTX) with citrovorum factor rescue (CFR) as is used for patients with osteogenic sarcoma. All five patients demonstrated a clinical response to chemotherapy. Three of four patients who underwent surgery had complete responses and one patient had greater than 90% tumor necrosis as documented by histologic examination of the resected primary tumor. All four patients who underwent surgery following preoperative chemotherapy are surviving free of disease from one to six years from the start of treatment; chemotherapy was discontinued after six to 11 months in these patients. The median disease-free survival time is 31.5 months. This study demonstrates the effectiveness of chemotherapy in MFH of bone, and in particular the effectiveness of HDMTX with CFR which caused measurable responses in all patients while receiving this therapy as a single agent.     

1513例骨肿瘤及肿瘤样病变统计分析

 本文统计分析了骨肿瘤及肿瘤样病变1513例。其中良性骨肿瘤907例,占59.95%;恶性骨肿瘤450例,占29.74%;肿瘤样病变156例,占10.31%。三组病例都好发于11—40岁,男性较女性多见,为2。28:1。好发部位较多见于股骨、胫骨和肱骨,不同病变有不同的好发部位。良性骨肿瘤中以骨软骨瘤最多见,其次为骨巨细胞瘤。恶性骨肿瘤中以骨肉瘤最多见,其余依次为软骨肉瘤、转移癌、尤文氏瘤、骨髓瘤、骨纤维肉瘤、巨细胞瘤、脊索瘤、皮质旁骨肉瘤、网织细胞肉瘤。骨的肿瘤样病变包括嗜伊红性肉芽肿、骨纤维异常增殖症,弧立性骨囊肿和动脉瘤样骨囊肿。     

Malignant fibrous histiocytoma: an analysis of 200 cases.

The clinicopathologic findings in 200 cases of malignant fibrous histiocytoma (MFH) with follow-up information are presented. This tumor occurred principally as a mass on an extremity (lower extremity 49%, upper extremity 19%) or in the abdominal cavity or retroperitoneum (16%) of adults (peak incidence 61-70 years of age). It typically involved deep fascia (19%) or skeletal muscle (59%) and only rarely was confined to the subcutis without fascial involvement (7%). The MFH had variable morphologic features and frequently showed transitions from areas having a highly ordered storiform pattern to less differentiated areas having a pleomorphic appearance. The rate of local recurrence of the tumor was 44%, and of metastasis, 42%. Metastasis was most frequently to the lung (82%) and lymph nodes (32%). Factors that influenced the rate of metastasis included depth, size, and inflammatory component of the tumor. Tumors that were small, superficially located, or had a prominent inflammatory component metastasized less frequently than larger, more deeply located tumors. In our experience the MFH is the most common soft tissue sarcoma of late adult life, and many tumors previously diagnosed as pleomorphic variants of liposarcoma, fibrosarcoma, or rhabdomyosarcoma are probably examples of MFH. Although the histogenesis of this neoplasm remains controversial, we feel it is best regarded as a primitive and pleomorphic sarcoma showing partial fibroblastic and histiocytic differentiation, as reflected by collagen production and occasional phagocytosis.     

纵隔原发性恶性纤维组织细胞瘤

为了研究原发性纵隔恶性纤维组织细胞瘤的临床病理特点。采用常规石蜡包埋ＨＥ 染色及免疫组织化学方法研究３例ＭＦＨ。３ 例ＭＦＨ 均位于中纵隔,肿瘤界限清楚有包膜或假包膜,术后无局部复发及转移,最长无瘤生存者已达９ ａ。纵隔原发ＭＦＨ的病理特点与软组织ＭＦＨ 相同,但局部复发率及转移率低,提示其预后好于软组织ＭＦＨ。     

Primary malignant fibrous histiocytoma of spleen with spontaneous rupture: a case report and literature review

Malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma that mainly occurs in the lower and upper extremities, trunk and retroperitoneum. However, primary MFH of the spleen is especially rare. Only 11 cases of splenic MFH have been reported in the English literature. In this report, we describe a 35-year-old man who was found to have a large accumulation of free fluid in the abdominal cavity and a tumor mass 6 cm in diameter with rupture within the spleen by the abdominal ultrasonography. A splenectomy was performed and the histological diagnosis was malignant fibrous histiocytoma. The patient died 7 months after the operation as a result of generalized metastasis. Compared with the 11 previously documented patients of splenic MFH, our patient is the youngest and the first case with spontaneous rupture, which makes our case exceedingly rare. A literature review of primary MFH of spleen is also provided.     

Unusual hematogenous brain metastasis in malignant fibrous histiocytoma of the maxillary sinus

Malignant fibrous histocytoma (MFH) of the maxillary sinus is believed to be a rare form of soft tissue sarcoma with a low frequency of distant metastasis. In this study, we provide a histological documentation of the hematogenous spread of MFH to the brain and report a case of maxillary sinus MFH with unusual metastasis to the brain. To our knowledge, this is the first case of a direct histological diagnosis of maxillary sinus MFH with brain metastasis via a hematogenous route.     

Osteogenic sarcoma of bones and soft tissues in older persons. A clinicopathologic analysis of 117 patients older than 60 years

Since 1930, 117 patients with well-documented osteogenic sarcoma of the skeleton and the soft tissues occurring in patients older than 60 years have been diagnosed and treated at Memorial Hospital for Cancer and Allied Diseases. This number represents approximately 10% of all osteogenic sarcomas treated at this Medical Center. Slightly more men than women (68 versus 49, respectively) were affected, with a mean and a median age of 68 and 66 years, respectively, ranging from 60 to 86 years of age. One hundred one lesions occurred in the skeleton and 16 in extraosseous sites. In contrast to osteogenic sarcoma in children and adolescents, where more than half of the tumors arise in the fastest-growing bony sites around the knee, this region was involved in only 14.5% of the older patients. In this latter age group, the axial skeleton was the most commonly affected (27%), in addition to the craniofacial bones (13%) and extraskeletal sites (11%). Contrary to expectations, the lytic destructive skeletal lesions were three times more common than any other radiographic presentation, with the fibrous (38%), the osteoblastic (25%), and the cartilaginous (17%) sarcoma variants predominating over all others on histologic examination. Whereas 97% of osteogenic sarcomas occurring in patients younger than 21 years arise anew, without any pre-existent osseous disease, in this study's older population, sarcomas were more frequently (56%) secondary to other bony conditions, such as Paget's disease, or followed irradiation. Five-year survival estimates were strongly dependent on whether the patients had primary de novo osteogenic sarcomas (37%) or whether the sarcomas arose secondary to other skeletal conditions (7.5%). There are no significant survival differences between patients treated before or after 1974, when adjuvant and neoadjuvant chemotherapy started to make its positive impact in the treatment of osteogenic sarcoma in children and adolescents.     

Malignant fibrous histiocytoma: a proposed cellular origin and identification of its characterizing gene transcripts

Although malignant fibrous histiocytoma (MFH) is one of the most diffuse and highly aggressive tumors among soft tissue sarcomas in adults, it is poorly characterized from the molecular point of view. The overt lack of expression of phenotypic markers in MFH cells and the hypothesis that MFH may originate from transformed multipotent stem/progenitor cells with mesenchymal features has led us to investigate this notion and search for 'MFH-specific' genes. To address this problem, we have undertaken a differential display-based three-pair comparative mRNA profiling of bone-marrow derived mesenchymal stem cells (MSC) and cells isolated by primary MFH, leiomyosarcoma and smooth muscle cells, fibrosarcoma and dermal fibroblasts. This approach highlighted pair-wise analogies in gene expression patterns between matched tumor and healthy cells and yielded direct access to 43 genes differentially expressed between MSC and MFH cells. Eleven of the identified genes were selected for comparative evaluation of their expression levels in other sarcoma types, as well as potential markers for the detection of circulating tumor cells. Several of these genes defined the stem/progenitor versus MFH cell and some of them have the potential to be exploited for disclosure of circulating sarcoma cells. The striking similarity in the gene expression patterns observed in the two cell types was further corroborated by a remarkable similarity in the cell phenotypic markers that these cells expressed ex vivo. The findings open now the possibility to examine, also functionally, genes not previously known to be implicated in MFH development and strengthen the hypothesis that MFH originates from a mesenchymal progenitor cell.     

Postirradiation malignant fibrous histiocytoma

Three patients who were treated successfully with postoperative external radiation therapy for ovarian carcinoma, endometrial adenocarcinoma and bilateral retinoblastoma respectively developed years later malignant fibrous histiocytoma (MFH) within the irradiated field. MFH is a recently described soft tissue sarcoma known for its dual fibroblastic and histiocytic differentiation resulting in a pleomorphic histologic appearance.