Extraskeletal myxoid chondrosarcomas do not show a chondrocytic phenotype.

Extraskeletal myxoid chondrosarcoma is a rare mesenchymal soft-tissue malignancy of putative chondrocytic differentiation. Occasional overt cartilage formation, positivity for S-100 protein, and ultrastructural analysis have supported this view. However, most extraskeletal myxoid chondrosarcomas do not show chondroid tissue formation, and S-100 protein is found much less commonly than has been reported. Both these observations cast doubt on the histogenetic classification of extraskeletal myxoid chondrosarcoma as a chondroblastic entity. Mostly using matrix proteins as markers of mesenchymal cell differentiation, we investigated the biochemical matrix composition and cellular phenotype of the tumor cells in representative specimens from 14 extraskeletal myxoid chondrosarcomas. In all but one tumor specimen, which showed histomorphologically overt cartilage formation, only occasional staining for the proteoglycan aggrecan was found. Specimens from two tumors showed presence of collagen type II, and none was positive for collagen type X. Instead, collagen types I, III, and VI were diffusely positive. Also, S-100 protein was largely absent. Our results suggest that the basic cellular phenotype of extraskeletal myxoid chondrosarcoma is not chondrocytic or prechondrocytic and that extraskeletal myxoid chondrosarcoma is not a chondrosarcomatous entity. Extraskeletal myxoid chondrosarcoma consists most likely of primitive mesenchymal cells with focal, multidirectional differentiation. Chondrocytic differentiation is an unusual facet in the spectrum of differentiation patterns exhibited by these lesions.     

Extraskeletal myxoid chondrosarcoma with neuroendocrine differentiation

We describe a case of extraskeletal myxoid chondrosarcoma with neuroendocrine differentiation. The tumor occurred in subcutaneous tissue of the right popliteal region in a 50-year-old man. It measured 5 cm in diameter, was well circumscribed, lobular and gelatinous, and lacked any necrosis or hemorrhage. Histologically, the tumor structure was a typical of extraskeletal myxoid chondrosarcoma. The lesion was lobulated and contained small to medium-sized chondroblast-like cells with ovoid hyperchromatic nuclei and without prominent nucleoli. The cells created cords and nests and showed focally a perivascular rosette-like arrangement. A few of the tumor cells were spindle shaped. The myxoid matrix was stained with alcian blue and this reaction was resistant to prior treatment with hyaluronidase. PAS-positive glycogen was found in the cytoplasm of some tumor cells. Immunohistochemically, the tumor cells were diffusely positive for neuron specific enolase, monoclonal synaptophysin and vimentin. Following antibodies gave negative results: desmin, actins, S-100 protein, pancytokeratin, epithelial membrane antigen, chromogranin A, neurofilament protein, myelinic basic protein, glial fibrillary acidic protein. The patient is well four years after the wide excision of tumor and radiotherapy. Neuroendocrine differentiation in extraskeletal myxoid chondrosarcoma was described at first by Chhieng et al. in 1998 (1). Our observation confirms this interesting finding.     

Chordomalike Soft Tissue Sarcoma in the Leg: A Light and Electron Microscopic and Immunohistochemical Study

A soft tissue tumor in the leg of a 67-year-old woman is described. This large tumor below the knee area infiltrated extensively the deep and superficial soft tissues but did not involve the bones. The tumor cells formed nodules resembling the architecture seen in chondroid tumors and chordoma. The tumor cells were often vacuolized, and there was extracellular myxoid matrix similar to that in chordoma or myxoid chondrosarcoma. Immunohistochemistry showed keratins 8 and 19, epithelial membrane antigen, and vimentin in most tumor cells, and there was also S-100 protein positivity in a number of tumor cells. Electron microscopy showed desmosomelike cell junctions and bundles of intermediate filaments resembling those seen in many epithelial neoplasms. Thus the tumor resembled chordoma in many respects. Because clinically no other primary tumor was found, this tumor is probably a chordomalike primary soft tissue sarcoma different from typical extraskeletal myxoid chondrosarcoma or chordoid sarcoma.     

Chordomalike Soft Tissue Sarcoma in the Leg: A Light and Electron Microscopic and Immunohistochemical Study

A soft tissue tumor in the leg of a 67-year-old woman is described. This large tumor below the knee area infiltrated extensively the deep and superficial soft tissues but did not involve the bones. The tumor cells formed nodules resembling the architecture seen in chondroid tumors and chordoma. The tumor cells were often vacuolized, and there was extracellular myxoid matrix similar to that in chordoma or myxoid chondrosarcoma. Immunohistochemistry showed keratins 8 and 19, epithelial membrane antigen, and vimentin in most tumor cells, and there was also S-100 protein positivity in a number of tumor cells. Electron microscopy showed desmosomelike cell junctions and bundles of intermediate filaments resembling those seen in many epithelial neoplasms. Thus the tumor resembled chordoma in many respects. Because clinically no other primary tumor was found, this tumor is probably a chordomalike primary soft tissue sarcoma different from typical extraskeletal myxoid chondrosarcoma or chordoid sarcoma.     

Dedifferentiated Chondrosarcoma: An Ultrastructural Study of Two Cases,with Immunocytochemical Correlations

The clinicopathologic features of two cases of dedifferentiated chondrosarcoma (DCS) are presented, in which anaplastic components showed the electron microscopic features of malignant fibrous histiocytoma, as well as immunoreactivity for alpha-1-antitrypsin and alpha-1-antichymotrypsin. Rare cells also displayed S100 protein in high-grade areas of the primary tumors, but a pulmonary metastasis lacked this determinant. These findings could be interpreted as reflecting a retained potential for primitive chondrogensis in primary DCS, which may be lost in its metastases. In all other respects, this tumor appears to assume the morphological and immunocytochemical attributes of a fibrohistiocytic neoplasm.     

Dedifferentiated Chondrosarcoma: An Ultrastructural Study of Two Cases, with Immunocytochemical Correlations

The clinicopathologic features of two cases of dedifferentiated chondrosarcoma (DCS) are presented, in which anaplastic components showed the electron microscopic features of malignant fibrous histiocytoma, as well as immunoreactivity for alpha-1-antitrypsin and alpha-1-antichymotrypsin. Rare cells also displayed S100 protein in high-grade areas of the primary tumors, but a pulmonary metastasis lacked this determinant. These findings could be interpreted as reflecting a retained potential for primitive chondrogensis in primary DCS, which may be lost in its metastases. In all other respects, this tumor appears to assume the morphological and immunocytochemical attributes of a fibrohistiocytic neoplasm.     

骨外黏液样软骨肉瘤2例报道及文献复习

目的探讨骨外黏液样软骨肉瘤的临床病理学特征。方法对2例骨外黏液样软骨肉瘤进行光镜观察及免疫组化染色标记,并通过相关文献复习,对病理诊断及鉴别诊断等指标进行分析。结果1例发生于足底,1例发生于乳腺。光镜下肿瘤呈分叶状,边界清。细胞为圆形及短梭形,成束状排列于黏液样基质中,局部可见围血管形成玫瑰花结样结构。部分肿瘤细胞异型性明显。免疫表型:vimentin、NSE、Syn均呈阳性;例1EMA灶性阳性,例2阴性;S-100蛋白、CgA及CK均阴性。结论骨外黏液样软骨肉瘤为罕见的软组织恶性肿瘤,具特异性的组织病理学特点。主要发生于四肢,少数可发生于实质器官,至今未有乳腺原发病例报道。部分肿瘤细胞可发生间变导致诊断困难,须与脊索瘤、骨内软骨肉瘤、化生性癌及黏液性肿瘤等鉴别。     

Extraskeletal myxoid chondrosarcoma: a light microscopic, immunohistochemical, ultrastructural and immuno-ultrastructural study indicating neuroendocrine differentiation

AIMS: Extraskeletal myxoid chondrosarcoma is a rare low-grade soft-tissue sarcoma with locally aggressive and metastasizing potential. Extraskeletal myxoid chondrosarcoma has distinctive clinical, light microscopic, immunophenotypic, cytogenetic and ultrastructural features. Evidence that extraskeletal myxoid chondrosarcoma often shows neuroendocrine features was first provided by Chhieng et al. on the basis of an immunohistochemical and ultrastructural study of seven cases. Our study aims to further confirm by immunohistochemistry and ultrastructural studies, including immunoelectron microscopy, that extraskeletal myxoid chondrosarcoma indeed may show neuroendocrine differentiation. METHODS AND RESULTS: Fifteen cases of extraskeletal myxoid chondrosarcoma and seven control cases of skeletal chondrosarcomas were studied. Extensive immunohistochemical analysis was performed in all cases and ultrastructural studies were done in 11 extraskeletal myxoid chondrosarcomas and three skeletal chondrosarcomas. Immunoelectron microscopy was performed on one case each of extraskeletal myxoid chondrosarcoma and skeletal chondrosarcoma. Extraskeletal myxoid chondrosarcomas expressed neuron-specific enolase (100%), synaptophysin (87%), S100 (50%), PGP 9.5 (40%), and epithelial membrane antigen (25%). Co-expression of synaptophysin and PGP 9.5 was observed in six tumours. Skeletal chondrosarcomas showed expression of S100 protein, vimentin and neuron-specific enolase in all cases. Synaptophysin, chromogranin and PGP 9.5 were not expressed in any skeletal chondrosarcoma case. Ultrastructurally, extraskeletal myxoid chondrosarcoma was characterized by distinct cords of cells immersed in a glycosaminoglycan-rich matrix. The cells were rich in mitochondria, had well-developed Golgi apparatus and there were numerous smooth vesicles. In three cases there were easily found 140-180 nm diameter membrane-bound dense-core granules in cell bodies and in processes, unrelated to the Golgi, compatible with neurosecretory granules. Fewer such granules were present in the remaining extraskeletal myxoid chondrosarcoma cases, three of which also contained intracisternal tubules typical of extraskeletal myxoid chondrosarcoma. The skeletal chondrosarcomas had scalloped cell surfaces, prominent rough endoplasmic reticulum focally distended with secretory product, and lacked neurosecretory granules. Intermediate filaments were prominent in both extraskeletal myxoid chondrosarcoma and skeletal chondrosarcomas. Immunoelectron microscopy showed synaptophysin expression in the extraskeletal myxoid chondrosarcoma but not in the skeletal chondrosarcoma case. CONCLUSIONS: This study confirms that a substantial proportion of extraskeletal myxoid chondrosarcomas show immunophenotypic and/or ultrastructural evidence of neuroendocrine differentiation, and are unlikely to be related to conventional skeletal chondrosarcomas.     

Extraskeletal myxoid chondrosarcoma of the nasopharynx

Extraskeletal myxoid chondrosarcoma is a rare but distinct entity with special clinicopathological, immunohistochemical, cytogenetical and outcome features. This tumor developed from soft tissues. A few cases have been reported in the head and neck in the literature. We report two new cases of extraskeletal myxoid chrondrosarcoma presenting in such an unusual site: one involved the left nasal cavity of a 67-year-old man and the second the sphenoidal sinus of a 71-year-old woman. The microscopic examination revealed nests of round small cells dispersed in a myxoid stroma. The myxoid material was stained with Alcian Blue with and without hyaluronidase application whereas no PAS staining was observed. The immunohistochemical staining showed reactivity with S-100 protein and vimentin in two cases and with EMA in one case. These results allowed us to exclude other differential diagnoses: soft tissue tumors with a myxoid stroma (myxoma, myxoid liposarcoma and myxofibrosarcoma). No staining with anti-KL1 allowed us to exclude chordoma. Curative surgery was not possible. Both patients were given radiotherapy and the tumor regressed in one.     

Soft tissue myoepithelioma,a rare tumor. A case report

Myoepithelioma of soft tissues is a rare and under-recognized tumor. We report a case of a myoepithelioma arising in the soft tissue of the wrist in a 37-year-old man. This 3cm, nodular, well circumscribed tumor consisted of a mixture of spindle and epithelioid cells in a fibrous or focally myxoid stroma. Nuclear atypia were mild and mitotic activity was 1 mitotic figure per 10 high-power fields. No tubular epithelial structure was found. The tumoral cells expressed cytokeratin (KL1) and S-100 protein. Smooth muscle actin and desmin were negative. The excision was complete. At 5 months, no recurrence was noted. Myoepithelioma of deep soft tissue has a predilection for extremity involvement. It has to be differentiated from extraskeletal myxoid chondrosarcoma, parachordoma and synovial sarcoma. Most of myoepitheliomas are benign. However, metastasis may occur in a minority of cases.     

Extraskeletal myxoid chondrosarcoma characterized by microtubular aggregates in the rough endoplasmic reticulum and tubulin immunoreactivity

A case is reported of a 66-year-old female with an extraskeletal myxoid chondrosarcoma which had originated in the lateral region of the right knee. The tumour tissue of the primary, recurrent, and metastatic deposits in the lungs was examined by electron microscopy and immunohistochemistry. Almost all the sarcoma cells in every tumour specimen harboured immunoreactivity to both alpha- and beta-subunits of S-100 protein. A large population of cells in the subcutaneous tumour at autopsy had numerous parallel arrays of microtubules within the rough endoplasmic reticulum in addition to the well-described ultrastructural features indicative of chondroblastic origin. These structures were present in round to polygonal, but not in fibroblastic, tumour cells. Tubulin immunoreactivity in the tumour cells showed the same tendency, being frequently positive in the large cells of the subcutaneous tumour but weakly positive in the fibroblastic and medium-sized cells of the recurrent and metastatic tumours. The parallel arrays of intracisternal microtubules therefore may be composed of tubulin protein, as in ordinary cytoplasmic microtubules.     

Malignant granular cell tumor of the esophagus. A case report with light and electron microscopic, histochemical, and immunohistochemical study

Malignant granular cell tumor of the esophagus found in a 70-year-old female was reported. Microscopically, the tumor showed a variety of the histology from compact proliferation of polygonal granular cells in pseudo-epitheliomatous pattern to plexiform proliferation of elongated granular and fibroblastic cells in neurofibromatous pattern, and the tumor cells frequently contained eosinophilic globules in the cytoplasm. Histochemically, argyrophilic neurofibrils in the stroma and argyrophilic cytoplasmic processes or grains were seen. Immunohistochemically, the tumor cells showed positive reaction with S-100 protein (S-100), but all reactions with myoglobin (MG), desmin (DM), fibronectin (FN), creatinine phosphokinase-mm (CPK), factor 8th-related antigen (F8RA), alpha-1-antitrypsin (A1AT), alpha-1-antichymotrypsin (A1ACT), keratin (KN), and carcinoembryonic antigen (CEA) were negative. Electron microscopy revealed that the tumor cells had typical lysosomal granules filled with proteinaceous electron dense materials and fine membrane-bound particles sized 15 to 45 nm resembling virus or neurosecretory granule.     

Recurrent breakpoints at 9q31 and 22q12.2 in extraskeletal myxoid chondrosarcoma

A cytogenetic study of extraskeletal myxoid chondrosarcoma cells revealed a complex t(9;22;15)(q31;q12.2;q25) as a primary chromosome change. A reciprocal translocation involving identical breakpoints on chromosomes #9 and #22 in this tumor has been reported in the literature. We suggest that the breakpoints 9q31 and 22.q12.2 are associated with extraskeletal myxoid chondrosarcoma, a comparatively rare tumor of adulthood.     

Extraskeletal myxoid chondrosarcoma: a clinicopathological study of six cases]

The clinicopathologic, ultrastructural, and immunohistochemical features of six cases of extraskeletal myxoid chondrosarcoma are described. Light microscopic examination disclosed a lobulated neoplasm consisting of cells that tended to be round or polygonal with plenty of eosinophilic cytoplasm. The tumor cells were arranged in strands and small nests surrounded by abundant myxoid extracellular matrix. Ultrastructurally, these tumor cells displayed the signs of chondroblastic differentiation. The cytoplasm contained numerous rough endoplasmic reticulum, mitochondria and scattered glycogen granules. The intercellular matrix showed amorphous material and electronic dense and fine granules. The tumor cells in all these six cases showed diffuse immunostaining for S-100 protein but were negative for keratin. The data obtained tend to support the chondroblastic origin of this tumor.     

Giant cell tumor of tendon sheath. An immunohistochemical study of 28 cases

An immunohistochemical study was carried out on 28 cases of giant cell tumor of tendon sheath. Although this tumor has been considered to be of histiocytic origin on the basis of light and electron microscopic findings, there remains some debate about the histogenesis of the tumor. To clarify this point, by using the PAP method, each surgical specimen was stained for alpha 1-antitrypsin, alpha 1-antichymotrypsin, lysozyme, ferritin, neuron specific enolase, and S-100 protein. Tumor cells in fifteen out of 28 cases were positively stained for alpha 1-antitrypsin, 19 for alpha 1-antichymotrypsin, 23 for lysozyme, 22 for ferritin, 22 for neuron specific enolase, but no case for S-100 protein. These results suggest that this tumor is composed of cells with histiocytic character. In addition, from the immunohistochemical point of view, at least two types of giant cells seem to exist in this disease.     

Non-X histiocytoma, similar to fibrous histiocytoma, in an infant

A case is presented of a female infant with an atypical histiocytoma. A gradually enlarging brown lesion was noted on the left side of the chest at the age of 2 weeks. Microscopic study of a biopsy revealed an ill-defined infiltration of spindle cells with indented nuclei. The tumor cells were positive for CD14, HLA-DR, lysozyme, alpha-1-antitrypsin and alpha-1-antichymotrypsin, and negative for CD1, CD3, CD8, CD10, CD19, CD68 and S-100 by immunohistochemis-try. Electron microscopy demonstrated no distinct Birbeck's granules, but aberrant granules were seen in a small number of cells. At 7 months of age, a nodule with similar histologic features was noted in the nuchal region, but was incompletely resected. The patient remains recurrence-free at 36 months of age. This case is thought to be a benign form of non-X histiocytoma.     

Extraskeletal myxoid chondrosarcoma: a histochemical and immunohistochemical study

In reviewing a large series of soft tissue sarcomas, nine cases of extraskeletal myxoid chondrosarcoma have been retrieved. These tumours, which principally presented in middle-aged adults, have been examined histochemically to determine the heteroglycan content of their myxoid matrix and immunohistochemically for the presence of S-100 protein. The principal mucopolysaccharides identified were chondroitin-4 and 6-sulphate and keratan sulphate; each of the tumours was S-100 positive. The relevance of these findings to the histogenesis and differential diagnosis of these uncommon neoplasms is discussed.     

Extraskeletal myxoid chondrosarcoma with neuroendocrine differentiation: a case report with fine-needle aspiration biopsy, histopathology, electron microscopy, and cytogenetics

Although extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma, its morphological, ultrastructural, and cytogenetical features have been well investigated. The authors describe a very rare variant of EMC with neuroendocrine differentiation. A 49-year-old woman presented with an 11-cm, deep-seated, lobulated soft tissue mass in the left thigh and a lymph node metastasis in the left groin. Analysis of fine-needle aspiration biopsy (FNAB) smears and a cellblock prepared from FNAB material, as well as histological sections of the excised tumor, showed a neoplasm composed of rounded and elongated cells arranged in strands and cords in a myxoid background matrix. The nuclei were rounded and often eccentric. The immunohistochemical phenotype was S-100 protein -, neuron specific enolase +, and chromogranin A+. Electron microscopy showed tumor cells harboring numerous mitochondria, partial basal lamina, and unequivocal neuroendocrine granules. Molecular genetic analysis revealed a TAF15/NR4A3 fusion, a characteristic rearrangement occurring in about 25% of cytogenetically investigated EMC. A few cases of EMC with neuroendocrine differentiation have been reported. However, the only previously described case with genetic information also displayed the t(9;17) instead of the more common t(9;22), suggesting an association between type of primary chromosome abnormality and neuroendocrine differentiation.     

Extraskeletal Myxoid Chondrosarcoma with Neuroendocrine Differentiation: A Case Report with Fine-Needle Aspiration Biopsy,Histopathology, Electron Microscopy,and Cytogenetics

Although extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma, its morphological, ultrastructural, and cytogenetical features have been well investigated. The authors describe a very rare variant of EMC with neuroendocrine differentiation. A 49-year-old woman presented with an 11-cm, deep-seated, lobulated soft tissue mass in the left thigh and a lymph node metastasis in the left groin. Analysis of fine-needle aspiration biopsy (FNAB) smears and a cellblock prepared from FNAB material, as well as histological sections of the excised tumor, showed a neoplasm composed of rounded and elongated cells arranged in strands and cords in a myxoid background matrix. The nuclei were rounded and often eccentric. The immunohistochemical phenotype was S-100 protein &#109, neuron specific enolase +, and chromogranin A+. Electron microscopy showed tumor cells harboring numerous mitochondria, partial basal lamina, and unequivocal neuroendocrine granules. Molecular genetic analysis revealed a TAF15/NR4A3 fusion, a characteristic rearrangement occurring in about 25% of cytogenetically investigated EMC. A few cases of EMC with neuroendocrine differentiation have been reported. However, the only previously described case with genetic information also displayed the t(9;17) instead of the more common t(9;22), suggesting an association between type of primary chromosome abnormality and neuroendocrine differentiation.     

Retroperitoneal extraskeletal myxoid chondrosarcoma

INTRODUCTION: Extraskeletal myxoid chondrosarcoma is a rare soft tissue tumor included by WHO in the group of tumors of uncertain differentiation because well formed cartilage is rarely seen in its setting; moreover some of the immunophenotype features of the tumor are still controversial. The reciprocal translocation t(9;22)(q22;q12) has recently been identified in many cases, and this chromosomal aberration is currently considered high specific of this tumor. CASE REPORT: We report the case of a 75-year-old female submitted to radical nephrectomy for a voluminous kidney tumor with radiological evidence of extrarenal extension. RESULTS: Grossly the lesion was set in the perirenal fat tissue. Histological examination revealed a malignant mesenchimal tumor with myxoid f eatures and areas of chondroid differentiation consistent with the diagnosis of extraskeletal myxoid chondrosarcoma. According with the diagnosis the tumor showed focal positivity to NSE by immunohistochemistry. DISCUSSION: Differentiated cartilage is seen in extraskeletal myxoid chondrosarcoma in about 30% of the cases. Our case is then interesting not only for the rare site of tumor location but also for the extension of chondroid differentiation areas found on histologic examination in the tumor setting. Moreover immunohistochemistry showed focal positivity of the neoplastic cells for NSE, according with recent studies demonstrating expression of some neural/neuroendocrine markers in extrascheletal myxoid chondrosarcoma.