Synovial Sarcoma: A Review and Update,with Emphasis on the Ultrastructural Characterization of the Nonglandular Component

Classic triphasic synovial sarcoma is usually not a problem in identification, whereas the monophasic spindle cell form continues to be a challenge in the differential diagnosis of spindle cell neoplasms. Most synovial sarcomas do not arise from a joint or tendon sheath, and by electron microscopy and immunohistochemistry they differ in several ways from nonneoplastic synovium. The cell of origin of synovial sarcoma is unknown, but certain features are rather consistently observed in the biphasic tumors and are useful in identifying monophasic samples. These features are apparent by immunohistochemistry and electron microscopy, both of which indicate early epithelial differentiation in the nonglandular component of the neoplasm. With immunohistochemistry, some of these cells stain for keratin. By electron microscopy, a gradient of differentiation from unclassifiable spindle cells to fully differentiated epithelial lining cells is demonstrable. A review and illustration of the ultrastructural characteristics in this spectrum of intermediate cells constitute the main emphasis of the article. The cells tend to be oval and polygonal; to be arranged in clusters surrounded by basal lamina or flocculent matrix; to have junctions, including tight junctions, and to form villuslike filopodia, true microvilli, canaliculi, and microlumina. This range of ultrastructural features is usually diagnostic of the nonglandular phase of synovial sarcoma.     

Ultrastructural Similarities and Differences of Synovial Sarcoma, Epithelioid Sarcoma, and Clear Cell Sarcoma of the Tendons and Aponeuroses

The ultrastructural features of synovial sarcoma, epithelioid sarcoma, and clear cell sarcoma of the tendons and aponeuroses were compared to identify differential markers and similarities. A continuous spectrum of modulation of morphologic features of synovial and epithelioid sarcomas was observed. Biphasic synovial sarcoma with pseudoglandular and stromal components represents one extreme of this spectrum. The gradual disappearance of the pseudoglands and the formation of nests of epithelial-like cells, which are characteristic of epithelioid sarcoma, were observed. The cells of clear cell sarcoma, as well as those of synovial and epithelioid sarcomas, form epithelial-like islands; however, the presence of premelanosomes in the former is a feature of neural crest derivatives.     

Synovial Sarcoma with Squamous Metaplasia

We report on a biphasic synovial sarcoma showing slight squamous cell differentiation of their epithelioid component under the light microscope. The electron microscopical examination revealed numerous tono-filaments arranged in dense bundles, which could be characterized as tonofibrils with keratohyalin granules in the same cells. The presence of such structures indicates the possibility of squamous metaplasia in biphasic synovial sarcoma.     

Ultrastructural Similarities and Differences of Synovial Sarcoma,Epithelioid Sarcoma,and Clear Cell Sarcoma of the Tendons and Aponeuroses

The ultrastructural features of synovial sarcoma, epithelioid sarcoma, and clear cell sarcoma of the tendons and aponeuroses were compared to identify differential markers and similarities. A continuous spectrum of modulation of morphologic features of synovial and epithelioid sarcomas was observed. Biphasic synovial sarcoma with pseudoglandular and stromal components represents one extreme of this spectrum. The gradual disappearance of the pseudoglands and the formation of nests of epithelial-like cells, which are characteristic of epithelioid sarcoma, were observed. The cells of clear cell sarcoma, as well as those of synovial and epithelioid sarcomas, form epithelial-like islands; however, the presence of premelanosomes in the former is a feature of neural crest derivatives.     

Synovial Sarcoma with Squamous Metaplasia

We report on a biphasic synovial sarcoma showing slight squamous cell differentiation of their epithelioid component under the light microscope. The electron microscopical examination revealed numerous tono-filaments arranged in dense bundles, which could be characterized as tonofibrils with keratohyalin granules in the same cells. The presence of such structures indicates the possibility of squamous metaplasia in biphasic synovial sarcoma.     

Ultrastructural Pathology of Glial Brain Tumors Revisited: A Review

The ultrastructural pathology of primary brain tumors of glial origin is examined. These are divided into two major groups. The first category comprises astrocytoma with the variants: fibrillary, protoplasmic, gemistocytic, and anaplastic. These are biologically aggressive tumors of a relatively high proliferative potential and include a substantial proportion of cases that transform into the most malignant secondary glioblastoma. The second category, comprised of rather benign tumors of a limited proliferative capacity and a reasonable good prognosis, includes such clinico-pathological entities as pilocytic astrocytoma, pleomorphic xanthoastrocytoma, and subependymal giant cell astrocytoma of tuberous sclerosis. There is no ultrastructural feature, however, which makes it possible to discriminate between major subclasses of astrocytes; but secondary glioblastoma cells, while still retaining the stigmata of neoplastic astrocytes, are characterized by nuclei that seem to be more indented, cisterns of the endoplastic reticulum may be distended, and intranuclear pseudoinclusions are frequently observed. Primary glioblastoma, which probably originates de novo, is characterized by poorly differentiated cells with a paucity of subcellular organelles and no obvious features of astrocytic origin. Granular cell tumor also belongs to neoplasms of astrocytic lineage and the hallmark of this entity is a cell characterized by the presence of numerous membrane-bound, electron-dense autophagic vacuoles. Its malignant analogue is the granular cell glioblastoma. Two subtypes of granular cell glioblastoma have been distinguished. The first is characterized by the presence of numerous granular, electron-dense bodies which correspond to autophagic vacuoles. The second type is characterized by numerous electron-dense, amorphous masses within cellular processes. These electron-dense inclusions are virtually indistinguishable from minute Rosenthal fibers. The pilocytic astrocytoma is virtually indistinguishable at the ultrastructural level from fibrillary astrocytomas but cells tend to be more elongated. Besides Rosenthal fibers, two types of distinctive structures are relatively common in pilocytic astrocytomas: eosinophilic hyaline droplets and round granular bodies, which are composed of large aggregates of electron-dense secondary lysosomes or small electron-dense bodies, respectively. Pleomorphic xanthoastrocytoma is characterized by astrocytes surrounded by basal membranes. It belongs to a peculiar category of astrocytic “desmoplastic” brain tumors occurring in younger patients, the common denominator for which is the presence of basal lamina. The last category in this group is subependymal giant cell astrocytoma, a tumor of bivalent (glial and neuronal) differentiation, the cells of which are characterized by the presence of peculiar crystalloids. The hallmark of oligodendroglioma is the presence of concentric arrays of membranes (so-called membrane laminations, whorls, or scrolls). A fragment of the cytoplasm sequestrated within a particular whorl may contain mitochondria, lysosomes, or abundant glycogen granules. Ependymomas are characterized by a florid picture dominated by the presence of microlumina, cilia with basal bodies (blepharoplasts), microvilli, and long, interdigitating intercellular junctions of the zonulae adherentiae type. Ganglioglioma, the last category covered by this review, is a mixed glio-neuronal tumor. While glial cells are indistinguishable from their counterparts encountered elsewhere (mostly pilocytic astrocytes), the ganglion cells are characterized by abundant intracytoplasmic dense-core vesicles, absence of intermediate filaments, and numerous microtubules. Occasionally a close apposition of ganglion cells and Rosenthal fibers is seen. Dense-core vesicles are pleomorphic and ranged in a diameter from small synaptic vesicles to large lysosome-like neurosecretory granules.     

Sarcoma and Look-Alikes: The Important Role of Ultrastructural Evaluation

Due to the variable light microscopic appearance of sarcomas, a large number of neoplasms may need to be considered in the differential diagnosis in some situations. In difficult cases, the surgical pathologist must approach the differential diagnosis using ancillary diagnostic techniques and should do so in an orderly fashion, recognizing that arriving at the correct diagnosis is without a doubt the most important goal. It is also imperative to take into account the expense and time that may be involved in arriving to the definitive diagnosis, which could influence how the workup is conducted. Therefore, the most reasonable route to address the differential diagnosis in order to make a final solid diagnostic assessment should be taken. Whether immunohistochemistry, electron microscopy, cytogenetics, and/or molecular diagnostics should be employed in a given case becomes the dilemma. In some instances a combination of the above-mentioned techniques is important not only to obtain an unequivocal diagnosis, but also to provide important additional information regarding prognosis and to facilitate the patient's management.     

Amianthoid Fibers in a Synovial Sarcoma and a Malignant Schwannoma

Amianthoid collagen fibers having typical collagen periodicity, but measuring up to 1000 nm in thickness, were observed in a synovial sarcoma of the leg and a malignant schwannoma of the orbit. Intracellular amianthoid fibers were present in the cytoplasm of many of the synovial sarcoma cells. The tumor cells in both lesions appeared to be actively synthesizing these unusual fibers.     

Amianthoid Fibers in a Synovial Sarcoma and a Malignant Schwannoma

Amianthoid collagen fibers having typical collagen periodicity, but measuring up to 1000 nm in thickness, were observed in a synovial sarcoma of the leg and a malignant schwannoma of the orbit. Intracellular amianthoid fibers were present in the cytoplasm of many of the synovial sarcoma cells. The tumor cells in both lesions appeared to be actively synthesizing these unusual fibers.     

Epithelioid Sarcoma: A Case Report with Ultrastructural Confirmation of Myofibroblastic Differentiation Based on Fibronexus Junctions

Epithelioid sarcoma is an uncommon but well-described malignancy, which is found predominantly in the soft tissues of the young and middle-aged, and which pursues an indolent to aggressive course. It shows a degree of both mesenchymal and epithelial differentiation. Myofibroblastic differentiation has been recorded in epithelioid sarcoma for some time, the evidence being based mainly on the presence of smooth-muscle-type myofilaments and, more recently, on α-smooth-muscle actin and muscle-specific actin immunostaining. Myofibroblastic differentiation based on the stricter criterion of the fibronectin fibril/fibronexus junction has not so far been demonstrated except for a single atypical case with spindle-cell morphology and a cytokeratin-negative immunophenotype. The authors describe a conventional epithelioid sarcoma showing myofibroblastic differentiation based on the presence of fibronectin fibrils and fibronexus junctions. The patient was a 35-year-old Chinese male with a tumor that initially developed on his left forefinger: it recurred, then metastasised first to the left arm and eventually to the scalp. Histologically, the tumors had the typical features of epithelioid sarcoma: by immunohistochemistry, cytokeratin, epithelial membrane antigen, and vimentin were positive. By electron microscopy, rough endoplasmic reticulum, intermediate filaments, peripheral myofilaments, and fibronexus junctions were observed. This is the first epithelioid sarcoma of conventional histological type to show myofibroblastic differentiation on the basis of the more stringent criterion of the fibronexus. The findings are discussed in relation to the unusually varied differentiation reported for this tumor.     

Idiopathic Fibrosing Alveolitis: A Review with Emphasis on Ultrastructural and Immunohistochemical Features

Fibrosing alveolitis is a usually chronic pulmonary disease affecting middle-aged men and women and causing progressive dyspnea. This review discusses the nosologic, etiologic, immunopathogenic, histologic, immunohistochemical and ultrastructural features of this condition. A hypothesis is presented suggesting microvascular damage as the primary pathologic change in cases associated with collagen vascular diseases and viral pneumonia.     

Idiopathic Fibrosing Alveolitis: A Review with Emphasis on Ultrastructural and Immunohistochemical Features

Fibrosing alveolitis is a usually chronic pulmonary disease affecting middle-aged men and women and causing progressive dyspnea. This review discusses the nosologic, etiologic, immunopathogenic, histologic, immunohistochemical and ultrastructural features of this condition. A hypothesis is presented suggesting microvascular damage as the primary pathologic change in cases associated with collagen vascular diseases and viral pneumonia.     

Intriguing Case: Primitive Pelvic Sarcoma Resembling Clear Cell Sarcoma of Kidney

Clear cell sarcoma of kidney (CCSK) is an aggressive childhood renal tumor of unknown histogenesis that has not been reported to occur outside the kidney. The article describes an extrarenal neoplasm arising in the pelvic soft tissues of a 13-year-old boy that was composed predominantly of uniform mesenchymal cells with optically clear cytoplasm supported by an arborizing network of small blood vessels, which was indistinguishable in appearance from CCSK. The electron microscopic findings, although nonspecific, were essentially identical to those of CCSK, with tumor cells displaying fine chromatin, electron-lucent cytoplasm, and intercellular collagen but no evidence of tissue-specific differentiation. Immunocytochemical studies showed positivity for vimentin but negative results for desmin, myoglobin, cytokeratin, epithelial membrane antigen, S-100 protein, neuron-specific enolase and factor VIII-related antigen. Tumor cells were also nonreactive with Ulex lectin. This unusual pelvic tumor and CCSK may both derive from primitive mesenchymal cells and may represent phenotypic but not necessarily histogenetic analogs.     

Human Osteogenic Sarcoma: Fine Structural Localization of Adenosine Triphosphatase

The localization of ATPases in 7 osteogenic sarcomas of osteoblastic, chondroblastic and fibroblastic type was investigated at the fine structural level using two types of substrates: one with lead as capturing ion and one with strontium (the latter presumed to reveal sites of Na⁺-K⁺-dependent transport ATPase).

Reaction product with the lead-ATP medium was located on the plasma membrane and the membranes bordering subjacent vesicles and vacuoles in all the various types of osteoblastlike and fibroblastlike cells and also in types 1 and 3 chon-droblastlike cells, and multinucleated giant cells believed to be neoplastic. Furthermore, deposits of reaction product were demonstrated in lysosome-like organelles in all the aforementioned cells. Except in the case of chondroblastlike cells, precipitates marking the localization of enzyme were confined to areas of the plasma membrane where adjacent cells were closely applied (the free surface lacked precipitates). In chondroblastlike cells the reaction product was usually deposited along the whole plasma membrane. Presence of L-Homoarginine or L-Tetramisole in the incubation medium in concentrations that have been shown to completely abolish alkaline phosphatase activity did not affect the occurrence of the reaction product with ATP as substrate indicating that the enzyme hydrolysing ATP was substrate-specific.

Reaction product marking sites of Na⁺-K⁺-dependent ATPase was confined to plasma membranes and lysosomes of cells in vessel walls.

The observations strengthen the notion obtained in studies on the localization of alkaline phosphatase, namely that osteoblastlike, chondroblastlike, and fibroblastlike cells in osteogenic sarcomas are histogenetically related to one another and to those multinucleated giant cells that presumably are of a neoplastic nature.     

Intriguing Case: Primitive Pelvic Sarcoma Resembling Clear Cell Sarcoma of Kidney

Clear cell sarcoma of kidney (CCSK) is an aggressive childhood renal tumor of unknown histogenesis that has not been reported to occur outside the kidney. The article describes an extrarenal neoplasm arising in the pelvic soft tissues of a 13-year-old boy that was composed predominantly of uniform mesenchymal cells with optically clear cytoplasm supported by an arborizing network of small blood vessels, which was indistinguishable in appearance from CCSK. The electron microscopic findings, although nonspecific, were essentially identical to those of CCSK, with tumor cells displaying fine chromatin, electron-lucent cytoplasm, and intercellular collagen but no evidence of tissue-specific differentiation. Immunocytochemical studies showed positivity for vimentin but negative results for desmin, myoglobin, cytokeratin, epithelial membrane antigen, S-100 protein, neuron-specific enolase and factor VIII-related antigen. Tumor cells were also nonreactive with Ulex lectin. This unusual pelvic tumor and CCSK may both derive from primitive mesenchymal cells and may represent phenotypic but not necessarily histogenetic analogs.     

Human Osteogenic Sarcoma: Fine Structural Localization of Adenosine Triphosphatase

The localization of ATPases in 7 osteogenic sarcomas of osteoblastic, chondroblastic and fibroblastic type was investigated at the fine structural level using two types of substrates: one with lead as capturing ion and one with strontium (the latter presumed to reveal sites of Na⁺-K⁺-dependent transport ATPase).

Reaction product with the lead-ATP medium was located on the plasma membrane and the membranes bordering subjacent vesicles and vacuoles in all the various types of osteoblastlike and fibroblastlike cells and also in types 1 and 3 chon-droblastlike cells, and multinucleated giant cells believed to be neoplastic. Furthermore, deposits of reaction product were demonstrated in lysosome-like organelles in all the aforementioned cells. Except in the case of chondroblastlike cells, precipitates marking the localization of enzyme were confined to areas of the plasma membrane where adjacent cells were closely applied (the free surface lacked precipitates). In chondroblastlike cells the reaction product was usually deposited along the whole plasma membrane. Presence of L-Homoarginine or L-Tetramisole in the incubation medium in concentrations that have been shown to completely abolish alkaline phosphatase activity did not affect the occurrence of the reaction product with ATP as substrate indicating that the enzyme hydrolysing ATP was substrate-specific.

Reaction product marking sites of Na⁺-K⁺-dependent ATPase was confined to plasma membranes and lysosomes of cells in vessel walls.

The observations strengthen the notion obtained in studies on the localization of alkaline phosphatase, namely that osteoblastlike, chondroblastlike, and fibroblastlike cells in osteogenic sarcomas are histogenetically related to one another and to those multinucleated giant cells that presumably are of a neoplastic nature.     

Ependymoma: Ultrastructural Studies of Two Cases

Several unusual ultrastructural findings in two ependymomas are reported. In case 1, a grade I ependymoma of the fourth ventricle, there were rosettes, perivascular pseudorosettes, and tumor cells having unusual intracytoplasmic vacuoles by light microscopy. Ultrastructurally, these vacuoles were frequently microrosettes as well as scattered, degenerated cytoplasmic processes of tumor cells. The lumina of some of the microrosettes were bordered by abnormally long and malformed zonulae adherentiae. In case 2, a recurrent grade III ependymoma of the third ventricle, there were rosettes and perivascular pseudorosettes as well as more cellular and anaplastic areas by light microscopy. Ultrastructurally, the cytoplasmic processes of tumor cells in perivascular pseudorosettes contained frequent dense-core vesicles and occasional parallel arrays of microtubules. These structures do not occur in normal mammalian ependymal cells but do occur in the ependymal tanycyte, a related cell that is plentiful in the walls of the third ventricle. Thus some of the tumor cells of this third ventricle ependymoma appear to have differentiated as tany-cytes.     

Ependymoma: Ultrastructural Studies of Two Cases

Several unusual ultrastructural findings in two ependymomas are reported. In case 1, a grade I ependymoma of the fourth ventricle, there were rosettes, perivascular pseudorosettes, and tumor cells having unusual intracytoplasmic vacuoles by light microscopy. Ultrastructurally, these vacuoles were frequently microrosettes as well as scattered, degenerated cytoplasmic processes of tumor cells. The lumina of some of the microrosettes were bordered by abnormally long and malformed zonulae adherentiae. In case 2, a recurrent grade III ependymoma of the third ventricle, there were rosettes and perivascular pseudorosettes as well as more cellular and anaplastic areas by light microscopy. Ultrastructurally, the cytoplasmic processes of tumor cells in perivascular pseudorosettes contained frequent dense-core vesicles and occasional parallel arrays of microtubules. These structures do not occur in normal mammalian ependymal cells but do occur in the ependymal tanycyte, a related cell that is plentiful in the walls of the third ventricle. Thus some of the tumor cells of this third ventricle ependymoma appear to have differentiated as tany-cytes.