Paraganglioma of the Cauda Equina: An Ultrastructural and Immunohistochemical Study of Two Cases

The ultrastructural and immunohistochemical features of 2 paragangliomas arising in the cauda equina are described. In both cases the tumor cells were arranged in small nests or cords and contained characteristic neurosecretory granules, lamellar stacks of rough endoplasmic reticulum (RER), and some well-developed Golgi apparatuses in their cytoplasm. The cells varied in electron density; the darker cells, occasionally resembling sustentacular cells, were probably dehydrated light cells because they contained a few neurosecretory granules. Sustentacular cells were difficult to identify by electron microscopy, but irregularly distributed S-100 protein and glial fibrillary acidic protein (GFAP) were found in these cells by immunostaining. Many tumor cells contained abundant neurofilaments. Curiously, a few cytokeratin-positive cells were found in 1 case. On microscopic examination, a small area of ganglioneuroma was found associated with the paraganglioma in 1 case. Ganglionic differentiation was concluded to be frequent in paragangliomas of the cauda equina region as in duodenal paragangliomas.     

Paraganglioma of the Cauda Equina

A case of paraganglioma of the cauda equina is reported. The patient was a 55 year old Japanese woman who complained of lower back pain and gradual weakening of the left lower extremity, she was diagnosed as having a spinal cord tumor, and the tumor was removed surgically. Histologically, the tumor was encapsulated, and consisted of solid nests of large, polyhedral epithelioid cells with abundant eosinophilic cytoplasm. The nests were separated from each other by a thin fibrovascular stroma. Grimelius staining revealed neurosecretory granules in the cytoplasm of the tumor cells. This was further confirmed by electron microscopic observation. The tumor cells were immunohistochemically positive for neuron-specific enolase (NSE), but negative for glial fibrillary acidic protein (GFAP). On the basis of the histologic, immunohisto-chemical and electron microscopic features of the tumor cells, the tumor was diagnosed as paraganglioma. The cauda equina is a rare location for this type of tumor, and only a limited number of cases have been reported.     

Duodenal Periampullary Gangliocytic Paraganglioma: Report of Two Cases with Immunohistochemical and Ultrastructural Study

We report two cases of Gangliocytic Paraganglioma (GP) of the ampulla of Vater occurring in a 63-year-old and a 34-year-old individual. The patients were both admitted for a long history of intermittent gastrointestinal bleeding and abdominal discomfort, with no other symptoms. At endoscopy, the GP appeared as a polypoid, ulcerated mass in the ampullar region, measuring 2.5x1.8 and 2 cm, respectively. Microscopically, the tumors showed similar features and were composed of epithelial cells (more than 50%), spindle cells, and ganglion-like cells. The epithelial cells showed clear cytoplasm and formed nests (zellballen or paraganglioma-like groups), and less frequently, cords (carcinoid-like), extending to mucosa and submucosa. Ganglion cells were sparse, constantly associated with the spindle cells. Both epithelial and ganglion cells were synaptophysin, chromogranin A, and anti-neurofilament immunoreactive. The spindle cells were all S-100 positive. Ultrastructural studies revealed dark and light cells, rare elongated cellular processes, secretory granules, and fine fibrils resembling neurofilaments. The histogenesis of GP is still a matter of debate, however its neoplastic nature is supported by the occasionally reported malignant evolution.     

Duodenal Periampullary Gangliocytic Paraganglioma: Report of Two Cases with Immunohistochemical and Ultrastructural Study

In an ultrastructural study of 24 cases of histiocytosis X, we were able to demonstrate Langerhans cell granules in all of 18 cases from which tissue had been submitted primarily for electron microscopy and in 4 of 6 cases from which only tissue retrieved from paraffin blocks was available for examination. In a subsequent correlative study we were able to demonstrate Langerhans cell granules in deparaffinized material from 11 of 14 cases (79%) in which they were known to exist. The incidence of histiocytes displaying Langerhans cell granules (in a single plane of section) fell from a median of 48% in samples processed primarily for electron microscopy to 14% in those retrieved from paraffin blocks. Our data suggest that electron microscopy, even when applied to the study of suboptimally preserved material, is a highly sensitive technique for confirming a diagnosis of histiocytosis X.     

Description of Six Cases of Child Cauda Equina Leptomeningitis: An Emerging Disease

Child cauda equina leptomeningitis (CCEL) is a typical clinical example of aseptic meningitis with patterns of an emerging disease, and it affects children aged 2–9. Here we will describe six cases of CCEL. After the prodromes, all children underwent an acute phase with hypoasthenia of the lower limbs, hyporeflexia, staggering and ataxia with steppage. Only in one case there were generalized fits and coma of grade 1–2 too. All children underwent a spinal Magnetic Resonance Imaging (MRI), proving pathologic enhancement of cauda equina and conus medullaris leptomeningitis. At the same time, MRI made possible the differential diagnosis between cauda equina leptomeningitis and isolated minor forms of Guillain-Barre syndrome involving the lower limbs.

Three hypotheses will be formulated for understanding the pathogen mechanism(s) of CCEL. The first one is based on the presence of an immediate viral damage on the meninges, the second one, the more likely, contemplates the occurrence of an immunomediated mechanism in a host genetically prone to react in an abnormal way from an immune viewpoint. The third hyphotesis consists in a two-time damage: an early immediate damage from the virus, and a later immunomediated reaction.     

Angiomyolipoma: Immunohistochemical and Ultrastructural Study of 14 Cases

Angiomyolipoma (AML) is a mesenchymal neoplasm of unclear histogenesis. In addition to varying amounts of smooth muscle, adipose tissue, and blood vessels, it contains a population of clear or pale eosinophilic epithelioid cells often arranged around blood vessels. Various phenotypes of AML have been described: leiomyoma-like, lipoma-like, epithelioid, and atypical. AMLs show consistent immunopositivity for HMB-45. This has been associated with the ultrastructural observation of melanosome-like structures in rare instances. In the present study, 14 AMLs from 13 patients were analyzed by electron microscopy and immunohistochemistry to determine the appearance and nature of cells composing AMLs. Overlap between cell types (spindle smooth muscle cells, epithelioid cells, and adipocytes) was found by both electron microscopy and immunohistochemistry. Melanosomes were found in 7 tumors. The cell of origin remains mysterious. Nevertheless, the study demonstrates that the AML is likely derived from a single cell that shares homology with the pericyte.     

Placental Site Trophoblastic Tumor of the Uterus: An Ultrastructural and Immunohistochemical Study and Immunohistochemical Study

Ultrastructural and immunohistochemical studies in a case of placental site trophoblastic tumor (PSTT) of the uterus were carried out in order to define the nature of the abnormal tissue. By electron microscopy, the large cells, whether mononuclear or syncytial, showed numerous ribosomes, prominent Golgi elements, and abundant rough endoplasmic reticulum (RER) filled with granular material. Pseudopods and microvilli were found on the cell surfaces. By immunofluorescence, the well-developed filamentous cyto-skeleton proved to be actin-rich. (3-HCG (human chorionic gonadotropin) and SP, (0,-specific pregnancy glycoprotein) were detected in only a few tumor cells, whereas most of them stained for HPL (human placental lactogen). The present results show the secretory nature of most of the tumor cells, which resemble the intermediate trophoblast of the placental bed. Together with previous studies, they suggest that a varying spectrum of syncytiotrophoblastic differentiation exists in PSTT. Decidual, myometrial, or histiocytic cells do not seem involved in the histogenesis of the tumor tissue.     

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.     

Intraductal Papilloma of the Male Breast: An Ultrastructural and Immunohistochemical Study

A case of intraductal papilloma of the male breast was studied by electron microscopy and immunohistochemistry. The major components of this lesion were the epithelial and myoepithelial cells. Intermediate cells showing ultrastructural features of both cell types were also observed. Squamous metaplasia was noted in many areas. Numerous intranuclear helioid inclusions were seen in the tumor cells. The features of this lesion are similar to those of papillomas of the female breast.     

Intraductal Papilloma of the Male Breast: An Ultrastructural and Immunohistochemical Study

A case of intraductal papilloma of the male breast was studied by electron microscopy and immunohistochemistry. The major components of this lesion were the epithelial and myoepithelial cells. Intermediate cells showing ultrastructural features of both cell types were also observed. Squamous metaplasia was noted in many areas. Numerous intranuclear helioid inclusions were seen in the tumor cells. The features of this lesion are similar to those of papillomas of the female breast.     

Warthin's Tumor: An Ultrastructural and Immunohistochemical Study of Basilar Epithelium

The cellular characteristics of the basilar epithelium in Warthin's tumor have had limited investigation. Ultrastructural examination of basal cells in 9 Warthin's tumors reveals that in addition to numerous mitochondria these cells possess a rich complement of tonofilaments. However, in three examples there are a proportion of these tonofilament-rich cells that have a narrow band of microfilaments in the peripheral cytoplasm adjacent to the basal lamina. Frozen sections of Warthin's tumor and normal salivary glands, doubly labeled with rhodamine-phalloidin for actin and monoclonal antibody 312C8-1 for cytokeratin 14, show that normal myoepithelial cells of acini and intercalated ducts have both of these filaments, as do a proportion of basal cells in the tumor. There are distinct differences in the cytokeratin polypeptide complement between normal luminal and myoepithelial cells as well as between luminal and basal cells in Warthin's tumor. Differences occur in the cytokeratin profiles between the luminal and basal cells of Warthin's tumor and comparable cells in the normal gland; however, there continue to be some similarities in the cytokeratin polypeptides of myoepithelium and the basal cells of normal salivary ducts and the basal cells of Warthin's tumor. These findings show that basal cells in Warthin's tumor are a mixed population with some capable of differentiating as myoepithelial-like cells, and that this tumor could arise from any level of the normal salivary gland duct system.     

Warthin's Tumor: An Ultrastructural and Immunohistochemical Study of Basilar Epithelium

The cellular characteristics of the basilar epithelium in Warthin's tumor have had limited investigation. Ultrastructural examination of basal cells in 9 Warthin's tumors reveals that in addition to numerous mitochondria these cells possess a rich complement of tonofilaments. However, in three examples there are a proportion of these tonofilament-rich cells that have a narrow band of microfilaments in the peripheral cytoplasm adjacent to the basal lamina. Frozen sections of Warthin's tumor and normal salivary glands, doubly labeled with rhodamine-phalloidin for actin and monoclonal antibody 312C8-1 for cytokeratin 14, show that normal myoepithelial cells of acini and intercalated ducts have both of these filaments, as do a proportion of basal cells in the tumor. There are distinct differences in the cytokeratin polypeptide complement between normal luminal and myoepithelial cells as well as between luminal and basal cells in Warthin's tumor. Differences occur in the cytokeratin profiles between the luminal and basal cells of Warthin's tumor and comparable cells in the normal gland; however, there continue to be some similarities in the cytokeratin polypeptides of myoepithelium and the basal cells of normal salivary ducts and the basal cells of Warthin's tumor. These findings show that basal cells in Warthin's tumor are a mixed population with some capable of differentiating as myoepithelial-like cells, and that this tumor could arise from any level of the normal salivary gland duct system.     

Paraproteinemic Crystalloidal Keratopathy: An Ultrastructural Study of Two Cases, Including Immunoelectron Microscopy

The ultrastructural appearances of corneal crystalloidal deposits are described in two patients with an IgG-k paraproteinemia of uncertain pathogenesis. The crystalloids in one patient were overwhelmingly intracellular and were found mainly in stromal keratocytes, but also in basal corneal epithelial cells and the limbal vascular endothelium. Four types of crystalloid or immunoprotein-containing granules were recognizable in this case: 1) fibrillary crystalloids with a curvilinear filamentous substructure; 2) angulated geometric crystalloids that often had a linear filamentous substructure and transverse or oblique periodicity; 3) cordlike crystalloids; and 4) lysosomelike granules with amorphous contents. Immunoelectron microscopy demonstrated that all of these structures labeled for k-light chains, and rectangular type 2 crystalloids showed approximately a twofold greater concentration of the colloidal gold probe than the type 1 fibrillary crystalloids. The evidence suggested development of the crystalloids within lysosomes, with a progression from the granules containing amorphous material, through fibrillary crystalloids, to the geometric structures. The circumferential distribution of the corneal deposits, as well as the presence of vascular endothelial crystalloids and reduplication of external laminae around limbal blood vessels, suggests that the crystalloids originated predominantly or entirely from the blood, with transport of immunoprotein across damaged limbal microvasculature. The abnormal vasculature may also have contributed to corneal edema, which in turn may have exacerbated corneal opacification. The crystalloidal deposits in the other case were exclusively extracellular; they were located beneath and between corneal basal epithelial cells, and predominantly as a mantle around individual keratocytes. The crystalloids in this case consisted overwhelmingly of thick-walled tubules about 40 nm in diameter that labeled for both k-light chains and γ chains with the colloidal gold immunoprobe. In addition, lucent vesicles within keratocytes were found only in sections labeled for k-light chains and were positive. The factors that might contribute to the formation of corneal crystalloidal deposits in immunoproliferative disorders are discussed, and include: 1) an inherent propensity for crystallization of some immunoglobulins or k-light chains, perhaps because of abnormal molecular structure; and 2) local factors in the cornea that might promote deposition and crystallization of immunoprotein, such as temperature, pH, the water content, and extracellular matrix components.     

Large Cell Calcifying Sertoli Cell Tumor of the Testis: A Clinicopathological, Immunohistochemical, and Ultrastructural Study of Two Cases

Large cell calcifying Sertoli cell tumor of the testis (LCCSCT) is a rare tumor that is usually benign and multifocal. It may be associated with hereditary endocrine anomalies such as Carney's and Peutz-Jeghers syndromes. Malignant forms are exceptional. Two cases of LCCSCT, one malignant and one benign are described. Both were composed of cords and trabeculae of large polygonal cells embedded in a myxoid and fibrous stroma with areas of calcification. The malignant tumor showed nuclear atypia, necrosis, and abundant mitoses. The cells were positive for vimentin and S-100 protein, and the intercellular space for laminin and collagen type IV. By electron microscopy, nucleolonemas and multilayered basal lamina were seen. The benign tumor was positive for vimentin and S-100 protein, and ultrastructurally showed less basal lamina.     

Cardiac Myxoma with Glandular Differentiation: An Immunohistochemical and Ultrastructural Study

A case of cardiac myxoma with glandular differentiation is reported. The patient did not have elements of the Carney triad or syndrome. The tumor was mainly composed of characteristic stellate cells in a focally collagenized, myxoid stroma, along with aggregates of glandular-forming epithelial cells, with mucin-containing intra- and intercellular lumina. Ultrastructurally, these gland spaces displayed short, straight microvilli and junctional complexes. The epithelial cells were positive for cytokeratin 7 and negative for cytokeratin 20. Calretinin was positive in the stellate cells and negative in the epithelial component. The potential origin from pluripotent mesenchymal cells or from seeded stem cells is hypothesized for glandular differentiation in myxomas. Further studies are required to unravel the relationship between stellate cells and the diverse heterologous components reported in these tumors.     

Clear Cell Sarcoma. An Immunohistochemical and Ultrastructural Study

The histogenesis of clear cell sarcoma was investigated by immunohistochemical examination of five tumors (two melanotic and three amelanotic) and electron microscopic examination of two of these tumors (one melanotic and one amelanotic). Melanin production was observed histologically in two of the tumors. The cytoplasm of ceils in both types of tumor contained various numbers of melanosomes. Melanoma-specific antibody (HMB-45), anti S 100 protein, and anti vimentin antibodies gave positive reactions in four tumors, while all tumors showed Leu 7 immunoreactivity. No cytokeratin or epithelial membrane antigen (EMA) was detected immunohisto-chemically in any tumor. The immunoreactivity of this type of tumor with HMB-45 antibody strongly suggests melanocytic differentiation rather than schwannian or synovial differentiation. The reaction of the cells of one tumor with only Leu-7 indicates the existence of undifferentiated clear cell sarcoma of neuroectodermal origin that does not show definite melanocytic differentiation. Acta Pathol Jpn 39: 321 327, 1989.     

Sarcomatoid Carcinoma: An Ultrastructural Study with Light Microscopic and Immunohistochemical Correlation of 10 Cases from Various Anatomic Sites

The histogenesis of sarcomatoid carcinoma has been an intriguing topic for pathologists for many years, and considerable evidence has accumulated in the fields of tissue culture, electron microscopy, and immunohistochemistry to support the concept that the sarcomatous cells derive by way of “divergent differentiation” (metaplasia) from the carcinomatous elements. We have studied a group of 10 cases of these tumors from various organs, using detailed ultrastructural analysis as well as light microscopic and immunohistochemical correlation. We found that there is an ultrastructural spectrum of differentiation from epithelial to mesenchymal type features and that the malignant spindle cells may be purely epithelial (3 cases), purely mesenchymal (3 cases), or a mixture of both (4 cases). Furthermore, individual cells may show biphasia, having desmosomes and tonofibrils as well as well developed rough endoplasmic reticulum and filaments with dense bodies. Electron microscopic and immunohistochemical results do not always correlate, illustrating the prudence of using several keratin antibodies, including wide-spectrum ones, and of performing electron microscopic examination on these tumors.     

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.