Sacral chordoma in early childhood: clinicopathological and immunohistochemical study

Two cases of sacral chordoma in a 7-year, 9-month-old boy and a 3-year, 4-month-old boy are presented. In addition to the typical histology of conventional chordoma, both tumors showed the less differentiated sarcomatoid appearance of atypical chordoma in the major portion. Immunohistochemically, in both cases neoplastic cells in areas of conventional as well as atypical chordoma were positive for keratins (CAM 5.2, AE1 and AE3), epithelial membrane antigen, vimentin, S-100 protein, carcinoembryonic antigen, and glial fibrillary acidic protein. Both patients underwent resection of the tumor and chemotherapy. In comparison with conventional chordomas in adults, however, these two tumors showed more aggressive clinical course and were less amenable to therapeutic control. The older boy died of multiple metastasis 1 year after initial diagnosis. At the last follow-up, 15 months after initial diagnosis, the younger boy was alive, but with recurrent and metastatic disease of the left parasacral area and chest wall. Our studies of these two cases and the reported cases suggest that sacral chordoma in children has distinctive clinicopathologic features denoting a highly aggressive tumor and that it should be treated as such.     

Low-grade myxoid chondrosarcoma of the temporal bone: differential diagnosis and report of two cases

Skull base chondrosarcoma and chordoma are rare tumors that generally have a poor prognosis. In 1973, Heffelfinger et al described a chondroid variant of chordoma, called chondroid chordoma that was found to have a significantly better prognosis than classic chordoma. However, recent evidence suggests that many of the tumors diagnosed as chondroid chordoma may, in fact, be low-grade myxoid chondrosarcomas. This report presents the diagnosis and treatment of two cases of skull base tumor that were diagnosed preoperatively as schwannoma because they were thought initially to be centred on the jugular foramen. Initial histologic evaluation suggested chondroid chordoma, but immunohistologic techniques and a review of the literature led to a diagnosis of low-grade myxoid chondrosarcoma.     

Automatic measurement of arterial pressure

PURPOSE: To identify patients with lymphoma at risk for tumor lysis after chemotherapy. PATIENTS AND METHODS: The case records of 102 patients receiving combination chemotherapy for non-Hodgkin's lymphoma (intermediate to high-grade histology) were reviewed. Patients were considered to have "laboratory tumor lysis" if two of the following metabolic changes occurred within 4 days of treatment: a 25% increase in the serum phosphate, potassium, uric acid, or urea nitrogen concentrations, or a 25% decline in the serum calcium concentration. "Clinical tumor lysis" was defined as laboratory tumor lysis plus one of the following: a serum potassium level greater than 6 mmol/L, a creatinine level greater than 221 mumol/L, or a calcium level less than 1.5 mmol/L, the development of a life-threatening arrhythmia, or sudden death. RESULTS: Laboratory tumor lysis occurred in 42% of patients and clinical tumor lysis in 6%. There was no statistical difference in the frequency of either tumor lysis syndrome among lymphoma subgroups. Clinical tumor lysis occurred more frequently in patients with pretreatment renal insufficiency (serum creatinine level greater than 132 mumol/L) than in patients with normal renal function (36% versus 2%; p = 0.01). The development of azotemia correlated with high pretreatment serum lactate dehydrogenase concentrations (p < 0.01; r2 = 0.11). CONCLUSION: Clinically significant tumor lysis is a rare occurrence in patients with lymphoma when they are receiving allopurinol. However, tumor lysis can occur in patients with all types of moderate to high-grade non-Hodgkin's lymphoma. Patients with a high serum lactate dehydrogenase level or renal insufficiency are at increased risk for metabolic complications after chemotherapy and should be closely monitored.     

Hemorrhagic chondroid chordoma mimicking pituitary apoplexy

We describe a hemorrhagic chondroid chordoma involving the sella turcica with suprasellar extension. The CT and MRI appearances mimiked a hemorrhagic pituitary adenoma. Chondroid chordoma is a variant composed of elements of both chordoma and cartilaginous tissue. An uncommon bone neoplasm, located almost exclusively in the spheno-occipital region, it is usually not considered in the differential diagnosis of a tumor with acute hemorrhage in the sellar region. We discuss the clinical and radiological characteristics which may allow one to differentiate chondroid chordoma from other tumors of this area.     

Chordomas of the skull base. Radiologic and clinical evaluation

Chordomas are uncommon skull base tumors, which are locally agressive and are usually not amenable to complete surgical resection. Proton beam irradiation, following surgery, is the preferred treatment modality. For diagnosis and determination of tumor site and extension, CT and MR imaging are the imaging modalities of choice. CT delineates bone destruction and the presence of calcifications and destroyed bone optimally. MR imaging is the modality of choice for better definition of the tumor margin from brain and other soft tissue structures (pharynx) and visualization of blood vessels. The signal intensities and enhancement pattern fail to differentiate chordoma from chondroid chordoma or chondrosarcoma. Chordomas arise from the clivus and therefore are located more centrally, whereas the majority of chondrosarcomas originate in the petroclival fissure and occur more laterally, although occasional overlap occurs in about one third of cases. Immunohistochemical methods allow differentiation of pure chordoma from chondroid chordoma and chondrosarcoma. Chordomas have a lower local control rate than chondrosarcomas.     

Chordoma with cutaneous metastasis

Chordoma is a neoplasm arising from the primitive notochord. Even though many chordomas follow a progressive course with multiple recurrences and metastases and eventual death due to tumor, reports of skin metastases from chordoma are rare. This report describes a case of chordoma with metastasis to the scalp in a 67-year-old man with a primary lesion of the sacrococcygeal region.     

Dedifferentiated (sarcomatoid) chordoma in the base of the skull. Report of a case

We report a case of "dedifferentiated" chordoma occurring in a 31-year-old man and involving the base of the skull. Morphologically, the tumor was characterized by a bifasic pattern (classical chordoma associates to sarcoma-like areas), and by coexpression of epithelial and stromal markers. Because of these traits, we believe this case shows features superimposable to those seen in sarcomatoid carcinoma.     

Cytology of cervical chordoma in cerebrospinal fluid from a child. A case report

The cytologic findings on cerebrospinal fluid examination of cervical chordoma in a 2-year-old girl are presented. The major cell type was a small, isolated, hyperchromatic cell with sharply defined nuclear membrane and granular cytoplasm. However, the characteristic cell of this neoplasm, the so-called physaliferous cell with typical bubbly cytoplasm, was also noted. Cytologic findings were compared to biopsy findings, with a good correlation of tumor morphology. Clinical follow-up revealed unusually aggressive tumor behavior, and the patient died a year later despite intensive chemotherapy. The differential diagnosis of the condition is also discussed.     

Limited importance of CD40/CD40L interaction in the B7-dependent generation of anti-MOPC-315 cytotoxic T lymphocyte activity by tumor bearer splenic cells stimulated in vitro in the presence of tumor necrosis factor

We have previously illustrated the importance of B7-2 expression for the enhanced generation of cytotoxic T lymphocyte (CTL) activity by stimulation cultures of tumor bearer splenic cells to which tumor necrosis factor alpha (TNFalpha) has been added. Here we show that the B7-1 molecule is also important for CTL generation by such stimulation cultures, although to a much lesser extent than the B7-2 molecule. In addition, we show the importance of CD40/CD40L interaction for the expression of the B7-2 molecule, but not the B7-1 molecule, by tumor bearer splenic cells stimulated in vitro in the presence of TNF. The CD40/CD40L interaction is also shown to be important for the generation of CTL activity by tumor bearer splenic cells stimulated in vitro in the presence of exogenous TNF. However, the CD40/CD40L interaction is less important for the generation of enhanced CTL activity than for the expression of an elevated level of B7-2. Specifically, blockade of CD40/CD40L interaction, which reduced the level of B7-2 expressed by tumor bearer splenic cells stimulated in vitro in the presence of TNF to the level of B7-2 expressed by tumor bearer splenic cells stimulated in vitro in the absence of exogenous TNF, failed to reduce the level of CTL generated to the level generated by tumor bearer splenic cells stimulated in the absence of exogenous TNF. Finally, blockade of CD40/CD40L interaction was inferior to blockade of B7-2/CD28 interaction in inhibiting the generation of CTL activity by tumor bearer splenic cells stimulated in the presence of exogenous TNF. Thus, although CD40/CD40L interaction is important for the generation of enhanced CTL activity by stimulation cultures of tumor bearer splenic cells to which TNF has been added, TNF also mediates its potentiating effect for CTL generation by such stimulation cultures via other mechanisms that are independent of CD40/CD40L interaction but dependent on B7-2 expression.     

Cutaneous metastasis of chordoma

A chordoma metastatic to the skin of the nose is reported. The patient (a 40-year-old man) had undergone excision of a sacral chordoma 16 months previously. In patients whose clinical histories are unknown, cutaneous metastases of chordoma can be confused with mixed tumors of sweat glands. Cytological features, including the presence of physaliphorous cells, and immunohistochemical coexpression of low molecular weight keratins and S-100 protein are helpful features that lead to a correct diagnosis.     

Estimation of different models of insulin therapy in noninsulin-dependent diabetes mellitus

A 21-year old woman underwent surgery in December 1996 for the removal of a presumed tuberculum sellae meningioma. However, some radio-clinical findings were proved somewhat intriguing:the patient's age, the presence of inflammatory and febrile syndromes together with the diagnosis of aseptic meningitis associated with perilesional edema intensity (an unusual feature in such cases) made us challenge the initial neuroradiological diagnosis evoked in connection with the tumoral location and dural attachment pattern. A right sub-fronto-temporal approach allowed complete tumor resection (confirmed with a postoperative MRI) and clinical recovery of the patient. But while pathological examination suggested a chordoma, the study of immunohistochemical stains revealed a meningioma. The final diagnosis was chordoid meningioma. Our review of the literature has shown that chordoid meningiomas display several areas of physaliferous cells which give the tumor a chordoma-like aspect. However, the results of immunohistochemical studies along with the location of the tumor were not consistent with the diagnosis of chordoma. Eight cases of chordoid meningiomas are reviewed in the literature. They are described as inducing systemic symptoms, particularly anemia. They could also be linked to Castleman's syndrome according to Kepes et al. After careful evaluation, we retained the hypothesis of a cause and effect relationship between the local and generalised inflammatory syndrome and chordoid meningioma.     

Functional mapping of the U3 small nucleolar RNA from the yeast Saccharomyces cerevisiae

The 2 f1-f2 distortion product otoacoustic emission (DP) was measured in 20 normal hearing subjects and 15 patients with moderate cochlear hearing loss and compared to the pure-tone hearing threshold, measured with the same probe system at the f2 frequencies. DPs were elicited over a wide primary tone level range between L2 = 20 and 65 dB SPL. With decreasing L2, the L1-L2 primary tone level difference was continuously increased according to L1 = 0.4L2 + 39 dB, to account for differences of the primary tone responses at the f2 place. Above 1.5 kHz, DPs were measurable with that paradigm on average within 10 dB of the average hearing threshold in both subject groups. The growth of the DP was compressive in normal hearing subjects, with strong saturation at moderate primary tone levels. In cases of cochlear impairment, reductions of the DP level were greatest at lowest, but smallest at highest stimulus levels, such that the growth of the DP became linearized. The correlation of the DP level to the hearing threshold was found to depend on the stimulus level. Maximal correlations were found in impaired ears at moderate primary tone levels around L2 = 45 dB SPL, but at lowest stimulus levels in normal hearing (L2 = 25 dB SPL). At these levels, 17/20 impaired ears and 14/15 normally hearing ears showed statistically significant correlations. It is concluded that for a clinical application and prediction of the hearing threshold, DPs should be measured not only at high, but also at lower primary tone levels.     

Anterior approaches to the spinal column: considerations of the surgical technic

The anterior approach to the vertebral column is indicated in the tumors or traumas of the vertebral body with prevalent anterior expression. This method allows to control easily all the structures in front of the rachis. Furthermore, the current reconstructive techniques require the exposure of a long tract of the vertebral column. The Authors report their experience with the anterior approach in 22 patients (9 males, 13 females) affected by different pathologies: 10 primary tumors divided as follows: 4 sacral chordomas, 1 L1 chordoma, 2 sacral neurinomas, 1 L5 malignant melanotic schwannoma, 1 D9 osteoblastoma, 1 D6 intraspinal cavernoma, and 1 D3 myeloma; 4 metastatic tumors (2 D10, 1 L4 and 1 L5); 5 fractures of the vertebral body (1 L1, 1 L1-L2, 2 L4 and 1 L5); 2 echinococcal cysts respectively arising from the D11 body, the sacrum and ilium. The Authors overall performed 8 thoracotomies, 6 for dorsal location; in 1 case of L1-L2 fracture a thoracophrenolaparotomy was performed; in 7 cases involving the L3-L5 segment an abdominal anterolateral extraperitoneal approach was followed; finally in 6 cases a transperitoneal laparotomy to approach the sacrum and ilium was performed.     

Cytotoxicity of sodium fluoride on human oral mucosal fibroblasts and its mechanisms

Because sodium fluoride (NaF) is widely used for prevention of dental caries, pathobiological effects of NaF were investigated on human oral mucosal fibroblasts. The results showed that NaF was cytotoxic to oral mucosal fibroblasts at concentrations of 4 mmol/L or higher. Exposure of cells to NaF for 2 h also inhibited protein synthesis, cellular ATP level and functional mitochondrial activities in a dose-dependent manner. However, incubation of cells with NaF up to 12 mmol/L for 2 h depleted only 13% of cellular glutathione level. The IC50 of NaF on cellular ATP level was about 5.75 mmol/L. Preincubation of the cells with pyruvate and succinate did not protect cells from NaF-induced ATP depletion. At concentrations of 4 mmol/L, 8 mmol/L and 12 mmol/L, NaF inhibited 31%, 56% and 57% of mitochondrial functions, respectively, after 2 h incubation. No significant inhibition for NaF was found at concentrations lower than 2 mmol/L (40 ppm). These results indicate that NaF can be toxic to oral mucosal fibroblasts in vitro by its inhibition of protein synthesis, mitochondrial function and depletion of cellular ATP. Because of repeated and long-term usage of NaF, more detailed studies should be undertaken to understand its toxic effects in vitro and in vivo.     

Immobilization of beta-fructofuranosidases from Aspergillus on methacrylamide-based polymeric beads for production of fructooligosaccharides

Three cases of chondromyxoid fibroma arising in the skull base are reported. The tumors arose in females 34, 65, and 66 (median 55) years of age. Two women presented with headaches, and one with nasal obstruction. Radiographic studies revealed that all three lesions were expansile soft tissue masses centered in the clivus, at least 4 cm in greatest diameter. One lesion involved primarily the clivus, the others extended from the clivus into the sphenoid and ethmoid sinuses. Two of the three cases were initially misdiagnosed as chordoma or chondrosarcoma. The initial treatment was curettage of gross disease in all three cases. One patient also received radiation therapy. One patient had local progression of disease, which was treated with surgery and radiation therapy. All patients are clinically free of disease 11 to 26 months following the most recent treatment. Chondromyxoid fibroma can and should be distinguished from chondrosarcoma and chordoma, two tumors which more commonly arise in the skull base and which have the potential to metastasize.     

Vacuolated meningioma. A light and electron microscopic study

Two unusual cases of meningioma with extensive vacuolization have been studied by light and electron microscopy. There were two kinds of vacuoles in the tumor cells which had the characteristic ultrastructure of meningioma as well. The smaller intracytoplasmic vacuoles were lipid droplets, while the larger, more prominent vacuoles were found to be extracellular spaces probably containing plasmatic fluid. The tumor cells were very much stellate with extremely thin and long cytoplasmic processes having desmosome junctions and forming cavernous intercellular spaces, some of which contained collagen fibers and fibrils. Although the xanthomatous change has been well known, the latter features provide a resonable interpretation for the histology of the present tumors and fat-negative vacuoles in the ordinary meningiomas. The picture may be recapitulation of the subarachnoid structure. Furthermore, recognition of this type of meningioma is practically important especially in frozen section diagnosis not to misinterpret the tumor as liposarcoma, chordoma or metastatic adenocarcinoma.     

Chordomas of the mediastinum: clinicopathologic, immunohistochemical, and ultrastructural study of six cases presenting as posterior mediastinal masses

Six cases of chordomas presenting as primary posterior mediastinal tumors are described. Three patients were female, and three were male between the ages of 8 and 65 years (mean, 40.6 years). In all cases, the tumors presented radiographically as relatively well-circumscribed, encapsulated soft tissue masses that did not seem to be related to the thoracic or dorsal spine. Only in one case, focal infiltration of bone at the level of T6-T7 was observed at the time of surgery. Histologically, the lesions showed a spectrum of features that ranged from sheets and cords of large cells with abundant vacuolated cytoplasm to small, stellate cells embedded within an abundant mucoid matrix. In one case, the cell population showed more pronounced nuclear atypia with loss of cytoplasmic vacuolization, frequent mitotic figures, necrosis, and solid areas characterized by a perivascular distribution of atypical spindle cells set against a myxoid stroma. Another case showed features of chondroid chordoma, with an immature chondroid-appearing matrix surrounding the atypical tumor cells. Immunohistochemical studies in all cases showed positive staining of the tumor cells with CAM 5.2 and broad-spectrum keratin, epithelial membrane antigen (EMA) and vimentin, and, to a lesser extent, with S-100 protein. Stains for muscle actin, carcinoembryonic antigen (CEA), and desmin were negative. Ultrastructural examination in two cases showed a spectrum of features that varied from large cells with abundant cytoplasm containing scattered ribosomes, glycogen granules, Golgi apparatti, abundant intermediate filaments, and small lumen formation with immature microvilli to smaller cells with elongated cytoplasmic processes, fewer intermediate filaments, rare desmosome type intercellular junctions, and complexes of mitochondria/rough endoplasmic reticulum. On clinical follow-up, two patients died with metastases to the lungs, chest wall, and liver from 1 to 3 years after diagnosis, and two patients are alive and well without evidence of disease after 3 and 16 years. Chordoma should be entertained in the differential diagnosis of posterior mediastinal tumors. Application of immunohistochemical stains or electron microscopy will be of aid in separating them from other conditions that may histologically closely resemble these lesions.     

Mutational analysis of the p73 gene localized at chromosome 1p36.3 in colorectal carcinomas

A case of chordoid meningioma occurring in a 15-year-old girl is presented. The patient manifested seizures as the initial symptom and subsequently exhibited subclinical microcytic hypochromic anemia. The tumor, located in the falcotentorial region and associated with diffuse edema, was totally resected. On histological examination of the surgical specimen, the clustering pattern of partly vacuolated cells in the mucoid stroma mimicked chordoma; however, positive staining of individual cells for vimentin and epithelial membrane antigen led to a diagnosis of meningioma. Interestingly, the tumor cells were surrounded by a periodic acid-Schiff- and type IV collagen-positive substance. Electron microscopy demonstrated a strikingly dense and thick basal lamina. The patient's microcytic hypochromic anemia disappeared after the tumor was removed. Both the clinical and pathological features of this case resemble those of chordoid meningioma, a rare meningioma variant.     

Circulatory and metabolic responses of malignant tumors during localized hyperthermia

The effect of localized hyperthermia on the circulatory responses and on the oxygen and glucose supply has been evaluated in tissue-isolated rat tumors utilizing an in situ perfusion system. On the average, localized hyperthermia caused a significant increase in total tumor blood flow after raising of the mean tumor temperature from 37 degrees C to 39.5 degrees C. At higher temperatures (42 degrees C) total tumor blood flow decreased to a level somewhat below the flow during normothermia. However, there were great interindividual differences in the response of blood flow to temperature. The changes in blood flow were paralleled by variations of the O2-consumption and of the glucose uptake of the tumor tissue. The alteration of the oxygen and glucose supply seem to be predominantly mediated through changes of tumor blood flow with temperature. Tumor microcirculation appears to be improved at moderate hyperthermic temperatures (39 degrees C -40 degrees C) and deteriorated at higher temperatures. Whereas a vasodilation of tumor vessels seems to be a paramount factor for flow improvements, a reduction of red blood cell flexibility due to severe tissue acidosis, multiple microthromboses as well as occlusions of microvessels should be taken into consideration as factors for flow impairments at higher tumor temperatures.