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Abstract: The objective of this study was to establish a simple and rapid immunocytochemical technique that can be used in veterinary diagnostic cytology. Air-dried impression smears were collected from canine tumors. Samples of epithelial tumors, mesenchymal tumors, and malignant peripheral nerve sheath tumors and melanomas were used for detection of cytokeratin, vimentin, and S-100 protein, respectively. The labeled streptavidin–biotin system was used in the present study. Optimal fixation was determined using standard immunocytochemical procedures, and acetone fixation was found to be the most effective. Optimal concentrations of primary and secondary antibodies were determined at a preset 5-min incubation. Omission of H2O2 treatment, shortening the time for blocking and labeled-streptavidin incubation, and simplifying washing did not decrease immunopositive intensities or enhance false-positive reactions. The described rapid protocol requires approximately 45min without the use of any special equipment. [Copyright &y& Elsevier]

Abstract: Although neurofibroma frequently occurs as a local manifestation of von Recklinghausen''s disease, solitary lesions in the oral and maxillofacial region are rare. Here, we describe an extremely rare solitary neurofibroma that arose in the maxillary sinus of a 41-year-old man. Panoramic radiography and a CT scan showed a slightly swollen maxillary sinus mucosa and a well-circumscribed cystic lesion suggesting a radicular cyst associated with a maxillary molar. The lesions were removed by radical sinusotomy under general anesthesia. A histopathological examination revealed that the nodular lesion of the sinus mucosa was not encapsulated and that it was composed of somewhat increased numbers of spindle cells accompanied by delicate hyperplastic fibers. These cells had flexed, wavy and linear spindle nuclei. Immunohistochemistry revealed that these tumor cells were positive for S-100 and neuron-specific enolase (NSE). A few spindle cells that were positive for α-SMA within the tumor were thought to be fibroblastic cells (myofibroblasts) derived from the endoneurium or surrounding connective tissue. These findings overall were compatible with the characteristics of neurofibroma. The cystic lesion was diagnosed as a radicular cyst. The patient remained free of tumor recurrence at 26 months of follow-up. [Copyright &y& Elsevier]

To clarify the clinicopathologic characteristics of retroperitoneal schwannomas, which are sometimes confused with other spindle cell tumors, 27 cases were studied microscopically and immunohistochemically. The 27 cases consisted of 17 females and 10 males, the ages of whom ranged from 31-79 (mean 57.4) years. Gross examination revealed well-demarcated, encapsulated tumors, 3-15 cm (mean 8 cm) in diameter. Microscopic review divided them into 13 cases of cellular/fascicular, 3 of conventional, 6 of intermediate, and 5 of ancient type. Cellular/fascicular schwannomas were composed of cellular fascicles of spindle cells, in which nuclear palisading, Antoni B area and cyst were unclear, while numerous foamy cells were intermingled. Immunohistochemical investigation revealed diffuse, strong positivity for S-100 protein and Sox10 in all tumors studied. In addition, glial fibrillary acidic protein (GFAP) was extensively expressed in 92% of the cellular/fascicular type, while it was less prominent in others. The present study suggests that retroperitoneal schwannoma often occurs in the middle-aged woman, grows to a large size, exhibits cellular/fascicular microscopic features in half of the cases, and may arise from GFAP-positive Schwann cells. The presence of hyalinized vessels and dense infiltration of foamy macrophages as well as diffuse immunoreactivity for S-100 protein and Sox10 are helpful for the differential diagnosis. [ABSTRACT FROM AUTHOR]

Abstract: Malignant triton tumor (MTT) is defined as malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation. Intracranial MTT is extremely rare, and only four cases have been reported in the literature. Here, we report a case of MTT occurring in the cerebellopontine angle, and describe its histopathological characteristics, immunohistochemical features, and prognosis. [ABSTRACT FROM AUTHOR]

Schwannoma is a benign, encapsulated, perineural tumor that arises from the Schwann cells. Approximately 25% of the reported cases originate from the head and neck region. Of these, approximately 1-12% occurs intraorally. The intrabony lesion accounts for less than 1% of the central neoplasms. We report a rare case of intraosseous schwannoma in an 8-year-old male patient characteristically originating from the mental nerve. Radiographic examination followed by histopathological evaluation was further confirmed by immunohistochemical markers, S-100 protein, and GFAP that stained intensely positive for the tumor. Thus, confirming the diagnosis of intraosseous schwannoma. [ABSTRACT FROM AUTHOR]

Abstract: Epithelioid variant of a malignant peripheral nerve sheath tumor (MPNST) is a rare sarcoma. Rarer still is its occurrence at uncommon sites like the uterine corpus where an index of suspicion for this diagnosis is extremely low. Herein, we report a rare case of a uterine epithelioid MPNST in a young girl who underwent a total abdominal hysterectomy for a uterine tumor that was initially diagnosed as an undifferentiated sarcoma and whose paraffin blocks were submitted to us for review. Biopsy sections showed a malignant tumor, predominantly composed of polygonal cells, including “rhabdoid” forms with conspicuous mitoses. On immunohistochemistry, tumor cells were diffusely positive for vimentin and S-100 and negative for smooth muscle actin, desmin, myogenin cytokeratin, epithelial membrane antigen, melan A, HMB-45, CD10, glial fibrillary acid protein inhibin, synaptophysin, chromogranin, MIC2, FLI-1, and neuron-specific enolase. Diagnosis of an epithelioid MPNST was offered. The case is presented in view of its rarity and also to highlight the value of immunohistochemistry in objectively identifying unusual sarcomas at uncommon sites. [Copyright &y& Elsevier]

Objective To study clinicopathological features, diagnosis, differential diagnosis of oral Langerhans cell histiocytosis (LCH), retrospective clinicopathologic study was carried on and a variety of immune phenotype were de -tected. Methods The clinicopathological features of 29 cases of oral LCH were analyzed. The immunohistochemical staining of S-100 protein, CDla, CD83 and Ki-67 were used in above cases by immunohistochemical streptavidinbiotin peroxidase (SP) and Elivison two-step method. Statistical analysis was adopted for the results. Results Of the 29 cases of LCH, the expression of S-100 protein and CDla were positive in 24 cases and negative in 5 cases, so 5 cases were excluded from the diagnosis of LCH. Among 24 cases of LCH, 15 patients were male and 9 were female. The median age was 7.50 years. 14 lesions were in the mandible, 5 were in the maxilla and 5 involved the mandible and maxilla. 9 cases were in stage I, 13 in stage II and 2 in stage III, according to Bartnick classification. Immunohistochemistry showed all 24 cases staining for S-100 protein and CDla were positive. Comparing with maxillofacial lesions involved soft tissue, Ki-67 positive rate was lower and CD83 positive rate was higher in maxillofacial single bone lesion. Conclusion The immunohistochemical staining of S-100 protein and CDla are important for the diagnosis of LCH. Maxillofacial bone single LCH might have lower proliferative activity and a higher state of maturity. Maxillofacial LCH involved soft tissue might have a higher proliferative activity and a lower state of maturity. [ABSTRACT FROM AUTHOR]

Abstract: Metanephric stromal tumor (MST) is a rare pediatric neoplasm unique to the kidneys that is currently included in the spectrum of metanephric tumors, along with metanephric adenoma and adenofibroma. We herein report an unusual case of pediatric renal stromal tumor overlapping with MST and solitary fibrous tumor (SFT). Histologically, the tumor was composed of bland-looking spindle to stellate cells embedded in a fibro-sclerotic stroma that focally surrounded native entrapped renal tubules or blood vessels with abortive rings or collarettes. Alternating hypercellular and hypocellular areas and a focal hemangiopericytomatous-like vascular pattern imparted to the tumor a resemblance to SFT. Angiodysplasia of intratumoral arterioles was also observed, but juxtaglomerular cell hyperplasia was not a feature. Immunohistochemically, the neoplastic cells showed a polyphenotypic profile, including diffuse expression of vimentin and CD34, and focal immunoreactivity for alpha-smooth muscle actin, EMA, and CD99. However, the most striking finding was diffuse nuclear and cytoplasmic expression of S-100 protein. Although this protein has been reported to stain the heterologous glial and/or cartilaginous components that can be occasionally encountered in MST, this marker has not been previously reported in the fibroblastic component of MST. Pathologist should be aware of similar unusual unclassified tumors to avoid potential confusion with other benign or malignant S-100 protein-positive tumors. [Copyright &y& Elsevier]

Abstract: Numerous reports have shown the effect of photoperiod and melatonin administration on the different hormone secreting cell types in the pituitary pars distalis. The viscacha (Lagostomus maximus maximus) is a rodent with photoperiod-dependent seasonal reproduction. The aim of this study was to examine the effect of photoperiod seasonal variations and melatonin administration on the folliculostellate cells in pituitary pars distalis of viscacha. Immunohistochemistry and image analysis were used to measure the percentage of S-100-positive area (total, cellular and colloidal) and the number of folliculostellate cells. The S-100 protein was immunolocalized at intracellular (folliculostellate cells) and extracellular (follicular colloid) levels. The morphometric parameters analyzed exhibited seasonal variations with highest values in the summer (long photoperiod) and lowest values in the winter (short photoperiod). The administration of melatonin caused a significant decrease of immunostaining. Results suggest that the natural photoperiod might be the most important environmental signal causing the decrease in folliculostellate cells immunostaining observed in the winter. These findings agree with seasonal changes previously reported in endocrine cells and suggest that folliculostellate cells may be involved in the paracrine regulation of the secretory activity of pituitary pars distalis through S-100 protein production. [Copyright &y& Elsevier]

In the anterior and intermediate lobes of the rat pituitary gland, non-hormone-producing cells that express S-100 protein coexist with various types of hormone-producing cells and are believed to function as phagocytes, supporting and paracrine-controlling cells of hormone-producing cells and stem cells, among other functions; however, their cytological characteristics are not yet fully understood. Using a transgenic rat that expresses green fluorescent protein under the promoter of the S100β protein gene, we immunohistochemically detected expression of the luteinizing hormone, thyroid-stimulating hormone, prolactin, growth hormone and proopiomelanocortin by S-100 protein-positive cells located between clusters of hormone-producing cells in the intermediate lobe. These findings lend support to the hypothesis that S-100 protein-positive cells are capable of differentiating into hormone-producing cells in the adult rat pituitary gland. [ABSTRACT FROM AUTHOR]

Objective. To study differences in the expression of various nerve markers between total colonic aganglionosis (TCA) and common-segment-type Hirschsprung’s disease (HD) using immunohistochemistry. Methods. All-layer colon and ileum specimens were extracted from 18 patients diagnosed with TCA and treated at the Children’s Hospital of Fudan University between January 1996 and December 2005. The reference group consisted of 10 cases each of common-segment-type HD and anorectal malformations (ARMs). Immunohistochemical comparison was conducted on the expression levels of the enteric nerve markers protein gene product 9.5 (PGP9.5), S-100 protein, neuron-specific enolase (NSE), and peripherin. Results. There were no statistically significant differences in expression of PGP9.5, S-100 protein, NSE, and peripherin in ganglionic intestinal sections from the TCA group, HD group, or ARM group (P > .05). A few mature and immature ganglion cells were observed in the transitional sections from the TCA group, and expression levels of the nerve markers were lower than in the HD group (P < .01). Ganglion cells were found in the far-end intestinal section in none of the 18 cases of TCA, where thick nerve trunks were fewer and nerve marker expression levels were lower than in the HD group (P < .01), most evidently in the cases of PGP9.5. Conclusions . The study revealed evident differences in the positive expression of nerve markers in the enteric sections when TCA and common-segment HD were compared, indicating differences in enteric nerve innervation in these conditions. [ABSTRACT FROM PUBLISHER]

A 54-year-old male presented with a painless, hard, irregular lump in his right breast, with fixation to the pectoralis muscle. Mammography and ultrasound showed a 2.5-cm mass suspicious of malignancy. The patient underwent a wide local excision. A 2.5-cm hard, stellate lump was found and sent to the pathologist, which revealed this to be a benign granular cell tumor. Granular cell tumor of the breast is a rare neoplasm, of unknown etiology, which is benign in 98% of cases, but mimics breast cancer, causing challenging diagnostic and therapeutic dilemmas. Traditional imaging techniques do not recognize any feature specific for this tumor. Only excisional biopsy allows the detection of the distinct histological and immunohistochemical profile of the lesion (granular cytoplasm and staining for the S-100 protein). Only local surgical excision is indicated. General and senologist surgeons must be aware of this entity to avoid unnecessary mastectomy or lymphadenectomy. [ABSTRACT FROM AUTHOR]

A higher expression of S-100 in tissue of thyroid papillary carcinoma (TPC) vs. thyroid follicular adenoma (TFA) ( p < .001) was observed as well as a higher expression of CD83 in the peri-cancerous tissues vs. TFA ( p < .001), oppositely, CD83 was negative in the cancerous net. TPC showed greater decreases in levels of CD80 and CD86 than did the TFA. These findings suggest that impaired immune function, absence of CD83-positive mature and activated dendritic cells in cancer nodules may have a role in the pathogenesis of TPC. The low expression of CD80 and CD86 in TPC may help them evade the immune system. [ABSTRACT FROM AUTHOR]

Sensory innervation consists of free nerve endings and endings terminated with corpuscular structures. Cutaneous innervation is closely associated with major skin functions such as wound healing, thermoregulation, and hair growth. Diminution in erotic sensation has been reported by some women after abdominal lipectomy. Hence, the lack of knowledge about the normal sensory distribution in the umbilical skin has been a problem. The purpose of this study was, therefore, to map the sensory innervation of the human umbilical skin using histological, immunohistochemical (S-100 protein), and ultrastructural techniques.Umbilical skin biopsies were obtained during surgical procedures for abdominal lipectomy in female participants. The specimens were processed for light and electron microscopic examinations.With light microscopy, abundant Meissner's, Ruffini, and innervated Merkel cells were observed. Numerous free nerve endings, comparable with those observed in male and female external genitalia, were observed surrounding the ducts and the acini of sweat glands. Pacinian corpuscles were also observed, but less frequently. Neurovascular bundles, closely related to those observed in female external genitalia, were also observed.The relatively dense sensory innervation in the umbilical skin that was comparable with that in lip, as well as in male and female external genitalia, can be correlated with the observed retardation in the erotic sensation in clinical studies after removal of a part of the umbilical skin. The frequently observed innervated Merkel cells and the widely scattered Meissner's corpuscles in the umbilical skin could explain the relatively high tactile sensation in this skin. [ABSTRACT FROM AUTHOR]

Abstract: A granular cell tumor (GCT) is relatively uncommon and objectively diagnosed with neural markers on immunohistochemistry (IHC). Recent studies have described additional markers for a GCT. Herein, we present morphologic spectrum of 12 GCTs of soft tissues and skin, including 10 benign and 2 malignant subtypes with an optimal diagnostic IHC panel. Eleven cases occurred in women and 1 in a man, with a mean age of 45.5 years. Six cases occurred in soft tissues and skin of extremities, 4 in the breast soft tissues, and 1 case each in the back and preauricular region, respectively. Cytologic smears in 2 cases displayed polygonal cells with abundant, eosinophilic, granular cytoplasm. On histopathology, all cases invariably revealed a nonencapsulated infiltrating tumor comprising groups and nests of granular cells with vesicular nuclei. In 5 cases, granular cells were noted in close proximity to the nerves. Two malignant GCTs revealed necrosis, mitoses, and nuclear atypia. Immunohistochemistry in 10 cases (83.3%) showed diffuse S-100 positivity in all 7 benign and 2 malignant cases: cytoplasmic CD68 positivity (all 10 cases) and membranous vimentin staining (all 4 cases). Inhibin showed cytoplasmic positivity in 3 of 6 cases. A single malignant GCT showed focal desmin reactivity. All were surgically managed. A GCT is a discrete tumor entity and can be identified from other granular lesions by its proximity to nerves and objective identification with diffuse S-100 positivity, CD68 positivity, and membranous vimentin positivity that form an optimal IHC panel in limited resource settings, irrespective of benign or malignant types. [Copyright &y& Elsevier]

Abstract: There are limited data concerning mechanoreceptors in normal human lumbar intervertebral discs. The aim of our study was to determine the types of mechanoreceptors in the two lower intervertebral discs in normal adult cadaveric donors and to review the literature. Twenty-five lumbar (L4–5 and L5–S1) intervertebral discs were retrieved from 15 fresh cadavers. We utilized immunoreactivity against the S-100 protein to localize specialized nerve endings. Immunoreactivity showed receptors in 92% of discs. The most frequent type had morphology resembling the Ruffini type receptor (88%), followed by the Golgi type. Free nerve fibers were frequently present. All neural structures were found in the superficial layers of the annulus fibrosus, in longitudinal ligaments, or between these two. The anterior part of the L5–S1 disc had a greater frequency of encapsulated receptors than the other parts (p =0.022), which may be correlated with the high shear forces to which the lumbosacral junction is subjected. [Copyright &y& Elsevier]

Juvenile xanthogranuloma (JXG) is a benign histiocytic tumour predominantly seen in the skin. Oral lesions are rare and the present article reports two cases of oral JXG, one that developed in the posterior palate of a 15 year old boy and the other which developed in the right side maxillary antrum of a 2 year old child. The purpose of this article is to describe two additional cases of oral JXG, one a histologically atypical JXG and the other a clinically rare JXG. [ABSTRACT FROM AUTHOR]

We carried out a detailed analysis of rat model of esophageal achalasia previously developed by us. Manifest morphological and functional disorders were observed in experimental achalasia: hyperplasia of the squamous epithelium, reduced number of nerve fibers, excessive growth of fibrous connective tissue in the esophageal wall, high contractile activity of the lower esophageal sphincter, and reduced motility of the longitudinal muscle layer. Changes in rat esophagus observed in experimental achalasia largely correlate with those in esophageal achalasia in humans. Hence, our experimental model can be used for the development of new methods of disease treatment. [ABSTRACT FROM AUTHOR]

Schwannomas are rare tumors originating from the Schwann cells, that form the neural sheath. These tumors occur most frequently in the head, neck, arms and limbs. Primary schwannomas of the colon and rectum are extremely rare. They are usually benign. Pre-operative biopsy examinations may be difficult and immunohistochemistry is necessary for the correct diagnosis. In contrast to gastrointestinal stromal tumors, schwannomas are negative for CD117 and positive for S100 protein and vimentin. In extremely rare cases, they can present with malignant degeneration if not surgically removed. Therefore, the gold standard treatment for schwannomas is surgical resection. [ABSTRACT FROM AUTHOR]

A 50-year-old woman presented with a large cervical polypoid mass. Grossly, the mass occupied a substantial proportion of the cervical canal, measuring 6 cm. Histologically, the mass showed a spindle cell malignancy arranged in large fascicles that penetrated deeply into the fibromuscular wall of the cervix. The spindle cells were immunoreactive for both S-100 protein and HMB-45 antigen, but were negative for Melan-A. Electron microscopy showed that cytoplasmic processes of the spindle to oval tumor cells contained microtubules and were lined by basal lamina and abundant intercellular collagen spacing with no melanosomes in any stage. As far as we are aware, this is the ninth reported case of cervical malignant peripheral nerve sheath tumor (MPNST), and the second reported case of MPNST expressing HMB-45 antigen. [ABSTRACT FROM AUTHOR]

Few neoplasms are unique to the sinonasal tract, but sinonasal undifferentiated carcinoma and olfactory neuroblastoma are malignant tumors which require unique management. Due to the rarity of these tumors, practicing pathologists are not always aware of their distinctive clinical, radiographic, histologic, immunohistochemical, and molecular features. These cases are frequently submitted for consultation, further suggesting the diagnostic difficulties inherent to these tumors. Specifically, olfactory neuroblastoma is a neoplasm that can histologically mimic many tumors within the sinonasal tract, making recognition of this tumor important, as the management frequently requires a bicranial-facial surgical approach, a trephination procedure which can be quite technically difficult and challenging to achieve a good result. The management is therefore quite unique in comparison to other sinonasal tract malignancies, setting it apart diagnostically and managerially from other lesions. [ABSTRACT FROM AUTHOR]

Rosai–Dorfman disease (RDD) involving an extranodal site is a diagnostic challenge. Reported herein is the case of a 67-year-old man who presented with a solitary superior mediastinal mass. The lesion was clinically suspected of malignancy including lymphoma because of its high uptake during a 67Ga-scintigram and 18F-fluorodeoxyglucose–positron emission tomography. There was no evidence of spread of the disease. Histology of thoracoscopic biopsy specimens indicated granulomatous lesion with infiltration of lymphocytes, plasma cells, and histiocytes with lymphocytes engulfed in their cytoplasm. The lesion did not contain lymph node or thymic elements. On immunohistochemistry the histiocytes were positive for S-100 protein, CD68, and CD163 but were negative for CD1a. These findings suggested a diagnosis of RDD. Despite lack of intervention, the lesion remained almost the same size for 3 years. To the best of the authors' knowledge this is the first case of RDD presenting as a solitary mediastinal mass. [ABSTRACT FROM AUTHOR]

Paragangliomas are neuroendocrine tumors. The thyroid gland is one of the anatomic sites in which paraganglia are not normally located and are exceptionally rare. We report a case of a 36-year-old Hispanic woman with a soft mass measuring about 30 mm in the right thyroid lobe. Patient was operated on and the neoplasm showed microscopically a typical nesting organoid pattern (zellballen). The inmunohistochemical analysis revealed that the tumor showed strongly and diffuse stain for NSE, Synaptophysin, Chromogranin A, and S-100 protein in the sustentacular cells, whereas no inmunoreactivity was detected with antibodies against thyroglobulin, calcitonin, TTF-1, CEA, and AE1-AE3. The MIB-1 labeling showed 7% of neoplastic cells. Head and neck paragangliomas usually develop slowly, and this tumor exhibited a low proliferative activity. In view of the uncertain malignant potential of paragangliomas, we recommended a careful long-term follow-up. [ABSTRACT FROM AUTHOR]

Myoepithelial tumours are rare clinicopathological identity. It has been found in parotid glands and salivary glands but never reported in infratemporal fossa or other sites of lateral skull base region. Unlike its benign counterpart, myoepithelial carcinoma is biologically very aggressive and prone to recur even after adequate therapy. Here, a rare case of myoepithelial carcinoma arising from infratemporal fossa has been described along with its treatment options and outcome. [ABSTRACT FROM AUTHOR]

Intracranial intraparenchymal Schwannomas are very rare. Twenty-eight cases of frontal intraparenchymal Schwannomas have been reported so far. These generally present with seizures, raised intracranial pressure, nasal stuffiness and epistaxis. We present a patient with frontal intraparenchymal Schwannoma who underwent frontal craniotomy and excision. At follow-up the patient is seizure free and is relieved of his symptoms. [ABSTRACT FROM AUTHOR]

Solitary fibrous tumour (SFT) rarely occurs in the kidney, with only one case exhibiting malignant behaviour. We report the case of a typical SFT of the kidney with sarcomatous overgrowth in a 34-year-old woman. This malignant component, grossly apparent as a nodular area arising in the context of the main tumour mass, consisted of CD34+ mitotically active atypical plump spindle- to epithelioid-shaped cells, including pleomorphic multinucleated giant cells. A novel immunohistochemical finding was diffuse and strong S-100 protein expression by sarcomatous cells. This should be kept in mind by pathologists to avoid confusion with other S-100 protein-positive malignant neoplasms. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) play a key role in the generation of antitumor immune responses as the most potent professional antigen-presenting cells. In this study we examined the distribution of DCs subsets in selected areas of liver metastases and adjacent liver tissue of 74 patients with gastrointestinal cancers (14 gastric, 47 colon, and 13 rectal) using immunohistochemistrty for the DCs markers S-100 protein, HLA-DR, CD1a, and CD83. S-100 protein-positive DCs were localized mainly in clusters in metastases and at the tumor border with the surrounding liver tissue, while HLA-DR-positive DCs were significantly more in number ( P < 0.0001) and were diffusely distributed in metastasis stroma and at the tumor border. S-100 protein-positive DCs with mature phenotype were presented around metastases and in the sinusoidal lumena, whereas S-100 protein-positive DCs with less mature phenotype based on their ultrastructure were scattered in the tumor stroma. CD1a- and CD83-positive DCs were observed predominantly in small groups or as single cells in the tumor stroma and in the invasive margin. The numbers of CD1a-positive DCs (immature) and CD83-positive DCs (mature) were comparable, but significantly lower than that of S-100 protein-positive ( P < 0.0001) and HLA-DR-positive cells ( P < 0.0001).We observed more S-100 protein-positive DCs and HLA-DR-expressing cells in the sinusoids and portal tracts of the liver tissue, surrounding metastases, than in control liver tissue. In conclusion, this study provides additional information on the functional subtypes and distribution of DCs infiltrating metastatic tissue and local liver environment in patients with liver metastases from gastrointestinal cancers. [ABSTRACT FROM AUTHOR]

Summary: Established markers of brain damage, neuron-specific enolase (NSE) and S-100b protein (S-100), may increase after status epilepticus, but whether a single tonic-clonic or complex partial seizure induces elevation of these markers is not known. Furthermore, it is unclear whether the risk of seizure-related neuronal damage in temporal lobe epilepsy (TLE) differs from that in extratemporal lobe epilepsies (XTLE). The aim of this study was to analyze NSE and S-100 in patients with TLE and XTLE after acute seizures. The levels of NSE and S-100 were measured in serum before (0h) and at 3, 6, 12, and 24h after acute seizures in 31 patients during inpatient video–EEG monitoring. The patients were categorized into the TLE and the XTLE group based on video–EEG recordings and MRI findings. Fifteen patients had TLE and 16 XTLE. Index seizures were mainly complex partial seizures (n =21). In TLE mean±S.D. values for NSE levels (μg/L) were 8.36±2.64 (0h), 11.35±3.84 (3h), 13.48±4.49 (6h), 12.95±5.46 (12h) and 10.33±3.13 (24h) (p =0.006, ANOVA). In XTLE the changes were not significant (p =0.3). There was less increase in the levels of S-100 in TLE (p =0.05) and no significant change in XTLE (p =0.4). The levels of markers of neuronal damage were increased in patients with TLE, not only after tonic-clonic but also after complex partial seizures. These data suggest that TLE may be associated with brain damage. [Copyright &y& Elsevier]

This paper supplements former studies on elasmobranch species with an immunohistochemical investigation into glutamine synthetase and S-100 protein, in addition to GFAP, and extends its scope to the representatives of almost every group of Elasmobranchii: squalomorph sharks, galeomorph sharks, skates (Rajiformes) and rays (Torpediniformes and Myliobatifomes). More glial elements were labeled by S-100 protein, and even more so by using glutamine synthetase immunostaining than by GFAP: more astrocytes (mainly non-perivascular ones) were detected in the telencephalon of sharks, skates and rays. Only the markers S-100 and glutamine synthetase, but not GFAP, characterized the Bergmann-glia of skates and rays and astrocyte-like non-ependymal cells in Squalus acanthias. Another squalomorph shark species, Pristiophorus cirratus, however, had GFAP immunopositive astrocytes. Of all the species studied, the greatest number of GFAP positive astrocytes could be observed in Mobula japanica (order Myliobatiformes), in each major brain part. According to anatomical location, perivascular glia comprised varied types, including even a location in Mobula, which can also be found in mammals. Remnants of radial glia were found in confined areas of skates, less so in rays. In the rhombencephalon and in the spinal cord modified ependymoglia predominated in every group. In conclusion, there was no meaningful difference between the astroglial architectures of squalomorph and galeomorph sharks. The difference in the astroglial structure between sharks and batoids, however, was confined to the telencephalon and mesencephalon, and did not take place in the rhombencephalon, the latter structure being quite similar in all the species studied. The appearance of astrocytes in the relatively thin-walled shark telencephalon, however, indicates that the brain thickening promoted the preponderance of astrocytes rather than their appearance itself. Although the evolutionary changes of astroglia had some similarities in Elasmobranchii and Amniota, there was one meaningful difference: in Elasmobranchii astrocytes did not prevail in conservative brain regions as they did in the progressive brain regions. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: S-100B is a calcium-binding protein that is expressed in astrocytes. We compared the kinetics of serum S-100B in left- and right-hemisphere strokes. Data from 38 acute ischaemic stroke patients who had serial serum S-100B measurements during the first 8 days were analyzed. Stroke severity at baseline, as assessed by the National Institutes of Health Stroke Scale (NIHSS), was similar in the two groups. Mean S-100B values were greater in the right-hemisphere stroke group at all time points. Maximum S-100B levels were low in all patients with lower baseline NIHSS scores, and began to rise at a baseline NIHSS score of 16 for right-hemisphere stroke and 20 for left-hemisphere stroke. S-100B levels were significantly correlated with language in left-hemisphere stroke and with neglect in right-hemisphere stroke. These results are consistent with previous clinical/radiological findings, suggesting that serum S-100B is brain-specific and reflects the extent of brain injury in acute ischaemic stroke. [Copyright &y& Elsevier]

Rosai-Dorfman disease (RDD) is a rare benign proliferative disorder of histiocytes in the lymph nodes with or without extranodal involvement. RDD limited to the skin without nodal involvement, known as cutaneous Rosai-Dorfman disease, is very rare. We describe a 34-year-old female with RDD of the skin over the chest. A large nodule with satellite lesions was excised for histopathological examination. Microscopically, there were many large histiocytes (Rosai-Dorfman cells) exhibiting emperipolesis, among many plasma cells, lymphocytes and neutrophils throughout the dermis and the subcutaneous tissue. The histiocytes were immunohistochemically positive for S-100 protein but negative for CD1a. Physical examination showed no lymphadenopathy or any extra-cutaneous lesions. Serological tests indicated a past infection with Epstein-Barr virus and cytomegalovirus. The diagnosis of cutaneous RDD may be difficult in the absence of associated lymphadenopathy or any specific features of the skin lesion. Hence, not only is histopathological examination required for definitive diagnosis but a high index of suspicion by the clinicians and pathologists is essential to help diagnose this very rare disease. [ABSTRACT FROM AUTHOR]

Calcifying epithelial odontogenic tumor (CEOT) is a rare benign odontogenic tumor. A case of CEOT in a 25-year-old female is presented here. Histologically, the case showed sheets of polyhedral epithelial cells with deep eosinophilic cytoplasm and prominent nuclei. Nuclear pleomorphism and hyperchromatism were evident. Globules of amyloid-like material among the tumor cells were prominent. Also found was a small area demonstrating a cribriform pattern. Immunohistochemical studies with antibodies against basement membrane proteins (laminins 1 and 5, collagen type IV and fibronectin), pan-cytokeratins AE1/AE3, vimentin, S-100 protein and CD 1a were performed. Tumor cells expressed laminins 1 and 5, fibronectin, cytokeratins and vimentin. The amyloid-like material was not reactive to all antibodies examined. A number of dendritic cells among sheets of tumor cells were revealed with strong staining for S-100 protein and CD 1a. These dendritic cells are likely to be Langerhans cells. Hence, immunohistochemistry is a useful method to study the variant of CEOT. [ABSTRACT FROM AUTHOR]

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Abstract: We prospectively examined the effect of arundic acid (AA; ONO-2506) on S-100β, an astrocyte-derived protein, in a phase I acute stroke study. Subjects with acute ischemic stroke were randomized to daily infusion of AA or placebo for 7 days. Serum S-100β levels were assayed pre-infusion on Days 1–7 and post-infusion on Days 1, 3, and 7, and correlated with National Institutes of Health Stroke Scale (NIHSS). Samples were obtained from 86 subjects (46 AA, 40 placebo). Increase in S-100β protein level from baseline was less in the AA cohort than in the placebo cohort at 7 (p =0.0471; t-test) and 12 (p =0.0095)-hours post-infusion on Day 3. Baseline NIHSS correlated with maximal S-100β levels between Days 1 and 3 in the AA (r =0.51; p =0.0003) and placebo (r =0.41; p =0.0084) cohorts and in the pooled aggregate (n =86; r =0.46; p <0.0001). The same correlations were observed between Day 10 NIHSS and Day 1–3 maximum serum S-100β levels. Treatment with AA was associated with lower serum levels of S-100β after acute ischemic stroke. Our results showing correlation between S-100β and NIHSS indicate that this protein is a clinically relevant marker of neurological deficit in acute stroke. [Copyright &y& Elsevier]

Immunohistochemistry, based on antibody anti-S100 protein, was used to evaluate the Langerhans cells (LC) in benign and malign skin neoplasias. These cells were quantitatively estimated using a computer image analysis (OPTIMAS software system, Version 6.1) in skin biopsies diagnosed as basal cell carcinoma (BCC), epidermoid carcinoma (EpC), trichoepithelioma (TE), keratoacanthoma (KA), seborreic keratosis (SK) and actinic keratosis (AK). The antibody anti-S100 protein recognized them. No significant variations were observed in the number of LC among malignant tumour (BCC = 23.25 ± 5.81 and EpC = 20.88 ± 4.24). Benign lesions (AK = 33.04 ± 7.11; TE = 55.74 ± 9.35; SK = 42.38 ± 9.92, and KA = 47.62 ± 10.4) presented a higher number of LC when they were compared among them and to malignant and normal tissues. No significant differences were observed in LC area and volume between benign and malign neoplasias. These results indicate possibly differences in the immunogenicity between benign and malign epidermic tumours. In conclusion, the experimental computer assessment method was reliable and consistent to morphometric analysis of tumoural tissues. [ABSTRACT FROM AUTHOR]

S-100 protein expression is present in various malignant tissues, yet its prognostic relevance is debatable. The aim was to assess in non-small cell lung cancer (NSCLC) patients’ prognostic value of S-100 protein considered alone or in relation with other variables. Tumour samples taken from 86 NSCLC patients during resection were assayed for S-100 protein expression with the use of polyclonal DAKO ZO311 antibody. S-100 expression was found in 32 cases (37%). Positive staining was not correlated with clinical characteristics including age, sex, pathology type of tumour, stage and cigarette smoking. There was a tendency for simultaneous expression of S-100 and P53 protein ( p =0.06). A median survival rate for the entire group was 2.3 years (95% CI, 0.9–3.6 years). The median and 5-year survival of patients with positive staining for S-100 protein was 1.5 years and 25%, respectively, compared with 3.0 years and 35%, respectively, in the S-100 negative group ( p =0.17). In the final model of a multivariate analysis, S-100 protein expression in tumour cells was associated with significantly decreased survival ( p =0.005). S-100 protein expression in tumour cells seems to be an independent predictor of poor prognosis in NSCLC patients. [ABSTRACT FROM AUTHOR]

Summary: Polyclonal antibody to S-100 protein has been routinely applied for initial screening of various types of tumors, including, melanocytic tumors and neurogenic tumors. S-100 protein has been shown to have a broad distribution in human tissues, including renal tubules. The potential utility of S-100 protein in renal cell neoplasms has not been extensively investigated. Using an EnVision–Horseradish Peroxidase (HRP; Dako, Carpinteria, Calif) kit, we evaluated the diagnostic value of S-100 protein on tissue microarray sections from 175 cases of renal epithelial neoplasm (145 primary renal neoplasms and 30 metastatic renal cell carcinomas) and 24 non-neoplastic renal tissues. Immunohistochemical stains for pancytokeratin, HMB-45, and Mart-1 were also performed. Western blot using the same antibody (anti–S-100 protein) was performed on 10 cases of renal cell neoplasm. The results demonstrated that nuclear and cytoplasmic staining pattern for S-100 protein was observed in 56 (69%) of 81 conventional (clear cell) renal cell carcinomas (RCCs), 10 (30%) of 33 papillary RCCs, 1 (6%) of 16 ChRCCs, and 13 (87%) of 15 oncocytomas. Among the 81 cases of CRCC, positivity for S-100 protein was seen in 41 (71%) of 58 and 15 (65%) of 23 cases with Furhman nuclear grade I/II and III/IV, respectively. Focal immunostaining was present in 22 (92%) of 24 normal renal tubules. Similar staining pattern was observed in 21 (70%) of 30 metastatic RCCs. Western blotting demonstrated the S-100 protein expression in both renal cell neoplasm and normal renal tissue. Overexpression of S-100 in oncocytomas compared with ChRCCs was confirmed by the data of Western blot and cDNA microarray analysis. Importantly, 14.8% (12/81) of clear cell RCC and 13.3% (4/30) of metastatic RCC revealed an immunostaining profile of pancytokeratin (−)/S-100 protein (+). These data indicate that caution should be taken in interpreting an unknown primary with S-100 positivity and cytokeratin negativity. In addition, it suggests that S-100 has a diagnostic value in differentiating oncocytoma from ChRCC. [Copyright &y& Elsevier]

Abstract: Background: Rosai-Dorfman disease is an idiopathic histiocytic proliferative disorder characterized by sinus histiocytosis and massive lymphadenopathy. Extranodal involvement is rare and central nervous system (CNS) involvement is unusual. We present a case of a multiple-level spinal involvement by Rosai-Dorfman disease without cervical lymphadenopathy, which is distinctly rare. Very few cases have been reported in literature. Its resemblance with meningiomas both clinically and radiologically makes its diagnosis all the more difficult. Case Description: A 23-year-old woman presented with quadriparesis and incontinence of urine and stool with a history of being operated on twice for dorsal spine tumor. On examination she had hypoesthesia below the C6 vertebra with anesthesia below D3, and absent joint position and vibration sensations. The patient had spasticity in lower limbs with normal tone in upper limbs. Deep tendon reflexes were hyporeflexic in upper limbs and hyperreflexic in lower limbs with bilateral ankle clonus with bilateral Babinski sign. Magnetic resonance imaging of the cervicodorsal spine was suggestive of multiple intradural extramedullary space-occupying lesion with probability of meningiomas. Surgical resection of 3 tumors was done and sent for histopathology, which was suggestive of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). The patient had good postoperative recovery and was followed up for 5 months with no new complaints. Conclusion: Rosai-Dorfman disease is a rare entity having clinical and radiological similarity to meningioma. It is similar to lymph node histiocytosis and rarely involves the CNS. It is a benign lymphohistiocytic proliferative condition of unknown etiology. Histopathology showing emperipolesis (lymphophagocytosis) and immunohistochemistry showing S-100 positivity is diagnostic. Surgical resection is the treatment of choice. [Copyright &y& Elsevier]

Abstract: Background: The molecular monitoring of circulating tumor cells by reverse transcriptase-PCR (RT-PCR) for patients with melanoma, is still under debate. It may be affected by: a) pre-analytical variability, b) frequency of melanoma-associated gene transcripts and c) the reliability of the methods employed. Few commercial methods are available for the detection of tyrosinase mRNA in blood. Objective: Comparison between two RT-PCR-nested methods with a third one based on real-time methodology, for detection and quantitation of tyrosinase transcripts, respectively. Methods: Sixty-two melanoma patients with different AJCC stages and 20 healthy subjects were enrolled. All blood samples were extracted in duplicate with two different methods. Two nested-PCR methods (one commercial and one in house) plus a real time commercial kit were employed. Results: The two nested PCR methods employed were overimposable, specific and sensitive, at least in the stage III, where there was a concordance between sentinel lymph nodes detection and blood tyrosinase positivity. The different extraction methods did not affect the quality of results, while the commercial real-time kit cannot be used. Conclusion: Tyrosinase mRNA detection may be therefore employed to monitor the melanoma patients over time in function of response to therapy. [Copyright &y& Elsevier]

Abstract: The distribution of the S-100 protein cell (folliculo-stellate cell) is very important to our understanding of the regulation of the anterior pituitary. In this study, 10 intact 60-day-old male Wistar–Imamichi rats, were separated equally into two groups. One was used for immunohistochemical study, and the other for electron microscopic analysis. Immunostained pituitary sections with S-100 protein antibody were photographed using a CCD camera equipped with a computer. The S-100 protein cells were then measured using NIH image software, and the three-dimensional distribution of the cells was analyzed. The distribution of the cells observed in each serial section showed that S-100 protein cells were dense at the basal zone of the gland and at the “transitional zone” where the pars tuberalis adjoined the anterior and intermediate lobes, where they represented over 50% of the total cell population. They then decreased in number with distance from this region to mid-way towards the sagittal axis before increasing again in the tail of the gland. The population of cells also decreased with increasing distance from the “transitional zone” to the wing and with distance from the basal zone. Portal vessels entered the anterior lobe through the “transitional zone” as thick capillaries, ran through the basal surface and penetrated into the central area of the anterior lobe. In all planes, S-100 protein cells encircled the capillaries. Ultrastructural observations confirmed the light microscopic findings indicating that clusters of agranular cells were densely located at the “transitional zone” and in the pars tuberalis. The distribution pattern of the folliculo-stellate cells and the capillaries showed good agreement and the spatial relationship between these two is detailed so as to better understand hypophyseal histophysiology. [Copyright &y& Elsevier]

Background. It is important to identify new biochemical markers of strokes to monitor and predict the neurological outcome, as well as to elucidate the multiple molecular mechanisms after ischemic brain infarction. Recently, an elevation of S-100 protein in serum were reported in strokes, but still, different biochemical techniques must be developed as soon as possible in order to help us to improve effective treatment. Modern neuroradiological techniques help to predict the outcome; however, repeating neuroradiological imaging is impractical. The aim of the study was to evaluate the serum levels of S-100 protein after brain infarction in correlation with clinical data and prognosis. Material and methods. S-100 protein serum levels were determined in 47 patients with an acute ischemic brain infarction in the first day (within 12 hours after the onset of symptoms) and sex and age matched control subjects. The clinical status was documented using the Scandinavian Stroke Scale. The functional deficit 4 weeks after stroke onset was scored with the Barthel Index. A cranial computed tomography (CCT) was performed after 2 days. Results. Elevated concentrations of S-100 protein were observed in patients with strokes. The S-100 concentrations in serum were significantly higher in patients with severe neurological deficits at the time of admission and correlated with the functional prognosis. Conclusions. The measurement of S-100 protein in serum is useful to diagnose and predict the outcome in patients after brain infarction. [ABSTRACT FROM AUTHOR]

Non-hormone-secreting cells in human adenohypophysis have been designated as either follicular cells (FC) or folliculostellate cells (FSC). They have similarly long cytoplasmic processes, and the difference between FC and FSC remains unclear. An immunohistochemical study for S-100 protein, cytokeratin (CK, detected by AE1/AE3) and glial fibrillary acidic protein (GFAP) was performed in autopsy pituitaries. Double immunohistochemistry for S-100 protein and CK revealed that there were numerous coexpressed cells. The most frequent type (‘CK-type cell’) was cells weakly positive for S-100 protein in the nucleus and for CK-immunoreactivity in the cytoplasm. The next numerous type (‘S-100 protein cell’) was cells strongly positive for S-100 protein and weakly positive or negative for CK. The CK-type cells were frequently observed in the vicinity of follicular structures and in neighborhood of adrenocorticotropic hormone -immunoreactive cells, and were most likely the cells termed FC. They were often observed around necrotic areas. The S-100 protein cells were individually found in the circumference of endocrine cell nest, and seemed to be the so-called stellate cells. GFAP-positive cells were rare. It is implied that S-100 protein-positive FSC could be divided into at least two main subtypes: FC (CK-type cells) and stellate cells (S-100 protein cells). [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose:: Patients resuscitated from cardiac arrest are at risk of subsequent death or poor neurological outcome up to a persistent vegetative state. We investigated the prognostic value of several epidemiological and clinical markers and two neuroproteins, neuron-specific enolase (NSE) and S-100 protein (S-100), in 97 patients undergoing cardiopulmonary resuscitation (CPR) after non-traumatic cardiac arrest between 1998 and 2002. Results:: 52.6% of the patients died, 28.8% survived with severe, moderate or without neurological disorders, and 18.6% remained in a persistent vegetative state. Unconsciousness >48h after CPR predicted a 60.6-fold (95% CI 14.3287–257.205, p=0.001) and a Glasgow Coma Scale (GCS) <6 points after 72h a 11.2-fold (CI 95%, 3.55–36.44, p<0.001) risk of poor neurological outcome. Serum levels ≥65ng/ml for NSE and ≥1.5μg/l for S-100 increased the risk of death and persistent vegetative state 16.8 (95% CI 2.146–131.520)- and 12.6 (95% CI 1.1093–99.210)-fold, respectively. By combination of the GCS with elevated serum concentrations of both neuroproteins above the cut off levels on third day after CPR a poor neurological outcome was predicted with a specificity of 100%. Conclusion:: The combination of GCS with the serum levels of both neuroproteins at 72h after CPR permit a more reliable prediction of outcome in post arrest coma than the single markers alone, independent of the application of anaesthetic agents. [Copyright &y& Elsevier]

Abstract: The value of normal S-100B levels to predict survival was evaluated in 145 patients with stage IV melanoma. Treatment consisted of temozolomide given alone or was followed by combined cytokine immunotherapy, given every three to four weeks, with an evaluation of response following two treatment-cycles. S-100B values were measured prior to and following each cycle of systemic therapy and regularly thereafter. Patients with normal initial S-100B values (n=32) had higher response rates and fewer and more favourable metastatic sites with better overall survival rates than patients with elevated S-100B levels (median 14.0 versus 6.6 months). Normal S-100B values increased in nearly all patients (28/31) after a median of 7.9 months. In addition, patients with rapid normalisation of their serum level (n=12) following systemic treatment experienced prolonged survival. However, upon multivariable analysis S-100B prior to treatment lost its independence as a prognostic factor, whereas lactate dehydrogenase (LDH) remained. When measured after treatment, both markers had independent value. [Copyright &y& Elsevier]

Dendritic cells (DCs) are the most efficient antigen-presenting cells and play a key role in a cellular antitumor immune response. In this study we investigated the exact localization of DCs within colorectal tumors and their relationship to tumor-infiltrating lymphocytes as well as clinical outcome of the patients. Primary tumor specimens of 104 patients with a diagnosis of colorectal cancer were identified retrospectively and analyzed with the dendritic cell markers S-100 protein and human leukocyte antigens (HLA) class II. The markers were individually combined with laminin as a second marker to facilitate the observation of the different tumor localizations. S-100 or HLA class II positive cells were found in the three different compartments of colorectal tumors: tumor epithelium, tumor stroma, and advancing tumor margin, but mainly present in tumor stroma and advancing tumor margin. S-100-positive tumor-infiltrating DCs in direct contact with tumor cells, i.e., in tumor epithelium, significantly correlated to the intraepithelial infiltration of CD4+ (p=0.02) and CD8+ (p=0.01) lymphocytes. High HLA class II+ cell infiltration in the tumor stroma correlated to a lower intraepithelial infiltration of CD8+ (p=0.02) lymphocytes. High intraepithelial infiltration of S-100-positive DCs suggested increased disease-free survival, but was not statistically significant, while high amounts of HLA class II+ cells in the tumor stroma correlated with an adverse survival outcome. Our results show that the infiltration of DCs in colorectal cancer, depending on both location and type of marker, is correlated with local immune interactions and patient prognosis, suggesting a central role for DCs in controlling local tumor immunity. [ABSTRACT FROM AUTHOR]

The distribution of LH-RH-positive nerve fibers in the median eminence was demonstrated in the 1970s and 1980s. A few LH-RH fibers have been reported to be present in the adjacent pars tuberalis of the pituitary, but their functional significance has not been clarified and still remains enigmatic. Adult male Wistar-Imamichi rats were separated into two groups: one for immunohistochemistry of LH-RH and S-100 protein (for the identification of folliculo-stellate cells) and the other for electron microscopy. For both immunohistochemistry and electron microscopy, the specimens obtained contained the pituitary gland connected with the hypothalamus. Numerous LH-RH-positive fibers were observed as tiny lines with several varicosities both on the primary vascular plexus and in the hypothalamus corresponding to the posterior half of the portal vein area. LH-RH-positive fibers were also noted around S-100-positive cells in the pars tuberalis. Weakly reactive S-100 cells were scattered in the pars tuberalis in the midsagittal plane, while clusters of strong reactive elements occurred 100–300 μm from the center. Similar observations were made using fluorescence immunohistochemistry for LH-RH and S-100, and at the electron-microscopic level. At the posterior portion of the portal vein system, bundles of the LH-RH-immunoreactive fibers invaded the pars tuberalis and terminated on agranular cells. Gap junctions were clearly seen among agranular cells corresponding to folliculo-stellate cells. It is postulated that the LH-RH message might be transmitted not only by the established hypophyseal portal vein system but also via the folliculo-stellate cells in the pars tuberalis to aid in the modulation of LH release. [ABSTRACT FROM AUTHOR]

Human neuroblastoma arises from the developing neural crest. Tumors are categorized clinically by their location, age at diagnosis, spread/metastasis, and degree of cellular maturation and heterogeneity. Our long-term studies have shown the presence in human neuroblastoma cell lines of three distinct cell types: I-type stem cells, N-type neuroblastic/neuroendocrine precursors, and S-type Schwannian/melanoblastic precursors. These distinct cell types can differentiate predictably along specific neural crest lineages in response to particular morphogens. As assessed by tumor formation in nude mice and anchorage-independent growth in soft agar, I-type stem cells are significantly more malignant than either N- or S-type cells. Recent research shows that three similar cell types are also present in human neuroblastoma tumors. Using immunocytochemical, laser-capture microdissection, or short-term culture methods to identify cell types in tumors of different stages and/or different outcomes, these studies have shown that (1) all tumors contain neuroblasts in various differentiation states; (2) presumptive I-type stem cells are present in tumors of all stages; and (3) stromal cells may be tumor-derived, i.e. S-type cells, as well as of normal origin. More importantly, there is a higher incidence of I-type cells in tumors that progress, consistent with the high malignant potential of this cell type in vitro. A better understanding of the cause and consequences of cellular heterogeneity of human neuroblastoma tumors is an important prerequisite to the development of more effective therapies for this often fatal disease. [Copyright &y& Elsevier]

Abstract Blue discoloration of the iris was found in the left eye of a male laboratory Beagle dog, which had a normal tricolor coat and clinically showed no visual impairment. Ophthalmoscopically, the affected eye revealed red-colored tigroid fundus, in which no tapetum was present. The retinal vasculature and the optic disc showed no noticeable changes. Histopathologically, in the left eye melanocytes had extremely few melanin granules in the anterior segment, including the anterior border layer, in the stroma and sphincter muscle of the iris and in the stroma of the ciliary body and choroid. However, the posterior pigment epithelium of the iris, the pigment epithelium of the ciliary body and the retinal pigment epithelium showed normal pigmentation. The tapetal elements were completely absent. Number and distribution of the S-100 protein-positive melanocytes with or without melanin granules in the iris, ciliary body and choroid of the left eye were similar to those of the normal right eye. Ultrastructurally, melanocytes in the anterior segment of the affected iris possessed no or few melanosomes which were incompletely melanized. In the right eye, no abnormal features were observed. Based on these results, the present case was diagnosed as unilateral ocular subalbinism with tapetal aplasia in a Beagle dog. [ABSTRACT FROM AUTHOR]