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PubMed1999

Distribution of unipolar brush cells and other calretinin immunoreactive components in the mammalian cerebellar cortex.

We have compared the distribution of unipolar brush cells (UBCs) in the cerebellum of Brazilian opossum (Monodelphis domestica), mouse, guinea pig, rabbit, cat, and Rhesus monkey, using an antiserum to calretinin which is present in those cells. The morphology and calretinin staining intensity of the UBCs remains constant across species. As a general trend, in all species studied, UBCs are particularly enriched in the vestibulocerebellum. Interspecies differences, however, were noted in the distribution of UBCs across other regions of the cerebellar cortex. A major variation involves the extent of the UBC-rich region of the ventral portion of the paraflocculus. The distribution of UBCs in non-vestibular vermal folia also varies substantially. UBCs are deployed in more or less distinct parasagittal zones in the vermis of the opossum, rabbit, cat, and macaque. The density of UBCs decreases progressively from medial to lateral portions of the same folium and is lowest in the lateral, posterior portions of the cerebellar hemispheres (crus II) and in the dorsal portion of the paraflocculus. In cat and macaque, the decrease in the density of UBCs across the intermediate cortex is more gradual than in the other species. The data indicate that the UBCs play a more prominent role in the modulation of sensorimotor transformations in carnivores and primates than in smaller mammals and should not be considered a vestigial form of neuron. In addition to the UBCs, calretinin antibody distinctly stains the following neurons in different species: granule cells and parallel fibers in all species except rabbit and cat; Golgi cells, especially in rat and macaque; Lugaro-like cells, especially in mouse, rat, and macaque; basket cells in macaque; subsets of mossy fibers in all species; and subsets of climbing fibers in all species but guinea pig. Usually, the distribution of UBCs is related to that of calretinin stained granule cells and mossy fibers.

Animals↗
PubMed2000

Unipolar brush cells develop a set of characteristic features in primary cerebellar cultures.

The unipolar brush cells (UBCs) are a class of excitatory interneurons recently discovered in the cerebellar granular layer. UBCs differ morphologically and biochemically from granule cells, although they share the same mossy fiber and Golgi cell inputs. To elucidate development of the UBCs, we sought to ascertain their presence in primary cerebellar cultures and the class-specific properties they develop in vitro outside of the context of the tissue. By light and electron microscopy, we demonstrate that primary cultures from embryonic and postnatal mouse and rat cerebella contain UBC-like neurons that are highly polarized and can be distinguished from granule cells on several grounds. Granule cells are more numerous in dissociated postnatal cultures than in embryonic cultures; express little, if any, calretinin immunoreactivity; and develop dendritic processes devoid of typical claw-like endings, but provided with small synaptic junctions. By contrast, UBC-like neurons occur more frequently in embryonic cultures than in postnatal cultures, are intensely calretinin-positive, and develop characteristic cell organelles, dendrites, and large synapses. In embryonic cultures, the UBC-like neurons have a clear nucleus and contain a special cytoplasmic array of ringlet subunits, resembling the botrysome. At 12-28 days in vitro, the UBC dendrites contain abundant mitochondria, are provided with clusters of non-synaptic appendages, and engage in glomerular arrays together with large and small axon terminals. The large terminals contain round synaptic vesicles, form extensive, asymmetric synapses with the cell bodies and the dendrites of the UBC-like neurons, and resemble mossy terminals, while the small terminals contain pleomorphic vesicles, form symmetric synaptic junctions, and resemble Golgi terminals. In postnatal cultures grown for 12 days, UBC-like neurons are rare and resemble in most aspects the cells observed in embryonic cultures, although they rarely develop elaborate dendritic brushes.

Animals↗
PubMedDate not supplied

The neurons of the ground squirrel retina as revealed by immunostains for calcium binding proteins and neurotransmitters.

Ground squirrel retinas were immunostained with antibodies against calcium binding proteins (CBPs) and classical neurotransmitters in order to describe neuronal phenotypes in a diurnal mammalian retina and to then compare these neurons with those of more commonly studied nocturnal retinas like cats' and rabbits'. Double immunostained tissue was examined by confocal microscopy using antibodies against the following: rhodopsin and the CBPs, calbindin, calretinin, parvalbumin, calmodulin and recoverin (CB, CR, PV, CM, RV), glycine, GABA, choline acetyltransferase (CHAT) and tyrosine hydroxylase (TOH). In ground squirrel retina, the traditional cholinergic mirror symmetric amacrine cells colocalize CHAT with PV and GABA and faintly with glycine. A second cholinergic amacrine cell type colocalizes glycine alone. CR is found in at least 3 different amacrine cell types. The CR-immunoreactive (IR) cell population is a mixture of glycinergic and GABAergic types. The dopamine cell type IR to tyrosine hydroxylase has the typical morphology of a wide field cell with dendrites in S1 but the "rings" seen in cat or rabbit retina are not as numerous. TOH-IR amacrine cells send large club-shaped processes to the outer plexiform layer. CB and CR are in bipolar cells, A- and B-type horizontal cells and several amacrine cell types. Anti-rhodopsin labels the low density rod photoreceptor population in this species. Anti-recoverin labels cones and some bipolar cells while PKC is found in several different bipolar cell types. One ganglion cell with dendritic branching in S3 is strongly CR-IR. We find no evidence for an AII amacrine cell in the ground squirrel, with either anti-CR or anti-PV. An amacrine cell with similarity to the DAP1-3 cell of rabbit is CR-IR and glycine-IR. We discuss this labeling pattern in relationship to other mammalian species. The differences in staining patterns and phenotypes revealed suggest a functional diversity in the populations of amacrine cells according to whether the retinas are rod or cone dominated.

Amacrine Cells↗
PubMed2005

Unipolar brush cells--a new type of excitatory interneuron in the cerebellar cortex and cochlear nuclei of the brainstem.

Published data and the authors' own studies on the morphology, neurochemical specialization, and spatial organization of unipolar brush neurons (UBN) in the cerebellar cortex and cochlear nuclei of the brainstem are reviewed. UBN represent an exclusive category of excitatory interneurons, with a single dendrite which forms a compact branching with a shape reminiscent of that of a brush in its terminal segment. These cells are characterized by an uneven distribution in the granular layer of the cerebellum, being located mainly in its vestibular zones. UBN synthesize glutamate, calretinin, and metabotropic and ionotropic glutamate receptors. The dendritic brush of UBN form giant synapses with the rosettes of glutamatergic and cholinergic mossy afferent fibers. UBN axons form an intracortical system of mossy fibers which, forming rosettes and glomeruli, make contact with the dendrites of other UBN and granule cells. In the circuits of interneuronal communications, UBN can be regarded as an intermediate component, amplifying the excitatory effects of mossy afferent fibers on granule cells in the cerebellar cortex and cochlear nuclei of the brainstem.

Animals↗
PubMed2002

Localized malignant mesothelioma of the epithelial type occurring as a primary hepatic neoplasm: a case report with review of the literature.

We report a localized malignant mesothelioma of the epithelial type, occurring as a primary hepatic neoplasm in a 64-year-old male. He was found to have a mass located in the right lobe of the liver. Surgery was carried out with resection of the mass from the right hepatic lobe, with partial resection of the diaphragm. Grossly, an ill-defined tumor was present in the hepatic parenchyma. Histologically, the tumor displayed a predominant tubular pattern of growth with a desmoplastic stroma. The tubules were lined by a single layer of cuboidal or flattened cells with pleomorphic vesicular nuclei. A hyaluronidase-digestible, mucin-like substance was demonstrated in the lumen and tumor cytoplasm. The tumor cells were immunohistochemically positive for calretinin, HBME-1, cytokeratin, i.e. AE1/AE3 and CAM 5.2, but negative for carcinoembryonic antigen, CD 34 and Leu M1. Moreover, the tumor cells showed nuclear accumulation of the p53 oncopotein and reacted frequently with Ki-67 antibody. These findings support the concept that malignant mesothelioma of the epithelial type may occur at extrapleural sites. To the best of our knowledge, this is the first reported case of localized malignant primary mesothelioma arising in the liver.

Biomarkers↗
PubMed2000

Solitary fibrous tumors are immunophenotypically distinct from mesothelioma(s).

INTRODUCTION: Solitary fibrous tumor is a soft tissue tissue tumor of unknown histogenesis. Based upon histologic similarities and CD-34 expression, it has been suggested that these neoplasms bear some relationship to mesothelioma, and may represent its extra-pleural equivalent. METHODS: In order to further investigate this possible relationship, we examined a series of five dermal and five extra-cutaneous solitary fibrous tumors with antibodies directed against the mesothelial markers calretinin and HBME-1. RESULTS: All the lesions failed to stain with the antibodies tested. This suggests that despite some similar histologic and immunophenotypic features, these lesions are not immunophenotypically identical. Mesotheliomas are CD-34(+), calretinin(+), HBME-1(+), while solitary fibrous tumors are CD-34(+), calretinin(-), HBME-1(-). CONCLUSIONS: The histogenesis of solitary fibrous tumor remains elusive. It is unlikely that tumor location or tumor de-differentiation accounts for the dichotomous staining properties, as these neoplasms show a similarly benign histologic appearance regardless of location.

Adult↗
PubMed2003

Primary purely intradermal pleomorphic liposarcoma.

INTRODUCTION: Pleomorphic liposarcoma (PLPS) is a high-grade pleomorphic sarcoma, containing multivacuolated lipoblasts, which usually develops during late adult life. It usually occurs in the deep soft tissues and uncommonly arises in the subcutis, the dermis representing an exceedingly rare site of occurrence. METHODS: We describe a case of PLPS arising in the dorsal aspect of the nose of a 75-year-old woman. Preoperative duration was 9 months. RESULTS: The lesion was intradermal well-circumscribed, dome-shaped, measuring 1.2 cm. It fulfilled the histologic criteria for inclusion in the PLPS category. The tumor cells focally expressed calretinin. A review of the literature yielded four cases documented, to which we add the present report. All the patients were adults with a mean age of 67 (range 39-95) years, and three of five cases arose on the scalp. Local recurrence occurred in one patient, but no distant metastases or disease-related deaths were observed. CONCLUSION: PLPS very rarely arises in the dermis. In spite of high-grade morphology, the intradermal tumor shows a relatively favorable prognosis. Diagnostic consideration includes pleomorphic lipoma, clear cell atypical fibroxanthoma, balloon cell melanoma, and metastatic clear cell carcinoma of renal origin. Recognition of this distinctive and rare type of liposarcoma is essential to avoid under- or misdiagnosis and inappropriate treatment.

Aged↗
PubMed2000

Stereocilia defects in the sensory hair cells of the inner ear in mice deficient in integrin alpha8beta1.

The mammalian inner ear contains organs for the detection of sound and acceleration, the cochlea and the vestibule, respectively. Mechanosensory hair cells within the neuroepithelia of these organs transduce mechanical force generated by sound waves or head movements into neuronal signals. Defects in hair cells lead to deafness and balance defects. Hair cells have stereocilia that are indispensable for mechanosensation, but the molecular mechanisms regulating stereocilia formation are poorly understood. We show here that integrin alpha8beta1, its ligand fibronectin and the integrin-regulated focal adhesion kinase (FAK) co-localize to the apical hair-cell surface where stereocilia are forming. In mice homozygous for a targeted mutation of Itga8 (encoding the alphabeta8 subunit), this co-localization is perturbed and hair cells in the utricle, a vestibular subcompartment, lack stereocilia or contain malformed stereocilia. Most integrin alpha-8beta1-deficient mice die soon after birth due to kidney defects. Many of the survivors have difficulty balancing, consistent with the structural defects of the inner ear. Our data suggest that integrin alpha8beta1, and potentially other integrins, regulates hair-cell differentiation and stereocilia maturation. Mutations affecting matrix molecules cause inherited forms of inner ear disease and integrins may mediate some effects of matrix molecules in the ear; thus, mutations in integrin genes may lead to inner-ear diseases as well.

Actins↗
PubMed2005

Granulocyte-colony stimulating factor- and interleukin 6-producing diffuse deciduoid peritoneal mesothelioma.

An autopsy case of granulocyte colony-stimulating factor (G-CSF)- and interleukin-6 (IL-6)-producing diffuse deciduoid peritoneal mesothelioma is reported. The patient was a 70-year-old man with abdominal distension and weight loss in the year prior to his death. Laboratory data suggested severe inflammation with marked leukocytosis, thrombocytosis and elevated serum levels of C-reactive protein, G-CSF and IL-6. Imaging studies showed an expansive mass occupying the entire abdomen and pelvic cavity. Histological diagnosis of tissue taken by needle biopsy was difficult due to the unusual sarcomatoid-appearance of the tumor. In addition, there was severe infiltration of numerous neutrophilic leukocytes. An autopsy revealed that the diffuse peritoneal tumor had a fresh fishmeat-like appearance with focal mucinous degeneration and entirely encased the abdominal organs. Histological examination showed a sheet-like proliferation of tumor cells with large ovoid or polygonal cytoplasm, large atypical nuclei and obvious nucleoli. The tumor cells showed abundant glycogen and hyaluronic acid, and were immunoreactive to cytokeratin, calretinin, epithelial membrane antigen (EMA), CA-125, and focally to vimentin. The tumor cells were immunoreactive to G-CSF and IL-6. Electron microscopy revealed long, slender microvilli on the tumor cell surface. This tumor was diagnosed as a G-CSF- and IL-6-producing, diffuse deciduoid mesothelioma. We report this case with special reference to the differential diagnosis of deciduoid peritoneal mesothelioma with paraneoplastic syndrome.

Aged↗
PubMed2006

The diagnostic utility of immunohistochemistry and electron microscopy in distinguishing between peritoneal mesotheliomas and serous carcinomas: a comparative study.

The histologic distinction between peritoneal epithelioid mesotheliomas and serous carcinomas diffusely involving the peritoneum may be difficult, but it can be facilitated by the use of immunohistochemistry and electron microscopy. D2-40 and podoplanin are two recently recognized lymphatic endothelial markers that can be expressed in normal mesothelial cells and mesotheliomas. The purpose of this study is to compare the value of these new mesothelial markers with those that are commonly used for discriminating between mesotheliomas and serous carcinomas, and also to determine the current role of electron microscopy in distinguishing between these malignancies. A total of 40 peritoneal epithelioid mesotheliomas and 45 serous carcinomas of the ovary (15 primary, 30 metastatic to the peritoneum) were investigated for the expression of the following markers: D2-40, podoplanin, calretinin, keratin 5/6, thrombomodulin, MOC-31, Ber-EP4, B72.3 (TAG-72), BG-8 (Lewis(Y)), CA19-9, and leu-M1 (CD15). All 40 (100%) of the mesotheliomas reacted for calretinin, 93% for D2-40, 93% for podoplanin, 93% for keratin 5/6, 73% for thrombomodulin, 13% for Ber-EP4, 5% for MOC-31, 3% for BG-8, and none for B72.3, CA19-9, or leu-M1. All 45 (100%) serous carcinomas were positive for Ber-EP4, 98% for MOC-31, 73% for B72.3, 73% for BG-8, 67% for CA19-9, 58% for leu-M1, 31% for keratin 5/6, 31% for calretinin, 13% for D2-40, 13% for podoplanin, and 4% for thrombomodulin. After analyzing the results, it is concluded that Ber-EP4 and MOC-31 are the best negative mesothelioma markers for differentiating between epithelioid mesotheliomas and serous carcinomas. The best discriminators among the positive markers for mesotheliomas are D2-40, podoplanin, and calretinin. From a practical point of view, Ber-EP4 and MOC-31, in combination with calretinin, and/or D2-40 or podoplanin allow the differential diagnosis to be established between mesothelioma and serous carcinoma in nearly all instances. As a clear distinction could be made between these two malignancies in all of the cases in which electron microscopy was performed, this technique can be very useful in establishing the correct diagnosis when the immunohistochemical results are equivocal or further support of a diagnosis of either mesothelioma or serous carcinoma is needed.

Antigens, Neoplasm↗
PubMed2006

Uterine tumors resembling ovarian sex cord tumors are polyphenotypic neoplasms with true sex cord differentiation.

In this study, we present the clinicopathologic features and immunophenotypic characteristics of five cases of uterine tumors resembling ovarian sex cord tumors and three cases of endometrial stromal tumors with sex cord-like elements, with emphasis on immunohistochemical markers of sex cord differentiation. The mean patient age was 42 years (range 19-69 years), and vaginal bleeding was the most common clinical presentation. The tumors were usually polypoid masses arising in the uterine fundus, with a mean tumor size of 6.7 cm. Sex cord patterns in uterine tumors resembling ovarian sex cord tumors, including anastomosing cords, trabeculae, small nests, tubules, and in one case, a striking retiform architecture with Leydig-like cells, comprised from 70 to 100% of the tumor volume. All uterine tumors resembling ovarian sex cord tumors were positive for two or more markers of sex cord differentiation; all five cases showed strong immunoreactivity for calretinin, with coexpression of CD99 (four cases), Melan-A (two cases), and inhibin (two cases). Endometrial stromal tumors with sex cord-like elements were less frequently positive for markers of sex cord differentiation, with each case positive for one marker (calretinin, two cases; CD99, one case). In addition, all eight cases were frequently positive for cytokeratin, CD10, vimentin, estrogen receptor, and progesterone receptor; desmin immunoreactivity, when present, was limited to minor foci of smooth muscle. Overall, the morphologic and immunohistochemical findings in uterine tumors resembling ovarian sex cord tumors strongly support that these unusual uterine tumors are polyphenotypic neoplasms with true sex cord differentiation.

12E7 Antigen↗
PubMed2006

Evaluation of 12 antibodies for distinguishing epithelioid mesothelioma from adenocarcinoma: identification of a three-antibody immunohistochemical panel with maximal sensitivity and specificity.

We evaluated the sensitivity and specificity of 10 monoclonal and two polyclonal antibodies for distinguishing epithelioid mesothelioma from adenocarcinoma (AdCA) using immunohistochemistry (IHC). The antibodies were directed against the mesothelial-associated antigens mesothelin, calretinin, cytokeratin 5, thrombomodulin, Wilms' tumor-1 (WT-1) gene product and HBME-1, and the nonmesothelial antigens Lewis-Y blood group (antibody BG8), MOC-31, BerEp4, CD15, and carcinoembryonic antigen (CEA) family. The 133 tumors evaluated included 65 malignant epithelioid mesotheliomas, 22 lung AdCAs, 27 ovarian serous carcinomas, 24 breast carcinomas, and five gastric carcinomas. Diagnoses were based on clinical, histologic, ultrastructural, and/or IHC findings. Calretinin had the best sensitivity for mesothelioma (95%), followed by HBME-1 (84%), WT-1 (78%), cytokeratin 5 (76%), mesothelin (75%), and vimentin and thrombomodulin (68%). Thrombomodulin had the best specificity for mesothelioma (92%), followed by cytokeratin 5 (89%), calretinin (87%) vimentin (84%), and HBME-1 (45%). When ovarian carcinomas were excluded from the analysis, the specificity of mesothelin and WT-1 for the diagnosis of mesothelioma increased to 90 and 81%, respectively. The sensitivity of the nonmesothelial antigens for AdCA was organ dependent, with BG8 performing best in the breast cancer group (96%), and BerEp4, BG8, MOC-31 performing best in the lung cancer group (100%). The specificity of the nonmesothelial antigens for AdCA was 98% for BG8 and CEA, 97% for CD15, 95% for BerEp4, and 87% for MOC-31. A novel statistical analysis technique employing logic regression analysis identified a three-antibody immunohistochemical panel including calretinin, BG8, and MOC-31, which provided over 96% sensitivity and specificity for distinguishing epithelioid mesothelioma from AdCA.

Adenocarcinoma↗
PubMed2006

Calretinin, CD34, and alpha-smooth muscle actin in the identification of peritoneal invasive implants of serous borderline tumors of the ovary.

The correct identification of invasive implants in the peritoneum in serous borderline tumors (SBTs) of the ovary is an important determinant of diagnosis, treatment, and prognosis. Although the histologic criteria to distinguish noninvasive from invasive implants have been defined, the distinction can still be difficult. We examined the presence and distribution of mesothelial cells, stromal fibrocytes, and myofibroblasts in invasive and noninvasive peritoneal implants in 100 noninvasive, 100 invasive, and 100 metastatic nests/foci from 20 cases of SBTs with peritoneal implants, 10 serous carcinomas with peritoneal metastasis, and 10 cases of endosalpingiosis by immunostaining for calretinin, CD34, and alpha-SMA. All 100 invasive nests from seven SBTs and all 100 metastatic nests from the cases of serous carcinoma showed loss of calretinin+ mesothelial cells and stromal CD34+ fibrocytes around the nests. In contrast, 72/100 noninvasive nests displayed the presence of mesothelial cells around the nests and 68 displayed preservation of surrounding stromal fibrocytes. Alpha-smooth muscle actin positive myofibroblasts were present as a stromal response in 100/100 metastatic nests, 100/100 invasive nests and 54/100 noninvasive nests. The loss of mesothelial cells and stromal fibrocytes surrounding invasive nests together with a proliferation of myofibroblasts as demonstrated by immunostaining proved to be a sensitive and specific tool to separate invasive from noninvasive implants and represents an important adjunct to morphologic diagnosis. Combined sensitivity and specificity of the three antibodies was 100 and 81%, respectively. These methods, however, may not be helpful for small biopsies of noninvasive desmoplastic implants. The distribution of these cells provides some insights into the histogenesis of invasive and noninvasive implants in SBTs.

Actins↗
PubMed2006

Mesothelioma with rhabdoid features: an ultrastructural and immunohistochemical study of 10 cases.

Mesotheliomas with rhabdoid morphology are rare and only two individual case reports have been documented in the literature. This author reports a series of 10 cases of mesotheliomas with rhabdoid features, nine of which originated in the pleura and one in the peritoneum. Eight of the patients were men and two were women. Six patients had a history of asbestos exposure. Histologically, seven of the mesotheliomas were epithelioid, two sarcomatoid, and one biphasic. The proportion of the rhabdoid cells seen in these cases constituted 15-75% of the individual tumors. Cytoplasmic staining in the rhabdoid cells was seen for pan-keratin and vimentin in all 10 cases, for keratin 7 in eight of eight, for calretinin in nine of 10, and for keratin 5/6 in seven of nine. Nuclear positivity for WT1 was observed in the rhabdoid cells of four of seven cases and membranous reactivity for mesothelin in four of six, and for podoplanin in two of six. Only one case showed desmin positivity in sparse cells in the nonrhabdoid component of the tumor. All of the cases were negative for CEA, MOC-31, TAG-72, CD15, CD34, bcl2, muscle-specific actin, and TTF-1. Ultrastructural studies revealed paranuclear collections of intermediate filaments, but no evidence of rhabdomyoblastic differentiation was seen. The mean survival of five of the six patients for whom this information was available was 3.8 months. The remaining patient had a survival time of 1 year. It is important for pathologists to be aware that mesotheliomas can present rhabdoid features, not only because they can be confused with other malignancies that can exhibit a similar morphology, but also because of their apparently unusually aggressive behavior. The value of immunohistochemistry and electron microscopy in the differential diagnosis of these tumors is discussed.

Aged↗
PubMed2006

The diagnostic utility of immunohistochemistry in distinguishing between epithelioid mesotheliomas and squamous carcinomas of the lung: a comparative study.

As both mesotheliomas and squamous carcinomas can present a wide variety of morphological patterns, they can on occasion be confused. Recently, some groups of investigators have called attention to the difficulties that sometimes exist in distinguishing between these malignancies and the need to define a panel of markers that can assist in reaching the correct diagnosis. The aim of the present study is to compare the value of the various immunohistochemical markers currently available for the diagnosis of mesothelioma and squamous carcinoma of the lung. A total of 30 epithelioid pleural mesotheliomas exhibiting a solid or predominantly solid pattern, and 30 nonkeratinizing squamous carcinomas of the lung were investigated for the expression of the following markers: podoplanin, calretinin, mesothelin, WT1, keratin 5/6, keratin 7, p63, carcinoembryonic antigen (CEA), MOC-31, Ber-EP4, B72.3, BG-8 (Lewis(y)), leu-M1 (CD15), and thyroid transcription factor-1 (TTF-1). All 30 (100%) of the mesotheliomas reacted for calretinin, mesothelin and keratin 7, 93% each for podoplanin, WT1 and keratin 5/6, 13% for Ber-EP4, 7% each for p63, MOC-31 and BG-8, and 0% for B72.3, CEA, leu-M1 and TTF-1. All 30 (100%) of the squamous carcinomas were positive for p63 and keratin 5/6, 97% for MOC-31, 87% for Ber-EP4, 80% for BG-8, 77% for CEA, 57% for keratin 7, 40% for calretinin and B72.3, 30% for leu-M1, 27% for mesothelin, 15% for podoplanin, and 0% for WT 1 and TTF-1. After analyzing the results, it is concluded that from a practical point-of-view, a combination of two positive mesothelioma markers (WT1 and calretinin or mesothelin) with two negative mesothelioma markers (p63 and MOC-31) would allow the differential diagnosis to be established between epithelioid mesotheliomas and squamous carcinomas of the lung in nearly all instances.

Biomarkers, Tumor↗
PubMed2001

Gelatinous ascites: a cytohistologic study of pseudomyxoma peritonei in 67 patients.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare condition characterized by gelatinous ascites. Although the histologic attributes of PMP have been well studied, the cytologic features remain ill defined. METHODS: We reviewed the peritoneal washings (PW) in 67 patients with PMP to identify cytomorphologic features useful in classifying cases as either disseminated peritoneal adenomucinosis (DPAM) or peritoneal mucinous carcinomatosis (PMCA). Histologic specimens were correlated with the cytologic diagnoses. Correlation between cytologic diagnosis and patient outcome was investigated. RESULTS: Neoplastic epithelial cells were identified in 63 of 67 PW (94%). Concordance with the histologic diagnosis was obtained in 61 of 63 cases. Of these 36.5% were cytologically classified as DPAM with primary appendiceal neoplasms in 19 cases. Thirty-four of 63 cases (53.9%) were cytologically diagnosed as PMCA based on PW cytology. Most were of appendiceal or colonic origin. Four cases displayed cytologic features of both DPAM and PMCA. Two discordant cases each with a cytologic diagnosis of PMCA had an appendiceal adenoma. Acellular mucin alone was identified in the PW in four cases. Analysis of follow-up data revealed that cases diagnosed as DPAM had a better prognosis than those diagnosed as PMCA. CONCLUSIONS: Cytomorphologic features of epithelial cells in PW material can accurately categorize cases of PMP as either DPAM or PMCA. Furthermore, this categorization appears to have important prognostic implications.

Adenocarcinoma, Mucinous↗
PubMed2005

Multiple origins of Cajal-Retzius cells at the borders of the developing pallium.

Cajal-Retzius cells are critical in cortical lamination, but very little is known about their origin and development. The homeodomain transcription factor Dbx1 is expressed in restricted progenitor domains of the developing pallium: the ventral pallium (VP) and the septum. Using genetic tracing and ablation experiments in mice, we show that two subpopulations of Reelin(+) Cajal-Retzius cells are generated from Dbx1-expressing progenitors. VP- and septum-derived Reelin(+) neurons differ in their onset of appearance, migration routes, destination and expression of molecular markers. Together with reported data supporting the generation of Reelin(+) cells in the cortical hem, our results show that Cajal-Retzius cells are generated at least at three focal sites at the borders of the developing pallium and are redistributed by tangential migration. Our data also strongly suggest that distinct Cajal-Retzius subtypes exist and that their presence in different territories of the developing cortex might contribute to region-specific properties.

Aging↗
PubMed2006

Meninges control tangential migration of hem-derived Cajal-Retzius cells via CXCL12/CXCR4 signaling.

Cajal-Retzius cells are critical in the development of the cerebral cortex, but little is known about the mechanisms controlling their development. Three focal sources of Cajal-Retzius cells have been identified in mice-the cortical hem, the ventral pallium and the septum-from where they migrate tangentially to populate the cortical surface. Using a variety of tissue culture assays and in vivo manipulations, we demonstrate that the tangential migration of cortical hem-derived Cajal-Retzius cells is controlled by the meninges. We show that the meningeal membranes are a necessary and sufficient substrate for the tangential migration of Cajal-Retzius cells. We also show that the chemokine CXCL12 secreted by the meninges enhances the dispersion of Cajal-Retzius cells along the cortical surface, while retaining them within the marginal zone in a CXCR4-dependent manner. Thus, the meningeal membranes are fundamental in the development of Cajal-Retzius cells and, hence, in the normal development of the cerebral cortex.

Animals↗