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Toshiki Uchihara - One of the best experts on this subject based on the ideXlab platform.
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REVIEW Silver diagnosis in neuropathology: principles, practice
2013Co-Authors: Toshiki Uchihara, T. UchiharaAbstract:Abstract Silver-staining methods are helpful for histological identiWcation of pathological deposits. In spite of some ambiguities regarding their mechanism and interpretation, they are widely used for histopathological diagnosis. In this review, four major silver-staining methods, modiWed Bielschowsky, Bodian, Gallyas (GAL) and Campbell– Switzer (CS) methods, are outlined with respect to their principles, basic protocols and interpretations, thereby providing neuropathologists, technicians and neuroscientists with a common basis for comparing Wndings and identifying the issues that still need to be clariWed. Some consider “Argyrophilia ” to be a homogeneous phenomenon irrespective of the lesion and the method. Thus, they seek to explain the diVerences among the methods by pointing to their diVerent sensitivities in detecting lesions (quantitative diVerence). Comparative studies, however, have demonstrated that Argyrophilia is heterogeneous and dependent not only on the method but also on the lesion (qualitative diVerence). Each staining method has its own lesion-dependent speciWcity and, within this speciWcity, its own sensitivity. This “method- and lesion-dependent ” nature of Argyrophilia enables operational sorting of disease-speciWc lesions based on their silver-staining proWles, which may potentially represent some disease-speciWc aspects. Furthermore, comparisons between immunohistochemical and biochemical data have revealed an empirical correlation between GAL+/CS-deposits and 4-repeat (4R) tau (corticobasal degeneration, progressive supranuclear palsy an
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Silver diagnosis in neuropathology: principles, practice and revised interpretation
Acta Neuropathologica, 2007Co-Authors: Toshiki UchiharaAbstract:Silver-staining methods are helpful for histological identification of pathological deposits. In spite of some ambiguities regarding their mechanism and interpretation, they are widely used for histopathological diagnosis. In this review, four major silver-staining methods, modified Bielschowsky, Bodian, Gallyas (GAL) and Campbell–Switzer (CS) methods, are outlined with respect to their principles, basic protocols and interpretations, thereby providing neuropathologists, technicians and neuroscientists with a common basis for comparing findings and identifying the issues that still need to be clarified. Some consider “Argyrophilia” to be a homogeneous phenomenon irrespective of the lesion and the method. Thus, they seek to explain the differences among the methods by pointing to their different sensitivities in detecting lesions (quantitative difference). Comparative studies, however, have demonstrated that Argyrophilia is heterogeneous and dependent not only on the method but also on the lesion (qualitative difference). Each staining method has its own lesion-dependent specificity and, within this specificity, its own sensitivity. This “method- and lesion-dependent” nature of Argyrophilia enables operational sorting of disease-specific lesions based on their silver-staining profiles, which may potentially represent some disease-specific aspects. Furthermore, comparisons between immunohistochemical and biochemical data have revealed an empirical correlation between GAL+/CS-deposits and 4-repeat (4R) tau (corticobasal degeneration, progressive supranuclear palsy and argyrophilic grains) and its complementary reversal between GAL-/CS+deposits and 3-repeat (3R) tau (Pick bodies). Deposits containing both 3R and 4R tau (neurofibrillary tangles of Alzheimer type) are GAL+/CS+. Although no molecular explanations, other than these empiric correlations, are currently available, these distinctive features, especially when combined with immunohistochemistry, are useful because silver-staining methods and immunoreactions are complementary to each other.
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Argyrophilic grains are not always argyrophilic—Distinction from neurofibrillary tangles of diffuse neurofibrillary tangles with calcification revealed by comparison between Gallyas and Campbell-Switzer methods
Acta Neuropathologica, 2005Co-Authors: Toshiki Uchihara, Ayako Nakamura, Kuniaki Tsuchiya, Haruhiko AkiyamaAbstract:Silver staining profiles of argyrophilic grains (AGs) and of neurofibrillary tangles (NFTs) of diffuse neurofibrillary tangles with calcification (DNTC, collectively as DNTC-NFTs) were examined for their relation to tau- and ubiquitin-like immunoreactivity (IR). Pairs of mirror sections were triple-fluorolabeled with an anti-PHF tau (AT8) antibody, an anti-ubiquitin antibody and thiazin red (TR), a fluorochrome that identifies fibrillary structures such as NFTs of Alzheimer’s disease (AD). One of the paired sections was subsequently stained with Gallyas method (GAL), and the other with Campbell-Switzer method (CS). Comparison of the same microscopic field on the paired fluorolabeled sections, subsequently silver-stained with either GAL or CS enabled the determination of five different profiles of each structure: AT8-IR, ubiquitin-like-IR, affinity to TR, Argyrophilia with GAL or CS staining. AGs, mainly composed of four-repeat (4R) tau, were argyrophilic with GAL but not with CS, and their affinity to TR and ubiquitin-like-IR was not intense. This staining profile of AGs is identical with those of tau-positive structures in the cortex of progressive supranuclear palsy/corticobasal degeneration, both composed of 4R tau. This selective affinity of AGs to GAL is in sharp contrast with Pick bodies, composed of three-repeat (3R) tau, that are positive for CS but not for GAL, as we reported previously. This contrast is explainable if the Argyrophilia with CS is related to deposits containing 3R tau, while that with GAL is linked to those containing 4R tau. Indeed, DNTC-NFTs, that contain both 3R and 4R tau, were argyrophilic with CS and GAL, and their affinity to TR and ubiquitin-like-IR were consistent, as we reported previously for NFTs of AD and of Down’s syndrome, both similarly composed of 3R and 4R tau. Taken together, differences in molecular composition of tau protein in these deposits are linked to their argyrophilic properties dependent on the staining method in these sporadic tauopathies. Although explanations for these empirical differences are not yet available, awareness of this clear distinction is potentially of diagnostic and pathological significance.
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Silver stainings distinguish Lewy bodies and glial cytoplasmic inclusions: comparison between Gallyas-Braak and Campbell-Switzer methods.
Acta neuropathologica, 2005Co-Authors: Toshiki Uchihara, Ayako Nakamura, Yoko Mochizuki, Masaharu Hayashi, Satoshi Orimo, Eiji Isozaki, Toshio MizutaniAbstract:Lewy bodies (LBs) of idiopathic Parkinson’s disease and glial cytoplasmic inclusions (GCIs) of multiple system atrophy are pathological deposits both composed of phosphorylated α-synuclein woven into different filaments. Although both LBs and GCIs are considered to be hallmarks for each independent synucleinopathy, until now they could not be clearly distinguished on the basis of their biochemical or immunohistochemical features. We have examined possible differences in their argyrophilic features and their relation to synuclein-like or ubiquitin-like immunoreactivity (IR). Pairs of mirror sections from different brain areas were triple-fluorolabeled with an anti-α-synuclein antibody, an anti-ubiquitin antibody and thiazin red (TR), a fluorochrome that labels fibrillary structures such as Lewy bodies or neurofibrillary tangles. One of the paired sections was subsequently stained using the Campbell-Switzer method (CS), and the other by the Gallyas-Braak method (GB). By comparing of the same microscopic field on the paired fluorolabeled sections, subsequently silver-stained with either CS or GB, five different profiles of each structure could be determined: α-synuclein-like IR, ubiquitin-like IR, affinity to TR, Argyrophilia with CS or GB. GCIs exhibited Argyrophilia with both CS and GB but lacked affinity to TR. In contrast, LBs exhibited Argyrophilia with CS but not with GB and some affinity to TR. These disease-specific profiles of Argyrophilia were consistent, and were not influenced by areas or cases examined. Although immunohistochemical features of LBs and GCIs were similar in exhibiting IR for α-synuclein and ubiquitin, the contrast in their argyrophilic profiles may indicate possible differences in the molecular composition or conformation of α-synuclein. Even though these empirical differences still remain to be explained, awareness of this clear distinction is potentially of diagnostic and pathological relevance.
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Silver staining profiles distinguish Pick bodies from neurofibrillary tangles of Alzheimer type: comparison between Gallyas and Campbell-Switzer methods
Acta Neuropathologica, 2005Co-Authors: Toshiki Uchihara, Ayako Nakamura, Kuniaki Tsuchiya, Haruhiko AkiyamaAbstract:Silver staining profiles of Pick bodies (PBs) and their relation to tau-like immunoreactivity were examined on hippocampal sections and compared with those of neurofibrillary tangles of Alzheimer type (NFTs). Pairs of mirror sections were double-fluorolabeled with an anti-paired helical filament tau (AT8) antibody and thiazin red (TR), a fluorochrome that identifies fibrillary structures such as NFTs. One of the paired sections was subsequently stained using the Gallyas method (GAL), and the other using the Campbell-Switzer method (CS). By comparison of the same microscopic field on fluorolabeled sections and on both silver-stained paired sections, four different profiles of each structure could be distinguished: AT8 immunoreactivity, affinity to TR, Argyrophilia with GAL or CS staining. PBs, containing mainly three-repeat (3R) tau, were positive for CS but not for GAL and its affinity to TR was, at most, weak. This selective affinity of PBs to CS is in sharp contrast with tau-positive structures of corticobasal degeneration/progressive supranuclear palsy, which are positive for GAL but not for CS, as we reported previously. This contrast is explainable if the Argyrophilia with CS is related to deposits containing 3R tau, while that with GAL is linked to those containing four-repeat (4R) tau. Indeed, NFTs, containing both 3R and 4R tau, are positive for both CS and GAL, as expected. Taken together, differences in molecular composition of tau protein in these deposits are linked to their argyrophilic properties that are dependent on the staining method. Although explanations for these empirical differences are not yet available, awareness of this clear distinction is potentially of diagnostic and pathological relevance.
Lucio Scopsi - One of the best experts on this subject based on the ideXlab platform.
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Mucinous carcinoma of the breast. A clinicopathologic, histochemical, and immunocytochemical study with special reference to neuroendocrine differentiation.
The American journal of surgical pathology, 1994Co-Authors: Lucio Scopsi, Salvatore Andreola, Silvana Pilotti, Rosaria Bufalino, M. T. Baldini, Alessandro Testori, Franco RilkeAbstract:We studied the clinical, histologic, histochemical, and immunocytochemical characteristics of 61 mucinous tumors (38 pure, 23 mixed) retrieved from a consecutive series of 1,689 infiltrating carcinomas of the female breast. The only statistically significant predictors of favorable survival were histologic (pure) type coupled with the absence of axillary lymph node metastases. Other factors, including classification into A and B types according to Capella et al., and neuroendocrine status, as assessed by the presence of Argyrophilia, granins, neuron-specific enolase (NSE), and synaptophysin (SYN),-all had no influence on survival. Argyrophilic cells were found in 16 pure mucinous tumors (42%) and in the mucinous component of four mixed tumors (17%). Granin (chromogranin A or B), NSE, and SYN immunoreactivities were demonstrated in all the argyrophilic tumors. We also found NSE- and SYN-immunoreactive cells in 31 of 41 and 16 of 41 nonargyrophilic (granin-unreactive) mucinous tumors, which supports the view that mucinous carcinomas of the breast as a whole are neuroendocrine-programmed tumors.
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Argyrophilia and granin chromogranin secretogranin expression in female breast carcinomas their relationship to survival and other disease parameters
The American Journal of Surgical Pathology, 1992Co-Authors: Lucio Scopsi, Salvatore Andreola, Silvana Pilotti, M. T. Baldini, Alessandro Testori, F Leoni, Luciano Lombardi, J C Hutton, F Shimizu, Patrizia RosaAbstract:Ninety-one tumors (5.6%) containing argyrophilic cells were identified in a series of 1,628 consecutive primary breast carcinomas diagnosed between 1968 and 1972 at the Istituto Nazionale Tumori, Milan, Italy. Histological evaluation of these argyrophilic tumors showed the presence, either throughout the whole tumor mass (pure form) or in some areas (mixed form), of distinctive though not pathognomonic cellular features. Immunocytochemistry revealed the presence of chromogranin A or chromogranin B (secretogranin I) immunoreactivity in 86% of these argyrophilic carcinomas and of neuron-specific enolase (NSE) immunoreactivity in all of them. The three neuroendocrine markers were also immunolocalized at the ultrastructural level in the dense-core granules (granins) and the cytoplasmic matrix (NSE). Immunoblotting studies confirmed the chromogranin A and B and NSE immunoreactivities and documented the presence of secretogranin II. We also studied the relation of the histologic, histochemical, and immunocytochemical features to prognosis. There was no significant correlation between Argyrophilia and such clinical parameters as age, menopausal status, tumor size, and overall survival; however, the pure form of argyrophilic tumors had a significant association with less frequent lymph node involvement and a low histologic grade.
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Argyrophilia and granin (chromogranin/secretogranin) expression in female breast carcinomas. Their relationship to survival and other disease parameters.
The American journal of surgical pathology, 1992Co-Authors: Lucio Scopsi, Salvatore Andreola, Silvana Pilotti, M. T. Baldini, Alessandro Testori, Luciano Lombardi, Leoni F, Shimizu F, Patrizia RosaAbstract:Ninety-one tumors (5.6%) containing argyrophilic cells were identified in a series of 1,628 consecutive primary breast carcinomas diagnosed between 1968 and 1972 at the Istituto Nazionale Tumori, Milan, Italy. Histological evaluation of these argyrophilic tumors showed the presence, either throughout the whole tumor mass (pure form) or in some areas (mixed form), of distinctive though not pathognomonic cellular features. Immunocytochemistry revealed the presence of chromogranin A or chromogranin B (secretogranin I) immunoreactivity in 86% of these argyrophilic carcinomas and of neuron-specific enolase (NSE) immunoreactivity in all of them. The three neuroendocrine markers were also immunolocalized at the ultrastructural level in the dense-core granules (granins) and the cytoplasmic matrix (NSE). Immunoblotting studies confirmed the chromogranin A and B and NSE immunoreactivities and documented the presence of secretogranin II. We also studied the relation of the histologic, histochemical, and immunocytochemical features to prognosis. There was no significant correlation between Argyrophilia and such clinical parameters as age, menopausal status, tumor size, and overall survival; however, the pure form of argyrophilic tumors had a significant association with less frequent lymph node involvement and a low histologic grade.
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Argyrophilic carcinoma of the male breast. A neuroendocrine tumor containing predominantly chromogranin B (secretogranin I).
The American journal of surgical pathology, 1991Co-Authors: Lucio Scopsi, Wieland B. Huttner, Patrizia Rosa, Salvatore Andreola, R. Saccozzi, Silvana Pilotti, Patrizia Boracchi, Alberto R. Conti, Antonia Manzari, Franco RilkeAbstract:Argyrophilic tumors were diagnosed in 28 of 134 (20.8%) consecutive male patients who had a carcinoma of the breast removed between 1961 and 1990. Histologically, most argyrophilic tumors showed uniform cellularity and prevalent expansive growth. Ultrastructural observation disclosed the presence of electron-dense cored granules in the cytoplasm of the tumor cells. By immunocytochemistry, 17 of 28 argyrophilic tumors (60.7%) contained chromogranin B (secretogranin I)-immunoreactive cells, whereas chromogranin A was present in four of these 17 tumors only (14.2%). Immunoblotting studies showed chromogranin B immunoreactivity similar to that found in normal neuroendocrine cells. Despite these findings, which would argue for a distinct morphologic and immunochemical entity, no statistically significant differences between argyrophilic and common male breast carcinomas were found when a number of clinicopathologic features and relapse-free survival were considered.
Patrizia Rosa - One of the best experts on this subject based on the ideXlab platform.
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Argyrophilia and granin chromogranin secretogranin expression in female breast carcinomas their relationship to survival and other disease parameters
The American Journal of Surgical Pathology, 1992Co-Authors: Lucio Scopsi, Salvatore Andreola, Silvana Pilotti, M. T. Baldini, Alessandro Testori, F Leoni, Luciano Lombardi, J C Hutton, F Shimizu, Patrizia RosaAbstract:Ninety-one tumors (5.6%) containing argyrophilic cells were identified in a series of 1,628 consecutive primary breast carcinomas diagnosed between 1968 and 1972 at the Istituto Nazionale Tumori, Milan, Italy. Histological evaluation of these argyrophilic tumors showed the presence, either throughout the whole tumor mass (pure form) or in some areas (mixed form), of distinctive though not pathognomonic cellular features. Immunocytochemistry revealed the presence of chromogranin A or chromogranin B (secretogranin I) immunoreactivity in 86% of these argyrophilic carcinomas and of neuron-specific enolase (NSE) immunoreactivity in all of them. The three neuroendocrine markers were also immunolocalized at the ultrastructural level in the dense-core granules (granins) and the cytoplasmic matrix (NSE). Immunoblotting studies confirmed the chromogranin A and B and NSE immunoreactivities and documented the presence of secretogranin II. We also studied the relation of the histologic, histochemical, and immunocytochemical features to prognosis. There was no significant correlation between Argyrophilia and such clinical parameters as age, menopausal status, tumor size, and overall survival; however, the pure form of argyrophilic tumors had a significant association with less frequent lymph node involvement and a low histologic grade.
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Argyrophilia and granin (chromogranin/secretogranin) expression in female breast carcinomas. Their relationship to survival and other disease parameters.
The American journal of surgical pathology, 1992Co-Authors: Lucio Scopsi, Salvatore Andreola, Silvana Pilotti, M. T. Baldini, Alessandro Testori, Luciano Lombardi, Leoni F, Shimizu F, Patrizia RosaAbstract:Ninety-one tumors (5.6%) containing argyrophilic cells were identified in a series of 1,628 consecutive primary breast carcinomas diagnosed between 1968 and 1972 at the Istituto Nazionale Tumori, Milan, Italy. Histological evaluation of these argyrophilic tumors showed the presence, either throughout the whole tumor mass (pure form) or in some areas (mixed form), of distinctive though not pathognomonic cellular features. Immunocytochemistry revealed the presence of chromogranin A or chromogranin B (secretogranin I) immunoreactivity in 86% of these argyrophilic carcinomas and of neuron-specific enolase (NSE) immunoreactivity in all of them. The three neuroendocrine markers were also immunolocalized at the ultrastructural level in the dense-core granules (granins) and the cytoplasmic matrix (NSE). Immunoblotting studies confirmed the chromogranin A and B and NSE immunoreactivities and documented the presence of secretogranin II. We also studied the relation of the histologic, histochemical, and immunocytochemical features to prognosis. There was no significant correlation between Argyrophilia and such clinical parameters as age, menopausal status, tumor size, and overall survival; however, the pure form of argyrophilic tumors had a significant association with less frequent lymph node involvement and a low histologic grade.
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Argyrophilic carcinoma of the male breast. A neuroendocrine tumor containing predominantly chromogranin B (secretogranin I).
The American journal of surgical pathology, 1991Co-Authors: Lucio Scopsi, Wieland B. Huttner, Patrizia Rosa, Salvatore Andreola, R. Saccozzi, Silvana Pilotti, Patrizia Boracchi, Alberto R. Conti, Antonia Manzari, Franco RilkeAbstract:Argyrophilic tumors were diagnosed in 28 of 134 (20.8%) consecutive male patients who had a carcinoma of the breast removed between 1961 and 1990. Histologically, most argyrophilic tumors showed uniform cellularity and prevalent expansive growth. Ultrastructural observation disclosed the presence of electron-dense cored granules in the cytoplasm of the tumor cells. By immunocytochemistry, 17 of 28 argyrophilic tumors (60.7%) contained chromogranin B (secretogranin I)-immunoreactive cells, whereas chromogranin A was present in four of these 17 tumors only (14.2%). Immunoblotting studies showed chromogranin B immunoreactivity similar to that found in normal neuroendocrine cells. Despite these findings, which would argue for a distinct morphologic and immunochemical entity, no statistically significant differences between argyrophilic and common male breast carcinomas were found when a number of clinicopathologic features and relapse-free survival were considered.
Jozef Maršala - One of the best experts on this subject based on the ideXlab platform.
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Neuroprotective Effect of Graded Postischemic Reoxygenation in Spinal Cord Ischemia in the Rabbit
Brain research bulletin, 1997Co-Authors: Nadežda Lukáčová, Martin Marsala, Halát G, Jozef MaršalaAbstract:Abstract Early ischemia/reperfusion-induced changes of four phospholipid compounds bound to the inner cell membrane leaflet, i.e., phosphatidic acid, inositol phospholipids, serine phospholipids, and ethanolamine plasmalogens, were studied in a model of spinal cord ischemia in the rabbit during normoxic and graded postischemic reoxygenation. Light and electron microscopic analysis after normoxic reoxygenation disclosed neuronal membrane Argyrophilia of the interneuronal pool located in lamina VII of L4-L6 segments. The number of small neurons (10–25 μ m in diameter) affected by somatodendritic Argyrophilia was greatly reduced, and concomitantly the ultrastructure of the endoplasmic reticulum, mitochondria, and Golgi complexes remained almost undamaged when graded postischemic reoxygenation had been applied. A statistically significant increase of phosphatidylserine and ethanolamine plasmalogen levels, and a decrease of phosphatidic acid, were detected after a short-lasting graded postischemic reoxygenation. The formation of thiobarbituric acid-reactive substances was significantly reduced during 60 min of graded postischemic reoxygenation and remained close to control or ischemic levels. The present data indicate that graded postischemic reoxygenation, which is considered to be neuroprotective, can prevent neuronal Argyrophilia and the development of reperfusion-induced alterations of organelles. Moreover, reoxygenation can positively modify ischemia-induced changes of some membrane-bound phospholipids.
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A new applicability of the suppressive Nauta method in the early phase of neuronal damage.
Functional and developmental morphology, 1993Co-Authors: Jozef Maršala, Martin Marsala, Ivo Vanický, Zachariás L, Judita OrendáčováAbstract:A new applicability of the suppressive Nauta impregnation method was tested allowing the detailed mapping of early neuronal damage expressed in the form of somatodendritic Argyrophilia. Two spinal cord ischemia-reperfusion models of rabbit and dog, a model of canine global brain ischemia-reperfusion, involving cardiac arrest followed by resuscitation, and a canine spinal cord compression-decompression model were used. Early phases of neuronal damage are characterized by conspicuous somatodendritic Argyrophilia permitting an exact evaluation of acute neuronal damage according to soma size, dendritic ramifications and localization of the affected neuronal neuronal pool. By its high sensitivity to somatodendritic damage the suppressive Nauta method appears to be a valuable neuropathological technique.
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Post cardiac arrest hyperoxic resuscitation enhances neuronal vulnerability of the respiratory rhythm generator and some brainstem and spinal cord neuronal pools in the dog.
Neuroscience letters, 1992Co-Authors: Jozef Maršala, Martin Marsala, Ivo Vanický, Ján Gálik, Judita OrendáčováAbstract:Selective neuronal vulnerability of the motor cortex, basal ganglia, brainstem, medulla, cerebellum, C6 and L6 segments of the spinal cord were studied after 15 min of cardiac arrest followed by 1 h of normoxic or hyperoxic resuscitation using the suppressive Nauta method in dogs. Hyperoxic resuscitation causes characteristic somatodendritic Argyrophilia of the interneuronal pool in the spinal cord and lower medulla. Cuneate, lateral reticular, supraspinal, and caudal trigeminal nuclei as well as the dorsal and ventral respiratory neuronal groups were heavily involved. Similarly, the Purkinje cells, neurons in the middle and deep portions of the mesencephalic tectum, perirubral, pretectal, posterior commissure, middle-sized striatal and giant pyramidal (Betz's) neurons in the motor cortex became argyrophilic. Hyperoxic resuscitation versus normoxic resuscitation causes statistically significant somatodendritic Argyrophilia of the dorsal respiratory group, cuneate, dorsal lateral geniculate and thalamic reticular nuclei.
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Silver impregnability of ischemia-sensitive neocortical neurons after 15 minutes of cardiac arrest in the dog
Anatomy and embryology, 1992Co-Authors: Ivo Vanický, Martin Marsala, Judita Orendáčová, Jozef MaršalaAbstract:The development of postischemic neuronal Argyrophilia and the subsequent fate of argyrophilic neurons were studied in dogs after 15 min of complete cerebral ischemia and survival varying from l h to 7 days. Histopathological examination of the vulnerable neocortical region was performed using the Nauta degeneration method, and the time course of cellular changes was described. Clear-cut neuronal Argyrophilia was found to precede cell body shrinkage and gradual disintegration corresponding to selective neuronal death. To clarify this initial stage of neuronal impregnability, the samples from the animals surviving 8 h postarrest were stained with toluidine blue or processed for electron microscopy, and the distribution of argyrophilic cells was confirmed to be identical with that of hyperchromatic or electron-dense cells. On the other hand, infrequently observed “tissue infarctions” exhibited no silver affinity in spite of apparent cellular damage. These findings indicate that enhanced impregnability is related to cyto-chemical processes incidental to the phenomenon of “selective neuronal death”, which can be readily detected by the Nauta method.
Silvana Pilotti - One of the best experts on this subject based on the ideXlab platform.
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Mucinous carcinoma of the breast. A clinicopathologic, histochemical, and immunocytochemical study with special reference to neuroendocrine differentiation.
The American journal of surgical pathology, 1994Co-Authors: Lucio Scopsi, Salvatore Andreola, Silvana Pilotti, Rosaria Bufalino, M. T. Baldini, Alessandro Testori, Franco RilkeAbstract:We studied the clinical, histologic, histochemical, and immunocytochemical characteristics of 61 mucinous tumors (38 pure, 23 mixed) retrieved from a consecutive series of 1,689 infiltrating carcinomas of the female breast. The only statistically significant predictors of favorable survival were histologic (pure) type coupled with the absence of axillary lymph node metastases. Other factors, including classification into A and B types according to Capella et al., and neuroendocrine status, as assessed by the presence of Argyrophilia, granins, neuron-specific enolase (NSE), and synaptophysin (SYN),-all had no influence on survival. Argyrophilic cells were found in 16 pure mucinous tumors (42%) and in the mucinous component of four mixed tumors (17%). Granin (chromogranin A or B), NSE, and SYN immunoreactivities were demonstrated in all the argyrophilic tumors. We also found NSE- and SYN-immunoreactive cells in 31 of 41 and 16 of 41 nonargyrophilic (granin-unreactive) mucinous tumors, which supports the view that mucinous carcinomas of the breast as a whole are neuroendocrine-programmed tumors.
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Argyrophilia and granin chromogranin secretogranin expression in female breast carcinomas their relationship to survival and other disease parameters
The American Journal of Surgical Pathology, 1992Co-Authors: Lucio Scopsi, Salvatore Andreola, Silvana Pilotti, M. T. Baldini, Alessandro Testori, F Leoni, Luciano Lombardi, J C Hutton, F Shimizu, Patrizia RosaAbstract:Ninety-one tumors (5.6%) containing argyrophilic cells were identified in a series of 1,628 consecutive primary breast carcinomas diagnosed between 1968 and 1972 at the Istituto Nazionale Tumori, Milan, Italy. Histological evaluation of these argyrophilic tumors showed the presence, either throughout the whole tumor mass (pure form) or in some areas (mixed form), of distinctive though not pathognomonic cellular features. Immunocytochemistry revealed the presence of chromogranin A or chromogranin B (secretogranin I) immunoreactivity in 86% of these argyrophilic carcinomas and of neuron-specific enolase (NSE) immunoreactivity in all of them. The three neuroendocrine markers were also immunolocalized at the ultrastructural level in the dense-core granules (granins) and the cytoplasmic matrix (NSE). Immunoblotting studies confirmed the chromogranin A and B and NSE immunoreactivities and documented the presence of secretogranin II. We also studied the relation of the histologic, histochemical, and immunocytochemical features to prognosis. There was no significant correlation between Argyrophilia and such clinical parameters as age, menopausal status, tumor size, and overall survival; however, the pure form of argyrophilic tumors had a significant association with less frequent lymph node involvement and a low histologic grade.
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Argyrophilia and granin (chromogranin/secretogranin) expression in female breast carcinomas. Their relationship to survival and other disease parameters.
The American journal of surgical pathology, 1992Co-Authors: Lucio Scopsi, Salvatore Andreola, Silvana Pilotti, M. T. Baldini, Alessandro Testori, Luciano Lombardi, Leoni F, Shimizu F, Patrizia RosaAbstract:Ninety-one tumors (5.6%) containing argyrophilic cells were identified in a series of 1,628 consecutive primary breast carcinomas diagnosed between 1968 and 1972 at the Istituto Nazionale Tumori, Milan, Italy. Histological evaluation of these argyrophilic tumors showed the presence, either throughout the whole tumor mass (pure form) or in some areas (mixed form), of distinctive though not pathognomonic cellular features. Immunocytochemistry revealed the presence of chromogranin A or chromogranin B (secretogranin I) immunoreactivity in 86% of these argyrophilic carcinomas and of neuron-specific enolase (NSE) immunoreactivity in all of them. The three neuroendocrine markers were also immunolocalized at the ultrastructural level in the dense-core granules (granins) and the cytoplasmic matrix (NSE). Immunoblotting studies confirmed the chromogranin A and B and NSE immunoreactivities and documented the presence of secretogranin II. We also studied the relation of the histologic, histochemical, and immunocytochemical features to prognosis. There was no significant correlation between Argyrophilia and such clinical parameters as age, menopausal status, tumor size, and overall survival; however, the pure form of argyrophilic tumors had a significant association with less frequent lymph node involvement and a low histologic grade.
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Argyrophilic carcinoma of the male breast. A neuroendocrine tumor containing predominantly chromogranin B (secretogranin I).
The American journal of surgical pathology, 1991Co-Authors: Lucio Scopsi, Wieland B. Huttner, Patrizia Rosa, Salvatore Andreola, R. Saccozzi, Silvana Pilotti, Patrizia Boracchi, Alberto R. Conti, Antonia Manzari, Franco RilkeAbstract:Argyrophilic tumors were diagnosed in 28 of 134 (20.8%) consecutive male patients who had a carcinoma of the breast removed between 1961 and 1990. Histologically, most argyrophilic tumors showed uniform cellularity and prevalent expansive growth. Ultrastructural observation disclosed the presence of electron-dense cored granules in the cytoplasm of the tumor cells. By immunocytochemistry, 17 of 28 argyrophilic tumors (60.7%) contained chromogranin B (secretogranin I)-immunoreactive cells, whereas chromogranin A was present in four of these 17 tumors only (14.2%). Immunoblotting studies showed chromogranin B immunoreactivity similar to that found in normal neuroendocrine cells. Despite these findings, which would argue for a distinct morphologic and immunochemical entity, no statistically significant differences between argyrophilic and common male breast carcinomas were found when a number of clinicopathologic features and relapse-free survival were considered.