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Immunohistochemical Examination (immunohistochemical + examination)
Selected AbstractsNoggin blocks invasive growth of murine B16-F1 melanoma cells in the optic cup of the chick embryo,,INTERNATIONAL JOURNAL OF CANCER, Issue 3 2008Christian Busch Abstract Melanoma cells originate from the neural crest and are characterized by high migratory potential and invasive growth. After transplantation into the neural tube of the chick embryo, melanoma cells spontaneously emigrate along the neural crest pathways without tumor formation or malignant growth. This emigration depends on the constitutive over-expression of bone morphogenetic protein-2 (BMP-2) and can be ablated by the BMP-antagonist noggin. When transplanted into the embryonic optic cup, melanoma cells invade the host tissue and form malignant tumors. Here, we asked if the invasive growth of melanoma cells in the optic cup could be influenced by BMP-2 or noggin. Mouse B16-F1 cells were grown as aggregates, treated with BMP-2 or noggin during aggregation and transplanted into the optic cup of 3-day chick embryos. After 3 days of subsequent incubation, embryos were evaluated for melanoma cell invasiveness. Immunohistochemical examination revealed that untreated and BMP-2-treated melanoma cells had grown malignantly into the host tissue. However, noggin pretreatment of the aggregates had blocked melanoma cell invasiveness and tumor formation. We conclude that invasive growth of melanoma cells in vivo is BMP-dependent and can be ablated by noggin, thus rendering noggin a promising agent for the treatment of BMP-over-expressing melanoma. © 2007 Wiley-Liss, Inc. [source] Congenital anaplastic astrocytoma differentiated into pilocytic astrocytoma: An autopsy caseNEUROPATHOLOGY, Issue 4 2008Yoshifumi Arai We report an autopsy case of congenital astrocytoma and its histopathological changes during 5 years of the patient's development from birth to death. At birth, a right exophthalmic tumor was observed, and MRI revealed that the tumor occupied the right orbital space and had also affected the suprasellar diencephalic structures. The right orbital tumor, which was enucleated at 2 months of age, was a highly cellular tumor with moderate pleomorphism resembling anaplastic astrocytoma. On the other hand, at autopsy, a brain tumor was found in the right diencephalic region with features of pilocytic astrocytoma, accompanied by leptomeningeal dissemination. A biopsy specimen, which was obtained from the chiasmatic part of the tumor at 4 months of age, showed an intermediate appearance between the orbital tumor and the brain tumor obtained at autopsy. Immunohistochemical examination confirmed that all three phases of the tumors showed an astrocytic lineage, and the Ki-67 labeling index decreased rapidly after 2 months of age. We believe that this congenital anaplastic astrocytoma differentiated into a pilocytic astrocytoma during the 5 years of the patient's development. The transformation of the congenital astrocytoma from anaplastic to pilocytic forms can be attributed to the nature of the tumor, namely postmitotic neoplastic cells are characterized by their ability to undergo self-differentiation, along with the organotropism of the developing brain. [source] Lymphoepithelioma-like cholangiocarcinoma not associated with EBVPATHOLOGY INTERNATIONAL, Issue 1 2008Shiro Adachi Reported herein is an unusual case of intrahepatic cholangiocarcinoma with lymphoepithelioma-like appearance in a 64-year-old man who was found to have an intrahepatic mass without cirrhosis. The tumor had two distinct histological patterns with dense lymphoplasmacytic infiltrate. The first was similar to nasopharyngeal undifferentiated carcinoma; the second pattern was a well-differentiated adenocarcinoma. Transition between the two components was observed in the same duct. Immunohistochemistry indicated that the tumor was immunoreactive with AE1/AE3 and cytokeratin (CK) 7, but negative for CEA and CK20. Stromal inflammatory infiltrate primarily consisted of plasma cells and lymphocytes. Immunohistochemical examination and in situ hybridization for EBV showed no integration of the virus in the tumor cells. Intrahepatic lymphoepithelioma-like carcinoma is rare, and most are associated with EBV. Only three cases were not associated with EBV. The authors would like to add one more example of the tumors not associated with EBV. [source] Comedonecrosis is an unfavorable marker in node-negative invasive breast carcinomaPATHOLOGY INTERNATIONAL, Issue 8 2003Hiroshi Yagata Breast carcinoma is usually accompanied by an invasive component with an intraductal component, and each component shows different morphological features. We evaluated whether the presence or absence of comedonecrosis is correlated with prognosis and biological features in node-negative invasive breast carcinoma. Ninety-four node-negative breast carcinomas with an intraductal component were classified into two types: comedo type (n = 36) showing comedonecrosis partly or extensively in the intraductal component, and non-comedo type (n = 58) showing either an absence or small foci of necrosis. The Kaplan,Meier method was used to calculate disease-free survival. Immunohistochemical examination for p53 and HER-2 was conducted on the comedo (n = 35) and non-comedo (n = 47) type tumor specimens. Disease-free survival was significantly shorter in the comedo type than in the non-comedo type (P = 0.019). The expression of p53 was observed in 16 (45.7%) of the 35 comedo type cases, but only in two (4.3%) of the 47 non-comedo type cases (P < 0.0001). HER-2 overexpression was observed in seven (20.0%) of the 35 comedo type cases, while none of the 47 non-comedo type cases overexpressed HER-2 (P < 0.0001). These results suggest that the presence of comedonecrosis may be predictive of an unfavorable prognosis with aggressive biological behavior in node-negative invasive breast carcinoma. [source] Classic type of Kaposi's sarcoma and human herpesvirus 8 infection in Xinjiang, ChinaPATHOLOGY INTERNATIONAL, Issue 11 2001Payzula Dilnur We report 17 cases of the classic type of Kaposi's sarcoma in Xinjiang, which is located in the north-western area of China surrounded by Mongolia in the east, Russia in the north and Kazakhstan in the west. Fifteen of the patients were of the Uygur people. All patients were male and did not have acquired immunodeficiency syndrome. Most of the lesions were found in the lower and/or upper extremities, with 16 patients showing multiple lesions. Immunohistochemical examination of the lesions revealed that human herpesvirus 8 (HHV-8)-encoded latency-associated nuclear antigen was expressed in the nuclei of spindle-shaped tumor cells. HHV-8 DNA was detected by polymerase chain reaction in all seven cases examined. Phylogenetic tree analysis revealed that DNA sequences of the HHV-8-encoded K1 gene in the seven Kaposi's sarcoma cases were classified as subtype C that was common in the Mediterranean, the Middle East and East Asian countries. In addition, using immunofluorescence we investigated the seroprevalence of HHV-8 in 73 Uygur patients with diseases other than Kaposi's sarcoma. Surprisingly, the serological study revealed that 34 of the patients (46.6%) were positive for antibodies against HHV-8, suggesting that HHV-8 infection is widespread in Xinjiang area. The occurrence of the classic type of Kaposi's sarcoma with a high seropositivity rate implies that Xinjiang is the most endemic area for HHV-8 infection in the world known to date. Considering that Xinjiang is located at the middle point of the Silk Road that used to extend from Rome to China, these data imply that the virus may have been in circulation in this area due to the migration of the people via the Silk Road. [source] Vascular amyloid of unknown origin and senile transthyretin amyloid in the lung and gastrointestinal tract of old age: Histological and immunohistochemical studiesPATHOLOGY INTERNATIONAL, Issue 5 2001Hironobu Matsutani The histological and immunohistochemical characteristics and the incidence of amyloid deposits in the tissues of the lung and gastrointestinal tract were investigated in 64 autopsied individuals who were 80 years and older (age range: 80,92 years; mean: 83.3 years). Immunohistochemical examination was performed with antibodies against amyloid A, transthyretin, immunoglobulin , and , light chain amyloid fibril proteins, ,2 -microglobulin, , protein, apolipoprotein AI, apolipoprotein AII, atrial natriuretic peptide, apolipoprotein E, and amyloid P component. Transthyretin amyloid fibril protein (ATTR) deposits were observed in five cases (7.8%). Gastrointestinal amyloid deposits of unknown origin were observed in the veins of the gastrointestinal tract in 26 cases (40.6%). This amyloid was regarded as portal amyloid with respect to distribution pattern. Pulmonary vascular amyloid deposits of unknown origin were observed in 12 cases (18.8%). These amyloid deposits were found mainly in medium-sized veins in the lungs and did not react with any antibodies against amyloid fibril proteins except apolipoprotein E and amyloid P component. Eleven of the 26 cases (42.3%) showing portal amyloid also showed pulmonary vascular amyloid of unknown origin. The pulmonary vascular amyloid deposits were similar to the portal amyloid deposits with respect to their morphological features and their relation to elastic fibers in the vessels. Further morphological investigation and biochemical analysis of the pulmonary vascular amyloid and portal amyloid will resolve questions of their origins and relation. [source] Keratan sulfate-containing proteoglycans in sheep brain with particular reference to phosphacan and synaptic vesicle proteoglycan isoformsBIOMEDICAL CHROMATOGRAPHY, Issue 5 2009Efstathios A. Sinouris Abstract Proteoglycans (PGs) are widely expressed in all areas of the brain. In this study, the keratan sulfate-containing PGs (KS-PGs) from cerebrum (CB), cerebellum (CL) and brainstem (BS) of young sheep brain were isolated, purified and characterized. The amount of KS-PGs in CL was significantly lower than that in CB and BS. KS-PGs were characterized by increased extent of glycosylation and heterogeneity of KS chains in CL. Western blot analyses demonstrated the presence of the KS-PGs phosphacan, SV2A and SV2B isoforms of synaptic vesicle proteoglycan in all three areas of the young sheep brain. Phosphacan predominated in BS and CB, showing significant molecular heterogeneity. SV2A and SV2B were found in two forms of high and low molecular sizes according to their extent of glycosylation in sheep brain. SV2A predominated in CL, where forms with very high molecular sizes were detected. Immunohistochemical examination revealed that SV2A was localized in the extracellular matrix of both gray and white matter. In contrast, phosphacan and SV2B were mainly localized in the white matter in all brain regions. The results of the present study demonstrated that KS-PGs are present in the three areas of the sheep brain, showing significant variations in their content, structure and localization among the distinct areas. These differences may be important for the physiology of the brain. Copyright © 2008 John Wiley & Sons, Ltd. [source] Androgen receptors frequently are expressed in breast carcinomasCANCER, Issue 4 2003Potential relevance to new therapeutic strategies Abstract BACKGROUND Several studies have demonstrated the biologic and therapeutic significance of estrogen and progesterone receptors (ER and PR) in breast carcinomas. The aim of the current study was to examine the presence of androgen receptors (AR) in breast carcinomas. METHODS Two hundred cases of breast carcinoma, consisting of 145 invasive and 55 noninvasive (ductal carcinoma in situ [DCIS]) lesions, were examined using a monoclonal antibody against AR on formalin-fixed, paraffin-embedded archival material. The results were analyzed for correlations with immunohistochemically determined ER, PR, and HER-2/neu expression. RESULTS Eighty-seven of the 145 cases (60%) of invasive carcinoma and 45 of the 55 cases (82%) of DCIS were AR-positive according to internationally standardized guidelines. The vast majority of Grade 1 carcinomas were positive for AR (90% of invasive Grade 1 carcinomas and 95% of Grade 1 DCIS), whereas in Grade 3 invasive carcinomas and DCIS, positive immunoreactions for AR were observed in 46% and 76% of cases, respectively. Among the cases of Grade 3 carcinoma, 33 invasive carcinomas (39%) and 17 DCIS lesions (68%) were ER-negative but AR-positive. Among Grade 1 carcinomas (invasive and DCIS), not a single case was positive for HER-2/neu, but most cases were intensely positive for AR. In contrast, many invasive Grade 3 carcinomas exhibited agreement between AR status and HER-2/neu status (AR-positive and HER-2/neu-positive, 30.5%; AR-negative and HER-2/neu-negative, 42.5%). CONCLUSIONS Androgen receptors are commonly expressed in DCIS and in invasive breast carcinoma. A significant number of poorly differentiated carcinomas are ER-negative and PR-negative but AR-positive. Immunohistochemical examination of AR would be desirable because it would provide additional information about steroid receptors in breast carcinomas. Cancer 2003;98:703,11. © 2003 American Cancer Society. DOI 10.1002/cncr.11532 [source] The Trigeminal Vasculature Pathology in Patients With NeuralgiaHEADACHE, Issue 9 2007Slobodan Marinkovi Objective.,To examine the possible pathological changes of the trigeminal vasculature in patients with neuralgia. Background.,Such a study has never been performed before. The alterations of the trigeminal vessels could have important pathophysiological implications in the trigeminal neuralgia pathogenesis. Methods.,The biopsy specimens for the electronmicroscopic (EM) and immunohistochemical examination were taken during a partial rhizotomy in 6 patients with trigeminal neuralgia and in 2 persons with trigeminal neuropathy. In addition, the 32 normal trigeminal nerves were used as the control specimens. Results.,The vascular pathological alterations were noticed in 3 out of 6 neuralgia patients. The EM study revealed signs of apoptosis or degeneration, respectively, of some endothelial and smooth muscle cells in the wall of the trigeminal arterioles. The immune reactions against CD31, CD34, and ,-smooth muscle actin in these cells were weaker than in the control specimens, but stronger against factor VIII. In addition, the arteriolar basement membranes, which were thickened, showed an intense laminin, fibronectin, and collagen IV immunoreactivity. Similarly, some endothelial cells and pericytes of the intratrigeminal capillaries also showed signs of apoptosis or degeneration, respectively. Their basement membrane was very thick and showed an intense immune reaction against laminin, fibronectin, and collagen IV. Conclusion.,The observed pathological changes of the trigeminal vasculature could be the primary factor, while demyelination of the trigeminal nerve fibers could be the secondary process in some patients with neuralgia. [source] Expression profiling in multistage hepatocarcinogenesis: Identification of HSP70 as a molecular marker of early hepatocellular carcinomaHEPATOLOGY, Issue 1 2003Makoto Chuma Hepatocellular carcinoma (HCC) associated with chronic liver disease evolves from precancerous lesions and early HCC to a progressed form. Nodule-in-nodule,type HCC (progressed HCC within early HCC) represents the transition from early to progressed HCC and, therefore, is useful in molecular genetic analysis of HCC progression during multistage carcinogenesis. We compared expression profiles among 7 early components and 7 progressed components of nodule-in-nodule,type HCCs and their corresponding noncancerous liver tissues with oligonucleotide array. Of the approximately 12,600 genes that were analyzed, a set of 95 genes provided a molecular signature that distinguished between early HCC components and their noncancerous liver tissues, and a set of 92 genes distinguished between progressed and early HCC components. Of these genes, the most abundantly up-regulated gene in early HCC components (P < .001) was heat-shock protein 70 (HSP70). Real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) confirmed this finding. Further immunohistochemical examination of HSP70 revealed its significant overexpression in early HCC compared with precancerous lesions (P < .001) and in progressed HCC compared with early HCC (P < .001). In conclusion, molecular signatures were clearly different in noncancerous liver tissue as compared with the early and progressed components of nodule-in-nodule,type HCC. Moreover, HSP70 could be a sensitive marker for the differential diagnosis of early HCC from precancerous lesion or noncancerous liver, a difficult distinction for pathologists due to very well differentiated histology with little atypia in early HCC. [source] Cutaneous sclerosing perineurioma of the digitINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 9 2006Toshitsugu Nakamura MD An 11-year-old Japanese girl noticed a small nodule, with mild tenderness, on the right index finger 5 years before visiting our outpatient clinic. She had no familial history of neurofibromatosis or past history of traumatic injury at the site of the tumor. Physical examination revealed a slightly elevated, subcutaneous, nodular tumor in the volar aspect between the proximal and distal interphalangeal joints of the digit (Fig. 1A). By magnetic resonance imaging examination, the tumor showed low density on both T1- and T2-weighted images, and was located just adjacent to the tendon with no invasive signs. The tumor was extirpated; at operation, it was well circumscribed and mobile without adhesion to adjacent tendon or nerve, and was easily removed. Figure 1. (a) Slightly elevated subcutaneous tumor (arrow) on the volar aspect of the right index finger. (b) gross appearance of the extirpated tumor, showing a well-circumscribed, whitish solid nodule Grossly, the tumor was a well-circumscribed, firm nodule (10 mm × 8 mm × 5 mm in size) (Fig. 1B). The cut surface was whitish, homogeneous, and solid without cystic lesions. Histologically, it was an unencapsulated, paucicellular dense, fibrous nodule with a concentric circular arrangement of collagen bundles (Fig. 2A). Amongst the fibrous bundles, a small number of ovoid/epithelioid or plump spindle cells were arranged in a corded, trabecular, or whorled (onion bulb-like) pattern (Fig. 2B); a storiform pattern was not noted. These cells were relatively uniform and had a somewhat elongated, slightly hyperchromatic nucleus with fine granular chromatin. Neither nuclear pleomorphism nor multinucleated cells were evident, and necrosis and mitotic figures were not observed. Periodic acid,Schiff (PAS) stain after diastase digestion highlighted the corded or whorled pattern of the tumor cells by encasing them. For immunohistochemical examination, formalin-fixed, paraffin-embedded serial tissue sections were stained by a labeled streptavidin,biotin method. The tumor cells were positive for vimentin and epithelial membrane antigen (EMA) (Fig. 3A), and negative for pan-cytokeratin, carcinoembryonic antigen (CEA), CD34, ,-smooth muscle actin, desmin, and CD68. Type IV collagen and laminin (Fig. 3B) were detected along the cords or whorls of the tumor cells, similar to the staining pattern of the diastase-PAS reaction. Schwann cells and axonal components, immunoreactive for S100 protein and neurofilament, respectively, were focally detected just adjacent to the cords or whorls, although the tumor cells per se did not express these proteins. Consequently, the tumor was found to be perineurial in origin and was diagnosed as cutaneous sclerosing perineurioma. Figure 2. (a) Low-power view of the tumor, showing an unencapsulated, paucicellular, dense, fibrous nodule with a concentric circular arrangement of collagen bundles (hematoxylin and eosin stain: original magnification, ×15). (b) Higher magnification of the tumor, showing ovoid or epithelioid cells arranged in cords or whorls in the abundant collagen bundles (hematoxylin and eosin stain: original magnification, ×150) Figure 3. Immunohistochemical profiles of the tumor. The tumor cells are positive for epithelial membrane antigen (a) and are surrounded by laminin (b) (original magnification, ×150) [source] Familial Hypocalciuric Hypercalcemia Caused by an R648stop Mutation in the Calcium-Sensing Receptor Gene ,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2002Mika Yamauchi Abstract In this study, we report an 84-year-old female proband in a Japanese family with familial hypocalciuric hypercalcemia (FHH) caused by an R648stop mutation in the extracellular calcium-sensing receptor (CaR) gene. At the age of 71 years, she presented with hypercalcemia (11.4 mg/dl), hypocalciuria (Cca/Ccr = 0.003), hypermagnesemia (2.9 mg/dl), and a high-serum parathyroid hormone (PTH) level (midregion PTH, 3225 [160,520] pg/ml). At the age of 74 years, a family screening was carried out and revealed a total of 9 hypercalcemic individuals (all intact PTH values <62 pg/dl) among 17 family members tested, thus, being diagnosed as FHH. Two and one-half of three clearly enlarged parathyroid glands were resected, because persistently high PTH levels (intact PTH, 292 pg/ml; midregion PTH, 5225 pg/ml) and the presence of a markedly enlarged parathyroid gland by several imaging modalities (ultrasonography, computed tomography [CT], magnetic resonance imaging [MRI], and subtraction scintigraphy) suggested coexistent primary hyperparathyroidism (pHPT); however, hypercalcemia persisted postoperatively. Histological and immunohistochemical examination revealed that the resected parathyroid glands showed lipohyperplasia as well as normally expressed Ki67, vitamin D receptor (VDR), and the CaR. Sequence analysis disclosed that the proband and all affected family members had a heterozygous nonsense (R648stop) mutation in the CaR gene. This mutation is located in the first intracellular loop; thus, it would be predicted to produce a truncated CaR having only one transmembrane domain (TMD) and lacking its remaining TMDs, intracellular loops, and C-terminal tail. Western analysis of biotinylated HEK293 cells transiently transfected with this mutant receptor showed cell surface expression of the truncated protein at a level comparable with that of the wild-type CaR. The mutant receptor, however, exhibited no increase in intracellular free calcium concentration (Ca2+i) when exposed to high extracellular calcium concentrations (Ca2+o). The proband's clinical course was complicated because of associated renal tubular acidosis (RTA) and nephrotic syndrome. However, it was unclear whether their association affected the development of elevated serum PTH and parathyroid gland enlargement. This report is the first to show that an R648stop CaR mutation yields a truncated receptor that is expressed on the cell surface but is devoid of biological activity, resulting in FHH. [source] Effect of heme oxygenase-1 induction by octreotide on TNBS-induced colitisJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 11 2007im Erbil Abstract Background and Aim:, Ulcerative colitis is a chronic inflammatory disease of the colon and rectum. Although the precise etiology of ulcerative colitis remains unknown, it is believed to involve an abnormal host response to endogenous or environmental antigens, genetic factors, and oxidative damage. The aim of the present study was to investigate whether heme oxygenase-1 (HO-1) induction by octreotide could protect against oxidative and inflammatory damage from induced colitis. Methods:, Rats received octreotide 50 µg/kg per day intraperitoneally for 5 days before 2,4,6 trinitrobenzene sulfonic acid (TNBS) solution administration and for 15 days following TNBS solution administration. Rats were killed on day 21, and colonic malondialdehyde (MDA) levels, glutathione (GSH) levels and HO-1 expression were measured. Nuclear factor (NF)-,B and HO-1 expression was evaluated by immunohistochemical examination of the colonic tissue. Results:, Rats with TNBS-induced colitis had significantly increased colonic MDA levels and HO-1 expression in comparison to the control group. Octreotide treatment was associated with increased HO-1 expression and GSH levels, but decreased MDA levels. Histopathological examination revealed that the intestinal mucosal structure was preserved in the octreotide-treated group. In addition, treatment with octreotide significantly increased HO-1 expression and decreased NF-,B expression by immunohistochemistry when compared to the TNBS-induced colitis group. Conclusion:, Octreotide appears to have protective effects against colonic damage in TNBS-induced colitis. This protective effect is, in part, mediated by modification of the inflammatory response and the induction of HO-1 expression. [source] Mycosis fungoides presenting with extensive pyoderma gangrenosum-like ulcersJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 4 2002SG Carbia Abstract Mycosis fungoides (MF) may present with atypical clinical manifestations. Usually it mimics various chronic dermatoses, with the appearance of ulcers during the tumour stage. Infrequently, cutaneous ulcers are the main or initial sign of lymphoma. We report the case of a man who presented multiple skin lesions that clinically appeared to be pyoderma gangrenosum (PG). However, histological and immunohistochemical examination revealed MF. This case illustrates that PG-like ulcers may be atypical cutaneous manifestations of MF and exceptionally the presenting sign of this disease. [source] Pigmented ependymoma with signet-ring cells and Rosenthal fibers: A rare variant of ependymomaNEUROPATHOLOGY, Issue 1 2010Yesim Ertan We report a rare case of ependymoma with vacuolar features, signet cells, pigmentation and numerous Rosenthal fibers arising in the fourth ventricle of a 35-year-old woman. The tumor was composed of cells with cytoplasmic vacuoles, signet cells and clear cells. The clear cells were compactly arranged resembling oligodendroglioma. Pseudovascular and ependymal rosettes were observed only in focal areas. Additionally, some tumor cells contained brown cytoplasmic pigment, which was histochemically compatible with lipofuscin and neuromelanin. On immunohistochemical examination, the tumor cells were positive for S100, glial fibrillary acidic protein and vimentin, and negative for synaptophysin, cytokeratin, neurofilament and HMB45. Epithelial membrane antigen staining showed dot-like and small vesicular reactivity. The case is presented to increase familiarity with these extraordinary variants of ependymoma. [source] Highly cystic brain tumor: Rare histological features in an ependymomaNEUROPATHOLOGY, Issue 4 2007Dorel Arsene Ependymoma is a slowly growing tumor appearing mostly in children and young adults. Several histological patterns are described. We report a case with unusual microscopic features, composed mostly of multiple cysts. Ultrastructural and immunohistochemical examination confirmed the diagnosis. Neuropathologists should be aware of this particular change which can generate some diagnostic difficulties. [source] Metaplastic breast carcinoma with melanocytic differentiationPATHOLOGY INTERNATIONAL, Issue 9 2009Antonia Bendic Metaplastic carcinoma of the breast is a rare heterogeneous malignancy, accounting for <1% of all invasive breast carcinomas, in which adenocarcinoma is found to coexist with an admixture of spindle, squamous, chondroid or bone-forming neoplastic cells. Metaplastic breast carcinoma composed of both epithelial and melanocytic elements is rare, and only seven cases have been reported so far. Reported herein is the case of a 38-year-old woman with a nodular mass in her left breast suspicious of malignancy, discovered during routine ultrasound examination. After histological and immunohistochemical examination of the resected tumor mass, initial diagnosis was collision tumor: ductal invasive carcinoma and metastatic melanoma. The patient underwent quadrantectomy, chemotherapy and radiotherapy. At 6 years follow up the patient was alive and healthy, without local recurrence or metastases. After revising slides and the literature, in addition to patient follow up, it was concluded that this case represents metaplastic carcinoma with melanocytic differentiation. [source] Adenomatoid tumor of the adrenal gland: Case report with immunohistochemical studyPATHOLOGY INTERNATIONAL, Issue 10 2005Akihiko Hamamatsu Adrenal adenomatoid tumor (AT) is a recently recognized disease with marked male predominance. Herein is presented a case of adrenal AT incidentally found in a 30-year-old man and results of immunohistochemical examination of the tumor. The left adrenal gland, weighing 17 g, contained a mass measuring 3 × 2.5 × 2.5 cm in the cortical tissue. Cut surface showed a relatively well-circumscribed firm tumor with a white solid appearance. Histologically, the tumor had the typical appearance of AT described in the genital tract. Immunohistochemically, the tumor cells were positive for calretinin, D2-40, WT1, mesothelial cell antigen, CA125, thrombomodulin, vimentin and cytokeratins (stained by AE1 + AE3, OV-TL 12/30, CAM5.2 and MNF116), and negative for endothelial markers (CD31, CD34 and factor VIII-related antigen) and CD56. CD56-positive adrenocortical cells were diffusely scattered in the tumor, especially in its periphery. Immunohistochemistry of estrogen, progesterone and androgen receptors was negative. These findings confirm mesothelial origin of the tumor and suggest that this tumor has little relation to sex hormone despite male predominance. [source] Small cell carcinoma of the extrahepatic bile duct: Case report and immunohistochemical analysisPATHOLOGY INTERNATIONAL, Issue 12 2003Kazuya Kuraoka A small cell carcinoma of the extrahepatic bile duct in a 75-year-old Japanese man is reported. The patient suffered from obstructive jaundice, and percutaneous transhepatic cholangiography-drainage (PTCD) revealed a massive lesion in the lower common bile duct. Because it was diagnosed as a malignant tumor, pancreaticoduodenectomy was performed. A nodular infiltrating tumor measuring 4.5 × 3.0 × 2.0 cm was located in the intrapancreatic portion of the extrahepatic bile duct. Histologically, the tumor was composed of a dense proliferation of small atypical cells with a little region of high-grade dysplasia in the adjacent epithelium of the common bile duct. Tumor cells were immunoreactive to neuroendocrine markers such as chromogranin A, synaptophysin, CD56, and Leu7. Although carcinoma cells invaded into pancreas and duodenum, there were no histological findings that indicated the carcinoma arose from the mucosa of either the pancreatic duct or duodenum. These results indicated that the tumor was a small cell carcinoma derived from the epithelium of the extrahepatic bile duct; a rare neoplasm with only a few cases reported. A few neuroendocrine cells were recognized in the adjacent epithelium of the extrahepatic bile duct, suggesting that the tumor cells might be derived from them. Using immunohistochemical examination, no p53 abnormality was found. Tumor cells showed positive nuclear staining for p16, while negative for cyclin D1, suggesting that functional retinoblastoma protein (pRB) might be lost in the p16/pRB pathway, as in small cell lung cancer. [source] Chromogenic in situ hybridization analysis of HER-2/neu status in breast carcinoma: Application in screening of patients for trastuzumab (Herceptin®) therapyPATHOLOGY INTERNATIONAL, Issue 8 2001Hiroyuki Kumamoto Evaluation of HER-2/neu status is important in the management of patients with breast carcinoma, especially in determining the possible application of trastuzumab, a humanized anti-HER-2/neu monoclonal antibody. Chromogenic in situ hybridization (CISH) detection of the HER-2/neu oncogene is a newly developed in situ hybridization method that utilizes a robust and unique-sequence DNA probe labeled with digoxygenin, and sequential incubations with antidigoxygenin fluorescein, antifluorescein peroxidase, and diaminobenzidine. In this study, we examined 20 archival specimens of human breast carcinoma using CISH, and we correlated findings with immunohistochemical findings for HER-2/neu. HER-2/neu immunohistochemistry was carried out with HercepTestTM, a standardized immunohistochemical examination system for HER-2/neu overexpression in surgical pathology specimens. CISH analysis could be done in 18 out of 20 cases examined. Gene copy signals for HER-2/neu were recognized as intranuclear brown dots in both neoplastic and non-neoplastic cells. Seven carcinomas showed an increased number or size of signals and were interpreted as being positive for HER-2/neu amplification. Eight cases were positive with the HercepTestTM. Seven out of eight carcinoma cases found to overexpress immunoreactive HER-2/neu also demonstrated HER-2/neu gene amplification following CISH analysis. There was a significant correlation between immunohistochemical and CISH analyses (P< 0.001). We found that CISH was a specific, sensitive and easily applicable method for the detection of HER-2/neu gene amplification, which may be used together with immunohistochemical examination for the evaluation of patients with breast carcinoma. [source] A Study of Moderately Differentiated Neuroendocrine Carcinomas of the Larynx and an Examination of Non-Neoplastic Larynx Tissue for Neuroendocrine CellsTHE LARYNGOSCOPE, Issue 7 2004Jin-Haeng Chung MD Abstract Objectives/Hypothesis: To determine the most appropriate terminology for neuroendocrine carcinomas (NEC) of the larynx, successive clinicopathologic studies are encouraged. The typical location and immunophenotype of laryngeal NEC raise a question of whether any precursor cells exist. Study Design: Six patients with laryngeal NEC were analyzed. Another 20 laryngectomy specimens were examined for the presence of non-neoplastic neuroendocrine cells. Methods: Tumor morphology and patient outcome were determined, and tumor tissue underwent immunohistochemical examination to identify cytokeratin, neuroendocrine markers (chromogranin, synaptophysin, CD56, calcitonin), S-100 protein, and p53 protein. A neuroendocrine marker study was also performed on non-neoplastic regions of another 20 laryngectomy specimens to identify any neuroendocrine cells. Results: Laryngeal NEC, all submucosal, exhibited various morphology with or without histologic evidences of neuroendocrine differentiation. The tumors showed frequent (67%) calcitonin expression, calcitonin secretion in one case, and common (50%) p53 over-expression. Three patients died within 3 years. In the non-neoplastic larynx specimens, Kulchitsky cell-like bipolar neuroendocrine cells were identified in the basal and middle layer of the respiratory epithelium of the ventricle and subglottis but none in the submucosal layer of the supraglottic region. The neuroendocrine cells did not express calcitonin. Conclusions: Moderately differentiated or large-cell NEC is a more favored term than atypical carcinoid until more refined classifications for upper respiratory tract NEC are agreed on. Despite the confirmed presence of neuroendocrine cells in the respiratory epithelium of the larynx, the origin of laryngeal NEC remains unknown. p53 mutation might be one of the major molecular steps in the pathogenesis of laryngeal NEC. [source] Pro-apoptotic protein glyceraldehyde-3-phosphate dehydrogenase promotes the formation of Lewy body-like inclusionsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2005Katsumi Tsuchiya Abstract Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has long been recognized as a classical glycolytic protein; however, previous studies by our group and others have demonstrated that GAPDH is a general mediator initiating one or more apoptotic cascades. Our most recent findings have elucidated that an expression of a pro-apoptotic protein GAPDH is critically regulated at the promoter region of the gene. Apoptotic signals for its subsequent aggregate formation and nuclear translocation are controlled by the respective functional domains harboured within its cDNA component. In this study, coexpression of GAPDH with either wild-type or mutant (A53T) ,-synuclein and less likely with ,-synuclein in transfected COS-7 cells was found to induce Lewy body-like cytoplasmic inclusions. Unlike its full-length construct, the deleted mutant GAPDH construct (C66) abolished these apoptotic signals, disfavouring the formation of inclusions. The generated inclusions were ubiquitin- and thioflavin S-positive appearing fibrils. Furthermore, GAPDH coimmunoprecipitated with wild-type ,-synuclein in this paradigm. Importantly, immunohistochemical examinations of post mortem materials from patients with sporadic Parkinson's disease revealed the colocalized profiles immunoreactive against these two proteins in the peripheral zone of Lewy bodies from the affected brain regions (i.e. locus coeruleus). Moreover, a quantitative assessment showed that about 20% of Lewy bodies displayed both antigenicities. These results suggest that pro-apoptotic protein GAPDH may be involved in the Lewy body formation in vivo, probably associated with the apoptotic death pathway. [source] Transgenic expression of CCK2 receptors sensitizes murine pancreatic acinar cells to carcinogen-induced preneoplastic lesions formationINTERNATIONAL JOURNAL OF CANCER, Issue 1 2005Anne Mathieu Abstract In humans, initial events of pancreatic carcinogenesis remain unknown, and the question of whether this cancer, which has a ductal phenotype, exclusively arises from duct cells has been raised. Previous studies have demonstrated that transgenic expression of the CCK2 receptor in acinar cells of ElasCCK2 mice plays a role in the development of pancreatic neoplasia. The aim of our study was to examine initial steps of carcinogenesis in ElasCCK2 mice, adding a supplementary defect by using a chemical carcinogen, azaserine. Results of posttreatment sequential immunohistochemical examinations and quantifications demonstrate that mice responded to azaserine. Transition of acinar cells into duct-like cells expressing Pdx1 and gastrin, as well as proliferation of acinar cells, were transiently observed in both transgenic and control mice. The carcinogen also induced formation of preneoplastic lesions, adenomas, exhibiting properties of autonomous growth. Importantly, expression of the CCK2 receptor increased the susceptibility of pancreas to azaserine. Indeed, treated ElasCCK2 mice exhibited larger areas of pancreatic acinar-ductal transition, increased cellular proliferation as well as larger adenomas areas vs. control mice. These amplified responses may be related to auto/paracrine stimulation of CCK2 receptor by gastrin expressed in newly formed duct-like cells. Our results demonstrate that activation of CCK2 receptor and azaserine result in cumulative effects to favor the emergence of a risk situation that is a potential site for initiation of carcinogenesis. © 2005 Wiley-Liss, Inc. [source] Histopathological and immunohistochemical analysis of calcifying odontogenic cystsJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 10 2001Mitsuhide Yoshida Abstract: Method and Results: Calcifying odontogenic cysts (COCs) were examined histopathologically and immunohistochemically to characterize the histological and cytological properties of these lesions. Histopathologically, COCs showed thin or thick lining epithelium with ghost cells. COCs were classified according to proliferative type or nonproliferative type lining epithelium, the presence or absence of ameloblastomatous appearance, and the presence or absence of odontoma in the cyst walls. Immunohistochemically, amelogenin protein was expressed chiefly in ghost cells, whereas cytokeratin 19 (CK19) and bcl-2 proteins were expressed chiefly in lining epithelial cells. The proportion of cases positive for bcl-2 protein was slightly higher in COCs with odontoma than in those without odontoma. Lining epithelial cells sporadically showed positive reactions for Ki-67 antigen. Mean Ki-67 labeling index was slightly greater in COCs with proliferative type lining epithelium, COCs with ameloblastomatous appearance of the cyst walls, and COCs with odontoma of the cyst walls than in COCs without these histological features. Our results suggest that ghost cells or lining epithelial cells show ameloblastic cytodifferentiation or odontogenic epithelial characteristics, that bcl-2 protein is associated with survival of lining epithelial cells in COCs, and that high proliferation potential is associated with ameloblastomatous proliferation or combined odontoma. COCs exhibited various histological features with several transitional forms, and immunohistochemical examinations revealed little or no difference in cytodifferentiation and cellular activity among COCs. Conclusion: We conclude that COCs with various histological features have neoplastic potential and may not be separate entities within the same histological spectrum. [source] Ten cases of sebaceous carcinoma arising in nevus sebaceusTHE JOURNAL OF DERMATOLOGY, Issue 11 2008Miki IZUMI ABSTRACT Although nevus sebaceus is known to develop various types of secondary neoplasms, it rarely causes carcinoma and only 14 cases of secondary sebaceous carcinoma have been reported. In this study, 10 cases of sebaceous carcinoma arising in nevus sebaceus were collected. The clinicopathological features and results of immunohistochemical examinations with adipophilin, perilipin and p53 were summarized. Sebaceous carcinoma arising in nevus sebaceous predominantly occurred on the scalp (8/10) of elderly women (mean age, 67.7 years). No case was associated with Muir,Torre syndrome. We found several pathological features of sebaceous carcinoma; that is, made up mainly of germinative cells, moderate nuclear atypia without pleomorphism and many mitoses (4,28/10 high-power field). Adipophilin and perilipin antibodies highlighted lipid drops in the cytoplasm of the malignant cells in all cases. Overexpression of p53 was seen in all cases. In two cases there were coexisting benign-looking sebaceous lesions at the periphery of the main cancer nodule, and in these lesions p53 showed low positivity compared with the clearly malignant area. There was co-occurrence of another neoplasm in three cases with trichoblastoma, sebaceoma and syringocystadenoma papilliferum, respectively. All cases were treated by excision of the malignant lesion, with or without inclusion of the nevus sebaceus. In a follow-up period of 1,7 years, there was no case of recurrence, lymph node metastases or distant metastases. With these specific pathological and immunohistochemical findings using adipophilin, perilipin and p53, we have to consider the possibility that there is a tendency to underdiagnose secondary sebaceous carcinomas in nevus sebaceus. These clinicopathological features of sebaceous carcinomas developing in the nevus sebaceus seem to indicate different biological entities from de novo sebaceous carcinoma. [source] | ||||||||||||||||||||||||||||