bluuebunny/crossref_metadata_2025 huggingface dataset:
Hürthle (Oncocytic) Cell Tumors of Thyroid: Etiopathogenesis, Diagnosis and Clinical Significance
Authors: Sobrinho-Simoes Manuel , Maximo Valdemar , de Castro Ines Vieira , Fonseca Elsa , Soares Paula , Garcia-Rostan Ginesa , de Oliveira Manuel Cardoso
Published: June 2007

The etiopathogenesis and the classification of oncocytic (Hurthle cell) tumors of the thyroid is reviewed with an emphasis on the role played by mitochondrial and nuclear genetic abnormalities that interfere with mitochondrial function. Oxyphilia is classified into primary or secondary and the so-called Hurthle cell carcinoma is divided into oncocytic (Hurthle cell) variants of papillary and follicular carcinoma.
Follicular Colonization of Nodal Marginal-Zone B-Cell Lymphoma Resembling Follicular Lymphoma: Report of 6 Cases
Authors: Kojima Masaru , Nakamura Shigeo , Murase Takuhei , Motoori Tadashi , Murayama Kayoko , Iijima Misa , Itoh Hideaki , Sakata Noriyuki , Masawa Nobuhide
Published: June 2007

The formation of neoplastic B-cell follicles is accepted as a diagnostic criterion of follicular lymphoma. However, extranodal marginal-zone B-cell lymphomas (MZBLs) of mucosa-associated lymphoid tissue (MALT) type also sometimes contain numerous lymphoid follicles and may even have a predominantly follicular growth pattern. However, morphologic, immunohistochemical, and genotypic findings suggest that lymphoid follicles in extranodal MZBLs are neoplastic follicles formed as the result of colonization of previously reactive follicles by tumor cells (centrocyte-like cells). We present here 6 cases of nodal MZBL demonstrating a follicular growth pattern. Immunohistochemical study demonstrated that the tumor cells were CD10-, CD20+, CD79a+,CD 138-, Bcl-2+, Bcl-6and IRF4+. Residual nonneoplastic follicular center cells were CD1O+, CD20+, CD79a+, Bcl-2-, and Bcl-6+. CD21/CD23 immunostain demonstrated a disrupted follicular dendritic cell pattern characteristic of follicular colonization in extranodal MZBL of MALT type. Taken in conjunction with the morphologic findings, nodal MZBL may also show a follicular growth pattern similar to extranodal MZBL of MALT type. The marginal-zone nature is most recognizable on immunohistochemistry, although the histologic appearance alone may cause some diagnostic problems. It is important for pathologists to consider this type of lesion in diagnostic practice.
Cytokeratin-Positive Meningeal Peripheral PNET/Ewing's Sarcoma of the Cervical Spinal Cord: Diagnostic Value of Genetic Analysis
Authors: Woestenborghs Heidi , Debiec-Rychter Maria , Renard Marleen , Demaerel Philippe , Van Calenbergh Frank , Van Gool Stefaan , Sciot Raf
Published: June 2007

Peripheral primitive neuroectodermal tumor (PNET)/Ewing's sarcoma (ES) of the central nervous system is extremely rare and should be differentiated from central PNET and other small blue round cell tumors. We describe a case of a meningeal peripheral PNET/ES of the spinal cord in an 11 -year-old boy. Immunohistochemically, the small blue round cell tumor showed expression of epithelial markers and of CD99, thus posing an important differential diagnostic problem with a poorly differentiated synovial sarcoma. Fluorescence in situ hybridization revealed rearrangement of the EWS gene, as seen in peripheral PNET/ES. Peripheral PNET/ES does occur in the central nervous system, but its diagnosis can be extremely difficult on morphologic and immunohistochemical grounds alone. Genetic analysis plays a key role in its distinction from other small blue round cell tumors.
Malignant Ectomesenchymoma in the Wrist of a Child: Case Report and Review of the Literature
Authors: Oppenheimer Orit , Athanasian Edward , Meyers Paul , Antonescu Cristina R. , Gorlick Richard
Published: June 2007

Malignant ectomesenchymomas, rare and potentially aggressive tumors, occur in children and exhibit mesenchymal and neuroectodermal components. This report describes the first patient diagnosed with a malignant ectomesenchymoma of the hand. The patient was a 17-month-old male who developed a hypothenar mass on his left hand that was surgically excised. Microscopic evaluation revealed ganglioneuroblastic, rhabdomyosarcomatous, and chondrosarcomatous elements. Following excisional biopsy he was treated with cyclophosphamide, doxorubicin, vincristine, ifosfamide, and etoposide. After 3 courses of chemotherapy the patient had a wide reexcision with no residual tumor. The patient is 4 years from diagnosis, without evidence of disease.
Simultaneous Occurrence of Hodgkin's Lymphoma and Kaposi's Sarcoma Within the Same Lymph Nodes of a Non-AIDS Patient
Authors: Ngan Kah-Wai , Kuo Tseng-tong
Published: June 2007

We report a case of simultaneous occurrence of Hodgkin's lymphoma and Kaposi's sarcoma within the same lymph nodes of a 61-year-old woman without human immunodeficiency virus (HIV) infection. Epstein-Barr virus (EBV) was detected in the Hodgkin cells and Reed-Sternberg cells by EBV LMP-1 immunostaining and Epstein-Barr virus encoded early RNA (EBER) in situ hybridization. In contrast, Kaposi's sarcoma cells were positive for human herpes virus 8. This case is documented because the occurrence of 2 independent tumors infected by 2 unrelated viruses within the same lymph nodes of a patient without HIV infection has rarely been observed.
Rosai-Dorfman Disease of the Gastrointestinal Tract: Report of a Case and Review of the Literature
Authors: Alatassi Houda , Ray Mukunda B. , Galandiuk Susan , Sahoo Sunati
Published: June 2007

Rosai-Dorfman disease (RDD) is a rare, acquired disease of unknown etiology that affects primarily children and young adults. It is characterized by a proliferation of distinctive histiocytes in the lymph nodes and/or extranodal sites. Involvement of the gastrointestinal tract is rare. We report a case of RDD in a 60-year-old woman who presented with hematochezia and was found to have RDD of the rectum presenting as a rectal mass. This report highlights the current pathogenetic mechanisms, immunohistochemical markers, and the gastrointestinal manifestations of RDD.
Multimodal Immunosuppressant Therapy in Steroid-Refractory Common Variable Immunodeficiency Sprue: A Case Report Complicating Cytomegalovirus Infection
Authors: Medlicott S. A. C. , Coderre S. , Horne G. , Panaccione R.
Published: June 2007

Immunodeficient patients can develop malabsorption, mimicking celiac disease clinically and histologically. Such individuals may also occasionally require immunosup pressive therapy for autoimmune disorders. We have identified a patient with common variable immunodeficiency (CVID)-associated sprue complicated by duodenal cytomegalovirus (CMV) infection following corticosteroid and ancillary immunomodulatory therapy. Ganciclovir and a modification of the immunosuppressant regimen improved both clinical symptoms and villous atrophy. To our knowledge, this is original documentation of duodenal CMV infection secondary to immunomodulatory therapy for steroid-refractory CVID-sprue.
CD10, Actin, and Vimentin Expression in Breast Phyllodes Tumors Correlates with Tumor Grades of the WHO Grading System
Authors: Tsai Wen-Chiuan , Jin Jong-Shiao , Yu Jyh-Cherng , Sheu Lai-Fa
Published: June 2007

The discrimination of borderline from malignant primary breast phyllodes (PT) tumor is still unclear. We studied 22 PT cases to investigate the immunohistochemical expression (staining of stromal CD10, SMA [smooth muscle actin], and vimentin) as well as the features of focal glandular atypia to determine whether these correlated with the histopathologic grading system. In our results, the stromal staining of CD10 was positive in 4 of 6 malignant and 2 of 5 borderline PT cases, but negative in all benign PT cases. Stromal actin and intraglandular vimentin-expressive tumor cells were found in 5 of 6 malignant PT cases but not in borderline and benign PT cases. There is a significant difference in the panel of stromal CD10, actin, and vimentin expression between borderline and malignant PT (p<0.05). Besides, the progression of malignant potential breast phyllodes tumor may cause glandular epithelium atypia with loss of polarity.
Merkel Cells in the Oral Mucosa
Authors: Righi Alberto , Betts Christine M. , Marchetti Claudio , Marucci Gianluca , Montebugnoli Lucio , Prati Carlo , Eusebi Leonardo H. U. , Muzzi Luciana , Ragazzini Teresa , Foschini Maria P.
Published: June 2007

Ninety-eight consecutive surgical biopsies of oral mucosa from 96 patients were evaluated immunohistochemically with an anti–cytokeratin 20 (CK 20) anti-body to evidence Merkel cells (MC). Fifteen cases, showing the highest number of MC, were additionally studied with chromogranin A, S-100 protein, neuro filaments, epithelial membrane antigen, and double immunostaining for CK 20 and Ki67 antibodies to evaluate MC proliferation. Electron microscopy was performed in 2 cases. MC were observed in 58 cases. The highest number of MC was found in the gingival, buccal, and palate mucosa, especially in chronically damaged oral mucosa (lichen and chronic aspecific inflammation) as well as in the mucosa overlying tumors rather than in normal or acute inflammation. MC were not observed in dysplastic or neoplastic epithelium. MC showed evidence of proliferation, as demonstrated by Ki67 positivity, in 3 cases. In conclusion, MC appear to play a role in the reparative processes of oral mucosa.
Unusual Renal Pathology Associated With a Wilms Tumor in a 15-Month-Old Infant
Authors: Rais-Bahrami Soroush , Argani Pedram
Published: June 2007

Beckwith-Wiedemann syndrome is an overgrowth dis-order that predisposes to the development of a variety of malignancies including Wilms tumor. Pathologists may suspect the presence of Beckwith-Wiedemann syndrome, which may be clinically subtle, on the basis of the histopathology of the renal parenchyma adjacent to a Wilms tumor. These kidneys typically harbor multiple nephrogenic rests (especially perilobar nephrogenic rests), and their medullas have blunted papillae resulting from excessive fibromyxoid stroma, decreased collecting ducts, and decreased Henle loops. This complex of findings constitutes the so-called Beckwith Medulla. Extensions of this stroma-rich medulla into the cortex results in characteristic dysplastic medullary-ray nodules. Identification of these histologic abnormalities by the pathologist should prompt the clinician to evaluate the child for Beckwith-Wiedemann syndrome. Proper screening of these children can allow for early detection of cancers and treatment while these cancers are curable.
Critical Comparison of 31 Commercially Available Digital Slide Systems in Pathology
Authors: Rojo Marcial García , García Gloria Bueno , Mateos Carlos Peces , García Jesús González , Vicente Manuel Carbajo
Published: June 2007

Advances in new technologies for complete slide digitization in pathology have allowed the appearance of a wide spectrum of technologic solutions for whole-slide scanning, which have been classified into motorized microscopes and scanners. This article describes technical aspects of 31 different digital microscopy systems. The most relevant characteristics of the scanning devices are described, including the cameras used, the speed of digitization, and the image quality. Other aspects, such as the file format, the compression techniques, and the solutions for visualization of digital slides, (including diagnosis-aided tools) are also considered. Most of the systems evaluated allow a high-resolution digitization of the whole slide within about 1 hour using a ×40 objective. The image quality of the current virtual microscopy systems is suitable for clinical, educational, and research purposes. The efficient use of digital microscopy by means of image analysis systems can offer important benefits to pathology departments.
Intrarenal Pure Yolk Sac Tumor
Authors: Kumar Yashwant , Bhatia Alka , Kumar Vijay , Vaiphei Kim
Published: June 2007

Yolk sac tumor (endodermal sinus tumor) is a malignant germ cell tumor that usually arises in the gonads. Extragonadal germ cell tumors are rare and have been described in case reports. We report a pure intrarenal yolk sac tumor in a 1-year-old boy who presented with a huge abdominal mass and was operated for suspected Wilms tumor. The tumor exhibited histopathologic and immunohistochemical features identical to those of an endodermal sinus tumor of gonadal origin. The purpose of this report is to add a rare tumor to the differential diagnosis of pediatric renal neoplasms.
Intravascular Papillary Endothelial Hyperplasia of the Jejunum
Authors: Mestiri Sarra , Karoui Mehdi , Charachon Antoine , Deux Jean-François , Chaumette Marie-Thérèse
Published: June 2007

Intravascular papillary endothelial hyperplasia is considered to be an unusual form of thrombus organization that is marked by an excessive papillary endothelial proliferation. This lesion has the propensity to occur in the skin and the subcutis. Occurrence in the gastrointestinal tract is very rare. The authors report an exceptional case of a 20-year-old young woman with intravascular papillary endothelial hyperplasia in the jejunum. The patient was referred to the hospital with a 1-week history of melena. The lesion did not recur after surgery. Histopathological examination revealed a papillary endothelial hyperplasia with an underlying arteriovenous malformation.
Endothelial Cells of Intramuscular (Infantile) Hemangioma Express Glut1
Authors: Drut Ricardo , Altamirano Eugenia
Published: June 2007

Glut1 is a marker of infantile hemangioma, and its positivity has resulted in defining this tumor at several sites (eg, skin, breast, salivary glands, liver, and placenta). We herein report on the presence of Glut1 positivity in the endothelial cells of 2 examples of intramuscular hemangioma, a peculiar tumor considered to be most probably congenital. The finding expands the sites where infantile hemangioma may be recognized and suggests that this intramuscular variety should be renamed intramuscular infantile hemangioma. An additional previously unreported finding was the presence of a strong membranous pattern of staining for Glut1 in the intralesional fat cells, a known component of the tumor, which parallels that of another endothelial marker, namely CD34. These findings could prove useful for diagnostic purposes in small biopsies.
The Significance of c-erbB-2 Overexpression and p53 Expression in Patients With Axillary Lymph Node—Negative Breast Cancer: A Tissue Microarray Study
Authors: Ko Seung-Sang , Na Youn-Sun , Yoon Chan-Seok , Park Ji-Young , Kim Hye-Sun , Hur Min-Hee , Lee Hae-Kyung , Chun Yi-Kyung , Kang Sung-Soo , Park Byeong-Woo , Lee Jee-Hyun
Published: June 2007

We conducted this study to examine whether the expression of c-erbB-2 and p53 is the prognostic indicator for patients with early-stage breast cancer in which axillary lymph node metastasis is absent. We examined 326 patients with early-stage breast cancer in which axillary lymph node metastasis is absent. Tissue microarrays were constructed. Following this, immunohistochemical staining was done for estrogen receptor (ER), progesterone receptor (PR), c-erbB2, and p53. The results were as follows: (1) expression of c-erbB-2 was correlated with other clinicopathologic factors (eg, patient's age, presence of menopause, tumor size, histologic and nuclear grade, and presence of hormone receptors such as ER and PR); and (2) expression of p53 was correlated with survival rate, patient's age, presence of menopause, and tumor size. However, these results were not statistically significant. In conclusion, our results indicate that expression of c-erbB-2 and p53 did not have any prognostic value in patients with early-stage breast cancer in which axillary lymph node metastasis is absent.
Adenocarcinosarcoma in Barrett's Esophagus
Authors: Rosty Christophe , Prévot Sophie , Tiret Emmanuel , Wendum Dominique , De Saint Maur Paul P.
Published: June 2007

Carcinosarcoma of the esophagus is a rare tumor with both carcinomatous and sarcomatous components. Usually the mesenchymatous component is predominant, and the carcinomatous part is a squamous cell carcinoma. We report the case of an old man having a large polypoid mass in the distal third of the esophagus, arising in Barrett's esophagus. The tumor consisted of a mixture of vimentin-positive sarcoma and keratin-positive adenocarcinoma. The adenocarcinomatous cells also expressed the epithelial membrane antigen and did not express vimentin. To the best of our knowledge, it is the second case of adenocarcinosarcoma in Barrett's esophagus published in the English literature. The prognosis of this peculiar tumor is uncertain.
Metanephric Adenoma of the Kidney
Authors: Picazo Mariá L. , Hardisson David , Rodríguez-Peralto José L. , Núñnez Carlos , Burgos Emilio , Perna Cristian
Published: June 2007

We report a metanephric adenoma of the left kidney in a 70-year-old woman. The tumor was composed of closely packed, small tubules lined by oval tumor cells without atypia. Blastema elements were absent. Ultrastructural examination confirmed the epithelial nature of the neoplasm. Flow cytometric DNA content analysis showed a diploid histogram. The tumor was excised by radical nephrectomy, and the patient remains asymptomatic 10 months after surgery.
Follicular Dendritic Cell Tumor in Castleman's Disease
Authors: Saiz Antonio D. , Chan Olivia , Strauchen James A.
Published: June 2007

We report two cases of follicular dendritic cell tumor associated with Castleman's disease, one of the hyaline vascular type and one a mixed hyaline-vascular and plasma cell type. The reactive lymphoid follicles in both cases contained a proliferation of abnormal follicular dendritic cells characterized by enlarged, irregular contoured nuclei and prominent nucleoli (in-situ component). Both tumors had similar histology. They were vaguely fascicular and composed by eosinophilic, ovoid to spindled cells with vesicular nuclei and prominent nucleoli admixed with small lymphocytes. Some of these cells seen in the reactive follicles were similar in appearance to the ones seen in the adjacent invasive tumors. The association of follicular dendritic cell tumor with Castleman's disease and the presence of in-situ follicular dendritic cell tumor within reactive lymphoid follicles suggests that there may be a progression from dysplastic follicular dendritic cells to follicular dendritic cell tumor in Castleman's disease. The sequence of events and the likelihood that patients with Castleman's disease showing follicles with dysplastic changes will develop follicular dendritic cell tumors is not known at this time owing to the limited number of cases reported.
Adenocarcinoma of the Uterine Cervix with Massive Signet-Ring Cell Differentiation
Authors: Mayorga Marta , García-Valtuille Ana , Fernández Fidel , Val-Bernal J. Fernando , Cabrera Ernesto
Published: June 2007

Primary signetring cell adenocarcinoma of the cervix is very rare and less common than metastatic signet-ring cell adenocarcinoma. To the best of the authors' knowldge only one genuine case has been reported to date. Tvvo cases of primary signeting cell adenocarcinoma of the uterine cervix in patients aged 68 and 74 years are presented. The tumors were in stage IB. The light microscopic findings were conirmed by histochemical and immunohistochemical study. DNA nuclear analysis by flow cytometry of the neoplasms revealed an aneuploid (tetraploid) pattern. The paients had no evidence of recurrent or metastatic disease 35 and 25 months after a radical hysterectomy with bilateral salpingo-oophorectomy and lymph node dissecion respectively. Primary signet-ring cell adenocarcinoma of the cervix should be diferentiated from metastatic adenocarcinoma, endocervical involvement by signeting cell carcinoma of the endometrium, benign mucinfilled signet-ring cell aggregates that may accumulate in mucosal folds, microglandular hyperplasia, muciarminophilic histiocytosis, and other malignant neoplasms that may have signet ringlike cells and deserve consideration such as squamous cell carcinoma, maligant lymphoma, myeloma, and malignant melanoma. Although very rare, signeting cell adenocarcinoma of the cervix can exist as a primary tumor. Distinction beween a primary neoplasm and a metastasis to the cervix is decisive for treatment and prognosis.
Behçet's Colitis Has Distinctive Pathological Features
Authors: Leonard N. , Palazzo J. , Jameson J. , Denman A. M. , Talbot I. C. , Price A. B.
Published: June 2007

Patients with Behçet's syndrome commonly have gastrointestinal symptoms. Less commonly, these symptoms are so severe as to necessitate surgery. The features of the colitis seen in Behçet's syndrome are not clearly defined histologically, and their similarity to Crohn's disease is often emphasized. After reviewing three cases with Behçet's colitis we feel that there is a specific constellation of gross and histologic features that, when combined with a relevant clinical history, should suggest Behçet's colitis. On gross examination Behçet's colitis is characterized by multiple punchedout ulcers of varying sizes with intervening normal mucosa. This appearance excludes ulcerative colitis, which should have adjacent architectural distortion with active inflammation, but not Crohn's disease, infectious colitis, or druginduced colitis. On histologic examination Behçet's colitis has cratershaped ulcers that often penetrate the serosa. Fissure ulcers, mural lymphoid aggregates, and granulomas are not seen in contrast to Crohn's disease. Similarly, microscopic features of infectious colitis such as cryptitis and crypt withering are not a feature. When the gross and microscopic features are combined with an appropriate clinical picture the pathologist should be able to suggest Behçet's colitis in a resection specimen rather than merely an atypical variant of Crohn's disease.
Lymphocytic Infiltrates in Solitary Parathyroid Adenomas
Authors: Lawton Thomas J. , Feldman Michael , LiVolsi Virginia A.
Published: June 2007

We describe four cases of solitary parathyroid adenomas with prominent lymphocytic infiltrates presenting as primary hyperparathyroidism. There was no involvement of the other parathyroid glands in the three cases in which they were biopsied. In two cases the thyroids were removed and were without lymphoid infiltrates. The infiltrates were composed of a mixed population of B and T lymphocytes in the three cases that had material available for immunohistochemistry. There was no evidence of parathyroid parenchymal destruction, and in none of the patients was an autoimmune disease present clinically or serologically. We hypothesize that lymphocytic infiltrates in parathyroid adenomas are an uncommon, but clinically innocuous, histologic finding and their presence does not imply an autoimmune disorder.
Intermediate Trophoblasts: Their Role in the Diagnosis of Intrauterine Pregnancy
Authors: Al-Tamimi Dalal M.
Published: June 2007

The presence of intermediate trophoblastic cells in uterine curettings is considered a reliable indicator of intrauterine implantation. However, this highly invasive trophoblast is difficult to recognize with conventional staining. Nevertheless, cytokeratin antibodies are reliable markers of this cell type. A previous study has described multiple deep clefts in the nuclei of these cells. The present study was performed to identify the specific histologic feature of intermediate trophoblasts and to test the accuracy of this finding in the diagnosis of intrauterine pregnancy in curettings lacking chorionic villi. The author reviewed 170 abortion specimens. The specimens were divided into two main groups: (1) intrauterine gestations with villi and (2) intrauterine gestation without villi. Each group was further divided into three subgroups on the basis of the presence or absence of large cells with multiclefted nuclei (MCN). In-termediate trophoblasts were identified in 97% of the cases in group I; 63% of these cells possessed MCN. On the other hand, Intermediate trophoblasts were identified in 59% of specimens of group II; 31% of those showed MCN. The nature of these cells was further confirmed by immunohistochemical staining. The author concludes that intermediate trophoblastic cells can reliably be identified by morphologic assessment of the routine H & E sections.
Acquired Diverticulosis of the Vermiform Appendix: A Disease of Multiple Etiologies
Authors: Medlicott S. A. C. , Urbanski S. J.
Published: June 2007

Acquired diverticular disease of the vermiform appendix is a rare condition that usually presents with the symptoms of acute appendicitis. This analysis was undertaken to determine the spectrum and prevalence of the associated lesions in acquired appendiceal diverticulosis. Thirty-one cases of acquired appendiceal diverticular disease were identified from files over a period of 15 years (1982-1996). Diverticulosis was the only abnormality in 17 cases (54.8%). An associated neoplastic epithelium was present in nine (29%) patients (seven adenomata and two goblet cell carcinoids), fecalith formation in three (9.7%), and a neuroma in two (6.5%). Although rare, diverticular disease of the vermiform appendix was frequently seen in association with an adenomatous mucosa. In our experience, one appendiceal adenoma coexisted with a colonic adenocarcinoma. In conclusion, the diagnosis of appendiceal diverticulosis necessitates the exclusion of coexisting appendiceal neoplasia.
Malignant Peripheral Nerve Sheath TuImor with Glandular and Rhabdomyoblastic Differentiation
Authors: Ordofiez Nelson G.
Published: June 2007

Malignant peripheral nerve sheath tumor with glandular and rhabdomyoblastic differentiation is a rare neoplasm: only six cases have previously been documented. The clinical evolution and immunohistochemical profile with use of a large battery of immunohistochemical markers of a case occurring in the right lumbar paraspinal region in a 28-year-old man is reported.
Current Topics in Pathology of Gynecologic Tumors
Authors: Matias-Guiu Xavier , Lerma Enrique , Prat Jaime
Published: June 2007

Over the last decade, the application of new technologieslargely immunohistochemistry and molecular genetics to the study of gynecologic tumors has provided new insights into their pathogenesis. Attempts to integrate the results of these investigations into the conventional clinicopathologic features of the tumors have been made. In this review, which does not intend to be comprehensive, several selected topics dealing with the pathogenesis of gynecologic neoplasms are briefly presented.
Expression of Cyclin E and Cyclin-Dependent Kinase Inhibitor, p27KIP1 in Uterine Endometrial Carcinoma: Relationship with p53 Status
Authors: Ahn Hee Jeong , Kwon Kae Won , Choi Yoon Jung , Cho Nam Hoon
Published: June 2007

In an effort to clarify the cell-cycle regulator factors that affect the development and growth of endometrial carcinoma, immunohistochemical analyses of cyclin E, p27KIPI, and p53 were performed in 36 cases of endometrial carcinoma (31 endometrioid and five serous carcinomas) and 40 cases of endometrial hyperplasia (20 simple hyperplasia and 20 complex hyperplasia). A correlation of expressions of these regulators with clinicopathologic features was analyzed. Overexpression of cyclin E was found in 0%, 30%, and 52.8% of simple hyperplasia, complex hyperplasia, and endometrial carcinoma, respectively. The p53 was overexpressed in 20%, 25%, and 69.4% of simple hyperplasia, complex hyperplasia, and endometrial carcinoma, respectively. Immunoreactivity of p53 in endometrial carcinoma was significantly higher than in simple and complex hyperplasia (p<.05). The immunoreactive indices of cyclin E and p53 in cases of stage Ic were higher than in cases of stage lb (p=.047, .021, respectively). Immunoreactivity of p27 in endometrial carcinoma was significantly lower than in normal and hyperplastic endometrium (p<.05). There was a significant correlation between expressions of cyclin E and p53 and an inverse correlation between expressions of p27 and p53 (p<.001). These results suggest that the overexpression of cyclin E and p53 and the downregulation of p27 are implicated in the development and early progression of endometrial carcinoma. The results also suggest that regulatory factors have a close relationship with each other in endometrial hyperplasia and carcinoma.
Role of the Perivascular Epithelium in the Histogenesis of Hassall's Corpuscles
Authors: Palestro G. , Novero D. , Geuna M. , Chiarle R. , Chiusa L. , Pagano M. , Pich A.
Published: June 2007

Thirteen human thymuses and one thymoma were morphologically and immunohistologically investigated to define the histogenesis of Hassall's corpuscles (HCs). The following monoclonal antibodies: antisquamous cytokeratin on paraffin sections and TE-4 and TE-8 on frozen sections, were used to show the distribution of the epithelial components; PAL-E on frozen and anti-CD31 and anti-CD34 on paraffin sections detected the endothelial cell distribution. In the thymoma, epithelial onion-like structures, looking like true HCs, were found to originate from the perivascular epithelium lining dilatated spaces and some of them partially obliterated the space where the blood capillary showed thickened wall and endothelial regressive changes. Antisquamous cytokeratin stained: (1) in the thymus: subcapsular, medullary, and HC epithelial cells; (2) in the thymoma: epithelial cells lining the perivascular spaces and forming HCs. TE-4 stained: (1) in the thymus: the subcapsular and medullary epithelium; (2) in the thymoma: the epithelium lining the perivascular spaces and epithelial cells forming HCs. TE-8 stained: (1) in the thymus: HCs only; (2) in the thymoma: HCs and perivascular epithelial cells. PAL-E, CD31, and CD34, which specifically react with endothelial cells, stained remnants of capillary structures in the core of some HCs. The results indicate that: (1) corpuscular structures in thymoma originate from perivascular epithelium; (2) thymus medullary epithelial cells stained by cytokeratin and TE-4 correspond to perivascular epithelial cells whose staining is well documented in thymoma; (3) the subcapsular-perivascular epithelium and HCs represent different steps of differentiation of a single ectodermal cell lineage; (4) the PAL-E-, CD31-, and CD34-positive reaction in the core of some HCs suggests that the perivascular epithelium would be stimulated to transform into HCs as a consequence of endothelial changes with fragmentation of the capillary included in the perivascular space.
Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma of the Thymus
Authors: Kim Duck Hwan , Nam Eun Sook , Yi Jeong Geun , Shin Hyung Sik , Kim In-Sun
Published: June 2007

We present a rare case of primary low-grade B-cell lymphoma of the thymus. The tumor showed the typical features of a MALT (mucosa-associated lymphoid tissue) lymphoma with epithelium-lined thymic cyst. Histologically, there were sheets of centrocyte-like (CCL) cells intermingled with small lymphocytes and plasma cells. CCL cells invaded the epithelium of the cyst and residual Hassall's corpuscles, forming characteristic lymphoepithelial lesions. Immunohistochemically, the tumor cells revealed positive immunoreaction for CD20 and monotypic cytoplasmic restriction of kappa light chain.
A Paratesticular Pseudosarcomatous Myofibroblastic Proliferation
Authors: Donnellan Rory , Bramdev Ashwin , Chetty Runjan
Published: June 2007

A 70-year-old man presented with a 3-year history of a slowly enlarging mass in the right scrotum. On examination there was a hard, slightly tender 6-cm-diameter, multinodular mass, palpable above the testis in the region of the spermatic cord. Right orchidectomy with excision of the mass was performed. Macroscopically, there was a well-circumscribed, homogeneous, pale-white, paratesticular lesion, sections of which showed a moderately cellular spindle cell proliferation. Some areas resembled fibroblasts in tissue culture, whereas in other areas the cells were pleomorphic, suggestive of sarcoma. However, the mitotic count per 10 high-power fields averaged at 1, and there were no abnormal mitoses. The cells stained positively with antibodies to actin and desmin, in keeping with a myofibroblastic origin. This lesion is consistent with the recently described “proliferative funiculitis,” a paratesticular pseudosarcomatous myofibroblastic proliferation.
Dedifferentiated Components Versus Well-differentiated Components in Dedifferentiated Lip sarcoma: A Comparative Study of Their Proliferative Activity and Interphase Cytogenetics Using MIB-1 Immunostaining and Fluorescence in Situ Hybridization
Authors: Tsuji Takahiro , Fukuda Toshiro , Tamiya Sadafumi , Tsuneyoshi Masazumi
Published: June 2007

We retrospectively analyzed the proliferative activity and the centromeric copy number of chromosomes 8, 12, and 17 in both well-differentiated components and dedifferentiated ones of 10 dedifferentiated lip sarcoma cases by using MIB-1 immunostaining and fluorescence in situ hybridization (FISH) on the paraffin-embedded tissue specimens. The MIB1 labeling index (LI) in dedifferentiated components was higher than that in the well-differentiated components (p<.01). Chromosomal aberrations such as gains in chromosomes 8, 12, and 17 were found in two dedifferentiated components of the seven cases in which signals were detected. The most frequent aberrations were a gain in chromosome 17 (cases 2 and 10), followed by gains in chromosomes 8 (case 10) and 12 (case 2). In contrast, no chromosomal aberrations were observed in any of the eight well-differentiated components in which signals were detected. Based on these findings, chromosomal aberrations in the dedifferentiated components may reflect aggresive tumor progression in dedifferentiated lip sarcoma.
The Relationship of N-myc Amplification and Apoptosis in Neuroblastoma
Authors: Chen Be-Fong , Chen Mong-Liang , Liang Der-Cherng , Liu Hsi-Che , Chen Shu-Huey
Published: June 2007

About 30% of neuroblastomas exhibit N-myc amplification. Neuroblastomas with Nmyc amplification tend to have a stroma-poor undifferentiated histopathologic phenotype and a high mitosis-karyorrhexis index (MKI). Karyorrhectic or pyknotic cells in neuroblastomas are closely related to apoptosis. Using fluorescence in situ hybridization (FISH) technique on formal in-fixed paraffin-embedded tissue, we conducted a retrospective study on 42 cases of neuroblastomas to investigate the relationship between N-myc amplification and apoptosis. The identification of apoptotic cells was based on morphology and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate (UTP)-biotin nick end labeling (TUNEL) method. Eleven (26%) of 42 tumors demonstrated N-myc amplification. After exclusion of nine tumors from patients who had prior chemotherapy, 3 3 tumors were available for thorough investigation. Based on the morphology of apoptotic cells, seven of the eight neuroblastomas with N-myc amplification had high apoptotic cell counts (more than 200 per 5,000 tumor cells), whereas only three of the 25 tumors without N-myc amplification revealed high apoptotic cells. Our results suggest that N-myc amplification can be readily detected in routinely processed tissue sections by FISH technique. Its presence has prognostic value and tends to be associated with a high number of apoptotic cells in neuroblastomas.
Isolated Idiopathic Granulomatous (Giant Cell) Vasculitis of the Prostate
Authors: Val-Bernal J. Fernando , Garijo M. Francisca
Published: June 2007

Vasculitis involving the prostate is uncommon and usually reflects systemic disease. Isolated prostatic vasculitis is very rare. Most of these cases are morphologically categorized as polyarteritis nodosa. We describe a 72-year-old man with idiopathic granulomatous vasculitis limited to the prostate. The vasculitis was identified incidentally upon microscopic examination of the suprapubic prostatectomy specimen removed for nodular hyperplasia. The transmural inflammation was centered on muscular arteries and veins and it was accompanied by narrowing of the lumen. Vasculitis was not associated with any secondary changes such as infarct or postinfarct fibrosis. Immunophenotyping of the vascular inflammatory infiltrate disclosed abundant macrophages and T-lymphocytes and virtual absence of B-lymphocytes. The patient is alive and well on no treatment for a follow-up period of 14 months. To our knowledge this is the second case report of prostatic involvement in localized idiopathic granulomatous vasculitis. It is important to distinguish cases of isolated granulomatous vasculitis in the prostate from systemic disease, because the latter implies a poor prognosis and requires an aggressive treatment.
Glomerular Detection of Schistosomal Antigen by Immunoelectron Microscopy in Human Mansonian Schistosomiasis
Authors: DeBrito T. , Nussenzveig I. , Carneiro Célia Regina W. , Nakhle Maria Cristina , Carvalho S. , Silva Ana Maria G. , Sandoval Marina , Saldanha L. B.
Published: June 2007

Schistosomal antigens (S. mansoni) were detected in glomeruli of nine patients with nephropathy and nephrotic syndrome by immunoelectron microscopy. The criteria for patients' selection were presence of intestinal schistosomiasis and absence of any surgical or other medical diseases, particularly lupus erythematosus, syphilis, and hepatitis B and C, which could explain the renal disease. When examined by light microscopy, kidney biopsies showed type I membranoproliferative glomerulonephritis in four patients, focal segmental glomerulosclerosis in two, and mesangioproliferative glomerulonephritis, membranous glomerulonephritis, and minimal change disease in one each of the remaining three patients. Immunofluorescence showed mainly immunoglobulin G (IgG), IgM, and different complement components (C3, Clq) deposits, particularly in the mesangial area, in eight patients. All patients had gold-labeled schistosomal antigen deposits in their glomeruli, chiefly in mesangial cells and matrix, along the glomerular membrane, and occasionally in the cytoplasm of epithelial cells. Although membranous glomerulonephritis has been rarely described in association with schistosomiasis and minimal change disease may be occasionally caused by an infectious disease like syphilis, the absence of definite experimental models and epidemiologic data suggests that coincidental pathologies without causal relationship with schistosomiasis cannot be ruled out to explain these findings.
Myelolipoma of the Liver
Authors: Hoang Mai P. , Ordoñez Nelson G.
Published: June 2007

A 49-year-old woman presented with a 2-year history of back pain. An abdominal computed tomography revealed a 15.0 × 12.0 cm hypodense lesion in the posterior right lobe of her liver. A right hepatic lobectomy was performed, which revealed a well-demarcated lipomatous tumor that microscopically proved to be a myelolipoma. Our case together with 10 other well-documented cases showed the median age of the patients as 55 years (range, 40-69), a predilection for the female gender, and the right lobe of the liver as the most commonly involved site.
Arterial Elastance and Wave Reflection Augmentation of Systolic Blood Pressure: Deleterious Effects and Implications for Therapy
Authors: Nichols Wilmer W. , Edwards David G.
Published: June 2007

Systolic and pulse blood pressures are stronger predictors of stroke, coronary heart disease, myocardial infarction, heart failure, end-stage renal disease, and cardiovascular mortality than diastolic pressure. Furthermore, diastolic pressure is inversely related to coronary heart disease and cardiovascular mortality. Increased elastance (or stiffness, inverse of compliance) of the central elastic arteries is the primary cause of increased systolic and pulse pressure with advancing age and in patients with cardiovascular disease, including hypertension, and is due to degeneration and hyperplasia of the arterial wall; diastolic pressure decreases as arterial elastance increases. As elastance increases, transmission velocity of both forward and backward (or reflected) traveling waves increases, which causes the reflected wave to arrive earlier in the central aorta and augments pressure in late systole. These changes in arterial wall properties cause an increase in left ventricular afterload and myocardial oxygen consumption and a decrease in myocardial perfusion pressure, which may induce an imbalance in the supply-demand ratio, especially in hypertrophied hearts with coronary artery disease. Also, an increase in systolic pressure increases arterial wall circumferential stress, which promotes fatigue and development of athersclerosis. Vasodilator drugs have little direct active effect on large elastic arteries but can markedly reduce wave reflection amplitude and augmentation index by decreasing elastance of the muscular arteries and reducing pulse wave velocity of the reflected wave from the periphery to the heart. This decrease in intensity (or amplitude) and increase in travel time (or delay) of the reflected wave causes a generalized decrease in systolic pressure and arterial wall stress and an increase in ascending aortic flow during the deceleration phase. The decrease in systolic pressure brought about by this mechanism is grossly underestimated when systolic pressure is measured in the brachial artery.
Dose Dependency of Fluvastatin Pharmacokinetics in Serum Determined by Reversed Phase HPLC
Authors: Siekmeier R. , Lattke P. , Mix C. , Park J.-W. , Jaross W.
Published: June 2007

Background: Fluvastatin is an inhibitor of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, effectively lowering serum cholesterol concentrations. A high-performance liquid chromatography (HPLC) assay was developed that determined the pharmacokinetics of fluvastatin in healthy individuals after administration of 40 and 80 mg fluvastatin.

Methods: The method was linear for serum concentrations between 10 ng/mL and 5,000 ng/mL, showing good coefficients of variations and sample stability. After administration of 40 mg fluvastatin, the mean values of the area under the serum concentration vs time curve (AUC), the maximum serum drug concentration (C,,4a), the time to reach CmaX (t.aJ, and the serum elimination half-life time were 528.5±8.8 ng/mL'h, 149.6 ±6.0 ng/mL, 60.0±30.0 minutes, and 108.0±7.9 minutes, respectively. The corresponding values for a dose of 80 mg fluvastatin were 1417.7 ±79.2 ng/mLh, 1024.7 +1085.1 ng/mL, 60.0 ±1.2 minutes, and 106.0 ±3.6 minutes, respectively. Doubling of the dose from 40 mg to 80 mg caused an overproportional increase of AUC and Cmax.

Results and Conclusion: Results suggest that the measurement of fluvastatin serum concentrations by means of HPLC provides reliable data within the broad range of physiological serum concentrations. The pharmacokinetic data after administration of high doses (80 mg) showed an overproportional increase of AUC and Cm,,, suggesting a saturation of the hepatic first-pass effect. Thus, in patients treated with additional substances interfering with fluvastatin metabolism, fluvastatin serum concentrations should be analyzed.
Comparative Effects of ACE Inhibitors and an Angiotensin Receptor Blocker on Atherosclerosis and Vascular Function
Authors: Sun Yi-ping , Zhu Bo-qing , Browne Amanda E. M. , Pulukurthy Satyavardhan , Chou Tony M. , Sudhir Krishnankutty , Glantz Stanton A. , Deedwania Prakash C. , Chatterjee Kanu , Parmley William W.
Published: June 2007

Background: Both angiotensin-converting enzyme inhibitors (ACE-IS) and angiotensin receptor blockers (ARBS) provide vascular protection. This study was designed to compare ACE-IS with widely differing tissue affinity (captopril and quinapril) and an ARB (losartan) on vascular protection against the adverse effects of high cholesterol.

Methods and Results: Forty-two New Zealand rabbits on a 0.5% cholesterol diet were ran-domized into control, captopril (10 mg/kg/d), quinapril (0.3 mg/kg/d), and losartan (8 mg/kg/d) groups for 14 weeks. Captopril, quinapril, and losartan significantly attenuated aortic lipid lesions (P = 0.001). Captopril and quinapril were more effective than losartan in preserving vascular relaxation.

Conclusions: Captopril, quinapril, and losartan had similar protective effects against atherogenesis. Captopril and quinapril were more effective than losartan in preserving vascular function. Increased bradykinin by ACE inhibition may be responsible for this improved vascular endothelial function.
Treatment of the Elderly with 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors: Focus on Drug Interactions
Authors: Davidson Michael H.
Published: June 2007

With the aging of the population, death from coronary heart disease (CHD) and stroke has become more prevalent. Cardiovascular disease (CVD) risk factors, such as hypertension, obesity, and diabetes mellitus increase with age as well. Recent secondary-prevention studies have established the positive effect of statins in decreasing the risk of CHD mortality through the lowering of cholesterol. Statins have an excellent safety record, at least with users under age 65, and provide a cheaper alternative to more costly medical options. The most serious side effect associated with their use is myopathy, which is infrequent. Drug interactions have been found with drugs that compete for the same CYP450 isoenzymes as statins. Several drugs have been shown to significantly inhibit the CYP3A4 pathway; in combination with statins such as lovastatin, simvastatin, atorvastatin, and cerivastatin, they have been shown to elevate serum concentrations of these statins, or may increase the risk of myopathy. Alternatively, other drugs can inhibit the CYP2C9 pathway and may elevate serum concentration of fluvastatin. Due to the number of medications the elderly receive, an understanding of the various metabolic pathways is of vital importance to minimize the potential for drug interactions. The elderly population, while at high risk for CVD, is currently undertreated. Statins can effectively lower low-density lipoprotein cholesterol levels and lessen the risk of CVD for this population.
Electrophysiologic and Antiarrhythmic Effects of the New Class III Antiarrhythmic Drug KCB-328 in Experimental Canine Atrial Flutter
Authors: Rahme Marc M. , Ungab GilAnthony , Wadhwa Manish , Al-Kandari Fawziah , Yao Biguang , Gupta Anuj , Lee Kiho , Kim Hak-Yeop , Feld Gregory K.
Published: June 2007

Background: The electrophysiologic and antiarrhythmic effects of a new class III antiarrhythmic drug (KCB-328), a delayed rectifier potassium current (IKr) blocker with minimal reverse use-dependent effect on atrial repolarization, were evaluated in the canine night atrial crush-injury model of atrial flutter (AFL).

Methods: Ten anesthetized, open-chest dogs, were studied after right atrial crush-injury. Atrial effective refractory period (ERP), conduction velocity (CV), wavelength, and dispersion of refractoriness were determined during programmed stimulation (S1S2 at SISI = 200, 300, 400, and 500 msec) at four sites via a mapping plaque sutured on the right atrial free wall. Right and left ventricular ERP were similarly measured at single sites. Electrophysiological parameters were determined at baseline and following sequential cumulative doses of KCB-328 (10, 30, 100. and 300,ug/kg).

Results: Sustained AFL was inducible in 7/10 dogs by rapid pacing following baseline electrophysiologic measurements. KCB-328 significantly prolonged sinus cycle length, but had no effect on PR interval, and prolonged QTc only at the highest dose level. KCB-328 significantly prolonged atrial ERP and wavelength and ventricular ERP, and significantly reduced dispersion of atrial refractoriness. KCB-328 significantly prolonged AFL cycle length, and increasing doses progressively terminated sustained AFL and prevented its reinduction by pacing. No adverse hemodynamic or ventricular proarrhythmic effects were observed.

Conclusions: The electrophysiologic profile of KCB-328 in this canine model of AFL, particularly its lack of reverse use-dependent effect on atrial refractoriness, suggests that it may have significant antiarrhythmic potential in treatment of atrial arrhythmias.