bluuebunny/crossref_metadata_2025 huggingface dataset:
Adrenocortical Oncocytic Tumors: Report of 10 Cases and Review of the Literature
Authors: Bisceglia Michele , Ludovico Ornella , Di Mattia Antonio , Ben-Dor David , Sandbank Judith , Pasquinelli Gianandrea , Lau Sean K. , Weiss Lawrence M.
Published: March 2006

Ten additional adrenocortical oncocytic tumors are presented: 2 benign oncocytomas, 4 borderline oncocytomas of uncertain malignant potential, and 4 oncocytic carcinomas. Histologically all tumors were entirely or predominantly composed of oncocytes. Immunohistochemically all tumors were immunoreactive for mitochondrial antigen mES-13. Electron microscopy was performed in 8 cases and was confirmatory of the oncocytic cell change. The morphologic parameters of the Weiss system, considered to be predictive of the biologic behavior of conventional (nononcocytic) adrenocortical tumors, are reviewed in the context of their possible application to the oncocytic tumor variant. Proposed major criteria (high mitotic rate, atypical mitoses, venous invasion) and minor criteria (large size and huge weight, necrosis, capsular invasion, sinusoidal invasion) in distinguishing malignant tumors are discussed, and definitional criteria (predominantly cells with eosinophilic and granular cytoplasm, high nuclear grade, diffuse architectural pattern) in common with all types of oncocytic tumors are outlined. The authors’ proposed working rules for diagnostic categorization of oncocytic adrenocortical tumors are defined, with the presence of 1 major criterion indicating malignancy, 1 to 4 minor criteria indicating uncertain malignant potential (borderline), and the absence of all major and minor criteria indicative of benignancy. Using these criteria, the diagnosis of malignancy was straightforward in 3 of the 4 cases designated as oncocytic carcinoma (presence of at least 2 major criteria and all the minor criteria), while in 1 case the original diagnosis of benign oncocytoma was reversed to malignant following critical review of the original pathologic material after local tumor recurrence. Tumor recurrence occurred in 2 carcinomas at 8 and 20 months, respectively, and was followed in 1 case by the patient’s death. The third patient expired at 6 months from unrelated causes, and the fourth patient is free of disease at the relatively short follow-up interval of 6 months. Regarding the 4 patients with borderline tumors, all are alive with no evidence of disease, with follow-up ranging from 10 to 61 months (mean 38.7 months). The 2 benign tumors have a follow-up of 25 and 30 months, respectively. Diagnostic difficulties are delineated and a complete review of the literature on this topic has also been performed.
Antigen Preservation in Infarcted Nodal B-Cell Lymphoma, with Special Reference to Follicular Center Cell Markers
Authors: Kojima Masaru , Nakamura Shigeo , Yamane Yuko , Nishikawa Masafumi , Murayama Kayoko , Shimizu Kazuhiko , Itoh Hideaki , Masawa Nobuhide
Published: March 2006

Among malignant lymphoproliferative disorders, an association with lymph node infarction appeared most frequently in diffuse large B-cell lymphoma (DLBCL), followed by that in follicular lymphoma (FL). However, little is known about antigen preservation in the infarcted lymphoid tissue. FLs eventually transformed to diffuse lymphomas, comprising a significant proportion of DLBCLs. To examine the antigen preservation of the follicular center cell markers in the infarcted lymphoma, we studied 7 DLBCLs and 4 FLs diagnosed concurrently with or following lymph node infarction. Sections of viable and infarcted tissue were immunostained in parallel by using a panel of antibodies effective in routinely processed, wax-embedded tissue. The panel included L26 (CD20), 56C6 (CD10), 124 (BCL-2), and polyclonal BCL-6 antibody. The present study indicated that CD20 (91%) and CD10 (80%) antigen appear to be well preserved even in infarcted lymphoma tissues and provide useful information regarding the infarcted material. However, BCL-2 (40%) and BCL-6 (0%) antigens were of little or no value in the infarcted lymphoid tissues.
Spinal Adrenal Cortical Adenoma with Oncocytic Features: Report of the First Intramedullary Case and Review of the Literature
Authors: Cassarino David S. , Santi Mariarita , Arruda Arnaldo , Patrocinio Regia , Tsokos Maria , Ghatak Nitya , Quezado Martha
Published: March 2006

Ectopic adrenal cortical neoplasms are extremely rare, and only a few have involved the CNS. We report the first case of an intramedullary oncocytic adrenal cortical neoplasm of the spinal cord with immunohistochemical (IMHC) confirmation. A 27-year-old man presented with progressive lower extremity weakness, spastic paraparesis, decreased reflexes, and hypoesthesia below T10. A spinal myelogram showed cauda equina blockade and obliteration of sacral nerve roots. This prompted emergent surgical intervention. A well-circumscribed, approximately 3 × 2 cm, light brown to tan, intramedullary tumor was identified at the level of the conus medullaris. Histologically, the tumor showed sheets and nests of plump, cytologically bland polygonal cells with abundant eosinophilic cytoplasm. A single mitosis, but no necrosis, was identified. By IMHC, the cells were positive for inhibin, melan-A, and synaptophysin, and negative for GFAP, EMA, cytokeratins, S-100, HMB-45, and chromogranin. Electron microscopy study performed from paraffin-embedded tissues demonstrated abundant mitochondria, and lipid vacuoles. This case confirms the occurrence of adrenal cortical neoplasms in the CNS and is the first report of an intradural, intramedullary adrenal cortical adenoma of the spinal cord, and the first to occur in a male. This tumor should be considered in the differential diagnosis of tumors of the CNS.
Epstein-Barr Virus-Infected Malignant T/NK-Cell Lymphoma in a Patient with Hypersensitivity to Mosquito Bites
Authors: Kase Satoru , Adachi Hironobu , Osaki Mitsuhiko , Murakami Masanao , Sairenji Takeshi , Hashimoto Kiyoshi , Teramoto Hidemi , Yamamoto Shisei , Makino Haruhiko , Shimizu Eiji , Watanabe Tessin , Ohsawa Tokuya , Hagari Yoshitaka , Mihara Motoyuki , Ito Hisao
Published: March 2006

We report an autopsy case of Epstein-Barr virus (EBV)-infected malignant lymphoma in a young male who had hypersensitivity to mosquito bites. The autopsy revealed multiple confluent lymphoma lesions in the lungs, and on the right leg irregular-shaped skin ulcers were seen. The left pleural effusion also contained a large number of lymphoma cells. The lymphoma cells were determined as T/NK-cell type cells by immunohistochemistry. EBV DNA was detected most intensively in the lungs and EBV-encoded small RNAs-positive lymphoma cells were also observed in the lungs at a high frequency. EBV latent membrane protein-1 expression and a high Ki-67 labeling indices were noted in the lymphoma cells of the lung lesions. These findings indicate that the development of the malignant lymphoma was associated with the proliferation of EBV-infected lymphoma cells, and the cells that infiltrated the whole the body, especially the lungs, caused the patient's death.
Liposarcoma of the Colon: A Case Report
Authors: Chen Karl T. K.
Published: March 2006

A 52-year-old woman presented with abdominal pain and hematochezia. A colonoscopy showed a polypoid mass in the descending colon. A left hemicolectomy revealed a well-differentiated liposarcoma forming a polypoid intraluminal mass and an ill-defined nodule in the adjacent mesocolon. She remained well 2 years later. A review of the literature revealed only 2 reported cases of colonic liposarcoma, 1 of the myxoid type, and the other of the pleomorphic type. Two other possible cases of well-differentiated liposarcoma of the colon were uncovered from the literature.
Polymorphous Low-Grade Adenocarcinoma in the Lung: A Case Report
Authors: Lee Victor K. M. , McCaughan Brian C. , Scolyer Richard A.
Published: March 2006

Although uncommon, it is well recognized that salivary gland-type tumors can occur as primary lung tumors, probably arising from minor salivary-type glands lining the bronchial tree. Polymorphous low-grade adenocarcinoma (PLGA) is a rare tumor that usually originates from oral minor salivary glands. There are only 2 reported cases showing metastasis to the lung; however, a primary lung tumor has not been reported so far. In this report we describe the clinical and pathological features of another case of PLGA involving the lung, but in a patient with no evidence of a previous oropharyngeal primary. While our case probably represents another example of metastatic PLGA to the lung, to our knowledge, it is the first description of a PLGA involving the lung in the absence of a history of a previous primary oral salivary gland tumor.
Relationship Between Thymidylate Synthase (TS) Genotype and TS Expression: A Tissue Microarray Analysis of Colorectal Cancers
Authors: Popat Sanjay , Wort Richard , Houlston Richard S.
Published: March 2006

Response of colorectal cancers to 5-fluorouracil appears to be influenced by differences in thymidylate synthase (TS) expression. To explore the relationship between TS 5’ genotype and expression, we analyzed paired tumor and normal tissue from 87 colorectal cancers by tissue microarray. A trend to an association between TS genotype and expression was observed, but the correlation was weak. Although the 2R homozygote was preferentially associated with TS expression (p<0.03), no relationship was observed for the 3R homozygote (p=1.0). The relationship between 5’ TS genotype and TS expression is not simple. For clinical trials incorporating TS status, detection of TS expression in tumors by immunohistochemistry must still remain the benchmark over genotype.
An Improved Technique for Mitosis Counting
Authors: Gal Rivka , Rath-Wolfson Lea , Rosenblatt Yevgenia , Halpern Marisa , Schwartz Ariel , Koren Rumelia
Published: March 2006

Mitosis counting remains one of the most valuable prognostic indicators in tumor pathology; however, as currently carried out it is time consuming and not reproducible. In this study, 6 different pathologists, using different microscopes, arrived at widely different mitotic counts on the same slide, ranging from 4 to 16. These differences were mainly due to the different field areas of the various microscopes used and the method used for counting and recording. In evaluating the most active 10 HPF, the count ranged from 10 to 19. Instead, when an average of 40 fields was recorded, the range was 4-11. Using the mitosis/volume index, which expresses the number of mitotic figures per mm2 of viable tumor, the counts ranged from 8 to 10, a marked improvement. However, this method is complicated and not “user-friendly.” We suggest a variation of the technique by which a 2 mm2 rectangle is drawn on a cover slip and mounted under the microscope, centered on the most mitotically active area of the tumor. The mitoses in that area are counted (=n) and the percent of viable tumor (=x%) is estimated under low magnification. The number of mitoses per mm2 of viable tumor (cs-MAI) is then calculated according to the formula Cs-MAI=100n/2x. Using this modified method, the range of mitoses counted by the different observers was very narrow (9 to 11), and the time required for the counting was only 5-10 minutes.
Atypical Adenomatous Hyperplasia (Adenosis) of the Prostate: DNA Ploidy Analysis and Immunophenotype
Authors: Lopez-Beltran Antonio , Qian Junqi , Montironi Rodolfo , Luque Rafael J. , Bostwick David G.
Published: March 2006

Atypical adenomatous hyperplasia (AAH) of the prostate is a microscopic proliferation of small acini that may be mistaken for adenocarcinoma. Although some data suggest that AAH is associated with adenocarcinoma arising in the transition zone, the clinical significance of this lesion is uncertain. Therefore we studied the DNA ploidy pattern and immunophenotype of AAH as compared with nodular hyperplasia and well-differentiated adenocarcinoma in 23 formalin-fixed, paraffin-embedded, whole-mounted retropubic prostatectomies. Representative sections were immunostained for keratin 34β-E12, chromogranin, bcl-2, c-erbB-2, ki67-MIB1, and factor VIII (microvessel density). DNA ploidy was determined by image analysis and Feul gen-stained sections. There were rare scattered immunoreactive cells for chromogranin, bcl-2, and c-erbB-2 in nodular hyperplasia and AAH (mainly in the basal cell compartment) and in carcinoma. The ki67-MIB1 labeling index was different between nodular hyperplasia and AAH (p<0.001) and carcinoma (p=0.003) but not between AAH and carcinoma (p=0.203). Microvessel density was different between AAH and carcinoma (p=0.001) but not between nodular hyperplasia and AAH (p=0.105) or carcinoma (p=0.0820). All foci of nodular hyperplasia, AAH, and carcinoma were diploid. Ploidy status and our selected panel of antibodies did not discriminate among these 3 entities reliably.
Clinical Implication of Florid Reactive Follicular Hyperplasia in Japanese Patients 60 Years or Older: A Study of 46 Cases
Authors: Kojima Masaru , Nakamura Shigeo , Itoh Hideaki , Shimizu Kazuhiko , Murayama Kayoko , Iijima Misa , Hosomura Yasuo , Ohno Yoshihiro , Yoshida Katsue , Motoori Tadashi , Sakata Noriyuki , Masawa Nobuhide
Published: March 2006

Florid reactive follicular hyperplasia (FRFH) of the enlarged lymph node in middle-aged or elderly patients requiring biopsy is a relatively uncommon phenomenon as compared with that in younger age groups. Between 1984 and January 2004, we encountered 46 patients, aged 60 years or older, in whom histology of biopsied lymph node specimens showed inappropriate FRFH for the patient’s age. An apparent cause of lymphadenopathy was initially identified in 17 cases (37%): 11 with autoimmune disease and related disorders, 3 with cancer-reactive lymphadenopathy, 2 with Epstein-Barr virus-associated lymph node lesion exhibiting transient autoimmune-disease-like clinical findings, and 1 with atypical mycobacterial infection. Among 29 patients without specific etiology, 16 patients (55%) exhibited histologic findings of progressive transformed germinal center (PTGC). Only 1 of our patients developed malignant lymphoma during the follow-up period. The present study indicates that PTGC is included in the etiology of FRFH in elderly Japanese patients as well as imbalance of the immune system such as autoimmune-disease-associated lymphadenopathy and idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia. By in situ hybridization, Epstein-Barr virus genomes were demonstrated in only 6 (15%) of 39 cases examined.
Noninclusion-Body Infantile Digital Fibromatosis: A Lesion Heralding Terminal Osseous Dysplasia and Pigmentary Defects Syndrome
Authors: Drut Ricardo , Pedemonte Luis , Rositto Alicia
Published: March 2006

This report describes the histologic and immunohistochemical features of a peculiar type of digital fibroma that shares some clinical and microscopic features with the more common inclusion-body type infantile digital fibromatosis. However, this type does not exhibit inclusion bodies and its cells are reactive for vimentin but not for actin. Significantly, it presents in combination with a constellation of other clinical findings, i.e., mainly positional and bone abnormalities of the fingers and toes, and skin pigmentary defects. Thus, noninclusion-body digital fibromatosis may represent the first clue for the diagnosis of the so-called terminal osseous dysplasia and pigmentary defects syndrome.
So-Called “Inflammatory Leiomyosarcoma”: A Series of 3 Cases Providing Additional Insights into a Rare Entity
Authors: Chang Anthony , Schuetze Scott M. , Conrad Ernest U. , Swisshelm Karen L. , Norwood Thomas H. , Rubin Brian P.
Published: March 2006

Inflammatory leiomyosarcoma, a rare entity first described in 1995, has been characterized by smooth muscle differentiation, a near-haploid karyotype, and a surprisingly good prognosis. The morphology is similar to that of conventional leiomyosarcoma admixed with a chronic inflammatory infiltrate. Thus far, only 15 cases have been reported in the English language literature. We report the clinical and pathological features of 3 additional cases of inflammatory leiomyosarcoma. Two women (ages 64 and 25, respectively) and 1 man (age 32) presented with a thigh, ovary, and lung mass, respectively. Inflammatory symptoms, such as anorexia, fever, night sweats, abdominal pain, and diarrhea, coincided with the thigh and ovarian primaries. Immunohistochemical studies revealed diffuse positivity for desmin and poor expression for other smooth muscle and skeletal muscle markers (muscle-specific actin [0/3], α-smooth muscle actin 1/3 [focal], calponin [1/3], caldesmon [0/3], and myogenin [0/3]). CD68 was diffusely positive in both the histiocytes and spindle cell component in all cases. Ultrastructural evaluation of 1 case (lung primary) lacked definitive smooth muscle differentiation. Cytogenetic analysis in 1 of 2 cases that were karyotyped, identified a near-haploid karyotype, which has been reported in other cases of inflammatory leiomyosarcoma. The other case showed 2 clonal populations of cells with interstitial deletions of the short arm of chromosome 8 and the long arm of chromosome 9, respectively. The case without cytogenetic data was intimately associated with an ovarian mature teratoma. These data also suggest that inflammatory leiomyosarcoma may lack smooth muscle differentiation, characterized by diffuse immunoreactivity for desmin but lack of immunoreactivity for α-smooth muscle actin, calponin, and caldesmon. In addition, 2 of the 3 cases developed distant metastases to the lungs, which suggests that these lesions may have a worse prognosis than previously believed.
Tumefactive Necrobiotic Granulomas (Nodulosis) of the Pancreas in an Adult with Long-Standing Rheumatoid Arthritis
Authors: Riedlinger Wolfram F.J. , Lairmore Terry C. , Balfe Dennis M. , Dehner Louis P.
Published: March 2006

Rheumatoid nodules are well-documented clinical and pathologic lesions in patients with seropositive rheumatoid arthritis (RA). The current report documents the occurrence of rheumatoid nodulosis of the pancreas in an adult woman with a 7-year history of seropositive RA who presented with upper abdominal pain and was found to have multiple masses in the body and tail of the pancreas by imaging studies. An elevated serum pancreatic polypeptide (PP) and the development of new lesions in the pancreas prompted a subsequent distal pancreatectomy. The lesions in the pancreas proved to be necrobiotic palisading and hyalinizing granulomas upon pathologic examination. Also, of interest, elevation of serum PP has been observed in patients with RA and other systemic noninfectious and infectious inflammatory disorders in the absence of a pancreatic or intestinal neuroendocrine neoplasm.
Mesothelioma of the Tunica Vaginalis Testis: Report of 2 Cases with Asbestos Occupational Exposure
Authors: Gorini Giuseppe , Pinelli Marco , Sforza Vincenzo , Simi Umberto , Rinnovati Andrea , Zocchi Giuseppe
Published: March 2006

We report here 2 cases of malignant mesothelioma of the tunica vaginalis testis. A 67-year-old man with a left testicular mass was referred for left inguinal orchidectomy. Histologic examination showed a malignant mesothelioma of epithelial type. There is no evidence of recurrence at 2-year follow-up. The patient had been exposed to asbestos 12 years previously for a 30-year period. An 80-year-old man presented a 5-year history of scrotal swelling. Clinical examination revealed a hydrocele. The patient underwent resection of the tunica vaginalis through scrotal incision. Microscopic examination showed a malignant mesothelioma of biphasic type. There is no evidence of recurrence at 2-year follow-up. The patient had been exposed to asbestos 52 years previously for a 5-year period.
A Subset of the Follicular Variant of Papillary Thyroid Carcinoma Harbors the PAX8-PPARγ Translocation
Authors: Castro Patrícia , Roque Lúcia , Magalhães João , Sobrinho-Simões Manuel
Published: March 2006

The occurrence of the PAX8-PPARγ fusion gene is thought to be restricted to follicular tumors (adenomas and carcinomas) of the thyroid (FTA and FTC). Using interphase fluorescent in situ hybridization (FISH), together with recombinant tissue-type polymerase chain reaction (RT-PCR) and immunohistochemistry, we detected the PAX8-PPARγ translocation in 4 of 8 cases of the follicular variant of papillary thyroid carcinoma (FVPTC) exclusively or almost exclusively (>95%) composed of follicles. The 4 tumors with the translocation were larger and apparently more invasive than the remaining tumors, but the series is too small to allow a statistically meaningful comparison of the data. Our findings show that follicular thyroid carcinoma (PTC) may also harbor the PAX8-PPARγ fusion gene and indicate that a subset of FVPTC shares some molecular features of FTA and FTC.
Simultaneous Bilateral Breast Carcinomas: A Category with Frequent Coexpression of HER-2 and ER-α, High Ki-67 and bcl-2, and Low p53
Authors: Bassarova Assia V. , Nesland Jahn M. , Sedloev Theophil , Lilleby Wolfgang , Hristova Svetlana L. , Trifonov Dimitar Y. , Torlakovic Emina
Published: March 2006

The aim of this study was to evaluate clinicopathological characteristics and immunophenotypes of simultaneous bilateral adenocarcinomas of the breast and their axillary metastases. Immunohistochemical analysis and in situ hybridization were performed using formalin-fixed/paraffin-embedded tissues. In total, 15 primary and 9 metastatic tumors from 8 patients were evaluated. The expression of estrogen receptor-alpha (ER-α), progesterone receptor (PR), Ki 67, p53, bcl-2, and bax were evaluated by immunohistochemistry. Her2 gene amplification was evaluated by chromogenic in situ hybridization (CISH). Four patients were younger that 40 years of age (mean 47 years). Six patients had pleomorphic lobular carcinoma in 1 breast. Four of these had invasive ductal carcinoma in the contralateral breast. One patient had atypical medullary carcinoma in both breasts and 1 patient had atypical medullary carcinoma in 1 breast and pleomorphic lobular carcinoma in the other. The phenotype of the primary tumors and corresponding metastatic tumors was similar for the expression of ER-α (p=0.001), PR (p=0.03), and HER-2 (p=0.018). While strong coexpression of HER-2 and ER-α is exceptional in hereditary breast carcinoma and sporadic breast carcinoma, 6/8 (75%) patients in this study had tumors with strong coexpression of HER-2 and ER-α. P53 protein expression was found in only 2/15 (13%) primary tumors, which is in contrast to BRCA1-related hereditary bilateral breast carcinomas, which often express p53 protein. Most of the patients presented with axillary metastases and had very aggressive course. Characteristically, the tumors showed high levels of expression of ER-α and Her2 amplification, were bcl-2 positive, and had high Ki-67 fraction. However, in patients with atypical medullary carcinoma there was no expression of ER-α or amplification of Her-2.
The Fast-Track Biopsy (FTB): Description of a Rapid Histology and Immunohistochemistry Method for Evaluation of Preoperative Breast Core Biopsies
Authors: Ragazzini Teresa , Magrini Elisabetta , Cucchi Maria C. , Foschini Maria P. , Eusebi V.
Published: March 2006

Thirty-six core breast biopsies from 32 patients were paraffin embedded by use of an automated microwave processor. In addition, a quick immunohistochemical method was used in selected cases. The quality of the hematoxylin and eosin (H&E) slides was very satisfactory, as were also the immunohistochemical stains for ER, PR, and Ki67 when compared to those obtained with the use of a conventional automated immunostainer. The time required to process the tissue to the final H&E stage averaged 2 hours 52 minutes, and the immunohistochemical method required 90 to 100 minutes. This procedure, which we named “fast-track biopsy” (FTB), is quick enough to be competitive with FNAC (fine-needle aspiration biopsy) in terms of turnaroundtimes. The superiority of core biopsy over FNA in terms of the morphologic information provided is widely acknowledged, the only major argument currently mentioned in favor of FNAC being the shorter duration of the procedure. With the advent of FTB, it would appear that even this last remaining advantage has been erased.
Identification of Mislabeled Specimen by Molecular Methods: Case Report and Review
Authors: Mariappan M. Rajan , Zehnder James , Arber Daniel A. , Lay Marla , Fadare Oluwole , Schrijver Iris
Published: March 2006

Specimen misidentification is a common cause of errors in surgical pathology. We report a case where bone-marrow biopsies from patients of different genders were mislabeled and molecular methods were applied to resolve the identity. A short tandem repeat (STR)-polymerase chain reaction-based assay, commonly used in paternity testing, was employed in an attempt to assign the correct identity to the specimens. However, the specimens had been processed by decalcification and the DNA yield was poor. One of the markers in the assay is the non-STR amelogenin locus that distinguishes the X and Y chromosomes. This amelogenin marker results in a product of low molecular weight, enabling unequivocal resolution of identity despite a poor DNA yield. The prevalence of errors in pathology due to specimen misidentifications is reviewed.
Comparative Histologic Assessment of Proctocolectomy Specimens from Japanese and American Patients with Ulcerative Colitis with or Without Dysplasia
Authors: Mitomi Hiroyuki , Okayasu Isao , Bronner Mary P. , Kanazawa Hideki , Nishiyama Yasuhiko , Otani Yoshimasa , Sada Miwa , Tanabe Satoshi , Igarashi Masahiro , Katsumata Tomoe , Saigenji Katsunori
Published: March 2006

There have been no reports of histologic differences in ulcerative colitis (UC) between Japanese and American patients. We therefore compared histology in proctocolectomy resection specimens between Japanese patients with UC (19 cases with and 21 without dysplasia) at the Kitasato University East Hospital and American patients with UC (21 cases with and 24 without dysplasia) at the University of Washington Medical Center. In cases of UC with, but not without dysplasia, cryptitis (p = 0.010) and epithelial apoptosis (p < 0.001) in the nondysplastic mucosa were more frequently observed in Japanese than in American cases, whereas lamina propria fibrosis was more prominent in American counterparts (p = 0.008). In patients with UC with dysplasia, the duration of disease was significantly longer in American than in Japanese patients (median, 17 vs 14 years, respectively; p = 0.038). This might, in part, explain the histologic variation. Another possibility for the differences is that the preoperative medications may have differed in the populations.
Reactive Lymphoid Hyperplasia of the Lymph Nodes with Giant Follicles: A Clinicopathologic Study of 14 Japanese Cases, with Special Reference to Epstein-Barr Virus Infection
Authors: Kojima Masaru , Nakamura Shigeo , Shimizu Kazuhiko , Iijima Misa , Murayama Kayoko , Ohno Yoshihiro , Itoh Hideaki , Sakata Noriyuki , Masawa Nobuhide
Published: March 2006

To clarify the clinicopathologic and immunohistochemical features of reactive lymphoid hyperplasia with giant follicles (RHGF) among Japanese, 14 patients were studied. The subjects consisted of 9 males and 5 females, ranging in age from 9 to 61 years, with a mean age of 30 years and a median age of 24 years. None of the patients exhibited systemic symptoms. The affected lymph nodes were located in the head and neck area except in 1 case. At the time of lymph node biopsy, 1 patient was diagnosed as having acute infectious mononucleosis (IM) and 2 patients had a recent history of acute IM. One each with myelogenous leukemia or diffuse large B-cell lymphoma had a history of peripheral blood stem cell transplantation. There were no recurrences during follow-up periods ranging from 3 to 50 months. Histologically, 14 lesions were characterized by numerous enlarged, coalescing lymphoid follicles with distortion rather than effacement of the lymph node architecture. By in situ hybridization, Epstein-Barr virus (EBV) genomes were demonstrated in 5 (36%) of 14 cases. The present study indicates that a portion of RHGF appears to represent a histologic finding of acute IM. Moreover, as previously stated, RHGF should be differentiated from follicular lymphoma, particularly the floral variant.
Distribution of Epstein-Barr Virus in Systemic Rheumatic Disease (Rheumatoid Arthritis, Systemic Lupus Erythematosus, Dermatomyositis) With Associated Lymphadenopathy: A Study of 49 Cases
Authors: Kojima Masaru , Motoori Tadashi , Itoh Hideaki , Shimizu Kazuhiko , Iijima Misa , Tamaki Yoshio , Murayama Kayoko , Ohno Yoshihiro , Yoshida Katsue , Masawa Nobuhide , Nakamura Shigeo
Published: March 2006

Among systemic rheumatic diseases (SRDs), lymphadenopathy is frequently found in patients with rheumatoid arthritis (RA) and systemic lupus erythematous (SLE). Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPDs) may occur in patients following methotrexate therapy for RA and dermatomyositis (DM). However, little is known about the distribution of EBV in reactive LPDs in patients with SRDs who had no history of methotrexate therapy. We analyzed 49 such patients (SLE=25, RA=23, DM=1) for the presence and distribution of EBV+ cells using Epstein-Barr virus (EBV)-encoded small RNA (EBER) specific in situ hybridization. A positive signal for EBERs was identified in 9 (SLE=5, RA=4) (18%) of 49 cases, and 3 main distribution patterns of EBER+ cells could be delineated: pattern A, more than 500 EBER-positive cells were located in the germinal centers as well as interfollicular area (SLE=2); pattern B, EBER + cells were located in a few germinal centers (RA=2); and pattern C, up to 100 EBER+ cells were located in the interfollicular area (SLE=3, RA=2). Recent EBV infection may be a cause of lymph node lesion in only 2 cases of patients with pattern A. However, the pathognomonic significance of pattern B and pattern C EBER+ cell distribution patterns still remains unclear. Our study indicates that the underlying immune deficits of patients with SRDs may also play an important role in the development of EBV-associated LPDs in SRDs, as previously suggested by several authors.
Regressed Cutaneous Malignant Melanoma Mimicking Lymphoma: A Potential Diagnostic Pitfall
Authors: Menasce L. P. , Shanks J. H. , Howarth V. S. , Banerjee S. S.
Published: March 2006

We report 2 cases of partially regressed malignant melanoma in which the brisk lymphocytic response closely resembled mycosis fungoides in 1 case and nodular sclerosing Hodgkin lymphoma in the other. Striking epidermotropism was present in both cases. The lymphocytes were predominantly of T8 cytotoxic subtype, and oligoclonal T-cell expansion was detected in 1 of the cases. The scanty residual melanoma cells were highlighted with HMB45 and S100 protein. We highlight the features of regression in melanoma that may lead to an erroneous diagnosis of lymphoma and discuss the finding of oligoclonal T-cell expansion in regressed melanocytic lesions.
Pigmented Mucoepidermoid Carcinoma of the Oral Cavity: A Case Report
Authors: Marucci Gianluca , Marchetti Claudio , Betts Christine M. , Foschini Maria P.
Published: March 2006

Melanocytes are normally present in the oral mucosa, but unlike the skin, melanocytic colonization and pigmentation of nonmelanocytic tumors rarely occur. A case of pigmented mucoepidermoid carcinoma (MEC) in a 36-year-old woman is reported. On H&E-stained sections, brownish granules were seen in intermediate and epidermoid neoplastic elements and in elongated or dendritic cells showing histologic and immunohistochemical features of melanocytes. Ultrastructurally numerous epithelial cells contained large aggregates of melanin granules, a feature suggestive of phagocytosis. In addition small individual melanin granules were observed at the external border of the epithelial cell membrane. These features suggest that melanocytes colonized the MEC and that neoplastic cells may phagocytose the granules, similarly to what occurs with epidermal melanocytes. The phenomenon of melanocyte colonization of nonmelanocytic tumors should be taken into consideration in dealing with pigmented lesions of the oral cavity.
Remarkably High Frequency of EGFR Expression in Breast Carcinomas with Squamous Differentiation
Authors: Bossuyt V. , Fadare O. , Martel M. , Ocal I. T. , Burtness B. , Moinfar F. , Leibl S. , Tavassoli F. A.
Published: March 2006

The human epidermal growth factor receptor (EGFR) is reportedly overexpressed in 15-20% of breast carcinomas. EGFR overexpression is associated with reduced survival and is inversely correlated with expression of estrogen receptor (ER). This study assessed EGFR expression in breast carcinomas with squamous differentiation. The immunohistochemical (IHC) expression of EGFR was evaluated in 39 breast carcinomas with squamous differentiation (30 pure squamous, 6 adenosquamous, 3 carcinosarcomas) by use of the pharmDx assay (clone 2-18C9, DakoCytomation®). Cases were considered positive if at least 10% of the cells showed 1+ positivity in the squamous component. Squamous differentiation was confirmed with IHC for CK5-6 (clone D5/16B4, DakoCytomation®). ER, PR, and HER2 status as well as clinical information regarding treatment and outcome were correlated. As a control, a tissue microarray comprising 280 lymph node positive breast carcinomas was evaluated with the same EGFR assay. The 39 patients ranged in age from 33 to 77 years (mean 52). The tumors measured 1.3-30 cm (mean 4.8). Sentinel or full axillary lymph node dissection was performed in 28 patients. Fourteen patients had positive lymph nodes. At the time of initial diagnosis, 3 patients had distant metastasis. Follow-up was available for 16 patients (mean 45 months). Disease-free survival at 3 years was 70%. Among the 39 tumors 87% (34) were positive for EGFR (p<0.0001). Sixty-nine percent (27 of 39) showed >50% 2+ EGFR staining. EGFR-positive tumor cells (showing squamous morphology) were also found in 1 bone, 1 lung, and 8 of 11 lymph node metastases available for evaluation. All 11 lymph nodes showed squamous differentiation. All but 1 of the EGFR+ tumors examined were ER and PR negative. Six EGFR-positive tumors were HER2 positive. No statistically significant differences in HER2 status, size, lymph node status and disease-free survival were observed between EGFR+ and EGFR-cases, but the number of EGFR-negative tumors was quite small. Nine of 280 (3%) of lymph node-positive invasive carcinomas on the tissue microarray were EGFR+; review of the initial diagnostic slides failed to reveal squamous features in all but 1 of the 9 EGFR+ tumors. Breast carcinomas with squamous differentiation are a distinct subgroup of breast tumors with a very high frequency of EGFR positivity. Breast carcinomas of this type would be ideal candidates for a trial with EGFR inhibitors.
p63 Expression in Salivary Gland Tumors: Role ofΔNp73L in Neoplastic Transformation
Authors: Foschini Maria P. , Gaiba Alessia , Cocchi Roberto , Pennesi Maria G. , Pession Annalisa
Published: March 2006

To illustrate the role of p63 and its truncated variants in salivary gland tumors, 23 consecutive tumors and 6 normal salivary glands were studied immunohistochemically with anti-p63 antibody and by reverse transcriptase (RT) and nested polymerase chain reaction (PCR) to detect p63 isoform expression. Normal salivary glands: p63 antibody-stained basal and myoepithelial cells; by RT and nested PCR, the 2 main isoforms were present, whereas ΔNp73L was absent. Tumors: p63 antibody was positive in the following: Warthin tumor (WT) (3/3), oncocytoma (OC) (1/1), pleomorphic adenoma (PA) (7/7), polymorphous-low-grade adenocarcinoma (PLGA) (3/3), adenoid-cystic carcinoma (ADCC)(3/4), epithelial-myoepithelial-cell carcinoma (EMC) (1/1), and myoepithelial-cell carcinoma (MCC) (1/1). By RT and nested PCR all tumors expressed p63 irrespective of their morphologic differentiation. The ΔNp73L isoform was present in tumoral tissue but absent in normal salivary gland. These data suggest that p63, particularly its splice variant ΔNp73L, is involved in the neoplastic transformation of salivary glands.
Osteoblastoma of the Larynx: A Case Report
Authors: Ledeboer Quirine C.P. , Kerrebijn Jeroen D.F. , Govaere Fabienne , den Bakker Michael A.
Published: March 2006

We describe a unique case of an osteoblastoma in the cricoid cartilage of a 50-year-old man who presented with hoarseness and progressive dyspnea. Panendoscopic examination revealed a reddish tumor at the left side of the cricoid cartilage. Computed tomography (CT) imaging showed a sclerotic lesion involving the cricoid cartilage, protruding in the airway lumen. The tumor was removed via an external procedure. Histology confirmed the diagnosis of osteoblastoma.
Anaplastic Large Cell Lymphoma: A Unique Presentation with Urinary Bladder Involvement
Authors: Murphy Amanda J. , O’Neill Paul , O’Brien Frank , Enright Helen , Jeffers Michael , Thornhill John A. , Loftus Barbara M.
Published: March 2006

Anaplastic large cell lymphoma (ALCL) is a T-cell lymphoma composed of large pleomorphic CD30-positive cells. While systemic ALCL frequently involves extranodal sites, involvement of the urinary bladder is extremely rare. We report a case of systemic ALCL presenting with bladder involvement. A 28-year-old man presented with hematuria, dysuria, and lower abdominal pain. Imaging revealed pelvic lymphadenopathy and a thickened bladder wall. Bladder biopsies showed diffuse infiltration of the lamina propria by large pleomorphic cells, with preservation of the overlying urothelium. Immunohistochemistry demonstrated cell membrane and Golgi region staining for CD30 and epithelial membrane antigen. This is the first documented instance of systemic ALCL presenting with bladder symptoms.
Urothelial Signet-Ring Cell Carcinoma of the Renal Pelvis with Collagenous Spherulosis: A Case Report
Authors: Hes Ondřej , Čuřík Romuald , Mainer Karel , Michal Michal
Published: March 2006

We present a unique case of urothelial carcinoma of the right renal pelvis. It occurred in a 58-year-old woman. The tumor was located in the renal pelvis with extension into the adjacent renal medulla and cortex. Two years after surgical excision the patient is free of recurrence and metastasis. The tumor was well demarcated, without capsule, firm, solid, and whitish on the cut surface. It was 3 × 4 cm in largest diameter and without signs of necroses and hemorrhages. The tumor did not infiltrate the ureter. Histologically the predominant pattern of the tumor was adenocarcinomatous differentiation, and only very rare foci of urothelial carcinoma composed of typical transitional cells were found. No signs of intestinal type of metaplasia and adenocarcinoma, changes similar to the cystitis cystica or cystitis glandularis, were found in the tumor or in its vicinity. Most of the tumor looked like solid nests composed of cells with intracytoplasmic lumens. The resulting appearance was that of typical signetring cell change. These solid nests were usually surrounded by columnar epithelium, which in many areas formed papillary structures. A very striking feature was formation of collagen spherules. Small collagen spherules were often surrounded by a layer of the neoplastic cells so that collagenous rosettes were formed. In some areas these collagenous spherules clustered together so that they formed areas of collagenous spherulosis. The collagen in the spherules reacted positively with collagen IV. Ultrastructurally these spherules were formed by basal membrane-like material. Intracytoplasmic lumens of the signet-ring cell change were endowed by slender microvilli at ultrastructural level.
Tracking Progression of Heart Disease with Cardiac Computed Tomography
Authors: Budoff Matthew J.
Published: March 2006

The ability to follow changes in atherosclerotic plaque burden over time should provide an accurate measure of efficacy for different cardiovascular therapies. Coronary calcifications are associated with atherosclerotic coronary artery plaque, and the amount of coronary calcifications has been shown to correlate with the overall coronary plaque burden. The presence and extent of coronary calcifications can be assessed noninvasively by monitoring the progression of coronary calcification with electron beam tomography. With annual progression rates of 22% to 52% and a median interscan variability of only 5% to 8%, this technology provides an opportunity to monitor patients to assess the clinical efficacy of medical therapies in studies as short as 1 year. Several studies have demonstrated that the successful pharmacologic reduction of low-density lipoprotein cholesterol significantly mitigated the progression of the calcium score. Studies using serial computed tomographic scans indicate that the annual progression of coronary calcium varies between 30% and 50% in symptomatic or high-risk individuals and from 0% to 20% in patients treated effectively with lipid-lowering medication. An increased rate of progression of coronary calcium seems to indicate a substantially increased risk for adverse cardiac events, suggesting that this modality can be used to monitor the efficacy of therapy.
Metabolic Mechanism by Which Mild Regional Hypothermia Preserves Ischemic Tissue
Authors: Simkhovich Boris Z. , Hale Sharon L. , Kloner Robert A.
Published: March 2006

Background: Our laboratory demonstrated that mild regional hypothermia reduced myocardial infarct size by an average of 65% in the rabbit model of regional ischemia. The exact mechanism for this benefit has not been explored. We hypothesized that a moderate reduction in regional myocardial temperature could preserve cardiac energy metabolism and thus protect the myocardium from sustained ischemic insult.

Methods and Results: Anesthetized open-chest rabbits were randomized to normothermic sham-operated (NS, n = 6), hypothermic sham-operated (HS, n = 6), normothermic ischemic (NI, n = 10), and hypothermic ischemic (HI, n = 10) groups. Both sham-operated groups received no occlusions, and both ischemic groups were subjected to 20 minutes of coronary occlusion. To achieve regional cooling of the hearts in the hypothermic groups, a bag of ice water was placed directly on the risk area 15 minutes prior to coronary artery occlusion/no intervention and maintained for the duration of the subsequent 20 minutes of ischemia/no intervention (in the HI and HS groups respectively). Hypothermia preserved adenosine triphosphate (ATP) and glycogen stores in the ischemic area by 42.9% and 84.2%, respectively (1.20 ± 0.11 µmoles ATP/g wet tissue vs 0.84 ± 0.06 µmoles ATP/g wet tissue and 8.16 ± 0.95 µmoles of glucosyl unit/g wet tissue vs 4.43 ± 0.44 µmoles of glucosyl unit/g wet tissue in the HI and the NI groups, respectively). In addition, hypothermia resulted in a trend toward creatine phosphate preservation in the nonischemic area.

Conclusions: This is the first demonstration that local therapy with mild reductions in myocardial temperature preserves energy metabolism both in the ischemic and the nonischemic areas as well. The preservation in ATP is the likely mechanism by which regional hypothermia is preserving ischemic myocardium.
Effects of Antihypertensive and Hypolipidemic Drugs on Plasma and High-Density Lipoprotein-Associated Platelet Activating Factor-Acetylhydrolase Activity
Authors: Tambaki Afroditi P. , Rizos Evangelos , Tsimihodimos Vasilis , Tselepis Alexandros D. , Elisaf Moses
Published: March 2006

Background: Human plasma platelet activating factor acetylhydrolase (PAF-AH) is a phospholipase A2 primarily associated with low-density lipoprotein (LDL). PAF-AH activity has also been found on high-density lipoprotein (HDL). Most of the clinical studies that have investigated the plasma levels of PAF-AH activity in cardiovascular disease have involved patients who were under treatment with various drugs, such as antihypertensive or hypolipidemic agents. However, the influence of these drugs on the enzyme activity has not been adequately studied.

Material and Methods: We evaluated the effects of representative antihypertensive and hypolipidemic drugs on the total plasma, as well as on the HDL-associated PAF-AH activity, in 121 patients with essential hypertension and in 90 patients with dyslipidemias of type IIA or type IIB. Serum lipids and enzymatic activities were determined at baseline and after 3 months of treatment.

Results: The administration of lacidipine (4 mg, n = 21), valsartan (80 mg, n = 26), indapamide (2.5 mg, n = 20), benazepril (20 mg, n = 20), or atenolol (50 mg, n = 34) did not affect either the total plasma- or the HDL-associated PAF-AH activity. In contrast, treatment with fluvastatin (40 mg, n = 50) or ciprofibrate (100 mg, n = 40) reduced by 25% plasma PAF-AH activity ( P < .001) associated with a decrease in serum levels of total cholesterol and LDL-cholesterol ( P < .001). Furthermore, ciprofibrate induced an increase by 26% in HDL-associated PAF-AH activity ( P = .004) along with an increase in serum HDL-cholesterol levels ( P = .02).

Conclusions: Among all types of drugs studied, only those that significantly affect lipid metabolism, such as statins and fibrates, significantly influence PAF-AH activity in human plasma.
Anticoagulation in Pregnant Women With Prosthetic Heart Valves
Authors: Elkayam Uri , Singh Harpreet , Irani Adil , Akhter Mohammed W.
Published: March 2006

Background: Pregnancy is associated with an increased risk of thrombosis in women with mechanical prosthetic heart valves. Effective anticoagulation is therefore critical in such patients but remains problematic, since oral anticoagulation and both unfractionated and low-molecular-weight heparin may be associated with important fetal and maternal side effects.

Purpose: To review information related to the use of anticoagulation with both warfarin and heparin and reassess the safety and efficacy of these therapies in pregnant women with mechanical prosthetic heart valves.

Data source and selection: A MEDLINE search from 1966 to October 2003 for English and non-English language articles that reported the use of anticoagulation in pregnancy was conducted. Articles were included if they reported use of anticoagulation in pregnancy with emphasis on those that included women with mechanical prosthetic heart valves.

Conclusions: Anticoagulation prophylaxis with both warfarin and heparin (unfractionated heparin and low-molecular-weight heparin) may be associated with important fetal and maternal side effects. Optional regimens for the treatment of low-risk and high-risk patients are proposed to minimize potential complications.
Current Perspectives of Electrical Remodeling and Its Therapeutic Implications
Authors: Wasson Sanjeev , Reddy H. K. , Dohrmann Mary L.
Published: March 2006

Electrical remodeling involves alterations in the electrophysiologic milieu of myocardium in various disease states, such as ventricular hypertrophy, heart failure, atrial tachyarrhythmias, myocardial ischemia, and infarction that are associated with cardiac arrhythmias. Although research in this area dates back to early part of the 19th century, we still lack the exact knowledge of ionic remodeling, the role of various genes and channel proteins, and their relevance for the newer antiarrhythmic therapies. Structural remodeling may also have an impact on the electrical remodeling process, although differences in both structural and electrical remodeling are associated with different disease states. Various electrophysiologic, cellular, and structural alterations, including anisotropic conduction, increased intracellular calcium levels, and gap junction remodeling predispose to increased dispersion of action potential duration and refractoriness. This constitutes a favorable substrate for early and late afterdepolarizations and reentrant arrhythmias. Studying the role of ionic remodeling in the initiation and propagation of cardiac arrhythmias has significant relevance for developing newer antiarrhythmic therapies, for identifying patients at risk of developing fatal arrhythmias, and for implementing effective preventive measures. Further research is required to understand the specific effects of individual ion channel remodeling, to understand the signal transduction mechanisms, and to address whether detrimental effects of electrical remodeling can be altered.