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The majority of salivary gland lesions arise in the major glands, especially the parotid, and are most often benign tumors such as pleomorphic adenoma (PA) and Warthin tumor (WT). (1,2) [...], * Context.-Fine-needle aspiration (FNA) is a well-established procedure for the diagnosis and management of salivary gland lesions, despite challenges imposed by salivary gland tumor diversity, complexity, and cytomorphologic overlap. Until recently, the reporting of salivary gland FNA specimens was inconsistent among different institutions throughout the world, leading to diagnostic confusion among pathologists and clinicians. In 2015, an international group of pathologists initiated the development of an evidence-based tiered classification system for reporting salivary gland FNA specimens, the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC). The MSRSGC consists of 6 diagnostic categories, which incorporate the morphologic heterogeneity and overlap among various nonneoplastic, benign, and malignant lesions of the salivary glands. In addition, each MSRSGC diagnostic category is associated with a risk of malignancy and management recommendations. Objective.-To review the current status of salivary gland FNA, core needle biopsies, ancillary studies, and the beneficial role of the MSRSGC in providing a framework for reporting salivary gland lesions and guiding clinical management. Data Sources.-Literature review and personal institutional experience. Conclusions.-The main goal of the MSRSGC is to improve communication between cytopathologists and treating clinicians, while also facilitating cytologic-histologic correlation, quality improvement, and research. Since its implementation, the MSRSGC has gained international acceptance as a tool to improve reporting standards and consistency in this complex diagnostic area, and it has been endorsed by the 2021 American Society of Clinical Oncology management guidelines for salivary gland cancer. The large amount of data from published studies using MSRSGC served as a basis for the recent update of the MSRSGC. (Arch Pathol Lab Med. 2024;148:1092-1104; doi: 10.5858/arpa.2022-0529-RA)

A shared language and framework of understanding are central components to the effective and safe practice of medicine. Although cytopathology shares some of the same language as histopathology, cytopathology specimens [...], * Context.--In recent years, several reporting systems have been developed by national and international cytopathology organizations to standardize the evaluation of specific cytopathology specimen types. Objective.--To assess the current implementation rates, implementation methods, and barriers to implementation of commonly used nongynecologic reporting systems in cytopathology laboratories. Design.--Data were analyzed from a survey developed by the College of American Pathologists Cytopathology Committee and distributed to participants in the College of American Pathologists Nongynecologic Cytopathology Education Program mailing. Results.--Nongynecologic reporting systems with the highest rate of adoption were the Bethesda System for Reporting Thyroid Cytopathology, 2nd edition (74.1%; 552 of 745); the Paris System for Reporting Urinary Cytology (53.9%; 397 of 736); and the Milan System for Reporting Salivary Gland Cytopathology (29.1%; 200 of 688). The most common reason given for not adopting a reporting system was satisfaction with a laboratory's current system. Implementation varied among laboratories with regard to which stakeholders were involved in deciding to implement a system and the amount of education provided during the implementation process. Conclusions.--The implementation of nongynecologic reporting systems in cytopathology laboratories was highly variable.

Malignant mesothelioma (MM) is mechanistically linked to previous asbestos exposure, (1,2) and it develops several decades after the initial exposure to asbestos fibers. Despite a ban on asbestos in Western [...], Context.--Early diagnosis of malignant mesothelioma (MM) is urgently needed because life expectancies and treatment options are limited in advanced stages of the disease. Malignant mesothelioma often presents with recurrent hemorrhagic or inflammatory effusions, which might mask the incipient stages of the disease and thereby delay the diagnosis. Despite difficulties in recognizing the malignant cells present in those early effusions, they are often the first available biologic material for diagnosis. Therefore, awareness is needed, and efforts should be made to distinguish the malignant cells by well-defined morphological criteria, combined with ancillary methods. Objectives.--To summarize the diagnostic criteria for the cytopathologic diagnosis of MM based on recently published guidelines and to evaluate the clinical utility of those criteria in clinical practice. Data Sources.--The guidelines for the cytopathologic diagnosis of epithelioid and mixed-type MM and data in recent literature constitute the sources of this review. Eighty-five epithelioid or mixed-type MMs diagnosed between 2004 and 2013 at the Department of Clinical Pathology and Cytology, Karolinska University Hospital, Huddinge (Stockholm, Sweden), were evaluated to determine the clinical utility of the criteria defined by the guidelines. Conclusions.--A conclusive diagnosis of MM can be obtained based on the criteria defined by the guidelines with high positive predictive value. When diagnosed in this way, subsequent therapy should be initiated without further delay. With the earlier diagnosis obtained by cytology, a better effect of chemotherapy can be expected, as shown by the longer overall survival in these patients compared with those with a histopathologic diagnosis. doi: 10.5858/arpa.2018-0020-RA

Mitochondrial Cytopathies Mitochondrial cytopathies are a diverse group of inherited and acquired disorders that result in inadequate energy production. They can be caused by inheritable genetic mutations, acquired somatic mutations, [...]

This special section on diagnostic immunohistochemistry (IHC) consists of a series of 10 articles from the first Chinese American Pathologists Association (CAPA) diagnostic pathology course, Best Practices in Immunohistochemistry in [...]

Accumulating evidence indicates that human herpesvirus 8 (HHV-8) is the infectious agent responsible for Kaposi's sarcoma in patients with and without HIV infection[1]. Several viral proteins with homologous human counterparts [...], Kaposi's sarcoma-associated herpesvirus encodes a chemokine called vMIP-II. This protein displayed a broader spectrum of receptor activities than any mammalian chemokine as it bound with high affinity to a number of both CC and CXC chemokine receptors. Binding of vMIP-II, however, was not associated with the normal, rapid mobilization of calcium from intracellular stores; instead, it blocked calcium mobilization induced by endogenous chemokines. In freshly isolated human monocytes the virally encoded vMIP-II acted as a potent and efficient antagonist of chemotaxis induced by chemokines. Because vMIP-II could inhibit cell entry of human immunodeficiency virus (HIV) mediated through CCR3 and CCR5 as well as CXCR4, this protein may serve as a lead for development of broad-spectrum anti-HIV agents.

The human met proto-oncogene product (Met), a member of the family of tyrosine kinase growth factor receptors, was identified by means of the activated oncogene tpr-met[1, 2]. Met is synthesized [...], The met proto-oncogene product (Met) and its ligand, hepatocyte growth factor/scatter factor (HGF/SF), have been implicated in cell mitogenic response, cell motility, and the promotion of the ordered spatial arrangement of tissue. By means of confocal laserscanning microscopy, it was shown that Met is expressed in cells bordering lumen-like structures that resemble ducts in the human mammary cell line T47D. In human breast tissue biopsies. Met staining was intense in normal cells bordering mammary ducts but was reduced in adjacent tumor tissue. Met staining in lumen-forming organs colocalizes with staining of antibody to phosphotyrosine, which suggests that the Met receptor and its substrates may be activated in lumen structures or ducts. HGF/SF treatment of human epithelial carcinoma cell lines resulted in the formation of lumen-like structures in vitro. Reduced expression on Met could be related to the extent of tumor cell differentiation.

Protein tyrosine phosphorylation is a common mechanism of signaling in pathways that regulate T cell receptor-mediated cell activation, cell proliferation, and the cell cycle. Because human immunodeficiency virus (HIV) is [...]

The College of American Pathologists (CAP) has conducted regular questionnaire surveys assessing cervical cytology laboratory practices since the inception of the Interlaboratory Comparison Program in Cervicovaginal Cytology. (1-5) These surveys [...], * Context.--Liquid-based preparations (LBPs) and human papillomavirus testing have led to changes in cervical cytology practices. The College of American Pathologists attempts to track practice patterns using a supplemental questionnaire, which allows laboratories to report diagnostic practices. Objective.--To analyze the 2006 reporting practices and to compare the results with the 2003 survey data. Design.--Questionnaire was mailed to 1621 laboratories. Participants included laboratories enrolled in the 2006 College of American Pathologists Gynecologic Proficiency Testing Program or the educational Interlaboratory Comparison Program in Gynecologic Cytology. Results.--Of the 679 responding laboratories (response rate, 42%), most (97.8%; n = 664) had implemented the Bethesda 2001 terminology. The median rate for all preparations with low-grade squamous intraepithelial lesions was 2.5% (2.9% for LBPs) compared with a 2003 median rate of 2.1%; the increase was confined to LBPs. Rates for high-grade squamous intraepithelial lesions (median, 0.5%) and atypical squamous cells have changed little. High-grade squamous intraepithelial lesions and unsatisfactory rates varied at statistically significant levels between types of LBPs. Most atypical squamous cell cases were subclassified as undetermined significance (median, 4.3%). The median ratio of atypical squamous cells to squamous intraepithelial lesions and carcinomas for all specimen types combined was 1.5, similar to the 2003 median ratio of 1.4. The median rates for findings of squamous cell abnormalities for 2006 were significantly higher for LBPs than for conventional smears. Conclusions.--Most responding laboratories have implemented the Bethesda 2001 terminology. There is an increase in LBP low-grade squamous intraepithelial lesion rates when compared with 2003 data. Liquid-based preparations have higher median squamous intraepithelial lesion and atypical squamous cell rates. (Arch Pathol Lab Med. 2010; 134:331-335)

Herpes simplex virus (HSV) is a common sexually transmitted disease that may induce cytologic changes identifiable on Papanicolaou tests. The cellular changes of HSV include large multinucleated or mononuclear epithelial [...], Context.--Herpes simplex virus (HSV) is a common sexually transmitted disease that is decreasing in prevalence. Herpes simplex virus challenge cases have performed well in the educational College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology. However, since gynecologic cytology proficiency testing (PT) was instituted, performance of HSV challenge cases has worsened. Objective.--To determine if the decrease in performance for HSV challenges is due to inexperience in identifying herpes virus or "gaming" of PT. Design.--We compare graded (field-validated) and ungraded (educational) slides with HSV prior to PT (1991-2005) and after PT (2006 and 2007) in an attempt to characterize changes in performance of slides demonstrating purely HSV cellular features. All HSV slides were negative for intraepithelial lesion with the specific reference interpretation of HSV. Slides were excluded from analysis if they Results.--A total of 40 634 HSV responses were evaluated. A significant difference existed in the diagnosis of HSV in PT compared with graded challenges prior to PT (96.6 versus 98.6; P < .001). No difference was seen in educational challenges pre-PT and post-PT (P = .14). No difference was present between slide preparation type; however, a difference was seen between cytotechnologist and pathologist response. Conclusions.--There is a change in the performance of slide challenges demonstrating the cellular features of HSV in PT, most likely due to testing strategies of participants, rather than lack of recognition of HSV secondary to decreased prevalence. (Arch Pathol Lab Med. 2009;133:1379-1382)

The relationship between ovarian mucinous and transitional cell neoplasms is enigmatic. Occasional mucinous cystadenomas contain a relatively small nodule of Brenner (transitional cell) tumor, with a reported incidence of about [...], * Context.--The origin of and relationship between ovarian mucinous and transitional cell (Brenner) neoplasms are enigmatic. The reported association ranges from 1% to 16%, and whether there is an association with Walthard cell nests is unknown. Objective.--To clarify the histologic relationship between mucinous and Brenner tumors. Design.--A total of 40 mucinous cystadenomas, 67 Brenner tumors, and 13 combined tumors were studied. Peritoneal surfaces were examined for Walthard nests in 83 patients compared with 272 controls. Results.--A total of 25% of tumors with a mucinous component contained a Brenner component, and 16% of tumors with a Brenner component contained a mucinous component. Most calcifications were spiculated (nonpsammomatous). In 6 combined tumors, the relative volume of the 2 components was less than 1:3000 (transitional-mucinous). Walthard nests were found in 50% of patients with Brenner tumors and 59% of patients with mucinous tumors. This was significantly higher than the 28% found in controls (P = .002 and P < .001, respectively). The number of fallopian tube blocks examined was correlated with the likelihood of finding Walthard nests, and accordingly, sampling accounted for 39% of the increase with Brenner tumors but strengthened the association with mucinous tumors. Conclusions.--The strong association of mucinous and transitional cell components, similar type of calcification, complementary size distributions, and frequent identification of a transitional component in the face of an exceedingly small estimated proportion of that component suggest that this association has been underestimated. The association of Brenner tumors with Walthard nests, although significant, appears weak and not strongly supportive of a histogenetic relationship. The stronger association of Walthard nests with mucinous tumors remains unexplained.

Prostatic stromal hyperplasia with atypia (PSHA) is a rare lesion that can be mistaken for sarcoma because of the presence of bizarre, degenerative myocyte nuclei. (1-10) The nuclear abnormalities are [...], * Context.--Prostatic stromal hyperplasia with atypia is a rare lesion that can be mistaken for sarcoma because of the presence of atypical, bizarre, degenerative myocyte nuclei. Objective.--To determine the diagnostic criteria and clinical significance of prostatic stromal hyperplasia with atypia. Design.--Eighteen cases of prostatic stromal hyperplasia with atypia were reviewed from the consultation file of one of the authors (D.G.B.). Results.--Prostatic stromal hyperplasia with atypia consists of 1 or more ill-defined, uncircumscribed, hyperplastic stromal nodules, with variable numbers of atypical, bizarre giant cells, with vacuolated nuclei, smudged chromatin, and frequent multinucleation infiltrating around benign acini. There was a hypocellular, loose, myxoid stromal matrix, with ectatic hyalinized vessels and mild to moderate chronic inflammation. Stromal cells displayed intense immunoreactivity for androgen receptors and vimentin, but moderate reactivity for desmin and actin. There were 3 local recurrences, with a mean follow-up of 6.3 years (range, 0.5-14 years), but none developed evidence of sarcomatous transformation or malignancy. Conclusions.--Prostatic stromal hyperplasia with atypia is a rare, benign lesion, composed of degenerative myocytes with atypia that is histologically and clinically reminiscent of benign counterparts in the myometrium, breast, vulva, vagina, and elsewhere. Recognition of this distinctive entity should allow separation from phyllodes tumor and sarcoma of the prostate. The phrase stromal tumor of uncertain malignant potential is inappropriate for this benign tumor, and its use is discouraged.

Body cavity fluid specimens are commonly encountered in daily practice; differentiating adenocarcinoma from reactive mesothelial cells is a daily dilemma. Since 1991, the ThinPrep (TP) processor has been approved by [...], * Context.--Newer liquid-based preparations differ morphologically from classic preparations (smears, filters, and cytocentrifuged preparations). Is adenocarcinoma more readily detected in liquid-based preparations? We reviewed responses from 16 750 fluid challenges of adenocarcinoma distributed in 2005 in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology (CAP NGC). Objective.--To compare the performance of body cavity fluid liquid-based preparations with adenocarcinoma to that in classic preparations in the CAP NGC. Design.--Responses for ThinPrep challenges were compared with classic preparations for exact match diagnoses of adenocarcinoma from pelvic washes, pleural fluid, pericardial fluid, and peritoneal fluids in the 2005 CAP NGC. Results.--A total of 13 690 pathologists, 8345 cytotechnologists, and 5958 laboratories submitted responses to fluid challenges in 2005. Adenocarcinoma comprised 16750 of the fluid challenges; 88% were classic preparations, and 12% were ThinPrep challenges. The exact match to the reference diagnosis of adenocarcinoma was seen in 77% of conventional preparations and 81% of ThinPrep challenges when a general category of "positive for malignancy" was assigned. When "suspicious for malignancy," an exact match diagnosis of adenocarcinoma was made in 5% and 4% of classic and ThinPrep challenges, respectively. Conclusions.--ThinPrep challenges performed slightly better overall, but only pelvic washings and peritoneal fluids demonstrated statistically significant improved performance with ThinPrep challenges. Use of liquid-based preparation is widespread for nongynecologic preparations and performs as well, and sometimes better than, classic preparations in an interlaboratory comparison program. (Arch Pathol Lab Med. 2008;132:1716-1718)

To the Editor.--I read with great interest the excellent article by Drs Toledo and Oliva (1) in which the authors enumerated a practical diagnostic approach to smooth muscle neoplasms of [...]

THE HURTHLE CELL: HISTORICAL PERSPECTIVES The Hurthle cell has consistently been the center of debate in the discussion of nonneoplastic and neoplastic lesions of the thyroid ever since it was [...], * Context.--Hurthle cells are eosinophilic, follicular-derived cells that are associated with a variety of nonneoplastic and neoplastic thyroid lesions. The differential diagnosis of Hurthle cell lesions is quite broad. Objective.--To review the pathologic conditions associated with Hurthle cells in the thyroid and to discuss pathology of thyroid lesions associated with oncocytic cytology. Data Sources.--A variety of thyroid nonneoplastic (autoimmune thyroiditis, multinodular goiter) and neoplastic conditions (Hurthle cell adenoma, Hurthle cell carcinoma) are associated with Hurthle cell cytology. In addition, there are several thyroid neoplasms that should be considered when one observes a Hurthle cell neoplasm in the thyroid (oncocytic variant of medullary carcinoma, several variants of papillary thyroid carcinoma). Conclusions.--Oncocytic cytology is seen in a variety of thyroid conditions that are associated with a broad differential diagnosis and care must be used for accurate diagnosis. Newer molecular-based techniques may be useful for further classification of thyroid neoplasms with oncocytic pathology. (Arch Pathol Lab Med. 2008;132:1241-1250)

Pheochromocytomas and extra-adrenal paragangliomas are tumors of neural crest--derived endocrine cells or organs, known as paraganglia, that exist throughout the distribution of the sympathetic nervous system and along supradiaphragmatic branches [...], Context.--Advances in genetics and gene expression profiling have led to new ways of thinking about the pathobiology of pheochromocytoma and extra-adrenal paraganglioma. These developments are concurrent with the publication and dissemination of the 2004 World Health Organization bluebook on pathology and genetics of endocrine tumors. Objective.--To summarize new information required by pathologists for effective participation in patient management and research. Data Sources.--Literature review and primary material from Tufts Medical Center. Conclusions.--The World Health Organization reserves the term pheochromocytoma for tumors arising from chromaffin cells in the adrenal medulla. Closely related tumors in extra-adrenal sympathetic and parasympathetic paraganglia are classified as extra-adrenal paragangliomas. A pheochromocytoma is an intra-adrenal sympathetic paraganglioma. Although arbitrary, this nomenclature emphasizes important distinctive properties of intra-adrenal tumors, including an often adrenergic phenotype, relatively low rate of malignancy, and predilection to occur in particular hereditary syndromes. Malignancy is defined by presence of metastases not local invasion. Occult germline mutations characteristic of familial syndromes are now found in more than 20% of patients with apparently sporadic tumors, bringing the percentage of tumors with a known genetic basis close to 30%. In addition, tumor location and risk of malignancy vary with the underlying genetic defect. The "10 percent rule" for pheochromocytoma/paraganglioma--10% familial, 10% malignant, 10% extra-adrenal--is therefore no longer tenable. Current roles of pathology are limited to diagnosing primary or metastatic tumors and identifying features suggestive of malignant potential or hereditary disease. Future roles may involve more definitive assessment of malignancy, genotype-phenotype correlation, and identification of targets for therapy. (Arch Pathol Lab Med. 2008;132:1272-1284)

Since 1994, the College of American Pathologists (CAP) has used survey questionnaires to assess practice patterns in cervicovaginal cytology. (1-5) These surveys have documented the widespread implementation of the first [...], Context.--Oncogenic, high-risk human papillomavirus (HR-HPV) testing is used to evaluate women who are older than 20 years with atypical squamous cells of undetermined significance (ASC-US) and in conjunction with a screening Papanicolaou test in women older than 30 years. Objectives.--To evaluate the 2006 laboratory practice data from laboratories incorporating human papillomavirus (HPV) testing with the Papanicolaou test. Design.--To use the College of American Pathologists (CAP) Supplemental Questionnaire Survey for 2006 to determine laboratory practices of participants in the CAP Interlaboratory Comparison Program in Cervicovaginal Cytology. Results.--A total of 679 laboratories responded to the questionnaire. Most (73%) refer HPV testing to reference laboratories. Nine percent perform HPV testing in cytology. Forty-five percent offer low-risk HPV (LR-HPV) testing. The most common reflex is ASC-US, although HR-HPV is also offered with low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), or any other Papanicolaou test result. Digene Hybrid Capture II is the most common method. Human papilloma virus median test volumes are 55 monthly. Frequency distributions of HPV test volumes are significantly different from those found in 2003. Laboratories performing in-house testing reported significantly higher monthly HPV volumes (P < .001). Median rates for HR-HPV positivity are 36.6% for ASC-US, 50.0% for atypical squamous cells, cannot exclude HSIL (ASC-H), and 4% for women 30 years of age and older in conjunction with a screening Papanicolaou test. Conclusions.--Reference HPV testing remains the most common pattern. The most common reflex indication is for ASC-US, but HPV testing is modified locally to include a variety of scenarios. LR-HPV testing is commonly offered despite its lack of clinical significance. These data form a baseline for ongoing monitoring of HPV testing practice trends. (Arch Pathol Lab Med. 2008;132:1290-1294)

Hereditary benign intraepithelial dyskeratosis (HBID) (Mendelial Inheritance of Man [MIM] identification 127600) is a rare autosomal dominant disorder characterized by elevated epithelial plaques located on the ocular and oral mucous [...], * Context.--Hereditary benign intraepithelial dyskeratosis (HBID) is a rare autosomal dominant disorder characterized by elevated epibulbar and oral plaques and hyperemic conjunctival blood vessels. The condition is predominantly seen in Native Americans belonging to the Haliwa-Saponi tribe located in northeastern North Carolina. Objective.--To determine whether HBID can be diagnosed using cytologic preparations of the conjunctiva, and whether the cytologic findings correlated with the genetic linkage involving a duplication in chromosome 4 (4q35). Design.--Cytologic preparations from conjunctival brushings in patients afflicted with HBID and from unaffected blood relatives with normal conjunctivas were compared in a masked fashion. Cytologic observations were correlated with molecular genetic analyses. Results.--Papanicolaou-stained preparations from the conjunctiva showed the typical cytologic features of HBID, including rounded squamous epithelial cells with dense homogenous orange cytoplasm and hyperchromatic, pyknotic, or crenated nuclei. All cases with the diagnostic cytologic findings of HBID had a duplication in chromosome 4 (4q35). Conclusion.--HBID is an entity with distinct clinical, histopathologic, and genetic features. The results of this study indicate the diagnosis can also be supported in an appropriate clinical setting when adequate epibulbar cytology preparations are obtained and the characteristic genetic attributes are present. (Arch Pathol Lab Med. 2008;132:1325-1328)

For decades, touch imprint cytology (TIC) has been used as a diagnostic tool for breast cancer. (1) The simplicity, speed, and cost-effectiveness of the technique, along with its ability to [...], Context.--Learning the characteristics of frozen tissue samples stored in tumor banks for biological studies remains a problem. Objective.--To assess the use of touch imprint cytology on fresh tissue samples as a rapid and reliable method of determining the presence and quantity of neoplastic cells before freezing. Design.--Touch imprint cytology was performed on 259 specimens of operable breast cancer. Touch imprints were prepared from fresh tissue specimens before freezing samples for storage. Each tumor sample was imprinted on a glass slide and stained with hematoxylin-eosin. Tumor cellularity was quantified as negative, poor, moderate, or rich. Results.--A significant correlation was found between samples with a tumor size greater than 2 cm and high tumor cellularity (P = .03; [chi square] test). Furthermore, 35% of ductal tumors showed higher tumor cellularity compared with lobular tumors (P < .001; [chi square] test). No association was found between lymph node status and tumor grade. When samples for which more than 2 imprints were available were examined, tumor cellularity among imprints of the same sample showed an overall agreement of 0.67 (P < .001; [kappa] statistic). It was also determined that the higher the cellularity, the higher the agreement. Our data also showed concordance of 0.87 (P < .001; [kappa] statistic) between touch imprint cytology imprints and histologic sections from contiguous tumor. Moreover, 11 randomly selected samples underwent DNA extraction, polymerase chain reaction, and sequencing to verify the feasibility of DNA analyses. We found that DNA from touch imprint cytology was ampliiable and suitable for direct sequencing. Conclusions.--Touch imprint cytology may represent an important step in the quality control of tumor cellularity of breast cancer specimens designed to be stored in tumor biobanks and a valid method for assessing the suitability of such tissue for further biomorphologic and biomolecular applications. (Arch Pathol Lab Med. 2008;132:974-978)

[3/03] BabA mediated Adherence is Important for IL-8 Induction and Cellular Morphological Changes caused by type 1 H. pylori Strains Background: Adherence to gastric epithelial cells might be an important [...]

Chromosomal rearrangements involving the RET gene are highly prevalent in radiation-induced thyroid tumors from children exposed to environmental radiation after the Chernobyl accident (1-3) and in thyroid cancers from patients [...], Rearrangements involving the RET gene are common in radiation-associated papillary thyroid cancer (PTC). The RET/PTC1 type of rearrangement is an inversion of chromosome 10 mediated by illegitimate recombination between the RET and the H4 genes, which are 30 megabases apart. Here we ask whether despite the great linear distance between them, RET and H4 recombination might be promoted by their proximity in the nucleus. We used two-color fluorescence in situ hybridization and three-dimensional microscopy to map the positions of the RET and H4 loci within interphase nuclei. At least one pair of RET and H4 was juxtaposed in 35% of normal human thyroid cells and in 21% of peripheral blood lymphocytes, but only in 6% of normal mammary epithelial cells. Spatial contiguity of RET and H4 may provide a structural basis for generation of RET/PTC1 rearrangement by allowing a single radiation track to produce a double-strand break in each gene at the same site in the nucleus.

Identification of Diseases Endemic to the Theater of Operations The United States deployed nearly 700 000 military personnel to the Persian Gulf region between August 1990 and February 1991 for [...], * Background.--Tens of thousands of Persian Gulf War veterans (GWVs) have presented with medical symptoms since Operation Desert Shield and Operation Desert Storm. The Kuwait Registry at the Armed Forces Institute of Pathology was established to act as a repository for surgical pathology, cytopathology, and autopsy material from GWVs. Objective.--To identify conditions known to be endemic to the theater of operations in our cohort of GWVs. Methods.--The Kuwait Registry database was searched by computer for listed conditions endemic to the Persian Gulf region included in the registry through December 31, 1997. Results.--Of the 2582 patients in this cohort, 1 patient with hepatitis B and 15 patients with hepatitis C were identified. Other known endemic conditions of the Persian Gulf region were not found. Conclusions--Viral hepatitis (B and C), which is prevalent in the US population, was the only listed endemic condition identified in surgical pathology or cytopathology specimens in our cohort of GWVs. (Arch Pathol Lab Med. 2000;124:1299-1301)

In 1858, Rudolf Virchow published a series of lectures as a book entitled Cellular Pathology (1), which altered medical research by turning the focus from the diseased cell's form to [...]

Abstract. A protoplast fusion method was developed to stably transfect human cells with pSV2-derived plasmids at frequencies greater than [10.sup.-3]. This procedure made it possible to test the biological effect [...]

Unexpectedly High Levels of HIV-1 RNA and Protein Synthesis in a Cytocidal Infection STUDIES OF HIV-1--INDUCED CELL killing have shown that HIV-1--envelope glycoproteins can kill cells by inducing the formation [...]

Long-Term Cultures of HTLV-III-Infected T Cells: A Model of Cytopathology of T-Cell Depletion in AIDS THE PATHOGENESIS OF THE ACquired immune deficiency syndrome (AIDS) involves a decrease in the number [...]

During infection by human immunodeficiency virus (HIV), the virus replicates in cells of the immune system (1). T lymphocytes expressing CD4 are preferred targets, and this subset of cells is [...]

Induction of HTLV-III/LAV from a Nonvirus-Producing T-Cell Line: Implications for Latency THE PRIMARY ETIOLOGIC AGENT OF the acquired immune deficiency syndrome (AIDS) has been identified as a human T-lymphotropic retrovirus [...]

Heterogeneity of Normal Human Diploid Fibroblasts: Isolation and Characterization of One Phenotype Resident fibroblasts are responsible for the production and maintenance of the connective-tissue matrix and for repair after injury. [...]