Showing papers in "American Journal of Clinical Pathology in 1996"

Solitary fibrous tumor of the meninges: a lesion distinct from fibrous meningioma. A clinicopathologic and immunohistochemical study.

Abstract: Seven solitary fibrous tumors (SFTs) of the meninges are presented and their clinicopathologic features are compared with those of 64 fibrous meningiomas (FM). Patients with SFT included 5 females and 2 males age 47 to 73 years. The dura-based tumors involved the parasagittal region (1), tentorium (2), cerebellopontine angle (2), and spinal region (2). One each showed invasion of brain and of a spinal nerve root. Of four SFTs with at least 1-year follow-up, one subtotally resected example recurred. No tumors metastasized. All consisted of spindle cells disposed in fascicles between prominent, eosinophilic bands of collagen. Whorls and storiform cell arrangements were lacking. Mitoses ranged from 1 to 7/10 400 x fields. MIB-1 labeling indices ranged from 1% to 18% (mean 4%). All were PAS negative and showed strong immunoreactivity for vimentin and CD34. Of cases studied, half were estrogen and all were progesterone receptor immunopositive. The majority (72%) of FMs occurred in females and most (72%) were supratentorial. Recurrence was noted in 15%. Mitotic activity varied from 0 to 3 mitoses per 10 400 x fields (mean < 1). MIB-1 labeling indices ranged from 1% to 5% (mean 1.5%). Unlike SFT, FMs were glycogen-containing and variously exhibited a storiform pattern (13 of 20), psammoma body formation (9 of 20), and calcification of collagen (4 of 20). Immunoreactivities included vimentin (100%), focal to patchy EMA (80%), S-100 protein (80%), collagen IV (25%), and patchy, mild-to-moderate CD34 staining (60%). Of cases studied, nearly half were estrogen and all were progesterone receptor staining positive. Meningeal SFTs represent a distinct morphologic entity, the morphologic and immunohistochemical features of which differ from those of FM and suggest a histogenetic relationship to pleural SFT. Although a minority histologically appear to be low grade malignant, our limited experience suggests that they behave in a benign fashion. The classification of mesenchymal tumors affecting the central nervous system must be expanded to include SFT.

Lymph node recovery from colorectal resection specimens removed for adenocarcinoma : Trends over time and a recommendation for a minimum number of lymph nodes to be recovered

Abstract: Recovery of pericolorectal lymph nodes from colectomy specimens has long been part of colorectal cancer staging. Recently, adjuvant therapy has been added for high stage carcinomas, providing further impetus for performing careful lymph node dissections. Pericolorectal lymph nodes were examined to determine if there has been a change over time in the number of lymph nodes recovered and proportion of specimens with pericolonic lymph node metastases from colorectal carcinoma resection specimens. Also, the authors attempted to establish a recommendation for a minimum number of lymph nodes that should be recovered before a colon can be considered free of metastases. Slides and reports of the first 20 consecutive pT3 colorectal carcinoma resections in each year from 1955 to 1995 at William Beaumont Hospital that did not have known metastases at the time of surgery were reviewed (750 specimens total). The mean number of lymph nodes recovered per specimen and incidence of detected lymph node metastases increased over the 41-year period, with the greatest increase occurring during 1992-1995. The greatest proportion of patients with lymph node metastases detected occurred in the 17 to 20 lymph nodes recovered per specimen group. Specimens with more than 20 lymph nodes did not have a higher proportion of lymph node metastases detected compared to specimens with 17 to 20 lymph nodes. Approximately 20% of the specimens with metastases had more than 17 lymph nodes recovered. These results suggest that pathologists should retrieve all the lymph nodes that can be recovered, but at least 17 lymph nodes should be recovered to insure accurate documentation of nodal metastases when present.

Reduced E-Cadherin Expression is Associated With Invasiveness and Unfavorable Prognosis in Breast Cancer

Abstract: E-cadherin (E-cad) is a calcium-dependent, epithelial cell adhesion molecule whose reduced or lost expression has been associated with tumor dedifferentiation and increased metastatic potential in human carcinomas. The authors studied immunohistochemically E-cad expression in frozen sections of 362 breast carcinomas using a monoclonal antibody (HECD-1). The immunohistochemical detection of reduced E-cad expression was confirmed by mRNA in situ hybridization with two different oligonucleotide probes. THe proportion of tumors with reduced or lost E-cad expression increased significantly from pure intraductal carcinomas (20%, 4 of 20) through invasive ductal (IDCs; 52%, 124 of 239) to recurrent carcinomas (64%, 18 of 28; chi square test for trend, P = .004). Invasive lobular carcinomas (ILCs) and IDCs differed from each other in their E-cad expression. None of the ILCs (n=55) retained normal E-cad expression in contrast to 48% (115 of 239) of the IDCs. In 259 primary IDCs, reduced E-cad expression was associated with high histologic grade (chi square test for trend, P < .001), negative estrogen receptor status (ER; Fisher's exact test; P = .042), and marginally with axillary node involvement (Fisher's exact test, P = .063). In a subset of 109 primary IDC patients whose clinical follow-up was available (median follow-up 51 months), reduced E-cad expression was associated with shortened disease-free survival (DFS; Mantel-Cox test, P = .027). In Cox's multivariate regression analysis, progesterone receptor status (P = .018) and E-cad expression (P = .072) were selected as independent predictors of DFS. Our findings provide clinical evidence that loss of normal E-cad expression is an indicator of increased invasiveness and dedifferentiation in breast carcinoma. E-cad is a potentially important prognostic factor in primary IDCs.

Primary body cavity-based AIDS-related lymphomas

Abstract: Five patients with advanced AIDS developed a unique type of high grade primary body cavity-based non-Hodgkin's lymphoma (NHL). The lymphomas were exclusively in serous effusions with no detectable mass disease in the body cavities and no lymphadenopathy or organomegaly. All of the lymphomas exhibited virtually identical morphology, which could not be precisely classified, but appeared to bridge features of large cell immunoblastic and anaplastic large cell lymphomas. Immunophenotypically the lymphoma cells lacked expression of any B- or T-lymphocyte antigens, but expressed CD45 and the activation antigens CD30, CD38, CD71, and HLA-DR. Clonally rearranged immunoglobulin heavy chain and kappa light chain genes were identified by Southern blot analysis. Molecular studies also revealed Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) genomes and germline configuration of the c-myc protooncogene. In two cases studied cytogenetically, the lymphoma cells manifested complex chromosome abnormalities. These lymphomas are clinically and biologically unique and found predominantly in patients with advanced AIDS, in many cases with pre-existing Kaposi's sarcoma.

Cytokine function: a study in biologic diversity.

Abstract: Cytokines are a group of hormone-like polypeptide mediators that play a variety of regulatory roles in both host defense and normal and abnormal homeostatic mechanisms. They may he produced by diverse cell types and exert their function on a variety of cells. Their effects (which may be suppressive or enhancing) are on cellular proliferation, differentiation, activation, and motility. In addition, cytokines can exert cytodestructive effects on infectious agents or tumor cells, either directly or by activating cells with cytodestructive potential. Any given cytokine may have many different biologic effects. However, two different cytokines may have similar or identical activities. Cytokines may be classified on the basis of their cell of origin, their spectrum of activity, the category of activity they influence, the cells that are their targets, or on specific features of their ligand-receptor interaction. The mode of action of many of the cytokines involves typical signal transduction events such as protein phosphorylation, and to date there is only limited understanding of the mechanisms that lead to one activity over another when a specific cytokine is involved in a specific biologic reaction. Nevertheless, elucidation of their role in other pathologic processes has provided insight into autoimmune and allergic diseases, as well as a variety of systemic disorders. Because of their broad spectrum of activity, cytokines have been used in a variety of therapeutic settings involving both infectious diseases and neoplasia. As the number of known cytokines continues to grow, it will be increasingly difficult for the non-"cytokinologist" to follow the exponentially expanding literature. Hopefully, this brief review will provide an overview that can serve as a framework for the understanding of this important area of biology and pathology.

Hepatocellular Carcinoma in Cirrhotic and Noncirrhotic Livers: A Clinico-Histopathologic Study of 804 North American Patients

Abstract: This study examined clinico-histopathologic differences between North American patients who developed hepatocellular carcinoma with and without cirrhosis Histologic slides and clinical records of cases were reviewed Cases were classified according to defined histopathologic criteria Analyses were performed using appropriate tests A total of 426% of cases were noncirrhotic The trabecular type of hepatocellular carcinoma was the most common growth pattern in both groups Patients with cirrhosis were significantly older, had high grade tumors, and local portal venous invasion significantly more often than patients without cirrhosis Encapsulated tumors occurred in significantly more in patients without cirrhosis Patients without cirrhosis survived longer than patients with cirrhosis (P < 0001) and had a better 5-year survival experience On average, in patients with cirrhosis, serum aspartate transaminase and total serum bilirubin were significantly greater, and serum albumin was significantly lower In general, hepatocellular carcinoma in North American patients with cirrhosis tended to be less well differentiated than those found among patients without cirrhosis The pathology, natural history, and prognosis of this tumor is significantly influenced by the presence or absence of cirrhosis in the nonneoplastic liver, and the presence of cirrhosis portends a poorer prognosis

Rubella immunity-Defining the level of protective antibody-

Abstract: The Rubella Subcommittee of the National Committee for Clinical Laboratory Standards has proposed lowering the breakpoint to define rubella immunity from 15 to 10 IU/mL. This recommendation stems from epidemiologic studies on vaccinated persons with low levels of antibody and anecdotal reports. Additional support comes from Centers for Disease Control and Prevention studies and reports. The effectiveness of rubella vaccination is well documented and the 10 IU/mL antibody level is protective in the vast majority of persons. Sporadic reports of viremia and/or reinfection among previously immunized persons with low antibody levels have been reported but proven cases of reinfection have also occurred in persons with titers greater than or equal to the 15 IU/mL cut-off. Despite the occasional occurrence of rubella reinfection in persons with low titers, the theoretical risks are small especially as compared with significantly greater risk in persons who have not been vaccinated. Immunity in a given patient is a clinical decision and the results of antibody tests for rubella, like other laboratory tests, must be evaluated in the context of the clinical setting.

bcl-2 Expression, p53 Accumulation, and Apoptosis in Ovarian Carcinomas

Abstract: Because little is known about the importance of apoptosis and its regulation in epithelial ovarian cancer, the authors looked for bcl -2 expression and p53 accumulation by immunohistochemistry in 148 ovarian carcinomas of different histologic types and stages. The number of apoptotic cells was assessed in situ by enzymatic detection of DNA fragmentation. Strong bcl -2 expression correlated with low histologic grade ( P = .004) and was most often seen in endometrioid carcinomas ( P = .001), whereas p53 accumulation was predominantly found in serous and undifferentiated carcinomas ( P <.001) and high grade tumors ( P <.001). p53 accumulation was associated with advanced tumor stage ( P <.001) and the presence of residual disease after surgery ( P <.001). Apoptosis increased with histologic grade ( P = .012); apoptotic cells were sparse or absent in tumors of low malignant potential and mucinous carcinomas, but found in all other carcinoma types ( P = .001). Apoptosis, bcl -2 expression, and p53 protein accumulation were not correlated with each other. The analysis of the postoperative course of 110 patients showed that survival depended on histologic tumor type ( P = .0037), histologic grade ( P = .0143), FIGO (International Federation of Gynecology and Obstetrics) stage ( P = .0001), and the absence or presence of postoperative residual tumor mass ( P = .0001). p53 accumulation was also associated with adverse prognosis ( P = .0001). However, bcl -2 immunohistochemistry identified a subgroup of patients with p53 and bcl -2 positive carcinomas who had a statistically significantly better outcome than patients with p53 positive and bcl -2 negative tumors ( P = .0443). Regarding FIGO stage and p53 alone in a Cox model, p53 proved to contribute additional prognostic information both in FIGO stages I/II as well as in FIGO stages III/IV. Thus, our observations point to different molecular alterations possibly underlying phenotypic diversity of ovarian carcinomas and provide clues for a better understanding of tumor progression in these neoplasms. Apoptosis plays a role in ovarian carcinomas, but seemingly is regulated in a different way than in nonneoplastic tissues.

CD5+ Extranodal Marginal Zone B-Cell (MALT) Lymphoma: A Low Grade Neoplasm With a Propensity for Bone Marrow Involvement and Relapse

Abstract: Three cases of extranodal marginal zone B-cell lymphoma (low grade B-cell lymphoma of mucosa-associated lymphoid tissue [MALT] type) in which the neoplastic B cells expressed the CD5 antigen are reported. The patients included 2 men and 1 woman, aged 44, 62, and 77 years. In all three cases, the histologic features were typical of marginal zone/MALT lymphoma, with reactive follicles, marginal zone (centrocyte-like) cells, and plasma cells. Pseudofollicles, prolymphocytes, and paraimmunoblasts were absent. In all cases, lymphoma from one or more sites expressed monotypic immunoglobulin (2 IgM kappa, 1 IgM lambda), pan B cell antigens and CD5. Two of 3 cases expressed CD43; one case expressed CD23. No case showed overexpression of the bcl-1 protein, cyclin D1. Interphase cytogenetic analysis revealed trisomy 3 in one of two cases examined. The two male patients presented with lymphoma in the ocular adnexa. One of them had marrow involvement, cervical lymphadenopathy and peripheral blood involvement at presentation; 24 months later, he developed a relapse in subcutaneous tissue. The second patient had marrow involvement 3 years later, at the time of recurrence of his orbital disease. The third patient presented with lymphoma at the base of the tongue. She subsequently developed lymphoma involving the left upper eyelid and right lacrimal sac and duct, the marrow, and the nasopharynx between 63 and 95 months after initial presentation. All of these patients presented with disease involving sites in the head and neck and all had multiple relapses or recurrences with bone marrow involvement at the time of presentation (1 case) or at relapse (2 cases). The presence of CD5 may be a marker for cases of MALT lymphoma with a tendency for persistent or recurrent disease, for dissemination to the marrow and other extranodal sites, and for leukemic involvement of the peripheral blood.

Solitary fibrous tumor of the soft tissue. An immunohistochemical and ultrastructural study.

Abstract: Solitary fibrous tumor is a rare spindle cell neoplasm of adults that usually arises in the pleura, recently reported in other locations. The authors describe three cases of solitary fibrous tumors in adults that occurred as circumscribed masses in the somatic soft tissue, including the arm, back, and abdomen. Histologically, they were characterized by a proliferation of spindle cells separated by thick bands of collagen and prominent vascularity often showing a hemangiopericytoma-like pattern. The spindle cells, having low mitotic figures and little nuclear atypicality, exhibited a variety of growth patterns, including storiform, fascicular and herringbone, and nuclear palisading. Vimentin and CD34 immunoreactivities were observed in many spindle cells of all tumors. They had ultrastructural features of fibroblast and myofibroblast in two cases examined. Solitary fibrous tumors seem to represent distinct mesenchymal neoplasms that require us to identify their unusual location other than the pleura and be familiar with their histologic appearances for arriving at the correct diagnosis.

Myocardial markers of injury. Evolution and insights.

Abstract: Knowledge of the pathophysiology of ischemic heart disease has advanced in parallel with awareness of the significant limitations inherent in clinical assessment. Biochemical assays, long established as the most reliable means of detecting myocardial injury, have improved significantly. Creatine kinase MB, now optimally measured by the newer mass monoclonal antibody assays, and also measurement of the cardiac troponins objectively identify adverse prognosis. Cardiac troponin I appears to have significant advantages over other markers and may become the assay of choice. This is attributable to the confirmation of cardiospecificity claims regarding this marker. These assays permit increased appreciation of the continuous spectrum of ischemic myocardial injury, earlier diagnosis, refinement of the clinical assessment of risk, and evaluation of alternative treatment regimens. Reassessment of the incorporation of biochemical indicators for thrombolytic therapy can be anticipated. This paper integrates the clinical and biochemical literature in reviewing these concepts.

Cardiac troponin T is elevated in asymptomatic patients with chronic renal failure.

Abstract: Patients with chronic renal failure (CRF) are at increased risk for myocardial events that are difficult to evaluate due to atypical symptoms and chronically elevated protein markers of cardiac damage. This study evaluated cardiac troponin T (cTnT), a sensitive marker of cardiac injury, in patients with CRF without myocardial infarction symptoms, and assessed potential causes for elevated cTnT. Blood was obtained from 38 patients with CRF immediately before hemodialysis and from 16 of them post-dialysis, from 21 peritoneal dialysis patients, 10 patients with CRF not on dialysis, 11 patients with cardiomyopathy, and 10 adolescent patients with CRF undergoing hemodialysis. Samples were analyzed for myoglobin, creatine kinase, creatine kinase isoenzyme- MB (CK-MB), lactate dehydrogenase, lactate dehydrogenase isoenzyme-1 (LD-1), and cTnT. Cardiac TnT was elevated in: 71% of patient with CRF undergoing hemodialysis with no significant differences between pre- and post-dialysis values, 57% of patients with CRF on peritoneal dialysis, 30% of patients with CRF without dialysis, 18% of patients with cardiomyopathy, and 20% of adolescent patients with CRF undergoing hemodialysis. Myoglobin was elevated in almost all patients with CRF undergoing hemodialysis and without dialysis, whereas CK-MB and LD-1 were rarely elevated. Cross-reacting dialyzable substances and myocardial stretch were not major causes for elevated cTnT. Until future studies clarify the etiology of elevated cTnT in patients with CRF, results should be interpreted cautiously.

Changes in blood coagulation during and following cardiopulmonary bypass: lack of correlation with clinical bleeding.

Abstract: Although previous studies have documented a wide variety of derangements in laboratory measurements of blood coagulation and platelets during cardiopulmonary bypass, limited data are available concerning the magnitude of these changes and any association with excessive bleeding. To determine whether abnormalities in commonly available laboratory tests for the evaluation of coagulation, fibrinolysis and hemostasis correlate with postoperative blood loss and transfusion requirements as measures of clinical outcome, 47 consecutive patients undergoing coronary artery bypass grafting with hypothermic cardiopulmonary bypass (CPB) were studied prospectively at 12 time points before, during, and following CPB. Routine blood coagulation tests, coagulation factor levels (fibrinogen, V, VII, VIII, and IX) and fibrinolysis (FDP) became abnormal within 15 minutes after patients were placed on CPB, remained abnormal for the duration of CPB, and recovered at varying rates after discontinuation of CPB. Mean factor V levels declined by the greatest percentage, to 15% of normal, followed by factor VIII which decreased to 30%. Platelet counts declined to below 100 x 10(9)/L after the initiation of CPB and remained low in the postoperative period. Twenty-eight percent of patients had mediastinal output > or = 100 mL per hour during the immediate postoperative period, and were considered to be "bleeders." There were no clinically relevant differences in any of the laboratory measurements between patients with normal postoperative blood loss and those defined as bleeders. Thus, the absence of significant correlations between various laboratory measurements of hemostasis and actual postoperative bleeding indicates that these laboratory derangements are transient, are not predictive of clinically important hemostatic abnormalities, and should not be used in isolation to guide the use of blood components in these patients. Furthermore, although bleeders received more blood components, there was surprisingly little effect on the coagulation factor levels measured.

Rapid detection of the staphylococcal mecA gene from BACTEC blood culture bottles by the polymerase chain reaction.

Abstract: A rapid polymerase chain reaction (PCR) method for the direct detection of the staphylococcal mecA gene from BACTEC blood culture bottles (Becton Dickinson, Sparks, MD) was developed. Published primer sequences and sample preparation using Achromopeptidase for cell lysis were adapted to the use of the Idaho Technology Air Thermocycler 1605 (Idaho Technologies, Idaho Falls, ID). The method was validated with 80 strains of coagulase-positive and coagulase-negative geographically diverse methicillin-resistant and susceptible isolates of staphylococci. There was a 100% correlation between the PCR results and the results of standard susceptibility testing methods. From BACTEC 9240 blood cultures, mixed aliquots of blood and broth containing gram-positive cocci in clusters were centrifuged at low speed to sediment red blood cells. After additional centrifugation and wash steps, PCR was performed on the resuspended pellet. The turnaround time from initial Gram stain detection of positive BACTEC bottles to PCR amplicon detection by agarose gel electrophoresis is less than 3 hours. In a clinical evaluation of 181 blood culture isolates, there was a 99% correlation with standard susceptibility results for Staphylococcus aureus. Discrepant results for Staphylococcus aureus isolates were verified by a Mueller Hinton plate supplemented with 6 microg/mL of oxacillin and 2% sodium chloride. For coagulase-negative staphylococci, the PCR method detected an additional seven resistant isolates that were reported by the Vitek as susceptible. Coagulase-negative staphylococcal susceptibility results that were in disagreement with the PCR assay were confirmed by the disk-diffusion method. This procedure is accurate, rapid and fits well into laboratory work flow. Rapid detection of the mecA gene on positive blood culture vials has become a routine test in the authors' clinical microbiology laboratory.

Diagnosis of Castleman's disease by identification of an immunophenotypically aberrant population of mantle zone B lymphocytes in paraffin-embedded lymph node biopsies.

Abstract: Castleman's disease (CD) is characterized by lymph node enlargement due to hyperplasia of abnormal lymphoid follicles and paracortical lymphocytic hyaline vascular (HV) stroma or plasmacytosis (PC). The lymphoid follicles in CD show involuted germinal centers and prominent mantle zone lymphocytes. Ninety-seven cases clinically suspected to be CD were analyzed according to conventional histologic criteria established by Castleman and Keller for diagnosis. Twenty-two cases were excluded as nonspecific hyperplasia (12); Hodgkin's and non-Hodgkin's lymphoma (9); and multiple myeloma involving lymph node paracortex (1). The 75 remaining cases, consisting of 51 cases of CD and 24 with altered follicles or paracortex suggestive of CD, were further analyzed immunohistologically for changes in follicular dendritic reticulum cells (FDRC) using the monoclonal antibody Ki-M4p, for germinal center proliferation with Ki-S5, for mantle zone immunophenotype with Ki-B3 and Ki-B5, for paracortical plasmacytoid monocytes with Ki-M1p, and for plasma cell clonality by applying antibodies to kappa and lambda immunoglobulin light chains. Lymph nodes showing nonspecific follicular and paracortical hyperplasia were included as controls. Hyaline vascular CD and plasma cell CD showed enlarged, polyploid FDRC with prominent nucleoli, decreased germinal center proliferation, and mantle zone populations of immunophenotypically aberrant, Ki-B3-negative B lymphocytes. Thirty-seven percent of hyaline vascular CD and plasma cell CD contained plasmacytoid monocytes, and 15% showed interstitial areas of lambda predominant plasma cells. Plasmacytoid monocytes were common in hyaline vascular CD but rare in plasma cell CD. Cases suspected to be CD that demonstrated a mantle zone population of Ki-B3-negative B lymphocytes had clinical finding of POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal paraprotein, and skin changes or sclerotic bone lesions) syndrome and were reclassified as hyaline vascular CD, plasma cell CD, and mantle zone CD with an aberrant mantle zone immunophenotype only (lacking follicular center and paracortical histologic or immunohistologic abnormalities). Immunohistochemistry was valuable for identification of dysplastic FDRC, decreased germinal center proliferation, and plasmacytoid monocytes. In addition, immunohistochemistry was essential for detection of plasma cell clonality, an aberrant mantle zone immunophenotype, and mantle-zone-restricted CD that was devoid of diagnostic alterations of germinal center or paracortex.

Calcifying fibrous pseudotumor of pleura. A report of three cases of a newly described entity involving the pleura.

Abstract: A newly recognized distinctive fibrous soft tissue lesion called "calcifying fibrous pseudotumor" (CFPT) was recently described in the soft tissues of the extremities, trunk, scrotum, groin, neck, or axilla. To date, CFPT has not been described in the pleura. The authors reviewed the clinical, radiologic, and pathologic features of three cases. A 23-year old woman and 34-year old man who presented with chest pain, and a 28-year old woman without chest symptoms were found to have a pleural mass on chest radiographs. Computed tomography (CT) scans of each patient revealed pleural-based nodular masses with central areas of increased attenuation due to calcifications. Each lesions consisted of circumscribed, but unencapsulated masses of hyalinized collagenous fibrotic tissue interspersed with lymphoplasmacytic infiltrates and calcifications, many of which had psammomatous features. The lesions were limited to the pleura and did not involve the underlying lung parenchyma. Electron microscopy in one case showed fibroblasts scattered in dense collagenous tissue. Calcifying fibrous pseudotumor is distinct from other pleural lesions such as fibrous tumor of pleura, calcified granulomas, calcified pleural plaques, and chronic fibrous pleuritis as well as intrapulmonary lesions such as hyalinizing granuloma, inflammatory pseudotumor, and amyloid. As in the soft tissues, local excision appears adequate therapy for CFPT of the pleura. If these lesions behave in a similar fashion to CFPT of soft tissues, one might expect a low frequency of local recurrence.

Telecytology: diagnostic accuracy in cervical-vaginal smears.

Abstract: Although cervical-vaginal telecytology is a promising tool, diagnostic accuracy has not been extensively evaluated. The authors examined the accuracy of five cytotechnologists who retrospectively reviewed 50 cervical-vaginal smears using the video monitor, and 2 months later, using the light microscope. Accuracy was expressed in terms of crude agreement with the original diagnosis and number of false positives (FPs) and false negatives (FNs). With a greater than one step difference as discrepant, the group crude agreement using the video monitor and the light microscope was 85.6% and 95.6%, respectively. The group number of FNs and FPs for the light microscope was 8 and 7, respectively, and for the video monitor was 34 and 7, respectively. There was a wide range of individual performance. We conclude that accuracy of telecytology is high, but less than that of light microscopy. The major reason for lower telecytologic accuracy was undercalling dysplasia.

Immunophenotypic identification of Sezary cells in peripheral blood

Abstract: Despite anecdotal literature that Sezary cells express the CD4+ CD7- immunophenotype, no formal validation has been published establishing the use of this immunophenotype for clinical or experimental purposes. Consequently, the only method presently available for Sezary cell identification is nuclear contour analysis, a labor-intensive procedure not generally available at most major medical centers. In this study, the accuracy of CD4+ CD7- subset quantitation for the identification of Sezary cells was examined. The study found that the percentage of CD4+ CD7- cells is elevated in many Sezary syndrome/MF patients relative to normal, healthy individuals. In addition, CD4+ CD7- enumeration correlates with enumeration by nuclear contour analysis in most patients (11 of 15) with elevated CD4/CD8 ratios. The CD4+ CD7- subset also correlates with the expression of other aberrant immunophenotypes, such as CD3low or CD4low. Lastly, CD4+ CD7- subset quantitation correlates with the number of clonal T lymphocytes, as measured using V beta-specific T-cell receptor monoclonal antibodies. The study found this method to be exceptionally accurate, with two caveats: (1) the absence of an expanded CD4+ CD7- subset in patients with a normal CD4/CD8 ratio is uninformative; and (2) in approximately 25% of patients with an elevated CD4/CD8 ratio, the Sezary cells are CD7+.

The evaluation of various mathematical RBC indices and their efficacy in discriminating between thalassemic and non-thalassemic microcytosis.

Abstract: The differentiation between thalassemic and non-thalassemic microcytosis has important clinical implications in hematology and medicine. A simplified index, based on red cell parameters derived from automated blood cell analyzers, which could be used to discriminate between microcytic patients with a high probability of thalassemia minor and those with a low probability, would be an extremely useful tool. Five mathematical indices have been proposed as useful for this purpose. These are the: Bessman index, Shine and Lai index, England index, Mentzler index, and mean cell volume (MCV) alone. This study was designed to prospectively evaluate the efficacy of these indices. Patient samples were chosen every fourth day from all patient samples referred to the hematology laboratory at St. Joseph’s Hospital over a 6-month period. All patient samples with an MCV < 80 fL and age ≥ 18 years were considered eligible for the study. After enrollment and laboratory analysis were complete sensitivities and specificities were calculated for each of the indices using a variety of cut-off values and receiver operator characteristic (ROC) curves were constructed. Based on statistical analysis of the area under these curves, the authors conclude that MCV alone is as effective as the Mentzler and Shine and Lai indices in selecting microcytic patient samples with a high probability of thalassemia minor for thalassemia testing. They also conclude that the Bessman index and the England index are ineffective indices for this purpose.

Hyperhomocysteinemia:An Emerging and Important Risk Factor for Thromboembolic and Cardiovascular Disease

Abstract: Homocysteine is an important contributing factor to thrombosis, vascular injury, and vascular disease. Mechanisms for homocysteine-induced vascular disease include alterations in coagulation as well as endothelial cell and vessel wall injury. Hyperhomocysteinemia (HH[e]) can occur when homocysteine metabolism is altered by mutations in enzymes responsible for homocysteine metabolism. Characterization of these mutations identifies patient groups at risk for vascular disease. Treatment of HH(e) consists of vitamins and raises the possibility that some forms of vascular disease may be easily, safely, and inexpensively treated.

Application of Clonal Analysis: Differential Diagnosis for Synchronous Primary Ovarian and Endometrial Cancers and Metastatic Cancer

Abstract: Simultaneous involvement of the endometrium and the ovary by carcinoma is a familiar problem in the routine practice of surgical pathology. Such cases may be considered either examples of a single primary carcinoma with metastasis or as synchronous primary neoplasms. The distinction between these two possibilities is made based on clinicopathologic observations, and therefore may not be definitive. In the present study, the authors used molecular techniques to analyze the clonal composition of five cases of concurrent adenocarcinomas of the endometrium and ovary that were clinicopathologically diagnosed as synchronous primary tumors. Patterns of X-chromosome inactivation, mutations in the K-ras gene, mutations or allelic loss of the p53 gene, or human papillomavirus detection were identical in both endometrial and ovarian lesions in three of the cases suggesting that those three cases represented single primary tumors with metastases. In both of the other two cases, the patterns of X-chromosome inactivation clearly demonstrated the presence of independent primary tumors. The application of molecular technology may play an important role for the differential diagnosis between synchronous primary carcinomas and a single carcinoma with metastasis.

Lung Tumors With a Rhabdoid Phenotype

Abstract: Six malignant tumors of the lung with a rhabdoid phenotype are described. All presented as lung masses in middle-aged to elderly adults (mean age 51 years), with no sex predilection. The tumors ranged from 1.3 cm to 8.0 cm in size and were generally associated with locally advanced disease. The distinctive (and defining) histologic feature was the presence of macronucleolated tumor cells with a large eosinophilic globular cytoplasmic inclusion. These "rhabdoid" elements comprised at least 10% of the neoplastic population. Immunohistochemistry revealed diffuse vimentin positivity in all cases. Epithelial and neuroendocrine markers were at least focally positive in five and in all six cases, respectively. Electron microscopy was performed in one case and it showed paranuclear aggregates of intermediate filaments, dense core granules, and intercellular attachments. Malignant tumors of the lung with a rhabdoid phenotype are very rare. The majority are poorly differentiated carcinomas, and they frequently show features suggesting a neuroendocrine differentiation.

Human Papillomavirus and Epstein-Barr Virus in Sinonasal Schneiderian Papillomas: An In Situ Hybridization and Polymerase Chain Reaction Study

Abstract: Using the polymerase chain reaction (PCR), it has been recently reported that the Epstein-Barr virus (EBV) is present in the majority of Schneiderian sinonasal papillomas (SNP) of the inverted type and may play a role in the pathogenesis of these lesions. The reported prevalence rates of human papillomavirus (HPV) in different types of SNP is also controversial and in need of clarification. Twenty-eight SNP from 27 patients were histologically classified and evaluated for evidence of EBV using PCR and 2 different sensitive and specific in situ hybridization (ISH) procedures for EBER1. Similarly, two methods of ISH were also used for the detection of HPV, using biotinylated DNA probes sensitive for 14 different HPV types as well as more sensitive and specific radioactive RNA probes for HPV types 6, 11, and 16. Polymerase chain reaction was successful in 19 papillomas, including 12 of 19 inverted SNP, 1 of 1 inverted SNP with squamous cell carcinoma, 4 of 5 fungiform SNP, and 2 of 3 oncocytic lesions. Southern blot hybridization of PCR products showed the presence of EBV DNA in two lesions, including one inverted SNP and the single inverted SNP with squamous cell carcinoma. By both DNA- and RNA-mRNA ISH, positivity for The nasal cavity and paranasal sinuses are predominantly lined by ciliated columnar epithelium referred to as the Schneiderian membrane, which develops as an invagination of olfactory ectoderm during the fourth week of embryonic development.1 This mucosa creates a transitional zone between the endodermally derived respiratory epithelium of the nasopharynx and the keratinizing squamous epithelium of the nasal vestibule. Three Schneiderian papillomas (SNP) arise from this unique mucosal lining, including inverted, fungiform, and oncocytic (cylindrical cell) types. From the 'Departments of Pathology. The University of Virginia Health Sciences Center. Charlottesville. Virginia; and 2The City of Hope National Medical Center. Duarte. California. Supported in part by grant #ROI-CA43629 from the Public Health Service to Mark H. Stoler. Manuscript received March 25, 1996; accepted April 29, 1996. Address reprint requests to Dr. Gaffey: Box 214, Department of Pathology, The University of Virginia Health Sciences Center, Charlottesville, VA 22908. EBER was detected in rare stromal lymphocytes but not the overlying epithelium in the inverted SNP with SCC. The remaining cases, including the other inverted SNP positive for EBV by PCR, were completely negative by both ISH techniques. Human papillomavirus was detected by ISH in 1 of 19 (5%) inverted, 1 of 1 (100%) inverted with squamous cancer, 5 of 5 (100%) fungiform, and 0 of 3 (0%) oncocytic SNP. Three SNP contained HPV 6 (all fungiform), three SNP labeled for HPV 11 (two fungiform and the inverted SNP with squamous cancer), and one inverted SNP contained HPV 16. Of the five fungiform SNP, four showed foci of koilocytosis. The results indicate that EBV is not present in sinonasal papillomas. The presence of EBV positive stromal lymphocytes in these lesions may account for a proportion of PCR-positive cases. Oncocytic SNP are unassociated with HPV, whereas inverted SNP contain HPV in a minority of cases. In contrast, fungiform SNP are consistently associated with HPV types 6 and 11 and usually show histologic evidence of viral infection.

Hematologic disorders associated with deletions of chromosome 20q: a clinicopathologic study of 107 patients.

Abstract: To study the pathogenetic significance of acquired del(20q), bone marrow morphology and clinical histories of 107 patients with hematologic disorders and the del(20q) were studied. In 84 cases representing myelodysplastic syndromes (47), myeloproliferative disorders (31), acute myeloid leukemia (3), pure red blood cell aplasia (2), and angioimmunoblastic lymphadenopathy with dysproteinemia (AILD)-like T-cell lymphoma (1), 20q- was the sole karyotypic abnormality. The break-points on chromosome 20 were not constant, and in 77% of cases, only a fraction of the studied metaphases had del(20q). In 23 cases, including myelodysplastic syndromes (13), myeloproliferative disorders (6), acute myeloid leukemia (2), and autoimmune disorders (2), 20q-occurred with other cytogenetic abnormalities, including del(5q), -7, +8, 13q deletion or translocation, and +21. Despite the diagnostic heterogeneity, the bone marrow morphologic abnormalities consistently involved the erythroid precursors and megakaryocytes. 20q- is a primary cytogenetic abnormality occurring in hematologic disorders unified morphologically by dysplasia in erythroid precursors and megakaryocytes. In conjunction with other studies of disorders involving del(20q) or genes on the long arm of chromosome 20, the findings suggest that del(20q) disproportionately affects a common megakaryocytic/RBC stem cell.

Paucicellular variant of anaplastic thyroid carcinoma : A mimic of Riedel's thyroiditis

Abstract: Anaplastic thyroid carcinomas usually pose no problems in histologic diagnosis because of the obvious invasive growth, high cellularity, and frank anaplasia. Two cases of a variant of anaplastic thyroid carcinoma with peculiar gross and histologic features closely mimicking those of Riedel's thyroiditis are described in this report. The clinical features were no different from those of the usual anaplastic thyroid carcinomas: occurrence in elderly subjects, presentation with rapidly enlarging neck mass associated with compression symptoms, and rapidly fatal outcome. The tumors were infiltrative, hard, fibrotic masses that partly or completely replaced one lobe of the thyroid, and extended to perithyroid tissues. Histologically, they were predominated by acellular fibrous or infarcted tissue with central dystrophic calcification, as well as hypocellular foci comprising mildly atypical spindle cells intermingled with collagen and small lymphocytes. Both cases showed permeation and plugging of the arteries by tumor. Lymph node metastasis was documented in one case. The spindle cells were positive for epithelial membrane antigen in both cases, and cytokeratin in one. The qualifying term "paucicellular variant" accurately describes this uncommon morphologic variant of anaplastic thyroid carcinoma. It is important to recognize this variant so as not to mistaken it for Riedel's thyroiditis, which is a reactive condition with a very favorable prognosis. The distinguishing features are as follows: presence of infarction, atypical cells in at least some areas, atypical spindle cells obliterating large blood vessels, and immunoreactivity for epithelial markers.

The Pathogenesis of Type II Diabetes Mellitus: A Polygenic Disease

Abstract: Diabetes mellitus is the most common endocrine disease, consuming almost 15% of annual health care expenditures in the United States. The focus of this review is on type II (non-insulin-dependent) diabetes mellitus, which accounts for approximately 90% of diabetic patients. The current understanding of the pathogenesis of type II diabetes is multifaceted. Complex defects in both insulin action and insulin secretion produce the metabolic derangements responsible for the disease. The pathophysiology is the result of a combination of polygene defects and environmental factors. The search for the responsible gene or genes is described and several candidate genes are discussed. Diabetogenes are addressed in the context of type II diabetes representing a prototype for the identification of the genetic basis of common diseases.