Biomedical subjects

Claire W Michael

Publications and source records attributed to Claire W Michael.

13 recordsLinked to original sources

PubMed2005

Differentiation of mesothelioma from adenocarcinoma in serous effusions: the role of hyaluronic acid and CD44 localization.

Differentiating cells of mesothelial origin from adenocarcinoma (ACA) based on morphology alone can be a diagnostic challenge, especially in cytological specimens. Malignant mesothelioma (MM) is characterized by accumulation of abundant intracellular hyaluronic acid (HA), a feature that is not reported in ACA. The purpose of this study was to evaluate the significance of cellular HA using an HA-specific binding peptide (HABP) and the expression of its principal receptor, the standard CD44 molecule (CD44S). Archival paraffin-embedded cell blocks of serous fluids from 28 cases of reactive mesothelial cells, 14 cases of MM, 20 cases of metastatic ovarian carcinomas, 17 cases of metastatic breast carcinomas, 12 cases of metastatic lung ACA, and 12 cases of metastatic gastrointestinal ACA were stained with HA using a biotinylated HABP and CD44S. Positive staining was defined as droplet to diffuse cytoplasmic staining for HA and uniform membranous staining for CD44S. All MMs and 93% (26/28) of the benign mesothelial cells were positive for intracytoplasmic HA vs. none of ACAs. CD44S was expressed in 100% (28/28) of mesothelial hyperplesia, 86% (12/14) of MMs, 70% (14/20) of ovarian carcinomas, 29% (5/17) of breast carcinomas, 25% (3/12) of gastrointestinal ACAs, and 8% (1/12) of lung ACAs. In MM and reactive mesothelial cells, CD44S stained cell membranes diffusely with highlights on the villous surfaces and in ACA it was focal and confined to cell membranes. Immunostaining with HA is a reliable marker that can distinguish between cells of mesothelial origin (reactive mesothelial cells and MM) and ACA. The CD44S staining pattern of cells of mesothelial origin is of diagnostic significance. CD44 may prove useful in conjunction with other stains in the differential diagnosis of mesothelioma and ADA.

Adenocarcinoma↗

PubMed2005

The expression pattern of beta-catenin in mesothelial proliferative lesions and its diagnostic utilities.

beta-Catenin is a component of the E-cadherin-catenin cell adhesion complex. It plays an important role in the Wnt/wg pathway, which conveys critical signals for cell proliferation and transformation. The beta-catenin mutation is an important event in the progression of a number of malignancies. In this study, we evaluated the immunohistochemical (IHC) pattern of beta-catenin in a spectrum of mesothelial lesions. Sixty-five formalin-fixed, paraffin-embedded blocks from 54 serous effusions and 11 pleural biopsies were examined. These cases consisted of 33 invasive mesotheliomas, 9 early mesotheliomas (with negative radiologic finding), so-called mesotheliomas in situ, and 23 reactive mesothelial proliferations. A distinct membranous and/or submembranous staining pattern was seen in 23 cases with normal and reactive mesothelium. In contrast, reduced membranous and/or submembranous antibody staining and markedly increased ectopic cytoplasmic and nuclear staining was seen in 26 cases of 33 mesotheliomas. Seven of 9 early mesotheliomas showed increased ectopic cytoplasmic and/or nuclear stain. On the basis of our findings, identification of beta-catenin staining pattern offers a useful marker in the diagnosis of mesothelial lesions and may help identify neoplastic change.

Ascitic Fluid↗

PubMed2005

Pulmonary lymphoma of the mucosa-associated lymphoid tissue type: Report of a case with cytological, histological, immunophenotypical correlation, and review of the literature.

A 59-year-old woman presented to The University of South Alabama, Mobile, Ala, with the complaint of shortness of breath. A chest radiograph showed bilateral nodules and interstitial infiltrates. The diagnosis of lymphoma was suggested on bronchial brush smears. Biopsy revealed a multifocal centrocyte-like lymphoid infiltrate involving the bronchial walls with lymphoepithelial lesions. The lymphocytes were positive for CD19, CD20, and CD22. A diagnosis of pulmonary lymphoma of the mucosa-associated lymphoid tissue type was established and the patient responded to chemotherapy treatment. Over the following 5 years, she suffered at least 2 recurrences involving the lung and breast for which she received additional treatment.

Antigens, CD↗

PubMed2004

Exaggerated pigmented granulomatous reaction to the artificial joint implant mimics metastatic melanoma.

Total joint replacement is a common orthopedic procedure. An artificial joint implant may fail due to mechanical mishap and a granulomatous reaction can be induced by the artificial joint debris after the mechanical failure. We report a case of an exaggerated pigmented granulomatous tissue response to metallic artificial joint implant debris in a 72-yr-old male that was mistaken for metastatic melanoma. The mass was soft, pigmented, ill-defined, and located in the right inguinal region. Fine-needle aspiration revealed numerous black-pigment laden cells. The cellular features were frequently obscured by the heavy pigmentation. Occasional cells exhibited atypia and prominent nucleoli. There were also abundant extracellular irregular small black particles dispersed in the background. The diagnosis of melanoma involving a lymph node was made. Since there was no prior history of melanoma, it was presumed that this represented metastatic melanoma from an unknown primary. A subsequent exploration of the groin was performed with the intent to resect the disease. At exploration, the mass was found to be contiguous with the hip joint and the frozen section of the mass revealed no evidence of melanoma. The final tissue diagnosis confirmed the frozen section report and showed a granulomatous reaction. This report underscores the diagnostic dilemma associated with the exaggerated pigmented granulomatous reaction due to an artificial prosthesis.

Aged↗

PubMed2004

Cryptococcal thyroiditis and hyperthyroidism.

We report a case of cryptococcal thyroiditis presenting with hyperthyroidism that evolved through a transient euthyroid phase to hypothyroidism and finally recovered to normal function. This four-phase clinical presentation is similar to that of subacute thyroiditis, and it is unusual in the setting of infectious nonviral thyroiditis. Cryptococcal thyroiditis is rare; only three cases have been reported. Our patient is the first who survived the disseminated cryptococcal infection with thyroid involvement, thus enabling longitudinal clinical and endocrinologic follow-up.

Adult↗

PubMed2004

Low-dose topical delivery of all-trans retinoic acid for cervical intraepithelial neoplasia II and III.

OBJECTIVE: The objective of this study was to determine an effective dose for all-trans retinoic acid (atRA) delivered with a cervical cap and sponge for 4 days to women with cervical intraepithelial neoplasia (CIN) II/III. METHODS: Study participants made up of 175 women with biopsy-proven CIN II/III were randomized to four consecutive days of atRA at one of three doses (0.16%, 0.28%, and 0.36%) or placebo. All subjects underwent a repeat colposcopy evaluation and biopsy of the cervix at 12 weeks. RESULTS: The study participants mean ages were 27.6 years. The racial distribution was 63% Caucasian, 27% African American, and 8% other. Among participants, 93% were human papillomavirus-positive at baseline with 68% positive for high-risk types. The disease response at 12 weeks to atRA or placebo was not significantly different (P = 0.49) among the four dose groups. Participants with CIN II at baseline were more likely to be free of disease at 12 weeks than participants with CIN III at baseline (P = 0.003). There were no reported systemic adverse events related to drug or placebo exposure and only mild local self-reported and clinician-detected toxicities. CONCLUSION: Lower concentrations of atRA applied with a cervical cap for 4 days were no more effective than placebo. However, the rate of histologic regression in biopsied CIN II/III patients was high even over a short time interval, and emphasizes the importance of having a placebo arm and an adequate sample size.

Adolescent↗

PubMed2003

Immunocytochemistry of serous effusion specimens: a comparison of ThinPrep vs cell block.

The ThinPrep Processor is gaining popularity in both gynecologic and nongynecologic cytologic samples, including effusion specimens. We compared immunocytochemical results on ThinPrep and cell-block preparations from the same effusion specimen with antibodies commonly used in effusion cytopathology. Samples from 17 reactive effusions and 79 effusions with metastatic adenocarcinomas were each prepared as monolayer ThinPreps and formalin-fixed, paraffin-embedded cell blocks. All slides were immunostained with antibodies against intermediate filaments (cytokeratins 8 and 18, and vimentin), cytoplasmic or membrane proteins (EMA, polyclonal CEA, B72.3, and BerEP4), and nuclear antigens (Ki67, PCNA, and p53), using the avidin-biotin procedure. ThinPrep and cell-block slides were stained simultaneously, using identical protocols. Both preparations showed similar results with respect to frequency of positivity, intensity, and distribution of stain for all nonnuclear markers tested. However, for the three nuclear markers Ki67, PCNA, and p53, the frequency and intensity of reaction with ThinPrep were significantly lower than with the cell-block preparation, particularly in malignant effusions. These findings suggest that immunocytochemical results obtained with ThinPrep match those of cell block for most markers tested. However, cell-block preparation are superior to ThinPrep for nuclear markers (Ki67, PCNA, and p53).

Adenocarcinoma↗

PubMed2003

Cytologic features of small-cell carcinoma on ThinPrep.

The use of ThinPrep (TP) technology for fine-needle aspiration (FNA) cytology has become widely accepted. However, some literature suggests that small-cell carcinoma may present a diagnostic pitfall due to morphologic alterations. In this study, we retrospectively compared 14 FNA of small-cell carcinoma prepared using TP with corresponding conventional smears (CS). We also examined the TP appearance of 23 other small round-cell lesions in order to determine if differential diagnostic features were preserved. TP and CS were evaluated semiquantitatively for background, architecture, chromatin quality, nuclear molding, nuclear smearing, nucleolar prominence, amount of cytoplasm, nuclear size, and single-cell necrosis. The data were analyzed using the McNemar chi(2) test. TP slides of small-cell carcinoma showed a cleaner background than CS (P < 0.005). Although some degree of nuclear molding was preserved, it was decreased in amount (P < 0.025) and subtler in quality. Similarly, nuclear smearing was present but decreased in amount (P < 0.05), and less prominent qualitatively. The amount of discernible cytoplasm was greater on TP (P < 0.005). No significant differences were found for any of the other parameters studied. The presence of nuclear molding was the single most useful feature in differentiating small-cell carcinoma from other small round-cell tumors on TP. Small-cell carcinoma may be diagnosed with confidence by FNA using TP. However, pathologists should be aware of certain morphologic alterations in order to avoid diagnostic pitfalls.

Biopsy, Fine-Needle↗

PubMed2003

Low-grade urothelial carcinoma: reappraisal of the cytologic criteria on ThinPrep.

The diagnostic criteria for low-grade urothelial lesions that have been described in the past were based on urinary specimens prepared by the cytospin method. Recognizing the recent popularity of the ThinPrep methodology and the cytologic alterations it introduces to the cellular features, we sought to evaluate the reproducibility of these criteria in ThinPrep urinary samples. One hundred twenty-six ThinPrep urinary specimens with a tissue diagnosis of low-grade urothelial carcinoma (LGUC) and 45 negative controls were evaluated. Three pathologists blindly reviewed the slides separately and the consensus on each feature was used in the study. Logistic regression analysis was used to determine which criteria in combination were most predictive of low-grade urothelial carcinoma. All specimens were evaluated for the following 18 features: nucleus/cytoplasm ratio, irregular nuclear border, cytoplasm homogeneity, cell clusters, high cellularity, prominent nucleoli, granular nuclear chromatin, hyperchromasia, acute inflammation, vesicular chromatin, nuclear molding, nuclear eccentricity, elongated nuclei, necrosis, anisonucleosis, irregular bordered fragments, absent cytoplasmic collar, and peripheral palisading. High nucleus-to-cytoplasm ratio, irregular nuclear borders, and homogeneous cytoplasm (combination sensitivity of 59% and specificity of 100%) were the best predictive features for LGUC. Minor predictive criteria were eccentric nuclei and nuclear molding. ThinPrep provides well preserved, cleaner specimens without significantly altering the morphology. The three key criteria applied in cytospin specimens to diagnose LGUC were reproducible in ThinPrep specimens.

Adult↗

PubMed2002

Global profiling of the cell surface proteome of cancer cells uncovers an abundance of proteins with chaperone function.

There is currently limited data available pertaining to the global characterization of the cell surface proteome. We have implemented a strategy for the comprehensive profiling and identification of surface membrane proteins. This strategy has been applied to cancer cells, including the SH-SY5Y neuroblastoma, the A549 lung adenocarcinoma, the LoVo colon adenocarcinoma, and the Sup-B15 acute lymphoblastic leukemia (B cell) cell lines and ovarian tumor cells. Surface membrane proteins of viable, intact cells were subjected to biotinylation then affinity-captured and purified on monomeric avidin columns. The biotinylated proteins were eluted from the monomeric avidin columns as intact proteins and were subsequently separated by two-dimensional PAGE, transferred to polyvinylidene difluoride membranes, and visualized by hybridization with streptavidin-horseradish peroxidase. Highly reproducible, but distinct, two-dimensional patterns consisting of several hundred biotinylated proteins were obtained for the different cell populations analyzed. Identification of a subset of biotinylated proteins among the different cell populations analyzed using matrix-assisted laser desorption ionization and tandem mass spectrometry uncovered proteins with a restricted expression pattern in some cell line(s), such as CD87 and the activin receptor type IIB. We also identified more widely expressed proteins, such as CD98, and a sushi repeat-containing protein, a member of the selectin family. Remarkably, a set of proteins identified as chaperone proteins were found to be highly abundant on the cell surface, including GRP78, GRP75, HSP70, HSP60, HSP54, HSP27, and protein disulfide isomerase. Comprehensive profiling of the cell surface proteome provides an effective approach for the identification of commonly occurring proteins as well as proteins with restricted expression patterns in this compartment.

Activin Receptors, Type II↗

PubMed2002

Can true papillary neoplasms of breast and their mimickers be accurately classified by cytology?

BACKGROUND: The cytologic accuracy in assessing malignancy in papillary breast neoplasms (PBNs) is controversial. This is further complicated by overlapping features observed in other breast lesions that produce papillary-like tissue fragments. METHODS: The authors reviewed 22 fine-needle aspirates (FNAs) from histologically proven papillary neoplasms: papillary carcinoma (PCA; 10 aspirates) and intraductal papilloma (IDP; 12 aspirates). They also reviewed 8 FNAs in which a papillary neoplasm was suggested by cytology but not confirmed by follow-up biopsy: fibroadenoma (6), mucinous carcinoma (1), and cribriform ductal carcinoma in situ (1). RESULTS: Papillary carcinoma can be distinguished from IDP by the higher cellularity, more complex papillae with thin disorganized fronds, mild to moderate nuclear atypia, and prominent dissociation with many single papillae. Fibrovascular cores (FVCs) were more common in PCA than IDP in which detached fibrous tissue fragments were frequently seen. Atypical IDP exhibited features intermediate between PCA and IDP. Apocrine metaplasia was variably present in IDP, atypical IDP, and fibroadenoma but absent in all carcinomas. Intraductal papilloma can be distinguished from fibroadenoma by their broad ruffled branches, scalloped borders, and tiny tongue-like projections. True papillae were commonly covered by tall columnar cells. Myoepithelial cells were few in IDP but were numerous in fibroadenoma. The epithelial fragments in nonpapillary lesions presented as cellular spheres and/or complex sheets with finger-like projections but lacked FVCs and columnar cells. CONCLUSIONS: Papillary breast neoplasms can be accurately classified by cytology. Closer evaluation of the tissue fragments architecture and the background can help in separating PBN from their mimics.

Adenocarcinoma, Mucinous↗

PubMed2002

Diagnosis of melanoma aspirates on ThinPrep: the University of Michigan experience.

The purpose of this study was to compare the cytologic features of melanoma fine-needle aspirates (FNAs) prepared by ThinPrep (TP) with those in conventional smears (CS) and to identify any diagnostic pitfalls. Fifty-one aspirates diagnosed as melanoma were obtained, 36 of which were prepared by both TP and CS. The preparations were evaluated for cellularity, cell aggregates, cellular appearance, melanin pigment, cytoplasmic, and nuclear features. Categorical data were analyzed by the chi-square test and continuous data by the Wilcoxin-signed rank test. Correlation was determined by Spearman's test for bivariate correlations (rho). Good correlation between the two methods was identified for the following features: cellularity, cell type, bi/multinucleated cells, cytoplasmic features, NC ratio, and presence of macronucleoli. TP exhibits coarser chromatin compared to CS (P = 0.005). Six of 36 CS contained large cellular groups; none of the TP contained them (P = 0.018). Twenty-five of 36 CS contained intranuclear inclusions as opposed to 12/36 TP (P < 0.001). The number of inclusions was significantly reduced on TP. The amount of intracellular melanin was the same with both techniques. Background melanin was markedly reduced on TP except when either trapped by fibrin or attached to cellular clusters (P = 0.006). Background blood was also markedly reduced on TP (P < 0.005). In summary, the cytological features of TP and CS for FNA evaluation of melanoma correlate well; however, one needs to be aware of the cytologic alterations introduced by TP. TP is a sufficient preparation method in the diagnosis of melanoma FNA aspirates when performed by clinicians. It is also a useful adjunct in bloody or low-cellular aspirates, where it tends to reduce the background blood and concentrate the cells.

Adult↗

PubMed2002

Atypical glandular cells of undetermined significance. Histologic findings and proposed management.

OBJECTIVE: To increase understanding of the clinical significance of atypical glandular cells of undetermined significance (AGUS) on cervical cytology and to suggest a management plan. STUDY DESIGN: All Pap smears classified as AGUS over a period of five years at the University of Michigan Medical Center were reviewed and the diagnosis confirmed. The charts of these patients were reviewed for demographics, significant previous medical history, symptoms, diagnostic studies performed and final histologic diagnoses. RESULTS: In 1993-1998, a total of 208,041 Pap smears were read. Two hundred seven smears from 189 patients were classified as AGUS, for an incidence of 0.1%. There were 136 patients with follow-up information and 114 patients with histologic diagnoses. In 55 of the 114 patients (48%), significant histologic abnormalities were observed, including 11 endometrial cancers, 1 invasive adenocarcinoma of the cervix, 3 adenocarcinomas in situ of the cervix, 18 CIN 3 lesions and 5 CIN 2 lesions. Among 20 patients with Pap smears subclassified as "atypical glandular cells of undetermined significance, favor benign process," there were two CIN 2, five CIN 3 and one adenocarcinoma in situ of the cervix. CONCLUSION: A diagnosis of AGUS requires an aggressive workup because of the high rate of cancer and precancerous lesions. The evaluation, at the very least, should include colposcopy with directed biopsies and endocervical curettage. Postmenopausal patients, those with irregular bleeding and those with high risk characteristics should also undergo endometrial biopsy.

Adenocarcinoma↗