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1.
AJNR Am J Neuroradiol ; 34(6): 1237-41, 2013.
Article in English | MEDLINE | ID: mdl-23306012

ABSTRACT

BACKGROUND AND PURPOSE: T2-weighted MRI shows potential in early posttreatment assessment of the primary tumor. Residual masses composed entirely of low T2-signal scar tissue suggest local control and those ≥1 cm of similar signal to untreated tumor suggest local failure. The purpose of this study was to investigate the diagnostic accuracy of T2-weighted MR imaging early after chemoradiotherapy for identifying primary tumor treatment failure in squamous cell carcinoma of the head and neck. MATERIALS AND METHODS: At 6 weeks after treatment, T2-weighted MR images of 37 primary tumors in 37 patients were assessed. Residual masses were divided into 3 patterns: pattern 1 = scar tissue only (flat-edged/retracted mass of low T2 signal intensity); pattern 2 = mass without features described in pattern 1 or 3; and pattern 3 = any pattern that included an expansile mass ≥1 cm of intermediate T2 signal intensity (similar grade of signal intensity to the untreated tumor). T2 patterns were analyzed for local outcome (Fisher exact test) and time to local failure (univariate and multivariate analysis of T2 pattern, age, T stage, and tumor size by use of the Cox regression model). RESULTS: Residual masses after treatment were present in 34 (92%) of 37 patients. Local failures occurred in residual masses with pattern 1 in 0 (0%) of 14 patients; pattern 2 in 6 (55%) of 11 patients; and pattern 3 in 9 (100%) of 9 patients. Significant associations were found between local control and pattern 1 (P = <.0001; sensitivity, 74%; specificity, 100%; PPV, 100%; NPV, 75%; accuracy, 85%), and between local failure and pattern 3 (P = <.0001; sensitivity, 60%; specificity, 100%; PPV, 100%; NPV, 76%; accuracy, 82%). Pattern 2 showed no significant associations with local outcome. Univariate analysis of time to local failure showed that the T2 pattern was significant (P < .0001) and remained significant on multivariate analysis. CONCLUSIONS: T2-weighted MR imaging is a potential tool for early posttreatment assessment of primary HNSCC treatment response. Awareness of correlation of the T2 pattern of any residual mass with treatment outcome at the primary site may contribute to patient treatment.


Subject(s)
Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy , Diffusion Magnetic Resonance Imaging/methods , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/therapy , Aged , Diffusion Magnetic Resonance Imaging/standards , Drug Monitoring/methods , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm, Residual/pathology , Neoplasm, Residual/therapy , Predictive Value of Tests , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity , Treatment Failure
2.
J Clin Pathol ; 61(8): 945-9, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18552172

ABSTRACT

BACKGROUND: Cytological diagnosis of mammary papillary lesions is difficult. AIM: To review the previous cytology diagnosis of 23 papillomas and 11 papillary carcinomas and specific cytological features that may assist in differentiating these entities. METHODS: The cytology preparations were reviewed for: (i) overall cellularity; (ii) epithelial cell ball devoid of fibrovascular cores; (iii) background single cells; and (iv) papillary fragments and their morphology. RESULTS: The overall diagnostic accuracy was 59%, atypical rate was 24%, and the error (combined false positive and negative) rate was 17%. For overall cellularity, 6, 14 and 3 cases of papillomas, and 6, 3 and 2 cases of papillary carcinomas showed low, moderate and high cellularity, respectively. Cell balls were present in mild to moderate number in 20 papillomas and 10 papillary carcinomas. The background single cells were absent, or present in low or moderate to high numbers in 7, 10 and 6 papillomas, and 3, 3 and 5 papillary carcinomas, respectively. Papillary fragments were absent, or present in small, moderate or large quantities in 9, 4, 8 and 2 papillomas, and 6, 3, 1 and 1 papillary carcinomas, respectively. There was no demonstrable quantitative difference between papilloma and papillary carcinoma for all these parameters. Qualitatively, the cell balls and single cells showed a higher degree of atypia in papillary carcinoma, and the papillary fragments were more elaborate and slender. CONCLUSION: Cytological diagnosis of papillary lesions shows a significant error rate with overlapping features. Cellular atypia and fragments with long and slender papillae with ramifying edges favour papillary carcinoma.


Subject(s)
Breast Neoplasms/pathology , Carcinoma, Papillary/pathology , Papilloma/pathology , Adult , Aged , Aged, 80 and over , Biopsy, Needle , Diagnosis, Differential , Female , Humans , Middle Aged , Sensitivity and Specificity
3.
AJNR Am J Neuroradiol ; 29(6): 1209-14, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18467517

ABSTRACT

BACKGROUND AND PURPOSE: The development of a new polyp or mass in the radiation field of a previously treated carcinoma is usually an ominous sign of a recurrent cancer, but rarely may it be caused instead by a nonmalignant process. The purpose of this study was to document the MR appearance of unusual nonmalignant polyps or masses (NMPMs) in the nasopharynx and sphenoid sinus arising after radiation treatment of nasopharyngeal carcinoma. MATERIALS AND METHODS: The MR imaging reports of patients undergoing imaging after radiation therapy for nasopharyngeal carcinoma were reviewed retrospectively to identify patients with unusual polyps and masses in the nasopharynx. The MR images of those patients with no evidence of malignancy on biopsy or follow-up were reviewed. RESULTS: The MR imaging reports of 1282 patients were reviewed, and 11 patients (1%) with NMPMs in the nasopharynx or sphenoid sinus were identified. Two patterns were identified: contrast enhancing nasopharyngeal polyps ranging in size from 1 to 5 cm (n = 5) and sphenoid sinus masses consisting of a nonenhancing mass filling a nonexpanded sinus (n = 4) and a heterogeneous enhancing mass expanding the sinus (n = 2). Osteoradionecrosis produced a large defect in the roof of the nasopharynx causing direct communication with the sphenoid sinus (n = 6). Histology revealed granulation tissue in all of the patients with variable amounts of fibrin and inflammatory cells. A direct infective etiology was not proved in any patient. CONCLUSION: NMPMs in the nasopharynx and sphenoid sinus are rare complications after radiation therapy to the skull base, but the radiologist needs to be aware of their appearance so that they can be considered in the differential diagnosis of suspected tumor recurrence.


Subject(s)
Magnetic Resonance Imaging/methods , Nasal Polyps/pathology , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/radiotherapy , Nasopharynx/pathology , Sphenoid Sinus/pathology , Adult , Female , Humans , Male
4.
J Clin Pathol ; 61(1): 11-9, 2008 Jan.
Article in English | MEDLINE | ID: mdl-17873114

ABSTRACT

Breast lesions with mucin represent a broad spectrum of entities, ranging from benign fibrocystic changes with luminal mucin to mucocele-like lesions (MLL), which can be associated with banal epithelial alterations, atypical ductal hyperplasia or ductal carcinoma in situ. Occasionally invasive mucinous carcinoma can be identified in contiguity with MLL. Diagnostic challenges are enumerated, histological differentials are discussed, and a practical approach towards resolving some of these issues is provided. In addition to these lesions with abundant extracellular mucin, there are also conditions that feature stromal mucinous or myxoid material, as well as rare entities that demonstrate both epithelial extracellular and stromal mucin.


Subject(s)
Breast Diseases/pathology , Breast Neoplasms/pathology , Mucins/analysis , Adenocarcinoma, Mucinous/pathology , Breast/pathology , Carcinoma, Ductal, Breast/pathology , Diagnosis, Differential , Female , Fibrocystic Breast Disease/pathology , Humans , Hyperplasia/pathology , Mucocele/pathology
5.
J Clin Pathol ; 60(3): 315-20, 2007 Mar.
Article in English | MEDLINE | ID: mdl-16698948

ABSTRACT

BACKGROUND: Histological differentiation of mammary papillary lesions can be difficult. The evaluation of myoepithelial cells can be helpful, with benign papilloma showing a continuous myoepithelial cell layer, which becomes attenuated or absent in malignant papillary lesions. METHODS: A large series of 100 papillomas (28 papillomas with florid epithelial hyperplasia) and 68 papillary carcinomas (9 invasive, 44 in situ, and 15 ductal carcinomas in situ (DCIS) involving papillomas) of the breast were stained for myoepithelial cells by immunohistochemistry using antibodies to smooth-muscle actin (SMA), p63, CD10 and cytokeratin (CK) 14. RESULTS: In the papillomas, using these four antibodies, myoepithelial cells were positive in 88%, 99%, 91% and 95% of cases, respectively, with SMA showing marked stromal component cell staining and CD10 showing epithelial and stromal staining. CK14 also showed epithelial staining in 71% of papillomas and 96% of papillomas with florid epithelial hyperplasia. In the papillary carcinomas, 36 (53%) cases showed staining of myoepithelial cells that were scattered, discontinuous and diminished in number and the remaining 32 (47%) cases did not show myoepithelial cells. Invasive papillary carcinoma has the lowest proportion (33%) with myoepithelial cells, and DCIS involving papillomas had the highest proportion (87%). CONCLUSIONS: p63 had the highest sensitivity and did not cross-react with stromal cells and only rarely with epithelial cells. CK14 has the added ability to distinguish between florid epithelial hyperplasia involving papilloma and DCIS involving papillomas. CK14 and p63 may be used as an adjunct in assessing difficult papillary lesions of the breast.


Subject(s)
Biomarkers, Tumor/metabolism , Breast Neoplasms/metabolism , Actins/metabolism , Adult , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Carcinoma, Intraductal, Noninfiltrating/metabolism , Carcinoma, Intraductal, Noninfiltrating/pathology , Carcinoma, Papillary/metabolism , Carcinoma, Papillary/pathology , DNA-Binding Proteins/metabolism , Diagnosis, Differential , Female , Humans , Keratin-14/metabolism , Middle Aged , Neoplasm Proteins/metabolism , Neprilysin/metabolism , Papilloma/metabolism , Papilloma/pathology , Papilloma, Intraductal/metabolism , Papilloma, Intraductal/pathology , Trans-Activators/metabolism , Transcription Factors , Tumor Suppressor Proteins/metabolism
6.
AJNR Am J Neuroradiol ; 27(8): 1654-7, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16971607

ABSTRACT

Although transcutaneous ultrasound combined with fine-needle aspiration is often used as initial modality for evaluating superficial neck masses, its role in management of deep-seated neck masses is limited. Intraoral ultrasound and guided biopsy helps in obtaining tissue from deep-seated neck masses for an accurate histologic diagnosis, providing useful information in treatment planning. This article discusses the role of intraoral ultrasound and presents 3 cases in which biopsy of deep-seated neck masses under intraoral ultrasound guidance helped in diagnosis and management.


Subject(s)
Biopsy, Needle , Nasopharyngeal Neoplasms/diagnostic imaging , Nasopharyngeal Neoplasms/pathology , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/pathology , Oropharyngeal Neoplasms/diagnostic imaging , Oropharyngeal Neoplasms/pathology , Pharyngeal Neoplasms/diagnostic imaging , Pharyngeal Neoplasms/pathology , Surgery, Computer-Assisted , Ultrasonography, Interventional , Adenoma, Pleomorphic/diagnostic imaging , Adenoma, Pleomorphic/pathology , Adult , Aged, 80 and over , Biopsy, Needle/instrumentation , Carcinoma/diagnostic imaging , Carcinoma/pathology , Diagnosis, Differential , Epstein-Barr Virus Infections/diagnostic imaging , Epstein-Barr Virus Infections/pathology , Female , Humans , Incidental Findings , Lymphatic Metastasis/pathology , Magnetic Resonance Imaging , Male , Middle Aged , Nasopharynx/diagnostic imaging , Nasopharynx/pathology , Nerve Sheath Neoplasms/diagnostic imaging , Nerve Sheath Neoplasms/pathology , Oropharynx/diagnostic imaging , Oropharynx/pathology , Pharynx/diagnostic imaging , Pharynx/pathology , Surgery, Computer-Assisted/instrumentation , Ultrasonography, Interventional/instrumentation
7.
J Clin Pathol ; 58(11): 1185-8, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16254109

ABSTRACT

BACKGROUND/AIMS: CD44s, the standard form of CD44, has been shown to be downregulated during malignant transformation of breast cancers. It has also been reported recently to be a useful marker in differentiating between benign and malignant papillary lesions of the breast, with high expression in the former. CD44s expression in benign and malignant papillary lesions was evaluated. METHODS: CD44s expression was assessed by immunohistochemistry in 101 benign papillomas and 59 papillary carcinomas (seven invasive papillary carcinomas, 41 papillary ductal carcinomas in situ, and 11 ductal carcinomas involving papillomas). RESULTS: Patients' age and tumour size were significantly different between the papilloma and papillary carcinoma groups (p < 0.0001). CD44s showed positive staining in 45 papillomas (45%) and five papillary carcinomas (8%), and the difference was significant (p < 0.0001). The myoepithelial cells, when present, were also positive for CD44s in both groups, with no observable differences. Using CD44s positive staining to differentiate between benign and malignant papillary lesions gives a sensitivity, specificity, and accuracy of 45%, 92%, and 62%, respectively. CONCLUSIONS: CD44s may be useful as an adjunct in the evaluation of morphologically problematic cases of papillary lesion of the breast.


Subject(s)
Biomarkers, Tumor/metabolism , Breast Neoplasms/diagnosis , Carcinoma, Papillary/diagnosis , Hyaluronan Receptors/metabolism , Papilloma, Intraductal/diagnosis , Adult , Aged , Aged, 80 and over , Antigens, Neoplasm/metabolism , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/diagnosis , Carcinoma, Ductal, Breast/pathology , Carcinoma, Papillary/pathology , Diagnosis, Differential , Female , Humans , Middle Aged , Papilloma, Intraductal/pathology , Sensitivity and Specificity
8.
Cancer J ; 11(2): 113-21, 2005.
Article in English | MEDLINE | ID: mdl-15969986

ABSTRACT

PURPOSE: One of the features of thyroid carcinoma is its predilection for women of reproductive age relative to men. An increased risk has also been documented in women who have used estrogens for gynecologic reasons. The aim of this study was to explore the mechanism by which sex hormones contribute to the development of thyroid carcinoma, which is not well understood at present. MATERIALS AND METHODS: In this study, we investigated the effects of estradiol and testosterone on cell proliferation in a human thyroid papillary carcinoma cell line (KAT5) by MTT assay. We also studied the expression of estrogen receptors and the levels of anti-apoptotic Bcl-xL protein, pro-apoptotic Bax protein, and messenger RNA in the cells by Western blot and reverse transcriptase polymerase chain reaction analysis. RESULTS: The results showed that estradiol promotes cell proliferation when compared with cells treated with testosterone and untreated cells, and that the growth-promoting effect of estradiol was attenuated by tamoxifen. The expression of Bcl-xL was markedly increased in a dose-dependent manner, resulting in an elevated ratio of Bcl-xL to Bax. DISCUSSION: We conclude that estradiol promotes KAT5 cell proliferation and that the underlying mechanism may be associated with up-regulation of Bcl-xL expression. The data provide insight into the molecular mechanism underlying the epidemiologic data that shows a two- to threefold increased prevalence of thyroid carcinoma in women relative to men. From the therapeutic point of view, the finding that estradiol enhances anti-apoptotic signaling pathways may be significant in the search for novel prevention and treatment strategies of thyroid carcinomas.


Subject(s)
Carcinoma, Papillary/metabolism , Estrogens/pharmacology , Proto-Oncogene Proteins c-bcl-2/metabolism , Testosterone/pharmacology , Thyroid Neoplasms/metabolism , Blotting, Western , Carcinoma, Papillary/epidemiology , Cell Proliferation/drug effects , Estrogens/metabolism , Female , Gene Expression Profiling , Humans , In Vitro Techniques , Male , Proto-Oncogene Proteins c-bcl-2/genetics , Receptors, Estrogen/drug effects , Receptors, Estrogen/metabolism , Receptors, Steroid/drug effects , Receptors, Steroid/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Sex Factors , Testosterone/metabolism , Thyroid Neoplasms/epidemiology , United States/epidemiology , bcl-X Protein
9.
J Clin Pathol ; 58(6): 600-4, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15917410

ABSTRACT

BACKGROUND: Nitric oxide synthase (NOS), particularly endothelial and inducible forms (e/i-NOS), are expressed in various cancers, including breast cancer. In mammary fibroepithelial lesions, NOS expression in stromal cells has been reported to be lower in fibroadenomas than in phyllodes tumours. AIMS: To investigate NOS expression in phyllodes tumours of varying degrees of malignancy. METHODS: One hundred and sixty seven mammary phyllodes tumours (97 benign, 47 borderline malignant, and 23 frankly malignant) were evaluated for e-NOS and i-NOS expression by immunohistochemistry. Correlations with previously reported expression of stromal vascular growth factor (VEGF) and microvessel density were also performed. RESULTS: Stromal expression of e-NOS was absent, weak, moderate, and strong in 43%, 31%, 13%, and 13% of benign tumours; 17%, 26%, 13%, and 44% of borderline malignant tumours; and 17%, 35%, 13%, and 35% of frankly malignant tumours, respectively. Stromal expression of i-NOS was 77%, 18%, 4%, and 1% in benign tumours; 42%, 28%, 19%, and 11% in borderline malignant tumours; and 43%, 13%, 26%, and 18% in frankly malignant tumours, respectively. Stromal expression of both i-NOS and e-NOS was significantly different between the benign and malignant (borderline and frank) groups of phyllodes tumours (p < 0.0001). Furthermore, the expression of i-NOS correlated with stromal VEGF expression and microvessel density. The expression of NOS in the epithelial cells was strong, and showed no differences between the different groups of tumours. CONCLUSIONS: Higher stromal expression of NOS in phyllodes tumours is associated with malignancy, suggesting a possible role in malignant progression, particularly metastasising potential.


Subject(s)
Breast Neoplasms/enzymology , Nitric Oxide Synthase/metabolism , Phyllodes Tumor/enzymology , Adolescent , Adult , Aged , Breast Neoplasms/blood supply , Breast Neoplasms/pathology , Disease Progression , Epithelial Cells/enzymology , Female , Humans , Middle Aged , Neovascularization, Pathologic , Nitric Oxide Synthase Type II , Nitric Oxide Synthase Type III , Phyllodes Tumor/blood supply , Phyllodes Tumor/secondary , Stromal Cells/enzymology , Vascular Endothelial Growth Factor A/metabolism
10.
Clin Radiol ; 60(5): 592-8, 2005 May.
Article in English | MEDLINE | ID: mdl-15851048

ABSTRACT

AIM: To evaluate the feasibility of performing in vivo proton magnetic resonance spectroscopy ((1)H-MRS) of cervical lymph nodes, and the clinical usefulness of the technique in the characterization of cervical lymphadenopathy. MATERIALS AND METHODS: Cervical lymphadenopathy was examined in 20 individuals with malignant disease, i.e. 10 with squamous cell carcinoma (SCC), 6 with undifferentiated carcinoma (UDC) and 4 with non-Hodgkin's lymphoma (NHL). Cervical lymphadenopathy was also examined in 4 individuals with benign disease, i.e. 3 with tuberculosis (TB) and 1 with Castleman's disease. A point-resolved spectroscopic sequence with echo times (TE) of 136 and 272 ms and a time-domain spectral fitting procedure were used to estimate peak amplitude of choline (Cho), creatine (Cr) and unsuppressed water. Cho/Cr and Cho/water ratios were measured for each lesion. The mean ratio for each lesion group was obtained and results were compared statistically. RESULTS: At TE of 136 ms, spectra were interpretable in all 24 cases and a Cr peak was identified with post-processing in 15 cases. The Cho/Cr and Cho/water ratios for NHL were 9.1 +/- 5.2 and 1.7 +/- 0.2 x 10(-3), for UDC were 4.4 +/- 0.9 and 1.2 +/- 0.4 x 10(-3), and for SCC were 2.1 +/- 0.6 and 0.5 +/- 0.3 x 10(-3), respectively. Both Cho/Cr and Cho/water ratios for UDC were significantly higher than SCC (p = 0.002 and 0.026, respectively). At TE of 272 ms, spectra were interpretable in 22 of 24 cases and a Cr peak was identified with post-processing in 11 cases. Cho/Cr and Cho/water ratios for NHL were 5.4 and 4.6 +/- 1.4 x 10(-3), for UDC were 4.2 +/- 1.5 and 2.6 +/- 1.0 x 10(-3) and for SCC were 2.5 +/- 1.1 and 1.3 +/- 0.6 x 10(-3), respectively. The Cho/water ratio for UDC was significantly higher than for SCC (p = 0.04). The Cho/Cr ratio for UDC was also higher than for SCC, but this difference was not statistically significant (p = 0.07). Neither Cho nor Cr was detected in the 3 cases of TB. CONCLUSION: In vivo (1)H-MRS is a feasible technique for the evaluation of cervical lymph nodes and it offers potential as a clinical tool in the investigation of cervical lymphadenopathy. However, further studies with larger patient cohorts are needed to validate the findings of this initial report.


Subject(s)
Lymphatic Metastasis/diagnosis , Magnetic Resonance Spectroscopy/methods , Adult , Aged , Aged, 80 and over , Carcinoma/diagnosis , Carcinoma/secondary , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/secondary , Castleman Disease/diagnosis , Diagnosis, Differential , Feasibility Studies , Female , Humans , Lymphoma, Non-Hodgkin/diagnosis , Male , Middle Aged , Neck , Tuberculosis, Lymph Node/diagnosis
11.
J Clin Pathol ; 58(2): 185-9, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15677540

ABSTRACT

BACKGROUND/AIMS: CD10 (CALLA) has recently been reported to be expressed in spindle cell neoplasia, and has been used to differentiate endometrial stromal sarcoma from leiomyoma and leiomyosarcoma. In the breast, myoepithelial cells express CD10, but there are few studies of the expression of CD10 in mammary fibroepithelial lesions. METHODS: Stromal CD10 expression was studied in 181 mammary phyllodes tumours (102 benign, 51 borderline malignant, and 28 frankly malignant) and 33 fibroadenomas using immunohistochemistry, to evaluate whether differences in expression correlated with the degree of malignancy. RESULTS: There was a progressive increase in the patients' age and tumour size, from fibroadenoma to phyllodes tumours with an increasing degree of malignancy (p < 0.001). Stromal CD10 expression was positive in one of 33 fibroadenomas, six of 102 benign phyllodes tumours, 16 of 51 borderline malignant phyllodes tumours, and 14 of 28 frankly malignant phyllodes tumours. The difference was significant (p < 0.001) and an increasing trend was established. Strong staining was seen in subepithelial areas with higher stromal cellularity and activity. Stromal CD10 expression had a high specificity (95%) for differentiating between benign lesions (fibroadenomas and benign phyllodes tumours) and malignant (borderline and frankly malignant) phyllodes tumours. CONCLUSIONS: CD10 may be a useful adjunct in assessing malignancy in mammary fibroepithelial lesions.


Subject(s)
Breast Neoplasms/immunology , Fibroadenoma/immunology , Neprilysin/immunology , Phyllodes Tumor/immunology , Stromal Cells/immunology , Adolescent , Adult , Aged , Breast Neoplasms/pathology , Female , Fibroadenoma/pathology , Humans , Immunohistochemistry/methods , Middle Aged , Phyllodes Tumor/pathology
12.
J Cell Biochem ; 92(6): 1246-56, 2004 Aug 15.
Article in English | MEDLINE | ID: mdl-15258907

ABSTRACT

Heme oxygenase-1 (HO-1) plays a role in the resistance to apoptosis of several types of cells, but its role in the development of thyroid cancer is unknown. In this study, we investigated the regulation of HO-1 in human papillary thyroid carcinoma cells (KAT5). The results show that HO-1 is significantly induced by hemin and cadmium. In addition to inducing HO-1, hemin and cadmium also cause a rise in the levels of p21, a cyclin-dependent kinase inhibitor. Cells with increased levels of HO-1 and p21 were more resistant to apoptotic stimuli than cells with normal levels. The cells resistant to apoptosis also displayed an increased arrest at the G(0)/G(1) phase of the cell-cycle. The induced levels of HO-1 and p21 were significantly reduced by p38 mitogen-activated protein kinase (p38 MAPK) and extracellular-regulated kinase (ERK) inhibitors. More importantly, KAT5 cells regained their sensitivity to apoptotic stimuli after they were treated with these kinase inhibitors, indicating that p38 MAPK and ERK are required for the resistance to apoptosis conferred by HO-1. Furthermore, we demonstrated that increased levels of HO-1 and p21 expression are associated with an increase in the activity of NF-kappaB and that inhibiting NF-kappaB leads to a block in the induction of HO-1 and p21. In summary, this study reveals that an increase in the level of HO-1 markedly reduces the sensitivity of papillary thyroid carcinoma cells to apoptotic stimuli. The HO-1 pathway of apoptosis resistance is associated with an increase in the levels of p21, involves a p38 MAPK and ERK-mediated mechanism and can be suppressed by inhibiting NF-kappaB.


Subject(s)
Apoptosis/physiology , Carcinoma, Papillary/pathology , Cycloheximide/pharmacology , Heme Oxygenase (Decyclizing)/physiology , Thyroid Neoplasms/pathology , Tumor Necrosis Factor-alpha/pharmacology , Cadmium/pharmacology , Cell Cycle , Cell Line, Tumor , Cell Separation , Flow Cytometry , Gene Expression Regulation/drug effects , Humans , NF-kappa B/physiology , Up-Regulation
13.
Acta Radiol ; 45(2): 148-53, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15191097

ABSTRACT

PURPOSE: To determine the potential role of a computer-assisted detection (CAD) algorithm as a second reader for experienced and inexperienced radiologists in mammography reading in Asian women. MATERIAL AND METHODS: Two-view mammograms performed in 124 consecutive patients who presented with palpable breast cancer masses were retrospectively evaluated by two experienced breast radiologists (7 and 10 years' experience). The original reports of the session radiologists with variable experience of reading mammograms (2 to more than 10 years) were also evaluated. The number of suspicious masses and microcalcification clusters detected in each patient by both groups of radiologists were recorded. The radiologists then re-evaluated the films with the CAD system as a second reader. Any improvement in the detectability of breast pathology by either the experienced radiologists and/or by the session radiologists was then assessed. A total of 127 breasts had biopsy-proven carcinoma; 74 breasts had mastectomy performed. All the imaging results were correlated with tru-cut biopsy or mastectomy histology. RESULTS: With CAD-aided interpretation, there were altogether 95 visible masses and 77 suspicious microcalcification clusters in 109 mammographically detectable cancers correlated with histology results. There was a 7.4% (7/95) and 10.4% (8/77) increase in the number of masses and microcalcification clusters detected, respectively, by the experienced radiologists after application of CAD, whereas the increase was 13.7% (13/95) and 27.3% (21/77) for detection of masses and microcalcifications by the session radiologists, respectively. In 9 patients, a secondary focus detected by CAD was confirmed by histology. Three patients had contralateral breast tumors, 1 had a satellite invasive tumor while 5 had ductal carcinoma in situ on the same breast. Based on the biopsies and 74 mastectomies, the true-positive and false-positive detection rate of CAD was 92.6% and 31.8% for detection of carcinomas. The true-positive and false-positive detection rates were 100% and 58.8% for microcalcification clusters. CONCLUSION: The current generation CAD algorithm helped to improve the detection rate of carcinomas, calcifications and multifocality in Asian breasts.


Subject(s)
Breast Neoplasms/diagnostic imaging , Radiographic Image Interpretation, Computer-Assisted , Adult , Aged , Aged, 80 and over , Algorithms , Calcinosis/diagnostic imaging , Female , Hong Kong , Humans , Mammography , Middle Aged , Observer Variation , Palpation , Retrospective Studies
15.
J Clin Pathol ; 57(3): 256-9, 2004 Mar.
Article in English | MEDLINE | ID: mdl-14990595

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome (SARS) is a newly described form of atypical pneumonia linked to a novel coronavirus. AIMS: To review the sputum cytology of 15 patients who fulfilled the World Health Organisation clinical criteria for SARS in an attempt to evaluate whether early diagnosis is feasible with routine sputum examination. METHODS: All sputum samples from patients with SARS from the four major hospitals in Hong Kong were reviewed; abnormalities were sought in the cellular component, including abnormal numbers and morphology of the component cells compared with those from age matched controls taken over the same period one year ago. RESULTS: Fifteen sputum samples from patients were compared with 25 control samples. In the patients with SARS, loose aggregates of macrophages were seen more frequently in the sputum. These macrophages frequently showed morphological changes, such as cytoplasmic foaminess, vacuole formation, and nuclear changes (including multinucleation and a ground glass appearance) when compared with the control samples. CONCLUSIONS: The cytological features of SARS are non-specific, but the observation of any of the described features should prompt further investigations, especially in patients with suspicious clinical features.


Subject(s)
Severe Acute Respiratory Syndrome/pathology , Sputum/cytology , Adult , Aged , Cell Nucleus/pathology , Cytoplasm/pathology , Female , Humans , Lung/pathology , Macrophages/pathology , Male , Middle Aged , Vacuoles/pathology
16.
J Clin Pathol ; 57(3): 260-5, 2004 Mar.
Article in English | MEDLINE | ID: mdl-14990596

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome (SARS) became a worldwide outbreak with a mortality of 9.2%. This new human emergent infectious disease is dominated by severe lower respiratory illness and is aetiologically linked to a new coronavirus (SARS-CoV). METHODS: Pulmonary pathology and clinical correlates were investigated in seven patients who died of SARS in whom there was a strong epidemiological link. Investigations include a review of clinical features, morphological assessment, histochemical and immunohistochemical stainings, ultrastructural study, and virological investigations in postmortem tissue. RESULTS: Positive viral culture for coronavirus was detected in most premortem nasopharyngeal aspirate specimens (five of six) and postmortem lung tissues (two of seven). Viral particles, consistent with coronavirus, could be detected in lung pneumocytes in most of the patients. These features suggested that pneumocytes are probably the primary target of infection. The pathological features were dominated by diffuse alveolar damage, with the presence of multinucleated pneumocytes. Fibrogranulation tissue proliferation in small airways and airspaces (bronchiolitis obliterans organising pneumonia-like lesions) in subpleural locations was also seen in some patients. CONCLUSIONS: Viable SARS-CoV could be isolated from postmortem tissues. Postmortem examination allows tissue to be sampled for virological investigations and ultrastructural examination, and when coupled with the appropriate lung morphological changes, is valuable to confirm the diagnosis of SARS-CoV, particularly in clinically unapparent or suspicious but unconfirmed cases.


Subject(s)
Coronavirus/isolation & purification , Lung/pathology , Severe Acute Respiratory Syndrome/pathology , Adult , Aged , Aged, 80 and over , Cell Division , Cell Nucleus/pathology , Cells, Cultured , Female , Humans , Immunohistochemistry/methods , Lung/virology , Male , Microscopy, Electron , Middle Aged , Pulmonary Alveoli/pathology , Severe Acute Respiratory Syndrome/virology
18.
J Clin Pathol ; 56(11): 866-7, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14600135

ABSTRACT

A 56 year old man with previously unsuspected recurrence of squamous cell carcinoma of the oesophagus presented with dyspnoea. Bronchoscopy and computed tomography suggested bronchopneumonic changes with an infectious cause. He suffered a rapidly deteriorating course and died despite active treatment, including antibiotics and mechanical ventilation. Necropsy revealed a florid pulmonary tumour microembolism mimicking alveolitis. No bronchopneumonia was seen. The emboli arose from loosely attached tumour vegetations in the tricuspid valve. In a patient with known malignancy, tumour microembolism should be considered as an uncommon cause of rapid respiratory failure, refractory to antibiotic treatment.


Subject(s)
Lung Neoplasms/diagnosis , Lung Neoplasms/secondary , Neoplastic Cells, Circulating/pathology , Pneumonia/diagnosis , Pulmonary Embolism/diagnosis , Carcinoma, Squamous Cell/complications , Diagnosis, Differential , Esophageal Neoplasms/complications , Fatal Outcome , Humans , Male , Middle Aged , Pulmonary Alveoli , Pulmonary Embolism/etiology
19.
J Clin Pathol ; 56(7): 519-21, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12835297

ABSTRACT

AIMS: Granulomatous mastitis (GM) is an uncommon breast lesion that mimics carcinoma. The fine needle aspiration cytological (FNAC) features of GM have rarely been discussed in the literature. These features are reported in eight histologically confirmed cases of GM. METHODS: A retrospective study was undertaken in which a diagnosis of GM had been made on histopathology, and the FNAC slides were reviewed and assessed for the presence of granulomas, necrosis, multinucleated giant cells, and inflammatory background cells. Polymerase chain reaction (PCR) for Mycobacterium tuberculosis was performed on the histological material to exclude tuberculosis. RESULTS: All cases were confirmed histologically and PCR for mycobacterial DNA was negative. In the FNACs, varying numbers of granulomas composed of epithelioid histiocytes were present in four cases. The same four cases showed giant cells of either foreign body or Langhan's type. No necrosis was noted. Six cases showed many histiocytes, some plump and others epithelioid, in the background. The number of epithelioid histiocytes corresponded to the presence of granulomas. Neutrophils were the predominant background inflammatory cells in most cases (six). CONCLUSIONS: The cytological diagnosis of GM is difficult because the features overlap with other aetiologies, including tuberculosis. Specific features are absent. The absence of necrosis and a predominantly neutrophilic infiltrate in the background favour a diagnosis of GM. This diagnosis should also be considered when abundant epithelioid histiocytes are seen in smears, even in the absence of granulomas. However, the definitive diagnosis of GM depends on histology from fine needle biopsies and negative microbiological investigations.


Subject(s)
Granuloma/pathology , Histiocytes/pathology , Mastitis/pathology , Adult , Biopsy, Needle , Diagnosis, Differential , Female , Granuloma, Foreign-Body/pathology , Granuloma, Giant Cell/pathology , Humans , Langerhans Cells/pathology , Middle Aged , Neutrophils/pathology , Retrospective Studies
20.
J Clin Pathol ; 56(6): 468-70, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12783976

ABSTRACT

Intravascular lymphomatosis (IVL) is a rare angiotrophic large cell lymphoma producing vascular occlusion of arterioles, capillaries, and venules. Antigenic phenotyping shows that these lymphomas are mostly of B cell type, and less commonly T cell or Ki-1 lymphomas. The central nervous system and skin are the two most commonly affected organs; patients usually present with progressive encephalopathy with mental status changes and focal neurological deficits and skin petechia, purpura, plaques, and discolouration. Other involved organs include adrenal glands, lungs, heart, spleen, liver, pancreas, genital tract, and kidneys. Bone marrow, blood, cerebrospinal fluid, and lymph nodes are typically spared. Fever of unknown origin is another common presentation. Only one case of IVL presenting with disseminated intravascular coagulation and anasarca (generalised oedema) has been reported in the literature. This report describes a postmortem case of a patient with IVL who initially presented with disseminated intravascular coagulation complicated by intracerebral haemorrhage.


Subject(s)
Disseminated Intravascular Coagulation/etiology , Lymphoma, Large B-Cell, Diffuse/complications , Vascular Neoplasms/complications , Adult , Cerebral Hemorrhage/etiology , Fatal Outcome , Female , Humans , Male
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