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1.
Appl Immunohistochem Mol Morphol ; 9(3): 215-21, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11556748

ABSTRACT

Prediction of biologic behavior in adrenocortical neoplasms is difficult because of the lack of availability of reliable clinical, biochemical, and pathologic prognostic markers. Reliable objective markers predictive of clinical outcome in adrenocortical neoplasms are needed to assign optimal treatment of potentially malignant tumors. In the current article, the authors evaluated a set of molecular markers (topoisomerase II alpha (Topo II alpha), MIB-1, p53, human epithelial cadherin (E-cadherin), retinoblastoma gene protein product, and HER-2/neu) and correlated their expression with histologic diagnosis and clinical outcome. Paraffin-embedded, formalin-fixed tissue blocks from 30 cases of adrenocortical neoplasms (15 benign and 15 malignant) were obtained from the surgical pathology archives at the University of Utah Health Sciences Center (Salt Lake City, UT) and the Medical College of Wisconsin (Milwaukee, WI). Age, gender, recurrence, tumor size and weight, hemorrhage, necrosis, pleomorphism, mitotic count, capsular and lymphovascular invasion, hyaline globules, intranuclear inclusions, and immunohistochemical expression of Topo II alpha, p53, MIB-1, E-cadherin, retinoblastoma gene protein product, and HER-2/neu were studied. Clinical data were obtained from the clinical charts, or communication with the treating physician, or both. Adrenocortical neoplasms with hemorrhage, necrosis, large size (>5 cm), weight more than 100 g, nuclear pleomorphism, lymphovascular invasion, and brisk mitotic rate (more than 5 per 30 high-power fields) were more likely to behave in a malignant fashion (P approximately 0.001-0.009). The difference in proliferation indices in benign and malignant neoplasms was statistically significant (P < 0.001). The difference in p53 staining in benign and malignant neoplasms also was statistically significant (P < 0.001). Higher p53 labeling index (>20%) was present in 73% (11/15) of malignant lesions but was found in only 1 of 15 (6.6%) benign lesions. The difference in retinoblastoma staining between benign and malignant neoplasms was statistically significant (P = 0.004). There was no significant difference in staining pattern of E-cadherin expression between benign and malignant lesions. HER-2/neu overexpression was not observed in any of the benign or malignant adrenocortical neoplasms.


Subject(s)
Adrenal Cortex Neoplasms/metabolism , Cadherins/metabolism , DNA Topoisomerases, Type II/metabolism , Nuclear Proteins/metabolism , Receptor, ErbB-2/metabolism , Retinoblastoma Protein/metabolism , Tumor Suppressor Protein p53/metabolism , Adrenal Cortex Neoplasms/genetics , Adrenal Cortex Neoplasms/pathology , Antigens, Neoplasm , Antigens, Nuclear , Cell Division , DNA-Binding Proteins , Genes, Tumor Suppressor , Humans , Immunohistochemistry , Ki-67 Antigen , Sensitivity and Specificity
2.
Mod Pathol ; 14(8): 806-10, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11504841

ABSTRACT

Hematoxylin-eosin (H&E)-stained sections may not allow proper evaluation of birefringence properties of the crystals in the lesions of pseudogout, gout, and tumoral calcinosis. This study was undertaken to verify the application of a special stain that could facilitate the evaluation of the birefringence properties of these crystals for definitive diagnosis. We evaluated previously described nonaqueous alcoholic eosin staining (NAES) method based on the principle of using alcoholic eosin without hematoxylin and any other aqueous reagents for staining of formalin-fixed, paraffin-embedded tissue sections. Two observers, in a blinded fashion, evaluated the sections stained with routine H&E and NEAS method without the knowledge about clinical diagnosis. All pseudogout (nine sections from seven cases) and gout (eight sections from five cases) lesions demonstrated birefringence in the sections stained with NAES method. H&E-stained sections showing the respective diagnostic histomorphology failed to demonstrate the birefringent crystals by polarizing microscopy in all the eight sections from gout and in seven of nine sections from pseudogout. Only two H&E-stained sections showed scant calcium pyrophosphate dihydrate (CPPD) crystals in pseudogout. None of the three sections from two cases of tumoral calcinosis showed birefringence with either stain. We conclude that CPPD in pseudogout and monosodium urate in gout may not polarize in the routine H&E-stained sections. However, polarizing microscopy of sections stained with NAES method allowed demonstration of CPPD crystals with positive birefringence in pseudogout, MSU crystals with negative birefringence in gout, and calcium hydroxyapatite crystals without birefringence in tumoral calcinosis. Section stained with NAES method is a significantly useful adjunct to the routine H&E stain for proper evaluation of the crystals under polarizing microscope in these lesions.


Subject(s)
Calcinosis/pathology , Chondrocalcinosis/pathology , Gout/pathology , Calcium Pyrophosphate/chemistry , Crystallization , Diagnosis, Differential , Durapatite/chemistry , Formaldehyde , Humans , Paraffin Embedding , Staining and Labeling/methods , Staining and Labeling/standards , Tissue Fixation , Uric Acid/chemistry
3.
Am J Surg Pathol ; 25(8): 1039-46, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11474288

ABSTRACT

Accurate diagnosis of micrometastases in sentinel lymph nodes of cutaneous melanoma is critical for proper clinical management. S-100 protein and HMB-45 are the traditional immunomarkers widely used for this purpose. However, the interpretation of micrometastases by these markers is difficult with significant reduction in the diagnostic accuracy. S-100 protein demonstrates immunoreactivity for other nonmelanoma cells and obscures nuclear details, which are crucial for the interpretation of single cell metastases. We compared the new melanoma markers, Melan-A (clone A103) and MART-1 (clone M2-7C10), with S-100 protein and HMB-45, by examining 77 formalin-fixed paraffin-embedded sections of sentinel lymph nodes from 13 cases of primary cutaneous melanoma. CD68 (PG-M1) and hematoxylin-eosin-stained sections were also studied. Four pathologists interpreted the staining pattern after concealing the identity of each immunomarker. Az values (area under receiver operating characteristic curve) with receiver operating characteristic curve were higher with Melan-A (0.9742) and MART-1 (0.9779) compared with S-100 protein (0.8034) and HMB-45 (0.8651), demonstrating a higher diagnostic accuracy with Melan-A and MART-1 with superior detection of melanoma micrometastases. Melan-A and MART-1 showed sharp cytoplasmic immunoreactivity, almost exclusively restricted to the melanoma cells. Therefore, Melan-A and MART-1 are recommended for the evaluation of micrometastases in sentinel lymph nodes of cutaneous melanoma as a routine alternative to S-100 protein and HMB-45.


Subject(s)
Lymph Nodes/pathology , Lymphatic Metastasis/diagnosis , Melanoma/diagnosis , Skin Neoplasms/pathology , Antigens, CD/analysis , Antigens, Differentiation, Myelomonocytic/analysis , Antigens, Neoplasm , Humans , Lymph Nodes/chemistry , MART-1 Antigen , Melanoma/chemistry , Melanoma/secondary , Melanoma-Specific Antigens , Neoplasm Proteins/analysis , Observer Variation , ROC Curve , Reproducibility of Results , S100 Proteins/analysis , Sentinel Lymph Node Biopsy , Skin Neoplasms/chemistry
4.
Am J Clin Pathol ; 115(6): 862-7, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11392883

ABSTRACT

CD10 expression in various grades and interfollicular infiltrates of follicular lymphoma (FL) has not been well documented. Immunohistochemical staining for CD10 (clone 56C6) was performed on paraffin-embedded tissue from 26 cases of classic FL. Negative or weak expression of CD10 was more frequent in grade III (5/6 [83%]) than in grade I FLs (3/15 [20%]). CD10+ interfollicular infiltrates were present in 16 cases. Six (38%) of 16 cases showed that CD10 expression was strong or moderate in follicular areas but weak or negative in interfollicular infiltrates. Our results suggest that CD10 expression is frequently weak to negative in grade III and in interfollicular infiltrates of FLs. Therefore, lack of CD10 expression on small specimens, such as from needle core biopsy or fine-needle aspiration, does not preclude the possibility of a diagnosis of FL. Furthermore, lack of CD10 expression in diffuse large B-cell lymphoma does not exclude the possibility that the neoplastic lymphocytes are of follicle center cell origin.


Subject(s)
Lymphoma, Follicular/diagnosis , Neprilysin/metabolism , Adult , Aged , Female , Flow Cytometry , Humans , Immunohistochemistry , Lymphoma, Follicular/metabolism , Lymphoma, Follicular/pathology , Male , Middle Aged , Neprilysin/immunology , Proto-Oncogene Proteins c-bcl-2/immunology , Proto-Oncogene Proteins c-bcl-2/metabolism
6.
Acta Cytol ; 45(1): 60-8, 2001.
Article in English | MEDLINE | ID: mdl-11213506

ABSTRACT

OBJECTIVE: To evaluate the possibility of routine use of air-dried smears (ADS) instead of wet-fixed smears (WFS). STUDY DESIGN: Intraoperative cytology (IC) smears from 293 specimens and fine needle aspiration cytology (FNAC) smears from 118 cases were studied. Cytomorphology of ADS processed with our protocol for hematoxylin-eosin (HE) and Papanicolaou (PAP) staining after saline rehydration and postfixation in 95% ethanol with 5% acetic acid were compared with respectively stained WFS. Additional ADS were stored up to 72 hours at room temperature prior to HE, PAP and Diff-Quik (DQ) staining to evaluate the effects of postponing rehydration and postfixation. Special stains for fungi were also studied in four cases. RESULTS: ADS were easy to prepare without air-drying artifact in the final HE- and PAP-stained smears. ADS were more cellular than WFS. Erythrocyte interference was frequent in WFS. HE and PAP staining of ADS stored up to 72 hours showed cytomorphology comparable to that of the similarly stained fresh smears. However, DQ staining was better if ADS were processed before 24 hours. ADS stained with special stain for fungi showed good morphology, similar to that in WFS. CONCLUSION: All ADS showed results comparable to or better than WFS. ADS could be stored up to 72 hours before staining with HE and PAP. ADS offers the flexibility of selecting a variety of staining methods and is a practical alternative to WFS.


Subject(s)
Biopsy, Needle/methods , Cytodiagnosis , Staining and Labeling/methods , Adult , Air , Artifacts , Cell Nucleus/ultrastructure , Humans , Intraoperative Period , Neoplasms/pathology , Neoplasms/ultrastructure , Sodium Chloride/chemistry , Tissue Fixation/methods
7.
Acta Cytol ; 44(6): 1015-22, 2000.
Article in English | MEDLINE | ID: mdl-11127730

ABSTRACT

OBJECTIVE: To evaluate the effect of fixation and methods of cytologic smear preparation on the immunoreactivity of commonly used anticytokeratin antibody AE1/AE3. STUDY DESIGN: Scrape cytology smears and formalin-fixed, paraffin-embedded tissue sections (FPTS) of 20 unfixed, fresh specimens submitted for intraoperative consultation were studied by the immunoperoxidase method. In addition to the morphologic examination, the smears and FPTS were evaluated for intensity and proportion scores. For each specimen, two scrape cytology smears were wet fixed in 95% ethanol, and 12 smears were air dried without fixation. Air-dried smears were either postfixed after rehydration in saline or fixed directly without rehydration by one of the three fixatives: alcoholic formalin, 95% ethanol with 5% acetic acid or 95% ethanol. RESULTS: Both intensity and proportion scores were higher with rehydrated, air-dried smears as compared to those without rehydration and were comparable to those with wet-fixed smears and FPTS. In the rehydrated group, the optimum results were achieved when the smears were postfixed with alcoholic formalin. CONCLUSION: The method of preparation and fixation had variable effects on the immunoreactivity of anticytokeratin antibody AE1/AE3. The optimum results were achieved with saline-rehydrated, air-dried smears post-fixed in alcoholic formalin. To evaluate the role of inter-sample variation, further, larger studies are recommended on this and other antibodies before applying them to different types of cytologic smears.


Subject(s)
Biopsy, Needle , Immunoenzyme Techniques , Keratins/metabolism , Tissue Fixation , Antibodies , Humans , Keratins/immunology , Neoplasms/pathology
8.
Appl Immunohistochem Mol Morphol ; 8(4): 267-74, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11127918

ABSTRACT

No reliable pathologic criteria have been identified that predict clinical behavior in adrenal and extra-adrenal pheochromocytomas (PHEOs). Reliable prognostic markers for the prediction of clinical outcome are needed to assign optimal treatment for potentially malignant tumors. In this report, we evaluated several molecular markers (topoisomerase II alpha, E-cadherin, HER-2/neu, and retinoblastoma (RB) gene protein) that have not been previously studied in PHEOs. Paraffin-embedded, formalin-fixed tissue blocks from 50 cases of PHEO (30 benign and 20 malignant, 31 adrenal and 19 extra-adrenal) were obtained from University of Utah Health Sciences Center, Salt Lake City, and the Medical College of Wisconsin, Milwaukee. Gross (tumor size, weight, local extension, cyst formation, hemorrhage, necrosis), microscopic (pleomorphism, hyaline globules, intranuclear inclusion, mitotic count, capsular and vascular invasion, ganglionic/neuronal differentiation), and immunohistochemical features (topoisomerase II alpha, p53, MIB-1, E-cadherin, RB, and HER-2/neu) were studied. With the exception of vascular invasion (P = 0.025), there were no unequivocal gross or microscopic characteristics that distinguished benign from malignant lesions (P approximately = 0.11-0.71). Topoisomerase III and MIB-1 indices in malignant lesions were significantly higher than those observed in benign lesions (P = 0.012 and 0.019). Differences in p53 expression were not statistically significant (P = 0.082). Loss in RB protein product expression was significantly more common in malignant lesions (P = 0.001), E-cadherin loss and HER-2/-neu overexpression were not observed in any of the benign or malignant lesions. We studied the immunohistochemical expression of topoisomerase II alpha, MIB-1, p53, RB gene protein product, E-cadherin, and HER-2/neu in a series of adrenal and extra-adrenal PHEOs. Overexpression of topoisomerase II alpha and MIB-1 and loss of RB protein product were more common in malignant lesions, whereas p53, E-cadherin, and HER-2/neu do not seem to have diagnostic utility in the prediction of biologic behavior in these neoplasms.


Subject(s)
Adrenal Gland Neoplasms/metabolism , Cadherins/biosynthesis , DNA Topoisomerases, Type II/biosynthesis , Immunohistochemistry/methods , Isoenzymes/biosynthesis , Nuclear Proteins/biosynthesis , Pheochromocytoma/diagnosis , Pheochromocytoma/metabolism , Receptor, ErbB-2/biosynthesis , Retinoblastoma Protein/biosynthesis , Tumor Suppressor Protein p53/biosynthesis , Adolescent , Adult , Aged , Aged, 80 and over , Antigens, Neoplasm , Antigens, Nuclear , Biomarkers, Tumor/metabolism , Cell Differentiation , DNA-Binding Proteins , Female , Humans , Ki-67 Antigen , Male , Middle Aged , Necrosis , Prognosis
9.
Am J Clin Pathol ; 114(5): 807-11, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11068557

ABSTRACT

The present study was designed to evaluate the lineage differentiation (particularly monocytic differentiation) of immature myeloid cells in granulocytic sarcoma (GS) by immunohistochemistry and correlate the results with lineage differentiation of blasts in the bone marrow and to determine the degree of maturation of the infiltrating myeloid cells in GS by immunohistochemistry using CD34 and HLA-DR. Immunohistochemical stains were performed on paraffin-embedded tissue from 17 GS lesions with lineage-associated markers: myeloperoxidase, CD68 (KP1), CD68 (PG-Ml), glycophorin A, factor VIII, and CD56; and with markers for blasts and immature myeloid cells: CD34 and HLA-DR. Our results show that positive staining with PG-M1, but not KP1, suggests monocytic differentiation of myeloid cells in GS and correlates with the monocytic differentiation of blasts in the bone marrow. Expression of CD56 is frequent in GS, especially when the marrow blasts have monocytic differentiation, and should not be interpreted as a primary natural-killer cell process. The immature myeloid cells in GS are frequently HLA-DR positive. However, CD34 positivity of the immature myeloid cells is relatively uncommon, except in cases with underlying myelodysplastic syndrome or chronic myelogenous leukemia.


Subject(s)
Granulocytes/immunology , Immunohistochemistry , Immunophenotyping , Sarcoma/pathology , Adolescent , Adult , Aged , Antigens, CD/analysis , Antigens, CD34/analysis , Antigens, Differentiation, Myelomonocytic/analysis , Bone Marrow Cells/pathology , CD56 Antigen/analysis , Cell Differentiation , Child , Child, Preschool , Female , Granulocytes/pathology , HLA-DR Antigens/analysis , Hematopoietic Stem Cells/immunology , Hematopoietic Stem Cells/pathology , Humans , Infant , Male , Middle Aged , Monocytes/immunology , Monocytes/pathology , Peroxidase/analysis , Retrospective Studies
10.
Arch Pathol Lab Med ; 124(9): 1291-4, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10975923

ABSTRACT

OBJECTIVES: Apoptosis is a phenomenon of physiological cell death in which each step is regulated, similar to the process of mitosis. We observed apoptosis in leukocytes during the review of peripheral blood smears. This study was undertaken to evaluate the morphologic features of apoptotic leukocytes in peripheral blood smears and to ascertain their clinical significance. DESIGN: Sixty cases (23 males and 37 females, aged newborn to 92 years) exhibiting apoptotic leukocytes in peripheral blood smears were studied. Medical records for each case were reviewed, and patients were categorized according to their clinical diagnoses. RESULTS: Neutrophils were the most common apoptotic leukocytes identified (85%), followed by lymphocytes (18%) and eosinophils (2%). The diagnosis most frequently associated with the presence of apoptotic leukocytes was infection (55%). Apoptosis in lymphocytes was comparatively less common, but when present, the most common associations were diabetes mellitus, glucocorticoid administration, and neoplastic diseases. CONCLUSIONS: Our findings suggest that the presence of apoptotic leukocytes in peripheral blood smears may help in the differential diagnosis and may be related to the severity of disease. We recommend further evaluation using additional special techniques for detecting apoptotic leukocytes.


Subject(s)
Apoptosis , Leukocytes/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Diabetes Mellitus/blood , Eosinophils/pathology , Female , Glucocorticoids/administration & dosage , Humans , Infant, Newborn , Infections/blood , Leukocyte Count , Lymphocytes/pathology , Male , Middle Aged , Neoplasms/blood , Neutrophils/pathology
11.
Arch Pathol Lab Med ; 124(8): 1233-6, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10923092

ABSTRACT

Primary non-Hodgkin lymphoma of the breast is a rare disease. Primary mucosa-associated lymphoid tissue lymphoma is even rarer, and bilateral involvement is exceptional. We describe a case of primary bilateral breast mucosa-associated lymphoid tissue lymphoma with bilateral atypical ductal hyperplasia and bilateral localized amyloidosis in a 64-year-old woman with a history of arthritis and systemic lupus erythematosus and its clinical, histologic, and immunohistochemical features. Microscopic examination of the breast lesion showed dense periductal and perilobular small and plasmacytoid lymphocytes with eosinophilic amyloid in the vessels and the stroma. Bilateral single foci of atypical ductal hyperplasia were also noted. Fine needle aspiration showed small and large lymphocytes and plasma cells. Molecular analysis demonstrated a heavy chain immunoglobulin H gene rearrangement. Flow cytometry studies showed an abnormal B-cell population. The combined histologic, paraffin immunohistochemistry, flow cytometry, and molecular results were considered diagnostic for low-grade mucosa-associated lymphoid tissue lymphoma. The patient underwent bilateral local breast radiation without other organ or site involvement.


Subject(s)
Amyloidosis/pathology , Breast Neoplasms/pathology , Hyperplasia/pathology , Lymphoma, B-Cell, Marginal Zone/pathology , Neoplasms, Ductal, Lobular, and Medullary/pathology , Neoplasms, Multiple Primary/pathology , Breast Neoplasms/radiotherapy , Calcinosis/pathology , Female , Flow Cytometry , Gene Rearrangement, B-Lymphocyte , Humans , Hyperplasia/complications , Hyperplasia/radiotherapy , Immunoglobulin Heavy Chains/analysis , Immunohistochemistry , Lymphoma, B-Cell, Marginal Zone/radiotherapy , Middle Aged , Neoplasms, Ductal, Lobular, and Medullary/complications , Neoplasms, Ductal, Lobular, and Medullary/radiotherapy , Neoplasms, Multiple Primary/radiotherapy
12.
Acta Cytol ; 44(4): 661-6, 2000.
Article in English | MEDLINE | ID: mdl-10934963

ABSTRACT

BACKGROUND: The histology of a few cases of adenocarcinoma simulating cervical microglandular hyperplasia (MGH-AdCa) has been reported. However, the cytologic features of MGH-AdCa in cervical smears and the immunohistochemical profile have not been described. CASE: A 73-year-old female presented with vaginal bleeding. The cervical Pap smear was initially interpreted by the cytotechnologist as "reactive endocervical cells" and was referred for cytopathologist review. The final interpretation was atypical glandular cells of undetermined significance (AGUS), probably neoplastic. Endometrial biopsy and total abdominal hysterectomy with bilateral salpingo-oophorectomy showed International Federation of Gynecologists and Obstetricians grade 1 endometrial carcinoma. The superficial component of the tumor resembled cervical microglandular hyperplasia (MGH); the deeper component had an endometrioid pattern. The Pap smear predominantly showed a glandular component with features of MGH. However, the presence of scattered single cells with hyperchromatic nuclei, one to three nucleoli, easily detectable mitotic figures, randomly scattered apoptotic bodies and focal, watery diathesis suggested a neoplastic process. Immunohistochemistry was studied on paraffin sections. In addition to other markers, the tumor cells were immunoreactive for carcinoembryonic antigen (CEA). CONCLUSION: Although the cervical Pap smear in this case had an MGH-like pattern, some features were atypical enough to suggest a diagnosis of AGUS, probably neoplastic. CEA immunoreactivity of MGH-AdCa could also help to differentiate it from MGH.


Subject(s)
Adenocarcinoma/diagnosis , Adenocarcinoma/pathology , Cervix Uteri/pathology , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/pathology , Aged , Diagnosis, Differential , Female , Humans , Hyperplasia/diagnosis , Hyperplasia/pathology , Papanicolaou Test , Vaginal Smears
13.
Diagn Cytopathol ; 23(2): 134-9, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10888761

ABSTRACT

The diagnostic role of intraoperative cytology (IC) has been demonstrated by many comparative studies. These studies have used sensitivity and specificity as statistical tools, based on binary principles. Statistical methods based on binary principles appear to be inappropriate for comparing anatomic pathology studies which involve significant human judgment with a range of subjective nonbinary result patterns. In this study, we applied the receiver operating characteristic (ROC) curve, which is based on probabilistic principles for the comparison of diagnostic accuracy with IC and frozen sections (FS). Seven observers studied a variable number of IC alone, FS alone, and IC/FS together from a pool of 446 specimens. The results were analyzed by ROC curve, using the MEDCALC software program (MedCalc Software, Mariakerke, Belgium). The accuracy with IC alone and FS alone was comparable. IC alone was diagnostic for many lesions, offering the choice of not freezing the tissue, and thus avoiding the introduction of artifacts. This strongly favors the routine practice of preparing IC during intraoperative consultation.


Subject(s)
Cytodiagnosis/methods , Frozen Sections/methods , Neoplasms/pathology , ROC Curve , Area Under Curve , Breast Neoplasms/pathology , Carcinoma/pathology , Carcinoma/secondary , Cystadenocarcinoma/pathology , Cystadenocarcinoma/secondary , Data Interpretation, Statistical , Female , Humans , Intraoperative Period , Male , Neoplasm Metastasis/pathology , Omentum/pathology , Ovarian Neoplasms/pathology , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/secondary , Reproducibility of Results , Soft Tissue Neoplasms/pathology , Soft Tissue Neoplasms/secondary
15.
Clin Exp Metastasis ; 18(6): 471-9, 2000.
Article in English | MEDLINE | ID: mdl-11592304

ABSTRACT

The purpose of this study was to determine if increased NF-kappaB activity of highly invasive PC-3 cells contributed to their invasive behavior. Increased NF-kappaB activity has been observed in several malignant tumors and it may have an important role in tumorigenesis, progression and chemotherapy resistance. By serial selection, we obtained invasion variant PC-3 cell sublines. The PC-3 High Invasive cells invade readily through a Matrigel reconstituted basement membrane while PC-3 Low Invasive cells have low baseline invasion activity. In these studies, we discovered that NF-kappaB DNA binding activity was increased in PC-3 High Invasive cells when compared to PC-3 Low Invasive cells by electrophoretic mobility shift assay (EMSA). Gel supershift assays showed a 4-fold increase in p65 containing complexes and a 2.2-fold increase in the p50 containing complexes in the PC-3 High Invasive cells. Luciferase reporter assays showed that NF-kappaB dependent transcription activity was increased 10.2 +/- 2.5-fold in the highly invasive cells (P < 0.002). The PC-3 High Invasive cells showed a constitutive increase in phospho-IkappaB alpha and introduction of the super-repressor IkappaB alpha S32/36A inhibited NF-kappaB activity to 19.2 +/- 2.5 percent of control transfected cells (P < or = 0.001). The IkappaBa super-repressor reduced the basement membrane invasion of PC-3 High Invasive cells from 6.2 +/- 1.1 to 3.8 +/- 0.4 percent (P < 0.002) with no decrease in cell viability or proliferation. These results demonstrate that increased NF-kappaB activity contributed directly to the invasive behavior of PC-3 High Invasive prostate cancer cells.


Subject(s)
NF-kappa B/physiology , Neoplasm Invasiveness , Prostatic Neoplasms/pathology , Prostatic Neoplasms/physiopathology , Base Sequence , Blotting, Western , Cell Division , DNA Primers , Genes, Reporter , Humans , Luciferases/genetics , Male , Phenotype , Tumor Cells, Cultured
16.
Arch Pathol Lab Med ; 123(11): 1093-7, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10539914

ABSTRACT

BACKGROUND: Lipochrome pigment granules (LPGs) and prostate-specific antigen (PSA) localization have been cited as helpful adjuncts in differentiating atypical histologic patterns of seminal vesicle-ejaculatory duct (SVED) from prostatic adenocarcinoma. However, LPGs have been described in both benign and neoplastic prostatic acini, and PSA expression within the intraprostatic SVED has not been fully explored. DESIGN: Fifty radical prostatectomy specimens were studied for LPGs and 9 cases for PSA expression. RESULTS: Two morphologic types of LPGs (type 1 and type 2) were observed. The reproducibility in classifying LPGs was evaluated by kappa statistics, which demonstrated a strong agreement between 4 observers. Type 1 was restricted to SVED in all 50 specimens. Type 2 was subclassified into 2A and 2B. Type 2 LPGs were observed in prostatic acini of different zones, high-grade prostatic intraepithelial neoplasia, prostatic adenocarcinoma, and occasionally with type 1 LPG in SVED. Focal reactivity for PSA in the distal portion of SVED near urethra was noted in 1 of 9 cases. CONCLUSION: Awareness about morphologic differences between the 2 types of LPGs could help to avoid a potential diagnostic pitfall of misinterpreting SVED epithelium for adenocarcinoma. Caution is recommended in interpreting PSA expression, since rare focal PSA reactivity was observed in the distal SVED.


Subject(s)
Adenocarcinoma/diagnosis , Adenocarcinoma/immunology , Cytoplasmic Granules/pathology , Ejaculatory Ducts/pathology , Prostate-Specific Antigen/metabolism , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/immunology , Seminal Vesicles/pathology , Adenocarcinoma/pathology , Aged , Aged, 80 and over , Diagnosis, Differential , Epithelium/pathology , Humans , Male , Middle Aged , Pigmentation , Prostatic Neoplasms/pathology , Staining and Labeling
17.
Am J Clin Oncol ; 22(2): 150-5, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10199449

ABSTRACT

Low-grade fibromyxoid sarcoma is a rare, benign-appearing soft tissue neoplasm with an aggressive clinical course characterized by multiple local recurrences over several years, with ultimate spread to lung and occasionally to bone. Thus far, a total of 24 cases of low-grade fibromyxoid sarcoma have been reported in the literature. The authors present an additional case that grossly and microscopically emphasizes a pronounced lobular pattern of contrasting areas of cellularity showing high proliferative activity, as demonstrated by a proliferation marker, Ki 67 with MIB-1, and hypocellular areas with prominent myxoid component and abundant collagen fibrils. There was predominance of delicate capillary-sized stromal vessels with collagenized walls in both cellular and myxoid areas. The unusual features in this case were osseous metaplasia, prominent intranuclear pseudoinclusions, DNA tetraploidy, and membrane-bound intracytoplasmic fat vacuoles. The immunoprofile and cytologic and ultrastructural features are described. After the excision of the tumor, the patient was treated with radiotherapy without chemotherapy. The patient has been observed for 26 months and is alive without the evidence of disease. The postoperative follow-up with axial computed tomography at 24 months showed no evidence of disease, except postsurgical fibrotic changes.


Subject(s)
Pelvic Neoplasms/pathology , Sarcoma/pathology , Adult , Biomarkers , Female , Humans , Immunohistochemistry , Pelvic Neoplasms/classification , Pelvic Neoplasms/metabolism , Pelvic Neoplasms/therapy , Ploidies , Sarcoma/classification , Sarcoma/metabolism , Sarcoma/therapy
18.
Acta Cytol ; 43(2): 207-13, 1999.
Article in English | MEDLINE | ID: mdl-10097711

ABSTRACT

BACKGROUND: There have been few studies describing the cytology of adrenal pheochromocytoma (PC). Although fine needle aspiration (FNA) for a preoperative diagnosis of PC is generally considered a contraindication, this tumor can be an unsuspected finding in adrenal FNA performed for other reasons. STUDY DESIGN: Scrape cytology smears prepared in five cases of PC were examined for different cytomorphologic features. The results were correlated with the corresponding permanent histologic sections. RESULTS: Previously described features, like cellular smears showing cells with abundant, poorly defined fragile cytoplasm, bare nuclei, anisonucleosis, "salt and pepper" chromatin, variable nucleoli and few ganglion cell-like cells, were noted. In addition, several previously unreported cytologic features were observed: (1) loosely cohesive PC cells along a ramifying, delicate central core; (2) intracytoplasmic microvesicular (not hyaline/homogeneous) globules; and (3) different arrangements of capillary-stroma and PC cells (Zellballen pattern; empty capillary rings; stroma with adherent, intact PC cells or fragments of disrupted PC cell cytoplasm). CONCLUSION: The cytologic appearance of PC may resemble that of other neuroendocrine tumors; however, it can be diagnostic when combined with proper clinical data and ancillary tests.


Subject(s)
Adrenal Gland Neoplasms/diagnosis , Adrenal Gland Neoplasms/pathology , Pheochromocytoma/diagnosis , Pheochromocytoma/pathology , Biopsy, Needle , Cell Nucleolus/pathology , Humans , Stromal Cells/pathology
19.
Acta Cytol ; 42(5): 1159-66, 1998.
Article in English | MEDLINE | ID: mdl-9755675

ABSTRACT

BACKGROUND: Solitary fibrous tumors (SFT) occur mainly in the pleura and other serosal sites. However, they have been found in extraserosal sites and should be considered in the differential diagnosis (DDx) of any spindle cell lesion, including those in the gastrointestinal tract. In this report, we describe fine needle aspiration (FNA) cytologic evaluation of a gastric SFT, emphasizing the role of immunocytochemistry in the DDx. CASE: Computerized tomography-guided FNA of a subserosal gastric mass in a 77-year-old female was performed. The moderately cellular smears showed neoplastic cells arranged in interlacing fascicles and in a "patternless" pattern. There was variable collagenous stroma. The cell block revealed a similar pattern, with a single mitotic figure. Nuclear atypia and necrosis were absent. The neoplastic cells were strongly reactive for vimentin and CD34, with weak focal reactivity for smooth muscle actin, suggestive of vessels in tangential section. They were nonreactive for muscle specific actin, desmin, S-100 and pancytokeratin. Other immunocytochemical markers were also studied. CONCLUSION: SFT should be considered in the DDx of spindle cell lesion of the stomach. Cell block and immunocytochemical markers, especially CD34, were extremely useful in the diagnosis of SFT on FNA.


Subject(s)
Neoplasms, Fibrous Tissue/diagnosis , Neoplasms, Fibrous Tissue/pathology , Stomach Neoplasms/diagnosis , Stomach Neoplasms/pathology , Aged , Antigens, CD34/analysis , Diagnosis, Differential , Female , Humans , Immunohistochemistry , Neoplasms, Fibrous Tissue/chemistry , Paraffin Embedding , Stomach Neoplasms/chemistry
20.
Am J Clin Pathol ; 95(1): 91-5, 1991 Jan.
Article in English | MEDLINE | ID: mdl-1987757

ABSTRACT

An easy, rapid, and economical method for concentration of Schistosoma mansoni ova in feces is described. The basic procedure involves 20 minutes of gravity sedimentation of a fecal suspension sieved through gauze and suspended in a 5% (volume/volume) solution of glycerol in tap water with Ig/L benzoic acid. There is excellent recovery of S. mansoni ova. It can be applied under field conditions and can be implemented by any laboratory with routine facilities. It also allows detection of other ova, larva, and to some extent, cysts.


Subject(s)
Feces/microbiology , Ovum , Parasitology/methods , Schistosoma mansoni/isolation & purification , Animals , Humans , Parasitology/economics , Preservation, Biological , Time Factors
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