Acta Cytol. 2003 Nov-Dec;47(6):1055-8.
Cytologic profile of rhabdoid tumor of the kidney. A report of 3 cases.
Barroca HM, Costa MJ, Carvalho JL.
Department of Anatomic Pathology, Hospital de S. Joao, Al. Hernani Monteiro-4200
Porto, Portugal. hbarroca@iol.pt
BACKGROUND: Malignant rhabdoid tumor of the kidney (MRTK) is a rare malignant
neoplasm that usually presents as an abdominal mass. The histogenesis is uncertain, and
cases outside the kidney have been reported. An association with separate primary
tumors of primitive neuroepithelial origin occurring in the midline of the posterior or
middle cranial fossa has been reported in approximately 15% of cases. CASES: Three
patients, a 7-month-old girl and two boys, aged of 6 and 2 months of age, underwent
fine needle aspiration biopsy (FNAB) for the diagnosis of renal masses. In 2 cases the
smears revealed round to polygonal cells, singly or arranged in irregularly shaped
clusters. The neoplastic cells did not differ much in shape and exhibited clear, empty
nuclei with prominent nucleoli; the cytoplasm was abundant and sometimes
eosinophilic. In the remaining case the aforementioned characteristics of the nuclei and
cytoplasm were not as prominent, and sheets of fibrovascular stroma, with attached
neoplastic cells, were seen. Diagnosis of MRTK was suspected in every case based
upon morphology and immunocytochemistry; the diagnosis was histologically
confirmed in the surgical specimens. CONCLUSION: MRTK may pose diagnostic
problems due to its broad morphologic spectrum. Distinction from Wilms' tumor and
clear cell sarcoma of the kidney is essential for therapeutic proposes. The results
obtained in the FNAB study of these 3 cases demonstrate that diagnosis of MRTK may
be proposed from fine needle aspiration smears using conventional methods together
with ancillary ones (immunocytochemistry and electron microscopy).
Publication Types: Case Reports
Diagn Cytopathol. 2003 Oct;29(4):194-9.
Flow cytometric S-phase fraction as a complementary biological parameter for the
cytological grading of non-Hodgkin's lymphoma.
Pinto AE, Cabecadas J, Nobrega SD, Mendonca E.
Department of Morphologic Pathology, Portuguese Oncologic Institute, Lisbon Center,
Portugal. apat@ipolisboa.min-saude.pt
Fine-needle aspiration cytology (FNAC) is a technique that can overcome tissuesampling disaggregation problems related to DNA flow cytometry analysis. The aim of
this study, with long-term follow-up (median, 72 mo), was to investigate the prognostic
value of DNA ploidy and S-phase fraction (SPF) in patients with non-Hodgkin's
lymphoma (NHL), and additionally, the relevance of SPF in the grading of NHLs, using
FNAC. The series comprised 76 patients with NHL (32 indolent and 44 aggressive
tumors, including 14 Burkitt lymphomas) and 30 patients with reactive lymph node
enlargement used as a control group. DNA flow cytometry was performed on fresh
samples obtained by FNAC. NHL grading was done according to the updated Kiel
classification. The 5-yr overall survival of patients with NHL was determined using the
Kaplan-Meier method. All samples of the control group and 81.6% of the NHLs showed
a DNA diploid pattern. Fourteen cases (18.4%) were DNA aneuploid with bimodal
distribution: slight hyperdiploidy and near-tetraploidy. Despite the higher incidence of
aneuploidy in aggressive than in indolent tumors (22.7% vs. 12.5%), no correlation
between DNA ploidy and NHL grading was observed. In contrast, SPF revealed a
strong correlation with grading (P=0.0001). The mean SPF values varied from 6.5% in
indolent NHLs, to 20.4% in aggressive not-otherwise-specified (NOS) NHLs, and to
35.3% in Burkitt lymphomas. Nearly all aggressive NHLs had an SPF >15%, while the
vast majority of indolent NHLs showed an SPF <10%. The mean SPF value in the
reactive node group was 6.6%. NHL grading significantly was correlated to survival
(P=0.004) only if the Burkitt lymphomas, which showed the best prognosis, were
analyzed as an independent group. There was a trend that did not reach statistical
significance (P=0.072) for a worse clinical outcome of patients with aneuploid tumors.
When mean SPF values were used as cutoff points to divide both indolent NHLs and
aggressive NOS NHLs into two proliferative subgroups, no differences in relation to
survival were found (P=0.763 and P=0.994, respectively). Also, no proliferative
difference was verified between indolent NHLs and the reactive lymph node group
(P=0.223). These results show that flow cytometric SPF is a valuable complementary
parameter for grading NHLs on FNAC samples, but it appears to give no additional
prognostic information on subset analyses. Copyright 2003 Wiley-Liss, Inc.
Int J Biol Markers. 2003 Jan-Mar;18(1):7-12
Overall survival in advanced breast cancer: relevance of progesterone receptor
expression and DNA ploidy in fine-needle aspirates of 392 patients.
Pinto AE, Andre S, Mendonca E, Silva G, Soares J.
Department of Pathology, Portuguese Oncological Institute, Lisbon, Portugal.
apat@ipolisboa.min-saude.pt
Fine-needle aspiration cytology (FNAC) is essential for making a diagnosis in advanced
breast cancer. The determination of hormone receptors in the material obtained is useful
for predicting patient response to endocrine therapy, but the prognostic value of
hormone receptor expression as well as the clinical utility of DNA flow cytometry are
controversial. The aim of this prospective study with long-term follow-up (median: 81
months) was to evaluate these biomarkers in relation to overall survival in a series of
392 patients with advanced breast cancer (stage IIB, n=106; IIIA, n=66; IIIB, n=174;
and IV, n=46) using FNAC. Estrogen and progesterone receptor expression was found
in 65.1% and 46.1% of the tumors, respectively. Hormone receptors were not found to
be associated with clinical staging. DNA aneuploidy was present in 70.9% of the cases
and the median S-phase fraction (SPF) was 9.4%. There was a significant correlation of
aneuploidy and high SPF with lack of hormone receptors. In univariate analysis,
advanced disease stage, absence of hormone receptors, DNA aneuploidy and high SPF
showed a statistically significant correlation with poor clinical outcome. In multivariate
analysis, disease stage, progesterone receptors and DNA ploidy retained independent
prognostic significance in relation to overall survival. These data indicate that
progesterone receptor expression and DNA ploidy are independent prognostic factors in
advanced breast cancer.
Acta Cytol. 2003 Jan-Feb;47(1):5-12
Preoperative diagnosis of suspicious parathyroid adenomas by RT-PCR using
mRNA extracted from leftover cells in a needle used for ultrasonically guided fine
needle aspiration cytology.
Cavaco BM, Torrinha F, Mendonca E, Pratas S, Boavida J, Sobrinho LG, Leite V.
Center for the Investigation of Molecular Pathobiology, Departments of Imagiology and
Endocrinology, Cytology Laboratory, Francisco Gentil Portuguese Oncology Institute,
Lisbon, Portugal.
OBJECTIVE: To determine the usefulness of reverse transcriptase-polymerase chain
reaction (RT-PCR) detection of parathormone (PTH) gene mRNA in needle aspirates to
confirm the parathyroid nature of suspicious cervical lesions in patients with
hyperparathyroidism. STUDY DESIGN: Ultrasound-guided fine needle aspiration
cytology (FNAC) was performed on 12 patients with suspected parathyroid adenomas.
The aspirates were subjected to cytologic and chromogranin A examination. Messenger
RNA was isolated from left-over cells within the needle, and RT-PCR was used to
amplify mRNA encoding PTH. RESULTS: The 12 aspirates were positive by PTH RTPCR, and molecular diagnosis was confirmed by histologic examination. The lower
sensitivity of cytologic and immunocytochemical methods was demonstrated,
respectively, by 67% and 50% of positive results. Sensitivity assays demonstrated that
with our system, PTH RT-PCR products are obtained from as few as 10 pg of
parathyroid mRNA. CONCLUSION: The present study showed that RT-PCR-based
analysis of PTH gene transcripts in aspirates, obtained by US-guided FNAC of cervical
lesions suspicious for parathyroid adenoma, is a feasible, sensitive and specific method
for preoperative diagnosis of parathyroid adenomas.
Publication Types: Evaluation Studies
Clin Cancer Res. 2003 Aug 15;9(9):3413-7.
Title : Detection of gene promoter hypermethylation in fine needle washings from
breast lesions.
Authors: Jeronimo C, Costa I, Martins MC, Monteiro P, Lisboa S, Palmeira C,
Henrique
R, Teixeira MR, Lopes C.
Department of Genetics, Portuguese Oncology Institute-Porto, 4200-072 Porto,
Portugal. cjeronimo@hotmail.com
PURPOSE: Fine needle aspiration (FNA) is used widely in diagnostic
assessment of breast lesions. However, cytomorphological evaluation depends
heavily on the proficiency of cytopathologists. Because epigenetic
alterations are frequent and specific enough to potentially augment the
accuracy of malignant disease detection, we tested whether hypermethylation
analysis of a panel of genes would distinguish benign from malignant breast
FNA washings. EXPERIMENTAL DESIGN: FNA washings were collected from 123
female patients harboring suspicious mammary lesions. Sodium
bisulfite-modified DNA was amplified by methyl-specific PCR (MSP) for CDH1,
GSTP1, BRCA1, and RARbeta to detect gene promoter CpG island methylation.
Paired samples of 27 breast cancer tissue and 7 fibroadenomas and 12 samples
of normal breast tissue, collected postoperatively, were also analyzed. MSP
results were compared with conventional cytomorphological diagnosis.
RESULTS: FNAs were cytomorphologically diagnosed as benign (25 cases),
malignant (76 cases), suspicious for malignancy (6 cases), and
unsatisfactory (16 cases). Percentages of methylated CDH1, GSTP1, BRCA1, and
RARbeta in FNA washings were 60, 52, 32, and 16%, and 65.8, 57.9, 39.5, and
34.2% for benign and malignant lesions, respectively. These differences did
not reach statistical significance. In all of the paired benign lesions
tested, there was absolute concordance. Sixty-seven percent (18 of 27) of
FNA washings displayed hypermethylation patterns identical to malignant
paired tissue. No methylation was found in the normal breast samples for any
of the genes. CONCLUSIONS: Detection of gene hypermethylation in FNA
washings by MSP analysis is feasible, but the selected gene panel does not
discriminate between benign and malignant breast lesions.
Acta Cytol 2004;48:57-63
Title: Thyroid Cell Proliferation in Graves' Disease: Use of MIB-1 Monoclonal
Antibody
Authors: Gláucia M. F. S. Mazeto, M.D., Ph.D., Maria Luiza C. S. Oliveira, Ph.D.,
Carlos R. Padovani, Ph.D., Mário R. G. Montenegro, M.D., Ph.D., Flávio F. Aragon,
Ph.D., and Fernando C. L. Schmitt, M.D., Ph.D., M.I.A.C.
Objective: To measure thyroid cell proliferation in patients with Graves' disease (GD)
before and during treatment with antithyroid drugs.
Study Design: Patients were assessed by fine needle aspiration biopsy before (n=20)
and after 4 (n=19) and 12 months of treatment (n=15) with propylthio-uracil or
methimazole. Cell proliferation index (CPI) was estimated by immunocytochemistry
using MIB-1. CPI was studied in relation to the cytologic parameters of the smears;
clinical parameters, such as Wayne's Clinical Index (WCI) and time without treatment;
laboratory parameters, such as 131I uptake and dosage of serum free thyroxin and
thyroid-stimulating hormone; and thyroid ultrasound.
Results: CPI varied from 0.00% to 25.00% before treatment, 0.00% to 23.00% at 4
months and 0.00% to 14.84% at 12 months. CPI median values were 6.50%, 4.30% and
3.30%, respectively (before and after 4 months and 12 months of treatment). CPI had a
positive correlation with WCI and FT4 at 12 months of treatment.
Conclusion: Thyroid CPI in GD varies from case to case. However, due to its
decreasing pattern during follow-up and its positive correlation with thyrotoxicosis
severity, CPI may indicate the functional status of the gland and contribute to a better
understanding of GD.
Keywords:Graves' disease, thyroid diseases, aspiration biopsy, monoclonal antibodies,
MIB-1
Acta Cytol 2004;48:187-193
Title: Comparison of Manual and Automated Methods of Liquid-Based Cytology: A
Morphologic Study
Authors: Venancio Avancini Ferreira Alves, M.D., Ph.D., Marluce Bibbo, M.D., Sc.D.,
F.I.A.C., Fernando Carlos Landèr Schmitt, M.D., Ph.D., M.I.A.C., Fernanda Milanezi,
M.D., and Adhemar Longatto Filho, M.Sc., Ph.D., P.M.I.A.C.
Objective: To evaluate the morphologic characteristics of gynecologic samples
prepared by 3 different methods of liquid-based cytology.
Study Design: Cytologic samples from representative cases of each diagnostic category
of squamous epithelial lesion, prepared by automated and manual liquid-based systems,
were analyzed by 3 laboratories in the United States, Portugal and Brazil. The systems
included: ThinPrep(r) (automated, U.S. Food and Drug Administration approved; Cytyc
Corp., Boxborough, Massachusetts, U.S.A.), Autocyte(r) PREP (South American
system, manual; TriPath Imaging, Inc., Burlington, North Carolina, U.S.A.) and
DNACITOLIQ(r) (manual; Digene Brazil, São Paulo, Brazil). A panel of 16
morphologic parameters was evaluated: cellularity, clean background, uniform
distribution, artifacts, cellular overlapping, architectural and cytoplasmic distortion,
cytoplasmic vacuolization, cellular elongation, imprecise cytoplasmic borders, folded
cytoplasmic borders, nuclear hyperchromasia, coarse chromatin, prominent nucleolus,
irregular nuclear borders, atypical mitosis and inflammatory infiltrate. Negative,
atypical squamous cells of undetermined significance, low grade squamous
intraepithelial lesion (LSIL) and high grade squamous intraepithelial lesion (HSIL)
cases were included. Cases without biopsies were confirmed by consensus.
Results: Cellularity was adequate in all samples. Clean background was observed in the
vast majority of samples with all liquid-based systems. Uniform distribution was
frequently found in ThinPrep(r) and Autocyte(r) PREP samples but not in
DNACITOLIQ(r). Artifacts were not present in DNACITOLIQ(r) samples, rare in
ThinPrep(r) and observed in 8 (34.7%) Autocyte(r) PREP. Cellular overlapping was
observed in all 3 system samples: 11 (31.42%) cases in ThinPrep(r), 16 (69.56%) in
Autocyte(r) PREP and 17 (68%) in DNACITOLIQ(r) System. Architectural and
cytoplasmic distortion were present in 3 cases of HSIL (13%) and cytoplasmic
vacuolization in 2 cases of LSIL and 1 HSIL of Autocyte(r) PREP. Cellular elongation
was found in 13 (56.5%) Autocyte(r) PREP and in 5 (20%) DNACITOLIQ(r) samples.
Inflammatory infiltrate was found in all 3 system samples but with more frequency in
the Autocyte(r) PREP (69.56%) and DNACITOLIQ(r) System (72%).
Conclusion: This study clearly indicated that in spite of the different methodologies,
the 3 methods adequately preserved cellular structure for morphologic evaluation. The
choice of method will depend on price, availability and procedures involved.
Keywords:cervix neoplasms, cervix diseases, mass screening, Papanicolaou smear,
ThinPrep(r), Autocyte(r) PREP, DNACITOLIQ(r) System