Publications by authors named "Čedna Tomasović-Lončarić"

22 Publications

  • Page 1 of 1

Comparison of Androgen Receptor, VEGF, HIF-1, Ki67 and MMP9 Expression between Non-Metastatic and Metastatic Stages in Stromal and Tumor Cells of Oral Squamous Cell Carcinoma.

Life (Basel) 2021 Apr 10;11(4). Epub 2021 Apr 10.

School of Dentistry, University of Zagreb, 10000 Zagreb, Croatia.

Objectives: Oral squamous cell carcinoma (OSCC) is the most common oral malignancy with low survival as it is very often diagnosed at an advanced stage, which is why the accurate profiling of the tumor is essential. The aim of this study was to, for the first time, compare in OSCC the frequency of AR, VEGF, MMP9, HiF1beta and Ki67 between the non-metastatic and metastatic disease.

Materials And Methods: In the study, 96 non-metastatic and 91 metastatic OSCC patients were analysed for AR, VEGF, MMP9, HiF1beta and Ki67 levels by immunohistochemistry.

Results: All of the tested biomarkers significantly differed between non-metastatic and metastatic disease. A significant association was found between >/=20% AR positive epithelium cells in cytoplasm, Ki67 and VEGF in cancer stroma. Ki67, HiF1beta, VEGF and MMP9 were significantly associated with TNM stages.

Conclusion: Our results show for the first time an interplay between AR, VEGF, MMP9, HiF1beta and Ki67 in OSCC which may contribute to better diagnostics and therapy selection.
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http://dx.doi.org/10.3390/life11040336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069576PMC
April 2021

Androgen Receptor as a Biomarker of Oral Squamous Cell Carcinoma Progression Risk.

Anticancer Res 2019 Aug;39(8):4285-4289

School of Dentistry, University of Zagreb, Zagreb, Croatia.

Background/aim: Oral squamous cell carcinoma (OSCC) is a cancer with poor prognosis due to therapy resistance, locoregional recurrences, and distant metastases. There is on increased interest in profiling the androgen receptor (AR) in cancer biology. The aim of this study was to compare AR and Ki-67 levels in the neoplastic epithelium and stroma between non-metastatic and metastatic stages of OSCC.

Patients And Methods: Tissue specimens of 101 non-metastatic and 95 metastatic OSCC patients were analyzed by immunohistochemistry.

Results: More than 20% of AR-positive cytoplasmic staining of OSCC epithelium was significantly associated with nuclear AR levels in the epithelium and increased AR levels in the stroma. In metastatic OSCC patients, Ki-67 was significantly higher than in non-metastatic OSCC patients.

Conclusion: More than 20% of AR-positive cytoplasmic staining in neoplastic OSSC epithelium is a significant predictor of OSCC progression risk.
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http://dx.doi.org/10.21873/anticanres.13593DOI Listing
August 2019

SONOELASTOGRAPHIC FEATURES OF HIGH-RISK BREAST LESIONS AND DUCTAL CARCINOMA - A PILOT STUDY.

Acta Clin Croat 2019 Mar;58(1):13-22

1Department of Diagnostic and Interventional Radiology, Dubrava University Hospital, Zagreb, Croatia; 2University of Zagreb, School of Medicine, Zagreb, Croatia; 3Department of Pathology, Dubrava University Hospital, Zagreb, Croatia; 4Department of Plastic and Reconstructive Surgery, Dubrava University Hospital, Zagreb, Croatia; 5Department of Physiology and Immunology, University of Zagreb, School of Medicine, Zagreb, Croatia.

The aim of this study was to evaluate the quantitative sonoelastographic values recorded on shear-wave sonoelastography (SWE) of high-risk breast lesions and ductal carcinoma (DCIS). We retrospectively analyzed histopathologic and SWE data (quantitative maximum, minimum and mean stiffness, lesion-to-fat ratio (E-ratio), lesion size) of 228 women referred to our Department for core needle breast biopsy during a four-year period. Among 230 lesions, histopathologic findings showed 34 high-risk breast lesions and 29 DCIS, which were compared with 167 ductal invasive carcinomas. High-risk lesions had lower values of all sonoelastographic features than ductal and invasive carcinoma, however, only E-ratio showed a statistically significant difference in comparison to DCIS (3.7 . 6, p<0.001). All sonoelastographic features showed significant difference between and invasive carcinoma. There was a significant correlation between lesion size and stiffness (r=0.36; p<0.001). Stiffness measured by SWE is an effective predictor of the histopathologic severity of sonographically detectable breast lesions. Elasticity values of high-risk lesions are significantly lower than those of malignant lesions. Furthermore, we showed that along with the sonographic appearance, which in most cases shows typical microcalcifications, DCIS had significantly different elasticity parameters than invasive carcinoma.
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http://dx.doi.org/10.20471/acc.2019.58.01.02DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6629205PMC
March 2019

Inter-laboratory comparison of Ki-67 proliferating index detected by visual assessment and automated digital image analysis.

Breast Dis 2019 ;38(2):73-79

Department of Pathology, General Hospital Slavonski Brod, Croatia.

Background: Proliferation rate is a major determinant of the biologic behavior of the tumor and provides information that can be used to guide treatment decisions.

Methods: This ring study included 27 pathologists from 14 Institutions, in order to assess inter-observer concordance between pathologists in Croatia. We analyzed Ki-67 proliferative index on ten randomly selected breast cancer samples comparing consistency between visual assessment using light microscopy compared to digital image analyses results from one central laboratory as a referral value.

Results: When we analyzed Ki-67 as numeric value high concordance rate was found between Ki-67 score visually assessed in all participating Institutions compared to referral value assessed by digital image analysis (ICC 0.76, 95% CI 0.58-0.91), and Krippendorff's alpha was 0.79 (95% CI 0.58-1.00). Concordance was better in slides with higher Ki-67 values. When we categorized Ki-67 values according to generally accepted 20% cut-off value we noticed the lower concordance rate among participants in our study.

Conclusion: Proliferation remains one of the most important parameters for tumor characterization helpful in making clinical decisions, but it should be used with great caution. Standardization of the Ki-67 assessment is essential and proliferating index should be expressed as exact numeric value. For patients with proliferative index near the cut-off value, other factors must be considered in making clinical decisions.
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http://dx.doi.org/10.3233/BD-180341DOI Listing
November 2019

Primary dural lymphoma mimicking meningioma: a clinical and surgical case report.

J Surg Case Rep 2018 Aug 6;2018(8):rjy189. Epub 2018 Aug 6.

Department of Neurosurgery, University Hospital Dubrava, Zagreb, Croatia.

Introduction: Primary central nervous system lymphoma and its subtype, primary dural lymphoma, are types of non-Hodgkin's lymphoma that only occur in the central nervous system without any dissemination. They are extremely rare cases of extra nodal lymphomas accounting for 1--5% of intracranial tumors.

Case Report: We present a patient diagnosed with primary dural lymphoma in right frontal brain region who underwent surgical resection. Histopathological analysis revealed diffuse B-type large cell non-Hodgkin lymphoma. Patient underwent four cycles of R-CHOP and intrathecal methotrexate protocol. Six months postoperative, no signs of newly onset infiltration were present.

Discussion: Primary dural lymphoma most likely presents with unusual radiological signs, which can easily be mistaken for meningioma, the main differential diagnosis. A thorough immunological, histopathological and clinical patients profile should be conducted in order to establish the certainty of diagnosis. Although there are few treatment options: surgery, radiotherapy or chemotherapy, there is no established treatment protocol.
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http://dx.doi.org/10.1093/jscr/rjy189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6077807PMC
August 2018

Significance of stroma in biology of oral squamous cell carcinoma.

Tumori 2018 Jan-Feb;104(1):9-14

11 Department for Oncoplastic and Reconstructive Surgery, Clinic for Tumours, Clinical Hospital Centre "Sisters of Mercy", Zagreb - Croatia.

The worldwide annual incidence of oral squamous cell carcinoma (OSCC) is over 300,000 cases with a mortality rate of 48%. This cancer type accounts for 90% of all oral cancers, with the highest incidence in men over 50 years of age. A significantly increased risk of developing OSCC exists among smokers and people who consume alcohol daily. OSCC is an aggressive cancer that metastasizes rapidly. Despite the development of new therapies in the treatment of OSCC, no significant increase in 5-year survival has been recorded in the past decades. The latest research suggests focus should be put on examining tumor stroma activation within OSCC, as the stroma may contain cells that can produce signal molecules and a microenvironment crucial for the development of metastases. The aim of this review is to provide an insight into the factors that activate OSCC stroma and hence faciliate neoplastic progression. It is based on the currently available data on the role and interaction between metalloproteinases, cytokines, growth factors, hypoxia factor and extracellular adhesion proteins in the stroma of OSCC and neoplastic cells. Their interplay is additionally presented using the Systems Biology Graphical Notation in order to sublimate the collected knowledge and enable the more efficient recognition of possible new biomarkers in the diagnostics and follow-up of OSCC or in finding new therapeutic targets.
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http://dx.doi.org/10.5301/tj.5000673DOI Listing
May 2018

Positron emission tomography-computed tomography and 4-hydroxynonenal-histidine immunohistochemistry reveal differential onset of lipid peroxidation in primary lung cancer and in pulmonary metastasis of remote malignancies.

Redox Biol 2017 04 11;11:600-605. Epub 2017 Jan 11.

Rudjer Boskovic Institute, LabOS, Zagreb, Croatia. Electronic address:

The Aim of the study was to reveal if PET-CT analysis of primary and of secondary lung cancer could be related to the onset of lipid peroxidation in cancer and in surrounding non-malignant lung tissue.

Methods: Nineteen patients with primary lung cancer and seventeen patients with pulmonary metastasis were involved in the study. Their lungs were analyzed by PET-CT scanning before radical surgical removal of the cancer. Specific immunohistochemistry for the major bioactive marker of lipid peroxidation, 4-hydroxynonenal (HNE), was done for the malignant and surrounding non-malignant lung tissue using genuine monoclonal antibody specific for the HNE-histidine adducts.

Results: Both the intensity of the PET-CT analysis and the HNE-immunohistochemistry were in correlation with the size of the tumors analyzed, while primary lung carcinomas were larger than the metastatic tumors. The intensity of the HNE-immunohistochemistry in the surrounding lung tissue was more pronounced in the metastatic than in the primary tumors, but it was negatively correlated with the cancer volume determined by PET-CT. The appearance of HNE was more pronounced in non-malignant surrounding tissue than in cancer or stromal cells, both in case of primary and metastatic tumors.

Conclusions: Both PET-CT and HNE-immunohistochemistry reflect the size of the malignant tissue. However, lipid peroxidation of non-malignant lung tissue in the vicinity of cancer is more pronounced in metastatic than in primary malignancies and might represent the mechanism of defense against cancer, as was recently revealed also in case of human liver cancer.
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http://dx.doi.org/10.1016/j.redox.2017.01.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5256674PMC
April 2017

The case of synchronous occurrence of primary adenocarcinoma and squamous cell carcinoma in the same lobe of the lung.

Acta Clin Belg 2017 Aug 26;72(4):289-292. Epub 2016 Sep 26.

c Department for Thoracic Surgery , Dubrava University Hospital , Zagreb , Croatia.

Synchronous occurrence of multiple lung cancers in the same lobe of the lung is very rare. Most of the tumors diagnosed in this way have the same histologic type. With imaging methods it is difficult to determine if the multiple lung lesions present hematogenous spread of lung cancer (or cancer from other origin) or these lesions present the second primary lung cancer. We report a rare and unusual case of synchronous occurrence of primary adenocarcinoma and squamous cell carcinoma in the same lobe of the lung. Our case demonstrates that in case of synchronous occurrence of multiple lung lesions each lesion should be sampled and histologic type of every lesion should be determined so the further treatment can be planned accordingly.
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http://dx.doi.org/10.1080/17843286.2016.1237697DOI Listing
August 2017

Canonical Wnt/β-Catenin Signaling Pathway Is Dysregulated in Patients With Primary and Secondary Myelofibrosis.

Clin Lymphoma Myeloma Leuk 2016 09 8;16(9):523-526. Epub 2016 Jun 8.

Department of Hematology, University Hospital Dubrava, Zagreb, Croatia; University of Zagreb, School of Medicine, Zagreb, Croatia.

Introduction: β-Catenin is a central effector molecule of the canonical wingless-related integration site (Wnt) signaling pathway. It is important for maintenance of stem cell homeostasis and its aberrant activation has been implicated in a wide array of malignant hematological disorders. There are few reports suggesting its dysregulation in Philadelphia chromosome-negative (Ph-) myeloproliferative neoplasms (MPNs).

Patients And Methods: We analyzed β-catenin mRNA expression in bone marrow (BM) aspirates of 29 patients with primary (PMF) and 4 patients with secondary, post Ph- MPN, myelofibrosis (SMF) using quantitative real-time polymerase chain reaction (qRT PCR). The control group consisted of 16 BM aspirates from patients with limited-stage aggressive non-Hodgkin lymphoma without BM involvement. We compared relative gene expression with clinical and hematological parameters.

Results: Relative expression of β-catenin differed significantly among groups (P = .0002), it was significantly higher in patients with PMF and SMF than in the control group, but did not differ between patients with PMF and SMF. A negative correlation was found regarding hemoglobin level in PMF (P = .017). No association according to Janus kinase 2 (JAK2) V617F mutational status or JAK2 V617F allele burden was detected.

Conclusion: Our results show for the first time that β-catenin mRNA expression is increased in patients with PMF and SMF and its upregulation might potentiate anemia. A number of inflammatory cytokines associated with PMF are capable of mediating their effects through increased β-catenin expression. Accordingly, β-catenin can induce expression of a number of genes implicated in processes of cell cycle control, fibrosis, and angiogenesis, which are central to the PMF pathogenesis. Therefore, β-catenin might represent an interesting new therapeutic target in these diseases.
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http://dx.doi.org/10.1016/j.clml.2016.06.004DOI Listing
September 2016

Shear-wave sonoelastographic features of invasive lobular breast cancers.

Croat Med J 2016 Feb;57(1):42-50

Gordana Ivanac, Department of Diagnostic and Interventional Radiology, Breast Unit, University Hospital Dubrava, University of Zagreb School of Medicine, Avenija G.Šuška 6, 10000 Zagreb, Croatia,

Aim: To evaluate shear-wave elastographic (SWE) and related gray-scale features of pure invasive lobular breast carcinoma (ILC) and compare them with invasive ductal breast cancers (IDC).

Methods: Quantitative SWE features of mean (El-mean), maximum (El-max), minimum (El-min) elasticity values of the stiffest portion of the mass, and lesion-to-fat elasticity ratio (E-ratio) were measured in 40 patients with pure ILC and compared with 75 patients with IDC. Qualitative gray-scale features of lesion size, echogenicity, orientation, and presence of distal shadowing were determined and compared between the groups.

Results: ILC were significantly larger than IDC (P=0.008) and exhibited significantly higher El-max (P=0.015) and higher El-mean (P=0.008) than IDC. ILC were significantly more often horizontally oriented, while IDC were significantly more often vertically oriented (P<0.001); ILC were significantly more often hyperechoic than IDC (P<0.001). Differences in stiffness between ILC and IDC determined by quantitative SWE parameters were present only in small tumors (≤1.5 cm in size), ie, small ILC had significantly higher El-max (P=0.030), El-mean (P=0.014), and El-min (P=0.045) than small IDC, while tumors larger than 1.5 cm had almost equal stiffness, without significant differences between the groups.

Conclusion: Specific histopathologic features of ILC are translated into their qualitative sonographic and quantitative sonoelastographic appearance, with higher stiffness of small ILC compared to small IDC. Gray-scale and sonoelastographic features may help in diagnosing ILC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800323PMC
http://dx.doi.org/10.3325/cmj.2016.57.42DOI Listing
February 2016

Simultaneous presentation of oral and skin anaplastic large T-cell lymphoma.

Acta Clin Croat 2014 Jun;53(2):246-51

We present case of oral and skin anaplastic T-cell lymphoma in a 68-year-old woman. The patient presented with extensive ulcerations and necrotic tissue on the left mandibular gingiva. Orthopantomogram finding showed extensive necrolytic lesions of the adjacent mandible. Biopsy finding of oral lesions and subsequently of the skin confirmed the diagnosis of anaplastic T-cell lymphoma. The bridge on the teeth 35-37 was taken out. After three cycles of chemotherapy, oral lesions subsided, unlike skin lesions. Dentists should be aware that differential diagnosis when dealing with oral ulcerations might be the result of certain malignant hematologic diseases.
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June 2014

Inflammatory pseudotumor presenting as a facial swelling.

Coll Antropol 2012 Nov;36 Suppl 2:143-6

University of Zagreb, Dubrava University Hospital, Department of Maxillofacial Surgery, Zagreb, Croatia.

We present a case of inflammatory pseudotumor (IPT) presenting as a facial swelling after an accidental hit on a right side of a face. As swelling did not resolve, dental examination and teeth extraction were done by a dentist presuming the swelling was misdiagnosed with infection of dental origin. Swelling grew even bigger and patient was referred to Department of Maxillofacial Surgery. CT scan of the face and FNA of the lesion was ordered. A homogenous tumor mass in the right infraorbital region in front of anterior wall of the maxillary sinus was seen on CT The result of the FNA was reactive hyperplasia of the lymph node. Since the lesion was easily accessible surgical exploration and complete extirpation was done. Pathohistological analysis indicated a low grade B-cell Non Hodgkin lymphoma. PCR showed policlonality of B cells discarding the diagnosis of lymphoma. Pathohistological review showed diffuse intramuscular, perineural and perivascular infiltration with small lymphocytes without formation of germinative centers. Imunohistochemistry was positive for CD20 and CD3. Taking into account all features the diagnosis of IPT was established. Diagnosis of IPT is a diagnosis by exclusion, combining clinical, radiological and pathohistological characteristics. Lack of clear histologic criteria makes differential diagnosis extremely difficult. Our case is unique regarding localisation of head & neck IPT no case presenting on the face in infraorbital region has been described in the literature. Although IPT is very rare in general and especially on the face, one should be aware of it when considering differential diagnosis of facial swelling.
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November 2012

Renal cell carcinoma with concurrent urothelial carcinoma of urinary bladder and non-Hodgkin lymphoma.

Coll Antropol 2012 Sep;36(3):1049-52

Dubrava University Hospital, Department of Pathology, Zagreb, Croatia.

We report a case of a 71-year-old male with multiple primary malignancies involving kidney and urinary bladder, combined with synchronous lymphoma. The patient was admitted to the hospital because of painless gross hematuria. Examination revealed tumor of the right kidney and papillary tumor in the urinary bladder and enlarged lymph nodes along aorta and inferior vena cava. Transurethral resection of bladder tumor (TUR), radical nephrectomy of the right kidney and retroperitoneal lymphadenectomy were performed. Pathohistologic evaluation, together with immunohistochemistry, gave the patient the final diagnosis of renal cell carcinoma (RCC), urothelial carcinoma of the urinary bladder and B- small cell Non-Hodgkin lymphoma (B-CLL).
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September 2012

Diffuse skin hyperpigmentation in CD30+ lymphoproliferation.

Ann Saudi Med 2012 May-Jun;32(3):318-20

Department of Internal Medicine, University Hospital Dubrava, Zagreb, Croatia.

CD30+ T-cell lymphoproliferative disorders (LD) comprise two main groups of diseases: CD30+ LD of the skin and systemic anaplastic large cell lymphoma (ALCL). The main feature of these disorders is the expression of CD30. We present a patient with an unusual clinical presentation of CD30+ lymphoproliferative disease in a 54-year old Caucasian male who presented with generalized lymphadenopathy and pronounced skin hyperpigmentation. In the lymph nodes and skin, CD30+ lymphoproliferation (ALCL) was diagnosed. The Prussian blue staining identified that the pigment responsible for the skin color was hemosiderin. Chemotherapy was started but the patient's condition progressively worsened and he died a week after the first cycle. The complete color transformation of the entire skin due to hemosiderin accumulation is, to the best of our knowledge, the first reported observation in a CD30+ lymphoproliferation/ALCL patient. We speculate that hemosiderin-loaded macrophages resulted from the paraneoplastic process by some still unknown mechanism.
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http://dx.doi.org/10.5144/0256-4947.2012.318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6081047PMC
October 2012

[Trends in stage and age characteristics of the female breast cancer treated in 11-year period at University Hospital "Dubrava"].

Lijec Vjesn 2011 Sep-Oct;133(9-10):312-4

Zavod za patologiju, KB "Dubrava", Zagreb.

In a retrospective study we analyzed and compared the factors of local spread of breast cancer, namely tumor size and status of regional lymph nodes and patient age in the period from 1997 to 2007. The study includes only those patients in whom the diagnosis was made in an open surgical biopsy and it was possible to determine the local extent of disease at the time of diagnosis (pT and pN stage), a total of 1202 patients. We also compared the findings in patients younger and older than 50 years. The average tumor size at diagnosis was 2.2 cm and ranged between 1.7 cm (2005) and 2.4 cm (1997, 1999). The percentage of metastases in regional lymph nodes varied between 37% (2001) and 50% (2000 and 2006). The average of 6% of all cases of breast cancer was diagnosed in non-invasive (in situ) stage. The mean patient age was 56.8 years and for the observed age ranged between 54.3 (1999) and 59.1 (2004) years. There was no statistically significant difference in relation to disease stage or patient age at diagnosis observed throughout the entire period of time. There was also no statistical difference in stage of disease at the time of diagnosis in patients younger and older than 50 years.
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January 2012

Tumor and breast volume ratio as a predictive factor for axillary lymph node metastases in T1c ductal invasive breast cancer: prospective observational clinico-pathological study.

Jpn J Clin Oncol 2011 Dec 27;41(12):1322-6. Epub 2011 Oct 27.

Department for Plastic, Reconstructive and Aesthetic Surgery, University Hospital 'Dubrava', A. Gojka Suška 6, 10 000 Zagreb, Croatia.

Objective: The status of the axilla is the single most important prognostic indicator of overall survival in patients with breast cancer. Sentinel-node biopsy has false-negative rates of 5-10%. The aim of this study was to assess the importance of tumor and breast volume ratio as a predictive factor for axillary lymph node metastases in patients with T1c ductal invasive breast cancer.

Methods: This study included 136 consecutive patients with T1c ductal invasive breast cancer. Three tumor diameters were measured. Tumor volume was calculated by the formula for ellipse. Breast volume was measured preoperatively. Tumor and breast volume ratio was calculated and shown per thousand.

Results: Tumor and breast volume ratio is a new independent predictive factor for axillary lymph node metastase in T1c ductal invasive breast cancer.

Conclusions: This predictive factor could help to define a subgroup of patients who will be at a higher risk for axillary lymph node metastase and would benefit from additional close follow up or axillary lymph node dissection.
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http://dx.doi.org/10.1093/jjco/hyr149DOI Listing
December 2011

Fine-needle aspiration cytology of apocrine hidradenoma.

Coll Antropol 2010 Jun;34(2):671-4

Department of Clinical Cytology and Cytometry, Dubrava University Hospital, Zagreb, Croatia.

An apocrine hidradenoma is a benign adnexal neoplasm, usually covered by intact skin, but may show superficial ulceration and serous discharge. This feature is raising the possibility of malignancy as it was in our case of macroscopically suspicious tumour. We described cytomorphologic features of cutaneous nodule that might be a lead to the cytologic diagnosis of hidradenoma, but primary or secondary malignant tumour has been ruled out first.
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June 2010

Intraoperative imprint cytological assessment of the subareolar tissue of the nipple areola complex (NAC).

Coll Antropol 2010 Jun;34(2):431-5

Department of Pathology, Dubrava University Hospital, Zagreb, Croatia.

One of the criteria of selection for skin sparing mastectomy (SSM) with nipple areola complex (NAC) preservation is to exclude the neoplastic involvement of subareolar tissue (NAC base) in order to minimize the possibility of local recurrence. The most common way to assess the possible neoplastic involvement is intraoperative frozen section of the NAC base tissue. Because of its limitations, particularly the false negative results due to unsampling, we tried to use intraoperative imprint cytology for more thorough intraoperative assessment. The aim was to compare intraoperative imprint findings with the definitive histology of the NAC base, to evaluate diagnostic accuracy of this method and possibility to substitute frozen section for intraoperative assessment of NAC base. A prospective clinical study was conducted of 208 consecutive female patients who underwent open biopsy because of carcinoma. Intraoperative imprints were taken from the excised subareolar tissue which was then routinely processed for definitive histology. Imprint findings designated positive, negative, suspicious or atypia, were compared with definitive histological findings. Our results with 7.5% false negative rate, 9.8% false positive rate, sensitivity of 50% and specificity of 87.58% argue that imprint cytology might not be sufficient as an exclusive method for the intraoperative assessment of the NAC base though it should be used routinely in conjunction with frozen section examination.
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June 2010

The accuracy of fine needle aspiration cytology and flow cytometry in evaluation of nodal and extranodal sites in patients with suspicion of lymphoma.

Coll Antropol 2010 Mar;34(1):131-7

University of Zagreb, School of Medicine, Zagreb, Croatia.

Today lymphomas are defined according to a combination of morphology, immunophenotype, genetic features and clinical presentation, so beside the pure cytomorphologic analysis in diagnosis of lymphoma ancillary techniques such as cytochemistry, immunocytochemistry, molecular diagnosis and flow cytometry (FC) are often used. Our goal was to determinate how is information given by fine-needle aspiration cytology (FNAC) and FC correlated with pathohistologic diagnosis and to evaluate ability to diagnose and subclassify malignant lymphomas by FNAC and FC. This study is a retrospective chart review of patients with suspicion of lymphoma processed at University Hospital Dubrava in Zagreb. After analysis 50 patients fulfilled inclusion criteria for this study (FNAC diagnosis with or without FC and consecutive confirmatory pathohistological diagnosis). When analyzing accuracy of FNAC according to suspicion of lymphoma or NHL and differential diagnosis lymphoma sensitivity was 97.7%, specificity 85.7% and the diagnostic accuracy was 96%. When analyzing accuracy of FNAC according to the subclassification of lymphoma, sensitivity was 74.4%, specificity 85.7% and the diagnostic accuracy 76%. Combined FNAC and FC improved sensitivity, positive predictive value, negative predictive value and diagnostic accuracy. Sensitivity was 79.1% and the diagnostic accuracy 80%. We have shown that these methods can distinguish benign lymphadenopaties from lymphomas and also subclassify lymphomas and quickly provide clinicians with that information.
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March 2010

Alpha-methylacyl-CoA racemase (AMACR) in fine-needle aspiration specimens of prostate lesions.

Diagn Cytopathol 2009 Nov;37(11):803-8

Department of Clinical Cytology and Cytometry, University Hospital Dubrava, Zagreb, Croatia.

The elevated expression of P504S gene and its product alpha-methylacyl-CoA racemase (AMACR) can serve as a molecular marker for prostate cancer. The goal of this study is to investigate P504S/AMACR expression in fine-needle aspiration smears and correlate it with cytological diagnosis. Immunocytochemistry was performed in 35 patients with morphological diagnosis of prostate carcinoma (n = 16), atypia (n = 15), and benign hyperplasia (n = 4). Among 16 malignant cases there were two low-grade, eight intermediate, and six high-grade prostate carcinomas. Cytoplasmic positivity is analyzed qualitatively as predominantly diffuse or focal and quantitatively as <5%, 5-50%, and >50% of cells. Benign cases showed no P504S/AMACR expression. Positive staining was recorded in 75% of malignant cases, but in the majority of them it was weak and focal or diffuse and in a small amount of cells. The most intensive staining was seen in low-grade carcinomas and some atypical cases. This observation indicates a correlation between P504S/AMACR expression and differentiation of cells. P504S/AMACR staining might be of great value in cytodiagnosis of prostate lesions as well as an example of the characterization of cells at the molecular level using fresh tissue obtained by fine-needle aspiration.
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http://dx.doi.org/10.1002/dc.21103DOI Listing
November 2009