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

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.

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.

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.

Inflammatory pseudotumor presenting as a facial swelling.

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.

[Trends in stage and age characteristics of the female breast cancer treated in 11-year period at University Hospital "Dubrava"]. / Analiza dobne distribucije i stupnja lokalne prosirenosti raka dojke kod bolesnica operiranih u 11-godisnjem razdoblju u Klinickoj bolnici "Dubrava".

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.

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

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.