Does Cytological Laboratory Holds the Responsibility for the Low Sensitivity of the PAP Test in Detecting Endometrial Cancer?

Endometrial cancer is the most common gynecological cancer but there is no economically justified screening method. Although we can detect endometrial cells in the sample using PAP test, many studies show low sensitivity and positive predictive value of PAP test for the diagnosis of endometrial cancer. The goal of this research was to determine significance of PAP test for the diagnostics of endometrial carcinoma. Sensitivity and specificity were analyzed with statistical parameters. VCE (vaginal, cervical, endocervical) smears of patients with histologically proven endometrial carcinoma were re-examined in order to determine the proportion of false negative results for endometrial cancer cells in the VCE samples. Study group consisted of all consecutive patients with PAP test performed at the Department of Clinical Cytology of the University Hospital Center Osijek from 2002 until the end of 2014. There was one inclusion criteria: subsequent hysterectomy or curettage within the six month after the PAP test, regardless of histological finding. From a total of 263 patients with previous PAP test and histologically proven endometrial cancer, endometrial cancer was cytologicaly diagnosed in 24.7% (including suspicious and positive findings), while 66.2% patients had normal cytological findings. The diagnostic value of PAP test in detection of endometrial cancer was statistically revealed with 25% sensitivity and 99% specificity. To determine false negative rate VCE samples were reviewed for patients with histologically proven endometrial cancer and negative VCE findings. There were a total of five negative results. In one case revision did not changed the original negative diagnosis, but benign endometrial cells, a lot of blood and inadequate cytohormonal status were found. In three out of four reviewed samples there were missed cells of endometrial adenocarcinoma. Review of remaining VCE sample upgraded the diagnosis from negative to suspicious for endometrial cancer. Proportion of error in the detection of endometrial cancer using cytological findings was 3.4% (true false negatives). Negative rate of the cytological findings in the detection of endometrial cancer was 66.2%. PAP test is not a suitable method for detection of endometrial carcinoma due to low sensitivity (25%). The main cause of negative findings in PAP test was lack of diagnostic cells in the sample.

Thermography--a feasible method for screening breast cancer?

Potential use of thermography for more effective detection of breast carcinoma was evaluated on 26 patients scheduled for breast carcinoma surgery. Ultrasonographic scan, mammography and thermography were performed at the University Hospital for Tumors. Thermographic imaging was performed using a new generation of digital thermal cameras with high sensitivity and resolution (ThermoTracer TH7102WL, NEC). Five images for each patient were recorded: front, right semi-oblique, right oblique, left- semi oblique and left oblique. While mammography detected 31 changes in 26 patients, thermography was more sensitive and detected 6 more changes in the same patients. All 37 changes were subjected to the cytological analysis and it was found that 16 of samples were malignant, 8 were suspected malignant and 11 were benign with atypia or proliferation while only 2 samples had benign findings. The pathohistological method (PHD) recorded 75.75% malignant changes within the total number of samples. Statistical analysis of the data has shown a probability of a correct mammographic finding in 85% of the cases (sensitivity of 85%, specificity of 84%) and a probability of a correct thermographic finding in 92% of the cases (sensitivity of 100%, specificity of 79%). As breast cancer remains the most prevalent cancer in women and thermography exhibited superior sensitivity, we believe that thermography should immediately find its place in the screening programs for early detection of breast carcinoma, in order to reduce the sufferings from this devastating disease.

Primary Ewing's sarcoma of the kidney: a case report.

Primary adult Ewing's sarcoma is a rare entity. They most commonly occur in children and young adults. 6% of them are localized extraosseously. We present a case of a 51 year old patient with primary renal Ewing's sarcoma and multiple metastases in liver and iliac bone. Patients with metastatic disease are usually treated with aggressive chemotherapy and have a poor outcome. Our patient underwent complete surgical excision of tumour, and was treated with aggressive chemotherapy, respectively. Two and half years after presentation he is well, without any symptoms.

Expression of Ki-67 and p27(Kip1) in fine-needle aspirates from breast carcinoma and benign breast diseases.

Cell atypia in breast fine needle aspiration (FNA) can introduce some diagnostic difficulties. Molecules reflecting proliferative cell potential, such as Ki-67 and p27(Kip1) , can help in recognizing the true biological nature of a cell. Thus, the objective of the study was to analyze the difference in Ki-67 and p27(Kip1) cell immunoexpression in breast FNA specimens between fibroadenomas, fibrocystic changes (FCC) with atypia, and breast carcinoma. Microscopic analyses of cell cytomorphology and Ki-67 and p27(Kip1) breast cell immunoexpression were done after standard Pappenheim and immunocytochemical staining (labeled streptavidin-biotin, LSAB) method in autostainer DakoCytomation TechMate™. The study included 50 patients with breast carcinoma, 20 patients with fibroadenoma, and 20 patients with FCC with atypia. High Ki-67 and low or absent p27(Kip1) were found in most patients with breast carcinoma, while majority of FCC with atypia were characterized by low Ki-67 and moderate to high p27(Kip1) cell immunoexpression. Majority of fibroadenomas were associated with low Ki-67 and low to moderate p27(Kip1) cell immunoexpression indicating progressive decrease in cell cycle inhibition, but still not so high proliferative activity as in carcinoma. However, although statistically significant difference for Ki-67 and p27(Kip1) was found between breast lesions in our study, the large ranges observed for each marker make them essentially useless for better cytological diagnosis in a single case. Regarding their opposite role in cell cycle, inverse correlation of Ki-67 and p27(Kip1) was noticed. Poorly differentiated carcinoma cells had mostly high Ki-67 and low p27(Kip1) cell immunoexpression.

Fine needle aspiration cytology in diagnosing rare breast carcinoma--two case reports.

In this paper, we are presenting the two cases of very rare tumors: breast sebaceous carcinoma, which has been described for the first time in Croatian medical literature, and pure breast squamous carcinoma. First case, sebaceous carcinoma, is still quite unknown regarding its morphological characteristics and biological behavior. In the second case, squamous carcinoma, also very rare, was found in a patient who previously had a number of diagnosed head and neck skin carcinomas, and was diagnosed as primary squamous breast carcinoma. As a first case we present a 85-year-old female with a two months history of swelling of the left breast under the mammilla. The second one, a 69-year-old female presented to our hospital in January 2008 with a two months history of a lump in the lower outer region of the left breast and enlarged lymph nodes in left axillary region. Fine needle aspiration cytology (FNAC) of the breast was performed in order to diagnose the exact type of both tumours. This methodology was found important in diagnosis, but in both cases showed certain limitations in diagnosing such rare tumors. The final diagnoses were determined after carefully synthesizing the histological findings and clinical data. Careful and accurate classification of these tumors is necessary. A detailed analysis of their biological behavior and response to the therapy is necessary in order to formulate definite recommendations in managing these patients/diseases.

Histological types of polypoid cutaneous melanoma II.

The aim of this study was to ascertain which histological types of melanoma can clinically and morphologically appear as polypoid melanomas. In 645 cases of primary cutaneous melanoma we have analyzed criteria for diagnosis of polypoid cutaneous melanoma and afterwards we have analyzed growth phase in each polypoid melanoma, histological type of atypical melanocytes, the number of epidermal ridges which are occupied by atypical melanocytes, and distribution according to age, sex and location, as well as the disease free survival. According to the criteria for polypoid melanomas we have found 147 (22.8%) polypoid cutaneous melanomas. Analyzing the growth phases, histological types of atypical melanocytes and the number of affected epidermal ridges in the group of polypoid melanomas we have ascertained 2 (1.4%) ALMs, 4 (2.8%) LMMs, 42 (28.6%) SSMs and 99 (67.2%) NMs. Our conclusion is that polypoid cutaneous melanomas are morphological forms of various histological melanoma types (ALM, LMM, SSM and NM) and they can all display polypoid morphological form. Polypoid cutaneous melanomas are most often of nodular histological type.

[p53, bcl-2 and Ki-67 in the diagnosis of insular thyroid gland cancer. Case report with a review of literature]. / p53, bcl-2 i Ki-67 U dijagnostici inzularnog karcinoma stitnjace. Prikaz bolesnika s pregledom literature.

The report covers the first case of insular thyroid cancer recorded in Croatian medical literature. A 71-year old female patient presented to our hospital with symptoms of inspiratory stridor. Clinical examination disclosed an expansive tumor mass. US guided FNA indicated anaplastic cancer and total thyroidectomy was accordingly indicated. Pathohistological analysis of H/E biopsies disclosed a tumor mass with a characteristic insular growth pattern of monomorphic tumor cells. Immunohistochemical analysis confirmed diagnosis by a diffuse positive reaction to thyreoglobulin, focally to TTF-1, and scant to cytokeratin, while calcitonin, FVIII, CD34 and LCA were clearly negative. P53 and bcl-2 were expressed in 35.9% and 85% of tumor cells, respectively. The proliferation index for Ki-67 was 4.19. According to our survey we suggest a panel of immunohistochemistry for diagnosing insular cancer. Even if partly present, insular cancer should be mentioned in the pathohistological description because of its prognostic meaning.

The relation between tumor marker Ca 15-3 and metastases in interpectoral lymph nodes in breast cancer patients.

OBJECTIVE: We aimed at analyzing the metastatic involvement in interpectoral (Rotter's) lymph nodes (RLN) in relation to tumor marker CA 15-3. METHODS: The study included 177 female patients undergoing surgery for primary breast cancer at the University Hospital for Tumors, Zagreb, Croatia from November 2001 to March 2004. In addition to the standard surgical procedure, interpectoral RLNs were removed in all of the patients. Levels of the serum tumor marker CA 15-3 was determined prior to surgery. RESULTS: Rotter's lymph nodes were identified in 66.2% of the patients, with metastatic involvement revealed in 18.6% of the RLNs. Metastatic involvement of RLNs in patients with negative axillary lymph nodes was 2.8% and positive in 34.6%. Elevated serum levels of tumor marker CA 15-3 had 22 (12.4%) patients. Of 33 Rotter's node-positive patients, 27.3% had elevated serum levels of tumor marker CA 15-3 and in Rotter's node-negative patients only 9% had elevated serum levels of tumor marker CA 15-3, with the level statistically significantly higher in Rotter's positive patients compared to those with negative (or absent) RLNs (chi2=8.22, p=0.004). CONCLUSION: Tumor marker CA 15-3 is more frequently elevated in patients with positive RLNs. Elevated values of tumor marker CA 15-3 could be warning for possible positive interpectoral nodes. The removal of the RLNs may be beneficial for patients with (massive) axillary nodal involvement. For axillary node negative patients, sentinel node biopsy could avoid the unnecessary removal of the RLNs.

Analysis of metastatic involvement of interpectoral (Rotter's) lymph nodes related to tumor location, size, grade and hormone receptor status in breast cancer.

AIMS AND BACKGROUND: This study was aimed at analyzing metastatic involvement in interpectoral (Rotter's) lymph nodes in relation to tumor location, size, grade and hormone receptor status in primary breast cancer. METHODS: The study included 172 female patients undergoing surgery for breast cancer at the University Hospital for Tumors, Zagreb, Croatia from November 2001 to August 2003. In addition to the standard surgical procedure, interpectoral (Rotter's) lymph nodes were removed in all of the patients. Serum levels of the tumor marker CA 15-3 were determined before surgery and hormone receptor status after surgery. RESULTS: Rotter's lymph nodes were identified in 67% of the patients, with metastatic involvement being found in 20% of the Rotter's nodes. Metastatic involvement of Rotter's nodes in patients with negative and positive axillary lymph nodes was 4% and 35%, respectively. When we looked at the location of the tumor in patients with metastatic involvement of Rotter's nodes, we found that tumors located in the upper quadrants were more prone to metastasis to Rotter's nodes; there was a significant positive correlation between tumor location and positive Rotter's nodes (r = 0.953, P = 0.012). As regards tumor size, Rotter's nodes were identified in 15%, 20% and 30% of stage T1 (< 2 cm), T2 (2-5 cm) and T3 (> 5 cm) tumors, respectively. Hormone receptor status showed no statistically significant difference in the expression of estrogen and progesterone receptors between patients with and those without positive Rotter's nodes. Of 35 Rotter's node-positive patients, 31.4% had elevated serum levels of CA 15-3; the level was significantly higher in Rotter's-positive patients compared to those with negative (or absent) Rotter's nodes. CONCLUSIONS: The results show that one-fifth of breast cancer patients, or even one-third of those with positive axillary lymph nodes, are discharged with positive interpectoral lymph nodes that remain undiagnosed. As the nodes can be surgically removed without additional mutilation, exploration of Rotter's lymph nodes should be introduced into routine clinical practice.

Is quadrant biopsy sufficient in men likely to have advanced prostate cancer? Comparison with extended biopsy.

We hypothesized that quadrant prostate biopsy (QPB) provides sufficient first-line pathological evaluation of patients with presumed advanced prostate cancer (PC). The aim of this study was to investigate whether the reduction of core number in first-line PB from 6-12 to 4 in patients with presumed advanced PC leads to loss of clinically relevant information. We retrospectively studied 113 men that underwent PB, classified in two groups: "H" (high) and "L" (low likelihood of having advanced PC), according to PSA, digital rectal and transrectal ultrasound findings. Pathological results of 6-12-core PB and QPB were retrospectively compared for the presence of malignancy, percentage of positive cores, Gleason score (GS), and the presence of high-grade prostatic intraepithelial neoplasia (HGPIN). PC detection rate was not impaired in group H but dropped significantly in group L, and the percentage of positive cores was not significantly changed in group H (p=0.39), but decreased in group L (p=0.04), due to sampling scheme reduction. No HGPIN was missed with QPB in group H, while 2 HGPINs were missed in group L. No significant change in GS in either group was observed (p=0.12, p=0.13) due to reduction to QPB. We conclude that in patients with presumed advanced PC, reduction of the number of cores in PB may be an acceptable diagnostic strategy, but further studies are needed to analyze the impact of PB scheme reduction on other relevant pathological information obtained from PB.