Low reproducibility of equivocal categories of the Bethesda System for Reporting Thyroid Cytology makes the associated risk of malignancy specific to the diagnostic center.

PURPOSE: Equivocal categories (III, IV, V) of the Bethesda System for Reporting Thyroid Cytology (BSRTC) are characterized by high variability of the estimated risk of malignancy. The aim of the study was to analyze the reproducibility of classification of nodules into an equivocal category and the frequency of malignancy (FoM) observed in such categories. METHODS: Five experienced cytopathologists from three centers (A, B, C) independently performed reclassification of smears obtained from 213 thyroid nodules with equivocal routine cytology and known results of the postoperative histopathological examination. RESULTS: The interobserver agreement among all cytopathologists was poor, with a Krippendorff's alpha coefficient equaling 0.34. The intra-center agreement was higher than the inter-center (fair vs poor). Pathologists of the center A classified smears into categories II and III significantly less often and categories IV and V more often than pathologists of centers B and C. The joint FoM of nodules classified into any of categories IV-VI (regarded as an indication for surgery) was different among centers (A: 40.0%, B: 66.7%, C: 80.6%). The FoM of category III nodules with features of nuclear atypia (AUS) in center B and C was two times higher than that of other nodules of category III (FLUS), while in center A the FoM was similar. CONCLUSIONS: The use of published data on the risk of malignancy in nodules of particular BSRTC categories without concern for the uniqueness of the diagnostic center may lead to erroneous conclusions.

The Usefulness of Cell-Based and Liquid-Based Urine Tests in Clarifying the Diagnosis and Monitoring the Course of Urothelial Carcinoma. Identification of Novel, Potentially Actionable, RB1 and ERBB2 Somatic Mutations.

Bladder cancer is one of the most common cancers in global statistics. One of the issues associated with this disease is the high incidence of cases with delayed diagnosis and what factors correlate with worse treatment outcomes. A possible reason for this may be the rather limited availability of non-invasive diagnostic tools. This short communication presents a case of a 68 year old male patient after an ineffective therapy, carried on for several years with symptoms commonly associated with prostate overgrowth that masked a carcinoma in situ of the urinary bladder. Implementation of several diagnostic techniques, including urine sediment cytology, immunocytochemistry, the fluorescence in situ hybridisation technique, the Bladder EpiCheck test and whole-genome sequencing, enabled the establishment of a correct diagnosis, implementation of appropriate treatment and provision of patient-friendly monitoring. The described case emphasises the usefulness of cell-based and liquid-based urine tests in bladder cancer diagnostic procedures.

[The value of Ki-67 antigen expression in tissue microarray method in prediction prognosis of patients with endometrioid endometrial cancer]. / Znaczenie ekspresji antygenu Ki-67 ocenianej metoda mikromacierzy tkankowych dla rokowania u chorych z gruczolakorakiem endometrialnym endometrium.

OBJECTIVES: To assess the prognostic significance of Ki-67 expression in the tissue microarray method (TMA) for disease free survival (DFS) and overall survival (OS) in endometrioid endometrial cancer (EEC). MATERIAL AND METHODS: The study examined 159 consecutive patients aged 37-86 (62.82 +/- 9.95) with EEC stages I-III according to FIGO, treated surgically at the Pirogow Memorial Hospital of Lodz between 2000 and 2007. Afterwards they were subsequently treated and examined at the Regional Cancer Center Copernicus Memorial Hospital of Lodz. Tissue cores 2 mm in size, in duplicate, were taken from the formalin-fixed and paraffin-embedded tissue donor blocks from surgery and constructed into the TMA recipient blocks. Using TMA method, the relationship between Ki-67 expression, DFS and OS was examined. DFS was defined as a period from primary surgery until relapse. OS was defined as a period from primary surgery until the end of the follow-up (60 months) or until the death of the patient. The study was approved by the Ethics Committee of the Medical University of Lodz (RNN/82/11/KE; KE/1673/12). RESULTS: The follow-up time varied between 3-60 months (51.42 +/- 15.87). In 31 patients (19.50%) the relapse of was diagnosed 1-59 months (24.97 +/- 16.08) after commencement of the treatment. During follow-up 32 patients (20.12%) died. DFS and OS were 80.50% and 79.88%, respectively The lack of Ki-67 expression was found in 37 cases (23.27%) while in 122 patients (76.73%) the expression was present (p < 0.001). The expression of Ki-67 in 1-10%, 11-20% and > 20% was present in 76 cases, 26 cases and 20 cases, respectively Positive correlation between the expression of Ki-67 and staging was present (r = 0.353; p < 0.001). In EEC patients with no relapse diagnosed during follow-up the expression of Ki-67 was present in 7.63 +/- 7.57% of EEC cells, when compared to 23.06 +/- 22.93% in EEC patients in relapsed disease (p < 0.001). The relationship between increased Ki-67 expression and increased grading was not statistically significant (r = 0.149; p = 0.061). The expression of Ki-67 did not depend on patient age (r = 0.040; p = 0.617). In univariate analysis negative correlation was found between the expression of Ki-67 and DFS (p < 0.001) and OS (p = 0.01). In multivariate analysis worse DFS was related to higher staging of EEC (p < 0.0 01) and increased expression of Ki-67 (p < 0.001). Worse OS was related to higher staging in multivariate analysis (p < 0.001). Ki-67 expression was not related to OS in multivariate analysis. Age of patients and grading of the EEC were not related to DFS and OS. CONCLUSIONS: The expression of the Ki-67 can significantly affect therapeutic decisions in selected EEC patients. The high Ki-67 expression in EEC patients is related to increased risk of relapse. The TMA technique is a good method for the assessment of the Ki-67 in studies conducted in EEC patients and makes it easier to carry out immunohistochemistry in large populations of patients.

[The value of progesterone and estrogen receptors expression in tissue microarray method in prognosis of patients with endometrioid endometrial cancer]. / Znaczenie ekspresji receptorów progesteronowych i estrogenowych ocenianej metoda mikromacierzy tkankowych dla rokowania u chorych z gruczolakorakiem endometrioidalnym endometrium.

OBJECTIVES: To assess prognostic significance of progesterone receptors (PR) and estrogen receptors (ER) expression in the tissue microarray (TMA) technique for disease free survival (DFS) and overall survival (OS) in endometrioid endometrial cancer (EEC). MATERIAL AND METHODS: The study included 151 consecutive patients, aged 37-86 years (62.80 +/- 9.99), with the EEC in stages I-III (FIGO), treated surgically at the Pirogow Memorial Hospital of Lodz between 2000 and 2007. Afterwards, they were subsequently treated and examined at the Regional Cancer Center, Copernicus Memorial Hospital of Lodz. Tissue cores 2 mm in size, in duplicate, were taken from the formalin-fixed and paraffin-embedded tissue donor blocks from surgery and constructed into the TMA recipient blocks. Using TMAs, the expression of PR and ER was examined and presented as Total Score (TS). The TS was determined by adding the intensity and marker distribution scores in a given case. The relationship between PR and ER expression, DFS and OS was examined. DFS was defined as the period from primary surgery until relapse. OS was defined as the period from primary surgery until the end of the follow-up (60 months) or until the death of the patient. The study was approved by the Ethics Committee of the Medical University of Lodz (RNN/82/11/KE). RESULTS: Lack of the PR and ER expression was found in 46 cases (30.46%) and 67 cases (44.37%), respectively. The expression of the PR and ER was weak in 24 cases (15.89%) and 22 cases (14.57%), respectively. Strong PR and ER expression was found in 81 patients (53.65%) and 62 patients (41.06%), respectively. Follow-up after surgery varied from 3 to 60 months (50.95 +/- 16.36). In 30 patients (19.87%) relapse was diagnosed 1-54 months (22.17 +/- 15.59) after surgery. During follow-ups, 29 patients (19.21%) died. In univariate analysis better DFS was related to the presence of PR (p = 0.010), higher TS of PR (HR = 0.81; 95% CI 0.71-0.94), the presence of ER (p = 0.001) and higher TS of ER (HR = 0.88; 95% CI 0.78-0.99). DFS differed significantly between the groups: without PR and ER expression (A), with presence of the PR but not ER expression (B), with the ER but not PR expression (C) and with the PR and ER expression (D) (p = 0.004). In univariate analysis OS was not related to PR expression (p = 0.110), TS of PR (HR = 0.89; 95% CI 0.80-1.02) and ER expression (p = 0.070). TS of ER was connected to better OS (HR = 0.83; 95% CI 0.72-0.96). The OS differed between groups A, B, C and D (p = 0.006). In multivariate analysis variants of PR/ER expression influenced the DFS (p = 0.039) and OS (p = 0.016). CONCLUSIONS: The expression of the PR and ER can significantly affect therapeutic decisions in selected patients with EEC. In EEC, common assessment of PR and ER expression is of higher prognostic value, than compared to single evaluation of PR and ER receptors.

Membrane expression of TRAIL receptors DR4, DR5, DcR1 and DcR2 in the normal endometrium, atypical endometrial hyperplasia and endometrioid adenocarcinoma: a tissue microarray study.

PURPOSE: To evaluate the membrane expression of DR4, DR5, DcR1 and DcR2 in the normal endometrium (NE), atypical endometrial hyperplasia (AEH) and endometrioid adenocarcinoma (EAC). METHODS: The study comprised 197 patients: 20 NE, 18 AEH and 159 EAC. Tissue microarrays were constructed. Membrane expression of DR4, DR5, DcR1 and DcR2 was examined and presented as total score (TS). RESULTS: In EAC, the membrane expression of DR4, DR5 and DcR2 was less common compared to NE (p < 0.001; p < 0.001; p = 0.018) and AEH (p < 0.001; p < 0.001; p = 0.004). In EAC the membrane expression of DcR1 did not differ when compared to NE (p = 0.055) and AEH (p = 0.173). A strong correlation was found between the type of endometrial tissue (NE/AEH/EAC) and the TS of DR4 (p < 0.001), DR5 (p < 0.001), DcR1 (p = 0.033) and DcR2 (p < 0.001). In EAC, the TS of DR4, DR5, DcR1 and DcR2 was not related to grading and staging. In EAC, the membrane expression of DR5, but not DR4, DcR1 and DcR2, was related to better disease-free survival (DFS). The overall survival (OS) was not related to membrane TRAIL receptors expression. CONCLUSIONS: The membrane expression of the receptors for TRAIL DR4, DR5, DcR1 and DcR2 is greater in NE than EAC. The level of membrane staining of the receptors in EAC is not dependent on grading and staging. In EAC patients, membrane expression of DR4, DR5, DcR1 and DcR2 are not independent predictors of survival.

[Effectiveness of tissue microarray technique for the assessment of estrogen and progesterone receptors expression in endometrioid endometrial cancer--preliminary report]. / Efektywnosc zastosowania techniki mikromacierzy tkankowych do oceny ekspresji receptorów estrogenowych i progesteronowych w gruczolakoraku endometrioidalnym endometrium--doniesienie wstepne.

OBJECTIVES: To assess the effectiveness of the donor-block biopsies with a 2 mm-size needle in endometrioid endometrial cancer (EEC) in the tissue microarray (TMA) technique and the application of the TMA for estrogen receptors (ER) and progesterone receptors (PR) expression in EEC. MATERIAL AND METHODS: The study examined EEC tissues from 60 patients. Tissue cores, 2 mm in size, in duplicate, were taken from the formalin-fixed and paraffin-embedded tissue donor blocks and constructed into the TMA recipient block. The presence of EEC tissue in the TMAs was analyzed, and the ER and PR expressions were examined. RESULTS: EEC tissue in TMAs was confirmed in 56 cases (93.33%). In 49 of them (81.67%), both cores presented with cancer tissues. In 4 cases (6.67%) EEC tissue was absent. All cases with ECC present on the TMA slides were appropriate for the ER and PR analysis. In 29 EEC cases (51.98%) both ER and PR were expressed. In 3 cases (5.36%) only ER was expressed, in 8 cases (14.29%) only PR was expressed, and in 16 cases (28.57%) ER and PR were assessed as negative. CONCLUSIONS: Two 2 mm-sized tissue cores from donor-block biopsies constructed into the TMA recipient block were sufficient to diagnose EEC and enabled the assessment of ER and PR expression in 93.3% of the cases. The use of the described TMA technique makes the immunohistochemical study of EEC easier and more time-efficient.

Comparison of prognosis in patients with endometrioid endometrial cancer staged IB in FIGO 1988 and 2009 classifications.

PURPOSE: Since 2009 the new FIGO Staging System of endometrial cancer, which changed the previous FIGO 1988 Staging System, has been in use. The aim of the study was to compare prognosis in patients with endometrioid endometrial cancer at stage IB of the 2009 FIGO Staging System and of the 1988 FIGO Staging System. METHODS: We analyzed 173 patients: 108 patients (group A) at stage IB in FIGO 1988 Staging System, and 68 patients (group B) at stage IB in FIGO 2009 Staging System from 262 consecutive endometrioid endometrial cancer patients. The disease-free survival (DFS) and overall survival (OS) were compared between these groups. RESULTS: The DFS rate was 96.3 % in group A and it was 87.7 % in group B (p = 0.029). Relapses were observed in 12 patients (6.4 %) from 6 to 57 months (mean 28.1; SD = 14.6) after initial surgery, and occurred in four patients from group A (3.7 %) and eight patients from group B (12.3 %) (p = 0.032). The OS rate was 94.4 % in group A and it was 83.1 % in group B (p = 0.018). During follow-up, 17 patients (9.8 %) died: six patients from group A (5.6 %), and 11 patients from group B (16.9 %). CONCLUSIONS: Stage IB in FIGO 2009 Staging System is associated with worse prognosis compared to stage IB according to FIGO 1988 classification. There seems to be a need to use exclusively the new FIGO 2009 classification worldwide to avoid therapeutic mistakes, which can be caused by diverse nomenclature.

[Endometrioid endometrial cancer--the prognostic value of selected clinical and pathological parameters]. / Gruczolakorak endometrium typu endometrioidalnego--analiza wartosci prognostycznej wybranych parametrów klinicznych i histopatologicznych.

OBJECTIVES: To assess the relationship between selected clinical and pathological factors and disease free survival (DFS) and overall survival (OS) in endometrioid endometrial cancer patients. MATERIAL AND METHODS: A retrospective review of 262 patients aged 37-86 (6.0 +/- 9.0) was performed. Selected clinical and pathological data were correlated with DFS and OS. RESULTS: Follow-up was 8-123 months (64.9 +/- 27.1). In 4 patients (1.5%) clinical progression was diagnosed during the treatment. In 43 patients (16.4%) relapse was diagnosed 2-61 months (23.9 +/- 15.7) after commencing treatment. DFS and OS were 82.1% and 81.3% respectively. In univariate analysis worse DFS was related to older patients (p = 0.007) and non-radical surgery (p < 0.001). In multivariate analysis worse DFS was related to older patients (HR = 1.058; 95% CI = 1.024-1.093; p < 0.001), younger at menopause (HR = 0.910; 95% CI = 0.851-0.973; p = 0.006), with higher staging (HR = 2.639; 95% CI = 1.968-3.539; p < 0.001) operated non-radically (HR = 0.220; 95% CI = 0.096-0.504; p < 0.001). In univariate analysis worse OS was connected with older patients (p = 0.018), diabetes type II (p = 0.019) and non-radical surgery (p < 0.001). In multivariate analysis worse OS was related to younger age at menopause (HR = 0.932; 95% CI = 0.873-0.996; p = 0.039), diabetes type II (HR = 2.372; 95% CI = 1.260-4.466; p = 0.008), higher staging (HR = 2.053; 95% CI = 1.482-2.845; p < 0.001), and non-radical surgery (HR = 0.240; 95% CI = 0.091-0.636; p = 0.004). CONCLUSIONS: Relapsed endometrial cancer developed in 90.7% during four years after commencing treatment. In 79.1% of these patients distant metastases were present. Most significant prognostic factors were radicality of surgery age of patients and staging. The presence of diabetes type II and early menopause were connected with worse prognosis.

[Low-grade endometrial stromal sarcoma firstly localized in colonic mesentery]. / Endometrialny miesak stromalny o pierwotnej lokalizacji w krezce jelita grubego.

There are only few papers describing extrauterine localisation of endometrial tumor sarcoma. Pathogenesis of this tumor is still not clear. Most of the authors suggest the heterotopic Mullerian ducts to be the origin of such tumors. We describe a case of 53 year old woman with endometrial tumor sarcoma localized in the mesenterium of the colon. Diagnostic problems and differential diagnosis is presented. The authors suggest to immunohistochemical methods (CK desmin) to facilitate diagnosis.

[Monochorionic, diamniotic triplet pregnancy complicated by twin reversed arterial perfusion sequence. Postpartum autopsy of placenta and acardiac fetus]. / Ciaza trojacza jednokosmówkowa dwuowodniowa powiklana wystapieniem zespolu "odwroconego kierunku przeplywu krwi". Badanie patomorfologiczne plodu "bez serca" i poplodu.

The twin reversed-arterial-perfusion sequence (TRAP) is a severe complication of monochorionic twin pregnancies characterized by the hemodynamic dependence of a "recipient" twin from a "pump" twin. The recipient twin exhibits lethal abnormalities including acardia and acephaly. The pump twin has a mortality rate of 50% as a result of high-output heart failure. We present a case of a 24-year-old female, gravida 2, para 2, with monochorionic diamniotic triplet pregnancy. The sonographic examination at 18 weeks' gestation revealed acardiac-acephalus fetus. Reversed arterial perfusion sequence was confirmed with Doppler sonography. Postpartum autopsy examination of placenta and acardiac fetus (acardius anceps) was detailed described.