SonjeHPV16 genotype, p16/Ki-67 dual staining and koilocytic morphology as potential predictors of the clinical outcome for cervical low-grade squamous intraepithelial lesions Objective: To evaluate the association of human papillomavirus (HPV) 16 and non-16 genotype, p16/Ki-67 dual staining and koilocytosis and their role in the prediction of the clinical outcome of low-grade squamous intraepithelial lesion (LSIL) cytology. Methods: One hundred and fifty-five patients with LSIL were followed up and recorded as progression, persistence or regression. HPV genotyping was performed for high-risk HPV (hrHPV) DNA-positive cases. Koilocytosis was reviewed and p16/Ki-67 dual staining was performed on reprocessed conventional cytology slides. Results: HPV16 was the most frequent genotype found in 16.3% of cases. p16/Ki-67 dual staining was positive in 36.1% of all cases. Progression, including concurrent cervical intraepithelial lesion grade 2 or above (CIN2+), was recorded in 13.8% of cases. A statistically significant difference between progressive and non-progressive cases was shown by the following: hrHPV-positive versus hrHPV-negative (P = 0.022), HPV16-positive versus non-16 HPV-positive (P < 0.001) and p16/Ki-67-positive versus p16/Ki-67-negative (P < 0.001) cases. Cases with combined HPV16 and p16/Ki-67 positivity showed the highest progression rate (58.3%). Non-koilocytic HPV16-positive cases showed a 50% progression rate compared with 10.1% for koilocytic non-16 HPVpositive cases (P = 0.010). The sensitivity of p16/Ki-67 dual staining for the detection of CIN2+ lesions was 80%, comparable with hrHPV (85%). The specificity of p16/Ki-67 dual staining was 71% and of hrHPV 42%. The highest specificity was found for HPV16 genotype presence (91%), but with low sensitivity (50%). Conclusion: HPV genotyping, p16/Ki-67 dual staining and koilocytic morphology can be useful in the prediction of clinical outcome in women initially diagnosed with LSIL cytology.

The majority of endometrial carcinoma are diagnosed at an early stage and exhibit a favorable prognosis. However, 10% to 15% of ECs recur and the majority are type II tumors which are high-grade carcinomas. The epithelial-mesenchymal transition (EMT) has been considered as a fundamental step for the development of the invasive phenotype of cancer cells. During EMT, many of epithelial surface markers, primarily E-cadherin disappear, and mesenchymal markers including N-cadherin gain. This feature resides predominantly at the invasive front (IF) of the tumor. Therefore, we examined the immunohistochemical expression of E-cadherin and N-cadherin at the IF, in central areas of the tumor and lymphovascular space, in type I and type II endometrial carcinoma. The association of each protein with the clinicopathologic features was also evaluated. Our results confirmed a stronger E-cadherin immunostaining in type I tumors indicating that the loss of E-cadherin may be responsible for a more aggressive behavior of type II ECs. In both types, E-cadherin was strongly expressed in central areas and the reactivity decreased toward the IF. On contrary, N-cadherin was overexpressed at the IF confirming an inverse relationship between these markers. In addition, a decrease in E-cadherin expression was observed in cells within the lymphovascular space. Downregulation of E-cadherin was associated only with high-grade tumors while no correlations between both markers and other clinicopathologic features were found. Our results confirm that EMT occurs at the IF that represents a critical interface between the tumor and the host.

Objective: The aim of the study was to evaluate the accuracy of the diagnostic Pap test (DPT) on three slides and punch biopsy and endocervical curettage (PB/ECC) compared with the final biopsy material in the detection of high-grade squamous intraepithelial lesion (HSIL). Materials and methods: Patients treated with conization after previous DPT and PB/ECC were analyzed. The findings of the DPT and PB/ECC as well as of the endocervical brush cytology and ECC were compared with the final conus histology. Results: 150 patients were analyzed, and final histology verified 145 cases of HSIL and 3 cancers. The percentage of confirmed HSIL cytology was 97%, while for PB/ECC it was 79% with 30/145 false negative results. The correlation between Pap test and PB/ECC showed that the diagnostic accuracy of DPT is significantly higher (p < 0.0001). Endocervical brush cytology confirmed HSIL+ in the endocervical canal in 83% and ECC in 35% of cases (p < 0.0001). Conclusion: The DPT on three slides enables better detection of HSIL compared to PB/ECC, particularly for lesions localized in the endocervical canal sampled with a cytobrush. A high quality DPT could represent a surrogate for PB/ECC and open the possibility of direct access to therapeutic procedure.

Sažetak. Cilj:Prikazati slučaj pacijentice s primarnim seroznim karcinomom jajovoda, opisati dijagnostički postupak te analizirati ulogu citološke dijagnostike u detekciji ovog tipa tumora. Prikaz slučaja: Pedesetogodišnja pacijentica prethodno je obrađivana u drugoj ustanovi zbog bolova u trbuhu i radiološki dokazanih uvećanih supraklavikularnih, aortokavalnih i ilijačnih limfnih čvorova. Nakon učinjene laparoskopske ekstirpacije limfnih čvorova zbog sumnje na limfoproliferativnu bolest, patohistološkom i imunohistokemijskom analizom utvrđeno je da se radi o metastatskom adenokarcinomu, vjerojatno podrijetla iz ginekološkog sustava ili dojke. Radiološkom obradom dojki nisu pronađene promjene suspektne na malignitet. PET/CT analizom (pozitronska emisijska tomografija/kompjutorizirana tomografija) uočeno je pojačano nakupljanje radiofarmaka u predjelu vrata i tijela maternice. U preoperativnoj obradi učinjena je citološka punkcija uvećanog supraklavikularnog limfnog čvora te je imunocitokemijskom analizom utvrđeno da se radi o metastatskom seroznom adenokarcinomu. U Papa-testu pronađene su maligne stanice jednake morfologije, bez tumorske dijateze, što je upućivalo na ekstrauterini adenokarcinom, a sugerirano je podrijetlo jajnika ili jajovoda. Učinjena je eksplorativna kiretaža, ali je patohistološki nalaz bio uredan. Pacijentica je predviđena za histerektomiju s obostranom adnekstektomijom. Tijekom operativnog zahvata uočeno je proširenje desnog jajovoda tumorskim tkivom koje je probijalo stijenku jajovoda. Učinjena je lavaža peritonealne šupljine u kojoj su pronađene maligne stanice adenokarcinoma. Patohistološka analiza potvrdila je da se radi o primarnom seroznom karcinomu jajovoda s metastazama u jajnicima. Zaključak: Zahvaljujući brzini i preciznosti primijenjenih citodijagnostičkih pretraga dijagnostičko-terapijski postupak pravilno je usmjeren i pravovremeno proveden. Prikazani slučaj potvrđuje da citološka analiza može pridonijeti dijagnostici tumora s neuobičajenom kliničkom prezentacijom ili tumora nejasnog podrijetla.

Sažetak. Papa-test je najbolji morfološki test probira za rak koji pomoću analize citologije vrata maternice otkriva predstadije i rane stadije raka vrata maternice. U Hrvatskoj se koristi u okviru oportunističkog probira, a od 1. 12. 2012. u organiziranom nacionalnom probiru. U svrhu klasifikacije i standardizacije citoloških nalaza vrata maternice u cijeloj Hrvatskoj koristi se modifikacija Bethesda klasifikacije. Obrazac sadrži kliničke podatke o pacijentici koje ispunjava ginekolog i citološki nalaz koji na osnovi analize Papa-testa pod svjetlosnim mikroskopom izdaje klinički citolog. U ovom preglednom radu opisuju se citomorfološke osobine abnormalnih pločastih i cilindričnih stanica vrata maternice te njihov klinički značaj. Zbog dokazane povezanosti humanog papiloma-virusa (HPV) s rakom vrata maternice sve češće se detekcija visokorizičnog HPV-a uvodi u probir za rak vrata maternice. U novije vrijeme metode temeljene na biološkim biljezima primjenjuju se na citološkim uzorcima u svrhu poboljšanja osjetljivosti i specifičnosti citologije u otkrivanju lezija visokog stupnja.