COMPARISON OF CYTOLOGIC FINDINGS OF NIPPLE DISCHARGE WITH GALACTOGRAPHIC FINDINGS

Uvod. Jedan od simptoma raka dojke je i iscjedak iz dojki. Citološki nalaz hiperplastičnih stanica bez anizocitoze te s anizocitozom, eritrociti i maligne stanice u iscjetku indikacija su za daljnju obradu – galaktografijom. Galaktografija je kontrastna pretraga tijekom koje se kanalić iz kojega je dobiven iscjedak ispuni kontrastom i slika. Prema nalazu galaktografije indicira se operativni zahvat. Cilj rada. U radu se željelo pokazati kolika je podudarnost između boje iscjetka, citološkog nalaza te galaktografskog nalaza. Materijal i metode. U razdoblju od 01. 01. 1993.do 31. 12. 2007. godine, u Ambulanti za bolesti dojke Klinike za ženske bolesti i porode KBC-a Zagreb učinjena je nakon citološke obrade iscjetka 91 galaktografija. Citologija iscjetka prema kojoj je indicirana galaktografija bio je nalaz hiperplastičnih stanica, bez ili s anizocitozom ili eritrociti, odnosno kombinacija oba nalaza. Tijekom očitavanja galaktografije promatrana je širina i pravilnost grananja kanalića, uz analizu stijenke i defekata punjenja unutar kanalića. Ukoliko se našao defekt punjenja, nepravilna proširenja kanalića ili oboje, bolesnica je bila upućena na biopsiju. Rezultati. Prema boji iscjedak je bio podijeljen u 5 kategorija: serozni i mliječni iscjedak nađen je u po 10 bolesnica (22%), njih 29 (31,8%) imalo je obojeni iscjedak (zelenkast, smeđi, žućkast), u 2 (2,2%) bolesnice bio je gnojni iscjedak dok je najveći broj bolesnica, njih 40 (44%), imalo krvavi iscjedak. Citološkom analizom iscjetka dobiveni su sljedeći rezultati: samo eritrociti nađeni su u 18 (19,8%) bolesnica, 19 (20,8%) bolesnica imalo je u iscjetku papilarne nakupine hiperplastičnih duktalnih stanica, u 7 (7,8%) bolesnica nađene su papilarne nakupine duktalnih stanica i anizocitoza, a u 47 (51,6%) bolesnica uz eritrocite su nađene i papilarne nakupine hiperplastičnih stanica. Razlikovale su se tri kategorije galaktografskih nalaza: uredan nalaz (19 bolesnica, 20,8%), hiperplazija – proširenja kanalića uz neravnosti stjenke (56 bolesnica, 61,6%), te suspektan nalaz – defekti punjenja kanalića, izrasline (16 bolesnica, 17,6%). Bolesnice sa suspektnim nalazom, njih 16, bile su upućene na biopsiju. Patohistološki nalaz u operiranih bolesnica bio je: u četiri (25%) papilom, 10 (62,5%) bolesnica imalo je duktalnu hiperplaziju, a u dvije (12,5%) nađen je karcinom. Prosječna dob bolesnica u kojih je bila indicirana galaktografija je bila 48 godina, dok je u bolesnica s karcinomom bila 63 godine. Zaključak. Naši rezultati upućuju na dobru korelaciju citološkog i galaktografskog nalaza. Hiperplazija duktalnih stanica u citološkom razmazu potvrđena je galaktografski u 62,5% ispitanica. Citološki, u svih 16 bolesnica u kojih su nađeni eritrociti uz hiperplaziju, što je upućivalo na intraduktalni proces, nalaz je ujedno dokazan i galaktografski. Sve ove ispitanice imale su krvavi iscjedak već pri uzimanju uzorka.Introduction. Nipple discharge is one of the symptoms of the breast cancer. Hemorrhagic discharge are always arousing suspicion for intraductal process (papilloma, carcinoma). The cytologic finding of red blood cells, atypical ductal cells and malignant cells in the discharge are indication for further analysis – including galactography. Objective. The aim was to show connection between colours of nipple discharge, cytologic findings and galactographic findings. Materials and methods. During the period January 1, 1993 and December 31, 2007 91 galactography were performed in Outpatient Clinic for breast disease, Department Gynaecology and Obstetrics, University Hospital Zagreb. Galactography was performed after cytological analysis of the discharge. Indication for galactography was the presence of red blood cells and atypical duct cells or combination of both. During the reading we observed the width and irregularity of ducts branching together with analysis of the wall and defects of filling (charging) within the ducts. In case of some irregularities the patients were referred to the biopsy. Results. Discharge was divided into 5 categories according to the colour: colourless or serous discharge was found in ten patients (11%), the same number had milky discharge, the largest number, 29 (31.8%) had coloured discharge (greenish, brownish, yellowish) and in 2 (2.2%) purulent discharge was found while in 40 (44%) patients the discharge was bloody. Cytological analysis gave the following results: red blood cells alone were found in 18 (19.8%) of the patients, papillary hyperplastic duct cells were found in 19 (20.8%) of the discharges and tight papillary clusters with anisocytosis were found in 7 (7.8%) patients and in 47 (51.6%) patients together with red blood cells, tight papillary cluster cell groups were found. Galactographical findings were divided into three categories: normal (19 patients – 20.8%), hyperplasia – proliferation of ducts with roughness of the wall (56 patients – 61.6%), and suspicious – defects in filling of the duct, tumours (16 patients – 17.6%). Patients with suspicious findings, 16 of them, were referred to surgery. Pathohisiological finding was papilloma in 4 (25%) of the surgical specimens, 10 (62.5%) had duct hyperplasia and carcinoma was found in 2 (12.5%) patients. Conclusion. Our results show good correlation between cytological and galactographical finding. It has been noticed that the presence of hyperplasia of duct cells in cytological smear is connected with hyperplasic changes of the ducts in 62.5% of the patients. In all 16 patients where red blood cells together with duct cells hyperplasia were found, cytological finding indicated to intraductal process, the finding was at the same time proven galactographgically as well

Cytologic characteristics of adenoid cystic carcinoma of the cervix uteri: case report [Citološke karakteristike adenoid cističnog karcinoma vrata maternice: prikaz slučajeva]

Adenoid cystic carcinoma is a rare malignancy, usually found in the salivary glands, although this unusual tumor can be found at other sites of the body. In particular, regarding adenoid cystic carcinoma of the cervix (ACCC) most frequently reports are given for postmenopausal women. In this respect, our work is one among very few in the literature that considers a cytologic picture of this uncommon cervix carcinoma. The case of 74 year old patient with postmenopausal bleeding is described. Both Pap smear and air dried smear of the uterine cervix were analyzed. The cytologic findings revealed very few small clusters of abnormal glandular cells, as well as some amorphous eosinophilic globule-like material, with granulomatous and necrotic background. The latter includes a lot of histiocytes, multinucleated giant cells, large aggregates of epitheloid cells and lymphocytes. Histology revealed the diagnosis of ACCC. We emphasize the importance of careful screening of Pap smear that might be crucial in the case of suspicious clinical findings in postmenopausal women, when the possibility of ACCC has to be considered

Cervical Cancer as a Public Health Issue – What Next?

Cervical cancer is the second most common cancer in women worldwide. There are about 60,000 newly detected cases and 30,000 deaths annually in Europe, with the highest incidence reported from Eastern Europe countries. According to data from the National Institute of Public Health, in Croatia the incidence of cervical cancer was 14.9/100,000 in 2006, ranking eighth most common malignancy in women. Croatia has a lower incidence of the disease compared to many countries of Central and Southeast Europe. A large study carried out in 1995 by the International Agency for Research on Cancer, which included cervical cancer material collected from 22 countries all over the world revealed HPV genome in 99.7% of cases. Efficient methods of cervical cancer detection and screening methods for identification of precancerous lesions (conventional Pap smear) are available. Cervical cancer prevention programs should include education (of health care providers and women), stressing the benefits of screening, the age of the peak cervical cancer incidence, and the signs and symptoms of precancerous lesions and invasive disease. The aim of screening actions is to detect precancerous lesions that may lead to cancer if left untreated. Screening can only be effective if there is a well-organized system of follow up, diagnosis and treatment. Cervical cytology, or Papanicolaou (Pap) testing, has for decades been a cornerstone of cervical cancer screening. According to recent guidelines issued by the World Health Organization Regional Office for Europe, the primary task of the public health system is the introduction of secondary prevention through properly organized screening programs. Launching the national immunization program is only possible in the countries with well-organized secondary prevention programs and in those that can afford it

Current Organisation of Clinical Cytology in Croatia

Current cytological service in Croatia is organised in 46 cytological organisational units in 23 towns with total of 350 employees: 101 specialists of clinical cytology, 20 residents in clinical cytology, 141 cytotechnologists (cytoscreeners), 45 health technicians, and 25 administrators and 18 auxiliary personnel. In spite of employment of significant number of cytotechnologists in the last ten years, there is still an unacceptable ratio of number of cytologists and cytotechnologists (1:1.4) which is the result of unresolved education of cytotechnologists which should be permanent, complete and acknowledged. Education and scientific promotion of cytologists is continuous and today our profession has 31 masters of science and 9 doctors of science, one of which is the assistant professor, and four of them are associate or full professors at medical schools in Zagreb and Osijek. Croatian cytology, in average, is in its »best years«, i.e. an average cytologist is 46 years old and cytotechnologist is averagely 43 years old, but »suffers« from personnel deficit. With regard to the type of activity, the most numerous are units dealing the entire diagnostic cytology (72%), 13% general cytology without gynaecological cytology, while 15% are engaged in one diagnostic field (gynaecological, pulmological or thyroid cytology). According to accessible data, total of 770996 cytological examinations were done in Croatia in 2008. The increasing application of additional methods (cytochemical, immunocytochemical, molecular, cytogenetics and computer-assisted image analysis) has become a trend in numerous cytological units. Exclusively morphological analysis of standard stained samples is performed in 37% of units, morphological and cytochemical staining methods are used in 17% of units, and additional immunocytochemical methods in 30% of units. According to the long tradition of cytology in Croatia, that has progressed thanks to the enthusiasm and great effort of our teachers, we believe that the following generations of cytologists will continue working on its improvement and will be able to concord the basic cytomorphology and sophisticated diagnostic procedures with other diagnostics, to stay the field of optimal results in the shortest time with the reasonable price

Zagreb 2016 classification of cervical cytology findings – modification of Zagreb 2002 and NCI Bethesda System 2014 classifications

The objective of the Zagreb 2016 classification as the third modification of the unique classification of cervical cytology findings based on the previous Zagreb 2002 and the latest Bethesda 2014 classifications is standardization of cervical cytology findings for the whole Croatia, according to the latest concepts on the biologic behavior of cervical cancer and its precursors. Besides cytomorphological lesions, Zagreb 2016 includes recommendations for diagnostic therapeutic procedures in line with the international recommendations and the experience of Croatian cytologists and gynecologists. It was presented and accepted by Croatian clinical cytologists at the Croatian Society of Clinical Cytology Convention held on December 12, 2016 in Zagreb. The main modifications relative to the Zagreb 2002 classification refer to the following: classification of ‘koilocytosis’, i.e. cytomorphological lesions associated with human papillomavirus, into the category of low-grade squamous intraepithelial lesions (LSIL); classification of ‘atypical glandular cells – probably reactive lesions’ into the category of non-neoplastic lesions; and the introduction of ‘atypical glandular cells – not othervise specified’ (AGC-NOS) into the category of abnormal glandular cells. In addition, the finding of endometrial cells in women aged ≥45 and absence of the transformation zone elements is highlighted

Zagreb 2016 classification of cervical cytology findings – modification of Zagreb 2002 and NCI Bethesda System 2014 classifications

The objective of the Zagreb 2016 classification as the third modification of the unique classification of cervical cytology findings based on the previous Zagreb 2002 and the latest Bethesda 2014 classifications is standardization of cervical cytology findings for the whole Croatia, according to the latest concepts on the biologic behavior of cervical cancer and its precursors. Besides cytomorphological lesions, Zagreb 2016 includes recommendations for diagnostic therapeutic procedures in line with the international recommendations and the experience of Croatian cytologists and gynecologists. It was presented and accepted by Croatian clinical cytologists at the Croatian Society of Clinical Cytology Convention held on December 12, 2016 in Zagreb. The main modifications relative to the Zagreb 2002 classification refer to the following: classification of ‘koilocytosis’, i.e. cytomorphological lesions associated with human papillomavirus, into the category of low-grade squamous intraepithelial lesions (LSIL); classification of ‘atypical glandular cells – probably reactive lesions’ into the category of non-neoplastic lesions; and the introduction of ‘atypical glandular cells – not othervise specified’ (AGC-NOS) into the category of abnormal glandular cells. In addition, the finding of endometrial cells in women aged ≥45 and absence of the transformation zone elements is highlighted

Atipične glandularne stanice u papa testu kao primarna prezentacija seroznog borderline tumora jajnika

The Pap test is designed as a screening test to detect primarily carcinoma of the cervix and its precursors, most often of squamous type. Rarely atypical or malignant cells found in cervical smear can be indication for the existence of an extrauterine disease. We present a case of a 26 year old woman with very small asymptomatic ovarian bilateral borderline tumors whose diagnosis was triggered by finding of atypical glandular cells with psammoma bodies on Pap smear. She had a history of abnormal Pap smears and was admitted to our Hospital for colposcopy. Pap smear was taken and reported as atypical glandular cells (AGC) with psammoma bodies. Colposcopically directed biopsy along with an endocervical curettage showed no abnormalities as well as transvaginal ultrasound examination. Three months later control Pap smear confirmed AGC with psammoma bodies (suggestive of endometrial or serous origin), ultrasound showed the presence of indistinctive, hyperechoic mass 2 cm in diameter in the left ovary along with slightly elevated CA-125 and diagnostic hysteroscopy and laparoscopy was performed. At laparascopy, both ovaries had surface cauliflower like papillary projections measuring up to 3 cm. A histological examination revealed bilateral serous borderline tumor.Papa test je test probira primarno namijenjen za rano otkrivanje karcinoma cerviksa i njegovih prekursora, najčešće pločastog tipa. Rijetko nalaz atipičnih ili malignih stanica u Papa testu može biti prvi znak tumora ekstrauterinog porijekla. U ovom radu prikazujemo slučaj 26 godišnje pacijentice s vrlo malim asimptomatskim bilateralnim borderline tumorima jajnika čija je dijagnoza pokrenuta nalazom atipičnih žljezdanih stanica sa psamomskim tjelešcima u Papa testu. Pacijentica je upućena u našu bolnicu na kolposkopiju radi abnormalnih nalaza Papa testa. Kod nas uzeti Papa test pokazao je atipične glandularne stanice (AGC) sa psamomskim tjelešcima. Kolposkopski vođena biopsija i endocervikalni ekskohleat nisu pokazali abnormalnosti, kao ni transvaginalni ultrazvučni pregled. Tri mjeseca kasnije ponovljeni Papa test potvrđuje AGC sa psamomskim tjelešcima (porijeklo endometralno ili serozno), ultrazvučni nalaz opisuje uz lijevi jajnik nejasnu hiperehogenu tvorbu promjera 2 cm, uz blago povišeni CA 125 zbog čega je učinjena dijagnostička histeroskopija i laparoskopija. Na operaciji su nađeni jajnici obostrano s tumorskim tvorbama karfiolastog izgleda veličine do 3 cm. Patohistološki je potvrđen serozni borderline tumor oba jajnika

Liquid-based cytology - new possibilities in the diagnosis of cervical lesions [Tekuća citologija - nove mogućnosti u dijagnostici lezija vrata maternice]

Liquid-based cytology (LBC) enables the use of supplementary methods in the diagnosis and prognosis of cervical lesions. The aim of this study was to analyze the correlation between p16INK4a immunoexpression in ThinPrep cervical cytologic samples and human papillomavirus (HPV) detection by polymerase chain reaction (PCR) from the same sample. LBC-ThinPrep (Cytyc, USA) cervical cytology samples, prepared and stained by Papanicolaou method, were analyzed using modified Bethesda cytologic classification named »Zagreb 2002«. A second ThinPrep slide, prepared from the same sample, was immunostained for p16INK4a using CINtec p16INK4a Cytology Kit (DakoCytomation, Denmark). Increased expression of the high-risk (HR) HPV E6 and E7 oncogenes results in a highly specific increase in p16 protein expression and overexpression of p16INK4a acts as a potential biomarker for cervical cancer progression from premalignant lesions. Brown nuclear and/or cytoplasmic staining of abnormal cells was considered a positive result. Residual material was used for 13 HR HPV-DNA detection by the PCR based AMPLICOR HPV test (Roche Molecular Systems). A total of 120 ThinPrep Pap tests with the following cytologic diagnoses: 17 within normal limits, 17 atypical squamous cell (ASC) (7 ASC of undetermined significance /ASCUS/ and 10 ASC of high-grade squamous intraepithelial lesions cannot be excluded /ASC-H/), 26 low-grade squamous intraepithelial lesions (LSIL) corresponding cervical intraepithelial neoplasia (CIN) I, 57 high-grade SIL (HSIL) i.e. 24 CIN II and 33 CIN III and 3 squamous cell carcinoma (SCC) were included in the study. All CIN III (n=33) and SCC (n=3) specimens expressed p16INK4a immunoreactivity, whereas the HR HPV test was positive in 97% (32/33) of CIN III and 100% (3/3) of SCC specimens. The p16INK4a biomarker was positive in 87.5% (21/24) of CIN II and 69% (18/26) of CIN I, while the HR HPV was positive in 75% (18/24) of CIN II and 50% (13/26) of CIN I. In ASCUS cytology, p16INK4a and HR HPV showed the same rate of positivity (28.5%; 2/7). Expression of p16INK4a was detected in all cytologic (10/10) ASC-H lesions, in contrast to HR HPV detected in only 20% (2/10) of ASC-H cases. These data suggest the p16INK4a evaluation in ThinPrep cervical samples to be significantly associated with HR HPV testing by PCR in the same sample for the diagnosis of HSIL lesions and cervical carcinomas. A prospective study with longer follow up may clarify the predictive values in the management of LSIL and ASC diagnosis

GYNECOLOGIC CYTOLOGY – CERVIX UTERI

Rak vrata maternice može se prevenirati zdravstvenim prosvjećivanjem (primarna prevencija) ili ranim otkrivanjem (sekundarna prevencija). Najraširenija metoda sekundarne prevencije je citološka analiza popularno nazvana »Papa test«. Klasifikacija citoloških nalaza, među inim, uključuje diferenciranje premalignih i malignih lezija, te identifikaciju uzročnika spolno prenosivih bolesti (bakterije, gljivice, paraziti) ili njihovog citopatskog efekta (virusi). Posljednji prijedlog klasifikacije bio je na svjetskoj razini »NCI Bethesda System 2001«, a u Hrvatskoj »Zagreb 1990«. Citologija se može koristiti kao metoda probira za otkrivanje lezija s podjelom nalaza na negativne i pozitivne ili kao diferencijalno-dijagnostička metoda s predskazivanjem histološke dijagnoze. U diferencijalnoj dijagnostici citologija predstavlja, uz kolposkopiju i histologiju, jednu od komplementarnih dijagnostičkih metoda, koje primijenjene zajedno omogućavaju točniju dijagnozu. Konvencionalni »Papa test«, kao metoda probira za rak vrata maternice, dokazala se je sniženjem mor¬biditeta i mortaliteta, te se preporuča za zemlje s razvijenom citološkom službom, kao što je naša. No, veća osjetljivost probira postiže se primjenom usavršenih citoloških metoda (LBC i kompjuterizirana citološka analiza) i njihovom kombinacijom s drugim metodama (HPV DNK tipizacija). Nacionalni citološki probir provodi se u mnogim zemljama Europske unije. U Hrvatskoj su ispunjeni osnovni stručni preduvjeti za probir na nacionalnoj razini, no potrebno je izraditi plan i program, te osigurati financijsku potporu.Cervical carcinoma can be prevented by health education (primary prevention) or early detection (secondary¬ prevention). Cytologic analysis, generally known as Papanicolaou (Pap) test, is the most widely used method of secondary prevention. Among other parameters, the classification of cytologic findings includes differentiation of premalignant and malignant lesions, and identification of the agents causing sexually transmitted diseases (bacteria, fungi, parasites) or their cytopathic effects (viruses). The latest classification proposal is the NCI Bethesda System 2001 at the international level, and Zagreb 1990 in Croatia. Cytology can be used as a screening method of lesion detection to discriminate between positive and negative findings, or as a differential diagnosis method to predict the histologic diagnosis. In differential diagnosis, cytology is one of the complementary diagnostic methods along with colposcopy and histology, which taken together allow for a more accurate diagnosis to make. The conventional Pap test as a screening method for cervical carcinoma has been confirmed through the morbidity and mortality decrease, and is recommended in countries with developed cytology service like Croatia. Even higher screening sensitivity is achieved by the use of sophisticated cytologic¬ methods (LBC and computed cytologic analysis) and their combination with other methods (HPV DNA typing). Nation-wide cytologic screening has been used in many European Union countries. In Croatia, the main professional preconditions for national screening have been met, however, the plan and program should be designed, and the financial support ensured