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Objective: The cell block (CB) is an important adjunct to cytological preparations in diagnostic cytopathology. Optimizing cellular material in the CB is essential to the success of ancillary studies such as immunohistochemistry (IHC) and molecular studies (MS). Our aim was to identify which CB method was most suitable in a variety of specimen types and levels of cellularity. Study Design: We assessed 4 different CB methods, thrombin clot method (TCM), MD Anderson method (MDAM), gelatin foam method (GFM), and agar method (AM), with descriptive observations and ranking of the methods based on quantity of cells and morphological features. Results: TCM performed best in ranking for both quantity of cells and morphological features, followed by MDAM, GFM, and AM. Lack of adjuvant in the MDAM resulted in some unique morphological advantages which, however, also resulted in inconsistent performance. In low cellularity cases insufficient cells were frequently identified on slides from MDAM and AM CBs. Technique touch time was similar for all methods, with total processing time being shortest for TCM followed by MDAM, GFM, and AM. Conclusions: TCM was the most robust CB technique, retaining high scores for ranking of quantity and morphology in a variety of specimen cellularities and specimen types.

Introduction: Seborrheic keratosis-like lesion of the cervix and vagina is a rare lesion and shows similar morphology to vulvar seborrheic keratosis; 3 of the 7 previously reported cases were associated with low-risk human papillomavirus (HPV) type 42. We report a case of seborrheic keratosis-like lesion of the cervix and provide the first description of the cytological features of this lesion. Case Presentation: A woman in her late forties presented with postcoital bleeding. She had a cervical screening test following which she underwent cervical biopsy, endocervical and endometrial curettage, large loop excision of the transformation zone of the cervix, and hysterectomy. Results: The liquid-based cytology preparation showed cohesive groups of mildly atypical squamoid cells with a spindle cell morphology, mildly increased nuclear to cytoplasmic ratio, prominent nucleoli, and occasional nuclear grooves. No koilocytes were identified. Molecular genotyping revealed positivity for HPV type 42. Discussion/Conclusion: This represents the first description of the cytological features of a seborrheic keratosis-like lesion of the cervix, which are distinctive and unusual. Whilst the mild squamous atypia raised the possibility of a low-grade squamous intraepithelial lesion, no koilocytes were identified. The association in our case with a low-risk HPV type, HPV 42, provides further evidence for a role of this HPV type in the pathogenesis of these lesions.

Mucinous colorectal adenocarcinoma (CRC) is conventionally defined by extracellular mucin comprising >50% of the tumour area, while tumours with ≤50% mucin are designated as having a mucinous component. However, these definitions are largely arbitrary and comparisons of clinico-molecular features and outcomes by proportion of mucinous component are limited. A cohort of 1643 patients with stage II/III cancer was examined for tumour mucinous component, DNA mismatch repair (MMR) status, BRAF mutation and tumour infiltrating lymphocytes (TILs). Tumours with ≤50% mucinous component exhibited similar characteristics as mucinous tumours, including association with female gender, proximal location, high grade, TIL-high, defective MMR (dMMR) and BRAF mutation. Proportion of mucinous component did not stratify disease-free survival (DFS). In univariate analysis dMMR status, but not histological grade, stratified survival for mucinous and mucinous component tumours; however, in multivariate analysis dMMR status was not an independent predictor. BRAF mutation prognostic value depended on mucinous differentiation and MMR status, with poor prognosis limited to non-mucinous pMMR tumours (HR 2.61, 95% CI 1.69-4.03; p

Summary Endometrial cancer is the most common malignancy of the female genital tract in the Western world. The second edition Endometrial Cancer Structured Reporting Protocol was published to the Royal College of Pathologists of Australasia (RCPA) website in December 2019, and relates to the reporting of endometrial cancer in hysterectomy specimens. This editorial discusses selected key issues from the second edition of the RCPA protocol, and addresses future challenges in pathology reporting of endometrial cancer.

Background A renewed National Cervical Screening Program (NCSP) was introduced in Australia in December 2017. Under the renewed NCSP, there are limited data to guide the management of discordant colposcopy and biopsy results after a liquid-based cytology (LBC) finding of 'possible high-grade squamous intraepithelial lesion' (pHSIL). Aims This study aims to determine the proportion of women referred with pHSIL who are found to have HSIL, identify influencing factors of women most at risk, and examine the role that cytopathology review plays in management decisions. Materials and methods Two-hundred and thirty-two women presenting to a tertiary women's hospital in Australia with pHSIL since December 2017 were identified. Women with HSIL following colposcopy directed biopsy were referred for treatment. When HSIL was not identified, these patients were referred for multidisciplinary clinicopathological review. Pathological outcomes and treatment recommendations are included. Main outcome measures The primary outcome of the study was histological confirmation of HSIL. Results Primary outcome data were available for 182 women (78.5%); 62 (34.1%) had HSIL on histology, three (1.7%) had adenocarcinoma in situ (AIS) and one (1%) had cervical squamous cell carcinoma (SCC). There was no association between age and the presence of HSIL. The presence of human papillomavirus 16 and/or 18 increased the likelihood of HSIL on histology (relative risk 1.9; 95% CI 1.27-2.80, P = 0.002). Fifty-nine (25.4%) women were referred for observation who had low-grade squamous intraepithelial lesion/no dysplasia. Conclusions Clinicopathological review optimises management and triage of patients with pHSIL on referral cytology. Understanding outcomes in these patients informs counselling and management.

Australia has implemented a high-coverage HPV vaccination program but has not, to date, established the distribution of HPV types that occur in cervical cancers in Australia. This information is important for determining the potential for cervical cancer prevention with both current and broader spectrum HPV vaccines. We analysed 847 cervical cancers diagnosed 2005 to 2015 in tertiary centres in the three most populous Australian states with resolution of specimens containing multiple HPV types using laser-capture microdissection. Archived FFPE tissue was reviewed by specialist pathologists, sandwich sectioned, and initially whole-tissue sections genotyped for HPV. Samples were first genotyped using SPF10-LiPA25 (version 1). Negative samples were screened with DNA ELISA kit HPV SPF10, followed by genotyping with SPF+ LiPA if ELISA positive. If still negative, samples were tested on a qPCR assay targeting the E6 region of HPV16, 18, 45 and 33. Of the 847 cancers (65.1% squamous, 28.7% adenocarcinoma, 4.3% adenosquamous, 2.0% other), 92.9% had HPV detected. Of the HPV-positive cancers, 607 of 787 (77.1%) contained HPV16 or 18, 125 of 787 (15.9%) contained HPV31/33/45/52 or 58, and 55 (7.0%) another HPV type. There was a strong correlation between HPV type and age, with younger women most likely to have HPV16/18 detected and least likely HPV negative. Our findings indicate that cervical cancers diagnosed in Australia more frequently contain HPV16/18 than in international series. This could be due to cervical screening in Australia increasing the proportion of adenocarcinomas, in which types 18 and 16 more strongly predominate, due to prevention of squamous cancers.

Study Objective To study the hypothesis that the levonorgestrel intrauterine device (LNG-IUD) can have a role in the treatment of endometrial polyps confirmed at outpatient hysteroscopy in premenopausal women. Design Canadian Task Force classification level II1 (a controlled trial that is not randomised). Setting Outpatient hysteroscopy. Patients Premenopausal women who had a polyp diagnosed at outpatient hysteroscopy. Interventions Premenopausal women who had a polyp diagnosed at outpatient hysteroscopy and had a LNG-IUD inserted were booked for general anesthesia hysteroscopy and polypectomy through the standard booking process. A contemporaneous control was taken sequentially from the outpatient hysteroscopy database to match the case. Measurements and Main Results The presence of a polyp at hysteroscopy under general anesthesia. A total of 39 patients were included in the study, with 19 in the intervention group and 20 in the control group. The mean age was 43.6 (standard deviation = 5.6) and 43.2 (standard deviation = 8.1) years in the 2 groups, respectively. No difference was found in the time interval between the 2 procedures in the intervention and control groups (mean = 92 vs 84 days, p = .73). However, the proportion of polyps present at the second procedure was significantly higher in the control group (80% vs 37%; relative risk = 2.17; 95% confidence interval, 1.16–4.07; p = .0062). Conclusion Our case-control study found that the LNG-IUD can have a role in the treatment of polyps for women who have heavy menstrual bleeding. This is the first study to show regression of endometrial polyps after treatment with LNG-IUD by direct visualisation at hysteroscopy.

ObjectiveTumour-infiltrating lymphocyte (TIL) response and deficient DNA mismatch repair (dMMR) are determinants of prognosis in colorectal cancer. Although highly correlated, evidence suggests that these are independent predictors of outcome. However, the prognostic significance of combined TIL/MMR classification and how this compares to the major genomic and transcriptomic subtypes remain unclear.DesignA prospective cohort of 1265 patients with stage II/III cancer was examined for TIL/MMR status and BRAF/KRAS mutations. Consensus molecular subtype (CMS) status was determined for 142 cases. Associations with 5-year disease-free survival (DFS) were evaluated and validated in an independent cohort of 602 patients.ResultsTumours were categorised into four subtypes based on TIL and MMR status: TIL-low/proficient-MMR (pMMR) (61.3% of cases), TIL-high/pMMR (14.8%), TIL-low/dMMR (8.6%) and TIL-high/dMMR (15.2%). Compared with TIL-high/dMMR tumours with the most favourable prognosis, both TIL-low/dMMR (HR=3.53; 95% CI=1.88 to 6.64; Pmultivariatemultivariate=0.001) showed poor DFS. Outcomes of patients with TIL-low/dMMR and TIL-low/pMMR tumours were similar. TIL-high/pMMR tumours showed intermediate survival rates. These findings were validated in an independent cohort. TIL/MMR status was a more significant predictor of prognosis than National Comprehensive Cancer Network high-risk features and was a superior predictor of prognosis compared with genomic (dMMR, pMMR/BRAFwt/KRASwt, pMMR/BRAFmut/KRASwt, pMMR/BRAFwt/KRASmut) and transcriptomic (CMS 1-4) subtypes.ConclusionTIL/MMR classification identified subtypes of stage II/III colorectal cancer associated with different outcomes. Although dMMR status is generally considered a marker of good prognosis, we found this to be dependent on the presence of TILs. Prognostication based on TIL/MMR subtypes was superior compared with histopathological, genomic and transcriptomic subtypes.

Australia has implemented a high-coverage HPV vaccination program but has not, to date, established the distribution of HPV types that occur in cervical cancers in Australia. This information is important for determining the potential for cervical cancer prevention with both current and broader spectrum HPV vaccines. We analysed 847 cervical cancers diagnosed 2005 to 2015 in tertiary centres in the three most populous Australian states with resolution of specimens containing multiple HPV types using laser-capture microdissection. Archived FFPE tissue was reviewed by specialist pathologists, sandwich sectioned, and initially whole-tissue sections genotyped for HPV. Samples were first genotyped using SPF10-LiPA25 (version 1). Negative samples were screened with DNA ELISA kit HPV SPF10, followed by genotyping with SPF+ LiPA if ELISA positive. If still negative, samples were tested on a qPCR assay targeting the E6 region of HPV16, 18, 45 and 33. Of the 847 cancers (65.1% squamous, 28.7% adenocarcinoma, 4.3% adenosquamous, 2.0% other), 92.9% had HPV detected. Of the HPV-positive cancers, 607 of 787 (77.1%) contained HPV16 or 18, 125 of 787 (15.9%) contained HPV31/33/45/52 or 58, and 55 (7.0%) another HPV type. There was a strong correlation between HPV type and age, with younger women most likely to have HPV16/18 detected and least likely HPV negative. Our findings indicate that cervical cancers diagnosed in Australia more frequently contain HPV16/18 than in international series. This could be due to cervical screening in Australia increasing the proportion of adenocarcinomas, in which types 18 and 16 more strongly predominate, due to prevention of squamous cancers.

The aim of this study was to establish a scoring method for ploidy analysis using silver in situ hybridisation (SISH) with a chromosome 17 centromere probe. SISH was performed using the Ventana chromosome 17 centromere probe on sections from formalin fixed, paraffin embedded archival cases of complete hydatidiform moles, partial hydatidiform moles and hydropic products of conception with previously established ploidy status (determined by flow cytometry or karyotyping). In order to determine ploidy status, a scoring method was developed based on both the average number of signals per nucleus (ASN) and the percentage of nuclei with three signals (N3S), enumerated in 50 villous cytotrophoblastic and/or stromal cells. The results of four independent observers were compared individually and collectively with previously established ploidy status. There was a highly statistically significant difference between diploid and triploid gestations for ASN (1.86 ± 0.13 and 2.70 ± 0.16 respectively, Student t-test, p 0.0001) and for N3S (1.14 ± 1.65 and 71.59 ± 14.25 respectively, Student t-test, p 0.0001). The sensitivity and specificity of the SISH-based assay was 99.1% and 100% respectively for ASN, and 100% and 100% respectively for N3S. A chromosome 17 centromere probe SISH-based assay can reliably distinguish between diploid and triploid gestations. This test has diagnostic utility in distinguishing partial hydatidiform moles from histological mimics.

In 2014 the Papanicolaou Society of Cytopathology (PSC) published a system of standardised terminology and nomenclature for pancreaticobiliary cytology (STNPC). In the present study, 232 previously reported pancreaticobiliary cytology specimens were categorised according to this set of guidelines in order to identify potential challenges to implementation of the PSC system into routine practice. Overall, 207 (89%) of the cases were found to comply with the PSC scheme in their original form. Twenty-five cases (11%) demonstrated that the application of the PSC system would result in a change of category. In the majority of these cases, the change was related to the method of categorising low grade and premalignant neoplasms, using the categories of 'Neoplastic: other' (a new category unique to STNPC classification scheme) and 'Atypical', for specimens deemed to be diagnostic of or suspicious for these lesions, respectively. The study also highlighted the emphasis on the inclusion of imaging context and cyst fluid analysis in the interpretation of endoscopic ultrasound guided fine needle aspiration specimens in the guidelines. The STNPC offers an approach to pancreaticobiliary cytology that reflects the considerable variation in the nature and treatment of the entities that may be encountered in these specimens. Challenges in utilisation of the scheme include awareness of the unique approach to the categorisation of premalignant and low grade neoplasms, and the amount and quality of available clinical and imaging information.

Stereotactic core biopsy (CB) using 14-gauge needles was adopted as the standard method of diagnosis of screen-detected breast microcalcifications (MC) at Sir Charles Gairdner Hospital in 1996. Fine needle aspiration (SFNA) was included as an adjunct, to optimise sensitivity and to provide immediate reporting. Recently, core imprint cytology (CI) has been shown to have a high sensitivity in diagnosing malignancy. The aims of this paper were to evaluate the accuracy of SFNA as an adjunct to CB, and whether CI could replace SFNA for immediate reporting in MC. Part A is a retrospective review of CB/SFNA of screen-detected MC from May 1998 to February 2000. A minimum of five cores was performed. SFNA samples were restricted to a maximum of three needle passes. Part B is a prospective study of CI from May to November 2000. In Part A, there were 406 MC in 353 women and 81 carcinomas were proven on excision. The complete sensitivity of CB for a diagnosis of malignancy was 97.5% and of SFNA was 65%. No false-positive diagnoses were made by either method. No extra carcinomas were detected using SFNA. In Part B, CB/CI were performed on 203 MC from 165 women. There were 38 carcinomas and 30 of these (79%) were diagnosed as malignant on CI. No false-positive diagnoses were made. The predictive value of a benign diagnosis was 95%. SFNA had little value as an adjunct to core biopsy in MC. CI promises to be useful in providing same day diagnosis for counselling purposes and for planning future surgery.

STUDY QUESTION: Can the presence of endometrial nerve fibres be used as a diagnostic test for endometriosis in women with pelvic pain?SUMMARY ANSWER: Endometrial fine nerve fibres were seen in the endometrium of women both with and without endometriosis, making their detection a poor diagnostic tool for endometriosis.WHAT IS KNOWN ALREADY: Laparoscopy and biopsy are currently the gold standard for making a diagnosis of endometriosis. It has been reported that small density nerve fibres in the functional layer of the endometrium are unique to women with endometriosis and hence nerve fibre detection could function as a less invasive diagnostic test of endometriosis. However, it may be that other painful conditions of the pelvis are also associated with these nerve fibres. We therefore focused this prospective study on women with pelvic pain to examine the efficacy of endometrial nerve fibre detection as a diagnostic test for endometriosis.STUDY DESIGN, SIZE, DURATION: This prospective case-control study conducted between July 2009 and July 2013 included 44 women with pelvic pain undergoing laparoscopic examination for the diagnosis of endometriosis. Immunohistochemical nerve fibre detection in endometrial curettings and biopsies using anti-protein gene product 9.5 was compared with surgical diagnosis.PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Paired endometrial biopsies and curettings were taken from patients with (n = 22, study group) and without (n = 22, control group) endometriosis. Tissue was analysed by immunohistochemistry and nerve fibres were counted whenever they were present in the functional layer of the endometrium.MAIN RESULTS AND THE ROLE OF CHANCE: Fine nerve fibres were present in the eutopic endometrium of patients both with and without endometriosis. The presence of nerve fibres in curettings was not effective for either diagnosing or excluding endometriosis; sensitivity and specificity were 31.8 and 45.5% respectively, positive predictive value was 36.8% and negative predictive value was 40.0%. Few endometrial biopsy specimens were found to have nerve fibres present; sensitivity and specificity for endometrial biopsy were 13.6 and 68.2% respectively, positive predictive value was 30.0% and negative predictive value was 44.1%.LIMITATIONS, REASONS FOR CAUTION: This was a relatively small sample size and studies like this are subject to the heterogeneous nature of the patient population and tissue samples, despite our best efforts to regulate these parameters.WIDER IMPLICATIONS OF THE FINDINGS: Our results demonstrate that fine nerve fibres are present in women with and without endometriosis. Future work should focus on the function of endometrial nerves and whether these nerves are involved with the subfertility or pain that endometriosis sufferers experience. Our study does not support the detection of endometrial nerve fibres as a non-invasive diagnostic test of endometriosis in women with pelvic pain.

Well-differentiated papillary mesothelioma (WDPM) is an uncommon tumor usually arising in the peritoneum and mostly an incidental finding during abdominal and pelvic surgery. Its natural history and association with other neoplasms is not clearly understood. We present a rare case of WDPM in association with high-grade endometrial carcinoma. To our knowledge, there are only two previously reported cases in the English literature of WDPM in association with endometrial carcinoma.A 62-year-old woman underwent pelvic surgery for a high-grade endometrial adenocarcinoma. At laparotomy an extensive peritoneal nodular fibrotic reaction was present, raising the clinical possibility of metastatic disease; however, intraoperative frozen section reported this as a mesothelial reaction. Cytologic examination of peritoneal washings revealed cohesive clusters of reactive-appearing mesothelial cells, some with papillary morphology, and no evidence of adenocarcinoma. The peritoneal biopsies showed no metastatic carcinoma. The endometrial tumor was an endometrioid adenocarcinoma.The cytologic diagnosis of WDPM may be difficult because it is an uncommon entity and there are overlapping features with other neoplastic and nonneoplastic lesions of the female genital tract and peritoneum. Compounding this, WDPM may occur in association with other neoplasms. We highlight the potential for surgical and pathologic misinterpretation of this entity.

Case presentation A 34-year-old woman presented with two months history of intermittent vaginal bleeding. Her only past medical history was severe endometriosis and subsequent hemicolectomy. Pap smear showed high grade squamous intraepithelial lesion and cervical biopsy showed adenocarcinoma in situ (AIS) and SMILE with strong p16 positivity. She underwent a cone biopsy which demonstrated a 9 mm adenosquamous carcinoma and SMILE. The decision was made for a trachelectomy. Discussion and conclusion Given the morphological overlap and significant association with both CIN and AIS and diffuse p16 positivity, Boyle and McCluggage1 suggested that SMILE is likely to arise from high risk human papillomavirus infected reserve cells with the potential for multidirectional differentiation. SMILE is considered a variant of AIS.2 However, it has been suggested to be categorised as a distinct lesion separate from AIS, especially since classic AIS is only present in a minority of cases.1 SMILE is best regarded as a form of high grade reserve cell dysplasia and management should be as for AIS.1

Background Mucoepidermoid carcinomas are common tumours of the minor salivary glands and have diverse clinical outcomes. The most important histological parameter for predicting tumour behaviour is the tumour grade. Methods and Results We report a case of an 87-year-old male with right cheek swelling. The lesion was excised and tissue sections from paraffin blocks were stained with H&E. Histological examination revealed a mucoepidermoid carcinoma arising in the buccal mucosa, with direct bone invasion and metastatic tumour in one Level 1 lymph node. Using the Armed Forces Institute of Pathology (AFIP) 1,2 grading system, the tumour was classified as low grade, but demonstrated biologically high grade behaviour. Discussion Mucoepidermoid carcinomas are currently graded into low, intermediate and high grades using a weighted system by Auclair and Goode from the AFIP. 1,2 An alternate method of grading has been proposed by Brandwein 3 which takes into consideration three features in addition to AFIP criteria including (i) lymphovascular invasion, (ii) bone invasion and (iii) pattern of tumour infiltration. This new system upgraded our tumour from low to high grade. This case illustrates some discordance between tumour grade and behaviour as defined by the AFIP system and demonstrates improved correlation between tumour grade and behaviour using the modified Brandwein system.