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OBJECTIVE: The aim of this study is to describe risk factors associated with either false-negative cervical cancer screening or deviations from screening guidelines that result in incidentally found invasive cervical cancer at the time of simple hysterectomy for benign indications.
METHODS: This is a retrospective review from 1990 to 2017 of subjects with incidental cervical cancer. Baseline demographics, preoperative evaluations, surgical data, and histopathologic characteristics were recorded. Deviations from screening guidelines or false-negative screenings were identified. Associations of independent risk factors according to age, insurance status, and histology were assessed.
RESULTS: Fifty-nine subjects with a median age of 43 years were found. Abnormal uterine bleeding was the most common indication for hysterectomy (61%, n = 36) and cervical dysplasia was present in 42% (n = 25) of these cases. Of those with inappropriate screening, 38% (n = 17) did not have documented Pap test, 22% (n = 10) had Pap that was not triaged appropriately, 18% (n = 8) received Pap and colposcopy but no indicated excisional procedure, and 22% (n = 10) had an excisional procedure that was not managed according to guidelines. False-negative screening occurred in 25% subjects (n = 15). There was no significant association between age, insurance status, or histology and risk of false-negative screening or inadequate screening.
CONCLUSIONS: The most common cause of incidental cervical cancer at the time of simple hysterectomy was failure to properly adhere to screening guidelines. Less frequently, false-negative screening was the cause. No independent risk factor in either group was identified in this single institutional study. Illustrated is the importance of continuing education of surgeons about adequate screening in the preoperative evaluation for benign hysterectomy.

Assessing fish liver status is common in aquaculture nutrition assays. This often implies determining hepatocytes profile areas in routine thin (5-7 μm) histological sections. However, there are theoretical problems using planar morphometry in thin sections: inherent sampling cells biases, too small numbers of sampled cells, under/overestimation of size, measuring size as areas when cells are three-dimensional (3D) entities. The gold standard for assessing/validate cell size is stereology using thick sections (20-40 μm). Here, we estimated the volume of hepatocytes and their nuclei by the nucleator and optical disector stereological probes (in thick sections), and, innovatively, in thin sections too (using single-section disectors). The liver of common carp eating feed containing either low or high level of lipids was targeted. Results were compared with prior profile areas from planar morphometry using thin sections, and with profile areas estimated here with the two-dimensional (2D) nucleator. Ratios between nucleus and cell/cytoplasm (N/C) areas and volumes were calculated and compared. There was high positive correlation between volumes in thin and thick sections (r = .85 to .89; p < .001), empirically validating the single-section disector. Strong correlations existed between profile-derived versus 2D-nucleator areas (r = .74 to .83; p < .001). There was systematic underestimation of cells and nucleus size using planar morphometry. The N/C ratios derived from the 2D-nucleator data were higher than those from planar morphometry. Despite theoretical premises for using simple planar morphometry in thin sections are flawed, our results support that such morphometry on carp/fish hepatocytes may offer some valid biological conclusions. Anyway, we advanced guidelines for implementing proper methods.

OBJECTIVE: In the era of potentially disease-modifying agents such as Janus kinase inhibitors, accurate grading and differentiation of bone marrow (BM) fibrosis has become more relevant to assess staging of disease and therapeutic effects. However, different fibrosis grading models have been used in the past without uniformity, including the proposal by the World Health Organization. Current scoring systems are based only on reticulin fibrosis. Therefore, additional assessment of collagen and the grade of osteosclerosis appear to be essential to discriminate all components of the complex BM fibrous matrix.
RESULTS: We evaluated problems and pitfalls regarding staining techniques and the interpretation of reticulin fibrosis on a total of 352 samples. Furthermore, we propose a minor modification of the current grading and separate scoring for collagen deposition and osteosclerosis. Reproducibility of gradings was tested among 11 haematopathologists in a blinded assessment. Overall, the inter-rater reliability of all three grading systems ranged between 0.898 and 0.926.
CONCLUSIONS: A standardized assessment of BM fibrosis with differentiation between reticulin, collagen and osteosclerosis is recommended to evaluate the various components of the fibrous matrix which may be delinked after therapy. In this regard, quality of staining and application of laboratory standards enable a highly reproducible scoring.

OBJECTIVE: To provide practical guidelines for the cytopathologic diagnosis of malignant mesothelioma.
METHODS: Cytopathologists with an interest in the field involved in the International Mesothelioma Interest Group (IMIG) and the International Academy of Cytology (IAC) contributed to this update. Reference material includes peer-reviewed publications and textbooks.
BACKGROUND: This article is the result of discussions during and after the IMIG 2012 conference in Boston, followed by thorough discussions during the 2013 IAC meeting in Paris. Additional contributions have been obtained from cytopathologists and scientists who could not attend these meetings, with final discussions and input during the IMIG 2014 conference in Cape Town.

BACKGROUND: There is increasing interest in using whole slide imaging (WSI) for diagnostic purposes (primary and/or consultation). An important consideration is whether WSI can safely replace conventional light microscopy as the method by which pathologists review histologic sections, cytology slides, and/or hematology slides to render diagnoses. Validation of WSI is crucial to ensure that diagnostic performance based on digitized slides is at least equivalent to that of glass slides and light microscopy. Currently, there are no standard guidelines regarding validation of WSI for diagnostic use.
OBJECTIVE: To recommend validation requirements for WSI systems to be used for diagnostic purposes.
METHODS: The College of American Pathologists Pathology and Laboratory Quality Center convened a nonvendor panel from North America with expertise in digital pathology to develop these validation recommendations. A literature review was performed in which 767 international publications that met search term requirements were identified. Studies outside the scope of this effort and those related solely to technical elements, education, and image analysis were excluded. A total of 27 publications were graded and underwent data extraction for evidence evaluation. Recommendations were derived from the strength of evidence determined from 23 of these published studies, open comment feedback, and expert panel consensus.
RESULTS: Twelve guideline statements were established to help pathology laboratories validate their own WSI systems intended for clinical use. Validation of the entire WSI system, involving pathologists trained to use the system, should be performed in a manner that emulates the laboratory\'s actual clinical environment. It is recommended that such a validation study include at least 60 routine cases per application, comparing intraobserver diagnostic concordance between digitized and glass slides viewed at least 2 weeks apart. It is important that the validation process confirm that all material present on a glass slide to be scanned is included in the digital image.
CONCLUSIONS: Validation should demonstrate that the WSI system under review produces acceptable digital slides for diagnostic interpretation. The intention of validating WSI systems is to permit the clinical use of this technology in a manner that does not compromise patient care.

Q fever has long been considered a rare disease. The extensive outbreak in the Netherlands generated a body of literature based solely on the consensus in the Netherlands. As a long-standing expert on Q fever, I offer my experience and recommendations to the E-CDC and the Dutch Q fever Consensus Group. My (biased) opinion is that experts deeply involved in the field continue to be useful in the management of outbreaks and can avoid decisions that produce an unfavorable progression in patients. Here, I propose that the definition of \"chronic Q fever\" be avoided and suggest a new score-based diagnosis for Q fever endocarditis and vascular infection.

We conducted a group consensus review of thyroid aspirates that were previously interpreted as \"atypia of undetermined significance/follicular lesion of undetermined significance\" (AUS/FLUS) and followed by surgical interventions. The study aimed to investigate if consensus review would minimize the diagnosis of AUS/FLUS with an optimal interobserver agreement and also promote a better cytohistologic concordance. A group of reviewers who were blinded to the corresponding histologic findings simultaneously evaluated a total of 50 aspirates at a multiheaded light microscope. Using the Bethesda System for Reporting Thyroid Cytopathology as a guideline, a consensus interpretation was reached upon review of each aspirate. Interobserver agreement was calculated and recorded. The cytohistologic correlation was then performed between the consensus interpretation and the corresponding histologic diagnosis. The consensus review reclassified 26 (52%) aspirates as non-neoplasia/benign, 10 (20%) as follicular neoplasm/suspicious for a follicular neoplasm, 1 (2%) as papillary thyroid carcinoma, and 2 (4%) as nondiagnostic. Eleven (22%) aspirates remained AUS/FLUS. The interobserver agreement across the five diagnostic categories ranged from 71.6% to 100% with an average level of 88.8%. Cytohistologic concordance was achieved in 24 of 26 (92.3%) and 9 of 11 (81.8%) aspirates that were reclassified as non-neoplasia/benign and neoplasia/malignancy, respectively. A diagnostic accuracy of 89.2% (33/37) was obtained in reclassified cases. In conclusion, the group consensus review minimized AUS/FLUS, offered an optimal level of interobserver agreement, and most importantly, promoted excellent cytohistologic concordance in reclassified cases and, therefore, could play a substantial role in the future in reducing reaspiration and/or unnecessary surgeries.

Donovanosis is a rare sexually transmitted infection now mainly seen in sporadic cases in Papua New Guinea, South Africa, India, Brazil and Australia. The causative organism is Calymmatobacterium granulomatis though a proposal has been put forward that the organism be reclassified as Klebsiella granulomatis comb. nov. The incubation period is approximately 50 days with genital papules developing into ulcers that increase in size. Four types of lesions are described - ulcerogranulomatous, hypertrophic, necrotic and sclerotic. The diagnosis is usually confirmed by microscopic identification of characteristic Donovan bodies on stained tissue smears. More recently, polymerase chain reaction (PCR) methods have been developed. The recommended treatment is azithromycin 1 g weekly until complete healing is achieved.

25-30% of families fulfilling the criteria for hereditary diffuse gastric cancer have germline mutations of the CDH1 (E-cadherin) gene. In light of new data and advancement of technologies, a multidisciplinary workshop was convened to discuss genetic testing, surgery, endoscopy and pathology reporting. The updated recommendations include broadening of CDH1 testing criteria such that: histological confirmation of diffuse gastric criteria is only required for one family member; inclusion of individuals with diffuse gastric cancer before the age of 40 years without a family history; and inclusion of individuals and families with diagnoses of both diffuse gastric cancer (including one before the age of 50 years) and lobular breast cancer. Testing is considered appropriate from the age of consent following counselling and discussion with a multidisciplinary team. In addition to direct sequencing, large genomic rearrangements should be sought. Annual mammography and breast MRI from the age of 35 years is recommended for women due to the increased risk for lobular breast cancer. In mutation positive individuals prophylactic total gastrectomy at a centre of excellence should be strongly considered. Protocolised endoscopic surveillance in centres with endoscopists and pathologists experienced with these patients is recommended for: those opting not to have gastrectomy, those with mutations of undetermined significance, and in those families for whom no germline mutation is yet identified. The systematic histological study of prophylactic gastrectomies almost universally shows pre-invasive lesions including in situ signet ring carcinoma with pagetoid spread of signet ring cells. Expert histopathological confirmation of these early lesions is recommended.