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As for the Bethesda system for cervical and thyroid cytopathology, a terminology for reporting urinary cytology has been published in 2015. The new "Paris System" provides a consensus terminology for urinary cytology which underlines the criteria for the recognition of high-grade urothelial carcinoma (HGUC) and of those excluding HGUC, or suspicious for HGUC. It also focuses on new rules to recognize and report the subgroup of "atypical urothelial cells". Here we describe and illustrate the various categories as in the reference book. We analyse the main diagnostic criteria, including microscopic features as well as the risk of malignancy associated to every diagnostic category., (Copyright © 2019. Published by Elsevier Masson SAS.)

Introduction: Diffuse malignant mesothelioma (MMD) is a rare disease. The diagnosis is difficult and needs an antibody panel. The tumor suppressor gene BRCA1 associated protein 1 (BAP1) is involved in several cancers, including MMD. Loss of BAP1 expression is correlated with BAP1 somatic or constitutional genetic defects. Our work assesses the value of integrating BAP1 in the panel of antibodies used for the diagnosis of MMD., Materials and Methods: Immunohistochemical techniques were performed on cytological and histological specimens of MMD and adenocarcinoma pleural metastasis., Results: Of the 26 patients with MMD and the 24 patients with adenocarcinoma pleural metastasis, loss of BAP1 expression was observed in 11 (48%) and one adenocarcinoma (6%) on cytological specimens and in 12 MMD (48%) and in one adenocarcinoma (5%) on biopsy specimens. The concordance between immunocytochemistry and immunohistochemistry was 100%. The specificity of BAP1 was 100% on cytological and biopsy specimen for the diagnosis of malignancy in case of mesothelial proliferation., Discussion and Conclusion: Loss of BAP1 expression is an indicator of MMD in a context of mesothelial proliferation. This immunohistochemistry could be integrated in the panel of immunostaining used for MMD diagnosis, either on histological or cytological samples. Furthermore, loss of BAP1 expression guides the patient to an oncology genetic counseling in order to eliminate a MMD developed as part of a constitutional genetic defect., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

May-Grünwald-Giemsa (MGG) stain is a Romanowsky-type, polychromatic stain as those of Giemsa, Leishman and Wright. Apart being the reference method of haematology, it has become a routine stain of diagnostic cytopathology for the study of air-dried preparations (lymph node imprints, centrifuged body fluids and fine needle aspirations). In the context of their actions of promoting the principles of quality assurance in cytopathology, the French Association for Quality Assurance in Anatomic and Cytologic Pathology (AFAQAP) and the French Society of Clinical Cytology (SFCC) conducted a proficiency test on MGG stain in 2013. Results from the test, together with the review of literature data allow pre-analytical and analytical steps of MGG stain to be updated. Recommendations include rapid air-drying of cell preparations/imprints, fixation using either methanol or May-Grünwald alone for 3-10minutes, two-step staining: 50% May-Grünwald in buffer pH 6.8 v/v for 3-5minutes, followed by 10% buffered Giemsa solution for 10-30minutes, and running water for 1-3minutes. Quality evaluation must be performed on red blood cells (RBCs) and leukocytes, not on tumour cells. Under correct pH conditions, RBCs must appear pink-orange (acidophilic) or buff-coloured, neither green nor blue. Leukocyte cytoplasm must be almost transparent, with clearly delineated granules. However, staining may vary somewhat and testing is recommended for automated methods (slide stainers) which remain the standard for reproducibility. Though MGG stain remains the reference stain, Diff-Quik(®) stain can be used for the rapid evaluation of cell samples., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

The search for biological and clinical significance of equivocal urinary cytology has emerged as the most promising application of fluorescence in situ hybridization (FISH). Using the multiprobe UroVysion(®) assay, a negative FISH result in the presence of atypical urothelial cells favors the presence of reactive, benign alterations and helps to avoid unnecessary invasive procedures. However, a negative FISH result in case of a negative or equivocal cytology does not exclude low-grade urothelial neoplasia. Equivocal findings are a notorious problem after conservative treatment, particularly after BCG immunotherapy of carcinoma in situ, where even benign reactive changes can appear worrisome. In this situation, a positive FISH result in spite of non-high grade cytology independently indicates persistent or recurrent urothelial carcinoma. However, chromosomal abnormalities are not restricted to malignancy but may also occur in benign cells. Tetraploidy with a balanced duplication of the whole genome, or polyploidy can occur in non-neoplastic conditions of the bladder such as Decoy cells, radiotherapy-induced changes and urolithiasis. Thus, a positive FISH result in a patient with a history of pelvic irradiation does not prove cancer unless there is unequivocal 9p21 deletion. Recent studies show that an aggressive workup of patients with a suspicious cytology+positive UroVysion(®) result and negative cystoscopy is not currently justified. However, multi-target UroVysion(®) FISH remains an excellent tool to improve diagnosis in urinary cytopathology, provided that FISH results are interpreted in the light of the clinical situation, and that one reminds that FISH adds no diagnostic value in case of clearly positive, high-grade cytology., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Aims: To investigate (1) whether sparse nuclear atypias involving deep urothelial cells have a diagnostic or prognostic value in urinary cytology, and (2) whether the terms atypical urothelial cells "of undetermined significance" (AUC-US) or "cannot exclude high grade" (AUC-H) might be used to standardize urinary cytology reports., Patients and Methods: Atypical urothelial cells (AUC) were defined as deep cells with nuclear abnormalities (increased N/C ratio, eccentric nucleus, hyperchromatism and/or irregular shape) in small number not allowing their categorization as malignant, high grade. We studied 435 urinary samples from 126 patients with AUC at any step of their clinical history, followed up over a 10-year period (1999-2009). Every case was compared with histopathology within 6 months and to long term follow-up including cystoscopy and histopathology combined., Results: A total of 183 AUC was recorded. AUC were associated with negative, benign or low grade histological results in 36 of 106 cases (33.9 %) within 6 months, but a high grade was simultaneously documented in 70 cases (66 %). AUC preceded high-grade lesions in 66 cases (36.1 % of all AUC) in a mean interval of 10.5±12.0 months. Overall, AUC were associated with or predictive of high-grade lesions in 135 cases (73.8 %)., Conclusion: AUC have a diagnostic and prognostic value. Applying the terms AUC-US and AUC-H to urinary cytopathology reports would allow, as for the Bethesda system for cervical or vaginal cytologic diagnoses, better appreciation of the risk of progression to high grade tumours in cases with atypias., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Cells from serous effusions can easily be concentrated by centrifugation. Thereafter, various procedures allow cells to be deposited on glass slides. Standard stains give excellent morphologic details for analysis. However, unsatisfactory specimens are frequently observed in daily practice. Standardization brought by liquid based cytology may be of some help for immunocytochemistry, but conventional methods remain essential. Several decades of experience and analysis of literature allow the authors to select the best criteria for interpretation, with emphasis on the differential diagnosis of malignant vs. benign effusions.

Immunocytochemistry may be of valuable help in typing most malignant serous effusions. Various preparatory methods are described including centrifugation and smearing, cytocentrifugation, cell blocks and liquid based cytology. The value and usefulness of immunocytochemistry depends on the experience of each pathologist. The use of a panel of antibodies associating markers of carcinomas with markers of mesothelial cells is recommended.

Objective: To assess 1) the value of fluorescence immunocytochemistry (uCyt+ test, DiagnoCure Inc., Quebec) in the detection of recurrent bladder tumour after transurethral resection (TUR) and 2) the predictive value of a positive uCyt+ test in patients with negative cystoscopy., Material and Methods: This study was based on 132 patients with a mean follow-up of 21.9 weeks after TUR. The initial tumours were pTa G1-2 in 66.7% of cases, and G3 in 28.8% of cases. Cystoscopy, urine cytology (UC) and uCyt+ test data were collected on the day of the first control visit (D0), and the patients were then reviewed at 6 and 12 months. All lesions detected on cystoscopy were biopsed., Results: The mean sensitivity of UC was 47.4% and the mean sensitivity of uCyt+ was 73.7% (84.2% in combination). In patients with negative cystoscopy on D0, a positive uCyt+ test has no predictive value at 6 months. At 12 months, 20.0% of patients with positive UC had relapsed, versus 16.7% of patients with negative UC (p = ns). On the other hand, at 12 months, 50.0% of patients with negative cystoscopy but positive uCyt+ test had relapsed, versus 16.4% of patients with a negative uCyt+ test (p < 0.01)., Conclusions: The uCyt+ test allows assessment of the risk of recurrence at I year, while UC alone only has a diagnostic value. These results raise the possibility of combining the tests in order to decrease the frequency of follow-up cystoscopy.

We analysed 150 cases of primary lung cancers investigated by bronchial aspirate and biopsy methods with clinical, radiologic and bronchoscopic findings. Among the 150 cases studied, three were characterized by mixed tumor cell components, thus allowing 153 cyto-histological comparisons. The cytologic and histopathologic typing agreed strictly in 102 cases of 153 (66.7%) and was considered as correct in 40 cases (26.1%). Only cases with divergent evaluation between small-cell carcinoma and non small-cell carcinoma were considered as discordant: such misclassification occurred in 11 specimens (7.2%), including two cases with mixed patterns. The cytologic typing was in agreement with the final diagnosis in all epidermoid carcinomas, adenocarcinomas, large-cell carcinomas and poorly differentiated carcinomas. In small-cell carcinomas, cytology was in agreement with histopathology in 20 of 26 cases (77%), and could only indicate undifferentiated features in four cases (15.4%). The analysis of bronchial aspirate specimens gave reliable typing in 92% of cases, and indicated a better tumor cell differentiation than histopathology in 6.5% of cases. The results obtained show that aggressive treatments can be reliably proposed on the basis of cytologic findings, even without tissue corroboration. This proposal is particularly helpful in cases where biopsy cannot be performed (peripheral lesions) or creates a danger to the patient (iatrogenic hemorrhage).

The proposal of an early diagnosis of prostate cancer through mass screening with digital rectal examination (DRE), transrectal ultrasound (TRUS) and serum tumor markers remains controversial: there is no high risk population. No study has proven that mass screening reduces the mortality from prostate cancer. However, when clinical and biological data give arguments for the presence of a cancer, every patient requires a prostate biopsy. We have studied the Positive Predictive Value (PPV) of each test in a selected population: 200 men over 50 years of age in which rectal examination or PSA assay was suspicious were investigated. Without any reference to the prostate volume, we considered that the PSA level was "suspicious" when it reached 3 times the upper reference value, or 12 ng/ml. DRE was suspicious in 73%, comprising 50% with prostate carcinoma. PSA assay was suspicious in 65%, comprising 61% with prostate carcinoma. 88% of cancers had a suspicious DRE or PSA assay. TRUS was suspicious in 89%, comprising 45% with prostate carcinoma. Ultrasound guided core biopsies were performed in each case, and allowed a positive diagnosis in 42% of cases, whereas bilateral fine-needle cyto-aspirates were positive in 87% of histologically proven carcinomas. Cytology alone was positive in 3 patients with negative biopsies. Both results show that the PPV of a suspicious DRE associated with an elevated PSA level is 84%. An increased PSA level is correlated with a cancer in 61%.(ABSTRACT TRUNCATED AT 250 WORDS)

The diagnostic sensitivity (Se) and specificity (Sp) of fine-needle aspiration cytology (FNAC) of the prostate can be evaluated by comparing its results to a histological reference: rates of reported Se range from 65-98%, Sp being equal or superior to 95%. Published series are heterogeneous in terms of cancer prevalence, with a 25-85% proportion of histologically proven adenocarcinomas, irrespective of the anatomical stage of the disease. The overall accuracy of screening by core biopsies or FNAC is lower than 5%, and does not justify wide-scale application of these tests. In 75%, cytological assessment of the tumor grade correlates with Gleason's histological score and grade. Severe intraductal dysplasias (DIC 3) are probably involved in some of the cytological grade I cases. Ultrasonographic guidance of FNAC is not recommended in comparison with histologically obtained data. The indications for performing FNAC of the prostate should be different from those of standard biopsies: the former should be carried out on suspicious lesions revealed by digital rectal examination or ultrasonography, or in a staging attempt. FNAC should be reserved for early diagnosis of prostate cancer in patients presenting with non-specific urologic symptoms. Samples should be obtained by digitally-guided transrectal bilateral FNAC.

Cytology is an old method of diagnosis: it is the microscopical observation of cells in the aim of their identification, of the recognition of morphological abnormalities to obtain diagnosis or prognosis informations. During the last 20 years, new technics have been developed: 1) Immunocytochemistry permits the identification of the tissue or the organ of which a tumoral cell population is born, the determination of its stage of differentiation, its kinetic and the diagnosis of bone marrow or lymph node metastasis. 2) With in situ molecular biology, it becomes possible to detect, at the cell level, virus, oncogenes or chromosomic abnormalities. 3) Flow and image cytometry are easy means for DNA content determination and for an objective and reproducible cell definition. None of these methods are able, at this time, to replace the cytological analysis, but they are useful, sometimes necessary, for the diagnosis and the prognosis evaluation of malignancy.

In this prospective study, flow cytometry DNA profile of 169 stage D2 prostatic carcinomas were compared with conventional cytologic data. Two transrectal fine-needle aspiration biopsies were performed in each patient. Aspirates were immediately fixed in 2% polyethylene glycol 1500* alcoholic solution (Merck). Suspensions were mixed and studied by a conventional cytologic technique (Papanicolaou) and by flow cytometry (propidium iodide stain on isolated nuclei). A highly significant correlation was found between the DNA profile and the cytologic grade (p less than 0.001). The DNA profile was bimodal in 14% (3/21) of aspirates containing benign or atypical cells, 18% (3/17) of grade I aspirates, 30% (13/43) of grade II aspirates and 71% (24/34) of grade III aspirates. Routine cytologic evaluation of cell suspensions evaluated by flow cytometry is important in clinical practice since both falsely unimodal and falsely bimodal profiles occur. Leukocytes or benign epithelial cells can interfere with the tumor cell population. In fine-needle aspirates, the broad range of non-malignant contaminating cells limits the value of immunocytochemistry and emphasizes the usefulness of routine conventional cytologic evaluation.

Thirty seven prostatic carcinomas at a D2 metastatic stage were studied after transrectal fine-needle aspiration in a prospective multicentric study. The number and the distribution of nucleoli were compared, in each cytological grade, to the flow cytometric nuclear DNA content. In 9 grade I, 13 grade II and 15 grade III the proportion of bimodal DNA profiles was 11%, 30.7% and 66.7%. The total number of nucleoli per 100 nuclei was respectively 114.11 (SD = 8.12), 158.31 (SD = 47.97) and 194.40 (SD = 58.42). A statistically significant difference (t = 2.78; P = 0.009) was found between the total number of nucleoli of unimodal (22 cases) and bimodal DNA profiles (15 cases). However, no significant difference in nucleolar parameters was found between unimodal (14 cases) and bimodal DNA profiles (14 cases) in cytological grades II and III. These results suggest that the nucleolar parameters do not necessarily parallel the increase in the nuclear DNA content, and that the two factors are independent of one another.

Systematic fine-needle aspiration biopsies and core biopsies were simultaneously obtained on 200 patients with suspected prostatic cancer over a 12-month period. The technical aspect of cellular aspiration and fixation was carefully adjusted. 6 to 8 transrectal bilateral aspirations per patient were performed, and their results were compared to those of core biopsies guided on suspicious areas revealed by rectal examination or transrectal ultrasound. The sensitivity of aspiration for the diagnosis of prostatic cancer is 87%. The specificity is 95%, with a positivity in 3 cases of prostatic cancer in which core biopsy is negative. No cytologic specimen is inadequate for diagnosis. The correlation between cytologic and histologic patterns shows that the proportion of Gleason grade 2 decreases with the cytologic grade, whereas the proportion of Gleason grade 5 increases gradually. Both results show the importance of multiple sampling in the cytological procedure, and confirm the diagnostic value of prostatic fine-needle aspiration method.

During a two-year period, 69 positive prostatic fine-needle cyto-aspirates were selected for a comparison between the cytological grade and the clinical data, and also with the Gleason score and grade obtained with needle-biopsy. The cytological grade is independent of stage, except for grade III that indicates an advanced tumor (T3-T4). On the other hand, the cytological grade provides valuable indications on the histopathological differenciation according to Gleason, with no grade II inferior to Gleason score 5, and no grade III inferior to Gleason 7. 90% of cytological grades III are Gleason grade 4. According to recent studies, we believe that the cytological grade I is related to invasive or in-situ carcinoma, but also to high-grade intra-ductal dysplasia. Thus, it is not surprising to find no correlation between grade I and the clinical status, nor between grade I and the Gleason score and grade, though grade I (or DIC 3) has a good diagnostic value.