[What contribution can make artificial intelligence to urinary cytology?] / Quel apport de l'intelligence artificielle en cytologie urinaire ?

Urinary cytology using the Paris system is still the method of choice for screening high-grade urothelial carcinomas. However, the use of the objective criteria described in this terminology shows a lack of inter- and intra-observer reproducibility. Moreover, if its sensitivity is excellent on instrumented urine, it remains insufficient on voided urine samples. Urinary cytology appears to be an excellent model for the application of artificial intelligence to improve performance, since the objective criteria of the Paris system are defined at cellular level, and the resulting diagnostic approach is presented in a highly "algorithmic" way. Nevertheless, there is no commercially available morphological diagnostic aid, and very few predictive devices are still undergoing clinical validation. The analysis of different systems using artificial intelligence in urinary cytology rises clear prospects for mutual contributions.

[Molecular and other ancillary tests proposed by The Bethesda system for reporting thyroid cytopathology 2023]. / Les tests moléculaires et autres techniques ancillaires en cytologie thyroïdienne selon Bethesda 2023.

For the first time the 2023 version of The Bethesda System for Reporting Thyroid Cytology dedicates a whole chapter (chapter 14) to ancillary studies almost exclusively represented by molecular testing. The latest data reported bring some evidence that molecular testing could help to optimize the diagnostic performance of « indeterminate ¼ categories (AUS and NF). Other studies suggest a promising role to guide the management of suspicious of malignancy and malignant categories. Indeed, the recognition of prognostic and predictive biomarkers analyzed on cytological samples, regardless of how it is collected, has progressed thanks to advances in our knowledge of molecular abnormalities of thyroid tumors. The chapter 14 is presented here highlighting the current and emerging roles of « in-house ¼ and commercialized molecular testing as presented by TSBRTC.

[Serous fluid cytopathology : International system: Ancillary studies for serous fluids and special considerations for peritoneal washings]. / Cytopathologie des séreuses : la classification internationale : À propos des techniques ancillaires prédictives et du cas particulier des lavages péritonéaux.

The International System for serous fluids cytopathology is a cytologic classification which purpose is to establish a consensus on diagnostic terminology. The exponential discovery of prognostic and theranostic molecular alterations in many cancers, particularly in advanced stages, led the authors to describe the indications and the feasibility of these new markers on cytological samples from serous effusions. The various immunocytochemistry techniques, FISH and those testing DNA and RNA are reported in regard to their ability to identify the main targets currently explored in routine practice. The vast majority of these crucial markers can be reliably tested on effusion fluids. The International System for serous effusion fluids also includes a chapter dedicated to peritoneal washings and the application of the classification to this particular type of sample. The objective is to "wash" the peritoneal cavity with a saline solution to unfix cells from the cavity's wall and collect those that have previously naturally detached. This procedure, performed before surgery of tumors and before any manipulation, allows a cytological analysis that specifies the staging of gynecological and non-gynecological tumors and excludes occult malignant cells in the presence of tumors appearing benign.

[Serous fluid cytopathology: International system]. / Cytopathologie des séreuses : la classification internationale.

The International System for Serous Fluid Cytopathology is a cytologic classification which purpose is to establish a consensus on diagnostic terminology. Five diagnostic categories are proposed associated to an increased rate of malignancy and specific cytological criteria. The categories are reported as: (I) Non-diagnostic (ND), the cells are insufficient for interpretation; (II) Negative for malignancy (NFM), only benign cells are present; (III) Atypia of undetermined significance (AUS), the cells present mild atypia more likely to be benign, but a malignant process cannot be definitively excluded; (IV) Suspicious for malignancy (SFM), the cells are present with atypia or in a number suspect of malignancy but with insufficient ancillary studies to give a positive malignant diagnosis; (V) Malignant (MAL), the cytological criteria are absolutely and definitively malignant. Malignant neoplasia can be primitive, it involves mesothelioma and serous lymphoma but most are secondary and correspond mainly to adenocarcinomas in adults and leukemia/lymphoma in children. The diagnostic should always be provided in the appropriate clinical context and be as definitive as possible. The ND, AUS and SFM are temporary or last intention categories. Immunocytochemistry in association with FISH or flow cytometry allow in most cases a conclusive diagnosis. These ancillary studies as well as ADN and ARN tests on effusion's fluids are particularly suited to give reliable theranostic results for personalized therapies.

Influence of A Continuous Very Low Dose of Gamma-Rays on Cell Proliferation, Apoptosis and Oxidative Stress.

We have previously shown a delay of death by lymphoma in SJL/J mice irradiated with continuous very low doses of ionizing radiation. In order to understand the mechanisms involved in this phenomenon, we have irradiated in vitro the Raw264.7 monocytic and the YAC-1 lymphoma cell lines at very low-dose rate of 4cGy.month(-1). We have observed a transient increase in production of both free radicals and nitric oxide with a transient adaptive response during at least two weeks after the beginning of the irradiation. The slight decrease of Ki67 proliferation index observed during the second and third weeks of YAC-1 cells culture under irradiation was not significant but consistent with the shift of the proliferation assay curves of YAC-1cells at these same durations of culture. These in vitro results were in good agreement with the slightly decrease under irradiation of Ki67 proliferative index evaluated on lymphomatous lymph nodes of SJL/J mice. A significant decrease of YAC-1 cells apoptotic rate under radiation appeared after 4 weeks of culture. Therefore very small doses of gamma-irradiation are able to modify the cellular response. The main observations did not last with increasing time under irradiation, suggesting a transient adaptation of cells or organisms to this level of irradiation.

Improving the cytological diagnosis of intraocular lymphoma from vitreous fluid.

AIMS: To improve the cytological diagnosis of retinal lymphoma on vitreous fluid using improved cell collection and systematic analyses. METHODS AND RESULTS: Since October 2010, we have developed and optimized in our department a method with which to perform the diagnosis of retinal lymphoma. The vitreous sample was collected in a tube containing RPMI-1640 medium, decomplemented fetal bovine serum, and gentamicin. The transport and technical steps were performed at 4°C. Systematically, cytological examination with May-Grünwald-Giemsa staining and immunocytochemistry (mainly anti-CD3, anti-CD20 and anti-CD68 antibodies) were performed on cytospins. Whenever possible, determination of B-cell clonality, flow cytometry and determination of the interleukin (IL)-10/IL-6 ratio were performed. From October 2010 to June 2013, with this optimized protocol, 38 vitreous cytological samples from 32 patients were analysed, and a final diagnosis was possible, avoiding a biopsy, in all cases except one. CONCLUSION: The preservation of vitreous fluid cells on culture medium led to the diagnosis of retinal lymphoma in 10 of 12 cases, and exclusion of this diagnosis in 26 cases. This protocol may be applied even when the delay in shipping from the surgery to the pathology departments exceeds 1 h.

Nonlinearity in MCF7 Cell Survival Following Exposure to Modulated 6 MV Radiation Fields: Focus on the Dose Gradient Zone.

The study of cell survival following exposure to nonuniform radiation fields is taking on particular interest because of the increasing evidence of a nonlinear relationship at low doses. We conducted in vitro experiments using the MCF7 breast cancer cell line. A 2.4 × 2.4 cm(2) square area of a T25 flask was irradiated by a Varian Novalis accelerator delivering 6 MV photons. Cell survival inside the irradiation field, in the dose gradient zone and in the peripheral zone, was determined using a clonogenic assay for different radiation doses at the isocenter. Increased cell survival was observed inside the irradiation area for doses of 2, 10, and 20 Gy when nonirradiated cells were present at the periphery, while the cells at the periphery showed decreased survival compared to controls. Increased survival was also observed at the edge of the dose gradient zone for cells receiving 0.02 to 0.01 Gy when compared with cells at the periphery of the same flask, whatever the isocenter dose. These data are the first to report cell survival in the dose gradient zone. Radiotherapists must be aware of this nonlinearity in dose response.

Cerebrospinal fluid cytologic findings of a pleomorphic xanthoastrocytoma: a case report.

BACKGROUND: Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic neoplasm with a relatively favorable prognosis. Characteristic histologic features include pleomorphic tumor cells and lipidized cells expressing glial fibrillary acidic protein (GFAP), corresponding to a World Health Organization grade 2 tumor. Cytologic features of PXA have been rarely described, only in squash specimens, but only 2 cases are reported in cerebrospinal fluid (CSF). CASE: A 45-year-old woman complained of severe headaches and diplopia. Computed tomography of the central nervous system revealed a supracallous periventricular tumor mass suggestive of either a lymphoma or a metastatic carcinoma. CSF revealed 18 cells/mm3 and contained numerous tumor cells highly pleomorphic in size and shape. Some atypical cells of moderate size were closely packed with well-defined cytoplasmic limits and a vacuolated appearance, suggesting an epithelial proliferation. On immunocytochemistry atypical cells were positive for GFAP, S100 protein and synaptophysin but were negative for pancytokeratins and epithelial membrane antigen. A primitive glial proliferation was found, and paraffin-embedded tumor tissue obtained by biopsy confirmed the diagnosis of anaplastic PXA. CONCLUSION: Observation of PXA in CSF might cause some differential diagnosis problems, especially with a metastatic epithelial malignancy. We present a case of anaplastic PXA with an unusual periventricular location and its cytologic features in CSF.

[Urine cytology pitfalls due to Polyomaviruses]. / Les difficultés diagnostiques liées aux Polyomavirus en cytologie urinaire.

Specific cytopathologic changes represent an important tool for the identification of a viral infection. After primary infection, generally during childhood, BK and JC polyomaviruses often remain latent within the urinary tract and can reactivate along life. These reactivations are usually encountered in immunosuppressed patients. In renal transplanted recipients, BK virus may cause a polyomavirus nephropathy inducing sometimes graft loss. A good morphologic sign of reactivation is characterized by the shedding in urine of viral-infected cells called decoy cells. The latter are easily identified in urine from renal transplanted patients but in other circumstances, they may be misdiagnosed as high-grade urothelial carcinoma cells. Correct cytological identification of decoy cells, confirmation of the diagnosis by urine PCR analysis and use of immunocytochemistry with anti-SV40 antibody are of good value for differential diagnosis in most cases. However, polyomavirus reactivation and urothelial carcinoma cells may be observed in the same urine specimen. The possible involvement of BK or JC virus in the pathogenesis of human urogenital tumors has been suggested by some studies but is not yet conclusively resolved.

[Extraskeletal myxoid chondrosarcoma of the nasopharynx]. / Chondrosarcome myxoïde extrasquelettique nasopharyngé

Extraskeletal myxoid chondrosarcoma is a rare but distinct entity with special clinicopathological, immunohistochemical, cytogenetical and outcome features. This tumor developed from soft tissues. A few cases have been reported in the head and neck in the literature. We report two new cases of extraskeletal myxoid chrondrosarcoma presenting in such an unusual site: one involved the left nasal cavity of a 67-year-old man and the second the sphenoidal sinus of a 71-year-old woman. The microscopic examination revealed nests of round small cells dispersed in a myxoid stroma. The myxoid material was stained with Alcian Blue with and without hyaluronidase application whereas no PAS staining was observed. The immunohistochemical staining showed reactivity with S-100 protein and vimentin in two cases and with EMA in one case. These results allowed us to exclude other differential diagnoses: soft tissue tumors with a myxoid stroma (myxoma, myxoid liposarcoma and myxofibrosarcoma). No staining with anti-KL1 allowed us to exclude chordoma. Curative surgery was not possible. Both patients were given radiotherapy and the tumor regressed in one.

Histiocytic sarcoma in C57BL/6J female mice is associated with liver hematopoiesis: review of 41 cases.

Forty-one cases of histiocytic sarcoma (HS) in C57BL/6J mice were histopathologically studied with special regard to unexpected associated hematopoietic disorders. These cases were retrieved among C57BL/6J female mice used as control mice in a chronic low-dose irradiation experiment. Hematopoietic characteristics were analysed by comparison to 41 disease-free mice from the same cohort. Tumoral involvement of the liver was observed in all 41 HS-bearing mice, followed by infiltration of the spleen (61.8%), lung (32.4%), bone marrow (14.3%), uterus (12.2%), lymph node (9.8%), and kidney (2.4%). By comparative analysis, we were able to demonstrate a significant association of HS with liver hematopoiesis (89.5% in HS group vs 15% in control mice, p < 0.00001), and with central hematopoietic disorders involving the myelocytic cells (decreased in HS, p = 0.003) and erythrocytic cells (increased in HS, p = 0.001). Microscopic characteristics of these 41 cases and physiopathology of the newly described hematopoietic features in HS are further discussed.

Inflammatory myofibroblastic tumor: a spinal case with aggressive clinical course and ALK overexpression. Case report.

The authors report on a case of spinal inflammatory myofibroblastic tumor (IMT) in a 22-year-oldwoman. Neuroradiological features of this intradural extramedullary mass were suggestive of a meningioma or neurinoma. The lesion was easily resected following a T-9 laminectomy. Light microscopy showed a proliferation of spindle cells with prominent nucleoli on a fibrous or edematous background with infiltration of numerous lymphocytes and plasma cells. Some spindle cells immunostained positively for ALK1. This led to the diagnosis of IMT. The patient's postoperative course was complicated by a multifocal local recurrence requiring a second surgery, which was followed by radio- and chemotherapy. The occurrence of IMT in the spinal cord has rarely been reported. In this case, ALK overexpression was associated with early multifocal recurrence. This has been recently reported in this tumor typein other locations.

Danon's disease (X-linked vacuolar cardiomyopathy and myopathy): a case with a novel Lamp-2 gene mutation.

Herein, we report a new case of Danon's disease in a 41-year-old Frenchman. This patient displays the typical clinical triad, with cardiomyopathy, mental retardation and myopathy, and a vacuolar myopathy without acid alpha-glucosidase deficiency. He has also developed a diffuse chorio-capillary ocular atrophy, and represents the second case of successful heart transplantation in this lysosomal disease. Interestingly, analysis of LAMP-2 protein expression in cultured fibroblasts revealed a primary deficiency of this lysosomal membrane protein. This defect resulted from a yet undescribed deletion in exon 7 of lamp-2 gene.

Expression of p27(Kip1) in bladder cancers: immunohistochemical study and prognostic value in a series of 95 cases.

Prognostic value of p27(Kip1) immunohistochemical expression was evaluated in a series of 95 bladder carcinomas. Low p27(Kip1) expression was correlated with higher tumor grade (P=0.01) and stage (P=0.009), associated with poor overall survival (P=0.01) and, for superficial cancers, with disease-free survival (P=0.05). Thirty-five cases exhibited a heterogeneous expression related in some instances to tumoral architecture. Seventeen cases showed a cytoplasmic reactivity related to low nuclear expression (P=0.057). Loss of p27(Kip1) expression is a pejorative event in bladder tumors and inhibition of p27(Kip1) degradation could offer new therapeutic ways.