Presence Of Abnormal Cells Research Articles

The Effect of Music Therapy on Declining Anxiety of Cancer Patients Undergoing Chemotherapy: Literature Review

Introduction: Chronic disease in the presence of abnormal cells that grow faster than the normal limits of cells in general with the most commonly used medical treatment being chemotherapy. Chemotherapy treatment has several side effects, one of which is anxiety. However, there is one non-pharmacological therapy that can be applied to reduce the feeling of anxiety, namely music therapy. The purpose of writing this literature review is to identify the effectiveness of music therapy against decreased anxiety in cancer patients undergoing chemotherapy. Method: The method used in writing is a literature review in the form of a literature review obtained from the PubMed, Google Scholar and Springerlink databases. After going through the selection stage using the Critical Appraisal Joanna Briggs Institute (JBI), 11 journals were obtained, 7 of which used randomized control and 4 journals used trial quasy experimental studie. Result: The results of the literature review showed that music therapy to reduce anxiety while undergoing chemotherapy uses various types of duration, namely most of them do music therapy as much as 30 minutes per session, done 2-3 times a week and carried out for 64 weeks. The average instrument used is the State Trait Anxiety Inventory with an assessment of 5.4 - 24.58 Conclusion: From the results of the literature review, it is hoped that nurses and families can apply music therapy interventions to cancer patients undergoing chemotherapy.

Significance of Immature Platelet Fraction in Diagnosed Patients of the Immune Thrombocytopenic Purpura

Objective: Determination of significance of immature platelet fraction (IPF%) in diagnosed patients of Immune thrombocytopenic purpura (ITP).
 Study Design: It was a cross-sectional study.
 Place and Study Duration: Haematology department, Armed forces Institute of Pathology (AFIP), Rawalpindi Pakistan June 2021 to December 2021.
 Methodology: Patients of all ages and genders diagnosed with ITP and platelets less than 100 x 109/L after a review of peripheral blood film were included in the study. Detailed history and examination were made, complete blood count (CBC) test was done on Sysmex XN-3000 automated haematology analyzer. Peripheral blood was stained with Leishman stain and examined under a microscope to rule out pseudo thrombocytopenia and the presence of abnormal cells and dysplasia. After adequate quality and control, the immature platelet fraction was performed on Sysmex XN 3000.
 Results: Seventy-two diagnosed cases of immune thrombocytopenic purpura were part of the study. The mean age of the patients was 21.00±14.50 years. 34 (48%) patients were males, and 38 (52%) were females. The mean platelet count was 49.40±24.60. Mean IPF was 17.90±9.50 per microliter. Immature platelet fraction (IPF%) was raised in all the patients with immune thrombocytopenic purpura, confirming our hypothesis that IPF% was an independent predictor for the detection of ITP.
 Conclusion: Immature platelet fraction is a unique parameter that can pick patients having thrombocytopenia due to peripheral destruction, including immune thrombocytopenic purpura.

Recent Methods and Challenges in Brain Tumor Detection Using Medical Image Processing

Abstract: A brain tumour is described by the presence of abnormal cells in the brain's tissues. Brain tumours can be benign (not cancerous) or malignant (cancerous). The malignant brain tumour is one of the leading and common cancers in the world. There are two types of tumours, primary tumours that develop in the brain and secondary tumours that start in another region of the body and then spread to the brain. The precise identification of the size and location of a brain tumour is crucial in the diagnosis of a brain tumour and is often diagnosed with magnetic resonance imaging (MRI). This book chapter discusses the major types of brain tumours and the advancements in computeraided approaches for detecting brain tumours. The manuscript gives an overview of various recent machine learning and medical image processing approaches developed recently for the identification and classification of brain tumours. Several medical image dataset available for the research works in this domain is also briefed in this article. The major research challenges which can be addressed by the researchers in the domain of brain tumour detection are also discussed in this article. Method: This manuscript mainly discusses various medical image processing methods to detect brain tumors. Results: The manuscript discusses the efficiency of the existing schemes and the key areas where further improvement is required Conclusion: This manuscript gives an overview of various categories of brain tumors, existing methods to detect brain tumors, the critical challenges in this domain and the medical image dataset available for the study.

Abstract 2199: Molecular dissection of a novel, highly proliferative lineage in a model of Helicobacter pylori-driven gastric metaplasia and dysplasia

Abstract At least 80% of gastric cancer cases are attributed to stomach infection with the bacterium Helicobacter pylori (Hp), which causes lifelong chronic inflammation. In some individuals, this inflammation can cause gastric atrophy, metaplasia (conversion of one normal cell type to another), dysplasia (presence of abnormal cells) and finally cancer, but the specific mechanism(s) through which Hp triggers this cascade are not well understood. Similar preneoplastic changes are recapitulated in a mouse model through tamoxifen-induced expression of active KRAS in the chief cells of the stomach (KRAS+ mice). We found that Hp infection of KRAS+ mice exacerbated disease: compared to Hp-KRAS+ mice, Hp+KRAS+ mice had an altered trajectory of metaplasia and accelerated dysplasia. In accordance with the hypothesis that Hp causes cancer through eliciting chronic inflammation, Hp+KRAS+ mice had severe inflammation marked by a ten-fold increase in T cells compared to Hp-KRAS+ mice. To understand gene expression changes in gastric cells in the context of metaplasia with and without active Hp infection, we performed single cell RNA-sequencing (scRNA-seq) on eight mouse stomachs (+/- Hp, +/- KRAS) using the 10x Chromium platform. Cluster analyses followed by UMAP (Uniform Manifold Approximation and Projection) visualization allowed us to identify 25 clusters, including epithelial and immune cell types. Hp+KRAS+ mice had a striking expansion of a population of metaplastic cells (most similar to surface mucus-producing “pit” cells), which comprised ~40% of epithelial cells in these mice. Metaplastic pit cells expressed markers of intestinal metaplasia and gastric cancer, and their abundance in the stomach was correlated with helper T cell abundance. Analysis of RNA velocity suggested that metaplastic pit cells arose from a progenitor cell type, rather than arising from pit cells directly. As well, a 10x Visium spatial gene expression experiment revealed the spatial organization of metaplastic pit cells near the lumen of the gastric epithelium. Finally, antibiotic eradication of Hp prevented metaplastic pit cell development and other disease phenotypes. Taken together, these studies provide new understanding of how Hp infection and inflammation cause gastric preneoplastic progression. Citation Format: Valerie Phoebe O'Brien, William C. Young, Greg Finak, Raphael Gottardo, Nina R. Salama. Molecular dissection of a novel, highly proliferative lineage in a model of Helicobacter pylori-driven gastric metaplasia and dysplasia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2199.

Deep multiple-instance learning for abnormal cell detection in cervical histopathology images

Cervical cancer is a disease of significant concern affecting women's health worldwide. Early detection of and treatment at the precancerous stage can help reduce mortality. High-grade cervical abnormalities and precancer are confirmed using microscopic analysis of cervical histopathology. However, manual analysis of cervical biopsy slides is time-consuming, needs expert pathologists, and suffers from reader variability errors. Prior work in the literature has suggested using automated image analysis algorithms for analyzing cervical histopathology images captured with the whole slide digital scanners (e.g., Aperio, Hamamatsu, etc.). However, whole-slide digital tissue scanners with good optical magnification and acceptable imaging quality are cost-prohibitive and difficult to acquire in low and middle-resource regions. Hence, the development of low-cost imaging systems and automated image analysis algorithms are of critical importance. Motivated by this, we conduct an experimental study to assess the feasibility of developing a low-cost diagnostic system with the H&E stained cervical tissue image analysis algorithm. In our imaging system, the image acquisition is performed by a smartphone affixing it on the top of a commonly available light microscope which magnifies the cervical tissues. The images are not captured in a constant optical magnification, and, unlike whole-slide scanners, our imaging system is unable to record the magnification. The images are mega-pixel images and are labeled based on the presence of abnormal cells. In our dataset, there are total 1331 (train: 846, validation: 116 test: 369) images. We formulate the classification task as a deep multiple instance learning problem and quantitatively evaluate the classification performance of four different types of multiple instance learning algorithms trained with five different architectures designed with varying instance sizes. Finally, we designed a sparse attention-based multiple instance learning framework that can produce a maximum of 84.55% classification accuracy on the test set.

Особенности мазков Папаниколау у женщин репродуктивного периода жизни с папилломавирусом 16, 18

Introduction. According to modern data, cervical diseases do not occur by chance. Precancerous lesions vary from person to person and become invasive over time. The need for specific diagnostic methods for early detection of cervical cancer in women of reproductive age always remains relevant. Over the years, numerous diagnostic, cytological and histological studies have been carried out to identify malignant lesions of the cervix. Human papillomavirus (HPV) is a widespread sexually transmitted infection that affects both women and men around the world and plays an important role in the development of cervical disease. It is the most common sexually transmitted virus in the United States of America. For the first time in 1942, Papanicolaou emphasized the possibility of using smears (PAP smears) from the cervix and from the vagina to diagnose cervical disease. PAP preparations of smears are mainly multilayered flat epithelial cells of the ectocervix and vagina, endocervical cylindrical cells, including mononuclear and polynuclear inflammatory cells that enter the vagina through diapedesis from the surface of the epithelial layer, mixing with the mucoid fluid produced by the endocervical epithelial fluid. Purpose — using objective criteria for cytological examination to identify neoplastic changes in the cervix. Materials and methods. The study included 100 women of reproductive age (18–45 years old) during 2015–2020. Of these, 20 were in the control group (group I — control) and 80 — in the high-risk group for cervical cancer (group II — the main group). Group II women were also divided into 2 subgroups: II A — with pathology of the cervix (n=41), II B — without pathology of the cervix (n=39). The study included patients with a positive result on HPV 16/18 including patients whose PAP smears revealed intracellular damage. Pap smears were included in the study according to the following criteria. The smears contained a sufficient number of squamous epithelial cells and their integrity was preserved. Endocervical cells were monitored in all PAP smears. The examination was carried out with at least 5 cells in each, not completely, and with 2 clusters of endocervical glandular or squamous metaplastic cells. Squamous epithelial cells covered at least 10% of the preparation. Bloody, technically artifactic preparations without clinical data have not been studied. The deficit rate did not exceed 3%, and high interest rates on artifacts were not included in the study. Despite the small number of cells in the presence of abnormal cells, this was unequivocally considered sufficient. Results. Interpretation of PAP smear results identified n=35 ASCUS patients, n=24 LSIL, n=21 HSIL patients in the PAP smear positive reproductive age group. HPV serotypes 16.18 were found in 24 of these patients. In women of the II B subgroup, no pathological changes in the cervix were observed. Conclusions. In women of reproductive age with positive HPV 16, 18, for the diagnosis of precancerous diseases of the cervix, taking pap smears is an integral part of the study. As a result of the study, it was revealed that, despite the absence of a clinical picture, pathological changes at the cell level are detected. Key words: HPV16, 18, ASCUS, LSIL, HSIL, PAP.

Abstract PO040: Chemoprevention and regression of estrogen-induced atypical endometrial hyperplasia by oral SHetA2 in a rat model

Abstract Introduction: The purpose was to evaluate the chemoprevention efficacy of SHetA2 (NSC 726189) in a rat model of atypical endometrial hyperplasia (AEH). Methods: Female Sprague Dawley rats were ovariectomized, rested for 2 weeks, and subcutaneously implanted with placebo or slow-release estrogen (E2; 1.5 mg/90-day) pellets on the lateral side of the neck. The rats were randomly divided for two studies: 1) AEH prevention, in which SHetA2 treatment was started one day after E2 pellet implantation; 2) AEH regression, in which SHetA2 treatment was started after AEH development (12 weeks after E2 pellet implantation) and continued for 4 weeks. SHetA2 was orally given as a suspension at three different doses of 30, 60 or 90 mg/kg/day. The suspension was prepared by first micronizing SHetA2 powder to < 63 µm and then ultrahomogenizing it in aqueous 30% Kolliphor HS15 until the size of drug particles in suspension was < 20 µm. The presence of AEH in H&E stained uterine sections was evaluated by two pathologists as the study endpoint by the presence of abnormal cells (nuclear enlargement, nuclear membrane irregularities, prominent nucleoli, nuclear hyperchromasia, nuclear pleomorphism, mitotic activity and/or loss of axial polarity) within tissue areas that exhibit at least one of the following features: increased gland to stroma ratio of >1:1, glandular complexity including irregular contours, and cribriform/papillary configurations. Results: E2-treated animals had reduced body weight gain compared to placebo-implanted animals (Repeated Measures ANOVA, p<0.0001). There were no effects of SHetA2 on rat body weights. In the prevention study, uterine to body weight ratios were significantly higher in E2-treated animals compared to placebo (Repeated Measures ANOVA, p<0.0001) and significantly reduced by 30 and 60 mg/kg/day SHetA2 doses (Repeated Measures ANOVA, p=0.0193 and 0.0108, respectively). Also, SHetA2 caused a dose-responsive decrease in AEH incidence in E2-implanted animals from 86.7% (13/15) in the untreated control to 53.3% (8/15), 26.7% (4/15) and 26.7% (4/15) in the 30, 60 and 90 mg/kg/day SHetA2 treatment groups, respectively (Chai Square Analysis p<0.0022). In the regression study, there were no significant differences in uterine to body weight ratios across all groups. Also, SHetA2 caused dose-responsive regression of AEH to normal histology in E2-implanted animals observed by lack of AEH in 18.2% (2/11) of the untreated control group and 83.3% (10/12), 81.8% (9/11) and 75% (9/12) in the 30, 60 and 90 mg/kg/day SHetA2 treatment groups, respectively (Chai Square Analysis p<0.0025). Conclusions: AEH can be induced by implantation of slow-release E2 pellets in ovariectomized rats. SHetA2 significantly prevented AEH development and caused AEH regression to normal endometrium histology in a dose-dependent manner. Further study is warranted to explore the mechanistic chemoprevention action of SHetA2 and translate these findings toward clinical trials. Funding: NCI PREVENT Program Contract HHSN26100008. Citation Format: Vishal Chandra, Rajani Rai, Stan S. Lightfoot, Manolya Kukut Hatipoglu, Lucila Garcia-Contreras, Doris M. Benbrook. Chemoprevention and regression of estrogen-induced atypical endometrial hyperplasia by oral SHetA2 in a rat model [abstract]. In: Proceedings of the AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; 2020 Nov 9-10. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(3_Suppl):Abstract nr PO040.

The Y chromosome disomy syndrome (47, XYY) in children with mental retardation, deviations of sex development and different genome anomalies: molecular cytogenetic studies

The article present the results of retrospectively analyzed children (4424 boys) with mental and psychomotor retardation, congenital malformations and/or developmental micro anomalies. 23 children had various forms of Y chromosome dysomy syndrome. The frequency of this syndrome in the studied cohort was 0.52%; and in this connection the authors discussed the role of Y-chromosome in the origin of mental retardation. Besides, the chromosome instability in sex and somatic cells is supposed to be a common mechanism of different chromosomal anomalies. The authors discussed the possibility of cytogenetic and molecular cytogenetic diagnosis, and also clinical polymorphism of the syndrome. The authors established the necessity of molecular cytogenetic technologies in the diagnosis of different forms of the syndrome, including mosaic forms and isodicentric chromosomes-connected forms. The severity of clinical symptoms doesn’t depend on presence of regular or mosaic forms of the syndrome. The study assumes a possible connection of clinical polymorphism with mosaisism, associated with the presence of abnormal cells (cell lines) in different tissues, together with the role of Y chromosome in the origin of mental retardation in children with Y- chromosome disomy syndrome and other chromosomal anomalies. The authors underline the necessity of molecular cytogenetic diagnosis of different forms of the syndrome for correct medical and genetic consultation.

Impact of mTOR hyperactive neurons on the morphology and physiology of adjacent neurons: Do PTEN KO cells make bad neighbors?

Hyperactivation of the mechanistic target of rapamycin (mTOR) pathway is associated with epilepsy, autism and brain growth abnormalities in humans. mTOR hyperactivation often results from developmental somatic mutations, producing genetic lesions and associated dysfunction in relatively restricted populations of neurons. Disrupted brain regions, such as those observed in focal cortical dysplasia, can contain a mix of normal and mutant cells. Mutant cells exhibit robust anatomical and physiological changes. Less clear, however, is whether adjacent, initially normal cells are affected by the presence of abnormal cells. To explore this question, we used a conditional, inducible mouse model approach to delete the mTOR negative regulator phosphatase and tensin homolog (PTEN) from <1% to >30% of hippocampal dentate granule cells. We then examined the morphology of PTEN-expressing granule cells located in the same dentate gyri as the knockout (KO) cells. Despite the development of spontaneous seizures in higher KO animals, and disease worsening with increasing age, the morphology and physiology of PTEN-expressing cells was only modestly affected. PTEN-expressing cells had smaller somas than cells from control animals, but other parameters were largely unchanged. These findings contrast with the behavior of PTEN KO cells, which show increasing dendritic extent with greater KO cell load. Together, the findings indicate that genetically normal neurons can exhibit relatively stable morphology and intrinsic physiology in the presence of nearby pathological neurons and systemic disease.

Regulation of tumor growth and metastasis: the role of tumor microenvironment.

The presence of abnormal cells with malignant potential or neoplastic characteristics is a relatively common phenomenon. The interaction of these abnormal cells with their microenvironment is essential for tumor development, protection from the body’s immune or defence mechanisms, later progression and the development of life-threatening or metastatic disease. The tumor microenvironment is a collective term that includes the tumor’s surrounding and supportive stroma, the different effectors of the immune system, blood platelets, hormones and other humoral factors. A better understanding of the interplay between the tumor cells and its microenvironment can provide efficient tools for cancer management, as well as better prevention, screening and risk assessment protocols.

Overwhelming bone marrow Leishmaniasis.

doi:10.5152/tjh.2011.97 Visceral Leishmaniasis (kala-azar) is caused by the intracellular parasitic organism Leishmania donovani and is transmitted by the bite of an infected sandfly Phlebotomus argentipes. Clinical manifestations of advanced disease usually include constitutional symptoms, such as prolonged fever, anorexia, weight loss, and marked enlargement of the spleen and liver, with varying degrees of pancytopenia [1]. Pakistan is a tropical country situated in the north-west region of South Asia; all of its neighboring countries are endemic for Leishmaniasis, including China, Afghanistan, Iran, and India [2-4]. Leishmaniasis was first reported from Pakistan in 1960 [5]. Initially, it was limited to the northern mountainous region, but currently it is widespread throughout the country with several endemic foci of varying climatic and geographic conditions [6]. Herein we present a 22-year-old female from Hyderabad, Sindh Province, Pakistan that was referred to our laboratory for bone marrow exanimation due to pyrexia of unknown origin. She had fever with chills and rigors that began 2 months earlier, which did not respond to treatment with antimalarials and multiple antibiotics. At presentation she had massive splenomegaly and marked pallor. Complete blood count showed the following: pancytopenia with hypochromic microcytic anemia; hemoglobin: 7.1 g/dL; hematocrit: 21.8%; MCV: 72.5 fL; MCH: 23.8 pg; MCHC: 29.7%; total white cell count: 1.5×109/L; absolute neutrophil count: 0.4×109/L; platelet count: 48×109/L. Peripheral blood smear did not show a leukoerythroblastic reaction or the presence of abnormal cells. Bone marrow examination showed hypercellular marrow and massive infestation with the amastigote form of Leishmania donovani in the bone marrow macrophages and in some granulocytes. Written informed consent was obtained from the patient. The visceral form of Leishmaniasis can be fatal if not treated in a timely fashion and stibogluconate (sodium antimony gluconate) is the drug of choice. Recently, other agents have become available for the treatment of new and resistant cases of visceral Leishmaniasis, including pentamidine isethionate, amphotericin B, miltefosine, and paramomycin [1]. The presented patient received anti-leishmanial treatment with sodium antimony gluconate 20 mg/ kg/d for 14 d. She began to exhibit improvement within 3 d and was clinically cured after the full course of therapy. She was last followed-up 1 month after completion of the treatment and was asymptomatic and healthy.

Improved Flagging Rates on the Sysmex XE-5000 Compared With the XE-2100 Reduce the Number of Manual Film Reviews and Increase Laboratory Productivity

Hematology analyzers generate suspect flags in the presence of abnormal cells. False-positive rates for flags are high on all analyzers. Sysmex, Kobe, Japan, has developed new software for its XE-5000 with improved algorithms for flagging blast cells, abnormal lymphocytes or lymphoblasts, and atypical lymphocytes. This study evaluated the efficiency of these flags in 1,002 samples. The XE-5000 was compared with the XE-2100 (Sysmex) and microscopic examination of cell morphologic features. On the XE-2100, the blast flag demonstrated 90 false-positives, 13 true-positives, and 3 false-negatives. The values on the XE-5000 were 27 false-positives, 14 true-positives, and 2 false-negatives. The abnormal lymphocyte/lymphoblast flag was assessed with the atypical lymphocyte flag. The XE-2100 showed 114 false-positives, 23 true-positives, and 20 false-negatives, and on the XE-5000, there were 45 false-positives, 22 true-positives, and 21 false-negatives. This more specific flagging reduces the number of films that require manual review.

Disseminated Mucor infection and thrombotic microangiopathy in lymphoma-associated hemophagocytic syndrome

A 23-year-old Japanese man was admitted to our hospital because of high fever, hepatosplenomegaly, and pancytopenia. Laboratory data on admission were as follows: WBC 2.4 9 10/L, Hb 7.9 g/dL, Plt 22.0 9 10/L, AST 348 IU/ L, ALT 343 IU/L, LDH 1,302 IU/L, T-Bil 5.65 mg/dL, CRP 2.5 mg/dL, ferritin 23,724 ng/mL, and soluble CD25 32,163 U/mL. Computed tomography showed severe splenomegaly containing multiple low density areas. Bone marrow examination showed a marked increase in hemophagocytic macrophages. Although presence of abnormal cells were not apparent, oligoclonal pattern of Epstein-Barr virus (EBV) terminal repeat and abnormal karyotype with [48, XY, ?13, ?22] were detected in the specimen. He was diagnosed as lymphoma-associated hemophagocytic syndrome. HLH2004 protocol (dexamethazone 18 mg/d, cyclosporine 300 mg/d and etoposide 270 mg 9 2/week) had been started. The following two courses of ESHAP chemotherapy (etoposide 68 mg/d d1–4, methylprednisolone 500 mg/d d1–5, araC 3.4 g/d d5, and cisplatin 42 mg/ d d1–4) relieved the fever, splenomegaly, and liver dysfunction only transiently. During the subsequent CHOP chemotherapy (cyclophosphamide 900 mg, adriamycin 80 mg, and vincristine 0.5 mg on d1 without prednisolone because of continuous administration of dexamethasone), a nodular lesion measuring 2 cm appeared in the right upper lung field, and progressively increased to more than 10 cm. Because b-D glucan level was high and pharyngeal culture detected Candida species, 400 mg of fluconazole and 100 mg of micafungin sodium were started. However, fragmentation of the red blood cells became apparent in the peripheral blood smear and haemolytic markers increased in a few days. To maintain platelet count around 20.0 9 10/L, daily platelet transfusion was necessary. The value of FDP remained almost within the normal range. These results indicated the presence of thrombotic microangiopathy (TMA). Hematemesis and tarry stool followed, and panendoscopy revealed acute gastric mucosal lesions and duodenal ulcer, which needed multiple crippings. Antifungal agents were changed after seven days of treatment to 125 mg daily of amphotericin B lipid preparation (AmBisome). However, he died of hemorrhagic infarctions in the cerebellum and brain stem only in three days. Autopsy showed a white nodule with massive necrosis and fibrosis in the spleen. Microscopic examination revealed infiltration of lymphoma cells with prominent nucleoli to both red and white pulps of the spleen, and also to cervical and mediastinal lymph nodes. Immunostaining of the spleen revealed lymphoma cells positive for LCA, CD3, CD8, CD45RO, TIA-1 and granzyme B, and negative for CD4, CD5, CD20, CD56, CD57, and CD79a. The cells were also EBER-positive. These results strongly suggested that the present case was hepatosplenic T cell lymphoma associated with EBV and having an activated cytotoxic profile previously reported by Ohshima et al. [1]. Pneumonic lesion contained angiodestructive infiltration of Mucor and scattered cytomegalovirus (CMV) inclusion bodies (Fig. 1). Extensive vascular occlusion and multiple emboli including Mucor and intracellular owl eyes were N. Inagaki K. Sugimoto (&) Y. Isobe Y. Yamamoto M. Sasaki A. Kato T. Mori K. Oshimi Division of Hematology, Department of Internal Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan e-mail: ksugimot@juntendo.ac.jp

Bilateral Hypopyon as the Presenting Feature of Chronic Myeloid Leukemia

Purpose: To report bilateral hypopyon as an unusual presenting feature of chronic myeloid leukemia (CML). Design: Observational case report. Methods: A 68-year-old male presenting with bilateral hypopyon uveitis underwent hematological investigations and cytology of hypopyon. Results: Blood smear revealed increased leucocyte count with presence of abnormal cells (myelocytes, band forms, and promyelocytes) suggestive of CML. Cytopathology of hypopyon revealed predominance of lymphocytes and few plasma cells. CML was confirmed by hematological investigations. Patient was initiated on chemotherapy under the care of an oncologist and is stable. Conclusions: Elderly patients presenting with hypopyon uveitis should be investigated to rule out masquerade syndrome.

Rapid prescreening of papanicolaou smears

Efficient quality control (QC) is essential to ensure high sensitivity of Papanicolaou (Pap) smears. For this purpose, rescreening of 10% random negative smears is ineffective. Rapid rescreening (RR) of all negative Pap smears is more practical and has received widespread acceptance, especially in Europe, although its sensitivity is difficult to monitor and its retrospective nature may influence the vigilance of the screeners. The method of rapid prescreening (RPS) overcomes these drawbacks because rapid review of Pap smears occurs before routine full screening. All routine conventional Pap smears over 2 months underwent RPS by 12 cytotechnologists. Approximately 30 seconds were allowed to prescreen each slide. The presence of abnormal cells (atypical squamous cells of undetermined significance [ASCUS] or above), infection or endometrial cells detected on RPS was documented. All slides subsequently underwent routine full screening. Results of both screening methods were compared. Of a total of 8364 Pap smears, 310 (3.7%) cases were categorized as abnormal after final diagnosis. Of those, 135 were also detected on RPS (sensitivity of 43.5%). Seventeen abnormal cases were detected only on RPS: these consisted of 13 ASCUS cases, 3 low-grade squamous intraepithelial lesions, and 1 high-grade squamous intraepithelial lesion. The sensitivity of RPS for infections and endometrial cells was 51.6% and 28.3%, respectively. Implementation of RPS did not significantly impact the work flow in our laboratory. RPS is an efficient and practical QC tool. It is a reliable method with which to monitor sensitivity and reduce the false-negative rate, and because it is done before finalizing the case, it allows for timely corrections to the diagnosis and avoids the need to amend reports.

Diagnosis at first glance: bladder parachute in an HIV-infected patient

Please refer to the article on pages 604–605 of this issue to view the case report to which this discussion refers. The endocervical cytology and the histology of the biopsies revealed low-grade dysplasia with acanthosis and hyperkeratosis (Figure 1) as well as the presence of abnormal cells in the stratum granulosum with irregular nuclei and large cytoplasmic vacuoles (koilocytes) (Figure 2). These findings are virtually always associated with human papillomavirus (HPV) infections.Figure 2Papanicolau stain (x400): typical koilocytes.View Large Image Figure ViewerDownload (PPT) Papillomavirus virions consists of a doubled-stranded supercoiled circular DNA molecule, enclosed within a capsule of viral protein with no outer membrane. There are three main types of lesions caused by HPV: cutaneous (plantar warts, Verruca plantaris), epidermal (epidermodysplasia verruciformis) and genital (flat condylomas, giant condyloma (with or without Squalous malignancy) or Buschke—Lowenstein tumor, condylomata acuminata (CAB) and high-grade squamous intraepithelial lesion). HPV is transmitted by physical contact with infected individuals or with objects contaminated by the infectious virus. The main mode of transmission of genital HPV is sexual contact. The HPV types 6 and 11 are responsible for 90% of cases of condylomata acuminata. This patient represents the second case of CAB of the bladder with recurrent urinary infections in an HIV-infected patient. Bladder and urethral (5–23%) infiltrations by HPV have been described in immunosuppressed patients. The prevalence of CAB in HIV patients is unknown, and only one previously reported case was found in the reviewed literature (MEDLINE 1966–2000). The method of choice for diagnosing HPV is nucleic acid hybridization; however, cytologic or histologic verification of HPV-related disease was considered sufficient until recently. Deeper biopsies are required in the case of wide lesions, in order to eliminate malignancy and avoid invasive cancer of the cervix. Initially, local lesions warrant conservative modes of treatment such as transurethral resection, electrocoagulation, and intracavitary chemotherapy; however, radical excision of the bladder is the elective therapy in cases of diffuse injury. Recurrences and/or malignancies are frequent, and a close follow-up of the course of the lesions is mandatory.

Diagnosis at first glance: bladder parachute in an HIV-infected patient

The endocervical cytology and the histology of the biopsies revealed low-grade dysplasia with acanthosis and hyperkeratosis (Figure 1) as well as the presence of abnormal cells in the stratum granulosum with irregular nuclei and large cytoplasmic vacuoles (koilocytes) (Figure 2). These findings are virtually always associated with human papillomavirus (HPV) infections. Papillomavirus virions consists of a doubledstranded supercoiled circular DNA molecule, enclosed within a capsule of viral protein with no outer membrane. There are three main types of lesions caused by HPV: cutaneous (plantar warts, Verruca plantaris), epidermal (epidermodysplasia verruciformis) and genital (flat condylomas, giant condyloma (with or without Squalous malignancy) or Buschke–Lowenstein tumor, condylomata acuminata (CAB) and high-grade squamous intraepithelial lesion). HPV is transmitted by physical contact with infected individuals or with objects contaminated by the infectious virus. The main mode of transmission of genital HPV is sexual contact. The HPV types 6 and 11 are responsible for 90% of cases of condylomata acuminata. This patient represents the second case of CAB of the bladder with recurrent urinary infections in an HIV-infected patient. Bladder and urethral (5–23%) infiltrations by HPV have been described in immunosuppressed patients. The prevalence of CAB in HIV patients is unknown, and only one previously reported case was found in the reviewed literature (MEDLINE 1966–2000). The method of choice for diagnosing HPV is nucleic acid hybridization; however, cytologic or histologic verification of HPV-related disease was considered sufficient until recently. Deeper biopsies are required in the case of wide lesions, in order to eliminate malignancy and avoid invasive cancer of the cervix. Initially, local lesions warrant conservative modes of treatment such as transurethral resection, electrocoagulation, and intracavitary chemotherapy; however, radical excision of the bladder is the elective therapy in cases of diffuse injury. Recurrences and/or malignancies are frequent, and a close follow-up of the course of the lesions is mandatory.

Nasopharyngeal carcinoma in situ (NPCIS)--pathologic and clinical perspectives.

Dysplasia or carcinoma in situ lesions (NPCIS) of the nasopharynx have rarely been reported. The prevalence, biologic behavior, and the transformation period of the pure preinvasive lesions have not been fully explained. All cases of NPCIS were retrospectively reviewed during the period between 1990 and 2000. The clinical features of all cases were studied. The biopsy samples were examined using light microscopy and in situ hybridization (ISH) for EBV-encoded RNA (EBER). The sera taken before and after the transformation were analyzed for anti-viral capsid antigen (VCA) EBV titers and circulating cell-free EBV DNA concentration. Three cases of NPCIS were identified. Two of the three cases subsequently developed into invasive NPC after initial presentation. The interval of transformation varied from 40 to 48 months. In all three cases, the specimens showed abnormal findings on light microscopy and positive staining for EBER. Elevated anti-VCA titers were present in two of the preinvasive lesions. No cell-free EBV DNA was detected in the sera of these patients during the preinvasive phase of the disease. Preinvasive NPC is a rare but distinct entity. Its transformation period can be as long as 4 to 5 years. Elevated anti-VCA titers, in the presence of abnormal cells on light microscopy, should alert the pathologist to perform ISH EBER studies to diagnose this rare condition.

Are women sufficiently well informed to provide valid consent for the cervical smear test?

Three hundred women attending colposcopy for the first time, following an abnormal cervical smear, were invited to fill in a questionnaire. This covered aspects of their understanding of the cervical smear test and the NHS Cervical Screening Programme (NHSCSP). In addition, it covered aspects of consent to the test. The response rate was 83%. Seventy percent thought that the NHSCSP is working well and 72% were aware that probably over 3000 cases of cervical cancer per year are being saved by the NHSCSP. However, 55% did not know that the death rate from cervical cancer is decreasing. 96% were aware that the main reason for a cervical smear is to prevent the development of cervical cancer, by finding early treatable abnormalities. Similarly, 94% were aware that the presence of abnormal cells on a cervical smear indicated a possible but not definitive indication of cervical precancer or cancer. Disappointingly, only 5 had seen the new NHSCSP information poster on the cervical smear test and only 44% had been given written information about the test. Consent for the test in 59% of women had been implied rather than expressed and 30% of women providing expressed consent had signed to that effect. In 42% of women, the smear taker or a doctor had failed to discuss the reason for having a cervical smear and had not explained about its advantages and limitations. In 72%, the smear taker or doctor had not explained that the cervical smear test can never be 100% accurate and that some laboratory errors are unavoidable. It is likely that women attending for colposcopy are a highly motivated cohort in relation to their understanding of the cervical smear test and the NHSCSP. Accordingly, understanding in the more general female population is likely to be considerably less. It would appear that women are often suboptimally informed to provide valid consent for the cervical smear test.

A study of chromosomal aberrations in amniotic fluid cell cultures.

This paper represents the analysis of 1916 routine amniotic fluid specimens harvested by an in situ fixation technique in a prospective study with regard to cultural chromosome anomalies. Excluding constitutional abnormalities, 2.9 per cent of 19,432 cells analysed showed some form of chromosome anomaly, terminal deletions (57 per cent) and chromatid/chromosome breaks and gaps (18 per cent) being the most frequent, followed by interchange aberrations (13 per cent) and trisomy (5 per cent). No case was found of more than one colony from the same culture showing the same anomaly without it being present in other cultures from the same fluid. The wholly abnormal colonies had a surplus of trisomies and from the mathematical considerations presented one may infer that these are likely to reflect the presence of abnormal cells in the amniotic fluid. Partly abnormal colonies appeared at a frequency that would correspond to virtual absence of selection against chromosomally abnormal cells when cultured in vitro. The aberrations found were similar to those seen as single cell anomalies, except for chromatid breaks and exchanges. The data suggest a basic preferential induction of trisomy for chromosomes 2, 18, 21, and the Y-chromosome. Structural aberrations showed a marked clustering of breakpoints around the centromeres. The frequency of mutant cells was low (1.4 X 10(-3)) before culture was initiated. At harvest, the frequency of abnormal cells was much higher (3 X 10(-2)) corresponding to 3 X 10(-3) mutations per cell per generation accumulating over approximately ten generations in vitro.