Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Prof. Somashekhar Nimbalkar
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On Sep 2018




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"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



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Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
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Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
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Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

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Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
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Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Original article / research
Year : 2022 | Month : April | Volume : 16 | Issue : 4 | Page : EC41 - EC43 Full Version

Utility of Intraoperative Imprint Cytology in Diagnosis and Grading of Glioma: A Cross-sectional Study


Published: April 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/53269.16259
Shivam Chakraborty, Chhanda Das, Sayantan De, Mamata Guha Mallick Sinha

1. Postgraduate 2nd Year, Department of Pathology, IPGMER and SSKM, Kolkata, West Bengal, India. 2. Assistant Professor, Department of Pathology, IPGMER and SSKM, Kolkata, West Bengal, India. 3. Postgraduate 3rd Year, Department of Pathology, IPGMER and SSKM, Kolkata, West Bengal, India. 4. Professor, Department of Pathology, IPGMER and SSKM, Kolkata, West Bengal, India.

Correspondence Address :
Dr. Chhanda Das,
31, 1st Road, Eastern Park, Santoshpur, Kolkata-700075, West Bengal, India.
E-mail: chhhdas@gmail.com

Abstract

Introduction: Gliomas are most common primary Central Nervous System (CNS) neoplasm in adult population. Gliomas predominantly arise from brain parenchyma. Invasion of adjacent normal parenchyma is a prominent feature.

Aim: To study the epidemiological incidence of glial tumours and the viability and accuracy of intraoperative cytology in diagnosis and grading glial tumours.

Materials and Methods: A cross-sectional study was done on 30 patients who underwent excision surgery at Department of Neurosurgery at Institute of Postgraduate Medical Education and Research IPGMER and SSKM, Kolkata, West Bengal, India. Clinically, radiologically confirmed cases of Space Occupying Lesion (SOL) of brain with a history of neurosurgical intervention were included. Patients medically unfit for surgery or without radiological evidence of SOL in the brain were excluded from the study. Intraoperative imprint touch cytology of the specimens was done. Part of the tissue was kept for Formalin Fixation and Paraffin Embedding (FFPE) and subsequent histopathological examination were done. Results of intraoperative imprint cytology were compared with final histopathology report and grading. Matthews correlation coefficient t-test, Kohen’s Kappa (κ), Chi-square test (χ2) were used for the statistical analysis. A p-value of p<0.5 was considered statistically significant.

Results: About 10 (33.3%) of the patients presented with frontal lobe lesion. Out of 30 cases 29 (96.6%) were histologically confirmed to be of glial origin, 1 (3.3%) was metastasis from other tumour. These 29 cases were diagnosed as different glial neoplasm on intraoperative imprint cytology and were confirmed by histology. According to histological subtype 12 (41.37%) were glioblastoma, 10 (34.48%) were diffuse astrocytoma, 3 (10.34%) were pilocytic astrocytoma, 3 (10.34%) was ependymoma. Intraoperative impression cytology diagnosis was compared with confirmatory histological diagnosis. Sensitivity and specificity was found to be 93% and 50%, respectively, Positive Predictive Values (PPV) 96%, Negative Predictive Values (NPV) 33%, diagnostic accuracy 89.65% and p<0.5 was statistically significant.

Conclusion: In the present study, confirmatory histopathology report showed a significant association with imprint cytology report. Hence, it can be concluded that intraoperative imprint cytology is a fairly accurate, rapid and inexpensive method of diagnosis and grading of gliomas.

Keywords

Central nervous system, Diagnostic accuracy, Glial tumours, Histopathology, Intraoperative

Gliomas are the most common primary neoplasm in the adult population. About 40% of all the intracranial neoplasms originate from neuroepithelium, 35% from meningothelial cells, 14.4% from oral ectoderm and 7.5% from peripheral nerve sheath elements. Lymphomas and germ cell tumours are rare and only make upto 2.3 and 0.5%, respectively (1). Approximately, 30% of all the neoplasms of brain are glioma, among them 75% gliomas are astrocytoma (2). Histological spectrum of glioma consists of nuclear atypia, mitotic activity, microvascular proliferations, tumour necrosis, grade of the tumour depends on various combinations of these factors (3). Grading of tumour is of crucial importance from the therapeutic aspect, because the course of chemotherapy and radiotherapy is dependent on it (4). It has been reported in past that squash cytology alone can be used to analyse cytomorphology of glioma cells, including nuclear morphology, coarse chromatin pattern, mitosis, tumour necrosis thus differentiating low grade and high grade gliomas (5),(6),(7),(8),(9),(10). Thus, a correct understanding of the biologic behaviour during the surgical intervention shall positively influence the outcome.

The study was undertaken to evaluate the epidemiological occurrence of glial tumour and to ascertain the validity and reliability of intraoperative diagnosis of glial tumour and correlate with subsequent histopathological diagnosis and to ascertain the subtyping and grading of glial tumour with respect to current World Health Organisation (WHO) classification of tumours of central nervous system (3).

Material and Methods

This present cross-sectional study was conducted from August of 2020 to August of 2021 at IPGMER and SSKM Hospital Kolkata in the Department of Pathology on the specimens received from 30 patients who underwent excision surgery at Department of Neurosurgery. The study was performed after obtaining the approval from Ethical Committee (IPGME&R/IEC/2021/019). The patients presenting with headache, vomiting, convulsion came to Department of Neurosurgery for evaluation. Radiological investigations like Computerised Axial Tomography (CAT) and Magnetic Resonance Imaging (MRI) scan was done. Upon locating intracranial SOL surgical intervention was planned. During the surgeries intraoperative imprint cytologic preparation were performed to understand the exact nature of the neoplasms.

Inclusion criteria: Patients diagnosed with neoplasms of glial origin were included in the study.

Exclusion criteria: Cases diagnosed as neoplasms other than glioma were excluded.

The specimens were sent to the Department of Pathology for further examination.

Study Procedure

Imprint smears preparation and cytological examination: In all the cases, intraoperative tumour tissue pieces were received from neurosurgery. Fragments from the tissue fragments were touched with clean glass slides with mild pressure to properly spread the cellular material after blotting excess blood. After air drying and fixation in 95% ethyl alcohol rapid Haematoxylin and Eosin staining (H&E) was done in imprint cytology smear and provisional diagnosis was given. The following morphologic features are observed for diagnosis and grading. Cellularity of the smear, shape of the cell nuclei (round, oval or spindle), nuclear atypia (to ascertain the grade and to differentiate neoplastic glial cells from gliosis), chromatin pattern (typical coarse and knobby chromatin of glial neoplasm), nuclear enlargement (disproportionately large cells signifies higher grade), cellular pleomorphism (degree of pleomorphism corroborates well with malignant nature), mitosis (number of mitosis per 10 HPF is crucial in asserting the grade). Tumour necrosis (present or absent), vascular proliferation and vessel morphology. A part of the tissue was preserved in formalin for paraffin embedding and histopathological examination. The histological subtyping and grading were done according to recent WHO classification of CNS to reach a confirmed diagnosis and prediction of accuracy of imprint analysis [Table/Fig-1-4]. Due to heterogeneity of CNS neoplasms and inadequacy in tissue sampling, there is difficulty in assessing grades and subtypes of gliomas in imprint smear. The evidence of brain invasion is not always apparent in imprint smears. Very often there is a downgrade of histological grade in imprint smear.

Statistical Analysis

All data was copied into Microsoft Excel and contingency charts were prepared for qualitative data. Data were analysed with the help of Statistical Package of the Social Sciences (SPSS) software version 20.0 (IBM, Armonk, New York,USA), Prism Graph Pad version 5. Matthews correlation coefficient t-test, Kohen’s Kappa (κ), Chi-square test (χ2) were used for the statistical analysis. p<0.5 was considered statistically important.

Results

The incidence of this tumors in this institute is approximately about 30 per year. Out of 30 patients 16 (53.3%) were males and 14 (46.6%) were females. Age of the patients was in the range of 3-80 years at the time of surgery. Mean age was 36.3±3.817. There was five patients within the age group of 20 years, 11 patients within 21-40 years, 11 patients within 41-60 years and four patients within 61-80 years. As per site of occurrence most of them 10 (33.3%) were in the frontal lobe, 5 (16.7%) were from the parietal lobe, 1 (3.33%) from frontoparietal lobe 5 (16.6%) were from temporoparietal lobe, 3 (10%) were from temporal lobe, 2 (6.66%) from posterior fossa 2 (6.66%) from parietooccipital lobe 1 (3.33%) from thalamus and 1 (3.33%) from frontotemporal lobe (Table/Fig 5).

The histological type of glioma was ascertained as per WHO 2016 CNS tumour classification. Most of the tumour 12 (41.37%), were glioblastoma followed by diffuse astrocytoma 10 (34.48%), pilocytic astrocytoma 3 (10.34%) and ependymoma 3 (10.34%). One case was metastastic deposit. The spectrum of histological grade of these 29 glioma cases was varied. Majority of the tumours (13/29) were WHO Grade IV followed by WHO Grade II (12/29), WHO Grade I (3/29), WHO Grade III (1/29). Out of 30 cases, 29 cases were histologically confirmed as glioma, one was metastatic deposit, so diagnostic accuracy was 89.65%. The correlation of intraoperative impression cytology and histological diagnosis were analysed and it was found to have sensitivity of 93%, specificity of 50%, PPV of 96%, NPV of 33%, false positive ratio (alpha) 50%, false negative ratio (beta) of 7%, positive likelihood ratio 1.86, negative likelihood ratio of 0.14 (Table/Fig 6).

Discussion

Intraoperative imprint cytology, in some aspects superior to frozen sections for rapid observation and assessment of cellular morphology and subsequent diagnosis and grading. Along with cellular morphology other factors like clinical profile, neuroradiological examination are cardinal for an accurate diagnosis. Intraoperative consultation with the pathologist assists the surgeon in deciding the method of surgery and subsequent follow-up and management. In a study by Fujita H et al., cellular morphology can clearly differentiate between low grade glioma and high-grade glioma and vascular morphology of squash preparation of astrocytoma can be useful in asserting the grade of the tumour (11). In a study with 63 patients, Samal S et al., showed complete correlation. Diagnostic accuracy of cytology for glialtumours were 88.24%. The sensitivity, specificity, positive predictive value in detecting neoplastic condition were 94.4%, 85.7%, 98.07% and 66.67%, respectively (12). Another study by Sharma S and Deb P with 90 cases showed that in case of pilocytic astrocytoma, ganglioglioma, glioblastoma and ependymoma diagnostic accuracy reached 100%, in case of low-grade glioma the diagnostic accuracy was 71.4% and only 50% accuracy in high grade glioma as one out of two cases was misdiagnosed as highgrade gliomas (13). In this study, there were 30 cases, among them 29 were glial tumour and one came out to be metastatic deposit in the brain. Mean age was 36 with a mild female preponderance. Frontal lobe was the most common site. The most common histological type was glioblastoma. In 26 cases intraoperative cytological diagnosis was corroborated with histopathological diagnosis. One case of anaplastic ependymoma was initially diagnosed as glioblastoma in intraoperative consultation. Another case of oligodendroglioma was diagnosed as diffuse astrocytoma in imprint cytology. A case of midline glioma was initially identified as glioblastoma intraoperatively. A case of metastasis to brain was initially identified in cytologic preparation and was confirmed by histopathology. Grade of the tumour was correctly predicted by imprint cytology in most of the cases A sensitivity level of 93%, PPV 96% and lower specificity of 50%, NPV of 33% was calculated in the present study. Hence, imprint cytology was found to be a highly sensitive process with a low specificity. As the results of the present study were compared with with studies in the past, they were found to be corroborative. Cellularity of a smear often indicates the grade of the tumour, higher grade tumour tends to demonstrate highly cellular smears, but the cellularity depends on the procedure of smear preparation and the quality of the sample. As in the present study a case of anaplastic ependymoma had a smear with scanty cells. Individual cellular and nuclear morphology is of paramount importance. Large cells along with cellular pleomorphism in smear corroborates well with the histopathological diagnosis and grading. Morphology of the chromatin plays an important role. Coarse and knobby chromatin with fibrillary background points to glial origin.

Tumour necrosis is an important factor in the diagnosis of glial tumour of higher grade. Homogeneous eosinophilic necrotic areas are seen in case of glioblastoma. Piloid changes like rosenthal fibres on an imprint cytology smear are seen in case of pilocytic astrocytoma. As per previous studies minimum of four core biopsy specimens could be essential for the highest diagnostic yield (89%) [14,15]. Samples from high risk areas like brain stem are often scanty in amount. In these situations, only a single suction aspiration biopsy may be performed usually permitting the application of only a single touch preparation. It has been suggested in the past that in such cases, the biopsy tissue is to be fixed in Karnovsky’s solution for plastic embedding and subsequent electron microscopic evaluation (16).

Limitation(s)

Limitations of this study have been the lack of genomic study of these tumours. In the time period, 30 cases were collected, a larger sample size could have provided a better statistical results.

Conclusion

Hence, it can be concluded here that intraoperative imprint cytology is a reasonable, fairly accurate, rapid and inexpensive procedure as far as the diagnosis of tumours of glial origin is concerned. In the present study it is clear that imprint cytology is a process with high sensitivity and low specificity. Timely and precise opinion of a neuropathologist in the intraoperative period helps to guide the course of treatment to the right direction.

References

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Ostrom QT, Gittleman H, Fulop J, Liu M, Blanda R, Kromer C, et al. CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2008-2012. Neuro Oncol. 2015;17 Suppl 4(Suppl 4):iv1-iv62. [crossref] [PubMed]
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Fujita H, Tajiri T, Machida T, Itoh H, Hiraiwa S, Imai M, et al. Vessel Morphologies of the Brain in Cytological Squash Preparations Are Useful for Intraoperative Diagnosis of High-Grade Astrocytomas. Acta Cytol. 2018;62(3):223-30. Doi: 10.1159/000487701. [crossref] [PubMed]
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Iqubal M, Shah A, Wani MA, Kirmani A, Ramzan A. Cytopathology of central nervous system. Part I. Utility of crush smear cytology in intraoperative diagnosis of central nervous system lesions. Acta Cytol. 2006;50:608-16. [crossref] [PubMed]
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Folkerth RD. Smears and frozen sections in the intraoperative diagnosis of central nervous system lesions. Neurosurg Clin N Am. 1994;5:01-18. [crossref]
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DOI and Others

DOI: 10.7860/JCDR/2022/53269.16259

Date of Submission: Nov 13, 2021
Date of Peer Review: Jan 20, 2021
Date of Acceptance: Feb 07, 2022
Date of Publishing: Apr 01, 2022

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. Yes

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Nov 16, 2021
• Manual Googling: Feb 04, 2022
• iThenticate Software: Feb 25, 2022 (12%)

ETYMOLOGY: Author Origin

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