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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.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
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
Original article / research
Full Version
Immunohistochemical Evaluation of Myxoid Sarcomas- A Tertiary Care Hospital Experience
Correspondence Address :
Dr. Karthik Sigamani,
F-3, Lakshmi Vilas, Plot No-87, Lalitha Nagar, Madambakkam, Guduvancherry,
Chennai-603202, Tamil Nadu, India.
E-mail: eversmile_kar@yahoo.com
Introduction: Myxoid sarcomas are a rare and heterogeneous group of tumours exhibiting overlapping histomorphological features with varied biological behaviour. Hence, additional ancillary techniques like Immunohistochemistry (IHC) are necessary for definite diagnosis and categorisation of the myxoid sarcomas.
Aim: To identify the distribution of myxoid sarcomas among patients and also to evaluate the utility of basic IHC in the diagnosis of myxoid sarcomas.
Materials and Methods: This was six years retrospective observational cross-sectional study carried out in the Department of Pathology, Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai, Tamil Nadu, India, during the period of January 2008-December 2013. Relevant pathological data of all the myxoid sarcomas reported during the study period were retrieved from the medical records. Corresponding Haematoxylin and Eosin (H&E) stained slides were reviewed and IHC was done using a panel of markers for confirmation.
Results: Among the 57 myxoid sarcomas, 46% occurred in the age group of 41-60 years with a striking male preponderance (74%). Myxofibrosarcoma was the most common histological type (33.33%). All cases of myxofibrosarcoma were positive for vimentin while two cases showed focal Smooth Muscle Actin (SMA) positivity and one case showed focal CD34 positivity. Low grade fibromyxoid sarcomas were positive for only vimentin. Myxoid liposarcomas and extra-skeletal myxoid chondrosarcomas showed vimentin and S100 positivity. Myxoid Dermato Fibrosarcoma Protuberans (DFSP) was positive for vimentin and CD34 while synovial sarcoma with myxoid change was positive for vimentin and Pancytokeratin (Pan CK). Myxoid Malignant Peripheral Nerve Sheath Tumour (MPNST) showed 100% vimentin and S100 positivity while CD34 was positive in 12.5% of cases. Leiomyosarcoma with myxoid change was positive for vimentin, SMA, desmin and Pan CK.
Conclusion: The IHC is a valuable adjunct to light microscopy for the diagnosis of myxoid sarcomas and can provide as a judicious tool for diagnosis of this uncommon and challenging group of malignant soft tissue tumours.
Glycosaminoglycans, Immunohistochemistry, Malignant, Soft tissue, Tumours
Soft tissue sarcomas are uncommon and heterogeneous group of malignant tumours that show differentiation towards connective tissue elements like vessels, fat, fibrous tissue, peripheral nerves and tendons. Soft tissue sarcomas are relatively rare lesions accounting for less than 1% of all malignancies (1). Among the soft tissue sarcomas, certain tumours are characterised by abundant extracellular myxoid matrix and are referred to as myxoid sarcomas (2). The myxoid matrix in these subset of sarcomas is composed of sulphated and non sulphated Glycosaminoglycans (GAGs) (3). The physical properties (increased viscosity and low compressibility) of GAGs favour the migration of tumour cells and the diffusion of metabolites thereby facilitating the growth of tumour cells (4),(5). Sulphated GAGs like chondroitin sulphate also modulate the survival of tumour cells by preventing apoptosis and promoting tumour cell proliferation. Myxoid matrix also possess high affinity for cell adhesion molecules and growth factors thereby facilitating cell to cell interaction and cell proliferation (6). All these factors contribute to the highly malignant behaviour of sarcomas with GAGs rich Extracellular Matrix (ECM). Many of these sarcomas exhibit overlapping histological features thereby necessitating additional ancillary techniques like IHC for definite diagnosis and categorisation of the myxoid sarcomas (2). IHC plays a vital role in the diagnosis of myxoid tumours of soft tissue and it is used as a complement to morphological diagnosis. It helps to rule out the non mesenchymal tumours and also for categorising the sarcomas into their specific lineage of differentiation (7). Use of a single immunostain will lead to potential misdiagnosis due to the lack of specificity and frequent aberrant reactivity of the immunological markers (8). Use of a panel of immunohistochemical markers based on the H&E differential diagnosis will lead to a correct diagnosis of this challenging group of tumours (9). The antibodies most commonly employed in soft tissue tumour pathology are Vimentin, SMA, Muscle Specific Actin (MSA), S100, CD34, CD99, Desmin, Myogenin, Cytokeratin and Epithelial Membrane Antigen (EMA). There is very limited comprehensive data in literature regarding the immunohistochemical characteristics of this broad group of myxoid sarcomas, though there have been isolated studies on few individual tumours in this group. Hence, this study was intended to determine the basic immunohistochemical profile of myxoid sarcomas. The objectives of this study was to identify the distribution of myxoid sarcomas among patients admitted in Rajiv Gandhi Government General Hospital, Chennai, Tamil Nadu, India, and to evaluate the utility of basic IHC in the diagnosis of myxoid sarcomas.
The present study was a six years retrospective observational cross-sectional study carried out in the Department of Pathology, Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai, Tamil Nadu, India, during the period of January 2008-December 2013 the analysis of the study was done from January to March 2014 after approval by the Institutional Ethics Committee. (IEC Ref No: MMC/03032012). Informed consent was obtained from all the patients while receiving the biopsy samples in the Department of Pathology.
Sample size calculation: A total of 57 samples were collected using purposive sampling technique for selection of desired samples according to the inclusion criteria.
Inclusion criteria: All cases of myxoid sarcomas diagnosed by histopathological examination. All types of samples including wide local excision, resection and incisional biopsy samples. Patients of all age groups and gender were included in the study.
Exclusion criteria: Soft tissue sarcomas without myxoid matrix. Tumour-like soft tissue lesions with myxoid areas. Benign myxoid soft tissue tumours were excluded from the study.
Study Procedure
Relevant pathological data of all the myxoid sarcomas reported during the study period were retrieved from the medical records of the Department of Pathology, Madras Medical College, Chennai, Tamil Nadu, India. H&E stained sections of the paraffin tissue blocks of these formalin fixed specimens were reviewed. The immunohistochemical panel of markers was decided based upon the histological picture and all the myxoid sarcomas were subjected to immunohistochemical evaluation. The basic panel of IHC markers covering all the lineages of soft tissue tumours that are commonly employed are Vimentin, SMA, MSA, S100, CD34, CD99, Desmin, Myogenin, Cytokeratin and EMA (9). Based on this the basic immunohistochemical markers used in this study were Vimentin, PanCK, CD34, Desmin, SMA, S100 and CD99.
• Vimentin- Positivity of vimentin indicates antigen preservation of the tissue and serves a control marker function (9).
• Cytokeratin- Among the soft tissue sarcomas, synovial sarcoma and epithelioid sarcoma characteristically display this antigen. Certain other sarcomas like leiomyosarcoma and MPNST show aberrant cytokeratin reactivity (9).
• Desmin- It is the specific marker of myogenic differentiation (9).
• SMA is a marker of smooth muscle differentiation. SMA reactivity is also seen in non muscle tissue with myoid phenotype like the various myofibroblastic lesions, myoepithelial lesions etc., (9).
• S100 was first isolated from Central Nervous System (CNS) where it is localised in the cytoplasm and nucleus of astrocytes, oligodendrocytes and Schwann cells. A wide variety of other mesenchymal tissues like adipocytes and chondrocytes also express this antigen (9).
• CD34- Among the sarcomas, CD34 immunoreactivity is found in solitary fibrous tumour, extra-gastrointestinal stromal tumours, DFSP, spindle cell lipoma and few nerve sheath tumours in addition to vascular neoplasms (9).
• CD99 is a cell surface glycoprotein uniformly expressed in Ewing sarcoma and Primitive Neuro Ectodermal Tumour (PNET). But it lacks specificity and is expressed in a number of soft tissue tumours including synovial sarcoma, rhabdomyosarcoma and desmoplastic small round cell tumour (9).
Immunohistochemical Evaluation
Immunohistochemical analysis was done in paraffin embedded tissue samples using the Next Generation Micro-Polymer Horse Radish Peroxidase (HRP) system based on non biotin polymeric technology provided by Thermo Scientific Ultravision Quanto detection system for IHC. 4μ thick sections from formalin fixed paraffin embedded tissue samples were transferred to gelatin coated slides. Heat induced antigen retrieval was done using microwave oven in appropriate temperature (480 watts, 640 watts, 800 watts and 800 watts for 5 minutes each) with appropriate buffer (Citrate buffer). The antigen was bound with monoclonal antibody. It was then detected by the addition of secondary antibody conjugated with HRP-polymer and diaminobenzidine substrate. The details of antibodies used for IHC is provided in (Table/Fig 1).
Interpretation and Scoring System
The immunohistochemically stained slides were analysed for the presence of reactivity, cellular localisation (nuclear/cytoplasmic/membranous), percentage of cells stained and intensity of reaction. In this study, IHC staining was graded by using semi-quantitative scale ranging from 0 (no immunoreactive cells) to 4+ (75-100% of the neoplastic cells are immunostained). The symbols 1+, 2+, and 3+ refer to the immunostaining of up to 25%, 25-50% and 50-75% of the neoplastic cells respectively (10).
Statistical Analysis
The data is shown in tables and results are expressed in terms of frequency and percentages.
A total of 57 myxoid sarcomas were reported during the six years study period and majority (46%) of them occurred in the age group of 41-60 years of age. Around 35% of myxoid sarcomas occurred in patients less than 41 years of age while 19% of them were encountered in patients more than 60 years of age. In the present study, myxoid sarcomas showed a striking male preponderance with 74% of cases occurring in male patients. Among the myxoid sarcomas, eight different histological types were encountered in this study with myxofibrosarcoma being the most common histological type accounting for 33.33% of cases. The other histological types are mentioned in (Table/Fig 2).
Immunohistochemical analysis was done for all the 57 cases of myxoidsarcomas using a panel of markers based on the light microscopic features of H&E stained sections. The Immunohistochemical markers employed were vimentin, PanCK, CD34, desmin, SMA, S100 and CD99.
Immunohistochemical results of myxoid sarcomas is shown in (Table/Fig 3): Immunohistochemical analysis of 19 myxofibrosarcomas showed (4+) positivity for vimentin in all the cases while 2 cases (10.5%) showed focal (1+) SMA positivity and one case (5.3%) showed focal (1+) CD34 positivity. S100 and Desmin were negative in all the 19 cases.
A panel of Vimentin and S100 were used for immunohistochemical confirmation of myxoid liposarcomas. All the 15 cases of myxoid liposarcomas in this study showed consistent (4+) positivity for vimentin and S100 (Table/Fig 4), (Table/Fig 5).
Immunohistochemical evaluation of eight cases of MPNST with myxoid change was carried out using a panel of markers including vimentin, S100, CD34, SMA, desmin and CD99. All the eight cases showed (4+) positivity of tumour cells for vimentin and S100 while one case (12.5%) showed focal (1+) CD34 positivity. Desmin, SMA and CD99 were negative in all the cases (Table/Fig 6), (Table/Fig 7).
The IHC of the four cases of low grade fibromyxoid sarcomas in this study showed negativity for all markers except vimentin (4+). Immunohistochemical study of all the four cases of DFSP with myxoid change showed diffuse strong positivity (4+) of the tumour cells for vimentin and CD34 while they were negative for S100. All the three cases of synovial sarcoma with myxoid change showed (4+) positivity for vimentin and PanCK while the tumour cells were negative for SMA, S100, CD34 and CD99. IHC was done for all the three cases of extra-skeletal myxoid chondrosarcoma in this study and they showed (4+) positivity for vimentin and S100 (Table/Fig 8), (Table/Fig 9). Immunohistochemical study of the one case of leiomyosarcoma with myxoid change in this study showed (4+) positivity of the tumour cells for vimentin, SMA, desmin and PanCK. S100 was negative.
Myxoid change encountered in benign and malignant soft tissue tumours can pose serious diagnostic challenge owing to their overlapping histomorphological features. There is very limited comprehensive study and data in literature regarding the immunohistochemical characteristics of this group of myxoid sarcomas, though there have been isolated studies on few individual tumours in this group.
The median age for myxoid sarcomas was 65 years as per World Health Organisation (WHO) statistics (11) unlike the present study where majority of cases were encountered in the 41-60 years age group. Coindre JM et al., from France and Yücetürk G et al., from Turkey reported male predominance of myxoid sarcomas similar to the present study (12),(13).
Out of the total 57 myxoid sarcomas, myxofibrosarcoma (33.33%) was the most common histological type followed by myxoid liposarcoma (26.32%) in this study which was in concordance with the studies of Coindre JM et al., from France and Yücetürk G et al., from Turkey (12),(13).
All the 19 cases of myxofibrosarcomas in this study showed positivity for vimentin while 10.5% of cases showed patchy SMA positivity and 5.3% of them showed focal CD34 positivity. Tumour cells were negative for desmin and S100. These results were identical to that of Mentzel T et al., (14).
Immunohistochemical analysis of 15 cases of myxoid liposarcoma showed consistent positivity of vimentin and S100 in all the cases. Graadt van Roggen JF et al., reported vimentin positivity in all the cases while S100 was positive in 35-50% of cases (2).
All the eight cases of MPNST with myxoid change showed vimentin and S100 positivity. One case (12.5%) showed focal CD34 positivity. Other markers including SMA, desmin and CD99 were negative in all the cases. These findings were in concurrence with that of Yamaguchi U et al., (15).
Only vimentin was positive in all the four cases of low grade fibromyxoid sarcoma while they were negative for SMA, desmin, S100, CD34 and CD99. Graadt van Roggen JF et al., reported consistent vimentin positivity similar to the present study while occasional cells showed positivity for SMA, desminand CD34 unlike this study (2). S100 was consistently negative in their study.
All the four cases of myxoid DFSP showed diffuse strong positivity for vimentinand CD34 while they were negative for S100. Reimann JDR and Fletcher CDM reported CD34 positivity in 95% of cases while all were S100 negative (16).
All the three cases of synovial sarcoma with myxoid change in this study were positive for vimentin and Pan CK while they were negative for SMA, S100, CD34 and CD99. These findings were similar to study done by Coli A et al., (17).
Three cases of extra-skeletal myxoid chondrosarcoma in this study showed positivity for vimentin and S100. Graadt van Roggen JF et al., claimed consistent positivity for vimentin while S100 was positive in 10-20% of cases (2).
The one case of leiomyosarcoma with myxoid change in this study showed vimentin, SMA, desmin and Pan CK positivity. S100 was negative in the tumour cells. Graadt van Roggen JF et al., reported consistent vimentin and SMA positivity, desmin positivity in 70% of cases while occasional Cytokeratin positivity. S100 was negative in all the cases (2).
Limitation(s)
Since, this is a rare group of malignancy, the sample size was less even though the study was carried out in a tertiary care referral hospital. Also, the prevalence of the individual histological subtypes of myxoid sarcomas was not uniform and was highly variable among population. Hence, future studies can be carried out by including more number of samples covering all the histological subtypes in adequate numbers by extending the study duration. This will provide a better picture of the pathological characteristics of all the individual histological subtypes of myxoid sarcomas.
The IHC is a valuable adjunct but never a replacement for light microscopy, particularly in this challenging group of myxoid neoplasms with overlapping histomorphological features. Though there are certain specific markers in practice for some of these sarcomas like myxoid liposarcoma and synovial sarcoma, the feasibility of usage of such markers in all the institutions is limited due to cost-effectiveness. Hence, with careful light microscopic examination and judicious usage of the basic routine immunohistochemical markers, accurate diagnosis is always possible in this uncommon and challenging group of malignant soft tissue tumours.
DOI: 10.7860/JCDR/2022/55509.16198
Date of Submission: Feb 07, 2022
Date of Peer Review: Mar 17, 2022
Date of Acceptance: Mar 25, 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
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