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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
Disorders of Sexual Differentiation: A Clinicopathological and Histological Study
Correspondence Address :
Neethu Tony Mampilly,
37/3292, Cherupilly Road, Kaloor, Cochin, Kerala, India.
E-mail: neets_mampilly@hotmail.com
Introduction: The term ‘Disorders of Sexual Differentiation’ (DSD) is defined as a congenital discrepancy between external genitalia, gonadal and chromosomal sex. The Chicago consensus based on the primary genetic defect is used for current nomenclature and classification. A child with DSD, if identified and treated early, may grow to become a well-adjusted, functional member of the society. Patients with DSD carry a low but definite risk of developing germ cell tumours which necessitates a histological analysis in all cases.
Aim: To describe the clinicopathological features of individuals with DSD and to classify the available cases according to the Chicago consensus which is based on karyotype and histopathology.
Materials and Methods: This retrospective descriptive study was done at a tertiary referral centre in South India, for a period of four months from May 2016 to August 2016. Case charts and histopathology slides of cases received in the Department of Pathology from January 2011 to May 2016 were included and reviewed. Cases where the histopathology slides/blocks were not retrievable/difficult to assess due to technical issues were excluded. Case charts and slides were reviewed retrospectively with a view to classify as per karyotypic or histological classification. The slides were reviewed by two Pathologists to help in the classification wherever possible. Statistical measures like mean and percentages were used to describe the results.
Results: A total of 22 cases of DSD were studied for which karyotype was available in 13 cases. Common clinical presentations were primary amenorrhoea, cryptorchidism and ambiguous genitalia. Age at presentation varied from nine months to 30 years. The initial diagnosis based on karyotype, clinical findings, hormonal assays and imaging were concordant with the final diagnosis in 11 cases. In two cases, histopathology was essential in arriving at a definitive diagnosis. Of the 13 cases with karyotype reports available, five were sex chromosome DSD, five were 46XY DSD and three were 46XX DSD. Gonadoblastoma was seen in three cases.
Conclusion: Histopathological examination together with karyotype plays a crucial role in proper categorisation of disorders of sexual differentiation. A multidisciplinary team approach for early diagnosis and management of DSD is essential for the psychosexual development of these individuals.
Germ cell tumour, Gonadal dysgenesis, Karyotype
Disorders of Sexual Differentiation (DSD) is defined as congenital conditions associated with atypical development of chromosomal, gonadal or anatomical sex (1). The birth of a child with ambiguous genitalia heralds a long term pathophysiological aberration of gender identity, gender role and sexual orientation (2) as well as psychosocial issues for the individual and the family members. Hitherto used terminology like ‘intersex’, ‘hermaphroditism’ and ‘pseudohermaphroditism’ have been replaced by DSD (3). The revised nomenclature as well as recommendations of treatment were laid down in a multidisciplinary meeting of medical and non medical experts at Chicago in 2006 (The Chicago consensus) (2).
The vast majority of DSD cases are 46XX DSD- congenital adrenal hyperplasia or 45XO/46XX DSD-mixed gonadal dysgenesis (3). The incidence of DSD varies among different populations and is estimated to be 1:5500 worldwide (3). Karyotype plays a central role in classification (2); however clinical presentation, physical findings and specific investigations are equally important. The diagnosis and treatment require a multidisciplinary team, intervening at various stages to enable the individual to evolve into a well-adjusted member of the society (2).
Despite the large number of cases managed in clinical practice, there is a paucity of published literature on DSD data from the Indian subcontinent. This study presents a diagnostic histopathology perspective from a tertiary care referral and teaching centre of Karnataka.
Objective:
1. To study the clinicopathological features of individuals with DSD.
2. To classify the available cases according to the Chicago consensus which is based on karyotype and histopathology.
3. To correlate histopathology with clinical details including karytotype.
4. To highlight the importance of histopathology in picking up in-situ lesions early.
A retrospective descriptive study was conducted at St. John’s Medical College, Bangalore, Karnataka, India. All the cases received in the histopathology Department from January 2011 to May 2016 were reviewed between May 2016 and August 2016.
Inclusion criteria: All cases received in the Histopathology Department for tissue diagnosis during the mentioned time frame were included. Cases from other referral hospitals were also included.
Exclusion criteria: Cases where the histopathology slides/blocks were not retrievable/difficult to assess due to technical issues were excluded.
Study Procedure
A total of 22 cases received during the study period, were included. Case details of DSD cases received in the department were retrieved from the Paediatric Surgery Department archives. The clinical details including the age at presentation, sex of rearing and phenotype, presenting complaints, physical findings, karyotype, hormonal profile, imaging and findings at genitoscopy/surgery were collected from the case records, if available. Several clinical details and results of preoperative investigations were lacking in five cases referred from elsewhere. The histopathology slides were reviewed by two Pathologists. The cases were classified as per the Chicago consensus (2), if karyotype was available. The rest of the cases were classified according to Aaronson’s classification (1), based on histology of the gonad. This classification does not contradict Chicago consensus, but provides a better understanding based on the histology.
Statistical Analysis
Statistical measures like mean and percentages were used to describe the clinical parameters using Statistical Package for the Social Sciences (SPSS) version 17.0.
Twenty-two cases were included in the study. The mean age of presentation was 9.9 years. Total 12/22 (54.5%) of these cases were reared as females. Out of 13 cases (where karyotype reports were available), there were five sex chromosome DSD cases (45XO/46XY mixed gonadal dysgenesis), five 46XY DSD cases and three 46XX DSD cases (Table/Fig 1), (Table/Fig 2). Of five 46XY DSD cases, the hormonal profile suggested Complete Androgen Insensitivity Syndrome (CAIS) and 17 beta-hydroxysteroid dehydrogenase deficiency in one each. There was one case of 46XX ovotesticular DSD (Table/Fig 3). Gonadoblastoma was seen in 3/22 cases (Table/Fig 4). Cases classified as per Chicago consensus are described in (Table/Fig 5). In nine cases, where karyotype was not available, histological classification was done, among which testicular DSD was the most common (Table/Fig 6).
The provisional diagnoses based on clinical features, karyotype, imaging and hormonal assays were concordant with the final diagnosis in 11/13 cases. In two, a mistaken clinical diagnosis was clarified by the histopathology findings. The first case was referred as congenital adrenal hyperplasia (case 5 in (Table/Fig 5)) but histopathological examination of the gonads showed ovotesticular DSD. In the second case (case 12 of (Table/Fig 5)), the gonad of a suspected right inguinal heterogenous gonad akin to a polar ovotestis contained only testicular tissue. In this case, only the suspicious gonad with variable consistency was biopsied. The other gonad showed uniform texture with well-developed vas and vessels intraoperatively.
Several clinical details and results of preoperative investigations (hormonal profile, imaging, endoscopy) were lacking in five cases, including cases referred from elsewhere.
Among 22 cases of DSD, the mean age at presentation was 9.9 years, much higher than the mean age of 27.4±38.4 months in another Indian study by Joshi RR et al., (5). Only two cases in this study were diagnosed in infancy. Total 61.9% cases were identified after the age of five years, similar to the findings by Ammini AC et al., Rajendran R and Hariharan S (6),(7). A 12/22 cases were reared as females. However, the earlier quoted studies had more number of cases reared as males. A study from Saudi Arabia by Al-Jurayyan NAM had more cases reared as females (8). Several cases reared as females presented at the pubertal age with primary amenorrhoea. A preferential male sex of rearing and late presentation is generally attributed to socio economic factors and stigma associated with DSD. There are no cases with congenital adrenal hyperplasia in this series, as they are generally diagnosed with investigations other than histopathology.
The DSD were traditionally classified into four groups: female pseudo hermaphroditism (46XX, ovarian gonads and variably virilised external genitalia), male pseudo hermaphroditism (46XY, testicular gonads, poorly virilised internal and/or external genitalia), gonadal dysgenesis (mosaic karyotypes, dysgenetic gonads) and true hermaphroditism (various karyotypes, combination of mature ovarian and testicular gonads) (9). According to Chicago consensus and revised nomenclature (2), cases were classified as sex chromosome DSD (n=5, 38.4%), 46XY DSD, (n=5, 38.4%) and 46XX DSD (n=3, 23.07%). Rajendran R and Hariharan S have also reported 40% cases of 46XY DSD, similar to this study (7). But in larger studies by Walia R et al., 46XX is the most common karyotype, the difference in this study could be due to the small sample size (10).
Of the five 46XY DSD cases, two had androgen insensitivity syndrome and one had 17 beta hydroxy steroid dehydrogenase deficiency (a defect of testosterone biosynthesis) (11). All three were reared as females. There was only one case of ovotesticular DSD seen among the three cases of 46XX DSD’s. Histopathology helps confirm a diagnosis of ovotesticular DSD as the karyotype can be one of a variety- 46XX, 46XY or mosaics (12). Sex chromosome DSD constituted another major group, 45X/46XY mixed gonadal dysgenesis with ambiguous genitalia or asymmetric gonads was common. Once karyotype and the presence/absence of a Mullerian remnant are ascertained by imaging/endoscopy, gonadal histology helps in assigning a final diagnosis. The distinction is especially important between a dysgenetic state with dysgenetic gonads (streak) and an ovotesticular DSD with mature ovarian/testicular/ovotesticular gonad. The distribution of ovarian and testicular tissue within ovotestis varies, with one moiety likely to predominate and other assuming a polar or hilar distribution. Therefore, it is recommended that gonadal biopsies be taken from pole to pole with tissue chunk preferably from deep into the hilum of the gonad for confirmation (13).
Gonadoblastoma was detected in 3/22 cases (13.63%), of which two had immature testicular tissue and one developed in a streak gonad. In one, karyotype (46XY) was available. The prevalence of germ cell tumours in patients with gonadal dysgenesis is estimated at around 30% and in patients with undervirilisation syndromes at 5-10% (14),(15). Kathrins M and Kolon TF describes the overall tumour risk of dysgenetic DSD between 15% and 33%, similar to our findings (16). The identification of in-situ precursor lesions in the gonad helps to decide between a strict wait and watch policy or a prophylactic gonadectomy to avert a subsequent invasive germ cell tumour (4). The highest risk of neoplasia is found in Testis Specific Protein Y encoded (TSPY) positive gonadal dysgenesis as well as in the intraabdominal gonads in Partial Androgen Insensitivity Syndrome (PAIS). The lowest risk is associated with CAIS and ovotestis (2).
The workup of individuals with ambiguous genitalia is best done at the earliest to facilitate an informed decision on the gender of rearing and chart a calendar of medical and surgical management. The evaluation must include a detailed clinical examination of the child including the external genitalia. Thereafter, laboratory investigations including serum chemistry and hormonal profile, imaging and endoscopic assessment are individualised and tailored to unravel the final diagnosis in an algorithmic manner (11). In fact, current prenatal diagnostic screening procedures include ultrasound, karyotyping from amniotic fluid, hormonal assays and molecular study of involved genes (3). Future of DSD diagnosis also includes genetic study of various genes involved in gonadal development by molecular research methods (17),(18). This series underlines the importance of documentation of clinical and investigative details before submission of tissue (gonadal, genital ductal) for biopsy and further interpretation.
Limitation(s)
The paucity of clinical and investigative details in several of our patients as well as the non availability of representative gonadal/genital ductal tissue in some others limited the complete histopathological interpretation and classification of the entity.
A karyotype is mandatory to categorise DSD. Hormonal profiling, imaging and endoscopy are important adjuncts in preoperative diagnosis. Histopathology of the gonads and internal genital ducts plays a confirmatory role. Early and accurate diagnosis of DSD facilitates optimal and multidisciplinary management of this difficult paediatric genitourological entity. It also facilitates surveillance of in-situ neoplastic lesions in the gonad prior to development of invasive germ cell tumours (low risk) or provides a basis for a prophylactic gonadectomy in high risk scenarios.
DOI: 10.7860/JCDR/2022/51433.15972
Date of Submission: Jul 23, 2021
Date of Peer Review: Sep 17, 2021
Date of Acceptance: Dec 02, 2021
Date of Publishing: Feb 01, 2022
AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? No
• Was informed consent obtained from the subjects involved in the study? No
• For any images presented appropriate consent has been obtained from the subjects. Yes
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