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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
Case Series
Full Version
Cytological Diagnosis of Malignant Pleural Effusion caused by Metastatic Squamous Cell Carcinoma: A Series of Four Cases
Correspondence Address :
Dr. Resmi Rajeev,
Velekkat House, P.O. Valapad, Thrissur-680567, Kerala, India.
E-mail: resmishigil@gmail.com
The majority of malignant pleural effusions are caused by adenocarcinomas, with the most common primary sites being the lung and breast in men and women, respectively. Metastatic squamous cell carcinoma in serous effusions is rare, accounting for less than 3% of all malignant effusions. The most common primary site of origin for metastatic squamous cell carcinoma involving serous effusions is the lung, followed by the head and neck, oesophagus, and cervix. Well-differentiated squamous cell carcinoma in pleural effusion, characterised by keratinised cells with hyperchromatic nuclei, tadpole cells, and fiber cells, is exceedingly rare. Poorly differentiated squamous cell carcinomas often present a diagnostic challenge and can be mistaken for poorly differentiated adenocarcinoma, malignant mesothelioma, or reactive mesothelial hyperplasia. Immunohistochemistry is often required for a definitive diagnosis. Making an accurate diagnosis is crucial for providing optimal treatment to the patient. In this series, four cases (56 years old male,69 years old male, 60 years old female and 81 years old male) of malignant pleural effusion caused by metastatic squamous cell carcinoma arising from the lung, oropharynx, cervix, and oesophagus were examined. While one of the cases involved a well-differentiated squamous cell carcinoma with characteristic cellular morphology that allowed for a straightforward diagnosis, the other three cases were poorly differentiated squamous cell carcinomas that required cell block preparation and immunohistochemistry for confirmation.
Immunohistochemistry, Keratinized cells, Neoplasm metastasis
Malignant effusions are most often caused by metastatic adenocarcinoma. Serous effusions due to metastatic squamous cell carcinoma are rare, accounting for only 0.5-2.7% of all malignant effusions (1). Well-differentiated squamous cell carcinoma cells exhibit characteristic cytologic features, enabling a reliable morphological diagnosis. Poorly differentiated squamous cell carcinoma in effusions, due to its rarity and lack of cytomorphological differentiation, may be misdiagnosed as poorly differentiated adenocarcinoma or sometimes as malignant mesothelioma (2). Squamous cell carcinoma, in comparison to adenocarcinoma, has a poorer prognosis. It has a lower diagnostic yield in pleural fluid cytology as its cells are shed less into effusions due to their tight intercellular junctions and robust anchors to the basement membrane (3).
This study describes four cases of malignant pleural effusion caused by metastatic squamous cell carcinoma. Two cases had no prior history of malignancy, and pleural effusion was the initial manifestation. The diagnosis of squamous cell carcinoma was made from pleural fluid cytology smears. Radiological investigations revealed a primary lung malignancy. Two patients with a history of squamous cell carcinoma of the cervix and oropharynx, respectively, were treated with chemoradiation and later presented with pleural effusion.
Case 1
A 56-year-old male patient presented with complaints of cough and dyspnoea lasting for two weeks. The patient was a smoker and had no history of tuberculosis or any other significant past medical conditions. Upon examination, the patient was afebrile, with a pulse rate of 90/min and a respiratory rate of 26/min. Dullness on percussion and decreased breath sounds were observed in the left 6th, 7th, and 8th intercostal spaces. A chest X-ray (Table/Fig 1)a revealed a left hilar mass and left-sided pleural effusion. The provisional diagnosis was lung carcinoma with malignant pleural effusion, with a differential diagnosis of TB lung with effusion. Pleural tapping was performed, and 5 mL of red-coloured fluid was sent for cytological study.
The pleural fluid cytology smear showed dispersed cells, both singly and in occasional clusters. The cells exhibited moderate to abundant dense eosinophilic to orangeophilic cytoplasm, well-defined cell borders, and pleomorphic hyperchromatic nuclei. Fiber cells and tadpole cells were also observed (Table/Fig 1)b-d.
A diagnosis of well-differentiated squamous cell carcinoma in pleural effusion was made. The final diagnosis was primary lung squamous cell carcinoma with metastasis to the pleural cavity. Unfortunately, the patient passed away after one cycle of chemotherapy.
$Case 2
A 69-year-old male patient presented with a cough, dyspnoea, and right-sided pleuritic chest pain lasting for three weeks. He was a non-smoker and non-alcoholic. The patient had a past history of oropharyngeal squamous cell carcinoma, for which he underwent radiotherapy one year ago. Upon examination, his vitals were stable, and breath sounds were diminished on the right-side of the chest. A chest X-ray revealed right-sided pleural effusion. A Computerised Tomography scan of the thorax showed a soft tissue density nodule with spiculated borders, measuring 15.3×15 mm in the apex of the right lung. The provisional diagnosis was lung and pleural metastasis from primary oropharyngeal squamous cell carcinoma, with a differential diagnosis of primary lung carcinoma with metastasis to the pleural cavity. A 5 mL red-coloured pleural fluid sample was sent for cytological study.
The pleural fluid cytology smears showed cells arranged in spherical clusters and dispersed singly (Table/Fig 2)a. The cells exhibited a moderate amount of cytoplasm, a high nuclear to cytoplasmic ratio, pleomorphic hyperchromatic nuclei with coarsely granular chromatin (Table/Fig 2)b. Occasional bizarre cells were observed. A cytological diagnosis of poorly differentiated carcinoma was made. Immunohistochemistry study was conducted on the cytology smears, revealing strong nuclear positivity for p63 (Table/Fig 2)c, which confirmed their squamous origin, and Thyroid Transcription Factor (TTF-1 negativity (Table/Fig 2)d, which ruled out the possibility of a non-squamous lung carcinoma.
A diagnosis of poorly differentiated squamous cell carcinoma in pleural effusion was made. The final diagnosis was primary oropharyngeal squamous cell carcinoma with metastasis to the lung and pleural cavity. The patient is currently undergoing chemotherapy.
Case 3
A 60-year-old female patient presented with breathlessness lasting for two weeks. She had a history of squamous cell carcinoma of the cervix, for which she underwent chemoradiation one year ago. Upon examination, she was afebrile, had tachypnea (respiratory rate-32/min), diminished breath sounds on the left-side of the chest, and an enlarged, single, hard left supraclavicular lymph node measuring 2×2 cm. A chest X-ray revealed a left-sided massive pleural effusion. One litre of red-coloured pleural fluid was sent for cytological study.
The pleural fluid cytology showed a cellular smear with cells dispersed singly and arranged in small clusters (Table/Fig 3)a. The cells had sharp cell borders, moderate to abundant cytoplasm, and pleomorphic hyperchromatic nuclei. Bizarre cells and multinucleated tumour cells were observed. Mesothelial cells were also seen in a background of blood.
The cell block preparation exhibited cells dispersed singly, with a moderate amount of cytoplasm and nuclei displaying irregular contours and coarse granular chromatin (Table/Fig 3)b.
The fine needle aspiration cytology smears of the left supraclavicular lymph node showed atypical cells in clusters. These cells had a moderate amount of dense eosinophilic cytoplasm and pleomorphic hyperchromatic nuclei (Table/Fig 3)c. The background displayed lymphocytes and blood. A cytological diagnosis of metastatic poorly differentiated carcinoma, possibly of squamous origin, was made for the pleural fluid and lymph node aspirate smears. Immunohistochemistry using p63 was performed on the lymph node aspirate smear, revealing diffuse strong nuclear positivity (Table/Fig 3)d, confirming squamous differentiation.
The final diagnosis was primary squamous cell carcinoma of the cervix with metastasis to the pleural cavity and supraclavicular lymph node. Unfortunately, the patient passed away one week after initiation chemotherapy.
Case 4
An 81-year-old female patient presented with dysphagia and weight loss lasting for one month, and dyspnoea lasting for two weeks. Upon examination, she appeared emaciated, had tachypnea (respiratory rate-34/min), and an 8×8 cm hard swelling over the sternum. Diminished breath sounds were observed on the left-side of the chest. A chest X-ray revealed a left-sided massive pleural effusion (Table/Fig 4)a. Endoscopic examination revealed an ulceroproliferative growth measuring 5 cm in the distal 7 cm of the oesophagus. Yellow-coloured pleural fluid, with a volume of one litre, was sent for cytological study.
The pleural fluid cytology smear showed cells dispersed singly and arranged in small clusters. The cells had a moderate to abundant cytoplasm, well-defined cell borders, and pleomorphic hyperchromatic nuclei (Table/Fig 4)b. The background displayed mesothelial cells.
Fine Needle Aspiration Cytology (FNAC) of the sternal swelling was performed. The smears showed cells dispersed singly, with a moderate amount of dense eosinophilic to orangeophilic cytoplasm and hyperchromatic pyknotic nuclei (Table/Fig 4)c,d. The background showed necrotic debris. The oesophageal biopsy revealed a poorly differentiated squamous cell carcinoma.
The final diagnosis was squamous cell carcinoma of the oesophagus with metastasis to the sternum and pleural cavity. All cases have been summarised in (Table/Fig 5).
Serous fluid cytology is an essential diagnostic test for detection and categorising malignancies based on their morphological characteristics. Metastatic adenocarcinoma accounts for the majority of malignant effusions in adults. Although squamous cell carcinoma is a common malignancy, it is rarely encountered in serous effusions. The pleural cavity is the most commonly involved body cavity, followed by the peritoneal and pericardial cavities (1). The lung, larynx, and cervix are the most common primary sites for squamous cell carcinoma metastasising to body cavities (2). In this case series, the primary sites of squamous cell carcinoma metastasising to the pleural cavity were the lung, oropharynx, cervix, and oesophagus.
The largest published series includes a study of 46 cases of metastatic squamous cell carcinoma collected from 9,297 effusions over a span of 33 years. Squamous cell carcinoma of the lung was the most common origin in the study, accounting for 13 out of 34 pleural fluid samples, 2 out of 4 pericardial fluid samples, and 1 out of 8 peritoneal samples. Other primary sites included the female genital tract and larynx (3).
In another study of 277 cases of non-small cell lung carcinoma with malignant pleural effusion, 29 were squamous cell carcinomas and 248 were adenocarcinomas. Pleural fluid cytology had a low diagnostic yield in cases of squamous cell carcinoma with malignant effusion, and these patients had reduced survival compared to those with adenocarcinoma (4). Squamous cell carcinoma cells have tight intercellular junctions and are firmly anchored to the basement membrane, resulting in reduced shedding of squamous cells in effusions compared to adenocarcinomas (5).
The diagnosis is straightforward when serous effusions are involved in metastatic, well-differentiated squamous cell carcinoma. It typically exhibits a predominantly single-cell pattern with occasional small clusters. The cells have well-defined cell borders, dense eosinophilic to orangeophilic cytoplasm, and pleomorphic hyperchromatic nuclei. Tadpole cells, fiber cells, anucleated cells, keratinous debris, and squamous pearls may also be observed (1). Serous effusions involved in other malignancies may show small degenerated/necrotic orangeophilic tumour cells that mimic keratinising cells of squamous cell carcinoma (6).
Making a diagnosis of poorly differentiated squamous cell carcinoma in serous effusions is challenging as its cytological features overlap with those of poorly differentiated adenocarcinoma, malignant mesothelioma, and reactive mesothelial hyperplasia (7). However, certain features such as a single-cell presentation, the presence of many bizarre nuclear forms, coarse chromatin, and cells with sharp cytoplasmic outlines can indicate a squamous cell carcinoma, especially in the context of a known clinical history of a primary squamous cell carcinoma (1). It is crucial to make an accurate diagnosis as squamous cell carcinoma requires a different treatment protocol compared to adenocarcinomas. Immunohistochemistry can aid in confirming the diagnosis. Squamous cell carcinoma cells will test positive for p63, p40, and Cytokeratin5/6 (8).
Metastatic adenocarcinoma reacts positively to Carcinoembryonic Antigen (CEA), Ber-EP4, and MOC-31 (9). Thyroid transcription factor-1 and Napsin A have high specificity for lung adenocarcinomas (4). Malignant mesothelioma cells will show positivity for mesothelial markers (Wilm’s tumour gene 1, calretinin) and Epithelial Membrane Antigen (EMA), while reactive mesothelial cells will show positivity for mesothelial markers (WT 1, calretinin) and desmin (10). Published literature suggests that the pleural cavity is the most commonly involved secondary cavity (Table/Fig 6) (4),(11),(12),(13),(14),(15),(16).
Metastatic squamous cell carcinoma involving serous effusions is rare, and well-differentiated squamous cell carcinoma causing malignant pleural effusion is exceedingly rare. Morphological mimickers of poorly differentiated squamous cell carcinoma in effusions include poorly differentiated adenocarcinoma, malignant mesothelioma, and reactive mesothelial hyperplasia. It is imperative to make a definitive diagnosis of squamous cell carcinoma as it has a worse prognosis and a different management protocol compared to adenocarcinoma. The clinical history of a primary squamous cell carcinoma and/or effusion fluid showing a predominance of a single cell population, numerous bizarre nuclear forms, and cells with a sharp cytoplasmic outline should raise the possibility of metastatic squamous cell carcinoma. Immunohistochemistry helps to confirm the diagnosis.
DOI: 10.7860/JCDR/2024/64623.19127
Date of Submission: Apr 10, 2023
Date of Peer Review: May 18, 2023
Date of Acceptance: Dec 07, 2023
Date of Publishing: Mar 01, 2024
AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• 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: Apr 08, 2023
• Manual Googling: May 23, 2023
• iThenticate Software: Dec 05, 2023 (12%)
ETYMOLOGY: Author Origin
EMENDATIONS: 8
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