We read with interest the recently published manuscript by Kir et al. entitled “High-risk human papillomavirus (HPV) detection in formalin-fixed paraffin-embedded cervical tissues: performances of Aptima HPV assay and Becton Dickinson (BD) Onclarity assay” [1]. The study evaluates the off-label use of commercial HPV assays on formalin-fixed paraffin-embedded (FFPE) specimens. The authors detail the performance of the Hologic Aptima RNA test and the BD Onclarity DNA test in a study of 189 cases (46 SCC, 107 HSIL and 36 benign/normal). They report that, while the specificity and positive predictive value (PPV) were 100% for both assays, the Aptima assay was more sensitive, detecting 99.4% (95% CI 96.46% to 99.98%) of CIN2+ cases, versus the BD Onclarity assay with a sensitivity of 75.9% (95% CI 65.27% to 84.62%) [1]. The authors conclude that “both assays are reliable methods for high-risk HPV detection and genotype determination in FFPE specimens” and that the “Aptima assay has the advantage of higher sensitivity”.
We believe that there are a number of deficiencies in the study design (not addressed in the discussion section) which call into question the validity of the conclusions. Firstly, this is not a split sample study, nor a true head to head comparison since the samples were not randomly assigned to each assay for testing. All 189 cases were first tested with the Aptima assay and only approximately half (n = 97) were subsequently tes...
We read with interest the recently published manuscript by Kir et al. entitled “High-risk human papillomavirus (HPV) detection in formalin-fixed paraffin-embedded cervical tissues: performances of Aptima HPV assay and Becton Dickinson (BD) Onclarity assay” [1]. The study evaluates the off-label use of commercial HPV assays on formalin-fixed paraffin-embedded (FFPE) specimens. The authors detail the performance of the Hologic Aptima RNA test and the BD Onclarity DNA test in a study of 189 cases (46 SCC, 107 HSIL and 36 benign/normal). They report that, while the specificity and positive predictive value (PPV) were 100% for both assays, the Aptima assay was more sensitive, detecting 99.4% (95% CI 96.46% to 99.98%) of CIN2+ cases, versus the BD Onclarity assay with a sensitivity of 75.9% (95% CI 65.27% to 84.62%) [1]. The authors conclude that “both assays are reliable methods for high-risk HPV detection and genotype determination in FFPE specimens” and that the “Aptima assay has the advantage of higher sensitivity”.
We believe that there are a number of deficiencies in the study design (not addressed in the discussion section) which call into question the validity of the conclusions. Firstly, this is not a split sample study, nor a true head to head comparison since the samples were not randomly assigned to each assay for testing. All 189 cases were first tested with the Aptima assay and only approximately half (n = 97) were subsequently tested with the BD Onclarity assay. Kir et al state that after collection of the Aptima samples H&E tissue staining was used to check to see if there was sufficient lesion remaining for BD Onclarity testing and they found that the lesion was depleted in 92, or almost half of the total available cases. The disease profile of the 97 remaining cases was SCC: n=40, 41.2%; HSIL: n=43, 44.3% and benign/normal: n=14, 14.4% which is different from that of the full cohort SCC: n=46, 24.3%; HSIL: n=107, 56.6%; benign/normal: n=36, 19.0%. Thus, the Aptima assay had the opportunity to evaluate 153 presumptive HPV positive cases, versus just 83 cases for Onclarity. The loss of almost half of the total samples to lesion depletion is surprising and can be explained by how the samples were processed. Firstly, 4 μm thick sections were cut from the block for separate immuno-staining with p16 and Ki67 to confirm both SCC and HSIL diagnoses. Thereafter, “from each tissue block, 8–60 (depending on tissue size) 4 μm thick sections” were harvested for Aptima HPV testing. The use of a minimum of 8, and as many as 60, sections for nucleic acid extraction is excessive in our experience. It is therefore not unexpected that the use of multiple sectioning extended past the lesion, rendering the sample unsuitable for further testing. The authors do not detail exactly how they used H&E to confirm lesion size/sample adequacy prior to BD Onclarity testing. Best practice is to use a sandwich method where both sides of the section(s) used for nucleic acid extraction are confirmed to have visible lesions by H&E staining [2]. The loss of ~50% of samples due to upstream sampling, where a minimum of 10 preceding sections were harvested, suggests that the residual samples tested by BD Onclarity were not of the same quality in terms of lesion size, and hence viral load. Moreover, Kir et al appear to have used just a single 5-10 micrometer section for BD Onclarity testing versus 8-60 sections for Hologic Aptima test. While this may reflect the different sample input requirements for each assay, it does underline the inequality in the workflows in terms of target concentration (and calls into question the assertion that the BD Onclarity assay is less sensitive). A simpler and improved study design would have been to randomly assign one of the 8-60 Aptima sections for testing with BD Onclarity assay. Our experience with FFPE tissue is that there is ample cellularity in a single section and that HPV is detected at high frequency provided there is a lesion present. This is evident from analysis of average beta-globin cellularity control Ct scores from both liquid-based-cytology (LBC) and single FFPE sections, which have a similar (normal) and overlapping distribution [3].
Kir et al. cite a prior BD Onclarity FFPE study where the sensitivity for CIN2+ was 90% [4] which compares favorably with the Aptima performance in their study and those of other assays in previously published work (Table 5) [1]. Two additional BD Onclarity studies (not cited in Table 5) investigated the performance of the assay using FFPE sections: Genta et al reported 84% HPV positivity in 292 cases of invasive cervical cancer [5] and Bottari et al. recently compared the performance in 99 FFPE samples to paired LBC specimens (26 CIN 1, 30 CIN 2, and 43 CIN 3+). After 15 samples were excluded due to sample quality, the remaining 84 samples recorded an overall agreement of 89% for HPV status between FFPE Onclarity samples versus LBC samples [6]. (It is also noteworthy that all three published Onclarity studies used the gold standard sandwich method to ensure that the lesion was present).
The afore-mentioned studies suggest that the performance of the BD Onclarity assay using FFPE specimens is similar to other published assays, and we respectfully submit that the apparent reduction in sensitivity in assay performance reported by Kir et al is likely due to sample quality/viral load differences between the Aptima and BD Onclarity samples. Finally, the authors interpret the higher sensitivity of the Aptima assay to mean that “choosing RNA [vs. DNA] for nucleic acid extraction from FFPE tissue will lead to better results”. This seems at odds with the known lability of RNA versus DNA [7] and is not in fact supported by the published work they cite to support this assertion [8]. The increased “sensitivity” is more likely to have resulted from the increased sample input volume (as much as 60-fold higher) for the RNA versus DNA assays compared in the study.
Sincerely,
REFERENCES
1. Kir G, Gunel H, Olgun ZC, McCluggage WG: High-risk human papillomavirus (HPV) detection in formalin-fixed paraffin-embedded cervical tissues: performances of Aptima HPV assay and Beckton Dickinson (BD) Onclarity assay. Journal of clinical pathology 2021.
2. Mena M, Lloveras B, Tous S, Bogers J, Maffini F, Gangane N, Kumar RV, Somanathan T, Lucas E, Anantharaman D et al: Development and validation of a protocol for optimizing the use of paraffin blocks in molecular epidemiological studies: The example from the HPV-AHEAD study. PloS one 2017, 12(10):e0184520.
3. Maus C, Vaughan, L, Adams M, Chen, C, Dixon, E, Gutierrez, E, Harris, J, Horlick, E, Leitch, S, McMillian, R, Murphy, P, Nelson, R., Nussbaumer, W, Peck, J, Porter, M, Richart, G, and Mertz, L.: Performance Of BD Viper™ HPV Assay Using Formalin-Fixed Paraffin-Embedded (FFPE) Samples. EUROGIN Conference Oral Presentation, Lisbon, Portual May 8-11 2011.
4. Castro FA, Koshiol J, Quint W, Wheeler CM, Gillison ML, Vaughan LM, Kleter B, van Doorn LJ, Chaturvedi AK, Hildesheim A et al: Detection of HPV DNA in paraffin-embedded cervical samples: a comparison of four genotyping methods. BMC infectious diseases 2015, 15:544.
5. Nogueira Dias Genta ML, Martins TR, Mendoza Lopez RV, Sadalla JC, de Carvalho JPM, Baracat EC, Levi JE, Carvalho JP: Multiple HPV genotype infection impact on invasive cervical cancer presentation and survival. PloS one 2017, 12(8):e0182854.
6. Bottari F, Passerini R, Renne G, Guerrieri ME, Sandri MT, Li A, Orlandini A, Iacobone AD: Onclarity Performance in Human Papillomavirus DNA Detection in Formalin-Fixed Paraffin-Embedded Cervical Samples. Journal of lower genital tract disease 2021, 25(3):216-220.
7. Groelz D, Viertler C, Pabst D, Dettmann N, Zatloukal K: Impact of storage conditions on the quality of nucleic acids in paraffin embedded tissues. PloS one 2018, 13(9):e0203608.
8. Ferrer I, Armstrong J, Capellari S, Parchi P, Arzberger T, Bell J, Budka H, Ströbel T, Giaccone G, Rossi G et al: Effects of formalin fixation, paraffin embedding, and time of storage on DNA preservation in brain tissue: a BrainNet Europe study. Brain pathology (Zurich, Switzerland) 2007, 17(3):297-303.
Dear Dr Kaushik, JCP, BMJ et al,
I hope this note finds You well
Years after this most excellent Article was composed regarding gene activation in Patients with the CFS (chronic fatigue syndrome), was surprised to see this discussion on how ultrasound would adversely effect, ie disrupt, the BBB (Blood Brain Barrier) causing nausea, fatigue and headaches
This might explain, at least partially, the events (Havana syndrome) at the US Embassy 2016 of unusual disease processes which occurred after presumed ultrasound exposure to Personnel
Anthony C. Zander et al
University of Adelaide,
Australia
September 8, 2004
Research has shown that airborne ultrasound has the potential to cause nausea,
fatigue, and headaches [3–8]
Apparently would be difficult to detect ultrasound presence but mismatched ultrasound devices of several types could present as audio frequency noise, possibly thought to be tinnitus
Best wishes always
Thank you for your assistance with this matter...
Dear Dr Kaushik, JCP, BMJ et al,
I hope this note finds You well
Years after this most excellent Article was composed regarding gene activation in Patients with the CFS (chronic fatigue syndrome), was surprised to see this discussion on how ultrasound would adversely effect, ie disrupt, the BBB (Blood Brain Barrier) causing nausea, fatigue and headaches
This might explain, at least partially, the events (Havana syndrome) at the US Embassy 2016 of unusual disease processes which occurred after presumed ultrasound exposure to Personnel
Anthony C. Zander et al
University of Adelaide,
Australia
September 8, 2004
Research has shown that airborne ultrasound has the potential to cause nausea,
fatigue, and headaches [3–8]
Apparently would be difficult to detect ultrasound presence but mismatched ultrasound devices of several types could present as audio frequency noise, possibly thought to be tinnitus
Best wishes always
Thank you for your assistance with this matter
To address the concern of potential cross-reactivity of SARS-CoV-2 with Architect HIV Combo assay (Abbott Laboratories, Abbott Park, Illinois, USA) reported in this article, we evaluated 846 COVID-19 convalescent plasma samples obtained from New York Blood Center (New York, New York, USA) using the Architect HIV Combo assay. Although all 846 samples were reactive in Architect SARS-Cov-2 IgG assay (Abbott Laboratories, Abbott Park, Illinois, USA), none of the samples were reactive in the Architect HIV Combo assay with average signal < 0.14 S/CO and standard deviation < 0.058 S/CO. Thus, the data shows no indication of cross-reactivity between SARS-CoV-2 infection and Architect HIV Combo assay.
Furthermore, it is well known that HIV-1 gp41 protein also shows striking structural similarity to the fusion pH-induced conformation of influenza virus HA2 protein (Weissenhorn et. al. Nature 1997, 387:426). However, to our knowledge, no cross-reactivity case from flu vaccinated samples has been reported with the Architect HIV Combo assay since its launch in 2004. Collectively, the cross-reactivity of SARS-CoV-2 infection with Architect HIV Combo assay should be extremely low.
We read with great interest the article by Marietjie Venter and Karin Richter on the diagnostic assay for COVID-19 [1]. We agree with the authors about delays in diagnoses, a severe shortage of tests and laboratory capacity for performing RT-PCR tests. This is especially true for many developing countries such as Bangladesh, which is faced with current health care crises to provide healthcare for more than 165 million population. A large number of people are being tested for COVID-19 and confirmed with the disease every day in Bangladesh, and many more remain undetected due to the lack of testing. Further, the delay to receive test results and lack of medical records cause COVID-19 patients to transmit the disease in the community and hamper proper treatments.
Prior to the COVID-19 test, several pre-conditional medical records are required to support the results. In Bangladesh, these records are generally gathered by health workers in the testing centres manually and ignoring many important symptoms and conditions. However, this
process is tedious and prone to omission, error and bias, leading to incomplete medical records. Further, participants are required to return to the centre the next day to collect test results which might increase community transmission. To mitigate such disadvantages, we developed a
smartphone-based RT-PCR record and monitoring app ‘mobEVID’.
This app has been built following Novel coronavirus RT-PCR app...
We read with great interest the article by Marietjie Venter and Karin Richter on the diagnostic assay for COVID-19 [1]. We agree with the authors about delays in diagnoses, a severe shortage of tests and laboratory capacity for performing RT-PCR tests. This is especially true for many developing countries such as Bangladesh, which is faced with current health care crises to provide healthcare for more than 165 million population. A large number of people are being tested for COVID-19 and confirmed with the disease every day in Bangladesh, and many more remain undetected due to the lack of testing. Further, the delay to receive test results and lack of medical records cause COVID-19 patients to transmit the disease in the community and hamper proper treatments.
Prior to the COVID-19 test, several pre-conditional medical records are required to support the results. In Bangladesh, these records are generally gathered by health workers in the testing centres manually and ignoring many important symptoms and conditions. However, this
process is tedious and prone to omission, error and bias, leading to incomplete medical records. Further, participants are required to return to the centre the next day to collect test results which might increase community transmission. To mitigate such disadvantages, we developed a
smartphone-based RT-PCR record and monitoring app ‘mobEVID’.
This app has been built following Novel coronavirus RT-PCR app developed by the Indian Council of Medical Research [2]. After developing a beta version of the app, we consulted with a group of national experts (including people engaged with RT-PCR testing, health policymakers,
hospital administrators, researchers and clinicians). We demonstrated the contents and designs of the app to the experts. The app was further modified based on expert recommendations. We translated the materials of the app into Bangla following a rigorous process of translation and
back-translation by two bilingual researchers. This app allows users and laboratory personals to record COVID-19 test results and individual
medical records in the app and transmit them to a secure server for storage and use by clinicians. The user account contains four parts such including: (i) add new entry, (ii) repeat test, (iii) view personal details, and (iv) incomplete records. The 'new entry' part allows to create a new patient ID and is split into two sections, A and B. In section A, test participants provide their contact information such as name, address, email, phone number etc. and select information related to collected samples. In section B, the exposure history and medical records of the test participant are entered, for example, if the participants have recently travelled abroad or had contact with COVID-19 cases/suspected cases. In addition, clinical symptoms and conditions are presented as a drop-down menu to enter the participant's medical history. Finally, the details of the participant's hospitalization information are entered. On the other hand, the app allows any participants in Bangladesh to download the app and self-register as a user freely.
If a participant is tested for COVID-19, they can receive their RT-PCR test results rapidly through this app. Data from the app are stored securely in a central repository and can be exported in different formats (excel/pdf) to the local authority. This app can be used either in Bangla or English, which makes it more user friendly and interpretable to the users.
The mobEVID is a flexible option for both test providers and users to share primary information and test results rapidly. The app also contains up to date information on COVID-19 following national recommendations and medical records of the participants. These records are also helpful for clinicians treating the cases and inform the participants about their condition immediately for contact tracing, taking necessary action and monitoring progress. This app might be useful for government and policymaker to record COVID-19 cases, maintain a patient database and help prevent rapid community transmission of COVID-19 in Bangladesh.
Acknowledgement: We are thankful to Dr. Newaz Mohammed Bahadur, Dr. Firoz Ahmed, and Koushik Chandra Howlader to support us to build this apps.
References
[1] Venter M, Richter K. Towards effective diagnostic assays for COVID-19: a review. Journal of Clinical Pathology 2020;73:370-377.
[2] NIC EGov Mobile Apps “RT-PCR - Apps on Google Play.” Google, Google, 3 June 2020, play.google.com/store/apps/details?id=nic.hp.niv_reporting&hl=en.
*Correspondence
Dr Sheikh Mohammed Shariful Islam, MBBS, MPH, PhD, FESC
NHMRC Emerging Leader and National Heart Foundation Senior Research Fellow
Institute for Physical Activity and Nutrition, Deakin University,
221 Burwood Highway, Burwood 3125, Melbourne, Australia
Telephone: +61451733373, Email: shariful.islam@deakin.edu.au
As a interested candidate for histopathology speciality training, I had the opportunity to attend a lung MDT in which roughly 25 cases were discussed. The case load was huge and some cases were rushed. The rushed cases were to be rediscussed which is a good form of safety netting although not ideal. The histopathology consultant requested reminders so immunohistology or second readings do not get missed. It would truely revolutionise MDT meetings if standard double reading could become a routine practice although already done in majority of cases.
The author has shed light on the importance of double reading of slides along with impressive figures.
A second review of slides could be a way to not only reduce error, but also improve quality of care in terms of management and immunohistology.
Thank you so much for highlighting the importance of a routine second review prior to MDT meetings. During the taster session, I asked the Histopathology consultants if they encourage second reviews and was informed that wherever there is the slightest doubt, another consultant or sub-specialist would be consulted. It was reassuring to know that histopathologists can always benefit from their colleagues expertise.
This practice safeguards patients in the sense that a correct diagnosis can be made in all cases minimising potential errors.
Dear Editor,
before COVID-19, in the era of targeted therapies, pathologists played a cornerstone role in providing information especially about cancer diagnoses.1 Therefore, scientific community felt that autopsies were out-dated. Now, in this emerging reality, we are assisting to the transformation of the pathologist’s role: instead of proceeding to the “future” of molecular diagnosis we are going back to the “past” of our “noir” connotation. This negative meaning was linked, in the popular culture, to frequent post-mortem examinations performed by pathologist forgetting the paramount value of this medical procedure in explaining pathogenetic mechanisms of all diseases.2 During COVID-19 pandemia, Italian Hospitals changed their usual health department strategy. Hospital Governments strengthened intensive care units and lung units and decreased surgical activities. Pathologists’ role shifted from microscopic diagnosis back to the original mortuary role, setting aside optical microscope, the principal pathologist’s tool, and leaving space to necropsy activity with management of dead bodies by mortuary staff and pathologists in the perspective of threat of transmission of SARS-CoV-2.2 For this reason, Government has promptly implemented extraordinary and detailed measures to restrict viral spread from this source.3 In Italy, pathologists fill in death certificate, a legal instrument and a permanent record of an individual’s death, that requires accuracy, promptness,...
Dear Editor,
before COVID-19, in the era of targeted therapies, pathologists played a cornerstone role in providing information especially about cancer diagnoses.1 Therefore, scientific community felt that autopsies were out-dated. Now, in this emerging reality, we are assisting to the transformation of the pathologist’s role: instead of proceeding to the “future” of molecular diagnosis we are going back to the “past” of our “noir” connotation. This negative meaning was linked, in the popular culture, to frequent post-mortem examinations performed by pathologist forgetting the paramount value of this medical procedure in explaining pathogenetic mechanisms of all diseases.2 During COVID-19 pandemia, Italian Hospitals changed their usual health department strategy. Hospital Governments strengthened intensive care units and lung units and decreased surgical activities. Pathologists’ role shifted from microscopic diagnosis back to the original mortuary role, setting aside optical microscope, the principal pathologist’s tool, and leaving space to necropsy activity with management of dead bodies by mortuary staff and pathologists in the perspective of threat of transmission of SARS-CoV-2.2 For this reason, Government has promptly implemented extraordinary and detailed measures to restrict viral spread from this source.3 In Italy, pathologists fill in death certificate, a legal instrument and a permanent record of an individual’s death, that requires accuracy, promptness, and completeness and therefore they must take care of this delicate and sad situation having contact with infectious dead bodies. As well as other sanitary staff working with SARS-CoV-2 infected people, pathologists must wear personal protective equipment, like a clean protective outer garment, disposable gloves, a disposable surgical mask and appropriate eye protection. Since SARS-CoV-2 has been categorized as a hazard group 3 pathogen, autopsies of suspected COVID-19 deceased have been centralized in specific Hospitals with adequate autopsy rooms (equipped with negative pressure).4 As it happened in past with the explanation of pathogenetic mechanisms of several diseases, results of COVID-19 autopsies are thought to elucidate the biological bases of this new infectious disease. The aim of this report is to underline that the pandemia of COVID-19 represents a step back to past for pathologists, confirming the gold standard role of post-mortem examination in the progress of medicine and health care, as it happened till the seventies of the 20th century. The occurrence of an emerging, new pathology like COVID-19 restored the dignity of autopsies that will remain an essential tool to learn physiopathological mechanisms of diseases.
References
1. Masood S. The changing role of pathologists from morphologists to molecular pathologists in the era of precision medicine. Breast J 2020;26(1):27-34. doi: 10.1111/tbj.13728. Epub
2. Diebold J. Clinical autopsy—its role in modern medicine. Praxis (Bern 1994) 2007;96(43):1667-71.
3. Regione Lombardia Nota Direzione Generale Welfare 12/03/2020“Emergenza da COVID-19. Indicazioni in materia di attività funebre”
4. Hanley B, Lucas SB, Youd E, Swift B, Osborn M.Autopsy in suspected COVID-19 cases. J Clin Pathol 2020 doi: 10.1136/jclinpath-2020-206522. [Epub ahead of print]
Elizabeth H Blackburn and Jack Szostak discovered that a unique DNA
sequence in the telomeres protects chromosomes from degradation. Carol
Greider and Elizabeth Blackburn identified telomerase, the enzyme that
makes telomere DNA. These discoveries explained how the ends of the
chromosomes are protected by the telomeres and that they are built by
telomerase. If the telomeres are shortened, cells age....
Elizabeth H Blackburn and Jack Szostak discovered that a unique DNA
sequence in the telomeres protects chromosomes from degradation. Carol
Greider and Elizabeth Blackburn identified telomerase, the enzyme that
makes telomere DNA. These discoveries explained how the ends of the
chromosomes are protected by the telomeres and that they are built by
telomerase. If the telomeres are shortened, cells age. Conversely, if
telomerase activity is high, telomere length is maintained, and cellular
senescence is delayed. This is the case in cancer cells, which can be
considered to have eternal life [1]. Cancer cells have the ability to
divide infinitely and yet preserve their telomeres. How do they escape
cellular senescence? One explanation became apparent with the finding that
cancer cells often have increased telomerase activity [1] Telomeres,
repeated sequences of DNA at the end of chromosomes, prevent degradation
of genetic material. Each time chromosomes replicate a small amount of
the DNA at both ends is lost, by an uncertain mechanism. Because human
telomeres shorten at a much faster rate than many lower organisms, we do
speculate that this telomere shortening probably has a beneficial effect
for humans, namely mortality. The telomere hypothesis of aging postulates
that as the telomeres naturally shorten during the lifetime of an
individual, a signal or set of signals is given to the cells to cause the
cells to cease growing (senesce). At birth, human telomeres are about
10,000 base pairs long, but by 100 years of age this telomere reduces to
about 5,000 base pairs. Scientists discovered an important enzyme that can
turn the telomere production on the DNA molecule "on" and "off." It's
called telomerase. It seems that as we get older, the amount of telomerase
in our cells decreases. Naturally, the exploration of this enzyme is now
the focus of much investigation, but unfortunately the research is aimed
at understanding how to turn telomeres "off" to limit the spread of
"immortal" cancer cells. Telomerase is actually an enzyme (a catalytic
protein) that is able to arrest or reverse this shortening process.
Normally, telomerase is only used to increase the length of telomeres
during the formation of sperm and perhaps eggs, thus ensuring that our
offspring inherit long "young" telomeres to propagate the species. The
telomere hypothesis of cancer is that the function of telomere shortening
is to cause cells that have lost normal control over growth to senesce
(i.e. stop growing) before being able to replicate enough times to become
a tumor, thus decreasing the frequency of cancer. Immortal cells like
cancer have an unfair advantage over normal human cells which are designed
to senesce. But nature seems to have planned this human telomere
shortening perhaps to prolong life by hindering the otherwise unchecked
growth of non-immortal or benign tumors. Malignant, or immortal tumors can
simply outlive the rest of the organism. Malignant cancer cells are being
studied because they appear to have altered the shortening of telomeres by
turning "on" the telomerase. Thus it appears that some cancers and aging
are both connected with the biology of telomeres. So telomerase-inhibiting
drugs would probably kill the cancer cells before much damage is done to
normal cell
Today reduction in mortality in breast cancer is due to early
detection through screening by mammography. However at least 25%
reduction in mortality could have been achieved due this screening
procedure [early-stage pre menopausal breast cancer, for example, 10-year
survival rates is today 68% for African Americans versus 77% for
Caucasians]. Besides these there played other factors also and these are
1) systemic or improved systemic treatment with chemotherapy 2) adjuduvant
therapies after surgery to eliminate micro metastasis like Her2 Nue
antagonist Herpentine and to prevent recurrences. Women with steroid
hormone receptor[ER+ or PR+] positive and negative cases are benefited by
Cyclopshomide & methotraxate & 5 FU chemotherapeutic agents. More
effective adjuduvant endocrine treatments are with variuous aromatase
inhibitors like letrozole or anastrozole.
Cases of breast cancers occur even when there is no family history or only
a few cases in elderly relatives are known as sporadic breast cancer.
Hereditary breast cancer is different from those of sporadic breast cancer
.The increased risk of breast cancer for those with a family history may
be caused by inherited factors (genes) like BRCA1 and BRCA2,[both the
genes protects breast cells from developing cancer. Certain mutations in
BRCA1 stop the gene working properly and therefore make it more likely
that breast cancer will develop],or a combination of inherited factors and
lifestyle like no breast feeding or unmarried women. Having an increased
genetic risk by mutation of these two genes can lead to breast cancer
developing even at an earlier age. BRCA1 and TP53 genes are of high
penetrance genes for breast Cancers. Mutations in the rare high
penetrance breast cancer predisposing genes are BRCA1 and BRCA2 and they
account for 16 to 25% of the inherited component of breast cancers in the
world scenario.This, in turn, can have an impact on raising your family.
So is it today possible to do BRCA1 gene test for people that know they
carry a specific mutation that predisposes them to suffer from breast
cancer. It is a real fact that most Breast cancers develop sporadically
and not related with a familial history or hereditary BRCA genes. It is
thought that less than 5% of people those develop breast or bowel cancer
do so because of an inherited fault. Unless there is a strong family
history of breast cancer in you it is unlikely that your child will
inherit a gene that increases the risk of developing cancer. So splicing
off BRCA1 gene before embryo may be an advancement for medical technology
[2]. Mutations in TP53, which at same time may cause the Li Fraumeni
syndrome, STK11 gene causing Peutz Jeghers syndrome, and PTEN causing
Cowden syndrome are however very uncommon sporadic causes of breast
cancers of NOS type, as are mutations in CDH1, although these mutations
may be highly penetrant for breast cancer The intermediate penetrance
breast cancer susceptibility genes are mutations in ATM, CHEK2, BRIP1,
BARD1, and PALB2. They can cause an increased odds ratio for breast cancer
of 2 to 4. These genes are all involved in the same DNA repair pathways,
but it is curious that they do not confer the high risk of breast cancer
seen in women who carry mutations in BRCA1 and BRCA2. Also of great
interest is that biallelic mutations in BRCA2, BRIP1, and PALB2 cause
Fanconi anaemia subtypes FANC D, J, and N respectively, further indicating
overlap in the functions of these genes. There are also good evidences now
that there are up to eight polymorphisms, which are reproducibly found to
influence breast cancer risk, particularly the FGFR2 gene. Carriers of two
low risk rs2981582 alleles at the FGFR2 locus (frequency 38% of the
population) have a relative risk of breast cancer of 0.83 compared with
the general population, carriers of one high-risk and one low-risk allele
(47%) have a relative risk of 1.05, and carriers of two high-risk alleles
(14%) have a relative risk of 1.26
Telomere crisis is also an important early event in the development
of breast cancer. In the breast, cells in a milk-collecting duct
occasionally proliferate excessively due to development of a regulatory
defect and results usual ductal hyperplasia." The chromosomes in these
growing cells lose a hundred or so base pairs of DNA every time they
divide," ,because the usual DNA replication processes don't copy DNA all
the way out to the ends of the chromosomes. This erodes the DNA sequences
that interact with proteins to form structures called telomeres, which
protect the chromosome ends. Eventually the DNA ends erode so much they
can no longer protect the chromosomes. When this happens the chromosomes
become unstable, and damage-control mechanisms kick in that kill the
unstable cells. This process, known as "telomere crisis Cells in which telomerase is activated can then proliferate indefinitely to form the next stage of cancer, known as 'ductal carcinoma in situ.' The mean telomere length is found decreased from normal tissue to carcinoma in situ, and decreased even more in invasive cancers of breast.
It was therefore proposed that breast cancer might be treated by eradicating telomerase. Several studies are underway in this area, including clinical trials evaluating vaccines directed against cells with elevated telomerase activity[1] "
Authors
Professor Pranab kumar Bhattacharya MD(cal), FIC path(Ind.)
Mr. Ritwik Bhattacharya, B.Com(cal)
Mr. Rupak Bhattacharya BSc
Mrs Dahlia Mukherjee BA (hons)
Miss Upasana Bhattacharya of Mahamyatala,
Dr. Debashis Bhattacharya Ms(cal) FRCS(Edin)
Dr. Diptendra Narayan Sarkar
Dr. Tarun Biswas MBBS(cal)-
Dr. Satyaki Mitra MD(PGT)
Dr. Avisnata Das MBBS(cal),
References
1] Press Release on the 5 October 2009 “The Nobel Prize in Physiology or
Medicine 2009� by The Nobel Assembly, consisting of at Karolinska
Institutet, Sweden
2] Response by Professor Pranab Kumar Bhattacharya Published by BMJ
on 4th feb 20009 .for the BMJ case reports Blog unnatural selection by
author Dean Jankens, published on 9th Jan 2009
Kapoor et al. (1) investigated pseudohyperkalemia in outpatients and
attributed many of the cases to hematological abnormalities or delay in
specimen centrifugation or clotting. Plasma is often recommended as the
preferred specimen in patients with leukocytosis, erythrocytosis or
thrombosis (2). Potassium released from ruptured cells during the clotting
process of serum specimens may result in false...
Kapoor et al. (1) investigated pseudohyperkalemia in outpatients and
attributed many of the cases to hematological abnormalities or delay in
specimen centrifugation or clotting. Plasma is often recommended as the
preferred specimen in patients with leukocytosis, erythrocytosis or
thrombosis (2). Potassium released from ruptured cells during the clotting
process of serum specimens may result in false-positive reporting and
unnecessary therapy (3). Others have reported on a phenomenon known as
reverse pseudohyperkalemia in patients with leukocytosis where potassium
concentrations in plasma specimens exceeded concentrations in serum (4).
We describe a similar case of reverse psuedohyperkalemia. A 87-year-
old man with chronic lymphocytic leukemia (CLL) was treated for the past 2
years as an outpatient. He received cyclophosphamide, vincristine, and
rituximab chemotherapeutic agents as part of his treatment plan. Blood was
collected in serum separator (SST) and EDTA tubes for routine metabolic
and hematology studies. The potassium concentration averaged 3.7 mmol/L on
a Beckman DXC chemistry analyzer (n=11). His white blood cell (WBC) and
platelet counts averaged 306 x 109 cells/L (94-97% lymphocytes) and 95 x
109 platelets/L over this time period. Recently, he was admitted to the
ED. Specimens were collected for metabolic (lithium-heparin specimen with
separator gel) and hematology (EDTA plasma) analyses. The specimens were
transported by pneumatic tube, and time from collection to analysis was
<60 min. The potassium concentration was 7.5 mmol/L; similar results
were obtained on a second analyzer. No hemolysis was observed. The
hematology results supported a known diagnosis of CLL but all other
laboratory data was within normal limits. Pseudohyperkalemia was
investigated. Additional venous blood specimens were collected in lithium-
heparin with a separator gel and a SST tubes. The specimens were
immediately transported to the lab by pneumatic tube (<5 min transport
time), promptly centrifuged (5 min at 3500 rpm) or allowed to clot (30
min; then centrifuged for 5 min at 3500 rpm) and analyzed. The plasma
specimen exhibited significantly higher potassium (7.4 mmol/L)
concentration compared with the serum specimen (3.9 mmol/L). A significant
layer of WBC was evident on the packed erythrocyte layer in the lithium-
heparin tube. No WBC layer was observed in the serum specimen. Four days
later, a similar occurrence (lithium-heparin potassium = 6.4; serum
potassium = 4.2 mmol/L) was observed on the same in-patient.
Some cells, especially malignant ones are susceptible to in-vitro
heparin-induced cell membrane damage during specimen processing resulting
in diffusion of potassium into the supernatant from ruptured leukocytes.
Similar cases in other leukemia patients have been observed in our
laboratory. Both laboratorians and clinicians should be aware of this
phenomenon to minimize false-positive reporting and unnecessary therapy.
1. A K Kapoor, AK, Ravi A, Twomey PJ. Investigation of outpatients
referred to a chemical pathologist with potential pseudohyperkalaemia. J
Clin Pathol 2009; 62:920-923.
2. Ifudu O, Markell MS, Friedman EA. Unrecognized pseudohyperkalemia
as a cause of elevated potassium in patients with renal disease. Am J
Nephrol. 1992;12(1-2):102-4.
3. Sevastos N, Theodossiades G, Savvas SP, Tsilidis K, Efstathiou S,
Archimandritis AJ. Pseudohyperkalemia in patients with increased cellular
components of blood. Am J Med Sci. 2006 Jan;331(1):17-21
4. Abraham B, Fakhar I, Tikaria A, Hocutt L, Marshall J, Swaminathan
S, Bornhorst JA. Reverse pseudohyperkalemia in a leukemic patient. Clin
Chem. 2008 Feb;54(2):449-51.
Of all the prospective candidates for thyroid replacement therapy(1),
even when due account is taken of the improvent in left ventricular
diastolic function attributable to this treatment modality in patients of
mean age 39.9 with subclinical hypothyroidism(SCH)(2), the over 65s with
SCH are probably the ones least likely to be at cardiovascular
disadvantage if they do not receive thyroid replacement t...
Of all the prospective candidates for thyroid replacement therapy(1),
even when due account is taken of the improvent in left ventricular
diastolic function attributable to this treatment modality in patients of
mean age 39.9 with subclinical hypothyroidism(SCH)(2), the over 65s with
SCH are probably the ones least likely to be at cardiovascular
disadvantage if they do not receive thyroid replacement therapy(3)(4). In
a longitudinal study of risk factors for development of cardiovascular
disease(CVD) in 3233 adults aged 65 or more with baseline serum
thyrotropin(TSH) levels(including 496 with SCH characterised by serum TSH
>4.5 mU/l but < 20.0 mU/l) no difference was documented between SCH
and euthyroidism for incident coronary heart disease and CVD death(3).
Likewise, among 427 subjects of mean age 73 with SCH(characterised by mean
TSH 8.1 mU/l) and coexisting type 2 diabetes, there was no relationship
between baseline TSH and cardiovascular mortality(4). Furthermore, on
follow-up of SCH for 5 or more years, this disorder was not additive to
the relatively higher cardiovascular risk attributable solely to type 2
diabetes(4). Finally, in a prospective longitudinal study evaluating
disability in daily life, depressive symptoms, cognitive function, and
mortality in 558 subjects aged 85(including 67 with TSH in the range 4.8
mU/l to 33 mU/l, some of whom were subclinically hypothyroid, and others
overtly hypothyroid), who were followed up for 4 years, all measures of
performance significantly deteriorated with time, but increasing baseline
levels of TSH were not associated with accelerated increase in disability
in activities of daily living, depressive symptoms, or cognitive decline
during follow-up. If anything, "increasing TSH levels at baseline were
associated with a significant(p=0.03) decelerated increase in disability
in instrumental ADLs(activities of daily living". Furthermore, increasing
baseline TSH levels were associated with lower mortality on 4 year follow-
up(5). Accordingly, especially in subjects aged 85 or more with SCH
characterised by TSH < 33 mU/l, there should be no "rush" to initiate
thyroid replacement therapy, because it appears to confer no improvement
in quality of life, and definitely neither cardiovascular benefit nor
survival benefit.
(2) Yazici M., Gorgulu S., Sertbas Y et al
Effects of thyroxin therapy on cardiac function in patients with
subclinical hypothyroidism: index of myocardial performance in the
evaluation of left ventricular function
International Journal of Cardiology 2004;95:135-143
(3)Cappola AR., Fried LP., Arnold AM et al
Thyroid status, cardiovascular risk, and mortality in older adults
JAMA 2006;295:1033-1041
(4)Sathyapalan T., Manuchehri AM., Atkin SL
Subclinical hypothyroidism is associated with reduced all-cause mortality
in patients with type 2 diabetes
Diabetes Care 2010;33:e37
(5)Gussekloo J., van Exel E., de Craen AJM et al
Throid status, disability and cognitive function, and survival in old age
JAMA 2004;292:2591-9
Further to our 2019 paper entitled ‘Impact and importance of a centralised review panel for lymphoma diagnostics in the WHO era: a single centre experience’, we write to report on the impact of the subsequent introduction of a centralised lymphoma review network in Ireland.
We previously described a discordance rate of 7.8% (14/179) between referral and review lymphoma diagnoses sent to St. James’s Hospital (SJH) Dublin for multi-disciplinary team (MDT) review between 2013-2016. Since then a formal lymphoma review network has been established in Ireland, resulting in a significant increase in lymphoma cases reviewed at SJH. 736 lymphoma cases were reviewed between 2017-2019, of which 0.007% had a discordant diagnosis (5/736). This rate is markedly lower than that previously reported in the published literature (6-48%) [1, 2].
This dramatic reduction in the level of discordant lymphoma diagnoses demonstrates the positive impact of centralized review networks with specialist haematopathologist input upon lymphoma diagnostics in Ireland. This trend is most likely attributable to the fact that cases are now referred directly to SJH for Specialist Haematopathologist opinion pre-diagnosis, where the necessary ancillary tests required for accurate diagnosis are available on site. Additionally, as previously discussed by Bowen et al, rates of diagnostic discrepancies tend to be higher in non-academic institutions compared to academic institutions...
Further to our 2019 paper entitled ‘Impact and importance of a centralised review panel for lymphoma diagnostics in the WHO era: a single centre experience’, we write to report on the impact of the subsequent introduction of a centralised lymphoma review network in Ireland.
We previously described a discordance rate of 7.8% (14/179) between referral and review lymphoma diagnoses sent to St. James’s Hospital (SJH) Dublin for multi-disciplinary team (MDT) review between 2013-2016. Since then a formal lymphoma review network has been established in Ireland, resulting in a significant increase in lymphoma cases reviewed at SJH. 736 lymphoma cases were reviewed between 2017-2019, of which 0.007% had a discordant diagnosis (5/736). This rate is markedly lower than that previously reported in the published literature (6-48%) [1, 2].
This dramatic reduction in the level of discordant lymphoma diagnoses demonstrates the positive impact of centralized review networks with specialist haematopathologist input upon lymphoma diagnostics in Ireland. This trend is most likely attributable to the fact that cases are now referred directly to SJH for Specialist Haematopathologist opinion pre-diagnosis, where the necessary ancillary tests required for accurate diagnosis are available on site. Additionally, as previously discussed by Bowen et al, rates of diagnostic discrepancies tend to be higher in non-academic institutions compared to academic institutions such as SJH [3]. We believe that the ongoing educational component of the centralized review network, involving regular feedback and annual teaching sessions for pathologists in referring hospitals, has further improved the initial discordance rate.
We anticipate that this new low rate of discordance will be maintained in our institution, providing patients with an accurate diagnosis with which to best direct therapeutic considerations.
Kind regards,
Dr. Kate Dinneen
Specialist Registrar in Histopathology
St. James’s Hospital, Dublin, Ireland
Trinity College Dublin, Ireland
Dr Richard Flavin
Consultant Histopathologist
St. James’s Hospital, Dublin, Ireland
Trinity College Dublin, Ireland
References
1. Lester, J.F., et al., The clinical impact of expert pathological review on lymphoma management: a regional experience. Br J Haematol, 2003. 123(3): p. 463-8.
2. LaCasce, A.S., et al., Comparison of referring and final pathology for patients with non-Hodgkin's lymphoma in the National Comprehensive Cancer Network. J Clin Oncol, 2008. 26(31): p. 5107-12.
3. Bowen, J.M., et al., Lymphoma diagnosis at an academic centre: rate of revision and impact on patient care. Br J Haematol, 2014. 166(2): p. 202-8.
Dear Editor,
We read with interest the recently published manuscript by Kir et al. entitled “High-risk human papillomavirus (HPV) detection in formalin-fixed paraffin-embedded cervical tissues: performances of Aptima HPV assay and Becton Dickinson (BD) Onclarity assay” [1]. The study evaluates the off-label use of commercial HPV assays on formalin-fixed paraffin-embedded (FFPE) specimens. The authors detail the performance of the Hologic Aptima RNA test and the BD Onclarity DNA test in a study of 189 cases (46 SCC, 107 HSIL and 36 benign/normal). They report that, while the specificity and positive predictive value (PPV) were 100% for both assays, the Aptima assay was more sensitive, detecting 99.4% (95% CI 96.46% to 99.98%) of CIN2+ cases, versus the BD Onclarity assay with a sensitivity of 75.9% (95% CI 65.27% to 84.62%) [1]. The authors conclude that “both assays are reliable methods for high-risk HPV detection and genotype determination in FFPE specimens” and that the “Aptima assay has the advantage of higher sensitivity”.
We believe that there are a number of deficiencies in the study design (not addressed in the discussion section) which call into question the validity of the conclusions. Firstly, this is not a split sample study, nor a true head to head comparison since the samples were not randomly assigned to each assay for testing. All 189 cases were first tested with the Aptima assay and only approximately half (n = 97) were subsequently tes...
Show MoreDear Dr Kaushik, JCP, BMJ et al,
I hope this note finds You well
Years after this most excellent Article was composed regarding gene activation in Patients with the CFS (chronic fatigue syndrome), was surprised to see this discussion on how ultrasound would adversely effect, ie disrupt, the BBB (Blood Brain Barrier) causing nausea, fatigue and headaches
This might explain, at least partially, the events (Havana syndrome) at the US Embassy 2016 of unusual disease processes which occurred after presumed ultrasound exposure to Personnel
https://en.wikipedia.org/wiki/Havana_syndrome
https://www.researchgate.net/publication/235923211_A_review_of_current_a...
A Review of Current Ultrasound Exposure Limits
Anthony C. Zander et al
University of Adelaide,
Australia
September 8, 2004
Research has shown that airborne ultrasound has the potential to cause nausea,
fatigue, and headaches [3–8]
Apparently would be difficult to detect ultrasound presence but mismatched ultrasound devices of several types could present as audio frequency noise, possibly thought to be tinnitus
Best wishes always
Show MoreThank you for your assistance with this matter...
To address the concern of potential cross-reactivity of SARS-CoV-2 with Architect HIV Combo assay (Abbott Laboratories, Abbott Park, Illinois, USA) reported in this article, we evaluated 846 COVID-19 convalescent plasma samples obtained from New York Blood Center (New York, New York, USA) using the Architect HIV Combo assay. Although all 846 samples were reactive in Architect SARS-Cov-2 IgG assay (Abbott Laboratories, Abbott Park, Illinois, USA), none of the samples were reactive in the Architect HIV Combo assay with average signal < 0.14 S/CO and standard deviation < 0.058 S/CO. Thus, the data shows no indication of cross-reactivity between SARS-CoV-2 infection and Architect HIV Combo assay.
Furthermore, it is well known that HIV-1 gp41 protein also shows striking structural similarity to the fusion pH-induced conformation of influenza virus HA2 protein (Weissenhorn et. al. Nature 1997, 387:426). However, to our knowledge, no cross-reactivity case from flu vaccinated samples has been reported with the Architect HIV Combo assay since its launch in 2004. Collectively, the cross-reactivity of SARS-CoV-2 infection with Architect HIV Combo assay should be extremely low.
Dear Sir,
We read with great interest the article by Marietjie Venter and Karin Richter on the diagnostic assay for COVID-19 [1]. We agree with the authors about delays in diagnoses, a severe shortage of tests and laboratory capacity for performing RT-PCR tests. This is especially true for many developing countries such as Bangladesh, which is faced with current health care crises to provide healthcare for more than 165 million population. A large number of people are being tested for COVID-19 and confirmed with the disease every day in Bangladesh, and many more remain undetected due to the lack of testing. Further, the delay to receive test results and lack of medical records cause COVID-19 patients to transmit the disease in the community and hamper proper treatments.
Prior to the COVID-19 test, several pre-conditional medical records are required to support the results. In Bangladesh, these records are generally gathered by health workers in the testing centres manually and ignoring many important symptoms and conditions. However, this
process is tedious and prone to omission, error and bias, leading to incomplete medical records. Further, participants are required to return to the centre the next day to collect test results which might increase community transmission. To mitigate such disadvantages, we developed a
smartphone-based RT-PCR record and monitoring app ‘mobEVID’.
This app has been built following Novel coronavirus RT-PCR app...
Show MoreAs a interested candidate for histopathology speciality training, I had the opportunity to attend a lung MDT in which roughly 25 cases were discussed. The case load was huge and some cases were rushed. The rushed cases were to be rediscussed which is a good form of safety netting although not ideal. The histopathology consultant requested reminders so immunohistology or second readings do not get missed. It would truely revolutionise MDT meetings if standard double reading could become a routine practice although already done in majority of cases.
The author has shed light on the importance of double reading of slides along with impressive figures.
A second review of slides could be a way to not only reduce error, but also improve quality of care in terms of management and immunohistology.
Thank you so much for highlighting the importance of a routine second review prior to MDT meetings. During the taster session, I asked the Histopathology consultants if they encourage second reviews and was informed that wherever there is the slightest doubt, another consultant or sub-specialist would be consulted. It was reassuring to know that histopathologists can always benefit from their colleagues expertise.
This practice safeguards patients in the sense that a correct diagnosis can be made in all cases minimising potential errors.
Dear Editor,
Show Morebefore COVID-19, in the era of targeted therapies, pathologists played a cornerstone role in providing information especially about cancer diagnoses.1 Therefore, scientific community felt that autopsies were out-dated. Now, in this emerging reality, we are assisting to the transformation of the pathologist’s role: instead of proceeding to the “future” of molecular diagnosis we are going back to the “past” of our “noir” connotation. This negative meaning was linked, in the popular culture, to frequent post-mortem examinations performed by pathologist forgetting the paramount value of this medical procedure in explaining pathogenetic mechanisms of all diseases.2 During COVID-19 pandemia, Italian Hospitals changed their usual health department strategy. Hospital Governments strengthened intensive care units and lung units and decreased surgical activities. Pathologists’ role shifted from microscopic diagnosis back to the original mortuary role, setting aside optical microscope, the principal pathologist’s tool, and leaving space to necropsy activity with management of dead bodies by mortuary staff and pathologists in the perspective of threat of transmission of SARS-CoV-2.2 For this reason, Government has promptly implemented extraordinary and detailed measures to restrict viral spread from this source.3 In Italy, pathologists fill in death certificate, a legal instrument and a permanent record of an individual’s death, that requires accuracy, promptness,...
Dear Editor,
Elizabeth H Blackburn and Jack Szostak discovered that a unique DNA sequence in the telomeres protects chromosomes from degradation. Carol Greider and Elizabeth Blackburn identified telomerase, the enzyme that makes telomere DNA. These discoveries explained how the ends of the chromosomes are protected by the telomeres and that they are built by telomerase. If the telomeres are shortened, cells age....
Dear Editor:
Kapoor et al. (1) investigated pseudohyperkalemia in outpatients and attributed many of the cases to hematological abnormalities or delay in specimen centrifugation or clotting. Plasma is often recommended as the preferred specimen in patients with leukocytosis, erythrocytosis or thrombosis (2). Potassium released from ruptured cells during the clotting process of serum specimens may result in false...
Dear Editor
Of all the prospective candidates for thyroid replacement therapy(1), even when due account is taken of the improvent in left ventricular diastolic function attributable to this treatment modality in patients of mean age 39.9 with subclinical hypothyroidism(SCH)(2), the over 65s with SCH are probably the ones least likely to be at cardiovascular disadvantage if they do not receive thyroid replacement t...
Dear Editor,
Further to our 2019 paper entitled ‘Impact and importance of a centralised review panel for lymphoma diagnostics in the WHO era: a single centre experience’, we write to report on the impact of the subsequent introduction of a centralised lymphoma review network in Ireland.
We previously described a discordance rate of 7.8% (14/179) between referral and review lymphoma diagnoses sent to St. James’s Hospital (SJH) Dublin for multi-disciplinary team (MDT) review between 2013-2016. Since then a formal lymphoma review network has been established in Ireland, resulting in a significant increase in lymphoma cases reviewed at SJH. 736 lymphoma cases were reviewed between 2017-2019, of which 0.007% had a discordant diagnosis (5/736). This rate is markedly lower than that previously reported in the published literature (6-48%) [1, 2].
This dramatic reduction in the level of discordant lymphoma diagnoses demonstrates the positive impact of centralized review networks with specialist haematopathologist input upon lymphoma diagnostics in Ireland. This trend is most likely attributable to the fact that cases are now referred directly to SJH for Specialist Haematopathologist opinion pre-diagnosis, where the necessary ancillary tests required for accurate diagnosis are available on site. Additionally, as previously discussed by Bowen et al, rates of diagnostic discrepancies tend to be higher in non-academic institutions compared to academic institutions...
Show MorePages