160 e-Letters

  • Hic est locus ubi mors gaudet succurrere vitae

    In the last few months, starting from the late 2019 in the area of Wuhan, China, an enormous increase in the number of infections due to SARS-coronavirus-2 (SARS-CoV-2) has been witnessed worldwide.[1-2] So far, 16 April 2020, the Situation report of the World Health Organization (WHO) has reported 1,914,916 confirmed cases and 123,010 deaths, of which 84,607 in the European Region.[2] This data could be itself sufficient to testify the importance of the on-going pandemic, which is further confirmed by the uncertainties regarding the possibility of gaining a natural or vaccine-mediated lifelong immunity. It is a matter of fact that, until the discovery of a vaccination, and maybe beyond that, it is likely that the world will have to deal with the virus and its long-time consequences for years. This necessarily imply that measures to deal with SARS-CoV-2 in all aspects, from life until death and post-mortem examination, have to be figured out and put in place.
    A growing issue regards the distinction between “died from” and died with” SARS-CoV-2, which would be fundamental in order to gain knowledge on several issues including lethality of the virus, trend of death rate, and to compare data from different countries and regions (e.g. higher SARS-CoV-2 death rate per 1,000 infections are reported for Italy, UK and Belgium, while it is very low in Germany, Turkey and South Korea.[3] A complete post-mortem examination is probably an irreplaceable mean of distinguishing bet...

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  • A report on the impact of the introduction of a centralised lymphoma review network in Ireland

    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...

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  • COVID-19 infection: "high risk to an individual but a low risk to the community"?

    Dear Editor,

    given the spread of Covid-19 infection with its serious consequences and given that the phenomenon has taken on partly unexpected epidemic dimensions which have required drastic Italian government restrictive measures to counteract its spread, in Our opinion it is legitimate to think of a reclassification of the risk category to which the pathogen Covid-19 belongs.

    As it is known, Covid-19 is a viral pathogen of relatively recent acquisition in the human species which in its changed forms has presented over time health problems of growing social impact in different parts of the world and currently in Italy.

    The SARS-1 (SARS-CoV, 2002, China) and MERS (2012, Saudi Arabia) forms have relatively little interest in Europe while the SARS-CoV-2 (China, Wuhan, 2019; Covid-19) has importantly spread in Italy.

    So far beta-coronaviruses capable of causing disease in humans have been classified by WHO in the Risk Group (RG) 3: ”viral agent with high individual risk, but with a risk of collective spread assessed as low-moderate”.

    So, the probability of propagation in the community of this virus was assessed as "moderate".

    Also the NIH Guidelines defines the risk groups 3 as “high risk to an individual but a low risk to the community”

    Furthermore, RG3 (NIH and WHO) is defined as to have efficient therapeutic approaches .

    However, the present experience has led us to realize that Covid-19 has a very hig...

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  • (In)appropriate JAK2 V617F mutation testing

    It is essential to remember that the goal of clinical pathology laboratory testing is not the acquisition of information itself, but to improve patient outcome through the promotion of proper laboratory test utilization, namely an appropriate test request and result utilization [1]. Given that pathology laboratory testing is reported to play a crucial role in 70% of clinical decisions and that the overall mean rate of inappropriate over-utilization is around 20% [2], innovations that rationalise and guide appropriate testing are welcome. Mahe et al are to be commended on defining an algorithm to determine which patients to test for the myeloproliferative neoplasm (MPN)-associated JAK2 V617F mutation [3]. Such an approach is particularly pertinent given that identification of this mutation has shifted from a confirmatory test for a relatively uncommon group of diseases to an advance screening test in the initial work up of patients in whom the numerous secondary causes that result in haematological indices similar to that of MPN have not been excluded. Also, the recent revision of World Health Organization classification of myeloid neoplasms lowered the threshold of haemoglobin level for considering a diagnosis of the MPN polycythaemia vera (PV) with a subsequent perceived and real impact on the level of JAK2 V617F testing [4, 5]. Using simple complete blood count (CBC) indices, Mahe et al found that application of their JAK2-tree algorithm to a historical dataset would hav...

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  • Regarding post-mortem genetic testing

    We found the paper ‘Long QT syndrome and sudden unexpected infant death’ by Van Niekerk and colleagues to be comprehensive and interesting. We would like to point out that there appears to be a misunderstanding as the authors state that in Australia and New Zealand all sudden and unexpected deaths are mandated to undergo targeted post-mortem genetic testing. Guidelines published by TRAGADY (Trans-Tasman Response AGAinst sudden Death in the Young) advocate that material suitable for DNA extraction must be obtained as part of the best practice guidelines for investigation of sudden death of a young person (1). However, subsequent genetic analysis is not mandated. A policy on the genetic investigation of cause of death in coronial autopsy cases has been recently released by the Royal College of Pathologists of Australasia (RCPA) (2). It is likely this policy document was not available at the time Van Niekerk and colleagues were writing their paper. The RPCA policy states that genetic testing of the deceased is not endorsed in the absence of engagement of the family of the deceased with a genetic counselling service and confirmation of a family history compatible with a heritable disorder. Ideally, there should be identification in the living relatives of a putative genetic defect (or defects) or phenotype for which testing is available. For a number of reasons, some of which are outlined in the RCPA policy document, mandatory post-mortem genetic testing may not be benefic...

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  • Canadian Certification vs Canadian Accreditation

    Letter to the Editor – Journal of Clinical Pathology

    We read with interest the invited editorial by Grealish et al. entitled “Standardisation of practice for Canadian pathologists' assistants.” First of all, we would like to congratulate the CAP-ACP Executive Committee on its accomplishments to date. Establishing a method for board certification of Canadian Pathologists’ Assistants (PAs) is an important achievement which promotes standardization and high quality anatomical pathology services.

    However, our primary reason for writing is to address an error of omission. The editorial correctly notes that there are four two year long Master’s PA training programs in Canada; however, it should be also noted that these vary considerably in size with a ten-fold difference between the largest and the smallest based upon the number of students currently enrolled. The editorial then implies that Canadian training programmes are not accredited and are in need of some new mechanism to become accredited. The editorial states that “the pursuit of creating a ... Canadian accrediting body for PA training programme is ongoing.” We respectfully disagree. The two large Canadian training programmes, hosted by the University of Calgary and Western University, respectively have each been accredited by the National Accrediting Agency for Clinical Laboratory Sciences (NAACLS) (https://www.naacls.org/about.aspx ). NAACLS...

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  • Loss of MMR proteins expression as predictive marker for immunotherapy in malignant melanoma patients

    El Jabbour T et al. (Jun 2017) described the association between immunohistochemical PD-L1 positivity and loss of MMR proteins in colorectal cancer. However, the evaluation of Mismatch Repair Deficiency (dMMR) as a immunotherapy predictive marker is lacking for Malignant Melanoma (MM) and other malignancies, such as genitourinary, prostate, bladder, head and neck cancers, that are treated with immune checkpoint inhibitors (ICPI).

    We recently assessed dMMR in MM patients treated with anti-PD-1/PD-L1 during 2014-2016 at University of Modena and Reggio Emilia: 7% of primary melanoma and 13% of metastasis showed the dMMR. We report a patient whose primary MM and metastasis showed dMMR with immunohistochemical lack of MSH6 expression. Her complex history was characterized by the regression of the multiple cerebral and visceral metastases after anti-PD-L1 therapy, and an extraordinary progression-free survival (1150 days) and overall-survival (2646 days). At present, she is still alive and well, and had the longest response to anti-PD-L1 treatment.

    Our results emphasize that the immunohistochemical assessment of MMR protein expression in MM patients represents a useful predictive marker, which may have crucial importance for the determination of the response of anti-PD-1/PD-L1 therapy for MM and potentially for other solid malignancies treated with ICPI therapy.

  • Authors' reply

    We were pleased to read the correspondence ‘Stage II patients can benefit from OSNA molecular lymph node staging’ from Cuatrecasas et al. and grateful for the authors’ interest and comments. Our study with one-step nucleic acid amplification (OSNA) for patients with colorectal cancer (CRC) primarily aimed to evaluate the accuracy of the test as compared with the standard care approach of a single H&E microscopic examination. We hoped to share with readers our experiences of working with this technology and highlight the challenges other centres will need to consider before introducing the service.[1]
    While we acknowledged the concern raised by Cuatrecasas et al. that our study cohort of 19 patients is small, we emphasise that we tested 82 lymph nodes with OSNA and feel our results show a fair indication of the concordance of the assay with routine histology. It is also important to point out that initially more patients were recruited for the study but several specimens had to be excluded due to faecal contamination, sealed perforation or macroscopic serosal (T4) disease – all of which could arguably lead to false positive results by OSNA. The significance of our data is that to our knowledge this was the first time OSNA had been fairly compared with routine histology rather than intensive work-up of multiple levels, immunohistochemistry (IHC) and conventional molecular methodologies. We agree that there is insufficient convincing evidence that intensive interrog...

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  • Response to Jones: “Never mind religion, how about desecration?”

    We are intrigued by, and sympathetic toward, Dr Jones’ argument; we had approached our argument from the existing case law rather than from the fundamental position that dissection without good reason is morally unacceptable. We can understand that that position is supported by the need for appropriate consent in circumstances outwith a coroner’s jurisdiction. We would agree that invasive dissection that serves no defined purpose cannot be consonant with autonomy, beneficence, non-maleficence and justice.

  • Stage II patients can benefit from OSNA molecular lymph node staging

    Dear Sirs,

    We have read with interest and concern the correspondence letter published in the July issue of your journal “OSNA testing for lymph node staging in colorectal cancer”.
    Although the authors state on the letter “We aim to provide unbiased data on the diagnostic accuracy of OSNA in detecting CRC nodal metastases and feedback the practicalities of running such a service in a National Health Service (NHS) cellular pathology department”, we think the information given in their article is somehow incomplete. Their conclusions are based on the analysis of 99 lymph nodes (LNs) from a small cohort of 19 cases, with only 5.2 LNs examined per patient. Current guidelines, including the guidance of The Royal College of Pathologists, recommend that at least 12 LNs should be assessed to ensure an adequate specimen evaluation and a reliable pathologic staging.[1] In contrast, several studies using colon cancer OSNA lymph node analysis have assessed 12 or more LNs.[2–4]
    We agree with their statement that intraoperative OSNA detection of LN metastasis does not have a role in CRC surgery, mainly because regional lymphadenectomy is invariably included with the colectomy specimen. But this is not the target of molecular lymph node assessment in CRC. The most important clinical application of molecular LN analysis in CRC is that it enables a more precise staging in early CRC than the one obtained with conventional H&E analysis, especially useful for stage II pa...

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