166 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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  • 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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  • 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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  • 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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  • 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.

  • Never mind religion, how about desecration?

    In their article considering the relationship between Articles 8 and 9 of the European Convention of Human Rights (ECHR) and coronial autopsies, Leadbeatter and James argue that recourse to invasive autopsy ought only to be made after an ‘issues based’ investigation establishes that this is necessary. This stands in stark contrast to current practice.

    Whilst Leadbeatter and James write to report their own research findings and discuss the decision in R (Rotsztein) v HM Senior Coroner for Inner London North, I was prompted to consider whether they were too restrained in their conclusions. My primary concern is that whilst redress to the ECHR may be legally and rhetorically attractive, it means that outcomes are dependent on the still living taking action. This may, or may not, promote the deceased person’s preferred course of action.

    Prior to addressing this point in more detail, however, a brief mention to the necessity of invasive autopsies where a death occurs in suspicious circumstances. Leadbeatter and James discuss this; I found their discussion of ‘injury’ (Box 2, Issue 4) particularly interesting. They give the example of road or train deaths, where their approach was to first review evidence from the scene, take toxicology samples and remove trace evidence. Another example might be where a person is shot in the head at close range, the events being caught on CCTV. These examples highlight that even in extreme circumstances evisceration of the body m...

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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.

  • Corroborating evidence for atypical breast aspirates

    Dear Editor
    RE: Atypical aspirates of the breast: a dilemma in current cytology practice. Shuang-Ni Yu, Joshua Li, Sio-In Wong, Julia Y S Tsang, Yun-Bi Ni, Jie Chen, Gary M Tse. J Clin Pathol 2017;0:1–9. doi:10.1136/jclinpath-2016-204138
    We read with interest the findings of Shuang-Ni Yu et al regarding “Atypical aspirates of the breast: a dilemma in current cytology practice” first published on May 29 2017 in Journal of Clinical Pathology.
    Breast fine needle aspiration (FNA) utilisation has been in decline for some time and there are several reasons for the drop in the uptake of cytology in the investigation of breast diseases. Although the main sited reason is increased demand for ancillary tests, greater subjectivity of cytology when compared to histology which is generally regarded as the gold standard, and the unpreparedness of pathologists to provide unequivocal diagnoses not only in the borderline lesions but also in low grade malignancies. The need to provide a consistently high quality service to engender confidence in our speciality has never been greater.
    The probabilistic approach to reporting FNA based on the 5 tier categories (C1 unsatisfactory; C2 benign; C3 atypical/indeterminate; C4 suspicious; and C5 malignant) does provide reliable accurate diagnoses for all categories except C1 unsatisfactory and C3 atypical/indeterminate categories. The C1 category highlights a failed FNA procedure whilst a C3 result indicates some diagnostic un...

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  • 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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