Dear Editor,

I entirely agree with the authors of 'A Survey of reporting of colorectal cancer in Scotland: compliance with guidelines and effect of proforma reporting'1 that proforma reporting should be standard across Scotland for reporting colorectal caner excision specimens. Although obvious, I feel it should be stated the 2007 RCPath dataset standards 2 were issued for a symptomatic population and, as stated in the study, these audited cases were both screening and symptomatic. Also, in their conclusions they allude to the potential impact that neo-adjuvant therapy could play in Serosal Involvement (SI), Lymph node retrieval and extramural venous invasion (EMVI) but state that this aspect could not be accurately assessed in this study. All reported cases in our Health Board are staged using TNM5 and, as such, will be prefixed with 'y' to identify them as having had neo-adjuvant therapy. If this was not known prior to reporting, a supplementary report will be issued after the case has undergone MDT discussion when the patient history is reviewed. This may be unique to our health board but, as it is part of the RCPath dataset, it should also be recorded.

I do find the wording used in 'What this paper adds', where it states that "....this is likely to have serious adverse consequences for patient care." hard to extract from the data presented and this claim is not reported in the article by the authors themselves. The data suggests that there may be a group of patients that are falsely node 'negative' due to insufficient nodal sampling and a further group in whom the EMVI or SI is not identified. However, it does not state the cross over between these groups or if the ones 'missing' the EMVI/SI are node positive patients. Taken together this suggests that a small percentage of patients may have been excluded the option of adjuvant therapy, but without looking at specific patient outcomes and the case slides is it fair to label this as 'serious adverse consequences for patient care'?

I do look forward to the results of the repeat data collection which will, hopefully, show proformas being used across all NHS Scotland boards as well as an uplift in the percentage of boards reaching all the standards. Further investigation of a national electronic dataset would also be welcomed especially if the data required for such audits can be extracted easily and possibly centrally from this. Given the existence of one in Norway maybe we should be moving to access that and use it throughout Scotland? I am sure the follow up audit will also take into account the influences of neo-adjuvant therapies on the audited adverse factors in the rectum, a treatment which is an established local practice, but also the emerging use of neo-adjuvant therapy in advanced colonic cancers. These data could be collated to allow reporting of all cases together and in different cohorts (Treatment naive V's neo-adjuvant) to try to identify the changes attributable to therapy.

Conflict of Interest:

I report GI resection specimens in a health board in Scotland that provided raw data for this survey. (Our board median nodal count is above 17 for both colonic and rectal excisions including post treatment cases)

To the Editor:

In their review article "Challenges and controversies in the diagnosis of mesothelioma: Part 1. Cytology-only diagnosis, biopsies, immunohistochemistry, discrimination between mesothelioma and reactive mesothelial hyperplasia, and biomarkers", Henderson et al.1 describe and illustrate "rod-like or cylindrical crystalloids as seen in numerous mesothelial cells in the pleural effusion of a malignant mesothelioma". The authors state "so far as we are aware they have been reported only in epithelioid malignant mesothelioma (MM)". In an effort to clarify/correct the impression that these inclusions are specifically associated with epithelioid MM, I report a series of 16 benign pleural fluids and 1 benign pericardial fluid each containing mesothelial cells with these rod-like or crystalloid inclusions (Figure 1,2). None of the 17 patients had a diagnosis of MM and none developed MM during follow-up (range from 1 to 7 yrs). The patients (13 males, 4 females) ranged from 13 to 91 years in age (median 78.5 yrs.) at thoracentesis/ pericardiocentesis. Clinical diagnoses included congestive heart failure, chronic renal disease, end stage liver disease, pneumonia, and CLL. Three of the 17 patients had a diagnosis of carcinoma (endometrioid endometrial, renal clear cell, and cutaneous squamous cell); none of these tumors involved the effusion. Others have also reported similar appearing crystalloids within mesothelial cells in effusions in a variety of benign conditions. 2, 3

References: 1. Henderson DW, Reid G, Kao SC, et al. Challenges and controversies in the diagnosis of mesothelioma: Part 1. Cytology-only diagnosis, biopsies, immunohistochemistry, discrimination between mesothelioma and reactive mesothelial hyperplasia, and biomarkers. J Clin Pathol 2013;66:847-853. 2. Zaharopoulos P, Wen JW, Wong J. Membranous lamellar cytoplasmic inclusions in histiocytes and mesothelial cells of serous fluids. Acta Cytol 1998;42:607-613. 3. Lang E, Uthman M. Pseudo-Gaucher cells in peritoneal fluid: An uncommon manifestation of extramedullary hematopoiesis. Diagn Cytopathol 1999;20:379-381.

Please note Figs 1,2 (jpgs) have been emailed to Mr. Rinon along with a copy of this letter.

Conflict of Interest:

None declared

Dear Prof. Feakins,

First of all we wish to express our congratulations for your excellent reporting guidelines about the diagnosis of IBD on biopsies published in JCP, September 2013.

About this important matter, we would like to make some comments based on our personal experience. Regarding the terminology in the histological diagnosis of IBD, it was stated (section "Probability" in the paragraph "Terminology") that "unfortunately, there are no universal agreed of terms to describe the various levels of certainty or uncertainty encountered by the histopathologists and the clinicians, unless the diagnosis is definite". In this meaning, the "level of uncertainty" of diagnosis defines the category of cases that do not satisfy the conventional criteria for a definite diagnosis of IBD or non IBD colitis, due to inadequate clinical information, as well as to inadequate number and quality of biopsies or unclear microscopic pattern (absence of IBD -specific lesions). This group of histological diagnoses with a significant level of uncertainty is relevant in IBD management for various reasons:

1) It represents a large portion of the patients that underwent endoscopy with a clinical suspicion of IBD, given the frequent inadequacy of the prerequisites of diagnosis in clinical practice, as stated in your recent paper, published in this journal. We confirmed this trend in a recent study of our group, based on the evaluation the clinical/endoscopic information, the sampling procedures and the histological characteristics of 353 histological reports collected from 13 of the most representative gastroenterological centres in Piedmont (Italy), that evidenced a low rate of adequacy (5% adequate clinical/endoscopic information, 13% adequate sampling and no case with a correct orientation of the samples). (The first results will be presented at the Congress of the Italian Pathologists Society - SIAPEC Rome October 2013 and then published).

2) The nomenclature of this category of cases is still heterogeneous, as well described in your paper, and often equated with a definite diagnosis in clinical practice.

3) There is no clear indication about the management of patients with this typology of histological diagnosis. In our opinion, the effect of these anomalies is often inappropriate treatment for these patients, with the consequent modifications of the endoscopic pattern, that reduces the chance of a further diagnostic setting. Moreover, these diagnoses may be misleading in the case studies. Thus, we think it might be useful to consider this item in the management of IBD patients and to improve the quality of the histological diagnosis in the first evaluation of patients with clinical/endoscopic pattern suggestive of IBD (see also our letter to the editor [World J Gastroenterol 2013 January 21; 19(3): 426-428]) by:

1. implementing a minimum mandatory set of clinical information and histological sampling that could fit with an appropriate diagnostic process in histology and using an univocal nomenclature for histological diagnosis that does not meet these requirements, with the goal of reducing the number of inconclusive or inappropriate diagnoses.

2. adopting the repetition of the endoscopy (after a brief discussion with the clinical staff) for all the cases with a significant "level of uncertainty" in histological diagnosis.

We hope that you agree with the need to obtain a more definite diagnosis for the patients, and we are strongly interested in your opinion about this topic. Thank you for your attention.

We look forward to your kind response,

Yours

Conflict of Interest:

None declared

'High risk medicolegal autopsies: is a full post-mortem examination necessary?'

Comment on the article by Fryer et al, J Clin Pathol 2013, 66:1-7

The article by Fryer et al raises several critical issues - I do not agree with them on all points - and leads to an important overall conclusion for the future prosecution of autopsies in the UK.

The piecemeal introduction of cadaveric imaging for non-homicide cases in (currently) a few centres in England is probably unstoppable, and has the backing of government (although not the central funding). As stated in their article, it is intended to avoid performing an open autopsy examination in a proportion of cases where a coroner has commanded a post-mortem examination. Interestingly whilst this article, and other publications like it, discuss replacing open autopsy with imaging, in public educational fora when presentations by pathologists and radiologists are made, the emphasis is more on imaging as an adjunct than a replacement for autopsy. What is not widely discussed anywhere is how the useful contribution of cadaveric imaging is critically dependent on clinical case-mix.

We would all agree that having imaging data prior to commencing a standard autopsy, whether the imaging was done under hospital care prior to death or done just prior to the autopsy as with deaths in the community, is valuable. It focuses attention to relevant clinical pathologies to be examined, and provides negative information for some organs (such as the brain in ?intracranial haemorrhage). An unintended and underused consequence of pre-autopsy imaging is enabling feedback to radiologists, particularly in the in-hospital setting, of their diagnostic performance. They necessarily receive plentiful such information in cancer multi-disciplinary meetings, but do not regularly obtain information on their diagnostic hits and misses when it comes to the moribund. Like all diagnosticians they are fallible.

High risk cases Fryer et al suggest that in cadavers of patients with suspected illicit drug intake, and known 'high-risk infection' (specifically Hazard Group category 3 infections, including HCV, HBV, HIV), an external examination plus blood sample toxicology can remove the need for autopsy in more than half the cases. The results, presented in % terms, are indeed persuasive. Toxicology alone provided the cause of death in 78% of cases, and CT scan alone in 25%. In the validation group (suspected drug abuse but no infection), the toxicology provided the cause of death in 87%.

The arguments presented for avoiding open autopsy on high risk cases include expense, disruption to busy mortuary work, and health risk to staff. Interestingly, the authors state that some pathologists in their centre are reluctant to perform autopsies on such cases. But these general statements do not stand up to scrutiny. And crucially the data arise from only a small numbers of cases examined.

In the 15 years covered by the study, only (my italics) 70 cases happened, ie 4.6 a year. Most were HCV+ve, 3 HIV+ve and one HBV+ve; the latter should really be excluded from the list of high risk infection in practice, since all NHS exposure-prone staff have to be successfully vaccinated against HBV and thus this poses no risk. I would contrast this very low cadaver infection rate with what happens at St Thomas' Hospital mortuary, where we see 1-2 HCV and/or HIV+ve cases a week, and have had no problems in performing them safely. Joint compilation of protocols for all eventualities by both anatomical pathology technologists (APTs) and pathologists ensures smooth, safe and efficient practice. I would suggest that the reported reluctance to perform such autopsies depends on unfamiliarity.

With the implementation of universal precautions for all autopsies, the true risks of high risk autopsy practice is minimal. When such infections are common, they do not disrupt the work flows, since all bodies are essentially treated the same, and they do not engender more expense. Let us not forget that in the recent times of good safe working practice, the likelihood of acquiring such an infection at work is vastly less than the risk to life of travelling to and from the workplace.

What are the consequences of reducing open autopsy practice by such minimal invasive techniques, and what are the opportunity costs? The focus here is on persons suspected of drug abuse with HCV or HIV.

Refinement of causes of death I am pleased that in Table 1, autopsies were indeed done to identify the alcoholic ketoacidosis syndrome and co-morbid infections. These variants of toxic pathology cannot be addressed without tissue samples, and preferably open autopsy examination of the relevant organs. But how much other important and/or interesting pathology might be missed by not doing open examinations? Table 1 lists a good number of lesions that may not be seen with CT: heart valve vegetations, tuberculosis (a public health notifiable infection), asthma, and cirrhosis (a disease of public health concern, and not reliably identified by imaging even in the living).

From my own observations I could add three generic scenarios: * The complicated and often critical contribution of co-morbidities, eg chronic lung and heart disease, to death from drug toxicity; it is much easier to evaluate the concepts of borderline toxicity and drug tolerance in individual cases when the whole pathology is known. * The contribution of sepsis from the IV injection habit pe se, both acutely with septic shock, and chronically through amyloidosis and renal failure. * The importance of considering the timing of a drug-related death, such as with evidence of aspiration pneumonitis, and addressing the questions of distressed relatives at inquest - for which there can be much evidence from the autopsy pathology.

Pathology education (or lack of) This is what disturbs me most about these trends towards imaging-only post -mortem examinations. Where and how are we going to teach the next generations of pathologists in the difficult arts of dissection and, even more importantly, histological examination? The current human tissue regulations already impact badly here, and removing yet more case work (drug-related deaths are indeed interesting and have significant internal pathologies that could become unfamiliar) takes away even more opportunity. Whilst some would argue that much of this type of examination is a waste of time, I hold that it provides practice in technique and interpretation, so that when a truly difficult and nuanced case emerges, it can be addressed with experience and reason.

Research opportunities Coronial autopsies are not intended for research but, basically, to determine whether a cause of death is natural, and an inquest may be dispensed with, or actually or potentially unnatural and so needs more investigations and inquiry. That said, because they provide >95% of adult autopsy work in the UK, they inevitably have a surveillance and potential research role. The epidemiology of diseases, including infections, changes constantly, and the autopsy provides one mode of monitoring and reporting on this.

The prime common example (I omit transmissible spongiform encephalopathies deliberately) is HIV disease. Much of what we know of the clinico-pathological cadence of HIV disease and results of new treatments (beneficial and adverse) comes from autopsy work. And it is published as such, although the commissioning coroners are probably not aware of that.

Coronial autopsies make a significant contribution to our understanding of cardiovascular disease in HIV-infected persons. Those not familiar with HIV may not realise the large clinical research, treatment and pharma interest into whether HIV per se and/or its anti-retroviral therapies do, or do not, activate endothelial cells and so augment arteriosclerosis, affecting the heart and brain in particular. HIV-infected suspected drug abusers thus contain within themselves at least two interesting pathological aspects (what is HIV doing and what are the drugs doing to that person), where a full autopsy can provide unique and cumulative evidence, to the ultimate benefit of public health.

Requirement for minimal invasive post-mortem examinations As Fryer et al state, the minimal invasive system requires two robust processes in place. First rapid toxicology, and they indicate one week as satisfactory. I would argue that this is not fast enough, since bodies do decompose even whilst refrigerated and important histopathological information is lost. More practically, in London, none of the laboratories offering services performs even that fast. That should be remediable, if the paymasters (the coroners) exercised their power to force the laboratories to turn over tests within, say, 3 working days.

Secondly, available imaging, particularly CT scanning. This is in practice impossible without proper funding; I pass over the availability of interested pathologists. At present, such non-forensic imaging is funded from now rather old government grants, or from individual initiatives such as jewish or moslem communities, or even interested radiologists with some surplus monies in their educational funds. But these are not appropriate for a nation-wide roll-out of cadaveric imaging - whether as replacement or (I would argue) as adjunct to open autopsy. These post-mortem examinations are done at the behest of coroners, and unfortunately they are not centrally but locally funded, with all that implies for variation in service provision.

So is there a future plan? The NHS has recently issued a large post- consultation document on cadaveric imaging {ref}, written by Prof Guy Rutty in Leicester and colleagues, with input from many other relevant specialities. I do encourage all autopsy-active pathologists (and coroners) to read it.

It provides the first realistic estimates of the actual costs of autopsies, with or without imaging costs, which alone make enlightening and disturbing reading for those involved in the economics of autopsy practice. But its main plank is the plan for future mortuary provision in England. Essentially, it is proposed that all mortuaries have attached dedicated CT scanners; that there need be only 30 such facilities in England (only 3 in London, the rest outside). And that all bodies are scanned prior to autopsy. The optimal funding for such an integrated pathology-radiology service is central government, not local source.

Conclusion There is much controversial material in this NHS document to discuss, but I certainly endorse the significant reduction of active mortuaries, with provision of imaging facilities on-site, and the resulting concentration of expertise in such places. As well as cases I still perform myself, I review many autopsies done by others and am frequently disturbed by their suboptimal or frankly dreadful quality. It is inevitable that experience, insight and - crucially - constant audit by, and consultation with, peers does sharpen and maintain practice standards. And so with autopsies: we should be doing them as a speciality interest practice, with similarly interested colleagues, in centres that do a lot of them very well. Which brings me back to the start of this Comment: in such facilities, 'high risk infections' will pose no problems for practitioners, who will be very familiar with them and their wrinkles. So isolating that category of cases for a qualitatively different approach to post-mortem examination from all the other cases will not be necessary.

Whether the NHS plan is rolled out as proposed, or through other exigencies the number of active mortuaries declines, the end result of fewer, but properly specialised facilities is appropriate. Pre-examination imaging will find it right place and 'high risk' cases will be optimally prosected.

Prof Sebastian Lucas Dept of Histopathology St Thomas' Hospital London SE1, UK Sebastian.lucas@kcl.ac.uk 28th Jan 2013

Reference "Can Cross-Sectional Imaging as an Adjunct and/or Alternative to the Invasive Autopsy be Implemented within the NHS?" Report from the NHS Implementation Sub-Group of the Department of Health Post Mortem, Forensic and Disaster Imaging Group (PMFDI). October 2012. The document can be downloaded from the East Midlands Forensic Pathology Unit. The full website address is: http://www2.le.ac.uk/departments/emfpu/Can%20Cross- Sectional%20Imaging%20as%20an%20Adjunct%20and- or%20Alternative%20to%20the%20Invasive%20Autopsy%20be%20Implemented%20within%20the%20NHS%20 -%20FINAL.pdf

Conflict of Interest:

None declared