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Recent eLetters

Displaying 1-10 letters out of 140 published

  1. Reply to Dr. G Stenhouse

    The correspondent points out that the RCPath standards of 2007 were written for a symptomatic population. This is not specifically stated in the standards, which were written just as the UK pilots of FOB screening were concluding. The current proposed standards (2014) are still in draft stage. It seems clear however that it will apply equally to all cancers. The issue of the effect of preoperative therapy on reporting of SI, EMVI and node number is important. Unfortunately in our retrospective audit the use of the prefix "y" in staging patients who have had preoperative therapy was not universally applied. It is also true that in many units, including our own, the pathologist is not always informed that the patient has been treated by an oncologist. A tighter prospective study is needed. It should be noted that the revised national standards do not make any allowance for the effect of chemotherapy and radiotherapy. The comment that the failure of some units to meet minimum standards "....is likely to have serious adverse consequences for patient care" is , we feel, justified. There is significant crossover in under-reporting as can be seen by inspection of the tabulated data. Unit 10 on our tables, for example, did not report serosal invasion in any rectal cancer, reports only 10% EMVI and has a mean node yield of 5 for rectum and 10 for colon. It is certain that this will have led to understaging and possibly to denial of treatment to patients who would have benefitted. I agree that electronic reporting systems would be a major asset. We would certainly hope to ask for documentation of preoperative treatment in our follow-up audit!

    Conflict of Interest:

    None declared

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  2. Comment on 'A Survey of colorectal cancer in Scotland: compliance with guidelines and effect of proforma reporting'.

    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)

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  3. Re:Mucosal large cell neuroendocrine carcinoma of the head and neck regions:inconsistent data

    Answers to the letter Dear Dr. Sir. 1. We confirmed that the patient was 79 years-old man on case 2. As the mitosis index and the Ki-67 labeling index were estimated with newly prepared sections, the indices were a bit different. We confirmed that the tumor cells were focally positive for chromogranin-A, but negative for synaptophysin on case 2. 2. Certainly, at the writing step of the review article (ref.3), the prognosis of our series of M-LCNEC was relatively good, but the prognosis became worse one year after that time. We concluded that the prognosis of M-LCNEC was relatively worse, like the LCNEC of other organs, in this recent paper (ref. 1). Moreover, we confirmed that three cases of M-LCNEC were positive for thyroid transcription factor(TTF)-1. 3. We confirmed that the age ranged from 52 to 74 years old in our M-LCNEC series and that four patients were alive without disease (31 months, 18 months, 24 months and 90 months).

    Dr. Kimihide Kusafuka, D.D.S., Ph.D. Pathology Division, Shizuoka Cancer Center Hospital and Research Institute

    Conflict of Interest:

    None declared

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  4. To the Editor

    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

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  5. Re:About uncertainty in IBD histological diagnosis

    Firstly, Dr Canavese and colleagues' interest in the guideline document is much appreciated. Before responding specifically, it is worth noting that there are two main diagnostic decisions to make when a patient presents with suspected chronic idiopathic inflammatory bowel disease (IBD): distinguishing IBD from other causes of inflammation; and classifying IBD as ulcerative colitis (UC) or Crohn's disease (CD). Even with full clinical details, comprehensive sampling, and assessment by a well-informed pathologist there will be a significant minority of IBD biopsies that cannot be classified confidently as UC or CD.[1, 2] There will also be a number that cannot even be categorised as IBD or non-IBD. However, I agree entirely that several other factors beyond the pathologist's control may also contribute to diagnostic uncertainty. Indeed, the proven importance of adequate clinical details and of thorough sampling are often noted in clinical guidelines.[1, 3-8] For example, limited sampling within and between sites may be one of the reasons why histopathologists are apparently less successful at diagnosing CD than diagnosing UC.[7-9] I also agree that pathologists have a responsibility to convey the level of diagnostic certainty as clearly as possible to the clinical teams. Proposed categories for the conclusion of an IBD biopsy report have been included in the BSG guideline ("PAID" scheme, Table 14).[10] The suggested terminology represents a consensus view on the best way to express probability. Accordingly, its adoption is recommended. Similarly, vague terms such as "in keeping with" are best avoided or used sparingly (Table 13).[10] Dr Canavese and colleagues' suggested solutions are helpful. I agree that the pathologist should insist on a minimum standard of clinical input. Indeed, provision of the endoscopy report to the pathologist will be recommended strongly in a forthcoming guideline for clinicians.[11] Similarly, identifiable deficiencies in the process should be noted by the pathologist interpreting the biopsies, especially if they interfere with assessment. Also, a statement in a histology report that repeat endoscopy and sampling might be informative would oblige the clinician to consider this option. However, enforcement of minimum clinical standards can be difficult. Overall, better communication between pathologists and clinicians, ideally in the setting of a regular clinicopathological meeting, is an excellent way to enhance diagnostic accuracy.[4, 10, 12] On a more general note, the scope and quality of IBD services and the reasons for suboptimal management may vary within and between countries. Attempts are being made to remedy the inconsistencies. Reassuringly, a UK services standards document for IBD includes guidance on the use of histopathology services and is cognisant both of the value of biopsy assessment and of the importance of interaction between pathologists and clinicians.[13]

    Yours sincerely,

    Professor R M Feakins

    Conflict of Interest:

    None declared

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  6. About uncertainty in IBD histological diagnosis

    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

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  7. Is the Intestinal Adenoma-microcarcinoid part of a Spectrum?

    Your recently published paper entitled: "Composite Intestinal Adenoma -microcarcinoid Clues to Diagnosing an Under-recognized Mimic of Invasive Adenocarcinoma", by Dr. Salaria, et al., (1) immediately reminded me of a non-cited paper that I co-wrote in 1985 (2) about 3 recto-sigmoid carcinomas that presented with hepatic metastases; two patients died within a year, while one had progressive disease. A 26-year-old homosexual, likely with HIV/AIDS had a 4-cm polypoid posterior rectal mass that on subsequent excision was an ulcerated small cell undifferentiated carcinoma (SCUC). A 78-year-old-woman had a 4-cm mass 8 cm from the anal sphincter that showed a nesting, trabecular, carcinoid type SCUC associated with a gland-forming infiltrating adenocarcinoma. A 51-year- old woman had a 3-cm sessile adenomatous polyp, 20 cm from the anal sphincter that contained both infiltrating adenocarcinoma and SCUC; a liver biopsy was of a neuroendocrine carcinoma with dense core granules (DCG). The three varied histologically and ultrastructurally, as well as in the appearance of their neuroendocrine (NE) cells and size and abundance of NEG; they resembled both carcinoid and SCUC tumors. At the ultrastructural level, GI adenocarcinomas can have an unsuspected neuroendocrine component and a variable behavior. This suggests the possibility that there a spectrum, from a serendipitously discovered combined adenoma with a locally invasive/infiltrating carcinoid (1) through a highly aggressive adeno-endocrine lesion, with a metastatic neuroendocrine component. Both endodermal components are likely derived from the same crypt stem cells. Similar combinations are found by TEM in adenocarcinomas of the lung. In both cases, the behavior doesn't necessarily parallel the light and ultrastructural appearance, e.g., carcinoid versus "oat cell" (2). Thus, care must be taken when analyzing GI adenomas, not just looking for an adenocarcinomatous component, but also for a SCUC/carcinoid component; if either feature is identified, the liver and lymph nodes (patient #3) may be involved and there may be other lesion in the patient (307). 1) Salaria SN, Abu Alfa AK, Alsaigh NY, et al. Composite Intestinal Adenoma-microcarcinoid Clues to Diagnosing an Under-recognized Mimic of Invasive Adenocarcinoma. J Clin Pathol 2013 66:302-6. 2) Schwartz AM, Orenstein, JM. Small-cell undifferentiated carcinoma of the rectosigmoid colon. Arch Pathol Lab Med 1985;109:629-32.

    Conflict of Interest:

    None declared

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  8. Comment on imaging and high risk autopsies

    '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

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  9. IgG4-related disease in synovial tissues

    Dear Editor, We read with interest the comprehensive review on IgG4-related disease (IgG4-RD) by Drs Culver and Bateman [1], and wish to add on IgG4-RD in synovial tissue. A previous report suggested that up to 10% of patients with IgG4-RD have arthritis [2]. Two reports of arthropathy by Umekita K et al and Shinoda K et al showed evidence of infiltration of IgG4-positive plasma cells in the synovium [3, 4]. It is therefore interesting to speculate if specific biomarkers of tissue IgG4-RD exist either in the plasma or clinically relevant tissue filtrate (i.e., CSF, synovial fluid etc) that is similar to the authors' concept of examining clinically non- involved tissues for IgG4-RD.

    Synovial fibroblasts or fibroblast-like synoviocytes in rheumatoid arthritis use B-cell activating factor (BAFF) and TLR3 to promote immunoglobulin class switch [5], that is evidence of perpetuation of autoimmunity in non-lymphoid tissue and possibly similar to what happens in IgG4-RD. Ugo Fiocco and colleagues from Italy have tried to identify candidate synovial biomakers in psoriatic arthritis, and showed that synovial fluid interleukin-6 (SF- IL-6) and SF-IL-1b levels along with synovial tissue (ST)-CD45+ and ST-CD31+ levels were altered significantly as well as disease activity after anti-TNF therapy [6]. A new report now suggests that basophil-TLR and basophil/B cell-BAFF interaction may lead to the development of IgG4-RD [7]. It is certainly not the end of the road for this intriguing disease.

    Conflict of interests: None declared

    Authors: Sujoy Khan, Consultant Allergy & Immunology, Apollo Gleneagles Hospital, Kolkata, India; Ratnadeep Ganguly, Consultant Histopathologist, Apollo Gleneagles Hospital, Kolkata, India

    References: 1. Culver EL, Bateman AC. IgG4-related disease: can non-classical histopathological features or the examination of clinically uninvolved tissues be helpful in the diagnosis? J Clin Pathol. 2012;65:963-9.

    2. Masaki Y, Dong L, Kurose N et al. Proposal for a new clinical entity, IgG4-positive multiorgan lymphoproliferative syndrome: analysis of 64 cases of IgG4-related disorders. Ann Rheum Dis 2009; 68; 1310-5.

    3. Umekita K, Kaneko Y, Yorita K et al. Arthropathy with infiltrate IgG4-positive plasma cells in synovium. Rheumatology (Oxford). 2012;51:580 -2. 4. Shinoda K, Matsui S, Taki H et al. Deforming arthropathy in a patient with IgG4-related systemic disease: Comment on the article by Stone et al. Arthritis Care Res 2011; 63: 172.

    5. Alsaleh G, Fran?ois A, Knapp AM et al. Synovial fibroblasts promote immunoglobulin class switching by a mechanism involving BAFF. Eur J Immunol. 2011;41:2113-22.

    6. Fiocco U, Oliviero F, Sfriso P et al. Synovial biomarkers in psoriatic arthritis. J Rheumatol Suppl. 2012;89:61-4.

    7. Watanabe T, Yamashita K, Sakurai T et al. Toll-like receptor activation in basophils contributes to the development of IgG4-related disease. J Gastroenterol. 2012 Jun 29. [Epub ahead of print]

    Conflict of Interest:

    None declared

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  10. Mucosal large cell neuroendocrine carcinoma of the head and neck regions:inconsistent data

    Dear Editor,

    I read with interest the recent original article entitled 'Mucosal large cell neuroendocrine carcinoma of the head and neck regions in Japanese patients: a distinct clinicopathological entity' by Kusafuka et al.[1] The patient (Case 2) in this article had been previously reported.[2] I note some discrepancies between these two papers. In this original article, the patient (Case 2) was a 65-year-old man. The mitotic rate of this tumor was not specified, but >15 per 10 high power fields. Immunohistochemically, the tumor cells were focally positive for chromogranin-A, but negative for synaptophysin. The Ki-67 labeling index was 90.8%[1]. In the case report[2], this patient was a 79-year-old man. The mitotic rate was 13 per 10 high-power fields. The tumor cells were focally positive for synaptophysin (shown in Figure 3c), but negative for chromogranin-A. The Ki-67 labeling index was 82%.

    There are also some discrepancies between this original article and their recent review article[3]. In the review[3], they mentioned that four of their eight mucosal large cell neuroendocrine carcinomas arose in the larynx (supraglottis). The follow up periods were 12-96 months, and only one patient died of disease. The authors concluded that the Japanese cases of mucosal large cell neuroendocrine carcinoma had a better prognosis than that reported in the literature. Three cases were immunopositive for thyroid transcription factor-1. But in this original article[1], four tumors occurred at the larynx, with three at the supraglottis and one at the infraglottis. Three patients died of disease, and one patient died of another disease (shown in Table 2), which led to the conclusion that their Japanese series of large cell neuroendocrine carcinoma also indicated a relatively poor prognosis as that reported in the literature. The follow up periods were 15-90 months (shown in Table 2). Only two cases were immunopositive for thyroid transcription factor-1.

    Discrepancies were also present in this original article[1]. In the section of Results, the age of the eight patients ranged from 52 to 75 years (mean 64.6 years). In the section of Discussion, they stated all the cases in the present series were aged >65 years and the follow up periods of the patients that have been disease-free were 24-108 months. But in Table 2, the age ranged from 52 to 74 years and four patients were alive without disease (31 months, 18 months, 24 months and 90 months after surgery, respectively).

    In conclusion, there are many inconsistent data in these articles concerning mucosal large cell neuroendocrine carcinoma by Kusafuka et al.[1-3] They should verify the original data and make a correction.

    Sincerely, Shaodong Yang. Department of Oral Histopathology, Hainan Medical College, 3 Xueyuan Road, Longhua District, Haikou, China.

    REFERENCES 1. Kusafuka K, Abe M, Iida Y, et al. Mucosal large cell neuroendocrine carcinoma of the head and neck regions in Japanese patients: a distinct clinicopathological entity. J Clin Pathol 2012;65:704-9. 2. Kusafuka K, Asano R, Kamijo T, et al. Large cell neuroendocrine carcinoma of the tongue base: case report of an unusual location with immunohistochemical analysis. Int J Oral Maxillofac Surg 2009;38:296-9. 3. Kusafuka K, Ferlito A, Lewis JS Jr, et al. Large cell neuroendocrine carcinoma of the head and neck. Oral Oncol 2012;48:211-5.

    Conflict of Interest:

    None declared

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