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 malignan...
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.
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 wit...
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]
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...
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.
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
homose...
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.
'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 n...
'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
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 malignan...
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 wit...
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...
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 homose...
'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 n...
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