Rewriting "Little Red Riding Hood" story may be dangerous
Maria Cecilia Mengoli,1 Giuseppe Bogina,2 Alberto Cavazza, 3 Giulio
Rossi 1
1Section of Pathology, Azienda Ospedaliero-Universitaria Policlinico,
Modena, Italy
2Section of Pathologic Anatomy, Hospital "Don Calabria", Negrar, Verona,
Italy
3Department of Oncology and Advanced Technologies, Operative Unit of
Oncology, Arcispedale S. Maria Nuova /...
Rewriting "Little Red Riding Hood" story may be dangerous
Maria Cecilia Mengoli,1 Giuseppe Bogina,2 Alberto Cavazza, 3 Giulio
Rossi 1
1Section of Pathology, Azienda Ospedaliero-Universitaria Policlinico,
Modena, Italy
2Section of Pathologic Anatomy, Hospital "Don Calabria", Negrar, Verona,
Italy
3Department of Oncology and Advanced Technologies, Operative Unit of
Oncology, Arcispedale S. Maria Nuova / I.R.C.C.S., Reggio Emilia, Italy
Corresponding author:
Giulio Rossi, MD
Section of Pathology, Azienda Ospedaliero-Universitaria Policlinico
Via del Pozzo, 71 - 41124 Modena (Italy)
Telephone: +39.059.4223890; Fax: +39.059.4224998;
Email: giurossi68@gmail.com
To the Editor:
We greatly appreciated the work by Klebe et al1 on the different
results of TTF-1 expression in lung and pleural neoplasms using different
clones, namely 8G7G3/1 and SP141. The authors reported TTF1 expression
with clone SP141 in normal bronchial mucosa, in about half of squamous
cell carcinomas and in 42% of sarcomatoid pleural mesotheliomas. By
contrast, no expression was noted with 8G7G3/1 in the same tissues.
We recently shared the same experience when clone SP141 momentarily
substituted 8G7G3/1 in our Lab. In addition, several colleagues sent us in
consultation cases of morphologically-overt squamous cell carcinomas
expressing p63 or p40 as well as strong TTF-1 positivity, TTF-1 positive
mesotheliomas and metastatic carcinomas from breast and gastrointestinal
tract cancers. The last TTF-1 positive case with clone SP141was a minute
mucous gland adenoma (Fig. 1A-B) incidentally discovered at bronchoscopy
in a 75 year-old man with a previous history of papillary carcinoma of the
thyroid. The positive staining with SP141 (Fig. 1C) raised the possibility
of a metastasis from thyroid cancer, but clinical and imaging findings,
and morphology strongly favoured a benign lesion from bronchus-associated
salivary glands. Indeed, TTF-1 staining with clone 8G7G3/1 was restricted
to entrapped pneumocytes (Fig. 1D).
Figure 1. Bronchoscopy showing an endobronchial millimetric lesion
with smooth, glistening surface (A) histologically appearing as well-
defined, submucosal proliferation of mucous-filled enlarged bland-looking
glands consistent with a mucous gland adenoma (B). Bronchial mucosa and
mucous glands expressing TTF-1 clone SP141 (C), while TTF-1 clone 8G7G3/1
stained only few entrapped pneumocytes (D).
When pathologists begun to use TTF-1 immunostaining in pulmonary
tissue in discriminating primary lung tumours from metastatic malignancies
or to distinguish some benign or malignant entities among a large spectrum
of pulmonary lesions, 8G7G3/1 was the only commercially available clone.
Then, we learned a huge amount of information from several studies
robustly indicating the diagnostic value of TTF-1 positivity and
negativity in different thoracic conditions (Table 1).
Table 1. A brief summary of positive and negative thoracic tumours
with TTF-1 clone 8G7G3/1
?, positivity is mainly restricted to peripheral-type carcinoids; *,
some variants of adenocarcinoma (e.g., mucinous, colloid, enteric types)
may be entirely negative
TTF-1 powerfully entered in all labs of surgical pathology and
promptly appeared as one of the most reliable antibody in the routine
practice.
By the way, controversial issues with TTF-1 clone 8G7G3/1 expression
occurred in neuroendocrine tumours (staining in peripheral rather than
central carcinoids or positivity in high-grade extrapulmonary
neuroendocrine carcinomas)2,3 or in a subset of metastatic tumors to the
lungs (e.g., gynaecological tumours).4
Although it is unclear the significance of the higher sensitivity/affinity
for TTF-1 protein of clone SP141 (or SPT24) when compared with clone
8G7G3/1, in our hands a weak nuclear signal from clone G8G7G3/1 does
appear more sincere than a strong signal from clone SP141.
TTF1 clone 8G7G3/1 is far from being perfect, but the higher specificity
of this clone in subtyping non-small cell lung cancer (NSCLC) and in
discriminating lung adenocarcinoma from mesothelioma or metastatic cancers
is not renounceable.5,6
Keeping in mind that the majority of thoracic tumours may be likely
diagnosed on morphology alone and immunohistochemistry is an ancilla of
the haematoxylin-eosin stain, the lessons learned from the story of TTF-1
immunostaining clearly indicate that the clone SP141 does represent the
"wolf in grandma", while clone 8G7G3/1 is the "good grandmother".
References
1. Klebe S, Swalling A, Jonavicius L, Henderson DW. An
Immunohistochemical comparison of two TTF-1 monoclonal antibodies in
atypical squamous lesions and sarcomatoid carcinoma of the lung, and
pleural malignant mesothelioma. J Clin Pathol 2015 doi
2. Du EZ, Goldstraw P, Zacharias J, et al. TTF-1 expression is specific
for lung primary in typical and atypical carcinoids: TTF-1 positive
carcinoids are predominantly in peripheral location. Hum Pathol
2004;35:825-831.
3. Agoff SN, Lamps LW, Philip AT, et al. Thyroid transcription factor-1 is
expressed in extrapulmonary small cell carcinomas but not in other
extrapulmonary neuroendocrine tumors. Mod Pathol 2000;13:238-242.
4. Siami K, McCluggage WG, Ordonez NG, et al. Thyroid transcription factor
-1 expression in endometrial and endocervical adenocarcinomas. Am J Surg
Pathol 2007;31:1759-1763.
5. Ordonez NG. Value of thyroid transcription factor-1 immunostaining in
tumor diagnosis: a review and update. Appl Immunohistochem Mol Morphol
2012;20:429-40.
6. Kadota K, Nitadori J, Rekhtman N, Jones DR, Adusumilli PS, Travis WD.
Reevaluation and reclassification of resected lung carcinomas originally
diagnosed as squamous cell carcinoma using Immunohistochemical analysis.
Am J Surg Pathol 2015;39:1170-80.
The paper by Turnbull and colleagues (1) on the decline of the adult
hospital autopsy rate in UK prompted me to review and extend the Norwich
data that they kindly quoted (2). I calculated the adult hospital autopsy
rate since our publication (including that relating to the first five
months of this year) using the method that we both employed. The modest
improvement that we reported in the adult hospital autopsy rate i...
The paper by Turnbull and colleagues (1) on the decline of the adult
hospital autopsy rate in UK prompted me to review and extend the Norwich
data that they kindly quoted (2). I calculated the adult hospital autopsy
rate since our publication (including that relating to the first five
months of this year) using the method that we both employed. The modest
improvement that we reported in the adult hospital autopsy rate in Norwich
between 2003 and 2005 was not subsequently sustained and the overall trend
continued downward. During the period since 1 January 2006, the mean
adult hospital autopsy rate in Norwich was 1.1% (range 0.1%-1.7%). The
rate in 2013 was 0.6%, in line with the data presented by Turnbull et al.
(1).
During 2006-2014, there has been a rising trend here in the annual
number of autopsies undertaken for HM Coroner (mean 1191; range 1037-
1355). Most such cases represented deaths in the community or in the A&E
Department, but some were patients who died in the wards after admission.
In such cases the attending clinicians were unable to complete a
certificate of the cause of death. While some such cases followed trauma
or other unnatural events, many were natural deaths in which the clinical
course was difficult to understand, sometimes despite detailed examination
and testing; no confident diagnostic label was attached before death.
Such Coroner's cases arising from within the hospital patient population
represent medicolegal quasi-hospital autopsies and provide a partial means
of alleviating the decline in consented adult hospital autopsies. It is
my experience that many such cases provide valuable opportunities to study
disease and the efficacy of diagnosis and treatment in the hospital
setting.
The continuing decline of the adult hospital autopsy is of great
concern. It is likely to multifactorial and to be influenced by the
attitudes of clinicians, pathologists and bereaved families (3,4). It
does have important implications for clinical audit, diagnostics and
medical education (3). While such matters can, at least in part, be
addressed by the coronial autopsies that are undertaken on certain
hospital deaths, such cases are relatively few and do not necessarily
reflect the normal population of patients who die in hospital; they are
likely to provide a skewed experience. We know little about the numbers
of such cases or what stimulates a clinician to discuss a seemingly
natural death with the Coroner, rather than to use clinical judgement and
suggest the most likely cause of death and complete a death certificate.
It may be that clinicians wish to have a greater degree of certainty than
such an approach allows.
While medicolegal quasi-hospital autopsies are an imperfect
substitute for properly conducted hospital autopsies, they are better than
nothing and should, perhaps, be considered when assessing adult hospital
autopsy rates. The whole matter clearly requires further research.
Autopsy practice in general is threatened by the decline in the numbers of
histopathologists who are prepared to undertake any such examinations.
That itself is a matter of concern and requires deeper understanding and
rectification. It chimes with Byard's view that the decline in the autopsy
is, at least in part, the responsibility of histopathologists (4).
References
1. Turnbull A, Osborn M, Nicholas N. Hospital autopsy: Endangered or
extinct? J Clin Pathol Published Online First: [15 06 2015]
doi:10.1136/jclinpath-2014-202700
2. Limacher E, Carr U, Bowker L, et al. Reversing the slow death of
the clinical necropsy: developing the post of the Pathology Liaison Nurse.
J Clin Pathol 2007; 60:1129-34.
3. Carr U, Bowker L, Ball RY. The slow death of the clinical post-
mortem examination: implications for clinical audit, diagnostics and
medical education. Clin Med 2004; 4:417-23.
4. Byard RW. Who's killing the autopsy? A new tool for assessing the
causes of falling autopsy rates. Med J Aust 2005; 183:654-5.
I read this article with interest. I totally agree with the authors'
statement that many requests for HFE mutation analysis are frequently
ordered in the community without measuring serum iron and transferrin
saturation (T-sat) first. While this report is intriguing, I am very much
interested to know if the samples for serum iron and T-sat in this study
were fasting samples or postprandial samples. The diet rich in iron...
I read this article with interest. I totally agree with the authors'
statement that many requests for HFE mutation analysis are frequently
ordered in the community without measuring serum iron and transferrin
saturation (T-sat) first. While this report is intriguing, I am very much
interested to know if the samples for serum iron and T-sat in this study
were fasting samples or postprandial samples. The diet rich in iron can
obviously increase the T-sat. Medications such as vitamin C, dietary
supplement containing iron, multivitamins with iron and oral contraceptive
pills (OCPs) and can increase the T-sat [1,2]. Another point to consider
is that about half of the adults in the western countries take vitamins
and other dietary supplements regularly and about three to three quarter
million women in Britain take OCPs [3,4]. This means the results of the
serum iron and T-sat obtained in the daily clinical practice can highly be
influenced by the iron-rich diet, vitamins, dietary supplements and OCPs.
I wonder how many patients in this current study are on those medications
and how many samples were drawn postprandially. Provided those patients
were excluded from this study, the actual number of the patients with T-
sat > 50% would be decreased. This translates to further saving of
money from unnecessary testing of HFE mutation analysis. Referring
physicians should submit fasting blood samples for serum iron and T-sat.
Patients who are on above-mentioned medications should avoid their
medications for at least 24 hours prior to the fasting blood draw [2].
Thein H. Oo, MD
References:
1. Transferrin saturation test.
http://www.cdc.gov/ncbddd/hemochromatosis/training/diagnostic_testing/testing_protocol.html
Accessed May 8, 2015
2. Transferrin saturation.
http://emedicine.medscape.com/article/2087960-overview Accessed May 8,
2015
3. Vitamins: How many Americans use them?
http://www.huffingtonpost.com/2011/04/13/vitamin-use_n_848777.html
Accessed May 8, 2015.
4. Contraception: patterns of use fact use.
http://www.fpa.org.uk/factsheets/contraception-patterns-use Accessed May
8, 2015
We are happy to address the points raised by Lee et al in their
commentary on our paper [1] and thank them for their interest in it.
Lee et al correctly note that our re-assessment was of the mitotic
count in these specimens. To clarify, these were carried out by either of
two observers (CAD, JL) blinded to the original core and excision grading.
The other elements of the tumour grade...
We are happy to address the points raised by Lee et al in their
commentary on our paper [1] and thank them for their interest in it.
Lee et al correctly note that our re-assessment was of the mitotic
count in these specimens. To clarify, these were carried out by either of
two observers (CAD, JL) blinded to the original core and excision grading.
The other elements of the tumour grade (tubule formation and nuclear
score) were not re-assessed, but were as per the original report, that is
to say, as reported prospectively by the original reporting pathologist.
Similar to Nottingham, in Edinburgh five pathologists with a specialist or
subspecialist interest in breast pathology were involved in reporting
these cases. The mitotic counts of cases in which our count on review
would have assigned the case to a different mitotic score (M) category
were reviewed jointly by both authors and a consensus count agreed. These
represented just 7% of our cases. It is thus very unlikely that this had
any significant effect on the assessment of grade between core and
excision.
Edinburgh is one of the largest breast cancer centres in the UK. We
follow the NHSBSP guidelines in our handling of specimens and are aware of
the potential difficulties of poor fixation. We do not however have this
problem, as evidenced by the grade distribution of tumours in our
department which is comparable to other centres on national audit.[2]
Lee's main concerns however appear to be that our series is selective
(presumably relating to our inclusion of breast conserving surgery tumours
only) and the low proportion of grade 3 tumours (on excision) in our
series, suggesting it would lower the potential impact of undergrading on
core biopsy.
We did not include tumours treated by mastectomy principally because
the majority of these (117/170) would have been excluded on the basis of
multifocal disease (56), having received neoadjuvant chemotherapy /
systemic therapy (31), having a past history of breast cancer (20) or
having had their core biopsy performed in another hospital and not
available for review (10). Had the remaining 53 cases been included they
would not have made a material difference to the outcome or conclusions of
our study and they would only have increased our proportion of grade 3
cancers to 29% (120/412).
More importantly in relation to the potential impact of the
proportion of grade 3 tumours in our series Lee at al fail to note that of
our symptomatic cases 48% (72/150) were grade 3 on excision. Neither the
whole symptomatic group nor the subset of 41 cases scored as (T3, N3, M1)
within it showed benefit from application of the modification of the
mitotic scores. Of the (T3, N3, M1) subset 14 would have been
reclassified as grade 3* on core biopsy, only 6 of which were grade 3 on
excision. As for all other subsets, in our experience there is a marginal
increase in the sensitivity counterbalanced by a larger reduction in the
specificity of cases designated as grade 3 on core biopsy using the
modified scores.
Finally, we do not seek to disprove the findings of Lee's group.
They have shown their utility in their own population.[3] We demonstrate
that they do not work in ours. Our conclusion remains that the current
recommended mitotic count thresholds are appropriate and should be
maintained. We agree that further studies could contribute to the debate,
but note that the treatment of the breast cancer population is changing to
include more cases receiving neoadjuvant therapy which may make repetition
more difficult.
References:
1. Dhaliwal CA, Graham, C, Loane J. Grading of breast cancer on
needle core biopsy; does a reduction in mitotic count threshold improve
agreement with grade on excised specimens? J Clin Pathol 2014; 67:1106-8
2. NHS breast screening programme and Association of Breast Surgery:
An audit of screen detected cancers for the year of screening April 2012
to March 2013; Public Health England, May 2014.
3. Lee A, Rakha E, Hodi Z et al. Re-audit of revised method for
assessing the mitotic component of the histological grade in needle core
biopsies of invasive carcinoma of the breast. Histopathology 2012; 60:
1166-7
Accurate histological grading of invasive carcinoma of the breast in
needle core biopsies is important for patient management, for example for
selecting patients for neoadjuvant chemotherapy. The grade in the core
biopsy tends to underestimate the grade in the excision specimen,
particularly due to underestimation of the mitotic count. We recently
proposed a reduction in the threshold for the mitotic count which we found...
Accurate histological grading of invasive carcinoma of the breast in
needle core biopsies is important for patient management, for example for
selecting patients for neoadjuvant chemotherapy. The grade in the core
biopsy tends to underestimate the grade in the excision specimen,
particularly due to underestimation of the mitotic count. We recently
proposed a reduction in the threshold for the mitotic count which we found
of particular value in tumours scored as T3, P3, M1 (less than 10%
tubules, marked nuclear pleomorphism and few mitoses) and therefore grade
2 on the core biopsy.(1,2)
Dhaliwal et al tested this approach in a 359 core biopsies in
Edinburgh and found it to be of no value either in the whole series or in
the T3, P3, M1 subset.(3) The two series of tumours show important
differences. The histological grade of the Edinburgh carcinomas was on
average lower: 27% of carcinomas were grade 3 in the surgical specimen
compared with 40% in our series from Nottingham. Potential explanations
for this difference include the high number of Edinburgh patients excluded
because they received neoadjuvant chemotherapy (22% in Edinburgh compared
with 4% in the older Nottingham series). Such patients often have grade 3
tumours. In addition the majority of Edinburgh cancers (58%) were detected
by screening (such tumours tend to be of lower grade than symptomatic
cancers as shown in tables 2 and 3 of the Edinburgh paper). Breast cancer
resections in Nottingham are received fresh in the laboratory and incised
immediately to ensure good fixation, which is important for accurate
assessment of grade. Poorly fixed specimens tend to have lower grade
including lower mitotic count. Were the specimens immediately incised in
Edinburgh? Finally it is not clear why only tumours that were excised with
breast conserving surgery were included.
Dhaliwal achieved 79% agreement between grade in the core biopsy and
the surgical specimen. As they state this is at the upper end of the range
reported in the literature. The mitotic counts were assessed by two
observers retrospectively and if there was a discordance with the original
report the biopsy was reassessed. In the Nottingham study the core grade
was assessed prospectively and independently by 5 different observers.
Double reporting as performed in Edinburgh may improve the assessment of
grade. The lower proportion of grade 3 tumours in Edinburgh reduces the
potential impact of undergrading on the core biopsy.
The Edinburgh study does not disprove the potential value of reducing
the mitotic threshold as their series is selective with a low proportion
of grade 3 tumours. Further studies including a good proportion of grade 3
tumours are needed to test whether reducing the mitotic threshold in the
core biopsy is of value in assessing histological grade.
1. O'Shea AM, Rakha EA, Hodi Z, Ellis IO, Lee AHS. Histological grade
of invasive carcinoma of the breast assessed on needle core biopsy -
modifications to mitotic count assessment to improve agreement with
surgical specimen. Histopathology 2011;59:543-548
2. Lee AHS, Rakha EA, Hodi Z, Ellis IO. Re-audit of revised method for
assessing the mitotic component of histological grade in needle core
biopsies of invasive carcinoma of the breast. (Letter) Histopathology
2012;60:1166-1167
3. Dhaliwal CA, Graham C, Loane J. Grade of breast cancer in needle core
biopsy: does a reduction in mitotic count threshold improve agreement with
grade on excised specimens? J Clin Pathol 2014;67:1106-1108
To the Editor:
Without doubt the hospital-based autopsy is an effective quality assurance
and learning tool. The study by Kuijpers et al. supports this.[1] However,
autopsy is a time-consuming and expensive procedure which may sometimes
cause distress to the deceased patient's family and be associated with
complex consent issues. It is therefore important to ask how far reaching,
beyond the pathologist and the referring cli...
To the Editor:
Without doubt the hospital-based autopsy is an effective quality assurance
and learning tool. The study by Kuijpers et al. supports this.[1] However,
autopsy is a time-consuming and expensive procedure which may sometimes
cause distress to the deceased patient's family and be associated with
complex consent issues. It is therefore important to ask how far reaching,
beyond the pathologist and the referring clinician, is the learning impact
of each individual autopsy?
The clinician requesting the autopsy is interested in the bullet-
point preliminary summary (based on the macroscopic findings) that is
signed out immediately. But how often is the final detailed multi-page
report followed up? Autopsies and the associated laboratory tissue-
processing usually do not take priority in a busy diagnostic department.
Final reports may not be verified for some time after the procedure,
decreasing their learning impact.
Frequency of minor diagnostic errors, as measured by the autopsy gold
standard, is increasing over time.[1] Improper use of imaging
investigations is contributing significantly to incorrect pre-mortem
diagnosis.[1] Could it be that the main problem is that there has been a
huge increase in the number of diagnostic investigations that can be
requested during life? More investigations at our fingertips do not
necessarily make things better for the doctor, or for the patient.[1] How
do we learn how to optimally use these investigations to avoid
misdiagnosis or alternatively to optimally learn from the inappropriate
use of past investigations, so that errors are not repeated?
Some of the current issues with use of diagnostic investigations are
as follows:
1. Understanding the tests:
a. Wrong test selected for the situation - whether it be imaging or
diagnostic pathology. This results in false positives or false negatives;
b. Sensitivity, specificity and positive/negative predictive value - these
parameters of a particular imaging modality or pathology test may not be
appreciated. Acting on the false result whether it is negative or positive
may have significant detrimental clinical impact;
c. With complex histopathology or imaging investigations, are the nuances
in the body of the report skipped or overlooked by the treating clinician?
2. Communication:
a. With immensely busy clinical loads, how often is the suitability of the
investigation or the unexpected final result discussed with the
radiologist or pathologist? In other words, how often do we practice in a
vacuum because of time constraints?
3. Clinico-pathological and radio-pathological correlation:
a. Were the radiologist or pathologist given any clinical information, and
if not did they seek such information before reporting?
Obviously selection and interpretation of diagnostic tests is often
not clear-cut in the real world. Furthermore, with increasing numbers and
complexity of diagnostic tests come increasing workloads for pathologists
and radiologists. There is increased expectation from both patients and
referring clinicians. Faced sometimes with extraordinary numbers of cases
to report each day, the pathologist may fail to look for or may miss a
vital component of the history that was provided to them by the
radiologist or clinician. This is easy to do in an electronic era where
most reports and referrals are scanned and it takes time to search. There
will also always be cases where only a proportion of slides or images were
viewed before issuing a report. Errors are part of the human condition.
The key is to learn from errors and to not repeat them.
In summary, autopsy has always been an excellent tool for quality
assessment in diagnostic accuracy. But is it a teaching and quality
assurance procedure that is time and cost-effective, with results that are
easy to disseminate with maximum learning benefit? Focus on development
and delivery of high impact and time-efficient continuing education
modules (particularly online) regarding quality assurance errors and
diagnostic and investigative medicine has already been demonstrated to be
of value,[2] so such modules may represent an alternative solution to
these issues.
References
1. Kuijpers C.C.H.J., Fronczek J., van de Goot F.R.W., et al. J Clin
Pathol 2014;67:512-519 doi:10.1136/jclinpath-2013-202122
2. Ritchie A., Jureidini E. and Kumar R.K. Educating Junior Doctors to
Reduce Requests for Laboratory Investigations: Opportunities and
Challenges. Med.Sci.Educ. 2014;24:161-163 DOI 10.1007/s40670-014-0041-2
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...
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!
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 stat...
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)
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
progno...
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
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.
Rewriting "Little Red Riding Hood" story may be dangerous
Maria Cecilia Mengoli,1 Giuseppe Bogina,2 Alberto Cavazza, 3 Giulio Rossi 1
1Section of Pathology, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy 2Section of Pathologic Anatomy, Hospital "Don Calabria", Negrar, Verona, Italy 3Department of Oncology and Advanced Technologies, Operative Unit of Oncology, Arcispedale S. Maria Nuova /...
The paper by Turnbull and colleagues (1) on the decline of the adult hospital autopsy rate in UK prompted me to review and extend the Norwich data that they kindly quoted (2). I calculated the adult hospital autopsy rate since our publication (including that relating to the first five months of this year) using the method that we both employed. The modest improvement that we reported in the adult hospital autopsy rate i...
I read this article with interest. I totally agree with the authors' statement that many requests for HFE mutation analysis are frequently ordered in the community without measuring serum iron and transferrin saturation (T-sat) first. While this report is intriguing, I am very much interested to know if the samples for serum iron and T-sat in this study were fasting samples or postprandial samples. The diet rich in iron...
Dear Sir / Madam,
We are happy to address the points raised by Lee et al in their commentary on our paper [1] and thank them for their interest in it.
Lee et al correctly note that our re-assessment was of the mitotic count in these specimens. To clarify, these were carried out by either of two observers (CAD, JL) blinded to the original core and excision grading. The other elements of the tumour grade...
Accurate histological grading of invasive carcinoma of the breast in needle core biopsies is important for patient management, for example for selecting patients for neoadjuvant chemotherapy. The grade in the core biopsy tends to underestimate the grade in the excision specimen, particularly due to underestimation of the mitotic count. We recently proposed a reduction in the threshold for the mitotic count which we found...
To the Editor: Without doubt the hospital-based autopsy is an effective quality assurance and learning tool. The study by Kuijpers et al. supports this.[1] However, autopsy is a time-consuming and expensive procedure which may sometimes cause distress to the deceased patient's family and be associated with complex consent issues. It is therefore important to ask how far reaching, beyond the pathologist and the referring cli...
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...
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 stat...
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 progno...
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...
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