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.
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.
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...
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...
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