Displaying 1-10 letters out of 147 published
Chronic neutrophilic leukaemia: a molecularly defined disease?
In their recent review, Uppal and Gong provided a comprehensive overview of the pathological findings in the uncommon myeloproliferative neoplasm of chronic neutrophilic leukaemia (CNL) . Subsequent to the landmark discovery of somatic mutations in the CSF3R gene in CNL patients which provided a rationale for adoption of tyrosine kinase inhibitor therapies, studies on further cohorts now suggest that activating CSF3R mutations are found solely in World Health Organization-defined CNL without a co-existing monoclonal gammopathy amongst other myeloproliferative neoplasms [2, 3]. Identification of CSF3R mutations would now make the diagnosis of CNL no longer one of exclusion. As discussed by Uppal and Gong, secondary mutations in other genes such as SETBP1, ASXL1 and CALR have been observed in conjunction with those in CSF3R.
How therefore are those rare CNL cases harbouring the JAK2 V617F mutation [4, 5] now to be classified given this proposal? Throughout the literature are several reports of polycythaemia vera and to a lesser extent, primary myelofibrosis, progressing to a proliferative neutrophilic phase (as opposed to myelofibrotic or leukaemic transformation) that mimics the morphological features of CNL. In one such recently reported case in which some of the characteristic morphological features of the underlying JAK2 V617F-positive polycythaemia vera persisted, no CNL- associated CSF3R mutations were found . Does the possibility therefore exist that those historical CNL JAK2 V617F-positive cases represent patients with polycythaemia vera or primary myelofibrosis presenting in this terminating neutrophilic stage? Anecdotal evidence supporting this speculation comes from the favourable clinical response of a JAK2 V617F- positive CNL patient treated with interferon-?; an agent with proven efficacy in other myeloproliferative neoplasms . Consequently it might therefore be argued that CNL is a distinct molecular entity and similar to World Health Organization-defined atypical chronic myeloid leukaemia, is a JAK2 V617F-negative disease .
It is acknowledged that there exists a spectrum of clinical, morphological and molecular features even in such a rare disease as CNL and it is hoped that the next revision of World Health Organization classification of haematopoietic malignancies provides both clarification and consensus.
1. Uppal G, Gong J. Chronic neutrophilic leukaemia. J Clin Path 2015;68:680-4.
2. Pardanani A, Lasho TL, Laborde RR, et al. CSF3R T618I is a highly prevalent and specific mutation in chronic neutrophilic leukemia. Leukemia 2013;27:1870-3.
3. Li B, Gale RP, Xiao Z. Molecular genetics of chronic neutrophilic leukemia, chronic myelomonocytic leuekmia and atypical chronic myeloid leukemia. J Hematol Oncol 2014;7:93.
4. McLornan D, Percy MJ, Jones AV, Cross NC, McMullin MF. Chronic neutrophilic leukemia with an associated V617F JAK2 tyrosine kinse mutation. Haematologica 2005;90:1696-7.
5. Lea NC, Lim Z, Westwood NB, et al. Presence of the JAK2 V617F tyrosine kinase mutation as a myeloid-lineage specific mutation in chronic neutrophilic leukemia. Leukemia 2006;20:1324-6.
6. Castelli R, Cugno M, Gianelli U, et al. Neutrophilic progression in a case of polycythemia vera mimicking chronic neutrophilic leukemia: clinical and molecular characterization. Pathol Res Pract 2015;211:341-3.
7.Zhang X, Pan J, Guo J. Presence of the JAK2 V617F mutation in a patient with chronic neutrophilic leukemia and effective response to interferon ?-2b. Acta Haematol 2013;130:44-6.
8. Fend F, Horn T, Koch I, Vela T, Orazi A. Atypical chronic myeloid leukemia as defined in the WHO classification is a JAK2 V617F negative neoplasm. Leuk Res 2008;32:1931-5.
Conflict of Interest:
Rewriting "Little Red Riding Hood" story may be dangerous
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: email@example.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
Positive tumors Papillary adenoma Sclerosing hemangioma/pneumocytoma Pneumocytic adenomyoepithelioma Carcinoid tumors ? Large cell neuroendocrine carcinoma (about 60%) Small cell lung cancer (about 80%) Atypical adenomatous hyperplasia Adenocarcinoma * Negative tumors Alveolar adenoma Salivary gland tumors Squamous cell carcinoma Mesothelioma
?, 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".
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.
Conflict of Interest:
Medicolegal quasi-hospital autopsies
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).
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.
Conflict of Interest:
Effect of diet and medicines on the serum iron and transferrin saturation
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 .
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
Conflict of Interest:
Authors Response: Histological grade in needle core biopsies of invasive carcinoma of the breast: the potential role of reduction of mitotic count threshold in improving agreement with grade in the surgical specimen
Dear Sir / Madam,
We are happy to address the points raised by Lee et al in their commentary on our paper  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.
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. 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.
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
Conflict of Interest:
Histological grade in needle core biopsies of invasive carcinoma of the breast: the potential role of reduction of mitotic count threshold in improving agreement with grade in the surgical specimen.
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
Conflict of Interest:
Comment on: 'The value of autopsies in the era of high-tech medicine: discrepant findings persist." Kuijpers C.C.H.J. et al. J Clin Pathol 2014;67:512-519 doi:10.1136/jclinpath-2013-202122
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. 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. Improper use of imaging investigations is contributing significantly to incorrect pre-mortem diagnosis. 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. 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, 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
Conflict of Interest:
Reply to Dr. G Stenhouse
The correspondent points out that the RCPath standards of 2007 were written for a symptomatic population. This is not specifically stated in the standards, which were written just as the UK pilots of FOB screening were concluding. The current proposed standards (2014) are still in draft stage. It seems clear however that it will apply equally to all cancers. The issue of the effect of preoperative therapy on reporting of SI, EMVI and node number is important. Unfortunately in our retrospective audit the use of the prefix "y" in staging patients who have had preoperative therapy was not universally applied. It is also true that in many units, including our own, the pathologist is not always informed that the patient has been treated by an oncologist. A tighter prospective study is needed. It should be noted that the revised national standards do not make any allowance for the effect of chemotherapy and radiotherapy. The comment that the failure of some units to meet minimum standards "....is likely to have serious adverse consequences for patient care" is , we feel, justified. There is significant crossover in under-reporting as can be seen by inspection of the tabulated data. Unit 10 on our tables, for example, did not report serosal invasion in any rectal cancer, reports only 10% EMVI and has a mean node yield of 5 for rectum and 10 for colon. It is certain that this will have led to understaging and possibly to denial of treatment to patients who would have benefitted. I agree that electronic reporting systems would be a major asset. We would certainly hope to ask for documentation of preoperative treatment in our follow-up audit!
Conflict of Interest:
Comment on 'A Survey of colorectal cancer in Scotland: compliance with guidelines and effect of proforma reporting'.
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)
Re:Mucosal large cell neuroendocrine carcinoma of the head and neck regions:inconsistent data
Answers to the letter Dear Dr. Sir. 1. We confirmed that the patient was 79 years-old man on case 2. As the mitosis index and the Ki-67 labeling index were estimated with newly prepared sections, the indices were a bit different. We confirmed that the tumor cells were focally positive for chromogranin-A, but negative for synaptophysin on case 2. 2. Certainly, at the writing step of the review article (ref.3), the prognosis of our series of M-LCNEC was relatively good, but the prognosis became worse one year after that time. We concluded that the prognosis of M-LCNEC was relatively worse, like the LCNEC of other organs, in this recent paper (ref. 1). Moreover, we confirmed that three cases of M-LCNEC were positive for thyroid transcription factor(TTF)-1. 3. We confirmed that the age ranged from 52 to 74 years old in our M-LCNEC series and that four patients were alive without disease (31 months, 18 months, 24 months and 90 months).
Dr. Kimihide Kusafuka, D.D.S., Ph.D. Pathology Division, Shizuoka Cancer Center Hospital and Research Institute
Conflict of Interest:
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