17 e-Letters

published between 2017 and 2020

  • Loss of MMR proteins expression as predictive marker for immunotherapy in malignant melanoma patients

    El Jabbour T et al. (Jun 2017) described the association between immunohistochemical PD-L1 positivity and loss of MMR proteins in colorectal cancer. However, the evaluation of Mismatch Repair Deficiency (dMMR) as a immunotherapy predictive marker is lacking for Malignant Melanoma (MM) and other malignancies, such as genitourinary, prostate, bladder, head and neck cancers, that are treated with immune checkpoint inhibitors (ICPI).

    We recently assessed dMMR in MM patients treated with anti-PD-1/PD-L1 during 2014-2016 at University of Modena and Reggio Emilia: 7% of primary melanoma and 13% of metastasis showed the dMMR. We report a patient whose primary MM and metastasis showed dMMR with immunohistochemical lack of MSH6 expression. Her complex history was characterized by the regression of the multiple cerebral and visceral metastases after anti-PD-L1 therapy, and an extraordinary progression-free survival (1150 days) and overall-survival (2646 days). At present, she is still alive and well, and had the longest response to anti-PD-L1 treatment.

    Our results emphasize that the immunohistochemical assessment of MMR protein expression in MM patients represents a useful predictive marker, which may have crucial importance for the determination of the response of anti-PD-1/PD-L1 therapy for MM and potentially for other solid malignancies treated with ICPI therapy.

  • Authors' reply

    We were pleased to read the correspondence ‘Stage II patients can benefit from OSNA molecular lymph node staging’ from Cuatrecasas et al. and grateful for the authors’ interest and comments. Our study with one-step nucleic acid amplification (OSNA) for patients with colorectal cancer (CRC) primarily aimed to evaluate the accuracy of the test as compared with the standard care approach of a single H&E microscopic examination. We hoped to share with readers our experiences of working with this technology and highlight the challenges other centres will need to consider before introducing the service.[1]
    While we acknowledged the concern raised by Cuatrecasas et al. that our study cohort of 19 patients is small, we emphasise that we tested 82 lymph nodes with OSNA and feel our results show a fair indication of the concordance of the assay with routine histology. It is also important to point out that initially more patients were recruited for the study but several specimens had to be excluded due to faecal contamination, sealed perforation or macroscopic serosal (T4) disease – all of which could arguably lead to false positive results by OSNA. The significance of our data is that to our knowledge this was the first time OSNA had been fairly compared with routine histology rather than intensive work-up of multiple levels, immunohistochemistry (IHC) and conventional molecular methodologies. We agree that there is insufficient convincing evidence that intensive interrog...

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  • Response to Jones: “Never mind religion, how about desecration?”

    We are intrigued by, and sympathetic toward, Dr Jones’ argument; we had approached our argument from the existing case law rather than from the fundamental position that dissection without good reason is morally unacceptable. We can understand that that position is supported by the need for appropriate consent in circumstances outwith a coroner’s jurisdiction. We would agree that invasive dissection that serves no defined purpose cannot be consonant with autonomy, beneficence, non-maleficence and justice.

  • Stage II patients can benefit from OSNA molecular lymph node staging

    Dear Sirs,

    We have read with interest and concern the correspondence letter published in the July issue of your journal “OSNA testing for lymph node staging in colorectal cancer”.
    Although the authors state on the letter “We aim to provide unbiased data on the diagnostic accuracy of OSNA in detecting CRC nodal metastases and feedback the practicalities of running such a service in a National Health Service (NHS) cellular pathology department”, we think the information given in their article is somehow incomplete. Their conclusions are based on the analysis of 99 lymph nodes (LNs) from a small cohort of 19 cases, with only 5.2 LNs examined per patient. Current guidelines, including the guidance of The Royal College of Pathologists, recommend that at least 12 LNs should be assessed to ensure an adequate specimen evaluation and a reliable pathologic staging.[1] In contrast, several studies using colon cancer OSNA lymph node analysis have assessed 12 or more LNs.[2–4]
    We agree with their statement that intraoperative OSNA detection of LN metastasis does not have a role in CRC surgery, mainly because regional lymphadenectomy is invariably included with the colectomy specimen. But this is not the target of molecular lymph node assessment in CRC. The most important clinical application of molecular LN analysis in CRC is that it enables a more precise staging in early CRC than the one obtained with conventional H&E analysis, especially useful for stage II pa...

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  • Never mind religion, how about desecration?

    In their article considering the relationship between Articles 8 and 9 of the European Convention of Human Rights (ECHR) and coronial autopsies, Leadbeatter and James argue that recourse to invasive autopsy ought only to be made after an ‘issues based’ investigation establishes that this is necessary. This stands in stark contrast to current practice.

    Whilst Leadbeatter and James write to report their own research findings and discuss the decision in R (Rotsztein) v HM Senior Coroner for Inner London North, I was prompted to consider whether they were too restrained in their conclusions. My primary concern is that whilst redress to the ECHR may be legally and rhetorically attractive, it means that outcomes are dependent on the still living taking action. This may, or may not, promote the deceased person’s preferred course of action.

    Prior to addressing this point in more detail, however, a brief mention to the necessity of invasive autopsies where a death occurs in suspicious circumstances. Leadbeatter and James discuss this; I found their discussion of ‘injury’ (Box 2, Issue 4) particularly interesting. They give the example of road or train deaths, where their approach was to first review evidence from the scene, take toxicology samples and remove trace evidence. Another example might be where a person is shot in the head at close range, the events being caught on CCTV. These examples highlight that even in extreme circumstances evisceration of the body m...

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  • Corroborating evidence for atypical breast aspirates

    Dear Editor
    RE: Atypical aspirates of the breast: a dilemma in current cytology practice. Shuang-Ni Yu, Joshua Li, Sio-In Wong, Julia Y S Tsang, Yun-Bi Ni, Jie Chen, Gary M Tse. J Clin Pathol 2017;0:1–9. doi:10.1136/jclinpath-2016-204138
    We read with interest the findings of Shuang-Ni Yu et al regarding “Atypical aspirates of the breast: a dilemma in current cytology practice” first published on May 29 2017 in Journal of Clinical Pathology.
    Breast fine needle aspiration (FNA) utilisation has been in decline for some time and there are several reasons for the drop in the uptake of cytology in the investigation of breast diseases. Although the main sited reason is increased demand for ancillary tests, greater subjectivity of cytology when compared to histology which is generally regarded as the gold standard, and the unpreparedness of pathologists to provide unequivocal diagnoses not only in the borderline lesions but also in low grade malignancies. The need to provide a consistently high quality service to engender confidence in our speciality has never been greater.
    The probabilistic approach to reporting FNA based on the 5 tier categories (C1 unsatisfactory; C2 benign; C3 atypical/indeterminate; C4 suspicious; and C5 malignant) does provide reliable accurate diagnoses for all categories except C1 unsatisfactory and C3 atypical/indeterminate categories. The C1 category highlights a failed FNA procedure whilst a C3 result indicates some diagnostic un...

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  • [Error figure 1] Sokal Score Formula

    Good Morning,

    I just want to put out a typo in figure (1) : the sokal score formula should be : exp(0.0116*(age - 43.4 ) + ... and not exp(0.0116*(age - 4.34 ) +... .

    If you use 4.34 all you patients will be in "High Risk Group".

    source : Sokal JE, Cox EB, Baccarani M, Tura S, Gomez GA, Robertson JE, et al. Prognostic discrimination in « good-risk » chronic granulocytic leukemia. Blood. 1 avr 1984;63(4):789‑99.


    Jim Canet