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• 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
  Joseph F Loane
  Published on: 18 April 2016
• 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.
  Andrew HS Lee
  Published on: 18 April 2016

• Published on: 18 April 2016

  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

  • Joseph F Loane, Consultant Pathologist
  • Other Contributors:
    • Catharine A Dhaliwal and Catriona Graham

  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...

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  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 (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

  Conflict of Interest:

  None declared

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  Conflict of Interest:
  None declared.

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• Published on: 18 April 2016

  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.

  • Andrew HS Lee, Consultant Histopathologist
  • Other Contributors:
    • Emad A Rakha, Zsolt Hodi, Ian O Ellis

  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...

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  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:

  None declared

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  Conflict of Interest:
  None declared.

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