J Pathol Transl Med.  2021 Nov;55(6):380-387. 10.4132/jptm.2021.07.29.

A multicenter study of interobserver variability in pathologic diagnosis of papillary breast lesions on core needle biopsy with WHO classification

• Kang HJ
• Kwon SY
• Kim A
• Kim WG
• Kim EK
• Kim AR
• Kim C
• Min SK
• Park SY
• Sung SH
• Yoon HK
• Lee A
• Lee JS
• Lee HI
• Lee HC
• Lim SC
• Jun SY
• Jung MJ
• Jung CW
• Cho SY
• Cho EY
• Choi HJ
• Park SY
• Kim JY
• Park IA
• Kwon Y

• KMID: 2522439
• DOI: http://doi.org/10.4132/jptm.2021.07.29

Abstract

Background
Papillary breast lesions (PBLs) comprise diverse entities from benign and atypical lesions to malignant tumors. Although PBLs are characterized by a papillary growth pattern, it is challenging to achieve high diagnostic accuracy and reproducibility. Thus, we investigated the diagnostic reproducibility of PBLs in core needle biopsy (CNB) specimens with World Health Organization (WHO) classification.
Methods
Diagnostic reproducibility was assessed using interobserver variability (kappa value, κ) and agreement rate in the pathologic diagnosis of 60 PBL cases on CNB among 20 breast pathologists affiliated with 20 medical institutions in Korea. This analysis was performed using hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for cytokeratin 5 (CK5) and p63. The pathologic diagnosis of PBLs was based on WHO classification, which was used to establish simple classifications (4-tier, 3-tier, and 2-tier).
Results
On WHO classification, H&E staining exhibited ‘fair agreement’ (κ = 0.21) with a 47.0% agreement rate. Simple classifications presented improvement in interobserver variability and agreement rate. IHC staining increased the kappa value and agreement rate in all the classifications. Despite IHC staining, the encapsulated/solid papillary carcinoma (EPC/SPC) subgroup (κ = 0.16) exhibited lower agreement compared to the non-EPC/SPC subgroup (κ = 0.35) with WHO classification, which was similar to the results of any other classification systems.
Conclusions
Although the use of IHC staining for CK5 and p63 increased the diagnostic agreement of PBLs in CNB specimens, WHO classification exhibited a higher discordance rate compared to any other classifications. Therefore, this result warrants further intensive consensus studies to improve the diagnostic reproducibility of PBLs with WHO classification.

Keyword

Papillary breast lesion; Core needle biopsy; Interobserver variability; Agreement rate

Figure

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  Fig. 1 Composition of the pathologic diagnosis in all 60 papillary breast lesions. SPC, solid papillary carcinoma; IDP, intraductal papilloma; ADH, atypical ductal hyperplasia; DCIS, ductal carcinoma in situ; PCIS, papillary carcinomas in situ; EPC, encapsulated papillary carcinoma; SPC, solid papillary carcinoma.

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  Fig. 2 Interobserver variability in the pathologic diagnoses of all 60 papillary breast lesions cases, intraductal papillary neoplasms (IDPN), and encapsulated/solid papillary carcinoma (EPC/SPC) with hematoxylin and eosin staining in all classifications. WHO, World Health Organization classification; 4-tier, 4-tier classification; 3-tier, 3-tier classification; 2-tier, 2-tier classification.

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  Fig. 3 Interobserver variability in the pathologic diagnoses of all 60 papillary breast lesions cases, intraductal papillary neoplasms (IDPN), and encapsulated/solid papillary carcinoma (EPC/SPC) with immunohistochemical staining in all classifications. WHO, World Health Organization classification; 4-tier, 4-tier classification; 3-tier, 3-tier classification; 2-tier, 2-tier classification.

Reference

References

1. Tay TK, Tan PH. Papillary neoplasms of the breast: reviewing the spectrum. Mod Pathol. 2021; 34:1044–61.

2. Jorns JM. Papillary lesions of the breast: a practical approach to diagnosis. Arch Pathol Lab Med. 2016; 140:1052–9.

3. Ni YB, Tse GM. Pathological criteria and practical issues in papillary lesions of the breast: a review. Histopathology. 2016; 68:22–32.

4. Lewis JT, Hartmann LC, Vierkant RA, et al. An analysis of breast cancer risk in women with single, multiple, and atypical papilloma. Am J Surg Pathol. 2006; 30:665–72.

5. Louwman MW, Vriezen M, van Beek MW, et al. Uncommon breast tumors in perspective: incidence, treatment and survival in the Netherlands. Int J Cancer. 2007; 121:127–35.

6. Yamaguchi R, Tanaka M, Tse GM, et al. Management of breast papillary lesions diagnosed in ultrasound-guided vacuum-assisted and core needle biopsies. Histopathology. 2015; 66:565–76.

7. Moon SM, Jung HK, Ko KH, Kim Y, Lee KS. Management of clinically and mammographically occult benign papillary lesions diagnosed at ultrasound-guided 14-gauge breast core needle biopsy. J Ultrasound Med. 2016; 35:2325–32.

8. Brogi E, Horii R, Mac Grogan G, et al. Papillary neoplasms. Lokuhetty D, White VA, Watanabe R, Cree IA, editors. WHO classification of breast tumors. 5th ed.Lyon: International Agency for Research on Cancer;2019. p. 49–67.

9. O’Malley F, Visscher D, MacGrogan G, Tan PH, Ichihara S. Intraductal papillary lesions. Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, van de Vijver MJ, editors. WHO classification of tumours of the breast. 4th ed.Lyon: International Agency for Research on Cancer;2012. p. 99–109.

10. Rakha EA, Ellis IO. Diagnostic challenges in papillary lesions of the breast. Pathology. 2018; 50:100–10.

11. Qiu L, Mais DD, Nicolas M, Nanyes J, Kist K, Nazarullah A. Diagnosis of papillary breast lesions on core needle biopsy: upgrade rates and interobserver variability. Int J Surg Pathol. 2019; 27:736–43.

12. Douglas-Jones A, Shah V, Morgan J, Dallimore N, Rashid M. Observer variability in the histopathological reporting of core biopsies of papillary breast lesions is reduced by the use of immunohistochemistry for CK5/6, calponin and p63. Histopathology. 2005; 47:202–8.

13. Jakate K, De Brot M, Goldberg F, Muradali D, O’Malley FP, Mulligan AM. Papillary lesions of the breast: impact of breast pathology subspecialization on core biopsy and excision diagnoses. Am J Surg Pathol. 2012; 36:544–51.

14. Ellis IO, Humphreys S, Michell M, et al. Best Practice No 179. Guidelines for breast needle core biopsy handling and reporting in breast screening assessment. J Clin Pathol. 2004; 57:897–902.

15. Elmore JG, Longton GM, Carney PA, et al. Diagnostic concordance among pathologists interpreting breast biopsy specimens. JAMA. 2015; 313:1122–32.

16. Koo JS, Han K, Kim MJ, Moon HJ, Kim EK, Park BW. Can additional immunohistochemistry staining replace the surgical excision for the diagnosis of papillary breast lesions classified as benign on 14-gage core needle biopsy? Breast Cancer Res Treat. 2013; 137:797–806.

17. Boecker W, Moll R, Dervan P, et al. Usual ductal hyperplasia of the breast is a committed stem (progenitor) cell lesion distinct from atypical ductal hyperplasia and ductal carcinoma in situ. J Pathol. 2002; 198:458–67.

18. Otterbach F, Bankfalvi A, Bergner S, Decker T, Krech R, Boecker W. Cytokeratin 5/6 immunohistochemistry assists the differential diagnosis of atypical proliferations of the breast. Histopathology. 2000; 37:232–40.

19. Lerwill MF. Current practical applications of diagnostic immunohistochemistry in breast pathology. Am J Surg Pathol. 2004; 28:1076–91.

20. Hoda SA, Rosen PP. Practical considerations in the pathologic diagnosis of needle core biopsies of breast. Am J Clin Pathol. 2002; 118:101–8.

21. Collins LC, Carlo VP, Hwang H, Barry TS, Gown AM, Schnitt SJ. Intracystic papillary carcinomas of the breast: a reevaluation using a panel of myoepithelial cell markers. Am J Surg Pathol. 2006; 30:1002–7.

22. Cui X, Wei S. Composite encapsulated papillary carcinoma and solid papillary carcinoma. Pathol Int. 2015; 65:133–7.

23. Hashmi AA, Faraz M, Rafique S, Adil H, Imran A. Spectrum of papillary breast lesions according to World Health Organization classification of papillary neoplasms of breast. Cureus. 2020; 12:e11026.

24. Agoumi M, Giambattista J, Hayes MM. Practical considerations in breast papillary lesions: a review of the literature. Arch Pathol Lab Med. 2016; 140:770–90.

25. Feinstein AR, Cicchetti DV. High agreement but low kappa: I. The problems of two paradoxes. J Clin Epidemiol. 1990; 43:543–9.

26. Tramm T, Kim JY, Tavassoli FA. Diminished number or complete loss of myoepithelial cells associated with metaplastic and neoplastic apocrine lesions of the breast. Am J Surg Pathol. 2011; 35:202–11.

27. Cserni G. Benign apocrine papillary lesions of the breast lacking or virtually lacking myoepithelial cells-potential pitfalls in diagnosing malignancy. APMIS. 2012; 120:249–52.

28. Wei S. Papillary lesions of the breast: an update. Arch Pathol Lab Med. 2016; 140:628–43.