The perfect pathology report after neodjuvant therapy

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1 The perfect pathology report after neodjuvant therapy Anna Sapino Department of Medical Sciences University of Torino (ITALY) Deptof LaboratoryMedicine AO Citta della Salute-Torino (ITALY)

2 Impossibile visualizzare l'immagine. Arch Pathol Lab Med. 2009;133: Conclusions Pathologists play a key role in the evaluation of pathologic response, which is extremely important as a prognostic factor for individual patients, as a short- term endpoint for clinical trials, and as an adjunct for research studies. Therefore, surgical pathologists must be familiar with the gross examination, sampling, and reporting of breast carcinomas after neoadjuvant therapy.

3 The Breast 22 (2013) S88eS91 Epilogue Neoadjuvant systemic treatments will be used more and more often both in clinical research and in the daily practice. Assessing tumourresponse to the different systemic treatments will become a major responsibility for the pathologists. Harmonization of protocols for macroscopic and microscopic evaluation of tumourresponse and for assessment of prognostic/predictive markers is urgently needed.

4 British Journal of Cancer (2013) Conclusion We found considerable variability in the completeness of reporting of surgical specimens within this national neoadjuvant breast cancer trial. This highlights the need for consensus guidelines among trial groups on histopathology reporting, and the participation of histopathologists throughout the development and analysis of neoadjuvant trials.

5 Pathologyreporting afterneoadjuvant treatment hasbeenprovenquite troublesome..

6 A perfect(optimal) histopathology report afterneoadjuvant chemo: Can onlybe achievedby a closecollaboration between distinct expertise because: - itreports info on a lesionthatmaynotbe presentor may be altered by treatment - the lesionmust be comparedwith the pre-treatment biopsy

7 Whatdo pathologistsneedto know? Thatthe patienthasreceivednac Viale G. The Breast 22 (2013) S88eS91

8 Whatdo pathologistsneedto know? PATIENT INFORMATION - Patient clinical information (age, size, metastasis) - NAT treatment (details)

9 Whatdo pathologistsneedto know? RADIOLOGICAL INFORMATION Radiological information before and after NAT size and location of the tumor, multifocality, radiological appearance, MR results Instrumental for the processing of the specimens

10 Whatdo radiologistsneed? DESCRIPTION OF MACROSCOPIC APPEARANCE AND MEASUREMENT OF DISEASE EXTENSION. The identification of the tumor bed may be very challenging in case of a substantial or complete response to the NACT Viale G. The Breast 22 (2013) S88eS91

11 Specimen radiographs may be needed to help identifying the clipand to ensure complete excision of the tumor bed whenever its precise location and extent is not readily apparent. Viale G. The Breast 22 (2013) S88eS91 Recognizing Pitfalls in Early and Late Migration of Clip Markers after Imaging-guided Directional Vacuumassisted Biopsy Esserman LE RadioGraphics 2004 If a tattoo method has been used to identify the site of the tumourthen this area should be easily identified macroscopically. European Guidelines for Quality Assurance in Breast Cancer Screening and Diagnosis Fourth edition Supplement

12 Whenever the lesion is not evident: Grossstandardization

13 Whenever the lesion is not evident:

14 Whenever the lesion is not evident:

15 Wheneverthe lesionisnotevident: Grossstandardization

16 Whatdo pathologistsneedto know? ACCURATE HISTOPATHOLOGICAL FEATURES ASSESSED BEFORE NAT MANDATORY INFO: - histotype, tumor cellularity, necrosis - grade - ER/PR/HER2/KI67 - sentinel lymph-node FNA/histology OPTIONAL INFO: - microscopic images (to be compared with the histopathological features of the surgical specimen)

17 J Natl Cancer Inst Monogr 2011;43:86 90 HER2 ER Tumour heterogeneity

18 Whatdo surgeons& oncologistsneed? DIAGNOSIS NON-pCR Mandatory info: -Tumor histological type (size, multifocality) + LN assessment - Staging (yptnm) - Grading - Surgical margins - Prognostic & predictive factors Optional info: - necrosis, fibrosis pcr Mandatory info: -Description of residual in situ lesions (if present) with margin evaluation Optional info: - Description of histopathological features induced by treatment (fibrosis, necrosis) both in the breast and in the axillary lymph-nodes (optional but recommended to perform radio-histological correlations)

19 Whatdo surgeons& oncologistsneed? Categorization of tumor response to therapy according to published classification systems (MANDATORY INFO): - In the mammary gland - In the axillary lymph-nodes Performed by comparing pre-nat core biopsy with surgical specimen

20 SYSTEMS TO CATEGORIZE PATHOLOGICAL RESPONSE TO PREOPERATIVE SYSTEMIC TREATMENT IN BREAST CANCER 1. Bonadonna G et al J Natl Cancer Inst Chevallier B et al. Am J Clin Oncol Sataloff DM et al. J Am Coll Surg Smith IC et al. J Clin Oncol Fisher ER et al. Cancer 2002 (NSABP B-18) 6 Ogston KN et al. Breast Symmans W et al. J Clin Oncol 2007 (RCB) Pinder SE et al. Penault-Llorca F. et al Histopathology 2007 Human Pathology 2007

21 Results: In all, 825 surgical reports from 816 patients were available for review. Out of 4125 data items there were 347 discrepant results (8.4% of classifications), which involved 281 patients. These involved grading of breast response (169 but only 9 involving pcr vs Minimal Residual Disease); laterality (6); presence of axillary metastasis (35); lymph node counts (108); and type of axillary surgery (29).

22 xcv pcr xc Human Pathology(2008) 39,

23 Penault-Llorca F et al. Human Pathology (2008) 39, patients with neoadjuvant treated breast cancer Chevallier B et al. Am J Clin Oncol 1993 Sataloff DM et al. J Am Coll Surg 1995 The pcr rate was 14.3% according to the Chevallier s and 25.8% according to the Sataloff's classification.

24 Excluding cases with pcr, only 45% of reports included any comment regarding response in the breast and 30% in the axillary lymph nodes. A formal comment about therapy response is missing in up to 55% of all non-pcr cases

25 In addition, reports were reviewed and interpreted by a pathologist and an oncologist and distinct interpretations were performed in some cases..as an example, the oncologist and chief investigator tended to interpret the pathology report as indicating the presence of chemotherapy response more frequently than the pathologist

26 Possibleissues: Margins Margins can be more difficult to evaluate after neoadjuvant therapy (NAT). The significance of tumor bed at the margin is unclear in patients with a pcr. In cases with scattered residual foci of invasive carcinoma or ductal carcinoma in situ throughout a tumor bed, tumor bed changes at the margin may be predictive of the possibility of residual carcinoma in the breast. Sahooand Lester, ArchPatholLab Med2009

27 Pathological Complete Response (pcr) Primary tumor: no residual carcinoma, or no residual invasive tumour but presence of in situcarcinoma in the surgical specimen Lymph node: no evidence of metastatic disease

28 Residual DCIS/Surgical margins Large Formalin fixed paraffin embedded section recommended BCT: DCIS on the surgical margins or close (2 mm), re-excision warranted to assure clear margins before irradiation J Clin Oncol 25:

29 Possibleissues: tumoremboli only Tumor emboli may be the only residual tumor (size= extension?) For unknown reasons, in some tumors, the in situ carcinoma and tumor emboli in vascular spaces (lympho- vascular invasion or LVI) are relatively resistant to treatment when compared to carcinoma invading the stroma. Sahoo and Lester Arch PatholLab Med. 2009

30 Modern Pathology (2010) 23,

31 Possibleissues: Lymph-nodes Complete pathologic response to prior metastatic involvement in some cases cannot be determined with certainty because metastasis can resolve without a scar or may leave small fibrous scars Pre-operative FNA demonstrating the presence of MTS on clinically or US suspect LN should be perfomed

32 The optimal pathology report after neodjuvant therapy Pathologists dealing with specimens obtained, before and after NAT should be expert breast pathologists PRE- NAT: Clinical, Radiological data POST NAT: accurate description of the specimen Accurate morphological diagnosis Accurate assessment of ER/PR/HER2/ki67 Classification of tumor response Participation to multidisciplinaydiscussion is mandatory