Frozen Section Analysis of Breast Lumpectomy Margins

Objectives: To evaluate breast lumpectomy margins by frozen section in breast conservation surgery. Methods: A retrospective study of frozen section of lumpectomy margins of one hundred ten patients was done at King Abdulaziz University Hospital from June 2007 to June 2013. All patients underwent lumpectomy + Sentinel lymph node biopsy. Patient records were studied for location of mass in breast, size of mass, site of breast, pre or postmenopausal, frozen section margins, new frozen section margins, permanent margins, reoperation. Complications like skin necrosis, numbness, and wound infection were studied. Result: Majority were Saudis (64.5%). Left breast was involved in 60%. Upper outer quadrant was involved in majority (51.9%). Size of mass was less than 1 cm in 14.8% cases, 1 2.9 cm in 43.5%, 3 4 cm in 13%, more than 4 cm in 10.2%. Lumpectomy plus sentinel lymph node biopsy was done in 96.4% and lumpectomy and axillary lymph node dissection was done in 1.8% cases. Gross margins were positive in 17.3% and frozen margins were positive in 28.2%. New margin on frozen section were positive in 3.6% and negative in 79.1%. Permanent section histology showed positive margins in 5.5% and negative in 94.5% cases. Re-operation was done in 7.3%. Lympho-vascular margins were positive in 20.9%. Skin necrosis was found in 2.2%, numbness was found in 4.4%, wound infection was in 2.2%. Conclusion: Lumpectomy margins with frozen section reduce re-operation and recurrence.

has many advantages, like maintaining the shape, less mutilating, and better psychological outcome.BCS has higher local recurrence than mastectomy [1] [2].Many factors play a role in recurrence after BCS, like tumor stage and grade, lympho-vascular invasion, molecular status and surgical margin.Positive surgical margin has 2 -3 times chances of recurrence than negative margin [3].Intra-operatively emphasis should be given to achieve negative margins.Frozen section analysis [FSA] is used for lumpectomy margins where freezing and sectioning of specimen is followed by thawing, fixation and staining and can be done in half an hour [4].Other method is imprint cytology where specimen is pressed onto glass slides and making imprint of all six margins with the principle that only malignant cells adhere to slides [5].BCS done for breast cancer and Ductal carcinoma in situ [DCIS] has positive margins from 15% to 47% [6] [7] [8] [9].Re-excision rates range from 23% to 59% [10] [11] [12].Previously more than 1 cm margins were considered safe [13] [14], but recent evidence shows equivalent rates of recurrence with 1 -2 mm margins [15] [16].We present our experience with lumpectomy margins and outcome.

Methods
At King Abdulaziz University Hospital, Jeddah between June 2007 to January 2013 a retrospective study of frozen section analysis of breast lumpectomy margins was done.Number of patients studied were 110.Inclusion criteria was females with breast lump over 18 years of age undergoing breast conservation surgery.Exclusion were patients undergoing modified radical mastectomy.Hospital records of Patients were studied by searching hospital information system.OPD records as well as inpatient records were studied regarding age, nationalities, menopausal status, location of mass in breast, size of mass, left or right breast mass, previous surgery or radiotherapy, radiological evaluation, type of surgery done, adjuvant or neo-adjuvant chemotherapy, gross margins, frozen section margins, new frozen section margins, permanent margins, reoperation, intra-operative radiotherapy[IOR], tumor type, lympho-vascular invasion, estrogen receptor [ER],progesterone receptor[PR], HER2, metastasis, stage of disease, tumor size, no. of lymph nodes, sentinel lymph node dissection [SLD] done.Post operative complications like skin necrosis, numbness, wound infection were studied.Operation done during this period were extensively studied for frozen section analysis of breast lumpectomy margins.Patients were followed for two years.This study was approved by hospital ethical committee.Statistical analysis was done using SPSS.

Results
Majority of patients were Saudis (64.5%), and rest were from different nationalities like Yemeni, Egyptians, Palestinian, Syrians, and Jordanians (Figure 1).
There was history of previous surgery in 9.1%.Menopausal status was studied and majority of our patients were post-menopausal (56.4%) and Pre menopausal were 43.6% (Figure 2).In majority of cases left breast was involved (60%) and   right breast in 40% of cases.Upper outer quadrant was involved in majority of cases (51.9%), upper inner quadrant in 13.9%, retro-areolar in 12.7%, lower inner quadrant in 6.4%, lower outer in 3.6%, supra-areolar in 1.8%, and infraareolar in 0.9% (Figure 3).In our study size of breast mass was mostly between 1 -2.9 cm (43.5%), 13% had mass between 3 -4 cm, more than 4 cm was found in 10.2% and subcentimetric was 14.5% (Figure 4).There was history of previous axillary surgery in minority of cases (3.7%).Pre-operative assessment by radiology was done in most of cases (68.2%).operating room.After lumpectomy breast mass was sent for frozen section analysis of margins which were found positive for malignancy in 28.2% of cases.A rim of tissue of the cavity was shaved and sent for frozen section again to confirm complete excision of malignant mass.These tissue showed new margins positive for malignancy on frozen section in 3.6% of cases.Most of cases were found negative for malignancy in frozen section (79.1%) in re-lumpectomy tissue.Permanent section histology showed positive margins in 5.5% of cases who were negative in frozen section.Permanent section negative margins were however in majority of patients (94.5%) (Figure 5).Re-operation of patients who were positive on permanent section was done in 7.3%.Intra-operative radiotherapy was done in 29.1%.Most of our patients underwent sentinel Lymph node biopsy (98.2%).More than two sentinel lymph nodes were retrieved in majority of cases.SLN on frozen section were found positive for malignancy in 25.5%, while on permanent section they were positive in 38.2%.Completion axillary dissection was done in 34.5%.

Discussion
Advent of breast conserving surgery has dramatically decreased mastectomies.
Lumpectomy margins are subject of debate as how much safety margin is safe.[NCCN] also recommends that if inked margins are negative for invasive cancer then no further surgery is required [18].For DCIS accepted negative margin is more than 10 mm.Meta-analysis showed that margin more than 10 mm has de- 59% [10] [11] [12] and some reports more than 50% [24] [25] but our re-excision rate is 28% which is similar to Uecker et al. [26].Completion mastectomy rate is 14% [27].Osborn et al. reported that patient who underwent lumpectomy without frozen section analysis had re-operation rate of 15% -50% while those who had frozen section at time of lumpectomy had re-operation rate of 3% [28].Our re-operation rate with frozen section analysis was 5.5%.Frozen section analysis of lumpectomy margins avoided re-operation and so saved patients from morbidity and recurrence.Permanent section analysis showed margins positive for malignancy in 5.5% of cases in our patients.Frozen section analysis of lumpectomy margins helped in reducing positive margins of 38.2% to 5.5% finally in permanent section.
To avoid re-excision which carry additional morbidity, there is a talk by some surgeons to perform cavity shaving [24] [29].Recurrence rate is inversely related with the distance of tumor foci from ink margin [5].Macrosopically it is difficult to distinguish tumor cells on lumpectomy margins, so frozen section analysis is an indispensible tool for complete excision of tumor.Incorporating routine frozen section analysis of breast lumpectomy margins in surgical practice will avoid complications and recurrence of disease.

Conclusion
Frozen section of breast lumpectomy margins is an indispensable step in breast conservation surgery as it decreases recurrence and re-operation rate.

Figure 2 .
Figure 2. General characteristics of Patients.