|Year : 2018 | Volume
| Issue : 3 | Page : 74-79
Comparing Frozen and Paraffin Section in the Detection of Metastases in Sentinel Lymph Node in Breast Cancer in Aminu Kano Teaching Hospital, Kano, North-Western, Nigeria
Abdurrahman A Sheshe1, Abubakar B Muhammad2, Amina El-Yakub1, Ibrahim Suleiman1
1 Department of Surgery, Bayero University Kano, Kano, Nigeria
2 Aminu Kano Teaching Hospital Kano, Kano, Nigeria
|Date of Web Publication||29-Jul-2019|
Dr. Abubakar B Muhammad
Department of Surgery, Aminu Kano Teaching Hospital, Kano
Background: Sentinel lymph node biopsy is an effective diagnostic procedure to determine the need to treat the axilla or otherwise in patients with early breast cancer to avoid its inherent complication and further morbidity. Frozen section is one of the acceptable methods of scrutinizing sentinel lymph nodes to enable decision be made intraoperatively. This study is aimed to determine the sensitivity of frozen section biopsy in the diagnosis of positive sentinel lymph nodes in patients with early breast cancer.
Materials and Methods: The study was conducted in the Surgery and Pathology Departments of Aminu Kano Teaching Hospital, Kano, from September 2015 to March 2017. Consecutive patients diagnosed with early breast cancer, who met the inclusion criteria, were recruited into the study after obtaining informed consent. Early breast cancer in this study was defined as stage I (T1, N0, M0) or stage IIA (T2, N0, M0). Additional information included age, sex, menopausal status, surgical procedures, duration of surgery, and the histopathological types. Statistical and comparative analysis was made.
Result: A total of 117 patients with breast cancer were seen at the General Surgery Outpatient Department during the study period. Out of these patients, 40 met the inclusion criteria and were recruited for the study. The age range of 28 to 70 years and mean age of 47.4 ± 11.6 years were recorded. Twenty-two (55%) patients were premenopausal. Eighty-two sentinel lymph nodes were harvested and analyzed. Twenty-eight (34.1%) sentinel nodes were found to be positive by frozen section, whereas 54 (65.9%) were negative. The paraffin section analysis showed that 44 (53.7%) out of 82 sentinel nodes were positive for malignancy, whereas 38 (46.3%) were negative. The sensitivity, specificity, and accuracy of frozen section were 70.8%, 100%, and 82.5%, respectively. The false-negative rate was 29.2% (P = 0.292, confidence interval = 90%).
Conclusion: Frozen section biopsy of sentinel lymph node is not as effective as routine staining technique in detecting malignant cells in patients with early breast cancer.
Keywords: Breast cancer, frozen section, sentinel node biopsy
|How to cite this article:|
Sheshe AA, Muhammad AB, El-Yakub A, Suleiman I. Comparing Frozen and Paraffin Section in the Detection of Metastases in Sentinel Lymph Node in Breast Cancer in Aminu Kano Teaching Hospital, Kano, North-Western, Nigeria. Sub-Saharan Afr J Med 2018;5:74-9
|How to cite this URL:|
Sheshe AA, Muhammad AB, El-Yakub A, Suleiman I. Comparing Frozen and Paraffin Section in the Detection of Metastases in Sentinel Lymph Node in Breast Cancer in Aminu Kano Teaching Hospital, Kano, North-Western, Nigeria. Sub-Saharan Afr J Med [serial online] 2018 [cited 2019 Nov 12];5:74-9. Available from: http://www.ssajm.org/text.asp?2018/5/3/74/263562
| Introduction|| |
Breast cancer is a major health burden worldwide. It is the most common cause of cancer among women in developed and third-world countries, including Nigeria. More than 1.1 million cases are diagnosed, and more than 410,000 patients die of it worldwide each year. The incidence of breast cancer is increasing, especially in sub-Saharan Africa, including Nigeria.
Tumor size, biology, grading, axillary lymph node status, and race are very important prognostic factors in predicting overall survival and locoregional recurrence in patients with potentially curable carcinoma of the breast. However, several studies indicate that axillary lymph node status plays an important role in the prognosis of breast cancer.,,
Unfortunately, physical examination and radiologic imaging of the axilla cannot accurately predict the occurrence of axillary metastases. Definitive diagnosis of axillary metastasis in patients with breast cancer requires excision and histological examination of axillary lymph nodes. This is, however, associated with significant postoperative complications, which include wound infections, lymphedema of the arm, limitation of arm movement, lymphangitis, and arm numbness. A less radical surgery is, therefore, desirable and necessary for diagnosing axillary lymph node metastasis.
Sentinel lymph node biopsy is a minimally invasive technique to select patients with sentinel node, which is the node that primarily receives direct lymphatic drainage from a primary tumor site.,
The pathological assessment of the nodes could be by touch imprint cytology, frozen section that would give immediate result within a few minutes, or paraffin section (formal histology) that takes a minimum of 3 days for the result to be available. Paraffin (permanent) section is the gold standard test that was used in this study for which comparison with frozen section was made.
In this study, we determined the sensitivity, specificity, and accuracy of frozen section in evaluation of sentinel lymph nodes in patients with breast cancer.
| Materials and methods|| |
The study was conducted at the General Surgical Unit and Pathology Department, both of Aminu Kano Teaching Hospital, Kano, north-west Nigeria. It was a prospective study of consecutive female adult patients with early breast cancer [patients with stage I (T1N0M0) or stage IIA (T2N0M0) disease] who met the inclusion criteria during an 18-month period (from September 2015 to March 2017). The exclusion criteria for this study were patients with palpable axillary lymph nodes, T3 or T4 tumors, and metastatic, recurrent, and inflammatory breast cancer.
All the patients were evaluated clinically and relevant investigations were performed to stage the disease. All the patients had sentinel lymph node biopsy after which they were offered appropriate surgery.
Intraoperatively, each patient was put under general anesthesia, positioned, prepped, and draped appropriately. Then 5 mL of methylene blue dye was injected subdermally in a fan-shaped manner to infiltrate the axillary side of the tumor and the periareola region. The injected area was continuously massaged to enhance uptake of the blue dye by sentinel lymph nodes for about 5 min.
A transverse skin crease incision was made in the axilla just below the hair-bearing area, and this was deepened into subcutaneous tissue and clavipectoral fascia. Blunt dissection was performed to identify a blue impregnated lymph node(s) that appeared blue and then excised and labeled. The sentinel lymph nodes were further processed separately for both frozen and paraffin impregnation. Patients were then further offered procedures based on the result diagnosis of the frozen section pathology. Patient with positive sentinel lymph nodes had mastectomy and clearance of the axilla or a wide local excision of the tumor wherein the sentinel lymph node (SLN) was diagnosed to be negative and suitable. Postoperatively, patients returned to their wards after recovery to continue bed rest, and analgesia and antibiotics were given as indicated.
Comparative analysis was made between the variables (frozen and paraffin sections) and the measures of data spread calculated. Student’s t-test and χ2-square test were used where indicated.
| Results|| |
A total of 117 patients having breast cancer were seen over a period of 18 months from September 2015 to March 2017, at the General Surgical Unit of Aminu Kano Teaching Hospital. Out of this total number, 40 patients met the inclusion criteria and constituted the patients of the study.
The age range of the patients was 28 to 70 years, with the mean age being 47.4 ± 11.6 years. Twenty-two (55%) patients were premenopausal, whereas 18 (45%) were postmenopausal.
The sizes of the breast tumor ranged between 2.89 and 4.69 cm with a mean of 3.84 ± 0.53 cm.
A total of 82 sentinel lymph nodes were harvested from 40 patients using methylene blue as identification agent. There was no report of hypersensitivity reaction to the blue dye. The distribution of sentinel nodes harvested is presented in [[Figure 1]].
All the patients had breast surgery after sentinel lymph node biopsy. Among these, mastectomy was offered to 37 (92%) patients, whereas three (8%) patients had wide local excision with 2-mm margin.
In addition, 24 (60%) patients had clearance of the axilla by removing levels I and II lymph nodes. Seventeen (71%) of these patients had positive sentinel lymph node by frozen section, whereas the remaining seven patients had positive sentinel lymph nodes by paraffin section. These seven patients were offered axilla clearance 4 to 6 weeks after confirming the histological result.
The number of axilla lymph nodes removed from these 24 patients who had axilla clearance ranged between 6 and 25 with a mean of 14.38 ± 5.04 nodes.
The time for both surgeries ranged between 82 and 179 min with a mean time of 140.42 ± 20.86 min.
In this study, 17 (43%) patients had their sentinel nodes positive for malignant cells by frozen section, whereas in 23 (57%) patients, the frozen section result was negative. The mean time for obtaining result for frozen section was 34.75 ± 5.20 min.
Furthermore, 24 (60%) patients in this study had their sentinel nodes positive for malignant cells by paraffin section, whereas in 16 patients, paraffin section was negative. The mean time of obtaining result for paraffin section was 16.20 ± 2.3 days.
Therefore, out of the 82 sentinel lymph nodes that were analyzed, 28 (34.1%) sentinel nodes were found to be positive by frozen section, whereas 54 (65.9%) sentinel nodes were negative. By paraffin section analysis, 44 (53.7%) out of 82 sentinel nodes were positive for malignancy, whereas 38 (46.3%) sentinel nodes were negative.
The sensitivity of frozen section in detecting malignant cells in sentinel node was 70.8% when compared with routine staining. The specificity was 100%, the positive predictive value was 100%, the negative predictive value was 69.6%, the false-negative rate was 30.4%, and the accuracy was 82.5%. Frozen section was found to be less effective than paraffin section in detecting malignant cells in sentinel lymph nodes [P = 0.292, confidence interval (CI) = 90%] (see [Table 1]).
|Table 1 Relationship between frozen section and paraffin section of sentinel lymph nodes|
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| Discussion|| |
The incidence and risk factors of breast cancer in developing countries such as Nigeria is rising; the prognosis remains poor. Delayed presentation with locally advanced or metastatic disease is a major cause of poor survival from breast cancer in Nigeria. In our study, about 66% presented with late disease and were excluded from the study.
In the literature, the lack of adequate healthcare infrastructure that is needed to provide modern and quality treatment for breast cancer in addition to lack of systematic screening programs have also been implicated as factors associated with poor prognosis.,
The practice of sentinel node biopsy in patients with early breast cancer has been well developed and almost perfected in many of the industrialized and developed countries of the world. Unfortunately, this is not the case in the third-world countries, including sub-Saharan Africa.,
The age range of the 40 patients who completed this study was 28 to 70 years and the mean age was 47.4 ± 11.6 years. Anyawu in South Eastern Nigeria reported a mean age of patients having breast cancer at presentation to be 46.9 years almost similar to our findings. Similarly, Abudu et al. in Sagamu reported a mean age 47.5 years for patients with breast cancer.
The finding of this study was almost similar to that of Moatasim et al. in Pakistan. They found 28 to 78 years and 49.8 ± 11.1 years as the age range and mean age, respectively, for patients with breast cancer.
In the developed world, the mean age for breast cancer was higher than in our study. Anderson et al. in the USA reported a mean age of 61.9 years for patients breast cancer.
Although breast cancer appears to occur 10 to 20 years earlier in African women, several authors have described this younger age of incidence in populations with lower life expectancy and limited access to healthcare services.,
The clinical characteristics of the 40 patients who completed this study were having the mean size of breast tumor 3.84 ± 0.53 cm measured with a Vernier caliper. Caliper measurement might give false higher figures probably because of inclusion of skin, subcutaneous tissue, and possible inclusion of peritumoral fibrosis with induration.
Findings from this study also revealed that 82 sentinel lymph nodes were harvested from 40 patients using methylene blue as identification agent. Although the yield from the harvest was high, the number of patients who had more than two nodes harvested was relatively low. This was because a single identification agent methylene blue was used in detecting the nodes. In addition, facilities for scintigraphy were unavailable in our center due to limited resources.
The pathological evaluation of sentinel node can be conducted by frozen section or paraffin section. Frozen section has the advantage of providing timely result, allowing intraoperative decision-making, and limiting extent of surgery in addition to one sitting single operation for the majority of patients. This practice is quite advantageous in our patients where majority were from low socioeconomic class and could not afford second operation. Their situation is further compounded by none or limited health insurance services.
However, Moatasim et al. noted that like any other technique, frozen section had its own disadvantages including cost, labor, requirement of a skilled histopathology technician, and a dedicated histopathologist for each surgical procedure. In a busy center where multiple patients undergo operation in a single day, the burden on the histopathology staff and department could be immense.
James et al. observed that frozen sections were prone to artifact during preparation, which made interpretation more difficult. The quality of the slide was also operator dependent. This could lead to inaccuracy in interpretation. Of particular concern is a false-negative result, which can falsely reassure patients leading to significant psychological trauma when the final result is revealed to the patient in addition to the need for a second operation.
Slides of paraffin sections are generally of a higher quality but take longer period to prepare without the option of an intraoperative result, therefore resulting in a second procedure at a later date in patients in whom the sentinel nodes were found to be positive.
In this study, comparison between frozen section and paraffin section in detecting metastasis revealed that frozen section has a sensitivity of 70.8%, specificity of 100%, and false-negative rate of 29.2% and accuracy of 82.5%. Therefore, frozen section is not as effective as paraffin section in detecting metastasis in sentinel lymph nodes (P = 0.292, CI = 90%).
Kilbas et al. in Ankara, Turkey, had reported a different finding. They found the sensitivity of frozen section in detecting metastases in sentinel node to be 84.7%. The specificity was 100%, the false-negative rate was 15.2%, and the accuracy was 95.7%.
Some researchers also had high false-negative rate similar to this study. Veronesi et al. in Milan, Italy, reported a sensitivity of 68% and false-negative rate of 32% for sentinel node biopsy using frozen section. The reason for their finding was micrometastases. In the same study, they improved on their technique by ensuring that a definitive diagnosis was provided by the pathologist intraoperatively but with 45 to 50 min added to the time of surgery. With this improved technique, analyses of sentinel nodes by frozen section in the subsequent 119 patients resulted in a false-negative rate of 5.5%.In an 8-year institutional audit by Nofech et al., the authors reported a high false-negative rate of 26.6%, although the overall accuracy was 94%. In their finding, all the false negatives were due to micrometastases.
The comparison of this study was performed with other studies mainly in the industrialized countries of the world. This was because specific researches regarding frozen section and sentinel node biopsies in breast cancer had not been extensively studied in sub-Saharan African countries. In addition, there were challenges of limited facilities in these countries with regard to modern management of breast cancer. Metwally noted that “Sentinel lymph node biopsy with/without completion nonsentinel lymphadenectomy for positive sentinel nodes is now the standard of care in axilla negative early breast cancer cases.” However, the relatively expensive gamma probes and the nonavailability of radioisotopes needed for radiometric sentinel node biopsy limit the wide practice of this approach in low-income countries.
A comparative study of treatment of breast cancer among women in Nigeria and the USA by Anele et al. showed that the Nigerian women reported in the study were less likely to have frozen section histology and sentinel lymph node biopsy. They added that modified radical mastectomy with its attendant plexopathy, lymphedema, and bridle scar was the predominant surgical intervention among these women.
There were, however, other studies on sentinel lymph node biopsy among patients with breast cancer in other parts of Africa outside the sub-Saharan countries (mainly in North Africa and Republic of South Africa). These studies were not directly comparable to my study, because the researchers did not specifically compare frozen section and paraffin section evaluation of sentinel lymph nodes.
| Conclusion|| |
In this study, frozen section is not as effective as paraffin section in detecting malignant cells in sentinel lymph nodes among patients with early breast cancer, being managed in Aminu Kano Teaching Hospital, Kano. It is still a useful procedure despite the high false-negative rate. Patients must be adequately counseled about this possibility and the need for second surgery if it turnout to be false negative.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Carol D, Jiemin M, Leah B, Ahmedin J. Breast cancer statistics, 2013. CA Cancer J Clin 2014;64:52–62.
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M et al.
Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E359-86.
Agba EA, Curado MP, Ogunbiyi O, Oga E, Fabowale T, Igbinoba F et al.
Cancer incidence in Nigeria: A report from population-based cancer registries. Cancer Epidemiol 2012;36:271-8.
Jacques F, Clarisse H, Phillipe A, Rengaswamy S. Global burden of breast cancer. In: Christopher IL, editor. Breast cancer epidemiology. New York: Springer 2010. pp 1-19.
Adetifa FA, Ojikutu RK. Prevalence and trends in breast cancer in Lagos State, Nigeria. Afr Res Rev 2009;3:1-15.
Bundred NJ. Prognostic and predictive factors in breast cancer. Cancer Treat Rev 2001;27:137-42.
Adebamowo CA, Ajayi OO. Breast cancer in Nigeria. West Afr J Med 2000;19:179-91.
Jatoi I, Hilsenbeck SG, Clark GM, Osborne CK. Significance of axillary node lymph node metatstasis in primary breast cancer. J Clin Oncol 1999;17:23-34.
Andersson Y, Frisell J, Sylvan M, Boniface J, Biergkrist L. Breast cancer survival in relation to metastatic tumour burden in axillary lymph nodes. J Clin Oncol 2010;28:2868-73.
Valente SA, Levine GM, Silverstein MJ, Rayhanabad JA, Weng-Grumley JG, Ji L et al.
Accuracy of predicting axillary node positivity by physical examination, mammography, ultrasonography and magnetic resonance imaging. Ann Surg Oncol 2012;19:1825-30.
Armando E, Giuliano MD, Michael JG, Donald LM. Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg 1994;220:391-401.
Marc AW, Gray B, Leonard RP, Luis C, Gloria B, Bercedes P et al.
Complications of axillary lymph node dissection for carcinoma of the breast. Cancer 1998;83:1362-8.
Pieter JT, Omgo EN, Renato AVO, Emiel JTR, Bin BRK. History of sentinel node biopsy and validation of technique. Breast Cancer Res 2001;3:109-12.
Min Y, Funda MB, Merrick IR, Jeri SA, Rosa FH, Anthony L et al.
How many sentinel nodes are enough during sentinel lymph node biopsy for breast cancer? Cancer 2008;113:30–7.
Akinkuolie AA, Etonyeaku AC, Olasehinde O, Arowolo OA, Babalola RN. Breast cancer patients’ presentation for oncological treatment: A single center study. Pan Afr Med J 2016;24:1-6.
Mbuka OD, Tumbo JM. Knowledge about breast cancer and reasons for late presentation by cancer patients seen at Princess Marina Hospital, Gaborone, Botswana. Afr J Health Care Fam Med 2013;5:1-7.
Sharma K, Costas A, Shulman LN, Meara JG. A systematic review of barriers to breast cancer care in developing countries resulting in delayed patient presentation. J Oncol 2012; 2012:1-8.
Wada N, Imoto S, Hasebe T, Ochiai A, Ebihara S, Moriyama N. Evaluation of intraoperative frozen section diagnosis of sentinel lymph nodes in breast cancer. Jpn J Clin Oncol 2004;34:113-7.
Liu LC, Lang JE, Lu Y, Roe D, Hwang SE, Ewing CA et al.
Intraoperative frozen section analysis of sentinel lymph nodes in breast cancer patients, a meta-analysis and single-institution experience. Cancer 2011;17:250-8.
Anyawu SNC. Temporal trends in breast cancer presentation in the third world. J Exp Clin Cancer Res 2008;27:17.
Abudu EK, Banjo AA, Izegbu MC, Agboola AO, Anunobi CC, Musa OA. Malignant breast lesions at Olabisi Onabanjo University Teaching Hospital (O.O.U.T.H), Sagamu—A histopathological review. Niger Postgrad Med J 2007;14:57-9.
Moatasim A, Mujtaba S, Faridi N. Intraoperative frozen section analysis of sentinel lymph nodes in breast carcinoma patients in a tertiary hospital in Pakistan. Int J Surg 2013;11:253-8.
Anderson WF, Chu KC, Sherman ME. Comparison of age-specific incidence rate patterns for different histopathologic types of breast carcinoma. Cancer Epidemiol Biomarkers Prev 2004;13:1128-35.
Fregene A, Newman LA. Breast cancer in sub-Saharan Africa: How does it relate to breast cancer in African-American women? Cancer 2005;103:1540-50.
Tetteh DA, Faulkner SL. Sociocultural factors and breast cancer in sub-Saharan Africa: Implications for diagnosis and management. Womens Health 2016;12:147-56.
Shoma A, Moutamed A, Ameen M, Abdelwahab A. Ultrasound for accurate measurement of invasive breast cancer tumour size. Breast J 2006;12:252-6.
James PLT, Lesley J, Emily D. Accuracy of frozen sections for breast cancer sentinel lymph node biopsies within a peripheral New Zealand hospital. N Z Med J 2016;129:46-9.
Kilbas Z, Yildiz R, Ozturk E, Mentes MO, Gorgulu S, Peker Y. The accuracy of intraoperative frozen section analysis of sentinel lymph nodes in patients with breast cancer. Arch Clin Exp Surg 2015;4:185-9.
Veronesi U, Paganelli G, Viale G, Galimberti V, Luini A, Zurrida S et al.
Sentinel lymph node biopsy and axillary dissection in breast cancer: Results in a large series. J Natl Cancer Inst 1999;9:368–73.
Nofech MS, Hanna WM, Cil T, Quan ML, Holloway C, Khalifa MA. Intraoperative consultation for axillary sentinel lymph node biopsy: An 8-year audit. Int J Surg Pathol 2010;18:129-37.
Metwally IH. Surgical oncology practice in low income countries; difficulties and practical solutions. Clin Surg 2017;2:129-35.
Anele AA, Bowling M, Eckert GJ, Gonzalez ELF, Kipfer H, Sauder C. Treatment of breast cancer: Imo State Nigeria versus Indiana, USA women—Comparative analytic study. J West Afr Coll Surg 2014;4:39-69.