|Year : 2021 | Volume
| Issue : 2 | Page : 253-256
A cytohistologic correlation study of breast carcinoma with reference to robinson's cytologic grading system
Rojalin Nanda, Alaka Sahu, Kaustav Mohapatra
Department of Pathology, VIMSAR, Burla, Odisha, India
|Date of Submission||08-Jan-2021|
|Date of Decision||17-Feb-2021|
|Date of Acceptance||08-Apr-2021|
|Date of Web Publication||18-Oct-2021|
Dr. Alaka Sahu
Department of Pathology, VIMSAR, Burla, Odisha
Source of Support: None, Conflict of Interest: None
Aim: The present study has been conducted on cases of infiltrating ductal carcinoma of the breast to correlate cytological Robinson's grading system with histological Nottingham modified Bloom–Richardson grading system. Settings and Design: This is a retrospective study conducted on fifty cytologically diagnosed breast carcinoma cases in the Department of Pathology, VIMSAR, Burla, Odisha. Materials and Methods: Fifty cases of cytologically diagnosed breast carcinoma were graded according to Robinson's system, and the respective histopathology slides were graded according to Nottingham modified Bloom–Richardson scoring system. The axillary lymph node (if any) status was also checked for any metastases. The sensitivity, specificity, positive predictive value, and negative predictive value of Robinson's cytological grading system were calculated. Results: The absolute concordance rate between cytological and histological grades was 78% which indicates a strong correlation and significant association. Sensitivity was maximum for Grade II tumors (88.00%) while specificity was maximum for Grade III tumors (97.50%). The positive predictive value was maximum for Grade III tumors (85.71%) while the negative predictive value was maximum for Grade I tumors (94.11%). Lymph node metastases were found in 42% (21 cases) of all the tumors; maximum was (100%) in Grade III tumors. Conclusion: Cytological grade strongly correlates with histological grade and is helpful in selecting the treatment regimen.
Keywords: Breast cancer, cytological grade, histological grade, prognosis
|How to cite this article:|
Nanda R, Sahu A, Mohapatra K. A cytohistologic correlation study of breast carcinoma with reference to robinson's cytologic grading system. J Datta Meghe Inst Med Sci Univ 2021;16:253-6
|How to cite this URL:|
Nanda R, Sahu A, Mohapatra K. A cytohistologic correlation study of breast carcinoma with reference to robinson's cytologic grading system. J Datta Meghe Inst Med Sci Univ [serial online] 2021 [cited 2021 Dec 4];16:253-6. Available from: http://www.journaldmims.com/text.asp?2021/16/2/253/328482
| Introduction|| |
The breast or mammary gland is a distinguishing feature of mammals and is modified tubuloalveolar apocrine sweat gland. These are structurally dynamic organs and vary with age, menstrual cycle, and reproductive status of women. However, during embryologic life, growth and development of breast tissue occur in both sexes.
Histologically, the breast is composed of fibrofatty tissue consisting of epithelial and stromal elements.
The morphofunctional unit of the breast is a single gland with a complex branching structure arranged into lobes. Lobes have two major components: the terminal duct lobular unit (TDLU) and the large duct system. The functional unit of a breast is the TDLU. The ductal lobular unit of the breast is lined by the double layer of the epithelium, the inner epithelial cell layer that has secretory and absorptive functions, and the outer myoepithelial layer. The epithelia rest on a basement membrane or the basal lamina. Worldwide, breast carcinoma is one of the most common malignant tumors in females and also is one of the leading causes of cancer deaths at a fatality rate of about 20%. Among Indian women, it is number one cancer and the age-adjusted rate is as high as 25.8/100,000 women and the mortality rate is 12.7/100,000 women. Incidence of breast cancer is in rise throughout the world due to a major change in the lifestyle., The incidence is relatively less in men, 1% of all malignancies in men and 1% of all breast malignancies. The determination of prognosis of a breast carcinoma requires an array of investigations such as fine-needle aspiration cytology (FNAC), mammography, lymph node assessment, and finally, histopathology. FNAC being cheaper and easily available in a developing country like ours has informative significance and recent progress in neoadjuvant therapy has led to the necessity of the prognostic evaluation from the cytomorphological picture. This can be brought about by grading the cancer which can guide the surgeon in deciding the treatment modality and even provide light on the morbidity or mortality rate associated with it.
| Materials and Methods|| |
The present study was conducted in our tertiary care hospital in the year 2019, where a total number of fifty cases of cytologically diagnosed infiltrating duct carcinoma breast were selected, which were also confirmed by the histopathology study. Those cases which underwent surgery without any neoadjuvant therapy were included in the study, whereas the patients who underwent chemotherapy or radiotherapy prior to histopathology study were excluded from the study, as staging and grading of the tumors might change.
The Diff-Quik and Pap-stained smears were retrospectively examined and graded as per the description by Robinson et al. Robinson's grading system used six parameters, namely cell dissociation, cell size, cell uniformity, nuclear margin, nucleolus, and chromatin. Each case was graded according to the cytological findings and was given a score from 1 to 3, and finally, the grade was deduced from the total score. Grade I, Grade II, and Grade III were given the scores as 6–11, 12–14, and 15–18, respectively. According to Robinson's cytologic grading system, a score of 1 each was given to each separate category if the cells had the following features, such as cells in clusters, cell having size of 1–2 times the size of a red blood cell (RBC), monomorphic in uniformity, indistinct nucleoli, smooth nuclear margin, and vesicular chromatin. A score of 2 was given to each of these following findings: cells in mixture of singles and clusters, individual cell having 3–4 times the size of an RBC, mild pleomorphism, noticeable nucleoli, folds in nuclear margin, and granular chromatin. A score of 3 was given to each tumor case if the cells had the following features: cells mostly present in singles, individual cells with more than five times the size of an RBC, higher degree of pleomorphism, prominent nucleoli, nucleus with budding or clefts, and clumped and cleared chromatin.
Hematoxylin- and eosin-stained sections of the respective cytological diagnosed cases of tumor were examined and graded according to Nottingham modified Bloom–Richardson's histopathologic grading system. Nottingham modified Bloom–Richardson's histopathologic grading is based on three parameters:
- Tubule formation
- Nuclear pleomorphism
- Mitotic figures per 10 high-power (×400) fields.
The total score ranged from 3 to 9 as each parameter was given a score ranging from 1 to 3. According to Nottingham modified Bloom–Richardson histologic grading system, a score of 1 each was given if: more than 75% of tumor cells showed tubule formation, the nuclei were small and regular, and mitotic count of 0–7 per high-power field. A score of 2 each was given if there were the following findings: 10%–75% of tumor cells showed tubule formation, the nuclei were of intermediate size, i.e., 1.5–2 times the size of normal duct nuclei, and mitotic count of 8–14 per high-power field. A score of 3 each was given if: <10% of tumor cells showed tubule formation, nuclear size was of high grade, i.e., more than 2 times the size of normal duct nuclei, and a mitotic count of more than 15 per high-power field. The total score was calculated and graded as follows: Grade I for score of 3–5, Grade II for score of 6–7, and Grade III for score of 8–9. The concordance rate for each grade was calculated. The sensitivity and specificity of each of the cytological grading system were also calculated. We also calculated the positive predictive value and negative predictive value for individual cytological tumor grades.
| Results|| |
Fifty cases were cytologically as well as histologically graded, respectively. On cytological grading of the FNAC slides of 50 cases, as per Robinson's grading system, 15 (30%) were Grade I [Figure 1]a, 28 (56%) were Grade II [Figure 1]b and 7 (14%) were Grade III [Figure 1]c. [Table 1]. According to Nottingham modified Bloom–Richardson system of histological grading, 13 (26%) cases were of Grade I, 27 (54%) cases were Grade II, and 10 (20%) cases were Grade III. Twenty-one cases (42%) out of all the fifty cases were found to have lymph node metastases. Out of the 21 cases, 10 were cytological Grade III and 11 were cytological Grade II. To conclude, all the cases with cytological Grade III had associated lymph node metastases while 40.74% of cytological Grade II cases were positive for lymph nodes.
|Figure 1: (a) Fine-needle aspiration cytology photomicrograph of Grade I breast carcinoma showing tumor cells in loosely cohesive clusters, monomorphic nuclei, and indistinct nucleoli (H and E, ×400). (b) Fine-needle aspiration cytology photomicrograph of Grade II breast carcinoma showing tumor cells in singles as well as clusters, moderately pleomorphic nuclei, granular chromatin, and noticeable nucleoli (H and E, ×400). (c) Fine-needle aspiration cytology photomicrograph of Grade III breast carcinoma showing cells scattered singly, highly pleomorphic nuclei with nuclear budding and clefting and prominent nucleoli (H and E, ×400)|
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|Table 1: Comparison between cytological tumor grade and histological tumor grade|
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Of the 15 cytologically diagnosed Grade I carcinomas, 13 were histologically confirmed to be Grade I. Twenty-seven out of 28 cytologically diagnosed Grade II were histologically confirmed. While seven cases were cytologically graded as Grade III, ten cases were histologically Grade III. The concordance rate between cytological and histological Grade I tumors was 73.33%, while for Grade II, it was 78.57%, and finally, for Grade III, it was 85.71%. The absolute concordance rate corresponding to all the three grades was found to be 78% [Table 1].
The sensitivity of cytological Grade I tumor was 85.71%, while that of Grade II tumor was 88.0% and that of Grade III tumor was 60%. The specificity of cytological grades calculated was 91.14% for cytological Grade I, 75.0% for Grade II, and 97.50% for Grade III. The positive predictive value for each of the cytological grades was calculated as 80.0% for cytological Grade I, 78.57% for Grade II, and 85.71% for Grade III. The negative predictive value was found to be 94.11% for cytological Grade I, 85.71% for cytological Grade II, and 90.70% for cytological Grade III breast carcinoma cases [Table 2].
|Table 2: Sensitivity, specificity, positive predictive value, and negative predictive value|
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| Discussion|| |
FNAC is the first line of invasive procedure done in order to diagnose a case of carcinoma breast prior to clinical staging and treatment. In most of the cases, FNAC is being able to grade the tumor and decide the treatment on its basis, proving to be very much helpful, where the higher grade tumor requires surgery whereas the lower grade tumors can be managed with chemotherapy.
Out of all the different cytological grading methods, the one proposed by Robinson et al. has been widely accepted. The concordance rate between the cytological and histological grades in our study was found to be 78%, similar to that of the study by Pal and Gupta.
Khan et al. found concordance rate to be in 89.1% of cases whereas similarly Kalhan et al. found a concordance rate of 88.1% in their respective studies., Whereas a separate study conducted by Rekha et al. showed a concordance rate of 82%, other two different studies by Ravikumar and Rout and by Chhabra et al. calculated their concordance rates to be 77.5% and 65%, respectively. Pandit and Parekh found a concordance rate of 64% in their study of 75 cases. A study conducted by Pathak et al. found a concordance rate of 65.9%. Sood et al., in their study, concluded to have a concordance rate of 75% for Grade I tumors, 70.67% for Grade II tumors, and 60% for Grade III tumors. Their absolute concordance rate corresponding to all three cytological grades was 68.97%. Kareem and Rahmatullah calculated an absolute concordance rate of 87.5%. The absolute concordance rate in a study by Sinha et al. was 69.5%.
The lack of correlation between cytological and histological grading was found in 22% of cases in our present study, which might have been due to the presence of varying degrees of atypia within the same tumor and interobserver subjectivity while assigning a cytological nuclear grade to a tumor. It also might have resulted due to difficulty in identifying features such as nuclear margins, chromatin clumping, and granularity on cytology smears.
In our study, we found sensitivity to be 85.71% for cytological Grade I, 88.0% for Grade II, and 60.0% for Grade III tumor cases. The sensitivity was lowest in Grade III which might have been due to the least number of cases we came across in Grade III tumors. It could have been avoided by taking a larger sample size. Similarly, Pal and Gupta in their study found a sensitivity of 45.45% for Grade III tumors. They found maximum sensitivity in Grade I tumors (100%). Sultana and Rahman found minimum sensitivity of cytological Grade III tumors (37.50%) and maximum (92.30%) for cytological Grade I tumors.
The specificity in our study was found to be 91.14%, 75.00%, and 97.50% for cytological Grade I, Grade II, and Grade III tumors, respectively. The specificity for Grade II tumors was least (75%) because of the highest number of false-positive Grade II cases, which was similar to the study done by Pal and Gupta, where the maximum specificity was found in Grade III tumors (94.87%) and minimum specificity in Grade II tumors (72.72%). In the study by Kareem and Rahmatullah, they found that cytological Grade I carcinomas had a sensitivity of 73.33% and specificity of 100%, cytological Grade II carcinomas had a sensitivity of 100% and specificity of 76%, and cytological Grade III carcinomas had the maximum sensitivity and specificity both 100%.
In our present study, out of 50 cases, we found the lymph node metastases in 21 cases (42%), which was highly associated with the higher grade of tumors. Very similar findings were also seen in studies conducted by Pal and Gupta. They found that 31 out of their 50 cases were positive for lymph node metastases, which were also high-grade tumors. Khan et al. also found a higher degree of association between high-grade carcinoma and lymph node metastases. Sinha et al. in their study found lymph node metastases in three cases of cytological Grade II tumors, 28 of Grade III tumors, and none in Grade I tumors.
Although there have been many studies conducted to determine the correlation between cytological and histological grading of breast carcinoma, very few studies have determined the sensitivity and specificity of Robinson's grading method, and even fewer have determined the positive predictive value and the negative predictive value. In our study, we have calculated sensitivity, specificity, as well as positive predictive value and negative predictive value.
FNAC smears provide a valuable information on the aggressiveness of tumors, which is a crucial parameter for selecting chemotherapy or hormonal therapy or radiotherapy or even surgery. The treatment plan is mostly based on the cytological evaluation report. Grade of the tumor provides additional information on the treatment regimen to be opted for better compliance of the patient. Not just for the diagnosis but even for the prognosis, National Cancer Institute, Bethesda, has recommended the use of tumor grading in cytology reports.
This present study was conducted on a small group of patients over 1-year duration, and very few cases of high-grade tumors were studied.
| Conclusion|| |
Our study concludes that grading of breast cancer in cytology smears is possible and it correlates well with the histological grades. The Robinson's cytological grade also provides additional information on aggressiveness of tumor, lymph node status, and finally, the prognosis. It acts as an aide to the surgeon in planning further management, thus increasing compliance and decreasing the burden over the patients. The tumor status can also be monitored cytologically while the patient is on neoadjuvant therapy. Thus, it is suggested that cytological grade should be incorporated while reporting breast carcinoma cytological smears.
However, as our study was limited to just only fifty cases of carcinoma breast for the cytological and histological correlation between the various grades of tumor, it was difficult to comment on the cases with higher grades as we found only 7 cytological Grade III. A study with large group could have been helpful to correlate both cytology and histology grades in a better and broader manner.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Michael HR, Pawlina W. Histology: A Text and Atlas: With Correlated Cell and Molecular Biology. 6th
ed. Philadelphia: Lippincott Williams and Wilkins; 2011.
Goldblum J, Lamps L, McKenney J, Myers J. Rosai and Ackerman's Surgical Pathology. 11th
ed. Philadelphia: Elsevier; 2017.
Kumar V, Abbas AK, Aster JC. Robbins and Cotran Pathologic Basis of Disease. 9th
ed. Philadelphia: Elsevier; 2015.
Malvia S, Bagadi SA, Dubey US, Saxena S. Epidemiology of breast cancer in Indian women. Asia Pac J Clin Oncol 2017;13:289-95.
Barry S, Ha KY, Laurie L. Carcinoma of the breast in men. Proc (Bayl Univ Med Cent) 2012;25:367-8.
Masood S. Assessment of prognostic factor in breast FNA. Am J Clin Pathol 2000;113:84-96.
Robinson IA, McKee G, Nicholson A, D'Arcy J, Jackson PA, Cook MG, et al.
Prognostic value of cytological grading of fine-needle aspirates from breast carcinomas. Lancet 1994;343:947-9.
Elton CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: Experience from a large study with long-term follow-up. Histopathology 1991;19:403-10.
Pal S, Gupta ML. Correlation between cytological and histological grading of breast cancer and its role in prognosis. J Cytol 2016;33:182-6.
] [Full text]
Khan N, Afroz N, Rana F, Khan M. Role of cytologic grading in prognostication of invasive breast carcinoma. J Cytol 2009;26:65-8.
] [Full text]
Kalhan S, Dubey S, Sharma S, Dudani S, Preeti P, Dixit M. Significance of nuclear morphometry in cytological aspirates of breast masses. J Cytol 2010;27:16-21.
] [Full text]
Rekha TS, Nandini NM, Dhar M. Validity of different cytological grading systems of breast carcinoma – A hospital-based study in South India. Asian Pac J Cancer Prev 2011;12:3013-6.
Ravikumar G, Rout P. Comparison of cytological versus histopathological grading of invasive ductal carcinoma of the breast with correlation of lymph node status. Middle East J Cancer 2015;6:91-6.
Chhabra S, Singh PK, Agarwal A, Bhagoliwal A, Singh SN. Cytological grading of breast carcinoma – A multivariate regression analysis. J Cytol 2005;22:62-5.
Pandit AA, Parekh HJ. Cytologic grading of breast carcinoma: Comparison of four grading systems. J Cytol 2000;17:39-44. [Full text]
Pathak R, Jha A, Neupane PR, Chalise S, Basnyat AS. Histopathological evaluation of carcinoma of breast. J Pathol Nepal 2016;6:922-7.
Sood N, Nigam JS, Yadav P, Rewri S, Sharma A, Omhare A, et al.
Comparative study of cytomorphological Robinson's grading for breast carcinoma with modified bloom-richardson histopathological grading. Patholog Res Int 2013;2013:146542.
Kareem NM, Rahmatullah NS. Prognostic role of Robinson cytological grading system in breast cancer in correlation with the histological grading of modified bloom Richardson in Iraq. Int J Res Med Sci 2018;6:1139-43.
Sinha S, Sinha N, Bandyopadhyay R, Mondal SK. Robinson's cytological grading on aspirates of breast carcinoma: Correlation with Bloom Richardson's histological grading. J Cytol 2009;26:140-3.
] [Full text]
Sultana T, Rahman AJ. Cytological grading of duct cell carcinoma, NOS of breast and its correlation with histological grading. Bangladesh Med Res Counc Bull 2006;32:49-54.
The uniform approach to breast fine-needle aspiration biopsy. National Cancer Institute Fine-Needle Aspiration of Breast Workshop Subcommittees. Diagn Cytopathol 1997;16:295-311.
[Table 1], [Table 2]