Journal of Cytology
Home About us Ahead of print Instructions Submission Subscribe Advertise Contact e-Alerts Login 
Users Online:221
  Print this page  Email this page Small font sizeDefault font sizeIncrease font size


 
 Table of Contents    
ORIGINAL ARTICLE  
Year : 2016  |  Volume : 33  |  Issue : 4  |  Page : 182-186
Correlation between cytological and histological grading of breast cancer and its role in prognosis


1 Department of Pathology, Rabindra Nath Tagore (RNT) Medical College, Udaipur, Rajasthan, India
2 Department of Pathology, Geetanjali Medical College, Udaipur, Rajasthan, India

Click here for correspondence address and email

Date of Web Publication13-Sep-2016
 

   Abstract 

Context: Assigning grade to breast cancer on FNAC provides prognostic information and guides optimal therapy.
Aims: The present study was undertaken to grade breast carcinoma on cytology by Robinson's grading system and correlate it with Elstons modified Bloom Richardson histological grading system.
Settings and Design: It is a prospective study done on fifty cases of breast cancer reported on cytology.
Materials and Methods: Fifty patients who underwent FNAC and mastectomy for breast carcinoma were cytologically and histologically graded. Correlation between cytological and histological grading system was determined. Sensitivity and specificity of Robinson's cytological grading system was calculated in each grade. All cases evaluated for presence of metastasis to axillary lymph nodes.
Statistical Analysis Used: Correlation between cytological and histological grading was established using the non parametric Spearmanâ€s correlation coefficient.
Results: Concordance rate between cytological and histological grade was 78%. The coefficient of correlation between cytological grade and histological grade was 0.804 and P value was <0.001 which indicated a strong correlation and significant association between the cytological and histological grade. Sensitivity was maximum in cytological grade I tumors (100%) and least in cytological grade III tumors (45.45%). Specificity was maximum in cytological grade III tumors (94.87%) and least in cytological grade II tumors (72.72%). The incidence of axillary lymph node metastasis was maximum in cytological grade III tumors and grade I tumors.
Conclusions: Cytological grade strongly predicts histological grade and is useful in selecting neoadjuvant chemotherapy.

Keywords: Axillary metastasis; breast cancer; cytological grade; prognosis

How to cite this article:
Pal S, Gupta ML. Correlation between cytological and histological grading of breast cancer and its role in prognosis. J Cytol 2016;33:182-6

How to cite this URL:
Pal S, Gupta ML. Correlation between cytological and histological grading of breast cancer and its role in prognosis. J Cytol [serial online] 2016 [cited 2020 Jun 3];33:182-6. Available from: http://www.jcytol.org/text.asp?2016/33/4/182/190449



   Introduction Top


The evaluation of prognostic parameters in breast cancer is of growing interest. These include axillary lymph node status, estrogen receptor status, histological grade, and cell proliferation index.[1] As neoadjuvant chemotherapy is gaining popularity as primary modality of medical treatment of breast cancer, much attention is being focussed on grading of breast cancer on fine-needle aspiration cytology (FNAC) smears.[2] Such grading would allow assessment of the tumor in situ, thereby guiding the selection of most suitable treatment before primary surgery, and hence avoiding the morbidity associated with overtreatment of low-grade tumors.[3]


   Materials and Methods Top


Fifty cases of infiltrating duct carcinoma (IDC) breast, diagnosed on cytology, and undergoing surgery were included in the study. May-Grunewald-Giemsa (MGG) stained smears were evaluated and the tumor was graded based on the grading system described by Robinson et al.[3] In the Robinson's grading system, six different cytological parameters, namely cell dissociation, cell size, cell uniformity, nucleolus, nuclear margin, and nuclear chromatin were used to grade the tumors. A score of 1-3 was given to each of these parameters, and the tumor was graded by adding up the scores. Cancers that were scored in the range of 6-11 were graded I, those that are scored in the range of 12-14 were graded II, and grade III was given for a score ranging from 15 to 18. The surgical specimens were evaluated and histologically graded according to the Elston's modification of Bloom-Richardson system.[4] Three parameters were taken into consideration: Degree of tubule formation, nuclear pleomorphism, and mitotic figures. Each parameter was given a score of either 1,2 or 3. The overall score for each case ranged from 3 to 9. Mitotic figures were scored using a Nikon Opitphot-2 microscope with a field diameter of 0.44 mm. Sections were stained by hematoxylin and eosin (H&E) stain. Statistical analysis was done employing Spearman rank correlation coefficient (r) to examine the degree of correlation between the cytological and histological grade. Sensitivity and specificity of Robinson's cytological grading method were calculated for each cytological grade. All 50 cases were evaluated for the presence or absence of metastasis to the axillary lymph nodes employing Chi-square test. Lymph nodes were obtained on histopathology specimens. Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) statistical software package version 16 (SPSS-Inc., Chicago, IL) and EPI-INFO version 6 (Centre of Disease Control and Prevention, Atlanta, Georgia, USA). P value <0.05 was considered statistically significant.


   Results Top


Fifty cases were cytologically graded on FNAC smears according to Robinson's grading system. The maximum number of cases i.e. 29 (58%) were cytological grade II, 14 (28%) cases were cytological grade I, and 7 (14%) cases were cytological grade III. All cases were subsequently graded on histology using Elston's modification of Bloom-Richardson grading system. On histological grading, 28 (56%) cases belonged to histological grade II, and 11 (22%) cases belonged to histological grade I and histological III each. [Table 1] shows comparison of the case distribution between the cytological grade and histological grade. Out of 14 cases of cytological grade I [Figure 1]a, 11 cases were correlated with histological grade I and the remaining 3 cases were upgraded grade II. Out of 29 cases of cytological grade II [Figure 1]b, 23 cases correlated with histological grade II and the remaining 6 cases were histologically upgraded to grade III. Out of seven cases that were cytological grade III [Figure 1]c, five cases correlated with histological grade III while two cases were downgraded to grade II on histology.
Table 1: Comparison of the case distribution between the cytological and histological grades

Click here to view
Figure 1: (a) Cytological grade I tumor showing cohesive clusters of cells with smooth nuclear membranes, vesicular chromatin, and inconspicuous nucleoli (MGG stain, x1000). (b) Cytological grade II tumor showing cells having visible nucleoli, granular chromatin, and moderate pleomorphism (MGG stain, x1000). (c) Cytological grade III tumor showing cells with highly pleomorphic nuclei, prominent nucleoli, and budding of nuclear membrane (MGG stain, x1000)

Click here to view


The concordance rate between grade I tumors on cytology and histology was 78.57%, while for grade II tumors it was 79.31% and for grade III tumors it was 71.42%. Thirty-nine cases out of 50 cases showed an agreement between the respective cytological and histological grades. The absolute concordance rate was 78%. The Spearman rank correlation coefficient (r) was 0.804, which indicates that there is a strong correlation between the cytological and histological grade. The high value of coefficient of correlation showed a significant and marked association (P < 0.001) between the grades assigned to FNAC smears and surgical pathology specimens [Table 2].
Table 2: Comparison of concordance rates between the cytological and histological grades

Click here to view


[Table 3] shows that in cytological grade I tumors, the sensitivity of Robinson's cytological grading system was 100% and specificity was 92.30%. In cytological grade II tumors the sensitivity was 82.14% and specificity was 72.72% and in cytological grade III tumors the sensitivity is 45.45% and specificity was 94.87%.
Table 3: Calculation of sensitivity and specificity of Robinson cytological grading system[3] in each cytological grade considering histological grade as a base*

Click here to view


Out of the 50 cases, 31 (62%) were positive for axillary lymph node metastasis. Lymph node metastasis was present in 3 out of 11 (21.43%) cytological grade I tumors, 21 out of 29 (72.41%) cytological grade II tumors, and all the 7 (100%) cytological grade III tumors [Table 4]. This association between the increasing cytological grade and measure of axillary lymph node metastasis was found to be statistically significant with a Chi-square value of 15.41, degree of freedom (df) of 2, and P value < 0.001.
Table 4: Association of each cytological grade with incidence of axillary lymph node metastasis

Click here to view



   Discussion Top


FNAC is a routinely used investigation for rapid diagnosis of breast cancer. The ability to predict the accurate grade on cytology smears would add to the diagnostic value of FNAC, without any additional morbidity or expense for the patients.

The purpose of prognostic grading on cytology is to identify high-grade tumors that are more likely to respond to chemotherapy than the low-grade tumors, which may be better suited to pretreatment with tamoxifen.[5] Assessment of biological aggressiveness by cytological grading without removing the tumor would therefore be valuable.[6]

Of the various cytological grading methods described for breast cancer, the method proposed by Robinson et al.[3] has been widely accepted. The concordance rate between the cytological grade (using Robinson's method) and histological grade, obtained in our study, was 78% that was found to be fairly comparable to that reported by previous studies [Table 5].[1], 2, [6],[7],[8],[9],[10],[11],[12],[13],[14] The lack of correlation between cytological and histological grading in 22% of our cases may be the presence of varying degrees of atypia within the same tumor and interobserver subjectivity when assigning a cytological nuclear grade.[14] Another possible reason for the discordance may be the difficulty in identifying features such as nuclear margins (smooth/buds/folds), chromatin clumping, and granularity on cytology smears.[6] We found a statistically significant correlation between the cytological and histological grade with a “r” = 0.804 and P value of <0.001 [Table 4].
Table 5: Comparison of concordance rates in different studies with the present study employing Robinson's cytological grading system[3]


Click here to view


In the present study, we found sensitivities of 100%, 82.14%, and 45.45% for cytological grade I, II, and III tumors, respectively. The sensitivity was lowest (45.45%) in cytological grade III tumors. The reason for this low sensitivity of grade III tumors on cytology, could be that in our study, out of all the cases, number of cases falling in cytological grade III category was the lowest which thereby resulted in a low sensitivity. Sultana and Rehman [8] reported a similar finding of lowest sensitivity of cytological grade III tumors (37.50%) as compared to 96.96% for cytological grade I and 87.18% for cytological grade II tumors. We found that Robinson's cytological grading system was highly specific for cytological grade I tumors (92.30%) and cytological grade III tumors (94.60%), while being moderately specific (72.72%) for grade II tumors, owing to the highest number of false positive cases in cytological grade II category. This low specificity could also be due to the variation in cytological features in different areas of tumor on histology, which cannot be appreciated in cytology because of limited area of approach.

In the present study, we found an increasing incidence of axillary lymph node metastasis with increasing cytological grade. Frias et al.[15] and Khan et al.[1] also reported an increased rate of axillary lymph node metastasis with increasing cytological grade. These findings indicate that FNAC is a useful tool for predicting axillary lymph node metastasis that is one of the most important prognostic factors for breast carcinoma.

Although many studies have been conducted on cytological grading of breast cancer, only a few of them have calculated the sensitivity and specificity of cytological grading system in each grade. In this study, we have separately calculated the sensitivity and specificity of Robinson's cytological grading system in each grade that conveys how accurately this system has diagnosed the grade I, II, and III cases on cytology. Cytological grading on FNAC smears provides information about the aggressiveness of the tumor, which is a crucial parameter for selecting neoadjuvant chemotherapy/hormonal therapy. FNAC is especially useful in low-resource settings, where core biopsy is not routinely performed for diagnosis, and the treatment is often based on the cytology report itself. The National Cancer Institute (NCI), Bethesda, sponsored conference has recommended that tumor grading on FNAC material should be incorporated in cytology reports for prognosis.[16]


   Conclusion Top


Our study shows that it is possible to grade breast cancer on fine-needle aspirates and that the cytological grade corresponds well with the histological grade. The cytological grade also provides relevant prognostic information regarding the aggressiveness of the tumor and lymph node metastasis. Thus, it is suggested that a conscious effort should be made to include the cytological grade in all the FNAC reports of breast cancer so as to guide the surgeon regarding the judicious use of neoadjuvant therapy and hence avoiding overtreatment of low-grade cancers.

Acknowledgment

We would like to thank Dr. Neha Singh, Assistant Professor, Department of Pathology, AIIMS Rishikesh, for her guidance in the study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Khan N, Afroz N, Rana F, Khan MA. Role of cytologic grading in prognostication of invasive breast carcinoma. J Cytol 2009;26:65-8.  Back to cited text no. 1
[PUBMED]  Medknow Journal  
2.
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.   Back to cited text no. 2
    
3.
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.  Back to cited text no. 3
    
4.
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.  Back to cited text no. 4
    
5.
Katz RL. A turning point in breast cancer cytology reporting: Moving from callowness to maturity. Acta Cytol 1994;38:881-3.  Back to cited text no. 5
    
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.  Back to cited text no. 6
    
7.
Das AK, Kapila K, Dinda AK, Verma K. Comparative evaluation of grading of breast carcinomas in fine needle aspirates by two methods. Indian J Med Res 2003;118:247-50.  Back to cited text no. 7
    
8.
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.  Back to cited text no. 8
[PUBMED]    
9.
Sinha SK, 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.  Back to cited text no. 9
[PUBMED]  Medknow Journal  
10.
Kalhan S, Dubey S, Sharma S, Dudani S, Preeti, Dixit M. Significance of nuclear morphometry in cytological aspirates of breast masses. J Cytol 2010;27:16-21.  Back to cited text no. 10
[PUBMED]  Medknow Journal  
11.
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.  Back to cited text no. 11
[PUBMED]    
12.
Lingegowda JB, MuddeGowda PH, Ramakantha CK, Chandrasekar HR. Cytohistological correlation of grading in breast carcinoma. Diagn Cytopathol 2011;39:251-7.  Back to cited text no. 12
[PUBMED]    
13.
Pandya AN, Shah NP. Comparative evaluation of Robinson's cytological grading with Elston and Ellis' Nottingham modification of Bloom Richardson histopathology grading for breast carcinoma. Natl J Community Med 2012;3:491-5.  Back to cited text no. 13
    
14.
Das S, Kalyani, Kumar H. Breast carcinoma aspirates: A study on cytological grading. Int J Basic Appl Med Sc 2012;2:189-95.  Back to cited text no. 14
    
15.
Robles-Frías A, González-Cámpora R, Martínez-Parra D, Robles-Frías MJ, Vázquez-Cerezuela T, Otal-Salaverri C, et al. Robinson cytologic grading of invasive ductal breast carcinoma: Correlation with histologic grading and regional lymph node metastasis. Acta Cytol 2005;49:149-53.  Back to cited text no. 15
    
16.
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.  Back to cited text no. 16
[PUBMED]    

Top
Correspondence Address:
Dr. Shweta Pal
9-A, Sewak Ashram Road, Dehradun, Uttarakhand
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0970-9371.190449

Rights and Permissions


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]

This article has been cited by
1 Cytological Grading of Breast Tumors—The Human and Canine Perspective
Krithiga Kuppusamy,Aarathi Rajan,Aarathy Warrier,Revathy Nadhan,Dipyaman Patra,Priya Srinivas
Frontiers in Veterinary Science. 2019; 6
[Pubmed] | [DOI]
2 Diagnostic efficacy of smear cytology and Robinson’s cytological grading of canine mammary tumors with respect to histopathology, cytomorphometry, metastases and overall survival
Izabella Dolka,Michal Czopowicz,Anna Gruk-Jurka,Agata Wojtkowska,Rafal Sapierzynski,Piotr Jurka,Douglas H. Thamm
PLOS ONE. 2018; 13(1): e0191595
[Pubmed] | [DOI]



 

Top
 
 
  Search
 
  
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  


    Abstract
   Introduction
    Materials and Me...
   Results
   Discussion
   Conclusion
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed3756    
    Printed41    
    Emailed0    
    PDF Downloaded514    
    Comments [Add]    
    Cited by others 2    

Recommend this journal