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OJHAS Vol. 23, Issue 1: January-March 2024

Original Article
Correlation of Cytological Features with Axillary Lymph Nodal Involvement in Invasive Ductal Carcinoma of Breast - A Retrospective Study

Authors:
Rakshitha HB, Associate Professor, Department of Pathology, Adichunchanagiri Institute of Medical Sciences, BG Nagara, Karnataka,
Aneesha Asok Kumar, Associate Professor, Department of Pathology, MES Medical College, Perithalmanna, Malapuram, Kerala,
Sanjay M, Professor, Department of Pathology, Adichunchanagiri Institute of Medical Sciences, BG Nagara, Karnataka,
Jalli Pravallika, Senior Resident, Department of Pathology, Venkateshwara Institute of Medical Sciences, Uttar Pradesh.

Address for Correspondence
Dr Jalli Pravallika,
Senior Resident,
Department of Pathology,
Venkateshwara Institute of Medical Sciences,
Uttar Pradesh, India.

E-mail: jallipravallika3016@gmail.com.

Citation
Rakshitha HB, Kumar AA, Sanjay M, Pravallika J. Correlation of Cytological Features with Axillary Lymph Nodal Involvement in Invasive Ductal Carcinoma of Breast - A Retrospective Study. Online J Health Allied Scs. 2024;23(1):8. Available at URL: https://www.ojhas.org/issue89/2024-1-8.html

Submitted: Jan 18, 2024; Accepted: Mar 29, 2024; Published: Apr 25, 2024

 
 

Abstract: Background: Fine needle aspiration cytology (FNAC) is very useful for the pre-operative diagnosis of breast cancer. The efficacy of FNAC to determine the prognosis in breast carcinomas has to be explored. Aims: The present study is designed to determine the prognostic role of FNAC by correlation of the cytological features of Invasive Ductal carcinoma of Breast (IDC) with the axillary lymph nodal metastasis, which is a known prognostic marker. Materials and Methods: A total of 68 cases of IDC of breast diagnosed on FNAC with subsequent modified radical mastectomy in our hospital were included in the study group. Both FNAC and histopathology slides were retrieved for all the cases. The FNAC smears were assigned cytological grades according to Robinson's grading system. The histopathological sections of axillary lymph nodes were assessed for metastasis. Correlation was done between cytological grade and lymph nodal metastasis. Results: Cytological grading of IDC and axillary lymph nodal metastasis showed a statistically significant correlation (P <0.05). Individual features like nuclear size, cell uniformity, nucleoli and nuclear margin showed positive correlation with axillary lymph node metastasis (P < 0.05). Conclusion: Positive correlation is observed between Robinson's cytological grading of IDC on FNAC with axillary lymph nodal metastasis, hence cytological grading on FNAC can be used as a prognostic tool. Possibility of axillary lymph nodal metastasis in cases with high cytological grade of IDC on FNAC must be considered by the treating oncologist for the adequate patient management.
Key Words: Invasive duct carcinoma, Fine needle aspiration cytology, Robinson's cytological grading, Axillary nodal metastasis

Introduction

Breast cancer is an important cause of cancer mortality in Indian women [1]. Biologic markers like histological grade of the tumor, Estrogen and progesterone hormone receptor expression, HER2 overexpression, and/or amplification and genomic panels are the important predictors of survival in breast carcinoma [2]. But in a remote resource poor setting, the TNM staging classification still continues to be an important predictor of cancer survival [3]. Lymph node metastasis is an important prognostic factor which plays a vital role in staging and management of patients [4]. Fine needle aspiration cytology is a reliable method for the diagnosis of breast carcinoma. There are various cytological grading systems for breast carcinoma of which Robinson’s grading system is one which has 6 cytological parameters [5]. Studies done in the past have shown correlation between cytological grading on FNAC and histological tumor grade [5-9]. These studies have concluded that the cytological tumor grading on FNAC can predict the tumor prognosis, especially for patients who have received neo-adjuvant therapy. Few studies have shown correlation between cytological tumor grade and axillary lymph nodal metastasis [7,9,10]. The present study is designed to explore the prognostic role of FNAC in Invasive Ductal Carcinoma of breast by correlating the cytological grade with axillary lymph node status.

Materials and Methods:

This is a retrospective study conducted in the department of Pathology in a tertiary rural teaching hospital in Mandya, Karnataka. The study group included 68 cases of Invasive Ductal Carcinoma of breast diagnosed on FNAC who subsequently underwent modified radical mastectomy in our hospital. FNAC slides of the breast tumor and the histopathology slides of axillary lymph nodes of all the cases were retrieved. The FNAC slides of all 68 cases of IDC were assessed for cytological grade using Robinson's grading system. (Table 1) The scores for all individual cytological criteria were recorded for all the cases.

Table 1: Robinson’s method for cytological grading

Parameter

Score 1

Score 2

Score 3

Cell dissociation

Cells mostly in clusters

Mixture of single cells and clusters

Mostly single cells

Cell size

1-2 times size of red blood cells

3-4 times size of red blood cells

≥ 5 times size of red blood cells

Cell uniformity

Monomorphic

Mildly pleomorphic

Pleomorphic

Nucleoli

Indistinct

Noticeable

Prominent

Nuclear margins

Smooth

Slightly irregular/folds and grooves

Buds and clefts

Chromatin

Vesicular

Granular

Clumped and cleared

The histopathology slides of axillary lymph nodes stained by Hematoxylin-and-eosin were analyzed for the presence of metastasis. Statistical analysis was done by SPSS statistical software package, version 14.0. Finally, the cytological tumor grade and all individual cytological features were correlated with the presence or absence of axillary lymph node metastasis using χ2 test and P < 0.05 was considered statistically significant.

Results:

The study group included a total number of 68 cases. Cytological grading of all the 68 cases were done using Robinson’s method (Table 1). 24 cases were assigned grade 1, 17 cases were assigned grade 2 and 27 cases were assigned grade 3 (Table 2) (Figure 1, 2 &amp; 3). Of the 68 cases of IDC breast, 51 cases (75%) showed metastasis to axillary lymph node (Figure 4) and 17 cases (25 %) did not show axillary lymph nodal metastasis (Table 3). Of the 24 cases with cytological grade 1, 14 cases (58.3%) showed lymph node positivity and 10 cases (41.6%) did not show lymph node positivity. Of the 17 cases with cytological grade 2, 13 cases (76.4%) showed lymph node positivity and 4 cases (23.5%) did not show lymph node positivity. Of the 27 cases with cytological grade 3, lymph node positivity was seen in 24 cases (88.8%) and negative in 3 cases (11.1%). (Table 3).

The cytological grade assigned were correlated with the presence and absence of lymph node metastasis using chi square test and a P value of <0.05 was obtained which was statistically significant.

Finally, the score of individual cytological criterias of Robinson’s system which are Cell dissociation, Nuclear size, Cell uniformity, Nucleoli, Nuclear margin and Chromatin pattern were correlated with the presence or absence of axillary lymph nodal metastasis (Table 4).

For Nuclear size cytological scores 1, 2 and 3, lymph node positivity was seen in 6 (11.7%), 16 (31.3%) and 29 (56.8%) cases respectively, whereas lymph nodes were negative in 1 (5.8%), 12 (70.5%) and 4 (23.5%) cases respectively. For Cell uniformity cytological scores 1, 2 and 3, lymph node positivity was seen 6 (11.7%), 20 (39.2%) and 25 (49%) cases respectively, whereas lymph nodes were negative in 7 (41.1%), 6 (35.2%) and 4 (23.5%) cases respectively.

For Nucleoli cytological scores 1, 2 and 3, lymph node positivity was seen in 9 (17.6%), 18 (35.2%) and 24 (47%) cases respectively, whereas lymph nodes were negative in 8 (47%), 7 (41.1%) and 2 (11.7%) cases respectively. For Nuclear margin cytological scores 1, 2 and 3, lymph node positivity was seen in 7 (13.7%),43 (84.3%) and 1 (1.9%) cases respectively, whereas lymph nodes were negative in 7 (23.5%), 6 (11.7%) and 4 (5.8%) cases respectively.

For these four cytological criteria, as the scores increased from 1 to 3 the proportion of cases with lymph node positivity also increased and the proportion of cases negative for lymph node metastasis decreased. This correlation between cytological scores and lymph node status showed statistically significant correlation.

The other two cytological criteria, cell dissociation and chromatin pattern did not show statistically significant correlation with the lymph nodal metastasis. For Cell dissociation cytological scores 1, 2 and 3, lymph node positivity was seen in 15 (29.4%), 25 (49%) and 11 (21.5%) cases respectively, whereas lymph nodes were negative in 7 (41.1%), 9 (52.90%) and 1 (5.8%) cases respectively. For Chromatin pattern cytological scores 1, 2 and 3, lymph node positivity was seen in 8(15.6%), 39 (76.4%) and 4 (7.8%) cases respectively, whereas lymph nodes were negative in 2 (11.7%), 14 (82.3%) and 1 (5.8%) cases respectively.

Table 2: Assignment of Robinson’s Cytological grades to the study group (n=68)

Robinson’s Cytological grade

Number of cases

Grade 1

24 (35.2%)

Grade 2

17 (25%)

Grade 3

27 (39.7%)

Total

68

Table 3: Correlation of Robinson’s cytological grade with axillary lymph node metastasis.

Robinson’s Cytological grade

Lymph node positive

Lymph node negative

Total

1

14 (58.3%)

10 (41.6%)

24 (100%)

2

13 (76.4%)

4 (23.5%)

17 (100%)

3

24 (88.8%)

3 (11.1%)

27 (100%)

Total

51 (75)

17 (25)

68 (100%)   

Chi square test- 6.35 P value-0.04 df-2

Table 4: Correlation of individual cytological features with the axillary lymph node status

Cytological criteria

Total

Chi square

P value


Score 1

Score 2

Score 3

Lymph node metastasis

Present

Absent

Present

Absent

Present

Absent

Present

Absent


Cell dissociation

15 (29.4%)

7 (41.1%)

25 (49%)

9 (52.90%)

11 (21.5%)

1 (5.8%)

51 (100%)

17 (100%)

2.36

0.3

Nuclear size

6 (11.7%)

1 (5.8%)

16 (31.3%)

12 (70.5%)

29 (56.8%)

4 (23.5%)

51 (100%)

17 (100%)

8.10

0.017

Cell uniformity

6 (11.7%)

7 (41.1%)

20 (39.2%)

6 (35.2%)

25 (49%)

4 (23.5%)

51 (100%)

17 (100%)

7.76

0.02

Nucleoli

9 (17.6%)

8 (47%)

18 (35.2%)

7 (41.1%)

24 (47%)

2 (11.7%)

51 (100%)

17 (100%)

8.68

0.013

Nuclear margin

7 (13.7%)

7 (23.5%)

43 (84.3%)

6 (11.7%)

1 (1.9%)

4 (5.8%)

51 (100%)

17 (100%)

16.98

0.0002

Chromatin pattern

8(15.6%)

2 (11.7%)

39 (76.4%)

14 (82.3%)

4 (7.8%)

1 (5.8%)

51 (100%)

17 (100%)

0.25

0.8



Figure 1: IDC with cytological grade 1 (H&E, X400). The cells are arranged in clusters in a hemorrhagic background. Figure 2: IDC with cytological grade 2 (H&E, X400). The cells are arranged in clusters and in singles.




Figure 3: IDC with cytological grade 3 (H&E, X400). The cells are arranged in singles. Figure 4: Axillary lymph node with IDC metastasis (H&E, X400).

Discussion:

Of the 68 cases of IDC breast, 51 cases (75%) showed metastasis to axillary lymph node and 17 cases (25 %) did not show axillary lymph nodal metastasis. Of the 68 cases, cytological grade 1, 2 and 3 were assigned to 24, 17 and 27 cases respectively (Figure 1, 2 &amp; 3). 0f the 24 cases with cytological grade 1, axillary lymph nodal metastasis was present in 14 cases (58.3%) and absent in 10 cases (41.6%). 0f the 17 cases with cytological grade 2, axillary lymph nodal metastasis was present in 13 cases (76.4%) and absent in 4 cases (23.5%). 0f the 27 cases with cytological grade 3, axillary lymph nodal metastasis was present in 24 cases (88.8%) and absent in 3 cases (11.1%). In our study, it is observed that as the cytological grading of the tumor increased from 1 to 3, the number of cases showing metastasis to lymph node increased and this correlation is statistically significant (p < 0.05).

Similar studies done in the past also showed a statistically significant association between cytological grade and presence of axillary metastasis (p < 0.05) [7, 9, 11, 12].

Few studies have shown that the cytological grade correlates well with the histological grade obtained by modified Nottingham- Bloom–Richardson system [ 13, 14].

It is observed in our study that the cytological scores of four cytological criteria of Robinson’s system which are Nuclear size, Cell uniformity, Nucleoli and Nuclear margin correlated well with the axillary lymph nodal metastasis and was found to be statistically significant, whereas the cytological scores of other two criteria, cell dissociation and chromatin pattern did not show significant correlation with lymph node metastasis. (Table 4).

Another study by Sinha A et al, showed that among the six criteria, cell uniformity and nuclear size showed significant positive correlation with the presence of metastasis in axillary lymph nodes [11].

In a study by Robles-Frias et al, three features, that is, cell uniformity, cell dissociation, and nuclear margin showed a positive correlation with metastasis to axillary lymph node [7]. Similar to Robles-Frias et al, our study also showed that cell uniformity and nuclear margin showed a positive correlation with metastasis to axillary lymph node, but cell dissociation was not found to have significant correlation to lymph nodal metastasis in our study.

Similar to a study by Sinha A et al, both cell uniformity and nuclear size showed significant positive correlation with the presence of metastasis in axillary lymph nodes in our study [11]. In addition to these criteria, the present study also found that nucleoli showed positive correlation with the presence of metastasis in axillary lymph nodes.

The present study showed that the cytological scores of Nuclear size, Cell uniformity, Nucleoli and Nuclear margin correlated well with the axillary lymph nodal metastasis. Nuclear pleomorphism is an important component of Bloom Richardson histological grading system and correlates with prognosis [15, 16]. Nuclear size and cell uniformity are the features of pleomorphism. Tumors with increased cytological scores of nuclear size and cell uniformity will have greater pleomorphism, which explains their correlation with axillary nodal metastasis.

Nuclei are required for DNA replication or transcription, and nucleoli constitutes a major part of nuclei. Few studies have demonstrated that nucleoli and nuclear margin are extremely important in differentiating cytological grades of malignant tumors [17, 18].

But the cytological scores of nucleoli and nuclear margins did not show statistically significant correlation with the axillary nodal metastasis in our study. This result is similar to the results of previous studies [7, 11].

Conclusion:

The Robinson’s cytological grading of IDC breast on FNAC correlates with the axillary lymph nodal metastasis. Hence cytological grading on FNAC can be used as an important prognostic tool. In patients of IDC with higher cytological grades on FNAC the possibility of axillary lymph nodal metastasis has to be considered by the treating oncologist which helps in proper patient management.

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