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Table of Content-Volume 12 Issue 2 - November 2019


 

Ductal carcinoma in situ: A study correlating histopathological patterns and grades

 

Lovely George1*, Muktha R Pai2

 

1Assistant Professor, Department of Pathology, Srinivas Institute of Medical Sciences and Research Centre, Mangalore.

2Professor and HOD, Department of Pathology, A.J Institute of Medical Sciences and Research Centre, Mangalore.

Email: lovegeorge123@gmail.com

 

Abstract               Breast cancer is the most common cancer in women worldwide representing nearly a quarter (25%) of all cancers with an estimated 1.67 million new cases diagnosed in 2012.1There is also a significant increase in the incidence and cancer-associated morbidity and mortality in Indian subcontinent as described in global and Indian studies2-4 Broadly, breast carcinomas can be classified as invasive and in situ carcinomas. Traditionally, breast cancers are morphologically typed according to the World Health Organization (WHO) guidelines. The World Health Organization Classification of Tumours, recognises at least 30 different invasive tumour types. Ductal carcinoma in situ (DCIS), conventionally regarded as a precursor of invasive carcinoma of the breast seems to be increasing in incidence particularly with the advent of mammography5. It is increasingly evident that DCIS is not a homogeneous disease. It shows different grades of malignant potential. Some subtypes of DCIS are more likely to recur, and some express biologic markers that are recognized as markers of poor prognostic outcome in invasive ductal carcinomas.6 Keeping these facts in mind this study was done to study the different subtypes of DCIS and correlate them with their histologic grades.

Key Words: DCIS, Comedo, Grading, In situ

 

 

INTRODUCTION

Breast cancer encompasses a heterogeneous group of tumours, which vary in morphology, clinical presentation, and behaviour. It is the most common cancer in women in developed countries, and 12% breast cancer occur in women between 20-34 yrs.7 In India, Breast Cancer is second to cancer of the Cervix among women, but is considered the leading cancer in certain metropolitan cities such as Mumbai and Bangalore. It is estimated that approximately 80,000 cases occur annually; the age adjusted incidence rates varying between 16 and 25/ 100,000 population. 8 Broadly, breast cancers are divided into in situ and invasive carcinomas. The World Health Organization Classification of Tumours, recognises at least 30 different invasive tumour types. Ductal carcinoma in situ (DCIS), conventionally regarded as a precursor of invasive carcinoma of the breast seems to be increasing in incidence particularly with the advent of mammography5. DCIS is defined as a clonal, neoplastic proliferation of epithelial cells with all the morphologic features of malignancy within the confines of the pre-existing ducts and lobules of the breast without invasion through the basement membrane.9 Ductal carcinoma in situ (DCIS) of the breast has been accepted as being a distinct clinical and histopathological entity since the 1940s.10 It includes a heterogeneous group of lesions with diverse morphologic features, genetic alterations, extent, presentation and clinical behaviour.6 It lies along a spectrum of preinvasive lesions originating within normal breast tissue, with histologic progression from atypical hyperplasia to invasive breast cancer.6 Diagnostic criteria for ductal carcinoma in situ depend, in part, on the degree of cytological atypia, but in general include cytonuclear and architectural features, clonality of the cell population and extent of the lesion6 It is increasingly evident that DCIS is not a homogeneous disease. It shows different grades of malignant potential. Some subtypes of DCIS are more likely to recur, and some express biologic markers that are recognized as markers of poor prognostic outcome in invasive ductal carcinomas.6 Keeping these facts in mind this study was done to study the different subtypes of DCIS and correlate them with their histologic grade.

 

MATERIALS AND METHODS

Present study was carried out in the department of Pathology, Father Muller Medical College, Mangalore. A total number of 60 mastectomy/lumpectomy specimens were included in the study.

Exclusion criteria: Specimens that did not show DCIS were excluded from the study

  • The clinical notes of all cases were reviewed for patient’s age and other relevant clinical data.
  • Sections from formalin fixed, paraffin embedded tissue were stained with hematoxylin and eosin stain.
  • All sections were examined and ductal carcinoma in situ was graded using the Lagios grading system.

Lagios classification for grading DCIS5

Low grade: Nuclear diameter of 1 to 1.5 times that of RBCs, Diffuse chromatin, Absence of nucleoli, Mitosis < 1 / 10 hpf and absence of Necrosis.

Intermediate grade: Nuclear diameter of 1 to 2 times that of RBCs, Coarse chromatin with Occasional Nucleoli, 1-2 Mitoses / 10 hpf and Necrosis 1+

High Grade: Nuclear diameter of more than 2 times that of RBCs, Vesicular nuclei with coarse chromatin, 1 or more nucleoli, 2 or more mitoses /10hpf and necrosis 3+

Statistical Analysis:

All the data was entered into Microsoft Excel 2010 spreadsheet and analysed using SSPS software version 13.0. Descriptive statistics were derived using frequency, percentage, mean, standard deviation. Chi square test and Fischer’s exact test were used to test the significance i.e. nominal significance at p value ≤ 0.05 level, for high significance the p value was ≤ 0.01 and for not significant the p value was > 0.05.

Correlation between DCIS grade and pattern of DCIS was done.

 

RESULTS

A total of 60 breast carcinoma cases were included in the study which included 58 mastectomy and 2 lumpectomy specimens. The age of the subjects ranged from 29 to 82 years, with a mean of 48.6 years (SD 11.21). The group of young women with breast cancer (< 40 years) included 10 patients (16.66 %) Majority of the tumours (57%) were in the left breast. In our study, the size of the tumour ranged from 1 to 8 cms, with a mean size of 3.55 cms (SD 1.45). The tumour measured > 5 cms in 11.7% (7/60) of the patients while the majority 68.3% (41/60) had tumours measuring 2 – 5 cms. The most common grade of IDC seen in the study was IDC grade 2 which constituted 58.3% of cases, this was followed by grade 3 (38.8%) cases and grade 1 (3.3%) cases.

Ductal carcinoma in situ grade:

High grade DCIS was most commonly encountered in our study and it constituted 63.3% of cases. This was followed by intermediate grade DCIS comprising of 31.7% cases. We also had 2 cases (3.3%) showing combined features of low grade and intermediate grade DCIS whereas 1 case (1.7%) showed intermediate and high grade DCIS (Fig 1)

Patterns of DCIS:

The most predominant pattern of DCIS was comedo (41.7%) followed by cribriform (30%). Other patterns included solid (18.3%), clear cell (6.7%) and micropapillary (3.3%) (Fig 2). Different patterns od DCIS are depicted in Fig 2.

1

 

       Figure 1: A 3D Cylindrical graph showing distribution of DCIS grades        Figure 2: A 3D conical graph showing patterns of DCIS

 

 

Other DCIS patterns

Mixed histology patterns i.e. a combination of different patterns of DCIS was observed in 30% of cases. The most commonly encountered combination was cribriform + comedo (6.66%) and solid + comedo (6.66%). The combinations of other patterns are illustrated below (Fig 3 – 6).

2

                                       Figure 3                                                                                         Figure 4

3

 Figure 5                                                                                                                   Figure 6

Figure 3: A bar diagram showing Clear cell DCIS (Dominant pattern) in combination with micropapillary DCIS; Figure 4: A 3-D conical graph representing cribriform DCIS (dominant pattern) in combination with other types of DCIS; Figure 5: A 3-D Cylindrical graph representing comedo DCIS (dominant pattern) in combination with solid type of DCIS; Figure 6: A 3-D bar diagram representing solid DCIS (dominant pattern) in combination with other types of DCIS

 

Patterns and DCIS grades:

A correlation between patterns and grades of DCIS (Fig 7) was done which was statistically significant (Fishers exact test p= .011, sig).

 

4

Figure 7: A cylindrical graph showing relation between patterns and grades of DCIS

1

 

Figure 8: Patterns of DCIS : A) Comedo type DCIS B) Clear cell DCIS C) Cribriform D) Solid DCIS E) Micropapillary DCIS

6

Figure 9: Intraductal carcinoma - Mixed histological type : Combination of clear cell and micropapillary DCIS (HandE Stain; 100x)

DISCUSSION

A total number of 60 cases with DCIS were examined in the present study In this study we used Lagios criteria for grading the DCIS component. High grade DCIS was seen in 38/60 (63.3%) cases, 19/60 (31.7%) showed intermediate grade DCIS whereas, 1 (1.66%) case showed intermediate to high nuclear grade and 2 (3.33%) cases exhibited low to high nuclear grade. Our results were found to be concordant with Cadman et al[11], whereas a deviation in results were seen between the present study and studies by Fischer et al[12] and Latta et al[13] ( Table 1)

 

Table 1: Grade of DCIS in various studies

 

No. of cases

Low grade

Intermediate grade

High grade

Dimorphic variants

Fischer et al[12]

78

48%

33%

19%

-

Latta et al[13]

136

7.3%

53.7%

39.0%

-

Cadman et al[11]

103

2%

37%

61%

-

Present study

60

-

31.7%

63.3%

5%

 


The cellular composition of intraductal carcinomas is typically monomorphic, which means that there is overall homogeneity in the cytologic appearance of the lesion. 9 Dimorphic variants 9 of intraductal carcinoma consisting of two distinctly different populations of cells, as seen in our study are unusual. (Table 1) In our study we employed Lagios system for grading DCIS as there are 2 major drawbacks in the application of systems that use a combination of nuclear grade and architectural pattern. One is the heterogeneity of architectural patterns within the same lesion; the other is the variation of nuclear grade within the same pattern subtype. For example, cribriform DCIS can show low, intermediate, and, less commonly, high nuclear grades. This problem can be avoided to a certain extent by using the Lagios system and Van Nuys system which uses nuclear grade as the main criterion with further subdivision by the presence or absence of necrosis. 5

PATTERNS OF DCIS

The most common pattern of DCIS encountered in our study was comedo type (41.7%) followed by cribriform (30%) and solid (18.3%). Other patterns included clear cell (6.7%) and micropapillary (3.3%). Overall, non comedo DCIS was more common. In our study, the most commonly encountered mixed histologic patterns were cribriform + comedo (6.66%) and solid + comedo (6.66%), which were in concordance with Rosen et al14 According to Rosen [14], mixed histologic pattern are found in 30% to 40% of cases and structural combinations like micropapillary-cribriform and solid-comedo occurred relatively more often than others.[14] We found 30 % of cases showing mixed histologic patterns.

 

CONCLUSION

In this study we found that there is a significant correlation between grades of DCIS and the different patterns of DCIS. As higher grades of DCIS are associated with worse prognosis, knowing the pattern of DCIS can help in predicting the biological behaviour of disease.

 

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