CLASSIFICATION OF BREAST TUMORS (1).pptx

breast carcinoma

1. CLASSIFICATION OF BREAST TUMORS Dr. P TEJASWI REDDY MBBS, MD ASST PROFESSOR (PATHOLOGY)

2. CONTENTS INTRODUCTION WHO CLASSIFICATION HISTOLOGICAL TYPES MOLECULAR CLASSIFICATION RECENTLY ADDED TYPES REFERENCES

3. I ntroduction Adenocarcinomas (95%) Invasive ductal carcinomas constituted 55% of breast carcinomas ORIGIN: TDLU Breast carcinomas is divided into DCIS and IDC DCIS: Non-invasive malignant intraductal proliferation of epithelial cells confined to ducts and lobules INVASIVE: anormal proliferation of neoplastic cells in the breast tissue which has penetrated through the duct wall into stroma DUCTAL LOBULAR

4. DCIS CHARACTERISTICS: 1. Limited to ducts 2. cellular and nuclear atypia 3. malignant potential Myoepithelial cells of outer layer are preserved, accentuated or decreased Lobular cancerization

5. WHO CLASSIFICATION OF BREAST TUMORS

6. MORPHOLOGICAL TYPES OF DCIS Historically, DCIS has been divided into five architectural subtypes: comedo , solid, cribriform, papillary, and Micropapillary signet ring cells, neuroendocrine differentiation or multinucleated giant cells ,  apocrine metaplastic cells ,  and squamous features (squamous cell carcinoma in situ) in cases .

7. COMEDO

8. Depending primarily on the degree of nuclear atypia , intraluminal necrosis, and, to a lesser extent, mitotic activity and calcification, DCIS is generally divided into three types: LOW, INTERMEDIATE and HIGH Cytological Features( LOW GRADE ) 1. Monotonous, uniform round cells population 2. Subtle increase in nuclear-cytoplasmic ratio 3. Equidistant or highly organized nuclear distribution 4. Round nuclei 5. Hyperchromasia may or may not present Architecture Features Arcades, cribriform, solid and or micropapillary pattern

9. INTERMEDIATE GRADE DCIS forming solid, micropapillary patterns but with some ducts containing intraluminal necrosis Nuclei with occasional nucleoli C oarse chromatin necrosis may or may not be present .

10. HIGH GRADE . It consists of one layer of highly atypical cells, forming micropapillae , cribriform, or solid patterns. Nuclei are of high grade, markedly pleomorphic, with irregular contour and prominent nucleoli. Mitotic figures+. comedo necrosis is characteristically surrounded by a solid proliferation of large pleomorphic tumor cells. highly anaplastic cells lining the duct in a flat fashion is sufficient

11. LCIS CHARACTERISTICS: It is the intralobular proliferation of small, fairly uniform, and loosely cohesive cells, originating in the TDLU, with or without pagetoid involvement of terminal ducts. Incidental M ulticentric Bilateral >50% of acini in atypical lobular neoplasia

12. pagetoid spread uniform population of round, small-to-medium-sized cells makes the ducts appear convoluted; this is called a cloverleaf pattern normochromatic nuclei filling the distended lobules in a noncohesive pattern . pleomorphism , mitosis, and necrosis are absent or rarely present . Intracellular mucin droplets are commonly seen sometimes with signet ring nuclei.

13. Classic LCIS Pleomorphic LCIS Florid LCIS ,

14. INVASIVE DUCTAL CARCINOMA Invasive ductal carcinomas are breast cancers having malignant ductal proliferation along with stromal invasion in the presence or absence of DCIS, apart from their relative proportion . IDC is classified into many histological subtypes according to a wide range of criteria cell type (as in apocrine carcinoma ) amount, type and location of secretion (as in mucinous carcinoma ) architectural features (as in papillary, tubular, and micropapillary carcinoma) and immunohistochemical profile (as in neuroendocrine carcinoma )

15. Tumor size, grade, relative proportion of tumor cell and stroma , and types of margins. heterogenous type of growth, including diffuse sheets, nests, cords, or singly distributed cells with variable amount of ductal differentiation 70 % of tumor tissue prominent nucleoli and numerous mitoses. areas of necrosis and calcification can be detected in 60% of cases . Foci of squamous metaplasia, apocrine metaplasia, or clear cell changes are sometimes present .

16. Histologic grading is based on the Nottingham / modified Bloom & Richardson Score ( Histopathology) Tubule formation (1 - 3 points): > 75% (1 point) 10 - 75% (2 points) < 10% (3 points) Nuclear pleomorphism (1 - 3 points): Small, regular, uniform, similar to normal ductal epithelial cells, 2 - 3x RBC (1 point) Moderate increase in size / variability (2 points) Large nuclei, marked variation, often vesicular chromatin with prominent nucleoli (3 points) Mitotic count (1 - 3 points), dependent on microscopic field area Total score (add points for tubule formation, nuclear pleomorphism and mitotic count): 3 - 5 points : grade 1 6 - 7 points: grade 2 8 - 9 points: grade 3

17. Tubular carcinoma Invasive cribriform carcinoma

18. MEDULLARY CARCINOMA MUCINOUS CARCINOMA

19. Invasive Lobular Carcinoma 1. Classic 2. pleomorphic lobular carcinoma 3. histiocytoid 4. signet ring cell carcinoma 5. tubulolobular carcinoma

20. Molecular Classification T o supplement the morphological classification of breast carcinoma with molecular parameters that can provide a clearer appreciation for the heterogeneity of breast cancer and for better prediction of tumor behavior to improve therapeutic strategies. distinct subgroups based on similarities in the gene expression profiles using the microarray technology therapeutic approach of breast cancers

21. LUMINAL A 50 % of invasive breast cancers. ER/PR positive or HER2 negative. low-grade variants, such as tubular carcinoma, cribriform carcinoma, low-grade IDC NST, and classic lobular carcinoma and usually expresses low molecular weight cytokeratins , which highlight the luminal ductal cells It has a good prognosis and is typically of low grade and ER positive

22. LUMINAL A

23. LUMINAL B 20 % of invasive breast cancers. The ER/PR is positive, while HER2/ neu expression is variable (positive or negative). The proliferation index rate expressed by Ki-67 and histological grades are higher than luminal A. It includes most of grade 2 IDC NST and micropapillary carcinoma. The response to endocrine therapy and chemotherapy is variable, and its prognosis is poorer than luminal A

24. LUMINAL B

25. HER2 15 % of all invasive breast cancers. The ER/PR is usually negative, while by definition, HER2/ neu is strong positive . The Ki-67 expression is high and TP53 mutation is common. These tumors are more likely to be of high grade and having lymph node metastasis. This group of breast cancer implies poor prognosis and shows the highest sensitivity to trastuzumab ( herceptin ) therapy

26. Molecular Subtypes of Breast Cancer - HER2-enriched:

27. BASAL LIKE The basal class is so named due to its pattern of expression that is similar to basal epithelial cells and normal myoepithelial cells of mammary tissue. It is typically CK5/6 and/or EGFR positive, ER/PR negative, and HER2 negative (triple negative),25 with a high expression of Ki-67 index and TP53 mutation , It comprises about 15% of all invasive breast cancers. The gene expression patterns include high expression of basal epithelial genes, positive for basal cytokeratins ; low expression of ER and associated genes; and low expression of HER2/ neu . good prognosis, which expressed low proliferation index rate of Ki-67, such as medullary, adenoid cystic, and secretory carcinoma, are also included in this group . It has no response to endocrine therapy or trastuzumab but sensitive to platinum-based chemotherapy and poly (adenosine diphosphate -ribose) polymerase inhibitors. It has generally poor prognosis (but not uniformly poor).

28. BASAL LIKE SQUAMOID TUMOR TYPE(CK5/6) SQUAMOID TUMOR TYPE(EGFR )

29. RARE VARIANTS OF IBC-NST Oncocytic , lipid rich, glycogen-rich, clear cell, sebaceous, carcinomas with choriocarcinoma , carcinomas with stromal giant cells Invasive BC with medullary pattern Neurroendocrine tumors Well differentiated liposarcoma in phyllodes tumor Mucinous cystadenocarcinomas Tall cell carcinoma with reverse polarity

30. REFERENCES Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, Van de Vijver MJ, editors. WHO Classification of Tumours of the Breast. Fourth ed. IARC; Lyon: 2012. ISBN.13. [Google Scholar] 2. Peter B, Bernard L. World Cancer Report. International Agency for Research on Cancer; WHO Press; Lyon, France: 2008 Rosai J. Rosai and Ackerman’s Surgical Pathology. Tenth ed. Elsevier; Lyon, France: 2011 .