5. breast carcinoma histopathology types and clinical features

Breast cancer histopathology types and clinical features

1. BREAST CANCER HISTOPATHOLOGY TYPES AND CLINICAL FEATURES Presentor : Dr G Santhi Priya Moderator: Dr Rajeev 7/25/2018 Seminar

2. CONTENTS Introduction Risk factors Pathogenesis Pathways of breast cancer developement Clinical presentations Classification 7/25/2018 Seminar

3. 7/25/2018 Seminar INTRODUCTION

4. 7/25/2018 Seminar

5. Risk factors 7/25/2018 Seminar

6. Risk factors 7/25/2018 Seminar

7. Risk factors 7/25/2018 Seminar

8. PATHOGNESIS 7/25/2018 Seminar Most common gene implicated in Breast c a rci n o ma

9. BRCA -1  Breast Cancer 1,Early onset ( Chr.17) BRCA-2, Breast Cancer 2,Early onset( Chr.13) p53( Chr.17) CHEK2( Chr. 22) FUNCTIONS: Transcription DNA Repair of double stranded breaks Ubiquitination T r a ns c r i p t i o n a l regulation. FUNCTIONS: Stability of the human genome DNA double strand break repair. FUNCTIONS Cell cycle control DNA replication DNA repair Apoptosis. FUNCTIONS Cell cycle checkpoint kinase, recognition and repair of DNA damage. Activates BRCA1 and p53 by p ho sp h or y l a t io n Germline point m u t a t i o ns / D e l e t io n s of BRCA1 gene  Hereditary breast & ovarian cancers. Mutations  20% Hereditary breast cancer, ovarian cancer, increased cancer risk in male carriers. Mutations  Sporadic breast cancers.  Li fraumeni syndrome Mutations - rare (<5%). Li fraumeni variant Increase breast cancer risk after radiation exposure 7/25/2018 Seminar

10. PATHWAYS OF BREAST CANCER DEVELOPEMENT 7/25/2018 Seminar

11. CLINICAL PRESENTATION 7/25/2018 Seminar Symptoms of breast disease

12. PRESENTATIONS OF BREAST CANCER 7/25/2018 Seminar More than half of cancers are asymptomatic and are detected by mammographic screening and about another one third present as palpable masses—almost all discovered by the patient

13. CLASSIFICATION Breast cancers are conventionally classified into different types by Morphological feature, Histological features, Tumor grade, Proliferation status, Lymphovascular invasion – prognostic variables 7/25/2018 Seminar

14. WHO Classification EPITHELIAL TUMOURS MESENCHYMAL TUMOURS FIBROEPITHELIAL TUMOURS TUMOURS OF THE NIPPLE MALIGNANT LYMPHOMA METASTATIC TUMOURS TUMOURS OF THE MALE BREAST 7/25/2018 Seminar

15. EPITHELIAL TUMOURS Invasive breast carcinoma Epithelial– myoepithelial tumours Precursor lesions Intraductal proliferative lesions Papillary lesions Benign epithelial proliferations 7/25/2018 Seminar

16. MOLECULAR SUBTYPES 7/25/2018 Seminar

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18. Histopathological classification 7/25/2018 Seminar

19. DUCTAL CARCINOMA IN SITU Most DCIS  detected by calcifications on mammography / mammographic density - periductal fibrosis surrounding a DCIS/rarely palpable mass/ nipple discharge/incidental finding on a biopsy for another lesion . Spreads through ducts & lobules  extensive lesions  entire sector of a breast . 7/25/2018 Seminar

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21. DCIS Characteristic Comedo Noncomedo Nuclear grade High Low Estrogen receptor Negative Positive HER2 overexpression Present Absent Distribution Continuous Multifocal Necrosis Present Absent Local recurrence High Low Prognosis Worse Better MORPHOLOGY 7/25/2018 Seminar

22. COMEDOCARCINOMA Solid sheets of pleomorphic cells with high grade hyperchromatic nuclei. Areas of central necrosis +nt. Necrotic cell membranes – calcify  clusters/linear & branching microcalcifications on mammography. Periductal concentric fibrosis & chronic inflammation. Extensive lesions – palpable as vague nodularity. 7/25/2018 Seminar

23. NONCOMEDO DCIS Monomorphic cell population – nuclear grades  low to high. CRIBRIFORM DCIS Intra-epithelial spaces – evenly distributed, regular in shape . COOKIE CUTTER – LIKE SOLID DCIS Completely fills the involved spaces. 7/25/2018 Seminar

24. NONCOMEDO DCIS PAPILLARY DCIS Grows into spaces along fibrovascular cores  lack myoepithelial cell layer . M I C R O P A P I LL ARY DCIS Bulbous protrusions without a fibrovascular core arranged in complex intraductal patterns . Calcifications – assoc.with necrosis/form on intraluminal secretions. 7/25/2018 Seminar

25. MANAGEMENT AND PROGNOSIS OF DCIS MASTECTOMY for DCIS – curative  > 95 % pts. In ER + ve DCIS  Post- op. radiation + Tamoxifen  recurrence risk – low. Death  < 2 % DCIS. 7/25/2018 Seminar

26. LOBULAR CARCINOMA IN SITU Incidental biopsy finding - no calcifications /stromal reactions  mammographic densities . Bilateral - 20% to 40 % . Young women . Loss of expression of E- cadherin (transmembrane cell adhesion protein  cohesion of normal breast epithelial cells). 7/25/2018 Seminar

27. LOBULAR CARCINOMA IN SITU - MORPHOLOGY Dyscohesive round cells with oval or round nuclei and small nucleoli . Absence of atypia, pleomorphism, mitoti activity, necrosis . ER and PR +ve. 7/25/2018 Seminar

28. LOBULAR CARCINOMA IN SITU Invasive carcinoma  1% per year . Both breasts - increased risk. Risk - slightly higher in the ipsilateral breast . Treatment: Bilateral prophylactic mastectomy. Tamoxifen. Close clinical follow-up. Mammographic screening. 7/25/2018 Seminar

29. INVASIVE CARCINOMA – CLINICAL FEATURES Palpable mass . Axillary lymph node metastases Fixity to the chest wall / skin dimpling . Nipple retraction Lymphatics - involved - block the local area of skin drainage  lymphedema , skin thickening . Tethering of the skin to the breast by Cooper ligaments  peau d'orange . Mammography  Radiodense mass 7/25/2018 Seminar

30. INVASIVE CARCINOMA- NST Majority (70% to 80%). Gross appearance: Most tumors - firm to hard ,irregular border . Less frequently - well- circumscribed border , softer consistency. When cut / scraped  characteristic grating sound d/t small, central pinpoint foci or streaks of chalky-white elastotic stroma and occasional small foci of calcification. 7/25/2018 Seminar

31. INVASIVE LOBULAR CARCINOMA Palpable mass/ mammographic density with irregular borders. Sometimes - tumor infiltrates the tissue diffusely – little desmoplasia, not palpable, no mammographic density. Metastases – difficult to detect . Bilateral - 5 – 10 %. Biallelic loss of expression of ( CDH1 ,  encodes E- cadherin ) d/t mutations. 7/25/2018 Seminar

32. INVASIVE LOBULAR CARCINOMA Morphology: Histologic hallmark  dyscohesive infiltrating tumor cells, often arranged in single file or in loose clusters or sheets  INDIAN FILE APPEARANCE. Tubule formation - absent. Signet-ring cells containing an intracytoplasmic mucin droplet are common. Desmoplasia - minimal or absent 7/25/2018 Seminar

33. MEDULLARY CARCINOMA MC - 6 th decade. May closely mimic a benign lesion clinically and radiologically/ present as a rapidly growing mass. MORPHOLOGY : Well – circumscribed,soft,fleshy mass - little desmoplasia  more yielding on palpation and cutting . . 7/25/2018 Seminar

34. MEDULLARY CARCINOMA - HPE . Solid, syncytium-like sheets of large cells with vesicular, pleomorphic nuclei, prominent nucleoli  > 75% of the tumor Frequent mitotic figures; Moderate to marked lymphoplasmacytic infiltrate surrounding and within the tumor. Pushing (noninfiltrative) border. 7/25/2018 Seminar

35. MEDULLARY CARCINOMA High nuclear grade, aneuploidy, hormone receptors - nt, HER2/neu overexpression – nt . L ym p h n o de m e ta s ta s e s - infrequent . S yn c y t i al gr o w th p a t t e rn a n d p us h i n g bor d e r s - d / t overexpression of adhesion m o l e c u l e s  i n t e rc e ll u lar c e ll a d h es io n m ol e c u l e a n d E - c a dh e r i n  l i m i t m e t a s t a t i c p o t e n t i al. 7/25/2018 Seminar

36. MUCINOUS/COLLOID CARCINOMA Older women (median age 7 1 )  gr o w s l o w ly - many years. Morphology: Tumor – soft/rubbery . Consistency & appearance of pale gray-blue gelatin. Borders - pushing / circumscribed. 7/25/2018 Seminar

37. MUCINOUS CARCINOMA - HPE Tumor cells - arranged in clusters and small islands within large lakes of mucin . Mucinous carcinomas  diploid, well to moderately differentiated, and ER positive . Lymph node metastases - uncommon . Overall prognosis is slightly better. 7/25/2018 Seminar

38. TUBULAR CARCINOMA Small irregular mammographic densities - late 40s . Uncommon . Morphology: Well-formed tubules + nt, myoepithelial cell layer, BM - nt  tumor cells in direct contact with the stroma. Apocrine snouts - typical . Calcifications - within the lumens . > 95% of all tubular carcinomas - diploid, ER + ve,HER2/neu – ve . Well differentiated. Excellent prognosis. 7/25/2018 Seminar

39. INVASIVE PAPILLARY & MICROPAPILLARY CARCINOMA Rare - 1% or fewer of all invasive cancers. More commonly seen in DCIS. I N VA S I V E P A P I LL A R Y C A . ER positive. Favorable prognosis. INVASIVE MICROPAPILLARY CA. ER negative,HER2 positive. Lymph node metastases - very common Prognosis is poor. 7/25/2018 Seminar

40. INFLAMMATORY CARCINOMA Tumors  swollen, erythematous breast - caused by extensive invasion and obstruction of dermal lymphatics by tumor cells. Underlying carcinoma - diffusely infiltrative - does not form a discrete palpable mass  confusion with true inflammatory conditions a  delay in diagnosis. Many patients  metastases at diagnosis / recur rapidly. 7/25/2018 Seminar

41.  METAPLASTIC CARCINOMA Includes a variety of rare types of breast cancer (<1% of all cases)  matrix-producing carcinomas, squamous cell carcinomas, and carcinomas with a prominent spindle cell component. ER-PR-HER2/neu “triple negative ”. Lymph node metastases - infrequent . Prognosis - poor. 7/25/2018 Seminar

42. References 1. Lester SC,The Breast. In Kumar V, Abbas A K, Aster J C, Robbins and cotran patholology basis of disease. 9 th ed. Elsevier Inc: 2016. P.1043-72. 2.Rosenblum M K,Rosai J. Breast.In : Rosai J, editors. Rosai and Ackerman's Surgical Pathology. 10th Ed. Philadelphia: Mosby Elsevier: 2011.p1631-718 3. Li CI,Uribe DJ,Daling JR.Clinical characteristics of different histopathologic types of breast cancer.BJCancer.2005(93),1046-1052 4. Rakha EA, Ellis IO. Molecular profiling of breast cancer. In: recent advances in histopathology. 24th ed. New Delhi: JP medical publisher; 2016. 13-25. 7/25/2018 Seminar