CLASSIFICATION OF TUMOURS

1. بسم الله الرحمن الرحيم

2. CLASSIFICATION OF TUMOURS

3. CLASSIFICATION OF TUMOURS Dr Mohamed Elkablawy ملاحظة ناقص اضافة الصور Neoplasia 2

4. CLASSIFICATION OF TUMOURS Intended Learning outcomes By the end of this talk you should Be aware of the calssification of tumours Know how tumours are named Be familiar with the differences between benign and malignant tumours Know how malignant tumours spread

5. CLASSIFICATION OF TUMOURS Calssification Of Tumours Usually on basis of presumed cell/tissue of origin OR On predicted behaviour

6. CLASSIFICATION OF TUMOURS Calssification Of Malignant Tumours Usually on basis of cell/tissue of origin Main groups are: Epithelial Connective tissue (mesenchymal) Lymphoid/haematological Mixture of all (teratomas)

7. CLASSIFICATION OF TUMOURS Nomenclature Tissue of origin Epithelial: cell of origin benign malignant Squamous cell Papilloma Sq C carcinoma Glandular Adenoma Adenocarcinoma Transitional TC Papilloma T C carcinoma Basal BC Papilloma B C carcinoma

8. CLASSIFICATION OF TUMOURS Nomenclature Tissue of origin Mesenchymal: cell of origin benign malignant Smooth Muscle Leiomyoma Leiomyosarcoma Striated Muscle Rhabdomyoma Rhabdomyosarcoma Blood Vs Heam(angioma) Angiosarcoma Nerves Neurofibroma Neurofibrosarcoma Adepose tissue Lipoma Liposarcoma Cartilage Chondroma Chondrosarcoma Bone Osteoma Osteosarcoma

9. CLASSIFICATION OF TUMOURS Nomenclature Tissue of origin Mesenchymal: cell of origin benign malignant Lymphoid Lymphoma Hemopoietic Leukemia Melanocytes Neavus Melanoma Embryonic tisue Totipotential cells Teratoma Malignant teratoma Unipotential cells Retinoblastoma Nephroblastoma

10. CLASSIFICATION OF TUMOURS Benign Tumours Generally slow growing Remain localised Do not invade surrounding tissues Do not spread to distant sites Resemble tissue of origin i.e. Well differentiated

11. CLASSIFICATION OF TUMOURS Benign Tumours (Microscopic) Mitotic activity is low Mitotic figures appear normal Nuclei appear normal No necrosis

12. CLASSIFICATION OF TUMOURS Benign Tumours (Effects) May be unsightly, removed for cosmotic purposes Damage tissue by pressure effects Block ducts such as a pancreas or bronchus Block flow of fluid in brain May secrete hormones May become malignant

13. CLASSIFICATION OF TUMOURS Malignant Tumours Generally rapid growing Irregular edges poorly defined margins Invade surrounding tissues Spread to distant sites May not resemble tissue of origin i.e. poorly differentiated or anaplastic

14. CLASSIFICATION OF TUMOURS Malignant Tumours (Microscopic) Mitotic activity is high Abnormal Mitotic figures Nuclei are hyperchromatic and pleomorphic Necrosis usually occur

15. CLASSIFICATION OF TUMOURS Malignant Tumours (Spread) Invade surrounding tissues Spread via lymphatic channels to lymph nodes Spread via blood stream to other organs i.e. metastasis Spread across body cavities

16. CLASSIFICATION OF TUMOURS Malignant Tumours - Effects Destruction of adjacent tissues causing pain and loss of function Pressure on structures leading to necrosis and infection Haemorrhage from surface ulceration Obstruction of flow through vital structures

17. CLASSIFICATION OF TUMOURS Malignant Tumours - Effects Secondary deposits (metastasis) causing damage at distant sites Cachexia (wasting) due to tumour necrosis factor- α Production of hormones either appropriate or inappropriate (ectopic) Paraneoplastic syndromes

18. carcinoma of breast . This is not a specific histologic type of breast cancer, but rather it implies dermal lymphatic invasion by some type of underlying breast carcinoma. Such involvement of dermal lymphatics gives the grossly thickened, erythematous, and rough skin surface with the appearance of an orange peel (" peau d'orange "). BACK

19. CLASSIFICATION OF TUMOURS Malignant Tumours - Metastasis Process by which neoplastic cells from primary tumour spread to distant sites. Involves primary tumour invation into surrounding tissues, specially vessels (lymphatic or blood) Then detachment within vessels and transport as emboli

20. CLASSIFICATION OF TUMOURS Malignant Tumours - Metastasis Extravasation (move from vessel to tissue) and growth at distant sites Lymphatic spread leads to lymph node involvement

21. CLASSIFICATION OF TUMOURS Malignant Tumours - Metastasis Blood vessel spread leads to haematogenous metastasis (liver, lung, bone and brain) Less commonly, transcoelomic spread occurs (across body cavities)

22. CLASSIFICATION OF TUMOURS Malignant Tumours Stage/Grade of tumours GRADE refers to how closely tumours resemble their tissue of origin STAGE refers to how far a tumour has spread at the time of presentation

23. CLASSIFICATION OF TUMOURS Malignant Tumours Stage/Grade of tumours Different systems exist for different tumours Dukes ’ stage predicts prognosis for colorectal tumours Duke ’ s A: 90% 5yrs, continued to bowel wall Duke ’ s B: 66% 5yrs, outside bowel wall, LN -ve Duke ’ s C: 33% 5yrs, LN +ve

24. CLASSIFICATION OF TUMOURS Malignant Tumours Stage/Grade of tumours TNM system T : Primary tumour size N : Lymph Node involvement M : Distant metastasis Different TNM for each different organ and tumour

25. Breast Blood + Lymphatic Supply Arterial: Anterior perforating branches of internal mammary artery (internal thoracic) Branches of external mammary artery (lateral thoracic) Venous: Axillary vein Internal thoracic vein

26. Breast Blood + Lymphatic Supply Lymphatic: 75% To ipsilateral axillary lymph nodes Central Pectoral Subscapular Remainder to infra/supraclavicular and parasternal lymph nodes, and to contralateral breast

27. Breast Histology

28. Breast Histology

29. Breast Histology (lobules)

30. carcinoma of breast . This is not a specific histologic type of breast cancer, but rather it implies dermal lymphatic invasion by some type of underlying breast carcinoma. Such involvement of dermal lymphatics gives the grossly thickened, erythematous, and rough skin surface with the appearance of an orange peel (" peau d'orange "). BACK

31. Duct Carcinoma In Situ (DCIS) Aka intaduct carcinoma Tumour cells confined to ducts and acini – no evidence of any invation of surrounding stromal tissue Tumour cells therefore have no access to lymphatics or blood vessels Approximately 3 – 5% cancers in symptomatic series and Up to 25% in screening series Clinical presentations: mass, nipple discharge, paget ’ s disease. Mammographic presentation: microcalcification

32. Duct Carcinoma In Situ (DCIS)

33. Breast Cancer Second most common cancer after lung 10.4% of all cancer incidence Commonly arises in lobules or ducts Can present with symptoms e.g. lump, lymphadenopathy, nipple discharge Can be identified on screening e.g. mammogram Requires triple assessment 1. Clinical examination 2. Radiology (mammogram, Ultrasound) 3. Tissue diagnosis (FANC, core biopsy, excisional biopsy)

34. Br Ca Macroscopic Appearance

35. Br Ca Lymph Nodes Historically, large groups were removed Side effects: lymphoedema Sentinel lymph node mapping - Examines first node(s) to drain tumour for evidence of malignancy - Identify with dye & radiation - Can prevent 65 – 70% of patients having unnecessary axillary node clearance

36. صورة

37. Invasive Carcinomas Invasive duct carcinoma (carcinoma of no special type [NST] Invasive lobular carcinoma Tubular carcinoma Mucinous carcinoma Medullary (like) carcinoma Metaplastic carcinoma Rarities

38. Ductal, NST Commonest up to 75% Contains <50% of special type characteristics Wide variety of histological appearances

39. Vertebral metastasis

40. Vertebral metastasis

41. Liver metastasis

42. Tumour staging Based on degree of tumour spread TNM classification T – local spread – size, involvement of local structures e.g. skin, chest wall N – Nodes – axillary (IPSL – and contralateral), internal mammary, supraclavicular. Number and size (very complicated) M – distant metastasis

43. Stage grouping Grouped into stage 0 – stage IV according to TNM classification Eg. Stage 1 – T1,N0,M0 Stage IV – M1, any T and N Useful for clinical trials

44. Prognostic indicators Lymph node stage Tumour size Tumour grade Tumour type Lymphovascular invasion (extensive DCIS at margins) (Margin clearance)

45. Surgery Treatment depends on stage Surgery is the mainstay Clear margins important 1. Wide local excision (lumpectomy/ breast conservative therapy) 2. Mastectomy if Multi-focal tumours Previous radiotherapy to breast Tumour large relative to breast Patient preference

46. Other treatments Radiotherapy - Reduces risk of local recurrence Chemotherapy - Systemic treatment, more advanced disease Hormone Therapy - Depending on ER/PR expression - Tamoxifen (ER antagonist) - Aromatase inhibitors (block oestrogen production) Monoclonal antibodies -Herceptin (HER2/neu receptor antagonist)

47. CLASSIFICATION OF TUMOURS Intended Learning outcomes By now you should Be aware of the calssification of tumours Know how tumours are named Be familiar with the differences between benign and malignant tumours Know how malignant tumours spread

48. Breast Carcinoma The most common malignancy in women In UK 1 in 10-12 chances 1 in 8 women in US Less incidence in Asia Majority of cancers arise in the ducts. Very rare before age 25

49. Normal Breast Large duct Lobules

50. Normal Breast A normal breast acinus. Note the epithelial cells lining the lumen demonstrate apocrine secretion with snouting, or cytoplasmic extrusions, into the lumen.

51. Comparison of the gross characteristics of a classic infiltrating ductal carcinoma on the left and a benign fibroadenoma on the right Crab like shape due to lines of infiltration

52. Infiltrating Duct Carcinoma Prominent bands of collagen Tendcy to form ductal strucures

53. Invasive Lobular Carcinom Indian File Strands

54. Infiltrating Duct Carcinoma Local Spread Retraction of nipple Fixation to underlying muscle

55. Here is a surgical excision of a small mass from the breast. The mass is well-circumscribed. Grossly it felt firm and rubbery. This is a fibroadenoma . The blue dye around the fibroadenoma was used to mark the lesion during needle localization in radiology so that the surgeon could find this small mass . BACK

56. Here is the microscopic appearance of a fibroadenoma . To the right is compressed breast connective tissue forming a "capsule " to this mass. The neoplasm itself is composed of a fibroblastic stroma in which are located elongated compressed ducts lined by benign appearing epithelium BACK

57. This is the gross appearance of fibrocystic changes in the breast . A 1.5 cm cyst is noted here. This can lead to palpation of an ill-defined "lump " in the breast. Sometimes, fibrocystic changes produce a more diffusely lumpy breast . BACK

58. Another example of microscopic fibrocystic changes of the breast are shown here. Fibrocystic changes account for the majority of "breast lumps " that are found in women of reproductive years , particularly between age 30 and menopause . BACK

59. This is the histologic appearance of fibrocystic changes in breast . There are cystically dilated ducts , areas of lobules that are laced with abundant fibrous connective tissue ( sclerosing adenosis ), and stromal fibrosis . There is even a small area of microcalcification seen just to the upper right of center. No atypical changes are seen here BACK

60. Prominent sclerosing adenosis , one of the features of fibrocystic changes , is demonstrated by the appearance of a proliferation of small ducts in a fibrous stroma. Although it is benign , the gross and mammographic appearance may mimic carcinoma, and it can be difficult to distinguish from carcinoma on frozen section . BACK

61. There is prominent Apocrine Metaplasia change of the cells lining the cysts in this example of fibrocystic changes of breast . Note the tall, pink, columnar nature of the epithelial cells. This appearance is benign . BACK

62. A small benign intraductal papilloma appears here in a breast duct, typically in one of the main lactiferous ducts beneath the areola . Note that the epithelial cells show no atypia and that there is a fine pink collagenous stroma within the papilloma . An intraductal papilloma may be associated with a serous or bloody nipple discharge , or it may cause some nipple retraction . BACK

63. Infiltrating ductal carcinoma , the pleomorphism of the carcinoma cells within the duct in the center (in a cribriform pattern ), as well as the neoplastic cells infiltrating through the stroma and fat, can be seen BACK

64. “Scirrhous carcinoma of the breast” , small nests and infiltrating strands of neoplastic cells with prominent bands of collagen between them. It is this marked increase in the dense fibrous tissue stroma that produces the characteristic hard "scirrhous " appearance of the typical infiltrating ductal carcinoma . Note the nerve surrounded by the neoplasm at the lower left . BACK

65. Lobular carcinoma in situ is seen here. Lobular CIS consists of a neoplastic proliferation of cells in the terminal breast ducts and acini. The cells are small and round . Though these lesions are low grade , there is a 30% risk for development of invasive carcinoma in the same or the opposite breast . BACK

66. The cells of this breast carcinoma are highly positive for estrogen receptor with this immunoperoxidase stain . Estrogen receptor positivity correlates with a better prognosis because such positive neoplastic cells are better differentiated and more sensitive to hormonal manipulation . BACK

67. Paget's cells of Paget's disease of breast have abundant clear cytoplasm and appear in the epidermis either singly or in clusters. The nuclei of the Paget's cells are atypical and, though not seen here, often have prominent nucleoli BACK

68. This variant of breast cancer is known as colloid, or mucinous, carcinoma . Note the abundant bluish mucin . The carcinoma cells appear to be floating in the mucin. This variant tends to occur in older women and is slower growing , and if it is the predominant histologic pattern present, then the prognosis is better than for non-mucinous, invasive carcinomas . BACK

69. carcinoma of breast . This is not a specific histologic type of breast cancer, but rather it implies dermal lymphatic invasion by some type of underlying breast carcinoma. Such involvement of dermal lymphatics gives the grossly thickened, erythematous, and rough skin surface with the appearance of an orange peel (" peau d'orange "). BACK

70. thank you