Why it is important to give the right name to a CANCER disease understanding the pathology and/or histology of CANCER cancer helps you: • to make a correct diagnosis (fundamental Nomenclature - Histopathology step for a correct therapy) • to formulate a better research question (fundamental for studying the etiology, the molecular pathogenesis, and the progression of the disease) • to design novel targeted therapeutic strategies Cancer is not a single static state Neoplasia but a progression and mixture of phenotypic and genetic/epigenetic • Benign tumours : changes that proceed toward – Will remain localized – Cannot (by definition= DOES NOT) spread greater aggressive biological to distant sites behavior – Generally can be locally excised – Patient generally survives Mutation in Mutation in Increasing • Malignant tumours: gene A gene B,C, etc. chromosomal aneuploidy – Can invade and destroy adjacent structure – Can (and OFTEN DOES) spread to distant Normal Cell Increased Benign neoplasia Carcinoma proliferation sites – Cause death (if not treated ) Cancer Hystopathology Diagnosis Neoplasia • Biopsy • two basic components: • Fine-Needle aspiration (FNA) – Parechyma: made up of neoplastic cells • Exfoliative cytology (pap smear) – Stroma: made up of non -neoplastic, • Biochemical markers (PSA, CEA, Alpha- host -derived connective tissue and fetoprotein) blood vessels The parenchyma: The stroma: Determines the Carries the blood biological behavior of the supply tumor Provides support for From which the tumour the growth of the derives its name parenchyma 1. Principle of nomenclature NOMENCLATURE (1) Benign tumors Attaching the suffix “-oma” to the type of cell (glandular, muscular, stromal, etc) The most basic classification plus the organ: e.g., adenoma of thyroid. of human cancer is the More detail: organ or body location in The name of organ and derived tissue/ cell + morphologic character + oma which the cancer arises e. g. skin papilloma, ovarian cyst adenoma (2) Malignant tumors (cancers) ② Sarcoma: malignant tumors arising in ① Carcinoma: Malignant tumors of epithelial cell origin mesenchymal tissue or its derivatives The name of organ and derived tissue/ cell + carcinoma. The name of organ e. g. adenocarcinoma of thyroid. and derived tissue/ cell + sarcoma More details: e. g. leiomyosarcoma of uterus The name of organ and derived tissue/ cell + morphologic futures + carcinoma e. g. papillary carcinoma of skin, ovarian cystadenocarcinoma, oat (small) cell carcinoma of lung, signet ring cell (cell with a large vacuole) carcinoma of stomach (3) Special nomenclature ③ Some malignant tumors, but called disease. ① Blastoma: tumours rigging in immature e. g. leukemias, paget’s disease tissue or nervous tissue, most of them are malignant ④ Some malignant tumors nominated by e.g. medulloblastoma retinoblastoma, scientists’ name nephroblastoma e. g. Hodgkin’s disease, Ewing’s tumor ② Some tumors attaching the suffix-oma. But ⑤ Mixed tumors: tumors which derived from malignant one germ layer may undergo divergent e. g. seminoma, lymphoma, melanoma, dysgerminoma, endodermal sinus tumor defferentiation creating e. g. mixed tumor of salivery gland Neoplasia nomenclature Teratomas: tumors containing mature ⑥ - historic eponyms – “first described by…” or immature cells or tissues Hodgkin ’s Malignant lymphoma (HL) of B Ly cell origin representative of more than one germ disease layer and sometimes all the three Burkitt tumor NHL – B Ly cell in children (jaw and GIT) layers. Ewing tumor Bone tumor (PNET) Grawitz tumor Kidney tumor - clear cell adenocarcinoma ⑦ Hamartoma: tumor-like malformation Kaposi sarcoma Malignant tumor derived from vascular epithelium composed of a haphazard arrangement (AIDS) of tissues indigenous to the particular Brenner tumor Ovarian tumor derived from Brenner cells site, which is totally benign. Askin tumor Malignant chest wall tumor of PNET Merkel tumor Skin tumor derived from Merkel cell Mesenchymal – connective tissue & endothelial Epithelial origin related Benign Malignant Benign Malignant • Squamous cell • Fibr oma • Fibro sarcoma carcinoma • Basal cell carcinoma • Lip oma • Lipo sarcoma • Aden oma • Adeno carcinoma • Chondr oma • Chondro sarcoma • Renal tubular • Oste oma • Osteogenic sarcoma aden oma • Renal cell carcinoma • Hemangi oma • Angio sarcoma • Liver cell aden oma • Hepatocellular carcinoma • Meningi oma • Invasive • Hydatidiform mole meningi oma • Chorio carcinoma • Synovial sarcoma • Semi noma • Mesotheli oma • Embryonal carcinoma Microscopic Criteria for Classification of: Macroscopic Criteria for Classification of: Benign Malignant Benign Malignant • Well differentiated • Generally less well • Structure typical of • Atypical structure • Uniform differentiated to tissue of origin • N:C = 1:4 or 1:6 undifferentiated • Locally invasive, (anaplastic) • Encapsulated infiltrating • Rare normal mitotic figures • Pleomorphic • Slow growth • Rapid & erratic • Normal orientation • N:C = 1:1 • No metastasis growth • Abundant stroma • Hyperchromatic • More mitoses, abnormal • Metastasis & bizarre • Loss of polarity • Tumor giant cells The first step toward epithelial neoplasia is cellular transformation Dysplasia Traditionally, two forms of cellular transformation have • “disordered growth” been recognized that are potentially reversible, but may be • Loss in uniformity of the individual cells steps toward a neoplasm. These are: • Loss of architectural orientation • Metaplasia : the exchange of normal epithelium for • Pleomorphism another type of epithelium. Metaplasia is reversible when • Hyperchromatic the stimulus for it is taken away. • Increased mitoses (normal) • Dysplasia : a disordered growth and maturation of an epithelium , which is still reversible if the factors driving it Carcinoma in situ are eliminated. • Dysplastic changes involve entire thickness of epithelium However, Hyperplasia : an increase in the number of • If left untreated, will progress to invasive cancer phenotypically normal cells , may also reflect an early stage of transformation. Neoplasia Dysplasia • Dysplasia : • Clinical significance: – Definiton: a loss in the uniformity of the individual cells and a loss in their architectural – It is a premalignant condition. orientation. – The risk of invasive cancer varies with: – Non -neoplastic V grade of dysplasia (mild, moderate, – Occurs mainly in the epithelia sever) – Dysplastic cells shows a degree of : V duration of dysplasia pleomorphism, hyperchrmasia,increased V site of dysplasia mitosis and loss of polarity. Dysplasia Features: Neoplasia • Nuclear abnormality • Dysplasia does not mean cancer Increased rate – Increased N/C ratio • Dyplasia does not necessarily progress to of – Irregular nuclear membrane cancer multiplication. Disordered – Increased chromatin content • Dysplasia may be reversible maturation. • If dysplastic changes involve the entire thickness of the epithelium it is called : • Cytoplasmic abnormalities due to failure of normal CARCINOMA IN -SITU CHANGES IN UTERINE CERVIX Neoplasia • Carcinoma in -situ – Definition: an intraepithelial malignancy in which malignant cells involve the entire thickness of the epithelium without penetration of the basement membrane. – Applicable only to epithelial neoplasms. Metastases Spread of Tumors • A primary neoplasm is more likely to appear • Direct invasion – infiltration & destruction within an organ as a solitary mass. of surrounding tissue • The presence of metastases are the best • Metastasis – noncontiguous spread to indication that a neoplasm is malignant. The original clone of cells that developed into a other organ/body locations neoplasm may not have had the ability to – Lymphatics – carcinomas , lymphatic drainage metastasize, but continued proliferation of the – Veins & arteries – sarcomas , renal cell neoplastic cells and acquisition of more genetic carcinoma, hepatocellular carcinoma mutations within the neoplastic cells can give – Implantation – “open field”, ovarian carcinomas, them the ability to metastasize. appendix = pseudomyxoma peritonei Nomenclature of tumors Nomenclature of tumors Tissue of Origin Benign Malignant Tissue of Origin Benign Malignant Composed of One parenchymal cell Type Mesenchymal tumors Fibroma Fibrosarcoma Blood cells and related cells Lipoma Connective tissue and derivatives Liposarcoma Hematopoietic cells Chondroma Chondrosarcoma Lymphoid tissue Osteoma Osteogenic sarcoma Muscle Leiomyosarcoma Endothelial and related tissues Smooth Leiomyoma Blood vessels Hemangioma Angiosarcoma Striated Rhabdomyoma Rhabdomyosarcoma Lymph vessels Lymphangioma Lymphangiosarcoma Epihelial tumors Synovium Synovial sarcoma Stratified squamous Mesothelium Mesothelioma Squamous cell papilloma Brain coverings Meningioma Invasive meningioma Basal cells of skin or adnexa Epithelial lining Glands or ducts Adenoma Papilloma Cystadenoma Nomenclature of tumors Nomenclature of tumors Tissue of Origin Benign Malignant Tissue of Origin Benign Malignant Epihelial tumors Respiratory passages Bronchogenic carcinoma Stratified squamous Squamous cell or epidermoid Bronchial adenoma Squamous cell papilloma Nevus Basal cells of skin or adnexa carcinoma Basal cell carcinoma Neuroectoderm (carcinoid) Renal tubular adenoma Epithelial lining Renal epithelium Malignant melanoma Liver cell adenoma Glands or ducts Liver cells Renal cell carcinoma Adenoma Transitional cell papilloma Adenocarcinoma Urinary tract epithelium (transitional) Hepatocellular carcinoma Papilloma Papillary carcinoma Placental epithelium