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Home , Choristoma, Mixed tumor

Why it is important to give the right name to a disease understanding the 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 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., 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 , ovarian adenoma

(2) Malignant tumors () ② : 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. of thyroid. and derived tissue/ cell + sarcoma More details: e. g. 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. , 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 : 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 (PNET)

Grawitz tumor Kidney tumor - clear cell adenocarcinoma ⑦ : tumor-like malformation Kaposi sarcoma Malignant tumor derived from vascular 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 • • Meningi oma • Invasive • Hydatidiform mole meningi oma • Chorio carcinoma • • 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 growth • Abundant stroma • Hyperchromatic • More mitoses, abnormal • Metastasis & bizarre • Loss of polarity • Tumor giant cells The first step toward epithelial neoplasia is cellular transformation 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 . 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 are eliminated. • Dysplastic changes involve entire thickness of epithelium However, : 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 .

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 – , lymphatic drainage metastasize, but continued proliferation of the – Veins & arteries – , 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 Blood cells and related cells Connective tissue and derivatives Hematopoietic cells Chondroma Chondrosarcoma Lymphoid tissue Osteoma Osteogenic sarcoma Muscle Leiomyosarcoma Endothelial and related tissues Smooth Leiomyoma Blood vessels Hemangioma Angiosarcoma Striated Lymph vessels Lymphangioma Lymphangiosarcoma Epihelial tumors Synovium Synovial sarcoma Stratified squamous Mesothelium 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 () 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 (trophoblast) Hydatidiform mole Transitional cell carcinoma Cystadenoma Cystadenocarcinoma Testicular epithelium (germ cells) Choriocarcinoma Seminoma Embryonal carcinoma

Nomenclature of tumors Nomenclature of tumors

Tissue of Origin Benign Malignant Tissue of Origin Benign Malignant

More Than One Neoplastic More Than One Neoplastic Cell Type- Mixed Tumors, Cell Type Derived From Usually Derived From One More Than One Germ Germ Layer Layer- Tera- fogenous

Salivary glands (mixed Malignant mixed tumor of tumor of salivary origin) salivary gland origin Totipotential cells in gonads Mature , dermoid Immature teratoma, Breast Malignant cystosarcoma phyllodes or in embryonic rests cyst teratocarcinoma Renal anlage Wilms tumor

Neoplasia TERATOMA

– Adenoma : benign epithelial neoplasms • Teratoma: – Teratoma contains recognizable mature or immature cells or producing gland pattern ….OR … derived from tissues representative of more than one germ -cell layer and glands but not necessarily exhibiting gland some times all three. pattern – Teratomas originate from totipotential cells such as those pattern normally present in the ovary and testis.

– Papilloma : benign epithelial neoplasms If all the components parts are well differentiated, it is a ben ign (mature) growing on any surface that produce teratoma. microscopic or macroscopic finger -like pattern If less well differentiated, it is an immature (malignant) tera toma. TERATOMA TERATOMA

• Such cells have the capacity to differentiate • If all the components parts are well into any of the cell types found in the adult differentiated, it is a benign (mature) body. So they may give rise to neoplasms teratoma. that mimic bone, epithelium, muscle, fat, • If less well differentiated, it is an immature nerve and other tissues. (malignant) teratoma.

• Most common sites are: ovary & testis

WHAT ARE AND CHORISTOMA? Hamartoma and Choristoma Hamartoma : a mass composed of cells native to the organ • They are distinguished from neoplasms by the fact that they do not exhibit continued e.g. pulmonary hamartoma. growth. they are group of tumor -like tissue Choristoma : a mass composed of normal masses which may be confused with neoplasms cells in a wrong location e.g. pancreatic choristoma in liver or stomach. • Malformation and not neoplasm.

Staging and

• Devised for malignant neoplasms • The stage and/or grade generally Staging and Grading determine the treatment and the prognosis • In general, the higher the stage, the larger a neoplasm is and the farther it has likely spread. • In general, the higher the grade, the more likely it is that the tumor is rapidly growing and will invade and metastasize. Staging Tumors: Staging of Malignant Neoplasms

Extent of Spread Stage Definition • Generally correlates better with Tis/T0 In situ, non-invasive (confined to epithelium) prognosis than histopathologic grading T1 Small, minimally invasive within primary organ site • Used in therapy selection T2 Larger, more invasive within the primary organ site T3 • Union Internationale Centre Cancer Larger and/or invasive beyond margins of primary organ site T4 (UICC) Very large and/or very invasive, spread to adjacent organs N0 No lymph node involvement – TNM system N1 Regional lymph node involvement • American Joint Committee (AJC) on N2 Extensive regional lymph node involvement N3 More distant lymph node involvement – Stages 0 – IV M0 No distant metastases M1 Distant metastases present

Grading = degree of differentiation

• Grading schema are based upon the microscopic appearance of a neoplasm with H&E staining. • In general, a higher grade means that there is a lesser degree of differentiation and the worse the biologic behavior of a malignant neoplasm will be. • A well-differentiated neoplasm is composed of cells that closely resemble the cell of origin • A poorly differentiated neoplasms have cells that are difficult to recognize as to their cell of origin. • Grading schema have been devised for many types of neoplasms, mainly carcinomas. • Most grading systems have three or four grades (designated with numbers or roman numerals). In the diagram above utilizing a lung carcinoma as an example, the principles of staging are illustrated:

Grading of Malignant Neoplasms

Grade Definition I Well differentiated II Moderately differentiated III Poorly differentiated IV Nearly anaplastic