Neoplasia Basics, Grading and Staging Kimiko Suzue MD, Ph.D. Department of Pathology Mt. Sinai Hospital

Neoplasia Unregulated cell proliferation Monoclonal –single precursor cell clone genetically altered Benign vs Malignant

Assessing Clonality Evaluate a gene which should be heterogenous or heterozygous Plasma Cells Each cell produces either kappa or lambda light chains

Plasma Cells All kappa light chain positive

Assessing Clonality In practice, most often used for hematologic malignancies T cell receptor gene rearrangement B cell immunglobulin gene rearrangement Normally very heterogenous

Assessing Clonality Evaluate a gene which should be heterogenous or heterozygous X-linked markers such as Glucose-6-phosphate dehydrogenase (G6PD) Human androgen receptor (HUMARA), methylation pattern

Neoplasia Unregulated cell proliferation Monoclonal –single precursor cell clone genetically altered Benign vs Malignant

Malignant Tumors Invasive Can cross basement membrane Downloaded from: StudentConsult (on 8 September :01 PM)

Downloaded from: StudentConsult (on 8 September :25 PM) © 2005 Elsevier Basement Membrane

Downloaded from: StudentConsult (on 8 September :25 PM) © 2005 Elsevier Basement Membrane

Downloaded from: StudentConsult (on 8 September :25 PM) © 2005 Elsevier Invasion

Malignant Tumors Invasive Can cross basement membrane Invade local structures Invade blood vessels/lymphatics Metastasis to distant sites Downloaded from: StudentConsult (on 8 September :01 PM)

Metastasis Implantation at distal site Mode of spread Lymphatic Hematogenous Seeding of body cavity/ surface

Malignant Tumors Grossly may be unencapsulated or not well- circumscribed Histologic features Increased nuclear to cytoplasmic ratio Nuclear changes Hyperchromatic, Vesicular Prominent nucleoli Pleomorphism Mitotic activity increased/abnormal forms Loss of cell polarity

Benign Tumors Do not metastasize Grossly may be encapsulated or well-circumscribed Histologic features Well-differentiated, resemble tissue of origin Uniform cells Low mitotic activity

Tumor Nomenclature Robbins Table 7-1 Many benign tumors have –oma Malignant Carcinoma Sarcoma Melanoma Lymphoma Mesothelioma Teratoma (benign/malignant)

Lipoma

Liposarcoma

Fibroadenoma Breast Carcinoma

Fibroadenoma

Breast, Invasive Carcinoma

Adenoma

Colonic Adenocarcinoma

Malignant Tumors - Histologic Grade Well differentiated Moderately differentiated Poorly differentiated Undifferentiated Grade cannot be assessed sometimes small sample size therapy

Malignant Tumors - Histologic Grade Well to moderately differentiated tumors retain functional capabilities Squamous cell carcinoma – Keratin pearls Adenocarcinoma – glands, mucin, bile Can try special stains to verify tumor type Immunohistochemistry (antibody) Histochemical reaction

Histologic Grade – Breast Glandular formation Nuclear size Mitotic activity

Histologic Grade - Prostate Downloaded from: StudentConsult (on 8 September :25 PM) © 2005 Elsevier

Well-DifferentiatedAdenocarcinomaWell-Differentiated Squamous Cell Carcinoma

Histologic Grade - Poorly Differentiated

Cancer Staging Size Extent of invasion Lymph node involvement Distant metastasis

Cancer Staging TNM Primary Tumor (T) Size Extent of invasion Lymph node involvement (N) Number Distant metastasis (M)

Colonic Adenocarcinoma

Lymph Node

Metastasis

Metastasis

Metastasis Well to moderately differentiated adenocarcinoma, but high stage

Tumor Grade and Stage Stage correlates better with prognosis than grade Low histologic grade/High stage High histologic grade/Low stage

Neoplasia Unregulated cell proliferation, Molecular Basis Damage of regulatory genes Please review from your handout

Multistep Carcinogenesis APCAPCK-RASp53

Damage of regulatory genes Growth-promoting proto-oncogenes Oncogenes-Constitutively active Growth-inhibiting tumor suppressor genes Two-hit Knudson hypothesis Genes which regulate apoptosis Genes involved in DNA repair

Multistep Carcinogenesis APCAPCK-RASp53

The End