Appunti Anatomia patologica (Anatomical Pathology, Biomolecular Basis of Anatomical Pathology)

Neoplasia and Tumor Classification

FAPo MENo neurofibromatosis type 1 and 2o Von Hippel-Lindau syndromeo➢ →familial cancers but role of inherited predisposition may not be clear in an individual casecolon/ovarian/breasto➢ autosomal recessive syndromes of defective DNA repairBRCA1/BRCA2o →certain forms of benign neoplasia also constitute pre-cancerous conditions, e.g. villous adenoma of colonit increases in size develops cancerous changes in up to 50% casesneoplasia➔ parenchyma: neoplastic cells➔ supportive stroma: connective tissue and blood vessels from hostbenign neoplasia➢ epithelial: classified based on gross morphology andmicroscopic architecture• benign epithelial tumors➔ adenoma➔ papilloma➔ cystadenoma➔ papillarypolypo➢ mesenchymal: attach suffix -oma to the cell of originand are classified depending on the original cell• mesenchymal benign tumors➔ leiomyoma➔ lipoma➔ rhabdomyoma➔ schwannoma➔ fibromamalignant tumors➢ carcinoma: malignant epithelial cell origin,

one germ layer, totipotential cell, usually all three (principally encountered in the gonads) → choristoma rest of normal tissue included in another tissue → hamartoma aberrant differentiation of disorganized mature cells (lung hamartoma contains islands of cartilage, blood vessels, bronchial-type structures and lymphoid tissue)

differences between benign and malignant tumors → differentiation = extent to which parenchymal cells resemble comparable normal cells, morphologically and functionally

benign tumors are constituted by well differentiated cells which maintain their normal relationship with other cells, maintain an organization like the normal tissue from which they derive + maintain power in control of proliferation (tumor limited in a certain area) → malignant tumors range from well differentiated to undifferentiated, no control of proliferation (increased proliferation and step-by-step loss of differentiation) leading to anaplasia + metastasis

→ anaplasia:

1. dystrophic calcification due to abnormal function of malignant neoplastic cells, e.g. calcification in one type of thyroid carcinoma (papillomatous carcinoma) characterized by follicles containing formation of multiple layers of calcification

1. layer and we have a severe dysplasia when all layers of the epidermal tissue are involved
2. when dysplastic changes are marked (= severe dysplasia) and involve the entire thickness of the epithelium, the lesion is considered a pre-invasion neoplasm and it is referred to as carcinoma in situ

Rate of growth: most benign tumors grow slowly over a period of years, whereas most cancers grow rapidly, sometimes at an erratic pace and eventually spread and kill their hosts. In general, the growth rate of tumors correlates with their level of differentiation and thus most malignant tumors grow rapidly compared to benign lesions.

Local invasion: nearly all benign tumors grow as cohesive expansile masses that remain localized to their site of origin and do not have the capacity to infiltrate, invade or metastasize to distant sites as malignant tumors do. They usually develop a rim of compressed connective tissue sometimes called a fibrous capsule.

The growth of cancers is accompanied by infiltration, invasion,

and destruction of theo surrounding tissuesinvasiveness is the most reliable feature that differentiates malignant from benign tumorso (e.g. blood vessel invasion)!! in situ carcinoma display the cytologic features of malignancy without invasion of thebasement membrane (mechanical barrier, used as a marker) !!

➔ metastasis: tumor implants discontinuous with the primary tumormetastasis unequivocally marks a tumor as a malignant because benign neoplasms do noto metastasizewith few exceptions, all cancers can metastasize:o 1. gliomas2. basal cell carcinoma of the skin (rodent ulcer due to its invasive destructiveness)→ only has capacity to have trophism to tissue belonging to the skin (attracted toperipheral nerves termination and bones)malignant cells secrete proteolytic enzymes able to degrade thebasement membranes, e.g. metalloproteinases able to digest basalmembrane around vessels→cancer cell going through vessel wall into the bloodstream possibility to have thrombi

disease grade I to IV with increasing anaplasia➔ G1 = maintaining of the architectural organization of cell pattern organization➔ G2 = anomalous architectural organization even if it is possible to recognize a normal organization(e.g. adenocarcinoma)➔ G3 = together with architectural pattern typical of original tissue we also have proliferation of single cells in the stroma indicating that we have the beginning in the loss of intercellular junctions➔ G4 = complete loss of architectural organization and only aggregates of neoplastic undifferentiated cells

grading of a cancer is based on the degree of differentiation of the tumor cells and number of mitoses within the tumor as presumes correlates of the neoplasm aggressiveness

correlation between histological appearance and biological behavior is less than perfect: in general, grading of cancer has proved of less clinical value than has staging

uterine adenocarcinoma

grade I grade II grade III

staging is based on the size of the primary lesion,

its extend of spread to regional lymphnodes and the presence or absence of blood borne metastases

TNM (UICC)

0-IV (AJC)

CNS tumors

2016 WHO classification of CNS tumors

1. neuroepithelial tumor
2. peripheral nerve tumor
3. meningeal tumor not neuroepithelial tumors, they are CNS tumors but are not represented in the cerebral mass, deriving from different cells originating not from the neuroepithelium
4. hematopoietic tumor and lymphomas
5. germ cell tumor
6. sellar tumor
7. metastatic tumor

even if there is an hematoencephalic barrier, making a sort of mechanical barrier between the brain and the body, it is possible to have metastases originating from other organs in the body (e.g. colon metastases)

CNS tumors have not the possibility to go outside of the brain because there are 2 main problems

1. presence of hematoencephalic barrier, therefore neoplastic cells are not able to pass through the blood vessels of the barrier to go out of the brain
2. they are limited in a "box"