Pre-Lab LectureDr. Renan

Neoplasia / “New Growth”

Abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues and persist in the same excessive manner after the cessation of stimuli, which evoked the change.

Fundamental to the origin of all neoplasms are heritable or genetic changes that allow excessive and unregulated proliferation that is independent of physiologic growth regulatory stimuli.

Oncology

The study of tumors

Benign Tumors Gross and microscopic

features are relatively innocent

Remain localized Cannot spread to other

sites Amenable to local surgical

removal Patient generally survives

Malignant Tumors Referred to as cancers Can invade tissues Can destroy adjacent

structures Spread to distant sites:

Metastasize to cause death.

Basic Tumor Components

Parenchyma Made up of transformed

neoplastic cells Largely determines the

tumors biological behaviorStroma

The supporting, host derived, non-neoplastic portion of the tumor.

Made up of connective tissue, blood vessels, host-derived inflammatory cells.

Provides support for the growth of parenchymal cells, carries blood supply.

Nomenclature

Benign Tumors Designated by attaching

the suffix: OMA to the cell type which the tumor attaches.

Ex: Fibroma – benign tumor

arising from fibrous tissue.

Chondroma – benign cartilaginous tumor

Adenoma – applied to benign epethial tumors producing gland patterns and neoplasm derived from glands.

Papilloma – composed of papillary structures.

Exceptions:o Lymphomao Mesotheliomao Melanomao Seminomao Hepatomao Dysgerminoma

Sarcoma Malignant neoplasm

arising from mesenchymal tissues or its derivatives

Ex: Fibrosarcoma –

malignant tumor of fibrous tissue origin.

Chondrosaroma – a neoplasm composed of malignant chrondocytes.

Carcinoma

Malignant neoplasm of epithelial cell origin.

Ex: Adenocarcinoma –

carcinomas that grow in a glandular pattern,

Squamous Cell Carcinoma – produce’s squamous cells.

Designated based on organ or tissue of origin.

o Renal Cell Carcinoma – kidneys

o Cholangiocarcinoma – bile ducts.

Mixed Tumors

Pleomorphic Adenomas (Salivary Gland) / Benign Mixed Tumor

Epithelial elements on a fibromyxoid stroma

Mesenchymal elements: islands of cartilage or bone.

Fibroadenoma (Breast) Proliferation of ductal

epithelial elements (adenoma_ Loose fibrous stroma

(Fibroma)

Teratoma Tumors containing mature of

immature cells representative of more than one, sometimes all three germ layers

Normally present in ovary or testis, sometimes in sequestered midline embryonic rest.

Should not be confused with mixed tumors.

Harmatoma A malformation that presents

as a mass of disorganized tissue indigenous to a particular site.

Choristoma A congenital anomaly

composed of heterotropic rest of cells, presenting as mass or nodule. (normal tissue in abnormal locations/site)

Ex: A small nodule of well developed and normally organized pancreatic tissue may be found in the submocusa of the stomach or duodenum.

Characteristics of Benign and Malignant Tumors

Differentiation Refers to the extent to which

the parenchymal cells resemble their normal forebears morphologically and functionally.

Desmoplasia

Stromal reaction induced by the tumor, producing a dense, abundant fibrous stroma.

Tumor Differentiation

Well Differentiated Closely resemble normal

counterparts. Retains the functional

capabilities found in normal counterparts.

Moderately Differentiated Some of the above criteria are

retained and can also be like normally resembling the normal counterparts.

Poorly Differentiated Do not resemble normal

counterparts. Looks primitive, disorganized

and immature.

(Squamous cell carcinoma)

Keratin pearl – automatically categorizes a tumor as well differentiated type. Anaplasia

“To form backward”. Dedifferentiation or loss of the

structural and functional differentiation of cells.

Hallmark for malignancy.

Pleomorphism Marked variation in size and

shape

Hyperchromasia Large, darkly staining nuclei

(increase in DNA)

Increased Nuclear to Cytoplasmic Ratio

Normal NC ration 1:4 to 1:6

Tumor Giant Cells One enormous nucleus or

several nuclei. Large/Prominent Nucleoli. Coarse and Clumped

Chromatin.

Presence of Abnormal Mitosis

Tumor Giant Cells characteristic of metastatic neoplasm

Atypical Mitosis (Tripolar form)

Loss of Polarity

Failure to develop recognizable patters of orientation to one another.

“Polarized” – nucleoli are only oriented to one direction.

Dysplasia

o Loss in the uniformity of individual cells and their architectural orientation in the epithelium.

o Disorderly but not neoplastic proliferation of cells.

o Exhibit pleomorphism, possess large, hyperchromatic nuclei.

o More abundant mitotic figures than usual, appearing in abnormal locations within the epithelium

“All anaplastic cells are dysplastic but no all dysplastic cells are anaplastic”

Carcinoma in Situo Dysplastic changes are

markedo Involvement of the

entire thickness of the epithelium

o Pre- invasive cancer

Invasion

Benign Tumorso Well-circumscribed and

remain localized at their site of origin.

o Does not have the capacity to infiltrate. invade of metastasize

o May be encapsulated or unencapsulated.

Malignant Tumorso Poorly circumscribedo Grow by progressive

infiltrationo Invade, destroy and

penetrate the surrounding

Metastasis Identifies a neoplasm as

malignant The most reliable feature that

distinguishes malignant from benign tumor.

The more anaplastic and larger the primary neoplasm, the more like is the metastatic spread.

Pathways

Seeding within the body cavities Typical of ovarian cancers /

most common in the peritoneal cavity

Lymphatic spread Typical of carcinomas

Hematogenous spread Typical of sarcomas

Simple Tumors Tumors of mesenchymal origin

o Connective tissues and derivatives

Fibrous tissues Fibrous and

Histolytic Fatty tissue Bone

o Endothelial and related tissues

o Blood cells and related cells

o Muscle

Tumors of Epithelial Origin

Spindle in shape with blond nuclei –benign

Interlacing fascicles of fibrous tissues, no hemorrhage, necrosis and mitotic figures.

Cells (nuclei) are pleomorphic, hyperchromatic and coarse pattern of chromatic, prominent nuclei, increased NC ratio.

“Adipose tissue”, prominent in the back and extremities.

Nuclei are confined the periphery rendering the appearance of singlet ring.

Histogenetic origin – MesenchymeCell Origin – adipocytes

Benign Tumor of the bone

Benign osteocytes rimming the forming bone

Presence of bone erosion, tumor invaded the bone and bone marrow.

Presence of hemorrhage.

Tumor giant cells with multiple nuclei

Endothelial & Related Tissue Blood Vessels Lymph Vessels

2 Types of Hemangioma Capillary Hemangioma

Small slit like capillaries Cavernous Hemangioma

Bigger and more dilated capillaries

Note: Dilated Lymph vessels and absence of RBC’s

Lymphadenopathies common on the cervical area, cannot diagnose without Reed sternberg cells. (binucleated, prominent macro nucleoli and shares common cytoplasm (acidophilic and eosinophilic)

RS cell is malignant.

Malignant cells are the lymphocytes.

Tumors of Epithelial Origin Stratified Squamous

Epithelium Basal cells of the skin Glandular Ductal Epithelial

lining Respiratory Epithelium Neuroectoderm Renal Epithelium Liver cell Urinary tract epithelium Placental Epithelium Testicular Epithelium

Fingerlike projection of the squamous epithelium

Ulcerated/Necrotic/Hemorrhagic

+ keratin pearls.

AKA: Rodents Ulcer

Basaloid Cells / Peripheral Palicading??? / Retraction artifact

Route of metastasis: Lymphatic

Nuclei are polarized and located basally/ no invasion/ necrosis / hemorrhage

Only difference is the presence of mucinous material in the cytoplasm

Route of metastasis: lymphaticHistogenic Origin: Epithelial

Glandular proliferation / Presence of inflammatory cell infiltrates.

Well differentiated – almost 100% glandular pattern.

Their should be fibrovascular core for diagnostic of “papillary” type of cancinoma.

+papillations.

+ Orphan Ani Nuclei.

+ Psammoma bodies

Hemorrhage/ necoris/ irregular distribution of papliations.

Cannot commit whether epithelial or mesenchymal - very prominent nucleoli and macro nucleoli / no particular pattern whether glandular, squamous or sarcomatous .

Trabecular – thickened composed of several layers of malignant hepatocytes.

Several layers of proliferating malignant transitional cells.

Presence of proliferation trophoblastic cells (syncytiotrophoblast and cytotrophoblast)

Extensive areas of hemorrhageShould not have the presence of villi

Germ Cell Tumor / Malignant Neoplasm of the testis.

Mixed tumor. Epithelial Components (duct architecture) and Mesenchymal Derivative (either cartilaginous of bony)

Triphasic tumor – 3 different cell types proliferation.

1. Stroma2. Ductal Epithelial Cell3. Blastema.

Teratogenous Tumor.

Benign – mature teratoma. Ex. Ovary

Malignant – immature

Presence of neuroectoderm signifies immaturity of the tumor

Histologic and Cytologic Features of Tumors

Benign Neoplasm Encapsulation Differentiation

Complete encapsulation – incomplete capsulation might be follicular carcinoma

Presence of capsule and proliferation of follicles, some does not contain colloid material.

Malignant Neoplasm Differentiation Features of Anaplasia Mitosis Tumor Giant Cells Tumor Necrosis Stromal Invasion and

Desmoplasia Metastasis

Keratin Pearl Dyskeratotic Cells / Individual

keratinization Intracellular Bridges – tight

junction connecting each keratonic cell

Features of Anaplasia Pleomorphism Hyperchromasia Increased N:C ratio Prominence of Nucleoli

Invasion at LOWER LEFT sidePresence of desmoplasia

Presence of malignant ductal cells in cords and tubular structures accompanied by a desmoplastic stroma.

Right side – remnants of normal lymph nodes, Left - metastatic cells.

Pre-invasive Lesions

Dysplasia Intact Basement Membrane

Ex: Cervical intraepithelial

neoplasia (CIN III), Cervix.

Intraductal Carcinoma-In-Situ, Breast

Left side – desplasticRight – normal

Full thickness dysplasia

Urinary Bladder Transitional cells Malignant

Lymph node

Metastasis

Lymphoid Tissue Metastasis Adenocarcinoma

Lipoma Adipocytes Histogenetic origin –

mesenchymal

Lipoma Adipocyes Mesenchymal Hematogenous

MalignantIntact Basement Membrane/Polarized NucleiSerous Adenoma

MalignantHyperchomicity/Increased NC ratio/Mitotic figures

LiverMalignant

Benign Pleomorphic Adenoma (mixed type)

Teratoma – 3 germ cell layers

Desmoplasia

Renal Cell Carcinoma

ThyroidPapillary Carcinoma of the ThyroidLyphatic Route

Metastatic Adeno Carcinoma

Cannon balling - classic sign, as a general rule metastasis are usually multiple against benign which is solitary

Metastatic Adenocarcinoma

BenignFollicular Adenoma of the Thyroid