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Dr.Nazar Jawhar

Dr.Nazar Jawhar
Definition: Literally: It is an abnormal mass of tissue the growth of which exceeds & is uncoordinated with that of the normal tissues & persists in the same excessive manner after cessation of the stimuli that evoked the change. It is purposeless, preys on the host & is autonomous (loss of responsiveness to normal growth control). It behaves like a parasite, competes with normal tissue for their metabolic needs.

Dr.Nazar Jawhar

Cancer is not one disease but many disorders that share a profound growth dysregulation. Results from genetic alterations that are passed down to the progeny of the tumor cells. These genetic changes allow excessive and unregulated proliferation that becomes autonomous (independent of physiologic growth stimuli),

Dr.Nazar Jawhar

Oncology: Tumor: Swelling Cancer: A common term for all type of malignant tumors. Derived from the Latin cancer (for crab), because cancer adheres to any part that seizes upon in an obstinate manner like a crab.

Dr.Nazar Jawhar

INCIDENCE:
More than 1 million individuals develop cancer every year, and cancer causes more than 560000 annual death in the state .It is the second leading cause of death after cardiovascular diseases.Neoplasms are important not only because of the mortality rate but also because of the great physical and emotional impact they inflict on the patients and their families.Recently, there has been dramatic improvements in the survival rates in some cancers ( especially leukemias & lymphomas). A greater proportion of cancers are being cured or arrested today than ever before.The only hope for controlling cancer lies in learning more about it’s etiology & pathogenesis.

Dr.Nazar Jawhar

CLASSIFICATION:
Clinically tumors are classified into: Benign tumors: Malignant tumors: Borderline malignant tumors:


Dr.Nazar Jawhar
Benign tumors: Characterized by
Having innocent gross & microscopical features.Remain localized.Cannot spread to other sites.Generally amenable to surgical excision.Usually not affecting patient’s survival ( with some exception).

Dr.Nazar Jawhar

Malignant tumors:
Having characteristic morphological features. Can invade & destroy adjacent tissues. Can spread to distant sites (metastasize). Can cause death.

Dr.Nazar Jawhar

Borderline malignant tumors:

Dr.Nazar Jawhar

All tumors have two basic components: Proliferating neoplastic cells that constitute the parenchyma. Supportive stroma made up of connective tissue & blood vessels NOTE: Some tumors have scanty stroma so the neoplasm is soft & fleshy, other tumors especially some cancers stimulate the formation of an abundant collagenous stroma ( referred to as desmoplasia) imparting a stony hard consistency to the tumor ( as scirrhous carcinoma of the breast).
NOMENCLATURE

Dr.Nazar Jawhar

Tumor either arises from epithelial cells, mesenchymal cells, hemopoietic, lymphoid cells, nerve cells, or from totipotential cells. Any of these tumors could be benign or malignant.

Dr.Nazar Jawhar

Tumors are named according to the type of cells from which they arise or according to the tissue they resemble.

Dr.Nazar Jawhar

Are designated by attaching the suffix –oma to the cell of origin. Either of benign epithelial tumors or benign mesenchymal tumors: BENIGN TUMORS

Dr.Nazar Jawhar

Benign epithelial tumors:
Adenoma: Applied to benign tumor derived from glands (e.g. salivary, sweat glands) or tumor forming glandular pattern (renal cell adenoma).

Dr.Nazar Jawhar

Papilloma: Benign epithelial neoplasm that produces finger like projections from epithelial surfaces (e.g. squamous papilloma).

Dr.Nazar Jawhar

Cystadenoma: Benign tumor producing hollow cystic mass, mostly seen in the ovary. Some times papillary cystadenoma

Dr.Nazar Jawhar

Polyp: Benign epithelial tumor produces a mass that projects above a mucosal surface. Mostly seen in the GIT.



Dr.Nazar Jawhar
Benign mesenchymal tumors
Named by attaching the suffix –oma to the cell of origin.Example: fibroma. Lipoma, neuroma, leiomyoma, osteoma, chondroma….

Dr.Nazar Jawhar

Carcinoma: Malignant tumors of epithelial cell origin. They are further classified into: Squamous cell carcinoma. Adenocarcinoma. Transitional cell carcinoma. Basal cell carcinoma.
MALIGNANT TUMORS

Dr.Nazar Jawhar

Sarcoma: Malignant tumors arising from mesenchymal tissues. e.g. fibrosarcoma, liposarcoma, leiomyosarcoma, osteosarcoma,….etc.

Dr.Nazar Jawhar

This term applied to a small group of tumors that are composed of a mixture of epithelial & mesenchymal components. They result from divergent differentiation of a single line of parenchymal cells. Benign mixed tumors: e.g. pleomorphic adenoma ( These tumors contain epithelial components scattered within a myxoid stroma that sometimes contains islands of cartilage or bone), fibroadenoma,.. Malignant mixed tumors: e.g. malignant mixed tumor of the salivary gland & carcinosarcoma.
MIXED TUMORS

Dr.Nazar Jawhar

This tumor arises from totipotential cells, so they have the capacity to differentiate into any cell types present in the body i.e. it contains tissue representative of more than one germ layer. Since they arise from totipotential cells, so they are principally encountered in the gonads (although rarely found in sequestered rest). e.g. dermoid cyst of the ovary. Teratoma could be benign or malignant.
TERATOMA

Dr.Nazar Jawhar

N.B: There are some exception to this nomenclature e.g. lymphoma, melanoma, glioma, seminoma,….


Dr.Nazar Jawhar
Table 6-1. Nomenclature of Tumors
Table: Nomenclature of tumors

Dr.Nazar Jawhar

What is hamartoma?

What is choristoma?

Dr.Nazar Jawhar
CHARACTERISTIC OF BENIGN & MALIGNANT TUMORS
The differentiation between benign and malignant tumors is one of the most important distinctions a pathologist can make. In the great majority of instances, a benign tumor may be distinguished from a malignant tumor with considerable confidence on the basis of: Differentiation & anaplasia: Rate of growth: Local invasion: Metastasis:

Dr.Nazar Jawhar

Refers to the extent to which parenchymal neoplastic cells resemble comparable normal cells, both morphologically & functionally. Neoplasm could be: - Well differentiated - Moderately differentiated - Poorly differentiated - Undifferentiated
Differentiation & anaplasia

Dr.Nazar Jawhar

Benign tumors are well differentiated. Malignant tumors vary from well-undifferentiated. Anaplasia implies a reversal of differentiation to a more primitive level. It usually results from lack of differentiation rather than dedifferentiation.

Dr.Nazar Jawhar

Determination of differentiation depends on a no. of morphological changes: Architectural pattern. Cytological features (degree of atypia): - Pleomorphism: - Hyperchromasia: - Nuclear enlargement & N/C: No. of mitosis &configuration: reflecting the higher proliferative activity of the parenchymal cells. Others as loss of polarity, tumor giant cells, necrosis

The better the differentiation of the transformed cell, the more completely it retains the functional capabilities found in its normal counterparts. Thus, benign neoplasms of endocrine glands frequently elaborate the hormones characteristic of their origin. Increased levels of these hormones in the blood are used clinically to detect and follow such tumors. Well-differentiated squamous cell carcinomas of the epidermis elaborate keratin, just as well-differentiated hepatocellular carcinomas elaborate bile. Highly anaplastic undifferentiated cells, whatever their tissue of origin, lose their resemblance to the normal cells from which they have arisen.


Despite exceptions, the more rapidly growing and the more anaplastic a tumor, the less likely it will have specialized functional activity. The cells in benign tumors are almost always well differentiated and resemble their normal cells of origin; the cells in cancer are more or less differentiated, but some derangement of differentiation is always present

Dr.Nazar Jawhar

In general most benign tumors grow slowly over a period of years, whereas most cancers grow rapidly and the rate of growth of malignant tumors correlates with their level of differentiation. HOW? There are some exceptions to this generalization.
Rate of growth

Dr.Nazar Jawhar

Benign tumor

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 do malignant tumor.
Local invasion



Dr.Nazar Jawhar
Because they grow and expand slowly, they usually develop a rim of compressed connective tissue, sometimes called a fibrous capsule, which separates them from the host tissue. This capsule is derived largely from the extracellular matrix of the native tissue due to atrophy of normal parenchymal cells under the pressure of an expanding tumor. Such encapsulation does not prevent tumor growth, but it keeps the benign neoplasm as a discrete, readily palpable, and easily movable mass that can be surgically enucleated. Some benign tumor are not encapsulated. For example, hemangiomas (neoplasms composed of tangled blood vessels) are often unencapsulated and may appear to permeate the site in which they arise.
Local invasion

Dr.Nazar Jawhar

Benign tumor

Cohesive expansile growth. Encapsulated. Localized, circumscribed &mobile. Amenable to surgical resection (enucleation). N.B: Not all benign tumors are encapsulated.

Dr.Nazar Jawhar

Malignant tumor The growth of cancers is accompanied by progressive infiltration, invasion, and destruction of the surrounding tissue. In general, malignant tumors are poorly demarcated from the surrounding normal tissue, and a well-defined cleavage plane is lacking. Most malignant tumors are obviously invasive and can be expected to penetrate the wall of the colon or uterus, for example, or fungate through the surface of the skin. They recognize no normal anatomic boundaries. Such invasiveness makes their surgical resection difficult or impossible.

Dr.Nazar Jawhar

Malignant tumor Progressive infiltration, invasion, & destruction of adjacent tissues Not encapsulated (no plane of cleavage). Excision with safety margin. N.B: Next to the development of metastasis, local invasion is the most reliable feature that distinguishes malignant from benign tumors.

Dr.Nazar Jawhar

Cut section of an invasive ductal carcinoma of the breast. The lesion is retracted, infiltrating the surrounding breast substance, and would be stony hard on palpation.


Dr.Nazar Jawhar
Indicates the development of secondary implants away from the site of primary tumor. Is the single most important feature that distinguishes malignant from benign tumors. The probability of metastasis increases as the primary tumor becomes more aggressive, the more rapidly growing, and the larger the primary neoplasm, the greater the likelihood that it will metastasize
Metastasis

Dr.Nazar Jawhar

Benign tumors do not metastasis. All malignant tumors eventually metastasis except: Approximately 30% of newly diagnosed patients with solid tumors present with distant metastasis. Metastasis strongly reduces the probability of cure.

Dr.Nazar Jawhar

Pathways of spread: Lymphatic spread: is the most common pathway for the initial dissemination of carcinomas. The pattern of lymph node involvement follows the natural routes of lymphatic drainage.

Dr.Nazar Jawhar

Enlargement of regional lymph nodes may be caused by: (1) the spread and growth of cancer cells or (2) reactive hyperplasia. Therefore, nodal enlargement in proximity to a cancer, while it must arouse suspicion, does not necessarily mean dissemination of the primary lesion.

Dr.Nazar Jawhar

The sentinel nodeTo avoid the considerable surgical morbidity associated with a full axillary lymph node dissection, biopsy of sentinel nodes is often used to assess the presence or absence of metastatic lesions in the lymph nodes. A sentinel lymph node is defined as "the first node in a regional lymphatic basin that receives lymph flow from the primary tumor.“

Dr.Nazar Jawhar

The sentinel node Sentinel node mapping can be done by injection of radiolabeled tracers and blue dyes, and the use of frozen section upon the sentinel lymph node at the time of surgery can guide the surgeon to the appropriate therapy. Sentinel node biopsy has been used for detecting the spread of melanomas, colon cancers, and other

Dr.Nazar Jawhar

Hematogenous spread: (artery vs vein, favored sites) Arteries, with their thicker walls, are less readily penetrated than are veins. With venous invasion the blood-borne cells follow the venous flow draining the site of the neoplasm, and the tumor cells often come to rest in the first capillary bed they encounter. Understandably the liver and lungs are most frequently involved in such hematogenous dissemination, because all portal area drainage flows to the liver and all caval blood flows to the lungs Other. N.B: Carcinoma vs sarcoma

Dr.Nazar Jawhar

Pathways of spread: Seeding the body cavities: occur whenever a malignant neoplasm penetrates into a body cavity as peritoenum & pleura. Such seeding is particularly characteristic of carcinomas arising in the ovaries, when, not infrequently, all peritoneal surfaces become coated with a heavy layer of cancerous glaze.

Dr.Nazar Jawhar

Microscopically, metastatic adenocarcinoma is seen in a lymph node here. It is common for carcinomas to metastasize to lymph nodes. The first nodes involved are those draining the site of the primary.

Dr.Nazar Jawhar

This is an example of metastases to the liver. Note that the tan-white masses are multiple and irregularly sized. A primary neoplasm is more likely to be a solitary mass. Metastasis is the best indication that a neoplasm is malignant

Dr.Nazar Jawhar

This computed tomographic (CT) scan without contrast of the abdomen in transverse view demonstrates multiple mass lesions resulting in a markedly enlarged liver extending from right to nearly the left side of the upper abdomen. These are metastases from a colonic adenocarcinoma. A normal sized spleen is seen at the lower left.

Dr.Nazar Jawhar

Both lymphatic and hematogenous spread of malignant neoplasms is possible to distant sites. Here, a breast carcinoma has spread to the lung.

Dr.Nazar Jawhar

Neoplasms can spread by seeding along body cavities,

Dr.Nazar Jawhar

Branches of peripheral nerve are invaded by nests of malignant cells. This is often why pain associated with cancers is unrelenting.

Malignant

Benign
Characteristics
Some lack of differentiation with anaplasia; structure often atypical
Well differentiated; structure sometimes typical of tissue of origin
Differentiation/anaplasia
Erratic and may be slow to rapid; mitotic figures may be numerous and abnormal
Usually progressive and slow; may come to a standstill or regress; mitotic figures rare and normal
Rate of growth
Locally invasive, infiltrating surrounding tissue; sometimes may be seemingly cohesive and expansile
Usually cohesive expansile well-demarcated masses that do not invade or infiltrate surrounding normal tissues
Local invasion
Frequently present; the larger and more undifferentiated the primary, the more likely are metastases
Absent
Metastasis

Dr.Nazar Jawhar

Disordered growth. - Dysplasia is encountered principally in epithelia. It means an abnormal but yet non-neoplastic proliferation of cells as a result of injury. There is loss of uniformity of the individual cells and loss of architectural orientation.
DYSPLASIA

Dr.Nazar Jawhar

Grading of dysplasia: Epithelial dysplasia does not indicate cancer but almost antedates the appearance of cancer ( i.e premalignant). The probability of progression depends on:

Dr.Nazar Jawhar

This term indicates the presence of severe architectural and cytological atypia in the epithelium (i.e. malignant features) BUT such changes are confined to the epithelium & do not extend beyond the basement membrane into the adjacent or subjacent tissue.
Carcinoma in situ

Dr.Nazar Jawhar

This is the next step toward neoplasia. Here, there is normal cervical squamous epithelium at the left, but dysplastic squamous epithelium at the right. Dysplasia is a disorderly growth of epithelium, but still confined to the epithelium. Dysplasia is still reversible.

Dr.Nazar Jawhar

When the entire epithelium is dysplastic and no normal epithelial cells are left, then the process is beyond dysplasia and is now neoplasia. If the basement membrane is still intact, as shown here, then the process is called "carcinoma in situ" because the carcinoma is still confined to the epithelium.



Dr.Nazar Jawhar

Dr.Nazar Jawhar

Microinvasive carcinoma




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