Neoplasia

Dr Suvarna Nalapat

Alterations in cell growth

physiologic (normal responses to stimuli) or
pathologic. alterations of cell growth are potentially reversible and include: Hypertrophy: increase in cell size. Increase in skeletal muscle fiber size is a physiologic response to exercise, but the cardiac hypertrophy above is a pathologic response to abnormally elevated blood pressure. Hyperplasia: a increase in number of cells. Postpartum breast lobules undergo hyperplasia for lactation, endometrial hyperplasia in postmenopausal woman is abnormal

Growth disturbances
increase in tissue size is
not necessarily neoplasia increase in the size of the myocardial fibers in response to an increased pressure load from hypertension cells increase in size, but not in number

 large fronds of
endometrium are a result of hyperplasia. resulted from increased estrogen. With hyperplasia, there is increase in cell numbers cells are normal in appearance. Sometimes hyperplasias can be "atypical" and the cells not completely normal. Such conditions can be premalignant.

cellular transformation.
The two forms of cellular transformation that are
potentially reversible, but may be steps toward a neoplasm, are metaplasia: the exchange of normal epithelium for another type of epithelium. Metaplasia is reversible when the stimulus for it is taken away. Dysplasia: a disordered growth and maturation of an epithelium, which is still reversible if the factors driving it are eliminated

 metaplasia of normal
respiratory laryngeal epithelium on the right to squamous epithelium on the left in response to chronic irritation of smoking

 biopsy of the lower

esophagus in a patient with chronic gastroesophageal reflux disease shows columnar metaplasia (Barrett's esophagus), and the goblet cells are typical of an intestinal type of epithelium. Squamous epithelium typical of the normal esophagus appears at the right

 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

 the normal cervical

squamous epithelium at the left merges into the dysplastic squamous epithelium at the right in which the cells are more disorderly.

 Some epithelia are

accessible, such as the cervix, that cancer screening can be done by sampling some of the cells and sending them to the laboratory. cervical Pap smear in which dysplastic cells are present that have larger and darker nuclei than normal squamous cells with small nuclei and large amounts of cytoplasm

 When entire epithelium is

dysplastic and no normal epithelial cells are left, the process is beyond dysplasia and is 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.

 This is a neoplasm.
Neoplasia is uncontrolled new growth. Note mass of abnormal tissue on surface of cervix. term "tumor" used synonymously with neoplasm, but "tumor" can mean any mass effect, whether inflammatory, hemodynamic, or neoplastic. Once a neoplasm, it is not reversible.

 microscopic appearance
of neoplasia, or uncontrolled new growth. Here, the neoplasm is infiltrating into the underlying cervical stroma. Of course, there can be carcinoma in situ in which a full-fledged neoplasm is present, but has not yet invaded

 squamous cell
carcinoma. Note the disorderly growth of the squamous epithelial cells in these large nests with pink keratin in the centers

 neoplasms can be benign

as well as malignant,. Here is a benign lipoma on the serosal surface of the small intestine. It has the characteristics of a benign neoplasm: it is well circumscribed, slow growing, and resembles the tissue of origin (fat).

 At low power
magnification, a lipoma of the stomach is seen to be well demarcated from the mucosa at the lower center-right. This neoplasm is so welldifferentiated that, except for its appearance as a localized mass, it is impossible to tell from normal adipose tissue

 Here is the lipoma at

high magnification. This is a good example of how a benign neoplasm mimics the tissue of origin.

 Benign neoplasms can be

multiple, leiomyomas of varying size, but all benign and wellcircumscribed firm white masses. most common neoplasm is a benign nevus (pigmented mole) of the skin, and most people have several. As a general rule, benign neoplasms do not give rise to malignant neoplasms.

 microscopic
appearance of a leiomyoma indicates that the cells do not vary greatly in size and shape and closely resemble normal smooth muscle cells.

 Multiple adenomatous
polyps of the cecum are seen here in a case of familial polyposis

 This schwannoma was

resected from a nerve. Note the circumscribed nature of this benign neoplasm.

 schwannoma is seen
microscopically to be composed of spindle cells (like most neoplasms of mesenchymal origin), but the cells are fairly uniform and there is plenty of pink cytoplasm.

 small fibroadenoma of the

breast, a benign neoplasm more commonly found in younger women of reproductive age. The blue dye was injected during a radiographic procedure to mark the location of the neoplasm so the surgeon could find it.

 the most common

neoplasm is a benign nevus (pigmented mole) of the skin, and most people have several, as seen here over the skin of the chest. As a general rule, benign neoplasms do not give rise to malignant neoplasms

 small hepatic adenoma, an

uncommon benign neoplasm, but one that shows how welldemarcated an benign neoplasm is. It also illustrates how function of the normal tissue is maintained, because the adenoma is making bile pigment, giving it a green color.

 In contrast, this
hepatocellular carcinoma is not as well circumscribed (note the infiltration of tumor off to the lower right) nor as uniform in consistency. It is also arising in a cirrhotic (nodular) liver.

 renal cell carcinoma

demonstrates distortion and displacement of the renal parenchyma by the tumor mass in the lower pole. This malignant neoplasm is variegated on cut surface, with yellow to white to red to brown areas.

 excision of skin
demonstrates a malignant melanoma, which is much larger and more irregular than a benign nevus.

 example of metastases to
the liver. Note that the tanwhite masses are multiple and irregularly sized. Like many large metastatic lesions, there is central necrosis. A primary neoplasm is more likely to be a solitary mass. The presence of metastases are the best indication that a neoplasm is malignant.

 This abdominal CT scan

demonstrates multiple variegated mass lesions, some with dark central necrosis, in a patient with widespread metastatic carcinoma. A normal sized spleen is seen at the lower left.

 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 neoplasm

 Both lymphatic and

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

 chest radiograph
reveals the presence of multiple rounded masses in all lung fields. These are metastases.

 Neoplasms can spread by

seeding along body cavities, and this pattern is more typical for carcinomas than other neoplasms. Note the multitude of small tan tumor nodules seen over the peritoneal surface of the mesentery shown here.

 microscopic evidence
of the spread of a carcinoma via body cavities. A focus of metastatic breast carcinoma is present along the pleura overlying the lung.

 small focus of metastatic

carcinoma to the epicardium .key feature of neoplasms--angiogenesis. Note the proliferation of many small capillaries adjacent to the neoplastic cells. Neoplasms can produce factors that promote vascular growth to provide a vascular supply and continued uncontrolled growt

 Malignant neoplasms
are also characterized by the tendency to invade surrounding tissues. Here, a lung cancer is seen to be spreading along the bronchi into the surrounding lung.

 squamous cell
carcinoma of the lung. It is a bulky mass that extends into surrounding lung parenchyma.

 chest CT scan
demonstrates a large squamous cell carcinoma of the right upper lobe that extends around the right main bronchus and also invades into the mediastinum and involves hilar lymph nodes.

 infiltrating ductal
carcinoma of the breast surrounding breast.central white area is very hard and gritty, because the neoplasm is producing a desmoplastic reaction with lots of collagen. This is often called a "scirrhous" appearance. There is also focal dystrophic calcification leading to the gritty areas

 the infiltrating ductal

carcinoma extends irregularly through the tissue as cords and nests of neoplastic cells with intervening collagen. There is a purplish microcalcification at the lower center right.

 the infiltrating ductal

carcinoma of breast has pleomorphic cells infiltrating through the stroma.

 invading
adenocarcinoma can be seen here. Normal gastric epithelium at the left merges into the carcinoma at the right, and irregular neoplastic glands infiltrate downward into the submucosa.

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

 The concept of
differentiation is demonstrated by this small adenomatous polyp of the colon. Note the difference in staining quality between the epithelial cells of the adenoma at the top and the normal glandular epithelium of the colonic mucosa below.

 normal colonic epithelium

at left contrasts with atypical epithelium of adenomatous polyp (tubular adenoma) at right. Nuclei darker more irregularly sized closer together in the adenomatous polyp than in normal mucosa. overall difference between them is not great, so this benign neoplasm mimics normal tissue and is, welldifferentiated.

 colonoscopy of
adenocarcinoma colon. bulky mass spreads over colonic mucosal surface. It has red areas because it is bleeding, and this led to positive occult blood in stool (screening method for detection). Neoplasms may not maintain the structure of normal tissues, there is irregular growth with necrosis and hemorrhage, in larger aggressive neoplasms.

 The infiltrating glands of

this colonic adenocarcinoma demonstrate less differentiation than the adenomatous polyp, although they still resemble glands. In general, less differentiation of a neoplasm means a greater likelihood of malignant behavior. This is the basis for grading.

 gastric adenocarcinoma is
positive for cytokeratin by immunoperoxidase. typical staining reaction for carcinomas and helps to distinguish carcinomas from sarcomas and lymphomas. Immunoperoxidase staining helpful to determine cell type of neoplasm when degree of differentiation, or morphology, does not allow exact classification

 By electron microscopy,
features of carcinoma seen. adenocarcinoma demonstrates several features typical of neoplasm of epithelial origin, including junctional complex (tight junction at the asterisk and the desmosomes at crosses). The mucin granule (M) and lumenal microvilli at upper right also typical for adenocarcinoma.

 normal squamous
epithelium at left merges into squamous cell carcinoma at right, infiltrating downward. neoplastic squamous cells are still similar to normal squamous cells, but are less orderly. This is a well-differentiated squamous cell carcinoma.

 a moderately
differentiated squamous cell carcinoma in which some, but not all, of the neoplastic cells in nests have pink keratin. In general, neoplasms with less differentiation are more aggressive.

 At high magnification,
squamous cell carcinoma demonstrates enough differentiation to tell that cells are of squamous origin. cells are pink and polygonal with intercellular bridges (seen as desmosomes or "tight junctions" by electron microscopy). neoplastic cells show pleomorphism, with hyperchromatic nuclei. A mitotic figure present near center.

 Features of a carcinoma
are seen in this electron micrograph. This squamous cell carcinoma demonstrates many desmosomes, along with cytoplasmic tonofilaments streaming to the left.

 This neoplasm is so poorly

differentiated that it is difficult to tell what the cell of origin is. It is probably a carcinoma because of the polygonal nature of the cells. Note that nucleoli are numerous and large in this neoplasm. Neoplasms with no differentiation are said to be anaplastic.

 Neoplasia in the pediatric

age range is not common. Childhood malignancies are rare, but those that occur often have the appearance of primitive "small round blue cell tumors" such as the neuroblastoma seen here

Childhood Malignancy
Leukemia Neuroblastoma Medulloblastoma Retinoblastoma Wilms tumor Ewing sarcoma

Blood, marrow, lymph

nodes Adrenal, extra-adrenal ganglia Cerebellum Eye

Kidney bone

Aneuploidy by flow cytometry-ca breast

 A mitotic figure in center,

surrounded by poorly differentiated squamous cell carcinoma with pleomorphic cells that have minimal pink keratinization in cytoplasm., mitoses are more likely to be seen in malignant neoplasms. Remember,, that normally cells are actively dividing in many tissues of body, including skin, bone marrow, gonads, and gastrointestinal tract.

 Here are three abnormal

mitoses. Mitoses by themselves are not indicators of malignancy. However, abnormal mitoses are highly indicative of malignancy. The marked pleomorphism and hyperchromatism of surrounding cells also favors malignancy.

 large fleshy mass in

retroperitoneum Sarcomas arise from mesenchymal tissues. "malignant fibrous histiocytoma" a wastebasket term for sarcomas that do not resemble striated muscle (rhabdomyosarcoma), smooth muscle (leiomyosarcoma), fat (liposarcoma), blood vessels (angiosarcoma), bone (osteosarcoma), cartilage (chondrosarcoma). Sarcomas tend to be big and bad.

 computed tomographic
(CT) scan of the abdomen at the level of the kidneys in which there is a large mass in the retroperitoneum that proved to be a sarcoma. The mass is just anterior to the right kidney and medial to the right lower lobe of liver.

 fleshy mass arising in the

soft tissues of the lower leg. The tibia and the fibula are seen in cross section. This neoplasm proved to be a malignant fibrous histiocytoma. Sarcomas tend to invade locally, as can be seen here by the ill-defined margins of the mass.

 Sarcomas tend to have

a spindle cell pattern. Note that some of the cells are much larger and very pleomorphic.

 sarcoma seen at medium

magnification is composed of very pleomorphic cells. The cell of origin of sarcomas is often difficult to determine because of their tendency to be poorly differentiated or even anaplastic.

 magnetic resonance
imaging (MRI) scan of the left leg, with a large sarcoma arising posterior to the knee, seen here at the level of the lower femur.

Vimentin-infiltrating to normal muscle is a sarcoma

liposarcoma

large bizarre lipoblasts

Paraneoplastic syndromes
A paraneoplastic syndrome occurs when a
neoplasm elaborates a substance that results in an effect that is not directly related to growth, invasion, or metastasis. Most paraneoplastic syndromes result from elaboration of hormonelike substances, but a variety of effects are possible. Sometimes the paraneoplastic syndrome may precede diagnosis of the neoplasm and may give a clue to its presence.

Syndrome Cushing's

Mechanism ACTH-like

Example Lung (oat

Hypercalcemi Parathormone- Lung a like (squamous Hyponatremia Inappropriate ADH Polycythemia Lung (oat

Erythropoietin- Renal cell like carcinoma

Trousseau's Syndrome Hypoglycemia

Hypercoagulabl Various e state carcinomas Insulin-like substance Various carcinomas and sarcomas

Carcinoid Syndrome

5-hydroxyMetastatic indoleacetic acid malignant (5-HIAA) carcinoid tumors

 process of neoplasia begins with cell

transformation. A variety of chemical carcinogens as diverse as benzene, cigarette smoke, and nitrites can initiate and/or promote this process. Radiation, either as low level long-term environmental gamma rays or as higher dose therapeutic radiation, can also produce genetic mutations. Infectious agents such as human papillomavirus can lead to cellular transformation as well

 Genetic damage with DNA alterations leads to

point mutations of genes, translocations of genetic material between chromosomes, and gene reduplication with amplification. These alterations transform proto-oncogenes into oncogenes. The proto-oncogenes may play a role in growth promotion and regulation in normal cells, perhaps in embryogenesis, but are typically "turned off" in adults. They are "turned on" by transformation.

 or uncontrolled cellular proliferation, can

result either from mutations that "turn on" the oncogenes that stimulate growth, or from mutations that result in loss of tumor suppressor genes and their products that inhibit growth.

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