Tumors

based on

of origin * biologic behavior

Benign

* cell

Malignant

Epithelial

Mesenchymal

Epithelial

Mesenchymal

Differences between benign and malignant tumors

Feature
Capsulation Mode of growth Differentiation Anaplasia

Benign
Usually present By expansion Well differentiated Absent

Malignant
Usually absent By infiltration Variable Present

Rate of growth
Metastases Recurrence Fate

Slow
Does not happen Usually do not recur Cured by excision ( if not in vital area)

Rapid
May occur Common Usually fatal

Benign
Histology Cells Nuclei Mitosis
Uniform in size and shape Equal Few or absent ( normal if present) Well formed

Malignant
Pleomorphic Hyperchramatic / N/C ratio Many ( abnormal)

Blood vascularisation

Poorly formed

Differentiation and Anaplasia

Benign tumors Well differentiated Malignant tumors Range from well to poorly differentiated Hallmarks of anaplasia: Cells and nuclei show pleomorphism Cells contain abundant DNA, coarse, clumped chromatin Large NC ratio (1:1) rather than (1:4) Large nucleoli Large # of mitoses Dysplasia Precancerous condition in epithelial tissue Anaplastic cells in epithelium Dysplasia does not always progress to cancer

Rate of Growth

Benign tumors

Generally grow slowly over a period of years Grow rapidly at an erratic pace

Malignant tumors

Local Invasion
Benign tumors grow as cohesive, expanding masses that remain localized to site of origin Do not have capacity to metastasize to distant sites Frequently are surrounded by a fibrous cap Malignant tumors Grow with progressive infiltration, invasion and destruction of host tissue Poorly demarcated from surrounding normal tissue

Benign

Malignant

Metastasis

Metastasis
Tumor implants that are discontinuous from the

primary tumors 30% of newly diagnosed patients with solid tumors present with metastases How do cancers spread?

Direct seeding of body cavities or surfaces (Ov CA) Lymphatic spread (carcinomas) Hematogenous spread (sarcomas)

6 Capabilities of Cancers
Self-sufficiency in growth signals
Insensitivity to growth inhibitory signal Evasion of programmed cell death

Limitless replicative potential

Tissue invasion and metastasis Sustained angiogenesis

Benign tumors
In general, benign tumors are designated by

attaching the suffix -oma to the cell of origin. Tumors of mesenchymal cells generally follow this rule.

fibroblastic cells fibroma, cartilaginous tumor chondroma, tumor of osteoblasts osteoma

Nomenclature of benign epithelial tumors is more

complex. They are variously classified, based on:

their cells of origin microscopic architecture macroscopic patterns.

Tumors

cell of origin
( basis of classification)

Parenchyma
I- Epithelial

Surface (papilloma)

Stromal

II- More than one germ layer ( ecto-endo- mesodermendoderm)

Glandular ( adenoma)

Benign epithelial tumors

I- Papilloma
origin

II Adenoma

III Nevus

surface

glandular

melanocytes

Papillomas
Definition

benign epithelial neoplasms producing microscopically or macroscopically visible finger-like or warty projections from epithelial surfaces.
it has a multiple finger-like projection with a fibrovascular core composed of hyperplastic typical squamous epithelium

Squamous cell papilloma

Squamous papilloma: the most common benign exophytic epithelial lesion of the oral cavity.

Squamous cells papilloma

Polyp
Definition

benign or malignant neoplasm which produces a macroscopically visible projection above a mucosal surface and projects, for example, into the gastric or colonic lumen

The term polyp is preferably restricted to

benign tumors. Malignant polyps are better designated polypoid cancers.

Colonic polyp. A, This benign glandular tumor (adenoma) is projecting into the colonic lumen and is attached to the mucosa by a distinct stalk. B, Gross appearance of several colonic polyps.

Adenomatous polyp (large intestine)

Villous adenoma

Tubular adenoma

Poliposis

Malignisated adenoma

Ulcerated carcinoma

Ulcerated and infiltrative carcinoma

Ulcerated and infiltrative carcinoma

Adenoma
Definition

benign epithelial neoplasm that forms glandular pattern tumors derived from glands but not necessarily reproducing glandular patterns. Types:

Pure adenomas Mixed adenomas (epithelial and stromal component Eg. fibroadenoma of breast) Functioning adenomas Cystadenomas - form large cystic masses with secretions are trapped inside the adenomatous tissues Eg. in the ovary, Papillary cystadenomas - papillary patterns that protrude into cystic spaces

Ovarian papillary cystadenoma

Fibroadenoma

Functioning adenomas
Tumors originating from epithelium of

endocrine glands They secrete hormones normally secreted by their non-neoplastic counterparts

Thyroid adenoma .T3 & T4 Pancreatic adenomas - Islet cell adenoma.Insulin/ Glucagon Adrenal cortical adenoma.Steroids

Thyroid Adenoma Well circumscribed; expansile.

adrenal adenoma

Lipoma
Definition Benign soft tissue tumor composed of differentiated fat cells. Clinical Features adult, fifth or sixth decade of life Any location containing fat, usually: upper half of body, particularly: trunk, neck subcutaneous Can occur in deep soft tissues: intramuscular or intermuscular Single or multiple Diffuse lipomatosis

Gross Pathology

Can be large

Usually encapsulated in superficial soft tissues

Soft, mobile, and painless (except angiolipoma)

Bright yellow fat separated by fine fibrous trabeculae Except for the circumscription, the appearance is indistinguishable from that of normal fat.

Histopathology
Mature adipose tissue - no cellular atypia May present: fat necrosis, infarction, calcification Important not to confuse histiocytes associated with fat

necrosis with lipoblasts Rarely foci of mature metaplastic: cartilage,bone Ultrastructurally: univacuolar mature adipocytes Variants:

Fibrolipoma Myxolipoma Chondroid lipoma Myolipoma Spindle cell lipoma Pleomorphic lipoma.

Lypoma

Lyposarcoma

Chondroid lipoma

Spindle cell lipoma

Pleomorphic lypoma

Leiomyomas
Definition: benign stromal tumor mainly composed of mature smooth muscle bundles
Greek:

leios = smooth muV = (myo) mouse or muscle oma = tumor Were first described by Virchow in 1854

Types: cutaneous leiomyomas: located in dermis, characteristically superficial, small, multiple, and grouped genital leiomyomas: solitary or multiple vascular leiomyomas (angioleiomyomas) deep-seated leiomyomas of nonvascular type: extremities and also pelvic region of females

Gross Pathology

- yellowish pink or white-gray - various size - sharply circumscribed - fairly firm - large tumors may present area of ischemic necrosis

Histopathology:

Fascicles of spindle cells that tend to intersect each other at right angles Cells fusiform in shape blunt-ended, elongated nuclei eosinophilic cytoplasm, limit not well distinct different range of cellularity minimal atypia and few mitotic figures occasionally, bizarre nuclear forms Could present ischemic necrosis

leimyoma

Epithelioid leiomyoma

Vascular leiomyoma

Leiomyoma

Leiomyosarcoma

Fibroma
Definition: banign autonome proliferation of

fibroblast and myofibroblast associated with excess of fibers They can grow in all organs, arising from mesenchyme tissue It have to be differentiated from fibrosis which is an excessive production of collagen fibers

Types:

hard fibroma (fibroma durum) consists of many fibres and few cells, e.g. in skin it is called dermatofibroma soft fibroma (fibroma molle) or fibroma with a shaft, consist of many loosely connected cells and less fibroid tissue e.g. fibroma pendulans angiofibroma - vasoactive tumor, with many dilated vessels cystic fibroma (fibroma cysticum) has central softening or dilated lymhatic vessels myxofibroma Others: chondromyxoid fibroma, desmoplasmic fibroma, nonossifying fibroma, ossifying fibroma, perifollicular fibroma, pleomorphic fibroma

Ovarian fibroma
sex cord-sromal tumor
most frequent during middle age gross pathological inspection: well circumscribed Solid, lobulated, firm Uniformly white billateral variants with edema are especially likely to be associated with Meigs syndrome

microscopic examination

Spindle stromal cells: closely packed, arranged in feather-stitched or storiform pattern May be: hyaline bands or edema
With or without thecomatous areas (fibrothecoma)

Occasionally bizarre tumor cells unaccompanied by mitoses

Ovarian fibroma showing hypocellular appearance, bland nuclear features, and a suggestion of a storiform pattern of growth.

Ovarian cellular fibroma. The tumor is hypercellular, but pleomorphism and mitotic activity are minimal

Tendon sheath fibroma. The lesion is hypocellular and contains abundant collagen

fibroblasts with no atypia forming a tumour

Chondroma
Definition: benign cartilage producing tumor most

common in the small bones of the hands and feet. Significant risk of malignant transformation in Ollier's disease and Maffucci's syndrome Enchondromas begin in spongiosa of diaphysis, from which they expand and thin cortex Juxtacortical Chondroma

less common than enchondroma Involve periosteal region of long bone or small bone of hand or foot May recur if incomplete excision

Gross Pathology
30% multiple if predominantly unilateral designated Ollier's disease associated with ovarian sex cordstromal tumors if also soft tissue hemangiomas (including spindle cell hemangioendotheliomas) designated Maffucci's syndrome Calcifying Enchondroma Variant presenting in metaphysis of long bones and characterized by massive calcification Juxtacortical Chondroma Characteristically erode and induce sclerosis of contiguous cortex

head of humerus affected by multiple chondromas in a patient with Ollier's disease

Arm of a patient affected by Maffucci's syndrome. Innumerable chondromas are seen concentrated in the distal aspect of the extremity

Gross appearance of juxtacortical chondroma. The tumor produces a semispherical expansion of the involved bone. Large asymptomatic enchondroma of femur in a 42-year-old woman. The tumor is extensively calcified.

Histopathology
Mature lobules of hyaline cartilage Commonly foci of: myxoid degeneration calcification endochondral ossification Juxtacortical chondroma: tends to be more cellular than medullary counterpart may contain occasional plump or double nuclei

Soft Tissue Chondroma

Enchondroma of phalanx. The tumor has a typical lobulated appearance

Rhabdomyoma
Definition: benign stromal tumors of the soft tissue

with skeletal muscle differentiation. Exceedingly rare Distinct subtypes with some overlap Adult Rhabdomyoma

Almost exclusively oral cavity and vicinity in adults May be multifocal and recur locally

Fetal Rhabdomyoma Almost exclusively: head and neck area (particularly retroauricular) in children <3 years vulvovaginal region of middle-aged women - genital rhabdomyoma

Histopathology
Adult Rhabdomyoma
Cells: well differentiated

large rounded or polygonal some have features of spider cells' Cytoplasm: abundant, acidophilic contains variable amounts of lipid and glycogen frequently: cross striations intracytoplasmic rod-like (jack straw') inclusions May be intranuclear inclusions No mitotic activity or nuclear atypia

Fetal Rhabdomyoma
Very cellular Formed by: immature skeletal muscle fibers: some containing cross striations primitive mesenchymal cells Development equivalent to fetal skeletal muscle of

712 weeks gestation No nuclear aberrations Mitoses rare Have been divided into:

classic intermediate

Fetal rhabdomyoma

Hemangioma
Definition: group of entities which has a common

morphologic characteristic, form well-differentiated blood vessels with endothelia and pericytes, and have a limited proliferative capacity.
Pathogenesis Gray zone between hamartomatous malformations and true neoplasms Frequently designated as tumors because: usually localized mass effect Consistent lack of chromosomal alterations against true neoplastic nature

Clinical Features
Benign
Can

become very large Usually:

child: many present at birth solitary when multiple (with or without associated lesions in internal organs) or affecting a large segment of body known as (multifocal) angiomatosis

head

and neck area: >50%, but also trunk or extremities

Classification According To Clinical Appearance And Caliber Of Vessel

Capillary hemangioma: small vessels of capillary caliber any organ Cavernous hemangioma: larger vessels with cystically dilated lumina thin walls Large-vessel hemangioma: may be composed of: vessels with structure of veins (venous hemangiomas) or combination of veins and arteries (racemose, cirsoid, or arteriovenous hemangiomas)

 Skeletal muscle (intramuscular) hemangioma

Spindle cell hemangioma:

currently classified as benign endothelial neoplasm, but variously described as:

low-grade angiosarcoma non-neoplastic lesion related to a vascular malformation

Hobnail hemangioma

hemangiomul cavernos

Lobular Capillary Hemangioma

skeletal hemangioma

Sinusoidal hemangioma.
The vascular spaces are widely dilated

Spindle Cell Hemangioma

Schwannoma
Synonyms: Neurilemoma, Neurinoma
Definition: benign, encapsulated tumors of

differentiated Schwann's cells, usually localized in peripheral nerves. Clinical Features

Almost always solitary Location:

most commonly:
flexor surfaces of extremities neck mediastinum retroperitoneum posterior spinal roots cerebellopontine angle

Gross Pathology
Encapsulated Nerve of origin:

often demonstrated in periphery flattened along capsule but not penetrating substance of tumor often contain cystic areas if large

Histopathology
Usually two different patterns:

Antoni A areas: quite cellular, composed of spindle cells: often palisading or organoid arrangement (Verocay bodies) Antoni B areas: tumor cells separated by abundant edematous fluid, which may form cystic spaces occasionally isolated cells with bizarre hyperchromatic nuclei common in ancient schwannomas no particular significance Mitoses: usually absent or scanty Blood vessels: can be prominent and simulate vascular neoplasm Variants: - Cellular Schwannomas - Psammomatous melanotic Schwannoma

Schwannoma of the cerebellopontine angle - 8th nerve

dense areas called Antoni A (black arrow) and looser areas called Antoni B (blue arrows). The cells are elongated (spindle shaped) and the nuclei have a tendency to line up Like normal Schwann cells, schwannoma cells are each surrounded by a basement membrane.

suggestion of nuclear palisading and hyaline thickening of vessel walls.

Large hyperchromatic nuclei in schwannoma. This is not necessarily an indication of malignant change

Cellular schwannoma. The tumor has a homogeneous hypercellular quality.

Osteoid Osteoma
Definition: is a benign painful (relieved by aspirin) bone

forming neoplasm usually less than 1 cm. Osteoblastoma is similar to osteoid osteoma with more aggressive behavior. Clinical:

Commonly 1030 years of age Male:female ratio 2:1 Most prominent symptom: intense pain:
often sharply localized unaccompanied by clinical or laboratory evidence of infection characteristically more intense at night

Vertebral lesions may be associated with scoliosis

Gross Pathology
Location: most frequently:

Femur, tibia,humerus,fibula bones of hands and feet vertebrae Lesions of long bones: metaphyseal centered in the cortex (85%) may be: epiphyseal, juxta- or intra-articular, in spongiosa (13%) or subperiosteal region (2%) Nidus surrounded by peripheral sclerotic reaction that may extend several centimeters along both sides of cortex

Histopathology

Sharply delineated central nidus: composed of more or less calcified osteoid: lined by plump osteoblasts growing within highly vascularized connective tissue without evidence of inflammation surrounded by variably thick layer of dense bone

wedge-shaped nidus protruding slightly above the surface and surrounded by sclerotic bone

The small, reddish central nidus is Surrounded by a thick layer of sclerotic bone

Exuberant new osteoid and bone formation by plump osteoblasts. The stroma is cellular and well vascularized

Myxoma
Definition: benign mesenchymal tumor with a hypocellular,

hypovascular, bland appearance, composed of fibroblasts embedded in an abundant myxoid matrix, commonly located in the intramuscular compartment. Clinical Features

Rare, usually adult, should be seriously questioned if a child More common in females Arise within: skeletal muscle, especially in thigh:
if multiple usually associated with fibrous dysplasia of bones of same extremity

juxta-articular region, particularly in the knee: skin, breast, and other locations:
if multiple consider Carney's syndrome, which also includes: spotty cutaneous pigmentation, nodular pigmented adrenal disease other endocrine abnormalities

Pathology
Gross: mucoid, slimy appearance Histopathology

Typically bland and hypocellular throughout Mitotic activity practically absent Blood vessels extremely scanty May be focal aggregates of foamy histiocytes:

contain neutral fat with oil red O stain should not be confused with lipoblasts of myxoid liposarcoma8

Ultrastructurally:

principal cell of intramuscular myxoma resembles fibroblast with:

prominent granular endoplasmic reticulum well-developed Golgi apparatus cytoplasmic filaments9

intramuscular myxoma

Note the hypocellular quality, lack of encapsulation, lack of atypia and paucity of vessels

Melanocytic nevus
Strictly speaking, the term nevus denotes any

congenital lesion of the skin (e.g., birthmark). Melanocytic nevus, however, refers to any congenital or acquired neoplasm of melanocytes, melanocytes have been transformed from highly dendritic single cells normally interspersed among basal keratinocytes to round cells Common acquired melanocytic nevi - clinical appearance:

tan to brown uniformly pigmented small (usually <6 mm across), solid regions of relatively flat (macules) to elevated skin (papules) with well-defined, rounded borders

Morphology
formed by melanocytes that grow in aggregates, or "nests, Nuclei of nevus cells: uniform and rounded in contour contain inconspicuous nucleoli show little or no mitotic activity Types junctional nevi the cell are growing along the dermoepidermal junction are believed to represent an early developmental stage in melanocytic nevi compound nevi eventually, most junctional nevi grow into the underlying dermis as nests or cords of cells intradermal nevi in older lesions, the epidermal nests may be lost entirely to form pure.

 maturation= nevus cells from the dermo-epidermal

junction progressive growth into the underlying dermis more superficial nevus cells

less mature, larger, tend to produce melanin, grow in nests,

deeper nevus cells more mature, are smaller, fusiform contours produce little or no pigment grow in cords, fascicles resembling neural tissue.
This sequence of maturation of individual nevus

cells is of diagnostic importance in distinguishing some benign nevi from melanomas, which usually show little or no maturation

Nevus

Nevocellular nevus, junctional type. lesions are small, relatively flat, symmetric, and uniform.

junctional nevus: rounded nests of nevus cells originating at the tips of rete ridges along the dermoepidermal junction.

Nevocellular nevus, compound type. dome shaped, the symmetry and uniform pigment distribution suggest a benign process.

combine the features of junctional nevi (intraepidermal nevus cell nests) with nests and cords of nevus cells in the underlying dermis.

Dysplastic nevus - often has a compound nevus component and an asymmetric "shoulder" composed of a junctional nevus component Presence of cytologic atypia (irregularly shaped, dark-staining nuclei) at high magnification.The dermis underlying the atypical cells characteristically shows linear, or lamellar, fibrosis