cours benign final

8/13/2019 Cours Benign Final

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Tumors based on

* cell of origin

* biologic behavior

Benign

Epithelial Mesenchymal

Malignant

Epithelial Mesenchymal


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Differences between benign and malignant tumors

Feature Benign Malignant

Capsulat ion Usually present Usually absent

Mode of grow th By expansion By infiltration

Differentiation Well differentiated Variable

Anaplasia Absent Present

Rate of grow th Slow Rapid

Metastases Does not happen May occur

Recurrence Usually do not recur Common

Fate Cured by excision

( if not in vital area)

Usually fatal


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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


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Rate of Growth

Benign tumors

Generally grow slowly over a period of years

Malignant tumors

Grow rapidly at an erratic pace


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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 anddestruction of host tissue

Poorly demarcated from surrounding normal tissue


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Benign

Malignant

Metastasis


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Metastasis

Tumor implants that are discontinuous from the

primary tumors

30% of newly diagnosed patients with solidtumors present with metastases

How do cancers spread?

Direct seeding of body cavities or surfaces (Ov CA)

Lymphatic spread (carcinomas)

Hematogenous spread (sarcomas)


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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


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Benign tumors

In general, benign tumors are designated byattaching the suffix -oma to the cell of origin.

Tumors of mesenchymal cells generally follow thisrule.

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.


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Tumors

cell of origin ( basis of classif ication)

Parenchyma

I- Epithelial

II- More than one germ layer( ecto-endo- mesoderm-

endoderm)

StromalSurface(papilloma)

Glandular( adenoma)


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Benign epithelial tumors

I- Papilloma II Adenoma III Nevus

origin

surface glandular melanocytes


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Papillomas

Definition

benign epithelial neoplasms producing

microscopically or macroscopically visible

finger-like or warty projections from epithelialsurfaces.

Squamous cell papilloma

it has a multiple finger-like projection with a

fibrovascular core

composed of hyperplastic typical squamous

epithelium


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Squamous papilloma: the most common

benign exophytic epithelial lesion of the oral cavity.


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Squamous cells papilloma


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Polyp

Definition

benign or malignant neoplasm which

produces a macroscopically visible projection

above a mucosal surface and projects, forexample, into the gastric or colonic lumen

The term polyp is preferably restricted to

benign tumors.

Malignant polyps are better designated

polypoid cancers.


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Colonic polyp. A, This benign glandular tumor (adenoma) is projectinginto the colonic lumen and is attached to the mucosa by a distinct

stalk. B , Gross appearance of several colonic polyps.


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Adenomatous polyp (large

intestine)


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Tubular adenoma

Villous adenoma

Poliposis

Malignisated adenomaUlcerated carcinoma

Ulcerated and infiltrativecarcinoma

Ulcerated and infiltrativecarcinoma


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Adenoma

Definition

benign epithelial neoplasm that forms glandularpattern

tumors derived from glands but not necessarilyreproducing 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 tissuesEg. in the ovary,

Papillary cystadenomas - papillary patterns thatprotrude into cystic spaces

Ovarian papillary cystadenoma


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Ovarian papillary cystadenoma


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Fibroadenoma


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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


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Thyroid Adenoma

Well circumscribed; expansile.


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adrenal adenoma


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http://www.pathconsultddx.com/pathCon/largeImage?pii=S1559-8675(06)70321-7&figureId=fig1


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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.



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Histopathology

Mature adipose tissue - no cellular atypia May present: fat necrosis, infarction, calcification

Important not to confuse histiocytes associated with fatnecrosis 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


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Lypoma Lyposarcoma



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Chondroid lipoma

Spindle cell lipoma

Pleomorphic lypoma

http://www.pathconsultddx.com/pathCon/largeImage?pii=S1559-8675(06)70321-7&figureId=fig8http://www.pathconsultddx.com/pathCon/largeImage?pii=S1559-8675(06)70321-7&figureId=fig5http://www.pathconsultddx.com/pathCon/largeImage?pii=S1559-8675(06)70321-7&figureId=fig2


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Leiomyomas

Definition: benign stromal tumor mainly composedof 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, andgrouped

genital leiomyomas: solitary or multiple vascular leiomyomas (angioleiomyomas)

deep-seated leiomyomas of nonvascular type:extremities and also pelvic region of females

http://en.wikipedia.org/wiki/Smoothhttp://en.wikipedia.org/wiki/Myohttp://en.wikipedia.org/wiki/Mousehttp://en.wikipedia.org/wiki/Musclehttp://en.wikipedia.org/wiki/Tumorhttp://en.wikipedia.org/wiki/Tumorhttp://en.wikipedia.org/wiki/Musclehttp://en.wikipedia.org/wiki/Mousehttp://en.wikipedia.org/wiki/Myohttp://en.wikipedia.org/wiki/Smooth


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Gross Pathology

- yellowish pink or white-gray

- various size

- sharply circumscribed

- fairly firm

- large tumors may present area of

ischemic necrosis


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Histopathology:

Fascicles of spindle cells that tend to intersecteach 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


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leimyoma



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Vascular leiomyoma

Epithelioid leiomyoma

Leiomyoma Leiomyosarcoma



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Leiomyoma Leiomyosarcoma


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Fibroma

Definition: banign autonome proliferation of

fibroblast and myofibroblast associated with

excess of fibers

They can grow in all organs, arising frommesenchyme tissue

It have to be differentiated from fibrosis which

is an excessive production of collagen fibers


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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


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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 Meig‘s syndrome


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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

http://upload.wikimedia.org/wikipedia/commons/1/14/Ovarian_Fibroma.jpg


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Ovarian fibroma showing hypocellular appearance,

bland nuclear features, and a suggestion of a storiform pattern of growth.

http://upload.wikimedia.org/wikipedia/commons/1/14/Ovarian_Fibroma.jpg


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Tendon sheath fibroma. The lesion

is hypocellular

and contains abundant collagen

Ovarian cellular fibroma. The

tumor is hypercellular,

but pleomorphism and

mitotic activity are minimal


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fibroblasts with no atypia forming

a tumour


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Chondroma

Definition: benign cartilage producing tumor mostcommon in the small bones of the hands and feet.

Significant risk of malignant transformation in Ollier'sdisease 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 ofhand or foot

May recur if incomplete excision


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Gross Pathology

≈30% multiple if predominantly unilateral designated Ollier's disease

associated with ovarian sex cord –stromal tumors

if also soft tissue hemangiomas (including spindle cell

hemangioendotheliomas) designated Maffucci'ssyndrome

Calcifying Enchondroma

Variant presenting in metaphysis of long bones andcharacterized by massive calcification

Juxtacortical Chondroma Characteristically erode and induce sclerosis of

contiguous cortex


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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


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Large asymptomatic enchondroma of femur in a 42-year-old woman.

The tumor is extensively calcified.

Gross appearance of juxtacortical chondroma.The tumor produces a semispherical

expansion of the involved bone.


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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


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Enchondroma of phalanx. The tumor has a typical lobulated appearance

Soft Tissue Chondroma


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Rhabdomyoma

Definition: benign stromal tumors of the soft tissuewith 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) inchildren


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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


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Fetal Rhabdomyoma

Very cellular

Formed by: immature skeletal muscle fibers: some containing cross

striations

primitive mesenchymal cells

Development equivalent to fetal skeletal muscle of7 –12 weeks’ gestation

No nuclear aberrations

Mitoses rare Have been divided into:

classic

intermediate


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Fetal rhabdomyoma


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Hemangioma

Definition: group of entities which has a commonmorphologic characteristic, form well-differentiatedblood vessels with endothelia and pericytes, andhave 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 trueneoplastic nature


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Clinical Features

Benign

Can become very large

Usually: child: many present at birth solitary

when multiple (with or without associated lesionsin 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


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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)


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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


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hemangiomul cavernos


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skeletal hemangioma

Lobular Capillary Hemangioma

http://upload.wikimedia.org/wikipedia/commons/c/cb/Capillary_hemangioma_of_skin_%282%29.jpg


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Spindle Cell Hemangioma

Sinusoidal hemangioma.The vascular spaces are

widely dilated

Schwannoma


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SchwannomaSynonyms: Neurilemoma, Neurinoma

Definition: benign, encapsulated tumors ofdifferentiated Schwann's cells, usually localized inperipheral nerves.

Clinical Features

Almost always solitary Location:

most commonly:

flexor surfaces of extremities

neck

mediastinum retroperitoneum

posterior spinal roots

cerebellopontine angle


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Gross Pathology

Encapsulated

Nerve of origin:

often demonstrated in periphery flattened

along capsule but not penetrating substanceof tumor

often contain cystic areas if large


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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


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Schwannoma of the cerebellopontine

angle - 8th nerve


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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.


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suggestion of nuclear palisadingand hyaline thickening of vessel walls.

Large hyperchromatic nuclei in schwannoma.

This is not necessarily an indication of malignant change


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Cellular schwannoma.

The tumor has a homogeneous hypercellular

quality.


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Osteoid Osteoma

Definition: is a benign painful (relieved by aspirin) boneforming neoplasm usually less than 1 cm.

Osteoblastoma is similar to osteoid osteoma with moreaggressive behavior.

Clinical: Commonly 10 –30 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


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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 ofcortex


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Histopathology

Sharply delineated central nidus:

composed of more or less calcified osteoid:

lined by plump osteoblasts

growing within highly vascularized connectivetissue without evidence of inflammation

surrounded by variably thick layer of dense bone


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The small, reddish central nidus is

Surrounded by a thick layer of sclerotic bone

wedge-shaped nidus protruding slightly

above the surface and

surrounded by sclerotic bone


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Exuberant new osteoid and bone formation by plump osteoblasts.

The stroma is cellular and well vascularized


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Myxoma

Definition: benign mesenchymal tumor with a hypocellular,hypovascular, bland appearance, composed of fibroblastsembedded in an abundant myxoid matrix, commonly locatedin 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: spottycutaneous pigmentation, nodular pigmented adrenal disease otherendocrine abnormalities


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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

http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675(06)70411-9http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675(06)70411-9http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675(06)70411-9http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675(06)70411-9


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intramuscular myxoma

Note the hypocellular quality, lack of

encapsulation, lack of atypia and

paucity of vessels

M l ti


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Melanocytic nevus

Strictly speaking, the term nevus denotes anycongenital lesion of the skin (e.g., birthmark).

Melanocytic nevus, however, refers to any congenitalor acquired neoplasm of melanocytes,

melanocytes have been transformed from highly

dendritic single cells normally interspersed amongbasal keratinocytes to round cells

Common acquired melanocytic nevi - clinicalappearance: tan to brown

uniformly pigmented small (usually


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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 inmelanocytic 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.


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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 nevuscells is of diagnostic importance in distinguishingsome benign nevi from melanomas, which usuallyshow little or no maturation

N


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Nevus


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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.


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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.


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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

li l ll fib i

cours benign final

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