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Flashcards in neoplasias Deck (12):

31. Neoplasia (definition) and preneoplasia (definition and examples)

 Definition:
 The neoplasm is a newly formed tissue that resulted from the progressive and uncontrolled proliferation of its component cells.
 The tumor (tumor = growth, pre-eminence) is the growth of a new tissue characterized by the uncontrolled multiplication of its cells

 Definition:
 preneoplasia is represented by a anatomo-clinical state with high risk malignant evolution.
 Examples:
 hyperplasia of the endometrium
 hyperplasia of the mammary glandular epithelium
 squamous metaplasia of the bronchus
 glandular metaplasia of the esophagus
 displasia of the colonic mucous membrane (in ulcerative colitis)


32. Classification of tumors according their behavior

 The classification of tumors according to their behavior
 Benign tumors
• they grow slowly
• they expand quickly (they compress the neighboring tissues)
• well delimitated
• they are mobile when palpated
• they do not produce metastases
• they do not remit after removal
 Malignant tumors
• they grow rapidly
• they grow by infiltration (they invade and destroy the neighboring tissues)
• they are poorly delimitated
• they are fixed (they adhere)
• they produce metastases
• they remit after removal (surgical removal is difficult)
 Borderline tumors situated between the benign status and the malignant status
• they remit after removal
• they rarely produce metastasis
• examples:
– basallcell carcinoma,
– cystadenoma of the ovary (borderline), etc.


33. Metastases: definition, metastasizing ways, morphology of metastases

 Definition:
 metastasis is a secondary tumor that appears in different organs through metastasizing.
 Metastasizing is the detachment of some cells from the original tumor, their migration through different ways and their proliferation in the organs where secondary tumors appear (metastases)

Metastasizing ways :
 Local invasion: the growth of the tumor occurs by the invasion of the tissues that neighbor the tumor
 The extension of the tumor along the tissular natural levels especially along the nerves (the perineural way)
 The transcelomic way allows the extension of the tumor through the serous cavities
 gastric cc  on the ovaries
 ovary cc  peritoneum
 mammary cc  pleura
 The CSF way in CNS tumors
 Direct implantation :
 cc of the superior lip  inferior lip
 visceral cc  in the abdominal wall (through the contact of the wound with the tumor)
 The lymphatic way
 more frequent in epithelial malignant tumors (carcinomas)
 the first affected are the regional ganglions (ex : mammary carcinoma  axilar lymph nodes).
 tumoral embolies can block the lymphatics leading to the appearance of a lymphedema.
 then the tumoral embolies can penetrate the blood, where it gets disseminated by the sanguinary way as well
 The hematogenous way (blood)
 more frequent in mesenchymal malignant tumors (sarcomas)
 the invasion of the blood-vessels usually through the veins (thin blood vessels)
 examples : abdominal tumors  in the liver, tumors of the organs tributary to the vena cava  in the lungs

The morphology of the metastases:
 Macroscopical features:
 nodular lesions, well delimitated, multiple, of various sizes, having the color and the consistency of the source tumor
 Microscopical features:
 have the same hystological aspect as the original tumor


1. Staging of tumors and tumoral markers

 Staging is a anatomo-clinical term that offers indicators about the size and the extension of the tumor
 The staging of the tumor gives data about:
 the localization of the primary tumor
 the characteristics of the local invasion
 the extension through the lymphatic nodes
 the presence or absence of visceral metastases

 The TNM system represents a diagram used in order to stage the tumor in which
 T (put down as T0, T1-T4, Tx) gives data about the size and the local extension of a primary tumor.
 N (put down as N0, N1-N4, Nx) gives data about the metastatic implication of the lymphatic nodes.
 M (put down as M0, M1-M4, Mx) gives data about the metastatic implication of the viceras.
 The TNM system (it has four stages) is an important prognosis indicator especially in the therapy that is going to be prescribed:
 the local stages can be treated through more conservatory means (ex : Stage I : T1N0M0)
 the advanced stages need more agressive measures (ex. Stage III : T3N3M1)

 Tumoral markers are used to diagnose and monitor the evolution of the tumors, which can be:
 Tissular markers:
• they rely on the AG-Ac reaction. Antibodies are used in the diagnosis of some slightly differentiated tumors (which contain antigen)
• The tumor considered as an antigen is treated with specific antibodies, and the appearance of a positive Ag-Ac reaction confirms the diagnosis of that tumor.
• Example: an undifferentiated tumor treated with anticytokeratin if it produces a positive reaction it means that it is an epithelial malignant tumor (there is a positive reaction between the anticytokearatin, which is the antibody, and the cytokeratin from the epithelial tumors, which is the antigene)
 Umoral markers
 have relied on detecting some substances secreted by the tumors in the blood. These substances can hel diagnose the tumor and monitor its evolution.
 Example:
• the alpha1-fetoprotein is an enzyme that is found in small quantities in normal blood, but it increases in certain tumors (liver, colon, testicle). It also increases in non-tumoral diseases (haemorrhagic rectocolitis), which makes this marker have a relative specificity in diagnosing. But it is successfully used in monitoring the treatment, so that a patient diagnosed with a malignant tumor because the level of this enzyme has risen is put under observation in time:
– if the level of the enzyme decreases after the operation, the prognosis is good
– if the level of the enzyme increases in time, this denotes remissions or metastases


34. Macroscopic and microscopic features of the tumors

 The shape of the tumors
 Nodular
• in the thickness of the organs : round, oval, lobated
• on the surfaces : curved or umbilical aspect
 Vegetating (exophytic) pre-eminence on the surface
• sessile : round, pre-eminence with a large base
• vegetating : pre-eminence with a large base and a villous surphace (papilloma)
• pediculated : pre-eminence with a narrow stem (polyp)
• cauliflower-shaped : large pre-eminece with irregular aspect
 Ulcerative : lack of substance on the surface (due to the partial necrosis of the tumor)
 Infiltrative (skirrhous) the tumor penetrates diffusely into the organ thickening it
 Cystic or cystic-papilliform (the cyst has a structure with its own wall and its content is liquid)
 The color of tumors
 benign tumors look like the tissues of origin :
• myoma : red
• lipoma : yellow
• osteoma : white
 Malignant tumors usually have the following colors :
• carcinoma : white-greyish
• sarcoma: rosy
• melanoma: brown-blackish
 The consistancy of the tumors
 Benign tumors have the consistency of the tissue of origin : lipoma : soft, osteoma : tough, etc
 Malignant tumors : have specific consistency : carcinoma : firm, sarcoma : fleshy
 The size of the tumors varies from a few millimeters (hypophysis tumor) up to a few cm (ovary tumors, lipoma etc)
 The number of tumors
 usually unique
 they can also be multiple : polyposis, papillomatosis

 The parenchyma
 is the cellular component of the tumor according to which the degree of differentiation is studied (degree of resemblance of tumoral cells with the cells of source tissue):
• Benign tumoral cells are well diferentiated, i.e. they resemble the source tissue
• Malignant tumoral cells can present variable degrees of ressemblance with the source tissue, so tumors can be weakly differentiated (they resemble little the source tissue) up to undifferentiated tissues (they do not ressemble the source cells – the anaplastic tumors).
 Malignant tumors the more anaplatsic they are, the more atypical they are. These celular atypicalities are :
• cellular pleomorphism : variations in shape, size and color of the tumoral cells
• nuclear modifications :
– large nuclei
– the N\C proportion in favor of N
– intensely colored nuclei (hypercromatic)
– large nucleoli
– numeorus mitoses often atypical
 Malignant tumors have a normal hystological arhitecture, cells are in groups of diffused in the tumor.

 The stroma is the interstitial component of the tumor, it is the tumoral cells support and it is represented by :
 The conjunctive tissue (when the tumor contains more conjunctive tissue, it is called desmoplastic)
 blood-vessels which feed the tumor but can be responsible for the secondary modifications in the tumor such as necrosis (ischemic blood-vessels) or haemorrhage (blood-vessels imperfectly structured)
 Tumoral blood-vessels (tumoral angiogenesis) appear through the burgeoning of the neocapillary blood-vessels from the pre-existing blood-vessels ; it begins from the periphery of the tumor and the higher its density is, the more reduced the survival rate of the patient is.

 The stroma-parenchyma relation is different in different tumors, but usually:
 in the malignant epithelial tumors, malignant cells are arranged in isles and between the isles there is stroma
 in the mezenchymal tumors, tumoral cells are dispersed, the stroma surrounds every separate cell


35. Classification and the most important morphological features of the benign epithelial tumors

 Benign epithelial tumors :
 papilloma
 polyp
 adenoma

 Definition:
 the papilloma is the benign tumor of the squamous epithelium and urothelia
 Localisation:
 squamous epithelium
• skin
• mucous membranes
• oral cavity, esophagus, anal region
• nasal region, larynx
• vagina, exocol, the foreskin of the penis
 Macroscopical features :
 vegetating shape with digitiform ramifications with a large base for implantation
 white-greyish color
 mobile in the subjacente areas
 Microscopical features :
 conjunctive-vascular axes (stroma)
 the squamous epithelium or urothelia arranged along the conjunctive-vascular axes
 Evolution:
 benign
 malignant transformation
 Definition:
 the polyp is a visible macroscopical proliferation which starts from the one-layer mucous membranes.
 (polyp = macroscopic term which defines a lesion with is projected into a lumen)
 Localization:
 at the level of the one-layer cylindrical epithelia
 Number:
 unique and multiple (polyposis)

 Macroscopically features:
 sessile : soft round nodules which are visible on the surface of the mucous membrane
 pedunculated: soft nodules connected to the mucous membrane through a narrow stem

 Microscopical aspect:
 benign tissular structures covered with a one-layer epithelium

 Types of polyps :
 adenomatous
 hyperplastic
 fibroepithelial
 inflammatory
 hamartomatous
 lymphoid
 mesenchymal

 Evolution:
 benign
 malignant transformation



 Definition:
 adenoma is a benign tumor of the glandular epithelias
 Localisation:
 in parenchymatous organs:
• endocrine glands: thyroid gland, parathyroid gland, hypophysis, suprarenal gland, endocrine pancreas.
• exocrine glands: salivary glands, exocrin pancreas, peribronsic glands
• organs: liver, kidneys, mammary gland
 On the mucous membranes :
• digestive tub
• uterine mucous membrane (endometrium)

 Macroscopically aspects:
 In organs:
• shape: nodular, cystic, cystic- papilifera
• number: unique or multiple
• size: variable from a few mm (hypophisis) to a few cm (liver, kidneys)
 On the mucous membrane:
• the shape of the polyp (adenomatous polyp) with a pedicle covered by a normal mucosa.
• sessile-like shape: without a pedicle, with a large base, villous aspect
• plain shape: the plate slightly elevated with a central lower area

 Microscopically aspects:
 In the organs:
• acinar, trabecular, follicular, solid, cystic, cystic- papilifer, mixed (fibroadenoma)
 On the surface:
• tubular adenomas (the pediculate ones) with a gland like aspect without a high risk of malignancy
• villous adenomas (the sessile ones) with papillary excrescences covered with epithelia
• tubulo-villous adenoma (the risk of malignancy increases proportionately with the villous component of the tumor).

 The malignant transformation:
 the epithelium has a dysplastic aspect: the cells with large nuclei, hyperchromia, low secretion of mucus, atypical cellular, mitosis.
 dysplasia is evaluated according to two grades:
• low degree dysplasia and
• high degree dysplasia.


36. Classification and the most important morphological features of the malignant epithelial tumors

 Malignant epithelial tumors: carcinoma
 pavement carcinoma
• spino-cellular (epidermoid)
• baso-cellular
 Adeno-carcinoma
 Undifferentiated carcinoma

 Definition:
 carcinomas (cc) are malignant tumors of the pavement, transitional and glandular epithelia.
 Age
 It frequently appears at people over 50 years
 It can also appear at children: hepato-carcinoma, rhino-pharyngeal cc., thyroid cc.
 Sex :
 Especially in men: pancreas cc., pulmonary cc., laryngeal cc.
 Especially in women: mammary cc., gall bladder cc.
Macroscopically aspects:
 Color:
 white-grayish
 exceptions: hepato-carcinoma (green), cc of the renal cells (yellow) choriocarcinoma (red).
 Consistancy:
 firm
 exceptions: mucinous carcinoma of the stomach
 Shape:
 on the surface: exophytic (vegetative), ulcerative, infiltrative (schirrous)
 in the organs: nodular
 Number:
 unique, rarely multiple
 Dimenions:
 variable

Microscopically aspects:
 Tumoral cells:
 arranged in isles or chains (trabecular)
 with atypical sizes, shapes, colors
 typical and atypical mitosis
 Stroma:
 connective-vascular tissues
 Secondary modifications:
 haemorrhages, necroses, Ca deposits

 Gradation:
 G1: well differentiated
 G2: moderately differentiated
 G3: low differentiated
 G4: undifferentiated
 Extension
 local: tissular invasion along the cleavage levels
 at distance: special metastases through lymphatic way, but possible also through the blood, transcelomical (mammary cc. in the pleura, ovarian cc. in the peritoneum, gastric cc. in the ovaries).


37. General features of the mesenchymal benign and malignant tumors

 1. Age:
 - Benign (B): variable (some congenital: hemangioma)
 - Malignant (M): in children (ex: rhabdomyosarcoma) in adolescents (ex. synovial sarcoma) in people over 40 years old (ex. liposarcoma)
 2. Rhythm of growth:
 - B: slow, they can stop growing or can rapidly grow
 - M; grow rapidly ( with rare exceptions)

 3. Localization
 - B: anywhere in the mesenchymal tissue, they are situated near the surface, above the superficial fascia (1% profound or in the muscle)
 - M: especially in the extremities (50-85%), torso (20%), retroperitoneal (15%), head-neck (5-10%) ; the majority are situated deep, under the superficial fascia
 4. Size
 - B: under 5 cm (95% among them)
 - M: over 5 cm (50-90% among them)
 5. Delimitation
 - B: well delimitated, encapsulated (exceptions : fibromatosis)
 - M: infiltrative (some with pseudoincapsulated aspect)

 6. Shape
 - B: nodular
 - M: nodular
 7. Color:
 - B: the same as the source tissue
 - M: pink ( as fish meat)
 8. Secondary modifications
 - B: usually absent, rarely necrosis and haemorrhages when the tumor grows fast (ex. leiomyoma)
 - M: frequent necroses, haemorrhages, areas of cystic degenaration, especially in the large tumors

 9. Microscopical features
 B: like the source tissue
 M: tumoral cells with some malignancy, very soft stroma, it surrounds every cells separately, the nutrition of the tumor is through vascular slits coated with tumoral cells



 1. Definition:
 sarcomas are malignant tumors of mesenchymal tissues
 2. Incidence:
 rare, 1% of all malignant tumors
 3. Etiology:
 - ionizing radiations: fibrosarcoma
 - vynil chloride: hepatic angiosarcoma
 - the herpes virus: Kaposi’s sarcoma at AIDS patients
 - chronic lymphoedema
 - hereditary predisposition: von Reklinghausen neurofibromatosis

 4. Macroscopic features:
 pinkish, or with the characteristics of various sarcomas
 5. Microscopic feature:
 the cells can be: fusiform, round, gigantic multinuclear, polymorph, strange
 the cells can be: differentiated (lyposarcoma, fibrosarcoma, etc) or undifferentiated (round-cellular, fuso-cellular, pleomorphic)
 the structure of the cells can be: fasciculate,
 palisadate, storiform, or alveolar.
 the stroma is absent or very soft, arranged around each cell
 the nutrition of the tumor is done through vascular lacunas: vascular slits coated with tumoral cells
 it can have secondary modifications: haemorrhages, necroses, pseudocystic degenerations

 6. The diagnosis of sarcomas
 - OM
 - EM
 - immunohistochemistry: vimentin + in mesenchymal cells, CD31 (for endothelial cells), desmin and actin (for muscular tissues)
 7. Sarcomas are graded according to:
 - cellular pleomorphism
 - mytotic activity
 - the areas of necrosis in the tumor
 8. The expansion of the tumor through infiltration along:
 - the fascial planes
 - nervous trunks
 - tendinous coats

 9. The metastasis occurs through:
 - the blood
 - lymph vessels (rare)
 10. Evolution
 - it remits after local excision
 - metastasis occurs at a distance, especially in the lungs, liver and bones


38. Mesenchymal tumors: examples of tumors from different tissues ( fibrous, muscular, vascular, adipose, cartilaginous, osseous)

 I. The fibroma:
 - benign tumor of the fibrous tissue
 - Macroscopic : 2-3 cm nodules, white-greyish
 - Microscopic : fibroblasts and mature, myofibroblasts, collagen fibres

 II. The Fibrosarcoma
 malignant tumor of the fibrous tissue
 Macroscopic: grayish nodule, lobular, over 10 cm, with necrosis and haemorrhages
 Microscopic: fibroblast fascicles arranged “like a fish-bone” (herringbone)
 The grading is done according to the cells, the mitoses (the high level fibro-myxoid sarcoma)

 Lipoma
 Definition: benign tumor of the adipose tissue
 Macroscopically:
• - well differentiated nodule
• - soft consistency, yellow
• - variable sizes (under 5cm  60cm)
• - often with a thin fibrous capsule at the periphery and fibrous stripes which cross the tumor

 Microscopically:
 it resembles the mature adipose tissue
 Liposarcoma
 Definition: malignant tumor of the adipose tissue
• area
 Macroscopically:
• large nodule, over 5 cm, yellow-greyish, jelly-like (mucinous), ecephaloid or cystic, with necrosis and haemorrhage areas

 Microscopically:
 - the diagnosis cell is the lipoblast which is a large cell, with vacuolate cytoplasm, with a central nuclear (these cells exist in all liposarcoma varieties)

 The tumors of the smooth muscle (with the prefix “leio”)
 Benign tumors:
• Leiomyoma
– most frequent: uterus, gastro-intestinal tract, breast, kidneys.
– macroscopic: single nodule or multiple nodules, well delimitated, variable sizes (mm  tens of cm), firm consistency, when sectioned it looks like a whirlpool (white fibers with red fibers), frequent secondary modifications (haemorrhages, necroses, calcifications)
– microscopic: smooth muscle fascicles, with elongated nuclei and abundant eosinophil cytoplasm.

 Malignant tumors:
 Leiomyosarcoma
• macroscopic:
– large nodule, fleshy, with necrosis, haemorrhages, cystic areas

 Leiomyosarcoma are very rare in the oral cavity.
The tumors of the striate muscular tissue (with the prefix “rhabdo”)
 I. Benign tumors:
 1. Rhabdomyoma

 Malignant tumors:
 Rhabdomyosarcoma

 The blood-vessel tumors

 Benign tumors:
 Hemangioma
• considered as a hamartoma
• it appears in children (rare in adults)
• it can remit
• Macroscopic:
– superficial: skin, subcutaneous area
– deep: liver, brain
– it looks like a spot, a plaque or a nodule
• Microscopic:
– multiplied blood-vessels, normally structured

Variants :
 Capillary hemangioma
• on the skin
• Macroscopic: stains or red-bluish plaques
• Microscopic: numerous capillary vessels, grouped in lobules, separated from the conjunctive stroma.
 Cavernos hemangioma
• on the skin or deep (liver)
• Macroscopic: red-violet, spongious
• Microscopic: distended sanguinary capillary vessels which contain a lot of blood separated in the conjunctive stroma (they resemble the cavernous bodies of the penis)
 Arterio-venous hemangioma
• in the head, throat, limbs
• Macroscopical: red-bluish nodules
• arterial and venous blood-vessels

Tumors with low malignancy level
 Kaposi’s sarcoma

Malignant vascular tumors
 Angiosarcoma
Other vascular tumors :
 Hemangioendothelioma: with limited malignancy (borderline)
 Hemangiopericytoma: with limited malignancy (borderline)
 Glomus tumors
 localization: the groin, palms, plantae, lungs, stomach
 clinically: painful nodule
 microscopic: arterio-venous anastomoses
 variants: glomangioma and glomangiomyoma
 evolution: it heals (after the excision), it remits (10%) or it becomes malignant (very rarely)
Lymphatic vessels tumors
 Lymphangioma
 in the newly born babies, children, the young adult
 malformation or acquired
 mascroscopic:
• spot, plaque or “grapes bunch” (large vesicles, with clear liquid)
 microscopic:
• distended lymphatic vessels, they contain lymph and lymphocytes
 Variants:
• cystic lymphangioma (cystic hygroma) : in the suckling, it is situated on the throat and in the retroperitoneal area
• lymphagiomyoma: hamartoma, with muscular cell proliferation in the walls of the lymphatic blood-vessels

 Neurofibroma
 Schwannoma (neurinoma, neurilemoma)
• benign tumor of the nerves
• in young adults

 Malignant schwannoma (neurofibrosarcoma)
 Osteochondroma
 the most frequent benign bone tumor
 in adolescent men

 Chondroma
 benign cartilaginous tumor
 it appears in youngsters
 single (chondroma) or multiple (chondromatosis)

 Chondrosarcoma
 malignant cartilaginous tumor
 in adults (40-60 years old)
 Osteoma
 benign bone tumor
 single and multiple (the Gardner’s syndrome)

 Osteosarcoma


39. Nevi and malignant melanoma

Benign melanocytic tumors
 Nevi
 The common acquired nevi
• the most frequent melanic tumor in humans
• their number grows with the age
• frequent localization: head, throat, torso, limbs (they can appear everywhere on the body)
• small dimension, under 6 mm
• variable color : from takes the skin color up to black
• ordinary shapes : plaque, papule, polyp

Variants of the common acquired nevi:
 The junctional nevus
 the fist stage of the melanocytic proliferation
 it can be preceded by lentigo (continual melanocytary proliferation in the basal stratum)
 macroscopic: spot or small papule, intensely pigmentated, without hair
 microscopic: melanocytic proliferation as nests of naevus cells, situated at the junction epiderm\derm which pushes the basal membrane
 evolution : towards another type which could become malignant
 The composed nevus
 macroscopic : more elevated and less pigmentated, it can have hair
 microscopic : they develop as the continuation of the junctional nevus, the MB breaks and nests of naevi form on the derma, then the MB recovers and the naevus remains with two components: junctional and dermal
 evolution : it can become malignant (because of it junctional component)

 The dermal nevus
 macroscopic: plaque or polyp (resembling the composed nevus)
 microscopic : the junctional component disappears (it regresses) and only a dermal component remains, which contains a type A (epitheliod) cells, type B (lymphoid) cells, and type C (neuroid) cells
 variant: halo nevus which presents a depigmentated margin
 evolution: it does not become malignant

 The Spitz nevus (fusocellular and epitheliod)
 in children and young adults
 localization: head, throat, upper limbs
 macroscopic: small nodule, reddish (it can be confused with a hemangioma)
 microscopic: fusiform and epitheliod cells which present atypical features (they can be confused with the malignant melanoma) with the richly vascularized stroma, with little pigment
 evolution : it can become malignant at a later time (after 20 years).

 The congenital nevus
 1% of newly born babies
 Macroscopic:
• big lesions (over 20 cm), called gigantic congenital nevus, intensly pigmentated, with thick hair strands, pigmentated, can have satellite lesions, high malignancy risk
• intermediate lesions (1.5 – 20 cm) with lower malignancy risk level
• small lesions (under 1.5 cm) with an imprecise malignancy risk level
 Microscopic:
• composed or dermal type
• naevus cells can infiltrate the derma and the hypoderma deeply, sometimes also infiltrating the sebaceous glands, the erector muscle of the hair, the lymphatic blood-vessels and the nerves
 evolution : some nevi can become malignant even in childhood

 The dysplastic nevus
 it appears de novo or on a pre-existent nevus
 macroscopic : single pigmentary lesion or multiple lesions, larger than the ordinary nevi (over 6mm), with irregular contur, variable distribution of the pigment on the surface of the lesion
 microscopic : cells with atypical features and mitoses
 evolution: high malignancy risk
 dysplastic nevus syndrome : transmitted AD, with tens/hundreds of dysplastic nerves with malignancy risk of one or several dysplastic nevi

Malignant melanocytic tumors
Malignant melanoma
 high occurrence
 de novo or on melanocytic lesions (acquired nevus, congenital nevus, displasic nevus)
 at any age but especially in adults
Signs of malignization of a nevus:
 the asymmetry of the lesion
 irregular and random distribution of the pigment (brown, black, blue, red, depigmentated areas)
 the lesion has irregular margins
 more than 6 mm diameter
 Factors that favor the malignization:
 preexsting melanic lesions
 solar radiations

The classification of the melanoma:
 1.”in situ” melanoma: above the MB, hard to diagnose clinically
 2. The invasive nontumoral melanoma
 - malignant lentigo (lentiginos melanoma)
 - melanoma with superficial extension
 - acral lentiginos melanoma
 3.the invasive tumoral melanoma
 a. The radial or orizontal growing phase (the nontumoral phase)
• - with limited tumoral melanocytes in the epiderma (> melanoma)
• - with tumoral melanocytes in the epiderma and superficial derma (microinvasive melanoma)
• - slow evolution (years)
• - it does not metastasize
 b. The vertical growth phase (the tumoral phase)
• - the melanic cells form tumoral masses which grow in the derma, on the horizontal (expansive)
• - cellular clones with metastasis capacity are selected

The stages of the malignant melanoma:
 1. Clark, according to the invasion of the skins strata :
 I > melanoma
 II in the papilar derma, incomplete
 III it fills the papillar derma until the interference with the reticular derma
 IV in the reticular derma, deep
 V in the hypoderma
 Breslow, according to the lesion thickness in mm :
 -under 0.7 mm with a good prognosis
 - the deeper the lesion, the worse the prognosis
The microscopy of the malignant melanoma
 Immunohistochemistry
 - Ag stains with Ac HMB45
 - S 100 protein

 The evolution of the malignant melanoma
 -vertical and orizontal growth
 - intraepidermic metastasis with the appearance of satellite nodules
 - metastases through the lymphatic way (in the ganglions) the hematogenic way (liver, pancreas)