Medicine 4 M di i

Pigmented Lesions of the Skin.

HSk13a This drawing shows the main cells that constitute the epidermis. Keratinocytes originate from the mitosis of basal cells and migrate progressively upwards, until they become keratinized and are shed. Langerhans cells are antigenantigenpresenting cells that have great importance in the immunological reactions that occur on the skin. Merkel cells are mechanoreceptors, that transmit neural impulses every time the skin is stretched. Melanocytes produce melanosomes, organelles that contain pigment that contributes to the colour ofour skin. i t th t t ib t t th l f ki

GSk13b Melanocytes are dendritic cells, that is, they have branches, like a tree. Melanosomes are produced and migrate to the tip of the cell p g p branches. Keratinocytes phagocytose this tip- membrane, cytoplasm tipand melanosomes together, and so acquire pigment. Keratinocytes are unable to make melanin themselves. Because melanosomes are inside phagosomes, the pigment is soon lysed by the keratinocyte lysosomes, so that the cells of the upper parts of the epidermis, in Caucasians, show little melanin.

SC: stratum corneum, made of dead, keratinized cells; SL: stratum lucidum, seen on palms and soles; SG: stratum granulosum, the cells show dense, dark granules in the cytoplasm granulosum dense containing filaggrin, that aggregates the filaments of keratin to form the tough cells filaggrin, of the horny layer; ML: Malpighian layer, also called spinous layer, because the layer layer polygonal cells are separated by "spinous" processes, which are, in fact, desmosomes; L: Langerhans cell; M: melanocyte; BK: basal keratinocyte.

 Histopathological

lesions:

Terms in pigmented

Junctional

naevus. Compound Naevus. Naevus Intradermal Naevus. Melanoma in situ. Superficial Spreading Melanoma. Melanoma Nodular Melanoma. Radial and Vertical Growth.

 ABCDE A B C D E

Checklist for Pigmented lesions Asymmetry Border Irregularity Colour Variation Diameter (> 6-7 mm) 6Ele ation o Nod la it levation or Nodularity Itching and bleeding are lesser g g

signs.

GSK13 A pigmented, elevated lesion, of uniform colour and wellwell-defined borders corresponds to a compound naevus naevus.

HSk02 Benign melanocytes are seen in the junction between epidermis and dermis, as well as deep in the dermis. This image corresponds to GSk 13, and is a compound naevus. Because naevus cells tend to migrate into the dermis, how can we tell the difference between benign melanocytes in this naevus, and malignant melanocytes of melanoma, which also tend to infiltrate the dermis?

Intra dermal Naevus. Naevus cells have finished migrating and they occupy the dermal layer.

GSk15

This preauricular naevus is elevated and fleshfleshcoloured. It corresponds to an intradermal naevus.

HSk19 The benign g melanocytes in this intradermal naevus are all in the dermis- there dermisare no nests of naevus cells at the epidermalepidermal-dermal junction. This image corresponds to clinical picture GSk 15. There is scanty pigment.

GSk17 A flat pigmented lesion, of homogeneous colour corresponds to a junctional naevus.

HSk18 Benign melanocytes, or naevus cells, form nests located in the junction between epidermis and dermis. Thi i d i This image corresponds to clinical picture d li i l i GSk 17, and is a junctional naevus.

A large lesion>1cm, l i 1 assymetrical y showing an irregular border raised and flat areas variable colour

malignant li t melanoma:

 Assymetry Border

Irregularity g y Colour Variation Diameter > 2 0 2.0 cm Elevation Bleeding had been noted d

HSK01 This is malignant melanoma The cytological features of malignancy are seen ( g y (cellular pleomorphism,; numerous mitoses). Note : Radial and Vertical growth Depth ( Breslow) i mm How do we measure that? h l ) in d h Heavy pigmentation. Attenuation of the epidermis above the nodule. nodule Lymphocytic reaction beneath the melanoma.

To T repeat : t Nests of malignant li t melanoma cells in the ll i th epidermis radial growth di l th phase

And Invasive malignant melanoma vertical i l growth phase Breslow measureme nt to the deepest melanoma l cell.

GL32 Thi patient was in This ti t i coma and developed bronchopneumonia, because of the difficult to expectorate mucus t t containing bacteria. The lung is congested, and shows multifocal yellow areas of pus-fill d alveoli f pus-filled l li surrounding bronchioles.

 ABCDE A B C D E

Checklist for Pigmented lesions Asymmetry Border Irregularity Colour Variation Diameter (> 6-7 mm) 6El levation or Nodularity ti N d l it Itching and bleeding are lesser g g

signs.

GSk12. GSk12. This is a superficial spreading melanoma. Note that the l N t th t th lesion is flat, with irregular, blurred borders and has a diameter of about 2cm Note that there is an area of depigmentation on the right edge of the lesion with fibrosis in the dermis. dermis This is interpreted as being an area of tumour regression and may represent an immunological response by the host to the tumour ( (a dense lymphocytic y p y infiltration may sometimes be seen on histological examination of some skin tumours, including melanoma).

GSk11 This is a nodular melanoma. Whereas superficial spreading melanomas stay restricted within the epidermis for many months, and only later invades the dermis and becomes elevated, the nodular melanoma is elevated from the start. This start form of melanoma is frequently misdiagnosed, so that the tumour has the time to penetrate the dermis deeply and give early metastases.

GSk 16 This is an atypical mole, or dysplastic naevus. It is atypical, atypical because: a) It is larger, b) shows nuclear atypia and larger c) some of the atypical naevi may turn into melanomas, whereas this change is very rarely seen in common naevi. Many dysplastic naevi have this fried-egg appearance: an elevated friedcentre, which is symmetric and of uniform colour, surrounded by a pigmented rim, which has well-defined borders and welluniform colour. The symmetry, well-d fi d b d if l h well-defined borders exclude ll l d melanoma.

 How

does melanoma spread? First to regional nodes and the corresponding area should be checked in di h ld b h k d i any suspicious pigmented lesion. y p pg Then haematogenously virtually anywhere but b t commonly liver lungs and brain. l liver, brain

GB12 This coronal section of the brain shows numerous black metastases of melanoma, that vary in diameter from a couple of millimetres to more than one centimetre. Because the brain has no lymphatics, all metastases to this organ have to arrive haematogenously.

malignant melanomalarge irregular nuclei,promi nuclei promi nent red nucleoli and l li d pigment

metastatic t t ti

The

Clark Method of measurement of Melanoma

Level

I: I: Melanomas confined to the outermost layer of the skin, the epidermis. Also epidermis. called "melanoma in-situ." in Level II: II: Penetration by melanomas into a o a o a o the second layer of the skin, the dermis. dermis. Levels III-IV: Melanomas invade deeper III-IV: through the dermis, but are still contained completely within the skin. skin Level V: Penetration of melanoma into the fat of the skin beneath the dermis, penetration dermis into the third layer of the skin, the subcutis.

The Breslow System of Measurement

Named

for the physician Alexander Breslow who in 1975 observed that as the thickness of the tumor increases, the chance of survival goes down. For example, a down example thickness of the melanoma of less than 0.76 illi t i 0 76 millimeters is associated with a 5-year i t d ith 5 survival of 97% of patients whereas a tumour thickness of more than 8.0 millimeters is associated with 5 year survival 5-year of 32%.