SKIN PATHOLOGY

EDITED BY

Dr. JUSUF FANTONI

SpPA,MScPath (Glasg)

Epidemiology
 Most common human cancer

 600,000 to 800,000 cases per year in U.S.
 Male:Female 2-3:1  80% arise in head and neck  SCCa over 60 years old  BCCa over 40 years old

Etiology
 Ultraviolet radiation

 ethnicity
 ionizing radiation exposure  chemical exposure - arsenic  burns, scarring  immunosuppression

Syndromes  Xeroderma pigmentosum  nevoid basal cell syndrome  albinism  epidermodysplastic verrucoformis  epidermolysis bullosa dystrophica  dyskeratosis congenital .

Skin  Largest organ  major functions     protection sensation thermoregulation metabolic .

Skin structure  Epidermis  dermis  hypodermis  epidermal appendages .

Skin Histology  Stratum corneum  stratum lucidum  stratum granulosum  stratum spinosum  stratum basale .

periorbital and anogenital skin . axillae and perioral. welldemarcated macules and patches of pigment loss. Clinical lesions are asymptomatic. Vitiligo often involves the hands and wrists. All ages and races are affected. their size varies from few to many cnetimeters. but lesions are most noticeable in darkly pigmented individuals. flat.DISORDERS OF PIGMENTATION and MELANOCYTES VITILIGO Vitiligo is a common disorder characterized by partial or complete loss of pigment producing melanocytes within the epidermis.

it is characterized by loss of melanocytes. vitiligo is indistinguishable from normal skin. . However. (2) neurohumoral factors toxic to melanocytes and released by nearby nerve endings. This is in contrast to some forms of albinism in which melanocytes are present but melanin pigment is not produced because of a lack of or defect in tyrosinase Pathogenesis Theories include: (1) autoimmunity.Morphology On histologic examination . and (3) self-destruction of melanocytes by toxic intermediates of melanin synthesis.

contain inconspicuous nucleoli.Melanocytic Nevus ( Pigmented Nevus. small ( usally < 6 mm across). Nuclei of nevus cells are uniform and rounded in contour. or “nests. Morphology. Melanocytic nevi are initially formed by melanocytes that have been transformed from highly dendritic single cells normally intersperesed among basal keratinocytes to round cells that grow in aggregates. Such lesions are believed to represent an early developmental stage in melanocytic nevi and are called Junctional nevi. . common acquired melanocytic nevi are tan to brown. Mole ) Most of us have at least a few moles. and show little or no mitotic activity. flat (macules) to elevated ( papules ) with well-defined rounded borders. Clinically.” along the dermoepidermal junction. uniformly pigmented.

Progressive growth of nevus cells from the dermoepidermal junction into the underlying dermis is accompanied by a process termed maturation. and grow in nests. more superficial nevus cells are larger. the epidermal nests may be lost entirely to form pure Intradermal nevi. deeper nevus cells are smaller. most junctional nevi grow into the underlying dermis as nests or cords of cells ( Compound nevi ). The most mature nevus cells may be found at the deepest extent of lesions where they often acquire fusiform contours and grow in fascicl. tend to produce melanin. compound and dermal nevi are often more elevated than junctional nevi. produce little or no pigment and grow in cords. . in older lesions.es resembling neural tissue.Eventually. more mature. Less mature. Clinically.

For example. esophagus. . or exposure to certain carcinogens. other sites of origin include the oral and anogenital mucosal surfaces. men commonly develop the tumor on the upper back.ignant melanoma. meninges and notably the eye. Sunlight appears to play an important role in the development of skin ma. Lightly pigmented individuals are at higher risk.Malignant Melanoma is a relatively common neoplasm. mostly arise in the skin. Othe predisposing factors include : the presence of a preexisting nevus (dysplastic nevus). whereas women have a relatively high incidence on both the back and the legs. hereditary factors.

radial growth indicates the tnedency of a melanoma to grow horizontally within the epidermal and superficial dermal layers. The most important clinical sign of the disease is change in color..Clinical Features. The clinical warning signs of melanoma are : (1) enalrgement of a pre-existing mole. During this stage of growth. superficial spreading and acral / mucosal lentiginous. melanoma cells do not have the capacity to metastasize. . zones of white or flesh-colored hypopigmentation are also present. Lentigo maligna. On occasion. (2) itching or pain. Growth Patterns and Morphology Simply stated. (4) irregularity of the borders. (3) development of a new pigmented lesion during adult life. Malignant melanoma of the skin is ususally asymptomatic. (5) variegation of color within a pigmented lesion. size.e. i. The majority of lesions are greater than 10 mm. often for a prolonged time. although itching may be an early manifestation. or shape in a pigmented lesion.

They arise spontaneously and may become numerous on the trunk. also the extremities. . and neck may also be involved. They contain large nuclei with irregular contours and prominent nucleoli. These cells proliferate as poorly formed nests or as individual cells at all levels of the epidermis The nature and extent of the vertical growth phase determine the biologic behaviour of malignant melanoma. Benign Epithelial Tumors Seborrheic Keratosis Occur frequently in middle-aged or older individuals.Individual melanoma cells are usually larger than nevus cells. head.

and show the effects of inflammation. flat. When sborrheic keratoses involve the epithelium of hair follicles. Interestingly. coinlike. Variable melanin pigmentation is present within these basaloid cells.They appear as round. They are composed of sheets of small cells that most resemble basal cells of the normal epidermis. They are uniformly tan to dark brown and show a velvety to granular surface. waxy plaques that vary in diameter from mm to several cms. Morphology Exophytic and demarcated sharply from the adjacent epidermis. such lesions are termed : Inverted follicular keratoses . when seborrheic keratoses become irritated and inflamed. Exuberant keratin production (hyperkeratosis occurs) and small keratin-filled cysts (horn cysts ) and invaginations of keratin into the main tumor mass ( invagination cysts ) are characteristic features. they may grow in an endophytic ( downward) fashion. they undergo squamous differentiation and characterized by foci of “ whorling “ squamous cells resembling eddy currents in a stream.

Ususally less than 1 cm. a series of progressively dysplastic changes occur. sandpaper-like consistency. rough. dorsum of hands ) are usually affected. they are calleg actinic keratoses.Premlignant and Malignant Epidermal Tumors ACTINIC KERATOSIS Before the development of overt malignancy of the epidermis. Other causes : exposure to ionizing radiation. or skincolored. Because this dysplasia is usualy the result of chronic exposure to sunlight and with build-up excess keratin . Some produce so much keratin that a “ cutaneous horn “ develop ( resemble the horn of animals ). arms. . tan-brown. red. hydrocarbons and arsenicals. Skin sites commonly exposed to sun ( face.

Morphology Cytologic atypia is seen in the lower-most layers of the epidermis and may be associated with hyperplasia of basal cells. blue-gray elastic fibers ( elastosis) a probable result of abnormal dermal elastic fiber synthesis by sun damaged fibroblasts within the superficial dermis. Thwe atypical basal cells usually have evidence of dyskeratosis with pink or reddish cytoplasm. with early atrophy of the epidermis. . Squamous Cell Carcinoma ( S C C ) = the second most common tumor arisin on sun-exposed aites in older people. ( in contrast to basal cell carcinoma ). Intercellular bridges are present. and unlike in normal skin. The dermis contains thickened. nuclei in the cells in this layer are often retained ( = parakeratosis ). or alternatively. The stratum corneum is thickened.

Except for lesions on the lower legs. ionizing radiation . When these cells break through the basement membrane. S C C is characterized by cells with atypical ( enlarged and hyperchromatic ) nuclei ast all levels of the epidermis. these tumors have a higher incidence in men. When the oral mucosa is involved. ingestion of arsenicals. They are rangin from well-differentiated to poorlydiffenrentiated . old burn scars. chronic ulcers and draining osteomyelitis.and (in the oral cavity) tobacco and betel nut chewing. the process has become invasive. Other factors : industrial carcinogens ( tars and oils ). a zone of white thickening may be seen ( caused by a variety of disorders ) referred to clinically as leukoplakia. Morphology S C Cs that have not invaded through the basement membrane is termed in situ carcinoma.

dilated subepidermal blood vessels ( telangiectasias ). Some contain melanin. Advanced lesions may ulcerate. extensive local invasion of bone or facial sinuses may occur after many years of neglect (=rodent ulcers ) .Basal Cell Carcinoma ( B C C ) = slow-growing tumors that rarely metastasize. Tendency to occur at sites of chronic sun exposure and in lightly pigmented people. B C C rises sharply with immunsuppresion and in patients with inherited defects in DNA repair. Clinically. as pearly papules often containing prominent.

trichoepithelioma )/. and often surrounded by many fibroblasts and lymphocytes. embedded in a mucinous matrix. They arise from the epidermis or follicular epithelium and do not occur on mucosal surfaces.Morphology Tumor cells resemble those in the normal basal cell layer of the epidermis. creating clefts or separation artifacts that assist in differentiating basal cell carcinomas from certain appendage tumors also characterized by proliferation of basaloid cells ( e. .g. Two patterns are seen : multifocal growths originating from the epidermis and extending over several square cms or more fo skin surface and nodular lesions growing downward deeply into the dermis as cords and islands of variably basophilic cells with hyperchromatic nuclei. The cells forming the periphery of the tumor cell islands tend to be arranged in approximately parallel alignment ( palisading ) The stroma shrinks away from the epithelial tumor nests.

5-FU.Actinic Keratosis  Most common  progress to malignancy in 5-20%  cryotherapy. TCA . shave excision.

Actinic Keratosis .

Keratoacanthoma  Solitary or multiple  rapid growth  1 to 2. Mohs' .5 cm  ulcer with keratinous material  spontaneous resolution  observe. 5-FU.

Keratoacanthoma .

Bowen’s Disease  Carcinoma in situ  erythematous plaque  irregular borders  non-exposed areas with arsenic exposure .

Bowen’s Disease .

with pearly border  prominent vasculature  ulceration  nodular most common .Basal Cell Carcinoma  Raised.

Pigmented Basal Cell  Produce brown pigment  often mistaken for melanoma  behave similar to nodular .

Superficial Basal Cell  Scaly patches  irregular borders  extremities. less common in head and neck .

Mohs’ surgery .Morpheaform Basal Cell  Indistinct margins  flat macule  scar-like  aggressive behavior  difficult to treat .

Morpheaform Basal Cell .

Basal Cell Carcinoma  Cells resemble those of stratum basale  connective tissue stroma  peripheral palisading  stromal retraction .

Keratotic Basal Cell  Differentiation toward hair structures  undifferentiated cells .

Cystic Basal Cell  Differentiation towards sebaceous glands  cystic spaces within tumor .

Adenoid Basal Cell  Pseudo-glandular formation  strands of epithelial cells in lace-like patterns .

Basal Cell Biologic Behavior  Dependent upon stroma  locally invasive  spread along resistant planes  metastasis rare .0028% to 0.1%  adenoid and keratotic types more likely .0.

Basal Cell Biologic Behavior  Embryonic fusion planes at risk for deep invasion       inner canthus philtrum chin nasolabial groove pre-auricular retro-auricular sulcus .

crusting  friable  adjacent induration  actinic vs. de novo . ulcerated.Squamous Cell Carcinoma  Sun exposure  erythematous.

Squamous Cell Metastasis
 Actinic lesions 3% to  

 

5% de novo 8% scar or chronic inflammation 10% to 30% deep invasion higher grade perineural invasion

Squamous Cell Histopathology
 Well, moderate and poorly differentiated

 generic
 adenoid  bowenoid  verrucous  spindle cell or pleomorphic

Squamous Cell Histopathology

Adenoid Squamous Cell  Pseudoglandular arrangement  dyskeratosis  acantholysis  periauricular .

acanthosis  invasion with pushing margins .Verrucous Squamous Cell  Rare on skin  cauliflower-like  well-differentiated  marked hyperkeratosis. parakeratosis.

Spindle Cell Squamous Carcinoma  Least common  poorly differentiated  anaplastic cells  absent keratinization  pleomorphic giant cells .

Staging .

Treatment .ED&C  Most useful with BCCa <2 cm  92% to 98% cure  advantages  quick and easy open wound scarring  disadvantages   .

well-circumscribed lesions  -30° F to -50° F  advantages   quick in-office prolonged healing with potential for scarring no margins  disadvantages   .Cryotherapy  Small.Treatment .

Treatment .Excision  Most often used by head & neck surgeons  93% to 95% cure  advantages   specimen for evaluation control of margins (3 to 5 mm) expensive time-consuming  disadvantages   .

Laser  Patients with medical diseases  multiple lesions  palliation .Treatment .

Treatment .Mohs’ Surgery  96% to 99% cure .

Treatment .Radiation  Prolonged course  radiodermatitis  carcinogenesis  useful in poor surgical patients  no control of margins  recurrence in 4.5% .4% to 9.

Treatment .Photodynamic Therapy  Photosensitive drug concentrated in tumor  porphyrin. argon ion dye pump laser most common  still experimental .

  low dose. intralesional  3 times a week  flu-like illness  erythema. pain  stimulation of macrophages and NK cells .Treatment .Interferon  Interferon .

most widely used  bleomycin  cyclophosphamide  5-fluorouracil  vinblastine .Chemotherapy  Retinoids  cis-platin .Treatment .

Regional Lymphatics  Deep invasion into muscle. bone. nerve  tumors >2 cm  recurrent tumors  tumors arising de novo or in scarred areas .Treatment .

Regional Lymphatics  Parotidectomy for periauricular tumors  spare uninvolved structures  post op XRT as indicated .Treatment .

Selection .Treatment .

Recurrence  BCCa 1-39%  Nodular 1-6%  Morpheaform 12-30%  3 years  SCCa variable recurrence rates   75% of recurrences occur within 2 years 95% of recurrences occur within 5 years .

nerve regional lymphatic involvement 47% recur 35% metastasize  perineural invasion   . muscle.Recurrence  70% recurrence risk for:    Size greater than 2 cm invasion of bone. cartilage.

000 deaths per year in U.  patients 65-70 years old  widespread SCCa arising in periauricular region .S.Mortality  Exact numbers not available .000 persons per year  2.not consistently reported  0.000 to 3.44 per 100.

Conclusion  Common tumors  best chance for cure is early diagnosis and treatment  prevent new lesions with sun protection .