dermatology - rongioletti

• There are 2/3 millions of non melanoma skin cancers and 100,000 melanomas every year
• Incidence of skin tumors is increasing

Keratinocyte Cancers

• Used to be called "non-melanoma skin cancers"
• Tumors are made by keratinocytes
• The most frequent tumors, ranking 1st in men and 2nd in women after breast cancer
• Over 100 patients out of 100,000 men and 90 out of 100,000 women get keratinocyte cancer
• Basal cell carcinoma and squamous cell carcinoma account for 8 out of 10 keratinocyte carcinomas

Predisposing Factors for Skin Tumors

• Exogenous and endogenous factors contribute to the development of skin tumors
• Exogenous factors include UV radiations (both natural and artificial), chemical oncogenes (smoke), and oncogenic viruses (HPV)
• Pre-cancerous lesions can progress to real skin carcinomas
• Endogenous factors mainly involve genetics
• Genetic mutations are often the initiating step for normal cells turning atypical
• Oncogenes favor tumor development and can be activated by exogenous factors (epigenetic)
• Genes that normally are active in preventing tumors can be stopped, allowing tumor development

UV Radiation and Skin Tumors

• UV radiation is the main exogenous factor in keratinocyte carcinoma development
• Chronic exposure include exposure of sailors or farmers
• Brief but intense exposure plays a significant role in melanoma

Genetic Factors in Skin Tumors

• People of Anglo-Saxon origin (blue eyes, red hair, pale white skin) are more likely to develop skin cancer than Mediterranean people
• Genetic diseases like scleroderma pigmentosum (DNA repair enzymatic defect) increase skin cancer risk at a young age

Actinic Keratosis (Solar Keratosis)

• Pre-cancerous lesion
• Can be the first sign of intraepidermal clonal expansion
• Atypical cells are confined to the epidermis, the superficial layer
• Common in elderly, especially with light Anglo-Saxon phototype
• Characterized by circumscribed, erythematous, sometimes brownish, maculo-papular lesions
• Located on sun-exposed areas like the face and scalp (in bald people)
• Can be detected by sensation of roughness when touched
• Backs of hands are often affected due to sun exposure
• Lesions are erythrematous and sometimes thick keratotic
• Actinic keratosis is not skin cancer unless it penetrates the epidermis to the dermis or subcutis
• Progression of actinic keratosis to skin cancer varies; estimates range from 5-10% to as high as 20%

Classification of Actinic Keratosis

• Clinical classification helps assess danger
• Grade one: barely visible actinic keratosis
• Detected by roughness without visible evidence until the lesion is visible, palpable, thick

Keratinocyte Cancers

• Include: Basal cell carcinoma and squamous cell carcinoma

Squamous Cell Carcinoma (SCC)

• Arises from epidermal keratinocytes with variable keratinization, indicating differentiation
• Well-differentiated SCC allows for recognition of keratinocyte morphology
• Undifferentiated SCC makes keratinocyte identification difficult and is the most malignant type
• Squamous cell carcinoma can metastasize, which is different from basal cell carcinoma
• Incidence is high, affecting approximately 2 million people worldwide, is more prevalent in men than women
• Can be classified as either: Actinic keratosis or Bowen's disease

Bowen's Disease

• Superficial type of squamous cell carcinoma
• Atypical cells are confined to the epidermis
• Atypical cells are confined only to the basal layers of the epidermis in actinic keratosis
• In Bowen's disease, atypical cells involve the entire thickness of the epidermis
• Bowen’s disease is a real carcinoma due to the proliferation involving all layers of the epidermis
• Actinic keratosis only involves the basal layers
• Bowen's disease is more severe, being a carcinoma in situ that doesn't penetrate the basal lamina

Clinical Presentation of Bowen's Disease

• Resembles actinic keratosis, but presents as a larger erythematous scale patch with sharp, irregular borders
• Bowen's disease typically presents as a solitary lesion, unlike actinic keratosis which are often multiple lesions
• Can mimic inflammatory conditions like psoriasis or eczema, which can be misdiagnosed as eczema, dermatitis, or psoraisis
• Evolves chronically and slowly
• Trunk, back, and chest are the most frequent location, faces are the most common locations to actinic keratosis
• Lesions are usually single and solitary but can be multiple, develops into invasive squamous cell carcinoma if left untreated

Actinic Keratosis and Bowen's Disease

• Actinic keratosis is more frequent on sun-exposed areas, and Bowen’s disease is more rare
• Actinic keratosis is a pre-cancerous lesion and can remain stable
• Actinic keratosis is usually located on the face, Bowen’s disease is more frequent on the trunk

Erythroplasia of Queyrat

• A type of Bowen's disease that affects the male genitalia
• Presents differently clinically but is carcinoma in situ histologically
• Clinical presentation is an erythematous shiny area on the gland, like an inflammatory skin disorder, they need to be taking into the biopsy

Squamous Cell Carcinoma Incidence

• Squamous cell carcinoma is the second most common skin cancer after basal cell carcinoma
• 8/10 skin cancers are basal cell carcinoma and 2/10 are squamous cell carcinoma
• Men are more often affected compared to women
• There has been a 200% increase in squamous cell carcinoma cases in the past 30 years, largely due to sun exposure
• In Italy, the anual annual incidence is 18 for males and 13 for females out of 100,000 individuals
• Australia (Queensland) has an incidence rate of 1000/100,000 inhabitants, due to people of Anglo-Saxon origin and sun exposure

Clinical Presentation of Invasive SCC

• Presents as a crusted or keratotic lesion, similar to actinic keratosis
• Usually thicker than actinic keratosis
• SCC arising from actinic keratosis is less aggressive than SCC originating independently

Signs of Actinic Keratosis Developing into SCC:

• Rapid lesion extension
• Erosion or bleeding
• Deep infiltration and inflammation

Presentation of SCC

• Thick deep nodule and a nodular keratotic squamous cell carcinoma
• The mucosa can also be involved
• Nodule with a keratotic crusted surface
• Cutaneous horn, mountain of the skin with underlying SCC

Diagnosis of SCC

• Histopathology is the gold standard for diagnosis
• Clinical suspicion is the gold standard for diagnosis
• May present as a growing verrucous plaque, or a vegetative growing lesion

Origin of SCC

• Can arise from actinic keratosis or independently
• Non-healing ulcer (mainly on male scalp) may be SCC
• Scalp lesion that does not heal despite patient history of trauma may actually be squamous cell carcinoma
• Special sites for SCC: lip, tongue, genital, and periungual area

Squamous Cell Carcinoma in Special Sites

• Lip: important site, primarily lower lip, frequently in male smokers, associated with worse prognosis than SCC on skin
• Tongue: squamous cell carcinoma on oral mucosa is aggressive with high metastasis risk due to vascularity
• Genital area has HPV involvement
• Fingers are rarely involved around the nail.

SCC from Chronic Inflammation

• May arise from chronic inflammatory scars (vascular ulcers, burns)
• Aggressive and metastatic early
• Called Marjolin’s ulcer
• First diagnosed clinically, but then the gold standard diagnosis is histopathological examination

Dermoscopy in SCC Diagnosis

• Dermoscopy helps examine with dermatoscope (microscope improving visualization of skin lesions)
• Squamous cell carcinoma may present with whitish areas and ulcerated lesions that are not always seen by the naked eye
• Is useful for differential diagnosis, but histopathology is the gold standard
• Can diagnose well-differentiated or poorly differentiated SCC, where poorly differentiated SCC has a worse prognosis

Risk Factors for Relapse and Metastasis of SCC

• Location (lips, genital area)
• Arising from chronic inflammation (burns/scars)
• Lesion size larger than 2 cm
• Differentiation that is defined by histopathological examination
• The "H pattern" on face indicates areas prone to metastasis/relapse sites

SCC and Organ Transplant

• Patients are cancer prone (usually, squamous cell carcinoma)

Aggressiveness of SCC

• SCC is considered potentially aggressive with possible metastasis
• Low mortality rate with early diagnosis as prevention focuses on photoprotection and treating lesions like actinic keratosis and scalp inflammation
• Prevention with drugs like beta-carotene and aspirin has been unsuccessful
• Photoprotection is still the most important factor in prevention
• Treatment is surgical excision

Basal Cell Carcinoma (BCC)

• Less aggressive compared to squamous cell carcinoma
• Cannot metastasize
• Metastatic events of basal cell carcinoma are very very rare
• Proliferating cells are blue and originate from those of the basal layer of the epidermis, while those of squamous cell carcinoma are similar to the keratinocytes of the spinous layer
• The most common malignant skin neoplasm globally
• Australia is incredibly high with 1000/2000 new cases out of 100,000 inhabitants per year
• Typically develops at ages 50-60, but also occurs in young adults aged 30

Sun Exposure and Basal Cell Carcinoma

• Risk factor is acute intermittent UV exposure, not chronic continuous exposure
• Exposure during holidays/occasional beach trips increases risk
• Acute intermittent exposure is the same for melanoms

Clinical Presentation of BCC

• Most common presentation is nodular, but it can also be a plaque
• Key diagnostic clue is the border, described as risen, pearly, shiny, irregular edge that is never seen in squamous cell carcinoma
• Diagnosed easily if this border is present
• Can be pigmented, acting as a mimicker of melanoma
• Must still see with an attentive look for the pearly risen borders of the lesion even if it is pigmented
• Can be ulcerated as well, where diagnosis is made through observation of the ulceration on the face but key risen, irregular, shiny border
• Can resemble a scar, where astute dermatologist can consider after biopsy
• Superficial type of BCC may mimic Bowen's disease, typically seen as an erythematous patch on the trunk or chest, but the pearly, risen, irregular borders can still be observed with BCC

Diagnostics and Prognosis of BCC

• Dermoscopy is helpful, using the dermatoscope
• Genetic disease exist, in which patients have increased basal cell carcinoma, such as Gorlin Goltz Syndrome
• Composed of blue islands of the lower epidermis cells
• Good prognosis is usually the case
• Risk of metastasis is almost zero, but BCC will relapse if the BCC is larger than 2 cm, or involves areas that are difficult to eradicate (around eyes or nose)
• Therefore not metastasis is the risk, but relapse in BCC
• Face can be impacted in H pattern, areas at risk for recurrence

Treatment of BCC

• Primary method is surgical excision, slow progression leading to tissue destruction if left untreated

Melanocytic Neoplasms

• Melanocytic nevi are the benign counterpart of melanocytic proliferation
• Occurs with benign proliferation made by melanocytes
• The most frequent cause 50/70% for dermatological clinic visits
• This is to discover the presence of melanoma
• The study of melanocytic nevi are for detection of malignant melanoma

Common Nevi

• The most frequent nevi are common acquired nevi
• Pigmented lesions with a round symmetrical border
• Normally people have 15/30 melanocytic nevi; also called “moles”

Types of Common Nevi:

• Miescher nevus: dome shaped papule on the face that usually is less pigmented than melanocytic nevi
• Unna nevus: looks like a fibroma, and common on the trunk, axilla
• differ from typical melanocytic nevi, where differences being from being asymmetrical, irregular borders, and non homogenous color
• Size: more than six millimeters in size

Signs and Risk Factors for Melanoma

• Dysplastic Atypical Nevus Syndrome: consider if a patient has many multiple atypical nevi, especially on the back or the trunk, or on the chest, increasing the risk for development of a melanoma
• Spitz nevus:
• typical nevus in pediatric age, where it is not very pigmented, where confused sometimes with angioma, where histologically it is a melanoma mimicker, but is a atypical nevus that makes it difficult to diagnose for dermatopathologists

Reed Nevus

• Black in color, and usually develops on the lower limbs in women
• Lesions appear suddeonly
• in addition to the black color and the well defined borders, is that histologically is made by spindle shaped cells
• Small sizer (1.5), and Medium Sizer, and large Sizer
• Large being at higher 20percent risk for developing a melanoma
• Then Bluve Nevus (Bluve Because located deep in the dermis, usually is benign

Melanoma

• The most important cancer for dermatologists, in being most deadly, than squamous.
• Must do it early or death Define (maignant neoplasm of Melanocytes , but not from a nevus Bob marley , had it in the foot, in the nail, 36,
• Black Silent Killer Name for melanoma comes because of it starting, from already non prexiting lesion

Origin of Melanoma

• 80 percetn for normal, and 20 percen with premalignant lesions
• Melymoma usually white, for melanocytes for those ppl.

Incidence of Melanoma

• 10 pecent in italy, 1/66 for men, "now i die pediatric age, melanoma are rare between 40-60

Siting and Location of Melanoma

• lower limps for women, and back for men

Development

• in sun exposed regions, Australia, but Italy is moderate, 10,000 pecent per. year (lifetime risk is high

Risk diagnosis

:because we show it to the dermo doctor..

Bus example

• One peoeple dies of Melanoma,

Risk factor/Endogenus

• The history of Family,
• Mutated gene, CDk

Risk factor

• phototype: anglo saxon 1/2 (Mediterranean is 3, India is 5,
• the number of nevi's

Exegonus factos

• pediactrica /and sunbrn,
• Tanin bed,

How can you diagnosed it, ABCDE

• Asimerical
• Border. (unregular defined)
• Color(various colors)
• Diameter( more than 6 mm) Everlution? melanoma grows between
• The horizontal, and then the verticale , if vertically good Prognosi=100 percetn

melanoma Types

• Superifical spreading melanoma (most common
• Nodular
• Lenigo- maligna melanoma (slow
• arcral- lentingos,,

Where the tumors comes from:

Dermla

• Atypoiacl dysplastic . nevus
• congenital nevi highyly.
• dysppllasti nevsu can be asymptrical, colors, If yes this called "sign of ugly duckling" where doctors see other types
• Someoimes, meoanoma can develop in congestional nvesus

dermatuscopee

Video for melanoma

Invasice, how to

On te lift normal On the wright, cancer

Factors to Prognostic , melanoma.

• (thikcnes
• we take out and see how thick is it If thick More than 8, less thin it is bette (histo)
• ulcerations

Staginf of melanoma

Staginf.Zero, 8 mm thinner

• Stage four,,very dangerous

Preventi

,Early diagnosis Sun

Photochemo , sun bads,

• remove fast

Surtureal removal

• drugs, for these ppl who are in stage 4 Sentil lymph node

Targent theroay= genetic mod