LEC 7 skin tumours

• Seborrheic Keratosis (benign):

  • Risk factors:
  • Aging
  • Chronic UV light exposure
  • Etiology:
  • Associated with somatic mutations in fibroblast growth factor receptor 3 (FGFR3)
  • FGFR3 stimulates RAS & PI3K/AKT pathway
  • Pathogenesis:
  • Benign keratinocyte proliferation
  • Morphology:
  • Single or multiple lesions, from mm to cm
  • Well-circumscribed, exophytic tan to dark brown lesions
  • Round, coin-like, waxy plaque appearance
  • Composed of sheets of basaloid cells resembling basal cells of the epidermis
  • Horn cysts and pseudohorn cysts
• • Variable melanin pigmentation
  • Hyperkeratosis
  • Clinical manifestations / Complications:
  • Site: Trunk, head & neck, extremities
  • Velvety to granular surface
  • Generally do not undergo malignant transformation
• • Rate of progression to squamous cell carcinoma is small (0.1% - 2.6% per year)
  • Treatment is given to prevent progression or for cosmetic reasons
  • Local eradication with cryotherapy or topical agents is effective & safe
  • Morphology:
  • Actinic keratosis presents as rough, scaly patches on the skin
  • Lesions are typically small, with a diameter ranging from a few millimeters to a few centimeters
  • Clinical Manifestations/Complications:
  • Actinic keratosis may progress to squamous cell carcinoma
• Actinic keratosis (premalignant):

  • Risk Factors:
  • Chronic sun exposure
  • Prolonged immunosuppression
  • Arsenic exposure
  • Ionizing radiation
  • Industrial hydrocarbons exposure
  • Chronic cutaneous inflammation
  • Etiology:
  • Associated with chronic sun exposure and immunosuppression
  • Can also be caused by arsenic exposure, ionizing radiation, industrial hydrocarbons, and chronic cutaneous inflammation
  • Pathogenesis:
  • Lesion may regress or remain stable
  • May progress to full thickness dysplasia – Squamous cell carcinoma in situ
• • Tumors arising from actinic keratosis may be locally aggressive but metastasize only after long periods of time
  • Tumors arising in burn scars, ulcers, and non-sun-exposed skin often behave more aggressively
• Squamous cell carcinoma (SqCC):

  • Risk factors:
  • Chronic sun exposure
  • Chronic immunosuppression
  • HPV infection
  • Ingestion of arsenicals
  • Ionizing radiation
  • Old burn scars
  • Aetiology:
  • Xeroderma pigmentosum
  • Environmental factors like industrial carcinogens
  • Pathogenesis:
  • Involves deeply invasive lesions with subcutis involvement
  • Morphology:
  • Presents as tumors commonly found on sun-exposed sites such as the scalp, face, and lower legs in females
  • Clinical manifestations:
• • Locally aggressive tumors that may metastasize after long periods of time, especially in cases where the lesion is deeply invasive with subcutis involvement
  • Complications:
  • Likelihood of metastasis, which is related to the thickness of the lesion and degree of invasion into the subcutis
  • Tumors arising from actinic keratosis may be locally aggressive but metastasize only after long periods of time
  • Tumors arising in burn scars, ulcers, and non-sun-exposed skin often behave more aggressively
• Basal Cell Carcinoma (BCC):

  • Risk Factors:
  • Chronic sun exposure
  • Geographical factor - increased incidence in sunny climates near the equator (e.g., Australia)
  • Ingestion of arsenicals
  • Ionizing radiation
  • Tobacco smoking
  • Genetic disorders: Nevoid basal cell carcinoma syndrome (Gorlin syndrome), Xeroderma pigmentosum
  • Aetiology:
  • Most common malignant skin tumor
  • Common in lightly pigmented elderly individuals
  • Exclusively found in the skin, particularly on the scalp and face
  • Slow-growing tumor
  • Locally aggressive, with rare metastasis
  • Pathogenesis:
• • Arises from the epidermis or follicular epithelium
  • Multifocal growth patterns, often nodular
  • Tumor nodules seen in the dermis
  • Tumor cells (basaloid cells) with scant cytoplasm, small hyperchromatic nuclei, inconspicuous nucleoli
  • Peripheral nuclear palisading, cleft retraction artifacts, mitoses
  • Myxoid/mucinous/fibrotic stroma with inflammatory infiltrate
  • Clinical Manifestations/Complications:
  • Slow-growing nodules or ulcerated lesions on sun-exposed areas, especially the face and scalp
• • Rarely metastasizes but can cause local tissue destruction, disfigurement, and functional impairment if left untreated
• Malignant melanoma:

  • Risk factors:
  • Fair-skinned individuals
  • Intense intermittent sun exposure, especially at an early age
  • Dysplastic naevus
  • Immunosuppression
  • Personal or family history of malignant melanoma
  • Germline mutations
  • Familial melanoma with mutations in CDKN2A locus
  • Chronic sun exposure
  • Geographical factor - increased incidence in sunny climates near the equator (e.g., Australia)
  • Ingestion of arsenicals
  • Ionizing radiation
  • Tobacco smoking
  • Genetic disorders such as nevoid basal cell carcinoma syndrome and xeroderma pigmentosum
• • Ulceration, bleeding, or oozing
  • Metastasis to regional lymph nodes, distant organs such as lungs, liver, brain, and bone
• • Aetiology:
  • Strong association with chronic UV light exposure
  • Arises from melanocytes
  • Site of occurrence: skin, oropharynx, gastrointestinal tract, genitourinary system, esophagus, meninges
  • Pathogenesis:
  • UV light-induced DNA damage leads to stepwise acquisition of driver mutations with increasing mutational burden
  • DNA sequencing begins with initiating mutation in BRAF or RAS, frequently seen in benign naevi
  • Naevi with atypia commonly harbor mutations involved in telomerase activation
• • Additional mutations in CDNK2A, p16, p53, and PTEN lead to tumor progression and metastasis
  • Morphology:
  • Varied morphologies including nodular, superficial spreading, lentigo maligna, and acral lentiginous melanoma
  • Can present as a pigmented or amelanotic lesion
  • Irregular borders, asymmetry, color variegation, and diameter >6mm (ABCDE criteria)
  • Clinical manifestations and complications:
  • Asymmetrical lesion with irregular borders, color variation, and diameter >6mm
  • Change in size, shape, or color of a pre-existing mole
  • Itching, tenderness, or pain in the lesion