Eyelid Lesions: Chalazion and Xanthelasma

Lesions of Eyelid: Chalazion

• Common inflammatory eyelid lesion
• Characterized by granulomatous inflammation with lipogranulomas
• More common in younger adults than in children, uncommon in late life
• History of chalazion and blepharitis is significant
• Rosacea, gastritis, anxiety, and smokingare less significant factors
• There is no evidence that cosmetics in the eyelid cause, aggravate, or protect from this condition
• Clinical feature is a slowly growing, solitary, nontender nodule, upper eyelid is more affected than the lower eyelid
• Microscopic description includes lipogranuloma, some lesions have granulation tissue, and early lesions can have necrotizing granulomas

Xanthelasma

• Soft, yellow, lipid-laden plaque on the medial aspect of eyelid skin
• More common in females than males
• Onset typically between 15-73 years, peaking at 30-50 years
• Half of patients have hyperlipidemia, increased likelihood of familial hyperlipidemia if presentation occurs at less than 40 years of age
• May be associated with atherosclerosis, diabetes mellitus, and thyroid disease
• Appears symmetric on eyelids
• Thin, yellow papules and plaques are symmetrically distributed on the medial upper or lower eyelids
• May be associated with cirrhosis, thyroid disorder, or nephrotic syndrome
• Periorbital hyperpigmentation is noted in more than 80% of women with xanthelasma
• Increased risk of recurrence is associated with all 4 eyelids being involved, underlying hyperlipidemia, and prior recurrence
• Lipid-laden foamy histiocytes are present in superficial dermis, clustering around blood vessel walls

Melanocytic Tumors

• Benign type is Nevus, malignant type is Melanoma

Benign Melanocytic Tumor (Nevus)

• Most common melanocytic tumor
• Clinically evident between ages 2-6 years
• More common in whites, less common in Asians and Africans
• Nevi are common on the head, neck, and trunk in Caucasians, and on acral sites in Asians and Africans
• Mostly occur in skin but also in mucosal membranes covered by squamous epithelium
• May occur in eye in iris choroid and ciliary body
• Appears as a papule or macule, tan-brown, uniformly pigmented, and small (≤ 0.6 cm)
• Often shows erosion or ulceration if adjacent to a hair follicle
• Nests of melanocytes uniform in size, distributed at the tips of the rete ridges
• Has cells with scanty cytoplasm containing coarse melanin granules, uniform round/oval nuclei slightly smaller than adjacent keratinocytes
• Deeper portion of lesion has smaller cells with less pigment, deep cells grow in smaller sized nests or single cells
• May resemble neural tissue
• Types are congenital and acquired
• Congenital as blue nevus and giant nevus
• Acquired as junctional, compound and intradermal nevi

Dysplastic Nevus

• Etiology is not well characterized; genetics and environment play roles dysplastic nevus development on any skin site, more common on trunk and sun-exposed skin
• Atypical nevi demonstrate: usually > 5 mm, irregular borders, some with a pigmented and erythematous rim, and variegated pigmentation with a mixture of pink, light and dark brown
• Dysplastic nevi show the same features as ordinary nevi except for some changes:
• Architectural changes: Bridging and irregular nesting
• Cytological changes: Cytologic atypia, increased nuclear size and hyperchromatic nuclei, irregular nuclear membrane, prominent nucleoli, pleomorphism, and multivacuolated melanocytes
• Epidermal changes: Acanthosis, focal parakeratosis and hyperkeratosis
• Nevus of special site: flexural, breast and genital nevi can be clinically and histologically atypical and simulate features of a dysplastic nevus or melanoma

Malignant Melanocytic Tumor (Melanoma)

• Incidence is 1% of skin cancer, more frequent in males.
• Risk factors include fair skin, family/personal history of melanoma, intense sun exposure, and dysplastic nevus
• Cutaneous sites are lower extremities in females, trunk in males
• Extracutaneous sites are uvea, anorectal region, upper digestive tract and sinonasal tract.
• Presents as flat, slightly elevated, nodular polypoid or verrucous pigmented lesion, the ABCDE rule applies.
• The ABCDE rule includes asymmetry, irregular borders, variation in color, diameter (>6mm), and evolution
• Favorable prognostic factors: young age, female, low-risk sites, severe tumor infiltrating lymphocytes
• Unfavorable prognostic factors: elderly patients, male, high-risk sites, high dermal mitotic rate, ulceration, absent/few tumor-infiltrating lymphocytes, lymphatic invasion, increasing angiogenesis
• Gross picture: flat, slightly elevated, nodular, polypoid or verrucous pigmented lesion
• Microscopic: Epithelioid/spindle shaped cell, nuclear pleomorphism, nuclear enlargement
• Cytologic features: nuclear hyperchromasia, coarse irregular chromatin pattern, prominent eosinophilic nucleoli, and dusty pigmented cytoplasm
• Stromal changes: variable inflammatory infiltrate, dermal fibrosis, and irregular distribution of pigment

Squamous Cell Carcinoma

• Definition: SCC is a malignant tumor of stratified squamous epithelium
• Sites: Skin; mucous membrane lined by stratified squamous epithelium (lip, tongue, oral mucosa, pharynx, larynx, esophagus, cervix, vagina, vulva, and anal canal) and on top of squamous metaplasia in the other mucous membranes
• Etiology: Prolonged exposure to ultraviolet light rays of sun ,genetic as Xeroderma pigmentosa, chronic irritation, human papillomavirus infection, occupational exposure to carcinogenic substances as Tars, coal and arsenic or squamous metaplasia and leukoplakia
• Gross picture: Fungating, ulcerating and infiltrating
• Microscopic: The dermis or submucosa is infiltrated by malignant squamous cells arranged in groups and nests variable keratin pearls formation separated by stroma
• Grading of SCC: According to Broder's classification depending on the percentage of keratin pearl formation

Basal Cell Carcinoma (Rodent Ulcer)

• Locally malignant tumor of the skin
• Arises from interfollicular or follicular epithelium
• Local aggressive course
• Affects sun-exposed areas mainly the face
• Appears as a firm red papule which ulcerates
• Ulcer: round/oval, rolled in "beaded" edge, fixed/indurated base, red necrotic floor
• Nests of basaloid cells with scanty cytoplasm and elongated hyperchromatic nuclei, epidermal connection, retraction artifact, and prepheral balisading
• Enlargement of cervical lymph node: secondary bacterial infection or malignant transformation of BCC to basosquamous/squamous cell carcinoma with lymph node metastasis
• BCC is more common than cutaneous SCC
• BCC microscopic: Nests of basaloid cells with peripheral palisading and epidermal connection
• SCC microscopic: Invasive cell nests of keratinocytes with various keratin pearls formation

Tumors of Childhood

• Tumors that occur before the age of twenty
• Majority of childhood cancers do not have a known cause
• Risk factors include chronic infections, genetic factors, and environmental/lifestyle factors
• Common types include lymphoid leukemia, brain and other central nervous system cancers, neuroblastoma, Wilms' tumor, and osteosarcoma

Neuroblastoma

• Primitive neoplasm of neuroectodermal origin, composed of immature neuroblasts
• Fourth most common malignant tumor in childhood
• Median age at presentation is 23 months, peak 0-4 years
• Slightly more common in boys
• Rarely diagnosed prenatally
• Occurs anywhere in the distribution of sympathoadrenal neuroendocrine system, commonly in the adrenal gland, urine biochemistry showing catecholamines
• Histologic classification systems are the Shimada Classification and the International Neuroblastoma Pathology Classification System (INPC)

Retinoblastoma

• Most common intraocular malignancy in children
• Characterized by hyperchromatic small round blue cells with scant cytoplasm arranged in sheets, nests, and trabeculae
• Prognosis depends on tumor invasion into anterior chamber, choroid, and optic nerve
• Sporadic retinoblastoma usually unilateral, inherited retinoblastoma often bilateral
• Clinical features include leukocoria, glaucoma, strabismus, eye pain, visual acuity, and retinal detachment
• Gross Description: Creamy white with chalky areas and yellow necrotic areas with micro features of hyperchromatic small round blue cells, Flexner-Wintersteiner/Homer-Wright rosettes, and fleurettes

Lesions of Nose and Larynx: Nasal Polyps

• Etiology is repeated attacks of allergic rhinitis and sinusitis
• Multiple soft pink polyps, projecting from the mucosa of the nose and sinuses
• Pseudostratified columnar ciliated epithelial covering and connective tissue core
• Complications: Nasal obstruction or epistaxis

Lesions of Nose and Larynx: Rhinoscleroma

• Granulomatous inflammation of the upper respiratory tract, caused by Klebsiella rhinoscleromatis common in Egypt
• Nose is the most common site, but pharynx, larynx, and upper trachea may be affected
• Features single/multiple hard nodular swelling which nasal mucosa that may show squamous metaplasia
• Submucosa shows inflammatory cells and Mikulicz cells and Russel bodies
• Complications: Nasal obstruction/deformity and ulceration/bleeding/secondary bacterial infection

Lesions of Nose and Larynx: Nasopharyngeal Fibroma (Juvenile Angiofibroma)

• An uncommon benign tumor arising from the periosteum
• Occurs more common in young boys
• Non capsulated grayish pink mass and angiofibroma
• Complications: Epistaxis, obstruction, and profuse bleeding during surgery
• It regresses after puberty.

Squamous Cell Carcinoma of Larynx

• Predisposing factors: smoking, alcohol, exposure to asbestos, irradiation, HPV
• Epidemiology: 2% of all cancers in men, after age 40, more common in males
• Gross features: ulcerated mass
• Microscopic features: squamous cell carcinoma ranging from well to poorly differentiated
• Spread: direct and by lymphatics (to cervical nodes), blood spread is late
• Anatomical sites: glottic and supra/infra glottis
• Well-differentiated SCC occurs in the glottis, while poorly differentiated SCC is more common in the supraglottic and infraglottic regions.