20. Solid Tumors

What are some solid primary cancers of the eye?

• Basal cell carcinoma

• Squamous cell carcinoma

• Cutaneous melanoma

• Uveal melanoma

• Retinoblastoma

Epidemiology of skin cancer

• light eye color: 1.8x risk

• fair skin: 1.8x risk

• inability to tan: 1.6x risk

Types of skin cancer:

1. basal cell carcinoma

2. squamous cell carcinoma

3. cutaneous melanoma

Basal cell carcinoma are what?

Cancer of epidermal basal cells. It is the most common skin cancer, 90% of all cases. They are slow growing, rarely metastatic, and rarely causes death.

What are the presentations of basal cell carcinoma?

• asymptomatic

• Pearly nodule (shiny)

• Extensive invasion w/o treatment

• Prominent telangiectasia (umbilicated bleeding center= ulcer)

• Disrupt lid margin (disfiguring)

• Madarosis (loss of lashes)

How is basal cell carcinoma treated?

• Excisional biopsy

  • wide margins

  • r/o squamous cell carcinoma

What is squamous cell carcinoma?

Cancer of squamous cell/epidermal keratinocytes. is 2nd most common skin cancer of eye. Squamous cell carcinoma as group most found in ocular region. 5% risk of metastasis.

What are the presentation of squamous cell carcinoma?

• Chalazion-like nodules from meibomian gland of tarsal plate and upper eye lid

• Greasy: yellow or gray

• Painful

• Telangiectasi: ulcerate easily

• Disrupt lid margin: disfiguring

• Madarosis

• Can metastasize with only 20% 5yr survival

Where does the squamous cell carcinoma metastasize to?

Orbit and/or intracranial cavity

What is a Nevi/Nevus?

Benign tumor/birthmark, beauty mark, or mole. It is a proliferation of melanocytes

What is cutaneous melanoma?

Cancer of melanocytes. 3rd most common skin cancer and #1 cause of skin-cancer related deaths.

What are the ABCDE’s Diagnostic criteria for melanoma?

A= asymmetrical
B= border irrgularity
C= color variation
D= diameter >6mm
E= evolving

What are the types of cutaneous melanoma?

• superficial spreading

• nodular

• lentigo maligna

• acral lentigious

What is a concern about cutaneous melanoma?

Highly metastatic: hematogenous spread

What antibody can be used to treat cutaneous melanoma?

Ipilimumab(Yervoy). Prevents apoptosis of CTLs by blocking CTLA-4 activation. Allowing CTLs to kill cancer and cause inflammation. Only 14.4% response rate with a 80% 5yr survival.

What are the side effects of Ipilimumab (Yervoy)?

• Inflammation

• Uveitis

• Eye pain

• Dry eye

• Allergy response

What are some other treatments for cutaneous melanoma?

Immunotherapy: PD-1 blockade: Pembrolizimab (keytruda). PD-1 Ligand interacts with CTL, causing it to undergo apoptosis. Pembrolizumab binds to PD1 or PD1-L and inhibits interaction with CTLs. CTLs do not apoptose and kill melanoma.

What happens when CTLA-4 and PD-1 blockade are combined?

Longer survival rate

Where is Uveal melanoma found?

• 95% in uveal tract

• 4% in conjunctiva

• 1% in eyelid/orbit

Is the #1 intraocular cancer in adults.

Where do uveal melanoma home towards?

Liver

Where are uveal melanomas found in?

• choroid: often asymptomatic

• iris

• ciliary body

What is the difference between a nevus and uveal melanoma?

Nevus: low risk, drusen, RPE atrophy, no growth

Uveal melanoma: high risk, looks young, no drusen, growth, orange pigment, subretinal fluid.

What are the treatments for uveal melanoma?

• Radiotherapy for choroidal melanoma: Particle beam radiotherapy or plaque radiotherapy

• No chemotherapy

• Surgery: resection, enucleation, exenteration

• Immunotherapy: CTLA4 blockade and PD1 blockade

What is unique about choroidal melanoma?

It is very hardy,

Complications of brachytherapy?

• Cataracts

• Chorioretinal scarring & retinal detachment

• Radiation retinopathy: neovascularization

What is retinoblastoma?

Cancer of horizontal interneurons from RB1 mutation. Most common intraocular cancer in children

What are the clinical presentations of retinoblastoma?

• Leukocoria: white pupillary reflex

• Strabismus

• Vision loss

• If diagnosed early, 95-99% 10yr survival.

• Metastasizes after 1 year

Are metastatic cancers more common than primary cancers?

Yes, metastatic in the brain is 10x more common than primary.

Where do most metastatic tumors of the eye and surrounding tissues come from?

• Breast

• Lung

• Prostate

• Lymphoma (with leukemia presentations)

Why do we need to biopsy the ocular tumors?

To determine the location of primary tumor and receive correct treatment for the specific primary tumors.

What is the 2nd most common caner in men and women?

Lung caner. It is also the leading cause of cancer-related deaths

Why does lung cancer have such poor survival rates?

• Fearful smokers

• Poor screening

• Mimics other respiratory diseases

How does lung cancer spread?

Lymphogenous and hemotogenous.

What are the 2 major classes of lung cancer?

1. 85% non-small cell carcinoma: can be associated with horner’s syndrome. is least aggressive and poor survival.

2. 10-15% small cell carcinoma (oat cell): paraneoplastic endocrine problems: ACTH, PTH, SIADH, Aldosterone. Most aggressive: 5% 5 yrs survival.

What treatments are used for non-small cell carcinoma?

• Resection

• PD1 blockers

What treatments are used for small cell carcinoma?

PD1 blockade

What is the leading cause of cancer in women?

Breast cancer.

What is the epidemiology of breast cancer?

• FHx (genetic component): Ashkenazi jew, BRCA1/BRCA2 positive

• Early menarche/last menopause= longer exposure to estrogen and progesterone

• Nulliparous >35 yrs old= never had a full-term pregnancy. Pregnancy causes terminal differentiation of breast tissue.

What are the key structures of of the breast?

• Lobules: produce and store milk

• Ducts: milk ejection

Estrogen is a trophic factor for tissue changes; tissue enlarges before menses and recede during or after

What can mimic breast cancer?

Benign cysts. Location does not change, size may vary.

What are the 2 types of breast cancer?

1. Ductal carcinoma in situ (DCIS)

2. Lobular CIS (LCIS)

What is the prognosis of breast cancer?

• nonmetastatic = 98% at 5 yr survival

• metastatic= 25% at 5 yrs

What treatments are used for breast cancer?

Based on subtype of breast cancer:

• Excisional biopsy

• Lumpectomy: with lymph node removal

• Mastectomy: w/ or w/out reconstruction

Estrogen and progesterone receptors blockers

• Tamoxifen: blocks estrogen receptors

• Aromatase inhibitors: blocks production of estrone: in postmenopausal women and in men.

Blocking tumors with Herceptin (anti-Her2) antibodies: Her2/Neu, tyrosine kinase receptors, stimulates cell growth and division

What types of breast cancers are difficult to treat?

Triple negative (15-20%): no Estrogen receptors, no progesterone receptors, no Her2/Neu.

What is the most common cancer in men?

Prostate cancer. 3rd cancer-related deaths. 1 in 9 men diagnosed. 1 in 41 men die.

What is the function of the prostate?

Produces 40% seminal fluid fluid to nourish and transport sperm

What does testosterone do to the prostate?

Trophic factor, causing it to grow.

What are the key structures of the prostate?

• Surrounds urethra

• Anterior to rectum: digital rectal exam

Epidemiology of prostate cancer:

• Age 60+

• Black

• FHx: BRCA1/BRCA2

What is benign prostatic hyperplasia (BPH)

A common condition in men where the prostate gland grows larger than normal. It does not increase risk for cancer and can mimic cancer presentation.

Presentation of Prostate Cancer:

• Asymptomatic

• If symptomatic:

  • Urinary presentation: interruptions

  • diminished stream

  • Blood in semen/urine

  • Erectile dysfunction (ED)

  • Perineal pain

  • Bone pain/renal

Treatment for prostate cancer

• watchful waiting with surveillance

• Target therapy: Androgen deprivation therapy

• Radiation or brachytherapy

• Nerve-preserving radical prostatectomy