Week 5 Flashcards
Describe the DNA damage that occurs from UV radiation and explain how this damage can lead to cancer.
- UV kills cells because of the accumulation of DNA damage
- Ultraviolet light is absorbed by a double bond in pyrimidine bases (such as thymine and cytosine in DNA), opening the bond and allowing it to react with neighboring molecules. If it is next to a second pyrimidine base, the UV-modified base forms direct covalent bonds with it. The most common reaction forms two new bonds between the neighboring bases, forming a tight four-membered ring. Other times, a single bond forms between two carbon atoms on the rings, forming a “6-4 photoproduct.”
How is UV damage fixed?
Our cells use a process known as “nucleotide excision repair” to identify and remove ultraviolet damage. Dozens of proteins work together to seek out corrupted bases, unwind the local DNA double helix and clip out a segment of about 30 bases around the damage. The normal DNA replication machinery then fills the gap, restoring the DNA to its proper form. Nucleotide excision repair is our sole defense against ultraviolet damage
normal cellular pathways of DNA repair after damage due to irradiation
Nucleotide excision repair: damaged nucleotide(s) are removed along with a surrounding patch of DNA. In this process, a helicase (DNA-opening enzyme) cranks open the DNA to form a bubble, and DNA-cutting enzymes chop out the damaged part of the bubble. A DNA polymerase replaces the missing DNA, and a DNA ligase seals the gap in the backbone of the strand
mechanisms of photoprotection
- Photoprotective clothing
- Sunscreens
clinical presentation for cutaneous melanoma
- A new or changing mole or blemish is the most common warning sign for melanoma.
- Variation in color and/or an increase in diameter, height, or asymmetry of borders of a pigmented lesion
- Symptoms such as bleeding, itching, ulceration, and pain in a pigmented lesion are less common
- Note: the majority of cutaneous melanoma arises de novo (ie, on normal-appearing skin and not in association with a precursor nevus aka existing mole/birthmark)
risk factors for cutaneous melanoma
• a persistently changed or changing mole • adulthood, • irregular varieties of pigmented lesions (including dysplastic moles and lentigo maligna) • a congenital mole • Caucasian race • a previous cutaneous melanoma • family history of cutaneous melanoma • immunosuppression • sun sensitivity -excessive sun exposure
ABCDE
Asymmetry, borders, color, diameter, evolving
general guidelines for excisional biopsy
, 1-3 mm of normal skin surrounding the pigmented lesion should be removed to provide accurate diagnosis and histologic microstaging
Biopsy margins
Wider margins (>1 cm) could theoretically disrupt afferent cutaneous lymphatic flow and affect the ability to identify the sentinel node(s) accurately
Sentinel lymph node biopsy
generally indicated for pathologic staging of the regional nodal basin(s) for primary tumors greater than 1 mm depth and when certain adverse histologic features (eg, ulceration, high mitotic rate, lymphovascular invasion) are present in thinner melanomas.
histopathology of cutaneous melanoma
- melanomas progress through two phases;
- radial (horizontal)growthphase (RGP), characterized by centrifugal spread of neoplastic melanocytes within the epidermis and infiltration of the papillary dermis by single cells or small nests
- second,verticalgrowthphase (VGP), is characterized by the presence of dermal nests/nodules of atypical melanocytes that are larger than and/or cytologically distinct from their intraepidermal counterparts
significance of genetic profiling in treatment of cutaneous melanoma
important to know where the mutation/problem originates. Whether it’s BRAF, RAS, or C-KIT gives you an indication of how it’s specifically causing melanoma and a better idea of how to treat it
rationale for lymphadenectomy
- patients who present with palpable lymphadenopathy, it is appropriate to confirm diagnosis with fine needle aspiration, core needle, or open biopsy of the clinically enlarged lymph node(s).
- absence of radiological evidence of distant metastases, wide excision of the primary site and complete dissection of the involved lymph node basin is indicated.
- staging purposes, the number of positive nodes, the total number of nodes examined and the presence or absence of extranodal tumor extension must be recorded.
use of 18FDG-PET/CT scanning in the evaluation and staging of cutaneous melanoma
Positron emision tomography (PET) with 2-deoxy-2-fluorine-18-fluoro-D-glucose (18FDG), an analogue of glucose, provides valuable functional information based on the increased glucose uptake and glycolysis of cancer cells
use of tyrosinekinase in immunoperoxidase staining method
-tyrosinekinase is made in melanocytes, it is used in staining of lymph to check for melanocytes in lymph which is indicative of met to the metastasis
