​Kembara Xtra - Medicine - Melanoma

​Kembara Xtra - Medicine - Melanoma 
Melanoma is a tumor that develops when pigment-containing cells called melanocytes, which are present in the stratum basale of the epidermis, undergo malignant transformation. The majority develop in the skin, but they can also appear as a primary lesion in any tissue, including the anorectal mucosa, ophthalmic (uvea), GI, GU, lymph node, paranasal sinuses, nasal cavity, and leptomeninges. A poor prognosis is associated with extracutaneous locations.
There are several different kinds of invasive cutaneous melanomas, including the following:
- Superficial-spreading melanoma: 70% of instances; occurs in sun-exposed areas (trunk, back, and extremities); majority are less than 1 mm thick at diagnosis; when detected in younger individuals, manifests as a flat, slowly expanding lesion with an uneven border.
- Nodular: 15–30% of instances; prevalent in elderly patients; propensity to ulcerate and bleed; typically thick and pigmented; most frequently melanoma >2 mm.
Lentigo maligna (subtype of in situ melanoma): slowest growing; older population; develops in sun-exposed areas (head, neck, forearms). Its invasive equivalent, lentigo maligna melanoma (LMM), is seen in 10-15% of instances and most frequently affects the head and neck of elderly adults.
Subungual melanoma is a significant subtype of acral lentiginous melanoma, which accounts for only 5% of all melanomas but is the most prevalent in black or Asian patients. It can mimic other skin abnormalities such as warts, calluses, tinea pedis, or ingrown toenails. Hutchinson nail sign occurs when brown or black pigment extends from the nail to the cuticle and proximal or lateral nail folds. It appears as a dark stripe under the nail plate and originates from the nail matrix.
Amelanotic melanoma, which accounts for about 5% of instances and is known as a "great pretender" because it can mimic benign skin disorders, can be overlooked and identified at a later stage.
- Desmoplastic melanoma: 1% of cases; "neurotropic melanoma" or "spindled melanoma" with a lot of fibrous tissue; exhibits sarcoma-like characteristics and increased hematogenous spread; appears as a slow-growing scar-like lesion (no history of injury at the site is noted); frequently found in the head and neck
Systems impacted: exocrine and/or cutaneous

Aspects of Geriatrics

Older patients are most frequently affected by lentigo maligna. This form is typically found on the face and starts as a macular patch that is confined and has mottled pigmentation in hues of dark brown, tan, or black.
Child Safety Considerations
A lifetime risk of malignant conversion of >2% is associated with large congenital nevi (>5 cm). Childhood sunburns that sting severely raise risk.
pregnant women's issues
Pregnancy has no increased risk of melanoma. It is advised to wait one to two years after melanoma therapy before trying to conceive since melanoma can spread to the placenta.

Prevention Incidence
It is predicted that 100,350 Americans would receive a melanoma diagnosis for the first time in 2020, with 6,850 deaths.
 The median age at diagnosis was 65 years.
Male is more common than female (1.5 times)
Minority populations have higher rates of metastasis, advanced stages at diagnosis, thicker initial lesions, earlier age at diagnosis, and overall worse outcomes. Melanoma is >20 times more common in whites than in African Americans.
Low socioeconomic level is linked to a higher melanoma incidence.
Prevalence
The fifth most frequent kind of cancer in the US is melanoma.
1.2% of all cancer-related deaths are men (1/28); women (1/4) over their lifetimes.

Pathophysiology and Etiology 
DNA damage caused by UVA and UVB exposure Tumor progression: initially restricted to the epidermis with lateral development, then possibly growing into the dermis with vertical growth
Genetics
Melanoma development is at danger due to the dysplastic nevus syndrome. Close observation is necessary.
8–12% of melanoma patients have a history of the disease in their families.
BRAF (V600E) mutations are linked to 50–60% of cutaneous melanomas.
 The clinical diagnosis of familial atypical mole malignant melanoma (FAMMM) syndrome includes >50 atypical moles and +FH of melanoma.

Risk factors include genetic predisposition, personal or family history of melanoma, exposure to UVA and UVB rays, history of more than five sunburns in one's lifetime, blistering sunburns as a child, previous pigmented lesions (especially dysplastic melanocytic nevi), fair skin, freckling, blue eyes, and blond or red hair, with a high number of nevi (>50) being the strongest indicator of risk.
70% of melanomas are de novo, meaning they develop spontaneously.
If you use a tanning bed for the first time before age 35, your risk is enhanced by 75%.
 A nevus that is changing (see "ABCDE" requirements)
living at a high altitude (more than 700 meters or 2,300 feet above sea level) having large (>5 cm) congenital nevi having chronic immunosuppression (chronic lymphocytic leukemia, non-Hodgkin lymphoma, AIDS, or posttransplant) having occupational exposure to ionizing radiation

Prevention 
Avoiding sunburns, especially when young. Seek shade to keep out the midday light.
Use a broad-spectrum sunscreen with a minimum SPF of 30 on all skin exposed to the sun. Reapply as needed, especially after swimming or toweling off.
Avoid tanning beds; they are classified as a class 1 carcinogen by the World Health Organization (WHO); screen high-risk persons, particularly males over 50; and educate yourself about accurate diagnosis as it plays a big role in prevention.
● Any worrisome lesions should be biopsied using a small excision with 1- to 3-mm margins that completely surround the lesion's breadth and provide enough depth. There are elliptical excisions, punch biopsies, and deep shave biopsies available.

Accompanying Conditions 
The syndrome of dysplastic nevi
● >50 nevi. Due to the fact that 30% of all melanoma develop in preexisting nevi, these people have a higher lifetime chance of developing the disease than the general population.
Giant congenital nevus: lifelong melanoma incidence of 6%
Psoriasis following psoralen-UV-A (PUVA) therapy is a rare illness linked to an exceptionally high risk of skin malignancies, including melanoma.


Obtain family and personal histories of melanoma or nonmelanoma skin cancer. Change in a pigmented lesion, such as hypo- or hyperpigmentation, bleeding, scaling, ulceration, or changes in size or texture.
 Obtain social history, such as employment, sun exposure, tanning, and other activities.

clinical assessment 
Asymmetry, Border irregularity, Color variegation (particularly red, white, black, and blue), Diameter greater than 6 mm, and Evolution through time are abbreviated as ABCDE.
Any new or changing nevus that is bleeding or ulcerated is at high risk for developing melanoma. It typically appears on the back and lower leg of Caucasians, while African Americans tend to get it on their hands, feet, and nails. It may also appear on mucosal surfaces (such as the nose and conjunctiva).

Differential diagnosis: blue nevi and dysplastic tissue
Traumatic hematoma, pigmented actinic keratosis, and vascular skin tumor
Seborrheic keratoses, pigmented basal cell carcinomas, and other changeable nevi
 Typical or uncommon melanocytic nevi
 Pyogenic granuloma Lentigo

Laboratory Results 

 Brain MRI if any CNS symptoms or physical findings; lactate dehydrogenase (LDH); chest/abdomen/pelvic CT with or without PET/CT at baseline and in monitoring progression in metastatic illness (stage IV);
Imaging scans are only useful in identifying and monitoring the development of metastatic illness.
Other/Diagnostic Procedures
Dermoscopy enlarges lesions, although there isn't much support for its practicality. The gold standard for diagnosis continues to be full-thickness excisional biopsy. Using an elliptical excision, punch biopsy, or scoop shave (saucerization) biopsy, any suspected nevus should be removed. Avoid shaving a suspicious lesion superficially. Full-thickness excision with 1- to 3-mm margins is the desired outcome. Excisional biopsy should be oriented to improve subsequent care.
Sentinel lymph node biopsy, a staging process, is still crucial for determining prognosis.
Nodular melanoma has mostly vertical growth, whereas the other three kinds have primarily horizontal growth.
According to estimates, 1/10,000 dysplastic nevi develop into melanoma each year.
Immunohistochemical analysis makes lymph node biopsies more sensitive.
The current American Joint Committee on Cancer (AJCC) standards for staging are based on the tumor-node-metastasis (TNM) criteria, which include:
thickness (mm) and ulceration; number of affected local lymph nodes; distant metastases; and serum LDH.
For further information, go to https:// www.cancer.org/cancer/melanoma-skincancer/detection-diagnosis-staging/melanoma-skincancer-stages.html.

Management 
The recommended main treatment for resectable/nonmetastatic melanomas is complete surgical removal of the melanoma. For recommended surgical margins, see below.
 Surgical excision is typically curative for stages I and II.

FDA-approved medications include the following for unresectable or metastatic melanoma treatment and are usually advised for treating patients in the setting of clinical trials:
- Monotherapy with anti-PD-1
Compared to ipilimumab alone, the combination therapy of Pembrolizumab (Keytruda), Nivolumab (Opdivo), and Nivolumab plus ipilimumab showed a 61% response rate.
- If the BRAF V600 activating mutation is present, the following combinations of target therapies may be used:
Vemurafenib/cobimetinib + atezolizumab (new FDA approval) Dabrafenib/trametinib 
Encorafenib/binimetinib is a medicinal treatment used as an adjuvant following complete surgical excision in high-risk patients who have lymph node involvement or metastases (Stage IIIA with sentinel lymph node metastases).
Dabrafenib/trametinib for BRAF V600-activating mutation - Stage IIB/C and IV with nodal recurrence; Pembrolizumab (Keytruda);
 Dabrafenib/trametinib for BRAF V600-activating mutation - Stage IV fully resection Pembrolizumab (Keytruda) Nivolumab (Opdivo)
Stage IV of Nivolumab (Opdivo) with nodal recurrence
Iplimumab is only advised if the patient has previously received anti-PD-1 therapy. Additional active regimens, such as dacarbazine [DTIC], temozolomide, paclitaxel, carmustine [BCNU], cisplatin, carboplatin, and vinblastine, are frequently reserved for patients who are not candidates for the recommended regimens.
Interferon was approved by the FDA as adjuvant therapy in 1995 (high dosage) and 2011 (pegylated) for the treatment of stage IIB to III melanoma; it has been demonstrated to reduce the rate of relapse after 4 years, but has no overall impact on survival; one-third of patients will stop taking it because of side effects (granulocytopenia, hepatotoxicity).

Referral Discussion with oncologist to discuss potential chemotherapeutic treatments
Depending on the severity of any nodal and/or metastatic disease, specialities in surgery may be needed.

Furthermore Treated 

Intralesional injections, topical imiquimod, laser ablation, and radiation therapy are examples of local therapies for stage III in-transit illness for patients when resection is not possible, earlier resection was ineffective, or the patient chooses to forego surgery and choose conservative management.
The intralesional injection of talimogene laherparepvec (T-VEC) is advised; other injections include those of IL-2, BCG, or IFN.

Surgical Procedures Early surgical excision with the following advised margins is part of the standard of therapy for melanoma.
- In situ cancer: 0.5 to 1.0 cm of room
- T1 thickness less than 1 mm: 1-cm margin
- 1.01 to 2.00 mm (T2) thickness: 1- to 2-cm margins
- 2-cm margins with a thickness of 2 to 4 mm (T3)
- Margin of 2 cm for thickness of >4 mm (T4).
Patients with T1b, T2, T3, and T4 stages melanomas should undergo a sentinel lymph node biopsy.
- Not advised in cases of in situ or T1a melanoma
Mohs micrographic surgery is being utilized to treat melanoma in situ, however because it uses the frozen section technique, it is not generally regarded as a therapy option for melanoma.
In addition to some head and neck lesions, lentigo maligna may be treated with radiotherapy; palliative radiation therapy may be used to treat metastatic melanoma.
Stage IIIB/C—intralesional injections in some circumstances if there are few in-transit metastases or if they cannot be completely removed surgically

Admission 
The majority of monitoring and therapy is carried out in an outpatient environment.

Take Action 

Close monitoring and skin protection (such as sunscreen and clothing with UV protection) are strongly encouraged after diagnosis and treatment.

patient observation
Routine clinical skin examination screening for individuals over 40 is debatable and has not been shown to be beneficial.
Dermoscopy and total body photography should be used to monitor skin lesions, most frequently in individuals with more than five atypical nevi.
The NCCN guidelines advise screening every 3 to 12 months based on the risk of recurrence, with annual exams if there has been no advancement of the disease for 5 years.
 At the discretion of the treating physician, surveillance chest x-ray, CT, brain MRI, and/or PET/CT scan should be performed every three to twelve months for three to five years. Patients with a history of brain metastasis should have more frequent brain MRIs.
After stage I to II melanoma has been diagnosed and treated, lab and imaging tests are not advised due to their low yield and high false-positive rates.

Patient Education – Teach all patients, especially those at high risk or who have had melanoma, to do routine full-body skin checks looking for ABCDEs.
Patients at high risk should check their skin on a monthly basis and be taught how to check hard-to-reach places.
Patients with a history of dysplastic nevus syndrome or melanoma should have routine complete body exams by a dermatologist.

Breslow depth (thickness) in millimeters continues to be one of the best indicators of prognosis.
The average age of death is 70.
 Metastatic melanoma has an average survival of 6 to 9 months; 15-20% 5-year survival with current treatment Stages I and II, appropriately treated, have 20-year survival rates of 90% and 80%, respectively. Women 45 years of age at diagnosis have the highest survival rates. 

Complications include: Metastatic spread and death; the phrase "great imitator" is frequently used to describe how many different ways metastatic disease can manifest itself; and unsatisfactory cosmetic outcomes.

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