Melanoma: Clinical sciences

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Introduction0:00–0:29

Melanoma is a very serious type of skin cancer arising from pigment-producing cells called melanocytes. It’s the fifth most common cancer in the United States and is associated with high rates of mortality.
Melanoma can develop anywhere on the body and has a high rate of spread, so early diagnosis and treatment are key to improve overall outcomes.
Alright, when a patient presents with a chief concern suggesting melanoma, the first step is to obtain a focused history and physical.

History and Physical Exam0:29–2:56

Typically, patients will report noticing a skin lesion with recent changes in size, color, or developing associated symptoms like pruritus.
Sometimes they might even notice bleeding from the lesion. A patient may also experience systemic symptoms that are alarming for malignancy, including fevers, chills, fatigue, bone pain, or weight loss.
History might reveal risk factors like a personal or family history of cutaneous malignancy or immunosuppression, as well as fair skin, a tendency to sunburn, chronic sun exposure, or previous sunburns.
On a physical exam, you’ll typically find a pigmented skin lesion like a macule, plaque, or nodule with an irregular border.
Make sure to do a full body exam checking for other similar lesions or nevi. Important findings can be summarized by the mnemonic ABCDE, which stands for Asymmetry; Border irregularities; Color variations, such as brown or black spots with other colors like red, blue, gray, or white; Diameter, often larger than 6 mm; and Evolution, like changes in size, shape, or color, depigmentation, development of streaks, pseudopods or irregular vascularity.
Some of the suspicious characteristics you should look for include bleeding, crusting, or ulceration. If you see a lesion that differs from other nevi, it is called the "ugly duckling sign".
Last but not least, remember to check regional lymph nodes for lymphadenopathy, which is concerning for possible metastasis.
If you see these findings, be very suspicious of melanoma.Here’s a clinical pearl! Primary care settings usually perform naked-eye physical examination, while dermatologic settings may also use support diagnostic tools like a dermatoscope, which acts as a magnifying glass to help evaluate the lesion in more detail.The best way to confirm the diagnosis is with an excisional or incisional biopsy of the lesion, which will provide histopathological information.

Biopsy2:56–4:54

When possible, an excisional or complete biopsy should be performed to remove the entire lesion. This is done by taking 1 to 3 mm margin of surrounding normal skin, including the depth of the thickest part of the lesion.
However, this might not be feasible if the lesion is large or located on the face, palms, or ears. In these cases, incisional, or partial, biopsy can be performed.
The important aspect of incisional biopsy is to ensure the full depth of the lesion is obtained within the sample, which is needed to determine the tumor depth.
Time for a clinical pearl! If you suspect melanoma, never obtain a shave biopsy, as it doesn’t obtain the full depth of the lesion, leading to inaccurate staging and inadequate treatment!Okay, histopathology findings consistent with melanoma include atypical melanocytes with hyperchromatic nuclei, or other abnormal nuclei or nucleoli characteristics, in addition to asymmetric, poorly circumscribed nests of melanocytes.
If findings aren’t consistent with melanoma, consider an alternative diagnosis; but if these findings are present, you can confirm your diagnosis of melanoma.
Here’s a clinical pearl! There are four main subtypes of melanoma.
Superficial spreading melanoma is the most common one, accounting for 60% of cases, followed by nodular melanoma, which makes up 15 to 30% of cases.
The last two types, lentigo maligna melanoma and acral lentiginous melanoma, are much less common. Other rare subtypes include amelanotic, dermoplastic, and spitzoid melanoma.Now that you’ve made your diagnosis, your next step is to assess the Breslow thickness as well as ulceration.

Histology4:54–6:15

The Breslow thickness examines the lesion’s depth, meaning its vertical growth in millimeters from the most superficial aspect of the tumor, usually within the epidermis, down to the deepest layer.
Depth, along with ulceration, are very important characteristics to help determine the appropriate treatment.Here’s a clinical pearl!
High mitotic rate, seen from the biopsy, greater than or equal to 1 per millimeter squared is no longer used to determine the staging of melanoma.
However, it’s a strong prognostic factor to keep in mind.And now a high-yield fact! In addition to the Breslow thickness, the lesion’s depth can be measured using the Clark level, although current practices are moving away from it.
Clark Level 1 indicates tumor extension into the epidermis, while Clark Level 2 represents invasion into the papillary dermis.
Clark Level 3 means the tumor has spread through the papillary-reticular interface, and Clark Level 4 represents extension into the reticular dermis.
Lastly, Clark Level 5 means the tumor has spread into the subcutaneous tissue.Okay, let's go back and talk about treatment options.

Breslow Thickness6:15–8:08

If the Breslow thickness is less than or equal to 0.8 mm, and the lesion has no signs of ulceration, wide local excision should be performed for any remaining lesion, inadequate margins, or if a biopsy scar remains, since there's a possibility that some malignant cells might still be present within these remaining tissues.Remember to assess the deep and peripheral margin status of the initial biopsy to see if all of the cancer was excised.
Generally, how much of the margin to take depends on the thickness of the lesion. Let's look at some examples: melanoma in situ involves lesions that haven’t invaded the basement membrane and are usually smaller than 0.5 mm in thickness, so a 0.5 cm to 1 cm margin is recommended.
For T1 melanoma that’s smaller than 1 mm in thickness, at least 1 cm margin should be taken. T2 lesions are between 1 and 2 mm in thickness, and 1 to 2 cm margin is recommended.
And lastly, for T3 and T4 melanomas, which have a depth greater than 2 mm, 2 cm margin should be taken. Keep in mind that margins are measured in all directions, including depth.
Once the wide local excision has been performed, continue surveillance of these patients every 6 months for the first 2 years, then annually.Alright, let's go back to the Breslow thickness.
For lesions that are greater than 0.8 mm in thickness, or lesions of any depth with ulceration, your next step is to determine the TNM staging.The purpose of TNM staging is to assess for any locoregional lymph node involvement or distant metastasis.

TNM Staging8:08–8:53

This is often done with CT of the chest, abdomen, and pelvis; as well as a PET CT scan, which involves administering a radiotracer that will be collected by cells with abnormally high metabolism, like cancer or inflammatory cells.
This way, it reveals areas of the body that might contain cancer cells. Sometimes CT of the neck is also done if the primary tumor is located on the face, head, or neck.
Lastly, an MRI of the brain can be obtained if there is a high suspicion for brain metastasis. Let’s start with patients with no distant metastases.
For isolated or locoregional disease, the treatment includes wide local excision to remove the entire tumor with appropriate margins.

No Distant Metastasis8:53–10:10

Also, consider a sentinel lymph node biopsy for patients who are at high risk for regional metastasis. Typically, that includes primary tumors with thickness from 1 to 4 mm and or diameter greater than 4 mm.
If the sentinel node is positive for melanoma, the next step is to perform a complete lymphadenectomy of the regional nodal basin.
Then, the excised specimen should be sent out to test for BRAF V600 mutation, which is the most common mutation found in melanoma.
Patients who are BRAF-positive can be considered for adjuvant immunotherapy, especially if they have node-positive disease.
Additionally, this therapy can be considered in patients who are at high risk for recurrence or regional metastasis. After the completion of primary therapy, patients will need close surveillance to monitor for recurrence.
Surveillance includes a total body skin and lymph node examination every 6 months for the first 2 years and then annually.Now let’s talk about patients who have distant metastases.
The presence of distant metastases means that the patient has stage 4 melanoma. Your next step is to assess the metastasis location, and test the patient’s BRAF V600 status.

Distant Metastasis10:10–11:21

Those with single or isolated metastases, like to the lung, might be candidates for surgical resection. However, this is a very complex decision based on many factors, including the patient’s prognosis, location of tumors, and the complexity of the operation, among others.
Even though treatment generally involves using systemic immunotherapy, if the tumor is BRAF-positive, adjuvant targeted therapy can be considered.
Now, if the patient has disseminated metastasis, treatment options are limited to immunotherapy based on BRAF status and palliative care.
Although immunotherapy can play a role in extending overall survival, the prognosis is still very poor, so palliative care should be offered.Alright, as a quick recap… Melanoma is diagnosed with a biopsy, and treated based on its Breslow thickness.
Tumors less than or equal to 0.8 mm in depth without ulceration can be treated with wide local excision. However, for tumors greater than 0.8 mm or the ones with ulceration, TNM staging guides treatment.

Review11:21–12:12

Melanoma without metastasis can be managed with wide local resection and adjuvant immunotherapy if BRAF-positive. For those with isolated metastasis, surgical resection can be considered, and adjuvant immunotherapy offered if the tumor is BRAF-positive.
Lastly, patients with disseminated metastases aren’t generally considered surgical candidates, so immunotherapy and palliative care should be offered.
if the tumor is B raf positive Lastly patients with disseminated metastases aren't generally considered surgical candidates So