Malignant melanoma diagnosis and management has advanced recently. Melanoma arises from melanocytes and can affect the skin, eyes, or internal organs. Recent trends include more accurate staging using tumor thickness, ulceration, and mitosis rate rather than Clark's level. Sentinel lymph node biopsy helps stage intermediate thickness melanomas. For advanced cases, targeted therapies like BRAF inhibitors and immunotherapies have improved outcomes. Wide local excision remains the main surgical treatment, with reconstruction to optimize function and allow adjuvant therapies. Long-term follow-up is important due to the risk of late recurrence.
Please find the power point (ppt.) on everything that you need to know about Malignant melanoma in very simple language by Sunil kumar Daha from very reliable references. Especially focused on surgical interventions. Thank you
Please find the power point (ppt.) on everything that you need to know about Malignant melanoma in very simple language by Sunil kumar Daha from very reliable references. Especially focused on surgical interventions. Thank you
Squamous cell carcinoma of skin | management -all medical aspects.martinshaji
Squamous cell carcinoma of the skin is a common form of skin cancer that develops in the squamous cells that make up the middle and outer layers of the skin. Squamous cell carcinoma of the skin is usually not life-threatening, though it can be aggressive. Squamous cell carcinomas may appear as flat reddish or brownish patches in the skin, often with a rough, scaly, or crusted surface. They tend to grow slowly and usually occur on sun-exposed areas of the body, such as the face, ears, neck, lips, and backs of the hands.
this is a detailed discussion on the topic
please comment
thank u
Melanoma
Cutaneous Melanoma
also known as malignant melanoma, is a type of cancer that develops from the pigment-containing cells known as melanocytes.
Classification Of Melanoma
I : De novo melanoma
A. Melanoma in situ (MIS)
B. Lentigo maligna melanoma (LMM)
C. Superficial spreading melanoma (SSM)
D. Nodular melanoma (NM)
E. Acral-lentiginous melanoma (ALM)
F. Melanoma of the mucous membranes
G. Desmoplastic melanoma
II Melanoma arising from precursors
Melanoma arising in dysplastic nevomelanocytic nevi
B. Melanoma arising in congenital nevomelanocytic nevi
C. Melanoma arising in common NMN
Etiology And Pathogenesis
The etiology and pathogenesis of cutaneous melanoma are unknown.
Epidemiologic studies demonstrate a role for genetic predisposition and sun exposure in melanoma development.
The major genes involved in melanoma development reside on chromosome 9p21.
Etiology
UVR, mostly of the UVB spectrum (290–320 nm) that induces mutations in suppressor genes. The propensity for multiple BCC may be inherited. Associated with mutations in the PTCH gene in many cases.
Predisposing Factors
Genetic markers (CDKN2a mutation)
Skin type I/II
Family history of dysplastic nevi or melanoma
Personal history of melanoma
Ultraviolet irradiation, particularly sunburns during childhood and intermittent burning exposures
Number (>50) and size (>5 mm) of melanocytic nevi
Congenital nevi
Number of dysplastic nevi (>5)
Dysplastic melanocytic nevus syndrome
Immune suppression (debatable)
Number (>50) and size (>5 mm) of melanocytic nevi
Congenital nevi
Number of dysplastic nevi (>5)
Dysplastic melanocytic nevus syndrome
Immune suppression (debatable)
Six Signs of Malignant Melanoma (ABCDE Rule):
A- Asymmetry in shape—one-half unlike the other half.
B- Border is irregular—edges irregularly scalloped, notched, sharply defined.
C- Color is not uniform; mottled—haphazard display of colors; all shades of brown, black, gray, red, and white.
D- Diameter is usually large.
E- Elevation is almost always present and is irregular—surface distortion is assessed by side-lighting. others use E for Enlargement— a history of an increase in the size of lesion is one of the most important signs of malignant melanoma.
Lentigo Maligna Melanoma (LMM)
Squamous cell carcinoma of skin | management -all medical aspects.martinshaji
Squamous cell carcinoma of the skin is a common form of skin cancer that develops in the squamous cells that make up the middle and outer layers of the skin. Squamous cell carcinoma of the skin is usually not life-threatening, though it can be aggressive. Squamous cell carcinomas may appear as flat reddish or brownish patches in the skin, often with a rough, scaly, or crusted surface. They tend to grow slowly and usually occur on sun-exposed areas of the body, such as the face, ears, neck, lips, and backs of the hands.
this is a detailed discussion on the topic
please comment
thank u
Melanoma
Cutaneous Melanoma
also known as malignant melanoma, is a type of cancer that develops from the pigment-containing cells known as melanocytes.
Classification Of Melanoma
I : De novo melanoma
A. Melanoma in situ (MIS)
B. Lentigo maligna melanoma (LMM)
C. Superficial spreading melanoma (SSM)
D. Nodular melanoma (NM)
E. Acral-lentiginous melanoma (ALM)
F. Melanoma of the mucous membranes
G. Desmoplastic melanoma
II Melanoma arising from precursors
Melanoma arising in dysplastic nevomelanocytic nevi
B. Melanoma arising in congenital nevomelanocytic nevi
C. Melanoma arising in common NMN
Etiology And Pathogenesis
The etiology and pathogenesis of cutaneous melanoma are unknown.
Epidemiologic studies demonstrate a role for genetic predisposition and sun exposure in melanoma development.
The major genes involved in melanoma development reside on chromosome 9p21.
Etiology
UVR, mostly of the UVB spectrum (290–320 nm) that induces mutations in suppressor genes. The propensity for multiple BCC may be inherited. Associated with mutations in the PTCH gene in many cases.
Predisposing Factors
Genetic markers (CDKN2a mutation)
Skin type I/II
Family history of dysplastic nevi or melanoma
Personal history of melanoma
Ultraviolet irradiation, particularly sunburns during childhood and intermittent burning exposures
Number (>50) and size (>5 mm) of melanocytic nevi
Congenital nevi
Number of dysplastic nevi (>5)
Dysplastic melanocytic nevus syndrome
Immune suppression (debatable)
Number (>50) and size (>5 mm) of melanocytic nevi
Congenital nevi
Number of dysplastic nevi (>5)
Dysplastic melanocytic nevus syndrome
Immune suppression (debatable)
Six Signs of Malignant Melanoma (ABCDE Rule):
A- Asymmetry in shape—one-half unlike the other half.
B- Border is irregular—edges irregularly scalloped, notched, sharply defined.
C- Color is not uniform; mottled—haphazard display of colors; all shades of brown, black, gray, red, and white.
D- Diameter is usually large.
E- Elevation is almost always present and is irregular—surface distortion is assessed by side-lighting. others use E for Enlargement— a history of an increase in the size of lesion is one of the most important signs of malignant melanoma.
Lentigo Maligna Melanoma (LMM)
Includes most common tumors of oral cavity including scc,bcc, melanoma, ameloblastoma, odontoma, fibromas, pindborg tumors etc.
Presented by Dr. Binaya Subedi
#Skin malignancy is the most common malignancy in fair-skinned populations.
#Skin malignancies are either non-melanoma or melanoma.
#A persistent skin lesion that does not heal is highly suspicious for malignancy and should be examined by a health care provider.
# Early detection and treatment can often lead to a highly favourable prognosis.
June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
unwillingness to rectify this violation through action requires accountability.
Postsecondary education is a unique opportunity for students to learn and have their ideas and beliefs challenged. However, universities receiving hundreds of millions of federal funds annually have denied
students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
• The Committee on Oversight and Accountability is investigating the sources of funding and other support flowing to groups espousing pro-Hamas propaganda and engaged in antisemitic harassment and intimidation of students. The Committee on Oversight and Accountability is the principal oversight committee of the US House of Representatives and has broad authority to investigate “any matter” at “any time” under House Rule X.
• The Committee on Ways and Means has been investigating several universities since November 15, 2023, when the Committee held a hearing entitled From Ivory Towers to Dark Corners: Investigating the Nexus Between Antisemitism, Tax-Exempt Universities, and Terror Financing. The Committee followed the hearing with letters to those institutions on January 10, 202
Safalta Digital marketing institute in Noida, provide complete applications that encompass a huge range of virtual advertising and marketing additives, which includes search engine optimization, virtual communication advertising, pay-per-click on marketing, content material advertising, internet analytics, and greater. These university courses are designed for students who possess a comprehensive understanding of virtual marketing strategies and attributes.Safalta Digital Marketing Institute in Noida is a first choice for young individuals or students who are looking to start their careers in the field of digital advertising. The institute gives specialized courses designed and certification.
for beginners, providing thorough training in areas such as SEO, digital communication marketing, and PPC training in Noida. After finishing the program, students receive the certifications recognised by top different universitie, setting a strong foundation for a successful career in digital marketing.
Executive Directors Chat Leveraging AI for Diversity, Equity, and InclusionTechSoup
Let’s explore the intersection of technology and equity in the final session of our DEI series. Discover how AI tools, like ChatGPT, can be used to support and enhance your nonprofit's DEI initiatives. Participants will gain insights into practical AI applications and get tips for leveraging technology to advance their DEI goals.
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
This presentation includes basic of PCOS their pathology and treatment and also Ayurveda correlation of PCOS and Ayurvedic line of treatment mentioned in classics.
Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
Thinking of getting a dog? Be aware that breeds like Pit Bulls, Rottweilers, and German Shepherds can be loyal and dangerous. Proper training and socialization are crucial to preventing aggressive behaviors. Ensure safety by understanding their needs and always supervising interactions. Stay safe, and enjoy your furry friends!
A review of the growth of the Israel Genealogy Research Association Database Collection for the last 12 months. Our collection is now passed the 3 million mark and still growing. See which archives have contributed the most. See the different types of records we have, and which years have had records added. You can also see what we have for the future.
Delivering Micro-Credentials in Technical and Vocational Education and TrainingAG2 Design
Explore how micro-credentials are transforming Technical and Vocational Education and Training (TVET) with this comprehensive slide deck. Discover what micro-credentials are, their importance in TVET, the advantages they offer, and the insights from industry experts. Additionally, learn about the top software applications available for creating and managing micro-credentials. This presentation also includes valuable resources and a discussion on the future of these specialised certifications.
For more detailed information on delivering micro-credentials in TVET, visit this https://tvettrainer.com/delivering-micro-credentials-in-tvet/
The simplified electron and muon model, Oscillating Spacetime: The Foundation...RitikBhardwaj56
Discover the Simplified Electron and Muon Model: A New Wave-Based Approach to Understanding Particles delves into a groundbreaking theory that presents electrons and muons as rotating soliton waves within oscillating spacetime. Geared towards students, researchers, and science buffs, this book breaks down complex ideas into simple explanations. It covers topics such as electron waves, temporal dynamics, and the implications of this model on particle physics. With clear illustrations and easy-to-follow explanations, readers will gain a new outlook on the universe's fundamental nature.
MATATAG CURRICULUM: ASSESSING THE READINESS OF ELEM. PUBLIC SCHOOL TEACHERS I...NelTorrente
In this research, it concludes that while the readiness of teachers in Caloocan City to implement the MATATAG Curriculum is generally positive, targeted efforts in professional development, resource distribution, support networks, and comprehensive preparation can address the existing gaps and ensure successful curriculum implementation.
Introduction to AI for Nonprofits with Tapp NetworkTechSoup
Dive into the world of AI! Experts Jon Hill and Tareq Monaur will guide you through AI's role in enhancing nonprofit websites and basic marketing strategies, making it easy to understand and apply.
How to Add Chatter in the odoo 17 ERP ModuleCeline George
In Odoo, the chatter is like a chat tool that helps you work together on records. You can leave notes and track things, making it easier to talk with your team and partners. Inside chatter, all communication history, activity, and changes will be displayed.
2. Malignant Melanoma
• Melanoma is a cancer of melanocytes and can, therefore, arise in
skin, mucosa, retina and the leptomeninges.
3. EPIDEMIOLOGY
• Cutaneous melanoma is caused by exposure to UVR. Its rise in
incidence reflects increased recreational activity in the sun
• It accounts for less than 5% of skin malignancy (and 1.6% of all
malignancy worldwide), it is responsible for over 75% of skin
malignancy-related deaths.
• It is the commonest cancer in young adults (20–39 years) and the
most likely cause of cancer-related death.
4. Clinical features
• Only 10–20% of MM form in pre-existing naevi, with the remainder
arising de novo in previously normally pigmented skin.
• The most likely naevi to form MM are atypical naevi, atypical
junctional lenitiginous naevi (usually facial) and giant pigmented
congenital naevi.
5. • Macroscopic features in naevi suggestive of malignant melanoma
● Change in size (diameter more than 6 mm)
● Shape
● Colour
● Thickness (elevation/nodularity or ulceration)
● Satellite lesions (pigment spreading into surrounding area)
● Tingling/itching /serosanguinous discharge (usually late signs)
7. • Head and neck—25%
• Trunk—25%
• Lower limb—25%
• Upper limb—11%
• Other sites—14%
Other sites: Eyes (iris, ciliary body, choroids), muco cutaneous junction
(anorectal region, genitalia), head and neck (meninges, oropharynx,
nasopharynx, paranasal sinuses)
8. Classifications
• Breslow’s classification
Based on thickness of invasion measured by optical micrometer—
most important prognostic indicator until nodal spread
I: Less than 0.75 mm
II: Between 0.76 to 1.5 mm
III: 1.51 mm to 4 mm
IV: More than 4 mm
9. • Clark’s levels
Level 1: Only in epidermis
Level 2: Extension into papillary dermis
Level 3: Filling of papillary dermis completely
Level 4: Extension into reticular dermis
Level 5: Extension into subcutaneous tissue
10.
11. There are four common macroscopic variants of MM
• Superficial spreading melanoma (SSM) 70%
• Nodular melanoma (NM) 12 - 25%
• Lentigo maligna melanoma (LMM) 7 -15%
• Acral lentigious melanoma (ALM) 5%
13. Superficial spreading melanoma (SSM)
• This is the most common presentation (70%),
• usually arising in a pre-existent naevus after several years of slow
change, followed by rapid growth in the preceding months before
presentation .
• Nodularity within SSM heralds the onset of the vertical growth
phase.
14.
15. Nodular melanoma (NM)
• Nodular melanoma accounts for 15% of all MM
• More aggressive than SSM
• Arise de novo in skin and are more common in men than women
• They typically appear as blue/black papules
• They lack the horizontal growth phase, so they tend to be sharply
demarcated.
• Up to 5% are amelanotic.
16.
17. Lentigo maligna melanoma LMM
• previously known as Hutchinson’s melanotic freckle.
• This variant presents as a slow-growing, variegated brown macule on
the face, neck or hands of the elderly.
• They are positively correlated with prolonged, intense sun exposure,
affecting women more than men.
• They account for between 5% and 10% of MM.
18.
19. Acral lentigious melanoma (ALM)
• ALM affects the soles of feet and palms of hands
• presents as a flat, irregular macule.
• 25% are amelanotic and may mimic a fungal infection or pyogenic
granuloma.
20.
21. subungual melanoma
Hutchinson’s sign:
nail fold pigmentation that widens progressively to produce a triangular
pigmented macule with associated nail dystrophy.
• The differential diagnosis is ‘benign racial melanonychia’, which
produces a linear dark streak under a nail in a dark- skinned
individual.
• Malignancy is unlikely if the nail fold is uninvolved
22. • MM under the finger nail are usually SSM rather than ALM. For finger
or toe nail lesions it is vital to biopsy the nail matrix, rather than just
the pigment on the nail plate.
23. Contrary to the Western countries, in India the more common varieties
seen of Melanoma are :
• Amelanotic,
• Acral lentiginous and
• Desmoplastic
They usually have no relation to UV exposure and occur often on
unexposed body areas.
24. • Amelanotic melanoma may present as a flesh-coloured, skin lesion
as a metastasis from an unknown skin primary;
or, in the gastrointestinal tract, with obstruction or intussusception.
25. • Desmoplastic melanoma is mostly found on the head and neck
region.
• It has a propensity for perineural infiltration and often recurs locally if
not widely excised.
• It may be amelanotic clinically.
26. MANAGEMENT -RECENT TRENDS
Malignant Melanoma management has undergone a paradigm change
due to
• better understanding of its genetics, histopathology, behavior
and discovery of various immuno modulators and target therapies.
27. Staging & Prognosis
• 1. Clarks level of tumour invasion is NO more a part of the AJCC TNM
staging.
• 2. Histopathology plays a crucial role in TNM staging with tumour
thickness, ulceration, mitosis rate.
• 3. Breslow’s tumour thickness in mm from histopathology forms the
main basis for staging.
• 4. The other important staging factors are Ulceration and Mitotic
Rate.
• 5. Mitotic rate >1/mm2 and presence of ulceration has poorer
prognosis.
28.
29.
30. Diagnosis
• 1. Excision biopsy with 1-2mm margins is the gold standard for
staging.
• 2. Partial biopsy techniques like incisional biopsy, punch biopsy and
shave biopsies may lead to inaccurate staging and possible effect on
subsequent surgical treatment.
• 3. Full thickness incisional biopsy may sometimes be indicated in
large lesions due to practical reasons but shave biopsies should be
avoided as they fail to provide the information about tumour
thickness necessary for proper staging.
However the type of biopsy has not been shown to alter survival or
recurrence.
31. • 4. Physical Examination must pay attention to other suspicious
lesions, tumour satellite lesions, in-transit metastases, draining
lymphnodes and systemic metastases.
• 5. T1 lesions ( ≤1mm) are considered low risk melanomas and need
no further investigations.
• Sentinel lymph node biopsy (SLNB).
32. Other Investigations
.
• FNAC of lymph node.
• US abdomen to look for liver secondaries (usually huge
hepatomegaly occurs).
• Chest X-ray to look for secondaries in lung (“cannon ball”
appearance).
• HRCT of chest is ideal
33. • Relevant other methods depending on site and spread, e.g. CT scan
of head, chest, abdomen, pelvis.
• Urine for melanuria signifies advanced disease.
• Tumour markers—LDH; Melan – A; S 100; tyrosinase; HMB 45 are the
tumour markers used.
• MRI of the area;
• PET scan to detect the spread—in seleted patients only.
34. • B-RAF mutation in a proto-oncogene responsible for making a
protein B-raf has been associated with poor prognosis but has also
lend itself to target therapy improving outcomes.
• Human melanoma black 45 (HMB 45) is a monoclonal antibody
against specific antigen (Pmel 17) present in melanocytic tumours.
HMB 45 has got 92% sensitivity.
35. Surgical Excision & Lymphnode Management
• Frozen sections are unreliable for checking accuracy of resected
margins as it fails to differentiate between normal melanocytes and
melanoma cells.
• Whenever possible Excision biopsy should be done with minimal
margins for staging and further excision margins can be decided on
the basis of Breslow thickness.
36.
37. • Melanomas with 1-2mm thickness the largest possible margin should
be taken as per guideline but a balance has to be struck between
oncological safety and resulting deformity more so in the case of the
face where usually 1cm margins are preferred over 2cm.
• Margins higher than 2cm have not been shown to give any advantage.
38. Sentinel Lymph Node Biopsy(SLND)
• SLND is only a staging procedure for N0 neck to check the draining
lymphnode basin for occult micro-metastases.
• SLND does not improve overall survival but has been shown to
improve 10yr disease free survival rates in intermediate thickness
melanomas(1-4mm) and should be done in all these cases.
• The risk of occult lymphnode involvement in intermediate thickness
melanomas is 20-40%.
• There is also evidence that SNLD has advantage in thin melanomas
>0.75mm especially when associated with high risk factors like
ulceration and high mitotic rates.
39. • FNAC is indicated for all palpable nodes in the regional draining basin
and CLND usually performed in all palpable node patients or positive
SNLD N0 is accompanied by a high complication rates especially
lymphedema.
40. Reconstruction strategies
• As surgical excisions are becoming ‘less radical’, reconstruction
techniques using split or full thickness skin grafts and flaps are being
used to do functional salvage of limbs and appendages.
• Reconstruction also allows for extensive resections in big tumours
improving disease free survival rates and also allows early adjuvant
therapies due to accelerated healing of surgical sites.
41. • Reconstructive techniques allow generous excision margins and good
functional rehabilitation.
• Incomplete margins of excision should be treated with Re-Excision
with 1-2cms margins.
• Surgical approach in many situations like Ear melanomas and Limb
melanomas is becoming ‘less radical’ and more function preserving.
42. • Facial melanomas post wide local resections are reconstructed with a
wide variety of advancement, transposition or pedicled flaps
43.
44. • Ear Melanomas are increasingly being treated with perichondrium
preserving techniques and skin grafting where there is no invasion
into the perichondrium.
• In cases with such invasions wedge resection and reconstructive flap
techniques like Antia-Buch advancement flaps give excellent aesthetic
results without compromising on tumour clearance.
45.
46. • Subungual and limb melanomas are also not being subjected to
amputations any more in most cases barring a huge tumour burden
or very aggressive disease based on its physical or histopatholgical
features.
• Heel melanomas are dealt with wide local excisions and
Microvascular free flap transfer reconstructions allowing normal
ambulation and weightbearing in these patients.
47.
48.
49. Adjuvant Therapies
• 1. No conclusive evidence has shown overall survival benefits of
adjuvant therapies like Elective Lymph Node Dissection (ELND),
Isolated limb perfusion, Radiotherapy or Chemotherapy in advanced
melanomas.
• 2. Surgical Excision of distant metastases if possible with minimal
complications should be the preferred palliative treatment. May have
survival benefits in some cases.
•
• 3. Radiotherapy plays a role in local control, pain alleviation and
palliation in brain metastases, bone, soft tissue and nerve
compressions.
50. • Radiotherapy combined with gene target therapy or immune-
modulating agents is under trials and showing promising results.
• However B-RAF inhibitor gene therapy agents are radio-sensitisers
and can cause increase radiation toxicity.
• With such patients stereotactic radiotherapy can be done instead of
whole brain irradiation to decrease radiation induced complications.
51. Systemic Therapies for Advanced Malignant Melanomas
• 1. Gene target therapy with monoclonal antibodies
• 2. Immunomodulating agents
52. • Gene target therapy with monoclonal antibodies
Vemurafenib against genetic mutations of B-RAF
Dabrafenib N-RAS genes.
Thus all advanced melanomas should now be subjected to genetic
testing with immunohistochemistry.
40% Melanoma patients show B-RAF mutations.
53. B-RAF inhibitors and MEK (Mitogen-activated-extracellular signal
regulated kinase) inhibitors can support first line therapies in patients
with
• High tumour burden,
• Brain metastases,
• Elevated LDH levels,
• Inflammatory syndrome
• Bone marrow involvement
• Pre-existing auto-immune disorders like Crohn’s Syndrome,
Rheumatoid arthritis, Wegner’s granulomatosis etc. which form a
contraindication for immunomodulatory agent administration.
54. • Immunomodulating agents are showing a huge promise in the rest majority
60% of advanced melanoma patients who do not show genetic mutations
in histopathology
• Anti-CTLA4 (cytotoxic T lymphocyte associated antigen-4) antibody
Ipilimulab has shown survival benefits even in stage IV disease.
• Anti-PDI (programmed death-I) antibodies Pembrolizumab & Nivolumab
have shown promising survival benefits in advanced melanomas.
• Combination of Ipilimulab and Nivolumab in recent trials such as
CHECKMATE 067 trial is showing wonderful results.
• Many patients on immune modulatory agents will develop vitiligo white
patches but these are considered as a marker of good response.
55. Chemotherapy
Indications:
a. Secondaries in lungs, liver, bones.
b. After surgery for melanoma.
Drugs are:
a. DTIC: Diethyl triamine iminocarboxamide.
b. Melphalan (Phenyl alanine mustard)
c. Carboplatin, vindesine.
d. CVD regime—is cisplatin, vinblastine and dacarbazine.
56. PROGNOSIS
• The Breslow thickness of the primary tumour offers the best
correlation with survival in stage I disease.
• The higher the mitotic index, the poorer is the prognosis of the
primary tumour. This has greater significance than the presence or
absence of ulceration.
• The presence of lymph node metastases is the single most important
prognostic index in melanoma, outweighing both tumour and host
factors.
• The number of affected nodes and the presence of extranodal
extension are also significant out- come predictors.
• Once regional nodes are clinically involved, 70–85% of patients will
have occult distant metastases.
57. Followup
• 90% melanomas recurrence happens in the first 5yrs of resection and
hence the frequency of follow-up has to be 3-6monthly.
• If feasible 10yr follow-up is recommended as melanomas can recur or
metastasize late.
• In thin melanomas no imaging is required
• In thicker melanomas ultrasound for lymph node basin should be done as
it is safe and relatively inexpensive.
• Abdominal, chest imaging and PET-CT Scan may be required for follow up
in advanced melanomas (Stage IIC and above)
• S-100 protein is a tumour marker that can denote disease relapse
especially relevant in advanced melanomas.