Malignant melanoma and Amelonatic

Malignant melanoma and Amelonatic

Introduction

Malignant melanoma it is a type from skin cancer which arise from epidermal skin layer  from melanocyte cells or pigment cells which responsible for release of melanin pigment which give the skin it is colour malignant melanoma can arise in any part in the body which containing melanocyte cells such as in the skin of the head and neck, trunk , lower and upper limbs
 There are special site of malignant melanoma  which can be arise such as mucosal as mucous membrane of the nose or the mouth( sublingual), eye as conjunctiva , choroid and pigmented layer of the retina and genitalia
 Also there are hidden area of malignant melanoma which can be found such as pia and arachnoid matter which they are  the layer of brain covering and adrenal medulla
 Malignant melanoma it is the most aggressive type of skin cancer which it is more common in Caucasian than black
Melanocytes produce melanin pigment during exposure to the sun to protect us from the burning effect of the sun

Skin cancer when arise from the basal layer of the epidermis is called basal cell carcinoma see here
When arise from squamous cell layer is called squamous cell carcinoma see here

When arise from the melanocytes cell producing pigment is called malignant melanoma
 
What are the causes of malignant melanoma
There are predisposing factors which associated with malignant melanoma formation such as
  • Exposure to the sunlight in which the ultraviolet rays cause damage to the DNA nucleous especially intermittent exposure is more closely associated with melanoma than regular exposure
  • Sunbeds and tanning lamps carry a potential risk
  • Albinism and xeroderma pigmentosum have higher risk
  • Red fair haired skin
  • Hereditary or genetic inheritance
  • Gaint congenital naevi of more than 20 cm in diameter have increased risk of malignant change which may occur in the first 10 years of life
What are premalignant condition of melanoma
  • Congenital gaint or bathing trunk naevus or mole
  • Melanosis of the eye conjunctiva
  • Hutchinson,s freckle or lentigo which mean presence of large area of pigmentation in old age patient more than 60 years on the face and is slow growing mainly smooth but may developed rough ares of junctional activity which are at increased risk of malignant change
  • Junction melanoma in which the melanocytes lies in the deep layers of the epidermis they appear as tiny dark points and look as if paint is sprinkled on the skin
  • Compound melanoma in which the melanocytes are present both in the dermis and epidermis
What are symptoms and signs of malignant melanoma

Any individual with mole or naevi in his skin body should be aware about the warring signs which if present this may indicated of malignant transformation  these warring signs such as
  • If the mole become increased in size
  • If the mole colour changed either decreased or increased pigment
  • If the mole become has fissuring 
  • If the mole become ulcerated
  • If the mole become painful
  • If the mole become bleeding
  • If the mole become indurated
  • If the mole become itchy
  • If the mole pigment spread as satellite nodules around it due to lymphatic permeation
The physician should be asked about
  • If there is family history of previous malignant melanoma
  • If there is family history of multiple melanoma syndrome
  • If there is recent history of mole changes in its colour size shape or become painful or ulcerated or itching or bleeding
  • If there is previous history of intermittent sun exposure
  • If there previous history of pancreatic cancer or astrocytoma
  • If there is previous history of skin cancer
The physician should be examined the whole body skin to detect any suspected lesion to deal with it also if the individual notice any abnormalities in the mole or naevi such as warring signs he should be immediately investigated by the physician to excluded any malignant transformation
   
What are the types of malignant melanoma
There are many types of malignant melanoma such as
Superficial spreading malignant melanoma
  • Account for about 65%
  • Commonest types
  • Can occur on any part of the body
  • Usually palpable but thin with irregular edge
  • Has variable colour but common black  with satellites
  • Occur on the leg of female and back of male also present in the palm of the hand and sole of the foot
Nodular melanoma
  • Account for about 27%
  • Thick protruding with a smooth surface and regular outline
  • May become bleeding and ulcerated
  • Commonly black lump with rapid growth
  • Most dangerous
 Lentigo maligna melanoma
  • Account for about 7%
  • Malignant melanoma arsing in Hutchinson melanotic freckle
  • Malignant areas are thicker than the surrounding pigmented skin
  • Usually dark in colour
  • Very rare to be ulcerated
  • Irregular common present in the face
  • Best prognosis
Acral lentiginous melanoma
  • Account for about 1%
  • Rare type
  • Can be present in the palm of the hand and sole of the foot
  • Can also present as a chronic paronychia or sub-ungual  haematoma
  • Has irregular expanding area of brown or black pigmentation on the palm ,sole or beneath a nail as sub-ungual melanoma
  • Poor prognosis
Amelanotic melanoma
  • Account for about 1%
  • May be pink with some pigmentation at the base
  • Presents with lymph nodes involvement
  • Worse prognosis
What are the classification and staging of malignant melanoma
The malignant melanoma can be classified and staged as follow
Histological classification

Clark-McGovern Level
Level 1 : In situ melanoma - melanoma confined to the basal epidermis with no dermal invasion
Level 2 : Invasion of the subepidermal and connective tissue known as the papillary dermis
Level 3 : Invasion of the level of the junction between the papillary and reticular dermis
Level 4 : Invasion of the reticular dermis
Level 5 : Invasion of the subcutaneous tissues
Breslow Tumor Thickness Measurement TTM
The thickness is measured by an optical micrometer from the top of the granular layer of the epidermis to the deepest melanoma cells in the dermis

A modified version of the American Joint C omittee on Cancer|Union Internationale Contre le Cancer AJCC|UICC staging system is the most widely used
pTx  Primary tumor cannot be assessed
pT0  No evidence of primary tumor
Clark level  I    pTis : Melanoma in situ intra-epidermal
Clark level  II   pT1 :Less than 0.75 mm thick and invades the papillary dermis
Clark level  lII  pT2 :0.75-1.5 mm thick with or without invades to papillary -reticular dermis interface
Clark level IV pT3 : 1.5-4 mm thick with or without invades reticular dermis
pT3a  1.5- 3 mm thick
pT3b  3-4 mm thick
pT4  more than 4 mm thick

TNM system T means tumor N mean lymph nodes M means distant metastases
Stage I       pT1|2 :N0.M0
 Stage II      pT3|4 : N0 ,M 0
 Stage III     Any pT:N1-2 ,M0
Stage IV   Any pT: any N,M1
Investigations of malignant melanoma
Laboratory
Complete blood count for surgical fitness
Lactic dehydrogenase may be raised
Other according to the case
Radiological
Chest X rays and CT scanning
Utrasound and CT scanning of the abdomen and pelvis
MRI scanning of the brain
PTE scanning for detection of metastases
Other investigations according to the case
Biopsy
Biopsy taken either from the primary tumor or from the regional lymph nodes

  Biopsy from the tumor

Either by removal part from the tumor called incisional biopsy or removal the whole tumor called excisional biopsy then the biopsy taken for histopathological examination under microscope for detection of cancer cells
Biopsy from the lymph nodes
Fine needle aspiration cytology FNAC
 For detection cytology of cancer cells such as loss of cellular cohesiveness : nuclei oriented in different directions and irregularly spaced cells become detached from one another
pleomorphism : variation in size ,shape and number of nucleoli
nuclear to cytoplasmic ratio increased abnormal mitoses and so on
Sentinal lymph nodes biopsy
Sentinal node means its the first lymph nodes received the cancer metastases and taken the dye in this technique the tumor is injected by special dye called patent blue dye around it then wait about 5-10 minute untill the dye can reach the regional lymph nodes then the sentinal nodes can by identified by gamma prob which appear as a hot spot  or by incision over the regional lymph nodes in which the sentinal nodes appear taken the blue dye and can be seen easily then taken for microscopic examination for detection of cancer cells in such case immunohistochemical staining can be used which give best result than cytological one
The aim from these sentinal nodes may to avoid complete removal of the regional lymph nodes but remove only the node taken the dye and have cancer cells to prevent the complications of removal of the all regional nodes such as lymph-edema
Treatment of the malignant melanoma
Treatment of malignant melanoma can be divided into treatment of the primary tumor ,treatment of the regional lymph nodes and treatment of inoperable case and distant metastases
Treatment of the primary tumor
Surgical removal or excision
Surgical removal of the tumor with safety margin which depend on the maximum tumor thickness according to Breslow method such as 
Melanoma in situ remove 5 mm margin , tumor thickness from 0,1-1.5 pT1-2 remove 10 mm margin
Thickness from 1.6-4 mm pT3 remove 10-20 mm margin
Thickness more than 4 mm pT4 remove 20-30 mm margin
Some prefer to remove 5 cm as safety margin including the deep fascia followed by plastic reconstruction of the defect left 
In case of melanoma of the eye treated by removal of the whole eye by operation called eye enucleation
In case of melanoma of digit or finger treated by removal of that affected digit or finger by operation called amputation
Treatment of regional lymph nodes
Prophylactic block dissection of the nodes in case of stage 1 or if there is no clinical lymph nodes are detectable surgical clearance after FNAC confirmation is indicated
Therapeutic block dissection of the lymph nodes as in case of stage 2
Sentinal lymph biopsy see above
Treatment of inoperable cases such as in case of stage 3 and 4 and recurrent melanoma and in transit metastases
Palliative surgical removal
Surgical removal or excision  of the tumor to relieve the pain itching ulceration or bleeding
Chemotherapy
Vincrestine - DTIC which can be given by intravenous infusion then reach the tumor throgh systemic circulation
Melphanan phenyl alanine mustard  it is most effective line of treatment for in transit metastases can be given by intra-arterial perfusion using special pump
For more details see here
 
Radiotherapy
  
Can be used for bone and brain metastases
For more details see here
 
Fast neutrons
Using high energy cyclotron better than irradiation
Immunotherapy
USING Interleukin 2 which responsible for induction cytotoxic T- cells
Interferon- beta has been used in the past for node positive patients but its benefit is unclear
Prognosis of malignant melanoma
This depend on the tumor thickness lymph nodes involvement metastases also depend on the anatomical site of the melanoma such as trunk and scalp melanoma have bad prognosis than peripheral lesion and type of the growth superficial spreading melanoma better than penetrating ulcerating lesion

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