Controversies in melanoma -Professor Torello Lotti, MD - University G.Marconi, Rome, Italy - and...

Controversies in

melanoma

Torello LottiDepartment of Dermatologic Sciences

University of Florence, Italy

The International School of Vitiligo & Pigmentary

Disorders

Barcelona, 2-5 November 2011

Controversies in melanoma’s…

- epidemiology: Melanoma epidemic: true or false? - epidemiology: Melanoma epidemic: true or false?

- etiopathogenesis: The role of sun exposure Hormons and melanoma

- etiopathogenesis: The role of sun exposure Hormons and melanoma - diagnosis & treatment: The role of Sentinel Lymph Node Biopsy The role of Contrast Enanched Ultra Sound The role of Electron Paramagnetic Resonance Excisional VS incisional biopsy

- diagnosis & treatment: The role of Sentinel Lymph Node Biopsy The role of Contrast Enanched Ultra Sound The role of Electron Paramagnetic Resonance Excisional VS incisional biopsy

- Epidemiology -

o The presence of a true melanoma epidemic has been a controversial topic for the past

decade.

o A dramatic increase in the incidence of cutaneous malignant melanoma in developed

countries is well documented, but mortality rates have not risen as rapidly.

The “melanoma epidemic theory” has generated much discussion.

Melanoma epidemic: true or false? Melanoma epidemic: true or false?

FAVOURABLE

AUTHORS

They assert there is a

true increase in disease.

FAVOURABLE

AUTHORS

They assert there is a

true increase in disease.

CONTRARY AUTHORS

They argument this is an

apparent phenomenon that may

be explained by multiple biases

and other factors.

CONTRARY AUTHORS

They argument this is an

apparent phenomenon that may

be explained by multiple biases

and other factors.

Erickson C, Driscoll MS. Melanoma epidemic: Facts and controversies. Clinic Dermatol 2010;28(3):281-286.

Florez A, Cruces M. Melanoma epidemic: true or false? Int J Dermatol 2004;43:405-7.

They believe that this

worldwide melanoma

incidence increase

represents a true epidemic

take the statistics at face

value, with the concept

“res ipsa loquitur”.


worldwide melanoma

incidence increase





FAVOURABLEFAVOURABLE

Rigel DS, Friedman RJ, Kopf AW, et al. Melanoma incidence: if it quacks like a duck. Arch Dermatol 1997;133:656–658

Beddingfield FC, The melanoma epidemic: res ipsa loquitur. Oncologist 2003;8 :459–465

Melanoma epidemic…? Melanoma epidemic…?

They pose multiple explanations for the

incidence data, including:

• length-time bias

• increased surveillance intensity

• diagnostic uncertainty

• medico-legal climate

• data quality

They pose multiple explanations for the

incidence data, including:

• length-time bias

• increased surveillance intensity

• diagnostic uncertainty

• medico-legal climate

• data quality


worldwide melanoma

incidence increase






worldwide melanoma

incidence increase





FAVOURABLEFAVOURABLE CONTRARYCONTRARY

LA Glocker-Reis, D Melber, M Krapcho, Editors et al., SEER Cancer Statistics Review, 1975-2005, National Cancer Institute (2008) Bethesda, MD


Rigel DS, Friedman RJ, Kopf AW. The incidence of malignant melanoma in the United States: issues as we approach the 21st century. J Am Acad Dermatol 1996;34:839-47

Florez A, Cruces M. Melanoma epidemic: true or false? Int J Dermatol 2004;43:405-7.

Schaffer JV, Rigel DS, Kopf AW, et al. Cutaneous melanoma—past, present, and future. J Am Acad Dermatol 2004;51:S65-9.

Rigel DS, Friedman RJ, Kopf AW, et al. Melanoma incidence: if it quacks like a duck. Arch Dermatol 1997;133:656–658


In general, the question posed of whether a melanoma

epidemic truly exists has not yet a definitive answer,

because of the absence of randomized controlled trials

which can evaluate the true effect of increased surveillance

and biopsies on mortality rates.

Erickson C, Driscoll MS. Melanoma epidemic: Facts and controversies. Clinic Dermatol 2010;28(3):281-286.

- Etiopathogenesis -

o Despite the evidence of an UV-induced damage to DNA, the exact

relationship between melanoma risk and sun exposure is not yet optimally

known.

Walker G. Cutaneous melanoma: how does ultraviolet light contribute to melanocyte transformation? Future Oncol 2008; 4: 841-56

The role of sun exposure in melanoma The role of sun exposure in melanoma

o Considering mechanisms that allow UV radiations to induce melanoma,

is now generally accepted that the sun exposure is one of the most

relevant risk factor for melanoma.

Narayanan DL, Saladi RN, Fox JL. Ultraviolet radiation and skin cancer. Int J Dermatol 2010; 49: 978-986

o The controversy lies in the assessment of

what kind of sun exposure, intermittent and

intense versus continuous and gradual,

causes cell degeneration.

Walker G. Cutaneous melanoma: how does ultraviolet light contribute to melanocyte transformation? Future Oncol 2008; 4: 841-56

UVA rays

free radical damage to DNA

immunosuppression: diminishing of the antigen-presenting cell

function

modulation of hypersensitivity reactions

facilitation of immunosuppressive

cytokines

contribute to 10-20% of all UV ray effects UVB rays

erythema, tanning, sunburn, photoaging

carcinogenic effect

DNA damages: formation of cyclobutane pyrimidine

dimers and6-4 photoproducts genetic transitions

(cysteine to thymine)

mutations to p53 gene

UV radiation effects UV radiation effects

o Stratospheric ozone thinning has permitted that an increased

number of rays, mainly the more carcinogenetic UVB, reach the earth’s

surface.

1% of ozone layer’s depletion ccauses to an increase of 1-2% in

melanoma mortality o Altitude and latitude role:

• 1000 meters in elevation correspond to an increase of UV intensity

of 10%

• incidence rates for melanoma correlate with latitude.

Narayanan DL, Saladi RN, Fox JL. Ultraviolet radiation and skin cancer. Int J Dermatol 2010; 49: 978-986

UV radiation effects UV radiation effects

o Patient-related factors making patients more or less susceptible to UV effects:

• pigmentation features

• melanocyte proliferative response

• DNA repair capability

• cutaneous microenvironmental capacity in contrasting

the proliferation of first mutated melanocytes.

Gradual and continuous

exposure can play a

protective role for the

photoexposed persons.

Gradual and continuous

exposure can play a

protective role for the

photoexposed persons.

Ricceri F. De Giorgi V. Lotti . Melanoma:un’ipotesi eretica relativamente alla fotoesposizione cronica. In: De Giorgi V, Aricò M, Lotti T, eds. Il melanoma. Prevenzione, diagnosi e terapia. Tortona: Fernando Folini; 2008. pp:15-20.

intermittent exposureintermittent exposure

Intermittent, acute and intense

exposure increases the possibility

to develop melanoma and basal

cell carcinoma (BCC).

Intermittent, acute and intense

exposure increases the possibility

to develop melanoma and basal

cell carcinoma (BCC).

Chronic intense UV exposure

is more typically associated

with the squamous cell

carcinoma (SCC) and actinic

keratosis.

Chronic intense UV exposure

is more typically associated

with the squamous cell

carcinoma (SCC) and actinic

keratosis. Among children, melanoma risk

is most associated with

intermittent sunburns.

Among children, melanoma risk

is most associated with

intermittent sunburns.

De Giorgi V, Gori A, Grazzini M et al. Sun exposure and children: what do they know? An observational study in an Italian school. Prev Med 2011; 52: 186-187.

continuous exposurecontinuous exposurevs

It is though to be harmless

for the melanoma.

It is though to be harmless

for the melanoma.

It is defined as “recreational” or

“vacation exposure”: melanoma

often appears in sites not usually

covered by the seasonal habits and

therefore attainable by UVR

It is defined as “recreational” or

“vacation exposure”: melanoma

often appears in sites not usually

covered by the seasonal habits and

therefore attainable by UVR

Moan J, Porojnicu AC, Dahlback A et al. Where the sun does not shine: Is sunshine protective against melanoma of the vulva? J Photochem Photobiol B 2010; 101: 179-183

Benefits of a gradual and continuous sun exposure


o A correct, gradual and continuous sun

exposure starts a protective, negative-

feedback mechanism which permits to

stimulate melanin and vitamin D production.

Abdel-Malek ZA, Kadekaro AL, Swope VB. Stepping up melanocytes to the challenge of UV exposure. Pigment Cell Melanoma Res 2010; 23: 171-186

Ivry GB, Ogle CA, Shim EK. Role of sun exposure in melanoma. Dermatol Surg 2006; 32: 481-492

Maddodi N, Setaluri V. Role of UV in cutaneous melanoma. Photochem Photobiol 2008; 84: 528-536

has photoprotective properties:

• greater resistance to degradation than pheomelanin

• antioxidant activity direct correlation between eumelanin amount and

catalase levels

• free radicals scavenger preserving DNA from pyrimidine base formation

• filtering and absorbing UV photons and transforming the UV

energy into heat

forming a supranuclear cap between the nucleus and the extracelluar

environment

EumelaninEumelanin

can halt malignant cells’ proliferation, facilitating tissue

differentiation and limiting UV-induced damages.

Vitamin DVitamin D



o A correct, gradual and continuous sun

exposure starts a protective, negative-

feedback mechanism which permits to

stimulate melanin and vitamin D production.

Abdel-Malek ZA, Kadekaro AL, Swope VB. Stepping up melanocytes to the challenge of UV exposure. Pigment Cell Melanoma Res 2010; 23: 171-186

Ivry GB, Ogle CA, Shim EK. Role of sun exposure in melanoma. Dermatol Surg 2006; 32: 481-492

Maddodi N, Setaluri V. Role of UV in cutaneous melanoma. Photochem Photobiol 2008; 84: 528-536

o Evidences supporting the hypothesis of a protective role of gradual sun

exposure against melanoma development:

• low melanoma incidence in darker-skinned persons is due to the photoprotection

guaranteed by increased epidermal melanin.

• cutaneous melanoma is more common among indoor workers than in outdoor ones.

• solar elastosis is often associated with better melanoma prognosis and shows an inverse

correlation with melanoma mortality

• there are studies showing a reversed latitude gradient for melanoma

Rigel DS. Cutaneous ultraviolet exposure and its relationship to the development of skin cancer. J Am Acad Dermatol 2008; 58: s129-132

o The question of whether hormones influence melanoma has been

investigated for many years, often leading to inconsistent conclusions.

Hormons and melanoma Hormons and melanoma

o Early case reports of the ‘80s and case series

suggested a negative impact of hormones on the

prognosis of melanoma.

Bain C, Hennekens CH, Speizer FE, et al. Oral contraceptive use and malignant melanoma. J Natl Cancer Inst 1982;68 :537–539.

Holly EA, Weiss NS, Liff JM. Cutaneous melanoma in relation to exogenous hormones and reproductive factors. J Natl Cancer Inst 1983; 70:827–831.

Beral V, Evans S, Shaw H, et al. Oral contraceptive use and malignant melanoma in Australia. Br J Cancer 1984;50 :681–685.

Adam SA, Sheaves SA, Wright NH, et al. A case-control study of the possible association between oral contraceptives and malignant melanoma. Br J Cancer 1981;44 :45–50.

o Some observations had led to

speculation concerning a relationship

between female hormones and

melanoma.

Beral V, Ramcharan S, Faris R. Malignant melanoma and oral contraceptive use among women in California. Br J Cancer 1977; 36:804–809.


o Some observations had led to speculation concerning a relationship

between hormones and melanoma.

• melanoma incidence is rare before puberty, rises throughout the

reproductive years until approximately age 50, and then decreases

during menopausal years.

• changes in pigmentation, such as melasma, are associated with

pregnancy, oral contraceptives (OCs), and hormone replacement

therapy (HRT).

• the recently identified estrogen receptor β, has been shown

to be expressed in benign nevi, dysplastic nevi, lentigo maligna,

and melanmas of varying depth.

Strouse JJ, Fears TR,Tucker MA, et al. Pediatric melanoma: risk factor and survival analysis of the surveillance, epidemiology, and end results database. J Clin Oncol 2005;23:4735–4741.

R.P. Gallagher, J.M. Elwood and G.B. Hill, et al. Reproductive factors, oral contraceptives and risk of malignant melanoma: Western Canada melanoma study. Br J Cancer 1985;52:901–907.

Schmidt A, Nanney LB, Boyd AS, et al. Oestrogen receptor-β expression in melanocytic lesions. Exp Dermatol 2006;15:971–980.

Ohata C,Tadokoro T, Itami S. Expression of estrogen receptor beta in normal skin, melanocytic nevi and malignant melanomas. J Dermatol 2008;35:215–

221.

o Recent clinical studies do not support a deleterious effect of

both exogenous hormones (OCs and HRT) and endogenous

hormones (pregnancy) on melanoma. o According to a recent review of all the controlled studies to

date, OCs and HRT do not appear to increase a woman's risk for

MM; however, there

is more extensive evidence concerning OCs than HRT. Pregnancy

does not appear to influence a woman's risk of melanoma, nor

does

to affect prognosis. Driscoll MS, Grant-Kels JM. Hormones, nevi and melanoma: an approach to the patient. J Am Acad Dermatol 2007;57:919–931.

Kaae J, Andersen A, Boyd HA, et al.Reproductive history and cutaneous malignant melanoma: a comparison between women and men. Am J Epidemiol 2007;165 :1265–1270.

Lea CS, Holly EA, Hartge P, et al. Reproductive risk factors for cutaneous melanoma in women: a case-control study. Am J Epidemiol 2007;165:505–513.

Koomen ER, Joosse A, Herings RM, et al. Estrogens, oral contraceptives and hormonal replacement therapy increase the incidence of cutaneous melanoma: a population-based case-control study. Ann Oncol 2009:20,358–564.

Gupta A, Driscoll MS. Do hormones influence melanoma? Facts and controversies. Clin Dermatol 2010;28(3):287-92.


- Diagnosis &

treatment -

The role of sentinel lymph node biopsyThe role of sentinel lymph node biopsy

o The term “sentinel node”(SN) is used to indicate the lymph node to

which the afferent lymphatic vessels drain first in the regional lymph

node basin.

o SN represents the first lymphatic station which receives

the metastasizing cells coming from the primitive tumour.

Leong SPL, Zuber M, Ferris RL et al. Impact of nodal status and tumor burden in sentinel lymph nodes on the clinical outcomes of cancer patients. J Surg Oncol 2011; 103: 518-530

o For this reason, the assessment of the

sentinel node’s histological features allow the

physician to predict the status of the other

neighboring structures of the lymphatic basin.

o Sentinel lymph node biopsy (SLNB) is included in staging guidelines

of the American Joint Committee on Cancer and in treatment guidelines of

the National Comprehensive Cancer Network , and most of the surgical

physicians who treat melanoma adopt it, especially in United States and

Australia.

Ross MI. Sentinel node biopsy for melanoma: An update after two decades of experience.Semin Cutan Med Surg 2010; 29:238-248

o Several studies have confirmed that SLNB is

the most likely site of metastasis, therefore:

• when it is histologically negative, no further

interventions are required

• when it is positive, a complete regional

lymphadenecetomy is suggested because the

other nodes of that lymphatic area probably

contain disease.


o An early preoperative assessment of the lymph drainage pattern from

the melanoma can be made through the injection of 99mTc-HSA colloid

and the succeeding lymphoscintigraphyic analysis some hours before

the sentinel node biopsy.

o Combination of the highest radioactivity detected and the presence of

the dye under the incised area, increases the accuracy through which the

physician identifies SN.

From: http://blogs.nejm.org/now/index.php/sentinel-lymph-node-biopsy/2011/05/06/

o The identification of the sentinel

node is permitted also injecting a

blue dye at the tumour site and

visually identifying it later inside the

first draining node.

Gershenwald JE, Ross MI. Sentinel-lymph-node biopsy for cutaneous melanoma.N Engl J Med 2011; 364: 1738-45

Lens M.Sentinel lymph node biopsy in melanoma patients.J Eur Acad Dermatol Venereol 2010; 24: 1005-1012


o A limited biopsy of the most likely node is performed rather than a

more invasive removal of the entire regional lymphatic chain.

o SN biopsy is often performed because it provides: - detailed nodal

staging

-

regional disease control

-

possible overall improved survival

o Roughly 20% of melanoma patients show presence of malignant cells’deposits in SN.

o Histopathological examination allows

dermatologist to know:

• the presence of metastasis inside the SN

• relevant features of the metastatic deposit (e.g.,

extension, location, extracapsular spreading

From: http://blogs.nejm.org/now/index.php/sentinel-lymph-node-biopsy/2011/05/06/

Gershenwald JE, Ross MI. Sentinel-lymph-node biopsy for cutaneous melanoma.N Engl J Med 2011; 364: 1738-45

Prieto VG. Sentinel lymph nodes in cutaneous melanoma. Arch Pathol Lab Med 2010; 134: 1764-1769


o Mitotic rate has been added by the American Joint Committee on Cancer

to their seventh edition staging system for melanomas, replacing the Clark

level of invasion.

o Otherwise, the exact significance of mitotic rate in melanoma is still

controversial.

o Some author consider it weakly predictive of SN status and argument it

is not an independent predictor of survival for melanomas of 1 mm or

thicker.

o Criteria for SNLB :

• melanoma ≥1 mm in Breslow thickness with no clinically

involved nodes

• melanoma ≥0,75 mm in Breslow thickness with ulceration

• mitotic rate ≥ 1/mm2

Sekula-Gibbs SA, Shearer MA, Sentinel node biopsy should be offered in thin melanoma with mitotic rate greater than one.Dermatol Surg 2011; 37: 1080-8

Roach BA, Burton AL, Mays MP et al.Does mitotic rate predict sentinel lymph node metastasis or survival in patients with intermediate and thick melanoma?Am J Surg 2010; 200: 759-764

Thompson JF, Shaw HM. Should tumor mitotic rate and patient age, as well as tumor thickness, be used to select melanoma patients for sentinel node biopsy?Ann Surg Oncol 2004; 11: 233-5


The question whether SNLB influences

positively the overall survival is still the subject

of debate.

All the authors admit the value of SLNB as a

widespread prognostic tool, able to stage patients with

cutaneous melanoma.

To date, a rising part of authors

is sceptical of this position, and

adduces a series of evidences,

which can be summarized

in 5 points.

To date, a rising part of authors

is sceptical of this position, and

adduces a series of evidences,

which can be summarized

in 5 points.

Some authors has argued

in favor of this technique

by postulating that removal

of a SN that resulted

positive at histologic

examination, followed by

lymphadenectomy, has a

therapeutic effect.

Some authors has argued

in favor of this technique

by postulating that removal

of a SN that resulted

positive at histologic

examination, followed by

lymphadenectomy, has a

therapeutic effect.


The postulate that all the positive sentinel nodes inevitably

progress to nodal disease is not correct, because it can happen

that some micrometastases in the sentinel node can disappear

for host immune processes or can remain in a dormancy state.

De Giorgi V, Grazzini M, Papi F et al.Sentinel lymph node biopsy: Is it an evolution of the management of cutaneous melanoma?Ann Surg Oncol 2011;18:597

De Giorgi V, Grazzini M, Massi D. Sentinel-lymph-node biopsy for cutaneous melanoma. N Engl J Med 2011; 365: 570-571

Thomas JM.Caution with sentinel node biopsy in melanoma.Br J Surg 2006; 93: 129-130

1

22 It has never been shown that the lymphadenectomy performed

after a positive SN finding really improves the survival of

melanoma patients.

Thomas JM. Time to re-evaluate sentinel node biopsy in melanoma postmulticenter selective lymphadenectomy trial. J Clin Oncol 2005; 23: 9443-4


The postulate that all the positive SN inevitably progress to

nodal disease is not correct, because it can happen that some

micrometastases in the sentinel node can disappear for host

immune processes or can remain in a dormancy state.

1

22

3

It has never been shown that the lymphadenectomy performed

after a positive SN finding really improves the survival of

melanoma patients.

Results from Multicentre Selective Lymphadenectomy Trials (MSLT-I and II) have

showed that SLNB do not significantly improve overall survival, by comparing the

observation group and the biopsy group, but it helps reducing time for lymph node

metastases detection earlier identification of the natural disease progression

Amersi F, Morton DL.The role of sentinel lymph node biopsy in the management of melanoma. Adv Surg 2007; 41: 241-256

De Giorgi V, Leporatti G, Massi D et al.Sentinel lymph nodes in melanoma patients: evaluating the evidence. Oncology 2006; 71: 460-2

De Giorgi V, Leporatti G, Massi D et al.Outcome of patients with melanoma and histologically negative sentinel lymph nodes: one institution’s

experience.Oncology 2007; 73: 401-6


Melanoma metastatization modalities limits so much the

diagnostical-therapeutical value of SN biopsy, and a following

potential lymphadenectomy.

Indeed, a melanoma can produce:

• cutaneous metastases, satellitosis or in-transit (20% of cases of

initial melanoma)

• regional nodal metastases (50% of cases)

• distant metastases (30%)

In half cases, there could be previous cutaneous and distant metastases not yet

detected at SN biopsy time.

44

The role of sentinel node biopsyThe role of sentinel node biopsy

5

Amersi F, Morton DL.The role of sentinel lymph node biopsy in the management of melanoma. Adv Surg 2007; 41: 241-256

De Giorgi V, Leporatti G, Massi D et al.Sentinel lymph nodes in melanoma patients: evaluating the evidence. Oncology 2006; 71: 460-2

De Giorgi V, Leporatti G, Massi D et al.Outcome of patients with melanoma and histologically negative sentinel lymph nodes: one institution’s

experience.Oncology 2007; 73: 401-6

SNLB frequently gives false negatives and false positives results.

Van Akkooi ACJ, Voit CA, Verhoef C et al. New developments in sentinel node staging in melanoma: controversies and alternatives.Curr Opin Oncol 2010; 22: 169-177

• malignant cells have not reached the node yet when the sentinel

node is examined, because they are still inside the lymphatic

vessels.

• not all the sentinel nodes are reached by 99mTc-HSA colloid during

the lymphoscintigraphy.

• part of the radiocolloid has cross the sentinel node arriving up to

other nodes, or it could enter inside “second line” bigger nodes.

• there is reduced lymphatic flow to the sentinel node due to the

obstruction by the metastatic bulk.

5 Causes of a possible false negatives result of SLNB techinque:

Van Akkooi ACJ, Voit CA, Verhoef C et al. New developments in sentinel node staging in melanoma: controversies and alternatives.Curr Opin Oncol 2010; 22: 169-177

The role of sentinel node biopsyThe role of sentinel node biopsy

The role of CEUS in melanoma diagnosis The role of CEUS in melanoma diagnosis

o Contrast-enhanced ultrasound system (CEUS) was recently

introduced as an alternative and less invasive procedure, in spite of SLNB, for the

detection of SN.

o Sometimes there is a reduced lymphatic flow to the sentinel node

due to the obstruction given by the metastatic bulk.

o In such cases, using an ultrasound-based evaluation can

successfully identify the node’s involvement.

o CEUS has demonstrated a negative predictive value of 100%,

so that all negative results were confirmed by negative SN

histological examination.

CEUS has shown an high diagnostic accuracy in detecting

occult non-palpable metastases in regional lymph nodes.

De Giorgi V, Gori A, Grazzini M, et al. Contrast-enhanced ultrasound: a filter role in AJCC stage I/II melanoma patients. Oncology 2010; 79: 370-5.

Catalano O, Setola SV, Vallone P, et al. Sonography for locoregional staging and follow-up of cutaneous melanoma: how we do it. J Ultrasound Med 2010;29(5):791-802.

o Electron paramagnetic resonance (EPR) has been recently

employed to melanoma field, because of its ability to detect free radicals

trapped in melanin pigments by using their paramagnetic properties.

o EPR can localize melanoma metastases with high precision and

can help assessing the contribution of UV rays to the initiation of

melanoma.

o EPR spectrometry and imaging largely improve the detection and

mapping of melanin pigments inside ex vivo and in vivo melanomas.

o However, this method has some limitations, and further investigations

are needed.

The role of EPR in melanoma diagnosis The role of EPR in melanoma diagnosis

Melanoma mtx in the lungs of mice and the

respective 2D transversal EPR image.

Godechal Q, Gallez B. The contribution of electron paramagnetic resonance to melanoma research. J Skin Cancer 2011;2011:273-280.

Godechal Q, Defresne F, Danhier P. Assessment of melanoma extent and melanoma metastases invasion using electron paramagnetic resonance and bioluminescence imaging. Contrast Media Mol Imaging 2011;6(4):282-8.

o Whereas the surgical excision is accepted world wide as primary treatment for

melanoma, the prognostic significance of incisional bopsy is discussed controversially,

and so far, no international consensus has been reached.

o Incisional biopsies are currently recommended for the histopathologic diagnosis of

large tumors in facial, mucosal, and acral locations.

o Evidence from latest trials and studies is that incisional biopsies of malignant

melanoma are not associated with an unfavorable prognosis for patients.

o Anyway, complete excision of primary melanoma is still the recommended standard of

care and is a precondition for accurate histopathologic diagnosis.

Excisional VS incisional biopsyExcisional VS incisional biopsy

Pflugfelder A, Weide B, Eigentler TK. Incisional biopsy and melanoma prognosis: Facts and controversies. Clin Dermatol 2010;28(3):316-8.

Leiter U, Eigentler TK, Forschner A, et al. Excision guidelines and follow-up strategies in cutaneous melanoma: Facts and controversies. Clin Dermatol. 2010 ;28(3):311-5.

From: http://www.glowm.com/resources/glowm/cd/pages/v1/v1c011.html?SESSID=cvrcbl8q7c00h40nmlti9r0na3

Cutaneous melanoma is an emerging and complex

health problem.

Management may require the expertise of multiple

specialties.

Although the outlook for advanced disease remains

very poor, there are major advances in the understanding

of melanoma.

As technology improves and information continues to

accrue, our increased understanding of melanoma will

lead to improved treatment of advanced disease.

Take home messagesTake home messages

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Controversies in melanoma -Professor Torello Lotti, MD - University G.Marconi, Rome, Italy - and...

Health & Medicine