Manejo quirúrgico de ca de piel melanoma (sin animación)...Generalidades ü Neoplasia maligna agresiva de los melanocitos ü OMS estima que las cifras de incidencia y mortalidad

+

Dra. Patricia Laime Veizaga

Hospital Clínico San Borja Arriarán

Universidad de Chile

Melanoma cutáneo:

Manejo quirúrgico

+Generalidades

ü Neoplasiamaligna agresiva de losmelanocitos

ü OMS estima que las cifras de incidencia y mortalidad anual son2,8 y 0,6 por 100.000 habitantes, respectivamente

ü Anivel nacional 434 casos nuevos al año

ü Menos frecuente que el Ca de piel no melanoma, pero muchomásmortal

ü 25 a 30%se ubica en cabeza y cuello

ü Factores de riesgo: exposición solar, ciertos fenotipos (ojosazules/verdes, cabello rubio/pelirrojo) lesiones precursoras(nevos congénitos > 20 cm, nevos displásicos, lentigo maligno),genética (Sd.Nevodisplásico,Xerodermapigmentoso)

ü Alto potencial de diseminación linfática ymetástasis a distancia

+Generalidades

n Subtipos:

• Melanoma de extensión superficial (75%)• Melanoma nodular (10-15%)• Léntigo maligno melanoma (5 – 10 %)• Melanoma lentiginoso acral (< 5%)

+Diagnóstico:

n Clínica: A, B, C, D

n Biopsia excisional:

• Se acepta realizar biopsia incisional en algunas áreas críticas (palma, planta o en lesiones muy extensas de cara)

• Margen 1-3 mm perilesional

+Diagnóstico

n El objetivo de la biopsia es definir tratamiento según:

• Breslow (espesor de la lesión mm)(Nivel de Clark zonas de piel delgada, ejm.: párpado)

Manejo del sitio primario

Manejo regional

Busqueda de metástasis a distancia

+Melanoma

ü Manejo tumor primario

ü Manejo regional (adenopatías)

ü Busqueda de metástasis a distancia

+MelanomaManejo del tumor primario: Márgenes

NCCN Guidelines Version 2.2018

NCCN Guidelines Version 2.2018Melanoma

NCCN Guidelines IndexTable of Contents

Discussion

Version 2.2018, 01/19/18 © National Comprehensive Cancer Network, Inc. 2018, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

Note: All recommendations are category 2A unless otherwise indicated.Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

ME-D

PRINCIPLES OF SURGICAL MARGINS FOR WIDE EXCISION OF PRIMARY MELANOMA

Tumor Thickness

In situ1

≤1.0 mm

>1.0–2 mm

>2.0–4 mm >4 mm

Recommended Clinical Margins2

0.5–1.0 cm

1.0 cm (category 1)

1–2 cm (category 1)

2.0 cm (category 1) 2.0 cm (category 1)

• Margins may be modified to accommodate individual anatomic or functional considerations.

1For large melanoma in situ (MIS), lentigo maligna type, surgical margins >0.5 cm may be necessary to achieve histologically negative margins; techniques for more exhaustive histologic assessment of margins should be considered. For selected patients with positive margins after optimal surgery, consider topical imiquimod (for patients with MIS) or RT (category 2B).

2Excision recommendations are based on measured clinical margins taken at the time of surgery and not gross or histologic margins, as measured by the pathologist (category 1).

Printed by PATRICIA LAIME on 5/13/2018 12:48:18 AM. For personal use only. Not approved for distribution. Copyright © 2018 National Comprehensive Cancer Network, Inc., All Rights Reserved.

+Melanoma

ü Manejo tumor primario

ü Manejo regional (adenopatías)

ü Busqueda de metástasis a distancia

+Melanoma

ü Paso intermedio clave entre la enfermedad localizada y la metastásica.

ü La enfermedad locoregional empeora claramente el pronóstico

Manejo Regional

+Melanoma

Estadio I y II Adenopatías (-)

Linfadenectomia regional profiláctica

Sobrevida 48,2% pctes con mtts ocultas v.s. 26,6% pctes con extirpación diferida *

Manejo Regional

* Immediate or delayed dissection of regional nodes in patients with melanoma of the trunk: a randomised trial.WHOMelanomaProgramme. Cascinelli N, et. al. Lancet1998Mar 14;351(9105):793-6. N=277

+MelanomaManejo Regional

T N M

Estadio 0 Tis N0 M0

Estadio IA T1a N0 M0 < 0.8 mm S/ulceración

Estadio IB T1b N0 M0 < 0.8 mm0.8-1.0 mm

C/ulceraciónC/S ulceración

T2a N0 M0 >1.0-2.0 mm S/ulceración

Estadio IIA T2b N0 M0 >1.0-2.0 mm C/ulceración


Estadio IIB T3b N0 M0 >2.0-4.0 mm C/ulceración

T4a N0 M0 > 4 mm S/ulceración

Estadio IIC T4b N0 M0 > 4 mm C/ulceración

Estadio III Any T, Tis > N1 M0

Estadio IV Any T Any N M1

Estadio Clínico TNM

+Melanoma

Estadio I y II Adenopatías (-)

Linfadenectomia regional profiláctica

Sobrevida 48,2%pctes con mtts ocultas v.s. 26,6% pctes con extirpación diferida *

Manejo Regional

* Immediate or delayed dissection of regional nodes in patients with melanoma of the trunk: a randomised trial.WHOMelanomaProgramme. Cascinelli N, et. al. Lancet1998Mar 14;351(9105):793-6. N=277

+Melanoma

✓ Primer linfonodo en recibir el drenaje linfático de un tumorde un sitio específico

✓ Su precisión supera el 98%

✓ Es el mas poderoso indicador de supervivencia en elmelanoma no metastásico

✓ La presencia de metástasis ganglionares, disminuye lasupervivencia a los 5 años en aprox 40%

Manejo Regional: Ganglio centinela

+Melanoma

ü Es la técnica menos agresiva y más efectiva para demostrarla presencia de metástasis ganglionares

ü La linfadenectomía regional tiene la misma utilidad, pero esuna técnica más agresiva

ü PET/CT técnica no invasivaWagner y cols.*: Detección de metástasis regionales

Sensibilidad Especificidad

VPP VPN

Ganglio Centinela 94,4% 100% 98,6%

PET/CT 16,7% 50% 81,9%


* Wagner JD, et. Al. Prospective study of fluorodeoxyglucose-positron emission tomography imaging of lymph nodebasins in melanoma patients undergoing sentinel node biopsy. J Clin Oncol. 1999 May;17(5):1508-15.

+Melanoma

n El grosor tumoral es el predictor mas confiable de un ganglio centinela

n Joseph E, et.al.*: N =600

• > 4 mm GC (+) 30%

• 1,5 a 4 mm CG (+) 18%

• 1 a 1.5 mm GC (+) 7%

• < 0,76 mm GC (+) < 5%


*Ann Surg Oncol 1998;5:119-25

+MelanomaManejo Regional: Ganglio centinela

T N M

Estadio 0 Tis N0 M0

Estadio IA T1a * N0 M0 < 0.8 mm S/ulceración












5 - 10%

< 5%

> 10%

Linfadenectomia regional terapéutica

* Considerar GC: indice mitotico ↑, borde profundo (+), edad muy joven de presentación, signos de regresión, nivel de Clark IV


Detección del ganglio centinela:

1) Linfocintigrafía preoperatoria con radioisótopos

2) Inyección de colorante azul

3) Utilización de sonda gamma portátil para localizar cantidades mínimas de un isótopo.

+Melanoma

Linfocintigrafia preoperatoria:



Inyección de colorante azul:


Utilización de la sonda portátil:

Review

IntroductionCutaneous melanoma is an increasingly common andpotentially fatal malignant disease that frequentlymetastasises via lymphatics (figure 1) to the regionallymph nodes. Compelling evidence suggests that earlydetection and removal of nodes that contain melanomametastases improves survival,1–3 and is therefore essentialfor rational management of patients with melanoma.Accurate knowledge of regional-node status is alsoimportant to estimate outlook reliably, and to stratifypatients in trials of adjuvant treatment.

Until recently, the identification of micrometastaticmelanoma in regional lymph nodes was almostimpossible. However, developments in lymphatic-mapping technology and the introduction andprogressive refinement of the highly selective sentinel-node biopsy technique4 have made it possible forpathologists to identify even a few metastatic melanomacells among the many millions of cells within the 20 ormore nodes that can be present within regional lymphnodes. Reliable localisation of such metastatic cells needsaccurate delineation of lymphatic vessels that have thepotential to transport cells from a primary melanoma siteto the nodes. A sentinel node is best defined as any nodeto which direct lymphatic drainage from a primarytumour site occurs.5 After localisation of the relevantsentinel node or nodes by preoperative lymphoscinti-graphy, the sentinel node can be excised, allowingdetailed histological assessment.

Here, we discuss the importance of lymphatic mappingin the management of patients with cutaneousmelanoma. However, the principles of lymphaticmapping and sentinel-node biopsy are widely applicable,6

and the procedure has been shown to be useful in theguidance of clinical decision-making and in prediction ofoutlook for patients with any other malignant diseasethat has a propensity to metastasise to the lymph nodes.

Historical assumptionsSeveral simplistic assumptions about cutaneouslymphatic-drainage pathways have been made pre-

viously on the basis of postmortem studies undertakenin small numbers of cadavers. However, the infor-mation now available from lymphoscintigraphy inlarge series of live patients with melanoma shows thatthese assumptions were probably incorrect in about30% of individuals. For example, lymphatic drainagefrom primary tumours on the trunk was known tobe ambiguous, but the extent of the unpredictabilityhave not been appreciated fully. Furthermore, thepossibility that lymphatic drainage from primarytumours on the arms (shoulder to hand) and legs(hip to foot) could also be to unexpected sites had notbeen considered.

Systematic mapping of the lymphatic system thatdrains the skin was first done in the 19th century byindividuals including Sappey, Meckel, Hunter,Cruikshank, and Mascagni.7 However, fundamental

Lancet Oncol 2005; 6: 877–85

Sydney Melanoma Unit,Sydney Cancer Centre, RoyalPrince Alfred Hospital,Camperdown, New SouthWales, Australia(Prof J F Thompson MD,R F Uren MD); and Discipline ofSurgery (J F Thompson) andDepartment of NuclearMedicine and DiagnosticUltrasound and Discipline ofMedicine (R F Uren) Universityof Sydney, Sydney, New SouthWales, Australia

Correspondence to:Prof John Thompson, SydneyMelanoma Unit, Royal PrinceAlfred Hospital, Missenden Road,Camperdown, New South Wales2050, [email protected]

http://oncology.thelancet.com Vol 6 November 2005 877

John F Thompson, Roger F Uren

In patients with primary cutaneous melanoma, knowledge of regional lymph-node status provides importantinformation on outlook. Evidence suggests that early removal of nodes that contain metastatic disease improvessurvival outcome. Lymphatic drainage occurs first to sentinel nodes, which are therefore the nodes most likely tocontain metastatic disease. Lymphatic mapping with lymphoscintigraphy is important to identify reliably sentinelnodes for removal and thus establish the status of regional nodes. Mapping studies in patients with melanoma haveprovided new insights into lymphatic anatomy and have shown previously unsuspected drainage pathways, whichhave important implications for accurate identification and removal of sentinel nodes. Because it is impossible topredict the site or sites of sentinel nodes clinically in individual patients, routine preoperative lymphoscintigraphy isa prerequisite if reliable results are to be obtained from sentinel-node biopsy.

Lymphatic mapping in management of patients withprimary cutaneous melanoma

Figure 1: Blue-stained afferent lymphatic from primary cutaneous melanoma on calf Blue-stained afferent lymphatic entering lower pole of sentinel node in groin, and blue-stained efferent lymphaticleaving upper pole of sentinel node. A separate afferent lymphatic channel bypasses this sentinel node en route toa second sentinel node higher in groin. Stained with patent blue.


Utilización de la sonda portátil:

+MelanomaManejo regional: Ganglio centinela

La combinación de las tres técnicas aumenta la presición de identificación del ganglio centinela

Gershenwald y cols* N = 626- Uso solo de azúl 87% v.s. técnica combinada 99%

- En el 92 % de los pctes que tuvieron algún ganglio con presencia demetástasis estas se producián en los ganglios que tenian mayorcantidad de radiocoloide

Bostick y cols**

- 144 ganglios extirpados, 8 tenián radioactividad pero no estabanteñidos de azul; 12 no tenían radioactividad y estaban teñidos de azul

- 17 ganglios ganglios que presentaban metástasis, uno de ellos fueidentificado sólo por el colorante azul

* Improved sentinel lymph node localization in patients with primary melanoma with the use of radiolabeled colloid.

Gershenwald JE, y cols. Surgery 1998 Aug;124(2):203-10

** Comparison of blue dye and probeassisted intraoperative lymphatic mapping in melanoma to identify sentinel nodesin 100 lymphatic basins. Bostick y cols. Arch Surg.1999 Jan;134(1):43-9

+Melanoma

Estadio III

Ganglio centinela (+), ganglios clínicamente (+)

Imágenes basales

Disección Ganglionar terapéutica

Manejo Regional

Sobrevida a 5, 10 y 15 años de seguimiento se estimó en 46%, 41% y 38%

Improved Long-term Survival After Lymphadenectomy of Melanoma Metastatic to Regional NodesMorton Donald L. M.D., et. al A nn surg O ct 1991 N = 1134 pctes

+MelanomaManejo Regional

T N M

Estadio 0 Tis N0 M0

Estadio IA T1a N0 M0 < 0.8 mm S/ulceración












Linfadenectomia regional terapéutica

+Melanoma

Estadio III

Ganglio centinela (+), ganglios clínicamente (+)

Imágenes basales

Disección Ganglionar terapéutica

Manejo Regional

* Sobrevida a 5, 10 y 15 años de seguimiento se estimó en 46%, 41% y 38%

* Improved Long-term Survival After Lymphadenectomy of Melanoma Metastatic to Regional NodesMorton Donald L. M.D., et. al A nn surg O ct 1991 N = 1134 pctes

+

Version 2.201 , 01/1 /1 National Comprehensive Cancer Network, Inc. 201 , All rights reserved. The NCCN Guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN . MS-19

NCCN Guidelines IndexTable of Contents

Discussion

NCCN Guidelines Version 2.2018 Melanoma

been conducted to directly address the impact of CLND on a number of these clinical endpoints.27 ,276

Likelihood of Non-Sentinel Lymph Node Positivity Among patients with a positive sentinel node, published studies have revealed additional positive non-sentinel nodes in approximately 20% of the CLND specimens (Table 4). Factors most predictive of additional non-sentinel node involvement include the largest size of the SLN metastasis,77,7 ,172,277-2 the number of SLNs involved,7 ,1 ,27 ,2 3,2 0 the distribution of metastasis in the SLN (subcapsular vs. parenchymal),172,2 1,2 2 and primary tumor characteristics of thickness277,27 ,2 1,2 -2 ,2 3,2 4 and ulceration.1 ,2 1,2 3,2 3,2 4 Several scoring systems have been developed to predict the likelihood of positive non-sentinel nodes based on SLN biopsy findings, primary tumor, and patient characteristics,2 ,2 -2 although the utility of each of these systems has been debated based on subsequent analyses. 0,2 1,2 3,300,301

Table 4. Rates of Positive Non-Sentinel Lymph Nodes

Study Patients with CLND, n Patients with Positive

NSLN, n (%) McMasters 2002 302 272 4 (16%) Dewar 20042 1 146 24 (16%) Sabel 200 27 221 34 (1 %) Kettlewell 2006303 10 34 (32%) Cascinelli 2006172 176 33 (1 %) Govindarajan 200727 127 20 (16%) Gershenwald 200 2 343 4 (16%) Cadili 201077 606 142 (24%) Leung 20132 3 32 7 (24%) Wevers 20132 130 30 (23%) Pasquali 2014304 1, 3 3 3 (23%) Bertolli 201 2 146 23 (16%) Rutkowski 201 2 7 473 132 (2 %) Kim 201 7 111 13 (12%) Total 4723 1010 (21%)

CLND, complete lymph node dissection NSLN, non-sentinel lymph node

Prognostic Value of Complete Lymph Node Dissection A number of retrospective studies have evaluated the prognostic value of NSLN involvement in patients who had a CLND after a positive SLN (no palpable lymph nodes). Compared to those without NSLN involvement detected by CLND, those with positive NSLN(s) have higher rates of recurrence 0,273,2 3 and poorer DFS,30 melanoma-specific survival, and OS. 0,172,2 7,2 3,304-306 In fact, in the studies that evaluated the clinical importance of NSLN positivity by multivariate analysis, it was consistently one of the most important independent predictor of DSS.273,2 3,304-306 Other factors identified to be independently associated with recurrence and survival include the number of positive

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MelanomaManejo regional: Ganglio centinela

21%

+Melanoma

• Si no se dispone de equipo para realizar Ganglio Centinela, adenopatías clínicamente (-)

Tratamiento estandar

Disección ganglionar profiláctica:

• Breslow < 1,5 mm No • Breslow > 1,5 – 4 mm Sí• Breslow > 4 mm No

Manejo Regional

+Melanoma

Ø En pacientes con GC (+) el rendimiento de las imágenes en la detección deenfermedad metastásica a distancia clínicamente oculta varía entre 0.5% y3.7% *

Ø En pacientes ganglios clínicamente positivos, el rendimiento de lasimágenes de rutina es un poco más alto que en los pacientes con ganglioscentinela positivos, informados entre el 4% y el 16%**

Ø PET/CT muy usado en la detección de la enfermedad metastásica subclínica

Metástasis a distancia

* G old JS, e t al. Y ie ld and predictors o f rad iologic studies for identify ing d istant m etastases in m elanom a patients w ith a positive sentinel lym ph node b iopsy. A nn Surg O ncol 2007;14:2133-2140.

** Kuvshinoff BW , e t al. C om puted tom ography in evaluation o f patients w ith stage III m elanom a. A nn Surg O ncol 1997;4:252-258

+Melanoma

Ø Melanoma estadio I y IIØ Sensibilidad 0 a 67%

Ø Especificidad 77 a 100%

Ø Melanoma estadio III y IVØ Sensibilidad 68 a 87%

Ø Especificidad 92 a 98%


F-18-fluoro-2-deoxyglucose positron emission tomography (PET) and PET/computed tomography imaging in primary staging of patients with malignant melanoma: a systematic review.

Schröer-Günther MA1, Wolff RF, Westwood ME, Scheibler FJ, Schürmann C, Baumert BG, Sauerland S, Kleijnen J.Syst Rev. 2012 Dec 13;1:62. doi: 10.1186/2046-4053-1-62.

+Tratamiento

Ø Fuera de alcance quirúrgico con intención curativa

Ø Terápia sistemica

Ø Radioterápia paliativa


+ Melanoma cutáneo H.C.S.B.A (revisión de 5 años mayo de 2013 a mayo de 2018)

Ubicación Frecuencia

Preauricular 1Ciliar 1Retroauricular 1Muslo 4Glúteo 1Palmar 2Plantar 2Hombro 1Cervical 1

Inguinal 1Mejilla 5Dorsal 10Talón 5Pie 6Dedo medio 1

1º ortejo 2Pierna 6antebrazo 2

Pared abdominal 2Lumbar 1

Tobillo 2Brazo 4Ala nasal 3

Cabeza y cuello 19%

N = 63

+

Injerto 17

Colgajo local 41

Colgajo regional 1

Amputación 4

Manejo del tumor primario:

Melanoma cutáneo H.C.S.B.A (revisión de 5 años mayo de 2013 a mayo de 2018)

+

Breslow Frecuencia

in situ 8

< 1 mm 7

1 - 1.5 mm 11

> 1.5 - 4 mm 22

> 4 mm 10

Tx 5

Disección ganglionar 30 pctes

3

26

1


+

Disección Ganglionar Nº Detalle

Ganglio centinela (+) 3 2 GC Ext.sis. / 1 H.C.S.B.A

Ganglios clínicamente (-) 19 4 Mtts 21%

Ganglios clínicamente (+) 8 8 Mtts 100%


+

Ganglio Centinela:

Ganglio Centinela 6

GC(+)* Axila derecha 1 Disección Gl

GC (-) 5

* Linfocintigrafía axila bilateral


+ Gracias

+

Dra. Patricia Laime Veizaga

Hospital clínico San Borja Arriarán

Universidad de Chile

Melanoma cutáneo:

Manejo quirúrgico

Documents

Manejo quirúrgico de ca de piel melanoma (sin animación)...Generalidades ü Neoplasia maligna agresiva de los melanocitos ü OMS estima que las cifras de incidencia y mortalidad