INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY
Vol. 27, no. 4, 639-644 (2014)
LETTER TO THE EDITOR
WRONG MELANOMA THICKNESS MEASUREMENT: CHECK IT OR LEAVE IT? A.A. CHOKOEVA1, G. TCHERNEV2, S. PHILIPOV3 , M. ZANARDELLP and T. LOTTI6,7
J.e. CARDOS04
'Onkoderma- Policlinicfor Dermatology and Dermatologic Surgery, General Skobelev 26 Sofia, Bulgaria; 'Pottcltntc for Dermatology and Venereology, Saint Kliment Ohridski University, Medical Faculty, University Hospital Lozenetz, Sofia, Bulgaria; 3Department ofGeneral and Clinical Pathology, Medical Faculty, "Saint Kliment Ohridski University" Sofia, Bulgaria; "Dermatology Department, University Hospital ofCoimbra,Praceta Mota Pinto, Coimbra Portugal; 'Department ofNeuroscience, Psychology, Drug Research and Child Health - NeurofarbaPharmacology and Toxicology Section, University ofFlorence, Italy; 'University ofRome "G. Marconi", Rome, Italy; 'Institute ofDermatology Life Cronos, Florence, Italy Cutaneous malignant melanoma (CMM) is one of the most aggressive forms ofskin cancer, accounting for about 90% of deaths from cutaneous neoplasms, and its incidence has increased significantly in recent years. According to "the 2012 European criteria for diagnosis and treatment of malignant melanoma, diagnosis should be based on the combination of clinical features, dermoscopic data and histological examination, preferably after excisional biopsy. Tumour thickness and other parameters for local staging according to the AJCC classification should be included in the pathology report. Although many factors influence the prognosis and course of the disease, it has been established in a number of studies that tumour thickness is the most important parameter. Therapy of malignant melanoma in its initial stages mostly consists of wide local excision with 1 to 2 cm margins, and sentinel lymph node biopsy that is usually performed in cases of tumours with a thickness greater than 1 mm, We present the case of a 58-yearold Bulgarian male with cutaneous superficial spreading malignant melanoma, in which, after complete excision, histological examination established an inaccurate tumour thickness (0.7 mm), with consequent inadequate staging and further management. After reassessment of the results in another institution (as well as their confirmation by two additional independent histopathology laboratories in our country 1.92 mm), in the National Oncological Hospital where the patient was initially evaluated, sentinel lymph node biopsy was not performed, contrary to the generally accepted European and World standards. With the present case we raise some current issues regarding diagnosis and therapy of Bulgarian patients (not only in the case presented) with malignant melanoma in the 21st century, and discuss the urgent need for external quality control procedures and standardization of the histopathologic reporting, which is of paramount importance in the staging and subsequent management of these patients. Cutaneous malignant melanoma (CMM) is one of the most aggressive forms ofskin cancer, accounting for about 90% of deaths from cutaneous neoplasms (1). Although it represents only about 3 to 5% of
'all skin cancers, malignant melanoma represents a serious public health problem as its frequency is increasing more rapidly than any other cancer in the world (1, 2). If in 1930, the risk of developing
Key words: diagnosis, surgical excision, malignant melanoma, treatment, SLNE, tumour thickness I ~ •.
Mailing address: Assoc. Prof. Georgi Tchemev, Policlinic for Dermatology and Venereology, Saint Kliment Ohridski University, Medical Faculty, University Hospital Lozenetz, Koziak street I, 1407 Sofia, Bulgaria Tel.: +359 885 588 424 e-mail: [email protected]
0394-6320 (2014)
639
.. Copyright © by BlOUFE, s.a.S. This publication and/or article is for individualuseerrly and may not be further reproduced without written permi~slo~'fro~ the copyright holder. Unauthorized reproduetionmayresultin frnancial.and other penalties DISCLOSURE: ALL AUTHORS J.ffiPO~:r..NOC:ONFLICTS OF IN1'EREST tU:LItVtiNT TocYins ARTICLE.
640
A.A. CHO KOEVA ET AL.
Fig. 1. a) Darkly pigmented lesion located on the interscapu lar area in a 58-year-old male patient. b) The lesion is asymmetrical, with irregular borders, and sharply demarcated fro m the surrounding skin lesion. c, d, e) Total surgical elliptical excision of the lesion, with 2-cm lateral margins and a depth to the underlying fasci a. j) Immediate postoperative aspect, aft er direct closure ofthe surgical def ect with a simple suture.
malignant melanoma was I in 1500 people/year, nowadays, in the 21st century, this risk is 1 in 74 people/year (3). Deaths caused by CMM have also been rising, since the mortality rate has increased nearly 2% per year from 1960 until the present day (3). According to the European Association of Dermato-oncology, therapy in cases of invasive melanoma in its initial stages consists of wide local excision with I to 2 em margins , and sentinel lymph node biopsy, mostly in case oftumours with more than 1 mm thickness (4). It can be performed in a singlestep or up to 3 weeks after the initial intervention, provided that there is no major reconstructive surgery causing significant changes in the regional anatomy and consequently in the lymphatic drainage. (4). The German Dermatologic al Society establishes 0.5 mm margins for melanoma in situ, 1 em for invasive melanoma up to 2 mm thickness, and 2 em
for tumours thicker than 2 mm (5). Sentinel lymph node biopsy is recommended in cases of melanoma with thickness greater than 1 mm (4, 5). Cancer staging should be performed by the TNM system, taking into consideration tumour thickness, status of locoregionallymph nodes and the presence ofdistant meta stases (6). Based on these results, the treatment plan, prognosis and patient follow-up program are defined (6). Regular control examinations are recommended for a period of 5-10 years (depending on tumour thickne ss), with a closer follow-up in the first three years (1, 4, 5). Despite all treatment recommendations, prevention, early diagno sis and surgical treatment remain the main therapeutic weapon against melanoma ( I, 2). With its increasing incidence we are indebted to update our approach in accordance with global standards in order to provide adequate care to all patients with CMM (1,2). The present case raises questions about current
Int. J. Immnnopathol. Pharmacol.
641
Fig. 2. a, b, c, tl) Histologicalfindings consistent with superficial spreading melanoma.
problems in diagnosis and treatment of melanoma in Bulgaria. Reflection on these issues and comparison with the European standards of care will hopefully stimulate better diagnostic and therapeutic strategies for melanoma in Bulgaria. Case report We present the case of a 58-year-old male, admitted to the Lozenets University Hospital, with a black lesion on the upper back, which had been present for 3 years, associated with local discomfort and pruritus . He had no significant comorbidities and there was no family history of malignant melanoma. The patient was in good general health, and there were no other subjective complaints. Examination disclosed a slightly elevated, darkly pigmented lesion on the interscapular area, which was asymmetrical, with irregular borders, and sharply demarcated from the surrounding skin (Fig. I a,b). Complete blood count with differential and biochemistry were within normal range. Diagnostic imaging: abdominal ultrasound - no abnormalities; thyroid ultrasound gland - no evidence of nodular
lesions; lymphadenopathy was found in the left supraclavicular area, with 3-4 lymph nodes 7-8 mm in size. The provisional diagnosis of superficial spreading malignant melanoma was established on the basis of clinical and dermoscopic examination. Complete excision under local anaesthesia was performed (Fig. 1 c,d,e). As per request of the patient, histopathological examination of the lesion was carried out in another public institution - the National Oncologic Hospital. The first histological examination reported a superficial spreading pigmented malignant melanoma with a thickness of 0.7 mm, Clark level 2, without evidence of established regression or ulceration. Computer tomography (CT) of the chest, abdomen and pelvis revealed no evidence of distant metastasis - MO. In face of the parameters initially assessed in the primary tumour, a sentinel lymph node biopsy was not performed. Later, a review of the pathology was undertaken in the Pathology Department of Lozenets University
642
A.A. CHOKOEVAET AL.
hospital (Fig. 2 a,b,c,d), confirming the diagnosis of superficial spreading malignant melanoma composed of both epithelioid and spindle-shaped melanocytes. However, maximum thickness was determined at 1.92 mm, after measurements at different points of the proliferation (respectively 0.87 mm, 1.63 mm and 1.92 mm). Mitotic count was 3110HPF, and there was focal ulceration associated with fibrin deposition and neutrophils. The adjacent epidermis was thinned, and there was a pronounced stromal reaction (Fig. 2 a.b.c.d). The pathological staging was upgraded to: pT2b Nx Mx VO LORO as the lymph nodes in the supraclavicular area were not taken into consideration. This diagnosis was further corroborated by two other independent evaluations in different histopathological laboratories in Bulgaria. DISCUSSION The present case elicits our concerns in view of the relevance of accurate measurement ofmelanoma thickness, which is of the utmost importance in the prediction of prognosis, and which guides further management of the patients, namely the indication for sentine1lymph node biopsy. According to the 2012 European criteria for diagnosis and therapy of malignant melanoma, the diagnosis should be based on clinical assessment, dermoscopic criteria and histological examination of the lesion after complete excision, with subsequent determination of tumour thickness and staging according to AJCC classification (1, 2, 4, 5). Although many factors influence the prognosis and course ofthe disease, a number of studies concur that tumour thickness is the most important of them (I, 2, 4, 5). Five-year survival in patients with earlystage disease (tumour thickness less than 1 mm) is estimated at 94%, and only 50% in those with lesions over 3 mm (1,5, 7). It is also important to stress that there is a likelihood of early lymph nodes metastases in 40% of patients with a lesion with thickness between 1 and 4 mm, and distant metastases in only 10% of them, while in patients with a tumour thickness greater than 4 mm, the risk of lymph node and distant metastases is approximately 60% and 70%, respectively (3, 4). These data emphasize the necessity of accurate staging of melanoma, namely
of its thickness, in order to estimate apatient's survival rate and risk of metastasis. Regarding the present case, initial histological assessment estimated a tumour thickness of 0.7 mm, corresponding to stage TlA (melanomas 0.75 mm, considering that SLNB is a method that provides highly valuable prognostic information for selection of subsequent treatment, coupled with a minimal risk of complications (10). In view of this, we consider that lymph node biopsy of the lymph nodes that were enlarged on the ultrasound examination would be indicated in our case, especially taking into account the primary tumour thickness of 1.92 mm, with a significant risk of locoregional metastases.
643
In conclusion, in cases of CMM we emphasize the importance of accurate tumour thickness measurements as well as SLNB, whenever indicated according to current practice. Based on this illustrative case, we wish to stress out the need for compliance with current guidelines of diagnosis and treatment of malignant melanoma by dermatologic surgeons and dermato-oncologists in Bulgaria. With this purpose in mind, precise and common strategies have to be carried out. For example, an Interdisciplinary Melanoma Board would be of value within the setting of Bulgarian Health Authorities in order to individualize diagnostic and therapeutic approaches for each patient. Setting up a "National Bulgarian Melanoma Register" would be most helpful in order to obtain accurate statistical data regarding the prevalence of melanoma and to promote correct follow-up of all cases. REFERENCES: 1.
2.
3.
4.
5.
6.
Tronnier M, Semkova K, Wollina U, Tchemev G. Malignant melanoma: epidemiologic aspects, diagnostic and therapeutic approach. Wien Med Wochenschr 2013; 163(15-16):354-8. Lotti T, Bruscino N, Hercogova J, de Giorgi V. Controversial issues on melanoma. Dermatol Ther 2012; 25(5):458-62. Rigel DS, Carucci JA. Malignant melanoma: prevention, early detection, and treatment in the 21st century. CA Cancer J Clin 2000; 50(4):215-36. Garbe C, Peris K, Hauschild A, et al.; European Dermatology Forum; European Association of Dermato-Oncology; European Organization of Research and Treatment of Cancer. Diagnosis and treatment of melanoma. European consensus-based interdisciplinary guideline- Update 2012. Eur J Cancer 2012; 48(15):2375-90. Pflugfelder A, Kochs C, Blum A, et al.; German Dermatological Society; Dermatologic Cooperative Oncology Group. Malignant melanoma S3-guideline "diagnosis, therapy and follow-up of melanoma". J Dtsch Dermatol Ges 2013; 6:1-26. Markovic SN, Erickson LA, Rao RD, et al.; Melanoma Study Group of Mayo Clinic Cancer
644
7. 8.
A.A. CHOKOEVA ET AL.
Center. Malignant melanoma in the 21st century, part 2: staging, prognosis, and treatment. Mayo Clin Proc 2007; 82(4):490-513. Diagnosis and treatment of early melanoma. NIH Consens Statement 1992; 27-29;10:1-26. de Vries M, Jager PL, Suunneijer AJ, Plukker IT, van Ginke1RJ, Hoekstra HJ. Sentinel lymph node biopsy for melanoma: prognostic value and disadvantages in 300 patients Ned Tijdschr Geneeskd 2005;
149(33):1845-51. Mitteldorf C, Bertsch HP, Jung K, Thoms KM, Schon MP, Tronnier M, Kretschmer L. Sentinel node biopsy improves prognostic stratification in patients with thin (pTl) melanomas and an additional risk factor. Ann Surg Onco12014; 21(7):2252-8. 10. Phan GQ, Messina JL, Sondak VK, Zager JS. Sentinel lymph node biopsy for melanoma: indications and rationale. Cancer Control 2009; 16(3):234-9.
9.
Vol. 27, no. 4, 639-644 (2014)
LETTER TO THE EDITOR
WRONG MELANOMA THICKNESS MEASUREMENT: CHECK IT OR LEAVE IT? A.A. CHOKOEVA1, G. TCHERNEV2, S. PHILIPOV3 , M. ZANARDELLP and T. LOTTI6,7
J.e. CARDOS04
'Onkoderma- Policlinicfor Dermatology and Dermatologic Surgery, General Skobelev 26 Sofia, Bulgaria; 'Pottcltntc for Dermatology and Venereology, Saint Kliment Ohridski University, Medical Faculty, University Hospital Lozenetz, Sofia, Bulgaria; 3Department ofGeneral and Clinical Pathology, Medical Faculty, "Saint Kliment Ohridski University" Sofia, Bulgaria; "Dermatology Department, University Hospital ofCoimbra,Praceta Mota Pinto, Coimbra Portugal; 'Department ofNeuroscience, Psychology, Drug Research and Child Health - NeurofarbaPharmacology and Toxicology Section, University ofFlorence, Italy; 'University ofRome "G. Marconi", Rome, Italy; 'Institute ofDermatology Life Cronos, Florence, Italy Cutaneous malignant melanoma (CMM) is one of the most aggressive forms ofskin cancer, accounting for about 90% of deaths from cutaneous neoplasms, and its incidence has increased significantly in recent years. According to "the 2012 European criteria for diagnosis and treatment of malignant melanoma, diagnosis should be based on the combination of clinical features, dermoscopic data and histological examination, preferably after excisional biopsy. Tumour thickness and other parameters for local staging according to the AJCC classification should be included in the pathology report. Although many factors influence the prognosis and course of the disease, it has been established in a number of studies that tumour thickness is the most important parameter. Therapy of malignant melanoma in its initial stages mostly consists of wide local excision with 1 to 2 cm margins, and sentinel lymph node biopsy that is usually performed in cases of tumours with a thickness greater than 1 mm, We present the case of a 58-yearold Bulgarian male with cutaneous superficial spreading malignant melanoma, in which, after complete excision, histological examination established an inaccurate tumour thickness (0.7 mm), with consequent inadequate staging and further management. After reassessment of the results in another institution (as well as their confirmation by two additional independent histopathology laboratories in our country 1.92 mm), in the National Oncological Hospital where the patient was initially evaluated, sentinel lymph node biopsy was not performed, contrary to the generally accepted European and World standards. With the present case we raise some current issues regarding diagnosis and therapy of Bulgarian patients (not only in the case presented) with malignant melanoma in the 21st century, and discuss the urgent need for external quality control procedures and standardization of the histopathologic reporting, which is of paramount importance in the staging and subsequent management of these patients. Cutaneous malignant melanoma (CMM) is one of the most aggressive forms ofskin cancer, accounting for about 90% of deaths from cutaneous neoplasms (1). Although it represents only about 3 to 5% of
'all skin cancers, malignant melanoma represents a serious public health problem as its frequency is increasing more rapidly than any other cancer in the world (1, 2). If in 1930, the risk of developing
Key words: diagnosis, surgical excision, malignant melanoma, treatment, SLNE, tumour thickness I ~ •.
Mailing address: Assoc. Prof. Georgi Tchemev, Policlinic for Dermatology and Venereology, Saint Kliment Ohridski University, Medical Faculty, University Hospital Lozenetz, Koziak street I, 1407 Sofia, Bulgaria Tel.: +359 885 588 424 e-mail: [email protected]
0394-6320 (2014)
639
.. Copyright © by BlOUFE, s.a.S. This publication and/or article is for individualuseerrly and may not be further reproduced without written permi~slo~'fro~ the copyright holder. Unauthorized reproduetionmayresultin frnancial.and other penalties DISCLOSURE: ALL AUTHORS J.ffiPO~:r..NOC:ONFLICTS OF IN1'EREST tU:LItVtiNT TocYins ARTICLE.
640
A.A. CHO KOEVA ET AL.
Fig. 1. a) Darkly pigmented lesion located on the interscapu lar area in a 58-year-old male patient. b) The lesion is asymmetrical, with irregular borders, and sharply demarcated fro m the surrounding skin lesion. c, d, e) Total surgical elliptical excision of the lesion, with 2-cm lateral margins and a depth to the underlying fasci a. j) Immediate postoperative aspect, aft er direct closure ofthe surgical def ect with a simple suture.
malignant melanoma was I in 1500 people/year, nowadays, in the 21st century, this risk is 1 in 74 people/year (3). Deaths caused by CMM have also been rising, since the mortality rate has increased nearly 2% per year from 1960 until the present day (3). According to the European Association of Dermato-oncology, therapy in cases of invasive melanoma in its initial stages consists of wide local excision with I to 2 em margins , and sentinel lymph node biopsy, mostly in case oftumours with more than 1 mm thickness (4). It can be performed in a singlestep or up to 3 weeks after the initial intervention, provided that there is no major reconstructive surgery causing significant changes in the regional anatomy and consequently in the lymphatic drainage. (4). The German Dermatologic al Society establishes 0.5 mm margins for melanoma in situ, 1 em for invasive melanoma up to 2 mm thickness, and 2 em
for tumours thicker than 2 mm (5). Sentinel lymph node biopsy is recommended in cases of melanoma with thickness greater than 1 mm (4, 5). Cancer staging should be performed by the TNM system, taking into consideration tumour thickness, status of locoregionallymph nodes and the presence ofdistant meta stases (6). Based on these results, the treatment plan, prognosis and patient follow-up program are defined (6). Regular control examinations are recommended for a period of 5-10 years (depending on tumour thickne ss), with a closer follow-up in the first three years (1, 4, 5). Despite all treatment recommendations, prevention, early diagno sis and surgical treatment remain the main therapeutic weapon against melanoma ( I, 2). With its increasing incidence we are indebted to update our approach in accordance with global standards in order to provide adequate care to all patients with CMM (1,2). The present case raises questions about current
Int. J. Immnnopathol. Pharmacol.
641
Fig. 2. a, b, c, tl) Histologicalfindings consistent with superficial spreading melanoma.
problems in diagnosis and treatment of melanoma in Bulgaria. Reflection on these issues and comparison with the European standards of care will hopefully stimulate better diagnostic and therapeutic strategies for melanoma in Bulgaria. Case report We present the case of a 58-year-old male, admitted to the Lozenets University Hospital, with a black lesion on the upper back, which had been present for 3 years, associated with local discomfort and pruritus . He had no significant comorbidities and there was no family history of malignant melanoma. The patient was in good general health, and there were no other subjective complaints. Examination disclosed a slightly elevated, darkly pigmented lesion on the interscapular area, which was asymmetrical, with irregular borders, and sharply demarcated from the surrounding skin (Fig. I a,b). Complete blood count with differential and biochemistry were within normal range. Diagnostic imaging: abdominal ultrasound - no abnormalities; thyroid ultrasound gland - no evidence of nodular
lesions; lymphadenopathy was found in the left supraclavicular area, with 3-4 lymph nodes 7-8 mm in size. The provisional diagnosis of superficial spreading malignant melanoma was established on the basis of clinical and dermoscopic examination. Complete excision under local anaesthesia was performed (Fig. 1 c,d,e). As per request of the patient, histopathological examination of the lesion was carried out in another public institution - the National Oncologic Hospital. The first histological examination reported a superficial spreading pigmented malignant melanoma with a thickness of 0.7 mm, Clark level 2, without evidence of established regression or ulceration. Computer tomography (CT) of the chest, abdomen and pelvis revealed no evidence of distant metastasis - MO. In face of the parameters initially assessed in the primary tumour, a sentinel lymph node biopsy was not performed. Later, a review of the pathology was undertaken in the Pathology Department of Lozenets University
642
A.A. CHOKOEVAET AL.
hospital (Fig. 2 a,b,c,d), confirming the diagnosis of superficial spreading malignant melanoma composed of both epithelioid and spindle-shaped melanocytes. However, maximum thickness was determined at 1.92 mm, after measurements at different points of the proliferation (respectively 0.87 mm, 1.63 mm and 1.92 mm). Mitotic count was 3110HPF, and there was focal ulceration associated with fibrin deposition and neutrophils. The adjacent epidermis was thinned, and there was a pronounced stromal reaction (Fig. 2 a.b.c.d). The pathological staging was upgraded to: pT2b Nx Mx VO LORO as the lymph nodes in the supraclavicular area were not taken into consideration. This diagnosis was further corroborated by two other independent evaluations in different histopathological laboratories in Bulgaria. DISCUSSION The present case elicits our concerns in view of the relevance of accurate measurement ofmelanoma thickness, which is of the utmost importance in the prediction of prognosis, and which guides further management of the patients, namely the indication for sentine1lymph node biopsy. According to the 2012 European criteria for diagnosis and therapy of malignant melanoma, the diagnosis should be based on clinical assessment, dermoscopic criteria and histological examination of the lesion after complete excision, with subsequent determination of tumour thickness and staging according to AJCC classification (1, 2, 4, 5). Although many factors influence the prognosis and course ofthe disease, a number of studies concur that tumour thickness is the most important of them (I, 2, 4, 5). Five-year survival in patients with earlystage disease (tumour thickness less than 1 mm) is estimated at 94%, and only 50% in those with lesions over 3 mm (1,5, 7). It is also important to stress that there is a likelihood of early lymph nodes metastases in 40% of patients with a lesion with thickness between 1 and 4 mm, and distant metastases in only 10% of them, while in patients with a tumour thickness greater than 4 mm, the risk of lymph node and distant metastases is approximately 60% and 70%, respectively (3, 4). These data emphasize the necessity of accurate staging of melanoma, namely
of its thickness, in order to estimate apatient's survival rate and risk of metastasis. Regarding the present case, initial histological assessment estimated a tumour thickness of 0.7 mm, corresponding to stage TlA (melanomas 0.75 mm, considering that SLNB is a method that provides highly valuable prognostic information for selection of subsequent treatment, coupled with a minimal risk of complications (10). In view of this, we consider that lymph node biopsy of the lymph nodes that were enlarged on the ultrasound examination would be indicated in our case, especially taking into account the primary tumour thickness of 1.92 mm, with a significant risk of locoregional metastases.
643
In conclusion, in cases of CMM we emphasize the importance of accurate tumour thickness measurements as well as SLNB, whenever indicated according to current practice. Based on this illustrative case, we wish to stress out the need for compliance with current guidelines of diagnosis and treatment of malignant melanoma by dermatologic surgeons and dermato-oncologists in Bulgaria. With this purpose in mind, precise and common strategies have to be carried out. For example, an Interdisciplinary Melanoma Board would be of value within the setting of Bulgarian Health Authorities in order to individualize diagnostic and therapeutic approaches for each patient. Setting up a "National Bulgarian Melanoma Register" would be most helpful in order to obtain accurate statistical data regarding the prevalence of melanoma and to promote correct follow-up of all cases. REFERENCES: 1.
2.
3.
4.
5.
6.
Tronnier M, Semkova K, Wollina U, Tchemev G. Malignant melanoma: epidemiologic aspects, diagnostic and therapeutic approach. Wien Med Wochenschr 2013; 163(15-16):354-8. Lotti T, Bruscino N, Hercogova J, de Giorgi V. Controversial issues on melanoma. Dermatol Ther 2012; 25(5):458-62. Rigel DS, Carucci JA. Malignant melanoma: prevention, early detection, and treatment in the 21st century. CA Cancer J Clin 2000; 50(4):215-36. Garbe C, Peris K, Hauschild A, et al.; European Dermatology Forum; European Association of Dermato-Oncology; European Organization of Research and Treatment of Cancer. Diagnosis and treatment of melanoma. European consensus-based interdisciplinary guideline- Update 2012. Eur J Cancer 2012; 48(15):2375-90. Pflugfelder A, Kochs C, Blum A, et al.; German Dermatological Society; Dermatologic Cooperative Oncology Group. Malignant melanoma S3-guideline "diagnosis, therapy and follow-up of melanoma". J Dtsch Dermatol Ges 2013; 6:1-26. Markovic SN, Erickson LA, Rao RD, et al.; Melanoma Study Group of Mayo Clinic Cancer
644
7. 8.
A.A. CHOKOEVA ET AL.
Center. Malignant melanoma in the 21st century, part 2: staging, prognosis, and treatment. Mayo Clin Proc 2007; 82(4):490-513. Diagnosis and treatment of early melanoma. NIH Consens Statement 1992; 27-29;10:1-26. de Vries M, Jager PL, Suunneijer AJ, Plukker IT, van Ginke1RJ, Hoekstra HJ. Sentinel lymph node biopsy for melanoma: prognostic value and disadvantages in 300 patients Ned Tijdschr Geneeskd 2005;
149(33):1845-51. Mitteldorf C, Bertsch HP, Jung K, Thoms KM, Schon MP, Tronnier M, Kretschmer L. Sentinel node biopsy improves prognostic stratification in patients with thin (pTl) melanomas and an additional risk factor. Ann Surg Onco12014; 21(7):2252-8. 10. Phan GQ, Messina JL, Sondak VK, Zager JS. Sentinel lymph node biopsy for melanoma: indications and rationale. Cancer Control 2009; 16(3):234-9.
9.
