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Malignant Cutaneous Melanoma - Criteria for Diagnosis and Prognosis Factors
Introduction
Malignant melanoma (MM) corresponds to a malign neoplasia of melanocytes, which is resistant both to chemotherapy and radiotherapy, and therefore its preferred treatment is surgical. Due to its high metastatic potential, the main aim is to diagnose and treat in the early stages of the illness. The first publication of this tumour was carried out by the French doctor René Laennec in 1806.(1)
On skin, MM usually begins on the epidermis from a mutation taking place in the melanocyte found there. It is termed in situ MM when it is confined to the epidermis, here including the anexial epithelial (hair follicles and sudorifarous glands). In this phase there is no risk of metastisation as the epithelium has no blood or lymphatic vessels.
The next step in the evolution of MM corresponds to the invasion of the dermis, and it is from this point on that MM becomes really “malignant”, as it gains the possibility to metastise into distant tissues and organs.
Only in about a fifth of the cases does MM originate from previous benign melanocytic lesion, such as naevi, principally the giant congenital naevi (when their axis is over 20 cm) and also in acquired naevi (dysplastic naevi or, very rarely, in blue naevi).
Criteria for Diagnosis
Diagnosis of MM is essentially based on the correlation between clinical practice and the microscopic observation of histological cuts representative of the whole tumour, coloured by haematoxylin and eosin (H&E), as there is still no immuno-histochemical marker that is 100% specific and sensitive for the diagnosis of MM that can allow us to replace the routine histological test.
MM usually consists of a single, hyperpigmented stain that progressively evolves into a pimple and then into a tumour, becoming a part of the so-called list of black cutaneous tumours.(2)
The homogenous colour of the initial lesion takes on other shades of colour over time, such as black, dark brown, light brown, red, blue and grey. The borders, which start out being regular, become irregular, and the surface, which is initially smooth, may alternate between atrophic areas (with possible secondary ulceration) and verrucose areas.
In the study of a melanocytic lesion the acronym ABCDE is a term that is widely used, with its initials corresponding to: Assymetric Skin Lesion, Border irregular, Colours varied, Diameter over 6 mm and Elevation/Evolving.
Nowadays one can carry out observation of suspect lesions with a polarised light dermatoscope (epiluminescence microscopy), that allows an increase of ten or more times.
In the clinical semiology of the MM that appears in a previous melanocytic lesion, not only should the appearing of areas of hipopigmentation be valorised, but also the rash, the haemorrhage and the ulceration.
MM mainly appears in Caucasian individuals over forty years old, with it being rare in puberty and exceptional in children. No predominance has been observed in either sex.
In a clinical-pathological perspective MM are classically divided into four types:
- Superficial Spreading MM
- Lentigo Maligna MM
- Nodular MM
- Acrolentiginous MM.
MM is amelanotic when it contains no (or little) melanic pigment, which makes its clinical diagnosis difficult. It is most commonly located of the faces of older people and is usually associated to a histological pattern of desmoplasia, forming a group known as desmoplasic MM, which was the subject of my PhD thesis.(3)
Incidence, Prevalence and Mortality
Incidence and prevalence of MM vary with the personal and environmental risk factors.
As personal risk factors we may list characteristics of each individual, such as personal or family history of MM,4 the presence of potential lesions that are precursors of MM (such as a large number of dysplatic naevi and even common naevi(5;6), skin susceptibility to the sun(7) and the presence of indicators of chronic actinic harm.
As environmental risk factors, remaining in places with greater exposure to ultraviolet radiation (lower latitude and greater altitude), principally in childhood.(8)
The highest incidence of MM occurs in the white population of the Australian continent, followed by North American continent and Southern Europe, with incidence rates according to age, per 100,000 inhabitants and by year of 37.7, 16.4 and 8.4 for the males ex, and 29.4, 11.7 and 10.0 for the female sex respectively.(9) In the United States of America the incidence of MM among the white population is about 20 times higher than that observed in the black population.(10) In Portugal there are no reliable statistics about its occurrence.
In the cases of acral MMl(11) or of the mucous areas it is difficult to understand the pathogenic action of ultraviolet radiation at its origin. Subungual MM represent about 20% of the MM observed in people with dark skin, including the oriental populations, while they correspond to 2% in the white population.(12) In a study of 406 subungual MM published in 2002,(13) the preferential location for MM was in the thumb (58%), and the big toe (86% on the hallux). These authors suggest trauma as the most probable cause for this type of MM.
Factors for Prognosis
Clinically we can state that the following are variables of the worst prognosis:
• Age – MM with the same thickness usually has a more aggressive behaviour in patients over 60 years old.(14)
• Anatomical Location – MM on the head and neck and on the trunk are associated with a higher rate of metastases and mortality than acral MM.(15) When MMs occur on the head, the scalp is the location associated to the worst prognosis.(16)
• Sex – MM with the same thickness usually have a more aggressive behaviour in men than in patients of the female sex.(17)
• Ulceration – Usually associated to a greater tumoral volume and therefore to a worse prognosis.(18)
Histological study of the whole of the piece excised allows us to study the histological variables of prognostic interest:
- Breslow’s Depth – corresponds to the MM thickness in mm measured on the vertical between the top of the granular layer and the tumour cell located more deeply.(19) In isolation it is the most important characteristic in the foreseeing of the survival time in patients which exclusively cutaneous MM.(15)
• Clark Level corresponds to the degree of tumour invasion, and is divided into five levels, with level 1 being when the lesion is confined to the epidermis and its annexes (MM in situ), level II when it is limited to the papillary dermis, III in the transition between the papillary dermis and the reticular dermis, level IV when it reaches the reticular dermis, up to level V, which corresponds to tumour invasion of the subcutaneous fat.(20) The percentage of patients with survival time free of illness at 10 years is in agreement with the 5 levels of 100%, 96%, 86%, 66% and 53%, respectively.(21)
• Ulceration is defined as a continuity solution in the epithelium that covers the tumour, with evidence of reaction by the host, in order to be able to exclude that which results from the biopsy trauma. It has been demonstrated that the ulceration worsens the prognosis in countless multi-variable analyses that have been published.(22)
• Regression corresponds to the “destruction” of parts of the MM by memory lymphocytes, which it is believed have metastised primarily to a regional ganglion and “regressed” to the tumour. This also makes us believe that the tumour had had a greater thickness in a phase previous to the recruiting of the inflammatory cells.(15)
• The mitotic index is expressed as low, medium and high, according to the number of mitoses per mm2, when they are: lower than 1, between 1 and 4, and over 4 mitoses, respectively. The presence of mitoses in the dermis is associated to a lowering of survival time. When the number of mitoses is equal to or higher than 6, the risk of metastisation is 12 times higher than that of a patient in whose tumour one cannot see any mitosis.(17)
• TIL or tumour infiltrating lymphocytes corresponds to the presence of lymphocytes infiltrating the tumour (among or alongside the tumour cells) and has been shown to have an independent prognostic meaning.(23) The prognosis is better when there is an intense inflammatory reaction, defined as a dense lymphocytary band underneath the tumour of diffusely infiltrating the tumour itself. Inversely, the absence of inflammatory infiltration is associated to a worse prognosis. The volume of the lymphocytary infiltration is inversely proportional to the thickness of the primary MM, with it usually being scarce in the tumours that are deeply invasive.
• Lympho-vascular invasion corresponds to the presence of tumour cells not only inside the lymphatic or blood vessels, but also in their wall (next to the endothelial cells) and is associated to a worse prognosis.(24)
• Neurotropism corresponds to the microscopic observation of malignant tumour cells in the perineural space of the nerves. Neurotropism can be intraneural, perineural or have aspects of neural differentiation, simulating Schwann cells. The extension of MM along peripheral cranial nerves may be a complication in some head and neck MM, principally in the desmosplasic variety. Then neurotropic MM dominate and may be associated to local infiltration, multiple relapses and metastases to the SNC.(25)
• Satellitosis corresponds to the presence of tumoral focuses that are isolated from the main tumour, located at less than 5 from the primary lesion. When the tumoral focuses appear in the same anatomical region, but at a greater distance than 5 cm, they are called transit metastases. The presence of satellitosis is an indicator of a bad prognosis, as it corresponds to stage IV of the American Joint Commission on Cancer Staging Committee (AJCC) classification system, even when the metastases are only microscopic.(26)
The aspects of the primary tumour (T) – thickness in mm (= 1.0, 1.01-2.0, 2.01-4.0, > 4.0), along with the presence or absence of ulceration, the number of mitoses per mm2 and the Clark Level (II/III and IV/V); the presence and the number of ganglion metastases (N) and the presence and location of distant metastases (M), in order to determine the state based on these three attributes (TNM). The seric increase of the lactic desidrogenasis enzyme, or LDH, is also of interest as a sign of bad prognosis.(26)
Information gathered by the AJCC concluded that thin MM (thickness equal to or less than 1 mm) have an excellent prognosis, with 90% survival at 5 years, in contrast to thick MM (thickness over 4 mm) that are associated to a worse prognosis, with about 45% survival at 5 years.(15;27)
Besides thickness, other factors are relevant for the establishing of the prognosis. The AJCC therefore proposed the separation of MM patients into subgroups with similar prognoses, with interest in the treatment and in research.
This classification, based on the linking of clinical and histopathological information, allows a separating of the patients into stages, between 0 and IV, with different prognoses. Stage 0 corresponds to MM in situ; stages I and II to exclusively primary cutaneous MM; stage III corresponds to ganglion metastisation, with the most relevant factor being, not the size of the ganglia involved, but rather their number (1, 2 or 3 and, 4 or more); stage IV corresponds to the MM phase with distant metastases (skin and subcutaneous cell tissue, lung and any other organ or when the value of the lactic desidrogenasis enzyme – LDH is high).
Survival at 5 years for patients with primary MM diagnosed at stages between 0 and II is about 80%, compared to a survival of 35% when the lymphatic ganglia are invaded (stage III). When there are distant metastases (stage IV) survival at 5 years is around 10%.15
Luís Soares de Almeida
Clínica Universitária de Dermatologia de Lisboa
luis.soares.almeida@gmail.com
Bibliography
1. Laennec RTH. "Sur les melanoses". Bulletin de la Faculte de Medecine de Paris 1806; 1: 24–26.
2. Esteves JA, Baptista AP, Rodrigo FG, Gomes MM. Disposição neoplásica. EM: Esteves JA, Baptista AP, Rodrigo FG, Gomes MM, eds. Dermatologia. Lisboa: Fundação Calouste Gulbenkian, 1992: 820.
3. Luis Soares de Almeida, Luis Requena, Arno Rütten, Heinz Kutzner, Claus Garbe, Dinis Pestana, Manuel Marques Gomes. Desmoplastic Malignant Melanoma: A Clinicopathologic Analysis of 113 Cases. Am J Dermatopathol 2008; 30: 207-215.
4. Aitken JF, Duffy DL, Green A, Youl P, MacLennan R, Martin NG. Heterogeneity of melanoma risk in families of melanoma patients. Am J Epidemiol 1994;140:961-73.
5. Elwood JM, Whitehead SM, Davison J, Stewart M, Galt M. Malignant melanoma in England: risks associated with naevi, freckles, social class, hair colour, and sunburn. Int J Epidemiol1990;19:801-10.
6. Newton JA, Bataille V, Griffiths K et al. How common is the atypical mole syndrome phenotype in apparently sporadic melanoma? J Am Acad Dermatol 1993;29:989-96. Fitzpatrick TB. The validity and practicality of sun-reactive skin types I through VI. Arch Dermatol1988;124:869-71.
7. Gallagher RP, Elwood JM, Threlfall WJ, Spinelli JJ, Fincham S, Hill GB. Socioeconomic status, sunlight exposure, and risk of malignant melanoma: the Western Canada Melanoma Study. J Natl Cancer Inst 1987;79:647-52.
8. de Vries E, Bray F, Coeberg JW et al. Malignant melanoma. Introduction. In: LeBoit P, Burg G, Weedon D, Sarasin A, eds. Pathology And Genetics of Skin Tumours. Lyon: IARC Press, 2006:52-65.
9. Elder DE, Elenitsas R, Xu X. Benign pigmented lesions and malignant melanoma. In: Elder DE, Elenitsas R, Johnson BL, Murphy GF, Xu X, eds. Lever's Histopathology of the skin. Philadelphia (PA): Lippincott Williams & Wilkins, 2009:699-789.
10. Mooi WJ, Krausz T. Pathology of Melanocytic Disorders. Great Britain: Hodder Arnold, 2007.
11. Krementz ET, Feed RJ, Coleman WP, III, Sutherland CM, Carter RD, Campbell M. Acral lentiginous melanoma. A clinicopathologic entity. Ann Surg 1982;195:632-45.
12. Takematsu H, Obata M, Tomita Y, Kato T, Takahashi M, Abe R. Subungual melanoma. A clinicopathologic study of 16 Japanese cases. Cancer 1985;55:2725-31.
13. Mohrle M, Hafner HM. Is subungual melanoma related to trauma? Dermatology2002;204:259-61.
14. Balch CM, Soong S, Ross MI et al. Long-term results of a multi-institutional randomized trial comparing prognostic factors and surgical results for intermediate thickness melanomas (1.0 to 4.0 mm). Intergroup Melanoma Surgical Trial. Ann Surg Oncol 2000;7:87-97.
15. Balch CM, Soong SJ, Gershenwald JE et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol 2001;19:3622-34.
16. Balch CM. Cutaneous melanoma: prognosis and treatment results worldwide. Semin Surg Oncol 1992;8:400-14.
17. Clark WH, Jr., Elder DE, Guerry D et al. Model predicting survival in stage I melanoma based on tumor progression. J Natl Cancer Inst 1989;81:1893-904.
18. Payette MJ, Katz M, III, Grant-Kels JM. Melanoma prognostic factors found in the dermatopathology report. Clin Dermatol 2009;27:53-74.
19. Kirkham N, Cotton DW. Measuring melanomas: the Vernier method. J Clin Pathol1984;37:229-30.
20. Clark WH, Jr., From L, Bernardino EA, Mihm MC. The histogenesis and biologic behavior of primary human malignant melanomas of the skin. Cancer Res 1969;29:705-27.
21. Elder D. Lever's Histopathology of the skin. Philadelphia (PA): 2009.
22. Vihinen PP, Pyrhonen SO, Kahari VM. New prognostic factors and developing therapy of cutaneous melanoma. Ann Med 2003;35:66-78.
23. Clemente CG, Mihm MC, Jr., Bufalino R, Zurrida S, Collini P, Cascinelli N. Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer 1996;77:1303-10.
24. Kashani-Sabet M, Sagebiel RW, Ferreira CM, Nosrati M, Miller JR, III. Vascular involvement in the prognosis of primary cutaneous melanoma. Arch Dermatol 2001;137:1169-73.
25. Gentile RD, Donovan DT. Neurotropic melanoma of the head and neck. Laryngoscope1985;95:1161-6.
26. Garnier JP, Letellier S, Cassinat B et al. Clinical value of combined determination of plasma L-DOPA/tyrosine ratio, S100B, MIA and LDH in melanoma. Eur J Cancer 2007;43:816-21.
27. Balch CM, Buzaid AC, Soong SJ et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 2001;19:3635-48.
Malignant melanoma (MM) corresponds to a malign neoplasia of melanocytes, which is resistant both to chemotherapy and radiotherapy, and therefore its preferred treatment is surgical. Due to its high metastatic potential, the main aim is to diagnose and treat in the early stages of the illness. The first publication of this tumour was carried out by the French doctor René Laennec in 1806.(1)
On skin, MM usually begins on the epidermis from a mutation taking place in the melanocyte found there. It is termed in situ MM when it is confined to the epidermis, here including the anexial epithelial (hair follicles and sudorifarous glands). In this phase there is no risk of metastisation as the epithelium has no blood or lymphatic vessels.
The next step in the evolution of MM corresponds to the invasion of the dermis, and it is from this point on that MM becomes really “malignant”, as it gains the possibility to metastise into distant tissues and organs.
Only in about a fifth of the cases does MM originate from previous benign melanocytic lesion, such as naevi, principally the giant congenital naevi (when their axis is over 20 cm) and also in acquired naevi (dysplastic naevi or, very rarely, in blue naevi).
Criteria for Diagnosis
Diagnosis of MM is essentially based on the correlation between clinical practice and the microscopic observation of histological cuts representative of the whole tumour, coloured by haematoxylin and eosin (H&E), as there is still no immuno-histochemical marker that is 100% specific and sensitive for the diagnosis of MM that can allow us to replace the routine histological test.
MM usually consists of a single, hyperpigmented stain that progressively evolves into a pimple and then into a tumour, becoming a part of the so-called list of black cutaneous tumours.(2)
The homogenous colour of the initial lesion takes on other shades of colour over time, such as black, dark brown, light brown, red, blue and grey. The borders, which start out being regular, become irregular, and the surface, which is initially smooth, may alternate between atrophic areas (with possible secondary ulceration) and verrucose areas.
In the study of a melanocytic lesion the acronym ABCDE is a term that is widely used, with its initials corresponding to: Assymetric Skin Lesion, Border irregular, Colours varied, Diameter over 6 mm and Elevation/Evolving.
Nowadays one can carry out observation of suspect lesions with a polarised light dermatoscope (epiluminescence microscopy), that allows an increase of ten or more times.
In the clinical semiology of the MM that appears in a previous melanocytic lesion, not only should the appearing of areas of hipopigmentation be valorised, but also the rash, the haemorrhage and the ulceration.
MM mainly appears in Caucasian individuals over forty years old, with it being rare in puberty and exceptional in children. No predominance has been observed in either sex.
In a clinical-pathological perspective MM are classically divided into four types:
- Superficial Spreading MM
- Lentigo Maligna MM
- Nodular MM
- Acrolentiginous MM.
MM is amelanotic when it contains no (or little) melanic pigment, which makes its clinical diagnosis difficult. It is most commonly located of the faces of older people and is usually associated to a histological pattern of desmoplasia, forming a group known as desmoplasic MM, which was the subject of my PhD thesis.(3)
Incidence, Prevalence and Mortality
Incidence and prevalence of MM vary with the personal and environmental risk factors.
As personal risk factors we may list characteristics of each individual, such as personal or family history of MM,4 the presence of potential lesions that are precursors of MM (such as a large number of dysplatic naevi and even common naevi(5;6), skin susceptibility to the sun(7) and the presence of indicators of chronic actinic harm.
As environmental risk factors, remaining in places with greater exposure to ultraviolet radiation (lower latitude and greater altitude), principally in childhood.(8)
The highest incidence of MM occurs in the white population of the Australian continent, followed by North American continent and Southern Europe, with incidence rates according to age, per 100,000 inhabitants and by year of 37.7, 16.4 and 8.4 for the males ex, and 29.4, 11.7 and 10.0 for the female sex respectively.(9) In the United States of America the incidence of MM among the white population is about 20 times higher than that observed in the black population.(10) In Portugal there are no reliable statistics about its occurrence.
In the cases of acral MMl(11) or of the mucous areas it is difficult to understand the pathogenic action of ultraviolet radiation at its origin. Subungual MM represent about 20% of the MM observed in people with dark skin, including the oriental populations, while they correspond to 2% in the white population.(12) In a study of 406 subungual MM published in 2002,(13) the preferential location for MM was in the thumb (58%), and the big toe (86% on the hallux). These authors suggest trauma as the most probable cause for this type of MM.
Factors for Prognosis
Clinically we can state that the following are variables of the worst prognosis:
• Age – MM with the same thickness usually has a more aggressive behaviour in patients over 60 years old.(14)
• Anatomical Location – MM on the head and neck and on the trunk are associated with a higher rate of metastases and mortality than acral MM.(15) When MMs occur on the head, the scalp is the location associated to the worst prognosis.(16)
• Sex – MM with the same thickness usually have a more aggressive behaviour in men than in patients of the female sex.(17)
• Ulceration – Usually associated to a greater tumoral volume and therefore to a worse prognosis.(18)
Histological study of the whole of the piece excised allows us to study the histological variables of prognostic interest:
- Breslow’s Depth – corresponds to the MM thickness in mm measured on the vertical between the top of the granular layer and the tumour cell located more deeply.(19) In isolation it is the most important characteristic in the foreseeing of the survival time in patients which exclusively cutaneous MM.(15)
• Clark Level corresponds to the degree of tumour invasion, and is divided into five levels, with level 1 being when the lesion is confined to the epidermis and its annexes (MM in situ), level II when it is limited to the papillary dermis, III in the transition between the papillary dermis and the reticular dermis, level IV when it reaches the reticular dermis, up to level V, which corresponds to tumour invasion of the subcutaneous fat.(20) The percentage of patients with survival time free of illness at 10 years is in agreement with the 5 levels of 100%, 96%, 86%, 66% and 53%, respectively.(21)
• Ulceration is defined as a continuity solution in the epithelium that covers the tumour, with evidence of reaction by the host, in order to be able to exclude that which results from the biopsy trauma. It has been demonstrated that the ulceration worsens the prognosis in countless multi-variable analyses that have been published.(22)
• Regression corresponds to the “destruction” of parts of the MM by memory lymphocytes, which it is believed have metastised primarily to a regional ganglion and “regressed” to the tumour. This also makes us believe that the tumour had had a greater thickness in a phase previous to the recruiting of the inflammatory cells.(15)
• The mitotic index is expressed as low, medium and high, according to the number of mitoses per mm2, when they are: lower than 1, between 1 and 4, and over 4 mitoses, respectively. The presence of mitoses in the dermis is associated to a lowering of survival time. When the number of mitoses is equal to or higher than 6, the risk of metastisation is 12 times higher than that of a patient in whose tumour one cannot see any mitosis.(17)
• TIL or tumour infiltrating lymphocytes corresponds to the presence of lymphocytes infiltrating the tumour (among or alongside the tumour cells) and has been shown to have an independent prognostic meaning.(23) The prognosis is better when there is an intense inflammatory reaction, defined as a dense lymphocytary band underneath the tumour of diffusely infiltrating the tumour itself. Inversely, the absence of inflammatory infiltration is associated to a worse prognosis. The volume of the lymphocytary infiltration is inversely proportional to the thickness of the primary MM, with it usually being scarce in the tumours that are deeply invasive.
• Lympho-vascular invasion corresponds to the presence of tumour cells not only inside the lymphatic or blood vessels, but also in their wall (next to the endothelial cells) and is associated to a worse prognosis.(24)
• Neurotropism corresponds to the microscopic observation of malignant tumour cells in the perineural space of the nerves. Neurotropism can be intraneural, perineural or have aspects of neural differentiation, simulating Schwann cells. The extension of MM along peripheral cranial nerves may be a complication in some head and neck MM, principally in the desmosplasic variety. Then neurotropic MM dominate and may be associated to local infiltration, multiple relapses and metastases to the SNC.(25)
• Satellitosis corresponds to the presence of tumoral focuses that are isolated from the main tumour, located at less than 5 from the primary lesion. When the tumoral focuses appear in the same anatomical region, but at a greater distance than 5 cm, they are called transit metastases. The presence of satellitosis is an indicator of a bad prognosis, as it corresponds to stage IV of the American Joint Commission on Cancer Staging Committee (AJCC) classification system, even when the metastases are only microscopic.(26)
The aspects of the primary tumour (T) – thickness in mm (= 1.0, 1.01-2.0, 2.01-4.0, > 4.0), along with the presence or absence of ulceration, the number of mitoses per mm2 and the Clark Level (II/III and IV/V); the presence and the number of ganglion metastases (N) and the presence and location of distant metastases (M), in order to determine the state based on these three attributes (TNM). The seric increase of the lactic desidrogenasis enzyme, or LDH, is also of interest as a sign of bad prognosis.(26)
Information gathered by the AJCC concluded that thin MM (thickness equal to or less than 1 mm) have an excellent prognosis, with 90% survival at 5 years, in contrast to thick MM (thickness over 4 mm) that are associated to a worse prognosis, with about 45% survival at 5 years.(15;27)
Besides thickness, other factors are relevant for the establishing of the prognosis. The AJCC therefore proposed the separation of MM patients into subgroups with similar prognoses, with interest in the treatment and in research.
This classification, based on the linking of clinical and histopathological information, allows a separating of the patients into stages, between 0 and IV, with different prognoses. Stage 0 corresponds to MM in situ; stages I and II to exclusively primary cutaneous MM; stage III corresponds to ganglion metastisation, with the most relevant factor being, not the size of the ganglia involved, but rather their number (1, 2 or 3 and, 4 or more); stage IV corresponds to the MM phase with distant metastases (skin and subcutaneous cell tissue, lung and any other organ or when the value of the lactic desidrogenasis enzyme – LDH is high).
Survival at 5 years for patients with primary MM diagnosed at stages between 0 and II is about 80%, compared to a survival of 35% when the lymphatic ganglia are invaded (stage III). When there are distant metastases (stage IV) survival at 5 years is around 10%.15
Luís Soares de Almeida
Clínica Universitária de Dermatologia de Lisboa
luis.soares.almeida@gmail.com
Bibliography
1. Laennec RTH. "Sur les melanoses". Bulletin de la Faculte de Medecine de Paris 1806; 1: 24–26.
2. Esteves JA, Baptista AP, Rodrigo FG, Gomes MM. Disposição neoplásica. EM: Esteves JA, Baptista AP, Rodrigo FG, Gomes MM, eds. Dermatologia. Lisboa: Fundação Calouste Gulbenkian, 1992: 820.
3. Luis Soares de Almeida, Luis Requena, Arno Rütten, Heinz Kutzner, Claus Garbe, Dinis Pestana, Manuel Marques Gomes. Desmoplastic Malignant Melanoma: A Clinicopathologic Analysis of 113 Cases. Am J Dermatopathol 2008; 30: 207-215.
4. Aitken JF, Duffy DL, Green A, Youl P, MacLennan R, Martin NG. Heterogeneity of melanoma risk in families of melanoma patients. Am J Epidemiol 1994;140:961-73.
5. Elwood JM, Whitehead SM, Davison J, Stewart M, Galt M. Malignant melanoma in England: risks associated with naevi, freckles, social class, hair colour, and sunburn. Int J Epidemiol1990;19:801-10.
6. Newton JA, Bataille V, Griffiths K et al. How common is the atypical mole syndrome phenotype in apparently sporadic melanoma? J Am Acad Dermatol 1993;29:989-96. Fitzpatrick TB. The validity and practicality of sun-reactive skin types I through VI. Arch Dermatol1988;124:869-71.
7. Gallagher RP, Elwood JM, Threlfall WJ, Spinelli JJ, Fincham S, Hill GB. Socioeconomic status, sunlight exposure, and risk of malignant melanoma: the Western Canada Melanoma Study. J Natl Cancer Inst 1987;79:647-52.
8. de Vries E, Bray F, Coeberg JW et al. Malignant melanoma. Introduction. In: LeBoit P, Burg G, Weedon D, Sarasin A, eds. Pathology And Genetics of Skin Tumours. Lyon: IARC Press, 2006:52-65.
9. Elder DE, Elenitsas R, Xu X. Benign pigmented lesions and malignant melanoma. In: Elder DE, Elenitsas R, Johnson BL, Murphy GF, Xu X, eds. Lever's Histopathology of the skin. Philadelphia (PA): Lippincott Williams & Wilkins, 2009:699-789.
10. Mooi WJ, Krausz T. Pathology of Melanocytic Disorders. Great Britain: Hodder Arnold, 2007.
11. Krementz ET, Feed RJ, Coleman WP, III, Sutherland CM, Carter RD, Campbell M. Acral lentiginous melanoma. A clinicopathologic entity. Ann Surg 1982;195:632-45.
12. Takematsu H, Obata M, Tomita Y, Kato T, Takahashi M, Abe R. Subungual melanoma. A clinicopathologic study of 16 Japanese cases. Cancer 1985;55:2725-31.
13. Mohrle M, Hafner HM. Is subungual melanoma related to trauma? Dermatology2002;204:259-61.
14. Balch CM, Soong S, Ross MI et al. Long-term results of a multi-institutional randomized trial comparing prognostic factors and surgical results for intermediate thickness melanomas (1.0 to 4.0 mm). Intergroup Melanoma Surgical Trial. Ann Surg Oncol 2000;7:87-97.
15. Balch CM, Soong SJ, Gershenwald JE et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol 2001;19:3622-34.
16. Balch CM. Cutaneous melanoma: prognosis and treatment results worldwide. Semin Surg Oncol 1992;8:400-14.
17. Clark WH, Jr., Elder DE, Guerry D et al. Model predicting survival in stage I melanoma based on tumor progression. J Natl Cancer Inst 1989;81:1893-904.
18. Payette MJ, Katz M, III, Grant-Kels JM. Melanoma prognostic factors found in the dermatopathology report. Clin Dermatol 2009;27:53-74.
19. Kirkham N, Cotton DW. Measuring melanomas: the Vernier method. J Clin Pathol1984;37:229-30.
20. Clark WH, Jr., From L, Bernardino EA, Mihm MC. The histogenesis and biologic behavior of primary human malignant melanomas of the skin. Cancer Res 1969;29:705-27.
21. Elder D. Lever's Histopathology of the skin. Philadelphia (PA): 2009.
22. Vihinen PP, Pyrhonen SO, Kahari VM. New prognostic factors and developing therapy of cutaneous melanoma. Ann Med 2003;35:66-78.
23. Clemente CG, Mihm MC, Jr., Bufalino R, Zurrida S, Collini P, Cascinelli N. Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer 1996;77:1303-10.
24. Kashani-Sabet M, Sagebiel RW, Ferreira CM, Nosrati M, Miller JR, III. Vascular involvement in the prognosis of primary cutaneous melanoma. Arch Dermatol 2001;137:1169-73.
25. Gentile RD, Donovan DT. Neurotropic melanoma of the head and neck. Laryngoscope1985;95:1161-6.
26. Garnier JP, Letellier S, Cassinat B et al. Clinical value of combined determination of plasma L-DOPA/tyrosine ratio, S100B, MIA and LDH in melanoma. Eur J Cancer 2007;43:816-21.
27. Balch CM, Buzaid AC, Soong SJ et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 2001;19:3635-48.
