Correspondence Clinical Letter
Clinical Letter Lentigo maligna and lentigo maligna melanoma as occupational skin diseases in a forestry worker with long-standing occupational UV-exposure
DOI: 10.1111/ddg.12378
Dear Editors, In an Scientific Opinion from 2013, the medical expert advisory panel “Occupational Diseases,” of the German Federal Ministry of Labor and Social Affairs, suggested the introduction of a new occupational disease termed “squamous cell carcinoma or multiple actinic keratosis of the skin due to natural UV light” [1]. Yet it remains unclear whether, and to what extent, lentigo maligna (LM) or lentigo maligna melanoma (LMM) lesions on skin damaged by chronic exposure to natural UV light are to be recognized as an occupational disease (according to Book VII, Section 2, Para. 9 of the German Social Security Code [SGB VII]) in outdoor workers. The Scientific Opinion only indicates that the various subtypes of malignant melanoma may be variously influenced by exposure to UV light, without taking a specific position on LM and LMM [1]. The current WHO classification distinguishes four melanoma types based on clinical and histological features: LMM, superficial spreading melanoma, nodular melanoma, and acrolentiginous melanoma [2]. LM is defined clinically as a usually poorly circumscribed macule, with irregular brown or black pigmentation which occurs on elastotic skin that has been chronically exposed to UV light. After persisting for many years, it often develops into invasive LMM, with a visible and palpable infiltrate or nodules. Histological analysis of an LM, which is considered to be melanoma in situ, reveals an atrophic epidermis over marked dermal elastosis, with atypical suprabasal melanocytes [3]. The epidermis may also have atypical melanocyte nests, often with spindle-like cells. Invasion of adnexal structures may also occur. Invasive LMM is present if there is penetration of the basement membrane and formation of dermal tumor nests. LMM should be distinguished from other melanoma types using molecular biological tests. The genetic signatures in dermatohistological classification suggest that melanoma is not a single entity, but rather a “family of different molecular diseases” [4]. Melanomas on areas of the skin which are not chronically sun exposed are often associated with BRAF and NRAS mutations, which are not found on chronically sun exposed skin; these areas have higher copy number of CDK4 and CCD1 and KIT mutations. These are new findings rela-
ted to Book VII, Section 2, Para. 9 of the SGB, which are not included in the Scientific Opinion, as they only came to light after it was published. Hence, there is a “general suitability,” given that LMM (or LM) may be caused by prolonged occupational exposure to natural UV light. The use of molecular biological studies (genetic signatures) allows one to identify the cause in individual patients. LMM is a rare disease (orphan disease) in accordance with the EU regulation 141/2000. These lesions account for 5–15 % of all cutaneous melanomas; the incidence of LMM in southern Germany is only about 1:100,000 per year [5]. Due to the low incidence and prevalence of the disease, the generally required evidence (according to Book VII, Section 2, Para. 9 of the SGB) of an increased risk in a specific group, based on an epidemiological study, resulting from “longterm surveillance of the disease to identify a larger number of similar diseases” cannot be achieved. In such instances of rare diseases, according to the German Federal Social Court (Bundessozialgericht, BSG), “for determining the effects of specific noxious influences in causing the disease in question, case reports, results from other countries, and disorders previously recognized as occupational diseases (…) and thus related medical/scientific knowledge may be applied.” “Using scientific methods and considerations, one must be able to justify that certain influences have the general potential to cause a specific disease” (decision of the BSG of 4 June 2002; B 2 U 20/01 R). An 85-year-old former forestry worker had a painful nodule excised from his right flank. The histologic diagnosis was undifferentiated squamous cell carcinoma. The results of staging studies were unremarkable. Multiple actinic keratoses on his arms, head, and upper back were treated with a fluorouracil-based topical preparation (Effudix ®). Six months later, at follow-up, the patient had several noticeable pigmented lesions. Excision and histological analysis revealed LMM (Breslow index 0.6 mm) on the right upper arm and on the left forearm (Breslow index 0.2 mm), and one LM each on the right scapula (Figure 1) and the right side of the vertebrae (Figure 2). With the patient’s consent, an occupational disease report was submitted (based on Book VII, Section 2, Para. 9 of the SGB) and the responsible insurance body initiated an assessment procedure; the patient was then referred for the purpose of an expert opinion. The now 88-year-old man with Fitzpatrick skin type II– III came to our clinic for a clinical examination. His nutritional status was good; his overall health was diminished fitting with his age. There was severe skin damage with poikiloderma due to sun exposure on his face, head, throat, neck, upper arms and forearms, as well as the lower legs, and to a slightly lesser extent on his back. His skin was marked by
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1210
915
Correspondence Clinical Letter
Figure 1 Dermatopathology: Lentigo maligna at the right scapula: atypical melanocytes in the basal epidermis over elastotic dermis. Hyperpigmentation of keratinocytes and pigment incontinence.
e lastosis, erythema, hyperpigmentation and loss of pigmentation, as well as telangiectasias; there was no sun damage on the thighs or buttocks. On the back of his right hand were several erythematous plaques with focal hyperkeratosis which were clinically diagnosed as actinic keratoses. On the back of his left hand was an erythematous plaque measuring 2.5 × 2 cm with focal hyperkeratosis. This was clinically diagnosed as field cancerization. There were five erythematous hyperkeratotic plaques (actinic keratoses) on the forehead. The man reported that as a forestry worker, he had spent nearly 100% of his work days outside for 40 years. His responsibilities mainly included planting and maintaining trees; building pathways; and cutting, splitting and loading wood. He worked from 7 a.m. to 4 p.m. with a 15-minute break, which was also outdoors, all year round. Depending on the weather, he sometimes wore a jacket; in the summer, he sometimes wore a tank top, and at other times did not wear any shirt at all. He usually wore long pants, although during the summer he occasionally wore shorts. Up until three years ago, he never used sunscreen, either at work or during his leisure time. According to the statement by the prevention service for occupational exposure, as a forester he had a history of more than 40 years (during which time he was covered by the accident insurer) of intense occupational exposure to UV light (15,350; standard erythema dose, SED). His private lifetime dose of solar exposure was 12,030 SED, although the standard figure for private solar exposure of 130 SED is presumably an overestimate, given that his individual UV exposure during his leisure time is much less than in the rest of the population. Yet, his occupational exposure exceeded his private cumulative solar exposure by at least 128 %; thus,
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Figure 2 Dermatopathology: actinic keratosis (left) associated with lentigo maligna (right) paravertebrally.
according to the evaluative paper, his occupational exposure did far more than double his risk for squamous cell carcinoma and actinic keratosis, which is already present at a 40% increase over private exposure [1]. Thus, it was advised that the histologically confirmed squamous cell carcinoma, and clinical documentation of multiple actinic keratoses, be recognized as an occupational disorder (according to Book VII, Section 2, Para. 9 of the SGB). In addition, we needed to determine whether the histologically confirmed LMM and LM on sun-exposed skin should be recognized as an occupational disease (according to Book VII, Section 2, Para. 9 of the SGB). Given that, on the one hand, there is broad consensus in the scientific literature that lifelong cumulative UV exposure is the main risk factor in LM and LMM, while other melanoma types are associated with intermittent UV exposure, especially during childhood, and the total number of melanocytic nevi of the entire integument [6], and on the other hand, that the cumulative UV exposure in our patient was primarily due to his occupation, according to the statement by the prevention service, it was likely that the LMM and LM lesions were caused by occupational influences. This was therefore also suggested, along with an estimated 30% reduction in earning capacity, given the presence of multiple tumors with high disease activity (based on the current Bamberg recommendations [Bamberger Merkblatt]) [7]. The 30% reduction in earning capacity seems adequate, if one takes into account the low Breslow indices of the LMM and the thus anticipated favorable prognosis, and as well as the number of jobs considered off limits as a result of having multiple squamous cell carcinomas. Based on the Scientific Opinion, “certain groups of people” are defined as those who work outdoors being subject to significantly greater solar exposure than the rest of the
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1210
Correspondence Clinical Letter
opulation [1]. Thus, p p ersons belonging to this group who have LM or LMM, and in whom suspicion of an occupational disease is justified (according to Book VII, Section 2, Para. 9 of the SGB), should be documented and brought to the attention of the accident insurers (with the consent of the insured persons) using a physician report of suspected occupational disease. Considering our patient's advanced age (similar to many others with a long history of solar exposure who do not develop skin cancer until after retirement), and given sociopolitical factors, it is all the more important to accelerate the evaluation procedure and the decision of the accident insurers.
References 1
2
3
4
5
Conflict of interest None.
Peter Elsner 1, Thomas Ludwig Diepgen2, Sibylle Schliemann1 (1) Klinik für Hautkrankheiten, Jena University Hospital, Germany (2) Abteilung Klinische Sozialmedizin, Berufs- und Umweltdermatologie, Heidelberg University Hospital, Germany
6
7
Ärztlicher Sachverständigenbeirat „Berufskrankheiten“. Berufskrankheiten-Verordnung „Hautkrebs durch UV-Licht“. Dermatol Beruf Umw 2013; 6152–75. LeBoit PE, Burg G, Weedon D, Sarasin A. WHO Classification of tumours. Pathology and genetics of skin tumours. Lyon: IARCPress; 2006. Reed JA, Shea CR. Lentigo maligna: melanoma in situ on chronically sun-damaged skin. Arch Pathol Lab Med 2011; 135(7): 838–41. Romano E, Schwartz GK, Chapman PB et al. Treatment implications of the emerging molecular classification system for melanoma. Lancet Oncol 2011; 12(9): 913–22. Lasithiotakis KG, Leiter U, Gorkievicz R et al. The incidence and mortality of cutaneous melanoma in Southern Germany: trends by anatomic site and pathologic characteristics, 1976 to 2003. Cancer 2006; 107(6): 1331–9. S3-Leitlinie „Diagnostik, Therapie und Nachsorge des Melanoms“. AWMF-Register-Nummer: 032-024OL. 2013. http://www.awmf.org/uploads/tx_szleitlinien/032-024l_S3_ Melanom_Diagnostik_Therapie_Nachsorge_2013-02.pdf Diepgen TL, Bernhard-Klimt C, Blome O et al. Bamberger Merkblatt: Begutachtungsempfehlungen für die Begutachtung von Haut und Hautkrebserkrankungen Teil II: Hautkrebs. Dermatol Beruf Umw 2009; 57: 3–17.
Correspondence to Prof. Dr. med. Peter Elsner Klinik für Hautkrankheiten Universitätsklinikum Jena Erfurter Straße 35 07743 Jena, Germany E-mail: [email protected]
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1210
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Clinical Letter Lentigo maligna and lentigo maligna melanoma as occupational skin diseases in a forestry worker with long-standing occupational UV-exposure
DOI: 10.1111/ddg.12378
Dear Editors, In an Scientific Opinion from 2013, the medical expert advisory panel “Occupational Diseases,” of the German Federal Ministry of Labor and Social Affairs, suggested the introduction of a new occupational disease termed “squamous cell carcinoma or multiple actinic keratosis of the skin due to natural UV light” [1]. Yet it remains unclear whether, and to what extent, lentigo maligna (LM) or lentigo maligna melanoma (LMM) lesions on skin damaged by chronic exposure to natural UV light are to be recognized as an occupational disease (according to Book VII, Section 2, Para. 9 of the German Social Security Code [SGB VII]) in outdoor workers. The Scientific Opinion only indicates that the various subtypes of malignant melanoma may be variously influenced by exposure to UV light, without taking a specific position on LM and LMM [1]. The current WHO classification distinguishes four melanoma types based on clinical and histological features: LMM, superficial spreading melanoma, nodular melanoma, and acrolentiginous melanoma [2]. LM is defined clinically as a usually poorly circumscribed macule, with irregular brown or black pigmentation which occurs on elastotic skin that has been chronically exposed to UV light. After persisting for many years, it often develops into invasive LMM, with a visible and palpable infiltrate or nodules. Histological analysis of an LM, which is considered to be melanoma in situ, reveals an atrophic epidermis over marked dermal elastosis, with atypical suprabasal melanocytes [3]. The epidermis may also have atypical melanocyte nests, often with spindle-like cells. Invasion of adnexal structures may also occur. Invasive LMM is present if there is penetration of the basement membrane and formation of dermal tumor nests. LMM should be distinguished from other melanoma types using molecular biological tests. The genetic signatures in dermatohistological classification suggest that melanoma is not a single entity, but rather a “family of different molecular diseases” [4]. Melanomas on areas of the skin which are not chronically sun exposed are often associated with BRAF and NRAS mutations, which are not found on chronically sun exposed skin; these areas have higher copy number of CDK4 and CCD1 and KIT mutations. These are new findings rela-
ted to Book VII, Section 2, Para. 9 of the SGB, which are not included in the Scientific Opinion, as they only came to light after it was published. Hence, there is a “general suitability,” given that LMM (or LM) may be caused by prolonged occupational exposure to natural UV light. The use of molecular biological studies (genetic signatures) allows one to identify the cause in individual patients. LMM is a rare disease (orphan disease) in accordance with the EU regulation 141/2000. These lesions account for 5–15 % of all cutaneous melanomas; the incidence of LMM in southern Germany is only about 1:100,000 per year [5]. Due to the low incidence and prevalence of the disease, the generally required evidence (according to Book VII, Section 2, Para. 9 of the SGB) of an increased risk in a specific group, based on an epidemiological study, resulting from “longterm surveillance of the disease to identify a larger number of similar diseases” cannot be achieved. In such instances of rare diseases, according to the German Federal Social Court (Bundessozialgericht, BSG), “for determining the effects of specific noxious influences in causing the disease in question, case reports, results from other countries, and disorders previously recognized as occupational diseases (…) and thus related medical/scientific knowledge may be applied.” “Using scientific methods and considerations, one must be able to justify that certain influences have the general potential to cause a specific disease” (decision of the BSG of 4 June 2002; B 2 U 20/01 R). An 85-year-old former forestry worker had a painful nodule excised from his right flank. The histologic diagnosis was undifferentiated squamous cell carcinoma. The results of staging studies were unremarkable. Multiple actinic keratoses on his arms, head, and upper back were treated with a fluorouracil-based topical preparation (Effudix ®). Six months later, at follow-up, the patient had several noticeable pigmented lesions. Excision and histological analysis revealed LMM (Breslow index 0.6 mm) on the right upper arm and on the left forearm (Breslow index 0.2 mm), and one LM each on the right scapula (Figure 1) and the right side of the vertebrae (Figure 2). With the patient’s consent, an occupational disease report was submitted (based on Book VII, Section 2, Para. 9 of the SGB) and the responsible insurance body initiated an assessment procedure; the patient was then referred for the purpose of an expert opinion. The now 88-year-old man with Fitzpatrick skin type II– III came to our clinic for a clinical examination. His nutritional status was good; his overall health was diminished fitting with his age. There was severe skin damage with poikiloderma due to sun exposure on his face, head, throat, neck, upper arms and forearms, as well as the lower legs, and to a slightly lesser extent on his back. His skin was marked by
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1210
915
Correspondence Clinical Letter
Figure 1 Dermatopathology: Lentigo maligna at the right scapula: atypical melanocytes in the basal epidermis over elastotic dermis. Hyperpigmentation of keratinocytes and pigment incontinence.
e lastosis, erythema, hyperpigmentation and loss of pigmentation, as well as telangiectasias; there was no sun damage on the thighs or buttocks. On the back of his right hand were several erythematous plaques with focal hyperkeratosis which were clinically diagnosed as actinic keratoses. On the back of his left hand was an erythematous plaque measuring 2.5 × 2 cm with focal hyperkeratosis. This was clinically diagnosed as field cancerization. There were five erythematous hyperkeratotic plaques (actinic keratoses) on the forehead. The man reported that as a forestry worker, he had spent nearly 100% of his work days outside for 40 years. His responsibilities mainly included planting and maintaining trees; building pathways; and cutting, splitting and loading wood. He worked from 7 a.m. to 4 p.m. with a 15-minute break, which was also outdoors, all year round. Depending on the weather, he sometimes wore a jacket; in the summer, he sometimes wore a tank top, and at other times did not wear any shirt at all. He usually wore long pants, although during the summer he occasionally wore shorts. Up until three years ago, he never used sunscreen, either at work or during his leisure time. According to the statement by the prevention service for occupational exposure, as a forester he had a history of more than 40 years (during which time he was covered by the accident insurer) of intense occupational exposure to UV light (15,350; standard erythema dose, SED). His private lifetime dose of solar exposure was 12,030 SED, although the standard figure for private solar exposure of 130 SED is presumably an overestimate, given that his individual UV exposure during his leisure time is much less than in the rest of the population. Yet, his occupational exposure exceeded his private cumulative solar exposure by at least 128 %; thus,
916
Figure 2 Dermatopathology: actinic keratosis (left) associated with lentigo maligna (right) paravertebrally.
according to the evaluative paper, his occupational exposure did far more than double his risk for squamous cell carcinoma and actinic keratosis, which is already present at a 40% increase over private exposure [1]. Thus, it was advised that the histologically confirmed squamous cell carcinoma, and clinical documentation of multiple actinic keratoses, be recognized as an occupational disorder (according to Book VII, Section 2, Para. 9 of the SGB). In addition, we needed to determine whether the histologically confirmed LMM and LM on sun-exposed skin should be recognized as an occupational disease (according to Book VII, Section 2, Para. 9 of the SGB). Given that, on the one hand, there is broad consensus in the scientific literature that lifelong cumulative UV exposure is the main risk factor in LM and LMM, while other melanoma types are associated with intermittent UV exposure, especially during childhood, and the total number of melanocytic nevi of the entire integument [6], and on the other hand, that the cumulative UV exposure in our patient was primarily due to his occupation, according to the statement by the prevention service, it was likely that the LMM and LM lesions were caused by occupational influences. This was therefore also suggested, along with an estimated 30% reduction in earning capacity, given the presence of multiple tumors with high disease activity (based on the current Bamberg recommendations [Bamberger Merkblatt]) [7]. The 30% reduction in earning capacity seems adequate, if one takes into account the low Breslow indices of the LMM and the thus anticipated favorable prognosis, and as well as the number of jobs considered off limits as a result of having multiple squamous cell carcinomas. Based on the Scientific Opinion, “certain groups of people” are defined as those who work outdoors being subject to significantly greater solar exposure than the rest of the
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1210
Correspondence Clinical Letter
opulation [1]. Thus, p p ersons belonging to this group who have LM or LMM, and in whom suspicion of an occupational disease is justified (according to Book VII, Section 2, Para. 9 of the SGB), should be documented and brought to the attention of the accident insurers (with the consent of the insured persons) using a physician report of suspected occupational disease. Considering our patient's advanced age (similar to many others with a long history of solar exposure who do not develop skin cancer until after retirement), and given sociopolitical factors, it is all the more important to accelerate the evaluation procedure and the decision of the accident insurers.
References 1
2
3
4
5
Conflict of interest None.
Peter Elsner 1, Thomas Ludwig Diepgen2, Sibylle Schliemann1 (1) Klinik für Hautkrankheiten, Jena University Hospital, Germany (2) Abteilung Klinische Sozialmedizin, Berufs- und Umweltdermatologie, Heidelberg University Hospital, Germany
6
7
Ärztlicher Sachverständigenbeirat „Berufskrankheiten“. Berufskrankheiten-Verordnung „Hautkrebs durch UV-Licht“. Dermatol Beruf Umw 2013; 6152–75. LeBoit PE, Burg G, Weedon D, Sarasin A. WHO Classification of tumours. Pathology and genetics of skin tumours. Lyon: IARCPress; 2006. Reed JA, Shea CR. Lentigo maligna: melanoma in situ on chronically sun-damaged skin. Arch Pathol Lab Med 2011; 135(7): 838–41. Romano E, Schwartz GK, Chapman PB et al. Treatment implications of the emerging molecular classification system for melanoma. Lancet Oncol 2011; 12(9): 913–22. Lasithiotakis KG, Leiter U, Gorkievicz R et al. The incidence and mortality of cutaneous melanoma in Southern Germany: trends by anatomic site and pathologic characteristics, 1976 to 2003. Cancer 2006; 107(6): 1331–9. S3-Leitlinie „Diagnostik, Therapie und Nachsorge des Melanoms“. AWMF-Register-Nummer: 032-024OL. 2013. http://www.awmf.org/uploads/tx_szleitlinien/032-024l_S3_ Melanom_Diagnostik_Therapie_Nachsorge_2013-02.pdf Diepgen TL, Bernhard-Klimt C, Blome O et al. Bamberger Merkblatt: Begutachtungsempfehlungen für die Begutachtung von Haut und Hautkrebserkrankungen Teil II: Hautkrebs. Dermatol Beruf Umw 2009; 57: 3–17.
Correspondence to Prof. Dr. med. Peter Elsner Klinik für Hautkrankheiten Universitätsklinikum Jena Erfurter Straße 35 07743 Jena, Germany E-mail: [email protected]
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1210
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