JEADV
LETTER TO THE EDITOR
A case of subungual melanoma with bone invasion: destructive local invasion and multiple skin metastases Dear Editor Subungual melanoma is rare and accounts for approximately 3% of melanomas in the Caucasian population and 10–20% in the Asian population.1,2 Bone invasion is a critical factor for patient survival, however detailed descriptions of subungual melanomas with bone invasion are limited.3 Here we present a case of a subungual melanoma with bone invasion and discuss its aggressive behaviour, including its destructive local invasion and multiple skin metastases. An 82-year-old Japanese female presented with a granulomatous nodule on the nail of the third digit of her right foot. The granulomatous nodule had been noticed after an injury and had gradually grown and destroyed her nail plate in 2 months. Physical examination revealed a 20 9 20 9 9 mm black and partially red granulomatous nodule and a destroyed nail plate of the third digit of her right foot, however Hutchinson’s sign had not been noticed (Fig. 1). Histopathological examination of a biopsy specimen from the granulomatous nodule showed a proliferation of tumour cells into the deep dermis manifest-
Figure 1 A 20 9 20 9 9 mm black and partially red granulomatous nodule on the nail of the third digit of her foot. The nail plate is completely destroyed due to the proliferation of melanoma cells.
JEADV 2015
ing a sheet-like appearance. Tumour cells were polygonal and atypical (Fig. 2a). Immunohistochemistry showed positive reactions for Melan-A and HMB-45, and a partially positive reaction for S-100 in the tumour cells. A diagnosis of subungual melanoma was made. A sentinel lymph node (SLN) biopsy and amputation of the third digit was performed. The SLN biopsy was negative and histopathological examination of the amputated digit showed that tumour cells had directly invaded into the bone and vessels (Fig. 2b,c). Seven months after the amputation, a right inguinal node metastasis and multiple skin metastases developed. A right inguinal and pelvic lymph node dissection and resection of all skin metastases were performed and treatment with dacarbazine 1000 mg/m2 and interferon-b 3 million IU was started. Treatment with interferon-b has been continued. Subungual melanoma has an aggressive behaviour and previous reports have discussed its aggressiveness in terms of the anatomical architecture of the nail unit apparatus.1,4 A critical factor of metastasis in subungual melanoma is the bone invasion. Although the anatomical architecture of the nail apparatus suggests that tumour cells should easily invade bone structures due to the short distance from the epidermis to the bone, the frequency of bone invasion in subungual melanomas is approximately 10%.1–3 This frequency seems to be low with its anatomical architecture taken into account but regional lymph node metastasis and distant metastasis might occur with a high frequency after bone invasion.5 In our case, multiple skin metastases and regional lymph node metastasis were recognized 7 months after amputation. Furthermore, the broken nail plate and the lack of Hutchinson’s sign suggested that melanoma cells have a capacity for destructive local invasiveness. A recent report suggested that a conservative surgical approach should be justified from the fact that the nail matrix area, which is in close proximity to the underlying bone, is resistant to invasion.6,7 However, subungual melanomas with an aggressive behaviour easily break the resistant dermis and invade the bone structure as in our case. This difference should depend on the destructive capacity of melanoma cells and this destructive capacity will be reflected as a breakage of the nail apparatus. The paucity of reported cases of subungual melanoma with bone invasion makes it difficult to discuss this destructive capacity with statistics. The accumulation of such cases is indispensable to decipher its clinical behaviour in order to assess the prognosis of the patient and determine appropriate therapeutics.
© 2015 European Academy of Dermatology and Venereology
Letter to the Editor
2
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(b)
(c)
Figure 2 (a) Histology of a biopsy specimen of the granulomatous nodule showing polygonal and atypical tumour cells with heterotypic mitosis and/or melanin deposition (H&E stain; original magnification, 9400). (b) Histology of the amputated digit showing invasion of tumour cells into the bone structures (H&E stain; original magnification, 910). A dotted box with letter of c indicates the location of Fig. 2c in the amputated digit. (c) In the deepest portion of the tumour, tumour cells have destroyed and invaded bone structures (H&E stain; original magnification, 940).
Funding None. Y. Sone, T. Namiki,* T. Munetsugu, M. Ueno, S. Tokoro, A. Nishizawa, K. Takayama, H. Yokozeki Department of Dermatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University Bunkyo-ku, Tokyo, Japan *Correspondence: T. Namiki. E-mail: [email protected]
References 1 Nakamura Y, Fujisawa Y, Teramoto Y et al. Tumor-to-bone distance of invasive subungual melanoma: an analysis of 30 cases. J Dermatol 2014; 41: 872–877. 2 Izumi M, Ohara K, Hoashi T et al. Subungual melanoma: histological examination of 50 cases from early stage to bone invasion. J Dermatol 2008; 35: 695–703. 3 Kleinerman R, Kriegel D, Amir I, Emanuel PO, Markinson BC. Osteoinvasive subungual melanoma: a case and review. J Drug Dermatol 2010; 9: 159–163.
JEADV 2015
4 Maekawa T, Komine M, Murata S, Ohtsuki M. Surgical treatment of subungual melanoma: a cases treated with bone splitting of the distal phalanx. J Dermatol 2014; 41: 944–946. 5 Gregorcyk S, Shelton RM, Ladaga LE, Perry RR. Pathologic fracture secondary to subungual melanoma. J Surg Oncol 1996; 61: 230–233. 6 Shin HT, Jang KT, Mun GH, Lee DY, Lee JB. Histopathological analysis of the progression pattern of subungual melanoma: late tendency of dermal invasion in the nail matrix area. Mod Pathol 2014; 27: 1461–1467. 7 Sureda N, Phan A, Poulalhon N, Balme B, Dalle S, Thomas L. Conservative surgical management of subungual (matrix derived) melanoma: report of seven cases and literature review. Br J Dermatol 2011; 165: 852–858. DOI: 10.1111/jdv.13102
© 2015 European Academy of Dermatology and Venereology
LETTER TO THE EDITOR
A case of subungual melanoma with bone invasion: destructive local invasion and multiple skin metastases Dear Editor Subungual melanoma is rare and accounts for approximately 3% of melanomas in the Caucasian population and 10–20% in the Asian population.1,2 Bone invasion is a critical factor for patient survival, however detailed descriptions of subungual melanomas with bone invasion are limited.3 Here we present a case of a subungual melanoma with bone invasion and discuss its aggressive behaviour, including its destructive local invasion and multiple skin metastases. An 82-year-old Japanese female presented with a granulomatous nodule on the nail of the third digit of her right foot. The granulomatous nodule had been noticed after an injury and had gradually grown and destroyed her nail plate in 2 months. Physical examination revealed a 20 9 20 9 9 mm black and partially red granulomatous nodule and a destroyed nail plate of the third digit of her right foot, however Hutchinson’s sign had not been noticed (Fig. 1). Histopathological examination of a biopsy specimen from the granulomatous nodule showed a proliferation of tumour cells into the deep dermis manifest-
Figure 1 A 20 9 20 9 9 mm black and partially red granulomatous nodule on the nail of the third digit of her foot. The nail plate is completely destroyed due to the proliferation of melanoma cells.
JEADV 2015
ing a sheet-like appearance. Tumour cells were polygonal and atypical (Fig. 2a). Immunohistochemistry showed positive reactions for Melan-A and HMB-45, and a partially positive reaction for S-100 in the tumour cells. A diagnosis of subungual melanoma was made. A sentinel lymph node (SLN) biopsy and amputation of the third digit was performed. The SLN biopsy was negative and histopathological examination of the amputated digit showed that tumour cells had directly invaded into the bone and vessels (Fig. 2b,c). Seven months after the amputation, a right inguinal node metastasis and multiple skin metastases developed. A right inguinal and pelvic lymph node dissection and resection of all skin metastases were performed and treatment with dacarbazine 1000 mg/m2 and interferon-b 3 million IU was started. Treatment with interferon-b has been continued. Subungual melanoma has an aggressive behaviour and previous reports have discussed its aggressiveness in terms of the anatomical architecture of the nail unit apparatus.1,4 A critical factor of metastasis in subungual melanoma is the bone invasion. Although the anatomical architecture of the nail apparatus suggests that tumour cells should easily invade bone structures due to the short distance from the epidermis to the bone, the frequency of bone invasion in subungual melanomas is approximately 10%.1–3 This frequency seems to be low with its anatomical architecture taken into account but regional lymph node metastasis and distant metastasis might occur with a high frequency after bone invasion.5 In our case, multiple skin metastases and regional lymph node metastasis were recognized 7 months after amputation. Furthermore, the broken nail plate and the lack of Hutchinson’s sign suggested that melanoma cells have a capacity for destructive local invasiveness. A recent report suggested that a conservative surgical approach should be justified from the fact that the nail matrix area, which is in close proximity to the underlying bone, is resistant to invasion.6,7 However, subungual melanomas with an aggressive behaviour easily break the resistant dermis and invade the bone structure as in our case. This difference should depend on the destructive capacity of melanoma cells and this destructive capacity will be reflected as a breakage of the nail apparatus. The paucity of reported cases of subungual melanoma with bone invasion makes it difficult to discuss this destructive capacity with statistics. The accumulation of such cases is indispensable to decipher its clinical behaviour in order to assess the prognosis of the patient and determine appropriate therapeutics.
© 2015 European Academy of Dermatology and Venereology
Letter to the Editor
2
(a)
(b)
(c)
Figure 2 (a) Histology of a biopsy specimen of the granulomatous nodule showing polygonal and atypical tumour cells with heterotypic mitosis and/or melanin deposition (H&E stain; original magnification, 9400). (b) Histology of the amputated digit showing invasion of tumour cells into the bone structures (H&E stain; original magnification, 910). A dotted box with letter of c indicates the location of Fig. 2c in the amputated digit. (c) In the deepest portion of the tumour, tumour cells have destroyed and invaded bone structures (H&E stain; original magnification, 940).
Funding None. Y. Sone, T. Namiki,* T. Munetsugu, M. Ueno, S. Tokoro, A. Nishizawa, K. Takayama, H. Yokozeki Department of Dermatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University Bunkyo-ku, Tokyo, Japan *Correspondence: T. Namiki. E-mail: [email protected]
References 1 Nakamura Y, Fujisawa Y, Teramoto Y et al. Tumor-to-bone distance of invasive subungual melanoma: an analysis of 30 cases. J Dermatol 2014; 41: 872–877. 2 Izumi M, Ohara K, Hoashi T et al. Subungual melanoma: histological examination of 50 cases from early stage to bone invasion. J Dermatol 2008; 35: 695–703. 3 Kleinerman R, Kriegel D, Amir I, Emanuel PO, Markinson BC. Osteoinvasive subungual melanoma: a case and review. J Drug Dermatol 2010; 9: 159–163.
JEADV 2015
4 Maekawa T, Komine M, Murata S, Ohtsuki M. Surgical treatment of subungual melanoma: a cases treated with bone splitting of the distal phalanx. J Dermatol 2014; 41: 944–946. 5 Gregorcyk S, Shelton RM, Ladaga LE, Perry RR. Pathologic fracture secondary to subungual melanoma. J Surg Oncol 1996; 61: 230–233. 6 Shin HT, Jang KT, Mun GH, Lee DY, Lee JB. Histopathological analysis of the progression pattern of subungual melanoma: late tendency of dermal invasion in the nail matrix area. Mod Pathol 2014; 27: 1461–1467. 7 Sureda N, Phan A, Poulalhon N, Balme B, Dalle S, Thomas L. Conservative surgical management of subungual (matrix derived) melanoma: report of seven cases and literature review. Br J Dermatol 2011; 165: 852–858. DOI: 10.1111/jdv.13102
© 2015 European Academy of Dermatology and Venereology
