Clinical and Experimental Dermatology 1992; 17: 366-368.
Malignant melanoma complicated by schwannoma N.MATSUMURA, T.KATO, N.KUMASAKA, M.WATANABE, K.KUMASAKA AND H.TAGAMI Department of Dermatology, Tohoku University School of Medicine, Sendai, Japan Accepted for publication 14 October 1991 were 3 and 4 cm in diameter, respectively and the one on the right thigh was accompanied by pain on palpation. We report two cases of malignant melanoma associated To treat the melanoma the patient underwent a wide with a schwannoma. Case 1 is a 32-year-old Japanese man excision and bilateral axillary lymph-node dissection at who had a nodular melanoma in his epigastrium, asso- the same time. Before and after the operation, combinaciated with one subcutaneous nodule on the neck and tion therapy with decarbazine (1000 mg), nimustine (100 another on the right thigh, both of which were histologi- mg), vincristine (1 mg) and interferon-beta was given. cally-proven schwannomas. Case 2 is a 48-year-old During the subsequent 18-month foUow-up period, three Japanese woman with an acral lentiginous melanoma on cutaneous metastatic melanomas were excised. her right sole who later developed a schwannoma of the The subcutaneous tumours were also excised. cerebello-pontine angle. Of a!! 146 malignant melanoma cases found in our clinic during the past 20 years, 14% were associated with a neurogenic tumour, a significant Histopathology association. Figure 1 shows the histological features of the primary lesion of the malignant melanoma. From the epidermis to Melanocytes and Schwann cells both originate from mid-dermis, there were proliferating nests of tumour neural crest cells.' Melanocytic naevi are recognized cells. Under higher magnification (b) they had large, pleohistologically to show neuroid patterns in the deep morphic nuclei with clear nucleoli and eosinophilic cytodermis.^ Moreover there are some melanoma cases whose plasm containing fine melanin granules. The eventual origin from melanocytes or schwann cells cannot be diagnosis was a nodular melanoma, Clark's level 4, determined.''^ We describe two cases of malignant pT3aNlM0(stage3). melanoma associated with schwannoma. They are interThe subcutaneous tumour on his neck was well esting because they represent a previously unreported encapsulated, yellow to white in colour and 4 cm in abnormal proliferation of two diflferent kinds of neural diameter (Fig. 2a). A nerve fibre was attached tightly to crest-derived cells in the same individual. the capsule. Histologically there were spindle-shaped Summary
Case report Case J
A 32-year-old Japanese male was referred to our hospital because of malignant melanoma. His past history revealed that a small black nodule that had been present in his epigastrium since childhood which gradually enlarged and bled easily. Excision biopsy by a local doctor revealed a malignant melanoma (nodular type). In addition to the malignant melanoma, he had noticed two soft subcutaneous nodules that had remained unchanged in size on the neck and right thigh since the age of 20. Physical examination demonstrated soft subcutaneous tumours, one in the right supraclavicular region and the other on the flexor aspect of the right thigh. Tumours Correspondence: Dr Noriko Matsumura, Department of Dermatology, Tohoku University School of Medicine, Seiryo-machi 1-1, Aoba-ku, 980 Sendai, Japan.
366
Figure 1. Histology of the primary malignant melanoma of Case 1. Tumour cells with pleomorphic nuclei and clear nucleoli proliferated and formed lobules beyond the basal layer. (H&E, (a) x 30 4 (b) x 52.)
MALIGNANT MELANOMA COMPLICATED BY SCHWANNOMA
367
tumour cells in an oedemarous siroma: tumour cells had slender nuclei and eosinophilic cytoplasm, some of them were wavy (Fig. 2b). These cells were positive for S-100 protein. The tumour of the right thigh showed similar features. The diagnosis of schwannoma was made in both tumours. (b)
Figure 2. A subcutaneous lumour ol" the neck in Case 1. (a) Operational specimen, (b) Histok)g\ of the lumour. There were slender spindle-shaped tumour cells in an oedemaious stroma. (H&E, X 52.)
Figure 3. (a) .Ntallgnanl melanoma of the right sole of (.ase 2. There was dark-gra>, Hal elevated tumour and surrounding brown macule
(b). Case 2 A 48-year-old Japanese female presented with a 6-month history of a pigmented tumour on her right sole. On physical examination (l'"ig. 3), there was a dark-gray, flat elevated tumour, 7 mm in diameter, based on a well demarcated dark brown macule, 1-5 cm in size, on the lateral side of the right sole. On the opposite side of the tumour, ill-defined light-brown macules and spotty pigmented macules were scattered. These clinical features were confimed histologically to be due to an acral lentiginous melanoma. The lesion was excised and a righr inguinal lymph-nodc dissection performed at the same time. Eighteen months alter the operation, a tumour 28 X 23 mm in diameter was discovered at the cerebellopontine angle by computed tomography, and was found to be a schwannoma at surgery. Three years after the operation of melanoma she died with multiple metastases of malignani meianoma. Histopathology Figure 4 shows the histopathological features of the melanoma of the righr sole. The tumour had invaded the mid-dermis (Fig. 4a). Tumour cells with an eosinophilic cytoplasm formed nests in the dermis (Fig. 4b). Histologicai study of the pigmented macule revealed a lentiginous-typc proliferation of atypical melanocytes in the
basal layer (Fig. 4c). The diagnosis was acral lentiginous melanoma, Clark's level 3, pT3aNOMO (Stage 2). r'igure 5 shows the histological features of the cerebello-pontine angle tumour. Tumour cells which had spindle-shaped, chromatin-rich nuclei and eosinophilic cytoplasm proliferated with a tendency to form bundles. Some cells had a wavy cytoplasm while others were arranged in a parallel row with straight elongated nuclei. Discussion .Malignant melanoma is much less frequent among orientals than Caucasians. We have experienced only 146 cases of malignant melanoma over the past 2?> years in our department. Thus the complication of schwannoma with melanoma has been found to have an incidence of 1 /73. In the Japanese, schwannoma accounts for 10% of the brain tumours occurring at an incidence of 14-5/U)Vyi;ar and about 30% of spinal cord tumours occurring at 2-5/10^ ycar.^'' Schwannomas are less frequent at other sites.' I'rom these data, the overall incidence would be expected to be no more than 3/IOVyear. The observation period is calculated as A7 years (mean age at diagnosis: 57 years plus U) years), 67x3/ 10'= 1/500. Thus, it would be accidental if one case of schwannoma was found in 500
368
N.MATSUMURA et al. cases of malignant melanoma. Therefore an incidence of 1/73 is more than coincidental. Reporting that neurofibromatosis accompanied phaeochromocytoma, another neural crest-origin tumour, in a small but significant number of cases, Hope and Mulvihiil mentioned that an association with malignant melanoma and neurofibromatosis was likely to be coincidental." However, racial differences in incidence as well as sites of predilection for melanoma are clear, particularly between Caucasians and orientals.^'"* As stated previously, malignant melanoma occurs much less frequently among the Japanese than Caucasians. Thus as far as orientals are concerned, we suggest that the relation between malignant melanoma and schwannoma is more than a coincidence. In fact there are sporadic reports of association between malignant melanoma of non-whites and other tumours of nerve-cell origin."-'^ References
Figure 4. Histopathology of the malignant melanoma of the right sole of d s e 2. Tumour cells invaded the mid-layer of dermis (b) and the macule showed lentiginous proliferation along the basal layer of the epidermis (c). (I I&K, (a) x 32, (b) x 300, (c) x 300.)
Figure 5. Histological features of the cerebello-pontine angle tumour (Case 2). Spindle-shaped cell with chromatin-rich nucleus and eosinophiiic cytosol proliferated with a tendency to form bundles (H&E, X 52).
1. Weston JA. The regulation of normal and abnormal neural crest cell development. .-Idvanced Neurology 1981; 29: 77-95. 2. Lever WF, Schaum berg-Lever G. Histopathology of the sktn, 7th edn. Philadelphia: Lippineott, 1990: 756-796. 3. Weidner N, Flanders DJ, Jochimsen PR, Stamler FW. NeurosareomatoUN malignant melanoma arising in a neuroid giant congenital melanocytic nevus. Archives of Dermatology 1985; 121: 13021306. 4. Krausz T. Azzopardi JG, Pearse E. Malignant melanoma of the sympathetic chain: with a consideration of pigmented nerve sheath tumours. Htstopathotogy 1984; 8: 881-894. 5. Sano K. Noushuyou (Brain Tumor). Tokyo: Igakushoin, 1981: 37. (In Japanese), 6. King TT. Clinical presentation and treatment of tumors of the cranial nerves and spinal roots. In: Dyck PJ, Thomas PK, Lambert EII, Bunge R eds. Peripheral Neuropathy, Vol. 2. Philadelphia: Saunders, 1984: 2204 2235. 7. Urich H, Path()l(>gy of tumors of cranial nerves, spinal nerve roots and peripheral nerves. In: Dyck PJ, Thomas PK, Lambert EH, Bunge R eds. Peripheral Neuropathy, Vol. 2. Philadelphia: Saunders, 1984: 2253-2299. 8. Hope DG, Mulvihiil JJ. Malignancy in neurofibromatosis. Advanced Neurology 1981; 29: 33-56. Kato T, Usuba Y, Takematsu H et at. A rapidly growing pigmented nail streak resulting in diffuse melanosis of the nail (A possible sign of subungal melanoma in-situ). Cancer 1989; 64: 2191-2197. MacKie RM. Tumours of the skin. In: Rook A, Wilkinson DS, Ebling FJG, Champion RH, Burton JL, eds. Texthook of Dermatotogy, 4th edn. Oxford: Blackwell Scientific Publications 1986: 2375-2478. Silverman Jl', Blahove M, Collins JL, Norris HT. Cutaneous malignant melanoma in a black patient with neurofibromatosis (von Recklinghausen's disease). American Journal of Dermatopatliology 1988; 10: 536--540. 12. Miyauchi T, Maruoka M, Nagayama T. Malignant melanoma of the penis associated with von Recklinghausen's neurofibroma tosis: report of a case. Hmyokika Kiyo 1988; 34: 710-713. (In Japanese).
Malignant melanoma complicated by schwannoma N.MATSUMURA, T.KATO, N.KUMASAKA, M.WATANABE, K.KUMASAKA AND H.TAGAMI Department of Dermatology, Tohoku University School of Medicine, Sendai, Japan Accepted for publication 14 October 1991 were 3 and 4 cm in diameter, respectively and the one on the right thigh was accompanied by pain on palpation. We report two cases of malignant melanoma associated To treat the melanoma the patient underwent a wide with a schwannoma. Case 1 is a 32-year-old Japanese man excision and bilateral axillary lymph-node dissection at who had a nodular melanoma in his epigastrium, asso- the same time. Before and after the operation, combinaciated with one subcutaneous nodule on the neck and tion therapy with decarbazine (1000 mg), nimustine (100 another on the right thigh, both of which were histologi- mg), vincristine (1 mg) and interferon-beta was given. cally-proven schwannomas. Case 2 is a 48-year-old During the subsequent 18-month foUow-up period, three Japanese woman with an acral lentiginous melanoma on cutaneous metastatic melanomas were excised. her right sole who later developed a schwannoma of the The subcutaneous tumours were also excised. cerebello-pontine angle. Of a!! 146 malignant melanoma cases found in our clinic during the past 20 years, 14% were associated with a neurogenic tumour, a significant Histopathology association. Figure 1 shows the histological features of the primary lesion of the malignant melanoma. From the epidermis to Melanocytes and Schwann cells both originate from mid-dermis, there were proliferating nests of tumour neural crest cells.' Melanocytic naevi are recognized cells. Under higher magnification (b) they had large, pleohistologically to show neuroid patterns in the deep morphic nuclei with clear nucleoli and eosinophilic cytodermis.^ Moreover there are some melanoma cases whose plasm containing fine melanin granules. The eventual origin from melanocytes or schwann cells cannot be diagnosis was a nodular melanoma, Clark's level 4, determined.''^ We describe two cases of malignant pT3aNlM0(stage3). melanoma associated with schwannoma. They are interThe subcutaneous tumour on his neck was well esting because they represent a previously unreported encapsulated, yellow to white in colour and 4 cm in abnormal proliferation of two diflferent kinds of neural diameter (Fig. 2a). A nerve fibre was attached tightly to crest-derived cells in the same individual. the capsule. Histologically there were spindle-shaped Summary
Case report Case J
A 32-year-old Japanese male was referred to our hospital because of malignant melanoma. His past history revealed that a small black nodule that had been present in his epigastrium since childhood which gradually enlarged and bled easily. Excision biopsy by a local doctor revealed a malignant melanoma (nodular type). In addition to the malignant melanoma, he had noticed two soft subcutaneous nodules that had remained unchanged in size on the neck and right thigh since the age of 20. Physical examination demonstrated soft subcutaneous tumours, one in the right supraclavicular region and the other on the flexor aspect of the right thigh. Tumours Correspondence: Dr Noriko Matsumura, Department of Dermatology, Tohoku University School of Medicine, Seiryo-machi 1-1, Aoba-ku, 980 Sendai, Japan.
366
Figure 1. Histology of the primary malignant melanoma of Case 1. Tumour cells with pleomorphic nuclei and clear nucleoli proliferated and formed lobules beyond the basal layer. (H&E, (a) x 30 4 (b) x 52.)
MALIGNANT MELANOMA COMPLICATED BY SCHWANNOMA
367
tumour cells in an oedemarous siroma: tumour cells had slender nuclei and eosinophilic cytoplasm, some of them were wavy (Fig. 2b). These cells were positive for S-100 protein. The tumour of the right thigh showed similar features. The diagnosis of schwannoma was made in both tumours. (b)
Figure 2. A subcutaneous lumour ol" the neck in Case 1. (a) Operational specimen, (b) Histok)g\ of the lumour. There were slender spindle-shaped tumour cells in an oedemaious stroma. (H&E, X 52.)
Figure 3. (a) .Ntallgnanl melanoma of the right sole of (.ase 2. There was dark-gra>, Hal elevated tumour and surrounding brown macule
(b). Case 2 A 48-year-old Japanese female presented with a 6-month history of a pigmented tumour on her right sole. On physical examination (l'"ig. 3), there was a dark-gray, flat elevated tumour, 7 mm in diameter, based on a well demarcated dark brown macule, 1-5 cm in size, on the lateral side of the right sole. On the opposite side of the tumour, ill-defined light-brown macules and spotty pigmented macules were scattered. These clinical features were confimed histologically to be due to an acral lentiginous melanoma. The lesion was excised and a righr inguinal lymph-nodc dissection performed at the same time. Eighteen months alter the operation, a tumour 28 X 23 mm in diameter was discovered at the cerebellopontine angle by computed tomography, and was found to be a schwannoma at surgery. Three years after the operation of melanoma she died with multiple metastases of malignani meianoma. Histopathology Figure 4 shows the histopathological features of the melanoma of the righr sole. The tumour had invaded the mid-dermis (Fig. 4a). Tumour cells with an eosinophilic cytoplasm formed nests in the dermis (Fig. 4b). Histologicai study of the pigmented macule revealed a lentiginous-typc proliferation of atypical melanocytes in the
basal layer (Fig. 4c). The diagnosis was acral lentiginous melanoma, Clark's level 3, pT3aNOMO (Stage 2). r'igure 5 shows the histological features of the cerebello-pontine angle tumour. Tumour cells which had spindle-shaped, chromatin-rich nuclei and eosinophilic cytoplasm proliferated with a tendency to form bundles. Some cells had a wavy cytoplasm while others were arranged in a parallel row with straight elongated nuclei. Discussion .Malignant melanoma is much less frequent among orientals than Caucasians. We have experienced only 146 cases of malignant melanoma over the past 2?> years in our department. Thus the complication of schwannoma with melanoma has been found to have an incidence of 1 /73. In the Japanese, schwannoma accounts for 10% of the brain tumours occurring at an incidence of 14-5/U)Vyi;ar and about 30% of spinal cord tumours occurring at 2-5/10^ ycar.^'' Schwannomas are less frequent at other sites.' I'rom these data, the overall incidence would be expected to be no more than 3/IOVyear. The observation period is calculated as A7 years (mean age at diagnosis: 57 years plus U) years), 67x3/ 10'= 1/500. Thus, it would be accidental if one case of schwannoma was found in 500
368
N.MATSUMURA et al. cases of malignant melanoma. Therefore an incidence of 1/73 is more than coincidental. Reporting that neurofibromatosis accompanied phaeochromocytoma, another neural crest-origin tumour, in a small but significant number of cases, Hope and Mulvihiil mentioned that an association with malignant melanoma and neurofibromatosis was likely to be coincidental." However, racial differences in incidence as well as sites of predilection for melanoma are clear, particularly between Caucasians and orientals.^'"* As stated previously, malignant melanoma occurs much less frequently among the Japanese than Caucasians. Thus as far as orientals are concerned, we suggest that the relation between malignant melanoma and schwannoma is more than a coincidence. In fact there are sporadic reports of association between malignant melanoma of non-whites and other tumours of nerve-cell origin."-'^ References
Figure 4. Histopathology of the malignant melanoma of the right sole of d s e 2. Tumour cells invaded the mid-layer of dermis (b) and the macule showed lentiginous proliferation along the basal layer of the epidermis (c). (I I&K, (a) x 32, (b) x 300, (c) x 300.)
Figure 5. Histological features of the cerebello-pontine angle tumour (Case 2). Spindle-shaped cell with chromatin-rich nucleus and eosinophiiic cytosol proliferated with a tendency to form bundles (H&E, X 52).
1. Weston JA. The regulation of normal and abnormal neural crest cell development. .-Idvanced Neurology 1981; 29: 77-95. 2. Lever WF, Schaum berg-Lever G. Histopathology of the sktn, 7th edn. Philadelphia: Lippineott, 1990: 756-796. 3. Weidner N, Flanders DJ, Jochimsen PR, Stamler FW. NeurosareomatoUN malignant melanoma arising in a neuroid giant congenital melanocytic nevus. Archives of Dermatology 1985; 121: 13021306. 4. Krausz T. Azzopardi JG, Pearse E. Malignant melanoma of the sympathetic chain: with a consideration of pigmented nerve sheath tumours. Htstopathotogy 1984; 8: 881-894. 5. Sano K. Noushuyou (Brain Tumor). Tokyo: Igakushoin, 1981: 37. (In Japanese), 6. King TT. Clinical presentation and treatment of tumors of the cranial nerves and spinal roots. In: Dyck PJ, Thomas PK, Lambert EII, Bunge R eds. Peripheral Neuropathy, Vol. 2. Philadelphia: Saunders, 1984: 2204 2235. 7. Urich H, Path()l(>gy of tumors of cranial nerves, spinal nerve roots and peripheral nerves. In: Dyck PJ, Thomas PK, Lambert EH, Bunge R eds. Peripheral Neuropathy, Vol. 2. Philadelphia: Saunders, 1984: 2253-2299. 8. Hope DG, Mulvihiil JJ. Malignancy in neurofibromatosis. Advanced Neurology 1981; 29: 33-56. Kato T, Usuba Y, Takematsu H et at. A rapidly growing pigmented nail streak resulting in diffuse melanosis of the nail (A possible sign of subungal melanoma in-situ). Cancer 1989; 64: 2191-2197. MacKie RM. Tumours of the skin. In: Rook A, Wilkinson DS, Ebling FJG, Champion RH, Burton JL, eds. Texthook of Dermatotogy, 4th edn. Oxford: Blackwell Scientific Publications 1986: 2375-2478. Silverman Jl', Blahove M, Collins JL, Norris HT. Cutaneous malignant melanoma in a black patient with neurofibromatosis (von Recklinghausen's disease). American Journal of Dermatopatliology 1988; 10: 536--540. 12. Miyauchi T, Maruoka M, Nagayama T. Malignant melanoma of the penis associated with von Recklinghausen's neurofibroma tosis: report of a case. Hmyokika Kiyo 1988; 34: 710-713. (In Japanese).
