Ophthalmologica, Basel 172: 70-74 (1976)
An Unusual Case of Metastatic Malignant Melanoma in the Orbit E. B alestrazzi Institute of Ophthalmology (Head: Prof. G. Scuderi), Bari University, Bari
Introduction Metastatic malignant melanoma in the orbit is very rare [T arkkanen , 1962]. Not long ago, metastatic melanoma in its advanced stage was con sidered incurable: indeed it was thought that those patients affected by it would not live longer than a few months. Before 1970, chemotherapeutic experiences had given results of no use. In these last years, new drugs in combination with each other have been used and have proved to be really efficacious; this has been demon strated by some statistical studies [A hman et al., 1972; C arter , 1971; C arter and K rementz , 1971; C ohen et al., 1972; C ostanza et al., 1972; L uce et al., 1970; V eronesi and B ajetta , 1973, and others]. These treat ments have been so efficacious that nowadays the prognosis of metastatic melanoma is considered in a very different way than it was done pre viously. With regard to this we think it right to describe a very significative case which we have observed.
Clinical History
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A 59-year-old white man had a malignant melanoma, removed in a single block together with lymphatic vessels and inguinal nodes from his right leg in January 1969. After the excision he remained in good health until December 1969, when one subcutaneous nodule appeared in his right calf. Histological examination showed the same picture. He then received in the USA a chemotherapy with intra-arterial per fusion in his right leg (azotic mustards), but another nodule immediately appeared in his left forearm. Then (February 1971) three other nodules appeared in his left
Ballstrazzi
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leg. He received immunotherapy with BCG inoculated in the nodules and oral chemo therapy (Melphalan). The nodules became necrotic and ulcerated, but other nodules appeared (April to August 1971) in his left pectoral and axillary region, in his left gluteal region and in his right knee. The axillary lymph nodes were removed surgically. He then developed (December 1971) two other nodules in the upper nasal region of his right orbit and many other nodules in his scalp. The orbital nodules were excised.
Pathology Microscopical examination. The subcutaneous orbital nodules were composed of a tissue rich in cells, sometimes with a fascicular or vorticose pattern. The cells appeared usually medium-sized, never juxtaposed, ovoid-shaped, with scanty cytoplasm; less frequently they looked volu minous, with a more abundant cytoplasm, showing a globular and spindle shape. The nuclei of the tumour cells were large and hyperchromatic. Many mitotic figures were present. With Fontana stain, no pigment was present. Diagnosis. Subcutaneous amelanotic metastasis of a malignant mela noma of the skin. Follow-up. After surgical excision of the orbital nodules (December 1971), the patient received further intravenous chemotherapy (a combina tion of actinomycin D, DTIC-imidazole-4-carboxamide,5-(3,3-dimethyl1-triazeno) and BCNU [l,3-bis-(2-chloroethyl)-l-nitrosurea). All the nod ules disappeared. The intravenous therapy was repeated periodically but in decreasing doses and at increasing intervals. The patient received the last chemotherapeutic cycle in February 1973. Now he is well and in good health, he is working regularly and without evidence of metastasis. At present there is an almost 6-year cure.
Before 1970, chemotherapy of malignant melanoma was practically non-existent. Nowadays, though there are not yet very wide casuistries, obvious progress has been made owing to the therapeutical use of DTIC, which is considered today the specific drug for melanoma. Besides, the combined employment, during a cyclic therapy, of DTIC with other chemotherapie agents (BCNU, vincristine, actinomycin D, procabrazine, cyclophosphamide, etc.) associated or not with immunotherapy, seems to
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/8/2018 6:12:43 AM
Comment
Balestrazzi
Fig. 1. Aspect of the orbital subcutaneous metastasis at small magnification. The existence of a capsule delimiting the neoplastic mass is obvious. Emat. Eos. x 63. Fig. 2. The neoplastic cells are arranged in fascicular agglomerations. No pig ment is present. Emat. Eos. x 160.
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Fig. 3 and 4. The section shows cellular pleomorphism; the nuclei appear dismetric and dismorphic. Emat. Eos. x 630.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/8/2018 6:12:43 AM
An Unusual Case of Metastatic Malignant Melanoma in the Orbit
74
Balestrazzi
increase in a very significative way the therapeutical efficacy. This case is reported because of its unusual course: (1) an initial highly malignant period with generalized subcutaneous and lymph-nodular metastasis; (2) a second unexpected benign period without evidence of tumour. It seems to us very important because it demonstrates that, contrarily to previously held opinions, it is still possible to save the patient even if here is generalized and, as far as we are concerned, orbital metastasis.
References A hman, D. L.; H ann, R. G., and B isei., H. F.: Clinical evaluation of 5-(3,3-dimethyl-
l-triazeno)imidazole-4-carboxamide (NSC-45388), melphalan (NSC-8806) and hydroyurea (NSC-32065) in the treatment of disseminated malignant melanoma. Cancer Chemother. Rep. 56: 369-372 (1972). C arter, S. K.: Clinical trials and combination chemotherapy. Cancer Chemother. 2: 81-97 (1971). C arter, S. K. and K rementz , E. T.: Combination treatment of metastatic malignant melanoma with CCNU, VCR and DTIC. Abstract No. 351. Proc. Am. Ass. Cancer Res. 12 (1971). C ohen , S. M.; G reenspan, E. M.; W einer , M. J., et al.: Triple combination therapy of disseminated melanoma. Cancer, N.Y. 29: 1489-1495 (1972). C ostanza, M. E.; N athason, L.; L enhard , R.; W olter, J.; C olsky, J.; O berfield , R. A., and Schilling , A.: Therapy of malignant melanoma with an imidazole carboxamide and bis-chloroethyl nitrosurea. Cancer, N.Y. 30: 1457-1461 (1972). L uce , J. K.; T hurman, W. G.; I saac, B. L., el al.: Clinical trials with antitumour agent 5,3-dimethyl-triazeno-imidazole-carboxamide (NSC-54388). Cancer Chemo ther. Rep. 54: 119-124 (1970). T arkkanen, A.: A case of metastatic malignant melanoma in the orbit (EOPS, London 1962). V eronesi, U. e BAJF.rrA, E.: Chemioterapia del melanoma maligno. Cancro 5: 307 (1973).
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/8/2018 6:12:43 AM
Dr. E. B alestrazzi, Institute of Ophthalmology, Bari University, Bart (Italy)
An Unusual Case of Metastatic Malignant Melanoma in the Orbit E. B alestrazzi Institute of Ophthalmology (Head: Prof. G. Scuderi), Bari University, Bari
Introduction Metastatic malignant melanoma in the orbit is very rare [T arkkanen , 1962]. Not long ago, metastatic melanoma in its advanced stage was con sidered incurable: indeed it was thought that those patients affected by it would not live longer than a few months. Before 1970, chemotherapeutic experiences had given results of no use. In these last years, new drugs in combination with each other have been used and have proved to be really efficacious; this has been demon strated by some statistical studies [A hman et al., 1972; C arter , 1971; C arter and K rementz , 1971; C ohen et al., 1972; C ostanza et al., 1972; L uce et al., 1970; V eronesi and B ajetta , 1973, and others]. These treat ments have been so efficacious that nowadays the prognosis of metastatic melanoma is considered in a very different way than it was done pre viously. With regard to this we think it right to describe a very significative case which we have observed.
Clinical History
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/8/2018 6:12:43 AM
A 59-year-old white man had a malignant melanoma, removed in a single block together with lymphatic vessels and inguinal nodes from his right leg in January 1969. After the excision he remained in good health until December 1969, when one subcutaneous nodule appeared in his right calf. Histological examination showed the same picture. He then received in the USA a chemotherapy with intra-arterial per fusion in his right leg (azotic mustards), but another nodule immediately appeared in his left forearm. Then (February 1971) three other nodules appeared in his left
Ballstrazzi
71
leg. He received immunotherapy with BCG inoculated in the nodules and oral chemo therapy (Melphalan). The nodules became necrotic and ulcerated, but other nodules appeared (April to August 1971) in his left pectoral and axillary region, in his left gluteal region and in his right knee. The axillary lymph nodes were removed surgically. He then developed (December 1971) two other nodules in the upper nasal region of his right orbit and many other nodules in his scalp. The orbital nodules were excised.
Pathology Microscopical examination. The subcutaneous orbital nodules were composed of a tissue rich in cells, sometimes with a fascicular or vorticose pattern. The cells appeared usually medium-sized, never juxtaposed, ovoid-shaped, with scanty cytoplasm; less frequently they looked volu minous, with a more abundant cytoplasm, showing a globular and spindle shape. The nuclei of the tumour cells were large and hyperchromatic. Many mitotic figures were present. With Fontana stain, no pigment was present. Diagnosis. Subcutaneous amelanotic metastasis of a malignant mela noma of the skin. Follow-up. After surgical excision of the orbital nodules (December 1971), the patient received further intravenous chemotherapy (a combina tion of actinomycin D, DTIC-imidazole-4-carboxamide,5-(3,3-dimethyl1-triazeno) and BCNU [l,3-bis-(2-chloroethyl)-l-nitrosurea). All the nod ules disappeared. The intravenous therapy was repeated periodically but in decreasing doses and at increasing intervals. The patient received the last chemotherapeutic cycle in February 1973. Now he is well and in good health, he is working regularly and without evidence of metastasis. At present there is an almost 6-year cure.
Before 1970, chemotherapy of malignant melanoma was practically non-existent. Nowadays, though there are not yet very wide casuistries, obvious progress has been made owing to the therapeutical use of DTIC, which is considered today the specific drug for melanoma. Besides, the combined employment, during a cyclic therapy, of DTIC with other chemotherapie agents (BCNU, vincristine, actinomycin D, procabrazine, cyclophosphamide, etc.) associated or not with immunotherapy, seems to
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/8/2018 6:12:43 AM
Comment
Balestrazzi
Fig. 1. Aspect of the orbital subcutaneous metastasis at small magnification. The existence of a capsule delimiting the neoplastic mass is obvious. Emat. Eos. x 63. Fig. 2. The neoplastic cells are arranged in fascicular agglomerations. No pig ment is present. Emat. Eos. x 160.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/8/2018 6:12:43 AM
72
73
Fig. 3 and 4. The section shows cellular pleomorphism; the nuclei appear dismetric and dismorphic. Emat. Eos. x 630.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/8/2018 6:12:43 AM
An Unusual Case of Metastatic Malignant Melanoma in the Orbit
74
Balestrazzi
increase in a very significative way the therapeutical efficacy. This case is reported because of its unusual course: (1) an initial highly malignant period with generalized subcutaneous and lymph-nodular metastasis; (2) a second unexpected benign period without evidence of tumour. It seems to us very important because it demonstrates that, contrarily to previously held opinions, it is still possible to save the patient even if here is generalized and, as far as we are concerned, orbital metastasis.
References A hman, D. L.; H ann, R. G., and B isei., H. F.: Clinical evaluation of 5-(3,3-dimethyl-
l-triazeno)imidazole-4-carboxamide (NSC-45388), melphalan (NSC-8806) and hydroyurea (NSC-32065) in the treatment of disseminated malignant melanoma. Cancer Chemother. Rep. 56: 369-372 (1972). C arter, S. K.: Clinical trials and combination chemotherapy. Cancer Chemother. 2: 81-97 (1971). C arter, S. K. and K rementz , E. T.: Combination treatment of metastatic malignant melanoma with CCNU, VCR and DTIC. Abstract No. 351. Proc. Am. Ass. Cancer Res. 12 (1971). C ohen , S. M.; G reenspan, E. M.; W einer , M. J., et al.: Triple combination therapy of disseminated melanoma. Cancer, N.Y. 29: 1489-1495 (1972). C ostanza, M. E.; N athason, L.; L enhard , R.; W olter, J.; C olsky, J.; O berfield , R. A., and Schilling , A.: Therapy of malignant melanoma with an imidazole carboxamide and bis-chloroethyl nitrosurea. Cancer, N.Y. 30: 1457-1461 (1972). L uce , J. K.; T hurman, W. G.; I saac, B. L., el al.: Clinical trials with antitumour agent 5,3-dimethyl-triazeno-imidazole-carboxamide (NSC-54388). Cancer Chemo ther. Rep. 54: 119-124 (1970). T arkkanen, A.: A case of metastatic malignant melanoma in the orbit (EOPS, London 1962). V eronesi, U. e BAJF.rrA, E.: Chemioterapia del melanoma maligno. Cancro 5: 307 (1973).
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/8/2018 6:12:43 AM
Dr. E. B alestrazzi, Institute of Ophthalmology, Bari University, Bart (Italy)
