in - transit metastases from malignant melanoma are subcutaneous lymphogenous metastases that invade regional lymph nodes and are commonly observed as a type of recurrence . a clear treatment strategy is yet to be established , and in many instances , physicians struggle while deciding treatment . here , we report a case of malignant melanoma with in - transit metastasis that responded to intravenous infusion of interferon ( ifn)-. the patient was a 77-year - old male with rash on the fifth toe of the left foot and lower left leg . his medical history included hypertension , diabetes , and malignant melanoma that was surgically removed ( fifth toe amputation ) at our department 14 years ago ( fig . three months before presentation , a skin ulcer appeared at the same site , and red nodules developed on the lower left leg . malignant melanoma was suspected , and the patient was referred to our department . at the amputation site on the left foot , there was a skin ulcer measuring 25  20 mm with several red nodules , primarily on the anterior surface of the lower left leg ( fig . skin biopsies were obtained from the red nodules on the lower leg and the skin ulcer on the left foot . histopathological examination of both lesion samples revealed tumor cells with eosinophilic cytoplasm and medium - to - large nuclei with distinct nucleoli extending through all layers of the dermis and into some fatty tissue . 3 ) . immunostaining was positive for vimentin , s-100 , hmb-45 , melanoma , and melan - a . the mib-1 index was 38.3% . based on these results , a diagnosis of recurrent malignant melanoma with in - transit metastasis subtotal integumentectomy was scheduled ; however , 2 weeks later , the patient developed acute myocardial infarction and was hospitalized at kariya toyota general hospital . treatment for acute myocardial infarction continued for 1 month ; thereafter , the patient was transferred to our department . as the myocardial infarction decreased the patient 's tolerance to surgery , intravenous infusion of ifn- initially , ifn- was administered at 3 million u / day for 10 consecutive days . as a countermeasure against fever , which is a side effect of ifn- , loxonin thereafter , the patient was treated as an outpatient , with intravenous infusion of ifn- 3 million u / day once a week . twenty - six weeks later , the skin ulcer on the fifth toe of the left foot was cured , the nodes on the left leg had disappeared , and only pigmentation was observed ( fig . , the regimen was changed to intravenous infusion of ifn- 3 million u / day once every 2 weeks . the patient 's progress has been satisfactory , with no evidence of recurrence or metastasis at 1 year and 9 months after treatment ( fig . the patient was a 77-year - old male with rash on the fifth toe of the left foot and lower left leg . his medical history included hypertension , diabetes , and malignant melanoma that was surgically removed ( fifth toe amputation ) at our department 14 years ago ( fig . three months before presentation , a skin ulcer appeared at the same site , and red nodules developed on the lower left leg . malignant melanoma was suspected , and the patient was referred to our department . at the amputation site on the left foot , there was a skin ulcer measuring 25  20 mm with several red nodules , primarily on the anterior surface of the lower left leg ( fig . skin biopsies were obtained from the red nodules on the lower leg and the skin ulcer on the left foot . histopathological examination of both lesion samples revealed tumor cells with eosinophilic cytoplasm and medium - to - large nuclei with distinct nucleoli extending through all layers of the dermis and into some fatty tissue . 3 ) . immunostaining was positive for vimentin , s-100 , hmb-45 , melanoma , and melan - a . the mib-1 index was 38.3% . based on these results , a diagnosis of recurrent malignant melanoma with in - transit metastasis subtotal integumentectomy was scheduled ; however , 2 weeks later , the patient developed acute myocardial infarction and was hospitalized at kariya toyota general hospital . treatment for acute myocardial infarction continued for 1 month ; thereafter , the patient was transferred to our department . as the myocardial infarction decreased the patient 's tolerance to surgery , intravenous infusion of ifn- initially , ifn- was administered at 3 million u / day for 10 consecutive days . as a countermeasure against fever , which is a side effect of ifn- , loxonin thereafter , the patient was treated as an outpatient , with intravenous infusion of ifn- 3 million u / day once a week . twenty - six weeks later , the skin ulcer on the fifth toe of the left foot was cured , the nodes on the left leg had disappeared , and only pigmentation was observed ( fig . , the regimen was changed to intravenous infusion of ifn- 3 million u / day once every 2 weeks . the patient 's progress has been satisfactory , with no evidence of recurrence or metastasis at 1 year and 9 months after treatment ( fig . with regard to primary malignant melanomas of the skin , circulating tumor cells were reportedly detected in 32%   of the patients with stage i disease using polymerase chain reaction analysis of melanocyte differentiation markers , and in 22%   of the patients with a tumor thickness of < 1 mm by screening according to cell size . these findings strongly suggest that malignant melanoma causes systemic dissemination of tumor cells in early - stage carcinogenesis . these cells may lie dormant for a long period in a state of growth arrest , but they eventually grow and become clinically detectable metastases . therefore , malignant melanoma is a systemic disease that causes dissemination of tumor cells during the early stage of carcinogenesis and it should be treated with adequate consideration of these biochemical characteristics . malignant melanoma is resistant to chemotherapy , and , at present , there is no effective chemotherapy . reports from the usa and europe deny the usefulness of postoperative adjuvant chemotherapy with dacarbazine and claim that the intravenous injection of ifn- is the only treatment method with demonstrated supporting evidence . in japan , the most commonly used postoperative adjuvant therapy for patients with stage ii / iii malignant melanoma is davferon therapy ( combined chemotherapy with dacarbazine , nimustine , and vincristine ) and local injection of ifn- into the primary lesion site . additional regimes include ifn therapy with daily injections of ifn- and long - term therapy with ifn administered once every 24 weeks the effectiveness of these postoperative adjuvant therapies was analyzed using data obtained from a national follow - up survey conducted by the prognosis and statistical investigation committee of the japanese skin cancer society . long - term ifn therapy significantly improved survival in all cancer stages , whereas davferon therapy and ifn therapy showed no effect [ 5 , 6 ] . however , some questions remain to be answered . first , is local injection of ifn- actually ineffective ( or minimally effective ) on cancer cells disseminated throughout the body ? second , following the injection of patent blue , which is used to obtain sentinel lymph node biopsies from near the site of scarring caused by surgical removal of the tumor , does the absence or lack of pigment flow indicate that ifn- has not been effectively administered ? moreover , it is believed that the anti - tumor action of ifn- involves direct inhibition of tumor cell growth via binding to tumor cells , with simultaneous indirect inhibition of tumor proliferation via activation of the host 's immune system . in our case , recurrent localized malignant melanoma on the fifth toe of the left foot with in - transit metastasis on the lower left leg responded to intravenous infusion of ifn-. therefore , intravenous infusion of ifn- may be more effective against malignant melanoma compared with local injection .
a 77-year - old man with a history of surgical resection of malignant melanoma involving the fifth toe of his left foot 14 years ago presented at the kariya toyota general hospital with a 3-month history of skin ulcer at the same site and red nodules on the lower left leg . 
 malignant melanoma was suspected , and the patient was referred to our department . on examination , 
 a skin ulcer measuring 25  20 mm was observed at the amputation site on the left foot . 
 in addition , multiple red nodules were observed on the lower left leg . 
 skin biopsies of the ulcer and nodules revealed recurrent malignant melanoma with in - transit metastasis . 
 two weeks later , he developed acute myocardial infarction and was hospitalized at the kariya toyota general hospital . 
 one month later , the myocardial infarction ameliorated , and he was transferred to our department . as the myocardial infarction had decreased the patient 's tolerance to surgery , interferon- was administered by intravenous infusion . 
 the skin ulcer and red nodules on the lower left leg disappeared 26 weeks after infusion had been initiated . 
 the patient 's progress has been satisfactory , with no evidence of recurrence or metastasis at 1 year and 9 months after the initiation of intravenous infusion .