a 57-year - old woman developed multiple ( > 20 ) melanoma in - transit metastatic nodules on her right thigh ( figure 1a ) , as confirmed by histological examination , after removal , six months earlier , of a primary 2.2 mm thick ulcerated nodular melanoma on her right leg for which the initial sentinel lymph node biopsy was negative . after completion of fdg pet - ct to exclude distant metastasis and assessment of the extent of limb metastasis , the patient was referred to a specialized center to receive , isolated limb perfusion ( ilp ) of melphalan under hyperthermia , tnf- and interferon . superficial and deep pelvic ( ilioinguinal ) lymphadenectomy was simultaneously performed and revealed two additional deep pelvic lymph node metastases . one month after the end of this procedure , most in - transit lesions had undergone necrosis . four months later , all lesions had healed and persisted as non - changing pigmented macules ( figure 1b ) with no clinical or radiological ( including fdg pet - ct ) signs of relapse . in order to confirm that none of the residual pigmented macules was an active lesion , two of them were excised after being previously examined by rcm . histological examination showed a persisting melanophage granuloma ( nodular melanosis ) within areas of fibrosis in the upper dermis with no sign of tumor infiltration ( figure 2a and 2b ) . rcm imaging , performed using the vivascope 1500 ( vivascope systems , munich , germany ) showed ill - defined aggregates of dermal bright cells , typical of melanophages with almost no visible nuclei . sometimes a characteristic ring - shaped deposit was seen within the network of bright collagen fibers and bundles ( figure 3 ) . such deposits could be seen in many areas of the excised lesions and correlated with the histological images . we then performed rcm imaging on 12 other main persisting pigmented lesions ( figure 1b ) in which a similar characteristic image was consistently seen . the patient has now been followed for more than a year without any clinical or radiological sign of relapse and most lesions have slowly resolved ( figure 4 ) . around 510% of patients with malignant melanoma develop lymphatic dissemination and in - transit metastasis . even in the era of effective systemic therapies , isolated limb perfusion ( ilp ) with hyperthermia performed using various agents ( melphalan , with addition of chemokines , i.e. , tnf- and/or other chemokines ) is still a valuable therapeutic approach and is being used for patients who develop numerous limb lesions simultaneously and are therefore considered inoperable . according to the literature nevertheless complete response can be difficult to assess if post - necrotic persisting pigmented lesions occur , especially if numerous and unresectable . these residual lesions occur mainly in the more superficial and pigmented types of metastatic disease . as it was the case with our patient , these lesions can often correspond to the residual melanophage granuloma ( nodular melanosis ) that persists after tumor tissues undergo complete necrosis and can be difficult to distinguish from partial response and persisting in - transit metastasis . rcm is a non - invasive technique that allows the exploration of the superficial dermis . confocal - histopathological correlation has been shown to be possible for the visualization of some histologic features in the superficial dermis up to 300um deep [ 36 ] where , in the case of superficial in - transit metastasis , post - necrotic residual melanophage granuloma ( nodular melanosis ) might be localized . morphologic features of melanophages under in vivo rcm have been well characterized , allowing their distinction from melanocytes . here , using combined rcm and histological examination of two sample lesions , numerous unresectable post - ilp limb residual pigmented lesions were considered by rcm to be non - active as confirmed by the subsequent dermoscopy follow - up . although in the case presented here there was not any doubt at follow - up regarding the absence of residual disease , considering that the deeper reticular dermis can not be explored with rcm , biopsy remains mandatory in case of doubt during the subsequent needed close follow - up .