Electrochemotherapy efficacy evaluation for treatment of locally advanced stage III cutaneous squamous cell carcinoma: a 22-cases retrospective analysis.

BACKGROUND: Extensive squamous cell carcinoma has few therapeutic options. In such cases, electrochemotherapy involving electroporation combined with antineoplastic drug appears to be a new potential option and may be considered as an alternative treatment. The aim of this retrospective single-center study was to evaluate electrochemotherapy efficacy in treatment of locally advanced stage III squamous cell carcinoma, in which surgical procedures would have entailed wide tissue sacrifice. METHODS: Clinical features, treatment response, and adverse effects were evaluated in 22 patients treated with electrochemotherapy with intravenous injection of bleomycin for extensive stage III cutaneous squamous cell carcinoma. Treatment of cutaneous lesions were performed according to the European Standard Operating Procedures of Electrochemotherapy. RESULTS: Overall response to electrochemotherapy treatment was observed in 18 (81.8%) patients. Clinical response with necrosis of tumor mass was observed from the first session and lasted for all follow up period that ranged between 5 and 48 months with a median of 34 months. Overall the treatment was well tolerated with a very low complication rate. CONCLUSIONS: Electrochemotherapy represents a safe and effective therapeutic approach, associated with a good tolerability.

Surgical management of sentinel lymph node biopsy outside major nodal basin in patients with cutaneous melanoma.

PURPOSE: To assess the incidence of nonmajor lymphatic basin sentinel nodes in patients with cutaneous melanoma in order to propose a correct nomenclature and inform appropriate surgical management. METHODS: This was a retrospective review of 1,045 consecutive patients with cutaneous melanoma who underwent sentinel lymph node biopsy and dynamic lymphoscintigraphy to identify sentinel node site. Nonmajor drainage sites were classified as uncommon (located in a minor lymphatic basin along the lymphatic drainage to a major classical nodal basin) or interval (located anywhere along the lymphatics between the primary tumor site and the nearest lymphatic basin) sentinel nodes. RESULTS: Nonclassical sentinel nodes were identified in 32 patients (3.0 %). Uncommon sentinel nodes were identified in 3.2 % (n = 17) of trunk melanoma primary disease and in 1.5 % (n = 7) of upper and lower extremity sites. Interval sentinel nodes were identified in 1.3 % (n = 7) of trunk primary lesions, with none from upper and lower extremities melanomas. The incidence of tumor-positive sentinel nodes was 24.1 % (245 of 1,013) in classical sites and 12.5 % (4 of 32) in uncommon/interval sites. CONCLUSIONS: The definition of uncommon and interval sentinel nodes allows the identification of different lymphatic pathways and inform appropriate surgical treatment. Wider experience with uncommon/interval sentinel nodes will better clarify the clinical implications and surgical management to be adopted in the management of uncommon and interval sentinel node sites.

Long-lasting response to electrochemotherapy in melanoma patients with cutaneous metastasis.

BACKGROUND: Treatment of early and multiple cutaneous unresectable recurrences is a major therapeutic problem with around 80% of patients relapsing within 5 years. For lesions refractory to elective treatments, electrochemotherapy (ECT) involving electroporation combined with antineoplastic drug treatment appears to be a new potential option. This study was undertaken to analyze the short- and long-term responses of lesions treated with ECT with intravenous injection of bleomycin in melanoma patients with in-transit disease or distant cutaneous metastases. METHODS: Between June 2007 and September 2012, 60 patients with relapsed and refractory cutaneous melanoma metastases or in-transit disease underwent 100 courses of ECT with intravenous injection of bleomycin. Response to treatment was evaluated three months after ECT. A long-lasting response was defined as no cutaneous or in-transit relapse after a minimum of six months. RESULTS: Three months after ECT, a complete response was observed in 29 patients (48.4%), a partial response in 23 patients (38.3%) and no change or progressive disease in 8 patients (13.3%). The objective response rate of all treated lesions was 86.6%. Thirteen patients (44.8% of complete responders) experienced a long-lasting response after one ECT session and were disease-free after a mean duration of follow-up of 27.5 months. CONCLUSIONS: The favorable outcome obtained in the present study demonstrates that ECT is a reliable, and effective procedure that provides long-term benefit in terms of curative and palliative treatment for unresectable cutaneous lesions without adversely impacting the quality of life of patients.

Superficial and deep lymph node dissection for stage III cutaneous melanoma: clinical outcome and prognostic factors.

BACKGROUND: The aims of this retrospective analysis were to evaluate the effect of combined superficial and deep groin dissection on disease-free and melanoma-specific survival, and to identify the most important factors for predicting the involvement of deep nodes according to clinically or microscopically detected nodal metastases. METHODS: Between January 1996 and December 2005, 133 consecutive patients with groin lymph node metastases underwent superficial and deep dissection at the National Cancer Institute, Naples. Lymph node involvement was clinically evident in 84 patients and detected by sentinel node biopsy in 49 cases. RESULTS: The 5-year disease-free survival was significantly better for patients with superficial lymph node metastases than for patients with involvement of both superficial and deep lymph nodes (34.9% vs. 19.0%; P = 0.001). The 5-year melanoma-specific survival was also significantly better for patients with superficial node metastases only (55.6% vs. 33.3%; P = 0.001). CONCLUSIONS: Metastasis in the deep nodes is the strongest predictor of both disease-free and melanoma-specific survival. Deep groin dissection should be considered for all patients with groin clinical nodal involvement, but might be spared in patients with a positive sentinel node. Prospective studies will clarify the issue further.

B-cell non-Hodgkin lymphoma of the breast in Waldenström's macroglobulinemia: a case report.

Background: Non-Hodgkin lymphoma (NHL) of the breast is a rare disease and can occur amongst patients affected by Waldenström's Macroglobulinemia (WM). WM is an indolent B-cell lymphoproliferative disorder with an overall incidence of about 1/100,000 in Europe. Breast imaging is not specific to breast lymphoma that often mimics benign lesions. The diagnosis is based on breast biopsy, the presence of MYD88L265P somatic mutation and immunoglobulin M (IgM) paraprotein detectable in the setting of lymphoplasmacytic infiltration by bone marrow (BM) biopsy. Case Description: A 60-year-old woman with personal and familial history of monoclonal gammopathy of undetermined significance (MGUS) and a lump in her right breast was referred to our hospital. Standard imaging showed round mass with smooth edges. The lump was biopsied and the pathology examination showed lymphoplasmacytic lymphoma (LPL) of the breast which led to final the diagnosis of WM. Conclusions: Lymphoma of the breast is a rare disease, often misdiagnosed because of the lack of specific features at mammogram and ultrasound. Core biopsy is crucial to make diagnosis of breast lymphoma and early diagnosis of WM has been shown to improve overall survival (OS). A comprehensive approach is required in order to assess patients affected by blood disorders presenting with a new breast mass that can lead to diagnosis of breast lymphoma.

Axillary node metastasis from differentiated thyroid carcinoma with Hürthle and signet ring cell differentiation. A case of disseminated thyroid cancer with peculiar histologic findings.

BACKGROUND: Differentiated thyroid cancer is usually associated with an excellent prognosis and indolent course. Distant metastases are rare events at the onset of thyroid cancer. Among these presentations, metastasis to the axillary lymph nodes is even more unusual: only few cases were previously reported in the literature; there has been no report of axillary lymph node metastasis from follicular thyroid carcinoma. Axillary lymph node metastasis generally arises in the context of disseminated disease and carries an ominous prognosis. CASE PRESENTATION: Here we present a case of axillary lymph node metastasis in the context of disseminated differentiated thyroid cancer. The patient underwent near total thyroidectomy and neck and axillary lymph node dissection. A histopathological diagnosis of poorly differentiated follicular carcinoma with "signet ring cells" and Hürthle cell features was established. The patient received radioactive iodine therapy and TSH suppression therapy. Subsequently his serum thyroglobulin level decreased to 44.000 ng/ml from over 100.000 ng/ml. DISCUSSION AND CONCLUSION: Currently there are only few reported cases of axillary node metastases from thyroid cancer, and to our knowledge, this is the first report on axillary lymph node metastasis from follicular thyroid carcinoma. "Signet ring cell" is a morphologic feature shared by both benign and, more rarely, malignant follicular thyroid neoplasm, and it generally correlates with an arrest in folliculogenesis. Our case is one of the rare "signet ring cells" carcinomas so far described.

Collagen sealant patch to reduce lymphatic drainage after lymph node dissection.

BACKGROUND: Seroma formation is a frequent complication following radical lymph node dissection (RLND) in patients with metastatic melanoma. Several strategies have been used to prevent fluid accumulation and thereby reduce the duration of postoperative drainage, including fibrin sealants. METHODS: This was a prospective, single-center study in which consecutive patients undergoing surgical treatment of stage III metastatic melanoma by axillary or ilio-inguinal RLND were randomized to receive standard treatment plus fibrinogen/thrombin-coated collagen sealant patch (CSP) or standard treatment alone. The primary endpoint of the study was postoperative duration of drainage. RESULTS: A total of 70 patients underwent axillary (n = 47) or ilio-inguinal (n = 23) RLND and received CSP plus standard treatment (n = 37) or standard treatment alone (n = 33). Mean duration of drainage was significantly reduced in the CSP group compared with standard treatment (ITT analysis: 20.1 ± 5.1 versus 23.3 ± 5.1 days; p = 0.010). The percentage of patients drainage-free on day 21 was significantly higher in the CSP group compared with the standard treatment group (86% versus 67%; p = 0.049). CONCLUSIONS: Use of the tissue sealant resulted in a significant reduction in duration of drainage. Further studies are warranted to confirm these results in different and selected types of lymphadenectomy.

Half forehead reconstruction with a single rotational scalp flap for dermatofibrosarcoma protuberans treatment.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a soft tissue neoplasm of intermediate to low-grade malignancy. Although metastasis rarely occurs, DFSP has a locally aggressive behavior with a high recurrence rate. In the head and neck area, resection involving a wide margin of healthy tissue can be difficult because of functional and cosmetic considerations. We describe a novel reconstructive method for half forehead defects with an innovative single local wide scalp flap following excision of DFSP with a 3 cm margin of healthy tissue. METHODS: Two patients underwent wide resection of forehead DFSP and reconstruction with a single rotational scalp flap. The scalp flap blood supply was provided from three main vessels: the superficial temporal artery, occipital artery and posterior auricular artery. RESULTS: No early or late complications were observed in either patient with no local recurrence after 18 months of follow-up. The donor area could be closed primarily in both cases and the flaps survived completely. CONCLUSION: This innovative technique allowed a radical excision of forehead DFSP with sufficient healthy margins, thus potentially decreasing tumor recurrence rate. Reconstruction was achieved avoiding microsurgery, skin expanders and large skin grafts. Moreover, all main reconstructive criteria, such as functional and cosmetic tissue characteristics, were completely fulfilled.

Preoperative localisation of nonpalpable breast lesions using magnetic markers in a tertiary cancer centre.

BACKGROUND: We retrospectively evaluated safety and performance of magnetic seed localisation of nonpalpable breast lesions. METHODS: We reviewed records of patients with nonpalpable breast lesions preoperative localised by placing magnetic Magseed® marker between February 2019 and December 2020. During surgery, Sentimag® magnetic probe was used to localise the marker and guide surgery. Safety, lesion identification and excision with tumour with free margins and re-excision rate were assessed. RESULTS: A total of 77 Magseed® devices were placed into the breasts of 73 patients, 44 under ultrasound and 33 under stereotactic guidance (4 bilateral). All devices were retrieved as were the target lesions. Magnetic marker placement was successful in all cases without any adverse event. Intraoperative identification and excision of the localised lesion were successful in 77 of 77 of cases (100%). In three cases (all of them calcifications with the seed placed under stereotactic guidance), the seed did not reach the exact target position of the biopsy clip; thus, larger excision was needed, with localisation failure attributed to incorrect clip insertion (n = 1) or to clip dislocation (n = 2). Migration of the marker was negligible in all patients. Complete excision after the initial procedure with at least 1-mm disease-free margins was obtained in 74 out of 77 (96.1%) lesions. The re-excision rate was 3 out of 77 (4%). CONCLUSIONS: Magnetic marker localisation for nonpalpable breast lesions was safe, reliable, and effective in terms of lesion identification, excision with tumour-free margins and re-excision rate.

Gallbladder metastasis: spectrum of imaging findings.

The objective of this study is to report the diagnostic features of hematogenous gallbladder metastasis using various imaging modalities. We carried out a single-center retrospective analysis of 13 patients with gallbladder metastasis. The primary malignancy was cutaneous melanoma (11 cases), hepatocellular carcinoma (1 case), and non-Hodgkin lymphoma (1 case). All patients underwent sonography (US), with color-power-Doppler assessment in 11 cases. Contrast-enhanced US (CEUS) was performed in 8 patients, MDCT in 8, and MR imaging in 1. Four subjects studied by whole-body PET. The gallbladder lesions were first detected with US in 9 cases and with MDCT in 3 cases. The remaining patient was investigated because of hepatic fluorodeoxyglucose uptake at PET; CEUS failed to detect any liver metastasis in this subject but identified a gallbladder lesion. Typical findings included multiplicity of gallbladder vegetations, broad base, limited mural thickening, presence of contrast enhancement, absence of gallstones and gallbladder bed infiltration, presence of combined lesions within other organs. Only two patients presented an isolated location in the gallbladder and were successfully treated with surgery. Gallbladder metastasis is a rare but possible occurrence. Knowledge of the typical imaging features and careful evaluation of the gallbladder may avoid an incorrect or false negative diagnosis.

Metastatic eccrine porocarcinoma: report of a case and review of the literature.

Eccrine porocarcinoma (EPC) is a rare type of skin cancer arising from the intraepidermal portion of eccrine sweat glands or acrosyringium, representing 0.005-0.01% of all cutaneous tumors. About 20% of EPC will recur and about 20% will metastasize to regional lymph nodes. There is a mortality rate of 67% in patients with lymph node metastases. Although rare, the occurrence of distant metastases has been reported.We report a case of patient with EPC of the left arm, with axillary nodal involvement and subsequent local relapse, treated by complete lymph node dissection and electrochemotherapy (ECT).EPC is an unusual tumor to diagnose. Neither chemotherapy nor radiation therapy has been proven to be of clinical benefit in treating metastatic disease. Although in the current case the short follow-up period is a limitation, we consider in the management of EPC a therapeutic approach involving surgery and ECT, because of its aggressive potential for loregional metastatic spread.

Lower Eyelid Orbicularis Oculi Myocutaneous Flap: A Feasible Technique for Full Thickness Upper Eyelid Reconstruction.

Basal cell carcinoma (BCC) is the most frequent malignant eyelid tumor, followed by squamous cell carcinoma, sebaceous gland carcinoma and malignant melanoma. These eyelid malignancies represent main reason for eyelid reconstruction in ophthalmoplastic surgery which can be challenging. Lower eyelid orbicularis oculi myocutaneous flap was used for reconstructive purpose in four consecutive patients with a full thickness upper eyelid BCC. Digital photographs were taken at baseline, 1 month, 3 and 6 months after surgery to assess clinical outcome. Four patients underwent full thickness upper eyelid reconstruction with a lower eyelid orbicularis oculi myocutaneous flap after BCC radical resection with 3-mm safe margins. Histological subtypes showed tumor complete excision in all cases. No patient showed local recurrence at a mean 12 months follow-up. The high functional-esthetical success rate of the modified Hughes procedure corresponds with the beneficial results, which have been reported in previous publications. None of the treated patients complained about forced temporary closure of eyelid. In all four cases treated, aesthetic and functional outcome were satisfactory.

Angiosarcoma of the breast, the unknown-a review of the current literature.

Angiosarcoma of the breast is one of the rarest malignancies. Breast angiosarcoma can be classified into primary when arising de novo and secondary to chronic lymphoedema or breast irradiation. Molecular pathways involved in angiosarcoma development have not been described clearly, yet some gene point mutations and protein altered expression levels have been detected. So far, their management is based above all on surgery. Hence, further studies starting from the few known key points may help to develop more effective strategies based both on target therapies, together with surgery.

Resection in the popliteal fossa for metastatic melanoma.

BACKGROUND: Traditionally metastatic melanoma of the distal leg and the foot metastasize to the lymph nodes of the groin. Sometimes the first site of nodal disease can be the popliteal fossa. This is an infrequent event, with rare reports in literature and when it occurs, radical popliteal node dissection must be performed. CASE PRESENTATION: We report a case of a 36-year old man presented with diagnosis of 2 mm thick, Clark's level II-III, non ulcerated melanoma of the left heel, which developed during the course of the disease popliteal node metastases, after a superficial and deep groin dissection for inguinal node involvement. Five months after popliteal lymph node dissection he developed systemic disease, therefore he received nine cycles of dacarbazine plus fotemustine. To date (56 months after prior surgery and 11 months after chemotherapy) he is alive with no evidence of disease. CONCLUSION: In case of groin metastases from melanoma of distal lower extremities, clinical and ultrasound examination of ipsilateral popliteal fossa is essential. When metastatic disease is found, radical popliteal dissection is the standard of care. Therefore knowledge of anatomy and surgical technique about popliteal lymphadenectomy are required to make preservation of structures that if injured, can produce a permanent, considerable disability.

Laparoscopic cholecystectomy for melanoma metastatic to the gallbladder: is it an adequate surgical procedure? Report of a case and review of the literature.

BACKGROUND: Only 2% to 4% of patients with melanoma will be diagnosed with gastrointestinal metastasis during the course of their disease. The most common sites of gastrointestinal metastases from melanoma include the small bowel (35%-67%), colon (9%-15%) and stomach (5%-7%), with a median survival of 6-10 months after surgery, and 18% survival at five years. Metastatic melanoma to the gallbladder is extremely rare and it is associated with a very poor prognosis. CASE PRESENTATION: We report a case of a 54-year old man presented to observation with diagnosis of 6.1 mm thick, Clark's level IV, ulcerated melanoma of the trunk, developing in the course of the disease metastatic involvement of the gallbladder as first site of recurrence, treated by laparoscopic cholecystectomy. To date only few cases of patients with metastatic melanoma of the gallbladder treated by this surgical procedure have been reported in literature. CONCLUSION: Gallbladder metastasis represents a rare event as a first site of recurrence. It must be considered a possible expression of systemic disease also despite radiological absence of other metastatic lesions. Laparoscopic approach has a possible therapeutic role, but open surgery has also a concomitant diagnostic purpose because gives the possibility of manual exploration of abdominal cavity, useful particularly to reveal bowel metastatic lesions, not easily identifiable by preoperative imaging examinations.

Effect of electrochemotherapy on human herpesvirus 8 kinetics in classic Kaposi sarcoma.

BACKGROUND: Electrochemotherapy (ECT) has shown to be an effective treatment for cutaneous and subcutaneous Kaposi sarcoma (KS) lesions. However, no study has investigated the impact of ECT treatment on the kinetics of human herpesvirus type 8 (HHV8), which is considered the necessary causal agent of KS. We aimed to evaluate HHV8 viral load and expression levels in patients affected by classic KS who received one or more ECT treatments and have been followed semi annually for up to four years. METHODS: A total of 27 classic KS patients were enrolled in this study. Tumour biopsies and blood samples were obtained before ECT treatment. Additional blood samples were collected at six month intervals for 12-48 months. HHV8 viral load and expression profiles of latent (ORF72 and ORF73) and lytic (K2, K8, K8.1, K10/K10.1, K10.5/K10.6 and ORF16) genes were assessed in all samples by real-time PCR. HHV8 ORF26 and K1 regions were amplified and subjected to direct nucleotide sequencing followed by phylogenetic analysis for variant identification. RESULTS: All KS biopsies and 46.4% of peripheral blood mononuclear cells (PBMCs) collected before ECT treatment were positive for HHV8 DNA. Viral load ranged from 0.02 to 2.3 copies per cell in KS lesions and 3.0 × 10-7 to 6.9 × 10-4 copies per cell in PBMCs. Overall, latent ORF72 and ORF73 as well as lytic K2, K8 and K10/K10.1 were expressed in all KS biopsies. ORF16 mRNA was detected in 71.4% and both K8.1 and K10.5/K10.6 mRNAs in 57.1% of KS samples. The ORF72, ORF73 and K2 transcripts were amplified in 37.5%, 25% and 25% of PBMCs collected before ECT, respectively. After the first ECT session, complete response was achieved in 20 out of 27 (74.1%) patients and HHV8 DNA was detected in four out of 27 (14.8%) PBMC samples at six month follow up. Phylogenetic analysis of ORF26 amplimers showed that most viral variants belonged to A/C (82.3%), and few to C2 (5.9%) or C3 (11.8%) subtype. The K1/VR1 variants fell into A (33.3%) and C (66.7%) HHV8 clade. No correlation was found between HHV8 subtypes and ECT complete response. CONCLUSIONS: ECT therapy has a significant effect on HHV8 kinetics in patients with classic KS. The complete remission of patients was accompanied by clearance of circulating virus.

Huge parathyroid carcinoma: clinical considerations and literature review.

BACKGROUND: Parathyroid carcinoma is a rare malignancy, with an incidence of 0.5 to 4% of all cases of primary hyperparathyroidism. Surgery is the only curative treatment. CASE PRESENTATION: We report the case of a 66-year-old man referred for a large suspicious substernal goitre associated with severe hypercalcemia due to hyperparathyroidism. After normalization of serum calcium levels, patient underwent surgery. The voluminous cervicomediastinal firm mass could not be removed through the cervical incision; therefore a cervicothoracic approach was employed. Histopathology revealed a giant parathyroid cancer of 450 grams. A review of the literature was also undertaken to summarize the current treatment approaches for this rare malignancy. CONCLUSION: Parathyroid cancer is usually not recognized either preoperatively or intra-operatively. En bloc resection of the tumour with the adjacent tissue is the treatment of choice and it is very important to avoid the rupture of the capsule during operation. Neither tumour size, nor the lymph node status appears to play a role in prognosis. The management of parathyroid carcinoma is a challenge even for experienced surgeons.

Electrochemotherapy in melanoma patients: a single institution experience.

AIM: This study was undertaken to update the outcome of the treated lesions with electrochemotherapy (ECT) plus intravenous injection of bleomycin in patients with in-transit disease or distant cutaneous metastases in melanoma patients. PATIENTS & METHODS: 89 patients with relapsed and refractory cutaneous melanoma metastases or in-transit disease were submitted to 126 treatments of ECT. RESULTS: 34 patients (38.2%) had a partial response and 43 had a complete response (48.3%). 12 patients (13.5%) had no change or progressive disease. The objective response rate was 67.5%. CONCLUSION: The favorable outcome obtained in the present study demonstrates that ECT is a reliable, easy, fast and effective procedure showing benefits in terms of curative and palliative treatment for unresectable cutaneous lesions respecting the quality of life.

Clinicopathologic features and surgical management of primary umbilical melanoma: a case series.

BACKGROUND: Primary umbilical melanoma is an uncommon tumor that is poorly described in the medical literature. The umbilical region is a particular anatomic site owing to the presence of embryonal remnants, which can be a potential metastatic pathway, as well as the braided lymphatic network drainage. Hence, primary malignant neoplasms affecting the umbilicus require a different and more radical surgical approach compared with other melanomas. CASE PRESENTATION: In this report, we describe a series of three patients of Caucasian ethnicity who presented with primary umbilical melanoma at the National Cancer Institute of Naples, Italy. All patients underwent wide excision of the tumor including the underlying peritoneum. No surgical complications, either immediate or delayed, were observed in any of the patients. Sentinel lymph node biopsy was negative in two cases. Two of the patients developed metastatic disease and died after systemic medical therapy. The other patient is currently in follow-up, and remains disease-free after 21 months. CONCLUSIONS: The umbilicus has vascular and embryological connections with the underlying peritoneum, so that early visceral involvement is more likely to occur with primary umbilical melanomas. As such, tumor resection including the underlying peritoneum is required to avoid local relapse, whilst sentinel lymph node biopsy appears to be of poor diagnostic value.

Assessing a novel immuno-oncology-based combination therapy: Ipilimumab plus electrochemotherapy.

Melanoma is responsible for most skin cancer-related deaths and is one of the most common cancers diagnosed in young adults. In melanoma, tumors can become established by activation of the negative regulator of cytotoxic T lymphocytes (CTLs), CTL antigen-4 (CTLA-4). Ipilimumab blocks the interaction of CTLA-4 with CD80/CD86 and augments T-cell activation and proliferation. In electrochemotherapy (ECT), local application of short high-voltage pulses renders cell membranes transiently permeable to chemotherapeutic drugs. The combination of ipilimumab and ECT may be beneficial for the treatment of metastatic melanoma; however, no prospective data are available to date. Here, we report the retrospective analysis of patients treated with ipilimumab in an expanded access program (EAP) who also received ECT. Fifteen patients with previously treated metastatic melanoma who received ipilimumab 3 mg/kg every three weeks for four cycles and underwent ECT for local disease control and/or palliation of cutaneous lesions with bleomycin 15 mg/m2 after the first ipilimumab infusion were included in the analysis. Over the study period, a local objective response was observed in 67% of patients (27% complete response [CR] and 40% partial response [PR]). According to immune-related response criteria, a systemic response was observed in nine patients (five PR and four stable disease [SD]), resulting in a disease control rate of 60%. Evaluation of circulating T-regulatory (T-reg) cells demonstrated significant differences between responders and non-responders. Overall, treatment was well-tolerated and without notable toxicity. In conclusion, the combination of ipilimumab and ECT appears to be beneficial to patients with advanced melanoma, warranting further investigation in prospective trials.