Paola Brandani

FIRST RECURRENCE ANALYSIS OF 840 CUTANEOUS MELANOMAS : A PROPOSAL FOR A FOLLOW-UP SCHEDULE

Aims and background A correct follow-up schedule for patients who underwent an excision for stage I cutaneous melanoma might allow the early detection of local and distant metastases. At present, there is no general agreement on follow-up protocols. In order to work out a follow-up guide, we have retrospectively evaluated the records of 840 stage I cutaneous melanoma patients surgically treated and followed during the postoperative period in the Division of Plastic Surgery of the University of Florence from 1975 to 1992. Methods We evaluated the patients’ records by analyzing time, pathway and site of any first recurrence in relation to the main prognostic factors such as patient sex, site, histological type and depth of invasion of each primary melanoma. A statistical analysis was performed. Results To summarize, the salient results were the following: 80% of relapses occurred in the first 3 years and they occurred significantly earlier when the primary melanoma was localized in the trunk and significantly later when the melanoma was localized in the lower limbs and for < 1.5 mm lesions. The first recurrence occurred earlier by the lymphatic than by the hematic pathway regarding the overall number of patients. The hematic pathway was the most frequent (with respect to the overall percentage of hematic metastases) for the melanomas localized in the head and neck region and for lentigo malignant melanomas, whereas the lymphatic pathway was most frequent for melanomas of the lower limbs and > 3 mm in thickness. Conclusions We suggest a follow-up schedule taking into consideration the postoperative behavior of stage I cutaneous melanoma patients (in terms of time and pathway of the first recurrence) in relation to the site and depth of invasion of the tumor.

Familial and sporadic melanoma: different clinical and histopathological features in the Italian population - a multicentre epidemiological study - by GIPMe (Italian Multidisciplinary Group on Melanoma).

Background  Having a familial member affected by cutaneous melanoma is a risk factor for this neoplasm. Only a few epidemiological case–control studies have been carried out to investigate whether familial and sporadic melanomas show different clinical and histopathological features.

Melanoma density and relationship with the distribution of melanocytic naevi in an Italian population: a GIPMe study--the Italian multidisciplinary group on melanoma.

The most frequent site for melanoma is the back in men and the lower limbs in women, where intermittent sun exposure has been reported to be an environmental agent, although studies on age-specific incidence have suggested that melanoma in chronically sun-exposed areas, such as the face, increases with age. To identify the preferential development of melanoma in chronically or intermittently sun-exposed areas and the relationship between body site distribution and parameters such as sex, age, distribution of melanocytic naevi, atypical naevi and actinic keratoses, a prospective epidemiological multicentre study was carried out on all the consecutive melanoma cases diagnosed in a 2-year period from 27 Italian GIPMe centres (GIPMe: the Italian Multidisciplinary Group on Melanoma). Both the relative density of melanoma (RDM), defined as the ratio between observed and expected melanoma for a specific body site, and the average nevi density were identified. The most common melanoma site was the back, a factor that was not affected by either age or sex, even if men had higher density values. Statistically significant higher RDM values were observed in women aged more than 50 years for leg lesions and in the anterior thighs for young women (<50 years), whereas the lowest values were observed in the posterior thighs in women of any age. Facial RDM was statistically significantly higher than expected in both male and female patients more than 50 years of age. Melanoma was associated with a significantly higher atypical naevi density only for the back, chest and thighs. Indeed, facial melanoma was related to the presence of more than four actinic keratoses and not naevi density. To the best of our knowledge, the RDM method was applied for the first time together with naevus density calculation to obtain these data, which strongly substantiate the ‘divergent pathway’ hypothesis for the development of melanoma, but not find a direct correlation between melanoma and nevi for each anatomical site.

A rare case of anal porocarcinoma treated by electrochemotherapy

We report the case of an old woman with an eccrine porocarcinoma unusually localized in the perianal area treated by electrochemotherapy, a new technique, emerging as a very effective local treatment of different skin metastases and selected primary tumors. Electrochemotherapy was performed taking into account patient wishes and refusal of demolitive surgery. The electrochemotherapy treatment was well tolerated by the patient, it gave an excellent clinical response and a complete clinical regression with no sphincter dysfunction and signs of relapse observed during follow-up. The case is of particular interest for the exceptional localization of porocarcinoma for the first time treated by electrochemotherapy in this area. Electrochemotherapy could be considered as an alternative option for selected cases of cutaneous tumors.

Saddle tailored upper eyelid island myocutaneous flap to repair full-thickness lower eyelid defects after melanoma excision.

Purpose: To perform an early melanoma diagnosis and to repair the full-thickness lower eyelid defect with an island upper eyelid myocutaneous flap tailored into a new shape. Methods: Two patients with pigmented lesion involving skin and tarsus of the lower eyelid were reported. Histologic examination, performed after diagnostic punch biopsy, confirmed the diagnosis of in situ melanomas in both cases. A full-thickness excision was done and a single pedicle island myocutaneous flap from the upper eyelid was performed. The flap was designed in a blepharoplastic manner and tunnelized to reach the lower eyelid defect. The flap was tailored into a “saddle” shape, doubled, and folded to restore both the internal and external eyelid walls in a single-stage procedure. Results: Good functional and aesthetic results were obtained with no complications. Interestingly enough, the tissue of the internal layer lost the features of skin epithelium due to metaplasia processes and appeared similar to the conjunctiva. After 3 years, no sign of melanoma recurrence was noted. Conclusions: Early diagnosis was performed in both reported lower eyelid melanoma cases. For the reconstruction, a modified upper eyelid island myocutaneous flap tailored into a “saddle” shape was used, which had the advantages of being a single-stage procedure and avoiding mucosa grafts. The technique could also be used to repair full-thickness lower eyelid defects from other causes.

Encephalocraniocutaneous lipomatosis: congenital alopecia treatment in a rare neurocutaneous syndrome

Abstract Encephalocraniocutaneous lipomatosis (ECCL) is a rare neurocutaneous syndrome that include skin, ocular, and neurological disorders. This study describes the case of a 16-year-old girl that came to observation for the treatment of a congenital alopecia causing great psychological distress. After two expansion procedures the hairless patch was restored with high patient satisfaction. The case met all the criteria for definite diagnosis of ECCL.

IDO and CD83 expression in human epidermal Langerhans cells

Langerhans cells (LCs) are a subset of dendritic cells (DCs) that side within epidermis and mucosae in immature state, self-antigens [3]. Furthermore von Bubnoff et al. [4] reported that mature IFN-g stimulated-LCs transiently expressed indoleamine 2,3-dioxygenase (IDO), a potent tolerogenic enzyme that induces immune peripheral tolerance [5], which is also involved in tumorinduced tolerance [6]. Therefore, IDO expression by LCs might indicate a possible regulatory/inhibitory function [4]. Resident LCs represent a promising target for cancer immunoth LC

Clinico-pathological characteristics of familial melanoma in a Mediterranean population.

Introduction To what extent familial and sporadic melanomas differ in their biological behavior and prognostic factors is still a matter of debate. First, an accurate identification of patients with a true family history can be difficult (because married-in members can be confused with biological relatives), and, second, a melanoma can be misclassified as a nonmelanoma skin cancer [1]. Previous estimates, though, of the proportion of melanomas reported a familial component range from 5 to 12% [2–4].

Melanoma metastases occuring 40 years after primary melanoma

tor nivolumab in a renal transplant patient with malignancy. Am J Transplant. 2016;16:2496–2497. [13] Gastman BR, Ernstoff MS. Tolerability of immune checkpoint inhibition cancer therapy in a cardiac transplant patient. Ann Oncol. 2016;27:2304–2305. [14] Herz S, Hofer T, Papapanagiotou M, et al. Checkpoint inhibitors in chronic kidney failure and an organ transplant recipient. Eur J Cancer. 2016;67:66–72. [15] Lipson EJ, Bagnasco SM, Moore J Jr, et al. Tumor regression and allograft rejection after administration of anti-PD-1. N Engl J Med. 2016;374:896–898. [16] Lipson EJ, Bodell MA, Kraus ES, et al. Successful administration of ipilimumab to two kidney transplantation patients with metastatic melanoma. J Clin Oncol. 2014;32:e69–e71. [17] Morales RE, Shoushtari AN, Walsh MM, et al. Safety and efficacy of ipilimumab to treat advanced melanoma in the setting of liver transplantation. J Immunother Cancer. 2015;3:22. [18] Ong M, Ibrahim AM, Bourassa-Blanchette S, et al. Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. J Immunother Cancer. 2016;4:64. [19] Ranganath HA, Panella TJ. Administration of ipilimumab to a liver transplant recipient with unresectable metastatic melanoma. J Immunother. 2015;38:211. [20] Spain L, Higgins R, Gopalakrishnan K, et al. Acute renal allograft rejection after immune checkpoint inhibitor therapy for metastatic melanoma. Ann Oncol. 2016;27:1135–1137. [21] De Toni EN, Gerbes AL. Tapering of immunosuppression and sustained treatment with nivolumab in a liver transplant recipient. Gastroenterology. 2017;152:1631–1633. [22] Qin R, Salama AK. Report of ipilimumab in a heart transplant patient with metastatic melanoma on tacrolimus. Melanoma Manag. 2015;2:311–314. [23] Varkaris A, Lewis DW, Nugent FW. Preserved liver transplant after PD-1 pathway inhibitor for hepatocellular carcinoma. Am J Gastroenterol. 2017;112:1895–1896. [24] Winkler JK, Gutzmer R, Bender C, et al. Safe administration of an anti-PD-1 antibody to kidney-transplant patients: 2 clinical cases of the literature. J Immunother. 2017;40:341–344. [25] Friend BD, Venick RS, McDiarmid SV, et al. Fatal orthotopic liver transplant organ rejection induced by a checkpoint inhibitor in two patients with refractory, metastatic hepatocellular carcinoma. Pediatr Blood Cancer. 2017;64. DOI:10.1002/pbc.26682. [26] Biondani P, De Martin E, Samuel D. Safety of an anti-PD-1 immune checkpoint inhibitor in a liver transplant recipient. Ann Oncol. 2018;29:286–287. [27] Dueland S, Guren TK, Boberg KM, et al. Acute liver graft rejection after ipilimumab therapy. Ann Oncol. 2017;28:2619–2620. [28] Jose A, Yiannoullou P, Bhutani S, et al. Renal allograft failure after ipilimumab therapy for metastatic melanoma: a case report and review of the literature. Transplant Proc. 2016;48:3137–3141. [29] Kittai AS, Oldham H, Cetnar J, et al. Immune checkpoint inhibitors in organ transplant patients. J Immunother. 2017;40:277–281. [30] Kwatra V, Karanth NV, Priyadarshana K, et al. Pembrolizumab for metastatic melanoma in a renal allograft recipient with subsequent graft rejection and treatment response failure: a case report. J Med Case Reports. 2017;11:73. [31] Owonikoko TK, Kumar M, Yang S, et al. Cardiac allograft rejection as a complication of PD-1 checkpoint blockade for cancer immunotherapy: a case report. Cancer Immunol Immunother. 2017;66:45–50. [32] Schvartsman G, Perez K, Sood G, et al. Immune checkpoint inhibitor therapy in a liver transplant recipient with melanoma. Ann Intern Med. 2017;167:361–362. [33] Haanen JBAG Carbonnel F, Robert C, et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol. 2017;28: iv119–iv142. [34] Germani G, Rodriguez-Castro K, Russo FP, Senzolo M, Zanetto A, Ferrarese A, et al. Markers of acute rejection and graft acceptance in liver transplantation. World J Gastroenterol. 2015;21(4):1061–1068. [35] Johncilla M, Misdraji J, Pratt DS, et al. Ipilimumab-associated hepatitis: clinicopathologic characterization in a series of 11 cases. Am J Surg Pathol. 2015;39:1075–1084. [36] Neuberger J. Incidence, timing, and risk factors for acute and chronic rejection. Liver Transpl Surg. 1999;5:S30–S36. [37] Wu O, Levy AR, Briggs A, et al. Acute rejection and chronic nephropathy: a systematic review of the literature. Transplantation. 2009;87:1330–1339.

Multiple Lymph Node Basin Drainage in Trunk Melanoma Is Not Associated with Survival of Sentinel Lymph Node-Positive Patients

Objectives: This study was aimed at investigating the prognostic role of multiple lymph node basin drainage (MLBD) in patients with positive sentinel lymph node (SLN) biopsy. Background: MLBD is frequently observed in patients with trunk melanoma undergoing SLN. The prognostic value of MLBD in SLN-positive patients is still debated. Methods: Retrospective data from 312 trunk melanoma patients with positive SLN biopsy (1991-2012) at 6 Italian referral centres were gathered in a multicentre database. MLBD was defined at preoperative lymphoscintigraphy. Clinical and pathological data were analysed for their association with disease-free interval (DFI) and disease-specific (DSS) survival. Results: MLBD was identified in 34.6% of patients (108/312) and was significantly associated with >1 positive SLN (37 vs. 15.2%; p < 0.001) and with >1 positive lymph node (LN) after complete lymph node dissection (CLND) (50.9 vs. 34.8%; p = 0.033). No differences were observed according to drainage pattern in patients who had negative and positive non-SLN at CLND. MLBD was not associated with either DFI or DSS. Multivariate analyses showed that tumour thickness, ulceration, and number of metastatic LNs were associated with worse DFI and DSS, while regression confirmed its protective role in survival. Conclusion: In positive SLN patients, MLBD has no association with survival, which is mainly related to American Joint Committee on Cancer (AJCC) prognostic factors. Since the overall number of positive LNs drives the prognosis, the importance of a CLND in all the positive basins is confirmed.