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Melanoma is an immunogenic neoplasm infiltrated by T cells, although these adaptive T cells usually fail to eradicate the tumor. Plasmacytoid dendritic cells (PDCs) are potent regulators of the adaptive immune response and can eliminate melanoma cells via TLR-mediated effector functions. The PDC compartment is maintained by progressively restricted bone marrow progenitors. Terminally differentiated PDCs exit the bone marrow into the circulation, then home to lymph nodes and inflamed peripheral tissues. Infiltration by PDCs is documented in various cancers. However, their role within the melanoma immune contexture is not completely known. We found that in locoregional primary cutaneous melanoma (PCM), PDC infiltration was heterogeneous, occurred early, and was recurrently localized at the invasive margin, the site where PDCs interact with CD8+ T cells. A reduced PDC density was coupled with an increased Breslow thickness and somatic mutations at the NRAS p.Q61 codon. Compared with what was seen in PCM, high numbers of PDCs were found in regional lymph nodes, as also identified by in silico analysis. In contrast, in metastatic melanoma patients, PDCs were mostly absent in the tumor tissues and were significantly reduced in the circulation, particularly in the advanced M1c group. Exposure of circulating PDCs to melanoma cell supernatant (SN-mel) depleted of extracellular vesicles resulted in significant PDC death. SN-mel exposure also resulted in a defect of PDC differentiation from CD34+ progenitors. These findings indicate that soluble components released by melanoma cells support the collapse of the PDC compartment, with clinical implications for refining TLR agonist–based trials.

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Melanoma is an immunogenic neoplasm infiltrated by T cells, although these adaptive T cells usually fail to eradicate the tumor. Plasmacytoid dendritic cells (PDCs) are potent regulators of the adaptive immune response and can eliminate melanoma cells via TLR-mediated effector functions. The PDC compartment is maintained by progressively restricted bone marrow progenitors. Terminally differentiated PDCs exit the bone marrow into the circulation, then home to lymph nodes and inflamed peripheral tissues. Infiltration by PDCs is documented in various cancers. However, their role within the melanoma immune contexture is not completely known. We found that in locoregional primary cutaneous melanoma (PCM), PDC infiltration was heterogeneous, occurred early, and was recurrently localized at the invasive margin, the site where PDCs interact with CD8+ T cells. A reduced PDC density was coupled with an increased Breslow thickness and somatic mutations at the NRAS p.Q61 codon. Compared with what was seen in PCM, high numbers of PDCs were found in regional lymph nodes, as also identified by in silico analysis. In contrast, in metastatic melanoma patients, PDCs were mostly absent in the tumor tissues and were significantly reduced in the circulation, particularly in the advanced M1c group. Exposure of circulating PDCs to melanoma cell supernatant (SN-mel) depleted of extracellular vesicles resulted in significant PDC death. SN-mel exposure also resulted in a defect of PDC differentiation from CD34+ progenitors. These findings indicate that soluble components released by melanoma cells support the collapse of the PDC compartment, with clinical implications for refining TLR agonist–based trials.

We report a case of a healthy 26-year-old male with multiple asymptomatic reddish papules and papule-nodules on the central area of the face, persisting from more than 2 months and gradually increasing in number. An incisional skin biopsy revealed a confluent dense granulomatous infiltrate centred by large areas of eosinophilic necrosis consistent with the diagnosis of lupus miliaris disseminatus faciei (LMDF). This is a rare dermatosis first described in 1878 by Fox, that often poses a clinical challenge as it is a disease process which is difficult to diagnose. In fact, in our case, a diagnosis of LMDF was made on skin biopsy. We think that collaboration among dermatologists and General Practitioners is very important for diagnosis of rare dermatosis and especially for management of it, in order to prevent the development of depressed scars.

Background The relationship between the occurrence of skin diseases and skin tattoos remains unclear. Dermatologic disorders have been reported to occur in about 2% of cases. In addition, tattoo pigment can migrate to the regional lymph nodes through the lymphatic vessels and subsequently mimic metastatic disease from melanoma. Methods A 23-year-old Caucasian man presented with a pigmented lesion on the left scapular region, which had slowly enlarged over time. The patient exhibited an extensive tattoo on the left upper arm, left shoulder, and part of the upper back. His medical history was unremarkable. The pigmented lesion was excised. Histology confirmed malignant melanoma. Ultrasound examination of the abdomen, neck, and inguinal and axillary lymph nodes and a total body computed tomography scan showed no sign of disease. A re-excision with 2-cm margins and sentinel lymph node biopsy (SLNB) were performed. Two grossly enlarged, black sentinel lymph nodes (SLNs) highly suggestive of melanoma metastases were removed. Results No evidence of melanoma metastasis was found in any of the sampled tissues. Large amounts of pigment were present within the subcapsular space and sinusoid areas of the two clinically suspicious lymph nodes. Immunohistochemical analysis was negative. Conclusions Sentinel lymph node biopsy is widely performed in cutaneous melanoma. Histologic confirmation of any enlarged, pigmented SLN is essential prior to radical surgery, especially when pigmented SLNs are found near a tattoo. Tattoo pigments may deposit in the regional lymph nodes and may clinically mimic metastatic disease. A history of tattooing should be considered in all melanoma patients eligible for SLNB. In a finding of darkly pigmented nodes during SLNB, radical lymphadenectomy should be withheld until immunohistologic confirmation of metastasis in the SLN is obtained.

Summary Background. The risk of a subsequent cancer is an important issue for patients with melanoma. The development of a second primary cancer in patients with a solitary melanoma has been discussed in several studies. However, to our knowledge, the incidence of second primary cancer (SPC) in patients with multiple primary melanoma (MPM) has not been thoroughly investigated. Aim. To quantify the incidence of SPC in patients with MPM, with the aim of possibly developing further preventive measures. Methods. In a retrospective study, 76 patients with MPM were identified from 2155 patients being followed up at our unit. Results. Of the 76 patients, 12 (16%) developed another neoplasm, with 59% of them having nonmelanoma skin cancer (NMSC), and 41% other noncutaneous cancers. By contrast, only 8% of those with single primary melanoma had other neoplasms (21% of whom had NMSC). Conclusions. Patients with MPM, especially men with skin phototype II, have a significantly increased incidence of developing SPC, particularly NMSC. Thus, careful monitoring is essential not only to detect recurrence of the original cancer or development of another primary melanoma, but also development of new malignancies of different types, particularly NMSC.

Summary A case of malignant epithelioid schwannoma in the skin is reported. This was a rare variant of a malignant tumour that arose on the back of a 35-year-old male without neurofibromatosis. Clinically the nodule appeared to be a benign cyst but as it was painful it was decided to remove it. Ultrastructural and immunohistochemical features of the lesion were consistent with those of malignant epithelioid schwannoma so a radical excision was performed. Most ordinary malignant schwannoma are located in the deep soft tissue of the proximal portions of the upper and lower extremities and trunk; to the best of our knowledge only 26 cases of malignant epithelioid schwannoma in the skin and subcutis have been described in the literature. For the 14 male and 12 female patients reviewed, the median age was 43 years (range 19–84). Upper extremities were the most common sites (10 of 26). Seven patients developed local recurrences and four developed metastases: two to lung, one to lung and lymph node, and one to lung, liver and brain. All patients with local recurrence and all except one who developed metastases did not undergo wide local excision. We can conclude that malignant epithelioid schwannoma in the skin and subcutis is eminently curable if treated with wide local excision.

Merkel cell carcinoma (MCC) is a skin cancer of neuroendocrine origin that occurs most often in sun-exposed areas. In the general population, it is a disease of older adults, with only 5% of cases occurring below the age of 50 years. Immunosuppression is the significant risk factor for the development of MCC and recently it was suggested that individuals with HIV have a relative risk of 13.4 to developed MCC in comparison with the general population. We report a case of MCC in an HIV-infected patient and we review nine patients with HIV with MCC. Our patient was a 54-year-old man who came to our attention without a known HIV diagnosis. He was apparently in good health and had no risk factor for HIV, but by the atypical site of the lesion and by the relative young age of the patient we suspected a case of immunosuppression and for this reason we did HIV test that had a positive result. The patient was treated with surgery and chemotherapy but died as a result of liver metastases 25 months after his tumor was diagnosed.

An association between Borrelia burgdorferi with primary cutaneous B-cell lymphoma (PCBCL) has long been suspected but just recently, thanks to a polymerase chain reaction technique, it had been possible to demonstrate B. burgdorferi-specific DNA in skin lesions of patients with different PCBCL subtypes. Locating cases of PCBCL that are related to B. burgdorferi infection could be really important for therapeutic implications; in fact, there are several reports of PCBCL responding to antibiotic therapy against B. burgdorferi. We report a case of B. burgdorferi-associated primary cutaneous marginal-zone B-cell lymphoma that, after specific antimicrobial therapy, did not show any clinical regression. We can conclude that additional studies are necessary in order to establish the use of antimicrobial therapy in B. burgdorferi-associated PCBCL.

Adenoid cystic carcinoma (ACC) of the salivary glands is a malignant tumor characterized by slow but relentless progression that is plagued by local recurrence, late metastases, and ultimately fatal outcomes. Twenty-four percent to 52% of ACCs of the salivary glands result in distant metastasis, primarily involving the lungs, bones, liver, and brain. Cutaneous metastasis of these tumors is rare and usually represents an advanced stage of disseminated disease. We report the case of a 61-year-old man with a history of ACC of the right submandibular region who was referred to our dermatology clinic 2 months following wide excision of the tumor. A nonspecific dermatitis had developed at the surgical site. A skin biopsy was performed due to the discovery of eruptive papules on the scalp and neck, which demonstrated the characteristic histopathologic features of metastatic ACC. Our case underscores the importance of conducting a complete skin examination in oncologic patients, especially focusing on cutaneous and subcutaneous nodules and papules that are eruptive or show rapid development.

Classically, dermatofibrosarcoma protuberans (DFSP) is a disease of adults. The world literature revision shows that several pediatric cases have been reported so far; this might suggest that the number of infants with the condition might be larger than that estimated previously. Here, we report the 183rd case of histologically confirmed DFSP in young age. A 14-year-old white male patient came under our care for a slowly growing, pale brownish lesion on the neck skin. A biopsy specimen showed a DFSP. Subsequently, a wide surgery excision with 3 cm of resection margins including the underlying fascia was performed. To date, the patient has been in follow-up for 6 years without evidence of recurrent disease. The clinical features and treatment of DFSP diagnosed in childhood and adolescence reported in the published literature are reviewed to provide new insights about this rare entity. The aim is to emphasize the importance of biopsy for histologic evaluation in the cases that show a persistent or a large cutaneous plaque or nodule without pathognomonic clinical features that permit a clinical diagnosis. An accurate knowledge of the disease is the prerequisite for a wider recognition and appropriate treatment.

Herein we report a case of a melanoma arising in a patient receiving adalimumab and methotrexate for rheumatoid arthritis. A limited number of studies reported melanoma growth in patients undergoing treatment with biologics. This case report with a brief review of literature suggests that patients under treatment with biologics should be counseled to identify new pigmented lesions or changes in preexisting nevi. Clinicians' collaboration will facilitate recognition and timely diagnosis of early melanoma. If there is any doubt, excision for histological evaluation should be considered. Pending new studies, careful observation is encouraged.

It is well shown that chronic wounds are populated by cells unable to respond to re-epithelising stimulus. Large ulcers that remain unhealed for several months are more difficult to treat probably because of the depletion of active factors. Yet in 1869 Reverdin realised that the partial coverage of an ulcer with small fragments of healthy skin was able to lead to wound healing; unfortunately, its employment was limited to granulating wounds. Recently, the importance of factors such as cytokines, chemokines and adhesion molecules in wound healing, and the involvement of all cellular types resident or transiting in the skin has been partially elucidated. In this study, we proposed to simultaneously provide a new cellular and molecular reservoir with the efficient stimulus to trigger it. We created receiving site inside the ulcer, able to contain a full-thickness graft taken from a donor site. Our aim was not to cover the entire defect, but to use the minigraft as 'fount' of functional cells and to give an acute stress through the chambers created inside the ulcer. A complete wound healing was obtained in all patients treated in a short period of time. This technique does not require special equipment and assistance in maintaining costs at very low levels.

Author(s): Manganoni, AM; Facchetti, F; Gavazzoni, F; Farisoglio, C; Manca, G; Sereni, E; Marocolo, D; Calzavara-Pinton, PG

Background. Recent studies have demonstrated that there exists a great variation in the lymphatic drainage in patients with malignant melanoma. Some patients have drainage to lymph nodes outside of conventional nodal basins. The lymph nodes that exist between a primary melanoma and its regional nodal basin are defined “interval nodes”. Interval node occurs in a small minority of patients with forearm melanoma. We report our experience of the Melanoma Unit of University Hospital Spedali Civili Brescia, Italy.Methods. Lymphatic mapping using cutaneous lymphoscintigraphy (LS) has become a standard preoperative diagnostic procedure to locate the sentinel lymph nodes (SLNs) in cutaneous melanoma. We used LS to identify sentinel lymph nodes biopsy (SLNB) in 480 patients.Results. From over 2100 patients affected by cutaneous melanoma, we identified 2 interval nodes in 480 patients with SLNB . The melanomas were both located in the left forearm. The interval nodes were also both located in the left arm.Conclusion. The combination of preoperative LS and intraoperative hand-held gamma detecting probe plays a remarkable role in identifying these uncommon lymph node locations. Knowledge of the unusual drainage patterns will help to ensure the accuracy and the completeness of sentinel nodes identification.

Background: Clear cell acanthoma is a rare solitary benign epidermal tumor of unknown etiology. The disease arises in the middle-age, with no sex predominance. It appears as a single reddish papule or papule-nodule and a peripheral scaling collarette is characteristic. Although solitary lesions are the rule, less than 30 cases of multiple Clear cell acanthoma have been described in the literature to date. Main observations: We report an unusual case of a healthy 74-year-old male with multiple clear cell acanthoma on the lower extremities treated successfully with cryotherapy. Conclusion: Despite significant progress in treatment of clear cell acanthoma, cryotherapy, based on liquid nitrogen, remains an important alternative in treating multiple clear cell acanthomas.

One of the most significant risk factors for melanoma is a positive family history of the disease. It is estimated that approximately 10 percent of melanoma cases report a first-or second-degree relative with melanoma. We reported the experience of the Dermato-Oncologic Unit of Brescia, Italy.

To the Editor: Nodular melanoma (NM) represents approximately 9% to 15% of invasive melanomas. The histopathologic definition of NM is based on the absence of a radial growth phase. Most frequently, it manifests itself in midlife with a median age at presentation of 53 years, and it is more common in males than in females. In 11% to 25% of the cases, NM is histologically associated with nevi. We report the experience of the Melanoma Unit of University Hospital Spedali Civili of Brescia, Italy. Between January 1, 1982 and October 1, 2009, 95 patients with cutaneous NM were identified from a group of 1865 patients with histologically confirmed melanoma; the incidence was 5.1% (95/1865). Of the 95 patients evaluated, 49 (51.6%) were males and 46 (48.4%) were females. All patients were white. The average age was 54.5 years (range, 15-91). Primary melanomas were found in different body sites as follows: eight (8.4%) lesions were on the head and neck, 32 (33.7%) on the trunk, 22 (23.2%) on the upper extremities, and 33 (34.7%) on the lower extremities. The lesions appeared most frequently on the trunk in male patients and on the lower extremities, upper extremities, and trunk in female patients. None of our 95 cases had a documented family history of melanoma. With regard to invasive melanomas, Breslow thickness ranged from 0.5 mm to 11 mm, with a mean thickness of 3.9 mm. The mean Breslow thickness was 4.4 mm in male patients and 3.4 mm in female patients. Ten out of 95 patients (10.5%) showed histologic evidence of an associated nevus; five patients were male and five were female. The average age of these 10 patients was 55.9 years. In seven patients, melanoma arose in association with an acquired nevus (2 dysplastic nevus and 5 other acquired nevi). In the remaining three patients, melanoma arose in association with a small congenital nevus. When examined by anatomic location, one lesion was on the head and neck, five were on the trunk, one was on the upper extremities, and three were on the lower extremities. The mean Breslow thickness for these 10 patients was 2.3 mm. When comparing the two groups (NM vs NM associated with nevi), the second group showed a thinner Breslow thickness (4.04 mm vs 2.3 mm). Our findings support the belief that in most cases, NM arises in absence of a precursor lesion. NM often fails to exhibit the original ABCD diagnostic criteria

(2) Extension of dermatitis by using ‘‘the rule of nines,’’ which considers: head = 9% (front and back), chest = 18%, back = 18%, right arm = 9%, left arm 9%, perineum = 1%, right leg = 18%, left leg = 18%. Since the body areas more often involved by follicular dermatitis reaction are the head, chest, and back, we classify the reaction as severe when the dermatitis involves more than 45% of the body and the type of lesion is papules, pustules, and plaques often covered by scales. It is important for dermatologists and oncologists to recognize this severe reaction and classify it in a uniform way in order to treat it properly. We believe that recognizing severe follicular rash may be useful to control signs and symptoms of skin toxicity in order to prevent therapy interruption, and also that it might be useful to understand treatment efficacy and mostly to improve patient quality of life.

Background.The clinical presentation of desmoplastic melanoma is often challenging. We report the experience of the Melanoma Unit of Spedali Civili University Hospital of Brescia, Italy.Method.Study subjects were drawn from 1770 patients with histologica confirmed melanoma. Within this group, desmoplastic melanoma developed in 5 patients. For each diagnosed melanoma, histological characteristics, treatment, and outcomes were evaluated.Results.Of the 5 patients described in this study, 2 were males and 3 females. The average age was 62.4 years ranging from 56 to 68 years. Breslow thickness ranged from 2.1 to 12 mm with a mean thickness of 5.8 mm. Primary treatment of 5 patients included a wide local excision of their primary lesions.Conclusions.Desmoplastic melanoma is a rare neoplasm which clinically may mimic other tumours or cutaneous infiltrate of uncertain significance. The diagnosis is hiastopathological and radical resection is necessary.

Background Sunlight modifies the size and the dermoscopic pattern of acquired melanocytic nevi (AMN). Objective We investigated whether repeated exposures to equally effective suberythemogenic doses of ultraviolet (UV)A or UVB can induce changes in the dermoscopic features of AMN. Methods Twenty volunteers received equally effective doses of narrowband UVB or UVA1. During exposures, an AMN was covered with an opaque tape, another was shielded with the sunscreen, and another was left unprotected. Results Nevi exposed to either narrowband UVB and UVA1 showed statistically significant changes in their dermoscopic features: increased size, increase of pigment network, overall color darkening, formation of focal branched streaks, and increased number and size of brown dots and globules. Limitations The study is a clinical cohort study on a small number of selected patients. Conclusion AMN show similar changes in size and dermoscopic pattern after narrowband UVB and UVA1 exposures.

Background Development of more than one primary melanoma in a patient is a relatively uncommon but well-recognized phenomenon. Its frequency has ranged from 1.2% to 8.2% in several series. This subgroup of patients with multiple primary lesions has not been characterized sufficiently. We report the experience of the Melanoma Unit of University Hospital Spedali Civili of Brescia, Italy. Method Study subjects were drawn from 1240 patients with histologically confirmed melanoma, including melanoma in situ. From this group, multiple melanomas developed in 47 patients (3.79%). Every one of our patients has been taught to perform self-examination of the skin to detect suspicious pigmented lesions. Results Of the 47 patients described in this study, 38 had two primary melanomas, 7 had three melanomas and 2 had 5 and 10 melanomas, respectively. Mean age at first diagnosis was 46.2 years. The majority of subsequent melanomas (74.5%) were removed within 5 years of the initial operation. Synchronous lesions were found in 10 patients. In male patients, the lesion appeared most frequently on the trunk; in female patients, melanoma appeared mostly on the lower extremities. The second primary melanomas developed in the same anatomic region from the first in 53.2% of our patients. The proportion of in situ to invasive melanomas was greater for the second melanomas compared with the first melanomas. Regarding invasive melanomas, the mean thickness of the first melanomas was 1.31 mm compared with 0.66 mm for the second ones. Dividing patients into two groups, of more and less than 50, it is highlighted that in older patients synchronous lesions appear more frequently (36.4% vs. 8.0%); the median time interval between sequential melanomas is longer (84 vs. 63.7 months); and the ratio between the primary and secondary melanoma mean thickness is lower (1.21 : 1.08 vs. 1.43 : 0.63 mm). Conclusions The study confirms that second primary melanoma is usually thinner than the first lesion, and it is more common in the same region of the body as the initial melanoma. The highest risk for a second melanoma is during the first 5 years, but a much longer time interval of 28 years is possible. Continued medical follow-up with complete skin examinations seems prudent, but it is very important to promote self-skin evaluation in patients to detect not only metastases but also subsequent primary melanomas in their earliest phases.