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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.

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

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

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.