Collapse of the Plasmacytoid Dendritic Cell Compartment in Advanced Cutaneous Melanomas by Components of the Tumor Cell Secretome.

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.

Lupus miliaris disseminatus faciei in a young male.

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.

Early cutaneous metastasis of adenoid cystic carcinoma of the salivary gland.

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.

Pigmentation of axillary sentinel nodes from extensive skin tattoo mimics metastatic melanoma: case report.

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.

Dermatofibrosarcoma protuberans in an adolescent: a case report and review of the literature.

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.

Cutaneous melanoma in patients in treatment with biological therapy: review of the literature and case report.

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.

Nested graft in chronic wounds: a new solution for an old problem.

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.

Important risk factors in melanoma from the Dermato-Oncologic Unit of Brescia, Italy.

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.

Multiple eruptive clear cell acanthoma.

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. CONCLUSIONS: Despite significant progress in treatment of clear cell acanthoma, cryotherapy, based on liquid nitrogen, remains an important alternative in treating multiple clear cell acanthomas.

Cutaneous epithelioid malignant schwannoma: review of the literature and case report.

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.

Repeated equally effective suberythemogenic exposures to ultraviolet (UV)A1 or narrowband UVB induce similar changes of the dermoscopic pattern of acquired melanocytic nevi that can be prevented by high-protection UVA-UVB sunscreens.

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.