SARS-CoV-2 Detection by Digital Polymerase Chain Reaction and Immunohistochemistry in Skin Biopsies from 52 Patients with Different COVID-19-Associated Cutaneous Phenotypes.

BACKGROUND: COronaVIrus Disease 19 (COVID-19) is associated with a wide spectrum of skin manifestations, but SARS-CoV-2 RNA in lesional skin has been demonstrated only in few cases. OBJECTIVE: The objective of this study was to demonstrate SARS-CoV-2 presence in skin samples from patients with different COVID-19-related cutaneous phenotypes. METHODS: Demographic and clinical data from 52 patients with COVID-19-associated cutaneous manifestations were collected. Immunohistochemistry and digital PCR (dPCR) were performed in all skin samples. RNA in situ hybridization (ISH) was used to confirm the presence of SARS-CoV-2 RNA. RESULTS: Twenty out of 52 (38%) patients presented SARS-CoV-2 positivity in the skin. Among these, 10/52 (19%) patients tested positive for spike protein on immunohistochemistry, five of whom had also positive testing on dPCR. Of the latter, one tested positive both for ISH and ACE-2 on immunohistochemistry while another one tested positive for nucleocapsid protein. Twelve patients showed positivity only for nucleocapsid protein on immunohistochemistry. CONCLUSIONS: SARS-CoV-2 was detected only in 38% of patients, without any association with a specific cutaneous phenotype, suggesting that the pathophysiology of cutaneous lesions mostly depends on the activation of the immune system. The combination of spike and nucleocapsid immunohistochemistry has higher diagnostic yield than dPCR. Skin persistence of SARS-CoV-2 may depend on timing of skin lesions, viral load, and immune response.

Syphilis: a mini review of the history, epidemiology and focus on microbiota.

Syphilis is a chronic systemic infectious disease caused by the spirochaete bacterium Treponema pallidum(syphilis treponeme). In recent decades there has been a drastic increase in cases of syphilis,with a relative increase in scientific interest in this regard. However, the data concerning the studyof microbiota in syphilis are few and very scattered.This brief review provides a quick update on the disease, with particular attention to the role of themicrobiota, an aspect not always adequately considered in the evaluation of the pathology. The usualcoexistence of different sexually transmitted diseases in the same patients led us to delve also intothe possible role of the microbiota in the pathogenesis of syphilis; indeed, not all sexual contactslead to infections, suggesting that host immunity and local microbiota could modulate the historyof sexually transmitted disease. In both males and females, alteration of the microbiota may be involvedin syphilis as well as in the other sexually transmitted diseases. Finally, since 9% of the totalproteome of T. pallidum is spent for transportome, the latter may provide essential nutrients, makingT. pallidum able to adapt to a diverse range of microenvironments and stresses in the human host.

Case Report of Dermoscopic Aspects and Reflectance Confocal Microscopy Description of Segmental Leiomyoma and Relative Management.

Cutaneous leiomyoma is a benign tumor, mainly composed of smooth muscle cells and arising from the arrector pili muscle of hair follicles. The diagnosis of leiomyomas is of paramount importance, as they can often be associated with underlying malignancies (e.g., renal cell carcinoma, leiomyosarcoma) and specific genetic mutations. We report the case of a 27-year-old Caucasian male patient that presented to our attention with a rare segmental and Zoosteriform type II leiomyoma. We performed an analysis of the cutaneous lesions using dermoscopy, reflectance confocal microscopy (RCM) and histology. We found that, using dermoscopy, the leiomyomas showed a dermatofibroma-like appearance with a central hypopigmented area, peripheral delicate hyperpigmentation and also erythematous areas and ectatic vessels. RCM, although not specific, showed groups of hypo-reflective areas distributed in the most superficial papillary dermis, which in histology and immunohistochemistry corresponded to the most superficial protrusions in the papillary dermis of the tumoral bundles. Finally, we discuss the management of patients with multiple leiomyomas and stress the fact that, in the cases of multiple leiomyomas, an annual sonography of the kidneys associated with dermatological and (in women) gynecological consultations are needed to ensure the early identification of an underlying tumor. A genetic consultation to detect an eventual FH mutation is recommended, but since in some cases the FH result may be negative, the above recommended controls remain always of paramount importance.

Efficacy of Siltuximab and 1,927 nm Fractional Laser for the Treatment of Cutaneous Manifestations in Castleman's Disease: The Role of Dermoscopy and Reflectance Confocal Microscopy for Lesion Evaluation.

Introduction: Multicentric Castleman's disease (MCD) with cutaneous involvement has rarely been discussed in dermatologic literature, with few reports. Cutaneous lesions in MCD may induce deep scars, causing a significant impact in the daily life of the patients. The treatment of Castleman's disease (CD) is usually a challenge, especially in case of cutaneous involvement. Case Presentation: We report the case of a 35-year-old Caucasian man with a 3-year-old history of MCD with cutaneous involvement that we treated with a combined therapy characterized by siltuximab and 1,927 nm fractional laser. The patient showed a therapeutic response, characterized by a reduction of systemic symptoms and cutaneous manifestations. Conclusion: We believe that the combination of siltuximab and 1,927 nm fractional laser might have a synergistic beneficial role in patients with cutaneous iMCD and maximize esthetic outcomes. Anyway, additional evidence is needed to validate our findings.

Widespread and Long-Enduring Hyperkeratosis Lenticularis Perstans (Flegel's Disease): Clinico-Pathological and Dermoscopic Features of a Rare Presentation.

Hyperkeratosis lenticularis perstans, also known as Flegel's disease (FD), is a rare cutaneous disorder affecting mainly the lower extremities of middle-aged people. Due to its rarity, this disease is usually not recognized by physicians resulting in a delay in diagnosis, especially in those cases with atypical cutaneous involvement. Herein, we present a 72-year-old woman who developed FD characterized by a generalized distribution, involving, in addition to the lower limbs, the trunk and the upper limbs as well. We performed a description of the dermoscopic and pathologic features of this rare entity, also carrying out a brief reappraisal of the cases of FD with a diffuse, atypical and generalized distribution that have been described in the literature. Histopathology with clinical correlation is the cornerstone of the diagnosis, even and especially in atypical cases. This patient with a disease duration of 58 years also represents the longest-lasting case of FD reported in the literature.

Combination treatment of dupilumab with bortezomib in a patient with IgG kappa gammopathy of renal significance, uremic pruritus and chronic lichenoid dermatitis.

Chronic pruritus (CP) is one of the most frequent symptoms among dermatological conditions, capable of reducing the quality of life (QoL). CP may be induced by atopic dermatitis or other dermatological and/or non-dermatological conditions. In this article, we report the case of a patient affected by generalized CP, characterised by multiple papulo-nodular and escoriatic lesions, developed after the onset of an immunoglobulin G (IgG) kappa monoclonal gammopathy of renal significance (MGRS), associated with renal insufficiency. Therefore, a combined treatment with dupilumab for CP and bortezomib for the hematologic malignancy was administered to the patient. The present case report highlights the efficacy of dupilumab for the treatment of CP. Moreover, no relevant side effects were recorded during the treatment in combination with other systemic biological drugs for other systemic pathologies.

Ex vivo enrichment of circulating anti-tumor T cells from both cutaneous and ocular melanoma patients: clinical implications for adoptive cell transfer therapy.

Tumor-infiltrating lymphocytes (TILs) have been successfully used for adoptive cell transfer (ACT) immunotherapy; however, due to their scarce availability, this therapy is possible for a limited fraction of cutaneous melanoma patients. We assessed whether an effective protocol for ex vivo T-cell expansion from peripheral blood mononuclear cells (PBMCs), suitable for ACT of both cutaneous and ocular melanoma patients, could be identified. PBMCs from both cutaneous and ocular melanoma patients were stimulated in vitro with autologous, irradiated melanoma cells (mixed lymphocyte tumor cell culture; MLTCs) in the presence of IL-2 and IL-15 followed by the rapid expansion protocol (REP). The functional activity of these T lymphocytes was characterized and compared with that of TILs. In addition, the immune infiltration in vivo of ocular melanoma lesions was analyzed. An efficient in vitro MLTC expansion of melanoma reactive T cells was achieved from all PBMC's samples obtained in 7 cutaneous and ocular metastatic melanoma patients. Large numbers of melanoma-specific T cells could be obtained when the REP protocol was applied to these MLTCs. Most MLTCs were enriched in non-terminally differentiated T(EM) cells homogeneously expressing co-stimulatory molecules (e.g., NKG2D, CD28, CD134, CD137). A similar pattern of anti-tumor activity, in association with a more variable expression of co-stimulatory molecules, was detected on short-term in vitro cultured TILs isolated from the same patients. In these ocular melanoma patients, we observed an immune infiltrate with suppressive characteristics and a low rate of ex vivo growing TILs (28.5% of our cases). Our MLTC protocol overcomes this limitation, allowing the isolation of T lymphocytes with effector functions even in these patients. Thus, anti-tumor circulating PBMC-derived T cells could be efficiently isolated from melanoma patients by our novel ex vivo enrichment protocol. This protocol appears suitable for ACT studies of cutaneous and ocular melanoma patients.

Leydig cell tumor of the spermatic cord in an adolescent affected by congenital adrenal hyperplasia.

We report the first case of a patient with extratesticular Leydig cell tumor associated with congenital adrenal hyperplasia. An 18-year-old congenital adrenal hyperplasia patient presented with a palpable and asymptomatic right extratesticular mass. Color Doppler sonography confirmed the presence of a capsulated and vascularised lesion. Sieric tumor markers were negative. The patient underwent surgical scrotal exploration through an inguinal right incision. The mass, 18 mm in size and located within the spermatic cord, was removed and final pathology diagnosed a benign Leydig cell tumor.

An Ecchymosis with Fulminant Evolution.

We present the case of an 83-year-old woman who presented with an advanced cutaneous angiosarcoma of the head. The tumor had first appeared as a small ecchymosis on her forehead 3 months before admission. There was an extremely rapid and dramatic evolution, as evidenced by photographic documentation by her relatives. Unfortunately, the delay in access to the healthcare system due to the COVID-19 pandemic lockdown and the fulminant growth were the main determinants for our patient outcome.

Mucosal Melanoma of the Hard Palate: Surgical Treatment and Reconstruction.

Mucosal melanomas of the head and neck region are uncommon pathologies that can affect the oral cavity, and are characterized by a high rate of mortality. Considering the lack of knowledge regarding risk and prognostic factors, current best clinical practice is represented by a large surgical excision with disease-free margins, eventually associated with a reconstructive flap. Indeed, given the frequent necessity of postoperative radiotherapy and fast healing process, a reconstruction of the surgical gap is advisable. Even if several flaps have been most commonly used, the submental island flap represents a valid alternative thanks to local advantages and similar oncologic outcomes compared to free flaps.

Immunohistochemical Evaluation and Clinicopathological Correlation of Mer and Axl Tyrosine Kinase TAM Receptors in Cutaneous Melanoma.

BACKGROUND: Malignant melanoma (MM) is potentially the most dangerous form of skin tumor. In the last few years, the so-called TAM receptors, a unique family of tyrosine kinase (TK) receptors, have become increasingly important. OBJECTIVES: To evaluate Mer and Axl TAM receptor expression to find clinicopathological features that could explain the biological behavior of MM. PATIENTS AND METHODS: Clinicopathological data were obtained from an MM electronic database at our Institute. We reviewed 24 cutaneous MM specimens. TAM receptor expression was assayed using immunohistochemistry. Combinative semiquantitative scoring was used for the evaluation of TAM receptor expression (MerTK and AxlTK). Appropriate statistical methods were used to evaluate a possible correlation between TAM receptor expression and the clinicopathological variables of the MM samples (univariate analysis and multivariate analysis). RESULTS: MerTK and AxlTK were expressed differently in the MM samples, with a major expression of the first receptor. The cells of the tumor microenvironment contributed to the majority of the total score. A significant association was found between AxlScore and the site of the tumor and between AxlScore and the variable ulceration; another correlation was found between MerScore and the following characteristics: pathological stage of the tumor (pT), sex, ulceration, and tumor-infiltrating lymphocytes. CONCLUSIONS: All correlations between the expression of MerTK and AxlTK with the clinical and histological variables of MM should be validated in a large group of people in order to increase the validity and the impact of our observations, with subsequently therapeutic implications in the era of the "targeted therapy."

Clinicopathological and dermoscopic features of amelanotic and hypomelanotic melanoma: a retrospective multicentric study.

BACKGROUND: Amelanotic and hypomelanotic melanoma (AHM) has a higher risk of delayed diagnosis and a significant lower 5-year melanoma-specific survival compared to pigmented melanoma. Our aim was the evaluation of the clinicopathological/dermoscopic features of amelanotic melanoma (AM) and hypomelanotic melanoma (HM). METHODS: All participants had a personal history of AHM. We defined HM as showing clinical/dermoscopic pigmentation in < 25% of the lesion's surface and histopathological focal pigmentation, while AM as melanomas with clinical/dermoscopic and histopathological absence of pigmentation. RESULTS: The most common phenotypic traits among the 145 AHM patients were as follows: phototype II, blue-grey eyes, and dark brown hair. Red hair was present in 23.8% AHM cases (AM = 22.60%; HM = 25.80%). The most affected area was the back (29.5%). A total of 67.1% were classified as AM and 32.9% as HM. The most represented hair colors in AM and HM were, respectively, blonde and dark brown hair. Median Breslow thickness was 1.7 mm, superficial spreading melanoma (SSM) and nodular melanoma (NM) were the most represented histotypes, and mitotic rate > 1 × mm2 was reported in 73.3% cases, and regression was significantly more present in HM. Dermoscopy showed high prevalence of white structureless zones (63.4%), linear looped vessels (58.8%), linear irregular vessels (50.0%), and arborizing vessels (47.2%). Multivariate logistic regression confirmed the association between the presence of pigmentation and the following: histological regression, dermoscopic globules, and arborizing vessels. CONCLUSIONS: Predominance of red hair in AHM patients was not confirmed. AHM affects mostly intermittent sun-exposed body areas. The deeper median Breslow thickness (versus pigmented melanoma), the association of AM with the nodular histotype, and the high mitotic rate highlight the AHM's aggressiveness. HM's higher levels of regression can be explained by the presence of pigmentation, driving the underlying immune response. AHM showed a polymorphous vascular pattern and significant presence of arborizing vessels (especially HM).