The authors report the results of a comparative experimental nerve study, using a biologic tissue glue (fibrin) and a synthetic glue (2-cyanoacrylate) in a rat model. A tension-free repair is necessary with the use of fibrin glue, or gapping may occur, thus limiting the use of the agent in promoting re-neurotization. In addition, the human origin of fibrin and thrombin allow for the possibility of viral transmission. The aim of the study was to verify if the synthetic glue is a viable alternative, or whether it causes cellular and tissue lesions. Their main finding was that the cyanoacrylate causes a foreign-body inflammatory reaction and retractile fibrosis, often reducing the nerve diameter up to two-thirds. Cyanoacrylate glue is thus not recommended for peripheral nerve repair.
Cowden syndrome (CS) is an autosomal dominant condition caused by mutations in the phosphatase and tensin homolog ( PTEN ) gene, and is characterized by multiple hamartomas and a predisposition to malignant tumors. Characteristic skin lesions include trichilemmomas, acral keratosis, mucocutaneous neuromas, oral papillomas, and penile macules, and are often the first clues to the underlying diagnosis. Here, we discuss the mucocutaneous manifestations of CS, differential diagnoses of genetic causes of each cutaneous finding, genetic analyses for patients with skin manifestations, management of patients with CS, and potential new targeted therapies for CS.
Decorative tattooing is very popular worldwide and is associated with cutaneous complications, ranging from infections to localized or generalized skin reactions. We report a case of a patient presenting with generalized violaceous pruritic papular lesions 1 month after obtaining a black ink tattoo. Histological examination of a papular lesion distal to the tattoo site showed focal band-like lymphocytic infiltrate. He subsequently developed bullae over the papular lesions, with elevated serum BP180 antibody levels. A diagnosis of generalized lichen planus and lichen planus pemphigoides was made. He responded to treatment with potent topical corticosteroids and ciclosporin. We also reviewed the presentation and treatment of published cases of lichenoid reactions in the literature. With the increasing popularity of tattoos, awareness of this potential complication and possible treatments is important.
The stem cell niche is a complex local signaling microenvironment that sustains stem cell activity during organ maintenance and regeneration. The mammary gland niche must support its associated stem cells while also responding to systemic hormonal regulation that triggers pubertal changes. We find that Gli2, the major Hedgehog pathway transcriptional effector, acts within mouse mammary stromal cells to direct a hormone-responsive niche signaling program by activating expression of factors that regulate epithelial stem cells as well as receptors for the mammatrophic hormones estrogen and growth hormone. Whereas prior studies implicate stem cell defects in human disease, this work shows that niche dysfunction may also cause disease, with possible relevance for human disorders and in particular the breast growth pathogenesis associated with combined pituitary hormone deficiency.
Programmed cell death-1 (PD1) inhibitors, a form of immune checkpoint inhibitor, are efficacious for metastatic melanoma but are associated with cutaneous adverse reactions (CARs). Studies in Europe and North America showed that CARs are associated with an increased overall survival. However, studies from Asia showed mixed results. There is a paucity of data regarding the efficacy of PD1 inhibitors and the effect of CARs on overall survival from Southeast Asia. A retrospective study of patients in the National Cancer Centre Singapore who were diagnosed with melanoma between 2015 and 2020 was conducted. Patients were included in the study if they had stage IV melanoma (advanced melanoma). Sixty-two patients were included in the study. The median age was 62.5 years and acral melanoma was the commonest subtype. Forty-three patients received PD1 inhibitors. Comparing patients who did not receive PD1 inhibitors to patients who received PD1 inhibitors, the former had a median overall survival of 6 months (95% CI: 5.07, 6.93), whereas the latter had a median overall survival of 21 months (95% CI: 13.33, 28.67;
Sir, A 65-year-old female with stage 4 invasive ductal carcinoma of the breast with bone metastasis on palliative chemotherapy was seen for crusted plaques and skin tightening over her chest wall three years after her cancer diagnosis. Examination showed hyperkeratotic crusted plaques with indurated erythematous borders encasing her chest [Figure 1a]. A clinical diagnosis of carcinoma en cuirasse was made, supported on skin biopsy which showed a dermal infiltrate of carcinomatous cells in linear cords invading between collagen bundles [Figure 1b]. Immunohistochemistry was positive for human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER) and GATA binding protein 3 (GATA3), but negative for progesterone receptor (PR), the same pattern as the original breast tumor.Figure 1: (a) Carcinoma en cuirasse involving the chest wall (b) Extensive dermal infiltrate of carcinomatous cells, disposed in linear cords and strands invading in between splayed collagen bundles. Hematoxylin and Eosin stain. Original magnification x40Three months after the diagnosis of carcinoma en cuirasse, she presented with skin tightening and induration affecting her hands, extending to the elbows [Figure 2a]. She described Raynaud's phenomenon, but not dysphagia, arthralgia, or sicca symptoms. Physical examination revealed limited mouth opening and nail fold telangiectasia. Biopsy of indurated skin from her forearm showed thickened and crowded bundles of collagen [Figure 2b and c], while biopsy from normal abdominal skin showed normal distribution of collagen fibers, consistent with the clinical diagnosis of systemic sclerosis. Possible causes included chemotherapy-induced scleroderma or paraneoplastic phenomenon. The former was deemed less likely due to the long latency between chemotherapy administration and scleroderma onset. Hence, chemotherapy was continued. Chemotherapy was started since her cancer diagnosis and consisted of herceptin with other agents including paclitaxel, pertuzumab, letrozole, tamoxifen, vinorelbine, and gemcitabine. Phototherapy and systemic therapy were considered for management of systemic sclerosis, but she preferred treatment with 0.1% betamethasone valerate cream and calcipotriol ointment. She unfortunately succumbed to pneumonia a month later, before her next clinic review of the cutaneous lesions.Figure 2: (a) Scleroderma extending from fingers to the forearms (b) Thickened and crowded bundles of collagen aligned parallel to the skin surface, with a sparse perivascular and periadnexal lymphocytic infiltrate (c) Higher magnification image of the boxed-up region in Figure 2b showing thickened collagen bundles in the dermis. Hematoxylin and Eosin stain. Original magnification x10This is a case of metastatic breast cancer presenting with two histologically distinct sclerodermoid manifestations in close temporal association—carcinoma en cuirasse and systemic sclerosis. Carcinoma en cuirasse, caused by direct skin infiltration of tumour cells, accounts for about 6% of cutaneous metastasis in breast cancer patients.[1] Treatment of carcinoma en cuirasse is mainly palliative. Our patient was continued on palliative chemotherapy, with minimal change to her carcinoma en cuirasse plaques. Scleroderma can also present as a paraneoplastic manifestation of breast cancer. A median of five years between breast cancer diagnosis and subsequent scleroderma development has been reported.[2] In terms of pathophysiology, recent data suggest that antigen mutation in tumor cells could drive auto-antibody production and the subsequent development of systemic sclerosis.[3] Indeed, the temporal association between cancer progression and development of systemic sclerosis in our patient raises the possibility of cancer-driven autoimmunity. Chemotherapy-induced scleroderma has been reported with taxanes, bleomycin, and gemcitabine,[4,5] with a latency of three to 21 months between taxane initiation and scleroderma onset in breast cancer patients,[4] and a latency of ten days between gemcitabine initiation and scleroderma onset in a bladder cancer patient.[5] Our patient received paclitaxel three years before scleroderma onset, and gemcitabine three months before scleroderma onset, hence chemotherapy-induced scleroderma is a possible differential. Interestingly, most reports of taxane-induced scleroderma do not describe systemic manifestations, such as Raynaud's phenomenon and dilated nail fold capillaries,[4] as seen in our patient. In conclusion, scleroderma in patients with breast cancer can be due to different causes, and this case demonstrates the occurrence of two histologically distinct sclerodermoid manifestations occurring metachronously in the same patient. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. Acknowledgement The authors thank Dr. Sim Chee Seng for histology images and descriptions. The patient in this manuscript has given written informed consent to publication of her case details.
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