Case Report on Leiomyosarcoma of the Vulva: A Rare Pathology

Leiomyosarcoma (LMS) of the vulva is rare. However it is the most common histologic subtype of vulvar sarcoma, accounting for approximately 1% of all vulvar malignancies. [1-8] Whether genetics and epigenetics play a role in pathogenesis is unclear. [1] The tumor is slow-growing with non-specific symptoms, has high metastatic potential, and follows a bimodal age distribution. [1-8] Diagnosis and prognosis are based upon immunohistochemical expression and criteria from early literature. [1,3,5-7] The most common therapeutic approach involves radical vulvectomy with lymph node resection. The value of adjuvant chemotherapy and radiation remains unknown. [1,3,5-8] Our case describes a 46-year-old Caucasian G2P2 female with LMS of the left labia

Lichen planus following tetanus–diphtheria–acellular pertussis vaccination: A case report and review of the literature

Lichen planus is an inflammatory dermatosis with a prevalence of approximately 1%. Recent meta-analyses show that patients with hepatitis C virus have a 2.5- to 4.5-fold increased risk of developing lichen planus. Lichen planus has also followed vaccinations and has specifically been attributed to the hepatitis B vaccine, the influenza vaccine, and the tetanus–diphtheria–acellular pertussis vaccine. We describe a case of lichen planus in a hepatitis C virus–infected African American male occurring in temporal association with the administration of the tetanus–diphtheria–acellular pertussis vaccine. The patient’s presentation was clinically consistent with lichen planus and confirmed by biopsy. It is likely that many cases of vaccine-induced lichen planus have gone unpublished or unrecognized. In areas with high prevalence of hepatitis C virus infection, we may expect to see more cases of vaccine-induced lichen planus especially in light of the updated Centers for Disease Control and Prevention tetanus–diphtheria–acellular pertussis vaccination recommendations. This case serves to educate healthcare providers about vaccine-induced lichen planus and, in particular, the need to counsel hepatitis C virus–infected patients about a potential risk of developing lichen planus following vaccination. We also reflect on current theories suggesting the T-cell–mediated pathogenesis of lichen planus and the role that hepatitis C virus and toxoid or protein vaccines may play in initiating the disease

Case Report on Leiomyosarcoma of the Vulva: A Rare Pathology

Leiomyosarcoma (LMS) of the vulva is rare. However it is the most common histologic subtype of vulvar sarcoma, accounting for approximately 1% of all vulvar malignancies. [1-8] Whether genetics and epigenetics play a role in pathogenesis is unclear. [1] The tumor is slow-growing with non-specific symptoms, has high metastatic potential, and follows a bimodal age distribution. [1-8] Diagnosis and prognosis are based upon immunohistochemical expression and criteria from early literature. [1,3,5-7] The most common therapeutic approach involves radical vulvectomy with lymph node resection. The value of adjuvant chemotherapy and radiation remains unknown. [1,3,5-8] Our case describes a 46-year-old Caucasian G2P2 female with LMS of the left labia

Current concepts in the diagnosis and pathobiology of intraepithelial neoplasia: A review by organ system

Answer questions and earn CME/CNE In this report, a team of surgical pathologists has provided a review of intraepithelial neoplasia in a host of (but not all) anatomic sites of interest to colleagues in various medical specialties, namely, uterine cervix, ovary, breast, lung, head and neck, skin, prostate, bladder, pancreas, and esophagus. There is more experience with more readily accessible sites (such as the uterine cervix and skin) than with other anatomic sites, and the lack of uniform terminology, together with divergent biology in various sites, makes it difficult to paint a unifying, relevant portrait. The authors' aim was to provide a framework from which to move forward as we care for patients with such precancerous lesions. CA Cancer J Clin 2016;66:408-436. © 2016 American Cancer Society

Multidimensional, quantitative assessment of PD-1/PD-L1 expression in patients with Merkel cell carcinoma and association with response to pembrolizumab

Abstract Background We recently reported a 56% objective response rate in patients with advanced Merkel cell carcinoma (MCC) receiving pembrolizumab. However, a biomarker predicting clinical response was not identified. Methods Pretreatment FFPE tumor specimens (n = 26) were stained for CD8, PD-L1, and PD-1 by immunohistochemistry/immunofluorescence (IHC/IF), and the density and distribution of positive cells was quantified to determine the associations with anti-PD-1 response. Multiplex IF was used to test a separate cohort of MCC archival specimens (n = 16), to identify cell types expressing PD-1. Results Tumors from patients who responded to anti-PD-1 showed higher densities of PD-1+ and PD-L1+ cells when compared to non-responders (median cells/mm2, 70.7 vs. 6.7, p = 0.03; and 855.4 vs. 245.0, p = 0.02, respectively). There was no significant association of CD8+ cell density with clinical response. Quantification of PD-1+ cells located within 20 μm of a PD-L1+ cell showed that PD-1/PD-L1 proximity was associated with clinical response (p = 0.03), but CD8/PD-L1 proximity was not. CD4+ and CD8+ cells in the TME expressed similar amounts of PD-1. Conclusions While the binomial presence or absence of PD-L1 expression in the TME was not sufficient to predict response to anti-PD-1 in patients with MCC, we show that quantitative assessments of PD-1+ and PD-L1+ cell densities as well as the geographic interactions between these two cell populations correlate with clinical response. Cell types expressing PD-1 in the TME include CD8+ T-cells, CD4+ T-cells, Tregs, and CD20+ B-cells, supporting the notion that multiple cell types may potentiate tumor regression following PD-1 blockade

Migratory and anti-fibrotic programmes define the regenerative potential of human cardiac progenitors

Heart regeneration is an unmet clinical need, hampered by limited renewal of adult cardiomyocytes and fibrotic scarring. Pluripotent stem cell-based strategies are emerging, but unravelling cellular dynamics of host-graft crosstalk remains elusive. Here, by combining lineage tracing and single-cell transcriptomics in injured non-human primate heart biomimics, we uncover the coordinated action modes of human progenitor-mediated muscle repair. Chemoattraction via CXCL12/CXCR4 directs cellular migration to injury sites. Activated fibroblast repulsion targets fibrosis by SLIT2/ROBO1 guidance in organizing cytoskeletal dynamics. Ultimately, differentiation and electromechanical integration lead to functional restoration of damaged heart muscle. In vivo transplantation into acutely and chronically injured porcine hearts illustrated CXCR4-dependent homing, de novo formation of heart muscle, scar-volume reduction and prevention of heart failure progression. Concurrent endothelial differentiation contributed to graft neovascularization. Our study demonstrates that inherent developmental programmes within cardiac progenitors are sequentially activated in disease, enabling the cells to sense and counteract acute and chronic injury. In this study, the authors report that pluripotent stem cell-derived ventricular progenitors target loss of myocardium and fibrotic scarring to promote heart regeneration, thus offering new potential therapeutic strategies for heart injury.Funding Agencies|European Research Council (ERC) under the European Union [743225, 788381, 101021043]; German Research Foundation, Transregio Research Unit 152; German Research Foundation, Transregio Research Unit 267; Swedish Research Council Distinguish Professor Grant; German Centre for Cardiovascular Research (DZHK)</p