Mixed germ cell sex cord-stromal tumors of the testis and ovary. Morphological, immunohistochemical, and molecular genetic study of seven cases

We present the morphological, immunohistochemical, and molecular genetic features of three cases of testicular and four cases of ovarian mixed germ cell sex cord-stromal tumors (MGSCT). The germ cells in the testicular MGSCTs morphologically differed from those in classical seminomas by lacking the typical square off quality of the nuclei. In contrast to the nuclei in classical seminomas, their size in testicular MGSCTs was smaller and nucleoli were inconspicuous and the cytoplasm was Periodic Acid-Schiff(PAS) negative. Quite on the contrary, the variability in the size of the nuclei of the germ cells in the testicular MGSCTs was more similar to that seen in the germ cells of spermatocytic seminomas. Immunohisto-chemically, the germ cells of MGSCTs in one case reacted positively with antibody to AE1-AE3 by paranuclear dotlike or rodlike positivity. All three testicular MGSCTs had a negative reaction with the rest of antibodies, including placental alkaline phosphatase (PLAP), OCT4, and c-kit protein. Ovarian MGSCT in our series differed from the testicular lesions in both the germ cell component and the sex cord component. The germ cells in all four ovarian cases had cytomorphological and immuno-histochemical features identical to those in classical seminomas/dysgerminomas. They possessed the typical square off quality of the nuclei, which were much more blastic, with more mitoses compared with the testicular tumors in our series, and they were PLAP (4/4), OCT4 (4/4) and c-kit protein (3/4) positive immunohisto-chemically. The cytoplasm of the germ cells in ovarian neoplasms contained PAS positive glycogen. Germ cells in one ovarian MGSCTs showed amplification of l2p. All other germ cells were negative for amplification of 12p. All five successfully analyzed cases showed no mutation in all studied exons and exon-intron junctions in c-kit and PDFGRA genes

Poor fluorinated graphene sheets carboxymethylcellulose polymer composite mode locker for erbium doped fiber laser

We report poor fluorinated graphene sheets produced by thermal exfoliation embedding in carboxymethylcellulose polymer composite (GCMC) as an efficient mode locker for erbium doped fiber laser. Two GCMC mode lockers with different concentration have been fabricated. The GCMC based mode locked fiber laser shows stable soliton output pulse shaping with repetition rate of 28.5MHz and output power of 5.5 mW was achieved with the high concentration GCMC, while a slightly higher output power of 6.9 mW was obtained using the low concentration GCMC mode locker

Nodular Mucinosis of the Breast in a Male : Reassessment of Diagnostic Criteria and Proposal for Its Classification as a Soft Tissue Tumor in the Myofibroblastoma and Spindle Cell Lipoma Spectrum

Nodular mucinosis of the breast (NMB) is a rare entity with only a few cases described in the literature, most of them in young girls. All cases are located in the nipple and areolar area and microscopically consist of a multinodular myxoid mesenchymal proliferation. Bands of sclerotic collagen containing preexisting breast ducts and abundant vascularization are other features typical of NMB. No relation to Carney complex has been reported, and an indolent behavior is the rule in all patients. We present a case of NMB occurring in the nipple of a 46-year-old man and analyze the clinicopathological features of the other cases of NMB reported in the English literature, concluding that two of them most likely correspond to trauma-induced cutaneous focal mucinosis of the mammary areola. Finally, we review diagnostic criteria for NMB and elaborate an ontogenetic hypothesis based on both its morphological resemblance to myofibroblastoma and its immunohistochemical profile

Pityriasis lichenoides et varioliformis acuta with numerous CD30(+) cells: a variant mimicking lymphomatoid papulosis and other cutaneous lymphomas. A clinicopathologic, immunohistochemical, and molecular biological study of 13 cases

Pityriasis lichenoides comprises a clinicopathologic spectrum of cutaneous inflammatory disorders, with the 2 most common variants being pityriasis lichenoides et varioliformis acuta (PLEVA) and pityriasis lichenoides chronica. The aim of the study was to describe 13 cases of a unique PLEVA variant characterized in the conspicuous CD30 component and thus mimicking lymphomatoid papulosis (LyP), a condition currently classified in the spectrum of CD30 lymphoproliferative disorders. The cohort included 10 female and 3 male patients whose ages at diagnosis ranged from 7 to 89 years (mean 41 y; median 39 y). The clinical manifestation was that of PLEVA, with small erythematous macules quickly evolving into necrotic papules. No waxing and waning was seen on follow-up in any of the cases. Histopathologically, typical features of PLEVA were present, but an unusual finding was occurrence of a considerable number of CD30 small lymphocytes as detected immunohistochemically. Over half of the cases also displayed a large number of CD8 cells and showed coexpression of CD8 and CD30 in the intraepidermal and dermal component of the infiltrate. Of the 11 cases of PLEVA studied for T-cell receptor gene rearrangement, 6 evidenced a monoclonal T-cell population, and 5 were polyclonal. Parvovirus B19 (PVB19) DNA was identified in 4 of 10 cases investigated, and positive serology was observed for PVB19 in 2 patients, altogether suggesting that PVB19 is pathogenetically linked to PLEVA at least in a subset of cases. The presence of CD30 lymphocytes and CD8 lymphocytes would be consistent with an inflammatory antiviral response, as CD30, even atypically appearing lymphoid cells have been identified in some viral skin diseases. The main significance of the PLEVA variant is, however, its potential confusion with LyP or some cytotoxic lymphomas. Admittedly, the CD30 PLEVA variant described herein and LyP show considerable overlap if one takes into account all known variations of the 2 conditions recognized in recent years, thus suggesting that LyP and PLEVA may be much more biologically closely related entities than currently thought or can even occur on a clinicopathologic spectrum

RegTransBase—a database of regulatory sequences and interactions in a wide range of prokaryotic genomes

RegTransBase is a manually curated database of regulatory interactions in prokaryotes that captures the knowledge in public scientific literature using a controlled vocabulary. Although several databases describing interactions between regulatory proteins and their binding sites are already being maintained, they either focus mostly on the model organisms Escherichia coli and Bacillus subtilis or are entirely computationally derived. RegTransBase describes a large number of regulatory interactions reported in many organisms and contains the following types of experimental data: the activation or repression of transcription by an identified direct regulator, determining the transcriptional regulatory function of a protein (or RNA) directly binding to DNA (RNA), mapping or prediction of a binding site for a regulatory protein and characterization of regulatory mutations. Currently, RegTransBase content is derived from about 3000 relevant articles describing over 7000 experiments in relation to 128 microbes. It contains data on the regulation of about 7500 genes and evidence for 6500 interactions with 650 regulators. RegTransBase also contains manually created position weight matrices (PWM) that can be used to identify candidate regulatory sites in over 60 species. RegTransBase is available at

Primary cutaneous anaplastic large cell lymphoma with angioinvasive features and cytotoxic phenotype: a rare lymphoma variant within the spectrum of CD30+ lymphoproliferative disorders

BACKGROUND: Primary cutaneous anaplastic large cell lymphoma (PCALCL) presents with solitary or grouped exophytic tumors and cohesive infiltrates of large CD30+ T cells. OBJECTIVE: To report an angioinvasive variant of PCALCL. METHODS: Retrospective analysis of clinicopathological features of this variant. RESULTS: The group consisted of six patients (median age 46 years) with a solitary flat necrotic lesion preferentially located on the upper extremity. Histologically, there were angiocentric and angiodestructive infiltrates of medium-sized to large pleomorphic and anaplastic cells co-expressing CD30 and CD8. Five patients were treated with surgical excision and one patient with radiotherapy. A relapse was observed in one patient with spontaneous regression of the lesions suggesting a link to the recently described angioinvasive lymphomatoid papulosis (type E). All patients were alive without evidence of disease after a median follow-up of 31 months (range 15-96), indicating an excellent prognosis. CONCLUSIONS: The angioinvasive variant of PCALCL is rare but distinctive and prone to misinterpretation as aggressive lymphoma due to its histological features

Metastatic acral lentiginous melanoma in a tertiary referral center in Switzerland: a systematic analysis

Acral lentiginous melanoma (ALM) is a unique histopathological subtype of melanoma with a poorer prognosis than other cutaneous melanomas. This study aims to evaluate the clinicopathological characteristics, metastatic pattern, prognostic factors, response to systemic therapy, and overall survival (OS) of ALM in a White population. This is a retrospective study of patients who were diagnosed and/or treated for ALM at the Department of Dermatology of the University Hospital Zurich, Switzerland, from January 2005 to December 2015. Overall, 172 patients with histologically confirmed ALM were included in the study. In univariate Cox regression, Breslow thickness (P<0.001), age (P=0.003), status of sentinel lymph node (P=0.005), and ulceration (P=0.008) were identified as significant prognostic factors for OS in ALM. In multivariate analysis, only Breslow thickness (P=0.0003) showed statistical significance. The median OS (mOS) was 155.7 months in the entire cohort (n=172) and 11.2 months for stage IV patients (n=36), irrespective of treatment. When first treatment was considered (n=35), mOS for stage IV patients was 8.9, 16.6, 21.7, and 3.7 months, for patients who had received chemotherapy (ChT) (n=17), immunotherapy (n=9), targeted therapy (TT) (n=3), and no therapy (n=6), respectively. The overall response rate was 44% (7/16 patients) to ChT, 100% to TT (3/3), and 25% to ipilimumab (2/8). In our study, Breslow thickness represents the best prognostic factor for OS. In stage IV ALM patients treated with either immunotherapy or TT, there is a trend for extended mOS compared with ChT

Report of three novel germline CYLD mutations in unrelated patients with Brooke-Spiegler syndrome, including classic phenotype, multiple familial trichoepitheliomas and malignant transformation

Brooke-Spiegler syndrome is a rare autosomal-dominant genetic disorder characterized by multiple adnexal tumors, including cylindromas, spiradenomas, spiradenocylindromas and trichoepitheliomas. It is caused by germline CYLD mutations commonly leading to a premature stop codon. We here report on 3 novel CYLD mutations in 3 unrelated BSS patients, including the classic phenotype, multiple familial trichoepitheliomas phenotype and malignant transformation. These included c.1821_1826+1delinsCT/L607Ffs*9, c.2666A>T/p.D889V and c.2712delT/p.905Kfs*8. By extending the spectrum of CYLD mutations, better understanding of the molecular mechanisms of BSS can be gained, which might later assist in finding new treatment options