Metastasizing aneurysmal dermatofibroma initially diagnosed as angiosarcoma confirmed by CD63::PRKCD fusion gene detection with nanopore sequencing.

Dermatofibroma (DF) is a benign tumor that forms pedunculated lesions ranging in size from a few millimeters to 2 cm, usually affecting the extremities and trunks of young adults. Histopathologically, DF is characterized by the storiform proliferation of monomorphic fibroblast-like spindle cells. In addition to neoplastic cells, secondary elements such as foamy histiocytes, Touton-type giant cells, lymphoplasmacytes, and epidermal hyperplasia are characteristic histological features. Several histological variants, including atypical, cellular, aneurysmal, and lipidized variants, have been reported; cases with variant histologies are sometimes misdiagnosed as sarcomas. We present a case of metastasizing aneurysmal DF that was initially diagnosed as an angiosarcoma on biopsy. A 26-year-old woman was referred to our hospital with a gradually enlarging subcutaneous mass in her lower left leg. Positron emission tomography-computed tomography revealed high fluorodeoxyglucose uptake not only in the tumor but also in the left inguinal region. On biopsy, ERG and CD31-positive atypical spindle cells proliferated in slit-like spaces with extravasation, leading to the diagnosis of angiosarcoma. Histology of the wide-resection specimen was consistent with DF, and lymph node metastasis was also observed. Nanopore DNA sequencing detected CD63::PRKCD fusion and copy number gain, although CD63 was not included in the target region of adaptive sampling. This report highlights the importance of recognizing the unusual clinical, radiological, and pathological features of DF to avoid misdiagnosis, and the potential diagnostic utility of nanopore sequencer.

1.5†µm wavelength NPN-type photonic-crystal surface-emitting laser exceeding 100 mW.

A 1.5 µm laser diode has applications in eye-safe light detection and ranging (LiDAR) and optical communications via photonic integrated circuits. Photonic-crystal surface-emitting lasers (PCSELs) have lens-free applications in compact optical systems because of narrow beam divergences (<1 degree). However, the output power has still been less than 1 mW for 1.5 µm PCSELs. For higher output power, one approach is suppression of p-dopant Zn diffusion in the photonic crystal layer. Therefore, n-type doping was used for the upper crystal layer. Moreover, an NPN-type PCSEL structure was proposed to reduce intervalence band absorption in the p-InP layer. Here, we demonstrate a 1.5 µm PCSEL with 100 mW output power, which exceeds previous reported values by two orders of magnitude.

Multi-focusing surface-emitting lasers.

Complete control of a beam pattern requires not only projecting a two-dimensional (2D) pattern but also focusing on a three-dimensional (3D) point cloud, which is typically achieved utilizing holography under the framework of diffraction. We previously reported direct focusing from on-chip size surface-emitting lasers that utilize a holographically modulated photonic crystal cavity based on 3D holography. However, this demonstration was of the simplest 3D hologram with a single point and single focal length, and the more typical 3D hologram with multiple points and multiple focal lengths has not yet been examined. Toward direct generation of a 3D hologram from the on-chip size surface-emitting laser, we here examined a simple 3D hologram featuring two different focal lengths with a single off-axis point in each to reveal the fundamental physics. Two types of holography, one based on superimposition and the other on random tiling, successfully demonstrated the desired focusing profiles. However, both types caused a spot noise beam in the far field plane due to interference between focusing beams with different focal lengths, especially in the case of the superimposing method. We also found that the 3D hologram based on the superimposing method consisted of higher order beams including the original hologram due to the manner of the holography. Secondly, we demonstrated a typical 3D hologram with multiple points and focal lengths and successfully showed the desired focusing profiles by both methods. We believe our findings will bring innovation to mobile optical systems and pave the way to developing compact optical systems in areas such as material processing, micro fluidics, optical tweezers, and endoscopy.

On-chip size, low-noise fringe pattern projector offering highly accurate 3D measurement.

Fringe pattern projectors are quite useful for highly accurate three-dimensional (3D) measurement when a projector or LED array is used for illumination. We have fabricated a 0.2 mm × 0.2 mm structured light source, which was an on-chip size surface-emitting laser that utilized a holographically modulated two-dimensional (2D) photonic crystal (PC). This will make possible an extremely compact 3D measurement system that will positively impact mobile systems. However, the fringe pattern tends to cause speckle-like noise that leads to severe positional error in 3D measurement. Here we present a simple approach to projecting a low-noise fringe pattern from our surface-emitting lasers by using a one-dimensional (1D) focusing hologram. This method improves the flatness of the fringe pattern by around four times.

Molecular and Morphological Assessment of Juvenile and Adult Forms in the Giant Worm Eunice Cf. Aphroditois (Annelida: Eunicidae) and Its Phylogenetic Position in the Family.

Eunice aphroditois (Pallas, 1788) is a large polychaete worm (up to 3 m in length) and the type species of the genus. In Japan, a similar but potentially different species, Eunice cf. aphroditois, is distributed mainly in the rocky shores of the temperate and warm Pacific coasts. Juveniles and adults were suggested to be distinguished by their body color. The juvenile form was previously regarded as distinct species, Eunice flavopicta Izuka, 1912 and Eunice ovalifera Fauvel, 1936, although they are now considered synonymous with E. aphroditois. In this study, we revisited the validity of the present taxonomy based on morphological observations including SEM and microCT, and three molecular markers (cytochrome c oxidase subunit I [COI], 16S rRNA, and histone H3 genes) and investigated the phylogenetic position of E. cf. aphroditois in the family Eunicidae using the combined dataset of three genes (COI + 16S rRNA + 18S rRNA). The adult and juvenile forms were different in body size, color, the distribution of the branchiae and subacicular hooks, and maxillae shape, but not in other characteristics. One individual showed an intermediate body color between the two forms. The adult and juvenile forms shared major haplotypes and the maximum K2P genetic distance of COI was 1.7%, which can be considered within intraspecific variation. In the phylogenetic tree based on the combined gene dataset, E. cf. aphroditois was closely related to Eunice roussaei Quatrefages, 1866 and Eunice cf. violaceomaculata Ehlers, 1887, which are large species from the Mediterranean Sea and the Caribbean Sea, respectively.

Antiphospholipid antibody positivity and the thrombotic risk in Japanese patients with anti-neutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVES: It has been reported that 21.0-51.7% of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) patients were antiphospholipid antibody (aPL)-positive. However, the clinical significance of aPL positivity in AAV is not fully understood. METHODS: We retrospectively assessed patients with AAV diagnosed from 2013 to 2020 at our hospital. Positivity of aPL was defined as positivity of anti-cardiolipin antibody, anti-cardiolipin ß2 glycoprotein 1 complex antibody, and/or lupus anticoagulant at least one time during the follow-up periods. The thrombotic risk of aPL positivity was examined by multivariate analyses with the Cox regression model. RESULTS: A total of 93 patients with a median age of 71.9 years were included in the study. The median follow-up period was 35.4 months. Thirty-one patients (33.3%) were aPL-positive. Twenty-two thrombotic events occurred in 17 patients (18.3%). Thrombotic events occurred more frequently in aPL-positive patients than in aPL-negative patients (P = 0.011). Multivariate analyses with two different models identified aPL positivity as a thrombotic risk factor (hazard ratios 4.302 and 5.956, 95% confidence intervals 1.546-11.968 and 1.940-18.281, respectively). CONCLUSIONS: The proportion of aPL-positive patients was 33.3%, and aPL positivity increased the thrombotic risk in Japanese patients with AAV.

Direct-focusing surface-emitting laser.

Focusing is a fundamental optical technique that has been widely implemented via lenses. Here, we demonstrate direct focusing from a band-edge surface-emitting laser, whose emission area is 200 µm × 200 µm, without any lenses. To achieve this, a phase-modulating layer is incorporated into the laser cavity. This layer acts simultaneously as a lasing cavity similar to that of a photonic crystal laser and as a holographic spatial-phase modulator, which transforms the output beam into a focusing beam by slightly shifting the positions of holes from a periodic square lattice. Beam profiles along the surface normal clearly show that direct focusing occurs with a focal length and focal spot size of 310 µm and 6.1 µm, respectively. The focal length agrees well with the theoretical value, and the focal spot size is 2.0 times the diffraction-limited size, which indicates that the higher transverse modes are sufficiently suppressed. In addition, the power density at the focus is 540 times higher than that at the near-field plane. Interestingly, a focus pattern is also observed in the opposite direction at the near-field plane, which indicates that a converging beam and a diverging beam are simultaneously emitted because of the nature of the in-plane band-edge laser. The conventional beam patterns of semiconductor laser cavities are limited to the regime of two-dimensional projection based on a Fourier hologram. In contrast, we demonstrate the simplest form of a three-dimensional point cloud based on a Fresnel hologram, which is quite useful for micro-sensing applications such as microfluidics, flow cytometry, blood sensors, and endoscopy.

A case of cervical clear cell carcinoma with serous component.

Cervical clear cell carcinoma (CCCC) is rare. This report describes the case of CCCC with a serous component. A 22-year-old woman presented with vaginal bleeding. A cervical tumor was discovered: pelvic magnetic resonance imaging revealed a tumor measuring 46 mm. Radical hysterectomy was performed based on the diagnosis of stage IB2 cervical cancer. After histological examination of the specimen revealed a coexisting invasive clear cell carcinoma (95%) and serous carcinoma (5%), five cycles of nedaplatin and irinotecan therapy were administered as postoperative adjuvant chemotherapy. Local recurrence in the vaginal vault was observed at 7 months after surgery. Radiation therapy and chemotherapy were administered. The patient is alive without evidence of recurrence at 26 months after surgery.

200×200 µm2 structured light source.

3D structured illumination is important in high-speed 3D metrology where beam patterns are roughly categorized into multi-dot and fringe patterns. For example, large-scale multi-dot patterns are utilized for facial recognition in an iPhone X on the basis of an active stereo method, while fringe patterns are utilized in Grey code patterns or fringe projection profilometry including Fourier transform profilometry and the phase shifting profilometry, which is suitable for high-resolution measurement. Among these applications, the light sources include a combination of vertical-cavity surface-emitting lasers (VCSELs) and diffractive optical elements (DOEs), a projector, and so on. Recently, we demonstrated static arbitrary two-dimensional beam patterns without a zero-order beam from needle-tip sized integrable spatial-phase-modulating surface-emitting lasers (iPMSELs). Due to their compactness (they are one order of magnitude smaller than DOE), surface-emitting device, lack of zero-order beam, and ease of switching the beam patterns electrically, iPMSELs will be suitable as an ultra-compact light source for 3D metrology that not only downsizes the conventional light source but also contributes to 3D inspections in narrow spaces such as dental and endoscope examinations. In this context, we have examined two beam patterns (multi-dot and fringe) both without a zero-order beam by using the iPMSELs. In the former, we have demonstrated projection of large-scale dot patterns of more than 10,000 points, which is the same order of magnitude as points in a practical device from a 200×200-µm2 emitter. Since the emitter has approximately 1 mega scattering points, this structure enables 1-mega-pixel images in the wavenumber space, which are comparable to the images of a typical projector emitting several-mega-pixel images from several tens of centimeters. In the latter, we successfully shifted the fringe patterns, which is vital to applying the phase shifting profilometry, despite the superposition of the conjugate ±1st order beam patterns.

Establishment and characterization of patient-derived organoids from a young patient with cervical clear cell carcinoma.

Cervical clear cell carcinoma (cCCC) constitutes an extremely rare subtype of cervical cancer. Consequently, its pathogenesis remains largely unknown, with no cell lines established from primary tumors. Here, we report the first establishment of cCCC organoids, from biopsy samples of a 23-year-old patient diagnosed with cCCC. By applying a protocol that we recently optimized for gynecological tumors, we were able to propagate a patient-derived cell line (PDC) for more than 6 months as organoids. This PDC tolerated cryopreservation and proliferated either as spheroids or adherent cells, and developed xenografts in immunodeficient mice, ensuring robust utility as a cell line. Intriguingly, the resected tumor focally contained serous carcinoma (SC) in a tiny protruding lesion. Both organoids and derivative xenografts resembled the CCC component of the original tumor in histology, immunostaining profile, and genome-wide copy number changes, including focal gain of MET. Genomic analysis revealed that both organoids and the CCC component harbored only a few mutations, of which 2 mutations were shared in common. In contrast, the SC component showed a mutator-phenotype and prominent genome instability along with biallelic inactivation of TP53, but none of them were found in organoids or the CCC component. The PDC proved sensitive to major chemotherapeutic agents and MET inhibitors. These observations clearly indicated that the PDC, designated as YMC7, can be used as a novel cCCC cell line and provide novel insights into the pathogenesis of mixed cervical adenocarcinoma. As a valuable resource for rare cancer, it will likely contribute to investigations in many fields.

Removal of surface-normal spot beam from on-chip 2D beam pattern projecting lasers.

Static arbitrary two-dimensional beam patterns have been demonstrated using on-chip size "integrable spatial-phase-modulating surface-emitting lasers," which use the band edge mode of a two-dimensional photonic crystal as an in-plane resonator, while the spatial phase of the lightwaves of the band edge mode are simultaneously modulated in a holographic manner by a local positional shift of holes from their lattice points. Meanwhile, the beam patterns include a spot beam in the surface-normal direction (0th-order beam), which corresponds to components of vertical diffraction of the band edge modes without spatial phase modulation. A promising method, used to remove the 0th-order beam, uses a structure that prohibits the vertical diffraction of band edge modes. For this purpose, we set the period of the virtual photonic crystal structure from the conventional Γ2 band edge to the Μ1 band edge, where vertical diffraction is prohibited. Moreover, the additional spatial phase modulation that cancels the in-plane component of the wavevectors of the lightwaves of the band edge modes at the Μ1 band edge are also imposed to output the beam patterns vertically. As a result, we successfully demonstrated two-dimensional beam patterns without a spot beam in the surface-normal direction.

Principle of beam generation in on-chip 2D beam pattern projecting lasers.

Integrable spatial-phase-modulating surface-emitting lasers, which utilize the band edge mode of two-dimensional photonic-crystals as resonators, project static arbitrary two-dimensional beam patterns from on-chip size. In this device, holes shifting from the lattice point of a two-dimensional photonic crystal provide spatial phase modulation to light waves, which form standing waves in the resonator. Thus far, the origin of the beam patterns has not been studied, especially the formation of subsidiary beam patterns against the designed beam pattern. In this work, we clarify the origin of beam patterns in two types of spatial phase modulating method, which impose in-plane shifting of holes according to circular and linear shift methods. Based on a theoretical study of spatial phase modulation, we reveal that the circular shift method provides a symmetric beam pattern, while the linear shift method causes an asymmetric beam pattern. Consequently, we demonstrated the asymmetric two-dimensional beam pattern by the linear shift method for the first time.

Effects of Supplementary Seleno-L-methionine on Atopic Dermatitis-Like Skin Lesions in Mice.

Effects of selenium supplementation on atopic dermatitis (AD) were investigated by administering seleno-L-methionine (SeMet) using a mouse model of AD caused by repeated application of 2,4,6-trinitrochlorobenzene (TNCB). BALB/c mice were sensitized with TNCB to the abdomen on day -7; then, TNCB was applied repeatedly to each ear three times a week from days 0 to 23. SeMet was orally administered to the mice from days 0 to 23. The efficacy of SeMet on AD was assessed by measuring ear thickness, histologic evaluation, serum total immunoglobulin (Ig) E levels, and expression of interleukin (IL)-4 in the ear and superficial parotid lymph node. Ear thickness was remarkably increased by repeated application of TNCB, and SeMet significantly suppressed ear thickness in BALB/c mice. SeMet inhibited epidermal hyperplasia and dense infiltration of inflammatory cells. The number of TNCB-induced mast cells was significantly decreased by SeMet. Serum total IgE levels that increased by the repeated application of TNCB were significantly suppressed by SeMet. Repeated application of TNCB induced expression of IL-4, a T-helper (Th) 2 cytokine, in the ear and superficial parotid lymph node of BALB/c mice and its expression was significantly inhibited by SeMet. These results demonstrated that SeMet supplementation suppresses AD-like skin lesions in BALB/c mice and inhibits the expression of total IgE and IL-4.

PCSEL pumped coupling optics free Yb:YAG/Cr:YAG microchip laser.

The passively Q-switched operation of a cryogenically cooled Yb:YAG/Cr:YAG microchip laser was demonstrated with end pumping by a photonic crystal surface emitting laser (PCSEL). This laser generated 70 µJ/1.7 ns/3.2 kHz pulses with near diffraction limited beam quality (M2=1.1) at 1029.4 nm. There were no coupling optics between the microchip laser crystal and PCSEL, which made the system simple and compact.

Demonstration of a photonic crystal surface-emitting laser pumped Yb:YAG laser.

We developed a cryogenically cooled Yb:YAG continuous wave oscillator directly pumped with a photonic crystal surface-emitting laser (PCSEL). A high slope efficiency of 65.7% was obtained at an output power of 208 mW. The beam quality was close to the diffraction limit, with M2<1.2 in both directions. To the best of our knowledge, this is the first PCSEL pumped solid state laser to be developed.

[Primary gastrointestinal follicular lymphoma of the small intestine with massive hemorrhage: a report of three cases].

Primary gastrointestinal follicular lymphoma (FL) has an indolent clinical presentation and many of cases are diagnosed incidentally during routine endoscopic examinations. Herein, we present 3 cases with FL of the small intestine developed massive intestinal hemorrhage that necessitated blood transfusion. In all three patients, upper and lower endoscopic examinations failed to detect the bleeding sites. Eventually, video capsule endoscopies identified ulcerative lesions in the jejunum and biopsies using single- or double-balloon endoscopy confirmed the FL diagnosis in our three cases. The respective clinical stages according to the Lugano system were I, II-1 and II-1. PET-CT did not play a significant role in identifying the gastrointestinal lesions. Two patients received rituximab monotherapy and achieved a complete response. The other remains under observation after termination of antiplatelet drug therapy. Generally, the macroscopic appearance of multiple whitish nodules and the absence of symptoms represent the typical clinical picture of gastrointestinal FL. However, this study demonstrates that patients with ulcerative lesions may be at risk for massive bleeding. Further discussion is required to determine the optimal indications for total endoscopic examination of the small intestine.

Spi-B is critical for plasmacytoid dendritic cell function and development.

Plasmacytoid dendritic cells (pDCs), originating from hematopoietic progenitor cells in the BM, are a unique dendritic cell subset that can produce large amounts of type I IFNs by signaling through the nucleic acid-sensing TLR7 and TLR9 (TLR7/9). The molecular mechanisms for pDC function and development remain largely unknown. In the present study, we focused on an Ets family transcription factor, Spi-B, that is highly expressed in pDCs. Spi-B could transactivate the type I IFN promoters in synergy with IFN regulatory factor 7 (IRF-7), which is an essential transcription factor for TLR7/9-induced type I IFN production in pDCs. Spi-B-deficient pDCs and mice showed defects in TLR7/9-induced type I IFN production. Furthermore, in Spi-B-deficient mice, BM pDCs were decreased and showed attenuated expression of a set of pDC-specific genes whereas peripheral pDCs were increased; this uneven distribution was likely because of defective retainment of mature nondividing pDCs in the BM. The expression pattern of cell-surface molecules in Spi-B-deficient mice indicated the involvement of Spi-B in pDC development. The developmental defects of pDCs in Spi-B-deficient mice were more prominent in the BM than in the peripheral lymphoid organs and were intrinsic to pDCs. We conclude that Spi-B plays critical roles in pDC function and development.

Long-term monitoring of serum p53 antibody after neoadjuvant chemotherapy and surgery for esophageal adenocarcinoma: report of a case.

We monitored serum p53 antibody (s-p53-Ab) titers in a 76-year-old man with esophageal adenocarcinoma, clinical stage III (T2N2M0), for over 4 years, including during the perioperative period and throughout follow-up after surgery. Screening tests for CA19-9 (205 IU/ml) and s-p53-Abs (381 U/ml) were positive before treatment. After neoadjuvant chemotherapy with 5-FU and cisplatin, CA19-9 decreased to the normal range, but the s-p53-Ab titer remained positive (224 U/ml). Pathological findings of surgically resected specimens showed stage T1b disease and no lymph node metastases. After surgery, s-p53-Ab titers consistently decreased, with no disease recurrence. Although the s-p53-Ab titer remained positive even after 4 years, it decreased to 8.66, 3.59, 2.38, and 1.92 U/ml, 1, 2, 3, and 4 years after surgery, respectively. Thus, monitoring perioperative changes in s-p53-Ab titers proved useful for detecting the presence of residual cancer cells in a patient with superficial esophageal adenocarcinoma.

A Case of Systemic Chemotherapy With Paclitaxel/Cisplatin Followed by Wide Local Vulvectomy in Pelvic Lymph Nodes-Related Stage IVB Vulvar Cancer.

Multimodality treatments, including chemotherapy, radiation, and surgery, have been evaluated to reduce the extent of resection and morbidity in patients with advanced vulvar cancer. Here, we report the case of a 55-year-old woman diagnosed with advanced vulvar cancer with inguinal and pelvic lymph node metastasis. She exhibited cancerous labia, which were entirely covered with ulcerated and exophytic lesions of squamous cell carcinoma, and underwent systemic chemotherapy consisting of combined paclitaxel-cisplatin. After eight cycles of this regimen, the tumors had nearly regressed, and we performed a wide local vulvectomy with a plastic musculocutaneous flap. Pathological examination revealed no residual carcinoma in the excised labia, indicating that the chemotherapy elicited a pathological complete response. The paclitaxel-cisplatin regimen may provide sufficient efficacy for selected patients with stage IVB vulvar cancer. In addition, surgical strategies should be tailored to avoid complications associated with extensive surgery and more emphasis should be placed on the patient's expected quality of life.

Calcium pyrophosphate crystal arthritis associated with immune checkpoint inhibitor successfully treated with intra-articular glucocorticoid: A case report.

Immune checkpoint inhibitors (ICIs) sometimes induce immune-related adverse events (irAEs), and arthritis is one of the irAE symptoms. Recently, crystal-induced arthritis, such as calcium pyrophosphate (CPP) crystal deposition disease and gout, has been reported to occur after ICI administration. However, the distinction between ICI-associated crystal arthritis and ICI-induced non-crystal arthritis is difficult because their symptoms are similar. Besides, optimal treatment for ICI-associated crystal arthritis has not been established. Here, we report a patient who developed CPP crystal arthritis twice after pembrolizumab (ICI) administration and was successfully treated with intra-articular glucocorticoid injection. He suffered arthritis and acute interstitial nephritis simultaneously after ICI administration. Musculoskeletal ultrasound of his affected joint suggests that his arthritis was crystal-induced arthritis, and arthrocentesis detected CPP crystal in synovial fluid. Thus, we diagnosed his arthritis as ICI-associated cystal arthritis. Therefore, our case encourages the use of musculoskeletal ultrasound in patients with arthritis after treatment with ICI because it may distinguish between ICI-associated crystal arthritis and ICI-induced non-crystal arthritis. Besides, ICI-associated crystal arthritis could be treatable by intra-articular glucocorticoid injection.