A case of excisionally remitted indolent NK-cell enteropathy in the oral cavity and a mini-review.

Benign natural killer cell enteropathy (NKCE) was first identified in the gastrointestinal (GI) tract. Notably, instances of NKCE have previously been observed at various sites other than the GI tract, including the gallbladder, lymph nodes, esophagus, and female genital tract. Typical NKCE manifests as an NK-cell immunohistological phenotype, with or without TCR rearrangement, and is characterized by the absence of Epstein-Barr virus (EBV) infection and protracted clinical progression. The misdiagnosis of NKT-cell lymphoma has resulted in some patients receiving chemotherapy, while in other instances, the patients' conditions resolved without treatment and showed no evidence of disease recurrence or progression during follow-up examinations. In this paper, we describe a unique case of EBV-negative NKCE occurring in the oral cavity, the first time such a case has been documented. The tumor completely resolved after an excisional biopsy, and subsequent follow-up did not reveal any signs of disease recurrence.

Multiband topological states in the Penrose-triangle photonic crystals.

The topological edge state (TES) and topological corner state (TCS) in photonic crystals (PCs) provide effective ways to manipulate the propagation of light. To improve the performance and integration of topological photonic devices, the realization of multiband topological states by PCs combined with quasi-periodic structure needs to be urgently explored. In this Letter, a Penrose-triangle (P-T) PC, which arranges the basic structural unit of a 12-fold Penrose-type photonic quasi-crystal (PQC) in a triangular lattice, is proposed. The TES and TCS at low- and high-frequency bands can be generated in the same structure, accompanied by the realization of three groups of TCSs. This will provide a new structure for the generation of TESs and TCSs in PCs, and will provide a new way to improve the performance and integration of topological photonic devices.

Multiband topological states in non-Hermitian photonic crystals.

Novel phenomena found in non-Hermitian systems and robust edge states have attracted much attention. When non-Hermitian parameters (gain and loss) are above a critical value, the non-Hermitian photonic crystal (PC) bandgaps close, leading to a mixture of the topological edge state (TES) and topological corner state (TCS) with the bulk state. Meanwhile, new bandgaps also open, in which new TES and TCS can appear. Thus, with appropriate non-Hermitian parameters, TES can emerge in both the original bandgaps and the newly opened bandgaps. The results described here will further enrich understanding of the topological properties of non-Hermitian systems.

Pseudo-spin-valley coupled topological states protected by different symmetries in photonic crystals.

The quantum spin Hall effect protected by C6 symmetry [realized in the domain wall (DW) formed by a trivial-photonic crystal (TPC) and a nontrivial-PC (NPC)] and the quantum valley Hall effect protected by C3 symmetry [realized in the DW formed by two valley PCs (VPCs)] have been widely researched due to their excellent topological properties. The topological edge states (TESs) and topological corner states (TCSs) at DWs between different symmetric structures remain to be explored, which is essential for connecting waveguides with different symmetries to construct optical communication devices. In this Letter, there is (are) one TES (two TESs) for the DW1 and DW3 (DW2 and DW4) between the TPC (NPC) and two VPCs. Through simulation calculations of the Wilson-loop of the TPC and NPC and the Berry curvature distribution of VPCs, the corresponding relationship between the topological invariant and the number of TESs is obtained. Based on the TPC, NPC, and two VPCs, the waveguides are constructed to verify the realization of TESs. The parity of the gapped TESs is analyzed, and its relationship with the TCSs is obtained. Moreover, box-shaped structures are constructed to verify the appearance of TCSs. These results have a guiding significance for the research of the interaction between topological states protected by different symmetries.

Higher-order topological states in two-dimensional Stampfli-Triangle photonic crystals.

In this Letter, the higher-order topological state (HOTS) and its mechanism in two-dimensional Stampfli-Triangle (2D S-T) photonic crystals (PhCs) is explored. The topological corner states (TCSs) in 2D S-T PhCs are based on two physical mechanisms: one is caused by the photonic quantum spin Hall effect (PQSHE), and the other is caused by the topological interface state. While the former leads to the spin-direction locked effect which can change the distribution of the TCSs, the latter is conducive to the emergence of multiband TCSs in the same structure due to the characteristics of plentiful photonic bandgap (PBG) and broadband in 2D S-T PhCs. These findings allow new, to the best of our knowledge, insight into the HOTS, and are significant to the future design of photonic microcavities, high-quality factor lasers, and other related integrated multiband photonic devices.

Coupled cavity-waveguide based on topological corner state and edge state.

The topological corner state (TCS) and topological edge state (TES) have created new approaches to manipulate the propagation of light. The construction of a topological coupled cavity-waveguide (TCCW) based on the TCS and TES is worth looking forward to, due to its research prospects in realizing high-performance micro-nano integrated photonic devices. In this Letter, the TCCW is proposed in two-dimensional (2D) photonic crystal (PC), which possesses strong optical localization, high quality factor, and excellent robustness compared with the conventional coupled cavity-waveguide (CCCW). This work will pave the way toward designing high-performance logic gates, lasers, filters, and other micro-nano integrated photonics devices and expanding their applications.

The expression of LRRN4 was correlated with the progression and prognosis of colon adenocarcinoma (COAD) patients.

Our present study aims to investigate the value of LRRN4 in the progression and prognosis of COAD patients. All COAD and adjacent sample data was downloaded from TCGA database. Survival analysis was performed according to Kaplan-Meier method. The real-time quantitative PCR and immunohistochemistry analysis were conducted for validation in cell lines and tissues. The GSEA was conducted to find functional KEGG pathways. Multivariate Cox regression proportional hazard mode was used to determine whether LRRN4 expression was an independent prognostic factor. The LRRN4 expression in COAD samples were significantly higher than that in adjacent samples, which was consistent with our experiments in cell lines and tissues. Along with the increase of TNM Stage, LRRN4 expression had an increasing tendency. The COAD patients with high LRRN4 expression showed undesirable prognoses. Additionally, the TGF-ß signaling pathway, WNT signaling pathway and other 25 pathways were significantly activated in the high LRRN4 expression group. In conclusion, high LRRN4 expression was closely related to the onset of COAD and it was a poor prognostic factor for COAD patients.

Large object distance and super-resolution graded-index photonic crystal flat lens.

In order to realize super-resolution imaging of point source at any positions within a large object distance range, a graded-index equivalent medium (GEM) flat lens, which can break through the object distance limit d (d is the lens thickness), is analyzed by negative refraction. Based on this analysis, graded-index photonic crystal (GPC) flat lens with a large object distance is designed. Its imaging resolution can reach up to 0.4λ at the maximum object distance of 5d, which breaks through the diffraction limit.

Broadband ultra-flattened dispersion, ultra-low confinement loss and large effective mode area in an octagonal photonic quasi-crystal fiber.

In this work, an octagonal Penrose-type photonic quasi-crystal fiber (PQF) with dual-cladding is proposed. By optimizing three geometric degrees of freedom, the PQF exhibits ultra-flattened near-zero dispersion of 0.014±0.293 ps/nm/km, ultra-low order confinement loss of 10-4 dB/km, and large effective mode area of over 16.2 µm2 in a broadband of wavelength from 1.27 to 1.67 µm, covering almost all optical communication bands. At the common communication wavelength 1.55 µm, completely opposite trends of the dispersion and the confinement loss varying with the air-filling factor in the inner cladding are demonstrated. In addition, the robustness of optical properties including dispersion, confinement loss, and effective mode area in this PQF is discussed, assuming a deviation ±3% of all air holes.

Refractive index sensor with high sensitivity based on circular photonic crystal.

A highly sensitive refractive index sensor is proposed that consists of a silicon ring surrounding a cavity in a circular photonic crystal (CPC). The bandgap of the CPC is determined from the transmission spectra. Relationships between the performance parameters and the structure parameters of the sensor are investigated. Transmission spectra of the optimized sensor filled with different analytes are analyzed, and a sensitivity of 1054 nm/RIU (refractive index units) and a quality factor of 18,206 are obtained. This work is expected to facilitate the application of sensors based on CPC.

[Clinicopathologic analysis of angioimmunoblastic T-cell lymphoma with Hodgkin/Reed-Sternberg-like cells].

OBJECTIVE: To study the clinicopathologic features and pathologic diagnosis and differential diagnosis of angioimmunoblastic T-cell lymphoma with HRS-like cells. METHODS: Six cases of angioimmunoblastic T-cell lymphoma with HRS-like cells were examined histologically and immunohistochemically (EliVision method) and in-situ hybridization for Epstein-Barr virus-encoded RNA (EBER), and the literature was reviewed. RESULTS: The cytologic and microscopic features of these imprints and lymph node samples showed a heterogeneous population of hematolymphoid cells, including small to intermediate lymphoid cells, immunoblasts, plasma cells, dendritic cells, and eosinophils, as well as small vessels that were surrounded by some of the abnormal cells. The neoplastic T-cells expressed CD3 and CD5 and partly positive for CD10 and bcl-6, CD21 showed expanded and irregular follicular dendritic cell (FDC) meshworks that surrounding the high HEV. The HRS-like cells were positive for MUM-1 and Ki-67, variable intensity positive for CD30, CD20, and PAX-5, but negative for CD15. EBV-positive cells included HRS-like cells and small to large-sized neoplastic T-cells, which formed small clusters or scattering in the background of the disease. CONCLUSIONS: The clinical course of angioimmunoblastic T-cell lymphoma with HRS-like cells is aggressive. Which present with histomorphology overlap with classical Hodgkin lymphoma (CHL), similar to CHL in EBER and immunophenotype, however, it is easy to misdiagnosis as HL. Thus, angioimmunoblastic T-cell lymphoma pathology diagnosis should comprehensive analysis of different kinds of materials, including clinical features, and histological structure, and EBER, and immunophenotype, and gene rearrangement.

[Significance of CD123 in histiocytic necrotizing lymphadenitis].

OBJECTIVE: To investigate the mode of presentation, cytologic features of the plasmacytoid dendritic cells (pDC), and the expression of CD123 and its significance in Kikuchi's disease. METHODS: CD123 expression was evaluated by EliVision immunohistochemical staining in formalin-fixed and paraffin-embedded tissues from 30 cases of Kikuchi's disease, 5 cases of T cell lymphoma, 10 cases of reactive lymphoid hyperplasia and 10 cases of chronic tonsillitis. RESULTS: Clusters of CD123 positive PDC were observed in Kikuchi's disease (28 of 30 cases, 93.3%) and the staining intensity was more prominent in the PDC at the periphery of the lesion and around the high endothelial venule-like vessels. CD123 showed three staining patterns: membranous (10 cases, 33.3%), cytoplasmic (10 cases, 33.3%), and membranous and cytoplasmic (8 cases, 26.7%). In the control group, CD123 showed cytoplasmic staining in reactive hyperplasia and chronic tonsillitis. Regarding the staining intensity, 12 of 28 cases (42.9%) were 3+ for CD123, 8 of 28 cases (28.6%) were 2+, and 8 of 28 cases (28.6%) were 1+. In contrast, PDC clusters with 1+ staining intensity were observed in 1 of 10 cases of reactive lymphoid hyperplasia; 2 of 10 chronic tonsillitis diseases; and much less in T cell lymphoma. CONCLUSIONS: Large cluster of PDC is detected in both proliferative and necrotizing types of Kikuchi's disease, making this a useful adjunctive diagnostic marker.

Extranodal NK/T-Cell Lymphoma Predominantly Composed of Anaplastic Cells: A Frequently Misdiagnosed and Highly Aggressive Variant.

Extranodal NK/T-cell lymphoma (ENKTL) is a non-Hodgkin lymphoma associated with the Epstein-Barr virus that primarily affects individuals in East Asia and indigenous populations in Central and South America. Morphologically, ENKTL typically consists of medium-sized cells or a combination of small and large cells. This report presents 10 cases characterized by predominantly anaplastic cells with diffuse expression of CD30, resembling anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (ALK-negative ALCL) and demonstrating highly aggressive behavior. The cohort included 9 males and 1 female, ranging in age from 29 to 65 years (median age: 47 y). Eight patients presented with nasal disease, while 2 had non-nasal disease. Five patients had stage I/II disease, and the remaining 5 had stage III/IV disease. Morphologically, necrosis was observed in 9 cases, angiocentric-angiodestructive growth in 3 cases, and pseudoepitheliomatous hyperplasia in 2 cases. Anaplastic cells predominated in all cases, with some displaying eccentric, horseshoe-shaped, or kidney-shaped nuclei (referred to as "Hallmark" cells). The morphology profile was monomorphic in 3 cases and polymorphic in 7 cases. Immunohistochemically, all cases tested positive for cytotoxic granule markers (TIA1 and granzymeB) and Epstein-Barr virus-encoded RNA. Cytoplasmic expression of CD3ε and CD56 was observed in 9 of 10 cases. Interestingly, most cases (7 of 8) exhibited variable expression of MuM1, ranging from 10% to 90%. All cases showed diffuse positivity for CD30 but were negative for ALK, resulting in 3 cases being initially misdiagnosed as ALK-negative ALCL. Compared with nonanaplastic cases, anaplastic cells predominant ENKTL had a significantly higher frequency of "B" symptoms, bone marrow involvement, hemophagocytic lymphohistiocytosis, and higher Ki67 proliferative index. These findings provide valuable information for pathologists, expanding their understanding of the cytologic spectrum of ENKTL. This rare variant of ENKTL, characterized by the predominance of anaplastic cells and diffuse CD30 expression, exhibits high aggressiveness and should be differentiated from ALK-negative ALCL. Awareness of this uncommon variant is crucial in preventing misdiagnosis and ensuring the timely initiation of therapy.

Accumulated cholesterol protects tumours from elevated lipid peroxidation in the microenvironment.

Elevated lipid peroxidation (LPO), usually present in the tumour microenvironment (TME), is profoundly implicated in antitumour immunity and may be targeted for the development of new antitumour therapies. However, tumour cells may also rewire their metabolism to survive elevated LPO. Here, we report a novel and nonantioxidant mechanism by which tumour cells benefit from accumulated cholesterol to restrain LPO and ferroptosis, a nonapoptotic form of cell death characterized by accumulated LPO. Modulating cholesterol metabolism, especially LDLR-mediated cholesterol uptake, shifted the susceptibility of tumour cells to ferroptosis. Elevation of cellular cholesterol content specifically restrained LPO triggered by GSH-GPX4 inhibition or oxidizing factors in the TME. Furthermore, depletion of TME cholesterol by MßCD efficiently enhanced the antitumour efficacy of ferroptosis in a mouse xenograft model. Distinct from the antioxidant effect of its metabolic intermediates, the protective role of cholesterol was ascribed to its ability to decrease membrane fluidity and promote lipid raft formation, which affects the diffusion of LPO substrates. A correlation between LPO and lipid rafts was also found in tumour tissues from renal cancer patients. Together, our findings have identified a general and nonsacrificial mechanism by which cholesterol suppresses LPO, which can be exploited to enhance the efficacy of ferroptosis-based antitumour strategies.

[Clinicopathologic analysis of intestinal follicular lymphoma first presenting with gastrointestinal symptoms].

OBJECTIVE: To study the clinical features, endoscopic findings, pathologic diagnosis and treatment options of intestinal follicular lymphoma first presenting with gastrointestinal symptoms. METHODS: The clinical features, pathologic findings and follow-up data were retrospectively studied in 9 cases of intestinal follicular lymphoma. Immunohistochemical study for CD3, CD5, CD20, CD21, Ki-67, bcl-2, bcl-6, CD10 and cyclin D1 was carried out. RESULTS: Seven of the 9 patients were females and two were males. The age of patients ranged from 5 to 60 years (mean = 44 years). The clinical manifestations included abdominal pain (5 cases), blood in stool (3 cases) and abdominal distension (1 case). The commonest site of involvement was ileocecal region (6/9). Endoscopic examination had been carried out in 6 patients and all showed the presence of multiple polyps. Five cases had undergone endoscopic biopsy. Histologic examination of the endoscopic biopsies showed lymphoma cells located mainly in mucosal layer, forming vague nodules with ill-defined boundaries. Plasma cells and eosinophils were not conspicuous. Immunohistochemically, the tumor cells in all cases diffusely expressed CD20, CD10 and bcl-2. The staining for CD3, CD5 and cyclin D1 was negative. Lymphoid cells with weak CD10-positivity were identified in the interfollicular regions. Four cases were treated with surgical resection and chemotherapy. The other 3 cases received chemotherapy only and the remaining cases were treated conservatively. All of them were still alive on follow up. CONCLUSIONS: Primary intestinal follicular lymphoma affects predominantly elderly patients and has a female predilection. The commonest site of involvement is ileocecal region. Endoscopic examination shows polypoid changes. The disease often runs a relatively indolent clinical course. The prognosis is better than that of primary nodal follicular lymphoma.

Mixed primary mucinous cystadenocarcinoma and invasive ductal carcinoma of the breast: a case report and literature review.

Background: Mucinous cystadenocarcinoma (MCA) mainly occurs in the ovary, pancreas, and appendix, whereas the breast is a rare primary site of occurrence. Invasive ductal carcinoma (IDC) is the most common breast malignancy. Only 31 cases of the breast MCA have been reported in the English literature, and the coexistence of MCA and IDC in the breast are rare. Case Description: Here, we describe a 61-year-old postmenopausal woman with no family history of breast cancer or other breast-related diseases, who presented with a palpable mass in her left breast lasting for 2 months. On ultrasonography examination, the tumor was a cystic-solid lesion with clear boundary. Magnetic resonance imaging (MRI) showed a mass with low signal intensity on T1 weighted imaging and high signal intensity on T2 weighted imaging. Intraoperative frozen sections revealed metastatic tumor cells in one sentinel lymph node (1/4). She then underwent left modified radical mastectomy with axillary dissection. The post-operative pathological examination showed the tumor consisted mostly of MCA (60%), with a small proportion of intermediate-grade IDC. The MCA had a well-demarcated cystic structure with papillary projections and abundant mucoid material. The epithelium lining cystic spaces was tall columnar, with mucin-producing cells that had basally located nuclei. The degree of cytological atypia varied considerably. Axillary lymph nodes were normal (0/15). The MCA was triple-negative for estrogen receptor (ER), progesterone receptor (PR), and HER2, and positive for CK7 but negative for CK20. Through next-generation sequencing, no mutations in the BRCA1 and BRCA2 genes were identified in our case, which was not highlighted in prior cases. After surgery, the patient underwent eight cycles of chemotherapy, and she has been disease-free during the 10-month follow-up. In addition to detailing this instance of mixed MCA and IDC of the breast, we reviewed relevant literature and compare our findings with other patients who had breast MCAs. Conclusions: Our results improved the understanding of mixed MCA and IDC, especially MCA, and provided a basis for its diagnosis and differential diagnosis from other metastatic diseases.

[Intravascular NK-cell lymphoma: a clinicopathologic study and literature review].

OBJECTIVE: To study the clinicopathologic features and disease outcome of intravascular natural killer-cell lymphoma (IVNKL). METHODS: The histologic features, immunohistochemical findings and results of in-situ hybridization for Epstein-Barr virus-encoded RNA (EBER) were analyzed in 2 novel cases of IVNKL. Seven cases of IVNKL previously reported in the literature were reviewed. RESULTS: The patients were a 68-year-old woman and a 22-year-old man. They both presented with erythematous patches and nodules on their trunk and extremities. Skin biopsies confirmed the diagnosis of IVNKL. The tumor cells were positive for CD3, CD56, granzyme B and EBER. Both patients died 2 months after the diagnosis. Amongst the 9 reported cases, including those from the literature, the male was 4 cases, the female was 5 cases. The mean age of the patients was 45.7 years and the median age was 47 years. Skin lesions represented the commonest clinical manifestations. Multiple organ involvement was found in 7 cases and central nervous system was involved in 3 cases. Six patients died during 2 to 17 months of follow-up. The median survival was 9 months and the one-year survival rate was (35.6±18.6)%. The clinical outcome of the patients with multiple organ involvement was worse than that with skin manifestations only. The difference however was not statistically significant (P=0.083). CONCLUSIONS: IVNKL is a rare disease. Diagnosis should be made according to typical histologic findings, immunophenotype and EBER in-situ hybridization results. The overall prognosis of IVNKL is poor. Early diagnosis and treatment before multiorgan involvement may be helpful in improving the clinical outcome.

[Clinicopathologic features of systemic EBV-positive T/NK-cell lymphoproliferative disease in adults].

OBJECTIVE: To study the clinicopathologic features, immunophenotype, clonality and Epstein-Barr virus (EBV) status of systemic EBV-positive T/NK-cell lymphoproliferative disease in adults (ASEBV(+)T/NK-LPD). METHODS: Twenty cases of ASEBV(+)T/NK-LPD were analyzed retrospectively with histopathologic review, immunohistochemistry and in-situ hybridization for EBV-encoded RNA (EBER). The follow-up data were collected. RESULTS: There were altogether 15 males and 5 females. The median age of the patients was 34 years. The average duration from onset of symptoms to diagnosis was 8.7 months. Fever (18/20), hepatosplenomegaly (18/20) and lymphadenopathy (17/20) were the main clinical manifestations. Eleven of the 17 patients died during follow-up, with a mean survival of 2.9 months. Histologically, there was obvious expansion of T zone of the involved lymph nodes, associated with diminished lymphoid follicles. The interfollicular areas were widened and infiltrated by small to median-sized lymphoid cells which showed only mild atypia. Scattered large lymphoid cells were not uncommon. The nodal capsule was thickened in 6 cases. Focal necrosis was seen in 9 cases. Sinus histiocytic proliferation with erythrophagocytosis was observed in 3 cases. In addition, there were mild atypical lymphoid cells infiltrate into the liver, spleen, intestinal mucosa and bone marrow. Immunohistochemical study and in-situ hybridization showed that the EBER-positive cells were of T-cell lineage, with CD3 expression. They were also positive for cytotoxic molecules (granzyme B or TIA-1). Only 1 case was CD56 positive. A predominance of CD8-positive cells was demonstrated in 8 of the 14 cases studied, while CD4-positive cells predominated in the remaining 5 cases. One case showed similar proportion of CD8 and CD4-positive cells. The number of EBER-positive cells ranged from 30 to more than 300 per high-power fields. These EBER-positive cells were of small to large size and located mainly in the expanded T zone and occasionally in the germinal centers. Three of the 7 cases exhibited clonal rearrangement of T-cell receptor gamma gene, while the other 4 cases exhibited polyclonal rearrangement of T-cell receptor gamma gene. CONCLUSIONS: ASEBV(+)T/NK-LPD is a systemic disease with a subacute or chronic clinical course. Most patients suffer from relapsing fever, lymphadenopathy and hepatosplenomegaly. The disease is characterized by proliferation of EBV-infected cytotoxic T cells. The T zone of the involved lymph nodes shows expansion by mildly atypical lymphoid cells. The disease is associated with poor clinical outcome and can be life-threatening. The patients often die of multiorgan failure and bleeding.

[Loss of pan-T cell antigens CD2, CD3, CD5 and CD7 in Kikuchi's disease].

OBJECTIVE: To study the possible loss of pan-T cell antigens CD2, CD3, CD5 and CD7 in Kikuchi's disease and to evaluate the role of T cell antigen loss in distinguishing benign from malignant T-cell lymphoid lesions. METHODS: Formalin-fixed and paraffin-embedded tissues of 33 cases of Kikuchi's disease and 15 cases of reactive lymphoid hyperplasia were studied by EliVision immunohistochemical staining for CD2, CD3, CD5 and CD7. RESULTS: Twenty-four of the 33 (72.7%) cases of Kikuchi's disease lost one or more of the pan-T cell antigens, including the loss of CD5 only (13 cases), CD7 only (1 case), CD2 only (1 case), CD2 and CD7 (2 cases), CD5 and CD7 (4 cases), CD2 and CD5 (2 cases), and CD2, CD7 and CD5 (1 case). Amongst these cases, the commonest antigen loss was CD5 (20 cases, 60.6%), followed by CD7 (8 cases, 24.2%) and CD2 (6 cases, 18.2%). Compared with the xanthomatous subtype of Kikuchi's disease, the loss of antigens was more commonly seen in the proliferative and necrotizing subtypes. Analysis of follow-up data showed that the loss of antigens in Kikuchi's disease was not significantly associated with the prognosis. In reactive lymphoid hyperplasia, the expression of CD2, CD3, CD5 and CD7 was seen in all cases with similar intensity, with no obvious pan-T cell antigen loss. CONCLUSION: Loss of one or more pan-T cell antigens in Kikuchi's disease is demonstrated in present study, suggesting that the immunophenotypic pattern is not unique in T cell lymphoma.