Infectious mononucleosis complicated by transitory Epstein-Barr virus infection of T and natural killer cells.

Epstein-Barr virus (EBV) typically infects B cells in infectious mononucleosis (IM), but a rare case shows EBV infection in T cells. Seven cases of lymphoproliferative disorder caused by EBV-positive cytotoxic T/natural killer (NK) cell proliferation in the lymph nodes, termed IM with transient EBV infection of T and NK cells (EBV + T/NK cells in IM), are reported here. The purpose of the study is to describe clinicopathological features of EBV + T/natural killer (NK) cells in IM of the lymph node. We retrospectively analysed seven cases of Chinese children and young people adults with EBV + T/NK cells in IM. We used morphological observation, immunohistochemical staining, EB virus in situ hybridisation detection, and analysis of T-cell receptor gene rearrangement. The patients were healthy prior to illness, experiencing sudden onset occurring in all the patients, with high fever as the first symptom, followed by lymphadenopathy and hepatosplenomegaly. Diagnosis occurred < 1.5 months of symptom onset. Most lymphocytes in lesions expressed CD3 and Granzyme B or TIA-1 and lacked CD5. CD56 was expressed in numerous cells in 5 of the 7 cases. EBV-encoded RNA (EBER) was detected in medium-to-large-sized cells (50-100 cells per cell/high-power field). T-cell receptor (TCR) gene rearrangement was seen in six cases, with monoclonal rearrangement in four cases. Treatment was conservative treatment but not chemotherapy. Four received anti-HLH therapy and others anti-inflammatory treatment. All patients survived with relapse after long-term clinical observation and follow-up. EBV + T/NK cells in IM can elicit malignant features that mimic T/NK-cell lymphoma pathologically and benign features mimicking IM clinically. These findings indicate that EBV + T/NK cells in IM could serve as valuable diagnosis. Additional clinical information, including age of onset (children and young people), nature of onset (sudden), disease course (short), symptoms (systemic), EBV infection status (acute), and lymph node involvement, is crucial for accurate diagnosis and prognostic evaluation.

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.

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.

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.

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.

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.

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.

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.

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.

Hemophagocytic lymphohistiocytosis secondary to composite lymphoma: Two case reports.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening disease caused by inherited pathogenic mutations and acquired dysregulations of the immune system. Composite lymphoma is defined as two or more morphologically and immunophenotypically distinct lymphomas that occur in a single patient. Here, we report two cases of HLH secondary to composite lymphoma with mixed lineage features of T- and B-cell marker expression both in the bone marrow and lymph nodes in adult patients. CASE SUMMARY: Two patients were diagnosed with HLH based on the occurrence of fever, pancytopenia, lymphadenopathy, splenomegaly, hemophagocytosis and hyperferritinemia. Immunohistochemical staining of the axillary lymph node and bone marrow in case 1 showed typical features of combined B-cell and T-cell lymphoma. In addition, a lymph node gene study revealed rearrangement of the T-cell receptor chain and the immunoglobulin gene. Morphology and immunohistochemistry studies of a lymph node biopsy in case 2 showed typical features of T cell lymphoma, but immunophenotyping by flow cytometry analysis of bone marrow aspirate showed B cell lymphoma involvement. The patients were treated with high-dose methylprednisolone combined with etoposide to control aggressive HLH progression. The patients also received immunochemotherapy with the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen immediately after diagnosis. Both patients presented with highly aggressive lymphoma, and died of severe infection or uncontrolled HLH. CONCLUSION: We present two rare cases with overwhelming hemophagocytosis along with composite T- and B-cell lymphoma, which posed a diagnostic dilemma. HLH caused by composite lymphoma was characterized by poor clinical outcomes.

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.

Primary cutaneous mantle cell lymphoma: Report of a rare case.

BACKGROUND: We describe the case of a 74-year-old man diagnosed with primary cutaneous mantle cell lymphoma (MCL), an extremely rare and controversial condition that is not included in the World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas. CASE SUMMARY: The patient presented diffuse cutaneous erythematous plaques and nodules throughout the body. Skin lesions were biopsied and histopathological examination showed diffuse monomorphic lymphocyte infiltration in the dermal and subcutaneous layers, sparing the epidermis. Immunohistochemical staining revealed CD20, cyclin-D1, CD5, and SOX-11 expression. Fluorescence in situ hybridization showed CCND1/IGH gene rearrangement. Correct diagnosis of primary cutaneous MCL requires ensuring that no other parts are involved; these cases require close follow-up to monitor their possible progression to systemic disease and for treating relapsed cutaneous disease. In this case, positron emission tomography scanning and clinical staging revealed no systemic involvement, and follow-up examination at 20 mo after diagnosis showed no evidence of systemic disease. The prognosis of primary cutaneous MCL is relatively good. Our patient received six cycles of chemotherapy, and the cutaneous manifestations presented almost complete remission. CONCLUSION: Primary cutaneous MCL is rare, and its prognosis is relatively favorable. However, correct diagnosis is a prerequisite for proper treatment.

A combination of LMO2 negative and CD38 positive is useful for the diagnosis of Burkitt lymphoma.

BACKGROUND: To evaluate the clinical utility of LIM Domain Only 2 (LMO2) negative and CD38 positive in diagnosis of Burkitt lymphoma (BL). METHODS: LMO2 and CD38 expression determined by immunohistochemistry in 75 BL, 12 High-grade B-cell lymphoma, NOS (HGBL,NOS) and 3 Burkitt-like lymphomas with the 11q aberration. RESULTS: The sensitivity and specificity of LMO2 negative for detecting BL were 98.67 and 100%, respectively; those of CD38 positive were 98.67 and 66.67%, respectively. The sensitivity and specificity of a combination of both for detecting BL were 97.33 and 100%, respectively. In our study, the combined LMO2 negative and CD38 positive results had a higher area under the curve than either LMO2 negative or CD38 positive alone. CONCLUSIONS: A combination of LMO2 negative and CD38 positive is useful for the diagnosis of Burkitt lymphoma.

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.

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.

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.

The degree of overlap between the follicular dendritic cell meshwork and tumor cells in mantle cell lymphoma is associated with prognosis.

This study concerning mantle cell lymphoma (MCL) investigated retrospectively an association between patient prognosis and the percentage of the total number of lymphoma cells found in the follicular dendritic cell (FDC) meshwork, that is, the degree of overlap of lymphoma cells. Two hundred and nine MCL patients were apportioned to grades I-III, in which the CD21-positive FDC meshwork covered ≤50%, 51%-89%, and ≥90% of the tumor area, respectively. Significant differences among the grades (all, P < 0.01) were found in the following: duration of disease (from onset of clinical manifestation to diagnosis); clinical staging; extranodal involvement (non-lymphoid organs); histological subtype; and Ki-67 proliferation index (PI). After removing the aggressive variants, the overall survival rates of grade I (n = 92) and II (n = 57) patients were similar. The overall survival rates of grade III (n = 46) patients differed from that of grade I + II patients (P < 0.01). The grades negatively correlated with the Ki-67 PI value (r = -0.234, P = 0.001). At each grade the OSR of patients with Ki-67 PI ≤30% was similar to that of patients with Ki-67 >30%. In the Ki-67 PI ≤30% group, the OSRs of the patients differed significantly among the grades. In the Ki-67 >30% group the OSRs of the grades were similar. The results of multivariate Cox regression analysis showed that the degree of overlap, age and Ki-67 PI was the independent prognostic factors of the OSRs of MCL patients. Our data suggests that MCL patients in whom there was a high degree of overlap between the FDC meshwork and tumor area have a better clinical prognosis. The degree of overlap correlates well with the Ki-67 PI, which can be used to predict the prognosis of patients.

CD38 expression on paraffin sections distinguishes follicular lymphoma from reactive follicular hyperplasia.

This study explored the utility of CD38 immunodetection in paraffin-embedded tissue sections for differentiating follicular lymphoma (FL) from reactive follicular hyperplasia (RFH) by examining RFH (n = 47) and FL (n = 178). In RFH specimens, uniform weak-to-moderate CD38 immunostaining was observed in centrocytes and centroblasts across germinal centers (GCs). Moreover, these specimens contained a subset of strongly CD38-positive cells predominantly located in the light zone, which may represent antigen-selected surviving centrocytes that are committed to differentiate into plasma cells, i.e., centrocytoid plasma cells (CPCs). In FL specimens, CD38 staining yielded two patterns. In pattern I (146 specimens), weak-to-moderate CD38 staining was observed in tumor cells within neoplastic follicles. Neoplastic follicles in 126 of the 146 specimens did not contain strongly CD38-positive CPCs. Furthermore, individual neoplastic follicles in the remaining 20 FL specimens contained very few strongly CD38-positive cells (which may represent normal residual CPCs). In pattern II (32 cases), neoplastic follicles exhibited loss of CD38 expression accompanied by disappearance of CPCs. In conclusion, compared with RFH, the decrease of strongly CD38-positive CPCs in neoplastic follicles was a striking alteration, reflecting blocks in the lymphoid differentiation pathway. Moreover, loss of CD38 expression in neoplastic GC B-cells in some FL specimens can serve as an immunophenotypic characteristic of FL.

EBV-positive T/NK lymphoproliferative diseases: analysis of prognostic factors for patients in China.

The Epstein-Barr virus (EBV) is a ubiquitous lymphotropic herpesvirus that infects the human body through the respiratory tract. Usually, primary infection with EBV is asymptomatic and occurs early in life, however adolescents or young adults are more likely to develop a self-limited symptomatic infection, which manifests as acute infectious mononucleosis (IM). Systemic EBV-positive lymphoproliferative disease (EBV + T/NK-LPD) has been described as a disease related to chronic or persistent EBV infection after acute EBV infection, with severe IM-like symptoms. EBV + T/NK-LPD is associated with high mortality and morbidity with life-threatening complications. Information on its prognostic factors remains limited, therefore in this study, we aimed to evaluate the association between prognostic factors and mortality and complications of EBV + T/NK-LPD in China by retrospectively reviewing 173 EBV + T/NK-LPD cases. We observed that the high mortality rate of EBV + T/NK-LPD was mainly due to serious and fatal complications. Fever, lymphadenopathy, hepatosplenomegaly, EBV-encoded RNA (EBER) > 50/HPF, Ki-67 > 30%, and other visible complications were closely associated with EBV + T/NK-LPD prognosis. In addition, fever, hepatosplenomegaly, decreased WBC count, and a Ki-67 index of > 30% were risk factors for complications. Thus, disease prognosis should be based on a comprehensive analysis of pathological and clinical data. Such data will help pathologists and clinicians to pay close attention to the changes in the clinical condition of the patients as well as take precautionary measures against the occurrence of fatal complications.