[Introduction on the update of the 5th edition WHO classifications of B-cell neoplasms].

The 5th edition WHO classification of B-cell tumors is a systematic update to the fourth revised version of the classification. The changes include updated names of entities, sharpened diagnostic criteria, and upgrades from provisional to definite entities. This review focuses on the changes in the content of each chapter of B-cell tumors, facilitating domestic colleagues engaged in the diagnosis and treatment of lymphohematopoietic tumors to understand the latest progress and guide daily work.

[Clinicopathological features of T-lymphoblastic lymphoma with Langerhans cell histiocytosis in the same lymph node].

Objective: To investigate the clinicopathological features, immunophenotypes, genetics and prognosis of T-lymphocyte lymphoma/myeloid sarcoma combined with Langerhans cell histiocytyosis (coexistence of T-LBL/MS and LCH). Methods: Clinical and pathological data of the 6 patients with coexistence of T-LBL/MS and LCH were analyzed, who were diagnosed at the Foshan Hospital of Sun Yat-sen University and the Friendship Hospital of Capital Medical University, from December 2013 to April 2019. The hematoxylin and eosin stain, immunohitochemistry (EnVision) and in situ hybridization were used. Related literatures were reviewed. Results: Four patients were T-LBL combined with LCH, 1 was T-LBL/MS combined with LCH, and 1 was MS combined with LCH. There were 2 male and 4 female patients, with age ranged from 5 to 77 years old (median, 59 years old). Three patients represented with only multiple lymph node swelling. The other 3 displayed both multiple lymph node swelling, and skin/liver or spleen lesions. Lymph node structure was destroyed in 5 cases, while 3 cases had several residual atrophic follicles. Histologically, there were two types of tumor cells: one type of the abnormal lymphoid-cells exhibited small to medium-sized blast cells, typically showing a nested distribution, and these cells were mainly identified in residual follicles and paracortical areas; the other type of histiocytoid cells had a large cell size and abundant pale or dichromatic cytoplasm. Their nuclei were irregularly shaped, showing folded appearance and nuclear grooves. These cells were mainly present in marginal sinus, medullary sinus and interstitial area between follicles. Eosinophil infiltration in the background was not evident in any of the cases. The lymphoid-cells of medium size showed TdT+/CD99+/CD7+, with variable expression of CD34/MPO/CD2/CD3. Ki-67 index was mostly 30%-50%. However, the histiocytoid cells showed phenotype of CD1a+/S-100+/Langerin+/-, while CD163/CD68 were positive in some degree. These cells did not express any T or B cell markers. The Ki-67 index mostly ranged between 10%-20%. None of the cases had Epstin-Barr viral infection. Among the 6 patients, 4 patients were followed up (6-63 months, median time, 18.5 months), of whom 1 patient died of the disease and 3 patients were alive at the end of follow-up. Conclusions: T-LBL/MS combined with LCH is a rare mixed type of immature hematopoietic disease, and mainly occurs in lymph node and skin. The clinical course is overall aggressive. Therefore, it is helpful to recognize and identify the two pathologic components in the same tissue for accurate diagnosis and proper treatment.

[Expression of myocyte enhancer factor 2B in mantle cell lymphoma and its clinical significance].

Objective: To investigate the expression of myocyte enhancer factor 2B (MEF2B) in mantle cell lymphomas (MCL), and to analyze the correlation between the expression of MEF2B and pathological subtypes, structural subtypes, SOX11 expression and its clinical significance. Methods: Paraffin-embedded tissues were stained with HE, immunohistochemistry (EnVision method) and fluorescence in situ hybridization (FISH) , in addition, the clinical and pathological data of 60 cases of MCL were collected at Sun Yat-sen University Foshan Hospital and Sun Yat-sen University Cancer Center from January,2002 to May, 2019 for analysis. Results: Of the 60 MCLs, males is predominant (M∶F=3∶1). Histologically, the typical MCL is the majority (classical MCL: variant type MCL=48 cases:12 cases) . Fifty cases were classified into non-complete FDC meshwork type MCL, and the remaining 10 cases were classified into the complete-FDC meshwork type MCL group. Patients with classical MCL were more than 60 years old. The coexistent lesion sites both node and extranode in pathological subtype or structural subtype was the most common lesion sites. SOX11(+) MCL was common in classical MCL (P=0.040) and tended to be complete-FDC meshwork type MCL (P=0.086). The expression rate of MEF2B in MCL was 60.0%(36/60). This rate of MEF2B in classical type, complete-FDC meshwork type and SOX11(+) MCL was significantly higher than that variant type, no complete-FDC meshwork type, SOX11(-)MCL (P<0.05), respectively. There was no difference in clinical characteristics of MCL between MEF2B positive and negative groups. Compared with SOX11(-)MCL, the percentage of MEF2B expressed in tumor cells of SOX11(+)MCL was significantly higher (P=0.027). The expression of MEF2B was not related to the proliferation of tumor cells (P=0.341). There was no significant difference in the survival rate between different expression groups of MEF2B and SOX11 (P=0.304 and P=0.819, respectively). Only the mortality of variant type (blastoid/pleomorphic) MCL within 2 years was significantly higher than that of classical type MCL (P<0.05). Conclusions: The expression of MEF2B in MCL is related to the pathological subtypes, structural subtypes and the expression of SOX11, but not to the proliferation and prognosis. The high mortality rate within 2 years is only found in variant MCL. However, the role of MEF2B in MCL needs to be further studied.

[Clinicopathologic features of primary mucosal CD30-positive T-cell lymphoproliferative disorders in head and neck region].

Objective: To study clinicopathologic features, prognosis and differential diagnoses of primary mucosal CD30-positive T-cell lymphoproliferative disorders of the head and neck(mCD30(+) TLPD-head and neck). Methods: Three cases of mCD30(+) TLPD-head and neck were collected from January 2014 to April 2017 at Sun Yat-Sen University Foshan Hospital. A literature review of mCD30(+) TLPD of head and neck was provided. Results: All three cases presented with either bulging/exophytic nodule or mucosal ulcer/erosion. Morphologically, the tumor consisted of diffuse proliferation of uniform, large atypical mononuclear lymphoid cells that showed irregular or polymorphic nuclei with small nucleoli, and abundant pale or amphophilic cytoplasm. Hallmark cells with eccentric, horseshoe, kidney-like, or doughnut-shaped nuclei were present. While mitotic figures were present, no tumor necrosis was found. Eosinophilc infiltration was obvious in the background. The atypical large lymphoid cells had a immunophenotype of CD30(+) /CD3(+) /CD4(+) /CD56(-) along with positive cytotoxic molecule. While being negative for EBER/ALK/CD20/CD8, TCR rearrangement was found in 2 out of 3 cases. Three patients were cured after excision without relapse and metastasis.The two patients with TCR rearrangement didn't show aggressive clinical course. Conclusions: mCD30(+) TLPD-head and neck is a rare benign lymphoproliferative disorder with spontaneous regression. It should be differentiated from cutaneous CD30(+) anaplstic large cell lymphoma, lymphomatoid papulosis, and EBV-related mucocutaneous ulcer. Correct recognition of mCD30(+) TLPD of head and neck is important to avoid overtreatment.

Structural and functional assessment of macula to diagnose glaucoma.

PurposeTo compare the diagnostic abilities of structural (ganglion cell-inner plexiform layer (GCIPL) thickness measured using spectral domain optical coherence tomography (SDOCT)) and functional (visual sensitivities measured using standard automated perimetry (SAP) and microperimetry (MP)) assessments of macula in glaucoma.MethodsIn a prospective study, 46 control eyes (28 subjects) and 61 glaucoma eyes (46 patients) underwent visual sensitivity estimation at macula (central 10°) by SAP and MP, and GCIPL thickness measurement at macula by SDOCT. Glaucoma was diagnosed by experts based on the optic disc and retinal nerve fiber layer changes. Area under the receiver-operating characteristic (AUC) curves and sensitivities at 95% specificity were used to assess the diagnostic ability of visual sensitivity and GCIPL measurements at various macular sectors.ResultsAUCs of GCIPL parameters ranged between 0.58 and 0.79. AUCs of SAP and MP sensitivities ranged between 0.59 and 0.71, and 0.59 and 0.72, respectively. There were no statistically significant differences between the AUCs of corresponding sector measurements (P>0.10 for all comparisons). Sensitivities at 95% specificities ranged from 31-59% for GCIPL parameters, 16-34% for SAP, and 8-38% for MP parameters. Sensitivities were significantly better with GCIPL compared with SAP and MP parameters in diagnosing glaucoma. Inferotemporal, inferior, and superotemporal sector measurements of GCIPL and visual sensitivity showed the best abilities to diagnose glaucoma.ConclusionsComparing the diagnostic abilities of structural and functional tests at macula in glaucoma, GCIPL thickness measurements with SDOCT performed better than the visual sensitivity measurements by SAP and MP.

JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma.

Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available.

High-hyperopia database, part I: clinical characterisation including morphometric (biometric) differentiation of posterior microphthalmos from nanophthalmos.

UNLABELLED: PURPOSE To characterise and differentiate posterior microphthalmos (PM) and nanophthalmos (NO) using morphometric parameters.Patients and methodsConsecutive case database of patients with hyperopia >+7.00 D sphere was analysed retrospectively for clinical and biometric characterisation. Thirty-eight consecutive high-hyperopic subjects (75 eyes) with axial lengths <20.5 mm underwent uniform comprehensive ocular evaluation. Twenty-five subjects were diagnosed as PM and 13 as NO based on the horizontal corneal diameter. Parameters analysed included visual acuity, refraction, horizontal corneal diameter, anterior chamber depth, lens thickness, axial length, fundus changes, and associated ocular pathology. PRIMARY OUTCOME MEASURES: ocular biometry difference between PM and NO. SECONDARY OUTCOME MEASURES: differences in associated ocular pathologies between PM and NO.RESULTS Hyperopia ranged from +7 to +17 D and was similar in the two groups. Lens thickness was statistically more in NO than in PM group (4.53±0.75 mm vs 3.82±0.48 mm, P <0.001), whereas anterior chamber depth was more in the PM than in NO group (3.26±0.36 mm, vs 2.59±0.37 mm, P<0.001). NO had higher association with angle-closure glaucoma (66.7% vs 0%) and pigmentary retinopathy (38.5 vs 8.0%) but lesser association with macular folds (0% vs 24%) as compared with PM. NO was associated with poorer visual acuity.CONCLUSION PM and NO have significant differences in lens thickness, anterior chamber depth, prevalence of glaucoma, pigmentary retinopathy, macular pathology, and visual acuity while being similar in hyperopic refraction.

Retinal nerve fiber layer evaluation of spectral domain optical coherence tomograph and scanning laser polarimeter to diagnose glaucoma.

PURPOSE: To compare the abilities of retinal nerve fiber layer (RNFL) parameters of spectral domain optical coherence tomograph (SDOCT) and scanning laser polarimeter (GDx enhanced corneal compensation; ECC) in detecting glaucoma. METHODS: In a cross-sectional study, 215 eyes of 165 subjects (106 eyes of 79 glaucoma patients and 109 eyes of 86 controls) referred by general ophthalmologists for glaucoma evaluation underwent RNFL imaging with SDOCT and GDx ECC. Ability of RNFL parameters of SDOCT to discriminate glaucoma eyes from control eyes was compared with that of GDx ECC using area under operating characteristic curves (AUCs), sensitivities at fixed specificities, and likelihood ratios (LRs). RESULTS: AUC of the average RNFL thickness of SDOCT to differentiate glaucoma from control eyes (0.868) was comparable (P=0.32) to that of GDx ECC (0.855). Sensitivity at 95% specificity was 63.2% for average RNFL thickness of SDOCT and 48.1% for the average RNFL measurement of GDx ECC. LRs of outside normal limits category of SDOCT parameters ranged between 5.6 and 7.7 while the same of GDx ECC parameters ranged between 3.1 and 3.7. LRs of within normal limits category of SDOCT parameters ranged between 0.18 and 0.24 while the same of GDx ECC parameters ranged between 0.20 and 0.32. CONCLUSION: Though AUCs and sensitivities at fixed specificities were comparable between the RNFL parameters of SDOCT and GDx ECC in diagnosing glaucoma, LRs indicated that the RNFL parameters of SDOCT were better in 'ruling in' glaucoma.

Agreement between event-based and trend-based glaucoma progression analyses.

PURPOSE: To evaluate the agreement between event- and trend-based analyses to determine visual field (VF) progression in glaucoma. METHODS: VFs of 175 glaucoma eyes with ≥5 VFs were analyzed by proprietary software of VF analyzer to determine progression. Agreement (κ) between trend-based analysis of VF index (VFI) and event-based analysis (glaucoma progression analysis, GPA) was evaluated. For eyes progressing by event- and trend-based methods, time to progression by two methods was calculated. RESULTS: Median number of VFs per eye was 7 and follow-up 7.5 years. GPA classified 101 eyes (57.7%) as stable, 30 eyes (17.1%) as possible and 44 eyes (25.2%) as likely progression. Trend-based analysis classified 122 eyes (69.7%) as stable (slope >-1% per year or any slope magnitude with P>0.05), 53 eyes (30.3%) as progressing with slope <-1% per year, P≤0.05 (sensitive criteria), and 37 eyes (21.1%) as progressing with slope <-1% per year, P≤0.01 (specific criteria). κ between sensitive criteria of GPA (possible combined with likely progression) and trend-based analysis was 0.48, and between specific criteria of GPA (possible clubbed with no progression) and trend-based analysis was 0.50. In eyes progressing by sensitive criteria of both methods (42 eyes), median time to progression by GPA (4.9 years) was similar (P=0.30) to trend-based method (5.0 years). This was also similar in eyes progressing by specific criteria of both methods (25 eyes; 5.6 years versus 5.9 years, P=0.23). CONCLUSION: Agreement between event- and trend-based progression analysis was moderate. GPA seemed to detect progression earlier than trend-based analysis, but this wasn't statistically significant.

Retinal nerve fiber layer and macular inner retina measurements by spectral domain optical coherence tomograph in Indian eyes with early glaucoma.

PURPOSE: To compare the diagnostic abilities of peripapillary retinal nerve fiber layer (RNFL) and macular inner retina (MIR) measurements by spectral domain optical coherence tomography (SD-OCT) in Indian eyes early glaucoma. METHODS: In an observational, cross-sectional study, 125 eyes of 64 normal subjects and 91 eyes of 59 early glaucoma patients underwent RNFL and MIR imaging with SD-OCT. Glaucomatous eyes had characteristic optic nerve and RNFL abnormalities and correlating visual field defects and a mean deviation of better than or equal to -6 dB on standard automated perimetry. Areas under the receiver operating characteristic curves (AUC), sensitivities at a fixed specificity and likelihood ratios (LRs) were estimated for all RNFL and MIR parameters. RESULTS: The AUCs for the RNFL parameters ranged from 0.537 for the temporal quadrant thickness to 0.821 for the inferior quadrant RNFL thickness. AUCs for the MIR parameters ranged from 0.603 for the superior minus inferior MIR thickness average to 0.908 for ganglion cell complex focal loss volume (GCC-FLV). AUC for the best MIR parameter (GCC-FLV) was significantly better (P<0.001) than that of the best RNFL parameter (inferior quadrant thickness). The sensitivities of these parameters at high specificity of 95%, however, were comparable (52.7% vs58.2%). Evaluation of the LRs showed that outside normal limits results of most of the RNFL and MIR parameters were associated with large effects on the post-test probability of disease. CONCLUSION: MIR parameters with RTVue SD-OCT were as good as the RNFL parameters to detect early glaucoma.

Asthma as a hidden disease in rural China: opportunities and challenges of standard case management.

OBJECTIVE: To assess the implementation of standard case management of asthma in Huaiyuan County, Anhui Province, China, in 2008. DESIGN: The study project began with the local adaptation of international asthma guidelines, followed by a situation analysis, pre-intervention study, training and intervention. Inhaled beclomethasone (US$15 for a 200-puff [250 µg/puff] inhaler) was prescribed for patients with persistent asthma. Treatment outcome was assessed at 1 year after enrolment. RESULTS: Asthma was never diagnosed in the participating facilities before the project was introduced. Of the 95 patients diagnosed with persistent asthma, 72 (75.8%) were prescribed inhaled beclomethasone, and 23 (24.2%) were not, because they either refused to use inhaled beclomethasone or did not return after the initial visit. At 1 year evaluation, of the 72 patients with persistent asthma treated with inhaled corticosteroids, 12 (16.7%) improved, 7 (9.7%) remained stable, none were worse, 1 (1.4%) had died, and 52 (72.2%) were lost to follow-up. Of the 52 patients lost to follow-up, 25 (48%) were found to be alive but had stopped using inhaled beclomethasone. CONCLUSION: Asthma is more frequently disabling and costly than had been recognised earlier. Asthma patients can be provided the care that they require, but affordable access to inhaled corticosteroids remains a challenge.

Bronchioloalveolar carcinoma mimicking miliary tuberculosis.

A case of bronchioloalveolar carcinoma, with widespread dissemination to both lungs and miliary mottling on chest X-ray is reported in a 40 year old male.

[Primary giant cell malignant fibrous histiocytoma of the lung].

A case of primary giant cell malignant fibrous histiocytoma (MFH) of the lung was reported. Gross findings showed two well demarcated isolated nodules located in the right lower lobe of the lung appeared yellowish-gray and gray-red on gross section with areas of focal calcifications, hemorrhage and necrosis. Microscopic findings showed that the tumor consisted of diffuse neoplastic histiocytes and spindle-shaped fibroblasts arranged in a prominent storiform pattern intermingled with numerous multinucleated tumor giant cells and osteoclast-like multinucleated giant cells. Focal osteoid tissue was mainly located at the periphery of the tumor. In addition, a number of scattered apoptotic multinucleated giant cells were observed. Tumor cells were positive for vimentin, alpha-1-antitrypsin, lysozyme and mac387, but negative for cytokeratin, actin, S-100, NSE, and NF. Primary giant cell MFH of the lung is a very rare malignant tumor. This tumor should be treated by prompt radical surgery.

[Preliminary study on 4 indices of basal body temperature in the evaluation of luteal phase insufficiency after clomiphene treatment].

The luteal phase insufficiency after Clomiphene treatment in 90 patients with polycystic ovary syndrome (PCOS) and other menstrual disorders was evaluated by four indices of BBT. The four indices of BBT are (1) BBT curve classification; (2) High phase score (HPS); (3) Planimetric nidation index (PNI); (4) Length of follicular phase. 90 patients (248 cycles) were divided into two groups: non-pregnant group (214 cycles) and pregnant group (34 cycles). The result indicated that 70% cycles of non-pregnant group, the types of BBT are type III-VI, HPS is less than 9; the mean value of PNI is 45.7; the follicular phase lists beyond 17 days, with a mean of 18.6 days. More than two-thirds of the study cycles are abnormal at least in two indices. In all cycles of the pregnant group, BBT curve are of type I, II, HPS greater than 9, PNI greater than 57. The results suggest that measurement of the four indices of BBT is a simple method which could be widely used for the evaluation of luteal phase insufficiency.