Interpreting flow cytometry with caution: A case report of follicular lymphoma in leukemic phase misdiagnosed as chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is a subtype of mature B-cell proliferative neoplasms characterized by abnormally increasing lymphocytes in circulation. The diagnosis of CLL is usually established on peripheral blood analysis and typical flow cytometric immunophenotype rather than biopsy. In particular, the high RMH (Royal Marsden Hospital Scoring System for CLL) score of immunophenotype has a highly sensitive weight for diagnostic value. However, immunophenotyping by flow cytometry may also be misleading in specific clinical situations. Here, we report a case on admission with lymphadenopathy and lymphocytosis, misdiagnosed as chronic lymphocytic leukemia by flow cytometry initially but finally confirmed as follicular lymphoma (FL) in the leukemic phase via lymph node biopsy. Since FL in the leukemic phase is uncommon at the time of diagnosis and indicates a poorer prognosis of FL, such misdiagnosis is worthy of attention. It is also thought-provoking that there had been conflicts between immunophenotype of bone marrow and immunohistochemistry of lymph node. Our case report aims to remind clinicians’ awareness that the immunophenotyping by flow cytometric analysis needs to be interpreted with caution especially when the results cannot account for all of clinical features, and it is significant to make the right decision about when to conduct further examination including lymph node biopsy for avoiding misdiagnosis

Circulating cell-free DNA and IL-10 from cerebrospinal fluids aid primary vitreoretinal lymphoma diagnosis

Primary vitreoretinal lymphoma (PVRL) is a rare variant of primary central nervous system lymphoma (PCNSL) that presents diagnostic challenges. Here, we focused on circulating cell-free DNA (cfDNA) and interleukin-10 (IL-10) isolated from cerebrospinal fluid. Twenty-three VRL patients (17 PVRL, 2 PCNSL/O, and 4 relapsed VRL, from 10/2018 to 12/2021) and 8 uveitis patients were included in this study. CSF samples from 19 vitreoretinal lymphoma patients had sufficient cfDNA for next-generation sequencing. Of these patients, 73.7% (14/19) had at least one meaningful non-Hodgkin lymphoma-related mutation. The characteristic MYD88L265P mutation was detected in the CSF of 12 VRL patients, with a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 63.2%, 100%, 100%, and 46.2%, respectively. No meaningful lymphoma related mutations were found in CSF samples from uveitis controls with typical intraocular lesions. Meanwhile, CSF IL-10 levels were elevated in 95.7% of the VRL patients, with a sensitivity, specificity, PPV, and NPV of 95.7%, 100%, 100% and 88.9%, respectively. Key somatic mutations like MYD88L265P and CD79B detected from CSF cfDNA and elevated CSF IL-10 levels can be promising adjuncts for primary vitreoretinal lymphoma diagnosis

Comparative study of endometrioid borderline ovarian tumor with and without endometriosis

Abstract Background Synchronous endometriosis has been poorly studied in women with endometrioid borderline ovarian tumors (EBOTs). The aims of this study were to compare the clinicopathological features and prognosis of EBOTs with or without endometriosis. Results Of 52 patients diagnosed with EBOTs, no death was observed and only one case had successful pregnancy during the follow-up period. Older, menopausal EBOT patients, EBOT patients with small tumors and relatively low CA125 level probably had better progression-free survival (PFS) outcomes. About 1/3 of EBOTs had concomitant endometrial lesions. Approximately 1/3 of EBOTs were associated with endometriosis. Patients were divided into two groups according to the presence or not of endometriosis in this retrospective cohort study. Patients with endometriosis-associated endometrioid borderline ovarian tumor (EAEBOT) were more likely to be younger and premenopausal. Variables such as PFS outcomes, endometrial lesions did not differ statistically between groups. However, in specific EBOT patients like parous patients, patients with CA125 ≥ 140 U/ml or patients without fertility sparing surgery, coexisting endometriosis perhaps predicted worse PFS outcomes. Conclusion We considered EAEBOT as an entity similar to non-EAEBOT. Closely follow-up for some particular patients with concomitant endometriosis was necessary

Characterizations and Assays of α-Glucosidase Inhibition Activity on Gallic Acid Cocrystals: Can the Cocrystals be Defined as a New Chemical Entity During Binding with the α-Glucosidase?

Cocrystallization with co-former (CCF) has proved to be a powerful approach to improve the solubility and even bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). However, it is still uncertain whether a cocrystal would exert the pharmacological activity in the form of a new chemical entity, an API-CCF supramolecule. In the present study, gallic acid (GA)-glutaric acid and GA-succinimide cocrystals were screened. The solubility, dissolution rate and oral bioavailability of the two cocrystals were evaluated. As expected, AUCs of GA-glutaric acid and GA-succinimide cocrystals were 1.86-fold and 2.60-fold higher than that of single GA, respectively. Moreover, experimental evaluations on α-glucosidase inhibition activity in vitro and theoretical simulations were used to detect whether the two cocrystals would be recognized as a new chemical entity during binding with α-glucosidase, a target protein in hypoglycemic mechanisms. The enzyme activity evaluation results showed that both GA and glutaric acid displayed α-glucosidase inhibition activity, and GA-glutaric acid cocrystals showed strengthened α-glucosidase inhibition activity at a moderate concentration, which is attributed to synergism of the two components. Molecular docking displayed that the GA-glutaric acid complex deeply entered the active cavity of the α-glucosidase in the form of a supramolecule, which made the guest-enzyme binding configuration more stable. For the GA and succinimide system, succinimide showed no enzyme inhibition activity, however, the GA-succinimide complex presented slightly higher α-glucosidase inhibition activity than that of GA. Molecular docking simulation indicated that the guest molecules entering the active cavity of the α-glucosidase were free GA and succinimide, not the GA-succinimide supramolecule

Clinical characteristics and prognosis of cystic degeneration in retroperitoneal schwannoma: A retrospective study of 79 patients

Abstract Background and Purpose Diagnosis of retroperitoneal schwannoma (RS), especially cystic RS, is frequently missed or delayed owing to its rarity, location, nonspecific symptoms, and similarities with other tumors on various imaging modalities. This study aimed to determine associations between clinical, radiological, and histopathologic features and outcome. Materials and Methods Seventy‐nine patients with pathologically confirmed RS who underwent tumor resection between June 2010 and June 2020 were retrospectively reviewed and analyzed. Patients were stratified into three groups according to degree of tumoral cystic degeneration. Results Cystic degeneration was significantly associated with multiple foci (p = 0.025), calcification (p = 0.012), and hemorrhage (p = 0.000), but not size (p = 0.08), high Ki‐67 (p = 0.094), malignancy (p = 0.115; prevalence of cystic degeneration in the benign and malignant groups were 53.9% vs 100%), rough margin (p = 0.162), or irregular shape (p = 0.369). Malignant RS was significantly associated with multiple lymph nodes enlargement (p = 0.034). Tumor size, margins, shape, or/and multiplicity did not significantly differ between benign and malignant tumors. No recurrence occurred in patients with benign RS (mean follow‐up, 45 months). All malignant tumors recurred; mean time to recurrence was 11.4 months (mean follow‐up, 33 months). Conclusion Since RS is misdiagnosed mostly as malignancy and diagnosis is often delayed, a suspicion is necessary for diagnosis when atypical features are present. In RS, cystic degeneration was not associated with tumor size, Ki‐67, or malignancy; however, it was significantly associated with multiple foci, calcification, and hemorrhage. Cystic degeneration and related factors are useful for the diagnosis of RS. Malignant RS should be considered when a mass involves multiple lymph nodes. Margins, morphology, and size are not associated with malignancy. Pathological tumor type, tumor location, and adjacent anatomic structures are associated with outcome

Growing Teratoma Syndrome with Synchronous Gliomatosis Peritonei during Chemotherapy in Ovarian Immature Teratoma: A Case Report and Literature Review

Coexistent growing teratoma syndrome (GTS) and gliomatosis peritonei (GP) arising during chemotherapy of ovarian immature teratoma (IMT) is extremely rare and can be misdiagnosed as recurrent or progressive disease. We present a 33-year-old woman diagnosed with GTS with synchronous GP during chemotherapy of IMT. She underwent ovarian cystectomy due to ovarian immature teratoma and chemotherapy were administered. The α-fetoprotein (AFP) concentration decreased from 28.7 ng/mL to normal after the second cycle. Four days after the third cycle of chemotherapy, ultrasound and CT revealed an 8-cm mass with negative tumor markers in the pouch of Douglas. An exploratory laparotomy was conducted, and a smooth round cystic-solid 8-cm mass was noted in the pouch of Douglas. Extensive peritoneal seeding glial nodules were also observed on the surface of the uterus, peritoneum, and omentum. The patient underwent a partial omentectomy, intact resection of the tumor, and resection of most of the glial nodules. Postoperative pathology demonstrated a pure mature cystic teratoma component in the mass, as well as diffuse GP involving the uterine serosa, peritoneum, and omentum; this diagnosis of GTS with synchorous GP should be considered in IMT patients with mass newly identified during chemotherapy while tumor markers are normal after treatment

Neuroendocrine Neoplasms of the Gallbladder: A Clinicopathological Analysis of 13 Patients and a Review of the Literature

Objectives. Mixed neuroendocrine–non-neuroendocrine neoplasms (MiNENs) are rare gallbladder neuroendocrine neoplasms (GB-NENs). This study is aimed at investigating the clinicopathological features of GB-NENs and identifying prognostic factors related to overall survival (OS) of GB-MiNENs. Methods. The clinical data and pathological features of 13 patients with GB-NENs in our hospital were retrospectively reviewed. Additionally, 41 GB-MiNENs cases reported in English literature were reviewed and survival analysis was performed. Results. The mean age of thirteen patients (6 males and 7 females) with GB-NENs was 57.2 years (range: 35-75 years). Two patients were diagnosed with NET grade 1 (G1), two patients with NEC (large cell/small cell=1/1), and nine patients with MiNENs. Of these 9 patients with MiNENs, 8 had composite tumors and 1 had amphicrine carcinoma. Microscopically, the adenocarcinoma component was located in the surface mucosa, and the neuroendocrine component was in the area of deep invasion, liver infiltration, and lymph node metastasis. Total analysis of 41 GB-MiNENs showed that patients were mainly elderly women (female/male ratio, 2.4 : 1.0; median age, 60 years). Kaplan-Meier’s analysis demonstrated that liver metastasis and TNM stage III-IV were associated with decreased OS (P<0.05), whereas age, sex, tumor size, grade of the neuroendocrine component, lymph node metastasis, and adjuvant chemotherapy were not significantly prognostic indicators of OS. Multivariate analysis identified liver metastasis (hazard ratio=4.262, 95%confidence interval=1.066‐17.044, P=0.040) as an independent unfavorable prognostic factor. Conclusions. GB-MiNENs were the most common type of GB-NENs in our case series, and neuroendocrine components exhibited more aggressive lymph node metastasis and local invasion than adenocarcinoma. Liver metastasis was a poor prognostic indicator in GB-MiNENs patients

Trace metals, organic carbon and nutrients in the Beidagang Wetland Nature Reserve, northern China.

This study aimed to determine sediment contamination in the Beidagang Wetland Nature Reserve to describe atmospheric deposition of trace metals. We analyzed Hg, Cd, Pb, TOC, TN, TP, δ13C, and δ15N, and studied their variations in surface sediments and in the vertical profiles of sediment cores collected from the reserve. Evaluation of environmental trace metal contamination using sediment quality guidelines and geochemical background values indicated that the risk of metal pollution in the reserve sediments was relatively low. Concentrations of Hg, Cd, and Pb in the sediments were much lower than concentrations in sediment samples from Bohai Bay and polluted rivers in Tianjin. Enrichment factors indicate that samples are moderately contaminated with Hg, Cd, and Pb; whereas the geo-accumulation index results classify the sediments as uncontaminated to moderately contaminated with Hg, Cd, and Pb. The distribution patterns of trace metal concentrations in the three core samples were uniform. δ13C and δ15N were used to track the sources of TOC and TN in sediments. Results show that TOC mainly originated from the residue and decaying matter of aquatic plants (e.g., algae, reeds, and Typha), while TN was derived from soil N and elevated atmospheric N deposition. Because domestic and industrial waste is not discharged into the Beidagang Wetland Nature Reserve, trace metals found in sediments mainly originate from atmospheric deposition. The results provide baseline data for analysis of trace metal accumulation in Beijing-Tianjin-Hebei, a region subject to atmospheric deposition in northern China