Expression of CD6 in Aggressive NK/T-cell Neoplasms and Assessment as a Potential Therapeutic Target: A Bone Marrow Pathology Group Study.

BACKGROUND: Aggressive NK/T-Cell neoplasms are rare hematological malignancies characterized by the abnormal proliferation of NK or NK-like T (NK/T) cells. CD6 is a transmembrane signal transducing receptor involved in lymphocyte activation and differentiation. This study aimed to investigate the CD6 expression in these malignancies and explore the potential of targeting CD6 in these diseases. MATERIALS AND METHODS: We conducted a retrospective study with totally 41 cases to investigate the expression of CD6 by immunohistochemistry, including aggressive NK-cell leukemia/lymphoma (ANKLL: N = 10) and extranodal NK/T-cell lymphoma (ENKTL: N = 31). A novel ANKLL model was applied for proof-of-concept functional studies of a CD6 antibody-drug-conjugate (CD6-ADC) both in vitro and in animal trial. RESULTS: CD6 was expressed in 68.3% (28/41) of cases (70% (7/10) of ANKLL and 67.7% (21/31) of ENKTL). The median overall survival (OS) for ANKLL and ENTKL cases was 1 and 12 months, respectively, with no significant difference in OS based on CD6 expression (p > 0.05, Kaplan-Meier with log-rank test). In vitro exposure of the CCANKL cell line, derived from an ANKL patient, to an anti-CD6ADC resulted in dose dependent induction of apoptosis. Furthermore, CCANKL engraftment in NSG mice could be blocked by treatment with the anti-CD6 ADC. CONCLUSION: To date, this is the first report to explore the expression of CD6 in ANKLL and ENKTL and confirms its expression in the majority of cases. The in vitro and in vivo data support further investigation of CD6 as a potential therapeutic target in these aggressive NK/T-cell malignancies.

Triple-Negative Primary Myelofibrosis: A Bone Marrow Pathology Group Study.

Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm driven by canonical gene mutations in JAK2, CALR, or MPL in >80% of the cases. PMF that lacks these canonical alterations is termed triple-negative PMF (TN-PMF). The pathologic and genetic characteristics of TN-PMF compared with those of conventional PMF with canonical driver mutations (DM-PMF) have not been well studied. We aimed to identify clinicopathologic and molecular genetic differences between patients with TN-PMF (n = 56) and DM-PMF (n = 89), all of whom fulfilled the 2016 World Health Organization diagnostic criteria for PMF. Compared with the control group, patients in the TN-PMF group were more likely to have thrombocytopenia and less likely to have organomegaly. The bone marrow in patients with TN-PMF showed fewer granulocytic elements and more frequent dyserythropoiesis. Cytogenetic analysis showed a higher incidence of trisomy 8. Targeted next-generation sequencing revealed a lower frequency of ASXL1 mutations but enrichment of ASXL1/SRSF2 comutations. Our findings demonstrated several clinicopathologic and molecular differences between TN-PMF and DM-PMF. These findings, particularly the observed mutation profile characterized by a higher frequency of ASXL1 and SRSF2 comutation, suggest that at least a subset of TN-PMF may be pathogenetically different from DM-PMF, with potential prognostic implications.

Prognostic Markers and Histologic Subtypes in Patients with Meningeal Carcinomatosis in Breast Cancer.

OBJECTIVE: Meningeal carcinomatosis (MC) is a rare complication in breast cancer patients. It is defined as a diffuse or multifocal leptomeningeal metastasis. STUDY DESIGN: From our institution database, we retrospectively studied 19 patients diagnosed with MC in the cerebrospinal fluid (CSF) in 1997-2015, in order to evaluate tumor prognostic markers, histologic subtypes, and clinical outcome. RESULTS: All patients were female, with a mean age of 53 years (range 36-75 years). The mean interval between diagnosis of breast carcinoma and MC was 28 months (range 6-62 months). The median survival from the time of diagnosis was 2 months (1-51 months). Sixteen cases (84%) were the ductal phenotype, 62% of which were of a high grade (grade 3), and 3 cases (16%) were lobular. Estrogen and progesterone receptors were positive on immunohistochemistry (IHC) in 53 and 33% of patients, respectively. HER2 IHC was positive (3+) in 20% of the cases; all were amplified by fluorescence in situ hybridization. The incidence of MC in triple-negative tumors was 40%. Twelve patients (63%) already had known metastasis at the time of diagnosis. CONCLUSIONS: Most cases of MC are high-grade ductal. MC is more common in triple-negative breast cancers. The outcome of these breast cancer patients with MC was poor. There was no survival difference according to age, histologic subtype, grade, or hormonal or HER2 status.

Anti-Tumor Necrosis Factor-α Induced Systemic Lupus Erythematosus().

Anti-tumor necrosis factor-alpha induced lupus (ATIL) represents a major diagnostic and therapeutic challenge. Most cases of ATIL are caused by infliximab, followed by etanercept and adalimumab. Symptoms can range from common, mild cutaneous lesions to rare, serious pleural or pericardial effusions, deep venous thrombosis, life-threatening pneumonitis, and neuritis. Constitutional symptoms often present in association with positive autoantibody serology. Diagnosis can be considered if there is a temporal relationship between symptoms and anti-tumor necrosis factor-α (TNF- α) therapy and at least one serologic and one non-serologic American College of Rheumatology criteria. Since it is contraindicated to use anti-TNF-α drugs in patients with systemic lupus erythematosus, it is recommended to perform a thorough immunological screening in any patient with polyarthritis to assure accurate diagnosis. In addition, prior to anti- TNF therapy, baseline immunological investigations (including antinuclear antibodies) should be performed, and there should be close follow up to assess the development of lupus manifestations. The main approach in the treatment of ATIL is withdrawal of the offending drug. Traditional therapy with corticosteroids and immunosuppressive agents may be required to achieve full resolution of lupus symptoms. In this review, we discuss the pathogenesis, clinical manifestations, and management of ATIL.

Pediatric burns in Western Saudi Arabia.

OBJECTIVE: To conduct a cross-sectional analysis of the demographical, etiological, clinical pattern, and the outcome of pediatric burn injuries. METHODS: A cross-sectional study of 459 pediatric burn patients admitted to Al-Noor Specialist Hospital in Makkah, Saudi Arabia from January 2008 to December 2010 were evaluated using a structured questionnaire. RESULTS: The mean age was 5.97, and the male to female ratio was 1.5:1. The most common cause was scalding (81.7%). Approximately 92.8% of patients had burn injuries involving 25% of the total body surface area, or less. The mean hospital stay was 9.51 days. Approximately 92% of patients were treated conservatively. CONCLUSION: Toddlers are at high risk of having scald burns. We also noted the number of admissions is increasing every year. Therefore, an effective scientific based prevention program is required.