- Lymphocytic Colitis: Pathologic predictors of response to therapy. [Journal Article]
- HPHum Pathol 2018 Feb 13
- While the presence of intraepithelial lymphocytosis with surface epithelial damage is a unifying feature of lymphocytic colitis, there are non-classical features that create morphologic heterogeneity...
While the presence of intraepithelial lymphocytosis with surface epithelial damage is a unifying feature of lymphocytic colitis, there are non-classical features that create morphologic heterogeneity between cases. Limited data are available on the significance of these secondary histologic features. Cases of lymphocytic colitis diagnosed between 2002 and 2013 were identified using the Research Patient Data Registry of a tertiary referral center. Diagnostic biopsy slides were reviewed and evaluated for histologic features of lymphocytic colitis. Clinical data including type of therapy and response to treatment were collected. Chi-square (or Fischer's exact test) and logistic regression analysis were used where appropriate. Thirty-two cases of lymphocytic colitis with complete clinical data and slides available for review were identified. The mean age was 56.4 years, and the female-to-male ratio was 3:2. Eleven (11) patients improved with minimal intervention (Group 1), 14 patients responded to steroid therapy (Group 2), and 7 patients responded to mesalamine, bismuth subsalicylate and/or cholestyramine therapy (Group 3). Histologic differences in the characteristics of the subepithelial collagen table (p=0.018), the severity of lamina propria inflammation (p=0.042) and the presence of eosinophil clusters (p=0.016) were seen between groups 2 and 3. Patients in group 1 were more likely to have mild crypt architectural distortion in their biopsies than patients in groups 2 and 3. Lymphocytic colitis is a heterogeneous disease and the evaluation of histologic factors may help identify various subtypes and predict therapy response.
- Highly similar genomic landscapes in monoclonal B-cell lymphocytosis and ultra-stable chronic lymphocytic leukemia with low frequency of driver mutations. [Journal Article]
- HHaematologica 2018 Feb 15
- Despite the recent discovery of recurrent driver mutations in chronic lymphocytic leukemia, the genetic factors involved in disease onset remain largely unknown. To address this issue, we performed w...
Despite the recent discovery of recurrent driver mutations in chronic lymphocytic leukemia, the genetic factors involved in disease onset remain largely unknown. To address this issue, we performed whole-genome sequencing in 11 individuals with monoclonal B-cell lymphocytosis, both of the low-count and high-count subtypes, and 5 patients with ultra-stable chronic lymphocytic leukemia (>10 years without progression from initial diagnosis). All three entities were indistiguishable at the genomic level exhibiting low genomic complexity and similar types of somatic mutations. Exonic mutations were infrequently identified in putative chronic lymphocytic leukemia driver genes in all settings including low-count monoclonal B-cell lymphocytosis. To corroborate these findings we also performed deep-sequencing in 11 known frequently mutated genes in an extended cohort of 28 monoclonal B-cell lymphocytosis/chronic lymphocytic leukemia cases. Interestingly, shared mutations were detected between clonal B cells and paired polymorphonuclear cells, strengthening the notion that at least a fraction of somatic mutations may occur before disease onset, likely at the hematopoietic stem-cell level. Finally, we identified previously unreported non-coding variants targeting pathways relevant to B-cell and chronic lymphocytic leukemia development, likely associated with the acquisition of the characteristic neoplastic phenotype typical of both monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia.
- [Small vessel-childhood primary angiitis of the central nervous system: a case report and literature review]. [Journal Article]
- ZEZhonghua Er Ke Za Zhi 2018 Feb 02; 56(2):142-147
- Objective: To summarize the clinical and pathological features of small vessel-childhood primary angiitis of the central nervous system (SV-cPACNS), discuss the immune therapy and...
Objective: To summarize the clinical and pathological features of small vessel-childhood primary angiitis of the central nervous system (SV-cPACNS), discuss the immune therapy and increase the attention to brain biopsy in SV-cPACNS.Methods:The clinical data, pathology of brain biopsy, treatment and outcome of an SV-cPACNS patient hospitalized in Beijing Children's Hospital in February 2016 were analyzed retrospectively. The cases reported at Pubmed, CNKI and Wanfang databases from 2007 to 2017 were searched, the clinical and pathological features, immunotherapy and prognosis of the disease were summarized according to the literature review.Results:A 70 months old girl had 6 times relapses during 5 months' disease course. Symptoms included convulsions, limb paralysis, blurred vision and speech difficulty. Multiple cortical lesions were found successively in brain MRI but CT angiography was negative. The pathology of brain biopsy revealed thickening of small vessel walls together with lymphocytic infiltration. After the treatment with rituximab, remission was achieved and remained stable without recurrence in 1 year follow up. A total of 44 pathologically confirmed cases reported in nearly 10 years were retrieved. Male to female ratio was 1∶3.5. The average onset age was 9.8 years. Clinical manifestations included seizures (37/45, 82%), headache (35/45, 78%), cognitive decline (28/45, 62%), speech regression(20/45, 44%), paralysis (15/45, 33%), and so on; 70% (19/27) patients experienced relapses. Erythrocyte sedimentation rate and C-reactive protein slightly elevated, antinuclear antibody and other autoimmune antibodies were mostly negative. Mild lymphocytosis in cerebrospinal fluid was found in 67%(29/43) patients. 53%(23/43) patients had elevated CSF protein level, several had elevated IgG and positive oligoclonal band. Bilateral multifocal lesions were revealed in 80% (36/45) brain MRIs, meanwhile all angiographies were unremarkable. The pathology showed small angiitis and immunohistochemistry positive for CD3 and CD20. Twenty-seven patients had detailed therapeutic information; 25 of them received immunosuppressive agents, including cyclophosphamide, mycophenolate mofetil and rituximab. One patient died, 26 patients achieved remission with 54% (22/44) had neurological sequelae.Conclusions:SV-cPACNS had varied clinical manifestations, there was no specificity in laboratory and imaging examination and angiography was often negative. The definite diagnosis relied on brain biopsy, which showed lymphocytic inflammation of small vessels. SV-cPACNS tended to relapse and induce neurologic deterioration. Treatment required long-term use of steroids and immunosuppressive agents. Rituximab could be an effective agent.
- Increased Aqueous Humor CD4+/CD8+ Lymphocyte Ratio in Sarcoid Uveitis. [Journal Article]
- OIOcul Immunol Inflamm 2018 Feb 08; :1-8
- CONCLUSIONS: Increased aqueous humor CD4+/CD8+ ratio in sarcoid uveitis. Immunophenotyping of localized lymphocytosis in aqueous humor could be utilized as an additional confirmatory marker for ocular sarcoidosis.
- Outcomes of a large cohort of individuals with clinically ascertained high-count monoclonal B-cell lymphocytosis. [Journal Article]
- HHaematologica 2018 Feb 01
- Sequential development of monoclonal B cell lymphocytosis-derived small lymphocytic lymphoma and plasma cell leukemia. [Letter]
- AHAnn Hematol 2018 Feb 07
- Reasons for initiation of treatment and predictors of response for patients with Rai stage 0/1 chronic lymphocytic leukemia (CLL) receiving first-line therapy: an analysis of the Connect®CLL cohort study. [Journal Article]
- LLLeuk Lymphoma 2018 Feb 07; :1-9
- A 'watch-and-wait' strategy is recommended for most patients with early-stage chronic lymphocytic leukemia (CLL) prior to treatment initiation. In the Connect®CLL registry, a prospective observationa...
A 'watch-and-wait' strategy is recommended for most patients with early-stage chronic lymphocytic leukemia (CLL) prior to treatment initiation. In the Connect®CLL registry, a prospective observational cohort study of 1494 patients treated in 199 US centers, median time to first-line treatment initiation was 3.8, 1.5, and 0.6 years for patients with Rai stage 0, 1, and ≥2, respectively. Only 60% of patients with Rai stage 0/1 underwent FISH/cytogenetic testing prior to initiation of a new line of therapy. Lymphocytosis and lymphadenopathy were the most common reasons for treatment initiation. Lymphocytosis as a reason for treatment initiation was associated with inferior event-free survival at Rai stage 0/1. Short treatment duration was associated with inferior overall survival regardless of Rai stage; sensitivity analyses confirmed the association. The Connect CLL registry provides valuable information on a real-world population of patients with CLL, clarifying both the timing and rationale for initiating therapy.
- The role of mTOR-mediated signaling in the regulation of cellular migration. [Review]
- ILImmunol Lett 2018 Feb 03; 196:74-79
- Mechanistic target for rapamycin (mTOR) is a serine/threonine protein kinase that forms two distinct complexes mTORC1 and mTORC2, integrating mitogen and nutrient signals to regulate cell survival an...
Mechanistic target for rapamycin (mTOR) is a serine/threonine protein kinase that forms two distinct complexes mTORC1 and mTORC2, integrating mitogen and nutrient signals to regulate cell survival and proliferation; processes which are commonly deregulated in human cancers. mTORC1 and mTORC2 have divergent molecular associations and cellular functions: mTORC1 regulates in mRNA translation and protein synthesis, while mTORC2 is involved in the regulation of cellular survival and metabolism. Through AKT phosphorylation/activation, mTORC2 has also been reported to regulate cell migration. Recent attention has focused on the aberrant activation of the PI3K/mTOR pathway in B cell malignancies and there is growing evidence for its involvement in disease pathogenesis, due to its location downstream of other established novel drug targets that intercept B cell receptor (BCR) signals. Shared pharmacological features of BCR signal inhibitors include a striking "lymphocyte redistribution" effect whereby patients experience a sharp increase in lymphocyte count on initiation of therapy followed by a steady decline. Chronic lymphocytic leukemia (CLL) serves as a paradigm for migration studies as lymphocytes are among the most widely travelled cells in the body, a product of their role in immunological surveillance. The subversion of normal lymphocyte movement in CLL is being elucidated; this review aims to describe the migration impairment which occurs as part of the wider context of cancer cell migration defects, with a focus on the role of mTOR in mediating migration effects downstream of BCR ligation and other microenvironmental signals.
- Lamotrigine-induced drug reaction with eosinophilia and systemic symptoms (DRESS) during primary Epstein-Barr virus (EBV) infection. [Journal Article]
- BCBMJ Case Rep 2018 Jan 23; 2018
- Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, potentially life-threatening idiosyncratic drug reaction that may result in skin eruption, mucous membrane involvement, eosi...
Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, potentially life-threatening idiosyncratic drug reaction that may result in skin eruption, mucous membrane involvement, eosinophilia, atypical lymphocytosis and lymphadenopathy, with wide-ranging internal organ involvement. The authors report the case of a 21-year-old man who was prescribed lamotrigine for anxiety disorder. After 2 weeks of treatment, he developed a pruritic morbilliform rash on his trunk and upper extremities that was associated with fever, sore throat, bilateral scleral injection, nausea, vomiting and abdominal pain. A laboratory work-up revealed elevated transaminases and atypical lymphocytosis. He was found to have an active Epstein-Barr virus infection. Lamotrigine was discontinued due to suspicion of DRESS; the patient received pulsed intravenous methylprednisolone followed by oral prednisone taper, which resulted in a significant improvement of symptoms. At follow-up 3 weeks later, signs and symptoms had completely resolved. Follow-up laboratory tests revealed that liver dysfunction had normalised.
New Search Next
- HIV gp120 in Lungs of ART-treated Individuals Impairs Alveolar Macrophage Responses To Pneumococci. [Journal Article]
- AJAm J Respir Crit Care Med 2018 Jan 24
- CONCLUSIONS: Despite ART, HIV-1, via gp120, drives persisting innate immune defects in AM microbicidal mechanisms, enhancing susceptibility to pneumococcal disease.