CASE PRESENTATION: A 30-year-old man was retrieved from the jungle with severe weight loss and abdominal symptoms. He succumbed to death despite 22 days of intensive medical treatment. An autopsy revealed a ruptured gangrenous ileal volvulus with peritonitis and subdiaphragmatic abscess. Further laboratory analysis detected systemic Candida tropicalis and intestinal gramnegative bacterial sepsis, systemic Zika virus viremia, leptospirosis complicating rhabdomyolysis and disseminated intravascular coagulopathy, Type I Herpes Simplex virus infection of the tongue and upper gastrointestinal tract. The cause of death was the ruptured ileal volvulus, complicated with upper gastrointestinal bleeding due to Herpes simplex virus esophagitis in a malnourished patient with resolving leptospirosis and underlying Zika virus co-infection.
CONCLUSION: Rare clinical scenarios of adult-onset intestinal volvulus with concomitant multiple infections precludes clinical diagnosis and early treatment, leading to devastating consequences of clinical outcome. The positive clinical and postmortem correlation is a good learning lesson in many disciplines of medicine and science.
MATERIALS AND METHODS: The study comprised a retrospective analysis of patients with DLBCL treated at a single centre. The outcome was compared with patients who were treated with R-CHOP like and CHOP like chemotherapy. Patients who were treated with lower dose of rituximab was subanalysed for outcome.
RESULTS: A total of 86 patients who had CHOP-like chemotherapy were included. Only 39 (45%) patients had rituximab and only 12 (29%) patients had the recommended dose. The overall response (OR) and complete response (CR) rates were 88% and 81% respectively. There was no significant difference in OR and CR in patients who had rituximab and those without rituxmab. Those with International Prognostic Index (IPI) score of ≤ 2 had significant higher CR rate, progression free survival (PFS) and overall survival (p<0.001).
CONCLUSIONS: The lack of significant improvement in CR and DFS in our patients may be due to an inadequate dose of rituximab.
Case presentation: A 68-year-old gentleman of Malay ethnicity presented with left sided weakness associated with reduced sensation for one month. The patient was healthy and denied any constitutional symptoms, joint pains, rash or seizures. There was no recent trauma. Physical examination revealed left upper and lower limb motor grade power of 3/5 with upper motor neurone weakness of the left facial nerve. He had brisk reflexes and an upgoing extensor plantar response. Brain imaging (Magnetic Resonance Imaging) showed two lesions: one occupying the right head of the caudate nucleus and the other seen at the right side of the body of the corpus callosum. Histomorphology and immunohistochemistry confirmed Diffuse Large B-Cell Lymphoma (DLBCL) of non-germinal center type. He was treated with De Angelis protocol which involves chemoradiotherapy consisting of high dose methotrexate and whole brain radiotherapy (WBRT), followed by high dose cytarabine. Brain imaging post chemoradiation showed complete remission.
Conclusion: Prompt detection with appropriate therapeutic protocol could significantly minimise the permanent neurological deficits in patients with this rare and challenging lymphoid malignancy.
METHODS AND RESULTS: Analysis of publicly available DLBCL microarray data sets showed that TRPM4 transcripts were up-regulated in DLBCL compared to normal germinal centre B (GCB) cells, were expressed more highly in the activated B cell-like DLBCL (ABC-DLBCL) subtype and higher TRPM4 transcripts conferred worse overall survival (OS) in R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone)-treated DLBCL cases (P < 0.05). Our immunohistochemical analysis showed that TRPM4 was expressed in various human tissues but not in normal B cells within lymphoid tissues (reactive tonsil, lymph node and appendix). TRPM4 protein was present in 26% (n = 49 of 189) of our cohort of R-CHOP-treated DLBCL cases and this was associated significantly with more aggressive clinical parameters, including higher lactate dehydrogenase (LDH), Eastern Cooperative Oncology Group (ECOG) scores or stage (P < 0.01 for each of the parameters) and the ABC-DLBCL subtype (P = 0.016). TRPM4 positivity conferred significantly worse OS (P = 0.004) and progression-free survival (PFS) (P = 0.005). Worse OS remained associated significantly with TRPM4 positivity in multivariate analysis, including higher International Prognostic Index (IPI) or the non-GCB DLBCL phenotype (P < 0.05).
CONCLUSIONS: TRPM4 protein expression is up-regulated in DLBCL cases compared to non-malignant B cells with preferential expression in ABC-DLBCL cases, and it confers significantly poorer DLBCL patient outcomes.
METHODS: 79 patients with DLBCL (nodal, 59% and extranodal, 41%) treated with rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) therapy were selected. Expression levels of BCR and linked signalling pathway molecules were inter-related with Lymph2Cx-based cell of origin (COO) types and overall survival (OS).
RESULTS: Activated B-cell (ABC) type DLBCL constituted 49% (39/79) compared with germinal centre B-cell (GCB) type DLBCL (29/79; 37%) and revealed poor prognosis (p=0.013). In ABC-DLBCL, high BTK expression exerted poor response to R-CHOP, while OS in ABC-DLBCL with low BTK expression was similar to GCB-DLBCL subtype (p=0.004). High LYN expression coupled with a poor OS for ABC-DLBCL as well as GCB-DLBCL subtypes (p=0.001). Furthermore, high coexpression of BTK/LYN (BTKhigh/LYNhigh) showed poor OS (p=0.019), which linked with upregulation of several genes associated with BCR repertoire and nuclear factor-kappa B pathway (p<0.01). In multivariate analysis, high BTK and LYN expression retained prognostic significance against established clinical predictive factors such as age, International Prognostic Index and COO (p<0.05).
CONCLUSIONS: Our data provide a clear association between high BCR activity in DLBCL and response to therapy in a distinct population. Molecular data provided here will pave the pathway for the provision of promising novel-targeted therapies to patients with DLBCL in Southeast Asia.
CONCLUSION: Optic nerve infiltration in systemic metastatic retinal lymphoma may have initial occult signs but with profound visual loss. Ocular infections like CMV retinitis and tuberculosis may mask and delay the diagnosis in immunocompromised patients.