Adjuvant Radiotherapy for Groin Node Metastases Following Surgery for Vulvar Cancer: A Systematic Review.

Background: Lymph node metastasis in vulvar cancer is a critical prognostic factor associated with higher recurrence and decreased survival. A survival benefit is reported with adjuvant radiotherapy but with potential significant morbidity. We aim to clarify whether there is high-quality evidence to support the use of adjuvant radiotherapy in this setting. Objectives: The aim of the study was to assess the effectiveness and safety of adjuvant radiotherapy to locoregional metastatic nodal areas. Search Methods: We conducted a comprehensive and systematic literature search of MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Google Scholar, ClinicalTrials.gov, and the National Cancer Institute. We considered only randomized controlled trials (RCTs). Main Results: We identified 1,760 records and finally retrieved only one eligible RCT (114 participants with positive inguinofemoral lymph nodes). All women had undergone radical vulvectomy and bilateral inguinal lymphadenectomy and had been randomized to adjuvant radiotherapy or to intraoperative ipsilateral pelvic lymphadenectomy without adjuvant radiotherapy. At 6 years, the overall survival (OS) was 51% versus 41% in favor of radiotherapy (HR 0.61; 95% CI 0.30-1.3) without significance and with very low certainty of evidence. At 6 year, the cumulative incidence of cancer-related deaths was 29% versus 51% in favor of adjuvant radiotherapy (HR 0.49; 95% CI 0.28-0.87). Recurrence-free survival at 6 years was 59% after adjuvant radiotherapy versus 48% after pelvic lymphadenectomy (HR 0.39; 95% CI 0.17-0.88). Three (5.3%) versus 13 (24.1%) groin recurrences were noted, respectively, in the adjuvant radiotherapy and pelvic lymphadenectomy groups. There was no significant difference in acute toxicities for pelvic lymphadenectomy compared to radiotherapy. In women with positive pelvic lymph nodes (20%), the OS at 6 year was 36% compared with 13% in favor of adjuvant radiotherapy. Late cutaneous toxicity rate appeared to be greater after radiotherapy (19% vs. 15%) but with less chronic lymphedema (16% vs. 22%). Conclusion: There is only very low-quality evidence on administering adjuvant radiotherapy for inguinal lymph node metastases. Although the identified study was a multicenter RCT, there was a reasonable imprecision and inconsistency because of small study numbers, wide confidence intervals in the data, and early trial closure, resulting in downgrading of the evidence.

Reduced Plasma Levodopa Fluctuations with More Frequent Administration of a Novel Carbidopa/Levodopa Functionally Scored Tablet.

Levodopa/carbidopa remains the gold standard for treating Parkinson disease (PD), but chronic pulsatile administration contributes to motor complications. This Phase 1 study used a new immediate-release (IR) formulation of carbidopa/levodopa 25/100 mg that is functionally scored for easy and precise splitting to evaluate the effects on levodopa plasma variability when smaller doses are taken more frequently. These functionally scored tablets were shown to be bioequivalent to carbidopa/levodopa 25-/100-mg IR generic reference tablets. Twenty-two healthy volunteers received a whole tablet every 4 hours versus half of the tablet every 2 hours. Plasma levodopa fluctuations were significantly reduced with half-tablets dosed every 2 hours, with a 44% reduction in peaks (P < .0001). While drug exposure did not differ, parameters that underlie motor response variations, including mean peak-to-trough difference and variance, were 51% and 56% less, respectively, with more frequent dosing (both P ≤ .0024). Safety and tolerability of both regimens were similar. In conclusion, more frequent administration of half-tablets of the new functionally scored IR formulation safely provided more constant levodopa levels than whole tablets dosed less often. This tablet technology could facilitate the benefits of more physiologic dopamine replenishment in patients with PD, particularly those with reduced manual dexterity.

Combined antifogging and antireflective double nanostructured coatings for LiDAR applications.

To increase the performance of optical systems, a good antireflective coating is required to ensure low reflectance and high transmittance of optical surfaces. Further problems, such as fogging that causes light scattering, negatively affect the image quality. This implies that other functional properties are also required. Presented here is a highly promising combination of an antireflective double nanostructure on top of an antifog coating with long-term stable properties, generated in a commercial plasma-ion-assisted coating chamber. It is demonstrated that the nanostructures do not affect the antifog properties and can be successfully used for many applications.

Assessing Bone Marrow Activity with [18F]FLT PET in Patients with Essential Thrombocythemia and Prefibrotic Myelofibrosis: A Proof of Concept.

Objectives: This study aims to assess the value of FLT-PET as a non-invasive tool to differentiate between patients with ET and Pre-PMF. This study is a pilot study to have a proof of concept only. Methods: This is a prospective, interventional study where a total of 12 patients were included. Each patient underwent FLT PET imaging as well as bone marrow examination (gold standard). In addition, semi-quantitative (SUVmax and SUVmean) measurements of FLT uptake in the liver, spleen, and Lspine, SUVmean, as well as the Total Lesion Glycolysis (TLG) of the Lspine were performed. Results from the two patient cohorts were compared using = Kruskal-Wallis statistical test. A P-value of <.05 is considered to be statistically significant. Results: The differences in FLT SUVmax and SUVmean measurements in the three organs (liver, spleen, and LSpine) between the ET and Pre-PMF patients were not statistically significant (P > .05). In contrast, TLG measurements in the LSpine were statistically different (P = .013), and therefore, compared to gold standard bone marrow results, TLG can separate ET and Pre-PMF patients. Conclusion: This study is a proof of concept about the potential to discriminate between ET and pre-PMF patients in a non-invasive way. TLG of the LSpine in FLT PET images is a potential quantitative parameter to distinguish between ET and pre-PMF patients.

The safety of activated eptacog beta in the management of bleeding episodes and perioperative haemostasis in adult and paediatric haemophilia patients with inhibitors.

INTRODUCTION: Haemophilia patients with inhibitors often require a bypassing agent (BPA) for bleeding episode management. Eptacog beta (EB) is a new FDA-approved recombinant activated human factor VII BPA for the treatment and control of bleeding in haemophilia A or B patients with inhibitors (≥12 years of age). We describe here the EB safety profile from the three prospective Phase 3 clinical trials performed to date. AIM: To assess EB safety, immunogenicity and thrombotic potential in children and adults who received EB for treatment of bleeding and perioperative care. METHODS: Using a randomized crossover design, 27 subjects in PERSEPT 1 (12-54 years) and 25 subjects in PERSEPT 2 (1-11 years) treated bleeding episodes with 75 or 225 µg/kg EB initially followed by 75 µg/kg dosing at predefined intervals as determined by clinical response. Twelve PERSEPT 3 subjects (2-56 years) received an initial preoperative infusion of 75 µg/kg (minor procedures) or 200 µg/kg EB (major surgeries) with subsequent 75 µg/kg doses administered intraoperatively and post-operatively as indicated. Descriptive statistics were used for data analyses. RESULTS: Sixty subjects who received 3388 EB doses in three trials were evaluated. EB was well tolerated, with no allergic, hypersensitivity, anaphylactic or thrombotic events reported and no neutralizing anti-EB antibodies detected. A death occurred during PERSEPT 3 and was determined to be unlikely related to EB treatment by the data monitoring committee. CONCLUSION: Results from all three Phase 3 trials establish an excellent safety profile of EB in haemophilia A or B patients with inhibitors for treatment of bleeding and perioperative use.

PERSEPT 3: A phase 3 clinical trial to evaluate the haemostatic efficacy of eptacog beta (recombinant human FVIIa) in perioperative care in subjects with haemophilia A or B with inhibitors.

INTRODUCTION: Surgical procedures in persons with haemophilia A or B with inhibitors (PwHABI) require the use of bypassing agents (BPA) and carry a high risk of complications. Historically, only two BPAs have been available; these are reported to have variable responses. AIM: To prospectively evaluate the efficacy and safety of a new bypassing agent, human recombinant factor VIIa (eptacog beta) in elective surgical procedures in PwHABI in a phase 3 clinical trial, PERSEPT 3. METHODS: Subjects were administered 200 µg/kg (major procedures) or 75 µg/kg eptacog beta (minor procedures) immediately prior to the initial surgical incision; subsequent 75 µg/kg doses were administered to achieve postoperative haemostasis and wound healing. Efficacy was assessed on a 4-point haemostatic scale during the intra- and postoperative periods. Anti-drug antibodies, thrombotic events and changes in clinical/laboratory parameters were monitored throughout the perioperative period. RESULTS: Twelve subjects underwent six major and six minor procedures. The primary efficacy endpoint success proportion was 100% (95% CI: 47.8%-100%) for minor procedures and 66.7% (95% CI: 22.3%-95.7%) for major procedures; 81.8% (95% CI: 48.2%-97.7%) of the procedures were considered successful using eptacog beta. There was one death due to bleeding from a nonsurgical site; this was assessed as unlikely related to eptacog beta. No thrombotic events or anti-eptacog beta antibodies were reported. CONCLUSION: Two eptacog beta dosing regimens in PwHABI undergoing major and minor surgical procedures were well-tolerated, and the majority of procedures were successful based on surgeon/investigator assessments. Eptacog beta offers clinicians a new potential therapeutic option for procedures in PwHABI.

P190 BCR-ABL1 in a Patient with Philadelphia Chromosome Positive T-Cell Acute Lymphoblastic Leukemia: A Rare Case Report and Review of Literature.

T-acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) is rare and aggressive leukemia. Philadelphia chromosome positive (Ph+) is the most common cytogenetic abnormality in chronic myeloid leukemia (CML) and B-acute lymphoblastic leukemia (B-ALL). Ph+ T-ALL is exceeding rare and has a therapeutic and prognostic significance. The incidence and outcome of Ph+ T-ALL are unknown. Differentiation between Ph+ T-ALL/LBL and T-cell lymphoblastic crises of CML may be difficult. We report a rare case of adult de novo T-ALL with significant monocytosis, having Ph+ with (P190 BCR-ABL1) as a cytogenetic abnormality. He was treated with ALL induction chemotherapy and imatinib and achieved complete remission, then relapsed twice and expired shortly after the last CNS relapse.

Aberrant Acquisition of T-cell Associated Markers in Plasma Cell Neoplasms: An Aggressive Disease with Extramedullary Involvement and Very Short Survival.

BACKGROUND: Plasma cell neoplasms can show aberrant expression of different lineage-related antigens; however, co-expression of T-cell-associated markers on malignant plasma cells is extremely rare. MATERIAL AND METHODS: This report describes clinicopathologic characteristics of three myeloma patients with emergent plasmablastic morphology and aberrant acquisition of T-cell-associated markers diagnosed in our center. An extensive literature search for similar cases was conducted, and the relevant pathologic, clinical, and prognostic characteristics were summarized. RESULTS: A total of 22 cases of plasma cell neoplasm (including the three cases reported here) showed aberrant co-expression of T-cell markers. We found an evident association between aberrant expression of T-cell markers on malignant plasma cells and extramedullary involvement, aggressive morphologic features, high proliferative index ki67 >90%, aggressive clinical course, an adverse outcome, and short survival. DISCUSSION & CONCLUSION: Due to the rarity of this aberrant phenotype and scarcity of the published data, the precise causative mechanism and its clinical implications have not yet been elucidated.

TET2 Drives 5hmc Marking of GATA6 and Epigenetically Defines Pancreatic Ductal Adenocarcinoma Transcriptional Subtypes.

BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) is characterized by advanced disease stage at presentation, aggressive disease biology, and resistance to therapy, resulting in an extremely poor 5-year survival rate of <10%. PDAC is classified into transcriptional subtypes with distinct survival characteristics, although how these arise is not known. Epigenetic deregulation, rather than genetics, has been proposed to underpin progression, but exactly why is unclear and is hindered by the technical limitations of analyzing clinical samples. METHODS: We performed genome-wide epigenetic mapping of DNA modifications 5-methylcytosine and 5-hydroxymethylcytosine (5hmc) using oxidative bisulfite sequencing from formalin-embedded sections. We identified overlap with transcriptional signatures in formalin-fixed, paraffin-embedded tissue from resected patients, via bioinformatics using iCluster and mutational profiling and confirmed them in vivo. RESULTS: We found that aggressive squamous-like PDAC subtypes result from epigenetic inactivation of loci, including GATA6, which promote differentiated classical pancreatic subtypes. We showed that squamous-like PDAC transcriptional subtypes are associated with greater loss of 5hmc due to reduced expression of the 5-methylcytosine hydroxylase TET2. Furthermore, we found that SMAD4 directly supports TET2 levels in classical pancreatic tumors, and loss of SMAD4 expression was associated with reduced 5hmc, GATA6, and squamous-like tumors. Importantly, enhancing TET2 stability using metformin and vitamin C/ascorbic acid restores 5hmc and GATA6 levels, reverting squamous-like tumor phenotypes and WNT-dependence in vitro and in vivo. CONCLUSIONS: We identified epigenetic deregulation of pancreatic differentiation as an underpinning event behind the emergence of transcriptomic subtypes in PDAC. Our data showed that restoring epigenetic control increases biomarkers of classical pancreatic tumors that are associated with improved therapeutic responses and survival.

Downregulation of Lymphoid enhancer-binding factor 1 (LEF-1) expression (by immunohistochemistry and/ flow cytometry) in chronic Lymphocytic Leukemia with atypical immunophenotypic and cytologic features.

INTRODUCTION: Lymphoid enhancer-binding factor 1 (LEF-1) overexpression has been recently remarkably reported in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and has shown utility in distinguishing CLL/SLL from other B-cell lymphomas. CLL has a well-defined immunophenotype, yet, some cases of CLL demonstrate atypical morphology/ phenotype reflected by low Matutes score (atypical CLL). Till date, LEF1 expression has not been systematically studied in cases of CLL with atypical features. METHODS: In this study, LEF-1 expression was assessed by two different techniques, (immunohistochemistry and flow cytometry), to investigate the expression profile of LEF-1 in cases of CLL/SLL, in comparison with other low-grade B-lymphomas and CLL with atypical features, including atypical immunophenotype and CLL with increased prolymphocytes or morphologically atypical cells. RESULTS: We found that LEF-1 expression is downregulated in CLL with atypical immunophenotype/features compared to classic CLL; Chi-Square P < .0001. The ratio for LEF-1 expression in malignant B-cells/NK (by flow cytometry) in CLL/SLL with classic immunophenotype was higher than atypical CLL and is significantly higher in other small B-cell lymphomas (P < .01). Absence of LEF-1 expression in CLL/SLL is correlated (P < .05) with downregulation of CD5, CD23, CD200, expression of FMC7, brighter expression of CD79b, brighter expression of surface light chain, increased prolymphocytes and lower Matutes score. CONCLUSION: As downregulation of LEF-1 expression is well correlated with atypical CLL, we suggest adding LEF-1 to Matutes score as a beneficial marker to differentiate classic from atypical CLL LEF-1 could also serve as a potential prognostic indicator for CLL clinical course.

Circulating biomarkers and outcomes from a randomised phase 2 trial of gemcitabine versus capecitabine-based chemoradiotherapy for pancreatic cancer.

BACKGROUND: The Phase 2 SCALOP trial compared gemcitabine with capecitabine-based consolidation chemoradiotherapy (CRT) in locally advanced pancreatic cancer (LAPC). METHODS: Thirty-five systematically identified circulating biomarkers were analysed in plasma samples from 60 patients enroled in SCALOP. Each was measured in triplicate at baseline (prior to three cycles of gemcitabine-capecitabine induction chemotherapy) and, for a subset, prior to CRT. Association with overall survival (OS) was determined using univariable Cox regression and optimal thresholds delineating low to high values identified using time-dependent ROC curves. Independence from known prognostic factors was assessed using Spearman correlation and the Wilcoxon rank sum test prior to multivariable Cox regression modelling including independent biomarkers and known prognostic factors. RESULTS: Baseline circulating levels of C-C motif chemokine ligand 5 (CCL5) were significantly associated with OS, independent of other clinicopathological characteristics. Patients with low circulating CCL5 (CCL5low) had a median OS of 18.5 (95% CI 11.76-21.32) months compared to 11.3 (95% CI 9.86-15.51) months in CCL5high; hazard ratio 1.95 (95% CI 1.04-8.65; p = 0.037). CONCLUSIONS: CCL5 is an independent prognostic biomarker in LAPC. Given the known role of CCL5 in tumour invasion, metastasis and the induction of an immunosuppressive micro-environment, targeting of CCL5-mediated pathways may offer therapeutic potential in pancreatic cancer. CLINICAL TRIAL REGISTRATION: The SCALOP trial was registered with ISRCTN, number 96169987 (registered 29 May 2008).

High-Grade Epstein-Barr Virus-Negative Biphenotypic Lymphoma with Expression of B- and T-Cell Markers and Leukemia Presentation: Case Report and Literature Review.

Lymphomas are presently categorized according to their origin from B or T lymphocytes. The co-expression of CD3 in B-cell lymphomas or CD20 in T-cell lymphomas has been rarely reported. Immature and less often mature lymphomas may incorporate the rearrangements of both B- and T-cell antigen receptor genes (dual genotype or bigenotype). Lymphoma cells with a sole genotype hardly concurrently express both B- and T-cell markers (biphenotypic lymphomas). We describe a 63-year-old female who was presented with obstructive jaundice and epigastric pain of 10 days. Initial CBC revealed 43×103/µL white blood cells, 11.2 g/dL hemoglobin, and 88x103/µL platelets. CT abdomen revealed hepatomegaly and suspected pancreatic mass with large retroperitoneal lymph nodal mass. Peripheral smear showed 56% lymphoid cells with blast morphology. The bone marrow (BM) aspirate smear was infiltrated by 83% immature-looking cells. BM biopsy showed interstitial to diffuse extensive infiltration by primitive-looking cells, positive for pan-B-cell antigens CD20, CD79, and PAX5 as well as the T-cell antigen CD4, CD5, CD3, while negative for all immaturity markers (CD34, TdT, and CD1a). In situ hybridization for Epstein-Barr virus (EBV)-encoded small RNA (EBER) was negative. Flow cytometry on BM aspirate showed an abnormal population (50%) expressing the B-cell antigens (CD19, CD20, CD79, CD22) and CD10, and showed lambda light chain restriction as well as the T-cell antigens cCD3 and CD4 with partial CD5. The analysis showed, also, another abnormal population of lambda restricted monotypic B cells (8%) with dimmer CD45 (blast gate) and showed the same immunophenotype (expressing the B-cell antigens), but negative for CD10, cCD3, CD5, and CD4. Conventional cytogenetic revealed complex karyotype. Molecular studies revealed rearrangements of the immunoglobulin heavy chain region consistent with a clonal B-cell population. TCR gene rearrangement analysis was equivocal concerning clonality but was not conclusive for clonal T-cell disease. Our final diagnosis was peripheral blood and BM involvement by EBV-negative high-grade lymphoid neoplasm (in leukemic phase with blast morphology) and an ambiguous immunophenotype with a differential diagnosis that may include the rare entity of bigenotypic lymphoma or an unusual case of high-grade B-cell lymphoma with aberrant expression of T-cell markers (biphenotypic lymphomas).

A study of 18F-FLT positron emission tomography/computed tomography imaging in cases of prefibrotic/early primary myelofibrosis and essential thrombocythemia.

The objectives of this research project are to study in patients with primary myelofibrosis (PMF) and Essential Thrombocythemia (ET); (1) the uptake patterns of FLT-PET (FLT-PET) and its value in diagnosing, staging, and treatment response monitoring of malignant hematopoiesis, (2) compare imaging findings from FLT-PET with bone marrow biopsy (standard of care), and (3) associate FLT-PET uptake patterns with genetic makeup such as JAK2 (Janus kinase 2), CALR (Calreticulin), MPL (myeloproliferative leukemia protein), Triple negative disease, and allele burden.This trial is registered in ClinicalTrials.gov with number NCT03116542. Protocol version: Mar 2017.

Transient Pleural Fluid Infiltration by Clonal Plasma Cells Associated with Pulmonary Tuberculosis.

Pleural effusion is a rare presentation of plasma cell myeloma, occurring in around 6% of patients during the course of their disease, most commonly as a consequence of a concurrent disease process like heart failure secondary to amyloid deposition. Direct infiltration of the pleural fluid by malignant cells leading to myelomatous pleural effusion is a rare mechanism occurring in less than 1% of patients with plasma cell myeloma, and it is associated with a worse prognosis. There are few case reports of myelomatous pleural effusion as an initial presentation of multiple myeloma. Pleural fluid infiltration by monoclonal plasma cells in the absence of an underlying plasma cell myeloma was not reported before in the literature. Tuberculosis is a known cause of polyclonal gammaglobulinemia, however few case reports described the coexistence of monoclonal gammopathy of undetermined significance and tuberculosis. Here we present an interesting case of pleural fluid infiltration by an abnormal looking clonal plasma cells associated with active pulmonary tuberculosis and parapneumonic effusion in a patient with a background of acute myeloid leukemia. Interestingly, the clonal plasma cell proliferation was confined to the pleural fluid without any evidence of an underlying plasma cell neoplasms (including monoclonal gammopathy of undetermined significance and plasmacytomas). Since our patient had an underlying meyloid neoplasm, we though about the possibility of secondary malignancy. However, in almost all patients with coexisting myeloid and plasma cell neoplasms, myeloid neoplasms developed following chemotherapeutic treatment of plasma cell neoplasms not the other way around. Given that, one must conclude localized extramedullary (pleural) plasma cell proliferation probably represents a transient reactive process to pulmonary tuberculosis which is an extremely rare phenomenon and not described before.

Acute Myeloid Leukemia in Qatar (2010-2016): Clinical, Biological, and Prognostic Factors and Treatment Outcomes.

The current study retrospectively evaluated cytogenetic profiles, various prognostic factors, and survival outcomes in 128 acute myeloid leukemia (AML) patients (14 ≤ age ≤ 70 years) admitted to the National Center for Cancer Care and Research (NCCCR), Hamad Medical Corporation, Doha, Qatar, between January 2010 and December 2016. The median age at diagnosis was 43 years, and 80% were less than 60 years old; 75% of patients were male. Cytogenetic analysis was integrated into the World Health Organization 2008 classification and showed that the percentages of normal and abnormal karyotypes were similar, accounting for 48.4% of each group of patients. The AML risk stratification based on cytogenetic analysis resulted in the following distribution: 18% in the favorable risk group, 57% in the intermediate-risk group, 24% in the unfavorable risk group, and 1% unknown. Only 88 patients received therapy with curative intent; 67% achieved complete remission, increasing to 81% after inductions 1 and 2. The median overall survival (OS) and disease-free survival (DFS) in AML patients were 26.6 and 19.5 months, respectively. The 3-year OS and DFS were 40 and 36%, respectively. Prognostic factors including age, gender, white blood cell count, and risk stratification were not significantly associated with treatment outcomes, whereas response to treatment vs. failure was significantly associated with the outcome (p = 0.01). The current study supports the importance of cytogenetics as a useful tool in diagnosis, prognosis, and risk assessment in AML treatment.

Characterization of circulating myeloma tumor cells by next generation flowcytometry in scleromyxedema patient: a case report.

INTRODUCTION: Scleromyxedema (rare cutaneous mucinosis), is characterized by the formation of lichenoid papules and presence of Serum monoclonal IgG in most cases, or all; after repeated testing. PATIENT CONCERNS: The patient is a 51-year-old male presented with thick, disfiguring elephant-like erythematous skin folds over the forehead, papular shiny eruptions over ears and trunk and waxy erythematous papules over arms and hands without dysphagia or respiratory or neurologic symptoms DIAGNOSIS: : Skin biopsy from right arm was consistent with scleromyxedema. Serum cryoglobulin was reported negative. Complete blood count and routine blood biochemistry were normal. Thyroid function tests were normal. Serum protein electrophoresis and immunofixation showed monoclonal band of 14.5 g/L typed as IgG lambda. INTERVENTIONS: Our patient was refractory to lenalidomide however improved clinically on immunoglobulins infusions on monthly basis without change in the MGUS level. OUTCOMES: NGF analysis revealed approximately 0.25% Lambda monotypic plasma cells in the bone marrow expressing CD38, CD138, and CD27 with aberrant expression of CD56 and were negative for CD45, CD19, CD117, and CD81. We also detected 0.002% circulating plasma cells (PCs) in peripheral blood. CONCLUSION: The immunophenotype of circulating tumor cells (CTCs) remain close to the malignant PCs phenotype in the BM. Hence, we report NGF approach as a novel diagnostic tool for highly sensitive MRD detection in plasma cell dyscrasias including scleromyxedema.

A Rare Case of Systemic Mastocytosis with Associated Hematologic Neoplasm (SM-AHN) Involving Chronic Myeloid Leukemia: A Case Report and Literature Review.

BACKGROUND Single or multiple cell line dysplasia is a characteristic feature of myelodysplastic syndrome. However, significant dysgranulopoiesis is not a feature of chronic myeloid leukemia (CML). Systemic mastocytosis (SM) with an associated hematologic neoplasm (SM-AHN) comprises 5% to 40% of cases of SM. All types of hematologic neoplasms have been previously reported, although CML has been rarely encountered. CASE REPORT A 28-year-old male presented with a 3-month-history of weight loss and massive splenomegaly. Peripheral blood revealed marked leukocytosis, shift to left with 13% blasts. There was evident dysgranulopoiesis that raised a provisional diagnosis of myelodysplastic/myeloproliferative neoplasm. Bone marrow (BM) examination revealed granulocytic hyperplasia with 10% blasts and significant dysgranulopoiesis. Unexpectedly, cytogenetic analysis revealed t(9;22) with BCR/ABL1 rearrangement, diagnostic of chronic myeloid leukemia in an accelerated phase. The patient was started on dasatinib 100 mg upfront, however, he failed to respond, with increasing leukocytosis. Repeat BM examination showed persistence of the findings with 8% blasts. At this time, aggregates of mast cells with aberrant expression of CD25 were elicited, thus concluding the diagnosis of SM-AHN. The patient failed multiple lines of treatment (dasatinib, nilotinib, hydroxyurea, cytarabine subcutaneous, 6-mercaptopurine and interferon) and progressed to the blast phase a few months later. CONCLUSIONS We report an unusual case of CML, presented with significant dysgranulopoiesis with an aggressive clinical course including SM uncovered during the disease course with subsequent transformation to the blast phase. The different biological behavior of this case underscores the need for studies on a larger number of cases to explore the significance of the aforementioned coexistent features.

Plasma Cell Myeloma with an Aggressive Clinical Course and Anaplastic Morphology in a 22-Year-Old Patient: A Case Report and Review of Literature.

BACKGROUND Plasma cell myeloma is a neoplastic plasma cell disorder that usually presents after the fifth decade of life; it is rarely described in younger population especially under 30 years of age. However, there are conflicting reports in the literature about the clinical behavior and overall survival in younger age groups. In approximately 2% of plasma cell myeloma, the morphology of the neoplastic cells is highly pleomorphic, quite anaplastic, and may resemble metastatic tumor cells. While this poses a challenge for morphological interpretation during diagnosis, it has been demonstrated that bone marrow morphologic features (including diffuse sheet growth pattern, immature cell morphology and high mitotic index) significantly correlates with high risk disease. Moreover, there is limited description available about the morphology of the neoplastic cells when correlating the age at presentation with the clinical outcome/biological behavior; hence, the need to report and collect such cases. CASE REPORT We report a case of plasma cell myeloma in a 22-year-old male who presented with non-specific clinical features and posed a diagnostic challenge during clinical, radiological, and laboratory examination. The pathology specimens showed anaplastic morphology. Unfortunately, after diagnosis, despite treatment with brotezomib, his disease had an aggressive clinical course and he passed away 4 months after diagnosis. CONCLUSIONS Although plasma cell myeloma is rare in patients younger than 30 years, it must be considered in the differential diagnosis and investigated properly especially in patients with clinical suspicion of a metastatic non-hematological tumor. The anaplastic variant in a young patient is a diagnostic challenge and is associated with bizarre morphology, aggressive presentation, adverse cytogenetics, resistance to chemotherapy, and poor, short-term, survival.

Composite Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Mantle Cell Lymphoma; Small Cell Variant: A Real Diagnostic Challenge. Case Presentation and Review of Literature.

BACKGROUND Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL) both have a common origin arising from mature CD5+ B-lymphocytes. Their distinction is crucial since MCL is a considerably more aggressive disease. Composite lymphoma consisting of CLL/SLL and MCL has been rarely reported. This type of composite lymphoma may be under-diagnosed as the 2 neoplasms have many features in common, both morphologically and immunophenotypically. CASE REPORT We report the case of a 57-year-old male patient who presented with a 4-month history of recurrent abdominal pain and distention with hepatosplenomegaly. Peripheral blood showed a high leukocytes count (46.7×10³/uL) with marked lymphocytosis of 35.0×10³/uL, mostly small mature-looking, with some showing nuclear irregularities, with approximately 3% prolymphocytes. Immunophenotyping by flow cytometry and immunohistochemistry revealed 2 immunophenotypically distinct abnormal CD5+monotypic B-cell populations. Fluorescence in situ hybridization (FISH) on peripheral blood demonstrated IGH/CCND1 rearrangement consistent with t(11;14) in 65% of cells analyzed. Accordingly, based on compilation of findings from morphology, flow cytometry, immunohistochemistry, and FISH, A diagnosis of composite lymphoma consisting of MCL; small cell variant and CLL/SLL was concluded. CONCLUSIONS We describe a case of composite lymphoma of MCL (small cell variant) and CLL/SLL that emphasizes the crucial role of the multiparametric approach, including vigilant cyto-histopathologic examination, immunophenotyping by flow cytometry and immunohistochemistry, as well as genetic testing, to achieve the correct diagnosis.

The Role of Integrated Positron Emission Tomography/Computed Tomography (PET/CT) and Bone Marrow Examination in Staging Large B-Cell Lymphoma.

INTRODUCTION: In the era of routine use of positron emission tomography/computed tomography (PET/CT) for staging, it is not yet clear whether PET/CT can replace bone marrow biopsy for the assessment of bone marrow involvement in large B-cell lymphoma. OBJECTIVES: To compare the clinical utility of bone marrow biopsy and PET/CT scanning in the staging of large B-cell lymphoma. METHODS: This was a retrospective analysis of all patients who presented to single center over a 4-year period with large B-cell lymphoma who had concurrent PET/CT and bone marrow biopsy performed in the assessment and staging of the lymphoma. RESULTS: Out of 89 patients, 24 had bone marrow involvement either by PET/CT, by bone marrow biopsy, or by both. Bone marrow biopsy identified 12 patients (sensitivity 50%, specificity 100%, negative predictive value 84%), whereas PET/CT identified 23 patients (sensitivity 96%, specificity 100%, negative predictive value 98%). No patients were upstaged by the bone marrow biopsy result, and no patients had their treatment plan changed based on the bone marrow biopsy result. CONCLUSION: The results show that PET-CT is more sensitive and has better negative predictive value than bone marrow biopsy. This suggests that PET-CT could replace bone marrow biopsy in detecting bone marrow involvement for staging of large B-cell lymphoma.