Best Practices in CD30 Immunohistochemistry Testing, Interpretation, and Reporting: An Expert Panel Consensus.

CONTEXT.­: Although CD30 testing is an established tool in the diagnostic workup of lymphomas, it is also emerging as a predictive biomarker that informs treatment. The current definition of CD30 positivity by immunohistochemistry is descriptive and based on reactivity in lymphomas that are defined by their universal strong expression of CD30, rather than any established threshold. Challenges include inconsistencies with preanalytic variables, tissue processing, pathologist readout, and with the pathologist and oncologist interpretation of reported results. OBJECTIVE.­: To develop and propose general best practice recommendations for reporting CD30 expression by immunohistochemistry in lymphoma biopsies to harmonize practices across institutions and facilitate assessment of its significance in clinical decision-making. DESIGN.­: Following literature review and group discussion, the panel of 14 academic hematopathologists and 2 clinical/academic hematologists/oncologists divided into 3 working groups. Each working group was tasked with assessing CD30 testing by immunohistochemistry, CD30 expression readout, or CD30 expression interpretation. RESULTS.­: Panel recommendations were reviewed and discussed. An online survey was conducted to confirm the consensus recommendations. CONCLUSIONS.­: CD30 immunohistochemistry is required for all patients in whom classic Hodgkin lymphoma and any lymphoma within the spectrum of peripheral T-cell lymphoma are differential diagnostic considerations. The panel reinforced and summarized that immunohistochemistry is the preferred methodology and any degree of CD30 expression should be reported. For diagnostic purposes, the interpretation of CD30 expression should follow published guidelines. To inform therapeutic decisions, report estimated percent positive expression in tumor cells (or total cells where applicable) and record descriptively if nontumor cells are positive.

NCCN Guidelines® Insights: Myelodysplastic Syndromes, Version 3.2022.

The NCCN Guidelines for Myelodysplastic Syndromes (MDS) provide recommendations for the evaluation, diagnosis, and management of patients with MDS based on a review of clinical evidence that has led to important advances in treatment or has yielded new information on biologic factors that may have prognostic significance in MDS. The multidisciplinary panel of MDS experts meets on an annual basis to update the recommendations. These NCCN Guidelines Insights focus on some of the updates for the 2022 version of the NCCN Guidelines, which include treatment recommendations both for lower-risk and higher-risk MDS, emerging therapies, supportive care recommendations, and genetic familial high-risk assessment for hereditary myeloid malignancy predisposition syndromes.

Wilson Disease Presenting With Acute on Chronic Liver Failure: A Single-Center Experience of Outcome and Predictors of Mortality in 68 Patients.

BACKGROUND AND AIMS: Acute on chronic liver failure (ACLF) is an emerging entity whose unique pathogenesis, presentation, and outcome are different from those with decompensated cirrhosis. Patients with Wilson disease (WD) often present with ACLF. The outcome in this setting and predictors of mortality have not been well delineated. We describe the clinical features, laboratory characteristics, and prognostic factors in patients with WD with ACLF. We compared the outcome in those without criteria for ACLF. PATIENTS AND METHODS: We analyzed the admission characteristics of 68 patients with WD presenting with features of ACLF among a cohort of WD patients from 1997 to 2017. WD was diagnosed as per European association for the study of the liver (EASL)/Leipzig criteria and ACLF by the Asia-Pacific Association of Study of Liver and World Gastroenterology Organization consensus criteria. Factors associated with mortality were analyzed by univariate followed by multivariate analysis and receiver operating characteristic curve. RESULTS: Of the 272 patients with WD, 68 fulfilled criteria for ACLF. The mean age was 14.4 years (Range 5-42 years). Males constituted 38/68 (56%). Acute viral or drug induced hepatitis as precipitating factors was seen in 11.7%. Forty-nine patients (49/67; 73%) died including 30/32 (93.8%) with encephalopathy and 45/62 (72.6%) with ascites. Prognostic factors on univariate analysis significant for mortality included encephalopathy, international normalized ratio, white blood cell count and model for end-stage liver disease (MELD) score. On multivariate analysis, only encephalopathy was significant with 82% accuracy in differentiating survivors versus non-survivors. Post mortem liver biopsy in 21 patients and explant biopsy in 2 patients showed features of cirrhosis in all. CONCLUSIONS: WD with ACLF is associated with a high mortality Precipitating factors such as viral and drug-induced hepatitis was seen in 11.7% patients. Liver histology in patients subjected to biopsy showed cirrhosis in all. Only encephalopathy is a prognostic marker of non-survival with an accuracy of 82%.

Acute promyelocytic leukemia during pregnancy: A case report and 10-year institutional review of hematologic malignancies during pregnancy.

Acute promyelocytic leukemia (APL) manifesting during pregnancy is a very rare but highly challenging gestational complication in part due to its associated profound coagulopathy. We present the case of a 23-year-old Gravida 3 Para 2002 woman admitted to our hospital at 26 weeks of gestation for severe pre-eclampsia with documentation of intrauterine fetal demise (IUFD), thrombocytopenia, and placental abruption. A peripheral blood smear revealed promyelocytes with azure granules, highly concerning for APL. Additional peripheral blood studies confirmed APL. Placental examination also revealed circulating blasts in decidual vessels and scattered blast entrapment in diffuse perivillous fibrinoid deposits, but none in the chorionic villi. Treatment for APL was initiated immediately and she is in complete molecular remission. Our case underscores the importance of close collaboration among obstetric, hematology, and pathology teams in the care of patients with pre-eclampsia, thrombocytopenia, and postpartum coagulopathy. We also describe five additional cases of gestations complicated by hematologic malignancies identified upon a 10-year institutional retrospective review.

Three neglected numbers in the CBC: The RDW, MPV, and NRBC count.

The complete blood cell count (CBC) is one of the most frequently ordered laboratory tests, but some values included in the test may be overlooked. This brief review discusses 3 potentially underutilized components of the CBC: the red blood cell distribution width (RDW), the mean platelet volume (MPV), and the nucleated red blood cell (NRBC) count. These results have unique diagnostic applications and prognostic implications that can be incorporated into clinical practice. By understanding all components of the CBC, providers can learn more about the patient's condition.

Optimization of Laboratory Ordering Practices for Complete Blood Count With Differential.

Objectives: To investigate the utilization of CBC and CBC with differential (CBC w/diff) tests at University of Alabama at Birmingham Hospital, and to determine if a reduction in CBC w/diff tests could be achieved without negatively impacting patient care. Methods: The quantity of testing and distribution of repeated tests before, during, and after an educational intervention were compared. Results: CBC w/diff tests were ordered 10-fold more frequently than CBC tests. The trauma burn intensive care unit ordered the most CBC w/diff tests, with repeat tests done every 4 or 12 hours. The educational intervention reduced the number of CBC w/diff tests ordered and tests repeated every 12 hours. Conclusions: The educational intervention changed the ordering practices of CBC w/diff and CBC tests. This was sustained after the intervention and no negative effects on patient care were noted. Similar interventions may lead to optimization of ordering practices of other laboratory tests.

Arthritis in sarcoidosis: A multicentric study from India.

INTRODUCTION: Ten to 15% of patients with sarcoidosis have associated arthritis. Chronic arthritis is fairly uncommon. There is a paucity of data on articular manifestations of the disease from India. METHODS: Case records of adult patients with sarcoidosis presenting to 11 rheumatology centers from 2005 to 2017 were retrospectively reviewed. Joint involvement was assessed clinically, classified as acute or chronic depending on duration of symptoms less or greater than 6 months, respectively. RESULTS: A total of 117 patients with sarcoid arthritis were reviewed. Forty-five patients were classified as having Lofgren's syndrome. The pattern of joint involvement revealed the ankle to be most commonly affected in both the groups. Shoulder, wrist, metacarpophalangeal, proximal interphalangeal joints of hands and knee joint involvement were significantly more common in chronic sarcoid arthritis. Peripheral lymphadenopathy and uveitis were significantly more frequent in chronic sarcoid arthritis. Forty out of 49 patients with acute arthritis followed up over a median of 1.8 years had achieved complete remission. Twelve out of 16 chronic sarcoid arthritis (median follow up 2.5 years) had achieved complete remission with 15, 12 and five patients on steroids, methotrexate and hydroxychloroquine, respectively. One patient with acute sarcoid arthritis with concomitant interstitial lung disease had died due to lung infection. CONCLUSION: Acute oligoarthritis was the commonest presentation with the ankle being the most commonly affected joint. Upper limb joint (predominantly distal) and knee involvement were more common as reported in our largest series worldwide of chronic sarcoid arthritis in adults. Hilar adenopathy and erythema nodosum were common extra-articular features in both acute and chronic sarcoid arthritis. A limitation of the study was the retrospective nature of the analysis.

Drug-induced acute liver failure in children and adults: Results of a single-centre study of 128 patients.

BACKGROUND & AIMS: Drugs producing acute liver failure (ALF) are uncommon and vary geographically. Here we review the implicated drugs, clinical features, laboratory characteristics and outcome of patients with drug-induced ALF (DIALF). We analysed the predictors of mortality and their relationship with MELD, King's College criteria (KCC) and ALFSG prognostic index. METHODS: We identified DIALF patients from our drug-induced liver injury (DILI) registry (1997-2017). RUCAM was used for case adjudication. Patients who fulfilled criteria for acute liver failure and drug-induced liver injury were included. Primary outcome measure was spontaneous survival or death. RESULTS: There were 128 cases of DIALF (14%) among 905 patients with DILI. Mean age was 38 years, 68 (53%) female and 21(16.4%) children <18 years. Combination anti-TB drugs (ATD) (n = 92, 72.4%) accounted for a majority of DIALF. Others were anti-epileptic drugs (AED, n = 11, 10%), dapsone (n = 7, 5.5%), hormones (n = 2), ferrous sulphate overdose (n = 2), acetaminophen (APAP) (n = 2), antiretroviral (n = 2), CAM (N = 2), chemotherapy agents (N = 3), amoxicillin-clavulanic acid (n = 2) and others (n = 3). Forty-four patients (34%) recovered spontaneously and 84(66%) including 13 children (62%) died. Females, ascites, albumin, bilirubin, INR and MELD were significantly associated with mortality. Mortality was 79% for ATD and 100% for APAP and iron overdose. Area under ROC was 0.76 for MELD and ALFSG index and 0.51 for KCC. CONCLUSIONS: Fourteen percent of DILI resulted in DIALF. ATD, AED, dapsone and antiretroviral drugs are most common agents. Spontaneous survival was only 34% with an even higher mortality with ATD. Non-ATD and non-APAP drugs had a better survival (51%).INR and MELD predicted mortality.

Pilot phase II study of metronomic chemotherapy in combination with bevacizumab in patients with advanced non-squamous non-small cell lung cancer.

INTRODUCTION: The goal of this study was to explore the efficacy and tolerability of metronomic chemotherapy, a novel anti-angiogenic treatment strategy, in combination with bevacizumab in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Subjects with newly diagnosed stage IV NSCLC were treated with 4-week cycles of paclitaxel 80mg/m2 and gemcitabine 300mg/m2 weekly for three weeks, plus bevacizumab 10mg/kg every two weeks. Radiologic assessments were performed every 8 weeks. The primary endpoint was progression free survival (PFS). An exploratory objective was to correlate plasma levels of angiogenic biomarkers with treatment response. RESULTS: Thirty-nine subjects were included in the intent to treat (ITT) analysis. The objective response rate (ORR) was 56%, the median PFS was 8.5 months, and median overall survival (OS) was 25.5 months. The PFS rate at 6, 12, and 24 months was 61%, 21%, and 11% respectively. The OS rate at 12 and 24 months was 74% and 53% respectively. Treatment was well tolerated, without significant myelosuppressive, gastrointestinal, or neurologic events. Subjects with less than median baseline values of angiopoietin-2 and IL-8 experienced significantly longer PFS. Longer OS was associated with subjects with less than the median baseline values for PLGF and angiopoietin-2. There were statistically significant differences in median values of several biomarkers between cycles 1 and 3 in subjects with objective responses. CONCLUSIONS: The combination of paclitaxel and gemcitabine, delivered in a metronomic schedule, in combination with bevacizumab, appears to be an effective and tolerable treatment strategy in patients with advanced NSCLC.

NCCN Guidelines Insights: Chronic Myeloid Leukemia, Version 1.2017.

The NCCN Guidelines for Chronic Myeloid Leukemia (CML) provide recommendations for the management of chronic-phase and advanced-phase CML in adult patients. The median age of disease onset is 67 years. However, because CML occurs in all age groups, clinical care teams should be prepared to address issues relating to fertility and pregnancy with patients who are of reproductive age at the time of diagnosis. CML is relatively rare in children and there are no evidence-based recommendations for the management of CML in pediatric population. These NCCN Guidelines Insights discuss special considerations for the management of CML during pregnancy and for the management of CML in the pediatric population.

Fat Embolism Syndrome Secondary to Bone Marrow Necrosis in Patients with Hemoglobinopathies.

Bone marrow necrosis with subsequent embolization of the fat and necrotic tissues into the systemic circulation causing fat embolism syndrome and multiorgan failure is a rare complication of patients with hemoglobinopathies. The exact etiology of this condition is not known. Because it occurs more often in patients with compound heterozygous conditions than in sickle cell disease, some patients are unaware of their predisposition. The initial symptoms are nonspecific, such as back and/or abdominal pain, fever, and fatigue, which may rapidly progress to respiratory failure and severe neurologic compromise. Common laboratory tests reveal anemia without reticulocytosis, thrombocytopenia, leukoerythroblastic picture with immature white cells and nucleated red blood cells, increased lactate dehydrogenase, high ferritin, and, sometimes increased creatinine. The diagnosis can be delayed because of an apparent lack of awareness about bone marrow necrosis with fat embolism syndrome, its rarity, and its similarities with other conditions such as thrombotic thrombocytopenic purpura. Although a bone marrow biopsy is diagnostic, waiting for it delays definitive treatment, which appears to be essential for the recovery of end-organ damage, such as neurologic and pulmonary damage. In our experience, either multiple units of red blood cell transfusion or, preferably, red cell exchange initiated promptly, is lifesaving.

Is Low Positive JAK2 V617F Mutation Test Result Clinically Significant?: Multi-Institutional Study.

OBJECTIVES: Acquired somatic mutation Janus kinase 2 (JAK2) V617F is associated with various myeloproliferative neoplasms (MPN). Allele-specific real-time polymerase chain reaction has been widely adopted to detect mutation; however, the utility of low positive results is not well understood. The aim of this study is to investigate the clinical significance of low positivity of JAK2 V617F. MATERIALS AND METHODS: Retrospective analysis was performed for JAK2 V617F mutation tests performed using JAK2 MutaQuant kit (Ipsogen) in molecular laboratories at 2 major academic medical centers between 2010 and 2012. Cases with low positive JAK2 V617F, defined as 0.2% to 5% mutant allele, were documented. Chart review was performed for the clinical correlation. RESULTS: A total of 1697 JAK2 V617F tests was performed. Forty-five cases (2.65%) yielded a low JAK2 V617F positivity (average 1.45%), the majority of which (n=26, 62%) had <1%. Eight cases had a history of MPN. The remaining cases were related to reactive conditions without a clonal disease. Our data indicate that a low positivity of JAK2 V617F can be seen in MPN as well as reactive conditions. CONCLUSIONS: An interpretation of JAK2 V617F status should not be performed simply following some arbitrary cutoff. Any low positivity of JAK2 V617F should be reported and a correlation with clinical information is warranted for proper interpretation.

Trisomy 21-associated transient abnormal myelopoiesis involving the maternal space of the placenta: a case report and literature review.

We report a case of a male newborn with trisomy 21 and transient abnormal myelopoiesis at birth whose placenta showed extravasated fetal blasts in the perivillous (maternal) space. Concern for possible maternal spread of fetal malignancy prompted a Kleihauer-Betke test and flow cytometric analysis of the maternal peripheral blood on postpartum day 2. Notably, no evidence of the persistence of fetal cells in the maternal blood was identified, a finding that likely reflected successful maternal immunologic clearance of the fetal blasts and erythrocytes, and/or blast cellular fragility and limited viability. Ours is the first report, to our knowledge, documenting maternal peripheral-blood follow-up evaluation of this disorder in the English literature. We discuss our case in the context of a comprehensive review of fetoneonatal solid tumor and leukemic proliferative disorders with placental involvement and evidence of maternal metastasis.

Out with the bad and in with the good; red cell exchange, white cell reduction, and platelet reduction.

Automated techniques for red cell [red blood cell (RBC)] exchange or depletion of malignant cells from the peripheral blood have allowed patients with life-threatening conditions to survive long enough to receive definitive treatment. Examples of such conditions include acute chest syndrome in sickle cell disease (SCD) or acute respiratory insufficiency due to leukostasis in acute leukemia. Conversely, other patients with SCD undergo RBC exchanges on a chronic basis to maintain a reasonable quality of life and prevent another stroke. In this review, we will discuss the techniques as well as indications for RBC exchange, leukocytapheresis, and thrombocytapheresis. To illustrate the uses of these therapeutic apheresis procedures, the authors included a summary of the most common diagnoses that comprise their use.

Soluble CD25 in serum: a potential marker for subclinical macrophage activation syndrome in patients with active systemic onset juvenile idiopathic arthritis.

OBJECTIVE: Laboratory and immunological abnormalities seen in overt macrophage activation syndrome (MAS) may be observed in patients with untreated new onset systemic onset juvenile idiopathic arthritis (SoJIA). We investigated the prevalence of clinical and traditional laboratory markers of MAS as well as soluble CD163 and soluble interleukin (IL)-2Rα (CD25) in active SoJIA patients. METHODS: Thirty-three consecutive patients with active SoJIA (International League of Associations for Rheumatology criteria), 11 patients with active polyarticular JIA (polyJIA) (disease control) and two patients with MAS with SoJIA were included in the study. Clinical data, complete blood count, coagulation profile, biochemical tests were performed. Soluble CD25 and soluble CD163 levels were estimated by enzyme-linked immunosorbent assay. RESULTS: Of the 33 active SoJIA patients, 22 were male, the mean age at onset of disease was 6.77 ± 4.48 years and the duration of disease was 4.39 ± 4.6 years. Of the 11 polyJIA patients seven were boys. None of the SoJIA patient had clinical features of MAS. Fibrinogen < 2.5 g/L was present in 14/33 patients with SoJIA but in only 1/11 in polyJIA. Both patients with MAS had thrombocytopenia, leucopenia and reduced fibrinogen levels. sCD25 > 7500 pg/mL seen in MAS was present in eight patients with active SoJIA. Among these eight patients, four had multiple laboratory abnormalities suggestive of MAS. Indeed, one of the patients had past history of MAS. Elevated sCD63 (> 1800 ng/mL) was seen in four patients with SoJIA. CONCLUSION: Laboratory abnormalities associated with MAS are not uncommon in active SoJIA. Soluble CD25 > 7500 pg/mL may be a marker to detect children with subclinical MAS.

Cardiac device-related invasive aspergilloma assessed by live/real time three-dimensional transthoracic echocardiography.

Cardiac device-related infection caused by Aspergillus species is a rare finding associated with high mortality. Prompt recognition and treatment is imperative, but difficult as blood cultures are often negative and diagnosis requires a high index of suspicion. Live/real time three-dimensional transthoracic echocardiography (3DTTE) provides incremental knowledge in the characterization of valvular vegetations. Here, we provide a detailed description of an invasive cardiac device-related infection caused by Aspergillus fumigatus using 3DTTE. Findings described here highlight the role for 3DTTE in the prompt diagnosis of invasive cardiac Aspergillus infections as well as surgical planning in such cases.

Endoscopic ultrasound and endobronchial ultrasound-guided fine-needle aspiration of deep-seated lymphadenopathy: Analysis of 1338 cases.

BACKGROUND: We retrospectively studied 1338 samples of lymph nodes obtained by endoscopic and endobronchial ultrasound-guided fine needle aspiration biopsy (EUS and EBUS-FNAB) with an objective of characterizing the utility of this diagnostic modality in the assessment of deep-seated lymphadenopathy. The secondary aims were to establish the utility in the diagnosis of lymphoma and to determine the number of passes required to obtain adequate cellularity for flow cytometric analysis. MATERIALS AND METHODS: On-site assessment was performed by a cytopathologist using Diff-Quik (American Scientific Products, McGraw Park, IL) stain. In addition, Papanicolaou and immunohistochemical stains were performed and additional samples were sent for flow cytometric analyses (n = 145). The final cytologic diagnosis was correlated with surgical pathology diagnosis and/or clinical follow-up. In select cases, fluorescence in situ hybridization analysis with specific probes was performed on Diff-Quik smears. RESULTS: Both morphology as well as ancillary studies (flow cytometry or immunohistochemical stain and/or fluorescence in situ hybridization) show that EUS and EBUS-FNA are effective techniques to detect and stage intrathoracic and intra-abdominal tumors. Operating characteristics show that these are highly sensitive (89%) and specific (100%) techniques for the diagnosis of lymphoma. At least two passes provided an average of 5.66 million cells (range, 0.12-62.32 million) for lymphoma cases. CONCLUSIONS: EUS and EBUS-FNA are powerful modalities to stage malignancies and at least two passes can provide adequate cells for flow cytometric analysis. We also demonstrate that fluorescence in situ hybridization analysis can be performed on Diff-Quik-stained and mounted smears.