Anaplastic Multiple Myeloma With a Novel Proliferation of Pleomorphic Binuclear Plasma Cells.

This study describes an unusual case of multiple myeloma that progressed to anaplastic multiple myeloma in the pleural fluid. The Wright-stained cytospin of the pleural fluid showed a predominant population of mononuclear plasma cells with pleomorphic nuclei, characterized by both small and large nuclei, which is typical of anaplastic multiple myeloma. However, there were also more binuclear plasma cells with pleomorphic nuclei. Morphometric analysis showed that the mean nuclear length was 1.9-fold and 2.3-fold higher in the large nuclei compared to the small nuclei for the mononuclear plasma cells and binuclear plasma cells, respectively (p<0.001). The patient received B cell maturation antigen chimeric antigen receptor T cell (CAR-T) therapy for relapsed disease, with a significant reduction of the serum monoclonal paraprotein level at day 51 post-therapy. Pathologists should be aware that pleomorphic binuclear plasma cells can be part of the morphologic spectrum in anaplastic multiple myeloma.

Application of the International Consensus Classification and World Health Organization 5th edition classification to a series of myeloid neoplasms.

OBJECTIVES: Two new classifications of myeloid neoplasms have recently been published: the International Consensus Classification (ICC) and the 5th edition of the World Health Organization classification (WHO5). We sought to examine the real-world impact of dueling classifications on patient diagnoses. METHODS: Our institutional pathology database was searched, and 237 specimens with a diagnosis of myeloid neoplasia were randomly selected. For each case, a classification based on the WHO5 and the ICC was assigned. The WHO5 and ICC diagnoses were compared to determine their degree of concordance. RESULTS: After applying the WHO5 and ICC diagnostic criteria, 134 (56.5%) cases were classified as concordant, 63 (26.6%) cases had terminological differences, 37 (15.6%) cases had minor diagnostic discrepancies, and 3 (1.3%) cases had major diagnostic discrepancies. Cases with minor diagnostic discrepancies included 25 cases of myelodysplastic syndrome (MDS), 10 cases of acute myeloid leukemia (AML), and 2 cases of myeloid precursor lesions. Cases with major diagnostic discrepancies included 2 cases that were diagnosed as MDS, not otherwise specified (NOS), according to the ICC but classified as AML with NPM1 alteration and AML with RBM15::MRTFA according to the WHO5 and 1 case that was characterized as chronic myelomonocytic leukemia according to the ICC and as AML with NPM1 alteration according to the WHO5. CONCLUSIONS: This study confirms that a majority of cases are classified similarly using the 2 systems. Given the overall similarity of the systems, future harmonization of the classifications should be pursued to avoid confusion and multiple diagnoses.

In-Hospital Outcomes and Recurrence of Acute Ischemic Stroke in Patients With Solid Organ Malignancy.

OBJECTIVE: To evaluate the influence of solid organ malignancies on the in-hospital outcomes and recurrent strokes among patients hospitalized with acute ischemic stroke (AIS). METHODS: Adult hospitalizations with a primary diagnosis of AIS were identified from the Nationwide Readmissions Database 2016-2018. Logistic regression was used to compare the differences in the utilization of acute stroke interventions and clinical outcomes in patients with and without malignancy. Survival analysis was used to evaluate the risk of readmission due to recurrent stroke after discharge. RESULTS: There were 1385840 hospitalizations due to AIS (mean±SD age 70.4±14.0 years, female 50.2%). Of these, 50553 (3.7%) had a concurrent diagnosis of solid organ malignancy. The five most common malignancies included lung cancer (24.6%), prostate cancer (13.2%), breast cancer (9.3%), pancreatic cancer (6.5%), and colorectal cancer (6.2%). After adjustment for baseline differences, patients with malignancy were more likely to have intraparenchymal hemorrhage (IPH) [odds ratio (OR): 1.11, 95% confidence interval (CI): 1.04-1.19], in-hospital mortality (OR: 2.15, 95% CI: 2.04-2.28), and discharge disposition other than to home (OR: 1.70, 95% CI: 1.64-1.75). Patients with malignancy were less likely to receive intravenous thrombolysis (tPA) and were more likely to undergo mechanical thrombectomy (MT). Among the subgroups of patients treated with tPA or MT, the outcomes were comparable between patients with and without malignancy, except patients with lung cancer remained at a higher risk of mortality and adverse disposition despite these acute stroke interventions. Patients with malignancy were at a higher risk of readmission due to recurrent AIS within 1 year of discharge (hazards ratio: 1.18, 95% CI: 1.11-1.25), and this risk was specifically driven by the lung and pancreatic cancers. CONCLUSION: While patients with malignancy generally have worse in-hospital outcomes as compared to those without, there is considerable variation in these outcomes according to the different cancer types and the use of acute stroke interventions. The use of tPA and MT is generally safe for eligible patients with an underlying malignancy. Patients with lung and pancreatic cancers have a higher early risk of recurrent stroke and might need more intensive surveillance and careful institution of the optimal secondary prevention measures.

Machine Learning-Based Multiparametric Magnetic Resonance Imaging Radiomics for Prediction of H3K27M Mutation in Midline Gliomas.

OBJECTIVE: H3K27M mutation in gliomas has prognostic implications. Previous magnetic resonance imaging (MRI) studies have reported variable rates of tumoral enhancement, necrotic changes, and peritumoral edema in H3K27M-mutant gliomas, with no distinguishing imaging features compared with wild-type gliomas. We aimed to construct an MRI machine learning (ML)-based radiomic model to predict H3K27M mutation in midline gliomas. METHODS: A total of 109 patients from 3 academic centers were included in this study. Fifty patients had H3K27M mutation and 59 were wild-type. Conventional MRI sequences (T1-weighted, T2-weighted, T2-fluid-attenuated inversion recovery, postcontrast T1-weighted, and apparent diffusion coefficient maps) were used for feature extraction. A total of 651 radiomic features per each sequence were extracted. Patients were randomly selected with a 7:3 ratio to create training (n = 76) and test (n = 33) data sets. An extreme gradient boosting algorithm (XGBoost) was used in ML-based model development. Performance of the model was assessed by area under the receiver operating characteristic curve. RESULTS: Pediatric patients accounted for a larger proportion of the study cohort (60 pediatric [55%] vs. 49 adult [45%] patients). XGBoost with additional feature selection had an area under the receiver operating characteristic curve of 0.791 and 0.737 in the training and test data sets, respectively. The model achieved accuracy, precision (positive predictive value), recall (sensitivity), and F1 (harmonic mean of precision and recall) measures of 72.7%, 76.5%, 72.2%, and 74.3%, respectively, in the test set. CONCLUSIONS: Our multi-institutional study suggests that ML-based radiomic analysis of multiparametric MRI can be a promising noninvasive technique to predict H3K27M mutation status in midline gliomas.

Utility of Flow Cytometry and Fluorescence In Situ Hybridization in Follow-up Monitoring of Plasma Cell Myeloma.

OBJECTIVES: We sought to investigate the clinical utility of flow cytometry (FC) and fluorescence in situ hybridization (FISH) in the workup of myeloma. METHODS: We retrospectively reviewed the reports of bone marrow biopsies received for myeloma evaluation between October 2015 and January 2019. RESULTS: A total of 1,708 biopsy specimens from 469 myeloma patients (mean age, 64.5 years [SD, 9.3]; female, 41.4%) were reviewed. Both FC and FISH had comparable detection rates at the time of initial diagnosis (97.6% vs 98.8%) and for follow-up cases (28.6% vs 28.2%). FC and FISH results were concordant in 98.8% of the initial diagnosis cases and 89.6% of the follow-up cases. The FISH-positive (FISH+)/FC-negative (FC-) discordance and FISH-/FC+ discordance occurred among 81 (5.0%) and 87 (5.4%) follow-up cases. In comparison with all concordant cases, FISH+/FC- discordant cases were more likely to have received treatment with daratumumab (P < .05). CONCLUSIONS: Plasma cell-enriched FISH and FC have comparable abnormal plasma cell detection rates, and approximately 10% of the follow-up cases have discordant FISH and FC results in which residual disease is detected by only one of these modalities. FISH testing should be considered for cases with negative FC, especially in patients who have received treatment with daratumumab or in cases in which there is concern about specimen adequacy.

Presurgical detection of brain invasion status in meningiomas based on first-order histogram based texture analysis of contrast enhanced imaging.

OBJECTIVE: Invasion of brain parenchyma by meningioma can be a critical factor in surgical planning. The aim of this study was to determine the diagnostic utility of first-order texture parameters derived from both whole tumor and single largest slice of T1-contrast enhanced (T1-CE) images in differentiating meningiomas with and without brain invasion based on histopathology demonstration. METHODS: T1-CE images of a total of 56 cases of grade II meningiomas with brain invasion (BI) and 52 meningiomas (37 grade I and 15 grade II) with no brain invasion (NBI) were analyzed. Filtration-based first-order histogram derived texture parameters were calculated both for whole tumor volume and largest axial cross-section. Random forest models were constructed both for whole tumor volume and largest axial cross-section individually and were assessed using a 5-fold cross validation with 100 repeats. RESULTS: In detection of brain invasion, random forest model based on whole tumor segmentation had an AUC of 0.988 (95 % CI 0.976-1.00) with a cross validated value of 0.74 (95 % CI 0.45-0.96). For differentiation of grade I meningiomas from grade II meningiomas with brain invasion, the AUC was 0.999 (95 % CI 0.995-1.00) and 0.81 (95 % CI 0.61-0.99) in the training and validation cohorts, respectively. Similarly, when using only the single largest slice, the cross-validated AUC to distinguish BI versus NBI and BI versus grade I meningiomas was 0.67 (95 % CI 0.47, 0.92 and 0.78 (95 % CI 0.52, 0.95) respectively. CONCLUSION: Radiomics based feature analysis applied on routine MRI post-contrast images may be helpful to predict presence of brain invasion in meningioma, possibly with better performance when comparing BI versus grade I meningiomas.

Platelet transfusion practices in immune thrombocytopenia related hospitalizations.

BACKGROUND: The role of platelet transfusions in management of Immune Thrombocytopenia (ITP) remains controversial. Current guidelines recommend that platelet transfusions in ITP be reserved for catastrophic hemorrhage or invasive surgical procedures. This study assesses the nationwide platelet transfusion practices in hospitalized children and adults with ITP. STUDY DESIGN AND METHODS: We studied hospitalizations with ITP as the primary admitting diagnosis from 2010-2014 in National Inpatient Sample (NIS), the largest all-payer inpatient database. Univariate and multivariable logistic regression analyses were used to determine factors predicting platelet transfusions. Sampling weights were applied to generate nationally representative estimates. Propensity score matching was used to perform sensitivity analyses. RESULTS: From 2010 to 2014, there were 78,376 admissions with ITP as the primary admission diagnosis (mean ± SD age: 45 ± 27 years; females 56%, children [age < 18 years] 22%) and 282,285 with ITP as one of all the admission diagnoses. Overall, 27% admissions with ITP as primary (children 4%) and 15% admissions with ITP as one of all the diagnoses documented at least one platelet transfusion. On multivariable adjustment the following factors were associated with worsening disease severity and a higher odds of platelet transfusion, adult age (adjOR = 9.03, 95% CI = 7.40-11.02), male gender (adjOR = 1.21, 95% CI = 1.11-1.31), bleeding occurrence (intracranial/gastrointestinal/genitourinary/epistaxis) (adjOR = 1.78, 95% CI = 1.61-1.96), admission to rural non-teaching hospital (adjOR = 1.85, 95% CI = 1.52-2.22), and small bed-size hospital (adjOR = 1.23, 95% CI = 1.05-1.45). Of admissions reporting platelet transfusions, only 26% reported a bleeding complication, and 11% had a major operating-room surgery/procedure. Overall, 65% of transfused patients had neither bleeding nor a major operative procedure during the hospitalization. Admissions with platelet transfusions had a significantly longer mean length of hospitalization 2.2 days (95% CI = 1.96-2.41, p < 0.001), and accrued higher mean total hospital charges; $31,150 USD (95% CI = 27,644-34,656, p < 0.001). However, platelet transfusions were not associated with in-hospital mortality (adjOR = 1.02, 95% CI = 0.73-1.45, p = 0.892). CONCLUSION: Platelets are administered to a small fraction of the hospitalized ITP patients. In a majority of these cases however, platelet usage does not appear to be concordant with the current guidelines or associated with improvement in clinical outcomes.

Does Hepatocyte Paraffin 1 expression stand a role in determining the site origin of an adenocarcinoma from unknown gastrointestinal primary?

BACKGROUND: Hepatocyte Paraffin 1 (Hep Par 1) was being extensively used to recognize the hepatocellular carcinomas, until recognition of its expression in tumors without hepatocellular differentiation. AIMS AND OBJECTIVES: The aim of this study was to analyze if Hep Par 1 stain can serve as a specific marker of the small intestinal (SI) adenocarcinomas, versus other gastrointestinal tract (GIT) primary tumors. MATERIALS AND METHODS: In this retrospective cross-sectional study, normal GIT mucosa (n - 60), corresponding adenocarcinomas (n - 60) and nodal metastatic foci (n - 60) from the same patients, including 10 cases each from the esophagus, stomach, SI periampullary region, colon, rectum, and gall bladder were included. H-score was calculated by multiplying the stain distribution and intensity scores. The H-scores were compared with other clinical and histological parameters. RESULTS: While normal SI mucosa showed diffuse strong Hep Par 1 staining, normal esophageal and gastric epitheliums were negative and normal colon, rectal, and biliary epithelium showed weak focal positivity. Adenocarcinomas from all these sites, however, showed Hep Par 1 expression, irrespective of the tumor type, site or origin, and tumor stage. The corresponding metastatic sites also showed variable Hep Par 1 positivity, without any site specificity. CONCLUSION: Hep Par 1 stain cannot help to determine the exact site of origin of primary GIT tumors. Its expression in adenocarcinomas across the GIT and their metastatic foci proves that it cannot be regarded as a marker of SI differentiation, especially in malignancy.

Intermediate-risk differentiated thyroid carcinoma patients who were surgically ablated do not need adjuvant radioiodine therapy: long-term outcome study.

OBJECTIVE: The mute question is whether patients with DTC of intermediate risk of recurrence, second most common presentation, who were surgically ablated in the first place, ever needed adjuvant RAI therapy? This study exclusively evaluated the long-term outcome in intermediate-risk patients with DTC. DESIGN: Two-arm retrospective cohort study conducted between years 1991 and 2012. SETTING: Institutional practice. PATIENTS: Intermediate-risk DTC patients, with pathologically proven T1/2 N1 M0, T3 with/without N1 M0 disease, with a minimum follow-up of 12 months, were included. Of 254 patients who fulfilled the inclusion/exclusion criteria, 125 patients were surgically ablated (Gr-I) and 129 patients had significant remnant and/nodal disease (Gr-II). No radioiodine in Gr-I and adjuvant RAI therapy was administered in Gr-II patients. MEASUREMENTS: Baseline characteristics were compared and overall survival, event-free survival, disease-free survival/overall remission rates and recurrence rates were calculated for both the groups. RESULTS: All baseline patient characteristics were comparable except 24-h RAIU between two groups. Depending on adjuvant radioiodine therapy outcome, Gr-II patients were subclassified as Gr-IIa (ablated) and Gr-IIb (not ablated). With a median follow-up duration of 10·3 years (range: 1-21 years), 12/125 (9·6%) patients had disease recurrence and 10 (8%) showed persistent disease in Gr-I. In Gr-IIa, 6/102 (5·9%) patients recurred but only one of them was successfully ablated with (131) I, and 5 (4·9%) had persistent disease. However, in Gr-IIb, 27 patients who failed first-dose adjuvant RAI therapy, 8/27 (29·6%) showed persistent disease (P = 0·000). Overall survival was 100%; however, disease-free survival rates were 92% and 90%, in Gr-I and Gr-II, respectively. CONCLUSION: Intermediate-risk surgically ablated patients do not need adjuvant RAI therapy and patients who failed to achieve ablation with first dose of (131) I may be dynamically risk stratified as high-risk category and managed aggressively.

Perioperative Management of Juvenile Nasopharyngeal Angiofibroma: A Retrospective Analysis of 56 Patients From a Single Tertiary Care Institute.

The present study was undertaken with the primary aim to analyze a large number of surgically treated patients with juvenile nasopharyngeal angiofibroma (JNA) in respect to preoperative embolization, different surgical procedures, and JNA stages. Ages of the patients ranged between 8 and 31 years. Mean blood loss was 1,240 mL (range, 50-6,000 mL). Preoperative embolization was performed in 23 patients (41%). Mean blood loss in patients who underwent embolization was not significantly different from those who did not; 1,580.4 mL vs 910.4 mL. Mean blood loss in stage IIB and above was more than 1 L. Intraoperatively 15 patients (37%) required 2 U of packed red blood cells. Postoperatively only 22 patients (39%) required packed red blood cells compared with 38 (67%) intraoperatively. The trachea was kept electively intubated in 46 patients (82%). We conclude that most of the JNA surgeries do not require replacement of more than 2 U of blood intraoperatively. Only 1 intravenous line is required in stages IB and IIA because of less blood loss. Not all patients need to be kept intubated electively in the postoperative period.

Influence of prior carbimazole on the outcome of radioiodine therapy in pediatric and adolescent Graves' disease.

OBJECTIVE OF THE STUDY: Therapeutic options for pediatric Graves' disease (PGD) include antithyroid drug therapy (ATD) as the first line and radioiodine (I-131) therapy as the second line of treatment. To date, controversies persist regarding the true effect of prior ATD in the outcome of I-131 therapy in PGD. This study evaluated the effect of prior carbimazole treatment on the outcome of I-131 therapy in PGD. METHODS: This is a retrospective study covering the years 1995-2012, with a median follow-up of 75 months. Records of 114 children (84 girls and 30 boys, age range: 5-20 years, mean 24-h radioiodine uptake, 58%) who had clinically and biochemically proven Graves' disease irrespective of prior ATD therapy were included. All patients were treated with fixed doses of 5 mCi (185 MBq) I-131 for Graves' disease; 74 had undergone prior carbimazole treatment (group 1) and 40 were drug naive (group 2). The endpoint of follow-up was stable euthyroid or hypothyroid in patients. The effect of prior carbimazole treatment on the outcome of I-131 therapy in PGD patients was evaluated. The success of radioiodine therapy was defined as the cure of hyperthyroidism. Variables were analyzed to identify the potential predictive factors for euthyroidism/hypothyroidism after treatment. RESULTS: The cure rate was 70% in group 1 and 83% in group 2 with a single dose of radioiodine (P=0.299). The success rate achieved at the end of 1-year follow-up in group 1 and group 2 was 81 and 87%, respectively (P=0.401). No independent predictor was associated with success or failure of treatment. At the median follow-up of 75 months (range: 12-216 months), 76% of patients were hypothyroid on replacement doses of levothyroxine and 24% still continued to be euthyroid. CONCLUSION: Prior carbimazole treatment does not alter the outcome of radioiodine therapy in PGD.

Radioiodine remnant ablation in low-risk differentiated thyroid cancer patients who had R0 dissection is an over treatment.

Low-risk (LR) differentiated thyroid cancer (DTC) patients should be ablated or not, albeit, with small dose of radioiodine is highly controversial. We hypothesized that those LR DTC patients who were surgically ablated need no radioiodine remnant ablation (RRA). This study aims to evaluate the long-term outcome in these two groups of patients. Retrospective cohort study conducted from January 1991 to December 2012. Based on extent of surgical resection and histopathology, LR DTC patients were classified as Gr-1: 169 patients, who were surgically ablated; Gr-2: 153 patients, who had significant remnant in thyroid bed. Basal parameters were comparable between two groups except pretherapy 24 h radioiodine uptake (0.16 ± 0.01% vs. 5.64 ± 0.46%; P < 0.001). No patient received RRA in Gr-1; Gr-2 patients were administered 30 mCi (131) I. Total number of events (recurrence, persistent, and progression of disease), with median follow up of 10.3 years, was observed in 10/322 (3.1%) of LR DTC patients. Only one patient had disease recurrence from Gr-1, who became disease-free after radioiodine therapy. Similarly, one patient from 126, who was ablated with single dose of RRA, had recurrence from Gr-2. However, 8/27 (29.7%) patients from Gr-2 had persistent disease; even two of them subsequently developed disease progression, who failed first-dose of RRA. The event-free survival rates were 99.4% and 94.1% (P = 0.006) in Gr-1 and Gr-2, respectively. RRA is an overtreatment in surgically ablated LR DTC patients. Successfully ablated RRA patients also had similar long-term outcome, however, those who failed, should be re-stratified as intermediate-risk category, and managed aggressively.

Differentiated thyroid cancer in patients over 60 years of age at presentation: a retrospective study of 438 patients.

OBJECTIVES: The aim of this study is to identify the prognostic factors predicting remission and subsequent disease relapse in patients with differentiated thyroid cancer (DTC) greater than 60years of age. MATERIALS AND METHODS: The institute thyroid cancer database had 4370 patients with DTC, of which 447 (10%) were aged>60. However, 9 patients were excluded due to follow-up less than 1year. The prognostic factors in the remaining 438 patients were studied. RESULTS: Among the 438 patients, 311 (71%) had only loco-regional disease (M0) and 127 (29%) had distant metastases (M1) at the time of initial presentation. The host factors predictive of distant metastases at presentation were female gender, primary tumor size (>4cm), follicular histology, and extra-thyroidal extension. Among Mo patients, 195 (63%) achieved complete remission while only 12 (9%) M1 patients did so. Average number of radioactive iodine ((131)I) doses administered to achieve complete remission was 2.3 (range, 1-6) and the mean cumulative dose was 3404MBq (range, 925-46,250MBq). In multivariate logistic regression among M0 patients, follicular histology, nodal metastases, and surgical treatment lesser than total/near-total thyroidectomy and among M1 patients, site of distant metastases (skeletal and multiple sites) were independent factors predicting non-remission. Among the patients (both M0 and M1) who achieved remission, factors associated with disease recurrence were primary tumor size (>4cm), nodal metastases, pulmonary metastases, and non-remission after first dose of radioactive iodine and were associated with greater chances of disease relapse. CONCLUSION: This study highlights that DTC in older patients behaves more aggressively than in adults age<60years, and identifies several prognostic factors for remission and subsequent relapse.

Prognostic factors in pediatric differentiated thyroid cancer patients with pulmonary metastases.

AIM: This study was aimed at identifying the prognostic factors predicting remission in pediatric differentiated thyroid cancer (DTC) patients presenting with pulmonary metastases. Little is known about the prognostic factors in reference to pediatric DTC patients presenting with pulmonary metastases. METHODS: Fifty-three DTC patients aged ≤21 years were diagnosed with pulmonary metastases at initial presentation. The demographic and disease characteristics were compared between the patients who achieved remission and those who did not. RESULTS: During the median follow-up of 72 months, 38 patients became disease free, 14 patients had biochemically and/or structurally persistent disease, and one patient died due to disease progression. Patient age >15 years, presence of macronodular pulmonary metastases, and surgical methods lesser than total/near-total thyroidectomy were identified as factors associated with reduced odds of remission. CONCLUSION: This study describes the disease course and depicts the disease related prognostic factors in pediatric DTC patients with pulmonary metastases.

Lung metastases from differentiated thyroid carcinoma: prognostic factors related to remission and disease-free survival.

OBJECTIVE: Distant metastases, although rare, account for maximum disease-related mortality in differentiated thyroid cancer (DTC). Lungs and bones are the most frequent sites of metastases. We sought to identify the prognostic factors in adult DTC patients presenting with pulmonary metastases at initial diagnosis. DESIGN: Retrospective cohort study. PATIENTS: From the medical records of 4370 patients, 200 patients aged more than 21 years who were identified to have pulmonary metastases at the time of diagnosis were included in the analysis. RESULTS: The sites of metastases were lungs alone in 133 (67%) patients, and additional sites in remaining 67 (33%) patients were as follows: bones in 59, liver in 4, brain in 2 and both bone and liver in two patients. During the mean follow-up of 61 months (range, 12-312 months), 76 patients achieved remission, 121 (60·5%) patients had biochemically and/or structurally persistent disease and three patients showed disease progression. Multivariate analysis revealed presence of macro-nodular (chest X-ray positive) pulmonary metastases and concomitant skeletal metastases as independent factors decreasing the likelihood of remission. Of the 76 patients with remission, 16 (21%) developed subsequent recurrence. Patient age >45 years and follicular histopathology were independently associated with greater hazards of developing recurrence. CONCLUSION: This study suggests that the patients with macro-nodular lung metastases and/or concomitant skeletal metastases have reduced odds of achieving remission. Moreover, significant number of patients recur even after complete remission with RAI treatment, hence strict surveillance is recommended especially in patients with age >45 years and/or with follicular histology of DTC.