Search

Detection of somatic genetic drivers is important for risk stratification and treatment selection in pediatric leukemias; however, newly recognized genetic markers may not be detected by routine karyotyping and fluorescence in situ hybridization (FISH). To identify the combination of assays that provides the highest detection rate for clinically significant molecular abnormalities, we tested 160 B- lymphoblastic leukemia (B-ALL) by karyotyping, FISH, chromosomal microarray analysis (CMA) and the custom next-generation sequencing (NGS) panel, OncoKidsⓇ. In addition, we tested 40 myeloid malignancies with karyotyping, chromosomal microarray analysis (CMA), and OncoKidsⓇ; 36/40 myeloid malignancies were also tested with FISH. In B-ALL, individual testing methods had the following diagnostic yields for the key genetic drivers: karyotype 34%; basic FISH panel 45%; FISH panel with IGH and CRLF2 probes 65%; CMA 48%; OncoKidsⓇ 39%. CMA and OncoKidsⓇ testing allowed detection of key genetic drivers in 42% of the samples that remained unknown upon testing by conventional methods. In myeloid malignancies, OncoKidsⓇ had the highest yield for detection of both primary and secondary DNA mutations and RNA fusions. Our data highlights the complementarity between CMA and NGS and conventional cytogenetics/FISH in pediatric leukemia diagnostics. Due to rapid turn-around-time, FISH may be useful as an initial screening method in B-ALL. Our data also suggests NGS testing with a comprehensive panel, despite a longer turnaround time, is a good alternative to karyotyping and FISH in pediatric AML due to its superior detection rate.

Immune checkpoint inhibitors have recently emerged as important and effective advanced cancer treatment options. Programmed cell death receptor-1 (PD-1) antagonists such as pembrolizumab and nivolumab have been approved by the US Food and Drug Administration for treatment of many advanced cancers. As anti-PD-1 checkpoint inhibitor use has been increasing, previously unreported rare side effects emerge. These checkpoint inhibitors upregulate humoral and cellular immune responses to tumor antigens. Consequently, they can be associated with immune-related adverse events including hematological-related reactions such as autoimmune hemolytic anemia, immune thrombocytopenia, neutropenia and pancytopenia. However, pure red cell aplasia (PRCA) induced by anti-PD-1 checkpoint inhibitors is rarely reported in the literature. We herein report cases of two patients who developed PRCA during treatment with anti-PD-1 checkpoint inhibitors. In both cases, a peripheral blood smear examination demonstrated reticulocytopenia. Bone marrow biopsies revealed severe erythroid hypoplasia with maturation arrest at the proerythroblast stage, relative granulocytic hyperplasia and lymphocytosis. Flow cytometry and immunohistochemistry revealed that the lymphocytes were predominantly CD8+ T cells. T lymphocytosis, especially in one of the two patients, mimicked a T-cell lymphoproliferative disorder; lack of clonality indicated a reactive process. Our findings, in addition to data presented in the literature, suggest that T cells play a critical role in the pathogenesis of immune-related PRCA. PRCA is an under-recognized immune-mediated adverse event that does not manifest during the clinical trial phase. It is a potentially life-threatening complication, which should be considered in the differential diagnosis of anemia in patients treated with anti-PD-1 checkpoint inhibitors.

Excisional biopsy of lymph node is a routine procedure for evaluating lymphoid pathology in patients with lymphadenopathy. A standard workup to rule out lymphoma is a comprehensive study, including histologic evaluation, immunohistochemical analysis, flow cytometry, cytogenetic study (i.e., FISH for targeted cytogenetic abnormalities), and/or molecular diagnostic tests. This chapter covers some general principles for handling specimens of lymphoma workup, clinical correlation with types of lymphoma, common morphological patterns of lymphomas or mimics, and judicial application of ancillary tests, based on clinical presentations and initial morphologic evaluation.

Objectives To assess bone marrow (BM) sampling in academic medical centers. Methods Data from 6,374 BM samples obtained in 32 centers in 2001 and 2011, including core length (CL), were analyzed. Results BM included a biopsy (BMB; 93%) specimen, aspirate (BMA; 92%) specimen, or both (83%). The median (SD) CL was 12 (8.5) mm, and evaluable marrow was 9 (7.6) mm. Tissue contraction due to processing was 15%. BMB specimens were longer in adults younger than 60 years, men, and bilateral, staging, and baseline samples. Only 4% of BMB and 2% of BMB/BMA samples were deemed inadequate for diagnosis. BM for plasma cell dyscrasias, nonphysician operators, and ancillary studies usage increased, while bilateral sampling decreased over the decade. BM-related quality assurance programs are infrequent. Conclusions CL is shorter than recommended and varies with patient age and sex, clinical circumstances, and center experience. While pathologists render diagnoses on most cases irrespective of CL, BMB yield improvement is desirable.

OBJECTIVES: To assess bone marrow (BM) sampling in academic medical centers. METHODS: Data from 6,374 BM samples obtained in 32 centers in 2001 and 2011, including core length (CL), were analyzed. RESULTS: BM included a biopsy (BMB; 93%) specimen, aspirate (BMA; 92%) specimen, or both (83%). The median (SD) CL was 12 (8.5) mm, and evaluable marrow was 9 (7.6) mm. Tissue contraction due to processing was 15%. BMB specimens were longer in adults younger than 60 years, men, and bilateral, staging, and baseline samples. Only 4% of BMB and 2% of BMB/BMA samples were deemed inadequate for diagnosis. BM for plasma cell dyscrasias, nonphysician operators, and ancillary studies usage increased, while bilateral sampling decreased over the decade. BM-related quality assurance programs are infrequent. CONCLUSIONS: CL is shorter than recommended and varies with patient age and sex, clinical circumstances, and center experience. While pathologists render diagnoses on most cases irrespective of CL, BMB yield improvement is desirable.

We present a case of angiosarcoma in small bowel, presenting with partial small bowel obstruction in a 79-year-old man with no history of radiation, chemotherapy, toxin exposure, or previous operative intervention. Angiosarcoma of small bowel is a rare entity which may present with nausea, abdominal pain, recurrent bleeding, and usually a history of prior radiation or exposure to specific toxins (polyvinyl chloride). Angiosarcoma of small bowel tends to spread rapidly and has a poor prognosis. We review the surgical and oncologic challenges. We report unique macroscopic findings of raised hyperemic margins, which are suggestive of a vasogenic lesion and the histologic feature of a partially retiform pattern with dense basement membrane material in an otherwise poorly differentiated lesion.

Patients with chronic myelogenous leukemia (CML) present typically with an elevated white blood cell count (WBC) and cytogenetic or molecular genetic evidence of t(9;22)/BCR-ABL1 fusion gene. Rarely, CML patients may present with a normal or mildly elevated WBC and are asymptomatic, and we describe 7 patients in this study. The WBC in these patients ranged from 3.6 to 14.3 K/mm(3) with 50% to 73% granulocytes and 0% blasts. In all patients, t(9;22)(q34;q11.2) was detected by conventional cytogenetics, and BCR-ABL1 fusion was shown, supporting the diagnosis of preleukemic CML (pre-CML). We compared these patients with a group of 5 cases of CML in chronic phase (CML-CP) and 5 bone marrow specimens with a leukemoid reaction (n=5). Reticulin, CD34, and CD61 immunostains were performed on all bone marrow biopsy specimens. Peripheral blood absolute basophilia (≥200/mm(3)) was noted in only 4 of 7 pre-CML cases, whereas it was present in all CML-CP cases and absent in leukemoid reaction cases. The mean ±SD of microvascular density of pre-CML cases (10.0 ± 4.3 vessels/200× field) was twice that of leukemoid reaction cases (5.0 ± 1.0) (P=.02; Student t test) but similar to that of CML-CP cases (12.5 ± 3.6). Microvessels in pre-CML, highlighted by CD34, were tortuous with abnormal branching, although to a lesser extent than those found in CML-CP. Microvessels in leukemoid reaction were generally straight. The percentage of small, hypolobated megakaryocytes, highlighted by CD61 in pre-CML, was 40%, 3 times that found in leukemoid reaction cases (13%) but less than that of CML-CP cases (86%). We conclude that pre-CML should be suspected in patients with a normal to mildly elevated WBC and absolute basophilia. Bone marrow examination can usually distinguish pre-CML from a leukemoid reaction based on the percentage of small, hypolobated megakaryocytes; microvascular density; and morphologic features.

BACKGROUND Bone marrow examination is essential in diagnosis, staging and monitoring of various hematologic disorders. The aspirate smears and core biopsy are complementary samples; current clinical benchmarks recommend an optimal core sample length of at least 15-20 mm. We assessed the core length in 2 cross-sectional cohorts from 2001 and 2011 in 32 academic medical centers from the US and Canada, the first such study to date. METHODS After IRB approval, participants collected data from pathology reports (including the preprocessing length) and measured aggregate postprocessing and evaluable marrow length using a uniform validated methodology on 100 consecutive marrow samples in 2001 and 2011 at each institution. Deidentified data was centralized at Roswell Park Cancer Institute (RPCI) and centers were anonymized. A total of 6374 samples were accepted for statistical analysis, performed using SAS (v. 9.4 or higher; SAS Institute, Cary, NC) at RPCI. Relationship between core length and NCCN status, geographic location, gender, age, and staging was assessed using the PROC MIXED and PROC GLIMMIX procedure using a random center effect and a nominal significance level of 0.05. RESULTS The study cohort included 56% men and 44% women, mean age 51 (range, 1-102) years, 88% adults (³18) and 12% children ( A core biopsy was obtained in 90% of 2001 and in 95% of 2011 samples. Most cores were unilateral (85%); bilateral sampling decreased from 10% to 4% between 2001 and 2011. An aspirate specimen was received in the pathology department in 86% of the cases; however, a clot section was prepared in only 56% of the cases. Preprocessing core length (PreCL; n=3141) documentation in pathology reports was missing in 9 centers for both years; in 3 centers it was available only for one year; its mean (standard deviation) was 16.9 (9.9) mm, decreasing from 2001 to 2011 [17.7 (11.9) to 16.2 (8); p=0.002]. Postprocessing core length (PostCL; n=5742) mean (SD) was 14.2 (8.5) mm, significantly shorter in women than in men (p Evaluable marrow space length (EML; n=5617) mean (SD) was 10.7 (7.5) mm and decreased from 2001 to 2011 [10.9 (8.5) to 10.6 (6.6); p=0.002]. Ninety-one samples (1.6%) with measureable PostCL were entirely devoid of evaluable marrow. PostCL was 15% shorter than PreCL. The EML measured 24% less than the PostCL and 33% less than the PreCL. Lymphoma staging samples (n=1222) were obtained from adults (96%) and children (4%); of these, only 45% and 28% reached the PostCL of 15 mm and 20 mm, respectively. Lymphoma involvement rate was 16%, 25%, 32%, 30%, and 23% when PostCL was There was no significant difference of PostCL mean based on geographic region or NCCN status. PostCL mean ranged from 8.8 to 29.6 mm and its median was ³15 mm in only 12 of 23, 9 of 32, and 2 of 32 centers for PreCL, PostCL, and EML, respectively (Fig 3). When compared to current benchmarks, only 53%, 38%, and 22% of all samples were ³15 mm and only 30%, 19%, and 10% were ³20 mm for PreCL, PostCL, and EML, respectively. CONCLUSIONS Current benchmarks for bone marrow core biopsy adequacy are met in only a minority of cases. Samples from women were shorter than from men. Bilateral sampling decreased and PreCL and EML diminished significantly between 2001 and 2011, while PostCL showed only minimal decrease. This discrepancy may be due to technical differences. Although staging cores were longer than non-staging ones, most did not meet the benchmarks. The wide variability among different centers suggests significant institutional differences and lack of standardization in bone marrow sampling. Over a third of all centers did not record preprocessing length, an important parameter which may guide operator assessment of adequacy at the bedside. PostCL and/or EML can be measured by the pathologist and integrated in the report to document adequacy. In staging samples, a minimal marrow space sampling should be required to avoid understaging. Consensus definition of an inadequate core biopsy is currently lacking but would be desirable for uniform pathology reporting, clinical protocols and management. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.