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Objectives Determination of bone marrow cellularity is a key part of bone marrow examination because it provides a small window into a patient's current state of hematopoietic well-being. Traditionally, bone marrow cellularity is estimated semiquantitatively through microscopic examination of core biopsy specimens harvested from the iliac crest of the pelvic bone. Bone marrow cellularity is then designated as hypercellular, normocellular, or hypocellular based on the patient's age. This assessment can have significant clinical impact, but the variation in the age-adjusted normocellularity range is not sufficiently characterized because of a lack of study data, especially in older patients (those older than 70 years of age). This study further established the normal range of bone marrow cellularity, particularly in older adults. Methods In this study, 570 benign staging and healthy donor bone marrows from patients 1 year to 93 years of age were analyzed for cellularity. Results Linear regression modeling demonstrates that cellularity in adults declines approximately 3% per decade, including after the seventh decade of life. The 90% reference interval for normocellularity in United States is 30% to 75% for those aged 18 to 90 years. Conclusions The findings revealed a more stable and slower rate of decline in cellularity with age in adults than the widely used linear model of "100% minus the patient age in decades." Normocellularity is better modeled based on age group. In those younger than 20 years of age, normocellularity ranges from 45% to 85% (mean [SD], 65% [20%]), as defined by Friebert et al in 1998. Based on our study finding of a little less than 3% decline per decade of age, the following is our recommendation for normocellularity range: For individuals 20 to 40 years of age, it ranges from 40% to 70% (mean [SD], 55% [15%]); for individuals 40 to 60 years of age, it ranges from 35% to 65% (mean [SD], 50% [15%]); and for individuals older than 60 years of age, it ranges from 30% to 60% (mean [SD], 45% [15%]). Interestingly, those older than 70 years of age do not show a significant decrease from those aged 60 to 69 years. [ABSTRACT FROM AUTHOR]

Background: Older adults represent a large oncologic demographic and are under-represented within oncology research despite constituting nearly two-thirds of the oncologic population in the United States. Because many social factors influence research participation, those who enroll in research do not reflect the oncology population at large, introducing bias and creating issue with external validity of studies. The same factors that influence study enrollment may also impact cancer outcomes, meaning that those who enroll in studies may already have an improved chance of cancer survival, further skewing results of these studies. This study evaluates characteristics that influence study enrollment in older adults and explore to what degree these factors may influence survival after allogeneic blood or marrow transplantation. Methods: This retrospective comparison study evaluates 63 adults aged 60 and above undergoing allogenic transplantation at one institution. Patients who elected and declined enrollment in a non-therapeutic observational study were evaluated. Demographic and clinical characteristics between groups were compared and assessed as predictors of transplant survival, including decision to enroll in the study. Results: Participants who chose to enroll in the parent study were not different with regard to gender, race/ethnicity, age, insurance type, donor age, and neighborhood income/poverty level compared to patients who were invited to participate but declined enrollment. The research participant group had higher proportion assessed as being fully active (23.8% vs. 12.7%, p = 0.034) and lower mean comorbidity scores (1.0 vs 2.47, p = 0.008). Enrollment in an observational study independently predicted transplant survival (HR = 0.316, 95% CI 0.12–0.82, p = 0.017). When controlling for relevant confounders of disease severity, comorbidities, and transplant age, enrolling in the parent study was associated with a lower hazards of death following transplant (HR = 0.302, 95% CI 0.10–0.87, p = 0.027). Conclusions: Despite being demographically comparable, persons who enrolled in one non-therapeutic transplant study had significantly improved survivorship than those who did not participate in observational research. These findings suggest that there are unidentified factors that influence study involvement that may also impact disease survivorship, over-estimating outcomes from these studies. Results from prospective observational studies should be interpreted with the consideration that study participants have an improved chance of survival at baseline. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction With proper logistical support and sponsorship, a laboratory in an industrialized nation might be able to act as a reference laboratory for clinicians based in a developing country. Methods We built on previous experience in the clinical laboratory to see whether a specialized histopathology service (hematopathology) could be provided to a developing country without the expertise or experience to do it in country. Results Over an 13-year period, 582 cases from 579 individuals were analyzed. Principal pathologic findings included acute leukemia in 84 cases (14%), dyspoiesis in one or more of the hematopoietic lineages in 65 cases (11%, including three cases with high-grade myelodysplasia), 23 cases (4%) with findings suspicious for a chronic myeloproliferative disorder, 35 cases (6%) with findings suspicious for a lymphoproliferative disorder, and infectious organisms (presumably Leishmania in most instances) in 9 (1%) of cases. Specimens from 45 cases (8%) were unsatisfactory owing to extreme hemodilution and/or specimen degeneration. Conclusion With proper support, a medical laboratory in an industrialized nation may serve as a reference facility for a developing nation. The use of existing infrastructure may be remarkably effective to achieve optimal turnaround time. Although the lack of ancillary studies and follow-up biopsies limit the ability to achieve a definitive diagnosis in many cases, this must be viewed in the context of the limited ability to diagnose or manage hematopoietic neoplasia in developing nations. [ABSTRACT FROM AUTHOR]

Objectives: Hematopathology (HP) is a rapidly changing field with insufficient data to provide guidance to program directors (PDs), the Accreditation Council for Graduate Medical Education, or the American Board of Pathology., Methods: Two surveys were performed-one for HP PDs and one, given twice, for HP diplomates doing Maintenance of Certification/Continuing Certification reporting in 2017 to 2018., Results: Bone marrow (BM), lymph node (LN), and flow cytometry interpretations and peripheral blood/fluid reviews are performed by more than 80% of hematopathologists and are the areas with the greatest amount of training. A smaller proportion of hematopathologists is involved in other HP-related activities. Most PDs believed fellows should perform BM procedures. Interpretation of 400 or more LNs and 500 BMs was PDs' median expectations for fellows. PDs and HP diplomates considered coagulation and benign RBC disorders overemphasized on the certification examination., Conclusions: These results highlight how varied the practice of HP is and can provide guidance to HP PDs, those responsible for assessing HP programs, and the American Board of Pathology., (© American Society for Clinical Pathology, 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Hepatosplenic T-cell lymphoma (HSTCL) is a rare type of lymphoma. Patients have a poor prognosis, and there is no standard of care. We evaluated 28 HSTCL patients to determine factors that may be associated with outcome. There were 19 men and 9 women with a median age of 32.5 years. Most patients had massive splenomegaly, and bone marrow showed sinusoidal involvement by lymphoma. The HSTCL cells expressed γδ T-cell receptor (TCR) in 20 (74%), αβ TCR in 5 (19%), and neither in 2 (7%) patients (1 case not assessed). Conventional cytogenetics and/or fluorescence in situ hybridization analysis in 24 patients at diagnosis showed isochromosome 7q (i7q) in 10 (42%) and trisomy 8 in 8 (33%) patients. Median overall survival (OS) and event-free survival (EFS) were each 28.3 months. Serum bilirubin level ≥1.5 mg/dL, αβ TCR expression, and trisomy 8 each correlated significantly with shorter OS and EFS. Patients with HSTCL received a variety of chemotherapy regimens with no regimen better than any other. However, patients who underwent stem cell transplant showed longer survival (OS: hazard ratio 0.3, P=0.09; EFS: hazard ratio 0.2, P=0.034). In conclusion, although HSTCL patients have a poor prognosis overall, the data presented support the novel suggestions that HSTCL patients can be stratified into 2 prognostic groups, with an elevated serum bilirubin level, αβ TCR expression, and trisomy 8 identifying a poorer prognostic group. In addition, the outcomes of this patient cohort suggest that stem cell transplantation has value for the treatment of patients with HSTCL.

Acute myeloid leukemia arising from chronic myelomonocytic leukemia is currently classified as acute myeloid leukemia with myelodysplasia-related changes, a high-risk subtype. However, the specific features of these cases have not been well described. We studied 38 patients with chronic myelomonocytic leukemia who progressed to acute myeloid leukemia. We compared the clinicopathologic and genetic features of these cases with 180 patients with de novo acute myeloid leukemia and 34 patients with acute myeloid leukemia following myelodysplastic syndromes. We also examined features associated with progression from chronic myelomonocytic leukemia to acute myeloid leukemia by comparing the progressed chronic myelomonocytic leukemia cases with a cohort of chronic myelomonocytic leukemia cases that did not transform to acute myeloid leukemia. Higher white blood cell count, marrow cellularity, karyotype risk score, and Revised International Prognostic Scoring System score were associated with more rapid progression from chronic myelomonocytic leukemia to acute myeloid leukemia. Patients with acute myeloid leukemia ex chronic myelomonocytic leukemia were older (P<0.01) and less likely to receive aggressive treatment (P=0.02) than de novo acute myeloid leukemia patients. Most cases showed monocytic differentiation and fell into the intermediate acute myeloid leukemia karyotype risk group; 55% had normal karyotype and 17% had NPM1 mutation. Median overall survival was 6 months, which was inferior to de novo acute myeloid leukemia (17 months, P=0.002) but similar to post myelodysplastic syndrome acute myeloid leukemia. On multivariate analysis of all acute myeloid leukemia patients, only age and karyotype were independent prognostic variables for overall survival. Our findings indicate that acute myeloid leukemia following chronic myelomonocytic leukemia displays aggressive behavior and support placement of these cases within the category of acute myeloid leukemia with myelodysplasia-related changes. The poor prognosis of these patients may be related to an older population and lack of favorable-prognosis karyotypes that characterize many de novo acute myeloid leukemia cases.

The incidence and presenting features of chronic lymphocytic leukemia (CLL) have changed significantly over the last century. Routine diagnostic techniques can now detect very low levels of CLL phenotype cells. Monoclonal B-cell lymphocytosis (MBL) is a relatively recent diagnostic category encapsulating individuals with an abnormal B-cell population but not meeting the diagnostic criteria for a B-cell malignancy. This review focuses on CLL-type MBL, which represents the majority of MBL cases identified in diagnostic laboratories. CLL-type MBL has a phenotype identical to CLL and shares the same chromosomal abnormalities even at the lowest levels detectable. Recent evidence suggests that the immunoglobulin gene usage plays a key role in whether the abnormal cells will develop in significant numbers. In most cases, CLL-type MBL is a stable condition with only 1% per year among those presenting for clinical attention developing progressive disease requiring treatment, although suppressed immune function may have a more significant impact on outcome.

Sentinel lymph node biopsy in women with breast cancer has become routine in many surgical practices; yet basic questions regarding the procedure remain unanswered. The National Surgical Adjuvant Bowel and Breast Project (NSABP) and the American College of Surgeons Oncology Group (ACOSOG) trials address the issues of morbidity, efficacy, safety, and the significance of low-volume disease. NSABP B-32 randomizes women to sentinel lymph node biopsy followed by a standard level I and II axillary dissection or sentinel lymph node biopsy without dissection unless metastatic disease is noted by H&E examination. Overall survival, disease-free survival, and morbidity serve as end points. Further pathologic evaluation of the lymph nodes with immunohistochemistry will be performed by the study center. This study is nearing its anticipated accrual goal. Patients enrolled in the now-closed ACOSOG Z0010 trial underwent bone marrow aspiration just prior to sentinel node biopsy. Immunocytochemical analysis of the marrow will be compared to sentinel lymph node (SLN) biopsy to determine prognostic accuracy. ACOSOG Z0011 randomizes women undergoing breast-conserving therapy with low-volume axillary disease to completion axillary dissection or observation. Overall survival, disease-free survival, local regional control, and morbidity serve as end points. This trial is currently enrolling patients.

Background: A report of neutralizing antibodies to recombinant human erythropoietin (rHuEPO) in European dialysis patients raised concerns that US dialysis patients may be at similar risk. We investigated the frequency of diagnosis codes that include pure red cell aplasia (PRCA) in the Medicare end-stage renal disease data., Methods: Medicare claims data were used to identify incident dialysis patients from 1995 through 1999 aged 67 years or older who did not have a diagnosis code for aplastic anemia (AA; which includes PRCA) or were not administered rHuEPO before dialysis therapy initiation. Patients were assessed for complicating conditions, rHuEPO dose, hematocrit level, blood transfusion, bone marrow testing, and AA diagnosis (maximal follow-up, 13 months)., Results: Of 101,782 patients eligible for study, 9,896 patients had diagnosis codes for AA after dialysis therapy initiation, 3,894 patients underwent bone marrow tests (required for PRCA diagnosis), 19 patients had diagnosis codes for AA based on bone marrow examination and no other complicating conditions, and 5 patients were administered blood transfusion in 1 or more months during follow-up, of whom only 1 patient had persistent low hematocrit levels while being administered rHuEPO and blood transfusion. This latter patient was identified from a total of 101,782 patients, or 70,706.75 person-years of rHuEPO exposure., Conclusion: Diagnosis codes in the Medicare data are inadequate for the conclusive study of PRCA in US dialysis patients. Despite limitations of this study, it appears that few cases of rHuEPO-associated PRCA have occurred in US Medicare dialysis patients. Additional investigation is needed to determine whether apparent differences between US complication rates and those elsewhere result from differences in the manufacturing and/or use of erythropoietin products.

Objective: To discuss a comprehensive diagnostic approach to an active duty patient presenting with dyspnea on exertion, fatigue, and pallor. A 50-year-old active duty E-6 white male in Al Udeid, Qatar, presented with progressive dyspnea on exertion, fatigue, and new pallor. This case illustrates the course of events from Al Udeid to the Walter Reed Army Medical Center, where the final diagnosis was made. Along the way, questions with discussions explore the various diagnostic and management aspects of his case and highlight military relevant issues that include efficient diagnostic algorithms in the field and transfusion of scarce blood products.