Bone Marrow Aspiration Biopsy Research Articles

Improving adequacy rates of bone marrow aspirate and core biopsies through training and a bedside X-ray device.

e23228 Background: Bone marrow (BM) evaluation is crucial to the diagnosis of hematolymphoid disorders. WHO requires an adequate number of well-spread-out spicules in aspirates and defines an adequate BM core biopsy as ≥1.5 cm with at least 10 inter-trabecular areas (ITA). Gross examination of the core biopsy at the bedside can be misleading due to attached clot, thick periosteum, and cortical bone, or tangential biopsies, which histologically results in biopsy without adequate ITAs. Suboptimal BM biopsies hinder appropriate diagnosis, delay patient care, and may require the patient to undergo additional BM biopsies. Bedside image analysis via a cabinet x-ray system can be utilized as a point-of-care tool to assess the amount of evaluable marrow permitting re-biopsy at the time of the procedure. Methods: The study was conducted over 5 months at Westchester Medical Center. We retrospectively estimated BM adequacy rates by analyzing the aspirate quality and measuring the BM core biopsy length. Subsequently, a training demonstration to the proceduralist (fellows in training) by an experienced attending was performed and the adequacy rates were reassessed. BM biopsies were analyzed with a cabinet x-ray system, Faxitron, soon after biopsy, then subjected to routine histology and processing. High-resolution images of the core biopsy were obtained. The length of the core biopsy and the number of ITAs were calculated from the x-ray images. Measurement of the gross biopsy length and microscopic assessment of evaluable marrow were compared to the measurements obtained by x-ray imaging. Results: Our adequacy rates which met aspirate quality were 5% (1/20) pre-intervention and 65% (13/20) post-intervention. The aspirate smear quality improved after the demonstration technique to 65%. Only 13/53 core biopsies exceeded the WHO standard of 1.5 cm by microscopy, while 34/53 were grossly estimated to be > 1.5 cm. There was general concordance between the number of ITAs and the length of core biopsies by microscopy. In approximately 20% of cases, the x-ray images highlighted suboptimal core biopsy ( < 10 ITA/cortical bone/cartilage), which weren’t apparent by gross examination alone at the bedside. Utilizing x-ray image measurements, core biopsy fragment length was shown to be in concordance with microscopic estimation of length and number of ITAs. X-ray imaging readily identified clot sections (non-radiopaque), sclerotic cortical bone (absence of trabeculae), and periosteum (soft tissue shadow) in all 10 sub-1 cm biopsies. Conclusions: We conclude that a standard instruction technique of slide preparation can improve the quality of bone marrow aspirate. Core biopsy length and number of ITAs can easily be estimated using bedside point-of-care x-ray analysis to ensure adequate BM evaluations. We propose training and the routine use of bedside x-ray machine to improve the adequacy rates of BM biopsies.

New Onset Pancytopenia in Adults: Clinico-etiological Profile at a Tertiary Care Hospital

Objective: To evaluate and compare common disorders leading to new onset pancytopenia among both genders.
 Methods: It was a cross-sectional study conducted at the Department of Pathology at Watim Medical College and Watim General Hospital, Rawat, from November 2020 to November 2021.A total of 98 adult patients with persistent pancytopenia for one week who gave consent for bone marrow aspiration and a trephine biopsy were selected. A blood-complete picture with peripheral smears along with bone marrow aspiration biopsy were done. Trephine needle biopsy and cytochemical staining were performed when required.
 Results: There were 44 males and 54 female patients. The mean age was 43.49 ±19 years. Common presenting complaints were pallor (82.6%), weakness (63.2%), petechial haemorrhages (45.9%) and fever (23.5%). The hemoglobin value, white blood cell count and platelet count were 6.5± 1.65 g/dl, 3.20 ±1.43 x 109/L and 55.21 ±28.01 x 109/L respectively. Major causes were megaloblastic anemia with female predominance (S.D: 0.003) in 43.8% patients, aplastic anemia with male predominance (S.D:0.001) in 17.3%, portal hypertension induced splenomegaly in 13.2%, infectious diseases in 7%, leukemias in 5.1% and Myelodysplastic syndromes in 3.1%.
 Conclusion: Megaloblastic anaemia is the major cause of pancytopenia in females and aplastic anemia in male pancytopenic patients.

Deciphering Disease: The Critical Role of Bone Marrow Aspirate and Biopsy in Diagnostic Medicine

Background: Haematological malignancies, such as non-Hodgkin lymphomas and multiple myeloma, present diagnostic challenges due to the heterogeneity and complexity of their presentation. The importance of accurate diagnostic methods, like bone marrow aspirate (BMA) and bone marrow biopsy (BMB), is paramount for patient prognosis and therapeutic decisions. Objective: This manuscript aims to critically evaluate the role of bone marrow aspiration and its efficacy with bone marrow biopsy in diagnosing and assessing different medical conditions, offering an in-depth understanding of their individual and combined implications. Methods: Diverse studies exploring on lymphomas, Leukaemia and research on multiple myeloma were analysed. The emphasis was on the diagnostic discrepancies and complementarities between BMA and BMB. Additionally, the evolving role of advanced tools like PET-CT, flow cytometry, and their integration with traditional methodologies were examined. Results: While BMA and BMB both play crucial roles in the diagnostic paradigm, there exists a tendency for BMA to underestimate plasma cell involvement in certain cases. Additionally, PET-CT scans and flow cytometry, when combined with conventional techniques, enhance diagnostic accuracy. However, the application of these techniques should be individualized based on specific clinical scenarios, with considerations for costeffectiveness and practical implications. Conclusion: The multifaceted diagnosis of haematological malignancies mandates a holistic approach, integrating both traditional and advanced methodologies. An interdisciplinary approach, prioritizing patient-specific nuances, ensures precise diagnoses, laying the groundwork for optimal therapeutic outcomes. Future research endeavours should focus on refining these diagnostic algorithms to align with the rapidly progressing field of haematology

A Mild DBA Phenotype Associated with a Non-Canonical Splice Site Mutation in RPS26

A 37-years-old Italian female came to the observation of an adult hematology unit for the first time because of an undefined form of congenital anemia. The patient's unrelated parents and her sister were apparently healthy. Hypochromic anemia was observed for the first time at the age of 11 months and treated with one blood transfusion. Oral iron supplementation was started but was ineffective (Hb around to 7 g/dL). At that time, Fanconi's anemia was excluded by cytogenetic analysis, as also DBA The patient showed normal growth and somatopsychic development. Hematology showed moderate macrocytic anemia (MCV ranging from 115-121 fl, Hb levels ranging from 7 to 9 g/dL) with anisocytosis and hypochromia, inadequate reticulocytosis, normal bilirubin and haptoglobin, increased serum ferritin, increased HbF (7-8%), slightly increased erythropoietin, but proportional to anemia, and erythroblastic hyperplasia with variable dyserythropoiesis on bone marrow aspiration and bone marrow biopsy. From the age of 20 onwards, Hb levels ranged between 6.8 and 7.5 g/dL, without transfusion support and allowing a normal working activity. The patient underwent cycles of steroid treatment with moderate benefit. Abdomen ultrasound analysis showed mild steatosis with presence of gallstones, and no signs of focal lesions. At the age of 38 years a first spontaneous pregnancy resulted in intrauterine loss of a female fetus at 21 weeks of gestation because of umbilical cord strangulation. During pregnancy worsening of anemia (Hb 5.8 g/dL) required four blood transfusions. A second spontaneous pregnancy resulted in embryonic loss. Subsequently, she was subjected to several IVF attempts: at 47 years a pregnancy resulted in embryonic loss at 8 weeks of gestation, whereas at 49 years a further pregnancy resulted in a healthy male now 9 years old. Hb levels around 8g/dL were maintained by 20 transfusions, starting at 4 months of gestation. The patient is now 59 and has not developed any tumors, so far. To ascertain the nature of anemia, the patient underwent several investigations: RBC morphology showed anysopoikilocytosis with 10% elliptocytes and 6% spherocytes. Osmotic fragility tests, Eosin-5' maleimide (EMA)-binding test, unstable hemoglobins, SDS-PAGE electrophoresis of red cell membrane proteins as well as the assay of RBC metabolism were normal, except for a decrease of pyruvate kinase/hexokinase (PK/HK) ratio (as sometime happens in presence of dyserythropoiesis). Targeted-NGS sequencing using a panel of 48 genes associated with congenital hemolytic anemias, including RBC membrane defects, RBC metabolism and congenital dyserythropoietic anemias was performed without finding any pathogenic variant. Clinical Exome Sequencing analysis showed the presence of a heterozygous mutation in RPS26 gene: c.3+5G>C. Reverse transcription PCR on total RNA extracted from the patient's PBMC showed that the variant is associated with activation of a cryptic splice site. The aberrant transcript, which is not present in controls, lacks the last 18bp of exon 2 including the ATG (hg19). The fact that the RPS26: c. 3+5G>C mutation does not alter the canonical GT suggests that the mutation may be leaky. This would explain the patient's mild phenotype. A minigene assay is needed to ascertain this hypothesis. In conclusion, if not identified in infancy, milder forms of DBA may be under- or misdiagnosed, further underlying the role of NGS in diagnosis of atypical inherited anemias. The present case further supports the hypothesis that mutations in RPS26 may be associated to a lower cancer risk in DBA.

МНОЖЕСТВЕННАЯ МИЕЛОМА: ОСОБЕННОСТИ ТЕЧЕНИЯ И ОТВЕТА НА ТЕРАПИЮ У ПАЦИЕНТОВ РАЗНЫХ ВОЗРАСТНЫХ ГРУПП

Background: Multiple myeloma (MM) remains an incurable disease with the development of relapses, sometimes with an uncontrolled course leading to death regardless of the age of the patient. The use of new schemes and methods of treatment has not only significantly improved outcomes in younger MM patients but also improved the quality of life and survival in people over 65 years of age. Objective: to determine the clinical features of the course of the disease and response to therapy in patients of different age groups with newly diagnosed multiple myeloma. Material and Methods: An analysis of the data of 139 patients with newly diagnosed MM was carried out. The median follow-up was 25 months, with a maximum of 58 months. Patients were divided into study groups depending on age at the time of diagnosis: the first group - age up to 65 years (n=65); the second group - age from 65 years and older (n=74). The material of the study was clinical and anamnestic data, the results of laboratory blood tests: biochemical analysis and immunochemical analysis. All the patients underwent the whole body CT scan, diffusely weighted whole body MRI and bone marrow aspiration biopsy with immunophenotypic study. As an induction therapy, according to international recommendations, courses of chemotherapy were used using various regimens containing bortezomib, depending on age and comorbidity. Results. The MM variant with IgA secretion occurred 1.76 times more often in the first group (p=0.128). In the first group hypercalcemia was somewhat more common (2.4 times, p=0.099) and an excess of LDH levels (2.9 times, p=0.072). In contrast, the presence of infectious complications (by 1.2 times, p=0.392), excess of the level of β2-microglobulin > 3 mg/l (by 1.6 times, p=0.086) and kidney damage (by 1.45 times, p=0.037) were more common in the second group, and in the latter case the differences were statistically significant. Disease stage (p=0.0001), excess of β2 microglobulin level (p=0.004), excess of LDH level (p=0.03), presence of anemic syndrome (p=0.003), hypercalcemia (p=0.02), presence of infectious complications (p=0.01) at the time of diagnosis were predictors of worse survival in the general group of MM patients. Conclusion. The active use of new therapeutic strategies and regimens improves treatment outcomes not only in patients under 65 years of age, but also in older patients. New studies are needed to identify prognostic factors in individuals of different age groups in order to start personalized therapy and improve treatment outcomes.

Evaluation of pancytopenia based on bone marrow examination in adults in a tertiary care hospital in Islamabad.

Objective: To evaluate etiological spectrum of pancytopenia in adults using bone marrow aspiration biopsy. Study Design: Randomized Prospective study. Setting: Department of Pathology, Pakistan Institute of Medical Sciences, Islamabad. Period: October 2018-October 2020. Material & Methods: Eight hundred bone marrow biopsies were performed out of which 250 patients came with pancytopenia. 135 patients out of these were in adult age group which are included in this study. Results: Out of 250 patients adults were 135 that presented with pancytopenia. Male to female ratio came out to be 1.22:1. The most common disorder that results in pancytopenia came out to be megaloblastic anemia that was 29.6%, after that 26.6% were infection related changes, 10.3% aplasia, 9.6% reactive marrow, 5.9% acute leukemia, 3.7% chronic leukemia and iron deficiency anemia followed by 2.9% myelodysplastic syndromes and hypersplenism, 2.2% multiple myeloma, 1.4% mixed deficiency anemia and 0.74% myelofibrosis. We also analyzed patients on their presenting complaints as well. Most common complaint of presentation was fever (54.8%), (31.85%) with fatigue and malaise, (31.1%) pallor, vomiting and diarrhea (25.9%) followed by bleeding (14.8%). On clinical examination 12% cases presented with hepatomegaly and 16.6% with splenomegaly. Conclusion: Pancytopenia is a common hematological finding in our setup with megaloblastic anemia to be the most common cause of it. Therefore, it’s very important to diagnose it as this is a curable (reversible) deficiency and patients can easily be managed to prevent serious hematological and neurological abnormalities.

Aplastic anaemia treated using eltrombopag in a dog

AbstractA 2‐year‐old, neutered, female beagle was presented to a referral hospital for investigation of pancytopenia. The patient had a history of recurrent infections and, on previous blood tests, anaemia, leukopenia and thrombocytopenia were detected. At the time of presentation, the patient had been treated for 2 weeks with omeprazole, amoxicillin‐clavulanic acid, marbofloxacin and gabapentin, and for 3 months with prednisolone, in decreasing doses. A bone marrow aspirate and core biopsy were performed. Hypoplastic bone marrow was observed. Once underlying infectious diseases and exposure to toxins were ruled out, a diagnosis of aplastic anaemia was made. The patient was treated with eltrombopag, a thrombopoietin receptor agonist that stimulates primitive haematopoietic stem cells, used for the treatment of aplastic anaemia in humans. One week after starting eltrombopag treatment, all the affected cellular lines were recovered. The patient continued in remission 7 months after treatment.

PATHOPHYSIOLOGY OF PANCYTOPENIA: UNDERSTANDING BLOOD CELL PRODUCTION AND REGULATION IN THE BONE MARROW

Objective: The bone marrow is the primary site for blood cell formation, responsible for the production and export of red cells, platelets, and granulocytes. Pancytopenia is a condition characterized by a reduction in all three types of cellular components in peripheral blood, leading to symptoms of marrow failure. The management and prognosis of pancytopenia depend on identifying the underlying pathology.
 Methods: The pathophysiology of pancytopenia involves various factors such as infections, toxins, malignant cell infiltration, suppression, or ineffective hematopoiesis. Bone marrow examination, including aspiration and trephine biopsy, is crucial for diagnosing pancytopenia, especially when the cause is unclear or when malignancy is suspected. Geographic distribution and genetic disturbances contribute to variations in the incidence of disorders causing pancytopenia.
 Results: The study aims to evaluate the various causes of pancytopenia and correlate peripheral blood findings with bone marrow aspirate and trephine biopsy. The collected data will assist in planning the diagnostic and therapeutic approach for patients with pancytopenia.
 Conclusion: Pancytopenia involves disruptions in blood cell production and regulation. Bone marrow aspiration and trephine biopsy are crucial for diagnosis. Understanding blood cell regulation provides insights. This study aims to enhance diagnostic and therapeutic approaches for pancytopenia.

FREQUENCY OF CAUSES OF PANCYTOPENIA IN BONE MARROW SAMPLES OF PATIENTS

Objective: The aim of this study is to find out the common causes that lead to pancytopenia in our population specially in the province of Punjab. Material and Methods: This is a cross sectional study that was conducted at Chughtai Institute of Pathology, Lahore. The duration of the study was from June 2020 to December 2021. A total of 210 patients were included in the study. A through history was taken and complete physical examination was done prior to the bone marrow biopsy procedure. Peripheral blood sample was run on Sysmex XN 9000 automated hematology analyzer. Bone marrow aspirate and trephine biopsy were thoroughly examined and immunohistochemical stains were applied where required. The data was analyzed using SPSS 23.0 and frequencies were calculated. Results: Most common causes of pancytopenia in our study were megaloblastic anemia (18.1%) followed by aplastic anemia (12.9%), immune mediated causes (12.4%), acute myeloid leukemia (11%), hypocellular marrow (9%) myelodysplastic syndrome (6.2%), hypersplenism (5.2%) and Precursor B acute lymphoblastic leukemia (5.2%) (Fig. 2). Other causes include B cell non-Hodgkin lymphoma (4.8%), mixed deficiency anemia (4.2%), hypersplenism (3.8%), Gaucher’s disease (1.4%), infections (1%) and other miscellaneous causes (4.8%). Conclusion: The study conducted at our institute showed that majority of patients had benign causes (69.2%) leading to pancytopenia, the most common cause being megaloblastic anemia. Malignant causes constitute only a minority of cases of pancytopenia. Key Words: Bone marrow biopsy, Frequency, Pancytopenia

Comparison of bone marrow aspiration and biopsy as diagnostic tool in pediatric age group

Objectives: Bone marrow examination is the final endpoint to the diagnosis of many haematological and nonhaematological disorders when all other clinical diagnostic tools have been done with. It consists of two tests each of which has their own role in making a final diagnosis. First bone marrow aspiration and second bone marrow biopsy. They complement each other and together provides a complete picture of the bone marrow. The study aimed to assess the diagnostic accuracy and to observe the degree of correlation (kappa value) between the two procedures. Material and Methods: This retrospective study was conducted in the department of pathology of our institution from July 2021 to August 2022. In 149 cases, both BMA and BMB was performed simultaneously and was included in the study. BMA slides was stained with Leishman Giemsa stain and BMB underwent tissue decalcification and tissue processing followed by staining with haematoxylin and eosin stain. Other special stains such as PAS, Reticulin and Perl’s, ZielNeelson (ZN) stain were also done on all relevant cases. Data were analyzed using Graphpad Instat 3 and Prism 5. Results: The mean age was 8.23±4.37. Of these, the Male: Female ratio was 1.8:1. The most commonly correlated diagnosis in the lower age group were for iron deficiency anemia (100%), Childhood Acute Leukemia (87.2%) and in higher age groups, the most correlated diagnosis were for Chronic myeloid Leukaemia (100%) and Acute Myeloid Leukaemia (72.72%). Kappa value in our study revealed that there was substantial agreement (0.6295) between the two procedures. the diagnostic efficacy of BMA is 77.18% and for BMB is 90.6%. Conclusion: Bone marrow aspiration and biopsy have upperhand over each other in their respective area. Both shows substantial agreement and hence these should be performed together and not in isolation to give a complete diagnosis.

E031 A rare case of diffuse osteosclerosis

Abstract Background/Aims Diffuse skeletal fluorosis is a common condition in countries with high content of fluoride in the ground water like India and China. Skeletal fluorosis in the UK is rare and presents with non-specific findings such as back pain, elevated ALP or bone sclerosis. We describe a case referred from haematology for investigation of osteosclerosis. Methods 74-year-old female presented to the emergency department on several occasions with recurrent abdominal pain, severe low back pain and swelling of her lower limbs. Her mobility had been reduced due to previous femoral nerve injury. Blood tests on admission showed mild macrocytic anaemia. Alkaline phosphatase, renal, liver function tests and electrolytes were within normal range. Furthermore, calcium, phosphate, vitamin D and parathyroid hormone levels were within normal limits. CT CAP was done and no obvious or sinister cause for abdominal pain was found. However, it showed diffuse bony sclerosis. Bone densitometry DXA scan results as follows: T-score of + 1.6 in the hip and +1.7 in the neck of femur, they were unable to scan the lumbar spine as the patient was unable to tolerate positioning for the scan. This confirmed relatively raised bone density for patient’s age despite having risk factors for osteoporosis like previous wrist fracture, strong family history of osteoporosis, early menopause following total hysterectomy at age 41, coeliac disease and multiple falls due to poor mobility. Results A bone marrow aspirate and trephine biopsy and immunophenotyping were carried out and did not demonstrate any evidence of myeloid or lymphoid neoplasm. The next line of investigations included an isotope bone scan and blood tests including serum tryptase, uric acid and fluoride levels. Fluoride level came back as 411 which is 8-times more than the normal value. Patient mentioned that she uses fluoride toothpaste and brushed her teeth at least 10-14 times/day. X-ray of the hands showed no evidence of periosteal reactions or sclerosis. We recommended that she use fluoride free toothpaste and referred her for a dental opinion. While there is no effective therapeutic agent to reduce fluoride levels, patient was encouraged to use fluoride free toothpaste and also consult with her dentist for further evaluation. Conclusion This case emphasises the need for a comprehensive history and maintaining a high index of suspicion of skeletal fluorosis when encountered with a patient with a high bone mineral density (BMD) score on the DXA scan or diffuse skeletal sclerosis. The increase in bone mineral density is thought to be related to fluoride’s enhanced osteoblastic activity. Disclosure S. Mohamed: None. A. Phillips: None. J. Thomas: None. D. Makkuni: None.

"A New Single Use Needle for Simultaneous Bone Marrow Aspiration and Trephine (Core) Biopsy Utilizing the Same Needle and Same Entry Site While Maintaining the Specimen Quality"

A needle is described for use in simultaneously taking a bone marrow aspirate and a core biopsy sample without sacrificing the quality of either specimen from the posterior iliac crest. The needle comprises a hollow tube with a front-end portion formed to a reduced diameter.

Bone marrow infiltration by Non-Hodgkin lymphoma: An experience in a tertiary care centre.

To determine the frequency and patterns of bone marrow infiltration in non-Hodgkin lymphoma patients. The cross-sectional study was conducted at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from April to October 2021, and comprised patients of either gender aged 20-80 years who had been diagnosed with non-Hodgkin lymphoma. Following assessment and as per standard protocol, bone marrow aspirate and trephine biopsy were done on all patients from the posterior superior iliac spine, and slides were prepared and assessed. Data was analysed using SPSS 25. Of the 100 patients, 67(67%) were males and 33(33%) were females. The overall mean age was 54.99±12 years, and mean duration of symptoms was 11.7±1.5 months. Diffuse large B-cell lymphoma was the commonest type 43(43%). Infiltration of marrow occurred in 38(38%) patients, with 12(12%) of them being cases of mantle cell lymphoma. The commonest infiltration pattern was diffuse in 17(17%) cases, followed by focal/nodular in 10(10%). Diffuse large B-cell lymphoma was found to be the commonest type of non-Hodgkin lymphoma, and marrow infiltration occurred most frequently in cases of mantle cell lymphoma.

Clinico-Hematological Pattern of Haematological Malignancies in Patients Referred for Bone Marrow Examination

Background: Chromosomal translocation is a common cause among hematological malignancies thus. a different diagnostic and treatment approach is required in these cases. Aim: To determine frequencies and clinic-hematological features of different hematological malignancies among patients. Methodology: It was a descriptive cross sectional study. Patients (n=284) with hematological malignancy were enrolled from total 1080 bone marrow biopsies. Detailed history, clinical examination and hematological parameters were recorded at time of presentation. Bone marrow aspiration and trephine biopsy were done as per the clinical indication. Data was evaluated by using SPSS version 23. Chi-square test was applied with p-value of less than 0.05 was considered significant. Results: The study showed the high percentage of hematological malignancies (24%) were observed among enrolled patients with CML being the commonest cancer among them. Practical Implication: This study established the clinic-hematological correlation and provided study based suggestions for better diagnosis and treatment of hematological malignancies while using bone marrow microscopic examination as an important diagnostic tool. Conclusion: It was concluded that acute leukemias were common in younger age whereas chronic leukemias and lymphoproliferative disorders in more advanced ages. Keywords: Hematological Malignancies, Bone Marrow Examination and Diagnosis.

Pancreatic tumor with hepatic metastases secreting vasoactive intestinal polypeptide: Treatment options and long-term follow-up results

Abstract Introduction Vasoactive intestinal polypeptide secreting tumor (VIPoma) are rare neuroendocrine tumors (NETs) and there isn't any robust recommendation for management. In here, we present a metastatic VIPoma case which is managed by multidisciplinary approach. Clinical Case A 64-year-old male patient presented with profuse watery, bloodless and mucous diarrhea and weight loss. In the laboratories analyzes, creatinine:1.02 mg/dL, sodium:136 mmol/L, potassium:2.9 mmol/L, chlorine:115 mmol/L, phosphorus:1.4 mg/dL, calcium:9.8 mg/dL were detected. Infectious and inflammatory causes of diarrhea were excluded. In abdomen magnetic resonance imaging (MRI), there were a 25×23×33 mm lesion in the tail of the pancreas and multiple metastatic liver lesions. Metastatic liver lesion biopsy revealed a NET. Plasma VIP level was 199 ng/L (23–63). Multidisciplinary committee was decided to distal pancreatectomy and metastatic liver lesions’ chemoembolization (TACE). Octreotide LAR 20 mg/month was started. Distal pancreatectomy revealed a 35 mm, grade 1 NET. TACE was done for metastatic liver lesions. At the 3rd month follow-up, the patient's symptoms had improved and he had gained 6 kg. Metastatic liver lesions’ size reduced and plasma VIP level was detected <20 ng/L. At 18th months, abdominal MRI revealed progression of liver metastases. Multidisciplinary committee was decided to re-TACE and octreotide LAR dose increased to 30 mg. At the 3rd month follow-up, it was found that the size of the liver lesions decreased and the VIP level was <20 ng/L. One year later, progression of liver metastases was detected. Plasma VIP level was 168 ng/L. Ga-68 DOTA-TATE PET/CT showed increased uptake in metastatic liver lesions. Peptide receptor radionuclide therapy (PRRT) was decided by the multidisciplinary committee. The patient received 8 cycles of Lu-177 treatment. However, PET/CT control revealed a newly developed metastatic lesion in liver. During this period, the patient applied to the emergency department with the complaint of fever. Hgb: 8.1 g/dL, thrombocyte: 60.1 10^3/uL, WBC: 11.3 10^3/uL were found. A leukoerythroblastic picture was observed in the peripheral blood smear. In bone marrow aspiration biopsy, 3.28% blasts were detected. The patient was evaluated as MDS secondary to PRRT with current results. EPO treatment was started. Since the monocyte count remained above 1000 10^3/uL for more than 6 months during the follow-up of the patient, chronic myelomonocytic leukemia was accepted and azacitidine treatment was started. However, the patient died at the end of the first cycle due to sepsis. CONCLUSION: VIPomas are rare NETs with characteristic symptoms; however, they are often detected with unresectable metastatic disease. Therefore, it is important to keep NETs in mind when evaluating watery diarrhea. Due to the rarity of these tumors, there is no consensus to guide treatment. Therefore, multidisciplinary management of the disease will be more effective.

Detection of focal lesions in the clot section with negative bone marrow aspirate and trephine biopsy-A series of 5 cases.

Bone marrow aspiration and trephine biopsies are commonly used procedures in clinical practice. The practice of making a clot section by using the leftover blood from the bone marrow aspirate material is not a commonly followed practice across centers. A clot section has the advantage of studying the added material with an increased possibility of detecting focal lesions such as myeloma, lymphoma, granuloma, and metastasis in the bone marrow. Bone marrow aspirate, trephine biopsy, and clot section were compared for the detection of focal lesions in a series of 5 patients, 3 of who presented with a history of fever and 2 were already diagnosed cases of Hodgkin lymphoma. Focal lesions were detected in the 5 cases in the clot section alone, whereas bone marrow aspirate and trephine biopsy did not show any focal lesion. Granulomatous infiltration was detected in 3 patients, and lymphomatous infiltration was detected in 2 patients in the clot section, whereas bone marrow aspirate and trephine biopsy were negative for any focal lesion in all 5 cases. A clot section is particularly useful in the detection of bone marrow lesions with a focal distribution. Hence, it must be studied alongside bone marrow aspirate smears, touch smears, and trephine biopsy to increase the diagnostic yield.

A comparative study of bone marrow aspiration and trephine biopsy: Experience in a tertiary care center

Abstract Introduction: A bone marrow examination involves the pathological analysis of samples from the bone marrow, which are obtained through bone marrow aspiration (BMA) and biopsy procedures. This examination is employed for the diagnosis of various hematological and nonhematological conditions. Both aspirate and biopsy samples are essential, offering a comprehensive bone marrow assessment. Objectives: In this study, we aim to compare the simultaneous evaluation of bone marrow aspirates and biopsies and to study diagnostic accuracy and concordance rate. Materials and Methods: This research was performed at the Department of Pathology, Shri Aurobindo Medical College, and Postgraduate Institute in Indore, Madhya Pradesh, India. The study was conducted from January 2019 to December 2019 and evaluated 200 patients. In 170 instances, bone marrow biopsy (BMB) and BMA procedures were conducted simultaneously, with 14 cases excluded due to issues like hemodilution or inadequate samples. Microscopic examinations were carried out on both aspirate slides and trephine biopsy sections, with the findings meticulously documented. Results: In the present research, the most prevalent clinical reason for performing a bone marrow examination was anemia (28.2%), closely followed by acute leukemias (21.9%). Among the 156 cases examined, BMA and biopsy led to a definitive diagnosis in 116 patients (74.3%), while biopsy alone diagnosed 27 cases (17.3%). Conclusion: While BMB continues to be the established benchmark for bone marrow analysis due to its heightened reliability and sensitivity, the combined use of both BMA and BMB enhances diagnostic yield significantly.

Frequency of Hematological Malignancies Based on Bone-Marrow Aspiration and Trephine Biopsy in Patients Presenting to Tertiary Care Hospital

Background: Hematological disorders are found commonly in the general population existing on both ends of the spectrum with minute disorders like iron deficiency anemia to as severe as bone marrow infiltration Objective: To assess the frequency of hematological malignancies based on bone-marrow aspiration and trephine biopsy in patients presenting to tertiary care hospital Methodology: The current study was cross-section descriptive study carried out at the Pathology department of Bacha Khan Medical College, Mardan from April 2013 to October 2021. Bone-marrow aspiration and trephine biopsy was done for all the patients. Data regarding gender, age, clinical examination and diagnosis was recorded on a proforma designed for this research. Results were analyzed by using IBM SPSS (version 23). Results: In our study, a total of 182 patients were included. The mean age (±SD) in the current study was 41 (12.6) years. Based on the malignant hematological disorder, acute myelogenous leukemia was diagnosed in 15 (23.08%) patients, acute lymphoblastic leukemia in (23.08%) patients, chronic myeloid leukemia in 14 (21.54%) patients, acute leukemias in 3 (4.62%) patients, Myeloproliferative neoplasms in 6 (9.23%) patients, Lymphoproliferative disease in 11 (16.92%) patients while plasma cell myeloma was diagnosed in 1 (1.54%) patients. Conclusion: Our study concludes that acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) is the most common hematological malignancies in Bacha Khan Medical College followed by chronic myeloid leukemia (CML) which is the second highest malignancies in Bacha Khan Medical College in this specific time. Keywords: hematological malignancies, bone-marrow aspiration, trephine biopsy

Study of Spectrum of Lesions in Bone Marrow Aspiration and Trephine Biopsy from a Tertiary Care Centre in South India

Bone marrow examination is an important diagnostic tool widely used in various haematological and non-haematological disorders. Bone marrow evaluation may either confirm clinically suspected disease or may provide the previously unsuspected diagnosis.

Prospective Study of the Usefulness of Liquid Biopsy in Patients with Unknown Fever Suspected of Malignant Lymphoma

Background: Malignant lymphoma, represented by intravascular large B-cell lymphoma (IVLBCL), is an important differential disease in classical fever of unknown origin (FUO). Bone marrow aspiration (BMA) and random skin biopsy (RSB) are useful in IVLBCL diagnosis, but their positivity rates are clinically insufficient and the procedures are invasive. The molecular genetic analysis of lymphomas using cell-free tumor DNA (cfDNA) in plasma (liquid biopsy) may be effective for IVLBCL (Shimada et al., Blood. 2021 Mar 18;137(11):1491). We conducted a multicenter prospective clinical trial to investigate the usefulness of liquid biopsy for early lymphoma diagnosis among patients with classical FUO. Methods: Patients with the following criteria were enrolled: (1) clinically suspected malignant lymphoma, (2) persistent fever for >3 weeks, refractory to antibiotics, (3) higher than standard lactate dehydrogenase, (4) unbiopsiable lesions, and (5) age ≥20 years. Liquid biopsies were performed as follows: (1) MYD88 L265P/CD79 Y196 mutation analysis using droplet digital PCR (ddPCR), (2) B-cell receptor (BCR)/T-cell receptor (TCR) reconstruction analysis using next generation sequencing (NGS), and (3) comprehensive genetic analysis using the hematopoietic oncogene panel (426 genes) and NGS. Pathological malignant lymphoma was diagnosed at each institution; later, a central diagnosis was made by two additional lymphoma pathology specialists. Results: Fifty patients were enrolled from 15 centers from October 2019 to September 2021; one was excluded. The median age was 73.5 (21-89) years; 28 patients (57.1%) were male. There were 29 cases (59%), 28 (57.1%), and one (2%) of hematologic malignancy, malignant lymphoma, and MDS/AML, respectively (Fig. 1A). Twenty (71%) malignant lymphomas were B-cell lymphomas (17 of which were IVLBCL [61%]), and 8 (29%) were mature T/NK-cell lymphomas. Nonhematologic diseases were present in 20 (41%) patients (7 collagen diseases [4 adult-onset Still's disease, 3 others], 2 solid tumors, 2 infections [1 syphilis, 1 tuberculosis], and 9 FUO). FUO pathological investigations were performed in 47 (97.9%) and 43 (87.6%) patients with BMA and RSB, respectively. IVLBCL had a 53% positivity rate for initial BMA (9/17) and RSB (8/15; Fig. 1B). Only 65% patients tested positive for either initial BMA or RSB and a majority (15/17) of them were diagnosed based on repeated evaluations during their lifetime. The BMA positive rate in patients with mature T/NK-cell lymphoma (8 cases) was high (75%). The mean cfDNA concentration was 215 (5.6-1320) ng/mL, with no significant difference between patients with lymphoma and those with other diseases (279 vs. 130 ng/mL, p=0.073). In ddPCR analysis, 85% of B-cell lymphoma cases (N=20) had either MYD88 or CD79B mutations; the mutation detection rate in IVLBCL (N=17) was 94% (Fig.1B, 2). All patients with non-B-cell lymphoma tested negative. The positive rate of patients with B-cell lymphoma in the NGS-based BCR reconstruction analysis was 90% and negative in two patients with IVLBCL. BCR reconstitution was also observed in two patients with T/NK-cell lymphoma. Comprehensive panel analysis demonstrated that 19/20 (95%) B-cell lymphoma cases showed MYD88 or CD79B mutations; all IVLBCL cases showed mutations. LymphGen algorithm analysis showed that 15, 1, and 1 IVLBCL cases were categorized as MCD (with MYD88 or CD79b mutations), composite (including MCD), and other, respectively (Fig. 2). In T/NK-cell lymphomas, TCR reconstitution was positive in 3/8 T/NK-cell lymphomas. Panel analysis could hardly predict T/NK-cell lymphoma. DdPCR results were returned to the physician within a median time of 14 days. Of the six patients who were not diagnosed with initial BMA and RSB, five were positive for the MYD88/CD79B mutation, according to the ddPCR results. Three of them were diagnosed through additional liquid biopsy testing. Two patients were diagnosed with IVLBCL based on central diagnosis after death. Conclusions: In the classical FUO cases with suspected malignant lymphoma, 57% and 35% had malignant lymphoma and IVLBCL, respectively. Compared to the classical diagnostic methods, liquid biopsy can be used to detect lymphoma-specific genetic mutations at an earlier stage, being clinically useful for the early diagnosis of difficult-to-diagnose malignant B-cell lymphomas. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal