BACKGROUND AND PURPOSE Leukoerythroblastic reaction (LER) is characterized by the presence of immature erythroid cells and myeloid precursors (metamyelocytes, myelocytes, promyelocytes, myeloblasts, and blasts) as well as, exclusively in myelofibrotic disorders, teardrop cells in the peripheral blood (J Pathol Bacteriol, 42, 1936, 541; Semaine Med, 22, 1902, 373). Research on how to interpret LER and its meaning in clinical practice is scarce, and there is no consensus on the diagnostic criteria. We summarize the current evidence with the aim of clarifying the knowledge on this subject. METHODS We conducted a comprehensive search of the PubMed-MEDLINE, EMBASE and ELSEVIER databases, the Cochrane Library, Google Scholar, and medical journals to identify relevant papers. RESULTS Our search identified 425 papers, of which, 35 (11 trials and 24 case reports) ultimately met the inclusion criteria. These showed two principal groups of diseases associated with leukoerythroblastosis (LEB), corresponding to solid and hematological malignancies. The other etiologies, in order of frequency, were hemolytic diseases, infection, and others, while hemorrhage was only reported in the trials group. CONCLUSION The literature on LER is scarce and heterogeneous. The etiological factors of LER are diverse, and its presence in malignant disease is an indicator of disease progression and an adverse prognosis suggesting poor survival. In those cases where LER had neither hematological nor solid neoplasms, its manifestation, prognosis and its impact on our daily clinical practice are unknown.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/ijlh.13238

Systematic review about etiologic association to the leukoerythroblastic reaction.

Background & objective Introduction: First detection of any solid tumour as metastatic deposits in bone marrow directs clinicians to start searching for the primary tumour. Detection of bone marrow metastasis determines the stage of the malignancy, prognosis, mode of treatment, chemotherapeutic response and follow-up in case of relapse. The aim of the current study was to analyse the clinico-haematological presentation and morphological pattern of infiltration of solid tumours detected first as metastatic deposits on bone marrow examination. Methods Three-year retrospective analysis of MGG-stained bone marrow aspiration smears and touch imprints of the bone marrow biopsy and Hematoxylin and Eosin (H&E) stained histopathological sections of biopsies was performed at the Department of Pathology at a tertiary care institute (January 2014 to December 2016). The morphological pattern of metastatic deposits and haematological profiles of the patients were analysed. Exclusion criterion was the presence of hematolymphoid malignancies. Results In 22 cases, bone marrow was the first site of detection of metastasis. The age of the patients ranged from 3 years and 10 months to 82 years, with equal gender predilection. Overall, 16 cases had cytopenias, 9 cases each had leucocytosis and leukoerythroblastic presentation. The metastasis was from Ewing's sarcoma, prostate carcinoma, gastric adenocarcinoma invasive duct carcinoma breast, gallbladder carcinoma, lacrimal duct carcinoma and invasive papillary urothelial carcinoma. Conclusions Bone marrow examination is a cheap and reliable investigation to detect metastasis in an unsuspecting case. Bilateral trephine biopsies are recommended to increase the efficacy of detecting bone marrow metastasis.

http://ijp.iranpath.org/article_30048_f0a92d3b32d92990a4cd607832167d7c.pdf

Beware of Bone Marrow: Incidental Detection and Primary Diagnosis of Solid Tumours in Bone Marrow Aspiration and Biopsies; A Study of 22 Cases.

Clear cell renal cell carcinoma (RCC) is the most frequently reported renal cell neoplasm, which commonly metastasizes to the lungs, bones, lymph nodes, liver, adrenal gland and/or brain. It is usually diagnosed as an incidental finding on radiological imaging, which can further be confirmed by histological examination of the neoplastic tissue. Bone marrow metastasis of renal cell tumors is a rare event and very few cases have been reported. Here we report an unusual case of a 68-year-male who presented with lytic bone lesions on imaging. This raised the suspicion of a bone marrow involvement by a hematolymphoid malignancy or metastatic disease and a bone marrow biopsy was performed. Incidentally, the biopsy revealed infiltration of bone marrow by clear cell RCC. The patient was referred to the oncology clinic where further workup was done which revealed a primary renal tumor.

Bone Marrow Metastasis in Clear Cell Renal Cell Carcinoma: A Case Study.

Small cell neuroendocrine carcinoma (SNEC) is a high grade and poorly differentiated neuroendocrine tumor which typically presents as a primary pulmonary neoplasm near the bronchial region. Due to the aggressive nature of the tumor, there are many ways it can initially present, mostly involving the lungs. We present a case of a 68-year-old male patient who initially presented with new-onset of severe thrombocytopenia with superimposed pneumonia. It was late in the progression of the disease that histopathology from the bone marrow confirmed SNEC, which presented only after it metastasized to the bone marrow by way of a rare paraneoplastic syndrome. Furthermore, the bone marrow biopsy revealed atypical markers not commonly seen in SNEC. Since this was such an atypical presentation of SNEC, management was limited to stabilization of the patient. The patient expired two weeks later.

A rare case of metastatic small cell neuroendocrine carcinoma of the lung presenting as isolated thrombocytopenia

Background- Bone marrow is an important site for metastasis in cases of non hematological malignancies and is routinely performed to stage the disease or to rule out metastasis in suspected cases..
Purpose- Purpose of the study is to evaluate bone marrow in cases of solid tumors and also to enumerate the types of tumors metastasizing to marrow at our institute.
Methods- This was a retrospective study and clinical and laboratory data were retrieved from case files and laboratory records. All the case where bone marrow aspirate was performed to rule out metastasis or for staging were included along with those cases where patient presented to us with hematological abnormalities and diagnosed to have a metastasis in marrow.
Results- Out of total 758 cases of total bone marrow performed, 89 were performed in proven cases of non hematological malignancies of which 31 showed tumor deposits. While in two cases metastatic deposits were first seen in marrow aspirate. Most common tumor metastasizing to marrow at our institute was adenocarcinoma of lung followed by breast and small cell carcinoma of lung. In pediatric age group most common tumor was Ewing’s sarcoma followed by rhabdomyosarcoma. Most common peripheral smear abnormality seen was thrombocytopenia followed by anemia and leukoerythroblastic blood picture.
Conclusion- Bone marrow aspiration is an easy, rapid and sensitive technique to determine metastasis of solid tumors in bone marrow and can be performed in hematological abnormalities to rule out any metastasis in otherwise unsuspected cases.

/pdf/bone-marrow-involvement-in-non-hematological-malignancy-a-41xnlxuhh9.pdf

Bone Marrow Involvement in Non-Hematological Malignancy: A Clinico-pathological Study From a Tertiary Hospital

Background: Bone marrow metastasis by a nonhematologic malignancy signifies advanced stage of disease and confers a poor prognosis. The aim of this study was to analyze clinical presentation, hematological profile, biochemical profile, radiological presentation, and patterns of bone marrow involvement in patients with metastatic nonhematologic malignancies retrospectively. Materials and Methods: Ninety bone marrow procedures were done in cases of nonhematologic malignancies for suspected involvement or as a part of staging procedure. Results: Sixteen out of 90 patients showed metastasis by nonhematologic malignancies. The most common malignancy to metastasize was malignant small round cell tumor (Ewing's sarcoma and rhabdomyosarcoma) followed by carcinoma breast and prostate. The most common clinical presentation was backache, fever anorexia, and abdominal pain. The biochemical findings included raised serum calcium and lactate dehydrogenase. 62.5% had anemia and 37.5% had thrombocytopenia. Leukocytosis was seen in 37.5% of patients. Leukoerythroblastic picture was seen in 43.75% cases. Of the eleven cases where both bone marrow aspirate and biopsies were done, 10 cases showed malignant cells in both. Immunohistochemistry was conclusive in four cases. The combined procedure of aspiration and biopsy gives a higher yield and are essential in patients with suspected bone marrow metastasis in nonhematologic malignancies.

Bone marrow metastasis in nonhematologic malignancies: Data from a cancer hospital

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Bone marrow metastasis in nonhematologic malignancies: Data from a cancer hospital