Original article
Granulomatous lesions in bone marrow: Clinicopathologic findings and significance in a study of 48 cases

https://doi.org/10.1016/j.ejim.2012.11.008Get rights and content

Abstract

Purpose

Granulomas in bone marrow are an infrequent finding related to various disorders. The aim of this study was to review our clinical experience with granulomatous bone marrow disease and to describe the contributions of recent diagnostic tools, such as 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG-PET) and molecular biology.

Methods

Clinical, laboratory and morphological data on patients with a granuloma based on bone marrow biopsy analysed in the University Hospital Lyon from May 2004 to July 2010 were reviewed.

Results

We identified 57 cases among 9641 bone marrow biopsies, representing an incidence of 0.59% in the series and an annual incidence of 9.5 cases per year. Nine biopsies performed for staging a known pathology were excluded from further analysis. Among the 48 remaining patients, associated disease was demonstrated in 79%, with infections being the most common (33%), following by sarcoidosis (21%), malignancy (19%) and therapy-induced granulomas (6%). One previously unpublished entity is described: infection with Bartonella henselae diagnosed using molecular biology from node and skin biopsies in two renal transplant patients. 18F-FDG-PET, performed in 13 cases, showed hypermetabolic foci consistent with sarcoidosis in two cases. Positive PCR result for an infectious pathogen was obtained in three bone marrow samples (Mycobacterium tuberculosis, n = 1; Mycobacterium genavense, n = 2).

Conclusion

In comparison to previous research, our study reports high proportions of cases caused by sarcoidosis and unknown causes. 18F-FDG-PET could show signs consistent with sarcoidosis and molecular biology is useful for the detection of fastidious bacteria in immunocompromised patients.

Introduction

Epithelioid granulomas are an infrequent finding in bone marrow biopsies and may be associated with a broad spectrum of disorders. The incidence of bone marrow granulomas ranges from 0.3% to 2.2% depending on the main series. Their significance has been a subject of interest in the past, and five large series from 1956 to 1988 have documented the incidence and aetiology of marrow granulomas [1], [2], [3], [4], [5]. Since the last review of the literature by Eid in 1996 [6], only one small Indian study on this topic has appeared in the English literature [7]. Moreover, previous studies did not distinguish granulomas found on bone marrow biopsy for staging a known pathology (i.e., lymphoma, disseminated tuberculosis) from granulomas found on biopsies for diagnosis. Accordingly, we have chosen in this work to retain only the diagnostic cases. During the past 15 years, progress has been made in diagnosing many of the diseases implicated in the pathogenesis of bone marrow granuloma using, for example, 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG-PET) and molecular biology. This study aimed to reevaluate the prevalence and aetiology of bone marrow granuloma and to evaluate the performance of these new diagnostic tools.

Section snippets

Material and methods

A retrospective case review was performed on bone marrow biopsies collected from the files of the haematology laboratory of the University Hospital Lyon, France. The records of all cases of bone marrow granulomas reported from May 2004 to July 2010 were obtained from this centre and reviewed by the same pathologist (MF) to confirm the presence of granulomas.

Bone marrow biopsies were performed by puncture of the posterior iliac crest using a Jamshidi needle. Undecalcified bone specimens were

Incidence of bone marrow granulomas

Over the six-year period of this study, 9641 bone marrow biopsies were referred to the laboratory of haematology. 57 samples revealed granulomatous lesions. This corresponds to an incidence of 0.59 per 100 biopsies and an annual rate of 9.5 cases per year.

Biopsy indication

Indications for bone marrow examination could be divided into two major categories: (i) determination of the aetiology of a specific finding in 48 patients (84.2%) and (ii) staging a known pathology in nine patients (lymphoma, n = 3;

Discussion

Bone marrow epithelioid granuloma is not a frequent finding in a bone marrow biopsy [1], [2], [3], [4], [5]. We have provided a more recent overview of the literature and assessed the value of new diagnostic tools such as FDG-PET and molecular biology.

Conclusion

The incidence of granulomatous bone marrow disease remains low, and its main aetiologies are the same as they were fifteen years ago, when the most recent case series were published. One previously unpublished entity is described: infection with B. henselae confirmed with molecular biology from node and skin biopsy in two renal transplant patients. We provide the first report of a favourable long-term course and prognosis of isolated granulomatous bone marrow disease. The percentage of

Learning points

  • Incidence of granulomatous lesions in bone marrow is low.

  • Most of them are associated with infectious disease.

  • Granulomatous lesions from unknown origin have a favourable long term course and prognosis.

  • PET-CT can be helpful in some cases and molecular biology is useful for detecting infection in immunocompromised patients.

Conflict of interests

None of the authors have conflict of interest in this article.

Acknowledgements

We thank Pr J. Ninet (Department of Internal medicine, Hôpital Edouard-Herriot, Lyon, France), Pr D. Peyramon (Department of Infectious and Tropical Diseases, Hôpital de la Croix-Rousse, Lyon, France), Pr I. Durieu (Department of Internal medicine, Hôpital Lyon Sud, Lyon, France), Pr B. Coiffier (Department of Hematology, Hôpital Lyon Sud, Lyon, France), Pr M. Michallet (Department of Hematology, Hôpital Edouard-Herriot, Lyon, France), Dr P. Bachet (Department of internal medicine, Hôpital St

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    This work has been presented as an oral communication at the 63rd Congress of the Société Nationale Française de Médecine Interne (SNFMI) in Poitier, France on June 9th, 2011.

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