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Year : 2019  |  Volume : 62  |  Issue : 3  |  Page : 493-494
Bone marrow granuloma in a child with pyrexia of unknown origin: A clue for diagnosis of brucellosis

1 Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
3 Department of Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

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Date of Web Publication26-Jul-2019

How to cite this article:
Suthar R, Bansal D, Suri D, Sharma P, Ray P. Bone marrow granuloma in a child with pyrexia of unknown origin: A clue for diagnosis of brucellosis. Indian J Pathol Microbiol 2019;62:493-4

How to cite this URL:
Suthar R, Bansal D, Suri D, Sharma P, Ray P. Bone marrow granuloma in a child with pyrexia of unknown origin: A clue for diagnosis of brucellosis. Indian J Pathol Microbiol [serial online] 2019 [cited 2021 Jun 13];62:493-4. Available from: https://www.ijpmonline.org/text.asp?2019/62/3/493/263497

Bone marrow culture and biopsy are an integral part of investigations in children with pyrexia of unknown origin (PUO). Granulomatous lesions are uncommon findings in bone marrow and only a few diseases are associated with them.[1] Brucella is an uncommon cause of granuloma formation in the bone marrow. Diagnosis of brucellosis is often delayed because of low clinical suspicion in non-endemic areas.

A 7 year-old-boy presented with fever for 2 months. There was no history of cough, dyspnea, rash, anorexia, weight loss, bleeding manifestations, eschar, arthralgia or bone pain and his parents confirmed no recent travel, contact with tuberculosis or exposure to pets or farm animals. He had received oral and intravenous antibiotics at outside clinics. On examination, subcentimetric cervical lymph nodes and hepato-splenomegaly 4 and 3 cm below respective costal margins were noted. Other systemic evaluationwas unremarkable.

Hemoglobin was 11.5 gm/dl; total leukocyte count was 9.2 × 10^9/L with 69% neutrophils and 25% lymphocytes. Platelet count was 278 × 10^9/L and the peripheral blood smear was normal. Peripheral smears and immunochromatographic test for malaria, blood culture, Widal test, rK39antigen, Mantoux test, sputum for acid-fast bacilli (AFB) and serology for Epstein barr virus and parvovirus were negative. Contrast-enhanced CT (CECT) chest was normal and CECT abdomen confirmed hepato-splenomegaly. Anti-nuclear antibodies, rheumatoid factor and serum ferritin were negative/normal.

Bone marrow was normocellular and the trephine biopsy revealed very few well-defined epithelioid granulomas [Figure 1]a as well as tiny, ill-defined paratrabecularcollections of epithelioid histiocytes [Figure 1]b in a few sections. However, no caseous necrosis or giant cell formation were seen. Stains for AFB and fungi were negative. Brucella standard tube agglutination test and serology were positive (Brucella IgM ELISA 1:2560 titer). Subsequently, blood culture on prolonged incubation showed growth of Brucella melitensis. The child was treated with intravenous gentamycin for 2 weeks and oral rifampicin and trimethoprim-sulfamethoxazole for 4 weeks. Fever subsided in a week. On follow-up, hepatosplenomegaly regressed and titers for Brucella serology declined.
Figure 1: (a) Bone marrow trephine biopsy showing a small non-caseating granuloma. (b) Tiny para-trabecular collection of histiocytes and lymphocytes (original magnification 400x, hematoxylin and eosin)

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Granulomatous inflammation represents a distinctive chronic inflammatory pattern characterized by focal accumulation of activated macrophages, which often develop an epithelioid appearance. It is non-specific, encountered in immune-mediated, infections and non-infectious conditions. Tuberculosis is the prototype, however typhoid fever, sarcoidosis, brucellosis, and malignancies like Hodgkin and non-Hodgkin lymphomas can also be associated with a granulomatous reaction.[1] Naseem et al. reported only two cases of granulomatous reaction in 990 bone marrow studies performed for evaluation of bicytopenia or pancytopenia in children.[2] The high frequency of tuberculosis in India leads to a risk of all granulomatous inflammations to be presumptively labelled as tuberculosis, which may delay the diagnosis of the actual underlying infection or neoplasm.[3]

Presence of granulomatous lesions in the bone marrow biopsy and subsequent positive blood culture confirmed the diagnosis of brucellosis in the index child. Brucella is among the most common zoonotic disease affecting humans. The disease in endemic in many parts of Asia including India.[4] Human Brucellosis remains under diagnosed and underreported, particularly in the non-endemic areas because of subtle clinical manifestations and a low index of clinical suspicion among physicians. Human infection occurs through consumption of unpasteurized dairy products and raw meat which may contain the bacteria.[5]

Brucellosis in children presents with osteo-articular manifestations in 70% and with non-specific fever in 20%.[6] In a large series of childhood Brucellosis, the most common clinical manifestations reported were fever, joint pain, and hepatomegaly.[7] Blood culture is the gold standard for diagnosis but its use is limited because of delayed growth of the organism resulting in low sensitivity that is further reducedby prior empirical antibiotic use. Hematological manifestations of Brucellosis include anemia, leucopenia, lymphocytic leukocytosis and rarely with thrombocytopenia, pancytopenia.[6],[7],[8] Bone marrow findings in cases complicated by pancytopenia include normocellular or hypercellular marrow, granulomas, hemophagocytosis, rarely myelofibrosis and hypoplasia.[8] The incidence of Brucella as cause of granulomatous lesions in bone marrow is reported to usually be between 0% to 25% in various case series.[1] Granulomas in Brucella are typically small, with epithelialized cells surrounded by a few lymphocytes and plasmacells. Hemophagocytosis may occur, but caseating necrosis is typically absent.[9]

In conclusion, Brucellosis is a rare but important infectious cause of granulomatous lesions in the bone marrow as well as an important and treatable cause of PUO even in non-endemic areas. Rare, small-sized non-caseating granulomas, as in our case represent important diagnostic clues and pathologists should employ serial sections to confirm their presence/absence.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Eid A, Carion W, Nystrom JS. Differential diagnoses of bone marrow granuloma. West J Med 1996;164:510-5.  Back to cited text no. 1
Naseem S, Varma N, Das R, Ahluwalia J, Sachdeva MU, Marwaha RK, et al. Pediatric patients with bicytopenia/pancytopenia: Review of etiologies and clinico-hematological profile at a tertiary center. Indian J Pathol Microbiol 2011;54:75-80.  Back to cited text no. 2
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Sharma P, Dhingra KK, Sural S, Mandal AK, Singh T. Langerhans cell histiocytosis masquerading as tuberculosis: A diagnostic dilemma resulting in inappropriate anti-tubercular therapy. Pediatr Blood Cancer 2009;53:111-3.  Back to cited text no. 3
Smits HL, Kadri SM. Brucellosis in India: A deceptive infectious disease. Indian J Med Res 2005;122:375-84.  Back to cited text no. 4
Sathyanarayanan V, Razak A, Saravu K, Ananthakrishna SB, Mukhyprana Prabhu M, Vandana KE, et al. Clinical profile of brucellosis from a tertiary care center in Southern India. Asian Pac J Trop Med 2011;4:397-400.  Back to cited text no. 5
Shaalan MA, Memish ZA, Mahmoud SA, Alomari A, Khan MY, Almuneef M, et al. Brucellosis in children: Clinical observations in 115 cases. Int J Infect Dis 2002;6:182-6.  Back to cited text no. 6
Bosilkovski M, Krteva L, Caparoska S, Labacevski N, Petrovski M. Childhood brucellosis: Review of 317 cases. Asian Pac J Trop Med 2015;8:1027-32.  Back to cited text no. 7
al-Eissa YA, Assuhaimi SA, al-Fawaz IM, Higgy KE, al-Nasser MN, al-Mobaireek KF, et al. Pancytopenia in children with brucellosis: Clinical manifestations and bone marrow findings. Acta Haematol 1993;89:132-6.  Back to cited text no. 8
Pease GL. Granulomatous lesions in bone marrow. Blood 1956;11:720-34.  Back to cited text no. 9

Correspondence Address:
Deepak Bansal
Department of Pediatrics, Advanced Pediatric Center, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_7_18

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