Tuberculoid granuloma in bone marrow biopsy can be a rare cause of pancytopenia

Dear Editor, Diagnosis of tuberculosis always remains a problematic area for clinicians even if the advancement of diagnostic modalities and evolving health technologies.[1] Evaluation of bone marrow is a very much useful diagnostic modality for evaluating different neoplastic and nonneoplastichematological diseases. The incidence of marrow granuloma is 0.3%–3% of all bone marrow biopsies, out of which tuberculoid granulomas constitute 6%–8% of cases.[2] Different diseases implicated in the formation of granulomas are tuberculosis, sarcoidosis, fungus, and Q fever. However, granulomas in the bone marrow due to tuberculosis always indicate an advanced stage of disease with a high rate of mortality. Here, we report the case of a 9-year-old boy who presented with pyrexia of unknown origin (PUO) and pancytopenia. Bone marrow biopsy revealed tuberculoid granulomas. A 9-year-old boy came to the hospital with a history of fever for 35 days, associated with cough and dyspnea on exertion. The fever was low grade, with no chills or rigor and relieved with antipyretic medications. There was no history of burning micturition, bone pain, jaundice, headache, or seizures. On examination, the pulse rate of the patient was 90/min, blood pressure-120/75 mmHg, body temperature was 102°F, and respiratory rate was 19/min. A moderate degree of pallor was noted. There was no icterus, cyanosis, or pedal edema. On systemic examination, there was no hepatomegaly. The cardiovascular examination was normal. Investigation revealed anemia, low white blood cell (WBC), and platelet count (Hb: 9.5 g/dl, WBC count: 1700/mm3, and differential leukocyte count-N71, L20, E01, M08, B00, and platelets 100,000/mm3). Anemia was normocytic normochromic in nature [Figure 1a]. The reticulocyte count was 1.3%. The liver function test was normal except for alkaline phosphatase which was raised i, e.,166 U/L. Kidney function test and urine routine examination showed a normal study. Malaria test, Widal test, and sputum for acid-fast bacilli (AFB) were negative.Figure 1: (a) Peripheral smear showing normocytic normochromic red blood cells with decreased total leucocyte count and platelet count (Lieshman, ×400). (b) Normocellularmarrow (marrow fragments - inset) with normal trilineagehematopoiesis. (Lieshman, ×400). (c-e) Bone marrow biopsy showing epitheloid granulomas Blue arrows (with focal necrosis (H and E, ×200, H and E, ×200, H and E, ×400), (f) Negative for AFB (Ziehl–Neelsen, ×400). AFB: Acid-fast bacilli, RBCs: Red blood cellsElectrocardiography and ultrasonography of the abdomen was normal. As a workup for pancytopenia and clinical history of PUO, a bone marrow study was performed. Aspiration and biopsy of the bone marrow were normocellular for age. There was normoblastic maturation in the erythroid series, whereas the myeloid series and megakaryocytic series were unremarkable. However, bone marrow biopsy showed few epithelioid cell granulomas [Figure 1b-e] with Langhans type of giant cells and a small focus of necrosis. Ziehl–Neelsen stain (20%) was done, but it was negative for AFB [Figure 1f]. Hence, provisional diagnosis of granulomatous inflammation favoring tuberculosis was made. Considering the financial constraint, confirmatory diagnosis by molecular methods could not be done. Empirically, the patient was put on anti-tubercular therapy. There was a dramatic response to antitubercular treatment and clinical condition improved after 15 days. There was a reversal of pancytopenia after 3 months of taking treatment. Tuberculosis-induced pancytopenia is very less according to the literature. Pancytopenia in tuberculosis may be attributed to infiltration of the bone marrow by tuberculous granulomas, phagocytosis of blood cells by histiocytes in the bone marrow, and hypersplenism.[3] Besides, pancytopenia can be caused by marrow suppression through the release of lymphotoxins and interferons. Another explanation of hematological findings could be due to the macrophage activation system (hemophagocytosis), which includes fever, pancytopenia, hyperferritinemia, and hypertriglyceridemia.[3] In clinical practice, exact etiology for granulomatous inflammation is required for treatment. In general noninvasive samples such as blood, serum, plasma, urine, saliva, and feces which are easy to access, commonly meet the need in the diagnosis of most of diseases.[3] However, bone marrow biopsy is feasible and very often needed in special circumstances like PUO or hematologicaldisorders.[4] Index case presented with PUO and pancytopenia, diagnosed as tuberculoid granulomas with focal necrosis in bone marrow biopsy. Normalization of peripheral blood parameters following antitubercular therapy supporting the diagnosis of tuberculosis. Bone marrow biopsy is extremely helpful over aspiration, particularly in granulomatous lesions in the bone marrow. Sometimes, it is very much helpful for diagnosing a case of PUO and pancytopenia. Although granuloma in bone marrow biopsy is rarely pathognomonic, it helps to point toward a spectrum of diseases. Hence, to reach the correct diagnosis, detailed clinical data and communication between the physician and the pathologist are very much helpful. 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 initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.