Bacillus Calmette-Guérin Vaccine-induced Mycobacterial Spindle Cell Pseudotumor in an Infant

To the Editors: Mycobacterial spindle cell pseudotumor (MSP) is a rare non-neoplastic disease resulting from mycobacterial infection, with a distinctive histopathology of spindle-shaped histiocytes proliferation containing acid-fast positive mycobacteria.1 The incidence is higher in immunocompromised patients, especially those with acquired immunodeficiency syndrome. It is uncommon in infants. We report a rare case of an infant with MSP induced by Bacillus Calmette-Guérin (BCG) vaccine, which confirmed by fine-needle biopsy and identification of Mycobacterium bovis by next-generation sequencing. A 4-month-old boy presented to Children’s Hospital with a 2-month history of intermittent fever, poor weight gain and a growing left axillary mass. He had received BCG vaccination at birth as part of the routine immunization protocol in the country. On physical examination, he had a spherical protruding mass (2.5 cm × 2.5 cm) with redness and edema in the left anterior axilla (Fig. 1A), multiple enlarged ipsilateral axillary lymph nodes (up to 1.5 cm) and an ulcerated BCG site. Chest computed tomography revealed bilateral consolidation in the posterior segments of the upper lobes. Laboratory tests showed leukocytosis (11.5 × 109/L) with neutrophilia (73.6%), elevated C-reactive protein (146 mg/L, normal range <8 mg/L) and procalcitonin (0.54 ng/mL, normal range <0.05 ng/mL). Mantoux test was nonreactive. HIV and interferon-gamma release assay were negative.FIGURE 1.: A: A spherical protruding mass (2.5 cm × 2.5 cm) with redness and edema in the left anterior axilla. B: After 12 months of treatment, the mass had significantly reduced in size. C: After 18 months of treatment, the mass had completely resolved. D: Low-power view (×100) of histopathology findings demonstrating numerous proliferating spindle cell aggregates without caseating necrosis (hematoxylin-eosin section). E: Higher magnification (×400) showing positive acid-fast bacilli stain within the spindle cells.Fine-needle biopsy was performed, and histopathologic examination revealed numerous proliferating spindle cell aggregates without caseating necrosis (Fig. 1B) and positive acid-fast bacilli stain within the spindle cells (Fig. 1C). Immunohistochemistry staining demonstrated diffuse and strong expression of CD68 in the proliferating spindle cells, indicating a monocytic/histiocytic origin for these cells. Mitotic activity was assessed by immunostaining for Ki-67 and was estimated to be less than 1%. The microscopic findings were consistent with the diagnosis of Mycobacterial spindle cell pseudotumor. M. bovis was subsequently identified by NGS-based microbial identification of the tissue. Further genetic testing detected a de novo mutation of c.819_822delTAAT in the IFNGR1 gene, leading to a diagnosis of autosomal dominant Mendelian susceptibility to mycobacterial disease. This patient was treated with a 4-drug antituberculosis regimen (isoniazid, rifampicin, prothionamide and moxifloxacin) for 12 months and had a significant reduction of axillary mass (Fig. 1D). Antituberculosis drug was then reduced to isoniazid and rifampicin for an additional 6 months, with complete resolution of axillary mass (Fig. 1E). Histopathologic diagnosis of MSP provides many challenges due to the rare incidence and nonspecific histology. The histopathological appearance of MSP resembles mesenchymal neoplasms, due to an exuberant spindle cell proliferation.2 The tissue morphology of MSP in children and adults is similar. However, adult MSP often occurs secondary to AIDS or organ transplantation, with most cases caused by Mycobacterium avium complex. In contrast, childhood MSP is rare, often associated with primary immunodeficiency diseases, with almost all cases caused by Mycobacterium tuberculosis complex.1 BCG vaccine-induced MSP is exceedingly rare, with only 5 cases reported in the literature so far.3–5 Fine-needle biopsy and antituberculosis chemotherapy were preferred as the initial approach. Although BCG vaccine-induced MSP is rare and the clinical presentation often mimics malignancy, we believe it is important for pediatricians to achieve an accurate diagnosis of this benign and treatable condition, which may affect the prognosis.