18 June 2026: Articles 
Disseminated Tuberculosis Mimicking Metastatic Cancer During Ruxolitinib Therapy for Polycythemia Vera: A Case Report and Literature Review
Mistake in diagnosis, Rare disease
Yuga Ono BCDEF 1*, Koji Oka
D 2, Kenichi Ishikawa D 3, Hisaharu Shikata D 2, Masahiko Kaneko D 2
DOI: 10.12659/AJCR.952683
Am J Case Rep 2026; 27:e952683
Abstract
BACKGROUND: Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) characterized by erythrocytosis resulting from the clonal overproduction of hematopoietic cells in the bone marrow and is closely associated with mutations in the Janus kinase 2 (JAK2) gene. Ruxolitinib, a selective JAK1/JAK2 inhibitor used to treat MPNs, predisposes patients to opportunistic infections. Herein, we report the case of a patient with PV treated with ruxolitinib who developed disseminated tuberculosis mimicking metastatic cancer.
CASE REPORT: A 71-year-old woman presented with imaging findings suggestive of metastases, elevated tumor markers, and a negative interferon-γ release assay. The diagnosis was confirmed by bone biopsy and a positive sputum Mycobacterium tuberculosis polymerase chain reaction test. The patient improved with standard 4-drug antituberculous therapy. In a focused review of 35 published cases of tuberculosis occurring during ruxolitinib therapy for MPNs, disseminated disease accounted for 50% of cases, whereas PV was reported in only 3 cases. Ruxolitinib-induced immunosuppression can lead to false-negative interferon-γ release assay results, and several tumor markers, including soluble interleukin-2 receptor, neuron-specific enolase, cancer antigen (CA)125, and CA15-3, are known to be elevated in tuberculosis.
CONCLUSIONS: Patients with PV treated with ruxolitinib can develop active tuberculosis, including disseminated forms. When tumor markers are elevated and imaging reveals lesions suggestive of metastases, clinicians should include disseminated tuberculosis in the differential diagnosis and pursue histopathological and microbiological investigations to enable timely diagnosis and appropriate treatment.
Keywords: Case Reports, Hematology, Neoplasms, Polycythemia vera, Ruxolitinib, Tuberculosis
Introduction
Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by erythrocytosis due to clonal overproduction of blood cells in the bone marrow and is strongly associated with mutations in the Janus kinase 2 (
Despite these benefits, inhibition of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) (JAK–STAT) pathway can impair both innate and adaptive immune responses by suppressing multiple cytokines, and rare but serious opportunistic infections – including hepatitis B virus reactivation, cryptococcosis, toxoplasmosis, disseminated tuberculosis, and progressive multifocal leukoencephalopathy – have been described [4]. Most ruxolitinib-associated infections reported to date have occurred in patients with primary or secondary myelofibrosis, rather than in those with PV [5].
Here, we report a case of a patient with PV receiving ruxolitinib who developed disseminated tuberculosis closely mimicking metastatic cancer of unknown primary and provide a focused review of tuberculosis occurring during ruxolitinib therapy.
Case Report
A 71-year-old woman diagnosed with JAK2 V617F mutation-positive PV in 2015 presented in September 2024 with bilateral lower extremity edema. She had been treated with hydroxyurea until 2023, when the drug was discontinued because of lower leg ulcers. Ruxolitinib therapy was initiated in December 2023. The patient had no known history of contact with individuals with tuberculosis.
On presentation, she had no respiratory symptoms, with an oxygen saturation of 97% on room air and a body temperature of 36.2°C. Physical examination revealed bilateral pitting edema of the lower legs with no other remarkable findings. Laboratory data showed leukocytosis (33 170/μL), anemia (hemoglobin 10.0 g/dL), and thrombocytosis (827 000/μL), along with a negative interferon-γ release assay (T-SPOT.TB). Elevated levels of several tumor markers were noted, including soluble interleukin-2 receptor (sIL-2R) (8106 U/mL), carcinoembryonic antigen (8.7 ng/mL), cancer antigen 125 (CA 125) (597.0 ng/mL), cancer antigen 15-3 (CA 15-3) (58.1 ng/mL), carbohydrate antigen 19-9 (CA 19-9) (78.2 ng/mL), and neuron-specific enolase (NSE) (32.6 ng/mL). These data are summarized in Table 1.
Non-contrast chest and abdominal computed tomography (CT) revealed multiple cavitary pulmonary nodules, mediastinal lymphadenopathy, peritoneal thickening, ascites, increased attenuation of mesenteric fat, and osteolytic lesions in multiple vertebral bodies (Figure 1A–1D). Whole-spine magnetic resonance imaging was subsequently performed. T1-weighted images demonstrated hypointense signals in the vertebral bodies at T6, T7, T8, T10, L1, L3, L4, and L5, as well as in the corresponding spinous processes (Figure 2A–2C).
Based on these findings, metastatic cancer of unknown primary origin was initially suspected. Further evaluations, including upper gastrointestinal endoscopy, positron emission tomography-CT (PET-CT), and bone biopsy, were performed. Endoscopy revealed no evidence of malignancy. PET-CT demonstrated increased fluorodeoxyglucose (FDG) uptake in the same regions identified on CT (Figure 3A–3J). A bone biopsy of the L1 vertebral osteolytic lesion showed nuclear abnormalities of polymorphonuclear leukocytes consistent with polycythemia vera, with no histological evidence of malignancy (Figure 4A).
Disseminated tuberculosis was then considered in the differential diagnosis. Sputum polymerase chain reaction testing for
Discussion
Patients with myeloproliferative neoplasms (MPNs) are at increased risk of infection (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.9–2.0) and death due to infection (HR, 2.7; 95% CI, 2.4–3.1) [6,7]. Ruxolitinib, a JAK1/JAK2 inhibitor used to treat MPNs, affects both innate and adaptive immunity by impairing the function of natural killer cells, dendritic cells, helper T cells, and regulatory T cells, thereby potentially increasing susceptibility to opportunistic infections. Indeed, serious opportunistic infections – such as hepatitis B virus reactivation,
We reviewed previously reported cases of tuberculosis developing during ruxolitinib therapy for MPNs with available clinical information. To the best of our knowledge, 35 such cases have been reported, of which only 3 involved PV [10–34] (Table 2). The mean age of reported patients was 64.0 years, and the male-to-female ratio was 2: 1. Primary myelofibrosis was the most common underlying disease, accounting for 72% of cases. The most frequent site of infection was lymph node involvement (63%), followed by pulmonary involvement (59%). Disseminated tuberculosis accounted for 50% of cases, markedly higher than the generally reported rate of 1% to 5% among all tuberculosis cases [35–38]. Because immunosuppression is a recognized risk factor for disseminated disease [39], this finding is not entirely unexpected. However, the 50% rate observed in patients receiving ruxolitinib exceeds reported rates in other immunosuppressed populations: 18.2% in solid organ transplant recipients (renal and liver) [40] and 34% and 28% among patients receiving tumor necrosis factor inhibitors for inflammatory bowel disease and rheumatoid arthritis, respectively [41,42]. These observations suggest that ruxolitinib therapy may warrant particular caution regarding the development of disseminated tuberculosis. Interferon-γ release assay screening prior to ruxolitinib initiation was not performed in 6 cases. The overall case fatality rate was 29%. The median interval from initiation of ruxolitinib to the onset of
In the present case, widespread metastatic cancer was initially suspected based on laboratory and imaging findings. The patient was receiving the JAK1/JAK2 inhibitor ruxolitinib, which can cause false-negative interferon-γ release assay results through immunosuppression, thereby complicating the diagnosis of tuberculosis [43]. Several tumor markers typically considered specific for malignancy are also known to be elevated in tuberculosis. For example, sIL-2R, a surrogate marker of T-cell activation, is often elevated in active tuberculosis [44,45]. NSE, a marker for neuroendocrine tumors, may be elevated in tuberculosis, possibly due to macrophage activation within tuberculous granulomas [46]. CA 125 frequently increases in tuberculosis involving the pleura, pericardium, or peritoneum [47], and CA 15-3 may be elevated [48]. Furthermore, disseminated tuberculosis can mimic malignancy on imaging studies, making differentiation challenging [49–51].
Conclusions
Patients with PV receiving ruxolitinib can develop active tuberculosis, including disseminated disease. When elevated tumor markers and metastaticappearing lesions on imaging are present, clinicians should consider disseminated tuberculosis and obtain histopathologic and microbiological evaluation to ensure early diagnosis and treatment.
Figures
Figure 1. Chest and abdominal computed tomography (CT) findings. (A) Chest CT showed multiple pulmonary nodules with cavitation. (B) Chest CT showed mediastinal lymphadenopathy. (C) Abdominal CT showed peritoneal thickening, ascites, and increased attenuation of mesenteric fat. (D) Chest and abdominal CT showed osteolytic lesions in multiple vertebral bodies. 
Figure 2. Whole-spine magnetic resonance imaging (MRI) findings. (A–C) Sagittal T1-weighted MR images demonstrate hypointense signal in the vertebral bodies at T6, T7, T8, T10, L1, L3, L4, and L5, as well as in the spinous processes at the corresponding levels. 
Figure 3. Positron emission tomography-computed tomography (PET-CT) findings. (A) Bilateral multiple pulmonary nodules and cavitary lesions with fluorodeoxyglucose (FDG) uptake in larger and clustered lesions. (B–D) Enlarged lymph nodes with FDG uptake in the right supraclavicular region, mediastinum (predominantly right mediastinum), right hilum, and para-aortic area. (E, F) Ascites, omental masses, and mesenteric nodules with FDG uptake. (G–I) Osteolytic changes with FDG uptake in the vertebral bodies, pelvic bones, left scapula, right 5th, 8th, and 11th ribs, and left 9th rib. (J) Whole-body scans. ![Bone biopsy. (A) Megakaryocytic hyperplasia with atypia is observed; however, no morphologic features suggestive of malignancy are identified (×40, hematoxylin and eosin [H&E] staining). (B) Ziehl-Neelsen staining demonstrates numerous acid-fast bacilli (×40).](https://jours.isi-science.com/imageXml.php?i=amjcaserep-27-e952683-g004.jpg&idArt=952683&w=1000)
Figure 4. Bone biopsy. (A) Megakaryocytic hyperplasia with atypia is observed; however, no morphologic features suggestive of malignancy are identified (×40, hematoxylin and eosin [H&E] staining). (B) Ziehl-Neelsen staining demonstrates numerous acid-fast bacilli (×40). References
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Figures
Figure 1. Chest and abdominal computed tomography (CT) findings. (A) Chest CT showed multiple pulmonary nodules with cavitation. (B) Chest CT showed mediastinal lymphadenopathy. (C) Abdominal CT showed peritoneal thickening, ascites, and increased attenuation of mesenteric fat. (D) Chest and abdominal CT showed osteolytic lesions in multiple vertebral bodies.Figure 2. Whole-spine magnetic resonance imaging (MRI) findings. (A–C) Sagittal T1-weighted MR images demonstrate hypointense signal in the vertebral bodies at T6, T7, T8, T10, L1, L3, L4, and L5, as well as in the spinous processes at the corresponding levels.Figure 3. Positron emission tomography-computed tomography (PET-CT) findings. (A) Bilateral multiple pulmonary nodules and cavitary lesions with fluorodeoxyglucose (FDG) uptake in larger and clustered lesions. (B–D) Enlarged lymph nodes with FDG uptake in the right supraclavicular region, mediastinum (predominantly right mediastinum), right hilum, and para-aortic area. (E, F) Ascites, omental masses, and mesenteric nodules with FDG uptake. (G–I) Osteolytic changes with FDG uptake in the vertebral bodies, pelvic bones, left scapula, right 5th, 8th, and 11th ribs, and left 9th rib. (J) Whole-body scans.Figure 4. Bone biopsy. (A) Megakaryocytic hyperplasia with atypia is observed; however, no morphologic features suggestive of malignancy are identified (×40, hematoxylin and eosin [H&E] staining). (B) Ziehl-Neelsen staining demonstrates numerous acid-fast bacilli (×40). Tables
Table 1. Laboratory data on admission.
Table 2. Literature review of previously reported cases of tuberculosis during ruxolitinib treatment in patients with MPNs.Table 1. Laboratory data on admission.Table 2. Literature review of previously reported cases of tuberculosis during ruxolitinib treatment in patients with MPNs. In Press
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