Large pulmonary solitary mass caused by Mycobacterium tuberculosis mimicking a malignant tumor in a child

Accepted Manuscript Large pulmonary solitary mass caused by Mycobacterium tuberculosis mimicking a malignant tumor in a child Yingqian Chen, Youyou Yang, Lang Chen, Miao Fan PII:

S2352-6211(17)30103-1

DOI:

10.1016/j.jrid.2018.08.002

Reference:

JRID 155

To appear in:

Radiology of Infectious Diseases

Received Date: 31 December 2017 Revised Date:

17 June 2018

Accepted Date: 6 August 2018

Please cite this article as: Chen Y, Yang Y, Chen L, Fan M, Large pulmonary solitary mass caused by Mycobacterium tuberculosis mimicking a malignant tumor in a child, Radiology of Infectious Diseases (2018), doi: 10.1016/j.jrid.2018.08.002. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Large pulmonary solitary mass caused by Mycobacterium tuberculosis mimicking a malignant tumor in a child

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Yingqian Chena ([email protected]), Youyou Yanga, Lang Chena, Miao Fana* a Department of Radiology, First Affiliated Hospital of Sun Yat-Sen University, 58th, The Second Zhongshan Road, Guangzhou, China *

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Declarations of interest: none

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Corresponding author: Miao Fan, Department of Radiology, First Affiliated Hospital of Sun Yat-Sen University, 58th, The Second Zhongshan Road, Guanzhou, China, 510080. Tel: +86 13527607211, E-mail address: [email protected]

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Large pulmonary solitary mass caused by Mycobacterium

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tuberculosis mimicking a malignant tumor in a child

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Abstract

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Tuberculoma, as a common characteristic of pulmonary tuberculosis (TB) in adults, is

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rarely seen in children. We report a very rare case of large pulmonary solitary mass

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caused by Mycobacterium tuberculosis in a 7-year-old boy, which was misdiagnosed

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for malignant lung tumor before the biopsy. Pathology and the following test proved it

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to be active TB. We also review the CT characteristics of TB and common thoracic

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neoplasms in children for differential diagnosis. We call for the awareness of the

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atypical imaging characteristics of TB in children.

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Keywords: Tuberculoma; Mycobacterium tuberculosis; Pediatric; Computed

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tomography imaging

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1. Introduction

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Though the morbidity of Mycobacterium tuberculosis (Mtb) infection is decreasing,

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there are around one third of the world’s population which are still infected with it[1].

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Mtb causes a substantial health burden in the world, especially in developing

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countries. In the most current national tuberculosis epidemiological survey in China

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in 2010, the prevalence of active and smear positive prevalence of pulmonary

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tuberculosis (TB) were 459/100 000 and 66/100 000 respectively, mostly attributed by

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rural area[2].

Pulmonary TB occurs relatively less in children. In 2016, children under 15 years old accounted for 6.9% of the new TB cases globally[1]. But it is hard to diagnose

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Mtb infection in children, since their symptoms vary from those in adults, and it is

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usually hard to get their sputum for acid-fast bacilli (AFB) smear or culture. Moreover,

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children get infected more easily with Mtb from other children and adults with active

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tuberculosis, which may cause a localized outbreak.Hence the imaging examinations,

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especially the chest radiograph and chest multi spiral computed tomography (CT)

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plays a critical role in the diagnosis and treatment of active pulmonary TB in children.

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Unlike the imaging appearances in adult, lymphadenopathy is the most common

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imaging manifestation in pediatric patients[3], follow by consolidation and pleural

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effusion[4]. While pulmonary solitary mass or nodule, which is also termed as

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tuberculoma in adult patients, is rarely seen in pediatric patients. Herein we report a

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case of pathology proved pulmonary TB with the imaging appearance of solitary mass

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which was misdiagnosed as malignant tumor before the biopsy.

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2. Case Report

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A 7-year-old boy was referred to our hospital with a 6-month history of cough. The

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boy was healthy ever before and no obvious predisposing cause was found. He had no

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expectoration, fever, chest pain, night sweat or weight loss. The laboratory test

ACCEPTED MANUSCRIPT showed a higher platelet count (377 × 109/L) and higher serum lactate dehydrogenase

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(LDH) level (300U/L, normal 114-240U/L). But other indexes of the whole blood cell

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test and other blood biochemical indexes were within the normal ranges (white blood

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cell: 7.10 × 109/L, neutrophils: 3.90 × 109/L, eosinophils: 0.22 × 109/L). The

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posterior-anterior and lateral chest radiographs revealed a mass with clear margin in

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his left upper lobe (Fig. 1A-B). Then chest CT imaging was recommended for a

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further examination. In the non-enhanced chest CT images, an oval, sharply

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marginated, shallow lobulated mass with a size of 47mm × 37mm × 33mm was found

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in the apicoposterior segment of the left upper lobe. The mass appeared as a

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homogeneous attenuation, which both nodular hypoattenuation areas and annular

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hyperattenuation inside (Fig. 2A-C). After contrast enhancement, the hypoattenuation

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areas showed no enhancement (Fig. 2D). Lymph nodes enlargement in the hilum or

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mediastinal were absent. According to these manifestations, a tentative diagnosis by

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radiologist of pulmonary malignant tumor was made. After that, more tests of serum

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tumor markers were done. The level of alpha fetoprotein (AFP), neuron-specific

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enolase (NSE), carcino-embryonic antigen (CEA) and CYFRA21-1 of the serum were

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all within the normal ranges. And the HIV antibody primary screening was also

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negative. What was more, to exclude metastasis, a 18F-fluorodeoxyglucose positron

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emission tomography-CT (18F-FDG-PET/CT) was done. The pulmonary mass

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appeared as high FDG consumption, with the highest standardized uptake value

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(SUVmax) to be 4.1, which remind the radiologist to consider the possibility of

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ACCEPTED MANUSCRIPT malignant tumor. However, no other area of abnormal high FDG uptake was found

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(Fig 3 A-B). Base on the image examinations, a preoperative diagnosis of malignant

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lung tumor was made. In order to make a definite diagnosis, the patient received a

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pulmonary needle biopsy after consultation. After H-E staining, large amount of

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caseous necrosis with focal accumulation of lymphocytes could be seen inside the

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tissue (Fig.3C). Tumor cell or abnormal mitoses were absent in the mass. Base on

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these findings, pathology diagnosis of inflammation (possibly TB) was made. Then

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the boy was transferred to the infectious disease hospital for further diagnoses and

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treatments. There, a positive sputum AFB smear and positive nucleic amplification

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test proved an active pulmonary TB. The pulmonary mass shrank after half-a-year’s

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antituberculosis therapy with isoniazid, rifampicin, ethambutol and pyrazinamide.

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Regretfully, for many reasons, the clear CT images after treatment were unobtainable.

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ACCEPTED MANUSCRIPT Fig.1. A-B: The anterior-posterior and lateral chest radiography shows a mass with clear

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margin located in the left upper lobe (arrow). And the other lung field is clear.

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Fig.2.A-B: The axial and coronal CT images show a solitary mass located in the

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apicoposterior segment of the left upper lobe. The mass has sharply margin, swallow

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lobulation and homogenous intensity. C-D: In the soft tissue window of non-enhanced and

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contrast-enhanced CT images, the non-enhanced nodular hypoattenuation areas (arrow) and

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annular hyperattenuation can be seen inside the tumor.

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Fig.3.A-B:18F-FDG-PET scan of the boy. Maximum intensity projection image and the axial

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scan of integrated PET/CT image shows the high 18F-FDG uptake of the mass (arrow),

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especially in the peripheral area. The hypoattenuation areas in CT image shows low uptake of

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18F-

FDG. C: Pathologic image (HE, original magnification × 200) reveal the red-stained

ACCEPTED MANUSCRIPT caseous necrosis inside the mass. Focal accumulation of lymphocytes can also be seen in the

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peripheral area (long arrow).

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3. Discussion and conclusion

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Herein we reported a case of large pediatric pulmonary tuberculoma. The boy was

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ever misdiagnosed as malignant tumor by CT imaging and

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diagnosis of pulmonary TB was not taken into account before the biopsy. Hence the

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prevention measure of the medical worker and his families to the active pulmonary

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TB was far from insufficient, which might cause regionally spreading of Mtb. Luckily,

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no medical workers or the families and classmates of the patient was found infected in

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this case. Besides, tuberculoma is considered as a late and severe complication of

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tuberculosis in childhood, which need timely and effective treatment. This experience

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calls for the vigilance to atypical imaging appearance of pediatric tuberculosis.

FDG-PET/CT. The

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The CT appearance of pulmonary tuberculosis in children is different from that of

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adult. The most common form of active pulmonary TB in children is primary disease.

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As the age increases, the morbidity of primary disease decreases and the postprimary

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TB increases. The primary TB in infants and children were characterized by

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lymphadenopathy and parenchymal diseases. The parenchymal disease most

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frequently shows as consolidation, followed by nodules of bronchogenic spread.

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Besides, pleural involvement is also usually seen in the children with TB[5, 6]. While

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tuberculoma, as a very common manifestation in adult with TB, is rarely seen in

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ACCEPTED MANUSCRIPT children. There are a few cases of pulmonary TB manifested as solid pulmonary

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nodule or mass in children published in articles. In 2014, Ushiki A et al. published a

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case of a 14-year-old girl with a solid pulmonary nodule in posterior segment of right

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lower lobe and reported that the tuberculoma is an infrequent form of TB in

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children[7]. Tomà P et al. reviewed 217 children with pulmonary TB and none of

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them manifested as tuberculoma[5]. This could be explained by that the immune

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system is not so mature in children, and the tuberculoma is a kind of outcome by the

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immune system against the Mtb.

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The pulmonary tuberculoma is characterized by the following:

1) Mostly locating in the apicoposterior lung segments or the apical segments of the

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lower lobes.

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2) Nodular caseous necrosis manifesting as non-enhanced hypoattenuation areas.

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3) Annular or patchy calcification around the necrosis areas[8].

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Nonetheless, the tuberculoma in our case was manifested with typical CT

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characteristic, which calls for the alertness that typical tuberculoma may also exist in

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children.

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Moreover, though solid pulmonary nodule or mass can be secondary to a varies of

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different cause, it is rarely found in children. The differential diagnosis may include

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metastatic tumor and primary pulmonary neoplasms like pleuropulmonary blastoma

ACCEPTED MANUSCRIPT (PPB) and pulmonary hamartoma[9]. Metastatic tumor can be differentiated by

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medical history and the primary cancer focus. Moreover, metastatic tumor usually

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manifests as multiple nodules rather than solitary pulmonary mass. PPB is the most

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common malignant pediatric primary lung parenchymal neoplasm. It can appear as

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both cystic and solitary masses on CT, according to its pathologic feature[10]. The

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absence of chest wall invasion, presence of pleural fluid and heterogeneous low

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attenuation are the CT characteristics of PPB. But calcification is rarely seen in

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PPB[11]. Pulmonary hamartoma in children appears as a smooth or lobulated

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peripheral mass with the classic popcorn calcification and fat on CT, just like its

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appearance in adult. Besides, the Kaposi sarcoma should be taken into account if the

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children has immune deficiency[9].

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In our case, the mass showed high FDG uptake on 18F-FDG-PET imaging. To some

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extent, it made the diagnosis to be more complicated.

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detect the glucose uptake of the mass, which is usually capable to differentiate the

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malignant form the benign mass. But for many infection diseases, the inflammation

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process can also consume glucose, which may cause the high uptake of

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this case, as a nonspecific tracer,18F-FDG cannot reliably distinguish tuberculomas

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from malignant lung lesions[12]. On the other hand, many studies have proved that

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the disease activity and monitoring the response to therapy as a non-invasive method,

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for the level of

F-FDG-PET can be used to

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F-FDG. In

F-FDG-PET can be used in Mtb infection for detection of active lesion, assessing

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F-FDG uptake can reveal the activity level of TB lesion in some

ACCEPTED MANUSCRIPT degree[13]. As in our case, the level of 18F-FDG uptake is high of the mass, which is

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consistent with the hyperactivity of the TB lesion. Regretfully, limited by the

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condition of the local hospital, 18F-FDG PET haven’t been used during the follow-up

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examinations in this case.

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Sputum culture plays a critical role in the diagnosis of active pulmonary TB, which has the highest specificity of 98%. But it takes too long (2-8 weeks) to get the result,

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which also has a high false negative rate, especially in children. While AFB smear and

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polymerase chain reaction (PCR) are hard to detect Mtb in children due to the poor

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bacteriologic specimen. QuantiFERON-TB (QFT) test for detection of interferon

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gamma (IFN-γ) concentration together with tuberculin skin test (TST) seems more

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reliable and exercisable in the TB detection of children[14, 15]. In developed

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countries, contact history to patient with active Mtb infection is a critical rule to the

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suspective of TB. However, the rate to contact with a patient with infectious TB are

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relatively high in China, especially in rural area. In this case, every patient suspective

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of TB by clinical manifestation, imaging examination or other laboratory tests should

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receive a primarily screen of TB.

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In conclusion, the report of our case reveals that the tuberculoma may also be seen

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in children. The clinical manifestations combine with the typical CT characteristic

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should call for the awareness of Mtb infection and the necessary protective measures

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should be taken to reduce the risk of infection.

ACCEPTED MANUSCRIPT Ethics statement

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The study was approved by the Research Ethics Committee of Sun Yat-sen University,

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China and the written informed consent was obtained from the subject.

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Financial disclosure

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This research did not receive any specific grant from funding agencies in the public,

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commercial, or not-for-profit sectors.

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