Thymoma: a fatal case report of recurring pneumonia from Tanzania

Abstract

Unlabelled:
Thymomas present either concurrently with myasthenia gravis, with local pressure symptoms, or asymptomatically as a mediastinal mass. Due to its variable presentation, the incidence is low, as not all cases would be identified. Thymomas can present with a rare entity of combined T-cell and B-cell immunodeficiency in adults. Thymectomy is the most important prognostic factor, including preventing autoimmune manifestations of thymoma, but immunodeficiency may persist after thymectomy.

Case presentation:
The authors report a case of thymoma with evidence of immunodeficiency, manifesting as recurrent pneumonia and respiratory distress in an HIV-seronegative 62-year-old man with a suspected diagnosis 3 years before admission. During his bouts of pneumonia, blood cultures revealed methicillin-resistant Staphylococcus aureus, which was initially treated with vancomycin and then with clindamycin. Although hypogammaglobulinemia was not established in our low-resource setting, there was a reduced CD4-cell count with an abnormal CD4/CD8 ratio. The patient responded well to the first course of antibiotics. However, the second attempt was unsuccessful, which led to his demise.

Conclusion:
Clinicians should be aware that thymoma can cause immunodeficiency. Clinical suspicion should be raised in patients who present with recurrent infections, particularly in thymoma cases with adult-onset immunodeficiency.

Full text

Thymoma: a fatal case report of recurring
pneumonia from Tanzania
Abid M. Sadiq, MMeda,e,*, Ruvimbo R. Mukamuri, MDc, Eugenie M. Kamabu, MDe, Faustini C. Kimondo, MDa,
Adnan M. Sadiq, MMedd,e, Gilbert Z. Nkya, MMedb,e
Introduction and importance: Thymomas present either concurrently with myasthenia gravis, with local pressure symptoms, or
asymptomatically as a mediastinal mass. Due to its variable presentation, the incidence is low, as not all cases would be identified.
Thymomas can present with a rare entity of combined T-cell and B-cell immunodeficiency in adults. Thymectomy is the most
important prognostic factor, including preventing autoimmune manifestations of thymoma, but immunodeficiency may persist after
thymectomy.
Case presentation: The authors report a case of thymoma with evidence of immunodeficiency, manifesting as recurrent
pneumonia and respiratory distress in an HIV-seronegative 62-year-old man with a suspected diagnosis 3 years before admission.
During his bouts of pneumonia, blood cultures revealed methicillin-resistant Staphylococcus aureus, which was initially treated with
vancomycin and then with clindamycin. Although hypogammaglobulinemia was not established in our low-resource setting, there
was a reduced CD4-cell count with an abnormal CD4/CD8 ratio. The patient responded well to the first course of antibiotics.
However, the second attempt was unsuccessful, which led to his demise.
Conclusion: Clinicians should be aware that thymoma can cause immunodeficiency. Clinical suspicion should be raised in patients
who present with recurrent infections, particularly in thymoma cases with adult-onset immunodeficiency.
Keywords: MRSA, pneumonia, ARDS, thymoma, case report, Tanzania
Introduction
Thymomas are rare mediastinal tumors that occur primarily in
the fourth to the seventh decade of life, with male and female
incidences being comparable
[1,2]
. Thymomas present either
concurrently with myasthenia gravis, with local pressure
symptoms, or asymptomatically as a mediastinal mass on chest
radiography
[2]
. Thymomas can be classified as benign or
malignant based on the degree of capsular invasion. Because of
the variable presentation, the incidence would likely be low, as
not all cases would be identified.
With a thymoma incidence of 0.19 and 0.17 per 100 000
population in the United States and Europe, respectively
[3]
,
the incidence in Africa is unknown. We present the case of a
62-year-old man who died as a result of acute respiratory distress
syndrome, a mediastinal mass, and a recurrent methicillin-
resistant Staphylococcus aureus (MRSA) infection.
The main purpose of this case described here is to report a case
of recurrent pneumonia caused by MRSA in an immunodeficient
man with a mediastinal mass, which is a rare association.
This case report has been submitted in accordance with the
Surgical CAse REport (SCARE) guideline criteria 2020
[4]
.
Case presentation
A 62-year-old male presented with 3 years of central chest pain
and a productive cough for 1 year, which were associated with
difficulty breathing and chest tightness. He came from a low
socioeconomic family and worked as a peasant farmer. Three
years before admission, he was found to have a mediastinal mass
but decided not to proceed with any therapy. Over the past year,
he had been using over-the-counter cough medications and
antibiotics that did not relieve his symptoms. He progressively
worsened with time and was referred to our center. Apart from
occasional alcohol consumption, there was no significant social
or familial medical history.
HIGHLIGHTS
•Thymomas are rare mediastinal tumors with low incidence
but a fatal outcome if untreated.
•Methicillin-resistant Staphylococcus aureus infection is
uncommon in Good’s syndrome.
•Suspect immunodeficiency in patients with recurrent infec-
tions and a mediastinal mass.
Departments of
a
Internal Medicine,
b
Pathology,
c
Surgery,
d
Radiology, Kilimanjaro
Christian Medical Centre and
e
Faculty of Medicine, Kilimanjaro Christian Medical
University College, Moshi, Tanzania
Sponsorships or competing interests that may be relevant to content are disclosed at
the end of this article.
Published online 28 March 2023
*Corresponding author. Address: Department of Internal Medicine, Kilimanjaro
Christian Medical Centre, P.O. Box 3010, Moshi, Tanzania. E-mail address: abid.
physician@gmail.com (A.M. Sadiq).
Received 4 October 2022; Accepted 12 February 2023
Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. This is an
open access article distributed under the Creative Commons Attribution-
NoDerivatives License 4.0, which allows for redistribution, commercial and non-
commercial, as long as it is passed along unchanged and in whole, with credit to the
author.
Annals of Medicine & Surgery (2023) 85:1018–1021
http://dx.doi.org/10.1097/MS9.0000000000000300
’
Case Report
1018

On examination, he was conscious, afebrile with a temperature
of 36.9°C, dyspneic at rest with oxygen saturation at 85%,
needing oxygen, with grade 2 finger clubbing, but no lower limb
edema. His blood pressure was 98/68 mm Hg, and his pulse rate
was 92 bpm. With reduced symmetrical chest expansion, bilateral
crepitations, and reduced breath sounds bilaterally, it was
suggested that he was in respiratory failure.
His chest radiography showed features of a large mediastinal
mass and bilateral ground-glass opacities (Fig. 1A). A rapid
antigen test for severe acute respiratory syndrome coronavirus 2
was negative. The serology for HIV was negative. His hemato-
logical investigations revealed a leukocyte count of 5.0 ×10
9
/l
with normocytic anemia of 9.1 g/dl and an elevated erythrocyte
sedimentation rate of 48 mm/h. His biochemical investigations
revealed lactate of 2.8, alanine transaminase of 388.8 U/l,
aspartate transaminase of 80.7 U/l, amylase of 80 U/l, and
creatinine of 130 µmol/l.
He was started on intravenous ceftriaxone 1 g once daily until
his blood culture results revealed MRSA, which was sensitive to
vancomycin. The patient was switched to intravenous vanco-
mycin 1 g three times daily. He improved clinically as his
respiratory distress resolved, but was still dependent on low-flow
oxygen.
Noncontrasted computed tomography of the chest revealed an
anterior mediastinal mass measuring 7 cm (Fig. 2), and a biopsy
was taken, which revealed a tumor with mixed cellularity, having
both spindle and epithelioid cells, suggesting a differential of
thymoma or sarcoma. Immunohistochemistry revealed a pan-
cytokeratin-positive and terminal deoxynucleotidyl transferase
(TdT)-negative type A thymoma (Fig. 3). According to the
Masaoka–Koga classification, the thymoma was stage IIB. His
CD4 was 407 cells/µl with a CD4/CD8 ratio of 0.8.
Surgical and oncological teams were consulted, and tumor
excision surgery was arranged. However, he started to have
difficulty breathing again while in the ward. His repeat full blood
count revealed a leukocyte count of 3.1 ×10
9
/l and normocytic
anemia of 8.3 g/dl. A repeat rapid antigen test for severe acute
respiratory syndrome coronavirus 2 was negative. A control chest
radiography revealed acute respiratory distress syndrome (Fig. 1B),
and he was started on intravenous piperacillin-tazobactam 4.5 g
thrice daily. A repeat blood culture grew MRSA with a different
antimicrobial sensitivity pattern, specifically to clindamycin. The
patient was switched to intravenous clindamycin 600 mg every 6 h.
A blood sample for immunoglobulin G was sent outside the
hospital, which revealed him to have hypogammaglobulinemia of
397 mg/dl (normal 600–1600 mg/dl). However, his clinical
condition deteriorated,and he developed septic shock, which led to
his death.
Discussion
Patients with thymoma present with several syndromes, generally
autoimmune conditions, compared with local symptoms
[5]
.
Abnormal regulation of lymphocytes in the thymus gland can result
in immunodeficiency or autoimmunity, causing myasthenia gravis,
redcellaplasia,orGood’s syndrome. In our case, we suspect that
our patient had immunodeficiency, which led to recurrent MRSA
infection and respiratory distress, which led to his demise.
Since its first description in 1954, Good’s syndrome is a rare,
adult-onset, acquired immunodeficiency in thymoma with
reduced to no B cells, a low CD4 T-cell count, an abnormal CD4:
CD8 T-cell ratio, and hypogammaglobulinemia
[6]
. The patho-
genesis of Good’s syndrome is still not known, as the literature
suggests that bone marrow abnormalities, autoimmunity,
and T-cell abnormalities play major roles
[7]
. Respiratory tract
infections are the hallmark of Good’s syndrome due to defects
in cell-mediated immunity and B-cell deficiency, causing
opportunistic infections.
Figure 1. Posterior anterior chest radiography (A) shows a left anterior mediastinal mass overlying the left hilum and left cardiac border. Hazy ground-glass opacities
are seen in both lung fields. Control chest radiography (B) shows an increase in ground-glass opacities and infiltrates in both lung fields, in keeping with acute
respiratory distress syndrome. The left anterior mediastinal mass remained unchanged.
Sadiq et al. Annals of Medicine & Surgery (2023)
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Patients with Good’s syndrome are susceptible to various
infections, including encapsulated bacteria (Haemophilus,
Pseudomonas,Klebsiella, and Streptococcus), fungi (Candida,
Pneumocystis jirovecii), viral (Cytomegalovirus), and protozoal
(Giardia) infections
[8]
. However, S. aureus is not commonly
identified in Good’s syndrome.
In our case, the patient presented with respiratory distress, which
mayhavebeencausedbyaMRSAinfection. Due to his immuno-
deficiency, the infection may have led to severe inflammation of the
lungs. However, thymomas also cause dyspnea, particularly when
they cause compression of the trachea, superior vena cava
syndrome, phrenic nerve paralysis, and myasthenia gravis
[9]
.
The spindle cells of thymoma with pan-cytokeratin are prob-
ably either type A or type AB thymoma. However, the presence of
a TdT-positive lymphoid population in a spindle cell thymoma is
probably a type AB thymoma
[10]
. Most TdT-negative thymomas
are either type A or type B3. Because of the negative TdT immu-
nohistochemistry and mixed cellularity of the tumor, our patient
was most likely suffering from a type A thymoma. In type A
thymoma, neuroendocrine tumors, paraganglioma, and synovial
sarcomas should be considered in the differential diagnosis.
Although no association has been found between the types of
thymoma and autoimmune complications, the diagnosis of
hypogammaglobulinemia is seen in relatively equal proportions
[8]
.
Figure 2. Axial (A and B) and coronal (C) noncontrast computed tomography of the chest show a well-defined left anterior mediastinal mass with peripheral
calcification exerting pressure on the main pulmonary trunk on the left upper lobe.
Figure 3. Histopathology shows a thymic tumor exhibiting epithelial islands that are intertwined with bundles of delicate spindle cells (A), which are
pan-cytokeratin-positive (B), and TdT-negative (C).
Sadiq et al. Annals of Medicine & Surgery (2023) Annals of Medicine & Surgery
1020

However, most types of thymoma with Good’ssyndromeare
benign and are characterized as spindle cell types
[6]
.
The treatment of thymoma is based on staging, but surgical
resection is the most important prognostic factor. The specific
treatment of Good’s syndrome includes high-dose intravenous
immunoglobulin to improve the humoral immune response and
prevent opportunistic infections. Thymectomy prevents auto-
immune manifestations of thymoma, but reports suggest that
hypogammaglobulinemia persists after thymectomy
[6]
.
Conclusion
Good’s syndrome should be suspected in patients with acute
respiratory distress syndrome and a mediastinal mass, even in
those presenting with uncommon recurrent infections.
Physicians should be aware of the complications of a thy-
moma, and early recognition and diagnosis are recommended
in any suspicious case.
Ethical approval
Our institution does not require ethical approval for reporting
individual cases or case series.
Consent
Written informed consent was obtained from the patient’s wife
for the publication of this case report and accompanying images.
A copy of the written consent is available for review by the Editor-
in-Chief of this journal on request.
Sources of funding
There was no funding.
Author contribution
A.S., R.M., E.K., and F.K. were involved with patient manage-
ment and preparation of the manuscript. A.S. reviewed the
inherent literature and edited the manuscript. R.M., F.K., A.S.,
and G.N. were involved with relevant investigations. A.S. and
G.N. provided the images. All authors approved the final version
of the manuscript.
Conflicts of interest disclosure
The authors declare no conflicts of interest.
Research registration unique identifying number
(UIN)
1. Name of the registry: NA.
2. Unique identifying number or registration ID: NA.
3. Hyperlink to your specific registration (must be publicly
accessible and will be checked): NA.
Guarantor
Abid M. Sadiq.
Provenance and peer review
Not commissioned, externally peer-reviewed.
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