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\begin{document}

\title{Pantoea abscess mimicking sarcoma in a HTLV-1-infected Indigenous
Australian man: case report and literature review}



\author[1]{Maja Susanto}%
\author[2]{Jacki Dunning}%
\author[3]{Rusheng Chew}%
\affil[1]{Redcliffe Hospital}%
\affil[2]{Alice Springs Hospital}%
\affil[3]{University of Oxford}%


\vspace{-1em}



  
  \date{May 19, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Gram-negative bacteria of the genus Pantoea are emerging bacterial
causes of diverse sporadic and outbreak-linked infections. Chronic
Pantoea abscesses are unusual and may give rise to a differential
diagnosis of malignancy. Foreign body retention and host immune defects
may be risk factors for such chronic infections.%
\end{abstract}%



\sloppy


\emph{Pantoea} \textbf{abscess mimicking sarcoma in a HTLV-1-infected
Indigenous Australian man: case report and literature review}

\textbf{Authors and affiliations}

Maja Susanto,\textsuperscript{1} Jacki
Dunning,\textsuperscript{2}Rusheng Chew\textsuperscript{3, 4, 5}

\textsuperscript{1}Infectious Diseases Unit, Redcliffe Hospital,
Brisbane, QLD, Australia; \textsuperscript{2}Department of Surgery,
Alice Springs Hospital, Alice Springs, NT,
Australia;\textsuperscript{3}Infectious Diseases Unit, Alice Springs
Hospital, Alice Springs, NT, Australia; \textsuperscript{4}Faculty of
Medicine, University of Queensland, Brisbane, QLD,
Australia;\textsuperscript{5}Centre for Tropical Medicine and Global
Health, University of Oxford, Oxford, UK

\textbf{Corresponding author contact details}

Dr Rusheng Chew, Centre for Tropical Medicine and Global Health, New
Richards Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LG
(chris@tropmedres.ac)

\textbf{Co-author contact details}

Dr Maja Susanto (maja.susanto@health.qld.gov.au), Dr Jacki Dunning
(jacki.elizabeth.dunning@gmail.com)

\textbf{Author contributions}

MS -- investigation, writing -- original draft; JD -- investigation,
writing -- original draft; RC -- conceptualization, methodology, writing
-- original draft; writing -- review and editing; supervision

\textbf{Key words}

\emph{Pantoea} ; abscess; sarcoma; Enterobacteriaceae; HTLV-1;
Indigenous Australians

\textbf{Word count:} 1901

\textbf{KEY CLINICAL MESSAGE}

Gram-negative bacteria of the genus Pantoea are emerging bacterial
causes of diverse sporadic and outbreak-linked infections.
Chronic\emph{Pantoea} abscesses are unusual and may give rise to a
differential diagnosis of malignancy. Foreign body retention and host
immune defects may be risk factors for such chronic infections.

\textbf{INTRODUCTION}

Members of the genus \emph{Pantoea} are Gram-negative motile
non-capsulated and non-spore forming rods belonging to the
Enterobacteriaceae family. The genus was established in 1989 and its 20
species are ubiquitous, being found in plants, insects, and animals as
well as water, soil, and air.(1) \emph{Pantoea} has traditionally been
regarded as plant pathogen, but certain species are increasingly
recognized as emerging opportunistic causes of human disease, including
nosocomial outbreaks.(2, 3) As such, while immunocompromise and contact
with plant material and healthcare environments are risk factors for
infections caused by \emph{Pantoea} , its widespread ecological niche
implies that sporadic infections without these risk factors are likely
to occur.(1, 3)

\textbf{CASE REPORT}

A 55-year-old Indigenous Australian male living in remote Central
Australia was admitted to Alice Springs Hospital in December 2015 for
pain and swelling at the right calf resulting in a limp. For context,
Central Australia is a rural region of over 1,000,000
km\textsuperscript{2} comprising approximately 10\% of the total
Australian landmass (Figure 1). It is sparsely populated by about 60,000
people.(4) Of these, approximately 40\% are Indigenous Australians who
are more likely to suffer from numerous chronic diseases and have poor
health literacy than their non-Indigenous counterparts.(5) Alice Springs
Hospital is the referral facility for this vast remote area.

The patient's relapsing-remitting symptoms had begun in 2012 following a
fall which, according to him, did not cause traumatic injury or skin
penetration. He was reviewed in the Orthopaedic clinic in 2014 where he
was noted to have an antalgic gait with a range of motion at the right
knee of 90-140\selectlanguage{ngerman}° and crepitus on movement, and a palpable medial
gastrocnemius lesion. MRI of the right leg showed heterogeneous
thickening of the medial gastrocnemius/soleus measuring 35×28×147 mm
with unusual tubular extension into the central aspect of the medial
gastrocnemius favouring post-injury haematoma, but raising the
possibility of a neoplastic process (Figure 2). Unfortunately, he was
lost to hospital follow-up until October 2015 when a further Orthopaedic
outpatient review showed no change in the morphology or character of the
lesion and continued observation was recommended.

His past medical history included poorly-controlled type 2 diabetes
mellitus complicated by macroalbuminuria, hypertension, hyperlipidemia,
obesity, complete heart block requiring pacemaker insertion,
osteoarthritis of the right knee and left shoulder, and right leg
varicose veins. His regular medications were aspirin 100 mg daily,
atorvastatin 40 mg daily, gliclazide MR 120 mg daily, metformin XR 2 g
daily, perindopril/indapamide 10/2.5 mg daily, sitagliptin 100 mg daily,
and tadalafil 20 mg as required. On examination at the time of
admission, there were distended superficial veins below the knee, and
marked hard swelling and tenderness of the ankle and right calf to the
level of the popliteal fossa. He was afebrile with a pulse rate of 96,
respiratory rate of 22, blood pressure of 99/90 mmHg, and oxygen
saturation of 97\% breathing air on admission. C-reactive protein was
raised at 177 mg/L (normal range 0-5), as he had a neutrophil
leukocytosis with total white cell and neutrophil counts of
16.3×10\textsuperscript{9}/L (4-11) and 10.4×10\textsuperscript{9}/L
(2.0-7.5), respectively.

A CT scan was performed to characterize the lesion further. This again
showed a cystic morphologically heterogenous structure, but also that it
had increased in size to 38×49×156 mm with a larger solid component,
again raising the possibility of sarcoma (Figure 3). This differential
diagnosis was also supported by the peripherally-enhancing,
multi-loculated nature of the lesion. The patient remained an inpatient
under the General Surgical team for three days, where he received
empirical cefazolin 1 g eight-hourly. Aspiration of the lesion for
histological and microbiological examination was planned, but deferred
by the patient to February 2016 when it was performed under ultrasound
guidance.

The aspirate demonstrated an inflammatory exudate comprising primarily
neutrophils and pigment-laden macrophages compatible with abscess. No
malignant cells were seen, but culture yielded pure growth
of\emph{Pantoea} spp. susceptible to amoxicillin/clavulanate, cefazolin,
ciprofloxacin, gentamicin, and trimethoprim/sulfamethoxazole but
resistant to ampicillin. Identification to species level was precluded
by laboratory technological limitations but, given the culture result,
the patient was referred to the Infectious Diseases clinic where he was
seen in April 2016. He reported never feeling systemically unwell or
febrile, and that, subsequent to the aspiration, the pain and swelling
had improved to the extent he was able to walk normally. The calf mass
remained palpable and hard to touch (Figure 4), but CRP had decreased to
11 and he no longer had a leukocytosis. Investigations for
immunodeficiency revealed no lymphocyte deficiency and negative serology
for HIV and \emph{Strongyloides} , but he was infected with HTLV-1, in
keeping with the very high prevalence in Indigenous Central
Australians.(6) A detailed occupational and exposure history was taken,
in which he denied performing agricultural work or gardening in the
course of his work as an Aboriginal Health Worker or recreationally, but
for cultural reasons would go into the desert surrounding his rural
community when required.

To confirm that the lesion was, indeed, an abscess a second aspiration
and tissue core biopsy was performed. Again, no malignant cells were
seen and pure growth of \emph{Pantoea} spp. was cultured. Insufficient
tissue was obtained to draw a definitive histological conclusion, but
the patient refused a second attempt as well as any surgical
intervention. As such, he was commenced on amoxicillin/clavulanate
875/125 mg in May 2016 for six weeks, ciprofloxacin being
contraindicated because of his history of arrythmia.

Despite successful completion of antibiotic therapy, the lesion was
still obvious at follow-up in October 2016 and the patient reported
similar symptom exacerbations in the preceding months which would
spontaneously resolve. His case was, thus, discussed at a specialist
sarcoma multi-disciplinary meeting where the consensus opinion was that
an abscess, rather than malignancy, was the most likely diagnosis.
Ongoing surveillance with imaging was recommended but the patient was
lost to follow-up until 2020, when an ultrasound scan requested by his
general practitioner showed persistence of the mass which had organized
into three separate collections measuring 150×25mm, 27×10 mm, and 31×28
mm. The patient declined further intervention for this problem and, at
the time this report was written in 2022, remained systemically well.
Apart from the six weeks of amoxicillin/clavulanate commenced in 2016,
he had not had any extended antibiotic courses for the abscess.

\textbf{DISCUSSION}

To place our case in context, we searched the MEDLINE database on 27
September 2022 to determine the spectrum of pathologies caused
by\emph{Pantoea} and associated risk factors. We used the search term
`\emph{Pantoea} ' with no restriction on publication date, and applying
the `human' and `English language' filters. This search yielded 278
results, from which 69 case reports, case series, and outbreak reports
were selected for data extraction. Patients included in these
publications were stratified by immune status and age, with children
defined as those \textless{}18 years old. We also extracted data on
clinical syndromes of sporadic cases, as well as sources of outbreaks.
The literature review is summarized in the flowchart shown in Figure 5.

As is evident from the flowchart, \emph{Pantoea} infections are rare,
with only 248 cases reported worldwide between 1991 and 2022, 53 of
which were outbreak cases stemming from various contaminated
environmental sources.(7-11) Sporadic adult and paediatric cases were
seen in equal proportions, with immunocompetent patients greatly
outnumbering their immunocompromised counterparts. Bacteraemia,(14-36)
followed by skin and soft tissue infections (SSTI),(31, 32, 37-42) were
the commonest manifestations of \emph{Pantoea} infection, but the range
of syndromes was wide, including peritonitis,(32, 43-52) bone and joint
infection,(32, 53-60) intra-abdominal abscess,(61-63) pneumonia,(31, 64)
urinary tract infection,(31, 32) ocular infection,(65-71) and
rhinosinusitis.(72) One case each of endocarditis,(15) prosthetic joint
infection,(55) and post-neurosurgical meningitis (73) was also reported,
as were four cases of neonatal sepsis.(74, 75) Only in 19 patients, all
of whom had either SSTI,(37, 41, 42) septic arthritis,(53, 56, 58, 59)
or ocular infection (66, 69) was there a history of penetrating plant
trauma, indicating that this risk factor is less important than
previously assumed. The vast majority (84\%) of infections were caused
by \emph{P. agglomerans} , with only four other culprit species
reported:\emph{P. dispersa} ,(16, 17, 25, 27, 28, 72) \emph{P. ananatis}
,(19, 21, 68) \emph{P. calida} ,(24, 73) and \emph{P. stewartii} .(18)
In four other cases, identification to species level was unable to be
performed,(39, 66, 67, 71) like in ours. However, the diversity of
\emph{Pantoea}species is not adequately differentiated by many
laboratory identification methods and, as such, many cases attributed to
\emph{P. agglomerans} may, in fact, have been cause by other
species.(76-78)

Our patient, therefore, exhibited a very atypical manifestation of
a\emph{Pantoea} SSTI mimicking malignancy, to the extent that both
clinical and radiological findings raised concerns for sarcoma. Sarcoma
is highly unlikely in our case, given the repeated pure growth
of\emph{Pantoea} spp., the long intervening period without death or
deterioration, and the expert opinion provided by the specialist sarcoma
multi-disciplinary meeting. While he denied any penetrating trauma,
whether plant-related or otherwise, it is possible that micro-abrasions
may have occurred when he fell, providing a portal of entry.
Furthermore, given his rural residence, it is likely that plant or
animal material was present on the ground, and his poor diabetic control
likely contributed to the development and progression of infection.

Only one other case of \emph{Pantoea} pseudotumour has been reported,
although this patient from India provided a clear history of penetrating
plant trauma due to his work in agriculture.(42) Like our case, this
patient also reported a distant history of a fall four years prior to
presentation. Regardless, both cases, despite the different management
approaches taken, resulted in good outcomes. While surgical drainage of
the lesion is ideal, as in the latter case, it is interesting that in
our patient the infection was successfully contained with him remaining
well ten years after symptom onset, even without surgical management. An
important clinical lesson, therefore, is that foreign bodies, especially
of plant origin which are not well-visualised on plain radiographs, may
be retained following such trauma and act as foci of chronic
inflammation leading to pseudotumour formation.

Our case raises some interesting questions. The first is whether the
patient's HTLV-1 infection further predisposes to the establishment of a
chronic bacterial infection. HTLV-1, unlike HIV, does not result in
overt immunodeficiency, but associations between HTLV-1 and
non-bacterial infections, such as scabies and strongylodiasis, are
well-described.(79) However, little is known about how HTLV-1 mediates
concurrent bacterial infections,(80) making this an important research
question of clinical significance for the many infected Indigenous
Central Australians in whom rates of bacterial infection far exceed
those of their non-Indigenous countrymen,(79) as well as people living
with this neglected tropical disease worldwide.

The second question arises from the ability of \emph{Pantoea} to secrete
products with bioremediative and immunogenic potential, facilitating its
adaptation to diverse ecological niches, including in hostile
environments.(1) It may well be that this has aided the establishment of
a well-contained infective focus in our patient, given that macrophage
activation and epithelial-mesenchymal transformation due to inflammatory
mediators released by \emph{P. agglomerans} leading to fibrosis has been
recently reported.(81) Such a process may have succeeded in walling off
the abscess, thus preventing cell-mediated immunity from eradicating the
infection but also preventing the development of sepsis. Unfortunately,
our laboratory was unable to speciate the causative organism, but other
species may also have this capability. As such, research to elucidate
the mechanisms of action of pathogen mediators released
during\emph{Pantoea} infections may be clinically useful.

\textbf{CONCLUSION}

In conclusion, we have reported, to our knowledge, the second case
of\emph{Pantoea} pseudotumour in the literature, and the first in a
patient with HTLV-1 infection. Through our analysis of this case, we
have also identified areas in which further research will have
clinically beneficial implications.

\textbf{FUNDING}

None required.

\textbf{POTENTIAL CONFLICTS OF INTEREST}

The authors declare no conflicts of interest.

\textbf{PATIENT CONSENT STATEMENT}

The authors confirm that the patient provided written consent for
publication of this report.

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\end{enumerate}

\textbf{FIGURE LEGENDS}

\textbf{Figure 1.} Map of Australia highlighting the Central Australia
region (shaded) and the location of the town of Alice Springs (red
marker).

\textbf{Figure 2.} MRI axial section of the right calf showing the
location of the pseudotumour (arrow) between the gastrocnemius (G) and
soleus (S) muscles.

\textbf{Figure 3.} CT sagittal section of the right leg showing the
extent of the multi-loculated pseudotumour (arrows) within the calf.

\textbf{Figure 4.} Photograph of the right calf mass four years after
its appearance.

\textbf{Figure 5.} Literature review flowchart showing sources and
clinical syndromes for outbreaks and sporadic \emph{Pantoea} infections,
respectively. Immunocompromise in the paediatric population included age
\textless{}28 days.\selectlanguage{english}
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