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\begin{document}

\title{Doege-Potter syndrome due to endothoracic solitary hypoglycemic fibrous
tumor}



\author[1]{Madaleine  Lopez-Hinostroza}%
\author[2]{Jeel Moya Salazar}%
\author[1]{Juan Dávila}%
\author[1]{Angélica  Absencio}%
\author[3]{Hans Contreras-Pulache}%
\affil[1]{Level IV Hospital Guillermo Almenara Irigoyen}%
\affil[2]{Hospital Nacional Docente Madre Nino San Bartolome}%
\affil[3]{Universidad Norbert Wiener}%


\vspace{-1em}



  
  \date{June 17, 2024}


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\selectlanguage{english}
\begin{abstract}
Doege-Potter syndrome leads to severe and sustained symptomatic
hypoglycemia and is associated with the solitary fibrous tumor. It is a
rare cause and its diagnosis requires a clinical suspicion and other
markers such as insulin-like growth factor-II. Here, we describe a case
of a patient with intrathoracic tumor and hypoglycemia%
\end{abstract}%



\sloppy


\textbf{Doege-Potter syndrome due to endothoracic solitary hypoglycemic
fibrous tumor}

Madaleine Lopez-Hinostroza\textsuperscript{1} *, Jeel
Moya-Salazar\textsuperscript{2,3} *, Juan D\selectlanguage{ngerman}ávila\textsuperscript{1},
Angélica Y. Asencio\textsuperscript{4}, Hans
Contreras-Pulache\textsuperscript{3}

\textsuperscript{1} Department of Respiratory Disease, Hospital Nacional
Guillermo Almenara Irigoyen, Lima, Peru.

\textsuperscript{2} Hospital Nacional Docente Madre Niño San Bartolomé,
Lima, Peru

\textsuperscript{3} South America Center for Education and Research in
Public Health, Universidad Norbert Wiener, Lima, Peru

\textsuperscript{4} Department of Pathology, Hospital Nacional Guillermo
Almenara, Lima, Perú.

* These authors contributed equally

\textbf{Correspondence:}

Dr. Hans Contreras-Pulache, South America Center for Education and
Research in Public Health, Universidad Norbert Wiener, Lima 51001, Peru.
Email: hans.contreras@uwiener.edu.pe

Dr. Madaleine Lopez-Hinostroza, 1380 Costanera Avenue, 1502 Dept., San
Miguel, Lima 15088, Peru. Email:

\textbf{Running tittle:} Solitary fibrous tumor causing Doege-Potter
syndrome



\textbf{Abstract}

Doege-Potter syndrome leads to severe and sustained symptomatic
hypoglycemia and is associated with the solitary fibrous tumor. It is a
rare cause and its diagnosis requires a clinical suspicion and other
markers such as insulin-like growth factor-II. Here, we describe a case
of a patient with intrathoracic tumor and hypoglycemia.

\textbf{Keywords:} Doege-Potter syndrome, Solitary fibrous tumor,
hypoglycemia, Non-islet cell tumor, Insulin-like growth factor II, Peru.

\textbf{Key Clinical Message}

Doege-Potter syndrome is a rare cause of symptomatic, severe, and
sustained hypoglycemia. This syndrome is associated with a solitary
fibrous tumor and its diagnosis is based on an acute set of clinical
characteristics and biological markers.



\textbf{1. Introduction}

Karl Doege and Roy Potter in 1930 described the presence of a
non-beta-pancreatic cell tumor associated with hypoglycemia in a patient
with a fibrous tumor in the mediastinum. Since then, the eponymous of
these authors has been used to refer to the presence of an intrathoracic
tumor associated with symptomatic, severe, and sustained hypoglycemia.
The pathophysiological mechanisms that explain the hypoglycemic syndrome
are glucose consumption by the tumor and excess secretion of
insulin-like growth factor II (IGF-II), a protein that inhibits the
release of glucose by the liver, and substances that inhibit its action
or the secretion of counterinsular hormones, which leads to the failure
of one of the mechanisms to prevent hypoglycemia.\textsuperscript{1}

The solitary fibrous tumor (SFT) is a slow-growing, large tumor of
mesenchymal origin that can cause Doege-Potter syndrome in about 2-4\%
of cases.\textsuperscript{2} The solitary fibrous tumor (SFT) is a
slow-growing, large tumor of mesenchymal origin that can cause
Doege-Potter syndrome in about 2-4\% of cases. SFT is difficult to
distinguish from other tumors, but on chest tomography, it generally
appears as a round and well-defined homogeneous mass, large tumors can
reach more than 20 cm in diameter, and 90\% of them have benign
features.\textsuperscript{3}

For its diagnosis, immunohistochemical markers such as CD34 + are used,
which is strongly expressed by this tumor, to differentiate it from
other cancerous tumors. Complete surgical resection to negative margins,
even for tumors classified as high risk, given the low global metastatic
potential and the lack of efficacious adjuvant therapy, is the mainstay
of localized SFT therapy.\textsuperscript{3,4}

Here, we describe for the first time an interesting case of a Peruvian
patient who accidentally discovered an intrathoracic tumor of
mesenchymal origin, accompanied by severe and persistent hypoglycemia.

\textbf{2. Case report}

A 74-year-old male patient with a history of hypertension 15 years ago,
type 2 diabetes mellitus 20 years ago with metformin 850mg q.d
treatment, presents with mMRC2 grade dyspnea, chest pain that has not
radiated for two weeks before admission. Due to sudden loss of
consciousness, he is taken by emergency, being immediately referred to
the Shock Trauma Unit (Glasgow 10/15), to control vital functions: BP:
170/90 mmHg, HR: 90 bpm, FR: 26 rpm, SATO2: 95\%, FIO2: 21\%, and on
preferential clinical examination: vesicular murmur is found abolished
in the left hemithorax and preserved in the right hemithorax, no added
sounds are heard.

We take capillary blood glucose (38 mg/dl), classifying it as acute
encephalopathy without neurological targeting and symptomatic
hypoglycemia. Glucose infusion serum treatment is administered,
recovering consciousness without any neurological sequelae. A
computerized axial tomography of the chest without contrast was
performed, showing a mass and left pleural effusion (Fig. 1). The
patient in his serial capillary glycemia controls presents episodes of
symptomatic, sustained and persistent recurrent hypoglycemia, for which
treatment with glucose serum is maintained. In hematic biometry controls
we found a glycosylated hemoglobin (HbA1c): 5.7\%, basal cortisol 8am of
5.9 mg/dl, insulin-like growth factor I (IGF I): 74 ng/ml, peptide C:
0.01 ng/dL, and basal insulin of 0.04 U/I.

\textbf{3. Investigation}

A bronchofibroscopy was performed, finding direct signs of malignancy
and stenosis of the left bronchial branch. For this reason,
transbronchial biopsy samples of the left lung mass and bronchial lavage
were taken, obtaining an SFT. The tumor immunohistochemistry results
were BCL2 +, CD34 + focal, CD99 Focal cytoplasmic, Actin negative, S100
negative, EMA negative, Panker negative (Fig. 2), and Papanicolaou and
Block cell with a positive result for malignant tumor cells. In
addition, Bone scintigraphy was performed with a negative result for
metastasis.

The patient continues to present symptomatic and recurrent hypoglycemia,
considering endogenous hyperinsulinism in the differential diagnosis.
Since the IGF II value was found to be 721 U/I, we considered non-island
cell hypoglycemia and paraneoplastic syndromes of IGF-II-producing
tumors as a definite diagnosis.

A pulmonary ventilation/perfusion scintigraphy was performed indicating
absence of left lung perfusion and preserved in the right lung. A
multidisciplinary medical meeting was carried out deciding to excise the
lung tumor by the chest surgery team. Surgical intervention was
performed 31 days after admission, and the operating time was 11 hours.
Complete removal of the endothoracic tumor (weight: 3.1 kg) was
successfully achieved, which was sent for a pathological study and two
left thoracic drainage tubes were placed: anterior and posterior (Fig.
3).

At 8.10 pm on the same day, the patient presented cardiorespiratory
arrest with asystole rhythm due to type III and IV acute respiratory
failure, and haemorrhagic shock. Cardiopulmonary resuscitation was
performed for 2 minutes with the administration of vasoconstrictor drugs
and transfusion of 4 concentrated blood cells. The patient responded to
extubation 2 days after the operation, and there were no sequelae of
cardiorespiratory arrest. Five days later, both chest drainage tubes are
removed. On the sixth day after surgery, the patient was discharged
without re-presenting hypoglycemic episode after surgery. On evaluation
by outpatient consultation 3 weeks after discharge, the chest radiograph
shows pulmonary reexpansion in the left hemithorax (Figure 4).

\textbf{4. Discussion}

This report is one of the few in Peru\textsuperscript{7} and agrees with
the clinical presentation reported by Han et al.,\textsuperscript{4} who
have reported that the most common cause of Doege-Potter syndrome is a
benign solitary fibrous tumor involving the Right hemothorax associated
with pleural damage. Han et al., reported 71 cases of Doege-Potter
syndrome, 43 of which (60.6\%) were malignant, including SFT of the
pelvis, bladder, and retroperitoneum associated with high-frequency
hypoglycemia.\textsuperscript{4}

The SFT associated with Doege-Potter syndrome reported in this
74-year-old patient has demonstrated positivity for BCL2 +, focal CD34
+, and Focal CD99 +. Mohammed et al.,\textsuperscript{5} have reported a
large number of lesions that are positive for CD34 + and CD99 +, as well
as other case reports, have shown immunoreactivity of these cellular
markers.\textsuperscript{6,7} However, the authors emphasize that these
immunohistochemical markers do not have high specificity and may be
present in many soft tissue neoplasms.

In this study, we reported negative for actin, S100 protein (S100), and
epithelial membrane antigen (EMA), which is different from previous
reports that showed positive for smooth muscle actin, EMA, S100, and
keratin. Given this particular performance of these markers, STAT6 has
turned out to be more specific, being positive in\textgreater{} 95\% of
the cases, recently reported as part of the pool of tests to address
these cases.\textsuperscript{8}

This clinical case has reported Doege-Potter syndrome secondary to the
SFT tumor. Although the main paraneoplastic symptom of SFT is
osteoarthropathy, hypoglycemia is less than 5\%, which is a rare
complication. Hypoglycemia is usually secondary to the tumor
overproducing IGF II precursor that leads to tumor growth, malignant
transformation, and carcinogenesis.\textsuperscript{9} Our patient had
an IGF II concentration of 721 U/I that exceeds the threshold of 10 U/I,
indicating an excess production of IGF II characteristic of non-islet
cell tumors.\textsuperscript{4,9,10}

Insulin is a 51-amino acid protein with hormone functions, and has
mediators such as peptide C in its production process. This hormone is
responsible for glycemic control, and in Doege-Potter syndrome it is
common for insulin levels to be decreased. As in previous
studies,\textsuperscript{5,6} our patient had low levels of basal
insulin (0.04 U / I) and C-peptide (0.01 ng / dL).

It has been described that the most frequent age of SFT is older adults.
Several studies have reported SFT in patients aged 67 and 83
years,\textsuperscript{5,9,11} although there are case series in
patients aged 48 years,\textsuperscript{12} 52
years,\textsuperscript{8}55 years,\textsuperscript{6} and 58
years.\textsuperscript{3} In this study, an elderly patient (74 years
old) with Doege-Potter syndrome secondary to benign SFT was reported for
the first time in Peru, which is different from previous
reports.\textsuperscript{6}

The definitive underlying treatment for Doege-Potter syndrome secondary
to benign SFT is palliative debulking, complete resection of the tumor
mass, chemotherapy, cryoablation, radiofrequency ablation, or
chemoembolization. Previous studies have described complete resection as
an effective treatment for this disease, as seen in some cases,
including the one we reported in this article.\textsuperscript{4,5,9} In
addition, other surgical techniques with a favourable prognosis have
been reported as successful.\textsuperscript{3,13}

With the discovery of the NAB2-STAT6 gene fusion as the characteristic
molecular driver of SFT, it is possible that embolization therapy and
radiation will be effective. Based on this, individualized therapies
aimed at inhibiting the descending pathways of NAB2-STAT6 could be
considered for the treatment of this rare group of
neoplasms.\textsuperscript{5}

Finally, there is a growing interest in SFT and Doege-Potter syndrome.
In Latin America, several cases have been reported in the
Argentine,\textsuperscript{14,15}
Peruvian,\textsuperscript{6}Chilean,\textsuperscript{16}
Brazilian,\textsuperscript{8}Colombian,\textsuperscript{7,11,17,18} and
Bolivian\textsuperscript{19}population, showing that even being a rare
cause of the paraneoplastic syndrome is of great interest in clinical
practice.

\textbf{5. Conclusion}

Doege-Potter syndrome associated with solitary fibrous tumor is a rare
cause of the paraneoplastic complication. Key to its diagnosis is the
quantification of IGF II, the glycaemic control profile, and
immunohistochemical markers. The surgery has been effective and its
follow-up is necessary, which generally presents a favourable prognosis.

\textbf{Authorship}

All authors contributed equally to this work.

\textbf{References}

\begin{enumerate}
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\textbf{Figures}

\textbf{Figure 1} Coronal section chest CT scan shows a mass with a
neo-proliferative appearance of the left lung measuring 24.9cm x 15.8cm
x 18.9cm, associated with ipsilateral laminar pleural effusion and mass
effect on the contralateral mediastinal structures.

\textbf{Figure 2} Solitary fibrous tumor, microscopy. Microscopy
revealed a storiform pattern arranged in hypocellular and hypercellular
areas, necrosis of 20\% of the tumor, and 6 mitoses in 10 high-power
fields. With the immunohistochemical markers it was possible to observe
positivity for CD99, CD34, Bcl-2, with actin and S100 being negative.
With these findings, the final diagnosis was a malignant solitary
fibrous tumor. \textbf{(a)} Storiform spindle cell
proliferation,\textbf{(b)} CD99 positive, \textbf{(c)} CD34 positive,
\textbf{(d)}Bcl-2 positive (all in 100x).

\textbf{Figure 3} Surgery processes. (a) complete removal of solitary
fibrous tumor (b) placement of 02 anterior and posterior TDT in the left
hemithorax. Solitary fibrous tumor, macroscopy. (c) Solid tumor
(25x20x15 cm) lobulated weighing 3.1 kg, areas of necrosis and
haemorrhage were identified in the laminations. (d) Solid whitish-brown
cut surface, with areas of necrosis and haemorrhage.

\textbf{Figure 4} Control chest X-ray 3 weeks after discharge, showing
lung expansion.

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