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\begin{document}

\title{Case Report of a Pediatric Undifferentiated Pleomorphic Sarcoma of the
Cecum}



\author[1]{Kathleen Condon}%
\author[2]{Desiree McCombs}%
\author[3]{Jessica Roybal}%
\author[4]{Raj Warrier}%
\author[3]{Corey Falcon}%
\affil[1]{Tulane University School of Medicine}%
\affil[2]{Ochsner Health UQ-Ochsner Clinical SchoolNew Orleans}%
\affil[3]{Ochsner Medical Center - New Orleans}%
\affil[4]{Ochsner Clinics}%


\vspace{-1em}



  
  \date{May 25, 2024}


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\selectlanguage{english}
\begin{abstract}
Undifferentiated pleomorphic sarcoma (UPS) is a high grade neoplasm
typically diagnosed in older adults and localized to the extremities or
retroperitoneum. Poor response to therapy with high rates of recurrence
confer this neoplasm a poor prognosis. This report of cecal UPS in a
12-year-old is rare due to the patient's age and tumor location. Only
two other cases of pediatric UPS located in the intestinal tract have
been reported.%
\end{abstract}%



\sloppy


\emph{Introduction}

UPS, formerly known as malignant fibrous histiocytoma (MFH), is a high
grade pleomorphic neoplasm without any definable line of
differentiation\textsuperscript{1}. UPS usually occurs in the
extremities or retroperitoneum, and primary tumors of the
gastrointestinal tract are uncommon. Only 14 cases of cecal or ascending
colon UPS are reported in the literature. The classification and
subdivision of these tumors went through several iterations until the
WHO 2002 classification eliminated the term MFH and replaced it with
UPS\textsuperscript{1}.

UPS are most common later in life, usually the 6th and 7th
decades\textsuperscript{2}, and account for roughly 20\% of all
soft-tissue sarcomas\textsuperscript{3, 4, 5}. UPS are more common in
men than women with a 2.4:1 ratio\textsuperscript{6}.

Risk factors for the development of UPS include genetics, radiation or
chemotherapy exposure, chemical carcinogens, chronic postoperative
repair, trauma, surgical incisions and lymphedema\textsuperscript{6,
7.}The cellular origins of UPS are unclear, but possibly arise from
primitive mesenchymal stem cells that retain both fibroblastic and
histiocytic potential and may present with markers and behaviors of both
cell lines\textsuperscript{8, 9}.

UPS typically presents as an enlarging lump that is often excised early
when located on an extremity. Unfortunately, intestinal UPS is often
discovered late with substantial tumor bulk. Presenting symptoms may
include abdominal distention and pain, altered bowel habits, weight
loss, anemia, blood in the stool, or palpable abdominal mass. Compared
to other types of colon cancer, UPS presents more frequently with a
right sided mass, less frequently with constipation, and in up to 25\%
of cases patients report fevers\textsuperscript{9}. Labs at diagnosis
may be normal, or may show elevated inflammatory markers, leukocytosis,
and anemia.

Diagnosis is based on a combination of microscopic features and
immunohistochemical staining techniques used to rule out other cell
lines of origin. Lesions are typically characterized by pleomorphic,
spindle-shaped cells with bizarre cytology and nuclear
atypia\textsuperscript{10}. Immunohistochemical staining is sometimes
positive for vimentin, actin, CD68, alpha 1-antitrypsin, alpha
1-antichymotrypsin, and laminin mRNA\textsuperscript{3, 10}.
Importantly, UPS has no reproducible immunophenotype or pattern of
protein expression that allows for further classification of the
tumor\textsuperscript{3} and exclusion of pleomorphic variants of other
neoplastic lines is required\textsuperscript{5}.

CT imaging typically shows a well-circumscribed and homogeneous mass, or
a low-density mass secondary to necrosis and
hemorrhage\textsuperscript{10}. Masses are sometimes large and
lobulated, and may also have calcifications, hemorrhage, myxoid
degeneration, necrosis, or tissue invasion\textsuperscript{3}.

Standard treatment for UPS is early complete surgical resection with
negative resection margins and en-bloc lymph node dissection. The role
of chemotherapy and radiation in the treatment of UPS is debated and
without strong evidence. Increasing number of reports suggest that
adjuvant chemo or radiation may improve prognosis in certain clinical
scenarios\textsuperscript{4, 10}. Data from large studies on outcomes
with different treatments is limited and most reported cases of
intestinal UPS were treated with surgery alone.

Prognosis for UPS is generally poor because of regional invasiveness,
distant metastases and frequent recurrence\textsuperscript{6}. A review
of 200 cases found that the 2 year survival rate was 60\%, 5 year
survival rate 47\%, and overall recurrence rate 44\%. Metastasis
occurred in 42\% of cases, most commonly to the lungs (82\%) but also to
lymph nodes (32\%)\textsuperscript{2}.

\emph{Results}

A 12-year-old African American female presented to an urgent care clinic
with one week of nausea and vomiting. She reported fatigue and chronic
intermittent cramping abdominal pain for four months and unintentional
weight loss of 25 pounds over the last three. On exam she had pale
conjunctiva, tachycardia and mild abdominal pain.

CBC revealed hemoglobin 7.3 g/dL (nL: 12.0--16.0), hematocrit 29.7\%
(nL: 36.0--46.0), MCV 62 fL (nL: 78.0--98.0), RDW 18.9\% (nL:
11.5--14.5) and platelets 708 K/uL (nL: 150-450). Serum iron was 10
ug/dL (nL: 30-160), TIBC 304 ug/dL (nL: 265--497), iron saturation 3\%
(nL: 20--50) and ferritin 5 ng/mL (nL: 16.0--300.0)

The patient had a positive fecal occult blood test (FOBT), suggesting
iron-deficiency anemia due to chronic intestinal blood loss. C-reactive
protein (CRP) was 3.01 mg/dL (nL: 0.0--0.9). There was initially concern
that the patient may have inflammatory bowel disease (IBD) given her
iron-deficiency anemia, elevated CRP and positive FOBT with the weight
loss and diarrhea. NSAID-induced gastritis was also considered given
daily NSAID use for abdominal pain.

Upper gastrointestinal endoscopy was performed which showed no
abnormalities. Colonoscopy showed a large, fungating, non-obstructing
\textasciitilde{}7 cm cecal mass (Figure 1). The remainder of the colon
was normal. Biopsy of the mass was consistent with UPS\emph{.} Tumor
cells were weakly positive for SATB2, negative for Keratin OSCAR,
Keratin AE1/AE3, desmin, myogenin, SMA, SOX10, S-100, CD34, WT-1, SALL4
and EMA. Computed Tomography (CT) of the abdomen and pelvis noted a
cecal mass and multiple enlarged pericolonic and mesenteric lymph nodes.
CT chest with contrast revealed a solid noncalcified subpleural nodule
(1.1cm) in the posterior inferior left lower lobe (LLL). Positron
Emission Tomography (PET) scan showed positive uptake in the right colon
mass and possible uptake in the mediastinum and LLL.

A formal right hemicolectomy was performed without complication. At the
time of surgery, an intraluminal cecal mass was noted to be causing
colo-colonic intussusception. The ileal and colon margins were negative
for malignancy. Thirty-nine regional lymph nodes were sampled and
returned negative.

After recovery from the colectomy and pathology review, the patient
underwent a video-assisted thoracoscopic surgery and wedge resection of
the pulmonary nodule. Pathology on the nodule identified a 1.1 cm
necrotizing granuloma. Small yeast with narrow-based budding without a
mucicarmine-positive capsule were confirmed with GMS and PAS-F
cytochemical stains. The pathological findings of the nodule were
consistent with \emph{Histoplasma capsulatum} and the patient completed
a six month course of itraconazole.

On a follow-up MRI of the abdomen 2 months post-operatively, there was
no evidence of disease and anemia had resolved.

\emph{Discussion}

UPS is a diagnosis of exclusion reserved for sarcomas with a distinct
combination of immunohistochemical and microscopic features, made only
after careful consideration of other differential diagnoses. This case
is unique both for being localized to the gastrointestinal tract, with
only 14 cases reported of cecal or ascending colon UPS, as well as the
young age of the patient. Only 2 other cases of gastrointestinal UPS
have been reported in the pediatric population\textsuperscript{12, 13}.

This patient developed a non-obstructing right sided colonic mass, with
systemic features of disease including elevated inflammatory markers,
anemia, and weight loss, which are consistent with the presentation of
UPS. In spite of the tumor's large size at diagnosis (7cm)\textbf{,} the
tumor was excised with clear margins, no positive lymph nodes, and no
signs of metastasis. A lung lesion that was initially suspicious was
resected and found to be \emph{Histoplasmosis.}

Chemotherapy was not given in this case as the tumor was resected with
clear margins and there was no lymph node involvement or metastatic
disease. She will be followed by oncology to monitor for recurrence
through periodic imaging and labs. Additional research into the role of
radiation and chemotherapy for abdominal UPS is needed, especially for
cases where surgical resection is not possible. Continued monitoring and
close follow-up are essential to a good long term outcome due to a
relatively high recurrence rate.

\textbf{Conflict of Interest statement:} no conflicts of interest
reported.

\emph{References}

Fletcher, CDM, et al. WHO Classification of Tumours of Soft Tissue and
Bone. IARC Press, 2013.

Weiss SW, Enzinger FM. Malignant fibrous histiocytoma: an analysis of
200 cases. Cancer. 1978;41(6):2250-2266.

Ziwei X, Yueming S. Recurrent adult intraabdominal undifferentiated
high-grade pleomorphic sarcoma infiltrated the descending colon: a case
report and review of the literature. J Gastrointest Cancer
2019;50:629-633

Ji W, Zhong M, You Y, Wu B. Primary malignant fibrous histiocytoma of
the colon: A case report and review of the literature. Mol Clin Oncol.
2016 Jun;4(6):1006-1008.

Diaz-Beveridge R, Melian M, Zac C, Navarro E, Akhoundova D, Chrivella M,
Aparicio J. Primary mesenteric undifferentiated pleomorphic sarcoma
masquerading as a colon carcinoma: A case report and review of the
literature. Case Rep Oncol Med. 2015;2015:532656.

Fu D, Yang F, Maskay A, Long J, Jin C, Yu X, Zhou Z, Ni Q. Primary
intestinal malignant fibrous histiocytoma: Two case reports. World J
Gastroenterol 2007 Feb 28; 13(8) 1299-1302.

Azizi R, Mahjoubi B, Shayanfar N, Anaraki F, Zahedi-Shoolami L.
Malignant fibrous histiocytoma of rectum: Report of a case. Int J Surg
Case Rep. 2011;2(6):111-3.

Gupta C, Malani AK. Primary Malignant Fibrous Histiocytoma of the Colon.
Clin Gastroenterol Hepatol. 2006 Jun;4(6):xxviii.

Okuba H, Ozeki K, Tanaka T, Matsuo T, Mochinaga N. Primary malignant
fibrous histiocytoma of the ascending colon: report of a case. Surg
Today. 2005; 35:323-327.

Lee JH, Kang DB, Park, WC. Primary Undifferentiated pleomorphic sarcoma
of the colon mesentery. Ann Coloproctol 2019;35(3):152-154.

Udaka T, Suzuki Y, Kimura H, Miyashita K, Suwaki T, Yoshino T. Primary
Malignant Fibrous Histiocytoma of the ascending colon: report of a case.
Surg Today. 1999; 29:160-164.

Huang Z, Wei K. Malignant fibrous histiocytoma of the ascending colon in
a child. Am J Gastroenterol. 1993;88(6):972-973.

Carip C, de Beaumont T. Histiocytofibrome malin localis\selectlanguage{ngerman}é à l'intestin
grêle chez un jeune patient immunodéprimé {[}Malignant histiocytofibroma
of the small intestine in a young immune deficient patient{]}.
\emph{Presse Med}. 2002;31(5):214-216.

\emph{Figure Legends}

Figure 1: Cecal mass on colonoscopy of 12 year old female revealed a
fungating, non-obstructing, 7 cm cecal mass.

Figure 2: PET scan demonstrating notable increased uptake to the cecal
mass in the right upper abdominal region.\selectlanguage{english}
\begin{figure}[H]
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\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

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\end{figure}\selectlanguage{english}
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\includegraphics[width=0.70\columnwidth]{figures/Figure-2/Figure-2}

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\end{figure}

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