Epithelioid angiosarcomas (EASs) arising in the gastrointestinal tract are rare, particularly in pediatric patients. Epithelioid angiosarcoma is known for its poor outcomes, with patient’s demise within months following diagnosis. An unusual case of colonic angiosarcoma has been reported in a 16-year-old female patient who was alive and well three years after surgery without adjuvant therapy [1],[2]. We present a similar case of EAS arising in a 3-year-old female who was alive and well seven years after surgery without adjuvant therapy. Our case, along with the case of the 16-year-old female, may shed light on a subtype of EAS arising in the gastrointestinal tract that may have different biological and/or molecular imprints that follow a different course with a favorable prognosis.

A female patient, 3 years and 5 months of age, presented with a 3-month history of progressively worsening emesis, intermittent abdominal pain, decreased appetite, and weight loss. A clinical workup identified a significant microcytic anemia [hemoglobin 19 g/L, mean corpuscular volume (MCV) 53 fL], initially thought to be secondary to iron deficiency due to her poor oral intake (serum iron 3 µmol/L, ferritin 19 µg/L, and platelets 828 × 109/L). Imaging studies revealed an infiltrative mass at the ileocolic area (Figure 1).

Open wedge biopsies of the mass were initially performed which yielded an inconclusive pathological diagnosis of atypical epithelioid vascular proliferation without obvious features of malignancy. Epithelioid hemangioendothelioma and a reactive vascular proliferation were also in the differential diagnosis on microscopy. A more extensive sampling or resection of the lesion was recommended.

At 3 years and 7 months of age, the patient underwent small bowel segmental resection that included the mass. There were no other lesions in the mesentery, omentum, lymph nodes, liver, or peritoneal surfaces. The mass was resected in multiple pieces, the largest being attached to the bowel wall and measuring approximately 5.5 × 3.5 × 3.0 cm (Figure 2). Despite the mass showing extensive areas of necrosis and hemorrhage, the small intestinal mucosa overlying the mass seemed unaffected with no notable gross ulceration. The patient’s family refused further therapy, including chemotherapy, and opted to follow up.

Microscopic examination of the lesion revealed a highly atypical vascular proliferation composed of large epithelioid to slightly spindled cells arranged in solid sheets with primitive vascular lumina. The neoplastic cells showed a moderate degree of nuclear pleomorphism, vesicular nuclei, prominent nucleoli, and brisk mitotic activity (up to 12 per 10 high-power fields) and extensive necrosis. Immunohistochemistry revealed that the tumor cells were diffusely and strongly positive for erythroblast transformation specific-related gene (ERG) and CD31, and patchy positive for CD34 (Figure 3).

CD117 focally highlighted some of the tumor cells but was considerably less intense than the more specific endothelial markers. It is worth mentioning that the native endothelial cells lining non-tumor capillaries were negative for CD117, thus acting as a negative built-in control. The tumor cells were negative for cytokeratin AE1/3, CK7, CK20, S-100, desmin, caldesmon, SMA, myogenin, CD163, D2-40, Human Herpesvirus-8 (HHV8), and Calmodulin binding transcription activator 1 (CAMTA1). Flow cytometry revealed a normal CD4/CD8 ratio at 1.57 and a normal kappa/lambda ratio of 1.78. There were no abnormal cellular clones. The resection margins were negative for tumor involvement. Cytogenetic evaluation showed a normal 46XX female karyotype. These findings were diagnosed as vascular neoplasm with atypical features consistent with EAS.

Following surgical resection, the patient did not receive adjuvant chemotherapy or radiation therapy. Serial multiple imaging post-resection revealed a stable thickened area of the terminal ileum, which had resolved on imaging 18 months following the surgery and did not re-appear in the follow-up imaging during the past seven years of follow-up. The patient remains clinically well at the 7-year follow-up, with no evidence of tumor recurrence or metastases.

Angiosarcomas affecting the small bowel are rare, occurring mostly in male patients, at a median age of 58 years [3]. A primary angiosarcoma of the small intestine with multiple metastases at the time of diagnosis has been reported in a male patient at age 59 years [4]. Angiosarcomas are even rarer in pediatric-age patients, especially in very young children. There is a report of a 16-year-old girl with a colonic angiosarcoma, who has remained in remission for 78 months (6.5 years) with surgical resection alone [2]. We report a 3-year-old female patient diagnosed with EAS, without evidence of metastases. She underwent surgical resection without adjuvant chemotherapy and radiation and is well, without recurrence, seven years post-resection.

Angiosarcomas as primary lesions in the gastrointestinal tract are rare and can be difficult to diagnose given a variety of histomorphological presentations [5] as well as a range of differential diagnostic considerations, both benign and malignant [6],[7]. Angiosarcomas have been most commonly described in deep soft tissues, including the retroperitoneum [8] as well as the skin [9],[10], but they may occur in any of a wide variety of locations [11],[12],[13].

Epithelioid angiosarcomas are often characterized histologically by a sheet-like undifferentiated presentation of otherwise bona fide EAS, which can be further defined using immunohistochemical stains [7]. The pan-cytokeratin marker AE1/AE3 is positive in a variable range of EAS. The differential diagnosis includes florid vascular proliferation which is a benign pseudo-neoplastic reactive proliferation of small vessels in the colon, which can mimic other benign or malignant vascular lesions. Florid vascular proliferation usually presents as a “mass” lesion and is associated with intussusception or colonic obstruction. However, the marked atypia and the unequivocal malignant histological features rule out this diagnosis. In addition, the aberrant immunostaining for CD117 in the endothelial tumor cells also tends to favor angiosarcoma over a reactive process. CD117 was positive in our case. Miettinen et al. (2000) reported positive CD117 in a subset of cases of angiosarcomas [14]. They indicated that KIT expression occurs in a subset of angiosarcomas, probably representing oncofetal regression (i.e., reversion of the tumor cell phenotype to that of fetal endothelial cells that may show KIT expression).

On similar grounds hemangiomas, including infantile hemangioma, were ruled out. Staining with GLUT1 may be positive in a minority of angiosarcomas but is specific for juvenile hemangioma [15].

The cellular proliferation index staining for Ki-67 with MIB-1 is usually high (>10%) in biologically more aggressive lesions. It usually, but not always, portends a worse clinical course including demise from disease in most of such patients. The converse is true for the prognosis if the MIB-1 is <10%. In less-differentiated cases, electron microscopy might be helpful by demonstrating features of endothelial differentiation including the possible presence of Weibel–Palade bodies.

Epithelioid angiosarcomas are essentially managed by surgical resection, while radiation and/or chemotherapy yield variable degrees of adjunctive benefits [15].

Our patient is a 3-year-old female with a surgically cured 5.5 cm angiosarcoma of the small bowel, clinically masquerading as Meckel’s diverticulum. There is no evidence of tumor recurrence or metastases seven years following surgical resection, even without the use of any other adjuvant treatment modality. Her angioformative tumor occurring in relation to a loop of ileum also makes it one of the rarer presentations of this primary malignant neoplasm. The impression at surgical resection as the lesion looking like a Meckel diverticulum is explained by the fact that the tumor was likely sitting astride the small bowel wall, partially infiltrating it to the level of the submucosa, without mucosal involvement, and partially protruding away from the intestine proper toward the free abdominal cavity.

Angiosarcomas are rare in children and they often have epithelioid features. Not all pediatric patients have adverse outcomes. Deyrup et al. in 2009 documented 3 out of 15 children who could be considered long-term survivors without evidence of disease at 52-month (14-year-old male with angiosarcoma involving the arm), 108-month (2-year-old female with angiosarcoma involving the mesentery), and 132-month (3-month-old female involving right atrium) [16]. Our case is an addition to these rare cases, being the only reported case of EAS occurring in the small bowel in the pediatric population, with a recurrence-free survival of 84 months (3-year-old at time of surgery involving the small bowel).

Future studies are necessary to understand the pathological and molecular nature of this unusual tumor in the pediatric population and its clinical course [17].

To the best of our knowledge, we report the youngest published patient presenting with a 5.5 cm primary EAS masquerading as Meckel’s diverticulum involving the wall of a loop of small intestine, and without evidence of tumor recurrence or metastases seven years following surgical resection in the English-language literature. Our report highlights that not all pediatric patients with gastrointestinal angiosarcoma have an adverse outcome.