Gastric epithelioid haemangioendothelioma

Abstract

Epithelioid haemangioendothelioma (EHE) is a rare tumour of vascular origin, characterised by celular proliferation, endotelial, epitelioid or hystiocitoid. It may develop in any organ, but it is more common in lung and liver. Surgery is the recommended treatment; however, in case of a potentially benign situation, an expectant attitude should be adopted. The case reports a 71-year-old female who underwent a laparotomy for a colonic adenocarcinoma. During surgery, a polypoid lesion in the dependency of the gastric wall was found incidentally, which was removed. Histopathology and immunohistochemical analysis confirmed the diagnosis of EHE. Gastric vascular neoplasms represent about 0.9–3.3% of all gastric tumours. Usually have a good prognosis, but due to the borderline biological behaviour of these tumours, it is important to have a detailed clinical evaluation at follow-up of these patients.

Background

Epithelioid haemangioendothelioma (EHE) is a rare tumour of vascular origin that involves soft tissue and visceral organs. It was first described in 1975 by Dail and Leibow¹ and was originally termed ‘intravascular bronchioloalveolar tumour (IVBAT)’. Corrin et al. first recognised the angiogenic nature of IVBAT based on the identification of Weibel–Palade bodies. It is characterised by an endothelial epithelioid or histiocytic cell proliferation.² Other proposed terms for this tumour included sclerosing endothelial tumour, sclerosing angiogenic tumour, sclerosing epithelioid angiosarcoma and sclerosing interstitial vascular sarcoma³; however, currently, none of those names are used.

It may develop in any organ, but it is more common in lung and liver. it presents predominance in females and in the sixth decade of life.⁴ The definitive diagnosis is only possible by histopathological examination and confirmed by immunocytochemistry. Generally, they are tumours of low malignant potential; however, it may present an aggressive behaviour.

Gastric vascular neoplasms represent about 0.9–3.3% of all gastric tumours. They are usually asymptomatic and manifested by abdominal mass. They usually have a good prognosis, but due to the borderline biological behaviour of these tumours, it is important to have a detailed clinical evaluation at follow-up of these patients.⁵

This report aims to highlight the rarity of this disease and the difficulty of preoperative diagnosis, which is not possible in many cases. After a review of the literature, we found that there are only three cases reported in English of gastric EHE. Thus, although more than 200 cases of EHE have been reported in the literature, many aspects of this disease remain unknown.

Case presentation

A female of 71 years, with a history of heart insufficiency, hypertension and heart surgery for prosthetic replacement of aortic valve was sent to external consultation of general surgery for suspected cancer of the colon. Total colonoscopy was performed, which showed vegetative neoformation with raised edges and central ulceration, 2 cm in greatest diameter; at the hepatic angle, biopsy was held. Histological examination concluded that it was a moderately differentiated adenocarcinoma of colon. The remaining staging exams, including abdominal ultrasound, revealed no other significant changes.

She underwent right haemicolectomy, uneventfully. During the laparotomy, it is observed an incidental finding of a polypoid lesion (figure 1), apparently dependent on the greater curvature of the stomach, was removed (figure 2). The postoperative period was uneventful. She was discharged, clinically asymptomatic on day 7.

Figure 1.

Intraoperative image.

Figure 2.

Operative specimen.

The anatomopathological examination disclosed a moderately differentiated colonic adenocarcinoma (T3N2M×R0). The lesion dependent of the gastric wall was described macroscopically as an ovoid nodule of 5.5×3×3 cm (figure 3), elastic, whitish at cutting. It was microscopically described as a mesenchymal tumour, very vascularised, with areas of epithelioid cells, without significant atypia, low mitotic rate (5 per 50 high power fields) and no areas of necrosis (figure 4A,B). The pathological examination was in favour of gastrointestinal stromal tumour. However, immunocytochemistry was positive for CD 34, CD 31, Factor VII, featuring vascular neoplasm (figure 5A,B). In addition, it was negative for other markers, including PS 100, CD 117, Desmin, SMA and CAM 5.2. Immunocytochemical profile of vascular tumour confirmed the diagnosis of EHE.

Figure 3.

Macroscopical appearance of the tumour.

Figure 4.

(A) Neoformative elements with large nucleus and evident nucleolus. (B) The cells circumscribe some vascular structures.

Figure 5.

(A and B) Immunostaining shows CD 34 positivity of many of the tumour cells.

In the Oncology Group Consultation, it was decided for chemotherapy for adjuvant treatment of the colonic adenocarcinoma.

Differential diagnosis

• ▶GIST
• ▶Leiomyoma.

Outcome and follow-up

The 12-month follow-up (gastroscopy, colonoscopy, radiology, abdominal and pelvic CT) has not demonstrated relapse of any neoplasm.

Discussion

Weiss and Enzinger proposed the term EHE in 1982 to describe a group of 41 soft tissue vascular tumours of endothelial origin. The malignant potential of the EHEs is not well established; however, based on cases reported in the literature, these neoplasms exhibit a biological behaviour intermediate between haemangioma and angiosarcoma, as well as potential for recurrence and metastasis. There are four types of haemangioendothelioma: EHE, spindle cell haemangioendothelioma, kaposiform haemangioendothelioma and endovascular papillary haemangioendothelioma (malignant tumour known as Dabska).³ The etiology and pathogenic factors of this tumour remain unknown.⁴

Haemangioendotheliomas may involve all portions of the digestive system. Single cases have been reported at the level of duodenum, ileum and liver; however, localisation in the lung, bronchial tract, mediastinum, skin, soft tissues and distal limbs is more frequent.⁵

In EHEs, as in most stromal gastric tumours, the unspecificity of the symptomatology makes an early diagnosis difficult. The tumour can present as an abdominal mass or with clinical features of gastric outlet obstruction⁵ or upper gastrointestinal bleeding.⁶ The preoperative diagnosis is very difficult, these lesions may go undetected in the imaging studies, as in this case. The differential diagnosis with all the other forms of benign or malignant mesenchymal neoplasia depends on the histological findings supported by immunohistochemistry.⁵

Histopathology and immunohistochemistry are crucial for the proper diagnosis of this rare disease. Histologically, this neoplasia, characterised by the presence of endothelial cells with a large amount of eosinophilic cytoplasm similar to histiocytes, contains cords and blocks of epithelioid endothelial cells, sometimes intumescent and located inside a fibromixoid stroma.³ Due to the predominant morphological characteristics, the EHEs can be confused with other lesions including haemangioma to squamous cell carcinoma, therefore, emphasises the importance of immunohistochemical analysis to establish the definitive diagnosis.^{7 8} These tumours are immunopositive for markers of vascular differentiation such as CD34, factor VII or the CD 31 and negative for markers of neuronal or muscular differentiation. Moreover, S-100 and smooth muscle actin negativity makes it possible to rule out the diagnosis of other stromal gastric tumours, such as neurinoma and leiomyoma.⁵

Some vascular tumours are unique in which they are composed of large endothelial cells with abundant eosinophilic cytoplasm and well-defined margins that mimic epithelial cells. These cells form large groups within small veins and sinusoids and can also develop a vascular lumen in their cytoplasm in which red blood cells become lodged.⁴ The lesion, in the case reported, exhibit cells with prominent cytoplasmic vacuoles, which represent primitive-appearing vascular channels; it is reported that these vacuoles are negative for mucin and erythrocytes occasionally seen in the lumina.⁷

The EHEs can exhibit mineralised material, reported by some authors as metaplastic bone formation, in addition to numerous osteoclast-like giant cells. It is reported that the metaplastic bone formation with significant cellular atypia, mitotic activity greater than one per 10 highpower fields, an increased proportion of spindle tumour cells and focal necrosis represents histopathological factors associated with a more aggressive behaviour of the lesion.^{5 7} Other clinicopathological parameters, such as tumour size, localisation and the presence of mucosal ulcerations are not considered to be statistically relevant to the biological behaviour of the neoplasia.⁵ The case reported here demonstrated no relevant cellular atypia, areas of focal necrosis or mitotic activity, which leads us to suggest that probably it could be a lesion with more indolent behaviour.

Surgery represents the treatment of choice; however, a conservative approach is preferred whenever possible. Radical surgery (gastric resection/total gastrectomy) has tended to often be performed in the past probably due to incomplete knowledge of this neoplasia, since it is similar to a haemangiopericytoma, arising from myoepithelial cells or Zimmerman’s pericytis, which is both histologically and biologically more aggressive than haemangioendothelioma.⁵

In the reported case, the absence of metastases, necrotic area, focal splinding of the cells and the relief of a low mitotic index, allowed the tumour resection to work as the curative treatment. Predictions regarding the biological behaviour of EHE in stomach are not entirely possible due to the rarity of the lesion.

Pleural EHE has been reported to respond to combination chemotherapy including carbaplatine and etoposide,⁹ but its value in gastric EHE is not known. The role of adjuvant chemotherapy and radiotherapy in malignant and recurrent disease remains also to be established.¹⁰

A review of the literature, relative to the period 1966–2010, done on PubMed using the key words of gastric EHE to stage the rarity of gastric localisation of this neoplasm, resulted in the identification of three cases (one without an abstract). The first was published in 1988, in which EHE presents as a gastric polyp.⁶ The second case, published in 2002, reports a man of 41 years, with a 4.5×3 cm tumour in the gastric antrum.⁵ The third report, in 2004, describes a 58-year-old man, with an ulcerated polypoid lesion of 5×3, 5 cm in the small gastric curvature.¹⁰ All patients underwent surgical resection, with no recurrences at the time of follow-up. Yet, considering the rarity of this neoplasia and its borderline behaviour, it is important that detailed clinical evaluations be carried out for such patients along with a thorough follow-up to identify and instances of long-term recurrence.⁵

Learning points.

• ▶EHE is a rare vascular tumour that can develop in the stomach.
• ▶In the absence of histological markers of aggressiveness, present a low potential for malignancy with a good prognosis.
• ▶The preoperative diagnosis is very rare.
• ▶The immunocytochemistry plays a crucial role for the definitive diagnosis of this pathology.
• ▶For their uncertain biological behaviour, a careful follow-up of these patients is recommended.