Dr. T.S. WONG, Dr. F. HIOE

Department of Clinical Pathology, Pamela Youde Nethersole Eastern Hospital, Hong Kong

Primary pleural angiosarcoma –A case report with literature review

Clinical history

The patient was a 68-year-old Chinese male who presented with blood-stained sputum, dyspnea, and

pleuritic chest pain. Chest X-ray showed significant left pleural effusion. Computer tomography (CT)

scan showed pleural effusion with smooth pleural thickening (Figure 1). Thoracoscopy showed diffuse

hemorrhagic surface with irregular growth. Repeated fine needle aspiration of pleural effusion showed

negative results. Pleural biopsies were taken and only scanty materials were sampled. Serial CT scans

showed similar pleural thickening and new vertebral and splenic lesions (Figure 2). Clinical diagnosis

was malignant mesothelioma with disseminated disease. He soon passed away and was referred to

coroner for possibility of occupational lung disease.

Introduction

Angiosarcoma is a rare malignant neoplasm of endothelial origin. It accounts for around 1% of all soft

tissue malignancy and commonly involves skin, soft tissue, breast, bone and viscera [1]. Primary pleural

angiosarcoma is an exceedingly rare malignant mesenchymal tumor of pleura. It was first described in

1943 [3]. As of 2010, there are less than 50 reported cases documented in literature [2]. We report a case

of primary pleural angiosarcoma of left pleura in a 68-year-old Chinese male, together with a brief

literature review on this entity.

Microscopic examination

Tumor growth along the left pleural surface showed atypical spindle cells with enlarged hyperchromatic

nuclei. Rudimentary vascular channels were seen in the tumor. These vascular channels were lined by

atypical cells (Figure 6). Atypical epithelioid cells forming sheets were also identified. These epithelioid

cells possessed abundant eosinophilic cytoplasm with enlarged oval nuclei and distinct nucleoli.

Cytoplasmic vacuoles containing red cells were focally seen (Figure 7). Both atypical spindle cells and

epithelioid cells were positive for CD31 and ERG (Figure 8). They also show cytoplasmic staining for

WT1 (Figure 8). The epithelioid cells were also positive for AE1/AE3 (Figure 8). They were all negative

for calretinin and CK5/6 (Figure 8). Features were consistent with angiosarcoma. Tumor showed

infiltration into lung parenchyma and intercostal soft tissue (Figure 9-10). There was no evidence of

asbestosis on extensive sampling.

Microscopic examination also confirmed tumor deposits in spleen and vertebra (Figure 11-12).Conclusion

Primary pleural angiosarcoma is an extremely rare and aggressive disease. Patients usually have a

dismal prognosis. Moreover, its clinical, radiological and histological features can mimic malignant

mesothelioma and the use of immunohistochemical studies is necessary for a correct diagnosis.

Discussion

Primary pleural angiosarcoma is an extremely rare malignant mesenchymal tumor of pleura. It was

first described in 1943 [3]. As of 2010, less than 50 cases of primary pleural angiosarcoma were

reported in literature [1,11]. The mean age of diagnosis is 58 years (22 - 80 years) with a male

predominant ratio of 6:1 [2, 4, 5].

Due to rarity of the tumor, definite pathogenesis and etiology are not yet defined. However, several risk

factors are reported, including exposure to asbestos, tuberculosis, chronic pyothorax, radiation therapy

or parasitic infestation [6-12]. In small case series of five cases, it was postulated that patients with

history of chronic pyothorax had 3600-fold increased risk of developing pleural angiosarcoma [11].

Clinical presentation includes chest pain, shortness of breath, hemoptysis, coughing and constitutional

symptoms [1]. On imagining studies, pleural effusion, usually bloody and pleural thickening are always

encountered [1, 2, 5]. These simulate the clinical presentation and radiological finding of malignant

mesothelioma. Diagnosis is usually made on decortication or resection specimens and examination of

cytology or small biopsy specimens usually do not give a definitive diagnosis [1, 13]. It is advised that in

cases of refractory bloody pleural effusion of uncertain etiology and pleural thickening, surgical biopsy

including debulking excision, pleurectomy and decortication should be performed for definitive

diagnosis [13]. In patients with late-stage disease, the disease is also diagnosed in autopsy setting [1].

Histological features of primary pleural angiosarcoma include malignant cells with epithelioid or

spindle appearance with vasoformative nature. Occasionally, cytoplasmic vacuoles containing red cells

can be seen. Common differential diagnoses include mesothelioma and sarcomatoid carcinoma.

Immunohistochemical study is needed to distinguish the lineage of malignant cells. Expression of

endothelial markers such as CD31, CD34, factor VIII, FLI-1 or ERG is required [1, 13]. Sarcomatoid

carcinoma and mesothelioma are usually negative for these markers. Positive cytokeratin staining

(CAM5.2 and CK7) was reported in a proportion of primary pleural angiosarcoma, approximately 60%

of cases, usually in the areas with epithelioid appearance [1, 13]. Mesothelioma and sarcomatoid

carcinoma can also show positivity to cytokeratin, especially pan-cytokeratin. They will be less useful in

confirming the diagnosis. Markers of mesothelial cells such as calretinin, CK5/6, D2-40 and WT1 is

useful to differentiating tumor of vascular origin from mesothelioma. Interestingly, nuclear expression

of WT1 is seen in mesothelial cells while strong cytoplasmic expression, as in our case, is reported to be

found in tumor of endothelial lineage [2].

Treatment modalities include surgery, radiotherapy and chemotherapy. Surgery can be useful for

localized tumor. Vascular embolization is reported to be helpful in shrinking the tumor for subsequent

surgical resection. Radiotherapy can be used in adjuvant setting [1].

Clinical course of primary pleural angiosarcoma is usually rapidly fatal. The mean survival is around 1

year [1]. Most patients died of the disease within 7 months [13]. Sites of metastasis include regional

lymph node, adrenal gland, bone, brain, oral cavity, liver, skin, spleen, gastrointestinal tract, kidney and

spinal cord [13].

Gross examination

Reference

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Figure 3.

Figure 1. Figure 2.

Figure 4. Figure 5.

Autopsy was performed. On gross examination,

there were bilateral blood-stained pleural effusion.

Diffuse tumor growth along the left pleural surface

encasing the left upper lobe was identified while the

left lower lobe was collapsed (Figure 3). Tumor

growth showed invasion into intercostal spaces.

Congestion and focal consolidation were identified

in right lung.

Spleen weighed 88 gm and there were multiple

tumor deposits measuring 0.5 cm to 2 cm across the

greatest dimension (Figure 4). There was also

involvement of multiple levels of vertebra (Figure

5). The rest of the internal organs were

unremarkable.

Figure 11.

Figure 7.

Figure 9.

Figure 10.

Figure 6.

Figure 12.

CD31

ERG

WT1

AE1/AE3

Calretinin

CK5/6

Figure 8.