Pleural epithelioid angiosarcoma with lymphatic differentiation arisen after radiometabolic therapy for thyroid carcinoma: immunohistochemical findings and review of the literature

Nine years earlier, in another hospital, the patient underwent total thyroidectomy for papillary carcinoma with dissection of the back-left jugular lymph nodes, one of which metastatic.

The tumor was located in the upper half of the left lobe and had a maximum diameter of 4,5 cm. The histologic examination revealed a well differentiated papillary carcinoma, classical variant, with multiple microscopic foci in both lobes of the thyroid gland; the tumor stained positively for TTF1 and Thyroglobulin. One out of 8 lymph nodes was metastatic.

After six months, PET and total body scintigraphy evidenced the presence of lymph node metastases on the left side of the neck (level III and IV), and the patient underwent RMT with iodine-131 (¹³¹I, 100 mCi).

Subsequently, he was subjected to surgical lymphadenectomy of 22 cervical and supraclavicular lymph nodes, three of which metastatic. Due to the persistence of residual lymph node metastases, he underwent three cycles of RMT (100 mCi; 3,7GBq orally). So, he received a cumulative dose of 400 mCi. It is noteworthy that before the third cycle of RMT, the total body scintigraphy evidenced low and widespread ¹³¹I uptake in both lungs and in the para-medial left mediastinal area, leading to the suspicion of mediastinal and lung involvement. Thoracic PET and CT did not evidence nodular lesions, ruling out the suspicion of metastasis.

Finally, a new lymphadenectomy was performed, due to the persistence of metastases in 2/4 retro-clavear lymph nodes, in 4/22 level II left lymph nodes and in level III left lymph nodes.

The chest x-ray showed an opaque left hemithorax, saving a small central lung area with contralateral cardio-mediastinal shift [Fig. 1]. CT images showed irregular circumferential pleural thickening with nodular soft tissue masses involving the mediastinal and diaphragmatic pleura, extending into the fissures and reducing the volume of the right lung. These features clinically suggested pleural mesothelioma, and multiple biopsies of the left parietal pleura were performed during Video-Assisted Thoracotomy (VATS).

On microscopic examination, the hematoxylin-eosin (H-E) sections of formalin-fixed paraffin-embedded biopsies showed a neoplastic proliferation of highly atypical epithelioid cells with mitoses and areas of necrosis. The tumor was composed of solid areas [Fig. 2a, b] and “vasoformative” areas with variably sized anastomotic vascular spaces, lined by atypical endothelial cells with plump and prominent nuclei. Most of the vascular spaces were lacking of red blood cells and contained certain amounts of Alcian blue positive material [Fig. 2c, d]. The immunohistochemical analysis showed positive immunostaining for Vimentin, CK7, D2–40 and focally for PanCK [Fig. 3a-d], both in the vascular and in the solid areas. The vascular endothelial lining showed focal positivity for CD31 [Fig. 4a].CD34, Factor VIII related-antigenand WT1 stained positively only in a few non-neoplastic vascular channels that were used as positive internal control [Fig. 4b-d]. CD99 showed a paranuclear pattern and/or granular pattern of positivity [Fig. 4e]. Nuclei of many tumor cells stained positively for c-MYC [Fig. 4f]. Calretinin, CK5/6, EMA, HBME-1, TTF-1, Thyroglobulin and CEA stained negatively [Fig. 5a-g]. The expression of Ki67 was high, with about 30% of positive neoplastic nuclei [Fig. 5h]. Finally, negative immunostaining was evidenced for p63, Bcl-2, EpCAM and LNA-1 HHV8. The overall morphologic and immunohistochemical features supported the diagnosis of pleural malignant epithelioid vascular tumor, consistent with epithelioid AS with lymphatic differentiation.