PMC5465412_01
The clinical features of Patient 1. A: Chest CT showing thin-walled cysts scattered throughout the lungs. B: A photograph of the milky-colored liquid excreted as stool. Note the presence of soft, loose materials. C: Magnetic resonance imaging (MRI) of the pelvis revealing large cystic lymphangioleiomyomas (arrowhead) and abnormalities of the sigmoid colon, i.e., thickening of its wall and interior fluid collection (arrow) (T2-weighted imaging). D: Lymphatic scintigraphy of the accumulated radioactivity in the pelvic lymphangioleiomyomas (arrowheads) and the leakage into the sigmoid colon (arrow) at 120 minutes after the subcutaneous injection of 99mTc-labeled HSA into the bilateral pedal skin. E: Fiberoptic colonoscopy of the edematous rectal mucosa. F: The biopsied rectal mucosa with dilated, thin-walled spaces (arrows) in the lamina propria (Hematoxylin and Eosin staining, x82) G: Anti-podoplanin antibody (clone D2-40) staining confirmed that the dilated, irregularly-shaped, thin-walled spaces were lymphatic vessels lined with lymphatic endothelial cells (arrows; x82) H: Pelvic MRI after treatment with sirolimus (1 mg/day for 2 years; T2-weighted imaging). Note the marked shrinkage of the pelvic lymphangioleiomyomas, a normalized sigmoid colon, and the disappearance of the interior fluid.
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Chest computed tomography (CT) showed thin-walled cysts scattered throughout the lungs (Fig. 1A); however, her pulmonary function was well-preserved (forced expiratory volume (FEV1) 103.9% of the predicted, FEV1/forced vital capacity (FVC) 91.7%). The patient's stool was a milky-colored liquid with some soft or loose materials (Fig. 1B). T2-weighted magnetic resonance imaging (MRI) of the pelvis depicted large retroperitoneal lymphangioleiomyomas and abnormalities of the sigmoid colon, including wall thickening and fluid collection (Fig. 1C). Lymphatic scintigraphy showed an accumulation of radioactive substances in the pelvic lymphangioleiomyomas and their leakage into the sigmoid colon at 120 minutes after the subcutaneous injection of 99mTc-labeled human serum albumin (HSA) into the bilateral pedal skin (Fig. 1D). Fiberoptic colonoscopy revealed an edematous appearance of the rectal mucosa (Fig. 1E). A pathological examination of the biopsied rectal mucosa revealed dilated lymphatic vessels in the lamina propria (Fig. 1F, G). Pelvic (T2-weighted) MRI at 2 years after the initiation of treatment showed the marked shrinkage of the pelvic lymphangioleiomyomas, while sigmoid colon appeared normal; the previous interior fluid collection had disappeared (Fig. 1H).
PMC5465412_02
The clinical features of Patient 2. A: Chest CT of the multiple thin-walled cysts in both lung fields. B: Abdominal MRI (T2-weighted imaging) of multiple-lobulated cystic lesions dorsal to the right kidney (arrow), a high signal intensity was observed in the tissues around the inferior vena cava, and duodenal wall thickening with interior fluid collection can be observed (arrowhead). C: Lymphatic scintigraphy at 5 minutes after the subcutaneous injection of radio-labeled HSA, which accumulated in an area corresponding to that in the MR image (B) (white arrow), as well as staining of the left subclavian area (black arrow), indicating the normal lymphatic flow of the axial lymphatics. However, radioactivity was prominent in the central area of the abdomen 120 minutes later, suggesting lymphatic leakage into the intestines (black arrow). D: Protein-losing scintigraphy (intravenous injection of 99mTc-labeled HSA) shows no leakage into the intestine at either 5 minutes or 120 minutes after the injection. E: Fiberoptic gastroendoscopy of the multiple whitish granules on the mucosal wall of the second portion of the duodenum. F: The biopsied duodenum with dilated, irregularly shaped thin-walled spaces (arrows) in the lamina propria of the duodenal mucosa (Hematoxylin and Eosin staining; x50) G: Anti-podoplanin antibody (clone D2-40) staining confirmed that the dilated, irregularly-shaped, thin-walled spaces were lymphatic vessels lined with lymphatic endothelial cells. (x50) H: Abdominal MRI after treatment with sirolimus (2 mg/day for 6 months) revealed that the lymphangioleiomyomas were markedly smaller, and that the duodenal wall thickening and interior fluid had disappeared.
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Chest CT showed a small number of thin-walled cysts in both lung fields (Fig. 2A). Abdominal MRI (T2-weighted imaging) revealed multiple cystic lesions around the upper pole of the right kidney, duodenal wall thickening, and interior fluid collection (Fig. 2B). HSA, indicating normal lymphatic flow in the axial lymphatics. However, the marked accumulation of radioactivity in the central area of the abdomen, suggesting lymphatic leakage into the intestines, was observed 120 minutes later (Fig. 2C). Protein-losing scintigraphy (intravenous injection of 99mTc-labeled HSA) showed no leakage into the intestine at either 5 minutes or 120 minutes after the injection (Fig. 2D). Fiberoptic gastroendoscopy revealed multiple whitish granules on the mucosal wall of the second portion of the duodenum (Fig. 2E). The pathological examination of the biopsied duodenum revealed dilated, irregularly shaped, and thin-walled lymphatic vessels in the lamina propria (Fig. 2F, G). At this point, her fat-restricted diet and the administration of sulfamethoxazole/trimethoprim were discontinued. After 6 months of sirolimus use, abdominal MRI showed a marked reduction in the size of her lymphangioleiomyomas, and the disappearance of the duodenal wall thickening and interior fluid collection (Fig. 2H).