A case of pulmonary lymphangioleiomyomatosis complicated with uterine and retroperitoneal tumors

Abstract

A 39-year-old female experienced dyspnea on exertion for eight months. Chest CT demonstrated findings of Lymphangioleiomyomatosis (LAM), including diffuse thin-walled cystic lesions. A surgical lung biopsy revealed human melanoma black-45-positive cell infiltration and aggregation, resulting in a diagnosis of sporadic LAM without tuberous sclerosis complex. Pelvic MRI showed two large tumors, one of which was in the myometrium and the other was in the retroperitoneal space. Because we were not able to exclude the presence of malignant tumors using MR imaging, the tumors were surgically resected. The histopathology demonstrated the resected tumors to be composed of LAM cells. The patient's symptoms worsened, and sirolimus was administered, which improved the dyspnea and pulmonary function. The adverse effect was mild liver damage. Following the initiation of treatment with sirolimus, transient elevation of the serum KL-6 level was detected without interstitial pneumonia. This LAM case complicated with large uterine and retroperitoneal tumors was successfully treated with surgical resection and sirolimus.

Keywords: KL-6; Lymphangioleiomyomatosis; Retroperitoneal tumor; Sirolimus; Uterine tumor.

Fig. 1

Chest CT and pelvic MRI. A and B. Chest CT demonstrates diffusely distributed small cystic lesions with reticular opacity. C and D. T2-weighted (C) and diffusion-weighted (D) MRI show two large tumors, one of which (arrow) is located in the myometrium and the other (arrowhead) is located adjacent to the pelvic wall. The diffusion-weighted MRI reveals that the two tumors have different patterns. The retroperitoneal tumor(arrowhead) is higher intensity than the uterine tumor. E. A sagittal section of pelvic MRI shows a tumor (arrow) in the myometrium of the uterus (asterisk) with a very strong contrasting effect.

Fig. 2

Histopathological findings of the surgical biopsy of the lung. A and B. Hematoxylin-Eosin staining of the lung biopsy samples shows diffusely distributed small cystic lesions. Some cyst walls exhibit the accumulation of spindle-shaped cells. (B: ×100). C–F. Immunohistochemistry demonstrates positive staining for αSMA, HMB45, estrogen receptor (ER) and D2-40. (C and F: ×100, D and E: ×400).

Fig. 3

Histopathological findings of the resected uterine and retroperitoneal tumors. A. A gross examination shows the uterine tumor resected via total hysterectomy with BSO. The tumor is in the right posterior wall of the uterus (arrow). The surface of the retroperitoneal tumor is rugged (inset). B. Low magnification view of the uterine tumor (H-E stain). C and D. High magnification view of the uterine tumor (H-E (C) and D2-40 (D) staining). (×100). E and F. High magnification view of the myometrium showing H-E (E) and D2-40 (F) staining. There are LAM cell clusters in the myometrium and slit-like lesions (D2-40-positive) which mean lymphatic vessels. (×100). G and H. High magnification view of the uterine tumor showing LAM cell infiltration in fat tissue (H-E (G: ×200) and D2-40 (H: ×400) staining). I. High magnification view of LAM cell cluster（LCC） enveloped by D2-40 positive lymphatic endothelial cells. LCC is composed by LAM cells with HMB-45 positive staining(inset). J, K, L and M. Low magnification view of the uterine tumor showing LAM cell infiltration (ER, PR, HMB45 and αSMA staining, ×100). N, O, P and Q. Low magnification view of the retroperitoneal tumor showing LAM cell infiltration (ER, PR, HMB-45 and αSMA staining, ×100).

Fig. 4

Clinical course Bronchodilators were initially introduced without any improvements in the patient's symptoms or pulmonary function. Uterine tumor resection concomitant with bilateral salpingo-oophorectomy (BSO) slightly reduced the decline in FEV₁. However, home oxygen therapy was administered following tumorectomy, and treatment with sirolimus was initiated. An apparent improvement in the FEV₁ was observed following the introduction of sirolimus treatment. No obvious regrowth of the uterine tumors has since been noted. The serum KL-6 level fluctuated during the sirolimus treatment.