Extrapulmonary lymphangioleiomyoma presenting as a mesenteric cystic mass

Authors


Correspondence
Seung Sam Paik, MD, Department of Pathology, Hanyang University College of Medicine, 17 Haengdang-dong, Seongdong-gu, Seoul 133-792, Korea. Email: sspaik@hanyang.ac.kr

ABSTRACT

Lymphangioleiomyoma (LAM) is a rare benign tumor characterized by a disorganized smooth muscle cell proliferation within the walls of pulmonary, mediastinal, and retroperitoneal lymphatic vessels. The mesenteric LAM is a quite unusual presentation. A 47-year-old woman was admitted to our hospital with a 7-year history of abdominal mass. A computed tomography showed a well marginated mass with soft tissue attenuation. Laparoscopic excision was performed. The specimen revealed a well circumscribed dark cystic mass. The cut surface showed a thin walled cystic tumor with haphazardly distributed trabeculated septa. Microscopically, the tumor showed variable sized ectatic spaces lined by flattened endothelial cells and surrounded by epithelioid or spindle-shaped cells. The lining cells were positive for D2-40, CD31, and CD34. The surrounding cells were positive for alpha-smooth muscle actin and human melanoma black-45. The final diagnosis was a solitary LAM arising in the mesentery. The patient showed an uneventful postoperative course for 10 months.

INTRODUCTION

Lymphangioleiomyoma (LAM) is a very rare benign tumor that reveals typical histologic features of a disorganized smooth muscle cell proliferation within the walls of pulmonary, mediastinal and retroperitoneal lymphatic vessels.1 This tumor mainly develops in females in the reproductive age. Most cases of this tumor primarily occur in the lungs.2,3 Extrapulmonary LAM is quite rare and mainly located in the pelvis, mediastinum and retroperitoneum.4 The mesentery as an involved site of extrapulmonary LAM is an extremely rare location. To the best of our knowledge, only three cases have been reported in the English-language literature.1,5 Here, we report a case of extrapulmonary LAM arising in the small bowel mesentery of a 47-year-old woman.

CASE REPORT

A 47-year-old woman was admitted to our hospital with a 7-year history of palpable abdominal mass. Her family history and medical history were unremarkable. The chest X-ray examination was unremarkable. Gynecological ultrasonography revealed a well defined large cystic mass with mixed echogenicity. The uterus and both adnexa were unremarkable. There was no ultrasonographic evidence of lymphadenopathy. An abdominal computed tomography showed a well-marginated mass with soft tissue attenuation and multifocal enhanced areas, which was located at the mesenteric area and abutted to the bowel loop (Fig. 1). There was a minimal amount of ascites in the pelvic cavity. Under the impression of mesenteric tumor, laparoscopic mass excision was performed. The resected specimen showed a well circumscribed dark cystic mass, which measured 17 × 12 × 10 cm. The tumor was located at the mesentery of the small bowel. The cut surface of the tumor showed a thin walled cystic mass with haphazardly distributed trabeculated septa and abundant hemorrhagic content in spaces (Fig. 2).

Figure 1.

(a, b) An abdominal computed tomography revealed a large cystic mass with a well defined margin and multifocal enhanced areas in the mesenteric area.

Figure 2.

The resected specimen showed a well circumscribed cystic mass in the small bowel mesentery (a). The cut surface showed a thin walled large cyst with haphazardly distributed trabeculated septa and abundant hemorrhagic content in spaces (b).

Microscopically, the tumor showed variable sized ectatic spaces lined by flattened endothelial cells and surrounded by epithelioid or spindle-shaped smooth muscle cells. The vascular spaces were empty or sometimes filled with eosinophilic fluid. The stromal cells were spindle-shaped or epithelioid with abundant eosinophilic cytoplasm and nuclei devoid of pleomorphism and mitotic activity. Neither necrosis nor hemorrhage was seen in the tumor. The lining endothelial cells were positive for D2-40, CD31, CD34 and factor VIII. The stromal epithelioid or spindle-shaped cells were positive for alpha-smooth muscle actin, caldesmon, and human melanoma black-45 (HMB-45) (Fig. 3). With the results of immunohistochemical stains, the tumor was diagnosed as a solitary LAM arising in the mesentery of the small bowel. The patient had an uneventful postoperative course and has been free of recurrence for 10 months.

Figure 3.

The tumor showed variable sized ectatic spaces lined by flattened endothelial cells and surrounded by epithelioid or spindle-shaped smooth muscle cells (a). The endothelial lining cells were positive for D2-40 (b). The epithelioid or spindle-shaped cells were positive for alpha-smooth muscle actin (c) and human melanoma black-45 (d).

DISCUSSION

Lymphangioleiomyoma is a rare benign tumor of a hamartomatous nature characterized by abnormal proliferation of lymphatic smooth muscle cells and affecting women in the reproductive age.3 The majority cases of LAM primarily occur in the lungs and represent cystic lung lesion, lymphatic abnormality and abdominal tumors. Pulmonary LAM is characterized by abnormal smooth muscle cell proliferation causing gradual obstruction of small airways, lymphatics, and vasculature. The patients with pulmonary LAM clinically present with progressive breathlessness or recurrent pneumothorax, chylous pleural effusion, or ascites.3,6,7

Lymphangioleiomyoma also can involve the extrapulmonary sites; however, extrapulmonary LAM is very rare and the etiology or the effective treatments are as yet unknown. Matsui et al.5 and Jaiswal et al.8 reviewed the cases of extrapulmonary LAM and described the clinicopathological features of extrapulmonary LAM. The clinical features of extrapulmonary LAM were palpable abdominal mass, abdominal pain, and chylous ascites. The tumors were mainly located in the retroperitoneum, pelvic cavity, and the posterior mediastinum along the lymphatic channels. As an involved site of extrapulmonary LAM, the mesentery is an extremely rare location. There were only three reported cases in the English-language literature. Matsui et al.5 reported two cases of mesenteric LAM in their review paper and Mboyo et al.1 reported a case of mesenteric LAM in an 11-year-old girl. The clinical and pathologic findings of mesenteric LAM are summarized in Table 1.

Table 1.  Clinicopathologic findings of mesenteric lymphangioleiomyomas
Case No.Age (years)Clinical findingsAssociated conditionsLocationOperationMass (n)Size (cm)Follow upReference
  1. AML, angiomyolipoma; E-LAP, excision of laparotomy; L-E, laparoscopic excision; P-LAM, pulmonary lymphangioleiomyomatosis.

111Abdominal massNoneMesenteryE-LAP1 810 yearsMboyo et al.1
243Abdominal massP-LAMMesenteryE-LAP1 811 yearsMatsui et al.5
351Abdominal massP-LAM, AMLMesenteryE-LAP115 NoneMatsui et al.5
Our case47Abdominal massNoneMesenteryL-E11710 months 

The exact pathogenesis of this tumor is still unclear. However, LAM occurs mainly in women, usually during their reproductive ages and the disease is exacerbated by pregnancy or hormonal therapy. Therefore, a hormonal cause has been suggested.7 LAM can be divided into a sporadic form or a tuberous sclerosis-associated form. There have been many studies regarding the genetic predisposition of LAM, especially associated with the mutation of tuberous sclerosis genes (TSC1 and TSC2).9,10 It has been shown that there is loss of heterozygosity of the TSC2 gene on chromosome 16 in both sporadic LAM and LAM from patients with tuberous sclerosis.11

The typical histology of LAM is a proliferation of smooth muscle cells arranged in fascicular, trabecular, and papillary patterns associated with slit-like vascular channels. The proliferating smooth muscle cells can vary from small, spindle-shaped cells to large epithelioid cells.12 Most cases of extrapulmonary LAM are confirmed after surgery. Immunohistochemical stains including alpha-smooth muscle actin, vimentin, desmin, caldesmon, and HMB-45 should be performed to differentiate from the other tumors. HMB-45 stain is specific for LAM and is essential for correct diagnosis.13,14 In view of HMB-45 positive cells, angiomyolipoma should be considered in the differential diagnosis. The incidence of angiomyolipomas in patients with LAM has been reported to be as high as 60%. However, angiomyolipomas are characterized by the presence of abundant adipose tissue and by disorganized components of blood vessels.7,15

The current treatment modality for LAM is primarily based on the antagonism of estrogen action. The fact that LAM usually develops in females of reproductive age, that the cells of LAM have receptors for estrogen and progesterone, and that the disease is exacerbated by pregnancy or administration of estrogen, supports that the etiology of this tumor is closely related to hormones.2 The most commonly used treatment is intramuscular progesterone injection, which became the standard of care following a case report by Sieker and McCarty16 in 1988. Recently, Harari et al.17 reported the effect of a gonadotrophin-releasing hormone analog on lung function in LAM. Despite a variety of treatment regimens developed since the first description of LAM, patient survival has not improved appreciably. LAM progresses slowly; however, most patients with LAM die within 10 years of diagnosis.18

In conclusion, we described an extremely rare case of extrapulmonary LAM arising in the small bowel mesentery of a 47-year-old woman. Although the incidence is quite rare, extrapulmonary LAM can develop in the mesentery and should be considered in the differential diagnosis of the mesenteric cystic mass.

Ancillary