Resection of Extrapulmonary Lymphangiomyoma and Post-Operative Management Considerations.

Background: Lymphangiomyomatosis is a rare disease involving the lymph vessels, causing obstruction and cystic formation with an incidence of 3-8 per million women. The disease might be sporadic or inherited. Lymphangiomyomatosis mostly affects the pulmonary system, whereas extrapulmonary Lymphangiomyomatosis may present in various site, occasionally as a localized abdominal mass. The diagnostic process might entail surgical resection to obtain a specimen for pathology that may also help to achieve a long-term control of the disease. Methods: Herein, we present a case of a 45 years old female, who suffered from pulmonary symptoms, and during her workup an abdominal mass was found. The patient underwent exploratory laparotomy with resection of a left retroperitoneal bilobar mass. Results: Histopathological report revealed Lymphangiomyoma. She had a complication of a lymphatic leakage that required a second laparotomy with satisfactory clinical outcome. Conclusions: Surgeons should be aware of the pathological lymphatics and manage post-operative complications by a trial of conservative.

Isolated sporadic uterine lymphangioleiomyoma with unusual clinical and pathological features.

We report a unique uterine neoplasm, favoured to represent an isolated extrapulmonary lymphangioleiomyoma with unusual pathological features, in a postmenopausal woman without tuberous sclerosis complex. The large neoplasm consisted of smooth muscle fascicles and cystic spaces lined by lymphatic cells, which were negative for the melanocytic staining that is characteristically positive in lymphangioleiomyomatosis (LAM). There are fewer than 30 cases of uterine LAM reported, none of which have demonstrated this morphology or these immunohistochemical findings. The origin of LAM cells in the more typical pulmonary LAM remains unclear; the unusual features in this case may represent a distinct pathological entity or a rare variant of typical extrapulmonary LAM, and may contribute to determining the cellular origin of these rare tumours. Conversely, this may represent a case of 'prepulmonary' LAM, providing supporting evidence for a possible gynaecological origin of these tumours in the broader affected (almost exclusively female) population.

Retroperitoneal lymphangioleiomyoma with lymph node involvement: A pathologic-radiologic correlation of a rare form of myomelanocytic tumor.

Lymphangioleiomyomatosis (LAM) is a rare and slowly progressive disorder that usually arises in the lung, affects exclusively women in their childbearing years, and typically presents with progressive dyspnea on exertion and pneumothorax. Infrequently, extra-pulmonary LAM can occur in the retroperitoneum, uterine wall, mediastinum and intraperitoneal lymph nodes. Histologically, LAM is characterized by a proliferation of perivascular epithelioid cells (PEC) that express markers for both melanocytes and smooth muscle cells. We report a case of a peripancreatic retroperitoneal mass that was incidentally discovered on magnetic resonance image (MRI) scan of a 38-year-old female. The morphologic findings and the immunohistochemical staining were consistent with a lymphangioleiomyoma. The radiologic and pathologic correlation along with differential diagnosis of this rare entity is discussed.

Probable initial pulmonary lymphangioleiomyomatosis and mediastinal lymphangioleiomyoma.

A 68 year old woman was submitted to a mediastinal lymphangioleiomyoma resection found in a follow-up study of lower left lung resection due to bronchiectasis complicated by chylothorax. This led to a revaluation of the pulmonary specimen that revealed, in addition to inflammatory bronchiectasis, small spindle cell nodules in the lung parenchyma, similar to minute pulmonary meningothelial-like nodules, but with smooth muscle actin immunohistochemical positivity. The possibility of initial pulmonary development of lymphangioleiomyomatosis is discussed.

Bilateral ovarian lymphangioma (lymphangioleiomyoma).

Lymphangiomas of the ovary are rare and are usually unilateral. We present a 50-yr-old patient who presented with irregular bleeding secondary to multiple uterine leiomyomas who was found to have bilateral ovarian lymphangiomas. There was no evidence of pelvic lymphatic obstruction or of lymphadenopathy, and this appeared to exclude the possibility of acquired lymphangiectasia. The ovarian tumors were associated with a prominent smooth muscle cell component that partly surrounded many of the dilated vascular spaces to the extent that the diagnoses of lymphangioleiomyoma and lymphangioleiomyomatosis were also considered. However, there was no clinical evidence of lymphangioleiomyomatosis in other sites and the smooth muscle cells did not express melanocytic markers immunohistochemically. Lymphangioma and lymphangioleiomyoma should be considered in the differential diagnosis of bilateral, multicystic ovarian neoplasms.

Solitary lymphangioleiomyoma of pancreas mimicking pancreatic pseudocyst--a case report.

INTRODUCTION: Lymphangioleiomyomatosis (LAM) is a rare disease characterized by proliferation of morphologically distinguishable smooth muscle cells in the lymphatics and lymph nodes of the pulmonary parenchyma in most cases. Extrapulmonary LAM is a rare condition and is found to occur concurrently, before or after pulmonary LAM, and show strong association with tuberous sclerosis. DISCUSSION: The literature regarding extrapulmonary LAM without associated pulmonary LAM is limited due to the extreme rarity of the cases. We hereby describe clinical, pathological and radiological features of primary pancreatic LAM presenting clinicoradiologically as pseudocyst of pancreas in a 43-year-old lady. CONCLUSION: The present case is unique as LAM in pancreas without associated pulmonary LAM has never been reported in the literature before.

Mediastinal lymphangiomyoma in an adult: Report of a case.

Lymphangiomyoma is a rare benign hamartoma of lymphatic origin. A 70-year-old woman presented with a 6-month history of a cough and dyspnea on exertion. Computed tomography and magnetic resonance imaging of the chest showed a 10 x 9 x 4 cm multiloculated tumor in the anterior mediastinum. We resected the tumor successfully, preserving all vital structures, even though the tumor margin was partially indistinct. The tumor was diagnosed as lymphangiomyoma based on the pathological and immunohistological findings. Hamartomatous lymphangiomyoma is not expressed by markers for secondary lymphangiomyoma of lymphangioleiomyoma, including human-melanoma-black-45 and progesterone receptor. The terminology and relevant literature on lymphangiomyoma are reviewed following this case report.

Signal transducer and activator of transcription 3 is required for abnormal proliferation and survival of TSC2-deficient cells: relevance to pulmonary lymphangioleiomyomatosis.

Tumor suppressor complex TSC1/TSC2 represents a key negative regulator of mammalian target of rapamycin (mTOR)-S6 kinase 1 signaling. Mutational inactivation of TSC1 or TSC2, linked to a rare lung disease, lymphangioleiomyomatosis (LAM), manifests as neoplastic growth of smooth-muscle (SM)-like cells and cystic destruction of the lungs that induces loss of pulmonary function. However, the precise mechanisms of abnormal cell growth in LAM remain uncertain. Here, we demonstrate increased signal transducer and activator of transcription (STAT) 3 expression, phosphorylation, and nuclear localization in SM-like cells in LAM lungs and in TSC2-null xenographic tumors. Treatment of TSC2-null tumors with mTOR inhibitor rapamycin attenuated STAT3 expression and phosphorylation. Increased STAT3 level and activation were also observed in LAM-dissociated (LAMD) cell cultures compared with normal human bronchus fibroblasts (HBFs) from LAM patients. Although interferon (IFN)-gamma inhibited proliferation of HBFs, IFN-gamma treatment had little effect on proliferation of LAMD and TSC2-null cells. Re-expression of TSC2 or treatment with rapamycin inhibited IFN-gamma-induced STAT3 phosphorylation and synergized with IFN-gamma in inhibiting TSC2-null and LAMD cell proliferation. Reduction of STAT3 protein levels or activity using specific small interfering RNA or inhibitory peptide, respectively, decreased proliferation and induced apoptosis in TSC2-null and LAMD cells and sensitized cells to growth-inhibitory and proapoptotic effects of IFN-gamma. Collectively, our data demonstrate that STAT3 activation is required for proliferation and survival of cells with TSC2 dysfunction, that STAT3 impedes growth-inhibitory and proapoptotic effects of IFN-gamma, and that TSC2- and rapamycin-dependent inhibition of STAT3 restores antiproliferative effects of IFN-gamma. Thus, STAT3 may provide a novel therapeutic target for diseases associated with TSC1/TSC2 dysfunction.

Pregnancy complicated by lymphangioleiomyomatosis.

Lymphangioleiomyomatosis, a multisystem disease characterized by cystic lung lesions can result in respiratory failure and is considered to be sex hormones related. No effective treatment for lymphangioleiomyomatosis is currently available. We report a 35-year-old patient in her second pregnancy. She also had experienced five episodes of spontaneous pneumothorax at the age of 30. Despite excessive estrogen production during pregnancy she had mild non-progressive exertional dyspnea without limitation of daily activities during pregnancy without deterioration of respiratory status.

Lymphangiomatosis: a differential diagnosis of lytic lesions of the temporal bone.

OBJECTIVE: We report a histologically proved case of lymphangiomatosis of the skull, involving the temporal bone and presenting as multiple lytic bone lesions. METHOD: A case report and a review of the literature concerning lymphangiomatosis are presented. RESULTS: Lymphangiomatosis affecting bones is a rare disorder caused by a congenital malformation of the lymphatic system, resulting in diffuse proliferation of the lymphatic channels and involving bones, parenchymal organs and soft tissue. Involved bones show massive osteolysis and progressive, localised bone resorption. CONCLUSION: Lymphangiomatosis should be kept in mind in the differential diagnosis of lytic lesions of the skull.

D2-40 labeling in lymphangiomyoma/lymphangiomyomatosis of the soft tissue: further evidence of lymphangiogenic tumor histogenesis.

We examined ten cases of extrapulmonary lymphangioleiomyoma/lymphangioleiomyomatosis (LAM; all patients female; median age 46.5 years) for immunohistochemical labeling with a monoclonal antibody against podoplanin (D2-40), which is specific for lymphatic endothelial lining. We found positive staining in thin-wall branching vessels reflecting the lymphatic nature of tumor vessels in all cases tested. In contrast, perivascular (HMB-45 positive) myoid cells were not detected by D2-40. The D2-40 labeling confirms the current concept of lymphangiogenic origin of the tumor vessels in LAM. In addition, this study makes a further contribution to the immunohistochemical mapping of this antibody in vascular tumors. Finally, the use of this commercially available antibody provides an additional help in the differential diagnosis of LAM from other soft tissue tumors.

Pulmonary lymphangioleiomyomatosis followed by a localized retroperitoneal lymphangioleiomyoma.

Lymphangioleiomyomatosis is a rare disease that affects females of reproductive age. Microscopically, it is characterized by abnormal proliferation of immature smooth muscle-like cells that grow diffusely in the lung. Extrapulmonary manifestations in the mediastinum, peritoneum and pelvic lymph nodes are uncommon. We here describe a patient who initially presented with pulmonary lymphangioleiomyomatosis and subsequently developed a localized retroperitoneal mass. Pathologic examination showed that the mass was a lymphangioleiomyoma. The result of the immunohistochemical study was the same as that for the pulmonary lesion. It is therefore suggested that metastatic lymphangioleiomyoma should be included in the differential diagnosis in the patient with pulmonary lymphangioleiomyomatosis presenting with an extrapulmonary lesion.

Retroperitoneal lymphangioleiomyoma mimicking ovarian tumor emerging after tamoxifen therapy.

BACKGROUND: Lymphangioleiomyomas are lymphatic masses that can be associated with lymphangioleiomyomatosis. They are usually associated with pulmonary involvement. CASE: A 44-year-old premenopausal woman with breast cancer treated with adjuvant tamoxifen presented with abdominal distension. A thoraco-abdominopelvic enhanced computed tomography scan showed a 22 x 21 x 12 cm well-encapsulated, complex pelvic mass. An ovarian cystadenocarcinoma was suspected. Surgery revealed a retroperitoneal mass that was removed with uterus and both adnexae. Histological and immunohistochemical studies diagnosed a lymphangioleiomyoma. Estrogen and progesterone receptors were positive on smooth muscle cells and human melanoma black 45 was negative. CONCLUSION: Isolated retroperitoneal lymphangioleiomyoma is rare and difficult to detect in the absence of pulmonary lymphangioleiomyomatosis. We speculate that tamoxifen treatment may play a role in the development of this benign tumor.

Extrapulmonary lymphangioleiomyomatosis presented as the asymptomatic retroperitoneal tumours--two cases report.

Lymphangioleiomyomatosis [LAM] is a rare lung disease affecting women and characterized by abnormal smooth muscle cells (LAM cells) proliferation along lung and lymphatic channels. The frequent occurrence of extrapulmonary LAM [e-LAM] has been reported as abdomen pelvic lymph nodes involvement, angiomyolipomas, lymphangioleiomyomas or lymphangiomas in LAM patients. An extrapulmonary manifestation as the initial LAM presentation preceding pulmonary disorders and as asymptomatic extrapulmonary LAM lesions are unusual. We report two women presented with asymptomatic retroperitoneal cystic masses accidentally found on ultrasound examination. The tumours were surgically removed and diagnosed as: 1-malignant mesothelioma and 2-tymphangiomyoma. The microscopical sections were reviewed and re-diagnosed as e-LAM at advanced pulmonary LAM development. Mesotheliosis present in e-LAM morphology is unique and was misleading for malignancy diagnosis. The second case illustrates the hormone dependent growth of lymphangiomyoma and LAM development in young women. It is difficult to prove the presence of pulmonary LAM at the time of tumours excision but both cases demonstrate importance of appropriate LAM diagnosis and being aware of such diagnosis in cases presenting with extrapulmonary extension of the disease.

Tissue inhibitor of metalloproteinase-3 downregulation in lymphangioleiomyomatosis: potential consequence of abnormal serum response factor expression.

Pulmonary lymphangioleiomyomatosis (LAM) is characterized by abnormal smooth muscle-like cell proliferation leading to tissue destruction and cyst formation. We demonstrate that serum response factor (SRF), a critical smooth muscle transcription factor, is overexpressed in LAM cells. To determine whether abnormal SRF levels might have a pathogenic role in LAM, we transfected SRF into mouse lung fibroblasts and performed a cDNA array analysis. High SRF level upregulated the expression of matrix metalloproteinase (MMP)-2 and MMP-14, two MMPs previously shown to be increased in LAM. In addition, SRF down-regulated tissue inhibitor of metalloproteinase (TIMP)-3, one of their inhibitors. TIMP-3 inhibition was further confirmed by reverse transcriptase/polymerase chain reaction, immunoblotting, and immunostaining of human lung fibroblasts transfected with SRF fused to DsRed2 (a red variant of green fluorescent protein). To determine the in vivo significance of our findings, we immunostained 12 LAM cases for TIMP-3. In eight of them, TIMP-3 was ubiquitously present in normal lung parenchyma, but it was absent in LAM lesions. In the remaining cases, including two out of five normal control lungs, the antibody immunoreacted exclusively with elastin, probably due to suboptimal tissue processing. Because timp-3-null mice develop spontaneous emphysema, our findings suggest that SRF-mediated TIMP-3 inhibition might contribute to the tissue damage seen in LAM.

Prognostic significance of pulmonary lymphangioleiomyomatosis histologic score.

Correlations were made between clinical and follow-up data and histopathologic findings in 105 women (mean age +/- standard deviation, 38.3 +/- 9.0 years) with pulmonary lymphangioleiomyomatosis (LAM). The actuarial survival (to pulmonary transplantation or death) of the patients from the time of lung biopsy was 85.1% and 71.0% after 5 and 10 years respectively. The histologic severity of LAM, graded as a LAM histologic score (LHS), was determined on the basis of semiquantitative estimation of the percentage of tissue involvement by the two major features of LAM: the cystic lesions and the infiltration by abnormal smooth muscle cells (LAM cells) in each case: LHS-1, <25%; LHS-2, 25% to 50%; and LHS-3, >50%. Analysis using the Kaplan-Meier method revealed significant differences in survival for patients with LHS-1, -2, and -3 (p = 0.01). The 5-and 10-year survivals were 100% and 100% for LHS-1, 81.2% and 74.4% for LHS-2, and 62.8% and 52.4% for LHS-3. Increased degrees of accumulation of hemosiderin in macrophages also were associated with higher LHS scores (p = 0.029) and a worse prognosis (p = 0.0012). Thus, the current study suggests that the LHS may provide a basis for determining the prognosis of LAM.

Microphthalmia transcription factor in the immunohistochemical diagnosis of metastatic melanoma: comparison with four other melanoma markers.

The diagnosis of metastatic malignant melanoma (MMM) may be difficult in surgical pathology, often complicated by the unpredictable spread of this tumor and its great variability on histologic evaluation. Traditionally used immunohistochemical markers on melanomas are insufficient because of either a relative lack of specificity (S100 protein) or variably reported sensitivity (HMB45). Information about some newer markers, such as tyrosinase (TYR) and Melan A, is more limited. Recently, based on the study of a small number of tumors, it was suggested that microphthalmia transcription factor (MITF) is 100% sensitive in the identification of metastatic melanoma. In the current study, we compared the diagnostic usefulness of MITF with that of four other markers in 266 cases of conventional metastatic melanomas from different sites, 33 cases of desmoplastic melanomas, and 1 case of melanoma with rhabdoid features. The specificity of MITF was evaluated by using a representative sample of control tumors. Microphthalmia transcription factor with nuclear positivity was seen in 235 of 266 cases of conventional MMM (88%), usually in more than 30% of tumor cells. However, some melanomas had only foci of MITF- and TYR-positive cells, whereas the majority of cells were generally S100 protein-positive. Only 1 of 30 desmoplastic melanomas (3%) had MITF-positive cells, representing epithelioid foci resembling conventional melanoma. Two cases had TYR in a similar pattern; all were HMB45-negative. One metastatic melanoma with rhabdoid features was negative for MITF and other markers except the S100 protein. Half of the S100 protein negative conventional melanomas (6 of 12) were MITF-positive, whereas 4 of 20 (20%) TYR-negative tumors had reactivity for MITF. The percentages of positive cases of MMM (10% or more tumor cells positive) diagnosed with the four other markers in descending order were 90% (S100 protein and TYR), 78% (melan-A), and 66% (HMB45). Microphthalmia transcription factor appeared to be specific, because significant reactivity was not found in 112 carcinomas, 20 lymphomas, 20 angiosarcomas, 20 fibrous histiocytomas, and 20 malignant peripheral nerve sheath tumors. However, positive nuclei were found focally among reactive histiocytes, especially in osteoclasts, epithelioid histiocytes, and sporadic other histiocytes. Microphthalmia transcription factor may be a valuable addition to the marker panel used in diagnosing melanoma, in combination with S100, TYR, and the other markers, but it is not present in cases of desmoplastic melanomas.