Cent. Eur. J. Med. • 6(3) • 2011 • 289-293 DOI: 10.2478/s11536-011-0009-1
Central European Journal of Medicine
Mediastinal lymphangioma and generalized lymphangiomatosis a case report Case Report
Edin M. Jusufovic1,2*, Dragan Keser1,2, Edin Zukic1 1
Polyclinic for lung disease, The Health Centre Tuzla, Albina Herljevica 1, 75000 Tuzla, Bosnia and Herzegovina
2
Medical Faculty, University in Tuzla, Univerzitetska 1, 75000 Tuzla, Bosnia and Herzegovina
Received 3 July 2010; Accepted 3 February 2011
Abstract: Lymphangioma is a malformation composed of a mass of dilated lymph vessels typically found in the cervical region in children. Mediastinal lymphangioma is a rare condition and accounts for 0.01% to 4.5% of all mediastinal tumors. Only 4 cases of mediastinal lymphangioma involving the heart and great vessels in adults have been described in the available literature. Extremely rarely, lymphangiomas occur as a generalized lymphangiomatosis. We present a case of a woman who coughed up small amounts of fresh blood during 6 months and showed signs of cardiac failure. Several years previously, the patient underwent surgical removal of cystic lymphangiomas from the left ovary, both fallopian tubes and small intestine. A chest radiograph showed an 8-cm round shadow located in the middle lobe. A computerized tomography (CT) scan of the chest with contrast verified the existence of a cyst in the anterior mediastinum. The radiologist suggested that the cyst could have originated in the pericardium . One small cyst also appeared in the projection of the left cardiophrenic sinus. A CT scan with contrast of the patient’s abdomen showed multiple cystic formations in the liver, spleen, kidneys, and left parapelvic region. A fine-needle biopsy of the mediastinal tumor verified the cystic lymphangioma, which was then completely removed surgically. A pathohistological examination confirmed the existence of cystic lymphangioma. The patient was discharged after a period of recovery. Keywords: Lymphangioma • Mediastinum • Generalized lymphangiomatosis © Versita Sp. z o.o.
1. Introduction A lymphangioma is a benign proliferation that results from failure of lymphatic system to communicate with the venous system. It is a mass of dilated lymph vessels [1,2]. In 1828 Redenbacker first described mediastinal lymphangioma [2], which are typically found in the cervical region in children [1,3]. Mediastinal lymphangioma is a rare condition and its prevalence is estimated to be 0.01% to 4.5% of all mediastinum tumors [2,4]. In the last 44 years of available literature, only 4 cases of mediastinal lymphangioma have been described involving the heart and great vessels in an adult [5]. Lymphangiomas can occur anywhere in the skin and the mucous membranes, and sometimes are found in the intestines, the pancreas, the mesentery and the spine [2,3,6]. In extremely rare cases, lymphangiomas occur
as a generalized lymphangiomatosis with extensive multifocal involvement of multiple organ systems [7]. Most adult patients are asymptomatic and are incidentally diagnosed after a routine chest radiograph [4]. Otherwise, the presenting signs and symptoms are often non-specific and may include fever, fatigue, cough, palpitations, hemoptysis, chest pain, dysphagia and superior vena cava syndrome, etc. [8,9]. It is difficult to differentiate mediastinal lymphangiomas on chest radiograms from other benign cystic mediastinal lesions such as bronchogenic, thymic, and pericardial cysts. However, lymphangiomas are easily differentiated on chest radiograms from low density lesions such as thymoma, lymphoma, and teratoma [8]. CT lymphangiography and MRI are helpful in determining both the extent of the disease and the cystic and lymphatic nature of the mass [3,10].
* E-mail:
[email protected] 289
Mediastinal lymphangioma and generalized lymphangiomatosis a case report
Figure 1.
Chest X-ray shows large well defined mass in the right hemithorax.
Figure 3.
HE - Hematoxylin and eosin-stained histological section of multilocular cystic lesion.
2. Case Report A woman, non-smoker aged 62 years, was referred to University Clinic of Respiratory and Allergic Diseases, Golnik, Republic of Slovenia suffering from an undefined and blunt pain in the back. She also had periodical dyspnea, as well as fatigue after minimal effort and for the past 6 months had frequent coughing up of small amounts of fresh blood. During the last five years she has been treated for high blood pressure. She had also undergone two abdominal surgical procedures, with removal of cysts from the left ovary and both fallopian tubes, and several intestinal cystic lesions. Pathohistological analyses verified cystic lymphangiomas on these organs. Physical examination showed mildly weakened respiratory sounds on the right paravertebral side. Arterial blood gas levels, ECG, and spirometric tests were normal. Her laboratory workup showed the presence of 290
Figure 2.
CT of the thorax after contrast application shows a well defined cystic mass in the anterior mediastinum with water density content. No septation or contrast enhancement is apparent.
sideropenic anemia. Chest x-rays disclosed a round mass about 8 cm in diameter projecting into the middle lobe. There were neither signs of infiltration of the lung parenchyma nor signs of pleural effusion (Figure 1). Video-assisted bronchoscopy examination revealed no pathological findings. During the video-assisted bronchoscopy, a biopsy was taken under control of ultrasound and radiography. A CT with contrast of thorax verified the existence of a cyst (8.5 x 7.4 x 13 cm in diameter) located in the anterior mediastinum. The radiologist suggested that the cyst could have originated in the pericardium. A 2.6 x 2 cm cyst was also detected in the projection of the left cardiophrenic sinus (Figure 2). A CT with contrast of the abdomen showed multiple cystic formations in the liver (size up to 1 cm), spleen (the largest one had dimensions of about 2.7 x 3.7 cm), the cortical part of both kidneys (size up to 2 cm), and in the left parapelvic region, a cyst 4.4 x 3 cm in diameter. There was also a significant amount of free intraperitoneal fluid. The radiologist suggested that this liquid could have originated from the ruptured cystic formations in abdomen. The cytological analysis of fine needle biopsy and aspiration suggested a lymphatic cyst. Surgical treatment of the mediastinal cystic was recommended. During the surgery, a cystic formation 8.6 x 7.8 x 13.2 cm in diameter was removed from the anterior mediastinum region. The tumor was well circumscribed and could be removed completely. In the transversal section, it was multiloculated. Microscopic examination showed that the lymphatic spaces were lined with an attenuated endothelium resembling a lymphatic structure (Figure 3).
E. M. Jusufovic, D. Keser, E. Zukic
Figure 4.
Immunohistochemical reaction positivity with podoplanin.
Figure 5.
Immunohistochemical reaction positivity with D2-40.
The spaces were filled with colloidal fluid. Immunohistochemically, the endothelial cells of the wall of the cyst were positive for D2-40 and podoplanin but negative for broad spectrum keratin (Figures 4, 5). The pathohistological diagnosis was cystic mediastinal lymphangioma. After surgical extirpation of the cyst and recovery, the patient was free of symptoms.
3. Discussion We report a case of mediastinal lymphangioma in a 62-year-old woman. This malformation is more prevalent in the pediatric population, whereas cases occur in adults only occasionally [3]. The cyst in the present case was located in the anterior mediastinum, and radiological indications suggested that the cyst could have originated in the pericardium. To our knowledge, there are only a few reports of mediastinal lymphangioma that arose in
the pericardium [3]. This is important, because tumors in the anterior mediastinum may have a poor prognosis given their proximity to vital organs [8,11]. Mediastinal lymphangioma is usually asymptomatic, but in this case because of the growth of the tumor, the patient developed a severe case of cardiac failure. Without surgery her prognosis would have been very poor. To our knowledge only eight cases of symptomatic cardiac lymphangiomas have been reported in infants and young adults taken together [12]. In chest radiograms, mediastinal lymphangiomas appear as round, well-circumscribed homogenous masses [8]. The radiogram described in this case was similar to the literature descriptions (Figure 1). A chest CT scan is recommended as the primary imaging modality for assessing masses localized within the anterior and middle compartments of the mediastinum. It can differentiate between solid mass structures or cystic formations containing calcium or fat; in addition, contrast enhancement can show the vascularization of the mass. A chest CT scan could also give the information on the precise location of the mass and its relationship to adjacent structures. MRI is superior to contrast-enhanced CT for assessing the relationships of the mass to vascular structures and in determining vascular invasion. Common descriptions of lymphatic cysts on CT include a wellcircumscribed, cystic, and homogeneous structure, although sometimes these cysts are inhomogeneous because of the presence of protein, fluid, blood, and fat. Contrast enhancement or calcification is very rare [10]. In this case the lymphangioma was well demarcated and there were no CT signs of contrast enhancement or calcification. Although the mass is usually multiloculated, CT demonstration of septa is infrequent (Figure 2). The differential diagnoses include cystic lymphangioma, bronchogenic, thymic cyst, pericardial cyst, enteric cyst, mesothelial cyst, simple parenchymal cyst, low grade cystic pleuropulmonary blastoma, and congenital pulmonary lymphangiectasis. The definite diagnosis is reached by histopathological examination. In our case, the macroscopic report described a large cystic and multilocular mass filled with chylous fluid containing lymphocytes and erythrocytes. Microscopic examination revealed large cystic spaces lined with attenuated endothelial cells. The walls of lymphatic cysts were composed of connective tissue with lymphoid aggregations (Figure 3). Attenuated endothelial cells of the wall of the cyst showed reactivity with D2-40 and podoplanin (Figures 4 and 5). The cells were negative for broad spectrum keratin. Podoplanin is a 38 kDa glomerular podocyte membrane mucoprotein that is also expressed in the endothelium of small lymphatic 291
Mediastinal lymphangioma and generalized lymphangiomatosis a case report
capillaries, but not in the blood vasculature. Among vascular malformations, podoplanin allows a differential diagnosis between lymphangiomas and hemangiomas. Moreover, in complex malformations, podoplanin labelling discriminates cystic cavities of lymphatic origin from cavities of hemangiomatous origin [12]. The monoclonal antibody D2-40, which reacts with the oncofetal membrane antigen M2A, is a new selective marker for lymphatic endothelium [13,14]. In our case, microscopic features correlated with those described in literature [12,15,16]. In the present case, the patient had multiple cysts in the liver, spleen, kidneys, left parapelvic region, left ovary, both Fallopian tubes, and intestines. For her entire life she has had no symptoms with the exception of symptoms from the ovaries and abdomen. She previously had an operation on her left ovary, both tubes, and intestines because of cystic formations. In her medical documentation we found that pathohistological analyses had verified cystic lymphangiomas on these organs. Considering the CT findings in her abdomen and pelvis, we strongly suspected that our patient suffered from generalized lymphangiomatosis. Extremely rare, lymphangiomas occur as a generalized lymphangiomatosis with extensive multifocal involvement of multiple organ systems [5]. According to the accessible literature, there are 33 described cases of mediastinal lymphangioma and lymphangiomatosis. But in last 35 years, only 12 reports have described diffuse
lymphangiomatosis in adults [17]. Common findings in generalized lymphangiomatosis are cystic lesions in parenchymal organs, mesenteric thickening, lytic bone lesions, diffuse thickening of the pulmonary interstitium, pulmonary nodules, mediastinal masses, and pleural and pericardial effusions [18]. The best treatment for mediastinal lymphangiomas is surgical resection [3]. Treated by surgery, the prognosis remains good [3,11,18], but still depends on the degree of resectability [4]. Surgical complications are chylothorax, complications resulting from incomplete excision, as well as injuries to the phrenic nerve, the vagus, the lung, and the great vessels [8]. In our case, there were no operative or post-operative complications. After a hospital recovery period, the patient was free of symptoms and ready to go home.
Acknowledgements This work was undertaken in University Clinic of Respiratory and Allergic Diseases Golnik, Republic Slovenia with support of Dr. Izidor Kern from The Department of Pathology, Dr. Igor Požek from The Department of Radiology and The Head of University Clinic of Respiratory and Allergic Diseases Golnik Prof. Dr. Sci. Med. Košnik Mitja.
References [1] Correia FM, Seabra B, Rego A, Duarte R, Miranda J. Cystic lymphangioma of the mediastinum. J Bras Pneumol. 2008, 34, 11, 982-4 [2] Park J.G., Aubry M.C., Godfrey J.A., Midthun D.E. Mediastinal Lymphangioma: Mayo Clinic Experience of 25 Cases. Mayo Clin Proc., 2006, 81, 9, 1197-1203 [3] Yildirim E., Dural K., Kaplan T., Sakinci U. Cystic lymphangioma: report of two atypical cases. Interactive Cardiovascular and Thoracic Surgery, 2004, 3, 63-65 [4] Saleiro S., Magalhães A., Moura C.S., Hespanhol V. Mediastinal cystic lymphangioma. Rev Port Pneumol. , 2006, 12, 6, 731-5 [5] http://www.ncbi.nlm.nih.gov/pubmed?term=meiastin al%20lymphangioma%20heart. Date last accessed: February, 2nd 2011. [6] McLoughlin G.S., Nuchtern J.G., Dauser R.C., Sciubba D.M., Gokaslan Z.L., Wolinsky J.P. Mediastinal lymphangioma presenting as an acute epidural hematoma. J Neurosurg Pediatrics., 2008, 292
1, 6, 474-6 [7] Zisis C., Spiliotopoulos K., Patronis M., Filippakis G., Stratakos G., Tzelepis G., Bellenis I. Diffuse lymphangiomatosis: are there any clinical or therapeutic standards? J Thorac Cardiovasc Surg. ,2007, 133, 6, 1664-5 [8] Bilgin M., Akçali Y., Oguzkaya F., Öktem T. Mediastinal Cystic Lymphangioma: A Rare Mediastinal Tumour. Turkish Respiratory Journal, 2004, 5, 3, 187-8 [9] Shenoy S.S., Barua N.R., Patel A.R., et al. Mediastinal lymphangioma. J Surg Oncol, 1978, 10, 523-8 [10] Oshikiri T., Morikawa T., Jinushi E., Kawakami Y., Katoh H. Five Cases of Lymphangioma of Mediastinum in Adult. Ann Thorac Cardiovasc Surg., 2001, 7, 2 [11] Teramoto K., Suzumura Y. Mediastinal cavernous lymphangioma in an adult. Gen Thorac Cardiovasc Surg., 2008, 56, 2, 88-90 [12] Sinzelle E., Van Huyen J.P.D, Breiteneder-Geleff S., Braunberger E., Deloche A., Kerjaschki D., Bruneval P. Intrapericardial lymphangioma with
E. M. Jusufovic, D. Keser, E. Zukic
podoplanin immunohistochemical characterization of lymphatic endothelial cells. Blackwell Science Ltd, Histopathology, 2000, 37, 85-94 [13] Dumoff K.L., Chu C., Xu X., Pasha T., Zhang P.J., Acs G. Low D2-40 immunoreactivity correlates with lymphatic invasion and nodal metastasis in earlystage squamous cell carcinoma of the uterine cervix. Mod Pathol., 2005, 18, 1, 97-104 [14] Kahn H.J., Bailey D., Marks A. Monoclonal antibody D2-40, a new marker of lymphatic endothelium, reacts with Kaposi's and a subset of angiosarcomas. Mod Pathol., 2002, 15, 434–440 [15] Ramani P., Shah A. Lymphangiomatosis: histologic and immunohistochemical analysis of four cases. Am J Surg Pathol., 1993, 17, 329-335
[16] Shin M.S., Berland L.L., Ho K.J. Mediastinal cytic hygromas. CT characteristics and pathogenetic consideration. J Comput Assist Tomogr., 1985, 9, 297-301 [17] http://www.ncbi.nlm.nih.gov/pubmed?term=media stinal%20lymphangioma%20and%20lymph angiomatosis. Date last accessed: February, 2nd 2011 [18] Marom E.M., Moran C.A., Munden R.F. Generalized Lymphangiomatosis. Radiologic-Pathologic Conferences of The University of Texas M. D. Anderson Cancer Center., 2004, AJR 182
293
