pedicle, of either omental or pericardia! origin. 9 Despite use of the latter "'bronchial pericardiopexy" technique, our patient developed a major bronchial dehiscence. It is unclear whether his anastomotic breakdown was primarily caused by irritation from the adjacent stone or occurred secondary to bacterial infection. Nevertheless, it is clear that his postoperative morbidity was increased by the presence of the broncholith. Management of the large symptomatic broncholith is controversial. Spontaneous expectoration may occur with smaller stones, but it is less likely with stones as large as that encountered in our patient. Removal via the rigid bronchoscope has been advocated with relatively high success rates lO and is currently favored over the smaller flexible bronchoscope due to the limited capabilities of the latter instrument should hemorrhagic complications occur. 11 An alternative approach for broncholith removal uses the YAG laser; stone fragmentation is followed by conventional retrieval of the fragments. 12 Massive hemoptysis, recurrent pulmonary infection, fistula, and suspicion of carcinoma are indications for surgical intervention." Associated mediastinal scarring usually makes resective surgery technically difficult. Our patient had undergone very recent thoracotomy, which would have made a surgical approach quite difficult. We opted for relatively conservative management, with partial stone fragmentation and removal via rigid bronchoscop~ Acceptable airway patency was restored, and the patient was able to avoid repeated thoracotomy with its attendant risks. At six-month follow-up, the patient had returned to full-time employment, with a stable respiratory status. To avoid the potential morbidity that can occur secondary to postoperative broncholithiasis, we recommend the removal of any calcified nodes of significant size during the lung transplantation procedure. REFERENCES 1 Arrigoni MG, Bernatz PE, Donoghue FE. Broncholithiasis. J Thorac Cardiovasc Surg 1971; 62:231-37 ISchmidt HW, Clagett OT, McDonald JR. Broncholithiasis. J Thorac Surg 1950; 19:226-45 3 Baum GI, Bernstein L, Schwartz J. Broncholithiasis produced by histoplasmosis. Am Rev Respir Dis 1958; 77:162-67 4 Faber L~ Jensik RJ, Chawla SK, Kittle CF. The surgical implication of broncholithiasis. J Thorac Cardiovasc Surg 1975; 70:779-89 5 Dixon GF, Donnerberg RL, Schonfeld SA, Whitcomb ME. Clinical commentary: advances in the diagnosis and treatment of broncholithiasis. Am Rev Respir Dis 1984; 129:1028-30 6 Davis E~ Katz S, Peabody JW Broncholithiasis, a neglected cause of bronchoesophageal fistula. JAMA 1956; 160:555-57 7 Bollengier WE, Guernsey JM. Broncholithiasis with aortotracheal fistula. J Thorac Cardiovasc Surg 1974; 68:588-92 8 Dias AR, Zerbini EJ, Curl N. Pleural stone. J Thorac Cardiovasc Surg 1968; 56:120-22 9 Kirk AJB, Conacher ID, Corris A, Ashcroft T, Dark JH. Successful surgical management of bronchial dehiscence after single lung transplantation. Ann Thorac Surg 1990; 49:147-49 10 Moersch HJ, Schmidt HW Broncholithiasis. Ann Otol Rhinol Laryn~oll959; 68:548-63 11 Brantigan CO. Endoscopy for broncholith. JAMA 1978; 240:1483 12 Miks VM, Kvale PA, Riddle JM, Lewis JW Broncholith removal using the YAG laser. Chest 1986; 90:295-97
1274
Pulmonary Abnormalities in Klippel-Trenaunay Syndrome* A Histologic, Ultrastructural, and Immunocytochemical StUdy MeghaJoshi, M.D.; Solon Cole, M.D.; David Knibbs, M.A.; and Daniel Diana, M.D.
K1ippel-Trenaunay (KT) syndrome is a rare, sporadic, congenital vascular disease of unknown etiology. We describe pulmonary findings in an 18-year-old male patient followed up since birth with the KT syndrome. The patient developed pleural and pericardial serous effusions that led to an open lung biopsy. Previous pulmonary findings have been limited to thromboembolic phenomena and pulmonary vein varicosities. On the other hand, reports of lymphatic hyperplasia, aplasia, and hypoplasia in KT have been limited to the extremities. For the first time, we describe lymphatic involvement of the lung in KT. The plexiform hyperplasia of the lymphatic channels with smooth muscle hyperplasia leading to lymphatic obstruction, pleural and pericardial effusions are new findings. The lymphatic nature of the plexiform channels was confirmed by immunohistochemistry. Von Willebrand factor and QD-END/IO monoclonal antibodies either did not react or reacted poorly with lymphatic endothelium, features used to distinguish lymphatic and venous endothelium. Ultrastructurally, the absence of basement membrane continuity further substantiated the lymphatic nature of the channels. From our findings, the lymphatic abnormality in the syndrome appears to be more generalized than previously thought. This entity should be distinguished from Iymphangioleiomyomatosis to which it bears a superficial morphologic appearance. (Chest 1992; 102:1274-77) KT = K1ippel-Trenaunay; LAM = Iymphangioleiomyomatosis; MADs = monoclonal antibodies
K
lippel-Trenaunay (KT) syndrome is a rare syndrome characterized by the triad of varicose veins, bony and soft tissue hypertrophy, and cutaneous hemangioma. I Since the first description of this syndrome in 1990 by Klippel and Trenaunay, approximately 140 cases have been published in the literature. 2 The etiology remains unknown and the syndrome is sporadic in occurrence. In its classic form, limb hemihypertrophy is seen along with arteriovenous malformations. Other associated anomalies include arteriovenous fistulas, lymphangiomatous anomalies, polydactyly/syndactyly, telangiectasia, asymmetric facial hypertroph~ and pleural involvement. The usual patient does well but surgical intervention is sometimes necessary. The patient described in this case report did not have the classic syndrome, but he had a variant of it. He had isolated enlargement of the face with telangiectasis and polydactyly. He presented in January 1990 with pulmonary infiltrates, pleural effusions, and cardiomegaly. Special studies revealed the cardiomegaly *From the Department of Pathology and Pediatric Cardiology, Hartford Hospital, Hartford, Conn. Reprint requests: Dr. joshi, Department of lbthology, New England Deaconess Hospital, Boston 02215 Pulmonary Abnormalities in Klippel-Trenaunay Syndrome (Joshi et 81)
to be due to massive pericardial effusion. Repeated thoracocentesis and pericardiocentesis failed to clear the effusions, which appeared to have become chronic. To determine the cause of these effusions, an open lung biopsy along with partial anterior pericardectomy was performed. The therapeutic pericardiectomy dealt effectively with the everpresent threat of cardiac tamponade from massive pericardial effusion. Pulmonary complications in the KT syndrome have been described',' and include thromboembolism and pulmonary vein varicosity. The incidence of pulmonary embolism is significantly high (22.4 percent as compared with 0.0055 percent in the general population) and necessitates prophylactic antithrombolytic therapy preoperatively.' Lymphatic abnormalities are characteristically seen in the limbs in most patients with KT syndrome, but involvement of pulmonary lymphatics by the same disease process has not hitherto been reported (to our knowledge). Pleural and pericardial effusions, too, are unreported complications and there is no literature discussing the management or long-term prognosis of such visceral involvement. MATERIALS AND METHODS
Specimens
Pleural and pericardial biopsy specimens for histolWc studies were fixed in 10 percent buffered formaldehyde. Routinely processed sections were stained with hematoxylin-eosin, Masson's trichrome, and elastic tissue stains. Electron Microscopy Specimens for electron microscopy were fixed in half-strength Karnovsky's fixative, postflxed in 2 percent osmium tetroxide, dehydrated through graded ethanol, and embedded in epoxy resin. Thin sections of60 nm were stained with uranyl acetate-lead citrate and examined on an electron microscope (Zeiss EM 10). Immunocytochemistry Immunoperoxidase labeling was performed as previously described.- Sections 5 ""m thick prepared from formalin-fixed, paraffin-embedded cell blocks were placed on slides coated with polyL-Iysine. Rehydrated sections were incubated overnight with the following dilutions of monoclonal antibodies (MAbs): Von Willebrand factor (1:2,000; DAKO Corporation, Carpinteria, Calif) and QB-END/IO" (1:100,000 Serotec, 22 Bankside, Staton approach, Kidlington, Oxford, United Kingdom). Following brief washes in PBS, sections were sequentially incubated with either biotinylated rabbit antimouse (1:500; DAKO) for QB-END/I0 or biotynlated F (ab'). swine anti-rabbit for Von Willebrand factor and streptavidinhorseradish peroXidase (1:11,000; Jackson ImmunoResearch, West Grove. Pal for 20 min each. Sites of peroxidase labeling were visualized with arnino-ethylcarbazole. Sections were counterstained with hematoxylin, covered (Crystal Mount, Biomeda, Foster City, Cali/). and permanently coverslipped. CASE REPORT
The male patient was 18 years old; he presented with cardiomegaly on chest roentgenowam. He was the term product from a Gl, PO-l, AbO 16-year-old mother who abused alcohol, nicotine, narcotics. and other drugs during the pregnancy. At birth he was noted to have swelling over the left side of his face causing the left eye to remain closed. an extra digit on the left hand, and mild congestion of his lungs, all of which required no special care. The left palpebral fissure eventually opened. but the left-sided facial swelling persisted. The extra digit was removed without difficulty at age 2 years.
FIGURE 1. Posteroanterior chest roentgenogram shows an enlarged cardiac silhoutte. Peribronchial cuffing and reticular interstitial thickening is present. There is widening of the minor fissure and blunting of the lateral
1274
Pulmonary Abnormalities in Klippel-Trenaunay Syndrome* A Histologic, Ultrastructural, and Immunocytochemical StUdy MeghaJoshi, M.D.; Solon Cole, M.D.; David Knibbs, M.A.; and Daniel Diana, M.D.
K1ippel-Trenaunay (KT) syndrome is a rare, sporadic, congenital vascular disease of unknown etiology. We describe pulmonary findings in an 18-year-old male patient followed up since birth with the KT syndrome. The patient developed pleural and pericardial serous effusions that led to an open lung biopsy. Previous pulmonary findings have been limited to thromboembolic phenomena and pulmonary vein varicosities. On the other hand, reports of lymphatic hyperplasia, aplasia, and hypoplasia in KT have been limited to the extremities. For the first time, we describe lymphatic involvement of the lung in KT. The plexiform hyperplasia of the lymphatic channels with smooth muscle hyperplasia leading to lymphatic obstruction, pleural and pericardial effusions are new findings. The lymphatic nature of the plexiform channels was confirmed by immunohistochemistry. Von Willebrand factor and QD-END/IO monoclonal antibodies either did not react or reacted poorly with lymphatic endothelium, features used to distinguish lymphatic and venous endothelium. Ultrastructurally, the absence of basement membrane continuity further substantiated the lymphatic nature of the channels. From our findings, the lymphatic abnormality in the syndrome appears to be more generalized than previously thought. This entity should be distinguished from Iymphangioleiomyomatosis to which it bears a superficial morphologic appearance. (Chest 1992; 102:1274-77) KT = K1ippel-Trenaunay; LAM = Iymphangioleiomyomatosis; MADs = monoclonal antibodies
K
lippel-Trenaunay (KT) syndrome is a rare syndrome characterized by the triad of varicose veins, bony and soft tissue hypertrophy, and cutaneous hemangioma. I Since the first description of this syndrome in 1990 by Klippel and Trenaunay, approximately 140 cases have been published in the literature. 2 The etiology remains unknown and the syndrome is sporadic in occurrence. In its classic form, limb hemihypertrophy is seen along with arteriovenous malformations. Other associated anomalies include arteriovenous fistulas, lymphangiomatous anomalies, polydactyly/syndactyly, telangiectasia, asymmetric facial hypertroph~ and pleural involvement. The usual patient does well but surgical intervention is sometimes necessary. The patient described in this case report did not have the classic syndrome, but he had a variant of it. He had isolated enlargement of the face with telangiectasis and polydactyly. He presented in January 1990 with pulmonary infiltrates, pleural effusions, and cardiomegaly. Special studies revealed the cardiomegaly *From the Department of Pathology and Pediatric Cardiology, Hartford Hospital, Hartford, Conn. Reprint requests: Dr. joshi, Department of lbthology, New England Deaconess Hospital, Boston 02215 Pulmonary Abnormalities in Klippel-Trenaunay Syndrome (Joshi et 81)
to be due to massive pericardial effusion. Repeated thoracocentesis and pericardiocentesis failed to clear the effusions, which appeared to have become chronic. To determine the cause of these effusions, an open lung biopsy along with partial anterior pericardectomy was performed. The therapeutic pericardiectomy dealt effectively with the everpresent threat of cardiac tamponade from massive pericardial effusion. Pulmonary complications in the KT syndrome have been described',' and include thromboembolism and pulmonary vein varicosity. The incidence of pulmonary embolism is significantly high (22.4 percent as compared with 0.0055 percent in the general population) and necessitates prophylactic antithrombolytic therapy preoperatively.' Lymphatic abnormalities are characteristically seen in the limbs in most patients with KT syndrome, but involvement of pulmonary lymphatics by the same disease process has not hitherto been reported (to our knowledge). Pleural and pericardial effusions, too, are unreported complications and there is no literature discussing the management or long-term prognosis of such visceral involvement. MATERIALS AND METHODS
Specimens
Pleural and pericardial biopsy specimens for histolWc studies were fixed in 10 percent buffered formaldehyde. Routinely processed sections were stained with hematoxylin-eosin, Masson's trichrome, and elastic tissue stains. Electron Microscopy Specimens for electron microscopy were fixed in half-strength Karnovsky's fixative, postflxed in 2 percent osmium tetroxide, dehydrated through graded ethanol, and embedded in epoxy resin. Thin sections of60 nm were stained with uranyl acetate-lead citrate and examined on an electron microscope (Zeiss EM 10). Immunocytochemistry Immunoperoxidase labeling was performed as previously described.- Sections 5 ""m thick prepared from formalin-fixed, paraffin-embedded cell blocks were placed on slides coated with polyL-Iysine. Rehydrated sections were incubated overnight with the following dilutions of monoclonal antibodies (MAbs): Von Willebrand factor (1:2,000; DAKO Corporation, Carpinteria, Calif) and QB-END/IO" (1:100,000 Serotec, 22 Bankside, Staton approach, Kidlington, Oxford, United Kingdom). Following brief washes in PBS, sections were sequentially incubated with either biotinylated rabbit antimouse (1:500; DAKO) for QB-END/I0 or biotynlated F (ab'). swine anti-rabbit for Von Willebrand factor and streptavidinhorseradish peroXidase (1:11,000; Jackson ImmunoResearch, West Grove. Pal for 20 min each. Sites of peroxidase labeling were visualized with arnino-ethylcarbazole. Sections were counterstained with hematoxylin, covered (Crystal Mount, Biomeda, Foster City, Cali/). and permanently coverslipped. CASE REPORT
The male patient was 18 years old; he presented with cardiomegaly on chest roentgenowam. He was the term product from a Gl, PO-l, AbO 16-year-old mother who abused alcohol, nicotine, narcotics. and other drugs during the pregnancy. At birth he was noted to have swelling over the left side of his face causing the left eye to remain closed. an extra digit on the left hand, and mild congestion of his lungs, all of which required no special care. The left palpebral fissure eventually opened. but the left-sided facial swelling persisted. The extra digit was removed without difficulty at age 2 years.
FIGURE 1. Posteroanterior chest roentgenogram shows an enlarged cardiac silhoutte. Peribronchial cuffing and reticular interstitial thickening is present. There is widening of the minor fissure and blunting of the lateral
