CAVITATING LUNG NODULES AND PNEUMO- THORAX IN CHILDREN WITH METASTATIC WILMS TUMOR*
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1 APRIL, 1976 ABSTRACT: CAVITATING LUNG NODULES AND PNEUMO- THORAX IN CHILDREN WITH METASTATIC WILMS TUMOR* By E. GEORGE KASSNER, M.D.,t HAROLD S. GOLDMAN, M.D.4 and ALBERTO ELGUEZABAL, M.D. BRONX AND BROOKLYN, NEW YORK Lung metastases evolved into large thin-walled Cysts in two children with Wilms tumor. Histologic examination of one lesion suggested that invasion of a small bronchus or bronchiole, leading to ball-valve obstruction, was responsible. One patient also experienced recurrent pneumothorax, probably on the same basis. The formation of thin-walled cysts has not previously been observed with metastatic Wilms tumor. Pneumothorax is a rare complication of metastatic Wilms tumor. C AVITATION of pulmonary metastases is very rare in children. This phenomenon has been reported in three children with metastatic Wilms tumor.3 5 We have observed two children with Wilms tumor in whom pulmonary metastases evolved into large thin-walled cysts. One of these patients had recurrent episodes of pneumothorax, a complication that has rarely been associated with metastatic Wilms tumor.4 REPORT OF CASES CASE I. (Jewish Hospital and Medical Center of Brooklyn.) A.R. had a right nephrectomy for Wilms tumor at two and one-half years of age. Tumor was present in the renal vein. Lung metastases were not detected in the initial chest roentgenogram. A course of actinomycin D was begun and 3,000 rads were delivered to the tumor bed using Co-6o teletherapy. Six months after nephrectomy a pulmonary metastatic nodule was seen in the right lower lobe. Alternating courses of actinomycin D and vincristine were administered and 300 rads were delivered to a small field encompassing the nodule. Sixteen months after nephrectomy another small pulmonary metastatic deposit appeared in the lingula and 300 rads were delivered to this lesion. After nine months without change the nodule in the right lung began to enlarge and was excised with a cuff of tumor-free lung. A second course of radiation therapy was administered to a small field that encompassed the metastasis in the left lung (Fig. ia). After 750 rads of a planned tumor dose of 2,250 rads had been delivered, a cavity was noted within the metastasis (Fig. ib). This cavity continued to enlarge and the heart was displaced to the right (Fig. i, C and D). The patient had a cough and was easily fatigued but he was not in acute distress. Radiation therapy was stopped after 1,050 rads and lingulectomy was performed, 16 months after the appearance of the metastatic deposit in the left lung and 25 months after nephrectomy. The resected lung specimen consisted of a collapsed empty sac, which measured 4 cm in diameter, partially surrounded by a solid tumor which measured 5X3.5X2 cm. Where it did not abut the tumor mass, the cyst wall was 1-2 mm thick. Microscopically the tumor was a typical Wilms tumor; the sarcomatous component predominated and there were a few scattered epithelial areas. Tumor completely surrounded the cyst and extended either to the lining epithelium, if present (Fig. 2, ii and B), or to the lumen in areas where the lining epithelium was absent. In most areas the cyst was lined with respiratory epithelium. There were foci of squamous metaplasia or flattened cuboidal epithelium. Where lining epithelium was absent the cyst wall was composed of a thin layer of tumor covered externally by subpleural * From the Departments of Radiology of the State University of New York, Downstate Medical Center,t and the Albert Einstein Medical Center, Bronx, New York4 and the Department of Pathology of The Jewish Hospital and Medical Center of Brooklyn. 728
2 VOL. 126, No. Cavitating Lung Nodules 729 ( L FIG. I. Case,. (A) March 7. Twenty degree right anterior oblique proiection of the chest shows a metastatic nodule in the lingula. (B) April i8. A cavity is visible within the nodule. (The changes on the right-basilar parenchymal infiltrate, pleural thickening and elevation of the hemidiaphragm-are the residua of previous surgery.) (C and D) May 26. A large thin-walled cyst with several septa has developed at the site of the nodule. The heart is displaced to the right. On the lateral projection the solid portion of the tumor is visible anteriorly. Lingulectomy was performed the following day. fibrous tissue and pleura. Tumor did not penetrate the pleura. Cartilage was not seen in the cyst wall. Necrosis, bizarre nuclei or other radiation changes were not present in the tumor. There was no evidence of acute radiation pneumonitis, vasculitis or fibrosis in the surrounding lung parenchyma. The only features that were prob- not obtained. ably related to radiation therapy were prominence of the endothelial cells of some vessels and squamous nietaplasia in a few bronchi. Subsequently tumor recurred in the left lung, mediastinuni, pleura and abdomen. He died at five and one-half years of age, 38 months after nephrectomv. Permission for autopsy was
3 730 E. G. Kassner, H. S. Goldman and A. Elguezabal APRIL, 1976 U I.,/-_ Bt. 7-: -i FIG. 2. Case I. (A) Photomicrograph of the excised metastatic nodule, showing an area in which the cyst abuts the main tumor mass. Tumor is visible just beneath the lining epithelium of the cyst. Two types of epithelium are present in this field: respiratory epithelium on the right and flattened cuboidal epithelium on theleft. (H & E, 300X magnification.) (B) High power. The cyst lining consists of respiratory epithelium. Tumor is present just beneath the epithelium. (H & E, 750X magnification.) CASE II. (Albert Einstein Medical Center.) M.C. had a left nephrectomy for locally invasive Wilms tumor at three years of age. There was no evidence of pulmonary metastases. Actinomycin D was administered and, because the tumor had ruptured during surgery, 3,300 rads were delivered to the entire abdomen using Co-6o teletherapy: the right kidney was shielded after rads. Several subsequent courses of actinomycin D were given. Twentyfour months after nephrectomy he was readmitted with a four day history of right chest pain. A chest roentgenogram showed a pneumothorax on the right and metastatic deposits in both lungs (Fig. 3A). A chest tube was inserted and actinomycin D and vincristine were begun. A tumor dose of I,600 rads was delivered by moving strip technique (eight fractions in ten days) to opposing fields that included both entire lungs. Cavitation of several metastatic deposits was observed about three weeks after the completion of radiation therapy (Fig. 3B). Some evolved into thin-walled cysts (Fig. 3C). He was re-admitted several times for treatment of recurrent right-sided pneumothorax. Several cysts in the right lung reached enormous size (Fig. 3D). He died at home at six years and five months of age, 38 months after nephrectomy. Autopsy was not performed. DISCUSSION Necrosis due to inadequate blood supply -often cited as the major cause of cavitation in lung metastases2-rarely if ever accounts for cavitation in small nodules or cavities in which the wall is extremely thin ( 1-2 mm).6 Breakdown of tumor usually results in cavities with thick, irregular walls which do not enlarge rapidly nor reach great size.2 Tumor necrosis does not adequately explain the rapid formation of large thin-walled cysts that occurred in our patients. Anderson and Pierce described six papatients with carcinomas of the bronchus which had the roentgenographic appearance of thin-walled cysts. Grossly, the cyst walls were smooth, gray, and shiny. Inflammation, if present, was minimal. Microscopically, the cyst walls consisted of fibrous tissue and squamous cell carcinoma. The lining consisted of malignant cells or squamous metaplastic epithelium, with malignant tumor just beneath the surface. In some instances, parts of the cavity wall were formed of compressed lung. Occasionally there was continuity between tumor in the cavity and the nodule of growth in an adj acent bronchus. Anderson and Pierce attributed the morphology of these tumors to a ball-valve
4 VOL. 126, No. Cavitating Lung Nodules 73 mechanism :* Growth of tumor into a small bronchus caused partial obstruction and led to cystic distention of distal air sacs. Subsequent growth of tumor into the cyst formed a secondary lining layer of tumor cells. Rupture of the lining of tumor cells by increases in intnacavitary pressure accounted for the portions of the cyst that were lined by respiratory epithelium or compressed lung. The resected metastasis in our patient with Wilms tumor (Case i) was morphologically similar to these cases of bronchial carcinoma. A ball-valve mechanism, nesuiting from growth of tumor into small bronchi or bronchioles, satisfactorily explains the initial cavitation and subsequent evolution into thin-walled cysts that charactenized the metastatic deposits in both of our patients. Although both children had received radiation therapy and chemotherapy, we believe that these changes in the metastatic deposits were the result of tumor growth rather than the consequence of therapy. No single explanation satisfactorily accounts for all instances of pneumothorax that have been associated with lung metastases.4 #{176} Most are probably due to the formation of malignant bronchopleural fistulas. This mechanism was documented in one of the rare instances in which pneumothorax and cavitation were observed in the same patient. Kew7 described a teenager with a solitary subpleural metastasis of osteogenic sarcoma that underwent * Dodd and Boyle have proposed that certain properties of squamous epithelium account for the thin-walled cavitary form of bronchial carcinoma and for thin-walled cystic metastases of squamous cell carcinoma. As the growing tumor breaks into alveoli, malignant squamous epithelium is likely to come in contact with air; the process ofcornification is facilitated and respiratory motion assists in stripping the keratinized surface layers from cavity walls. Meanwhile, growth progresses peripherally, so that the size of the cavity increases while its wall maintains a relatively constant thickness. In some instances, a ball-valve mechanism-manifest on serial roentgenograms as an alternately smooth and crenated appearance of the external wall-may assist in the growth of thin-walled cystic neoplasms. Dodd and Boyle suggested that inherent properties of the normal primary tissue might account for thin-walled cystic metastases that occasionally occur with other tumors. We are not aware of any property of embryonal tissue that would explain this phenomenon in metastatic Wilms tumor. cavitation. At thoracotomy, the pleura was carefully inspected. When the anesthetic bag was pumped, gas escaped from a small hole in the pleura overlying the cavity. Both the cavity and the pleural defect were lined with tumor. Lodmell and Capps9 adapted the airblock theory of the Macklins to explain cases in which pleural invasion by tumor was not present. They suggested that peripheral tumor nodules sometimes caused partial bronchiolar obstruction. Intercommunication between alveoli of adjacent lobules usually prevented the development of excessive local pressures, but in some patients strategically-placed tumor nodules produced a ball-valve effect. Relatively small changes in intra-alveolar pressure, e.g., with coughing and sneezing, could result in dissection of air along vascular sheaths and, in some instances, lead to pneumomediastinum and pneumothonax. Lodmell and Capps cited the presence of interstitial emphysema and subpleural blebs in one of their patients as evidence in support of this concept. Regression of tumor and radiation therapv do not appear to predispose patients with lung metastases to pneumothorax.8 2 Our patient (Case II) had his first episode of pneumothorax before radiation therapy to the lung was begun. E. George Kassner, M.D. Department of Radiology State University of New York Downstate Medical Center 450 Clarkson Avenue Box 45 Brooklyn, New York REFERENCES 1. ANDERSON, H. J., and PiERCE, J. W. Carcinoma of bronchus presenting as thin-walled cysts. Thorax, 1954, 9!, CHAUDHURI, M. R. Cavitary pulmonary metastases. Thorax, 1970, 25, I. 3. COUSSEMENT, A. M., and GOODING, C. A. Cavitating pulmonary metastatic disease in children. AM. J. ROENTGENOL., RAD. IHERAPY & NUCLEAR MED., 1973, 117, D ANGlo, G. J.,and IANNACCONE, G. Spontane-
5 732 E. G. Kassnen, H. S. Goldman and A. Elguezabal APRIL, 1976 FIG. 3. Case u. (A) September 21. Metastatic deposits are present in the hilar lymph nodes and in the midzones of both lungs. A small pneumothorax is present on the right. (B) November 3. The right lung has reexpanded. Nodules in both lungs have undergone cystic change. (C) November 20. There is a large pneumothorax on the right; a portion of the right lower lobe is adherent to the parietal pleura. Numerous thinwalled cysts are present in both lungs. (D) May 17 (five weeks before death). Numerous giant thin-walled cysts have almost totally replaced the right lung and there is a marked mediastinal shift to the left. Several thin-walled cysts are visible on the left. There is a small pneumothorax on the left. Solid masses of tumor are present in the mediastinum and in both lungs. ous pneumothorax as complication of pulmonary metastases in malignant tumors. AM. J. ROENTGENOL., RAD. THERAPY & NUCLEAR MED., 1961, 86, I092-I DECK, F. W., and SHERMAN, R. S. Excavation of metastatic nodules in lung: roentgenographic considerations. Radiology, 1959, 72, DODD, G. D., and BOYLE, J. J. Excavating pulmonary metastases. AM. J. ROENTGENOL., RAD. IHERAPY & NUCLEAR MED., 1961, 85, KEw, M. C. Cavitating pulmonary metastasis associated with spontaneous pneumothorax. Lancet, 1966, 86,
6 VOL. 126, No. 4 Cavitating Lung Nodules LAuclus, J. F., BRODOVSKY, H. S., and HOWE, C. D. Spontaneous pneumothorax and pneumomediastinum as complications of sarcoma. 7. Thoracic & Cardiovasc. Surg., 1972, 6, LODMELL, E. A., and CAPPS, S. C. Spontaneous pneumothorax associated with metastatic sarcomas. Radiology, 1949,52, SHERMAN, R. S., and BRANT, E. E. X-ray study of spontaneous pneumothorax due to cancer metastases to lungs. Dis. Chest, 1953, 26, II. SPITTLE, M. F., HEAL, J., HARMER, C., and WHITE, W. F. Association of spontaneous pneumothorax with pulmonary metastases in bone tumors of children. C/in. Radiol., 1968, 19, STOLZENBERG, J. G., and CLEMENTS, J. P. Bilateral simultaneous pneumothorax during radiation therapy for metastatic disease from osteogenic sarcoma: case report and review of literature. Radiol. C/in. Biol., 970, 39,
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