Pulmonary Blas toma. A Case Report and Review of the Literature. Jimmy L. Cox, M.D., Robert L. Fuson, M.D., and John T. Daly, M.D.
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1 Pulmonary Blas toma A Case Report and Review of the Literature Jimmy L. Cox, M.D., Robert L. Fuson, M.D., and John T. Daly, M.D. P rimary pulmonary blastoma was first recognized as a distinct pathological entity in 1952 [l]. It was originally classified in the group of miscellaneous malignant tumors of pulmonary origin [6], but many authors feel it represents a distinctive group of carcinosarcomas [3, 5, 8, 11, 131. Only 18 cases of pulmonary blastoma have been recorded; thus it is appropriate to report the following unique clinical problem. A 58-year-old man was admitted to Duke University Hospital for evaluation of a right upper lobe lung mass. Two years prior to admission he had developed a mild, nonproductive cough. Two months prior to admission the cough had become more frequent and was accompanied by paroxysms of dull, aching, right anterior chest pain. Occasional night sweats occurred, but were not accompanied by chills, fever, or weight loss. Hemoptysis was noted three weeks prior to admission, and chest roentgenograms at that time demonstrated a mass in the right upper lobe (Fig. 1). Physical examination revealed slight deviation of the trachea to the left with dullness to percussion, increased fremitus, and markedly decreased breath sounds over the right upper hemithorax anteriorly and posteriorly. No lymphadenopathy or hepatomegaly was detected. The admission hemogram revealed a leukocyte count of 5,500 per cubic millimeter with a 34% eosinophilia which decreased to 9% at one point during the hospitalization only to return to 30% by the time of discharge. Skin tests for histoplasmosis, coccidioidomycosis, blastomycosis, and tuberculosis (intermediate strength P.P.D.) were negative. Sputum cells also were normal. Bone-marrow examination revealed erythroid hyperplasia with increased numbers of plasma cells, but with no tumor cells present. An anterior scalene node biopsy was unrewarding, but a needle biopsy of the lung mass revealed a malignant tumor of unknown origin. Bronchoscopy demonstrated a stenotic right upper lobe orifice. A biopsy of the bronchus in the area of stenosis showed no tumor involvement. Bronchial washings obtained at bronchoscopy revealed atypical cells that strongly suggested malignancy but were nondiagnostic. An exploratory thoracotomy was performed through a standard right lateral incision, revealing a large mass confined to the right upper lobe with no gross involvement of the hilar or mediastinal lymph nodes. Several frozen-section biopsy specimens suggested a malignant tumor or a benign teratoma. A right upper lobectomy was then performed with resection of From the Department of Surgery and the Department of Pathology, Duke University Medical Center, Durham, N.C. Accepted for publication Nov. 26, Address reprint requests to Dr. Cox, Department of Surgery, Duke University Medical Center, Durham, N.C THE ANNALS OF THORACIC SURGERY
2 CASE REPORT: Pulmonary Blastoma A B FIG. 1. Chest roentgenograms taken 3 weeks prior to admission show opacification of the entire right upper lung field. Note the atelectasis adjacent to lower border of lung mass. At operation the mass was confined to the right upper lobe. the entire lesion. The patient tolerated the operation well and had no postoperative difficulties. He is now being followed in the outpatient department, where he has received postoperative irradiation to the chest wall and mediastinum. Grossly, this discrete solid tumor measured 15 cm. x 15 cm. x 18 cm. It was an irregular, soft, red-white mass that compressed the pulmonary parenchyma. On microscopical examination most of the tumor appeared necrotic. The viable areas had a dimorphic pattern that included a loose, spindle cell stroma with scattered tubular and glandular elements. The stroma was composed of small spindle cells with scanty eosinophilic cytoplasm and oval, somewhat irregular basophilic nuclei. It demonstrated a variable cellularity, being most cellular around the tubular and glandular structures (Fig. 2). The lining of the tubules and glands varied from a single layer of nonciliated columnar cells to a pseudostratified columnar epithelium (Fig. 3). The eosinophilic cytoplasm of some of these cells contained fine vacuoles; the nuclei were basal, and some nuclear pleomorphism was present. There was mild mitotic activity present both in the stroma and in the glandular and tubular elements. The morphology of this neoplasm is distinctive and suggests a primitive, embryonal quality similar to that which has been described in pulmonary blastomas. As previously stated, however, many authors consider this a variant of the pulmonary carcinosarcoma which more characteristically possesses squamous carcinoma within a frankly sarcomatous stroma. REVIEW OF THE LITERATURE Of the 18 previously reported cases of pulnionary blastoma, 2 cases lacked adequate clinical and pathological material for comparison with the present case. Clinically, there are no features that distinguish pulmonary blastoina from other primary pulmonary neoplasms [7]. The VOL. 9, NO. 4, APRIL,
3 COX, FUSON, AND DALY FIG. 2. Scattered tubular and glandular elements in spindle cell stroma. Stromal cellularity greatest about tubular and glandular elements. (H&E; ~120.) age distribution ranges from 19 to 74 years with a mean of 48 years, which is somewhat younger than the mean age for bronchogenic carcinoma [lo]. Of 13 cases in which the preoperative clinical picture was presented, 9 patients had a chief complaint of persistent cough or hemoptysis or both. Three of the patients had yet to develop any symptoms at the time the lung mass was discovered on chest roentgenogram. One patient presented with signs of cerebral metastasis with no pulmonary symptoms. His pulmonary tumor was discovered at the time of autopsy. FIG. 3. Tubules and glands composed of nonciliated pseudostratified columnar epithelium. No vacuoles are present in cytoplasm. Stroma composed of small spindle cells with scanty cytoplasm. (HQE; ~425.) 366 THE ANNALS OF THORACIC SURGERY
4 CASE REPORT: Pulmonary Blastoma Great difficulty has been encountered in the preoperative diagnosis of pulmonary blastomas using the common procedures employed in the routine work-up of a pulmonary mass. In addition to these standard procedures (chest roentgenogram, bronchoscopy, sputum cytology, and scalene node biopsy), a needle biopsy was performed in our patient; the specimen suggested the presence of an unusual neoplasm. It is interesting to note that in 8 of 12 cases reported, the lesion seen on chest roentgenogram was located in the left lung. Bronchoscopy has been of no value in differentiating this tumor from other pulmonary neoplasms, probably because of the peripheral origin of the tumor. Cytology has been essentially negative in all cases except one in which the patient coughed up a cast of malignant cells prior to operation. Only 4 patients have undergone scalene node biopsy prior to operation, and findings in all have been negative. The table summarizes the various operative procedures that have been employed as well as the pathological findings and the postoperative course. The size of the lesion at the time of operation has varied from 2.5 X 2.5 cm. to 20 X 26 cm. and appears to bear no definite relationship to survival time, although too few cases exist at present to offer a firm conclusion on this matter. At the time of operation, involvement of regional lymph nodes was noted in 5 patients, all of whom died within 12 months postoperatively as a direct result of the tumor or of operation. The long-term survival of 4 patients (for 24, 15, and two for 11 years) and the survival of 3 patients for more than 2 years indicates that in some instances the prognosis in cases of pulmonary blastoma may be somewhat better than in cases of other primary pulmonary malignancies. One patient (No. 9) was particularly interesting in that at the time of operation a secondary subpleural nodule was noted in the lingula. A left pneumonectomy was performed; two years later several nodules appeared in the right lung, but these cleared with irradiation. Eight years later, however, the patient developed a pulmonary blastoma in the right lower lobe which eventually caused her death 11 years after the original operation. Patient No. 12 had a strikingly similar course. It should be noted that of the 5 women in this series, 3 had survival rates of 15 years or 11 years and another patient was alive and well 2 years postoperatively. The fifth patient s tumor was unresectable at the time of diagnosis. The significance of eosinophilia in the present case is not known, but it was suspected that an unknown type of allergy coexisting with the patient s other problems was the cause. This suspicion was reinforced by the presence of numerous eosinophils in a swab taken from the patient s nostrils.
5 Patient No. & 1 [21 SUMMARY OF THERAPY AND RESULTS IN 17 REPORTED CASES. Reference Pathology Operation Follow-up._ 2 r ~ 12 x 7 x 7-an. gray circumscribed mass in RUL; Right pneumonectomy Well 15 yr. postop. bronchial cast with malignant cells coughed up prior to operation 8-an. solid mass in LUL within a pulmonary cavity or capsule; regional lymph nodes involved 4 x 3.5-cm. solid mass in superior segment of LLL; invasion of LUL bronchus and regional lymph nodes Smooth, gray-white %an. mass surrounded by compressed tissue in LLL 5 x &an. mass in RUL with metastasis in left cerebral hemisphere; regional nodes not involved 5 x 6-an. hard, rubbery mass in LUL 10 x 7 x 7-an. mass in LUL; regional lymph nodes not involved 5-an. cavitating, subpleural tumor in anterior segment of LUL; metastatic to regional nodes 5 x 4 x 4-cm. extrabronchial tumor at junction of upper and lower lobe bronchi; subpleural nodule in lingula Left upper lobectomy Segmental resection None Wedge resection and rib resection Died 4 mo. postop. of bleeding due denal ulcer; autopsy showed widespread metastases Died 5 mo. postop. of bronchial stump rupture and empyema; no recurrence found at autopsy Well 2 yr. postop. Died 5 days after admission; autopsy showed RUL tumor with cerebral metastasis Died 3 mo. postop. with severe cachexia Well 2 yr. postop. Died 7 mo. postop. of metastases Several nodules in right lung 2 yr. postop., cleared with radiation therapy; development second pulmonary blastoma in RLL 10 yr. postop.; died 11 yr. after original operation of widespread metastases
6 10 [ x 2.5-cm. subpleural, unencapsulated, nod- Left lower lobectomy Well 3 yr. postop. ular, white circumscribed mass in LLL 11 r31 Multiple well-demarcated, soft, friable nodules Right lower lobectomy Doing well postop.; RLL masses in RLL first seen on roentgenogram 24 yr x 5 x 3-cm. lesion in LUL and lingula 13 [ x 4 x 4-cm. lesion with central cavity in LUL 20 X 26-cm. (roentgenogram) lesion in right lung Bronchial biopsy, cobalt 60 and nitrogen mus- tases tard Right middle and partial lower lobectomy prior to thoracotomy were found to be pulmonary blastomas at that time Radiation therapy 1949 and 1959; died 11 yr. postop. of metastasis to RLL Died 6 mo. postop. of clinical metastasis to hilar nodes Died 7 mo. postop. of clinical metas- 15 [I31 5 x 4 x 4-an. lesion in RML with metastasis to Alive 1 yr. postop. right retroperitoneal space c Tumor mass completely filling right chest with Right pneumonectomy Development of metastatic nodule 0 P apparent metastasis to hilar nodes near thoracotomy scar 8 mo. postop.; responded to cp radiation z therapy; died 1 yr. postop. of car-? cinomatosis + 17 [present 15 x 18-an. red-white, shaggy, necrotic-appearing Right upper lobectomy Well 2 mo. postop. k report] mass in RUL 'Two additional cases were inadequately reported and are not included. RUL = right upper lobe; LUL = left upper lobe; LLL = left lower lobe; RLL = right lower lobe; RML = right middle lobe.
7 COX, FUSON, AND DALY COMMENT Several theories concerning the origin of this neoplasm exist, each theory being based on a different concept of lung embryogenesis. The classic view of the embryogenic development of the lung proposes that the entire pulmonary parenchyma, including the alveoli, originates from a progressive branching of the laryngotracheal bud. A more recent theory proposed by Waddell [14] holds that the distal lung parenchyma may develop from a common mesenchymal blastema growing in apposition to the terminations of the laryngotracheal bud and that through a process of canalization within aggregations of mesenchymal cells, the distal air passages are formed and later fuse with the more proximal bronchiolar terminations. Since the pulmonary blastema is bipotential, tumors arising from it may undergo differentiation into both the epithelial (glandular) and mesenchymal (stromal) elements seen in the pulmonary blastoma (Fig. 2). This proposed mode of histogenesis might well explain the absence of any epidermoid elements [ill, the consistent peripheral location of the tumor [7], and its strong resemblance both in appearance and in behavior to the nephroblastoma that develops from a renal blastema [lll. The proper treatment of this neoplasm is not known with certainty. The most important step would seem to be the surgical removal of the mass along with any involved lymph nodes in the area. Whether this entails removal of a segment, a lobe, or an entire lung is obviously dictated by the size and degree of extension of the tumor. The effect of radiation therapy is also unknown, although the disappearance of the nodules in the right lung following radiation (Patient No. 9) is a favorable sign if these nodules did in fact represent recurrent tumor. SUMMARY A report of the nineteenth case of pulmonary blastoma is accompanied by a review of the literature. Although pulmonary blastoma is. now a well-recognized clinical and pathological entity, the diagnosis has been made only at operation or autopsy. The neoplasm has an apparent predilection for adult males and for the left lung and may carry a better prognosis than other primary pulmonary malignancies. One theory of the histogenesis of the tumor is discussed as it relates to the embryological development of the lung. It is possible that the tumor develops from a primitive pulmonary blastema, much as a nephroblastoma develops from a renal blastema. Until more information can be assimilated, and in view of the known instances of regional spread, it would seem most feasible at the present time to perform at least a lobectomy when this neoplasm is 370 THE ANNALS OF THORACIC SURGERY
8 CASE REPORT: Pulmonary Blastoma diagnosed at operation and to follow this with postoperative irradiation; however, too few cases have been reported thus far to establish this as the definitive treatment for a pulmonary blastoma. REFERENCES 1. Barnard, W. G. Embryoma of lung. Thorax 7:299, Barrett, N. R., and Barnard, W. G. Some unusual thoracic tumours. Brit. J. Surg. 32:447, Bauermeister, D. E., Jennings, E. R., Beland, A. H., and Judson, H. A. Pulmonary blastoma, a form of carcinosarcoma. Amer. J. Clin. Path. 46:322, Campesi, G., and Sommariva, V. Rarissima neoformazione polmonare di tip0 adeno-sarcomatoso. Arch. De Vecchi Anat. Pat. 36: 109, Chitambar, 1. A., Gujral, J. S., and Aikat, B. K. Embryonal sarcoma of the lung. J. Thorac. Cardiovasc. Surg. 57:657, Galofre, M., Payne, W. S., Woolner, L. B., Clagett, 0. T., and Gage, R. P. Pathological classification and surgical treatment of bronchogenic carcinoma. Surg. Gynec. Obstet. 119:51, Minken, S. L., Craver, W. L., and Adams, J. T. Pulmonary blastoma. Arch. Path. (Chicago) 86:442, Parker, J. C., Jr., Payne, W. S., and Woolner, L. B. Pulmonary blastoma (embryoma). J. Thorac. Cardiovasc. Surg. 51 :694, Peabody, C. N. Carcinosarcoma of lung of peripheral origin. J. Thorac. Cardiovasc. Surg. 37:766, Rubin, P. Bronchogenic Carcinoma. Current Concepts in Cancer. New York: American Cancer Society, Souza, R. C., Peasley, E. D., and Takaro, T. Pulmonary blastomas: A distinctive group of carcinosarcomas of the lung. Ann. Thorac. Surg. 1:259, Spencer, H. Pulmonary blastomas. J. Path. Bact. 82:161, Stackhouse, E. M., Harrison, E. G., Jr., and Ellis, H. F., Jr. Primary mixed malignancies of lung: Carcinosarcoma and blastoma. J. Thorac. Cardiovasc. Surg. 57:385, Waddell, W. R. Organoid differentiation of the fetal lung: A histologic study of the differentiation of mammalian fetal lung in utero and in transplants. Arch. Path. 47:227, 1949.
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