OCCULT BRONCHOGENIC CARCINOMA Endosco;J,ic Localixntzon and Trliwzsion 1)ocitrnPntnfion

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1 OCCULT BRONCHOGENIC CARCINOMA Endosco;J,ic Localixntzon and Trliwzsion 1)ocitrnPntnfion BERNARD R. MARSH, MD, JOHN I<. FROST, MD,~ YENER S. EROZAN, MD,* AND DAKKW. CAIITEK, MD~ Early bronchogenic carcinoma detected by sputum cytology frequently cannot be localized by conventional bronchoscopic techniques. Six occult tumors were localized in this study with new techniques in differential cytology and flexible fiberoptic equipment. A three-phase study is carried out including: 1. Cytologic localization, 2. Fiberoptic survey, and 3. Histologic mapping of bronchial margins. Findings are recorded by means of a color television documentation system. A review of the surgical pathology in our four cases has revealed a relatively large area of in-situ carcinoma in the region of very small invasive tumors. D, EFINITIVE TREATMENT or? EARLY I~KONCHO- genic carcinoma has seldom been achieved in spite of early detection by sputum cytology. Conventional Iironchoscopes do not allow detailed exploration of the bronchial segments where tumors originate, and tlilferential cytologic techniques have been imprecise and unreliable. Thus, early therapy hiis awaited more effective methods for itlentifying the specific bronchus involved when radiologic studies fail to demonstrate the lesion. N~ATEKIAI.S AND METHODS Six consecutive, x-ray negative, sptuni positive patients with broncliogenic carcinoma were referred for localization to the Rroyles Bronclioscopic Clinic of The Johns Hopkins Hospital between December I969 :und December The management of this group forms the basis for our report on newer endoscopic tecliniques and equipment being developed to localize the occult tiimor. One of our cases (no. 3) was an asymptomatic screenee lrom local industry, while two at1tlition;il cases (nos. I, 4) had no symptoms of chest disease at the time a cytologic tliagno-.;is of cancer was made (Table 1). Since cells shed from the upper aerotligestive system are mixed in the sputum with tliose from the lung, a careful examination of these areas must be inclutled in the preoperative work-up for bronchoscopy. In one sputum positive screenee referred following his routine executive physical examination, an asymptomatic carcinoma of the nasopliarynx wiis tliscoveietl while the bronchoscopic study revealed no eviclence of malignancy. A three-phase endoscopic study is carried out to provide not only tumor localization but also color television documentation and marginal biopsies. General anesthesia is used in order to provide more precise cough control antl patient comfort during a study which may require more than 2 hours. PHASE I From the Division of Laryngology and Otolog) ant1 Department of Pathology, The,Johns Hopkins ttniver?.ity School of Mctlicinc, Baltimore, Mtl. Supportcd, in part, by National Cancer Institute Contract NIH * Avsistarit Professor of 1-aryngology antl Otology. t?lssociate Professor of Pathology. % Assistant Professor of Pathology. B Assistant Professor of Pathology. ** Commercial Electronics, Inc., Mountain Vicw, Calif. Atltlrcss for reorints: B. R. Marsh. MD. [J.S. Public Hcalth Service Hospital, 5100 Wyman Park Drite. Baltimore, Md Recei\,etl for publication August 3, IW This procedure is performed in order to obtain cytologic specimens of sufficient accuracy to localize the tumor to one lung should the following fiberoptic phase fail to demonstrate the lesion. In this case, a secondary procedure woiiltl be required for precise localization. Bronclii;il brushing tecliniques, while valuable ;is a detection method, are of poor localizing value for the x-ray negative lesion. Therefore, new equipment has heen developed to provide more reliable differential cytology.

No. 5 OCCULT BRONCHOCENIC CARCINOMA * Marsh et al. 1349 TABLE 1. Clinical History Summary Case Age Smoking Hx. Patient condition when sputum cytology was obtained 1 54 1 ppd.

Hospitalized with gout, weight loss 5 66 1 PPd. Questionable history of hernoptysis 6 57 1 rmd. Chronic cough; recurrent carcinoma of cervix.

2 No. 5 OCCULT BRONCHOCENIC CARCINOMA * Marsh et al TABLE 1. Clinical History Summary Case Age Smoking Hx. Patient condition when sputum cytology was obtained ppd. Patient hospitalized with acute pancreatitis SPd. Previous pneumonia which cleared completely ssd. Asymptomatic screenee (from local industry) fppd. Hospitalized with gout, weight loss PPd. Questionable history of hernoptysis rmd. Chronic cough; recurrent carcinoma of cervix. A Holinger ventilating bronchoscope has been modified with a distal, inflatable cuff. This instrument* is passed into one main bronchus and the cuff inflated to exclude secretions from the opposite lung. As a telescopic examination of the major bronchi is carried out, the patient awakens sufficiently to regain his cough reflex. At this time, four separate cytologic specimens are obtained using a newly developed lavage aspirator? (Fig. 1). This instrument provides improved control over lavaging fluids and eliminates loss of specimen. Each specimen is labeled chronologically in order to establish whether contamination of the bronchoscope has occurred in its passage through the upper airway. If such is the case, the contamination can be expected to come out in the first or second lavage specimen while later specimens more nearly reflect the true character of the bronchial cytology within the lung under study. The patient is then reparalyzed, the bronchoscope flushed with Hanks (a balanced salt solution), the cuff deflated, and the instrument positioned in the opposite main bronchus where the procedure is repeated with clean lavage equipment. allowing simultaneous general anesthesia and flexible fiberoptic bronchoscopy (Fig. 2). The color television system is then attached for recording not only the video image of the entire study, but also a running narrative by the surgeon. This provides magnificent permanent records as well as an extremely valuable communications medium and teaching facility. A detailed serial study is then begun through all bronchi of both lungs to the fifth generation (sub-subsegmental level). Following the survey, specimens are obtained from all suspicious areas with brush, curette, and biopsy instruments as required. The relative safety of microbiopsy techniques provides for a comprehensive survey with multiple specimens whenever indicated. The fiberscope and endotracheal tube are then removed. PHASE I1 The patient is then intubated with a standard endotracheal tube fitted with a T-adapterr * Becton Dickinson Research Laboratory (BD-RL), Raleigh, N.C. t BD-RL. t RD-RL. FIG. 1. Lavage aspirator. FIG. 2. T-adapter.

3 1350 CANCER November 1972 VOl. 90 PHASE 111 The rigid ventilating bronchoscope is then reintroduced in any case where an apparent lesion has been found. Observations have demonstrated widespread in-situ disease surrounding even small invasive tumors. It is, thereiore, imperative to obtain preoperative marginal biopsies with standard bronchoscopic forceps. Currently available microforceps are not entirely satisfactory for the biopsy of lobar spurs or the carina. Improved equipment now under development will ultimately solve this problem and allow these biopsies to be obtained with flexible equipment. The instrument is removed and the patient transferred to the Recovery Room. RESULTS Each of our six x-ray negative cases was successfully localized. In cases 3 through 6, the Phase I differential cytology procedures were proven to be reliable in demonstrating the involved lung. (In case 1, we had not yet developed the technique, and, in case 2, a previous neck injury prevented use of the rigid bronchoscope.) In all six cases, the lesion was discovered by fiberoptic bronchoscopy. Findings varied from subtle mucosal pallor to roughened mucosa and thickened segmental spurs (Table 2). A review of the surgical pathology on the four cases operated on demonstrates the relatively extensive spread of in-situ carcinoma with foci of infiltrating cancer. In cases 1-4, the lesions were resected. In case 5, the patient has refused further studies and therapy, and in case 6, the lesion was documented by biopsies, but, because of recurring cervical carcinoma, therapy for the pulmonary lesion has been deferred. CASE REPORTS Case 1. Sputum cytology revealed well-differentiated squamous cell carcinoma. Bronchoscopy demonstrated roughened, friable mucosa of the right upper lobe bronchus at the segmental level. Pneumonectomy was performed, and infiltrating squamous carcinoma was present within the upper lobe while insitu carcinoma extended down the bronchus intermedius and proximally to the tracheal resection margin. It was this observation which led to our use of marginal biopsies on all subsequent cases. Case 2. Well-diff erentiated squamous cell carcinoma was found in cytologic examination TABLE 2. Bronchoscopic and Pathologic Findings Case Findings Cytologic diagnosis Tissue diagnosis Treatment Roughened, friable mucosa, rt. tipper lobe bronchus Roughened, thickened rt. upper lobe apical, posterior segments Sqiianious carcinoma In-sit11 and infiltrating squamous carcinoma In-situ squamous carcinoma right upper lobe bronchus with 1.2 crn Pneumonectomy Lobectomy iiivasive carcinoma surrounding apical segment Pale, mucosa, posterior basilar segment area, rt. lower lobe Roughening of rt. lower lobe bronchus with thickened mucosa of anterior basilar segmental spur Irregular, rigid posterior segment, left upper lobe, bleeding Thickening of apical posterior segment It. tipper lobe Squanioiis carcinoma (right lung) (right lung) (left lung) (left lung) Extensive in-situ Lobectomy squamous carcinoma with microinvasive squamous carcinoma posterior basilar segment Extensive squamous car- Lobectomy cinoma in-situ with 7-mm area of invasion Refused Biopsies: In-situ Radiotherapy for resquamous carcinoma in current cervical car- It. upper lobe and It. cinoma only lower. lobe bronchi, invasive squamous carcinoma in apical posterior segment

Bronchial washings, curette, and brush material from the right upper lobe showed squamous cell carcinoma.

4 No. 5 OCCULT BRONCHOGENIC CARCINOMA - Mawh et al. of the sputum. Bronchoscopy revealed roughening and thickening of the right upper lobe bronchus mucosa at the level of the apical and posterior segments. Bronchial washings, curette, and brush material from the right upper lobe showed squamous cell carcinoma. Biopsies from the right upper lobe bronchus revealed in-situ carcinoma, and a right upper lobectomy was performed, Pathologic examination revealed in-situ squamous cell carcinoma of the right upper lobe bronchus extending into the apical segment over a distance of 3 cm and into the posterior segment in the proximal 3 mm. There was also a tubular-shaped invasive squamous cell carcinoma surrounding the apical segment bronchus for a distance of 1.2 cm and extending a maximum of 10 mm from the bronchial lumen Case 3. Squamous cell carcinoma was discovered in sputum examination of this asymptomatic patient. Bronchoscopy revealed slight pallor of the right posterior and lateral basilar segmental regions. Differential bronchial washings revealed squamous cell carcinoma in the right lung (Fig. 3). Biopsy from the posterior basilar segmental bronchus showed squamous cell carcinoma in-situ (Fig. 4). A right lower lobectomy was performed. Extensive in-situ carcinoma was present in the lateral and posterior basilar segments with an area of invasive carcinoma in the posterior basilar segment bronchus approximately 1.5 cm from its origin (Fig. 5). The tumor was microinvasive and extended approximately 2 FIG. 3. cell from bronchial washing (~1000). mm from the bronchial lumen, A 3-mm focus of in-situ carcinoma was also found in the superior segmental bronchus. FIG. 4. In-situ squa, mous carcinoma (XIOO).

5 1352 CANCER Nouem ber 1972 Vol. 30 FIL. 5. Invasive squamous carcinoma (~35). Case 4. Sputuni cytology was diagnostic of squamous cell carcinoma. Bronchoscopy showed roughening and thickening of the right lower lobe bronchus with edema of the anterior basilar segmental spur. Bronchial washings and material obtained by brush and curette from the right lower lobe revealed squamous cell carcinoma. Material from the left lung was negative. Biopsy from the right lower lobe bronchus revealed in-situ squamous cell carcinoma, and right lower lobectomy was performed. In pathologic examina- tion, there was an in-situ squamous cell carcinoma extending from the right lower lobe bronchus distally 9 mm in the medial basilar segment bronchus, 6 mm in the posterior basilar segment bronchus, and 3 mm in a subsegmental bronchus. An area of invasive carcinoma 7 mm in maximum diameter was found extending from the trifurcation of the right lower lobe bronchus into the area around the anterior, lateral, and posterior segmental bronchi.

squamous-cell carcinoma1

Thorax (1975), 30, 152. Local ablative procedures designed to destroy squamous-cell carcinoma1 J. M. LEE, FREDERICK P. STITIK, DARRYL CARTER, and R. ROBINSON BAKER Departments of Surgery, Pathology, and