Percutaneous Needle Biopsy of the Lung for Diffuse Parenchymal Disease

Percutaneous Needle Biopsy of the Lung for Diffuse Parenchymal Disease

105 Percutaneous Needle Biopsy of the Lung for Diffuse Parenchymal Disease * C. Roger Youmans, [r., M.D.,.· John .\1. stiddlcton, M.D., F.C.C.P.,§ Jo...

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Percutaneous Needle Biopsy of the Lung for Diffuse Parenchymal Disease * C. Roger Youmans, [r., M.D.,.· John .\1. stiddlcton, M.D., F.C.C.P.,§ John R. Derrick, M.D., F.C.C.P.,.· Luis B..\Iorettin, ~I.D.t and Dieter Assor, M.D.t

Percutaneous needle lung biopsies were perfonned on 61 patients with dIffuse parenchymal disease. A specimen was obtained in 90 per cent of all cases. Diagnosis was established in 8S per cent of all cases. A chest tube was left indwelling in aU patients foUowing lung biopsy. CompUcations were few. On the basis of this experience and a brief review of the literature, the foUowing conclusions are made: 1) lung biopsy is valuable as an early dIag. nostic procedure; 2) percutaneous needle biopsy of the lung in dilfuse parenchymal disease is a safe procedure with a high diagnostic yield; 3) when physically possible, the insertion of a chest tube in all cases is thought to be an added safety factor; 4) a culture from the specimen is a useful adjunct and should be done in all cases; S) needle lung biopsy should be considered prior to all cases of open biopsy for diffuse disease except when thoracotomy is otherwise indicated; 6) except when contraindicated, needle biopsy of the lung is indicated in any diffuse pulmonary disease for which the etiology is not apparent on rontine chest medical work.up.

Ixrnonucrrox Diagnosis of diffuse pulmonary parenchymal disease is frequently dependent upon the microscopic examination of lung tissue. The advantage of early lung biopsy in these cases has been clearlv established." Considerable controversv still exist~ however, concerning the relative m~rits of ~e~: cutaneous needle biopsy and open lung biopsy, For example. advocates of needle biopsy point out that this method affords a ready diagnosis, avoids thoracotomy and general anesthesia. and shortens the expense of hospitalization.'·2.M.12 Proponents of open lung biopsy have countered that needle biopsy tissue is rarely obtained from the span,,'), air-containing lung. that a study of structural relations is not possible, that the specimen of any "blind" needle biopsv may not be representative of the disease as a whole. and that complications such as pneumothorax. air embolus, empyema. hemorrhage. and sudden death have been reported. 2.'-'''·111 Ovcrholt-" has recent lv referred to the biopsy needle where applied to the diagnosis of "From the University of Texas ~Iedical Branch. Galveston, Texas. oODivision of Thoracic and Cardiovascular Surgery. ~Dt'partn)('nt of Internal ~Icdi<:irl('. I Department of Hadiology. t Department of Pathology,

DIS. CHEST, VOL. 54, NO.2. AUGUST 1968

lung pathology as a "hollow divining rod." Even advocates of the needle biopsy technique have included diffuse parenchymal disease as a contraindication of this procedure, A review of existing reports on needle lung biopsy for diffuse disease points out the two complications of this procedure: 1) difficul~' in obtaining tissue, and 2) air leak into the pleural space.I.M.1l Bl'ginning with the assumption that a properly placed chest tube left overnight in the pleural spaee carries little more risk than a routine thoracentesis. it was elected to re-evaluate the question of needle biopsy for diffuse parenchymal disease with a postbiopsy chest tube left in all cases. This added safetv factor theoretically would afford tbe physician ~ore aggressiveness 'in obtaining tissue and prevent the serious possibility of a tension pneumothorax occurring after the physician has left the bedside. This report considers the questions that any biopsy procedure must answer: 1) is it productive, 2) when productive, is it diagnostic. and 3) in all cases. is it safe? TEOI:-;IQUE

Pl/tient Orientation: 111e patient is familiarized

with the procedure. He is instructed to breathe normally. informed that a chest tube will be left

25

106 for a short period after the procedure, and warned that hemoptysis may occur. Performed at patient's bedside: All needle biopsies in this report were performed at the patient's bed, which emphasizes the minor nature of this procedure. Routinc preoperatice medications: Preprocedure administration of analgesics, sedatives, and parasympatholytic drugs are necessary for the suppression of apprehension and vagovagal reflex. Local anesthesia: Following routine preparation and draping of chest wall, local anesthesia is employed along the track of the biopsy needle from the skin across the superior border of an adjacent rib to the pleura. Needle biopsy: An area of maximum involvement is selected from the chest x-ray. With the patient in a horizontal position and breathing normally, to lessen the possibility of air embolization, a small incision is made through the skin. A FranklinSilverman biopsy needle with inner stylet is then introduced at an angle away from the hilum and mediastinum. The needle is passed well beyond the visceral pleura into lung parenchyma. Failure to do this may result in pneumothorax and retraction of lung tissue beyond the reach of the biopsy needle. The stylet is then removed and the cutting blades inserted. Following the advancement of the outer sheath, the entire needle is rotated and removed. If no tissue is recovered, the biopsy may be repeated. If four or five needle biopsy attempts are unsuccessful, the procedure should be cancelled and reconsidered for a future date. If failure is due to the presence of pneumothorax. the biopsy may be repeated following chest tube insertion and lung expansion. If the specimen obtained is not considered diagnostic, the procedure is repeated prior to removal of the safety factor of the chest tube. Division of 'fllecimen: The specimen is removed from the biopsy needle and placed in a solution of sterile saline. Larger fragments of tissue are removed from the sterile solution and placed in formalin for permanent sections. The remaining tissue and saline are then utilized for routine fungus and mycobacterial cultures. I/lSerlion of chest tube: A small chest tube is inserted through the biopsy site in all patients. A No. 14 or No. 16 catheter is passed through a chest trocar for approximately three inches beyond the level of the parietal pleura. The chest tube is then connected to suction adapted water sealed drainage. A No. 14 plastic angiocath was used initially, but was found to be unreliable. Chest x-ray: A chest x-ray examination on the

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YOUMANS ET AL

evening of the biopsy confirms the elimination of any pre-existing pneumothorax. The chest tube is left in place until 24 hours after alI evidence of air leak has stopped. Antibiotics: Antibiotics have not been found necessary for this procedure. Alternative technique: An alternative approach has been used for patients with inflammatory disease processes adjacent to the pleural space. In these patients the pleural space is usuaIly obliterated. Visualization by image intensifier of the needle penetrating the chest wall is helpful not only in positioning the needle in an area of maximum involvement, but in immediately inspecting the patient for evidence of pneumothorax. If pleural air of any degree is encountered, a chest tube is inserted. If no pneumothorax is seen, the patient is followed hy a repeat chest x-ray examination in four hours. CLINICAL ~fATEIIIAL

Over a 36-month period, percutaneous needle biopsy of the lung was performed on 85 patients. Sixty-one cases were examined for the purpose of diagnosing diffuse lung disease. The results of these biopsies are listed in Table I. A biopsy specimen was obtained from 55 patients

Table I.-Re...", 01 Perc,,'aneo... Needle Biop.,. 01 Ihe L .. n/f ••• Tolal

Number of Cases Specimen Obtained o/,;-all cases Confirmed Diagnosis


Specific Diagnosis (;;;-al1 diagnoses

85 Cue.

Diff IISC Disease 60 55 90

Local Disease 23 23

51

20 87 20 100

8-l

17

33

100

(90 per cent of all cases). Four of these diagnoses were proved incorrect, two by repeat needle biopsy. and two at autopsy. In the remaining SI cases (8S per cent of all patients), the tissue diagnosis has been confirmed by surgery, autopsy, or clinical follow-up. By comparison, a diagnosttc accuracy of 87 per cent was established in patients with localized lung lesions. During the same period of time. open lung hiopsy for diffuse parenchymal disease was carried out in IS cases. Thirteen of these biopsies were dlaznostic. This incidence of 83 per cent is comparable to that reported in the literature.s There was one death in this latter group of patients. Diagnoses of Diffuse Lung Disease: The accumulated diagnoses obtained by percutaneous needle biopsy are listed in Table 2. Microscopically, these cases fan under three categories: 18 cases of pulmonary fibrosis, 17 cases of granulomatous in8ammation. and a miscellaneous group consisting of 20 cases. Of the tissue diagnoses established for difTuse lung disease. one-third were speci6e, sucb as alveolar carcinoma, tuberculosis, etc, The remaining diagnoses were non-specific. including such entities as diffuse interstitial fibrosis, granulomatous in8ammation, organizing pneumonia, etc. It will be noted that Boeck's sarcoid.

DIS. CHEST, VOL. 54, NO.2, AUGUST 1968

107

PERCUTANEOUS NEEDLE BIOPSY OF LUNG Tabl" 2.-Ti...... Diapooe. from lI/udk Biopsy O/'M L"n. /0' DiU".e Parenchymal Disea.e Diffuse Interstitial FibrosisGranulomatous InflammationTuberculosis Coccidioidomycosis Histoplasmosis Sarcoidosis Miscellaneous-cOrganizing pneumonia Xorrnal 11In~

Chronic inflammation and fibrosis )I(>ta....,tatic adenocarcinoma"

Desquumntivo interstitinl pneumonitis" Alveolar proteinosis"

7

18 17

1 1

8

4 4

20

3

2 2

Pseudolymphorna" Alveolar carcinoma"

Hemosiderosis .. Lipoid pnournoniu" TOT,\L

;,5

"Specific Diagnosis.

a diagnosis of exclusion and follow-up, is listed in the nonspecific group. Confirmation of Diagnosis: A disadvantage of any needle hiopsy is the possihility of obtaining tissue not representative of the primary disease process. This point is well exemplified by two lung biopsies for diffuse parenchymal disease noted on roentgenogram that were reported as normal I11n~. Repeat biopsies revealed granulomatous in8ammation in each case. As noted in Table 3, two additional misdiagnoses were established at autopsy. One case, diagnosed as diffuse interstitial fibrosis. was found to have a specific type of pulmonary fibrosis-Hamman-Rich syndrome. Another patient who was found to have diffuse interstitial fibrosis with needle biopsy was placed on steroids with initial improvement in symptomatology, Three months later the patient died suddenly and at autopsy was found to have disseminated histoplasmosis in addition to pulmonary fibrosis. It is conceivable that this disease process was contracted after the biopsy or that steriod therapy produced a flare-up in a previously dormant focus. 'Nonetheless, this case must be listed as a misdiagnosis. Of the

Frcuae 2. Nore appearance of rtght upper lobe infiltrate.

remaining cases, diagnosis was confirmed at autopsy in nine cases, thoracotomy in sewn cases, and by clinical follow-up of from two to 36 months in the remaining 35 cases. From another point of view, of the 18 cases re-evaluated by autopsy and open biopsy, 16 diagnoses (89 per cent] were found to be correct. Open lung biopsy following seven cases of needle biopsy afforded us the opportunity of examining the punctured lung for evidence of damage. In no case was the specimen obtaincd at surgery found to be of more diagnostic assisranee than the specimen obtained with the needle. In all seven cases, the area of needle hmR' puncture was found with difficulty and air leak and bleeding were minimal

or nonexistent. Results of Cnltnre of the Biopsy Specimen: The usefulness of the cultures that were done at the time of needle biopsy can best be seen in evaluating the etiology of the 17 cases that were reported as granulomatous inflammation. As demonstrated in Tabl(' 4, all of these patients had

negative acid-fast sputum smears. Six patients produced cultures positive for tuberculosis. one for bistoplasmosis, and one for coccidioidomycosis. Three of the six patients with positive mycobacterial tissue cultures had negative 01' I: 100 skin tests. The patient with Coccidioides immitis had a negative skin test. sputum studies. and complement fixation studies for this organism. Complieation." Safety is a necessary prerequisite for any diagnostic procedure. Open hllll( biopsy is quite safe with an operative mortality of less than 3 per cent.v....l't. 7 .21 Percutaneous needle lung biopsy may be performed with

Table 3.-Pe,e"'aneo,,. lI/ertlle Biop.y 0/ 'he £Un. lor DiUuse Parenchymal Diseaoe Confirmation of Diugnosis-sAutopsy Surgery

Repeat hiopsy

FIGURE

1. Admission chest x-ray film.

DIS. CHEST. VOL. 54, NO.2, AUGUST 1968

Clinical follow-up (2 to 3u months) Total.

Confirmed Disproved ~ 2 7 o 2 2 () 3.1

51

'4

27

108

Sputum Smear

No Sputum

YOUMANS ET AL

Sputum Culture +TB -eHistop1asmosis +TB ~o Sputum

CompliPositive ment Cultureof SkinTest Fixation Biopsy

-s-Histoplasmosis +TB +TB +Histoplaamosis

+ Histop1asmosis +TB +/lisloplasmosis

Special Stains

+TB +/listo-

plasmosis

+TB +TIl +TB

-:-'[1-\-

+TBC -,-Tile

+COCC1U+Coccidioidomycosis ioidomycosis +TIl

+TB

even greater safety as exemplified by review of literahlfe l,l".l1 and the experience of the present study. Biopsies for diffuse disease in the present series have been performed with few complications and no death. These complication, are illustrated in Table 5. Persistent air leak occurred in 19 cases (33 per cent of all patients). Because of the chest tube placed in each case, air leak was never a serious problem. The chest tube was removed from eight of these cases within 24 hours. Eleven patients cantinued to produce bubhles for more than 24 hours. two for as long as five davs. It is felt that these cases would certainly have pres~nted serious problems without the presence of the indwelling chest tube. Hemoptysis occurred in 23 per cent of the patients, usually of mild degree. Three cases produced 50 to 2.50 ml of bloody sputum. In each case. however, bleeding was self-limited and stopped within several minutes. Intraparenchymal hemorrhage was noted tu a small degree in three cases. Follow-up demonstrated

FICL'RE

4. Chest x-ray film shortly before death.

rapid resolution without difficulty. One vagovagal reflex occurred prior to the use of preoperative medications. Other complications such as hemothorax, empyema, air emboli, etc., were not encountered. Case Report: A 20-year-old woman from Corpus Christi. Texas was admitted with a one-year history of diffuse joint pain, recurrent fever of undetermined origin, and progressive weakness. She was found to have hepatosplenomezaly and anemia. Laboratory studies revealed moderately abnormal liver function studies, a reversed A/G ratio, thrombocytopenia, and anemia. Lumbar puncture, LE preparations, Bence-jones protein, muscle biopsy, lymph node biopsy, bone marrow aspiration. liver biopsy, intravenous pyelogram, upper GI x-ray series. ECG. blood cultures, and hone survey were unremarkable. A renal biopsy was comparable with collagen disease. Chest x-ray examination on admission was normal.

Table S.--Complicaliono 0/ Needle Biopoy 0/ d,,, LunlI lor Di8uae Parenchymal Diopaop Total 61 Cases Deaths

28

("; uf .\11 ('a",',

0

0

Air Leak Less than 24 hours 24 to 48 hours Greater than 48 hours

l!l

:13 14 12 7

Hemoptysis :-linimal :-Ioderate (25 to 150 mil

13 10 3

23

0

0

Intrapulmonary Hematoma :-Iinor Major

3 3 0

.'\ .'\ 0

Vago Vagal Reflex

I

2

0

0

Severe

FICURE 3. Appearance on day of needle biopsy. Note diffuse parenchymal involvement. Patient in oxygen tent.

Xo. Ca:oot·s

Other ComplkationsHemot horux Empyema Air Emboli Etc.

8 7 4

III

.'\

DIS. CHEST, VOL. 54, NO.2, AUGUST 1968

PERCUTANEOUS NEEDLE BIOPSY OF LUNG Table 6.--Comparalire EJCperienu -

Author Dahl!:ren" (l!166)

~lanfredi8

(1963)

~mithl

(1964)

)Ofannl ' (1966)

Krumholz ll (1966) Youmans (Present report)

xe.

109

A,piration Needle lor

~al

Di..,a.., and Cattin« Needle lor DiDa.e Di..,,.Ie

Needle

:,\ppcim«"11 c/c

Local

Aspiration

74.2

86.6

20

16

Diffuse

F-S"

73

56

13

61

Combined

V_So

79

64

41

50

Pneumoconiosis

Jack

50

24

Combined

F-S"

80

66

16

Diffuse

F-S"

90

84

33

365

112 61

Lesion

Diagnosis cit-

Pneumothorax

·Franklin-Sih·erman. ··Vim-~il\'('rman.

Initial therapy consisted of administration of steroids and antibiotics. Chest x-ray examination one month followinK admission revealed a suspicious infiltrate in the peripherv of the right upper lobe. Two weeks later, definite nodul~r densities had appeared in both lung fields. Medical chest work-up, including sputum studies, skin tests, and cornplement fixation serology, gave negative result:s. Because of progressive increase in pulmonary insufficiency, the patient was placed in an oxygen tent. Needle biopsy of the lung was performed at this time through the right second anterior intercostal space. A small chest tube was inserted through the site of the lnng biopsy and connected to water-sealed drainage. A minimal air leak was present for two hours, Examination of the biopsy specimen revealed granulomatous inBammation containing Coccidioides immilis spores. A culture of the biopsy specimen was also positive for this organism. Appropriate therapy was instituted, but the patient deteriorated rapidly and she expired three days after the biopsy was performed. COMMEl\;T

This case points out the approach too often selected for diagnosis of diffuse pulmonary disease processes. Almost four weeks elapsed from the time the diffuse pulmonary disease appeared until lung biopsv was considered. At the time of

FICURE 5. Microphotograph of needle biopsy specimen. Note necrotizing pneumonitis and Coccidioides immiti8 endospores .

DIS. CHEST, VOL. 54, NO.2, AUGUST 1968

the biopsy, the patient required continuous oxygen therapv and was certainly not a candidate for open lun~ hiopsy. Even a small pneumothorax in such a patient could have been detrimental. The anteriorly placed chest tube prevented such a problem and was removed the morning after the biopsy. There was no complication from the needle biopsy or from the insertion of the chest tube. It is not difficult to suppose, in retrospect, that the outcome may have been influenced by earlier application of specific therapy. DISCUSSION

Needle biopsy of the lung has experienced two phases: aspiration and cutting. The /irst aspiration biopsy of the lung was done by Leyden" in 1883 to demonstrate the causative "parasitic cocci" in cases of pneumonia. Three years later, Menetrier'" first diagnosed a large lung carcinoma with the needle. In 1909, Hordner-" first reported this technique in the English literature for diagnosis of "septic lung disease." A number of subsequent reports advocated the use of the aspiration needle for the diagnosis of lung masses. 12 .",.2. The largest experience with this technique has been reported hy Dahlgren and Nordenstrom'< of Sweden. Whereas aspiration biopsy is usually acceptable in localized lung pathology, it was not found applicahle to the larger amount of tissue that is necessary for diagnosis in diffuse disease. The second phase of lung biopsy can be said to have begun with the introduction of Silverman's cutting biopsy needle in 1938.311 Sarin'" in 1959 and Manfredi and co-workers'< in 1960 reported the use of a VimSilverman cutting biopsy needle for percutaneous biopsy of lung tissue. Other reports advocating this technique soon followed, reaching a recorded total" in 1966 of over 400 cases without death resulting from this procedure. All reports, however, were not enthusiastic regarding needle lung biopsy.

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YOUMANS ET AL

110 In 190418 and 1909,33 reports cite cases of sudden death following needle lung biopsy. No detailed information regarding these deaths or the technique used is available. A number of articles soon followed suggesting complications of hemorrhage, empyema, pneumothorax, and dissemination of tumor cells along the needle track. l3 •n .,. These publications apparently fonn the basis for much of the current feeling against the use of needle biopsy for lung tissue. It has been well shown, however, that the incidence of empyema following needle biopsy of inflammatory lesions is the same as the incidence of empyema in those cases in which no needle biopsy was done." Dissemination of tumor cells along the needle track has not been encountered by those with the greatest experience.3.U.ll.lt Although this complication is surely a possibility, there is only one well-documented case in the literature. 3 ' Such an implant, should it occur, could be excised. Serious hemorrhage, either in the fonn of hemoptysis, hemothorax, or intrapulmonary hematoma has been encountered only once in the more recently reported series.!" Pneumothorax continues to be the major complication of needle biopsy for diffuse lung disease, occurring in from 13 to 51 per cent of the cases.' .•·I • The present study has employed the use of a chest tube in all cases as an added safety factor. This approach is valid if the complications of the tube do not exceed the incidence of the complication for which it is used. It has been appreciated that when the pleural space is obliterated the chest tube may be introduced from two to three inches into the lung parenchyma. In spite of this possibility, no serious chest tube complications have heen encountered. It is appreciated that some degree of the air leak encountered may have resulted from insertion of the chest tube. Table 6 illustrates a comparison of the experience of Dahlgren with the aspiration needle for local disease and recent reports of cutting biopsy for local and diffuse pulmonary disease. Indications for Needle Biopsy: Any diffuse pulmonary parenchymal disease that cannot be diagnosed through a routine medical chest work-upincluding history, physical examination, skin tests, sputum cytology, acid-fast bacilli smears and cultures, fungus cultures and x-rays and complement fixation studies-should be considered for needle biopsy. In these cases, bronchoscopy, tomograms, arteriograms, mediastinoscopy, bronchograms and scalene node biopsy where no palpable nodes are present may be costly, time-consuming and unnecessary. Many patients who are not acceptable risk patients for open thoracotomy may wen be ac-

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eeptable for needle biopsy. Five patients required continuous oxygen therapy during the needle biopsy. Indications for Open Lung Biopsy: Open lung biopsy is indicated for any patient who is an acceptable surgical risk in whom percutaneous biopsy has been previously considered. On the basis of this report, whether it be done in the patient's bed or in the operating suite, whether under local anesthesia or general anesthesia, needle biopsy should he considered before all cases of open biopsy unless thoracotomy is otherwise indicated. Contraindications of Percutaneous Lung Biopsy: The primary contraindications to percutaneous needle biopsy are anticipated thoracotomy that will not be influenced by the results of needle biopsy and cysts or blebs in the area of the biopsy. The risks of poor patient cooperation, bleeding disorders, poor cardiopulmonary reserve, general debility, ete., should be weighed against the advantage of obtaining a tissue diagnosis. Pulmonary hypertension has been listed as a contraindication by others. We have not experienced difficulty in this regard, but wish a longer period of evaluation on this point before drawing a conclusion. An occasional contraindication is the patient in whom special studies may require more tissue than can be obtained with the needle. Advantages and Disadvantages: On the basis of the experience presented herein, certain conclusions can be drawn concerning the advantages and disadvantages of needle biopsy of the lung. Advantages are listed as follows: 1) a ready method for early diagnosis; 2) avoids thoracotomy and general anesthesia; 3) less expensive than open biopsy and shorter hospital stay; 4) safe procedure with few complications; and 5) applicable to many patients considered too sick for thoracotomy. The disadvantages of this procedure appear to he: 1) no specimen obtained in 10 per cent of biopsies, and 2) "hlind" biopsy may not be representative of the disease as a whole. REFERENCES

1 S~fITH, W. G.: Needle biopsy of the lung with special reference to diffuse lung disease and the use of a new needle, Thorax, 19:68, 1964. 2 GAESSLER. E. A., MOISTER, III. V. B., AND H,u'M, J.: Open lung biopsy in diffuse pulmonary disease, New Eng. ]. Aled.• 270: 1319, 1964. 3 THEOOOS, P. A., ALLBRITTES, F. F., JR., AND BRECICESIUDGE, R. L.; Lung biopsy in diffuse pulmonary disease, Dis. Chest. 27;637,1955. 4 KLAssES, K. P., ASLYAS, A. J., A'''' CURTIS, G. M.: Biopsy of diffuse pulmonary lesions. Arch. Surg., 59: 694,1949.

5 EFFLER, D. B.,

VAN ORnsntAND,

H. 5.,

McCoR1'lACK,

L.

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PERCUTANEOUS NEEDLE BIOPSY OF LUNG

J.,

Al\'D GANCEIlO, H. A.: Surgical biopsy. Amer. Rev.

Tuberc., 71:668, 1955.

6 ANDREWS, N. C .• AND KLAssEN, K. P.: Eight years' exenoe with pulmonary biopsy, I.A.M.A., 164:1061. 1957. 7 GRANT, L. J .• AND TRIVEDI, S. A.: Open lung biopsy for diffuse pulmonary lesions, Brit. Med. I .• 1:17. 1960. 8 MANFREDI, E., ROSENBAUM, D., AND BERND, R. H.: Percutaneous needle biopsy of the lung in diffuse pulmonary disease. Ann. Intern. Med., 68:773. 1963. 9 MANFREDI, F., AND KRUMHOLZ, R.: Percutaneous needle biopsy of the lung in evaluation of pulmonary disorders, I.A.M.A, 198:178. 1966. 10 MANN, B., AND SINHA, C. N.: Jack needle biopsy in pneumocomicosis, Dis. Chut. 50:504. 1966. 11 KRUMHOLZ, R., MAl\'FRDlI, F., WEC, J. C., AND ROSENBAUM, D.: Needle biopsy of the lung-report on its use in 112 patients and review of the literature, Ann. Intern. Med., 65:293, 1966. 12 DAHLGREN, S., Al\'D NORDESSTIlOM, B.: Transthoracic needle biopsy, Year Book Medical Publishers, Inc., Chicago.I966. 13 0tnaA. F. R., Al'o'D GERACI, C. L.: Needle biopsy of the lung, I.A.M.A., 155:21, 1954. 14 GLADHILL, E. Y., SPRIGGS, J. B., AND BINFORD, C. H.: Needle aspiration in the diagnosis of lung carcinoma -report of experiences with seventy-five aspirations, Amer. I. Clin. Path, 19:235. 1949. 15 OsCHSER, A., AND DEBAJ
Lanc"'.

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19 RtDo'HOFF, W. F., Ja.: The present status of the surgical treatment of carcinoma of the lung. I.A.M.A., 126:1123, 1944. 20 OVERHOLT. R. H.: Editorial. Dis. Chut, 50:555, 1968. 21 KLASSEN. K. P.• AND ANDREWs, N. C.: Biopsy of diffuse pulmonary lesions-A seventeen-year experience, Ann. Tho,. Su,g., 4:117,1967. 22 LEYDEN, O. 0.: Ueber Infectiose Pneumonie, Deutsche Med. Wsch,., 9:52, 1683. 23 MENETRIER, P.: Cancer primitif du poumon, Bull. Soc. AllOt. DeBarQ8. 4:643, 1886. 24 HORDNER, R. J.: Lung puncture-A new application of clinical pathology, 2:1345, 1909. 25 STEWART. F. W.: The diagnosis of tumoJS by aspiration, Arne,. I. Path., 9:81, 1932. 26 MARTIN, H. E., AND ELLIS, E. B.: Biopsy by needle puncture and aspiration, Ann. Su,g.• 92: 169. 1930. 27 MARTIN. H. E., AND ELLIS. E. B.: Aspiration biopsy, Su,g. GlInec. and Obat"'., 59:578, 1934. 28 CRAVER, F. L., AND BINn.I!Y, J. R.: Aspiration biopsy of tumors of the lung, I. Thor. Su,g.• 8:436. 1939. 29 RosD'oND, W. G., BURNETT, W. E., AND HALL, J.: Value and limitations of aspiration biopsy for lung lesions, Radiology, 52:506, 1949. 30 SILVERMAN. I.: A new biopsy needle, Amer. I. Su,g., 40:671. 1928. 31 SARIN, L. R., AND BHATNACARL: Needle biopsy of the lung-Case reports, Indian I. Med. Sci., 13:901, 1959. 32 MAsmDll, F .• BucnEY, C. E., Ill, PATRlCI<, R. L., BARRY, W. F., AND SICI
Lanc"'.

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