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Ann Thorac Surg 2002;73:1552-1556
© 2002 The Society of Thoracic Surgeons

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Original article: general thoracic

Diagnosis of visceral pleural invasion by lung cancer using intraoperative touch cytology

^a Department of Surgery II, Nagoya City University Medical School, Nagoya, Japan

Accepted for publication December 30, 2001.

* Address reprint requests to Dr Fujii, Department of Surgery II, Nagoya City University Medical School, 1, Kawasumi, Mizuhoku, Nagoya 467-8601, Japan
e-mail: yosfujii{at}med.nagoya-cu.ac.jp

	Abstract

Top Abstract Introduction Patients and methods Results Comment References

 
Background. Invasion to the visceral pleura is an important component of lung cancer staging and an independent prognostic factor. However, the accuracy of pathologic examination depends on how the sections are made, and the pathologist may miss the most invaded part of the pleura. Therefore, we have designed "touch" cytology in an effort to more accurately diagnose the pleural invasion by lung cancer.

Methods. Immediately after thoracotomy, the surface of the visceral pleura just above the tumor was gently touched by a glass slide without scrubbing in 100 patients who simultaneously underwent pleural lavage cytology or cytology of the subclinical pleural effusion.

Results. Seventeen percent of the tumors were diagnosed as invading the visceral pleura by touch cytology. Lavage cytology was found to be positive in 7%. In reference to the pathologic examination of the tumor specimen, touch cytology was found to be positive in all of p3, 5 out of 6 of p2, 5 out of 30 of p1, and 5 out of 62 of p0 cases. Touch cytology correctly diagnosed all the positive cases detected by lavage or effusion cytology.

Conclusions. This study suggests that our method is useful in detecting the visceral pleural invasion and raises a possibility that pathologic p0 and p1 lung cancers include a subset of patients with tumor cells exposed on the pleural surface.

	Introduction

Top Abstract Introduction Patients and methods Results Comment References

 
Invasion to the visceral pleura is an important component of lung cancer staging and an independent prognostic factor [1–3]. The presence of pleural invasion in carcinoma smaller than 3 cm increases the staging descriptor T1 to T2 [4]. Significant differences in survival have been recorded between the T1 and T2 disease [5–6].

In most cases, the visceral pleura in one or two sections are examined by the pathologist for the diagnosis of pleural invasion. Pathologic examination is thus limited by the way the sample is cut from the specimen and the pathologist may fail to examine the most invaded part of the pleura. Lavage cytology is a good complementation to the diagnosis of pleural invasion. Once the cancer cells are released to the chest cavity from the tumor that invaded the pleura, there is a good chance of detecting the malignant cells by the lavage cytology. However, the sensitivity of this method may be low if the invasion reaches the surface of the pleura but releases few cancer cells. We have designed "touch" cytology in which we gently touch the pleura overlying the tumor with a piece of glass slide. We hoped that this touch method may improve the sensitivity of detecting the pleural invasion by lung cancer. In this article we report 100 patients of lung cancer who underwent touch cytology together with lavage cytology or cytology of the subclinical pleural effusion.

	Patients and methods

Top Abstract Introduction Patients and methods Results Comment References

 
From July 1998 to September 2000, 175 patients underwent surgical resection at Nagoya City University Medical School. Of these, 108 patients were available for evaluation of touch cytology of the visceral pleura. Among these, 100 patients also underwent pleural lavage cytology or cytology of the pleural effusion, which was not apparent before the operation. These 100 patients were the subjects of the present study. Patients with apparent pleural effusion preoperatively were excluded. There were 73 adenocarcinomas, 21 squamous cell carcinomas, five adenosquamous carcinomas and one small cell carcinoma. Preoperatively 18 patients had undetected pleural effusion; the effusion was subjected to cytology. Ninety-four patients underwent lavage cytology. Twelve patients underwent both effusion and lavage cytology.

Our method of touch cytology is as follows. Immediately after thoracotomy, the surface of the visceral pleura just above the tumor is gently touched by a glass slide without scrubbing (Fig 1). This method is repeated 4 to 5 times using a new piece of glass slide each time. Subsequently, 100 mL of saline solution is instilled into the chest cavity and the washing is aspirated for lavage cytology. There is no manipulation of the lung before or during this procedure. In our preliminary studies, we checked the section of the touched lung and confirmed that touching the pleura by a piece of glass did not affect the subsequent pathologic examination of the pleura and lung.

View larger version (23K): [in this window] [in a new window]   Fig 1. The technique of touch cytology was used to detect visceral pleural invasion of a tumor. Immediately after thoracotomy, the pleura overlying the tumor was gently touched by a piece of glass slide. This was repeated five times. Care was taken not to scrub the surface.

For the routine histologic diagnosis of pleural invasion, parts of the tumor that appeared to have macroscopic visceral pleural invasion were sliced. In most cases the visceral pleura of one or two cut slices of the resected tumor were examined by one pathologist. Elastic fiber was stained using Victoria Blue to identify the pleura. Visceral pleural involvement was classified according to the rules of the Japan Lung Cancer Society [7] as follows: p0 = no visceral pleural involvement; p1 = penetration through the visceral pleura elastic tissue but not to the surface of the visceral pleura; p2 = penetration through to the surface of the visceral pleura; and p3 = involvement of the parietal pleura.

Chi-square test was used to determine the significance of the relationship between the two variables. A p value of less than 0.05 was considered significant.

	Results

Top Abstract Introduction Patients and methods Results Comment References

 
Of the 100 tumors, 17 tumors were diagnosed as invading the visceral pleura by touch cytology. Lavage cytology detected only 7 of these (7% positive). Cytology of the pleural effusion, which was found at the time of operation, was positive in only 3 of 18 patients (Table 1). The frequency of positive touch cytology in patients with adenocarcinoma, squamous cell carcinoma, adenosquamous carcinoma, and small cell carcinoma was 21% (15 of 73), 4.8% (1 of 21), 0% (0 of 5), and 100% (1 of 1), respectively (Table 1).

View larger version (81K): [in this window] [in a new window]   Fig 2. Pathologic findings of representative patients. Hematoxylin & eosin (HE) staining: (A), (C), (E), and (G). Elastic fiber staining (blue): (C), (E), and (G). Touch cytology: (B), (D), and (F). (A) and (B) show a p2 patient. (A) HE staining shows lung cancer invading the pleura (arrow). (B) Touch cytology shows tumor cells (arrow) among mesothelial cells. (C) and (D) show a p1 patient. In (C) the tumor cells apparently invade the elastic lamina (arrow), but they do not seem to be exposed to the surface, which is covered by a thick fibrous tissue thus leading to a diagnosis of p1. In this patient, touch cytology shows many clusters of malignant cells (arrow) as shown in (D). (E) and (F) show a p0 patient with no pleural involvement as shown by the blue elastic stain, (E). However, in (F) a few malignant cells (arrow) are found in the touch cytology specimens among mesothelial cells. (G) A case with pleural invasion (arrow) at the bottom of a deep groove made by the pleural retraction. No tumor cells could be identified by touch cytology in this patient (not shown).

	Comment

Top Abstract Introduction Patients and methods Results Comment References

We found positive touch cytology in 5 of 62 (8.1%) and 5 of 30 (16.7%) pathologic p0 and p1 patients, respectively. This may be attributed to inappropriate preparation of sections for pathologic examination, and there may actually have been tumor cells exposed on the pleural surface. In this case pathologic examination failed to detect about 11% of true positives. Alternatively it could be argued that by touching the pleura we may have been damaging the pleura by exposing the otherwise unexposed tumor cells. However, this is unlikely because the pathologist did not observe damaged pleura in any of the patients. Among 62 pathologic p0 cases, touch cytology showed positive findings in 5 patients. It is rather difficult to imagine that at one section the tumor does not even reach the elastic fibrous sheet of the pleura and at another region of the same pleura it may be exposed on the surface. Kondo and colleagues [8] suggested that the exfoliation of cancer cells into the pleural cavity may occur not only when the tumor is exposed on the pleural surface but also when subpleural lymphatics are invaded by the tumor. However, we could not demonstrate lymphatic spread in our series of patients with positive touch cytology and a pathologic diagnosis of p0. Because morphologic distinction between reactive pleural mesothelial cells and adenocarcinoma cells could be difficult, the accuracy of cytologic examination remains to be one of the problems to be solved. In patients like the one shown in Figure 2C (in which pathologic p1 tumors that invade the elastic fiber but are retained under the pleural surface), it is conceivable that touch cytology can detect tumor cells on the surface, whereas in some sections, tumor cells are retained within the confinement of the fibrous tissue of the pleural surface. In many p1 patients, touch cytology revealed 5 or more clusters of tumor cells, which strongly suggests truly positive tumor cells on the pleural surface.

In only 1 patient of pathologic p2 lung cancer, touch cytology failed to show tumor cells on the slide that touched the pleura overlying the tumor (Fig 2G); this was one example of adenocarcinoma that had pleural indentation and tumor cells that were found to be exposed at the bottom of the deep crevice formed by the retracted pleura. This may have been a patient that was p0 in practice. The lavage cytology was also negative in this patient. In another 7 p2 and p3 patients, touch cytology could correctly identify the tumor cells (Table 2).

Lavage cytology of the pleural space proved valuable in predicting the outcome of lung cancer patients. Okumura and colleagues [9] reported a 17.4% recurrence rate of p1 lung cancers with positive lavage cytology compared with 0.7% with negative lavage cytology. Kondo and coworkers [8] and Dresler and coworkers [10] reported 3-year survival rates of lavage cytology positive and negative stage I lung cancers to be 68.7% and 22.9% (Kondo and colleagues [8]) and 69% and 0% (Dresler and colleagues [10]), respectively. Other methods for more accurate detection of visceral pleural invasion have been proposed. Ichinose developed a method using a jet stream of saline solution [11]. These studies have suggested that a significant number of patients with otherwise early stage disease will have positive pleural cytology results and subsequently have a poorer prognosis than patients with negative cytology results. In our study, the touch cytology results had a good correlation with effusion or lavage cytology results (Table 3). Cases with negative touch cytology were always negative with effusion or lavage cytology. Without compromising specificity, touch cytology achieved better sensitivity than the effusion or lavage cytology.

Our study raises a possibility that pathologic p0 and p1 lung cancers include a subset of patients with tumor cells exposed on the pleural surface. We have to wait for the follow-up study of these patients to see if the positive touch cytology has an impact on the survival of patients with otherwise early stage lung cancer.

	References

Top Abstract Introduction Patients and methods Results Comment References

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Saito, Y. Articles by Fujii, Y. Search for Related Content PubMed PubMed Citation Articles by Saito, Y. Articles by Fujii, Y. Related Collections Lung - cancer Related Article