The Use of Cytology to Evaluate Pericardial Effusions

Transcription

1 ANNALS O CLINICAL AND LABORATORY SCIENCE, Vol. 9, No. 1 Copyright 1979, Institute for Clinical Science, Inc. The Use of Cytology to Evaluate Pericardial Effusions DONALD T. KING,.D. and ROBERTA K. N IEB ERG,.D. Department of Pathology, Harbor General Hospital Campus, UCLA School of edicine, Torrance, CA ABSTRACT Pericardial effusions from 27 patients w ere exam ined cytologically during the five-year period of alignant cells were found in eight cases (30 percent). In three of these patients m alignancy was unsuspected clinically, and this was the first time the cancer was diagnosed. In addition, cytology often suggested the specific histological types and possible primary sites to be determ ined. Special stains were also found helpful. There were no false positive reports. Although the pericardial effusions from the rem aining 19 patients were negative for tum or cells, metastatic carcinoma to the pericardium was discovered at autopsy in two of these cases. Thus, cytologic exam ination of pericardial fluid is an im portant tool in the diagnosis of m alignancy, but false negative results may occur. P ericardial effusions are associated with a wide range of diseases and often present a difficult and perplexing diagnostic problem. Cytological examination of p e ricard ial fluid offers a practical m ethod for establishing a diagnosis. This is especially true for pericardial effusions owing to malignancy. The purpose of this paper is to underscore the usefulness as well as limitations of this important diagnostic modality. aterials and ethods T he re su lts from p e ric ard ial flu id specimens received by the cytopathology laboratory for the five-year period w ere review ed. The cytological reports indicated the presence or absence of m alignant cells in the specim ens. In the pericardial fluids positive for cancer, the histological type was described. In addition, hospital records including clinical notes, surgical pathology reports and autopsy protocols w ere review ed to d e term ine, if possible, the etiology of the pericardial effusions. The pericardial effusions were brought fresh to the cytology laboratory. The specim ens were centrifuged and smears and cell buttons using collodion bags were prepared from the sediment. The smears were stained by the Papanicolaou m ethod. Sections from the cell blocks were stained w ith hematoxylin and eosin as w ell as special stains when indicated. Results Among the 27 patients included in this /79/ $00.90 Institute for Clinical Science, Inc.

2 U SE O CY T O L O G Y T O E V A LU A T E P E R IC A R D IA L E U S IO N S 19 TABLE I alignant P e r ic a r d ia l E ffu sio n s C ase Sex A ge I n itia l C lin ic a l D ia g n o s is 1 25 Tuberculous pericarditis 2 46 Viral pericarditis Tuberculous pericarditis stud y, m alig n an t cells w ere found in th e p ericard ial fluid o f eig h t (30 percent). Six of th e s e re p re s e n te d m etastases from th e lu n g an d tw o w ere from th e b reast. T h e h is to lo g ic a l ty p e s are s u m m a riz e d in ta b le I. In th ree o f th e se p atien ts m alig n an cy was n o t su sp e c te d clinically, and th e in itial d iagnosis was m ade by cytolog- C y to lo g ic a l R e s u lts L o c a tio n o f P r im a r y a lig n a n c y Papillary adenocarcinoma with psammoma bodies Large cell carcinoma, poorly differentiated Squamous cell carcinoma Squamous cell carcinoma Adenocarcinoma Small cell undifferentiated carcinoma Infiltrating ductal adenocarcinoma Infiltrating ductal adenocarcinoma Breast Breast ical exam ination of th e p ericard ial fluid. Since th e se cases clearly d em o n strate th e im portance o f cytology in the in v estig a tion o f p eric ard ial effusions o f u n d ia g n o sed etiology, th ey are briefly re v ie w ed. Case 1: A 25-year-old exican male was admit ted with pericardial effusion. He had been in excel lent health until three weeks prior to admission ut s. ig u r e 1. Cell button of pericardial effusion (Case 1) showing papillary adenocarcinoma with psammoma bodies (Hematoxylin and eosin, x 375).

3 20 K ING AND N IE B E R G when he began to experience a non-productive cough and pleuritic chest pain. He had been ex posed to an active case of tuberculosis one month prior to adm ission and had a p ositive secon d strength tuberculin skin test. T he patient had smoked one pack of cigarettes per day for five years. Initial physical examination was unremarkable except for a 25 mm Hg pulsus paradoxus. Chest roentgenograms showed a pericardial effusion. The patient s condition deteriorated rapidly. Pericardiocentesis was performed. Although acidfast organisms were not identified in the pericardial fluid or numerous sputa, a clinical diagnosis of tu berculous pericarditis was made and treatment with ethambutol and isoniazid was begun. However, cytological examination of the pericardial fluid re vealed mucin-producing papillary adenocarcinoma with psammoma bodies (figure 1). Subsequently, examination of sputa and pleural fluid, as w ell as the pericardium and cervical lymph nodes, showed the same malignancy. Radiological re-examination of the lungs by tomograms demonstrated a nodule in the left upper lobe. ollowing palliative radiation therapy, the pa tient returned to exico and expired. An autopsy was not performed. Case 2: A 46-year-old white female was admit ted because of hypotension and progressive dys pnea. Past medical history included smoking two packs of cigarettes per day for 30 years and flu-like symptoms for 10 days prior to admission. Physical exam in ation rev ea led a 30 mm Hg p u lsu s paradoxus. A clinical diagnosis of viral pneumonia and pericarditis with cardiac tamponade was made, and a pericardiocentesis was done which showed markedly anaplastic, large malignant cells (figure 2). The pericardial effusion rapidly reaccumulated and the following day a pericardial window proce dure was performed. icroscopic sections o f the pericardium showed similar malignant cells. No gross pulmonary lesions were noted at the time of surgery. Postoperatively, re-evaluation of the ad mission chest roentgenogram showed a hilar mass w ith diffuse lym phangitic spread, and sputum cytology was positive for poorly differentiated car cinoma. After a stormy hospital course, the patient expired. An autopsy was not performed. Case 3. The patient was a 58-year-old white male who had smoked two packs of cigarettes per day for 30 years. During a recent evaluation for in creasing dyspnea, a positive PPD was noted. D e spite negative smears and cultures of sputa for acid- igure 2. Smear of pericardial effusion (Case 2) showing anaplastic, large, malignant cells (Hematoxylin and eosin, x 600).

4 U SE O C Y T O L O G Y T O E V A LU A T E P E R IC A R D IA L E U S IO N S fast organisms, pulmonary tuberculosis was diag nosed clinically, and the patient was treated with isoniazid and ethambutol. Soon thereafter, he was readmitted in severe congestive heart failure owing to cardiac tamponade. A pericardiocentesis was done w ith im m ediate c lin ic a l im provem ent. Cytological examination of the pericardial fluid re vealed squamous cell carcinoma (figures 3A and 3B). The malignant effusion reaccumulated, neces sitating a pericardiectomy. At the time of surgery, small nodules were noted in the lungs, pericardium and myocardium. H istologic examination of the 21 pericardium showed squamous cell carcinoma. The patient expired shortly thereafter, and an autopsy was not performed. N in e te e n p eric ard ial effusions d id not co n tain m alig n an t cells. In 17 o f th e se, th e e ffu s io n s w e re a ttrib u te d to n o n m a lig n a n t e tio lo g ie s w h ic h in c lu d e d id io p ath ic (5), tu b erc u lo sis (2), rh e u m a tic h e a rt d isease (2), m yocardial in farctio n 3A ' -A ** * ** ' '7- #% A «* i àsk I -Z*J-*.,» ip ^» - YV * > v I*' y 3B?»C" <!># \ ' ig u r e 3A. Smear of pericardial effusion (Case 3) showing clusters of malignant cells with clear cyto plasmic vacuoles (Hematoxylin and eosin, x 600). ig u r e 3B. Cell button of pericardial effusion (Case 3) showing malignant tissue (Hematoxylin and eosin, x 400).

5 22 KING AND N IEB ER G (2), id io p a th ic cardiom yopathy (1), rheum atoid arthritis (1), urem ic pericarditis (1), hypothyroidism (1), trauma (1) and hem orrhagic pericardial effusion secondary to anticoagulant therapy (1). All of these patients have followed a benign course from five to 60 months. However, the two additional patients w hose pericardial effusions lacked m alignant cells were found at au topsy to have squam ous carcinoma of the lung with pericardial métastasés. A pulmonary malignancy was recognized prem ortem in one of these two patients, whereas there was no clinical suspicion of neoplasm in the other patient who was clinically thought to have a pericardial effusion secondary to congestive heart failure (table II). Discussion etastatic tumors to the pericardium and heart are not uncommon in patients with advanced m alignant disease. The reported incidence varies among different autopsy series, ranging b etw een 0.1 and 6.4 percent in unselected autopsies and 1.5 and 20.6 percent in autopsies of patients dying w ith m alignant disease.2 Although th e o re tic a lly every prim ary neoplasm can give rise to a cardiac m etastasis, the most common are carcinoma of the lung and breast, malignant melanoma, leukem ia and lym phom a.1 étastasés more frequently involve the pericardium than other areas of the heart. Recently, there has been a steady increase in the incidence of cardiac metastases. This is attributed to a general rise in the incidence of lung and breast cancer and to advances in the therapy of m alignant diseases enabling patients to live longer and thus develop m ore extensive tum or dissem ination.2 D espite the frequency of secondary malignancies of the pericardium and heart, they are often not diagnosed premortem. This is due to a num ber of factors. etastatic involvement may sometimes be relatively asymptomatic. W hen they do result in circulatory impairm ent, it is often attributed to cardiac disease unrelated to the neoplasm. A 30 percent rate of positive pericardial fluids in our series is comparable to the 28 percent reported by Zipf and Johnston.3 In light of a significant frequency of m alignant pericardial effusions, it is important to have a high index of suspicion. This is em phasized by the three cases described in which the diagnosis of cancer was clinically unsuspected, and the diagnosis was initially m ade from the cytological m aterial. This high rate of positivity of pericardial effusions (30 percent) is especially noteworthy in comparison to pleural and abdominal effusions where the positivity rate is 15 p e rc e n t in th e a u th o rs institution. By means of pericardial fluid cytology, not only can malignancy be docum ented, but also a specific m orphologic classification (adenocarcinom a, squam ous cell car- TABLE I I Negative P e ric a rd ia l Effusions with P e ric a rd ia l etastases A g e C l i n i c a l D i a g n o s i s A u t o p s y Squamous cell carcinoma, lung, with metastases to pericardium and hilar lymph nodes Coronary artery disease with Squamous cell carcinoma, lung, with cardiac arrythmias and metastases to pericardium, vertebrae, congestive heart failure diaphragm, left atrium

6 USE O CYTOLOGY TO EVALUATE PERICARDIAL E U SIO N S 23 cinoma, oat cell carcinoma, etc.) as well as a possible primary site can be suggested. Special stains may be helpful. or example, in Case 3, many of the malignant cells in the smears w ere clustered and contained prom inent clear cytoplastic vacuoles. T his a p p e ara n ce su g g ested a mucin-producing adenocarcinoma (figure 3A). However, in the cell button, where a fragment of m alignant tissue suggested a squamous cell carcinoma, the cytoplasmic vacuoles did not stain with mucicarmine and were positive for glycogen using the periodic acid Schiff stain w ith diastase digestion, consistent with squamous cells (figure 3B). Subsequent tissue biopsy from the lung substantiated the diagnosis of squam ous cell carcinoma. In this series, two patients had a negative pericardial effusion despite involvement of the pericardium as proven by autopsy. Zipf and Johnston3 also reported two false negatives. This illustrates that pericardial fluid cytology is a very useful diagnostic tool but has limitations. Hence, a negative cytology re p o rt m ay not n ecessarily elim inate malignancy as a possible cause of pericardial effusion. When there is a strong clinical suspicion of cancer, surgical exploration may be required to establish the correct diagnosis. References 1. r e i m a n, A. H.: Cardiovascular disturbances associated with cancer. ed. Clin. N. Amer. 50: , W ENGER, N. K.: Cardiac tumors. The Heart, Arteries and Veins, 3rd ed. Hurst, J. W., Logue, R. B., Schlant, R. C., and Wenger, N. K., eds. New York, cgraw-hill, 1974, pp Zipf, R. E. and J o h n s t o n, W. W.: The role of cytology in the evaluation of pericardial effusions. Chest 62: , 1972.