Cardiovascular Pathology 10 (2001) 157 – 168

Surgical pathology of the parietal pericardium:

A study of 344 cases (1993–1999)$
Kirstine Y. Oha, Michio Shimizub, William D. Edwardsc,
Henry D. Tazelaarc,*, Gordon K. Danielsond
a
Mayo Medical School, Mayo Clinic, Rochester, MN, USA
b
Department of Pathology, Saitama Medical School, Saitama, Japan
c
Division of Anatomic Pathology, Hilton 11, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA
d
Division of Cardiovascular Surgery, Mayo Clinic, Rochester, MN, USA
Received 5 February 2001; received in revised form 15 May 2001; accepted 17 May 2001

Abstract

Among 344 cases with surgically resected parietal pericardium, ages ranged from 1 to 87 years (mean, 55), and 64% were male. Causes of
pericardial disease included neoplastic (33%), idiopathic (30%), iatrogenic (23%), and others (14%). Pericardial constriction (Group 1)
represented the largest group (143 cases, 76% male). Maximal pericardial thickness was 1 – 17 mm (mean, 4). Fibrotic thickening occurred in
96%. Chronic lymphoplasmacytic inflammation affected 73% (mild or moderate in 97%). Calcification was uncommon (gross in 28%,
microscopic in 8%), and granulomas were rare (4%, none tubercular). Constriction was idiopathic in 49% and iatrogenic (postpericardiotomy
or postirradiation) in 41%. Neoplasms and cysts (Group 2) represented the second largest group (96 cases). Among 43 cases with secondary
pericardial involvement, carcinomas accounted for 53% and lymphomas 21%. Forty cases (Group 3) had pericardial effusions (75% chronic),
which were idiopathic in 28% and postpericardiotomy in 23%. Thirty-three cases (Group 4) had acute or recurrent pericarditis clinically,
which was idiopathic in 70%. Lastly, 32 cases (Group 5) had pericardial resection for conditions unrelated to primary pericardial disease. In
conclusion, pericardial constriction tended to be nontubercular (100%), nongranulomatous (96%), idiopathic or iatrogenic (90%), and
noncalcific (64%), and it could occur with normal pericardial thickness (4%). Because considerable overlap in the gross and microscopic
features existed among cases with noncalcific pericardial constriction (Group 1), pericardial effusions (Group 3), and pericarditis (Group 4),
clinical information was necessary to provide an accurate clinicopathologic interpretation. D 2001 Elsevier Science Inc. All rights reserved.

Keywords: Constrictive pericarditis; Pericardial neoplasm; Pericarditis; Pericardial effusion; Pericardium; Surgical pathology

1. Introduction 2. Methods

Although valvular and ischemic diseases result in the
greatest number of surgically excised specimens from the
heart, pericardial disorders now represent an appreciable
proportion of the cases at our institution. The reasons for
pericardial resection are numerous, but have been described
in only one surgical pathology series [1]. Given these
considerations, the current study was undertaken to evaluate
the pathology of pericardial disease in a relatively large
number of surgical cases from a single institution.
$
Presented in part as a poster on 14 October 2000 at the annual
meeting of the American Society of Clinical Pathologists in San Diego, CA.
* Corresponding author. Tel.: +1-507-284-1192; fax: +1-507-284-
1599.
E-mail address: tazelaar.henry@mayo.edu (H.D. Tazelaar).
2.1. Study group
All parietal pericardial specimens surgically excised at
Mayo Clinic Rochester from January 1, 1993 through
December 31, 1999 were reviewed, as approved by the
Institutional Review Board. Of the 358 cases initially
identified, 14 were excluded due to insufficient pericardium
histologically, thus leaving a study group of 344 cases.
2.2. Clinical features
From medical charts, the age and gender of the patient
and the duration, clinical diagnosis, and etiology of the
pericardial disease were recorded. Duration was defined as
acute ( < 1 week), subacute (1 week – 1 month), chronic

1054-8807/01/$ – see front matter D 2001 Elsevier Science Inc. All rights reserved.
PII: S 1 0 5 4 - 8 8 0 7 ( 0 1 ) 0 0 0 7 6 - X
158 K.Y. Oh et al. / Cardiovascular Pathology 10 (2001) 157–168

Table 1 ies, echocardiography, computerized tomography (CT), elec-

Demographic features in 344 surgical cases of pericardial disease
tron beam (ultrafast) CT, or magnetic resonance imaging.
Age (year) Gender Cases Pericardial effusions were classified by duration. Pericarditis
Clinical category Mean Range M F M/F No. % (including acute and recurrent types) was distinguished from
Constriction 57 12 – 81 109 34 3.2 143 42 pericardial effusions by the presence of the syndrome of
Neoplasm or cyst 56 4 – 80 55 41 1.3 96 28 chest pain, friction rub, fever, shortness of breath, cough,
Effusion 57 3 – 87 25 15 1.7 40 12 elevated erythrocytic sedimentation rate, and electrocardio-
Pericarditis 47 11 – 81 18 15 1.1 33 9
graphic changes.
Other 51 1 – 80 14 18 0.8 32 9
Total 55 1 – 87 221 123 1.8 344a 100 Surgical procedures were classified as radical, subtotal,
or partial pericardiectomy or as pericardial window, resec-
M = males; F = females.
a
Among the 341 patients, an 11-year-old boy had two operations for tion (for neoplasms), biopsy, or unknown, as recently
pericarditis and one operation for pericardial constriction, and a 64-year- reviewed by Ling et al. [2]. Radical pericardiectomy implied
old man had two operations for a pericardial neoplasm, thereby producing removal of the pericardium anteriorly (between the right and
344 cases. left phrenic nerves, from the level of the great arteries to the
diaphragmatic surface), left laterally (posterior to the left
( > 1 month), or unknown. Neoplasms and recurrent peri- phrenic nerve), inferiorly (along the diaphragmatic surface),
carditis were considered chronic processes. and posteriorly (to the atrioventricular junction). In contrast,
Each case was assigned to one of five categories, based on a subtotal pericardiectomy indicated resection only of the
the most prevalent type of pericardial disease: constriction pericardium between the two phrenic nerves. A partial
(Group 1), neoplasm or cyst (Group 2), effusion (Group 3), pericardiectomy represented any other major removal of
pericarditis (Group 4), or other (Group 5). A preoperative the pericardium, including a ‘‘completion’’ pericardiectomy,
diagnosis of constriction was established on the basis of in which a portion had been previously resected. Pericardial
clinical features of right heart failure and one or more of the windows were small resections performed to drain the
following: cardiac catheterization with hemodynamic stud- pericardial space. All nonpericardial cardiac operations were

Table 2
Clinical features in 344 surgical cases of pericardial disease
Clinical diagnostic category Total
Clinical feature Constriction Neoplasm or cyst Effusion Pericarditis Other No. %
Duration
Acute 0 0 1 2 0 3 1
Subacute 1 0 4 3 0 8 2
Chronic 137 96 30 27 0 290 84
Unknown 5 0 5 1 32a 43 13
Total 143 96 40 33 32 344 100

Etiology
Neoplasm or cyst 0 96 9b 0 7b 112 33
Idiopathic 70 0 11 23 0 104 30
Postpericardiotomy 43 0 9 3 0 55 16
Postirradiation 16 0 3 3 3c 25 7
Autoimmune 9d 0 1e 2f 0 12 3
Infection 1g 0 1h 2i 2j 6 2
Sarcoidosis 2 0 2 0 0 4 1
Other 2k 0 4l 0 20m 26 8
Total 143 96 40 33 32 344 100
a
Patients had no primary pericardial disease.
b
Neoplasm was only in adjacent structures, not in the pericardium.
c
Without pericardial constriction.
d
Six with rheumatoid arthritis, and three with Dressler’s syndrome.
e
Dressler’s syndrome.
f
One with scleroderma, and one with Dressler’s syndrome.
g
Coxsackie B viral pericarditis.
h
Mixed bacterial and fungal pericarditis.
i
One bacterial and one fungal infection.
j
Two aspergillus infections.
k
One chest trauma and one pericarditis following atrioventricular nodal ablation with right ventricular perforation.
l
One chest trauma, one uremia, one ascending aortic dissection, and one right ventricular perforation during pacemaker placement.
m
Twelve congenital heart disease (including nine Ebstein’s anomaly), two valve surgery, one ascending aortic dissection, one ascending aortic aneurysm
in Marfan’s syndrome, one restrictive cardiomyopathy, one chest trauma, one incidental pericardial inflammatory nodule at operation, and one unknown.
 K.Y. Oh et al. / Cardiovascular Pathology 10 (2001) 157–168 159

recorded, as was the presence of coexistent ischemic, Pericardial disease was chronic in 84% of the cases. It
valvular, and congenital heart disease; heart failure; and was neoplastic in 33%, idiopathic in 30%, iatrogenic in
pleural effusions. 23%, and of other cause in 14% (Table 2). The most
common surgical procedure was a radical pericardiectomy,
2.3. Pathologic features which was performed in 30% of the cases (Table 3).

Surgical pathology reports and corresponding micro- 3.1.2. Pathologic features

scopic slides were reviewed in each case. From the report
or the slide, the maximal pericardial thickness was recorded
to the nearest millimeter. The following, if present, were
also recorded: calcification (gross or microscopic), inflam-
mation (acute or chronic, and graded semiquantitatively as
mild, moderate, or marked), granulomas (caseating or non-
caseating, with the results of special stains for organisms),
and fibrosis, granulation tissue, fibrin deposition, hemosi-
derin, and mesothelial hyperplasia. The presence of neutro-
phils, primarily within small vessels, was considered
surgery-related, whereas prominent extravascular neutro-
philic infiltrates were considered disease-related. If a neo-
plasm was present, no other microscopic information was
recorded for that case.
3. Results
3.1. General findings
3.1.1. Clinical features
Among the 341 patients, one had two pericardial oper-
ations and another had three, resulting in 344 cases. Ages at
operation ranged from 1 to 87 years (mean, 55), and
children were present in each of the five clinical categories
(Table 1). Males accounted for 221 (64%) of the cases and
were particularly prone to develop constriction.
On average, four pieces of parietal pericardium were
evaluated microscopically from each case (Table 4). Peri-
cardial thickening was due to fibrosis in 67%. It occurred in
all five groups, but was greatest in patients with constriction
or pericarditis. Mild to moderate chronic inflammation was
present in 56% of the cases. Granulomas were observed in
only 3%, and none were due to tuberculosis.
3.1.3. Coexistent heart disease
Among the 341 patients, 83 (24%) had coronary artery
disease, 51 (15%) had valvular disease, and 20 (6%) had
congenital heart disease. Of the 78 patients with heart
failure, none were New York Heart Association (NYHA)
Class I, 4 were Class II, 18 were Class III, and 24 were
Class IV; the NYHA class was not specified in 32 patients,
of whom 7 had right heart failure. At the time of pericardial
resection, 48 patients also had resection of a neoplasm
outside the pericardium, 43 underwent valve repair, 33
had coronary artery bypass grafting, and 20 underwent
repair of congenital cardiac anomalies.
3.2. Pericardial constriction (Group 1)
3.2.1. Clinical features
Patients with symptoms related to pericardial constriction
represented the largest group (143 cases), of which 76%
were male. In addition, another 16 patients with features of

Table 3
Types of surgical procedures for parietal pericardial disease in 341 patientsa
Clinical diagnostic category Total
Surgical procedure Constriction Neoplasm or cyst Effusion Pericarditis Other No. %
Radical 75 0 14 21 0 110 30
Partial 36b 3 7c 4 14 64 18
Resection 0 61 0 0 2d 63 17
Biopsy 1 34 7 5 10 57 16
Subtotal 31 0 3 1 1 36 10
Window 0 12 13 3 4 32 9
Unknown 0 0 1 0 1 2 <1
Total 143 110e 45f 34g 32 364a 100
a
One patient had three operations and one patient had two operations (accounting for 344 cases), and 20 patients had two procedures during the same
operation, resulting in 364 procedures. Not included are 64 focal epicardial resections (from 50 patients with constriction, 3 with neoplasms, 6 with effusions, 4
with pericarditis, and 1 with other pericardial disease).
b
Includes 11 completion pericardiectomies (for six prior resections for constriction, and five prior windows).
c
Includes two completion pericardiectomies (one prior window, and one prior 40% excision).
d
Resection of two pericardial masses, found at operation to be non-neoplastic.
e
Fourteen patients had two pericardial procedures during the same operation.
f
Five patients had two pericardial procedures during the same operation.
g
One patient had two pericardial procedures during the same operation.
160 K.Y. Oh et al. / Cardiovascular Pathology 10 (2001) 157–168

Table 4
Pathologic features in 344 surgical cases of pericardial disease
Clinical diagnostic category Total
Pathologic feature Constriction (n = 143) Neoplasm or cyst (n = 96) Effusion (n = 40) Pericarditis (n = 33) Other (n = 32) No. %
No. of specimens (microscopic)
Mean 5 3 5 4 4 4
Range 1 – 16 1–7 1 – 14 1 – 10 1 – 14 1 – 16

Maximal thickness (mm)

Mean 4 3 4 3 3 4
Range 1 – 17 1–5 1–9 1 – 13 1–6 1 – 17

Acute inflammation
Absent 131 94 30 26 26 307 89
Mild 9 1 5 3 4 22 6
Moderate 3 0 4 2 0 9 3
Marked 0 1 1 2 2 6 2

Chronic inflammation
Absent 39 80 5 9 11 144 42
Mild 82 13 21 18 13 147 43
Moderate 19 2 13 6 5 45 13
Marked 3 1 1 0 3 8 2

Granulomas
Absent 137 95 38 33 31 334 97
Noncaseating 5 1 2 0 0 8 2
Caseating 1 0 0 0 1 2 1

Calcification
Absent 91 95 37 30 26 279 81
Gross and microscopic 40 0 1 2 6 49 14
Microscopic only 12 1 2 1 0 16 5

Other features
Fibrotic thickening 137 11 33 26 23 230 67
Fibrin deposition 48 5 26 9 5 93 27
Hemosiderin pigment 40 3 15 5 7 70 20
Granulation tissue 20 4 18 7 6 55 16
Mesothelial hyperplasia 5 2 10 2 1 20 6

constriction were listed in different clinical categories (3
with neoplastic involvement and 13 with prominent effu-
sions), and are discussed with Groups 2 and 3, respectively.
Pericardial constriction was chronic in 96% (Table 2).
There was a history of previous pericarditis in 25 (17%) and
pericardial effusions in 20 (14%). The surgical pericardiec-
tomy was radical in 52% and subtotal or partial in 47%
(Table 3). Eleven patients had had previous pericardial
operations (six resections for constriction, and five pericar-
dial windows).
3.2.2. Pathologic features
The maximal pericardial thickness ranged from 1 to 17
mm (mean, 4) (Table 4); thickening was present in 96%
and was due to fibrosis (Fig. 1). Calcification was present
in only 36% (grossly visible or palpable in 28% and
detectable only by microscopy in 8%). Pericardial thick-
ness ranged from 1 to 12 mm (mean, 4) in specimens with
calcification, 2– 8 mm (mean 4) in those with only micro-
scopic calcification, and 1– 17 mm (mean 5) for cases
without detectable calcium. Importantly, 4% showed no
calcification, fibrosis, or increased thickness. Inflammation
was chronic and lymphoplasmacytic in 73% and was mild
to moderate in 97% of these. Acute inflammation coex-
isted in 8%. Six patients had granulomas (none with
organisms detected by special stains; two due to sarcoi-
dosis). Fibrin was detected in 34%, and hemosiderin (due
to previous hemorrhage) was seen in 28%.
3.2.3. Causes of constriction
There was no identifiable cause for pericardial con-
striction in 49% of the patients (Table 2). The two most
prevalent known causes were both iatrogenic and included
previous pericardiotomy (30%) and irradiation (11%).
Radiotherapy had been used to treat 11 lymphomas, 3
breast cancers, 1 lung cancer, and 1 unknown malignancy,
and the time interval between radiation and pericardiec-
tomy ranged from 2 to 42 years (mean, 23). Eleven
patients had had incomplete prior pericardial resections
without relief of symptoms and then underwent a com-
 K.Y. Oh et al. / Cardiovascular Pathology 10 (2001) 157–168 161

Fig. 1. Photomicrographs from patients with constrictive pericarditis. (A – C) Low-power views of the pericardium (taken at the same magnification),
showing fibrotic thickening (A), plate-like calcification (B), and normal thickness (C, between arrows). (D,E) Chronic nongranulomatous
lymphoplasmacytic inflammation, of mild degree at the border between the pericardium and adjacent adipose tissue (D), and of moderate degree within
fibrotic pericardium (E).

pletion pericardiectomy. There were no cases of posttu-
bercular constriction.
3.3. Neoplasms and cysts (Group 2)
3.3.1. Clinical features
Neoplasms and cysts represented the second largest
group and included 96 cases and 110 specimens (Table 3).
There was no appreciable gender predilection (Table 1). The
two most frequently performed procedures were resection
(55%) and biopsy (31%). An additional seven patients had
pericardial procedures to rule out neoplastic disease and are
included in Group 5.
Overall, metastatic disease accounted for 64%, primary
benign tumors and cysts 23%, and mesotheliomas 13%
(Table 5). Carcinomas and lymphomas were the most
prevalent forms of secondary involvement. Among the
18 cases with tumor identified only in adjacent tissues
and not in the pericardium directly, there were no lym-
phomas or mesotheliomas.
Three patients had symptoms of constriction due to
neoplastic encasement of the heart (two pericardial meso-
theliomas, one metastatic adenocarcinoma of the lung).
Seven patients had both pericardial effusions and pericardial
neoplasms. Fifteen patients also had pleural effusions.
3.3.2. Pathologic features
The maximal pericardial thickness ranged from 1 to 5
mm (mean, 3), excluding two cases with oblique tissue
orientation on the slide. Thickening was tumor-related in
all cases, with coexistent fibrosis in 11% (Table 4).
Chronic lymphoplasmacytic inflammation was present in
only 17% and was mild in 81% of these. A noncaseat-
ing granuloma was found in pericardial tissue from a
patient with an unresectable squamous cell carcinoma of
the lung.
3.4. Pericardial effusions (Group 3)
3.4.1. Clinical features
Of the 40 patients with pericardial effusions, 63% were
male (Table 1). Effusions were chronic in 75% (Table 2).
Specific gravity was determined in six cases, and all were
transudative. The two procedures performed most often
162 K.Y. Oh et al. / Cardiovascular Pathology 10 (2001) 157–168

Table 5 3.5. Pericarditis (Group 4)

Neoplasms or cysts in 96 patients with pericardial resection
Total
In the In adjacent 3.5.1. Clinical features
Neoplasms or cysts pericardium tissues No. % The smallest group included 32 patients with pericarditis,
Secondary (n = 61) 30% of whom also had a pericardial effusion. There was no
Carcinoma 23a 15b 38 40 gender predilection (Table 1). One patient had two pericar-
Lymphoma 9c 0 9 9
dial operations, and another had two pericardial procedures
Other 11d 3e 14 15
during the same operation, yielding 33 operations and 34
Primary (n = 22) specimens. Of the 33 operations, 82% were for chronic
Cyst 20 0 20 21 recurrent disease (Table 2). A radical pericardiectomy was
Lymphangioma 1 0 1 1 performed in 62% (Table 3).
Lipoma 1 0 1 1
In an 11-year-old boy, a pericardial window was made
Mesothelioma (n = 13) to relieve a septic streptococcal effusion, and a subsequent
Pleural 11 0 11 11 partial pericardiectomy was performed when sterile peri-
Pericardial 2 0 2 2 carditis occurred 1 month after the first operation. Within
another month, he developed pericardial constriction and
Total 78 18 96 100
underwent a completion pericardiectomy (included in
a
Twenty-one adenocarcinomas (15 lung, 4 breast, 1 esophagus, 1 Group 1).
colon) and two squamous cell carcinomas (one lung, one esophagus).
b
Seven adenocarcinomas (five lung, two esophagus), four squamous
cell carcinomas (three lung, one esophagus), three non-small cell 3.5.2. Pathologic features
carcinomas of lung, and one mediastinal embryonal carcinoma. Maximal pericardial thickness ranged from 1 to 13 mm
c
Six B-cell lymphomas, two T-cell lymphomas, and one nodular (mean, 3), and fibrosis was present in 79%. Chronic
sclerosing Hodgkin’s disease.
d lymphoplasmacytic inflammation was observed in 73%
Five malignant thymomas (four Type I, one Type II) and six others
(osteosarcoma, liposarcoma, synovial sarcoma, peripheral nerve sheath and was mild to moderate in all (Table 4) (Fig. 3). Acute
tumor, endometrial mixed mullerian tumor, and mediastinal mixed germ neutrophilic inflammation, often with edema, occurred in
cell tumor with yolk sac and mature teratoma components). 21%, and acute and chronic inflammation coexisted in four
e
Three others (Type I thymoma, synovial sarcoma, and mediastinal cases. Both examples of severe acute inflammation were in
germ cell tumor).
the 11-year-old boy.

3.5.3. Causes of pericarditis

were radical pericardiectomy (31%) and pericardial window
(29%) (Table 3).
Eighteen patients had isolated effusions. Of the remain-
ing 22 patients, 9 had both a pericardial effusion and
hemodynamic evidence of constriction due to ventricular
compression by loculated fluid or hematoma. Four patients
had effusive – constrictive disease (that is, a pericardial
effusion and constriction by the epicardium rather than
by the parietal pericardium) [3]. The remaining nine cases
(not included in the neoplastic group above) each had both
a pericardial effusion and a neoplasm that did not involve
the pericardium.
3.4.2. Pathologic features
The maximal pericardial thickness ranged from 1 to 9
mm (mean, 4), and fibrosis was identified in 83% (Table 4).
Chronic lymphoplasmacytic inflammation was present in
88% (mild to moderate in 97%) (Fig. 2). Acute inflamma-
tion was observed in 25%, and fibrin deposition in 65%.
Old postoperative foreign-body granulomas were found in
two cases.
3.4.3. Causes of effusions
Pericardial effusions were idiopathic in 28%. The two
most common known causes were previous pericardiotomy
and neighboring neoplasms (23% each).
In most cases (68%), the cause of pericarditis was
unknown (Table 2). Previous pericardiotomy and mediasti-
nal irradiation each accounted for 9%.
3.6. Other pericardial disorders (Group 5)
3.6.1. Clinical features
Thirty-two patients had pericardial resection for causes
unrelated to primary pericardial disease (Table 1). Twelve
patients had surgery to repair congenital cardiac anoma-
lies, during which excessive parietal pericardium was
also removed. For seven patients with clinically suspect-
ed primary pericardial neoplasms, surgery ruled out
their presence. The other 13 patients are described in
Table 2. A partial pericardiectomy was performed in
44% (Table 3).
3.6.2. Pathologic features
The maximal pericardial thickness ranged from 1 to 6 mm
(mean, 3), excluding two cases with oblique tissue orienta-
tion on the slide. For patients with congenital heart disease,
the thickness was only 1 –3 mm (mean, 2). Chronic lym-
phoplasmacytic inflammation was present in 66% and
included six cases with coexistent acute neutrophilic inflam-
mation (Table 4). A pericardial caseating granuloma without
 K.Y. Oh et al. / Cardiovascular Pathology 10 (2001) 157–168 163

Fig. 2. Photomicrographs from a patient with pericardial effusion. (A) Low-power view of moderately thickened and fibrotic pericardium, with fibrin along the
inner surface and inflammatory infiltrates near the outer surface. (B – D) Inflammation along the outer border of the pericardium (B), showing both a chronic
lymphoplasmacytic infiltrate with a germinal center (C) and an acute neutrophilic infiltrate (D).

identifiable organisms was observed in a patient with
invasive pulmonary aspergillosis.
4. Discussion
Much has been written about the clinical features,
causes, treatment, and operative results of pericardial
diseases [3 –8]. However, little has been published con-
cerning the pathology of surgically resected tissues [9– 15],
and only one consecutive series of all pericardial resections
(35 patients) has been reported [1]. The current investiga-
tion uniquely reviewed the pathology of the parietal
pericardium in a large number (344 specimens) of recent
cases from a single institution.
As in other studies, pericardial operations in the present
study were performed for constriction, neoplasms, effusions,
pericarditis, or other disorders, and the surgical procedures
included radical, subtotal, or partial pericardiectomy and
pericardial window, resection (of neoplasms), or biopsy.
Patients ranged in age from 1 to 87 years (mean, 55), and
each of the clinical categories included children. The most
commonly performed procedure was a radical pericardiec-
tomy for constriction or effusion. For the microscopic
evaluation of non-neoplastic pericardial disorders, four or
more representative pieces were usually obtained, decal-
cified if necessary, embedded and cut on edge, and stained
with hematoxylin – eosin.
4.1. Pericardial constriction
4.1.1. Clinical features
Pericardial constriction comprised the largest group
(42%) in the present investigation. Similarly, in other
studies from North America and Europe, constric-
tion represented 25 – 44% of all pericardial operations
[1, 16– 18]. Constriction accounted for 79% of the peri-
cardial excisions in Turkey, where tuberculosis is still
prevalent [4].
Although pericardial constriction usually affects adults,
the age range is broad and includes children. There is a
notable male preponderance, as reflected by a male-to-
female ratio of 3:1 in the current study and 2:1 –3:1 in
other reports [2,9,19 – 23].
164 K.Y. Oh et al. / Cardiovascular Pathology 10 (2001) 157–168

Fig. 3. Photomicrographs from patients with chronic or recurrent pericarditis. (A) Pericardium thickened by edema and neovascularization, with minimal
inflammation, from a patient treated with corticosteroids. (B) Granulation tissue with clumps of residual compact fibrin. (C,D) Chronic lymphoplasmacytic
infiltrates within fibrotic pericardium (C) and within edematous pericardium (D).

4.1.2. Pathologic features
In the current study, the pericardial thickness ranged from
1 to 17 mm (mean, 4). Thickening was due primarily to
fibrosis, and calcification was grossly visible in only 28% of
the cases. Inflammation, when present, was mild and of
chronic lymphoplasmacytic type in 79%. These general
morphologic findings are similar to those described in other
studies of pericardial constriction [1,9 –11,13,24]. Pericar-
dial neovascularization and mesothelial pseudocysts have
also been described; both were identified in the current
study, but were not quantitated.
Agarwal and Chopra [9] described two microscopic
patterns. One was characterized by dense fibrosis, lympho-
plasmacytic infiltrates, neovascularization, mesothelial
pseudocysts, and calcium or bone formation, and the other
consisted primarily of dense fibrosis with prominent gran-
ulomas and neovascularization. The granulomatous pattern
was often associated with tuberculosis. Only the lympho-
plasmacytic pattern was encountered in the current study.
Interestingly, 4% of the cases in the present study showed
no fibrosis, calcification, or thickening — an observation
also reported by others [7]. Thus, symptomatic pericardial
constriction can occur in the setting of a noncalcified and
nonthickened pericardium, a fact that should be borne in
mind when evaluating patients preoperatively. Conversely,
since patients with pericardial neoplasms, pericardial effu-
sions, or pericarditis also commonly have appreciable
thickening, not all patients with a thickened pericardium
will have features of constriction.
4.1.3. Causes of constriction
In most cases, the cause of chronic constriction cannot be
determined. Idiopathic disease accounted for 49% of the
cases in the present study and 33 – 83% of the cases in other
series [2,15,19,22]. Though speculative, viral pericarditis is
considered the most likely cause of idiopathic constriction.
Iatrogenic disease is currently the most common known
cause of pericardial constriction and is usually the result of
prior cardiac surgery or mediastinal irradiation. It develops in
0.3% of all patients undergoing cardiac surgery [25]. Con-
striction was the result of previous pericardiotomy in 30% of
the current patients. It accounted for 18% of the cases
 K.Y. Oh et al. / Cardiovascular Pathology 10 (2001) 157–168 165

reviewed by Ling et al. [2] and for 11% of those reported by
Cameron et al. [22] including 29% of their patients who
presented after 1980. The reported time interval between
cardiac surgery and a diagnosis of postoperative pericardial
constriction has ranged from 2 weeks to 21 years (mean,
2 years) [19,25]. Multiple pathogenetic theories have been
proposed, including the formation of adhesions due to organ-
ization of fibrinous exudates or pericardial blood, the use of
povidone or other antiseptic solutions in the pericardial space,
or simply pericardial trauma during the operation [26]. Of the
52 patients in the current study with constriction and a history
of prior cardiac surgery, 14 also had symptoms of the
postpericardiotomy syndrome, another condition that may
predispose patients to develop constriction [25,27,28].
Acute pericarditis with an effusion is often a precursor to
constriction [7]. In contrast, recurrent pericarditis occurs less
frequently and rarely proceeds to constriction, although
cases have been observed. Among patients with constric-
tion, a previous history of acute pericarditis was docu-
mented in 6% of the cases reported by Cameron et al.
[22], 16% of those by Ling et al. [2], and 17% of those in
the current investigation. It should be emphasized, however,
that the majority of patients in each study had not had
pericarditis. Other causes of pericardial constriction include
infections (tuberculosis, bacteria, fungi, viruses, and para-
sites), autoimmune diseases (systemic lupus erythematosus,
rheumatoid arthritis, and Dressler’s syndrome), neoplasms
(especially lymphomas, carcinomas of the lung and breast,
and mesotheliomas), drugs (such as the ergot alkaloids), and
miscellaneous disorders (uremia, sarcoidosis, amyloidosis,
asbestosis, trauma, and chylopericardium) [2,3,19,22].
Interestingly, the most prevalent causes of constriction
have changed appreciably during the past century. Tuber-
culosis, though once a common cause in Asia, Europe, and
North America, has steadily decreased in frequency (Table 6)
[2,9,11,16,17,19 –23,29 – 32]. There were no cases of tuber-
culosis in the current study, from 1993 to 1999. On a
worldwide basis, however, tuberculosis is still a relatively
frequent cause of pericarditis and constriction [33].
4.2. Pericardial neoplasms and cysts
4.2.1. Clinical and pathologic features
Among various large studies, the pericardium has shown
diverse neoplastic involvement. Nonetheless, carcinomas of
the lung and breast and lymphomas were the three most
commonly encountered tumors in our investigation and in
others (Table 7) [34 – 41]. Although melanoma frequently
metastasizes to the heart, most patients also have wide-
spread extracardiac metastases that preclude cardiac surgery.
Thus, there were no examples of pericardial melanoma in
the current surgical study.
Effusions occurred in 7 of our 96 patients, but the 3 who
underwent pericardiocentesis preoperatively had no malig-
nancy identified cytologically. This is somewhat unusual, as
the reported specificity of cytologic analysis has ranged
from 73% to 93% [42,43].
Pericardial mesotheliomas represent fewer than 1% of all
malignant mesotheliomas and may produce arrhythmias,
compression syndromes, or pericardial constriction [34].
Both cases in the current study produced symptoms of cardiac
tamponade. One was diagnosed as effusive – constrictive
disease by echocardiography, and the other as possible
constrictive pericarditis.
It is important to emphasize that patients with underlying
malignancies may have pericardial disease due to non-

Table 6
Frequency of pericardial constriction due to tuberculosis (TB) by region and year in 15 surgical studies
Reference (study, by continent) Country Time span Pt. no. % TB
Asia
[21] India 1954 – 1985 118 61
[9] India 1960 – 1976 86 38
[4] Turkey 1983 – 1993 105 38
[30] Japan 1952 – 1976 57 14

Europe
[20] Denmark 1953 – 1983 34 79
[31] France 1979 – 1989 84 12
[29] Ireland 1958 – 1983 32 9
[19] Germany 1970 – 1990 71 4

North America
[16] USA (TN) 1930 – 1971 45 62
[11] USA (OH) 1930 – 1950 61 28
[32] USA (CA) 1955 – 1982 31 19
[17] USA (GA) 1974 – 1980 26 8
[23] USA (MN) 1936 – 1982 231 6
[22] USA (CA) 1970 – 1985 95 2
[2] USA (MN) 1985 – 1995 133 1
Current study USA (MN) 1993 – 1999 143 0
Pt. no. = number of patients; CA = California; GA = Georgia; MN = Minnesota; OH = Ohio; TN = Tennessee; USA = United States of America.
166 K.Y. Oh et al. / Cardiovascular Pathology 10 (2001) 157–168
Table 7
Three most common sites of primary malignancies among 798 cases of metastatic involvement of the pericardium from seven autopsy or surgical series
Reference Carcinoma of lung
[35] 8 7
[41] 52
[39] 10
[36] 66
[38] 32
[34] 80
Current studya 16
Total
Number 264
Percentage 33
a
Includes only the 43 cases with pericardial involvement (see Table 5).
neoplastic causes. Pericardial effusions or constriction may
be a consequence of mediastinal irradiation, infections,
drugs, or idiopathic pericarditis [37]. They may cause
symptoms alone or in various combinations, with or without
pericardial metastases.
4.3. Pericardial effusion
4.3.1. Clinical features
This complex category includes isolated effusions, con-
striction or neoplasms with an effusion, and effusive –
constrictive disease. Constriction with an effusion, affecting
23% of the patients in the current study, results from
loculated fluid that produces constrictive hemodynamics
[7]. In contrast, effusive– constrictive pericarditis, involving
10% of the current patients with an effusion, is characterized
by constriction by the epicardium and by a tense pericardial
effusion. Its diagnosis relies on both hemodynamic and
clinical findings [3].
4.3.2. Pathologic features
Other than for patients with malignancy, irradiation, or
uremia, there are few descriptions of the pericardial histol-
ogy associated with effusions. In an older study from the
Mayo Clinic, Wychulis et al. [44] described the microscopy
from 26 patients who had undergone surgery for effusions
or recurrent pericarditis; the pericardium was normal or only
mildly fibrotic in 18 and showed pericarditis with chronic
lymphoplasmacytic inflammation in 8, among whom 2 had
tuberculosis. Olsen et al. [40] found acute and chronic
inflammation in 76% of patients with benign effusions
and in 77% of those with idiopathic effusions. In the present
study, specimens showed acute or chronic inflammation in
90%, fibrosis in 83%, and fibrin deposition in 65%. It is not
surprising that fibrosis is associated with both effusions and
constriction, since effusion may represent a stage in the
development of constriction [44].
4.3.3. Causes of effusions
Idiopathic disease accounted for 30% of the cases in the
present study and 13– 39% in other large surgical series
Carcinoma of breast Lymphoma Other primary site Total
2 5 22
35 38 64 189
6 3 9 28
34 24 93 217
8 2 41 83
61 13 62 216
4 9 14 43
155 91 288 798
19 11 36 100
[40,45 –47]. The most common known cause was neoplastic
disease, affecting 23% of the 40 patients in the current
investigation and 33 – 50% in other series [40,45 – 47].
Among our nine patients with effusions and a neoplasm in
adjacent structures, neither biopsy nor pericardiectomy had
revealed the malignancy in pericardial tissues, and only two
patients had malignant effusions by pericardiocentesis. Sim-
ilar discrepancies between biopsy and cytology have been
reported in 30– 58% of such cases [45,48,49].
Radiation-induced effusions should be distinguished
from malignant effusions. Radiation injury is thought to
progress from acute pericarditis to effusion and then to
constriction, often with many intervening asymptomatic
years [14,50,51]. Of the 15 patients undergoing operation
for pericardial effusions reported by Piehler et al. [47],
features of constriction were present in only 40% overall
but in all 3 patients with a history of mediastinal irradiation.
Uremia caused an effusion in 2% of the current cases and
in 8– 20% in three series of pericardial windows for effu-
sions [45,46,49]. Other causes of effusions for which surgery
may be performed include infections, autoimmune connec-
tive tissue diseases, trauma, sarcoidosis, iatrogenic perfora-
tion during pacemaker placement, and other rare disorders.
4.4. Pericarditis
4.4.1. Clinical features
This category includes both acute pericarditis and relaps-
ing or recurrent pericarditis. An episode of acute pericarditis
will become recurrent in 15– 32% of cases [7,12]. Patients
with pericarditis are frequently treated with nonsteroidal
anti-inflammatory agents, with some relief of symptoms, but
often require long-term treatment with corticosteroids. In the
current study, 18 of the 23 patients with idiopathic recurrent
pericarditis were steroid-dependent. Indications for pericar-
diectomy include unresponsiveness to therapy and intract-
able or disabling pain [12].
Pericarditis tends to affect adults, but may occur in
children and adolescents, and has a male predilection.
Among 215 patients in two large series, ages ranged from
3 to 81 years (mean, 42), and 66% were male [6,44,52].
 K.Y. Oh et al. / Cardiovascular Pathology 10 (2001) 157–168
Similarly, in the current study, ages ranged from 11 to 81
years (mean, 47), and 55% were male.
4.4.2. Pathologic features
Although histopathologic descriptions of hemorrhagic
and purulent pericarditis are plentiful, those of acute or
recurrent noninfectious pericarditis are sparse. Kluge and
Hall [13] described smoldering pericarditis with irregular
mesothelial destruction, and Mambo [1] reported nonspe-
cific chronic fibrous pericarditis with layers of fibrosis and
inflammation and a denuded mesothelium. In 11 patients
with recurrent pericarditis reported by Fowler [12], 5
showed fibrosis with adhesions, 3 had only mild fibrosis,
2 exhibited fibrinous exudates, and 1 had inflammation
without fibrosis. Radiation-induced acute fibrinous pericar-
ditis may also later become fibrotic [51].
In the current study, although all patients had acute or
recurrent pericarditis clinically, inflammation was absent
microscopically in 18% (and in 25% when the two cases
of infectious pericarditis were excluded) and was of only
mild degree in 72% of the noninfected cases. This was
attributed to the effects of preoperative treatment with
steroids. The relative paucity of fibrin, hemosiderin, and
granulation tissue is also understandable. Thus, it should be
emphasized that previous therapy may appreciably affect the
microscopic appearance.
4.4.3. Causes of pericarditis
The disease was idiopathic in 68% of the current cases
and in 38 – 86% of patients in other series [52 –54]. Prior
pericardiotomy and mediastinal irradiation each accounted
for 9% of the current cases. Epidemics of Coxsackie B and
other viruses have been responsible for episodic increases in
the incidence of pericarditis. Tuberculosis may also cause
acute pericarditis [33], although the current study contained
no such cases. Additional causes of pericarditis that may
lead to surgical intervention include other infections, auto-
immune connective tissue diseases, uremia, neoplasms, and
other rare disorders [6,52,55].
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