Edward Bernard
Lubat, MD A. Birnbaum,
#{149} Alec
MD
J. Megibow,
MD
#{149} Morton
A. Bosniak,
#{149} Emil MD
J. Balthazar,
MD
#{149} Alec
Extrapulmonary Pneumocystis in AIDS: CT Findings’ Clinical
tomographic cases of extrapulmonary Pneumocystis carinii infection in patients with acquired immunodeficiency syndrome (AIDS) were reviewed. Proved sites of involvement included the spleen (n = 2), bone marrow (n i), liver (n = i), and penitoneal and pleural fluid (n = i). CT findings included focal low-attenuation splenic lesions that became progressively calcified in rimlike or punctate fashion; punctate calcifications in the liver, renal cortices, and adrenal glands; calcification of lymph nodes; and pleural and peritoneal effusions with subsequent calcifications of the pleural and peritoneal surfaces. Although rare both before and since the onset of the AIDS epidemic, extrapulmonary P carinii infection in AIDS patients has been reported with increasing frequency in recent years, and more cases with radiologic manifestations should be expected. (CT)
and
findings
computed in three
P
NEUMOCYSTIS
the
most
carinii pneumonia common opportunistic
with
increasing
terms: Abdomen, CT, 70.1211 #{149} Abdomen, infection, 70.2075 #{149} Acquired immunodeficiency syndrome (AIDS) #{149} Adrenal gland, diseases, 86.81 #{149} Kidney. calcification, 81.81 #{149} Kidney, infection, 81.2075 #{149} Liver, calcification, 761.81 #{149} Lymphatic system. infection, 99.20 #{149} Peritoneum, calcification, 791.81 #{149} Pleura, diseases, 66.81 #{149} Spleen, diseases, 775.81 Radiology
1990;
174:157-160
frequency
in
RSNA.
1990
lesions
with
lower
attenuation
than
that of contrast material-enhanced splenic parenchyma and measuring from several millimeters to 8 cm in diameter (Fig i). Attenuation measurements
of the
lesions
ranged
from
in all
proved
fection
seen
December
METHODS
and radiobogic in three patients extrapulmonary P carinii inat our institution between
1988 and June
1989.
The three patients were homosexual men, 31, 43, and 54 years old. All were seropositive for antibodies to the human immunodeficiency
treated period
virus.
treated
received
All
with azidothymidine ranging from 4 weeks
prophylactic
being
(AZT) for a to 8 months.
had been
for P carinii
were
previously
pneumonia
and
treatment
had
with
aerosolized pentamidine; the third patient had no respiratory symptoms and had never undergone bronchoscopy. Symptoms at the time of the hospital admission during which the diagnosis of cxtrapuimonary P carinii infection was made were abdominal pain and weight loss in one patient; ascites, chest discomfort, and lower extremity edema in one; and only cough (due to bronchoscopicably proved P carinii pneumonia) in the third; all three were febrile.
was performed
in
sis,
EL.
renal glands in one, and the peritoneal and pleural cavities in one. Initial CT scans in each patient demonstrated multiple focal splenic
with
AND
to
C
RESULTS
Clinical, laboratory, findings were reviewed
PATIENTS
Departments of Radiology (EL., B.A.B., M.A.B.) and Medicine (A.S.G.), Bellevue Hospital and New York Univemsity Medical Center, 550 First Ave. New York, NY 10016. Received August 17, 1989; accepted September 1 1 . Address reprint requests
the
E.J.B.,
Infection
approximately iO to 50 HU. In one patient, the largest lesions initially contained central calcifications. One spleen was enlarged. Follow-up scans
CT of the abdomen
‘From
#{149}
Abnormal CT findings were present in the spleen in all three patients, the kidneys in two, the lymph nodes in two, the liver in one, the ad-
each patient prior to pathologic documentation of extrapulmonary P carinii infection. Repeat CT scans were also obtamed in each, at an interval ranging from 1 to 3 months. Diagnosis of extrapubmonary P carinii infection was accomplished by means of fine-needle aspiration of the liver and/or spleen in two patients and by thoracente-
A.J.M.,
MD
is
recent years, but radiologic findings have, to our knowledge, not yet been reported. We add three such patients to the literature and describe the computed tomographic (CT) findings in each.
Two of the patients Index
carinli
infection in patients with acquired immunodeficiency syndrome (AIDS) (i), recognized in the earliest reports of the disease in i98i (2,3). Extrapulmonary involvement by P carinii in patients with AIDS has been documented
S. Goldenberg,
paracentesis,
in one.
and
bone
marrow
biopsy
patients
demonstrated
a de-
crease in size of these lesions and development of rim calcification and! or resolution of the low-attenuation foci and neplacement by punctate calcifications
On
(Fig
the
patients
2).
follow-up
scans
demonstrated
only,
two
calcification
of
multiple lymph nodes, the peniportal nodes in one and the peniportal, lessen omental, netnoperitoneal, and netnocnural nodes in the other (Figs 2b, 3). These
scans
also
demonstrated
punctate calcifications in the renal cortices (Fig 3). In one patient, pleural effusions and a large amount of ascites were present on initial images (Figs ib, 4a); repeat scans 3 months later showed resolution of the ascites, diminution and small
and
of the pleural caicifications
peritoneal
surfaces
effusions, of the pleural
(Fig
4b).
This
patient’s initial scan also showed possible small, low-attenuation lesions in the adrenal glands (Fig ib), with
Abbreviations: ficiency syndrome.
AIDS AZT
acquired immunodeazidothymidine.
157
subsequent calcification (Fig 2b). One patient had several punctate hepatic calcifications at initial CT; follow-up scans demonstrated a marked increase in the number of these calcifications. At the time of acquisition of the follow-up scans in this patient, plain radiognaphs of the abdomen also demonstrated the punctate calcifications in the liver and spleen. Fine-needle aspiration of the spleen was performed in two patients; one demonstrated P carinii, the other P carinii and Candida organisms. Aspiration of the liver in the patient with hepatic calcifications and of the ascitic and pleural fluids in the patient with ascites and effusions were positive for P carinii. Bone marrow biopsy specimens in the latter patient also contained P carinii.
DISCUSSION 28 cases of extnapulmonary infection reported in the medical literature, i4 were not associated with AIDS (4-14). Of these, seven were associated with primary Of
the
P carinii
immunodeficiency
disorders
(5,6,8-
with immunodeficiency secondary to underlying malignancy or prior renal transplantation (6,7,i2,i3), and two with no undenlying disease (4,6). All patients had pulmonary involvement by P carinii prior to on at the time of diagnosis of extrapulmonary disease. The most common sites of extrapulmonary involvement were lymph nodes (n iO), suggesting a primarily lymphatic mode of dissemination. Spread to other sites of the neticuloendothelial system, namely spleen (n 7), bone i i,i4),
marrow occurred.
five
(n Three
5), and liven (n 3), also of the 14 non-AIDS
patients had involvement outside the reticuloendothelial system (7,iO,i i), indicating a hematogenous route of spread as well; organs involved included kidneys, pancreas, pemicardium, heart, thymic capsule, thymus, and the gastrointestinal tract. Fourteen AIDS patients with extrapulmonary P carinii infection were previously described (i5-27). Ten of these patients had involvement of ongans outside the reticuloendothelial system (i5-i8,2i-24,27), including kidneys, adrenal glands, heart, netina, skin of the external auditory canals, thyroid, gastrointestinal tract, and pleura. Eight reports mention neticuloendothelial involvement (i6,i8-2i,23,25,26), including lymph nodes (n = 4), spleen (n 4), bone marrow
(n
158 #{149} Radiology
5), and
liven
(n
3). Al-
a. Figure
b.
1. CT scans of the upper abdomen in two patients. (a) Multiple round, bow-attenuation splenic lesions are seen. One contains calcifications (arrow). (b) Multiple smaller, lowattenuation lesions seen in the spleen of a different patient. Note suggestion of a bow-attenuation
focus
though
in the
this
right
adrenal
distribution
gland
(arrowhead).
appears
in the
somewhat non-AIDS ed that, non-AIDS
different from that in the patients, it should be notunlike the determinations in patients, the results from most (n = 9) of the AIDS patients were obtained without autopsy and that the complete extent of dissemination cases.
is therefore Nevertheless,
not clear in these in those patients with extrapulmonary P carinii infection, it seems that hematogenous dissemination is more common in the AIDS population.
The
three
patients
we studied
had
pathologically
proved involvement of the spleen (n = 2), bone marrow (n = i), liven (n = i), and penitoneal and pleural fluid (n i). Radiologically, the spleen was abnormal in all three
patients,
the
nodes
in two,
kidneys the
and iiver
lymph
in one,
the
ad-
renal glands in one, and the penitoneal and pleural surfaces in one. Radiologic findings were mentioned in only
one
previous
report,
ed that a CT scan cal splenic defects, ses” sions
which
demonstrated suggesting
stat-
“foabsces-
(i8). Such low-attenuation were seen in the spleen
leon
the
initial CT scan in our three patients and possibly in the adrenal glands one. On follow-up CT scans, these sions
became
smaller
on disappeared
and became progressively calcified, either in rimlike on punctate fashion. The patient with penitoneal and pleural involvement demonstrated similar
evolution, and effusions
progressing from to calcification
ascites of the pemitoneal and pleural faces. Two patients showed creasing cations nodes, findings
evidence in these
sunan in-
number of punctate calcifiin the kidneys and lymph and one patient had the same in the liver. There was no
of low-attenuation organs
similar
lesions to those
Ascites
in le-
Given
is present.
spleen.
the
finding
of calcification
in all our patients, it is of interest that gross calcification was noted both histologically and radiologically in the small bowel of one of the pneviously described AIDS patients (23), and four of the non-AIDS case meports include histologic evidence of calcification in the lungs, spleen, and/or lymph nodes involved by P carinji (6,8,iO). The authors of one of these latter reports suggest that cxtensive necrosis and calcification in the lungs, atypical for P carinii pneumonia, may lead to increased host phagocytic activity, including phagocytosis of live organisms, with resultant extrapulmonary dissemination (10). However, why such necrosis and calcification should develop in certain patients is not addressed, and other case reports of dissemination describe more typical pathologic lung involvement (ii,2i). It should be noted that in the 14 previous AIDS patients with extrapulmonary P carinii infection, five never had clinical evidence of pulmonary P carmu infection (8,i i-i3). The same was true in one of our three cases, but pathologic proof of the absence of pulmonary infection is lacking in all these cases. Given the prevalence of P carinii pneumonia in immunodeficient patients both before and since the onset
of the AIDS epidemic, extrapulmonany dissemination has been mane. Proposed explanations for this include as yet unknown local that are beneficial carinii cytosis
(21), the of these
factors to the
infrequency organisms,
fact that the organisms em with anastomosing making blood
access vessels
to the difficult
in the growth
lung of P
of phagoand the
clump togethmembranes, lymphatic on (iO). However,
January
1990
2a.
2b.
Figures
2, 3.
(2a)
has developed attenuation
Same
patient
as in Figure
rim calcification splenic
lesions
(arrow).
3.
Follow-up
(2b) Same
by punctate
now), the renal cortex (arrowhead), roperitoneal lymph nodes (arrow)
ia.
CT scan
patient
calcifications.
obtained
as in Figure
Similar
1 month
lb. Follow-up
shows
that
the
splenic
lesions
are
smaller.
One
3 months later shows replacement of the loware present in portal and lesser omental lymph nodes (curved anarrow). (3) Same patient as in 2b. CT scan shows calcification of ret-
calcifications
and the right adrenal gland and renal cortex (arrowhead).
later
(straight
CT scan
of P carinii in AIDS patients will be seen with increasing frequency in the future. Disseminated Kaposi sarcoma, lymphoma, and Candida microabscesses may cause low-attenuation lesions in the spleen and liver similar
to those
in the
spleens
of our
patients (prior to calcification), and they should be considered in the differential diagnosis. However, we do not know of any cases in which these or other entities progressed to calcification as in our patients. U References a.
1.
Centers quired United
2.
Centers
b.
Figure 4. (a) Initial CT scan (b) Follow-up scan 3 months cification along pelvic panietal
it is interesting ously reported
that cases
of pelvis
later
in same
demonstrates
penitoneal
stitution of patients
has
served a large with AIDS since
Presently,
one
can
only
in-
scnibed
in the
in the
other
solized
literature
therapy
AZT
(26,27).
is not
12 reported
Pneumocysf
MMWR
is
1981;
istration.
Perhaps
dissemination of our patients,
this
literature Again,
cannot
dissemination, in the literature
explain
Masur H, Michelis MA, Greene JB, et a!. An outbreak of community-acquired Pneumocystis carinii pneumonia: initial manifestation of cellular immune dysfunction. N EngI J Med 1981; 305:1431-
4.
Anderson
S.
cysfis carinii pneumonia in an adult. Am Clin Pathol 1960; 34:365-370. Jarnum 5, Rasmussen EF, Ohlsen AS, Sor-
Aero6.
7.
to
of the organas well as
(26,27), received this treatment
8.
9.
extrapulmonary
since i2 of the do not mention
reports aero-
solized pentamidine treatment, and one of our patients also never meceived this treatment. It seems likely that dissemination
Barrie
HJ.
Fatal
Pneumo-
AWS. Generalized Pneumocystis infection with severe idiopathic hypoproteinemia. Ann Intern Med 1968; 68:138-145. Barnett RN, Hull JG, Vontel V. Schwarz J. Pneumocystis carinii in lymph nodes and spleen. Arch Pathol 1969; 88:175-180. Awen CF. Baltzan MA. Systemic dissemination of Pneumocystis carinii pneumonia. Can Med Assoc J 1971; 104:809-812. carinii
is now
contributes
CD,
ensen
mentioned
which
systemic ism. Two
alone
Control.
Los Angeles.
3.
de-
How-
cases.
pentamidine,
in the therapy.
Disease
1438.
of
being used for treatment and prophylaxis of P carinii pneumonia (28), results in lower systemic pentamidine levels than intravenous admin-
speculate
for
pneumonia:
cal-
ac-
30:250-252.
new modes three patients two patients
this
1
of
It is particularly
two
174 #{149} Number
ascites.
development
tempting
is
Volume
and
immunosuppmessed.
ever,
number the nec-
of P carinii
lb demonstrates
ascites
(arrow).
being recognized with increasing frequency. The increasing number of documented AIDS cases and the increasing life span of these patients may be at least partly responsible. A change in P carinii virulence factors must also be considered. Theme is no evidence that these patients are more
dissemination
of
to implicate AIDS treatment. Our received AZT, as did
ognition of the disease, our three cases have all been diagnosed since December i988. (We have also seen two additional cases during the same interval with similar radiologic findings in the spleen but without pathologic proof.) as to why
as in Figure
resolution
surfaces
of the 14 previof extrapulmon-
any dissemination in patients with AIDS, all but one have appeared since 1987. In addition, while our
patient
for Disease Control. Update: immunodeficiency syndromeStates. MMWR 1986; 35:757-760.
10. 1 1.
LeGolvan
carinii
Pathol 12.
DP,
Heidelberger
KP.
Dissemi-
nated granulomatous Pneumocystis carinii pneumonia. Arch Pathol 1973; 95:344-348. Livingstone CS. Pneumocystis carinli pneumonia occurring in a family with agammaglobulinemia. Can Med Assoc J 1964; 90:1223-1225. Burke BA, Good RA. Pneumocystis carinii infection. Medicine 1973; 2:23-1. Rahimi SA. Disseminated Pneumocystis in
thymic
1974;
Price RA, Pneumocystis
alymphoplasia.
Arch
97:162-165.
Hughes carinhi
WT.
Histopathology
infestation
and
Radiology
of
infec-
#{149} 159
tion
in malignant disease in childhood. Pathol 1974; 5:737-752. Rossi JF, Dubois A, Bengler C, et al. Pneumocystis carinii in bone marrow (better). Ann Intern Med 1985; 102:868. Henderson DW, Humeniuk V, Meadows R, et al. Pneumocysfis carinhi pneumonia with vascular and lymph node involvement. Pathology 1974; 6:235-241. Kwok S, O’Donnell JJ, Wood IS. Retinal cotton wool spots in a patient with Pneumocystis carinii infection (letter). N EngI Med 1982; 307:184-185. Grimes MM, La Pook JD, Bar MH, Wasserman HS, Dwork A. Disseminated Pneumocystis carinii infection in a patient with
19.
Hum
13.
14.
iS.
16.
acquired 17.
18.
immunodeficiency
syndrome.
Hum Pathol 1987; 18:307-308. Coulman CU, Greene I, Archibald RWR. Cutaneous pneumocystosis. Ann Intern Med i987; 106:396-398. Macher AM, Bardenstein OS, Zimmerman LE, et al. Pneumocystis carinii choroiditis in a male homosexual with AIDS and disseminated pulmonary and extrapulmonary P carinii infection (letter). N Engl Med 1987; 315:1092.
Pilon
VA,
Echols
RM,
Celo
JS, E!mendorf
SL. Disseminated Pneumocystis fection in AIDS (letter). N Eng!
carinii
25.
J Med 26.
1987; 316:1410-1411.
20.
21.
22.
23.
24.
Heyman MR, Rasmussen P. Pneumocystis carinii involvement of the bone marrow in acquired immunodeficiency syndrome. Am J Clin Pathol 1987; 87:780-783. Ungen PD, Rosenblum M, Krown SE. Disseminated Pneumocystis carinhi infection in a patient with acquired immunodeficiency syndrome. Hum Pathol 1989; 19:113-i 16. Gallant
JE,
Enniquez
RE,
Cohen
KL,
GR, Mullen
Poblete
RB,
Rodriguez
MP.
marrow 109:253.
K, Foust
(let-
RT,
Reddy
R, Saldana MJ. Pneumocystis carinii hepatitis in the acquired immunodeficiency syndnome (AIDS). Ann Intern Med 1989; ii0:737-738. 27.
Dyner
TS,
Lang
W,
Busch
DF,
Gordon
PR.
Intravascular
and pleural involvement by Pneumocystis carinii in a patient with the acquired immunodeficiency syndrome (AIDS) (letter). Ann Intern Med 1989; 111:94.
Ham-
mers LW. Pneumocystis carinii thyroiditis. Am J Med 1988; 84:303-306. Carter TR, Cooper PH, Petri WA Jr. Kim CK, Wabzer PD, Guenrant RL. Pneumocystis carinii infection of the small intestine in a patient with acquired immune deficiency syndrome. Am J Clin Pathol 1988; 89:679-683. Breda SD, Gigliotti F, Hammerschlag PE, Schinella R. Pneumocystis carinii in the
MC, Garner
Raviglione
Pneumocysfis carinhi in bone ter). Ann Intern Med 1988;
in-
28.
Masur
H,
Kovacs
JA.
Treatment
phylaxis of Pneumocystis carinii nia. Infect Dis Clin North Am 428.
and
pro-
pneumo1988; 2:419-
temporal bone as a primary manifestation of the acquired immunodeficiency syndrome. Ann Otol Rhinol Laryngol 1988; 97:427-431.
160 . Radiology
January
1990
Lubat, MD A. Birnbaum,
#{149} Alec
MD
J. Megibow,
MD
#{149} Morton
A. Bosniak,
#{149} Emil MD
J. Balthazar,
MD
#{149} Alec
Extrapulmonary Pneumocystis in AIDS: CT Findings’ Clinical
tomographic cases of extrapulmonary Pneumocystis carinii infection in patients with acquired immunodeficiency syndrome (AIDS) were reviewed. Proved sites of involvement included the spleen (n = 2), bone marrow (n i), liver (n = i), and penitoneal and pleural fluid (n = i). CT findings included focal low-attenuation splenic lesions that became progressively calcified in rimlike or punctate fashion; punctate calcifications in the liver, renal cortices, and adrenal glands; calcification of lymph nodes; and pleural and peritoneal effusions with subsequent calcifications of the pleural and peritoneal surfaces. Although rare both before and since the onset of the AIDS epidemic, extrapulmonary P carinii infection in AIDS patients has been reported with increasing frequency in recent years, and more cases with radiologic manifestations should be expected. (CT)
and
findings
computed in three
P
NEUMOCYSTIS
the
most
carinii pneumonia common opportunistic
with
increasing
terms: Abdomen, CT, 70.1211 #{149} Abdomen, infection, 70.2075 #{149} Acquired immunodeficiency syndrome (AIDS) #{149} Adrenal gland, diseases, 86.81 #{149} Kidney. calcification, 81.81 #{149} Kidney, infection, 81.2075 #{149} Liver, calcification, 761.81 #{149} Lymphatic system. infection, 99.20 #{149} Peritoneum, calcification, 791.81 #{149} Pleura, diseases, 66.81 #{149} Spleen, diseases, 775.81 Radiology
1990;
174:157-160
frequency
in
RSNA.
1990
lesions
with
lower
attenuation
than
that of contrast material-enhanced splenic parenchyma and measuring from several millimeters to 8 cm in diameter (Fig i). Attenuation measurements
of the
lesions
ranged
from
in all
proved
fection
seen
December
METHODS
and radiobogic in three patients extrapulmonary P carinii inat our institution between
1988 and June
1989.
The three patients were homosexual men, 31, 43, and 54 years old. All were seropositive for antibodies to the human immunodeficiency
treated period
virus.
treated
received
All
with azidothymidine ranging from 4 weeks
prophylactic
being
(AZT) for a to 8 months.
had been
for P carinii
were
previously
pneumonia
and
treatment
had
with
aerosolized pentamidine; the third patient had no respiratory symptoms and had never undergone bronchoscopy. Symptoms at the time of the hospital admission during which the diagnosis of cxtrapuimonary P carinii infection was made were abdominal pain and weight loss in one patient; ascites, chest discomfort, and lower extremity edema in one; and only cough (due to bronchoscopicably proved P carinii pneumonia) in the third; all three were febrile.
was performed
in
sis,
EL.
renal glands in one, and the peritoneal and pleural cavities in one. Initial CT scans in each patient demonstrated multiple focal splenic
with
AND
to
C
RESULTS
Clinical, laboratory, findings were reviewed
PATIENTS
Departments of Radiology (EL., B.A.B., M.A.B.) and Medicine (A.S.G.), Bellevue Hospital and New York Univemsity Medical Center, 550 First Ave. New York, NY 10016. Received August 17, 1989; accepted September 1 1 . Address reprint requests
the
E.J.B.,
Infection
approximately iO to 50 HU. In one patient, the largest lesions initially contained central calcifications. One spleen was enlarged. Follow-up scans
CT of the abdomen
‘From
#{149}
Abnormal CT findings were present in the spleen in all three patients, the kidneys in two, the lymph nodes in two, the liver in one, the ad-
each patient prior to pathologic documentation of extrapulmonary P carinii infection. Repeat CT scans were also obtamed in each, at an interval ranging from 1 to 3 months. Diagnosis of extrapubmonary P carinii infection was accomplished by means of fine-needle aspiration of the liver and/or spleen in two patients and by thoracente-
A.J.M.,
MD
is
recent years, but radiologic findings have, to our knowledge, not yet been reported. We add three such patients to the literature and describe the computed tomographic (CT) findings in each.
Two of the patients Index
carinli
infection in patients with acquired immunodeficiency syndrome (AIDS) (i), recognized in the earliest reports of the disease in i98i (2,3). Extrapulmonary involvement by P carinii in patients with AIDS has been documented
S. Goldenberg,
paracentesis,
in one.
and
bone
marrow
biopsy
patients
demonstrated
a de-
crease in size of these lesions and development of rim calcification and! or resolution of the low-attenuation foci and neplacement by punctate calcifications
On
(Fig
the
patients
2).
follow-up
scans
demonstrated
only,
two
calcification
of
multiple lymph nodes, the peniportal nodes in one and the peniportal, lessen omental, netnoperitoneal, and netnocnural nodes in the other (Figs 2b, 3). These
scans
also
demonstrated
punctate calcifications in the renal cortices (Fig 3). In one patient, pleural effusions and a large amount of ascites were present on initial images (Figs ib, 4a); repeat scans 3 months later showed resolution of the ascites, diminution and small
and
of the pleural caicifications
peritoneal
surfaces
effusions, of the pleural
(Fig
4b).
This
patient’s initial scan also showed possible small, low-attenuation lesions in the adrenal glands (Fig ib), with
Abbreviations: ficiency syndrome.
AIDS AZT
acquired immunodeazidothymidine.
157
subsequent calcification (Fig 2b). One patient had several punctate hepatic calcifications at initial CT; follow-up scans demonstrated a marked increase in the number of these calcifications. At the time of acquisition of the follow-up scans in this patient, plain radiognaphs of the abdomen also demonstrated the punctate calcifications in the liver and spleen. Fine-needle aspiration of the spleen was performed in two patients; one demonstrated P carinii, the other P carinii and Candida organisms. Aspiration of the liver in the patient with hepatic calcifications and of the ascitic and pleural fluids in the patient with ascites and effusions were positive for P carinii. Bone marrow biopsy specimens in the latter patient also contained P carinii.
DISCUSSION 28 cases of extnapulmonary infection reported in the medical literature, i4 were not associated with AIDS (4-14). Of these, seven were associated with primary Of
the
P carinii
immunodeficiency
disorders
(5,6,8-
with immunodeficiency secondary to underlying malignancy or prior renal transplantation (6,7,i2,i3), and two with no undenlying disease (4,6). All patients had pulmonary involvement by P carinii prior to on at the time of diagnosis of extrapulmonary disease. The most common sites of extrapulmonary involvement were lymph nodes (n iO), suggesting a primarily lymphatic mode of dissemination. Spread to other sites of the neticuloendothelial system, namely spleen (n 7), bone i i,i4),
marrow occurred.
five
(n Three
5), and liven (n 3), also of the 14 non-AIDS
patients had involvement outside the reticuloendothelial system (7,iO,i i), indicating a hematogenous route of spread as well; organs involved included kidneys, pancreas, pemicardium, heart, thymic capsule, thymus, and the gastrointestinal tract. Fourteen AIDS patients with extrapulmonary P carinii infection were previously described (i5-27). Ten of these patients had involvement of ongans outside the reticuloendothelial system (i5-i8,2i-24,27), including kidneys, adrenal glands, heart, netina, skin of the external auditory canals, thyroid, gastrointestinal tract, and pleura. Eight reports mention neticuloendothelial involvement (i6,i8-2i,23,25,26), including lymph nodes (n = 4), spleen (n 4), bone marrow
(n
158 #{149} Radiology
5), and
liven
(n
3). Al-
a. Figure
b.
1. CT scans of the upper abdomen in two patients. (a) Multiple round, bow-attenuation splenic lesions are seen. One contains calcifications (arrow). (b) Multiple smaller, lowattenuation lesions seen in the spleen of a different patient. Note suggestion of a bow-attenuation
focus
though
in the
this
right
adrenal
distribution
gland
(arrowhead).
appears
in the
somewhat non-AIDS ed that, non-AIDS
different from that in the patients, it should be notunlike the determinations in patients, the results from most (n = 9) of the AIDS patients were obtained without autopsy and that the complete extent of dissemination cases.
is therefore Nevertheless,
not clear in these in those patients with extrapulmonary P carinii infection, it seems that hematogenous dissemination is more common in the AIDS population.
The
three
patients
we studied
had
pathologically
proved involvement of the spleen (n = 2), bone marrow (n = i), liven (n = i), and penitoneal and pleural fluid (n i). Radiologically, the spleen was abnormal in all three
patients,
the
nodes
in two,
kidneys the
and iiver
lymph
in one,
the
ad-
renal glands in one, and the penitoneal and pleural surfaces in one. Radiologic findings were mentioned in only
one
previous
report,
ed that a CT scan cal splenic defects, ses” sions
which
demonstrated suggesting
stat-
“foabsces-
(i8). Such low-attenuation were seen in the spleen
leon
the
initial CT scan in our three patients and possibly in the adrenal glands one. On follow-up CT scans, these sions
became
smaller
on disappeared
and became progressively calcified, either in rimlike on punctate fashion. The patient with penitoneal and pleural involvement demonstrated similar
evolution, and effusions
progressing from to calcification
ascites of the pemitoneal and pleural faces. Two patients showed creasing cations nodes, findings
evidence in these
sunan in-
number of punctate calcifiin the kidneys and lymph and one patient had the same in the liver. There was no
of low-attenuation organs
similar
lesions to those
Ascites
in le-
Given
is present.
spleen.
the
finding
of calcification
in all our patients, it is of interest that gross calcification was noted both histologically and radiologically in the small bowel of one of the pneviously described AIDS patients (23), and four of the non-AIDS case meports include histologic evidence of calcification in the lungs, spleen, and/or lymph nodes involved by P carinji (6,8,iO). The authors of one of these latter reports suggest that cxtensive necrosis and calcification in the lungs, atypical for P carinii pneumonia, may lead to increased host phagocytic activity, including phagocytosis of live organisms, with resultant extrapulmonary dissemination (10). However, why such necrosis and calcification should develop in certain patients is not addressed, and other case reports of dissemination describe more typical pathologic lung involvement (ii,2i). It should be noted that in the 14 previous AIDS patients with extrapulmonary P carinii infection, five never had clinical evidence of pulmonary P carmu infection (8,i i-i3). The same was true in one of our three cases, but pathologic proof of the absence of pulmonary infection is lacking in all these cases. Given the prevalence of P carinii pneumonia in immunodeficient patients both before and since the onset
of the AIDS epidemic, extrapulmonany dissemination has been mane. Proposed explanations for this include as yet unknown local that are beneficial carinii cytosis
(21), the of these
factors to the
infrequency organisms,
fact that the organisms em with anastomosing making blood
access vessels
to the difficult
in the growth
lung of P
of phagoand the
clump togethmembranes, lymphatic on (iO). However,
January
1990
2a.
2b.
Figures
2, 3.
(2a)
has developed attenuation
Same
patient
as in Figure
rim calcification splenic
lesions
(arrow).
3.
Follow-up
(2b) Same
by punctate
now), the renal cortex (arrowhead), roperitoneal lymph nodes (arrow)
ia.
CT scan
patient
calcifications.
obtained
as in Figure
Similar
1 month
lb. Follow-up
shows
that
the
splenic
lesions
are
smaller.
One
3 months later shows replacement of the loware present in portal and lesser omental lymph nodes (curved anarrow). (3) Same patient as in 2b. CT scan shows calcification of ret-
calcifications
and the right adrenal gland and renal cortex (arrowhead).
later
(straight
CT scan
of P carinii in AIDS patients will be seen with increasing frequency in the future. Disseminated Kaposi sarcoma, lymphoma, and Candida microabscesses may cause low-attenuation lesions in the spleen and liver similar
to those
in the
spleens
of our
patients (prior to calcification), and they should be considered in the differential diagnosis. However, we do not know of any cases in which these or other entities progressed to calcification as in our patients. U References a.
1.
Centers quired United
2.
Centers
b.
Figure 4. (a) Initial CT scan (b) Follow-up scan 3 months cification along pelvic panietal
it is interesting ously reported
that cases
of pelvis
later
in same
demonstrates
penitoneal
stitution of patients
has
served a large with AIDS since
Presently,
one
can
only
in-
scnibed
in the
in the
other
solized
literature
therapy
AZT
(26,27).
is not
12 reported
Pneumocysf
MMWR
is
1981;
istration.
Perhaps
dissemination of our patients,
this
literature Again,
cannot
dissemination, in the literature
explain
Masur H, Michelis MA, Greene JB, et a!. An outbreak of community-acquired Pneumocystis carinii pneumonia: initial manifestation of cellular immune dysfunction. N EngI J Med 1981; 305:1431-
4.
Anderson
S.
cysfis carinii pneumonia in an adult. Am Clin Pathol 1960; 34:365-370. Jarnum 5, Rasmussen EF, Ohlsen AS, Sor-
Aero6.
7.
to
of the organas well as
(26,27), received this treatment
8.
9.
extrapulmonary
since i2 of the do not mention
reports aero-
solized pentamidine treatment, and one of our patients also never meceived this treatment. It seems likely that dissemination
Barrie
HJ.
Fatal
Pneumo-
AWS. Generalized Pneumocystis infection with severe idiopathic hypoproteinemia. Ann Intern Med 1968; 68:138-145. Barnett RN, Hull JG, Vontel V. Schwarz J. Pneumocystis carinii in lymph nodes and spleen. Arch Pathol 1969; 88:175-180. Awen CF. Baltzan MA. Systemic dissemination of Pneumocystis carinii pneumonia. Can Med Assoc J 1971; 104:809-812. carinii
is now
contributes
CD,
ensen
mentioned
which
systemic ism. Two
alone
Control.
Los Angeles.
3.
de-
How-
cases.
pentamidine,
in the therapy.
Disease
1438.
of
being used for treatment and prophylaxis of P carinii pneumonia (28), results in lower systemic pentamidine levels than intravenous admin-
speculate
for
pneumonia:
cal-
ac-
30:250-252.
new modes three patients two patients
this
1
of
It is particularly
two
174 #{149} Number
ascites.
development
tempting
is
Volume
and
immunosuppmessed.
ever,
number the nec-
of P carinii
lb demonstrates
ascites
(arrow).
being recognized with increasing frequency. The increasing number of documented AIDS cases and the increasing life span of these patients may be at least partly responsible. A change in P carinii virulence factors must also be considered. Theme is no evidence that these patients are more
dissemination
of
to implicate AIDS treatment. Our received AZT, as did
ognition of the disease, our three cases have all been diagnosed since December i988. (We have also seen two additional cases during the same interval with similar radiologic findings in the spleen but without pathologic proof.) as to why
as in Figure
resolution
surfaces
of the 14 previof extrapulmon-
any dissemination in patients with AIDS, all but one have appeared since 1987. In addition, while our
patient
for Disease Control. Update: immunodeficiency syndromeStates. MMWR 1986; 35:757-760.
10. 1 1.
LeGolvan
carinii
Pathol 12.
DP,
Heidelberger
KP.
Dissemi-
nated granulomatous Pneumocystis carinii pneumonia. Arch Pathol 1973; 95:344-348. Livingstone CS. Pneumocystis carinli pneumonia occurring in a family with agammaglobulinemia. Can Med Assoc J 1964; 90:1223-1225. Burke BA, Good RA. Pneumocystis carinii infection. Medicine 1973; 2:23-1. Rahimi SA. Disseminated Pneumocystis in
thymic
1974;
Price RA, Pneumocystis
alymphoplasia.
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Radiology
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in malignant disease in childhood. Pathol 1974; 5:737-752. Rossi JF, Dubois A, Bengler C, et al. Pneumocystis carinii in bone marrow (better). Ann Intern Med 1985; 102:868. Henderson DW, Humeniuk V, Meadows R, et al. Pneumocysfis carinhi pneumonia with vascular and lymph node involvement. Pathology 1974; 6:235-241. Kwok S, O’Donnell JJ, Wood IS. Retinal cotton wool spots in a patient with Pneumocystis carinii infection (letter). N EngI Med 1982; 307:184-185. Grimes MM, La Pook JD, Bar MH, Wasserman HS, Dwork A. Disseminated Pneumocystis carinii infection in a patient with
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Hum
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Hum Pathol 1987; 18:307-308. Coulman CU, Greene I, Archibald RWR. Cutaneous pneumocystosis. Ann Intern Med i987; 106:396-398. Macher AM, Bardenstein OS, Zimmerman LE, et al. Pneumocystis carinii choroiditis in a male homosexual with AIDS and disseminated pulmonary and extrapulmonary P carinii infection (letter). N Engl Med 1987; 315:1092.
Pilon
VA,
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Heyman MR, Rasmussen P. Pneumocystis carinii involvement of the bone marrow in acquired immunodeficiency syndrome. Am J Clin Pathol 1987; 87:780-783. Ungen PD, Rosenblum M, Krown SE. Disseminated Pneumocystis carinhi infection in a patient with acquired immunodeficiency syndrome. Hum Pathol 1989; 19:113-i 16. Gallant
JE,
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GR, Mullen
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K, Foust
(let-
RT,
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R, Saldana MJ. Pneumocystis carinii hepatitis in the acquired immunodeficiency syndnome (AIDS). Ann Intern Med 1989; ii0:737-738. 27.
Dyner
TS,
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Ham-
mers LW. Pneumocystis carinii thyroiditis. Am J Med 1988; 84:303-306. Carter TR, Cooper PH, Petri WA Jr. Kim CK, Wabzer PD, Guenrant RL. Pneumocystis carinii infection of the small intestine in a patient with acquired immune deficiency syndrome. Am J Clin Pathol 1988; 89:679-683. Breda SD, Gigliotti F, Hammerschlag PE, Schinella R. Pneumocystis carinii in the
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160 . Radiology
January
1990
