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27
Visceral Patients
and Nodal Calcification with AIDS-Related Pneumocystis carinhi Infection
D. Randall Radin1 Edward L. Baker2’3 Edward C. Klatt4 Emil J. Balthazar5 R. Brooke Jeffrey, Jr.3 Alec J. Megibow5 Philip W. RaIls1
in
Clinical and radiologic findings in nine patients with AIDS and disseminated Pneumocystis carinii infection were analyzed retrospectively. The diagnosis was confirmed by autopsy (five patients) and by biopsy (two patients). All nine had a history of P. carinll pneumonia. CT showed parenchymal calcifications in the spleen (seven patients), liver (six patients), kidneys (six patients), abdominal lymph nodes (three patients), adrenal glands (two patients), and mediastinal lymph nodes (one patient). Multiple punctate calcifications in the liver, spleen, kidneys, and/or adrenal glands were visible on plain films in three patients. Sonography showed diffuse tiny echogenic foci without shadowing in the liver, spleen, and kidneys. In one patient, CT showed multiple hypodense lesions in the spleen. p. carinil infection should be included in the differential diagnosis when calcifications or focal lesions are detected at one or more extrapulmonary sites in an immunodeficient patient, even if there is no history or evidence of P. carinll pneumonia. 154:27-31,
AJR
January
1990
The spectrum of radiographicfindings caused by Pneumocystis carinii pneumonia is well known. However, the imaging findings of disseminated infection with P. carinll have not been reported. We describe the clinical and radiologic findings in nine
AIDS
visceral
patients
Materials
Received June 16, 1989; September 5, 1989.
accepted
after revision
‘Department of Radiology. University of Southern California School of Medicine, L.A. County/USC Medical Center, 1200 N. State St., Los Angeles, CA 90033-1084. Address reprint requests to 0. A. Radin. 2 Department of Radiology, Pacific Presbyterian Medical
Center,
Department nia, San Francisco,
San Francisco, of Radiology,
were
CA 94120. University
of Califor-
CA 94110.
4Department Medical Center, CA 90033.
of Pathology, 1200 N. State
5Departrnent Medical Center, 10016.
of Radiology, New York University 560 First Ave., New York, NY
0361 -803X/90/1 541-0027 © American Roentgen Ray Society
L.A. County/USC St., Los Angeles,
visible
seen
abnormalities at four
infection
fine-needle two
findings
was
centers
documented
aspiration
patients
evidence
of other
pathologic infection
suggestive
nine
patients
patients
eight of whom
sonograms,
and/or
retrospectively.
by autopsy proof
conditions
sickle were
who
or neoplasm.
of other
men,
in five
associated
of P. carinhi
had
CT scans.
of the
(Fig.
of extrapulmonary
1A)
and
and
nine
patients
visceral
hemochromatosis,
radiologic had
calcifications
mercury
years old, with a 6-month
P.
by percutaneous
Also included
in two patients. clinical
pneumonia
and New York between
The diagnosis
similar with
a history
patients
or kidney
had None
cell disease,
24-38
with
San Francisco,
in Los Angeles,
of the liver and spleen
without
such as histoplasmosis, trast infusion. The
infection,
on plain films,
in nine AIDS
medical
May 1988 and June 1989 were analyzed carinii
P. carinll
extrapulmonary
calcification
and Methods
The radiologic who
with
and nodal
findings clinical
were and
no
or autopsy
or hyperdensity,
injection,
and Thoro-
to 2-year history of AIDS.
AIDS
risk factors included homosexuality (seven patients), IV drug use (one patient), and remote blood transfusion (one patient). All nine were seropositive for antibodies to the human
immunodeficiency virus and were treated with of recurrent episodes of P. carinll pneumonia. azidodeoxythymidine (AZT). CT of the abdomen was performed in eight Abdominal sonography was performed in two radiographs. Medical records of each patient results,
and follow-up.
maintenance aerosolized pentamidine because Eight of the nine patients also were receiving patients. One patient also had CT of the chest. patients, and three patients had plain abdominal were reviewed for clinical findings, laboratory
RADIN
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28
Fig. 1.-Case
ET AL.
AJR:154,
1990
9.
A, Photomicrograph of calcified granuloma in liver shows scattered Pneumocystis carinii organisms within granuloma silver nitrate, x200). Inset (lower left) shows organisms in detail (x400). B, Radiograph of upper abdomen shows multiple calcifications in liver, spleen, kidneys, and adrenal glands.
Results The CT findings and follow-up in the nine patients are listed in Table 1 . CT showed calcifications in the spleen (seven patients), liver (six patients), kidneys (six patients), abdominal lymph nodes (three patients), and adrenal glands (two patients). In some cases, calcifications that were obvious on unenhanced CT were barely perceptible after enhancement with IV contrast material. The appearance ranged from several scattered punctate foci (Figs. 2 and 3A) to innumerable calcifications throughout the organ (Fig. 4A). In two patients, the spleen was almost completely calcified (Figs. 2 and 3A). In
six of the seven patients
with visceral calcifications,
the spleen
showed the greatest degree of involvement. Renal calcifications were confined to the cortex, with sparing of the medulla (Fig. 4A). Diffuse punctate calcifications in the liver, spleen, kidneys, and/or adrenal glands were visible on plain films in three patients, one of whom did not undergo CT (Fig. 1 B). Sonography showed diffuse tiny echogenic foci without shadowing in the liver, spleen, and kidneys (Figs. 3B and 3C). In the patient with the densest splenic calcification, the ultra-
sonic beam was completely spleen.
January
In the one
were seen in multiple
patient
reflected who
at the surface
had chest
hilar and mediastinal
of the
CT, calcifications
nodes (Fig. 4B). In
one patient, the only CT abnormality was an enlarged spleen containing multiple hypodense noncalcified masses (Fig. 5). The only abdominal symptom was mild or moderate pain in
six of the nine patients.
Abnormal
laboratory
values
in the
nine patients included mild to moderate elevation in the serum alkaline phosphatase level (seven patients), mild elevation in the serum transaminase level (four patients), and mild elevation in the serum creatinine level (one patient).
Discussion Before the AIDS epidemic, only 13 cases of extrapulmonary infection by P. carinii were reported [1]. Ten of the 13 patients
(Grocott-Gomori
methenamine-
had primary or secondary immunodeficiency. Lymph nodes and spleen were the most common sites of involvement. Only two patients had widely disseminated P. carinll infection. Twelve patients with AIDS and extrapulmonary P. carinll infection have been reported [i-i 1 }. In seven cases, extrapulmonary involvement was diagnosed in the absence of a history of P. carinii pneumonia [3-5, 8-1 0]. In three patients with hearing loss, biopsy of a polyp in the external auditory canal yielded P. carinll [3, 1 0]. In a patient with swelling on the left side of the neck, fine-needle aspiration showed P. carinll in thyroid tissue [8]. P. carinll was identified in the
spleen of a patient
with hypersplenism
[5]. In a patient
with
an acute abdomen, an ulcerated intramural small-bowel mass was resected and found to consist of masses of P. carinll organisms [9]. P. carinii was found on bone-marrow biopsy in two patients [6, 1 1 ]. Autopsy showed retinal involvement in one patient [2] and widely disseminated P. carinii infection in three patients [1 4, 7]. Each of our nine patients had a history of P. carinll pneumonia when extrapulmonary involvement was detected. Be,
cause there was no evidence that extrapulmonary infection was responsible for significant morbidity abdominal
pain
in any of our
patients,
no change
P. carinii other than in treatment
was made. Although six of the nine patients died 1 week to 3 months after discovery of disseminated P. carinll infection,
the extrapulmonary disease did not appear to contribute to the deaths. The cause of death was extensive pulmonary disease in five patients and sepsis due to cecal perforation by cytomegalovirus
infection
in one patient.
Extrapulmonary
sites of P. carinii infection found at autopsy included the skin, CNS, retina, thyroid and parathyroid glands, bone marrow, heart, mediastinum, pleura, alimentary tract, abdominal lymph nodes, liver, spleen, gallbladder, pancreas, kidneys, and adrenal glands. Because extrapulmonary involvement may be asymptomatic, disseminated P. carinll infection may occur more frequently than has been reported. Between January 1988 and
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CALCIFICATION
AJR:154,
January
1990
TABLE
1: Radiologic
Findings
and Follow-up
Calcifications
AND
in Nine AIDS Patients
P.
29
INFECTION
CARINII
with Extrapulmonary
Pneumocystis
carinhl Infection
on CT
Case No.
Liver
Spleen
Kidneys
1
+
++
++
2
-
-
-
3
+
Other Findings
Comments Autopsy:
Disseminated P. carinhi with calcified granulomas. Mycobacterium avium-intracellulare in spleen only-without calcification. Autopsy: Disseminated P. carinll with noncalcified lesions in spleen, colon, and mesentery and calcified lesions in liver, lungs, pleura, and mediastinum. Cytomegalovirus in lungs and cecum. Cutaneous Kaposi sarcoma. (Had not re-
Calcified mediastinal lymph nodes and adrenal glands
Enlarged spleen with multiple hypodense noncalcified masses
ceived +++
+
Calcified
abdominal
lymph
azidodeoxythymidine.)
Autopsy: Disseminated P. carinii with calcified granuiomas. M. avium-intracellulare in liver
nodes
and spleen-without tion. 4
+
+++
tinum. Fine-needle
abdominal lymph nodes and adrenal glands
++
Lymphoma
Calcified
aspiration
Hepatic,
visible
+
++
6
++
++
+
7
+
++
+
on plain film.
splenic, and renal
calcifications raphy. +
of kidney
yielded P. carinii. Alive and relatively well 6 months after CT. Splenic and renal calcifications
5
calcificain medias-
seen on sonog-
Autopsy: Calcified
abdominal
lymph
Disseminated P. carinhi with calcified granulomas. Fine-needle aspirations of liver and spleen yielded P. carinii. Alive but debilitated 3 months after CT. Hepatic and splenic calcifications visible on plain film. Not proved. Died 3 months after
nodes
CT. Hepatic and splenic calcifications seen on sonography. Not proved. Normal CT 5 weeks earlier. Alive but debili-
8
-1-
9
CT not performed
tated 8 months after CT. Hepatic, splenic, renal, and adrenal calcifications visible on
plain film. Autopsy: Disseminated P. carinii with calcified granulomas. Note.-+ calcifications.
=
several
scattered
punctate
calcifications:
++
=
innumerable
punctate
calcifications;
+++
=
almost
complete
calcification
of organ:
-
=
no
June 1 989, the prevalence of dissemination at autopsy at one of our hospitals was 3% of all patients with AIDS and 5% of patients with AIDS and a history of P. carinll pneumonia. It
there was no mention of such treatment in the previously reported cases. It should be noted that the serum level of pentamidine is not as high after administration in the aerosol-
appears
ized form as after IV administration [1 1]. Thus, although the organism may be eradicated from the lungs, it might be able to survive in extrapulmonary locations. Persistence of P. carinll in such extrapulmonary sites could then be a source for recurrent pulmonary infection [5J. Unusual pathologic features of Pneumocystis infection seen
that the organism
spreads
by both lymphatic
and
hematogenous routes. Why dissemination should occur in some patients with AIDS and not in others is not clear. Neither the degree of host immunodeficiency nor the duration or severity of the pulmonary infection seems to be significant [7]. Although it is possible that previous treatment with prophylactic aerosolized pentamidine or AZT may have somehow played a role in the dissemination of P. carinll in our patients,
in our patients were granuloma formation and calcification. It has been suggested that a granulomatous response to P.
RADIN
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30
ET AL.
AJA:154, January 1990
carinii infection is an indication of improved host defenses, perhaps due to treatment with AZT in some cases [12]. Grossly detectable calcification has been described only once before in extrapulmonary P. carinll infection in AIDS [9]. Although preoperative abdominal films were unremarkable, specimen radiographs showed stippled calcification in both a small-bowel lesion and regional mesenteric lymph nodes involved by P. carinhi. In the only previous report of abdominal CT findings in extrapulmonary P. carinll infection [4], multiple focal splenic and renal “defects consistent with abscesses” were de-
Fig. 2.-Case 3. Unenhanced T scan shows almost complete calcification of spleen, several calcified lymph nodes, and scattered punctate calcifications in liver and left kidney.
Fig. 3.-case A, unenhanced B, Longitudinal C, Longitudinal
scribed, similar to the hypodense splenic lesions seen in one of our patients. This appearance is nonspecific. The radiologic differential diagnosis in a patient with AIDS includes other infections, especially mycobacterial and fungal abscesses, as well as lymphoma
and Kaposi
sarcoma.
4.
ci scan shows almost complete splenic calcification and punctate calcifications
sonogram sonogram
of right lobe of liver shows abnormal texture with multiple of right kidney shows increased cortical echogenicity.
echogenic
in adrenal glands, left kidney, and liver. dots.
Fig. 4.-case A, Unenhanced
numerable
1. CT scan
shows
in-
punctate renal cortical cal-
cifications.
B, Unenhanced Ci scan at level of cams reveals calcified right hilar, precarnal, and aorticopulmonary lymph nodes. Bilateral pleural hemorrhage was confirmed at autopsy.
AJA:154,
January
CALCIFICATION
1990
AND P. CAR/NIl
INFECTION
In conclusion,
31
Pneumocystis infection should or focal lesions are detected sites in an immunodeficient is no history or evidence of P. carinll
disseminated
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be considered when calcifications at one or more extrapulmonary
patient, even if there pneumonia. With appropriate stains, confirmed by percutaneous fine-needle
the diagnosis aspiration.
can
be
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Intern Med 1987;106:396-398 4. Macher
AM,
Bardenstein
OS, Zimmerman
LE, et al. Pneumocystis
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choroiditis
in a male homosexual with AIDS and disseminated pulmonary and extrapulmonary P. carinll infection. N EnglJ Med 1987;316:1092 5. Pilon VA, Echols AM, Celo JS, Elmendorf SL. Disseminated Pneumocystis
The CT demonstration
of multiple
calcifications
in the liver,
spleen, kidneys, adrenal glands, and lymph nodes due to P. carinll infection, as seen in our patients, has not been reported before. Although we are not aware of any cases with a similar constellation of findings, mycobacterial and fungal infections probably should be included in the radiologic differential diagnosis in addition to P. carinll infection. There has been a single case report of an AIDS patient with combined renal cortical and medullary calcifications due to Mycobacterium avium-intracellulare
renal calcifications
infection
[13].
were confined
In our
patients,
however,
to the cortex.
Findings in our limited series suggest that the low-density lesions and the calcifications represent different manifestations of extrapulmonary P. carinhi infection rather than active and healed phases, respectively, as has been reported in disseminated candidiasis [14]. Follow-up CT 1 and 5 months later in two patients with visceral calcifications showed progression with numerous new calcifications involving parenchyma that had been normal in density. Follow-up CT 1 month later in the patient with hypodense splenic lesions showed increased size and number of lesions without calcification.
carinii infection in AIDS. N Engl J Med 1987;316: 1410-1411 6. Heyrnan MA, Rasmussen P. Pneumocystis carinii involvement of the bone marrow in acquired immunodeficiency syndrome. Am J Clin Pathol 1987; 87:780-783 7. Unger PD, Aosenblum M, Krown SE. Disseminated Pneumocystis carinii infection in a patient with acquired immunodeficiency syndrome. Hum Pathol 1988:19:113-116 8. Gallant JE, Enriquez RE, Cohen KL, Hammers LW. Pneumocystis carinhi thyroiditis. Am J Med 1988:84:303-306 9. Carter TA, Cooper PH, Petri WA Jr, Kim CK, Walzer PD, Guerrant AL. Pneumocystis carinii infection of the small intestine in a patient with acquired immune deficiency syndrome. Am J Clin Pathol 1988;89: 679-683 1 0. Breda SD, Gigliotti F, Hammerschlag PE, Schinella A. Pneumocystis carinii in the temporal bone as a primary manifestation of the acquired immunodeficiency syndrome. Ann Otol Rhinol Laryngol 1988;97:427-43i ii. Raviglione MC, Garner GA, Mullen MP. Pneumocystis carinii in bone marrow. Ann Intern Med 1988;i 09:253 12. Klein JS, Warnock M, Webb WA, Gamsu G. Cavitating and noncavitating granulornas in AIDS patients with Pneumocystis pneumonitis. AJR 1989; 152:753-754 13. Falkoff GE, Aigsby CM, Rosenfield AT. Partial, combined cortical and medullary nephrocalcinosis: US and CT patterns in AIDS-associated MAI infection. Radiology 1987:162:343-344 14. Shirkhoda A. CT findings in hepatosplenic and renal candidiasis. J Comput Assist Tomogr 1987:11:795-798