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"Inflammatory Pseudotumor" of Liver with Occlusive

Phlebitis
Report of a Case in a Child and Review of the Literature

AYTEN SOMEREN, M.D.

Someren, Ayten: "Inflammatory pseudotumor" of liver with Departments of Pathology, Emory University School of
occlusive phlebitis. Report of a case in a child and review of the Medicine and Grady Memorial Hospital, Atlanta, Georgia
literature. Am J Clin Pathol 69: 176-181, 1978. An unusual
"tumor" involving the right lobe of the liver of a young child is
reported. Morphologically, the lesion had the features of
"inflammatory pseudotumor." We were able to find only one served identical changes in an inflammatory pseudo-
previous report of a similar case in the literature. Unusual tumor of the parotid gland. 33
changes, which may be designated "occlusive phlebitis," were
present in the medium-sized and large veins. Histologically, the

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lesion, including the vascular changes, had similarities to the Report of a Case
entities included in the group of "multifocal fibrosclerosis." It
is believed that these unusual vascular changes, which have also A 4'/i-year-old white boy was admitted to Grady Memorial
been observed in a case of "inflammatory pseudotumor" of the Hospital on April 2, 1975, with a four-week history of lassitude and
parotid gland, probably contributed to the disease process. weakness. The child allegedly had been well until five weeks prior to
(Key words: Inflammatory pseudotumor of liver; Post- admission, when he had started having periumbilical abdominal pain
inflammatory tumor of liver; Plasma cell granuloma of liver.) and occasional vomiting.
On admission to Grady Memorial Hospital, the child had an
HEPATIC TUMORS in childhood are rare. Included in enlarged liver, mild generalized lymphadenopathy, and a temperature
of 102 F. A grade II — III functional systolic murmur was heard. The
this category are infantile hemagioendotheliomas,
abdomen was distended and slightly tender. Laboratory studies showed
mesenchymal hamartomas, hepatoblastomas, tera- a hemoglobin of 7.2 mg/dl (1.12 /xmol/l), hematocrit of 25.4%, leukocyte
tomas, and malignant mesenchymomas. Hepatocellular count of 9,300 with a differential of 48% polymorphonuclears, 33%
carcinomas, hemangiomas, and nodular hyperplasias lymphocytes, 13% monocytes, 3% eosinophils and 3% band/cells, an
can also occur in infants and children. A variety of adequate platelet count, and a reticulocyte count of 2%. IgG was
3,300 mg/dl, IgM 300 mg/dl, and IgA 630 mg/dl. Total protein was 9.0
infectious and inflammatory processes, including
g/dl. Albumin was 2.2 g/dl. Serum iron was 16 /ug/dl (2.9 /xmol/1) and
pyogenic and amebic abscesses and cysts, may also alkaline phosphatase was 254 mU/ml. Mono-test and test for febrile
manifest as tumor masses in this age group. agglutinins were negative. A bone marrow aspiration biopsy on April
To our knowledge, a solitary tumor-like lesion of 4 showed plasmacytosis ( < 12%), granulocytic hyperplasia, and
liver that can be classified as "inflammatory pseudo- megaloblastoid erythroid hyperplasia on the smear, and granulocytic
hyperplasia with plasmacytosis of < 10% in bone marrow sections.
tumor" has not been reported to occur in children. We Liver scan on April 4 showed a space-occupying lesion in the inferior
were able to find only one previous report of a similar portion of the right lobe. Needle biopsy was attempted, but on
hepatic lesion, and it involved the right lobe of the liver histologic examination only fibrous connective tissue was seen.
of a 40-year-old man. 25 Biopsy of a cervical lymph node, on April 9, was interpreted as
showing sinus histiocytosis. Selective celiac and mesenteric
It is our purpose to report an additional case of
arteriograms were performed on April 18. Interpretation was that
"inflammatory pseudotumor," occurring in the right of a large hepatic mass, located in the inferior lateral aspect of the
lobe of the liver in a young child. We wish to emphasize right lobe of the liver, with abnormal blood vessels. The differential
the unusual vascular changes, seen in the veins of this diagnosis included hamartoma and hepatoblastoma.
lesion, which can be classified as "occlusive phlebitis." On April 22, the patient underwent exploratory laparotomy. There
This type of vascular change has also been described to was a large solitary mass in the right lobe of the liver. Right hepatic
lobectomy with cholecystectomy were performed. The operative
occur in Riedel's thyroiditis and idiopathic retroperi-
diagnosis was hepatoblastoma.
toneal fibrosis,23 both of which may be associated with Postoperatively, the patient did well. He had a small pleural
inflammatory pseudotumors. 10,36 We have recently ob- effusion, which was slowly resolving, at the time of discharge from
the hospital.
Received December 15, 1976; received revised manuscript January When he was last seen, six months postoperatively, the child's
21, 1977; accepted for publication January 21, 1977. condition was much improved, with a completely healed wound and
Address reprint requests to Dr. Someren: Grady Memorial mild lymphadenopathy. The anemia and weakness had abated. Chest
Hospital, Department of Pathology, 80 Butler St., SE, Atlanta, x-rays showed slight blunting of the right costophrenic angle from old
Georgia 30303. pleural reaction.
0002-9173-78-0200—0180$00.75 © American Society of Clinical Pathologists

176
Vol. 69 • No. 2 CASE REPORTS 177
Pathology
Gross
The specimen consisted of the right lobe of the liver,
which weighed 440 g and measured 15 x 12 x 7 cm. On
sectioning, an 8 x 6 x 6 cm mass was seen, immediately
under the capsule, on the free edge of the liver. The cut
surfaces of the lesion were yellowish-white and firm. It
appeared fairly well circumscribed but not encapsulated
(Fig. 1). The excision margin of the liver was 8 mm from
the main tumor mass. Surrounding liver tissue
appeared grossly normal. The gallbladder showed no
gross abnormality.
Microscopic
Multiple sections of the lesion were examined. In Fio. 1. Parallel sections through the resected right lobe of the liver,
showing a fairly well circumscribed mass.
addition to routine hematoxylin and eosin stains,
Masson's trichrome, Verhoeff's elastica, Gram, peri-

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odic acid-Schiff (PAS), silver methenamine, crystal showed fibroblasts in interlacing laminated or whorled
violet, and Congo red stains were employed. The lesion patterns, and for the most part there was extensive
was composed primarily of densely hyalinized col- hyalinization (Fig. 2). In focal areas, this homogeneous
lagenous tissue infiltrated with variety of cells, acellular hyaline material resembled "amyloid," but
peripherally extending into, and enclosing areas of, none of the stains for amyloid was positive. Throughout
hepatic parenchyma. Some portions of the stroma the fibrous stroma, there were infiltrates of cells among

••:':T,~ :'• Fi^jJ*m£M&^ :>


FIG. 2. Low-magnification photomicrographs of the lesion, showing collagenous stroma infiltrated by mononuclear cells of various types,
peripherally extending into the surrounding parenchyma (left), and areas showing extensive hyalinization of collagenous stroma (right).
Hemotoxylin and eosin. x78.
A.J.C.P. . February 1978
178 SOMEREN

Pathology. The concensus, as reported by Kamal G.


Ishak, M.D., Ph.D., was that the lesion in the liver was
an "inflammatory pseudotumor, etiology undeter-
mined."

Discussion
Lesions classified as "inflammatory pseudotumor,"
"post-inflammatory tumor," or "plasma cell gran-
uloma" have been found in a variety of locations: The
lung,1'4-6'14'19-22-27-35'3739 orbit, 2 - 1018 parotid gland, ,7 ' 33
pleura, 5 stomach, 32 ovary, 38 and liver, 25 and probably
the heart, 15 among other areas, have been the locations
of such lesions. These localized benign proliferations,
composed predominately of plasma cells and other
elements supported by fibrous stroma, are of unknown
etiology, and the terms "inflammatory pseudotumor,"
"post-inflammatory tumor," and "plasma cell gran-
uloma" provide no information about the essential

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nature of these lesions. They probably occur in
response to a local injury of uncertain type, and they are
self-limited.
There is a great deal of continuing confusion in the
literature concerning the nomenclature accorded this
relatively rare entity. According to Spencer, it was first
reported to occur in the lung, in 1937, as "vascular
endothelioma." 34
Voegt, in 1938, published six cases of "extramedul-
lary plasma cell tumor," one of which involved the
FIG. 3. Fibroblasts and plasma cells of the lesion. ovary. He considered this particular lesion in the ovary
Hemotoxylin and eosin. x315. to be a "plasma cellular granuloma," while the other
which mature plasma cells predominated (Fig. 3). Some five were described as true neoplasms. 38
of these cells were multinucleated. Occasional Russell Brunn, in 1939, described a similar lesion found in the
bodies were also seen among bundles of fibroblasts or lung of a 5-year-old girl, which he called "subacute
within collagen and hyaline material. Intermingled granulomatous mass or plasma cell granuloma." 6
among the plasma cells were histiocytes, occasional The term "post-inflammatory tumor" was first
polymorphonuclear leukocytes, and variable numbers coined for the lesions occurring in the lung by Uniker
of lymphocytes, sometimes occurring in clumps. and Iverson. 37 Similar lesions in the lung have been
Occasional eosinophils were also present. No atypical described by other investigators under a variety of
or neoplastic cells were identified. names, including xanthogranuloma, 1 plasma cell
Interesting changes were observed in the large and tumor, 11 plasma cell granuloma, 4 ' 7 ' 20 mast cell gran-
medium-sized veins. Various stages of what might be uloma, 31 mast cell tumor, 9 inflammatory pseudo-
called "occlusive phlebitis" were seen in most of the tumor, 14 ' 22 ' 27,37 xanthomatous pseudotumor, 8 ' 3539 histio-
sections within the lesion and the adjacent liver tissue, cytoma, 1221 xanthoma, 1321 ' 30 and fibroxanthoma.12
and they seemed to develop in progressive fashion (Fig. Some authors combined "post-inflammatory tumor"
4). There was evidence, in some areas, of inflammation and "sclerosing hemangioma" 3,21,24 ' 29 of the lung into a
involving the vessel walls, with gradual filling of the single group. 812 ' 21 ' 24,35 Others used the term "pseudo-
lumen with connective tissue rich in capillaries and tumor" for both "pseudolymphoma" and "sclerosing
inflammatory cells, resembling granulation tissue. hemangioma" of the lung, adding further to the
Many of the veins showed complete obliteration of their confusion. The lesions occurring in the lung have also
lumens with total sclerosis. Arteries did not show been called "plasmacytoma,'' 16 ' 26 a term which must be
significant alterations. Special stains for fungi and reserved for malignant proliferation of plasma cells.
bacteria were non-revealing. Multiple sections and a Similarities of the lesions occurring in the lung to
variety of special stains failed to reveal additional mediastinal "giant lymph node hyperplasia of plasma
information concerning the etiology and pathogenesis cell type," 6 and to "post-inflammatory tumors of
of this lesion. pleura" 4 ' 5 have also been mentioned, and the relation-
This case has also been reviewed by members of the ships are not clear.
staffs of several Divisions at Armed Forces Institute of Histologically, the "inflammatory pseudotumors,"
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FIG. 4. Occlusive phlebitis in medium-sized veins in various stages (progression: upper left, upper right, lower left, lower right): inflammation
involving the vessel walls with gradual filling of the lumen, first with inflammatory cells, later with connective tissue rich in capillaries, and
finally, complete obliteration with total sclerosis. Hemotoxylin and eosin. x78.
SOMEREN A.J.C.P. . February 1978
180
especially these with sclerosing features, also have Bahadori and Liebow, 4 who prefer the designation of
similarities to invasive fibrous thyroiditis of Riedel, as "plasma cell granuloma" for inflammatory pseudo-
well as to idiopathic retroperitoneal fibrosis, and tumors of lung, reviewed 40 cases, in detail, and
mediastinal fibrosis, as was reported by others. 1 - 4 In concluded that these lesions are nonneoplastic, and
fact, various combinations of these fibrous processes have structural features and a natural history quite
have been described. 23 "Multifocal fibrosclerosis," as distinct from those of sclerosing hemangioma and
defined by Comings,'" and "multifocal idiopathic plasmacytoma.
fibrosclerosis," as defined by Uilman,:iti include: Portions of inflammatory pseudotumors of lung were
Riedel's thyroiditis, retroperitoneal fibrosis, mediastinal grown in tissue culture by Sherwin and associates,
fibrosis, sclerosing cholangitis, and pseudotumors of revealing growth in a granulomatous pattern, suggesting
the orbit, parotid gland, lacrimal glands, and lung. an inflammatory process. 31
The term "inflammatory pseudotumor" has been Electron microscopic studies of pseudotumors of the
used for a variety of chronic sclerosing inflammatory lung also revealed findings supportive of an inflamma-
processes in the orbit with no definite etiology but rather tory nature of these lesions, distinguishing them from
distinct histopathologic appearances. Included in this pulmonary sclerosing hemangiomas, malignant plasma
group are: lymphoid pseudotumors, plasma cell cell tumors, and pseudolymphomas. 719 ' 39
pseudotumors, orbital myositis, vasculitis, dacryo- Several investigators have observed inflammatory
adenitis, lipogranuloma, and sclerosing pseudotumors. 18 and obliterative changes in blood vessels in inflamma-

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It appears from the review of the literature that the tory pseudotumors 433 and related fibroproliferative
lesions called "inflammatory pseudotumors" may be disorders. 17,2328 Roulet was the first to describe peculiar
grouped into three histopathologic subtypes: (1) those changes in the veins in patients with Riedel's
with a prominent histiocytic component (xanthogran- thyroiditis. 28 These vascular changes are very similar to
uloma type); (2) those with a prominent plasma cell those seen in the present case and those reported to
component (plasma cell granuloma type); (3) those with occur in two cases of multifocal fibrosclerosis by Meyer
markedly sclerotic features (sclerosing pseudotumors). and Housmann. 23 We have recently observed identical
Various combinations of these histopathologic patterns, vascular changes in a case of inflammatory pseudotumor
however, may be seen in a single lesion. of the parotid gland.
It appears also that those inflammatory tumors with a We feel that the present case can best be classified as
prominent histiocytic component and/or sclerosing an "inflammatory pseudotumor" of the liver. Vascular
features have, in the past, been confused with changes ranging from cellular proliferation in the walls
sclerosing hemangiomas (fibroxanthomas), and those of the veins to complete obliterative sclerosis are
with a predominant plasma cell component, with probably of etiologic importance in lesions of this type,
plasmacytomas. as they have also been observed in inflammatory
The etiology and pathogenesis of "inflammatory pseudotumors occurring in other locations, and in
pseudotumors," occurring either as isolated lesions or related fibroproliferative disorders. The possibility that
in combination with other fibroproliferative entities, these vascular changes may be secondary to the
are unknown. fibrosclerotic process, however, should also be
The possibility of infection has been entertained by considered. It appears also that an infectious or
many investigators, but no evidence of an infectious immune etiology, or both, cannot be ruled out in
organism could be demonstrated in any of these considerations of inflammatory pseudotumors and
pseudotumors or related entities, with the possible related lesions, on the basis of currently available
exception that some examples of sclerosing mediastin- evidence.
itis can be manifestations of histoplasmosis. 4 We were able to find one previous report of a similar
An immunologically determined pathogenesis has hepatic lesion. 25 Although only a very brief microscopic
also been considered for these lesions because of the description of the lesion was given, its structural
presence of large numbers of plasma cells. The similarities to "pseudotumor" (plasma cell granuloma)
statement has been made, however, that "it is difficult of the lung were mentioned. Vascular changes were not
to conceive of such mechanism, especially in localized described.
lesions, unless the lesion is primarily infectious and
with a large immunologic component." 4 Acknowledgments. Dr. KamalG. Ishak and other Staff Members of
AFIP reviewed the ease. Mr. Robert Beveridge provided the
Autoimmunity has been suggested as a pathogenetic photographs.
mechanism for "multifocal fibrosclerosis," which may
include variety of "inflammatory tumors." 2 3 References
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Vol. 69 • No. 2 CASE REPORTS 181
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Interstitial Pneumonitis Associated with


Azathioprine Therapy

DENNIS D. WEISENBURGER, M.D.

Weisenburger, Dennis I).: Interstitial pneumonitis associated with Department of Pathology, University
azathioprine therapy. Am J Clin Pathol 69:181-185,1978. A 24- of Iowa Hospitals and Clinics,
year-old female patient with rapidly progressive renal failure sec- Iowa City, Iowa
ondary to membrano-proliferative glomerulonephritis is thought
to have subsequently had acute interstitial pneumonitis as a conse-
quence of azathioprine therapy. The occurrence of the pulmonary
injury coincided with the rapid onset of severe renal failure
and was reversible with cessation of the drug. Accumulation
Received July 29, 1976; received revised manuscript November
15, 1976; accepted for publication November 15, 1976. of toxic metabolic products of azathioprine with subsequent
Address reprint requests to Dr. Weisenburger: Department of injury to the pulmonary interstitium is suggested as the etiol-
Pathology, University of Iowa Hospitals and Clinics, Iowa City, ogy. Azathioprine should be considered in the differential
Iowa 52242. diagnosis of interstitial pneumonitis in all patients taking the
0002-9173-78-0200—0181$00.75 © American Society of Clinical Pathologists