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Pseudorheumatoid nodule in the liver of anadolescent male

Shehzad A. Saeeda,*, David R. Kellyb, William D. Hardin Jr.c

aDepartment of Pediatrics, Division of Pediatric Gastroenterology and Nutrition Sciences,

Children’s Hospital and the University of Alabama at Birmingham, Birmingham, AL 35233, USAbDepartment of Pathology and Laboratory Medicine, Children’s Hospital and the University of Alabama at Birmingham,

Birmingham, AL 35233, USAcDepartment of Pediatric Surgery, Children’s Hospital and the University of Alabama at Birmingham, Birmingham,

AL 35233, USA

0022-3468/$ – see front matter D 2006

doi:10.1016/j.jpedsurg.2006.04.036

* Corresponding author. Tel.: +1 205

E-mail address: ssaeed@peds.uab.ed

Index words:Pseudorheumatoid nodule;

Focal nodular hyperplasia;

Meckel diverticulum;

Deep granuloma annulare

Abstract Focal hepatic lesions in the pediatric population are rare and are usually found on incidental

imaging of the abdomen. The most common lesions are focal nodular hyperplasia and hemangioma, but

the differential diagnosis is quite broad. We present a case of an adolescent male who was found to have

a large pseudorheumatoid nodule of the liver that was successfully resected. Only one previous case is

reported in the literature and none in the pediatric age group.

D 2006 Elsevier Inc. All rights reserved.

1. Case

A 14-year-old male presented with vague complaints of

right-sided chest pain. Persistence of these complaints

necessitated an evaluation that included a chest computed

tomography (CT) scan, which revealed a space-occupying

lesion greater than 3 cm in the right lobe of the liver. A

contrast CT scan of the abdomen demonstrated a 4.0� 4.0�3.3 cm enhancing lesion in the posterior segment of the right

lobe of the liver. Delayed imaging showed filling of the

central region of the lesion, suggestive of a hemangioma. A

tagged red blood cell (RBC) scan was, however, negative. A

technetium sulfur colloid scan, done to evaluate for the

presence of focal nodular hyperplasia, was also normal. The

patient’s physical examination was normal, with no evi-

dence of hepatosplenomegaly, subcutaneous nodules, or

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939 9918; fax: +1 205 939 9919.

u (S.A. Saeed).

rashes. Laboratory evaluation revealed a normal complete

blood count with no evidence of hemolysis and a normal

prothrombin time and a-fetoprotein concentration. Liver

function studies (alanine aminotransferase [ALT]; aspartate

aminotransferase [AST], alkaline phosphatase, albumin, and

bilirubin concentrations) were normal.

An exploratory laparotomy was subsequently performed,

and a nodular, well-demarcated lesion was removed from the

right lobe of the liver (Fig. 1). A Meckel diverticulum, found

incidentally during routine examination of the bowel, was

resected. Cholecystectomy was also performed. Pathologic

evaluation of the liver specimen showed a circumscribed

3.8 � 3.1 � 3.0 cm nodular mass that was surrounded by

normal appearing liver parenchyma. Histologically, the

mass consisted of small granulomas surrounded by a rim

of scarred, remodeled nodular liver parenchyma. Most of

the granulomas were stellate-shaped and had a necrobiotic

appearance characterized by palisading histiocytes with a

sprinkling of lymphocytes surrounding central areas of

Journal of Pediatric Surgery (2006) 41, 1479–1482

Fig. 1 Circumscribed nodular mass in the right lobe of the liver.

S.A. Saeed et al.1480

fibrinoid necrosis (Fig. 2). Necrotic collagen and reticulin

fibers coursed through the center of the granulomas

(Fig. 3). A Masson trichrome stain demonstrated coarse

collagen bands separating small rounded liver cell nodules

adjacent to the more centrally located granulomas (Fig. 4).

Many of the collagen bands contained clusters of proli-

ferated bile ductules. The liver parenchyma adjacent to the

mass was normal, with preservation of the acinar

architecture, liver cell cords, and sinusoids. There was

no significant alteration of the portal tracts or blood ves-

sels. Special stains for fungi, the cat scratch organism

(Bartonella henselae), syphilis, mycobacteria, and para-

sites were negative.

An evaluation for rheumatologic disease was negative.

The patient had normal antinuclear antibody and rheumatoid

factor titers but an elevated erythrocyte sedimentation rate

(52 mm/h), which was normal (7 mm/h) when repeated

Fig. 2 A, One of many necrobiotic granulomas within the liver mass. B

in one of the granulomas (hematoxylin-eosin, �33 [A] and �132 [B]).

2 months later and remained normal through the subsequent

serial measurements. A liver function panel checked

2 months after resection was normal with normal ALT,

AST, and albumin concentrations.

The patient did well over the course of the next 2 years

before presenting with postprandial epigastric and upper

abdominal pain associated with episodic loose stools and

occasional blood per rectum with hard stools. Biochemical

evaluation (complete blood count, amylase, lipase, erythro-

cyte sedimentation rate, C-reactive protein, antinuclear

antibody, gamma glutamyltranspeptidase, liver function

studies, Prometheus IBD serologies [perinuclear antineutro-

philic cytoplasmic antibody, anti-Saccharomyces cerevisiae

antibody, and a-anti–outer membrane of porin C], and stool

studies) was normal. A minimally elevated indirect bilirubin

concentration (2 mg/dL) was noted and correlated with a

paternal history of jaundice during periods of stress. An

upper gastrointestinal small bowel follow through and a

magnetic resonance imaging of the abdomen were also

normal. Upper and lower endoscopic evaluation revealed

reflux esophagitis and normal colonic biopsies with no

evidence of chronic inflammatory bowel disease. The patient

has done well on Proton Pump Inhibitor therapy (Prevacid,

TAP Pharmaceuticals, Inc, Lake Forest, Ill) and antispas-

modic treatment, with normal weight gain and resolution of

abdominal pain symptoms.

2. Discussion

We believe that this is the first reported pediatric case of

hepatic pseudorheumatoid nodule. One case of a hepatic

rheumatoid nodule has been previously reported [1]. That

case was an autopsy report of a 54-year-old woman with

, Palisading histiocytes surround a central area of fibrinoid necrosis

Fig. 3 Necrotic collagen (coarse blue fibers) (A) and reticulin (coarse black fibers) (B) extend through the center of one of the granulomas

(A: Masson trichrome, �132; B: Gordon and Sweet reticulin, �132).

Case report: pseudorheumatoid nodule in the liver of an adolescent male 1481

rheumatoid arthritis of several years’ duration who died as

result of complications from chronic renal failure, amyloid-

osis, and septicemia. Liver histology revealed a hemangi-

oma and multiple discrete nodules with a central zone of

necrosis, histiocytic proliferation at the periphery, fibrosis,

and chronic inflammation. The histologic features were

similar to several concurrent subcutaneous nodules. Our

case differs in that there are no associated subcutaneous

lesions, and no evidence of rheumatologic disease has been

found so far.

Our patient presented with nonspecific symptoms and

was found to have an incidental hepatic mass. Evaluation

of the liver histology was unremarkable for the usual

Fig. 4 Scarring with nodule formation (A, B) and bile duct prolif

(hematoxylin-eosin, �33 [A, B] and �132 [C]).

entities associated with granulomatous inflammation. The

histologic features were also not consistent with focal

nodular hyperplasia (normal blood vessels and portal tracts

as well as absence of lymphocytic infiltration). The patient

had no fevers, chest radiographs did not show hilar

adenopathy, and cultures and special stains were negative

for mycobacteria, cat scratch disease, syphilis, parasites,

and fungi. Special stains (S-100 protein, CD1a) were also

negative for Langerhans cell histiocytosis. Serologies were

normal for autoimmune/rheumatological and inflammatory

bowel diseases. Radiological evaluations (abdominal CT,

magnetic resonance imaging, and barium studies) have

shown no evidence of primary hepatobiliary or gastroin-

eration (C) in the liver immediately adjacent to the granulomas

Table 1 Differential diagnosis of hepatic granulomatoid

lesions

Infections Medications

Viral Fungal Allopurinol

Cytomegalovirus Histoplasmosis Carbamazepine

Epstein-Barr virus Cryptococcosis Halothane

Varicella Candidiasis Hydralazine

Viral hepatitis Coccidioidomycosis Phenylbutazone

Phenytoin

Bacterial Parasitic Quinidine

Mycobacteria

Mycobacterium

avium-intercellulare

complex

Brucellosis

Tularemia

Whipple disease

Granuloma inguinale

Psittacosis

Yerseniosis

Leprosy

Leprosy

Schistosomiasis

Toxoplasmosis

Visceral larva

migrans

Visceral

leishmaniasis

Rickettsial

Q fever

Spirochetal

Syphilis

Sulfonamides

Miscellaneous

Sarcoidosis

Crohn disease

Chronic

granulomatous

disease

Wegener

granulomatosis

Hepatic diseases

Primary biliary

cirrhosis

Reactive hepatitis

Granulomatous

hepatitis

Fatty liver

S.A. Saeed et al.1482

testinal disease. An incidental note was made of minimal

indirect hyperbilirubinemia in the absence of signs of

hemolysis on the peripheral blood smear, features sugges-

tive of Gilbert syndrome.

Typical lesions of pseudorheumatoid nodule (also known

as deep or subcutaneous granuloma annulare [DGA]) are

soft tissue nodules found on the tibial, scalp, forearm, or

periorbital regions in children [2,3]. These children seldom

have rheumatoid disease. The pathology is characterized by

subcutaneous location, necrobiosis, mild eosinophilic infil-

tration, and palisading mononuclear cellular infiltrate. In

addition to DGA, other entities to consider in the differential

diagnosis for a palisading granulomatous lesion include

rheumatoid nodule of rheumatic fever, juxtaarticular rheu-

matoid nodule of rheumatoid arthritis, and necrobiosis

lipoidica diabeticorum. None of these entities are common

in children, and none have been identified in our patient.

The granulomatous lesions in the liver are not consistent

with the typical features of hepatic granulomas [4,5], and

the clinical features and evaluation for most of these

etiologies are negative (Table 1).

To our knowledge, this is the first case report of a

pseudorheumatoid nodule in the liver of a pediatric patient

who currently has no clinical features of a rheumatologic

disease. We plan to follow the patient closely to determine

the natural history of this entity.

References

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1986;10:1211-3.

[2] McDermott MB, Lind AC, Marley EF, et al. Deep granuloma annulare

(pseudorheumatoid nodule) in children: clinicopathologic study of 35

cases. Pediatr Dev Pathol 1998;1:300-8.

[3] Evans MJ, Blessing K, Gray ES. Pseudorheumatoid nodule (deep

granuloma annulare) of childhood: clinicopathologic features of twenty

patients. Pediatr Dermatol 1994;11:6 -9.

[4] Denk H, Scheuer PJ, Baptista A, et al. Guidelines for diagnosis

and interpretation of hepatic granulomas. Histopathology 1994;25:

209 -18.

[5] Irani SK, Dobbins III WO. Hepatic granulomas: review of 73 patients

from one hospital and survey of the literature. J Clin Gastroenterol

1979;1:131-43.