Inflammatory pseudotumor of the liver: Case report and review of the literature

Inflammatory Pseudotumor of the Liver: Case Report and Review of the Literature By Masato Sakai, Hitoshi Ikeda, Norio Suzuki, Atsushi Takahashi, Minoru Kuroiwa, Junko Hirato, Shin-itsu Hatakeyama, and Yoshiaki Tsuchida Gunma, Japan

Inflammatory pseudotumor is a rare lesion that generally is considered to be benign in biological behavior, although some may recur or metastasize. The authors report on a patient with inflammatory pseudotumor of the liver whose preoperative radiologic findings resembled those of focal nodular hyperplasia. The biological investigation showed a

polyclonality of the cells and diploidy of the DNA content and suggested benign characteristics of the lesion. J Pediatr Surg 36:663-666. Copyright © 2001 by W.B. Saunders Company.

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enhanced on the early phase after bolus injection of contrast material. And then the mass was enhanced from the periphery and was finally homogeneously enhanced on the delayed phase (4 minutes after injection). On magnetic resonance (MR) imaging the mass was hypointense on T1-weighted images and was hyperintense on T2-weighted images, and the central area showed a high signal intensity on T2-weighted images (Fig 2). Preoperative angiography showed that the mass was hypervascular and had a peripheral venous network. The blood vessels appeared to be proliferating and radiating from the central area toward the periphery of the mass. The patient’s laboratory data and radiologic findings suggested the presence of an inflammatory pseudotumor of the liver, but the radiologic findings also were compatible with a diagnosis of focal nodular hyperplasia. Hepatoblastoma was unlikely, but it was included in the differential diagnosis. To obtain a histologic confirmation, a laparotomy was scheduled, but it was postponed for 10 days because of fever of up to 39°C. At operation, it was found that the capsule of a white-yellowish, firm mass was ruptured spontaneously. A biopsy was done, and a frozen section showed that it was an inflammatory pseudotumor of the liver. The mass, 5.5 ⫻ 4.5 ⫻ 4.5 cm in size, was resected by a partial resection of the anterior inferior segment of the right lobe. Histologically, the mass was circumscribed with a pseudocapsule and was characterized by proliferation of fibroblastlike spindle cells with diffuse infiltration of plasma cells and lymphocytes (Fig 3). There was an intervening myxoid matrix that was stained with alcian blue preparation and was dissolved by hyaluronidase. The central area of the mass was pseudocystic and contained myxoid ground substances. Immunohistochemical stainings showed that the infiltrating lymphocytes were positive for T-cell markers (CD3, CD45), B-cell markers (CD20, CD79), and kappa and lambda light chains of immunoglobulins (Fig 4). A DNA content analysis by means of flowcytometry showed that the mass was diploidy. Bacteriologic examinations, stains, and cultures for bacteria and

NFLAMMATORY PSEUDOTUMOR, also called inflammatory myofibroblastic tumor or plasma cell granuloma, is a rare lesion that affects both children and adults.1,2 Histologically, it is characterized by a proliferation of spindle-shaped cells, myofibroblasts mixed with inflammatory cells consisting of plasma cells, lymphocytes, and, occasionally, histiocytes.1 The lesion arises in a variety of tissues and organs including the lungs, mesentery of the intestines, omentum, stomach, and liver.1-5 The liver is a relatively common site of origin, but the number of inflammatory pseudotumors of the liver reported in the literature is so far only approximately 50, including children and adults.4,5 The lesion generally is considered to be benign, but some inflammatory pseudotumors may recur or metastasize, and some patients die of the disease.4,6 Recently, we treated a case of inflammatory pseudotumor of the liver in which biological investigation showed benign characteristics. Although the literature review of hepatic inflammatory pseudotumors in children showed that the clinical outcome is generally favorable, we still think that resection is necessary to confirm the histologic diagnosis, to examine the biological characteristics, and to control the disease. CASE REPORT A 2-year-old girl was admitted to our hospital because of an abdominal mass that was palpated by a local physician whom she visited because of parotid swells caused by mumps. On admission, physical examination showed a tender mass in the right upper quadrant. Laboratory values including serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, bilirubin, and alpha-fetoprotein (AFP) levels were all within the normal ranges except for the white blood cell (WBC) count, 11,400/mm3; hemoglobin, 9.8 g/dL; and C-reactive protein (CRP), 6.8 mg/dL. Ultrasound examination showed a single, lobulated solid mass in the anterior inferior segment of the liver. The mass was hypoechoic compared with the surrounding parenchyma of the liver and had a central hypoechoic area with radiating hypoechoes (Fig 1). On dynamic computed tomography (CT) the central area was Journal of Pediatric Surgery, Vol 36, No 4 (April), 2001: pp 663-666

INDEX WORDS: Inflammatory pseudotumor, liver.

From the Departments of Surgery and Radiology, Gunma Children’s Medical Center and the First Department of Pathology, Gunma University School of Medicine, Gunma, Japan. Address reprint requests to Hitoshi Ikeda, MD, Department of Pediatric Surgery, Koshigaya Hospital, Dokkyo University School of Medicine, 2-1-50, Minami-Koshigaya, Koshigaya, Saitama 343-8555, Japan. Copyright © 2001 by W.B. Saunders Company 0022-3468/01/3604-0032$35.00/0 doi:10.1053/jpsu.2001.22316 663

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Fig 3. Histologically, the mass was characterized by proliferation of fibroblastlike spindle cells with diffuse infiltration of plasma cells and lymphocytes. (H&E, original magnification ⴛ 200.)

Fig 1. Ultrasound examination showed that the mass was hypoechoic compared with the surrounding parenchyma of the liver and had a central hypoechoic area with radiating hypoechoes.

funguses, were negative. The c-reactive protein (CRP) level dropped to normal after surgery without any specific treatment. The postoperative course was uneventful without an episode of fever, and she is now doing well 18 months after surgery.

DISCUSSION

Since the first description of inflammatory pseudotumor of the liver in a 1-year-old girl by Hertzer et al7 in

Fig 2. On magnetic resonance (MR) imaging the mass was hypointense on T1-weighted images (A) and was hyperintense on T2-weighted images (B). The central area showed a high signal intensity on T2-weighted images.

Fig 4. The infiltrating lymphocytes were positive for kappa (A) and lambda (B) light chains of immunoglobulins. (Immunostaining, original magnification ⴛ 400.)

INFLAMMATORY PSEUDOTUMOR OF THE LIVER

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Table 1. Inflammatory Pseudotumor of the Liver in Children Patient No.

Age

Sex

Site

Hertzer et al7

1

1 yr

F

Porta hepatis

Solitary

?

Someren8 Kaneko et al9

2 3

4 yr 10 mo

M F

Right lobe Left lobe

Solitary Solitary

8 ⫻ 6 ⫻ 6 cm 15 ⫻ 12 ⫻12 cm

Heneghan et al10

4

8 yr

F

Right lobe

Solitary

?

Anthony and Telesinghe11 Anthony and Telesinghe11 Vujanic et al12 Hata et al13

5

10 yr

F

Right lobe

Solitary

6

12 yr

M

Right lobe

7 8

15 yr 7 yr

M M

Hata et al13 Newbould et al14 Broughan et al15 Loke et al16 Passalides et al17 Hsiao et al18

9 10 11 12 13 14

6 yr 3 yr 13 yr 2 yr 14 yr 5 yr

Current report

15

2 yr

Study

Solitary or Multiple?

Size

Treatment

9 cm

Biopsy and prednisone Right lobectomy Left lateral segmentectomy Total hepatectomy and liver transplant Right lobectomy

Solitary

5 cm

Left lobe Right lobe

Multiple Multiple

F M M F F F

Left lobe Left lobe Right lobe Left lobe Right lobe Left lobe

Solitary Solitary Solitary Solitary Solitary Solitary

? 4 ⫻ 4 ⫻ 3.5 cm 1 ⫻ 1 cm 9 ⫻ 6 ⫻ 6 cm 2 cm 10 ⫻ 6 ⫻ 5 cm 5.5 ⫻ 5.5 cm 9 ⫻ 8 ⫻ 6 cm 5.5 ⫻ 5 ⫻ 4.5 cm

F

Right lobe

Solitary

5.5 ⫻ 4.5 ⫻ 4.5 cm

1971, 15 cases including our own case were identified from the literature review (Table 1).7-18 The age at diagnosis of the patients, 6 boys and 9 girls, ranged from 10 months to 15 years (median, 6 years). The lesion was solitary in 13 patients and multiple in 2, and the size of the lesion exceeded 5 cm in 9 patients. Surgical resection was the usual treatment except for 1 patient whose unresectable lesion was treated with prednisone. All the patients recovered, and no death was reported. Inflammatory pseudotumor has been believed to be a lesion caused by an inflammatory reaction. Affected patients have varying degrees of nonspecific symptoms and inflammatory responses, such as fever, impaired growth, leukocytosis, anemia, thrombocytosis, hypergammaglobulinemia, and an increase in the erythrocyte sedimentation rate or CRP.1-5 In some patients, inflammatory pseudotumor arises after trauma, surgery, or infection. A preceding illness was described in 4 of the 15 pediatric patients with hepatic lesion. Wilms’ tumor was a preceding illness in 2 patients, but the etiologic significance of the tumor was not clarified.12,14 There are no specific laboratory or radiologic findings in inflammatory pseudotumor of the liver. The radiographic appearance is varied, and it is difficult to make a specific diagnosis based on the findings of imaging studies. In the current case the radiologic findings also were compatible with those of focal nodular hyperplasia. Focal nodular hyperplasia usually is ultrasonographically isoechoic but can be hypoechoic.19 A central stellate scar containing blood vessels, bile ducts, and inflammatory infiltrating cells is enhanced on dynamic CT, and is usually hypointense on T1-weighted images and hyperintense on T2-weighted images on MR.19 However, in-

Outcome

Preexisting Illness

Recovery (portal hypertension) Recovery Recovery

— — —

Recovery

—

Recovery

—

Resection

Recovery

—

Left lobectomy Right lobectomy

Recovery Recovery

Wilms’ tumor —

Left lobectomy Resection Right lobectomy Left lobectomy Resection Left lobectomy

Recovery Recovery Recovery Recovery Recovery Recovery

Resection

Recovery

— Wilms’ tumor — — — Severe congenital neutropenia (Kostmann’ disease), varicella Mumps

flammatory pseudotumor of the liver is enhanced by extravasation of contrast material in fibrous tissue on delayed-phase CT (3 to 6 minutes after the injection of contrast material), whereas no characteristic enhancement pattern is seen on the early phase (40 to 100 seconds).20 The signal characteristics on MR are nonspecific.21 The presence of a central pseudocystic area containing myxoid ground substances in our patient made the radiologic findings similar to those of focal nodular hyperplasia with a central stellate scar. In addition, the preoperative angiography was not useful in making a differential diagnosis, because the hypervascularity and peripheral venous network are angiographic findings that can be seen in both lesions. It is known that some inflammatory pseudotumors actually regress and completely resolve without treatment.21 The favorable outcome of the 15 collected cases with hepatic inflammatory pseudotumor also indicates that the lesion is benign in character. Histologically, it usually lacks mitoses and pleomorphism of cells. Infiltrating inflammatory cells were immunohistochemically positive for heavy and light chains of different subclasses of immunoglobulins, indicating that inflammatory pseudotumor is a polyclonal nonneoplastic lesion.5,11 It is, however, known that some inflammatory pseudotumors recur or metastasize, and some patients die of the disease.4,6 A cytogenetic study in an inflammatory pseudotumor of the intestine showed chromosomal abnormalities and a monoclonality of the cells, suggesting that inflammatory pseudotumor is not merely a tissue reaction to inflammation.2 By means of flow cytometric analysis Biselli et al6 showed that 4 of the 9 inflammatory pseudotumors in his series were aneuploid. Interest-

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ingly, local recurrence or distant metastases occurred in the 3 patients with aneuploid lesion, and 2 of them died of the disease. No recurrence was observed in the patients with diploid lesion. In our patient, immunohistochemical stainings showed that the infiltrating lymphocytes were positive for T-cell and B-cell markers and kappa and lambda light chains of immunoglobulins, and a DNA content analysis showed diploidy of the lesion, suggesting that the patient can undergo follow-up without any other treatment. Although further analyses are necessary to understand this enigmatic lesion, it may be stressed that inflammatory pseudotumors are biologically heterogeneous and include a wide range of lesions, from those that may regress to those that may recur or metastasize.

Based on our experience with this patient, we think that a surgical procedure is necessary to confirm the histologic diagnosis when a child has a mass lesion associated with fever, leukocytosis, a high erythrocyte sedimentation rate, and high CRP values. Less invasive techniques, such as percutaneous biopsy or endoscopy-assisted biopsy, may be considered in patients in whom open surgery is not indicated. Conservative treatment with steroids or antibiotics can be an alternative to surgery when the lesion is multiple or unresectable. But when the diagnosis is resectable inflammatory pseudotumor, resection should be the best way to examine the biological characteristics and to control the disease.

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12. Vujanic GM, Milovanovic D, Aleksandrovic S: Aggressive inflammatory pseudotumor of the abdomen 9 years after therapy for Wilms tumor. Cancer 70:2362-2366, 1992 13. Hata Y, Sasaki F, Matsuoka S, et al: Inflammatory pseudotumor of the liver in children: Report of cases and review of the literature. J Pediatr Surg 27:1549-1552, 1992 14. Newbould MJ, Kelsey A, Lendon M, et al: Inflammatory pseudotumor of the liver masquerading as a metastasis in a child treated for nephroblastoma. Med Pediatr Oncol 20:172-175, 1992 15. Broughan TA, Fischer WL, Tuthill RJ: Vascular invasion by hepatic inflammatory pseudotumor: A clinicopathologic study. Cancer 71:2934-2940, 1993 16. Loke KL, Chan CS, Wijesinha SS: Case report: Inflammatory pseudotumor of liver: Review of clinical and radiological features. Clin Radiol 49:575-577, 1994 17. Passalides A, Keramidas D, Mavrides G: Inflammatory pseudotumor of the liver in children: A case report and review of the literature. Eur J Pediatr Surg 6:35-37, 1996 18. Hsiao CC, Chen CL, Eng HL: Inflammatory pseudotumor of the liver in Kostmann’s disease. Pediatr Surg Int 15:266-269, 1999 19. Berdon WE, Condon VR, Currarino G, et al (eds): Caffey’s Pediatric X-Ray Diagnosis. St Louis, MO, Mosby, 1993, pp 957-958 20. Fukuya T, Honda H, Matsumata T, et al: Diagnosis of inflammatory pseudotumor of the liver: Value of CT. Am J Roentgenol 163:1087-1091, 1994 21. Flisak ME, Budris DM, Olson MC, et al: Inflammatory pseudotumor of the liver: Appearance on MRI. Clin Imaging 18:1-3, 1994