Hepatic angiomyolipoma resembling an inflammatory pseudotumor of the liver. A case report

Hepatic angiomyolipoma resembling an inflammatory pseudotumor of the liver. A case report

Pathology – Research and Practice 200 (2004) 713–716 www.elsevier.de/prp TEACHING CASE Hepatic angiomyolipoma resembling an inflammatory pseudotumor ...

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Pathology – Research and Practice 200 (2004) 713–716 www.elsevier.de/prp

TEACHING CASE

Hepatic angiomyolipoma resembling an inflammatory pseudotumor of the liver. A case report Masaru Kojimaa,b,, Shigeo Nakamurac, Yoshihiro Ohnod, Shiro Sugiharae, Noriyuki Sakataf, Nobuhide Masawab a

Department of Pathology and Clinical Laboratories, Gunma Cancer Center Hospital, 617-1 Takabayashinishi-cho, Ohta 373-8550, Japan b Department of Pathology, Dokkyo University School of Medicine, Mibu, Japan c Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan d Department of Pathology, Tone Central Hospital, Numata, Japan e Department of Pathology, Gunma Health Foundation, Maebashi, Japan f Department of Pathology, Fukuoka University School of Medicine, Fukuoka, Japan

Abstract Hepatic angiomyolipoma (AML) may demonstrate a marked histologic diversity and is frequently misdiagnosed. HMB45 is a promising marker for this tumor and is expected to facilitate the recognition of some AMLs with unusual morphology. We report on a case of hepatic AML exhibiting histologic features that were similar to inflammatory pseudotumor (IPT) or to IPT-like follicular dendritic cell (FDC) tumor of the liver. The patient was a 21-year-old Japanese woman with a mass in the left lobe of the liver (70  73 mm). There were no clinical features of tuberous sclerosis. Histologically, numerous inflammatory cells, including small lymphocytes, plasma cells, and histiocytes, showed diffuse infiltration throughout the lesion. However, the present case also shared some of the morphologic findings of hepatic AML, including clusters of smooth muscle cells with clear cytoplasm, a few scattered adipose cells, and thick-walled blood vessels. Moreover, the smooth muscle cells consisted of spindle-shaped cells or larger, more rounded cells with either clear cytoplasm or eosinophilic epithelioid cell features positive for vimentin, muscle-specific actin, and smooth muscle actin. HMB45 immunostaining confirmed the diagnosis of AML. The present case indicates that IPT or IPT-like FDC tumor should be added to the list of differential diagnoses for AML of the liver. r 2004 Elsevier GmbH. All rights reserved. Keywords: Angiomyolipoma; Liver; Inflammatory pseudotumor; Follicular dendritic cell tumor; HMB45.

Introduction

Corresponding author. Department of Pathology and Clinical Laboratories, Gunma Cancer Center Hospital, 617-1 Takabayashinishi-cho, Ohta 373-8550, Japan. Tel.: +81-276-38-0771; fax: +81276-38-8386. E-mail address: [email protected] (M. Kojima).

0344-0338/$ - see front matter r 2004 Elsevier GmbH. All rights reserved. doi:10.1016/j.prp.2004.08.001

Angiomyolipoma (AML) is a rare benign mesenchymal tumor of the liver. Tumors are characteristically composed of smooth muscle cells, mature adipose tissue, and blood vessels, although the proportions of the various components vary considerably from case to case, and AMLs may show a marked histologic diversity

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[4,6,10]. However, positivity on HMB45 immunostaining has recently been shown to be a promising marker for renal and hepatic AMLs [6,9,10]. Inflammatory pseudotumor (IPT) of the liver was initially proposed as a non-neoplastic process [1,5,7]. However, some IPTs of the liver have recently been recognized as a peculiar variant of Epstein–Barr virus (EBV)-associated follicular dendritic cell (FDC) tumor [3,8]. We report here on a case of hepatic AML exhibiting histologic findings that were similar to IPT or IPT-like FDC tumor of the liver.

Case report The patient, a 21-year-old Japanese woman, was hospitalized with fever of unknown origin. There were no clinical features of tuberous sclerosis. A physical examination revealed no abnormality. Laboratory data on admission were within the normal limits except for mild leukocytosis (WBC 11000/mm3). Hepatitis B surface antigen and hepatitis C virus antibody were negative. Ultrasound imaging demonstrated a hypoechoic mass in the left lobe of the liver, measuring 70  73 mm2. The tumor presented as a mass of low density on computed tomography. On needle biopsy, the lesion was tentatively diagnosed as IPT of the liver. The patient underwent resection of the left lobe of the liver and has remained well for 65 months since surgery.

Materials and methods Tissue specimens were fixed in formalin, routinely processed, and embedded in paraffin. For light microscopic examination, the sections were stained with hematoxylin–eosin (HE), Periodic-acid Schiff, the Masson–Fontana stain, and the Azan–Mallory method. For immunohistochemistry, the sections were stained using a Ventana automated (BenchMarkTM) stainer. We used a panel of antibodies against human immunoglobulin light chain (kappa and lambda) (Novocastra, Newcastle, UK), polyclonal-CD3 (CD3; Dako A/S, Glostrup, Denmark), L26 (CD20; Nichirei Co., Tokyo, Japan), a cocktail of 2G9 (CD21; Novocastra ) and RB L25(CD35; Novocastra), 1B12 (CD23; Novocastra), CD45RO (Nichirei Co.), PGM-1 (CD68; Dako A/S, Glostrup, Denmark), JCB117C (CD79a; Dako A/S, Glostrup, Denmark), 2A10(S-100X; IBL Co., Fujioka, Japan ), anti-FDC antibody (CNA.42; Dako), V9 (Vimentin; Dako.), muscle-specific actin (HHF35; Dako), 1A4 (smooth muscle actin; Dako), 5A4 (p80; Novocastra), and HMB45 (melanosome; Dako). The primary antibodies were replaced by normal rabbit- and mouse serum as a negative control.

In situ hybridization (ISH) with EBV-encoded small RNA (EBER) oligonucleotides was performed to investigate formalin-fixed, paraffin-embedded sections for the presence of EBV small RNA. ISH was also done using a Ventana automated (BenchMarkTM) stainer.

Results Gross examination of the surgically obtained liver specimen demonstrated a yellow-white tumor with a clear border but no capsule. Histologically, at lower magnification, smooth muscle cells and a few mature fat cells were obscured by abundant inflammatory infiltrate (Fig. 1). Higher magnification revealed inflammatory cells composed of small lymphocytes, mature plasma cells, and histiocytes with or without epithelioid cell features (Fig. 2). Smooth muscle cells consisted of spindle-shaped cells or larger, more rounded cells with either clear cytoplasm or eosinophilic epithelioid cell features (Fig. 2). These smooth muscle cells usually formed small clusters (Fig. 2). None of the smooth muscle cells contained melanin pigment. A few fibroblasts were also present in the lesion. The vascular component of the tumor was sometimes thick walled, with marked narrowing of the lumen (Fig. 3). No hematopoietic foci were found in the tumor. Smooth muscle cells were usually positive for HMB45 (Fig. 4), vimentin, muscle-specific actin and alphasmooth muscle actin, while there was no positivity using a cocktail of CD21 and CD35, CD23, anti-FDC antibody, CD68, S-100, and p80 in the smooth muscle cells.

Fig. 1. In the medium power field, the lesion contained numerous inflammatory cells, scattered spindle-shaped cells, and mature fat (arrow). HE  50.

M. Kojima et al. / Pathology – Research and Practice 200 (2004) 713–716

Fig. 2. High-power field of Fig. 1. Numerous small lymphocytes, mature plasma cells, and histiocytes with or without epithelioid cell features were present. The smooth muscle cells consisted of spindle-shaped cells or rounded cells with either clear cytoplasm or eosinophilic epithelioid cell features. Note the clusters of smooth muscle cells with clear cytoplasm (arrows). HE  100.

Fig. 3. Thick-walled artery with marked narrowing of the lumen. Azan–Mallory  50.

Staining with CD20 and 79a, as well as with CD3 and CD45RO, showed the mixed nature of the small lymphocytes. The plasma cells were demonstrated to be polytypic with a kappa- to lambda ratio of 1:1. CD68 immunostain highlighted the large number of histiocytes with or without epithelioid cell features. EBER-positive cells were not detected.

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Fig. 4. Small clusters of smooth muscle cells showed HMB45 positivity. Note the prominent inflammatory infiltrate in the background.  100.

Discussion Hepatic AML may demonstrate a marked histologic diversity and is frequently misdiagnosed [6,10]. For this tumor, HMB45 is a promising marker that is expected to facilitate the recognition of some AMLs with unusual morphology [9,10]. Among the morphologic variations of AMLs, an IPT pattern is infrequent and is usually identified focally in the lesion [10]. However, in the present case, numerous inflammatory cells, including small lymphocytes, plasma cells, and histiocytes, showed diffuse infiltration throughout the lesion. Myofibroblasts in IPT were occasionally positive for vimentin, muscle-specific actin, and smooth muscle actin [6]. IPT-like FDC tumor of the liver is a very rare EBVassociated tumor [2,3,7]. IPT-like FDC tumor shows a marked female predominance and an indolent clinical behavior [3]. The histomorphologic findings of this tumor were very similar to those of IPT. [3] However, spindle-shaped tumor cells usually express FDC markers such as CD21, 23, 35 and anti FDC antibody, as well as anaplastic lymphoma kinase (p80) [2,3,8]. The overall histologic and immunohistochemical findings of the present case were similar to those of IPT or IPT-like FDC tumor of the liver. However, the present case also shared some of the morphologic findings of hepatic AML, including the presence of clusters of smooth muscle cells with clear cytoplasm, a few scattered adipose cells, and thick-walled blood vessels. The tumor cells did not express FDC markers. Moreover, no EBER-positive cells were detected. HMB45 immunostain confirmed the diagnosis of AML.

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In conclusion, the microscopic appearance of hepatic AML may imitate several types of malignant tumors such as leiomyosarcoma, malignant fibrous histiocytoma, and hepatocellular carcinoma. The present case demonstrated an IPT pattern that was distributed throughout hepatic AML, indicating that an IPT pattern or an IPT-like FDC tumor should be added to the differential diagnoses for AML of the liver.

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