Primary Hepatic Schwannoma: Case Report and Literature Review

Abstract

Primary hepatic schwannoma is an extremely rare tumor with a good prognosis. Preoperative diagnosis is often challenging due to nonspecific clinical symptoms and its rarity. Here, we report a case of a 56-year-old male patient misdiagnosed with malignant liver tumor, later identified as primary hepatic schwannoma. Furthermore, clinical and histopathological features of 19 cases of primary hepatic schwannoma are also documented. The age of the patients ranged from 38 to 72 years, with a mean age of 56.4 years, and the disease was more common in females. Patients typically presented without clinical symptoms and were not associated with neurofibromatosis type 1. Histopathological features of the tumor were similar to soft tissue schwannoma, characterized by a thick capsule consisting of Antoni A and Antoni B areas. Immunohistochemically, the tumor showed strong positivity and diffusely stained with S-100, while being negative for CD34, CD117, and SMA. Complete resection of the tumor was achieved in all patients. The prognosis was favorable, with no signs of recurrence. Follow-up examinations revealed disease-free survival ranging from 6 to 27 months. Differential diagnosis of primary hepatic schwannoma from malignant liver tumors and metastatic liver tumors can be made based on histopathological features and immunohistochemical staining with S-100.

Introduction

Schwannoma is a benign neoplasm of the nerve sheath that is primarily composed of well-differentiated Schwann cells and characterized by its encapsulated nature. It is the most prevalent benign peripheral nerve tumor in adults and typically occurs in the head and neck, upper and lower extremities, posterior mediastinum, and retroperitoneum. ¹ Their occurrence in hepatic tissue is extremely rare. The clinical manifestations of the tumor depend on its location and size, making preoperative diagnosis challenging and difficult to differentiate from malignant hepatic tumors.^1,2 In the present study, a comprehensive literature review was conducted, and a total of 19 cases of hepatic schwannoma were identified after careful exclusion of duplicate reports and those with insufficient clinical data. This study describes a case of hepatic schwannoma and provides a relevant review of the existing literature.

Case Report

A 56-year-old male was incidentally discovered to have a hepatic mass during a routine check-up, as observed on abdominal ultrasound. The patient was subsequently referred to our hospital for further evaluation and treatment. There were no notable findings in the patient’s medical or family history.

Physical examination did not reveal any abnormal findings. Routine hematological and blood biochemistry tests yielded normal results. All markers associated with hepatitis B and C were negative. The levels of tumor markers, including alpha-fetoprotein and carbohydrate antigen 19-9, were within the normal range.

Abdominal ultrasound revealed a hypoechoic, lobulated mass in segments II and III of the liver. Abdominal computed tomography (CT) exhibited a low-density mass measuring 9 × 7 cm in the left lobe of the liver before contrast material administration, which showed less enhancement compared to the surrounding liver parenchyma after contrast material injection (Figure 1). The adjacent liver parenchyma appeared to be mildly compressed by the mass, yet remained normal with no signs of fibrosis, fatty degeneration, or any other abnormalities. There were no indications of cirrhosis or other hepatic pathologies outside the tumor region. No enlarged lymph nodes adjacent to the mass or involvement of other organs were observed. Magnetic resonance imaging (MRI) demonstrated a mass in the left lobe of the liver, exhibiting low signal intensity in T1-weighted images and slightly high signal intensity in T2-weighted images (due to some technical and archival issues, the MRI images are no longer available).

Figure 1.

(A) Abdominal CT image demonstrated a 9 × 7 cm size, hypoattenuating mass in the left lobe of the liver prior to contrast material administration. (B) After contrast material injection, the mass exhibited less enhancement compared to the surrounding liver parenchyma (white arrow).

Based on the suspicion of a malignant hepatic tumor, a left hepatectomy was carried out. Due to the considerable size of the liver tumor, coupled with the non-specific findings from imaging diagnostics and the absence of distinctive markers from laboratory tests, a definitive determination of the lesion as benign or malignant was challenging. Multiple differential diagnoses were considered pre-operatively, such as hepatocellular carcinoma, intrahepatic cholangiocarcinoma, focal nodular hyperplasia, hepatic adenoma, mesenchymal tumors in the liver (such as leiomyoma, solitary fibrous tumor or neurofibroma), metastatic tumors to the liver like gastrointestinal stromal tumor, and leiomyosarcoma of the inferior vena cava, etc. Despite the uncertainties, the decision was made to proceed with surgery without a prior core biopsy, due to concerns about potential complications that might arise from biopsying such a large tumor. The patient underwent a limited liver resection with a 30 cm J-shaped incision. The surgery was completed in 220 minutes, with an estimated blood loss of around 200 ml. The tumor was entirely excised.

Macroscopic examination revealed a well-defined, lobulated, yellowish-white mass measuring 10 cm in maximum diameter (Figure 2A). Histological analysis demonstrated a tumor surrounded by a fibrous capsule. The tumor consisted of uniform spindle cells arranged in interlacing bands. These spindle cells exhibited elongated nuclei arranged in a palisading pattern, along with a mild infiltration of chronic inflammatory cells, including lymphocytes and histiocytes. No significant evidence of nuclear atypia, mitotic activity, or necrosis was observed (Figure 2B-D). Immunohistochemical staining indicated tumor cells were diffusely and strongly positive for S-100, but negative for CD117, DOG-1, SMA, CD34, Desmin and ALK-1 (Figure 3). The histopathological findings confirmed the final diagnosis of primary hepatic schwannoma. The patient’s postoperative recovery was uncomplicated, and there have been no indications of recurrence during the 6-month follow-up period.

Figure 2.

(A) Macroscopically, a distinct, lobulated, yellowish-white mass measuring 10 cm in maximum diameter was observed. (B and C) Microscopic examination revealed a tumor with a fibrous capsule (black arrow) and interlacing bands of uniformly spindle-shaped cells with elongated nuclei arranged in a palisading pattern. (D) Additionally, there was a mild infiltration of chronic inflammatory cells, including lymphocytes and histocytes. No evidence of nuclear atypia, mitosis, or necrosis was observed (Hematoxylin-Eosin, Bx40, Cx100, Dx200).

Figure 3.

Immunohistochemistry (magnification x100) revealed that tumor cells were diffusely and strongly positive for (A) S-100, but negative for (B) CD117, (C) DOG-1, (D) SMA, (E) CD34, and (F) ALK-1. The histopathological findings confirmed the final diagnosis of primary hepatic schwannoma.

Discussion

Literature in the English medical community has documented the clinical and pathological characteristics of 19 cases of primary hepatic schwannoma, including the case presented in this study (Table 1).^{3 -18}

Table 1.

The clinicopathological characteristics of 19 cases of primary hepatic schwannoma.

Author/year	Sex/age	Symptoms	Clinical diagnosis	Treatment	Diameter (cm)	Gross features	Location	IHC	Outcome	Follow up
Our case	M/56	Asymptomatic	Malignant hepatic tumor	Surgery	10.0	Well-defined, lobulated, yellowish-white mass.	Left	S100 (+), CD117 (-), CD34 (-), DOG1(-), SMA (-), Desmin (-), ALK-1 (-)	Survival	6 months
Hytiroglou, 1993 3	M/67	Right flank and black pain	Liver tumor	Surgery	13.0	Well-defined mass, areas of hemorrhage, necrosis, calcification.	Right	-	Survival	-
Heffron, 1993 4	F/38	Right upper quadrant abnormal pain	Schwannoma	Surgery	5.0	Encapsulated, well-defined, yellow-tan and soft tumor, cystic foci.	Left	S100(+), Desmin (−) Vimentin(-)	Survival	18 months
Yoshida, 1994 5	F/56	Epigastrium and chest discomfort	Liver tumor	Surgery	16.0	Encapsulated tumor, areas of cystic degeneration and hemorrhage.	Right	-	Survival	-
Wada, 1998 6	F/64	Asymptomatic	Liver tumor	Surgery	4.0	Yellowish, elastic-hard, globular, well-defined tumor.	Left	S100(+), Desmin (+), SMA (−), EMA (−), Vimentin (-), CD34 (−).	Survival	-
Wada, 1998 6	F/69	Asymptomatic	Liver tumor	Surgery	15.0	Yellowish, elastic-hard, globular, well-defined tumor, cystic space.	Left	S100 (+), Desmin (+), NSE (+), SMA (−), EMA (−), Vimentin (−), CD34 (−).	Survival	-
Flemming, 1998 7	F/57	Upper abdominal pain	Hydatid disease	Surgery	Huge	Large mass, cystic area.	Right	S100(+) diffuse strong	Survival	-
Kapoor, 2005 8	F/mid-aged	Epigastric lump and dull pain	Liver adenoma	Surgery	23.0	Large mass, soft to firm, central necrosis.	Left	S100(+), CD117 (−), NSE (-), SMA (−).	Survival	6 months
Lee, 2008 9	F/36	Vague, constant Epigastric discomfort	Benign mesenchymal tumor	Surgery	5.0	Encapsulated, round, cystic mass	Right	S100 (+) strong, CD34 (−), CD117 (−), SMA (−)	Survival	18 months
Momtahen, 2008 10	F/52	Asymptomatic	Schwannoma	Surgery	4.4	Oval-shaped mass	Right	S100(+), Vimentin (+)	Survival	-
Akin, 2009 11	F/66	Asymptomatic	Breast cancer metastasis	Surgery	5.0	Yellowish, soft, capsulated tumor	Left	S100(+) diffuse strong	Survival	-
Ozkan, 2010 12	F/56	Epigastric pain	Liver hydatid cyst	Surgery	15.0	Hemorrhagic, brown colored, irregular surfaces mass, elastic density.	Left	S100 (+), NSE (+), SMA (−)	Survival	22 months
Kim, 2010 13	M/52	Asymptomatic	Malignant or Inflammatory tumor	Surgery	4.5	Well demarcated yellowish, solid round mass.	Left	S100(+), CD117 (−), CD34 (−), SMA (−)	Survival	-
Ota, 2012 14	F/72	Asymptomatic	Malignant epithelial tumor	Surgery	4.5	Well-defined, whitish/brownish, localized mass, surrounded by a fibrous capsule.	Right	S100 (+), Vimentin (+), NSE (+), SMA (−), CD34 (−), CD117 (-), HMB45 (−)	Survival	12 months
Hayashi, 2012 2	M/64	Asymptomatic	GIST metastasis	Surgery	2.3	Well-defined, solid mass	Left	S100 (+), CD117 (−), CD34 (−)	Survival	27 months
Yamamoto, 2016 15	M/47	Asymptomatic	HCC or colorectal liver metastases	Surgery	5.0	Well-defined, white-gray tumor, focal cystic changes.	Right	-	Survival	6 months
Wan, 2016 16	M/64	Upper abdominal pain	ICC	Surgery	11.5	Hard protruding mass.	Left	S100 (+), Vimentin (+), CD117(−), Desmin (−), SMA (−) CD34 (−)	Survival	16 months
Choi, 2018 17	M/56	Asymptomatic	Liver tumor	Surgery	3.0	Solid mass.	Left	S100 (+), CD117 (−), CD34 (−), SMA (−)	Survival	-
Haradome, 2018 18	F/50	Asymptomatic	Liver tumor	Surgery	7.8	Encapsulated, yellowish mass, multi-cystic with multisepta	Left	S100 (+), Neurofilaments (−)	Survival	-

Abbreviations: F, female; GIST, gastrointestinal stromal tumor; HCC, hepatocellular carcinoma; ICC, intrahepatic cholangiocarcinoma; M, male.

Schwannomas exhibit a wide age distribution, but they are predominantly observed in individuals aged between 30 and 60 years. In our investigation, the patients’ ages ranged from 38 to 72 years, with a mean age of 56.4 years, and a female-to-male ratio of approximately 2:1.^{3 -5}

Clinical manifestations and symptoms of patients are influenced by the tumor’s anatomical location and size. The majority of patients (approximately 58%) were asymptomatic, with hepatic masses incidentally detected during routine or follow-up examinations related to prior medical conditions. Some patients presented with upper abdominal pain (37%), back and hip pain (5%), and chest discomfort (5%). Notably, none of the patients had a history of neurofibromatosis type 1.^{5 -7}

Schwannomas, when visualized through imaging techniques, present distinct characteristics. On CT scans, they typically appear as well-defined hypodense regions. Enhanced CT further reveals an irregular internal pattern characterized by peripheral enhancement. This delayed peripheral enhancement, evident until the late venous phase, suggests the presence of a fibrous capsule and an internal fibrillary component. MRI results commonly show hypointensity on T1-weighted images. On T2-weighted images, schwannomas can manifest as inhomogeneously hyperintense masses, or in certain instances, as masses with a mixed internal hypo- and hyperintensity. Such radiological manifestations are indicative of secondary degenerative changes, including pseudocystic regression and hemorrhage. Interestingly, FDG-PET has shown abnormal uptake, highlighting the high cellular density inherent to schwannomas. However, achieving a preoperative diagnosis of a schwannoma based solely on its radiological appearance remains a significant challenge, even with the insights provided by FDG-PET.^{7 -9}

According to research by Yamamoto et al,^2,15 the predominant CT findings for schwannomas include a low-density appearance during a plain phase and a clearly demarcated lesion with varied enhancement. These imaging characteristics align with those observed in standard acoustic schwannomas or those originating from more prevalent sites. Another study by Ota et al ¹⁴ highlighted the utility of contrast-enhanced ultrasound in diagnosing hepatic schwannoma, revealing minute arterial flow into the tumor during the vascular phase and subsequent enhancement of solid regions during the postvascular phase.

Despite these detailed imaging characteristics, accurately diagnosing a schwannoma preoperatively is challenging, primarily due to its rarity and its radiological resemblance to other tumors like mucus-producing tumors or adenocarcinomas. Expert radiological advice is crucial when a schwannoma is suspected. Notably, radiological features don’t seem to vary between malignant and benign hepatic schwannomas, making differentiation based solely on preoperative imaging challenging. If a preoperative diagnosis confirms a schwannoma, surgical removal remains the recommended course of action due to the potential for malignant transformation. It’s worth noting that about half of all documented hepatic schwannomas have been identified as malignant.^5,9,13

Regarding gross characteristics, primary hepatic schwannomas were predominantly located in the left liver lobe (63.2%) and right liver lobe (36.8%). The tumors exhibited a maximum diameter ranging from 2.3 to 23 cm, with a mean diameter of 8.5 cm. Most cases demonstrated well-defined margins, encapsulation, and a grayish-white or yellowish-white appearance. Larger tumors occasionally exhibited areas of cystic degeneration, hemorrhage, or calcification upon gross examination.^{10 -12}

Microscopically, typical schwannomas were encapsulated by a thick fibrous capsule and displayed distinct Antoni A and Antoni B areas. Antoni A areas (cellular areas) consisted of spindle-shaped cells with uniform nuclei, arranged in a palisading or storiform pattern. In contrast, Antoni B areas (hypocellular areas) exhibited myxoid or degenerative stroma. The relative proportion of these 2 components varied. Additionally, the tumor tissue could contain areas of cystic changes and inflammatory cell infiltration, particularly lymphocytes, histiocytes, and foamy histiocytes. Malignant transformation of schwannoma is exceedingly rare; nevertheless, a few reported cases exist. Malignant peripheral nerve sheath tumors (MPNSTs) originating from a preexisting schwannoma were diagnosed based on histopathological features, including atypical nuclei, increased cell density, and the presence of mitotic figures (⩾5/10 high-power fields).^{13 -16}

Differential diagnoses of primary hepatic schwannoma encompass malignant liver tumors, hepatic hydatid disease, metastatic gastrointestinal stromal tumors (GISTs), and inflammatory pseudotumors, etc. Immunohistochemical analysis revealed strong expression of S-100 protein and negativity for CD34, CD117, and smooth muscle actin (SMA) in the tumor tissue. Positive staining for Vimentin and NSE may also be observed.^7,17,18

All patients underwent complete surgical resection of the tumors, resulting in a favorable prognosis with no evidence of recurrence during the follow-up period, ranging from 6 to 27 months.

Conclusion

Primary hepatic schwannoma is an extremely rare tumor, and it needs to be distinguished from primary malignant liver tumors and metastatic liver tumors. Preoperative diagnosis remains challenging. The histopathological diagnosis of the tumor is determined after surgical resection, and it consists of Antoni A and B areas. The tumor tissue shows strong positivity for S100 protein and negativity for immunohistochemical markers CD34, CD117, and SMA.