Reactive lymphoid hyperplasia (RLH), also termed as nodular lymphoid lesion [
The data of all cases diagnosed as hepatic RLH or pseudolymphoma and treated by surgery in Eastern Hepatobiliary Surgery Hospital, a tertiary university hospital in China, between January 1996 and June 2011 were obtained from the computerized files. Results of imaging studies such as ultrasonography (US), computerized tomography (CT), and magnetic resonance imaging (MRI), the clinicopathological findings and the outcomes of followup of the patients were retrospectively reviewed.
All the patients underwent surgery with complete resection of lesion(s). The resected specimens were fixed in 4% buffered formalin, processed, and embedded in paraffin. Histologic sections were stained with hematoxylin and eosin. Immunohistochemistry of paraffin sections was carried out using EnVision system (a two-step staining technique) as described previously [
After surgery, all the patients were monitored by serumtumor markers, abdomen US, and chest X-ray every 1 to 3 months. If recurrence suspected, the patients underwent CT or MRI for further evaluation. The last followup was completed on December 31st, 2011 and the data were analyzed after the last followup.
From January 1996 to June 2011, a total of 45,000 patients with occupied lesion(s) in liver were admitted to our hospital for partial hepatectomy. In 7 of them, hepatic RLH was confirmed by pathological examination of resected specimens. There were 6 females and 1 male, with a median age of 46 years (range: 33–76 years). The patients were either asymptomatic or had mild nonspecific symptoms such as abdominal discomfort. Hepatitis B surface antigen was negative in 6 female patients, but positive in the male patient who was accompanied by cirrhosis. Hepatitis C virus antibody was negative in all the patients. Tumor markers including AFP, CEA, and CA19-9 were within normal range in all cases. Hepatic function tests and blood routine test were normal. Hemangiomas happened to occur simultaneously with RLH in two patients, and gall bladder calculi and fibroadenoma of breast are found in two female patients. In this series, the sizes of hepatic lesions varied from 13 × 15 mm to 105 × 65 mm on US scan, and the lesion of the male patient progressed during three years before operation (from 1.0 × 1.2 cm to 4.0 × 2.0 cm). Preoperatively, hepatocellular carcinoma (HCC) was suspected in 6 patients and intrahepatic cholangiocellular carcinoma in the other one.
All the patients underwent curative local resections, and the postoperative course was uneventful in all cases. After surgery, no patient received subsequent therapy for hepatic RLH. Recurrence did not occur in any of our patients during a median followup of 68 months (range: 6–228 months).
All the lesions of RLH were revealed as well-defined hypoechoic masses on US examination. The lesions were presented as hypodense masses on plain CT scan, slightly enhanced in the arterial phase, hypodense in the portal phase and the delayed phase as compared with liver parenchyma. MRI depicted hepatic RLH as nodular lesions with hypointense signal masses on T1-weighted imaging (Figure
Comparison of appearances of hepatic RLH (a–e) with hepatocellular carcinoma (f–j) on fast spoiled gradient recalled echo (FSPGR) MRI. (a) On unenhanced T1-weighted image, the lesion is hypointense signal relative to normal liver parenchyma. (b) The lesion is hyperintense signal in the same location on T2-weighted image. (c) The lesion is enhanced in the arterial phase. (d) The lesion is hypodense in the portal phase. (e) The lesion is unclear in the delayed phase. (f) On plain T1-weighted imaging scan, the lesion is hypointense signal relative to normal liver parenchyma. (g) The lesion is hyperintense signal in the same location on T2-weighted image. (h) The lesion is significantly enhanced in the arterial phase. (i) The lesion is hypodense in the portal phase. (j) The lesion became more hypodense in the delayed phase.
On the cut sections, the lesions were grossly distinct firm nodules well demarcated from the surrounding liver tissue, sometimes encapsulated (5/7), with small areas of hemorrhage and necrosis (3/7) (Figure
(a) Macroscopically, a cut section of the resected liver showed a well-circumscribed, encapsulated, yellow-white nodular lesion in segment 6, with small areas of hemorrhage and necrosis. (b) Microscopically, the lesion was well demarcated and encapsulated, and comprised a massive infiltration of mature lymphoid cells, forming follicles and germinal centers (H&E staining, 100x magnification). (c) The infiltrated lymphoid cells was mature and heterogeneous, with no nuclear atypia or polymorphism (H&E staining, 100x magnification). (d) Note the lymphocytic infiltration in the portal tracts around the lesion (H&E staining, 100x magnification).
(a) Immuno.histochemistry showed that germinal centers mainly comprised CD20 (+) B lymphocytes (100x magnification) (b) Germinal centers mainly comprised LCA (+) lymphocytes (100x magnification) (c) T lymphocytes in interfollicular area and surrounding germinal centers were CD45RO (+) (100x magnification) (d) Germinal centers mainly comprised CD20 (+) B lymphocytes (400x magnification).
RLH is a benign condition that may occur, besides in liver, in the gastrointestinal tract [
The incidence rate of this disorder seems to be increasing, calculated by the time when reported.
At present, this is the largest case series review of hepatic RLH. In total, 41 cases of hepatic RLH are reported, including 36 females and 5 males (median age of 57 years; range, 15–85 years). All hepatic RLH patients were adults except for one 15-year-old female. A female predilection of this disease was obvious in both the present series (6/7) and when considering the sum of all cases (36/41). 6 cases have multiple hepatic lesion of RLH, and there were 49 hepatic lesions altogether. The average size (in greatest dimension) of hepatic lesions of our cases was 45.0 mm (range: 15–105 mm), which was bigger than that (15.6 mm in average; range: 4–60 mm) of the reported cases. The background data and the clinical characteristics of these 41 patients were summarized in Table
Background data and clinical characteristics of all cases including the reported.
Background data and clinical characteristics | |
---|---|
Variables | Cases |
Age (Y) | |
15–30 | 1 |
31–60 | 21 |
60–85 | 19 |
Sex | |
Female | 36 |
Male | 5 |
Concomitant disease | |
Chronic hepatitis | 7 |
Sjögren's syndrome | 1 |
CREST syndrome | 1 |
Autoimmune thyroiditis | 5 |
Malignant tumor | 12 |
Hepatic hemangioma/FNH | 3 |
PBC | 4 |
DM | 2 |
Immunodeficiency | 2 |
Size in the greatest dimension of lesions (cm) | |
|
37 |
>4 | 4 |
Number of lesions | |
Solitary | 35 |
Multiple | 6 |
Location | |
Rt. lobe | 21 |
Lt. lobe | 13 |
Lt. lobe and Rt. lobe | 2 |
NA | 5 |
Treatment | |
Surgical resection | 34 |
Transplantation | 2 |
CNB and PEI | 1 |
CNB and observation | 3 |
Autopsy | 1 |
Rt: right; Lt: left; Seg: segment
The exact etiology of this disease remains unclear. An association between the development of hepatic RLH and some disease such as autoimmune diseases [
It is very difficult to make a correct diagnosis of hepatic RLH before operation, as almost all of the cases including the reported have been misdiagnosed. Hepatic RLH has most frequently been misdiagnosed as HCC, as preoperative diagnosis are HCC (6/7) for our cases, while HCC (15/41) for all cases including the reported. Thus, differential diagnosis between hepatic RLH and HCC is important but difficult, given their similarity on radiological appearances. However, in our cases, we found subtle differences in radiological findings between hepatic RLH and HCC. On MRI scan, hepatic RLH is always moderately enhanced in the arterial phase (Figure
Preoperative imaging findings of hepatic RLH of all cases including the reported.
Preoperative imaging findings | Cases |
---|---|
US | |
Hypoechoic mass | 7 |
CT | |
Plain: hypodense | 18 |
Arterial: significantly/slightly/peripherally enhanced | 12 |
Parenchymal and portal: clearly/vaguely low | 12 |
MRI | |
Plain T1: low; T2: high | 13 |
Arterial: highly/slightly enhanced | 8 |
Portal and delayed: peripherally ring enhanced or |
8 |
Angiography | |
Hypervascularity | 10 |
US: ultrasonographic; CT: computerized tomography; MRI: magnetic resonance imaging.
It is difficult to definitely recognize hepatic RLH by routine histologic evaluation alone. Common morphologic features include a well-demarcated region, hyperplastic lymphoid follicles with active germinal centers, hyalinized trabecular structures, and lymphocytic infiltration in the portal tracts around the nodular lesion [
Pathological characteristics of hepatic RLH of all cases including the reported.
Histological, immunohistochemical, and molecular findings | Cases |
---|---|
LIPTANL | 22 |
Germinal center CD20/L26 (+) | 26 |
Germinal center LCA (+) | 6 |
Interfollicular area and surrounding germinal centers CD45RO/UCHL1 (+) | 15 |
Area surrounding germinal centers CD3 (+) | 11 |
Ductal structures at the periphery of the nodule CK7 (+) | 5 |
Polyclonal in |
26 |
Massive infiltration of heterogeneous mature lymphoid cells with no nuclear atypia, forming follicles and germinal centers | 41 |
LIPTANL: lymphocytic infiltration in the portal tracts around the nodular lesion; NA: not available; L26 = CD20; UCHL1 = CD45RO.
Although hepatic RLH is generally thought to be benign, it might transform into malignant lymphoma [
In conclusion, hepatic RLH is a rare disease which mostly occurs in females, and the exact etiology of this disease is still unknown. Hepatic RLH has similar features with malignant liver tumors on radiological findings, but subtle differences such as “the lesion becomes unclear in the delayed phase on MRI scan with injection of contrast agents” can be found to be helpful for differential diagnosis. An accurate postoperative diagnosis of this disease depends not only on morphologic findings, but also on immunohistochemical analysis and molecular investigations. Given that hepatic RLH may grow with time or might even transform into malignant lymphoma, surgical resection is suggested, both for the safety and for good prognosis of the disease.
L. Yuan, Y. Zhang, Y. Wang, W. Cong, and M. Wu have no conflict of interests or financial ties to disclose.