Different cytokeratin and neuronal cell adhesion molecule staining patterns in focal nodular hyperplasia and hepatic adenoma and their significance

Differentiating focal nodular hyperplasia from hepatic adenoma can be challenging. Cytokeratin 7, neuronal cell adhesion molecule, and cytokeratin 19 are differentially expressed in hepatocytes, biliary epithelium, and possibly hepatic progenitor/stem cells. CD34 is known to have altered expression patterns in the hepatic endothelium in conditions associated with abnormal perfusion and in hepatocellular carcinoma. The purpose of this study was to examine the expression pattern of these markers in focal nodular hyperplasia and hepatic adenoma and assess their diagnostic use. Ten resection specimens each of hepatic adenoma and focal nodular hyperplasia (including a case of telangiectatic focal nodular hyperplasia) were selected for the study. Immunohistochemical analysis was performed using antibodies against cytokeratin 7, cytokeratin 19, neuronal cell adhesion molecule, and CD34 on formalin-fixed, paraffin-embedded sections from each case. The staining patterns and intensity for each marker were analyzed. In hepatic adenoma, the cytokeratin 7 stain revealed strong positivity in hepatocytes in patches, with a gradual decrease in the staining intensity as the cells differentiated towards mature hepatocytes. Although bile ducts were typically absent in hepatic adenoma, occasional ductules could be identified with cytokeratin 7 stain. In focal nodular hyperplasia, cytokeratin 7 showed strong staining of the biliary epithelium within the fibrous septa and staining of the peripheral hepatocytes of most lobules that was focal and weaker than hepatic adenoma. Cytokeratin 19 and neuronal cell adhesion molecule showed patchy and moderate staining in the biliary epithelium of the ductules in focal nodular hyperplasia. While in the hepatic adenoma, cytokeratin 19 showed only rare positivity in occasional cells within ductules, and neuronal cell adhesion molecule marked occasional isolated cells in the lesion. CD34 showed staining of sinusoids in the inflow areas (periportal areas) in both focal nodular hyperplasia and hepatic adenoma. One case of telangiectatic focal nodular hyperplasia revealed both hepatic adenoma–like and focal nodular hyperplasia–like staining patterns. Distinct cytokeratin 7, cytokeratin 19, and neuronal cell adhesion molecule staining patterns are seen in hepatic adenoma and focal nodular hyperplasia possibly suggest activation of different subsets of hepatic progenitor/stem cell and can be diagnostically useful.     

Hepatic sinusoidal ectasia.

Oral contraceptive-associated sinusoidal ectasia is a rare lesion of unknown pathogenesis. We describe the case of a 31-year-old woman who had used oral contraceptives for 10 years and was found to have abnormal liver function tests on "routine" examination. A single 9 x 5 x 4 cm hypervascular lesion was demonstrated radiographically. The hepatic immuno-diacetic acid and liver-spleen scans were normal. One subcapsular lesion was identified in the resected right hepatic lobe; it was characterized by focal marked dilatation of the sinusoidal spaces associated with rare hepatocyte necrosis and early intrasinusoidal fibrosis. The subcapsular location and the vascular nature of this wedge-shaped lesion suggest it may represent the telangiectatic precursor of a centrally scarred focal nodular hyperplasia.     

Nodular transformation of the liver in hereditary hemorrhagic telangiectasia

A case of hereditary hemorrhagic telangiectasia with prominent nodular transformation of the liver is described. The presence of enlarged arteries was documented morphometrically. Artery-to-portal vein shunts were also found. The association of abnormal vessels with hepatic nodules supports the hypothesis that abnormalities of blood flow cause nodular transformation. Nodular transformation may be the lesion that has heretofore been termed cirrhosis hepatis telangiectasia or atypical cirrhosis.     

Histiocyte-rich reactive lymphoid hyperplasia of the liver: unusual morphologic features

Reactive lymphoid hyperplasia (RLH) of the liver is a rare entity and has also been termed nodular lymphoid lesion or pseudolymphoma of the liver. We report a case of hepatic RLH exhibiting unusual histiocyte-rich histologic features in a 47-yr-old woman in conjunction with a renal cell carcinoma. A follow-up computed tomography scan was done 14 months after a right radical nephrectomy for renal cell carcinoma revealed a nodular lesion in segment 5 of the liver. The lesion was interpreted as metastatic renal cell carcinoma or hepatocellular carcinoma based on the history of the patient and radiologic findings. Wedge resection of segment 5 was done with sufficient distance from the mass. Microscopically, the lesion was composed predominantly of peculiar histiocytic proliferation and was characterized by lymphoid aggregates forming a lymphoid follicle with germinal centers. The present case and prior cases reported in the literature suggest that RLH of the liver appear to be a heterogenous group of reactive inflammatory lesions that are often associated with autoimmune disease or malignant tumors.     

Benign multilocular cystic nephroma (author's transl)]

A case of benign multilocular cystic nephroma in a 12 month old male infant is reported. The patho-anatomical features of this rare renal lesion are demonstrated. Its possible histogenesis and relationship to nephroblastoma are discussed.     

A pathological study of nephroblastoma with congenital aniridia

A pathological study was conducted on four patients with nephroblastoma associated with aniridia. The age at diagnosis. was one year in three cases and 4 years in one case. Chromosomal analysis was performed in three cases, and showed 11p13 deletion in all. Each nephroblastoma consisted of metanephric blastemal, epithelial, and mesenchymal cells. All the tumors were centrilobar, and in one case an additional polypoid tumor grew into the renal pelvis. Histological examination showed conspicuous heterotopic cells, such as striated muscle and adipose tissue. Striated muscle was seen in all four cases, while both adipose tissue and smooth muscle were seen in two cases. Squamous epithelium was present in two cases. A literature survey revealed a high incidence of bilateral occurrence in cases of nephroblastoma associated with aniridia. Intralobar nephroblastomatosis was observed in all four cases, and it is proposed that this is the precursor lesion of nephroblastoma associated with aniridia.     

A Pathological Study of Nephroblastoma with Congenital Aniridia

A pathological study was conducted on four patients with nephroblastoma associated with aniridia. The age at diagnosis was one year in three cases and 4 years in one case. Chromosomal analysis was performed in three cases, and showed 11p13 deletion in all. Each nephroblastoma consisted of metanephric blastemal, epithelial, and mesenchymal cells. All the tumors were centrilobar, and in one case an additional polypoid tumor grew into the renal pelvis. Histological examination showed conspicuous heterotopic cells, such as striated muscle and adipose tissue. Striated muscle was seen in all four cases, while both adipose tissue and smooth muscle were seen in two cases. Squamous epithelium was present in two cases. A literature survey revealed a high incidence of bilateral occurrence in cases of nephroblastoma associated with aniridia. lntralobar nephroblastomatosis was observed in all four cases, and it is proposed that this is the precursor lesion of nephroblastoma associated with aniridia.     

Focal nodular hyperplasia of the liver: A clinicopathologic study and review of the literature

We reviewed the clinical records and pathologic material of 20 patients with biopsy proven hepatic focal nodular hyperplasia. The majority of the patients were females of child bearing age, five of whom had a history of oral use of contraceptives. In every instance focal nodular hyperplasia was an incidental finding; liver function tests were always normal. Focal nodular hyperplasia is a distinct histopathologic entity, distinguishable from liver cell adenoma. Specifically it consists of nodular aggregates of cytologically normal hepatocytes with foci of intranodular bile duct proliferation. Focal nodular hyperplasia appears to be a benign entity, even in patients in whom the lesion was not excised. The association between focal nodular hyperplasia and oral use of contraceptives may be coincidental, although hormonally related vascular changes may be responsible for rupture of the lesion.     

An unusual case of solid hamartoma in the liver

An unusual case of solid hepatic hamartoma, which could not be correctly categorized under the WHO classification, is reported. The well defined, solid nodular lesion, arising in the anterior edge of the left hepatic lobe, was found in a 15-month-old female infant. The lesion was composed of irregularly shaped yellow islands of parenchyma and white-gray nodules of fibrous stroma of various sizes, which were intermingled revealing a mosaic pattern. Prominent bile ductal proliferation was observed histologically in the fibrous stroma, associated in parts with dense or loose periductal bundles and vascular proliferation. The stromal proliferation seemed to result in erosion of the islands of differentiated parenchymal cells with no regeneration. Alpha-fetoprotein was demonstrated immunohistologically in the parenchymal cells of the lesion. From these findings, the essential component of this solid hamartoma was thought to be markedly proliferating bile ducts associated with periductal fibrosis, resulting in a fibroadenomatous pattern.     

True congenital nephroblastoma (author's transl)

A case of true congenital nephroblastoma is reported. The macroscopic and histologic features of this extremely rare renal lesion are depicted in detail and compared with those of congenital mesoblastic nephroma (fetal mesenchymal hamartoma).     

Nodular lymphoid lesion of the liver with simultaneous focal nodular hyperplasia and hemangioma: discrimination from primary hepatic MALT-type non-Hodgkin’s lymphoma

Nodular lymphoid lesion (NLL) of the liver is a rare but unique entity and has also been termed reactive lymphoid hyperplasia of the liver. We describe the histological, immunohistochemical and molecular biologic findings of a case with NLL and two other tumors of the liver. The nodular lymphoid mass found in the liver was composed of heterogeneous small lymphocytes forming reactive follicles. Plasma cells, few immunoblasts, centroblasts, few macrophages, epithelioid cells, and giant cells were seen. The lymphoid infiltrate displaced the adjacent hepatic parenchyma. By immunohistochemistry and molecular studies, the lymphocytes were found to be polyclonal. The diagnosis of NLL was made. In addition to NLL, focal nodular hyperplasia and hemangioma were detected. The discrimination of NLL from primary hepatic malignant non-Hodgkin’s lymphoma of mucosa- associated lymphoid tissue-type may pose diagnostic difficulties and may require the use of immunohistochemical and molecular techniques. The simultaneous occurrence of NLL with focal nodular hyperplasia and hemangioma in the liver has not been described before.     

A hypervascular pseudotumor in the liver with angiodysplasia in the center of the lesion: a new entity or a variant of focal nodular hyperplasia?

A unique case of hypervascular pseudotumor in the liver consisting of central angiodysplasia surrounded by atrophic liver tissue is described. A 45-year-old woman was referred for the incidentally found hepatic lesion. Computed tomography with contrast showed strong enhancement of the lesion in the arterial phase, and the effect persisted to the parenchymal phase. Doppler ultrasonography showed winding dilated blood flows into the lesion. Because the pathological examination of the biopsy specimen showed the possibility of a well-differentiated hepatocellular carcinoma, she underwent surgery. Final pathological findings showed that the lesion demonstrated atrophic change of the liver tissue with a cluster of abnormal vessels of various sizes in the center. Although there was no primary liver disease, multiple liver metastases from laryngeal carcinoma were found coincidentally. The present lesion could represent a new entity or a variant (or an unknown stage of development) of focal nodular hyperplasia.     

AN UNUSUAL CASE OF SOLID HAMARTOMA IN THE LIVER

An unusual case of solid hepatic hamartoma, which could not be correctly categorized under the WHO classification, is reported. The well defined, solid nodular lesion, arising in the anterior edge of the left hepatic lobe, was found in a 15-month-old female infant. The lesion was composed of irregularly shaped yellow islands of parenchyma and white-gray nodules of fibrous stroma of various sizes, which were intermingled revealing a mosaic pattern. Prominent bile ductal proliferation was observed histologically in the fibrous stroma, associated in parts with dense or loose periductal bundles and vascular proliferation. The stromal proliferation seemed to result in erosion of the islands of differentiated parenchymal cells with no regeneration. Alpha-fetoprotein was demonstrated immunohistologically in the parenchymal cells of the lesion. From these findings, the essential component of this solid hamartoma was thought to be markedly proliferating bile ducts associated with periductal fibrosis, resulting in a fibroadenomatous pattern. ACTA PATHOL JPN 38: 75–82, 1988.     

Reactive lymphoid hyperplasia of the liver characterized by an angiofollicular pattern mimicking Castleman's disease

A case of reactive lymphoid hyperplasia of the liver exhibiting a characteristic angiofoillcular pattern is reported. A hepatic nodular lesion was discovered by abdominal echography during clinical follow-up of abnormal liver function tests. It was diagnosed as hepatocellular carcinoma because of Its hypervascularity when observed by angiography, and surgically resected. Grossly, the lesion was well-demarcated and measured 2 cm In diameter. Microscopycally, the nodule was composed of lymph follicies with germinal centers, and the hyalinized Inter-follicular space contained abundant hyalinized vasculature and plasma cells. The surrounding liver tissue exhibited chronic Inflammation with some pecullar angiofolllcular structures mimicking Castleman's disease. An Immunohistoehemical study revealed that the angiofoillcular structure had the same characteristics as a lymph follicle with a general center, and that the plasma cells proliferating in the inter-follicular space had polyclonal Immunophenotypes. These histological and immunohistochemical findings Indicated that the angiofoillcular structure observed was a kind of reactive lymph follicle, and that this hepatic lesion was reactive lymphoid hyperplasla rather than Castleman's disease or an inflammatory pseudotumor.     

Focal nodular hyperplasia of the liver associated with portal vein agenesis: a morphological and immunohistochemical study of one case and review of the literature

Congenital absence of portal vein (CAPV) is a rare malformation. To our knowledge, sixteen cases are reported in western literature. All the cases are associated with other diseases, cardiac malformations (12/17 patients; 16 plus the present case) and hepatic neoplasms being the most frequent observations. We present the case of a girl with a complex malformative syndrome consisting of multicystic kidney dysplasia, CAPV and nodular tumor-like mass of the liver. Angiography showed that the splenic vein and superior mesenteric vein joined to form a common trunk directly entering the inferior vena cava above the liver. A review of the CAPV cases of the literature and the clinical and pathological features of the hepatic lesion, classified as Focal Nodular Hyperplasia (FNH), are extensively discussed.     

Hepatocellular adenoma(s) arising in nodular regenerative hyperplasia in a patient with systemic lupus erythematosus

Hepatocellular adenoma (HCA) is a rare benign tumor of the liver with low risk of malignant transformation. It is associated with oral contraceptives/anabolic steroid use, metabolic disease, and rarely, vascular abnormalities. We report an interesting case of HCA arising in a background of diffuse hepatic nodular regenerative hyperplasia (NRH) in a 40-year-old female patient with systemic lupus erythematosus (SLE). She presented with sudden-onset refractory ascites, elevated liver enzymes, diffuse hepatic nodularity and mass lesions on imaging concerning for malignancy. Targeted biopsies of the mass lesion were performed with inconclusive diagnoses. The patient ultimately underwent resection of the mass, which was confirmed as HCA, inflammatory type, arising in a background of NRH. It is not uncommon for SLE patients to have liver manifestations such as NRH, but HCA arising in NRH has not been previously reported. Our case reveals an unusual relationship between HCA and hepatic vasculopathy in the clinical context of a systemic inflammatory condition, the mechanism by which is not fully understood.     

Fine-needle aspiration cytology of extranodal natural killer/T-cell lymphoma

Extranodal NK/T-cell lymphoma, nasal type, is a predominantly extranodal lymphoma characterized histologically by prominent necrosis, angiocentric growth, and vascular destruction. Only one report describing its fine-needle aspiration (FNA) cytologic features is available and shows highly unusual findings for a lymphoma. The present case concerns a 58-yr-old patient that presented with a soft tissue mass of the thigh in addition to an ulcerative lesion of the palate and nodular hepatic and splenic lesions. FNA cytology of the thigh tumor was interpreted as a malignant mesenchymal lesion (sarcoma). The subsequent pathologic study revealed an NK/T-cell lymphoma. Our findings are very similar to those previously reported. They were highly unusual for a lymphoma and consisted of polymorphic, round to spindle neoplastic cells distributed in irregular aggregates, and single cells. No significant number of lymphoglandular bodies were present.     

ALAGILLE'S SYNDROME

A male case of Alagille's syndrome associated with a hamartomatous nodule of the liver is described. The patient developed jaundice soon after birth, and was diagnosed as the syndrome with signs such as paucity of the intrahepatic bile ducts, pulmonary stenosis and embryotoxon in the cornea at 15 years of age. The liver was examined in recurrent biopsies and other tests. However, no evidence of liver cirrhosis was confirmed until his 15th year. The patient died of hepatic dysfunction when he was 17 years old. At autopsy, a large hamartomatous nodule was found in the liver showing biliary cirrhosis. Morphology of the nodule resembled that of focal nodular hyperplasia. Abnormalities of the large vessels were noted around the liver. Vascular abnormalities were also seen in the mass. The relation of these vascular abnormalities to etiological background of the syndrome and occurrence of the nodular lesion is discussed.     

An ischemic skin lesion after chemoembolization of the right internal mammary artery in a patient with hepatocellular carcinoma

A huge nodular hepatocellular carcinoma located at the anterior superior portion of the left lobe in a patient with hepatocellular carcinoma was treated with transcatheter arterial chemoembolization through the left hepatic artery. Three months later, however, there was a re-elevation of the serum alpha-fetoprotein level and evidence of a marginal recurrence at the left side of the previously embolized tumor was noted on the postembolization computed tomographic scan. Although the hepatic artery was intact in the second hepatic arteriography, we found that the right internal mammary artery was feeding the recurred hepatocellular carcinoma. This internal mammary artery was successfully treated with Lipiodol-transcatheter arterial chemoembolization. However, an ischemic lesion occurred in the skin of the anterior chest and abdominal wall several days after internal mammary artery embolization. We report here a very rare case of ischemic skin lesion on the anterior chest and abdominal wall following transcatheter arterial chemoembolization of the right internal mammary artery. This internal mammary artery was embolized because it had developed a collateral tumor feeding vessel following the initial chemoembolization of a hepatocellular carcinoma.     

Alagille's syndrome. A case with a hamartomatous nodule of the liver

A male case of Alagille's syndrome associated with a hamartomatous nodule of the liver is described. The patient developed jaundice soon after birth, and was diagnosed as the syndrome with signs such as paucity of the intrahepatic bile ducts, pulmonary stenosis and embryotoxon in the cornea at 15 years of age. The liver was examined in recurrent biopsies and other tests. However, no evidence of liver cirrhosis was confirmed until his 15th year. The patient died of hepatic dysfunction when he was 17 years old. At autopsy, a large hamartomatous nodule was found in the liver showing biliary cirrhosis. Morphology of the nodule resembled that of focal nodular hyperplasia. Abnormalities of the large vessels were noted around the liver. Vascular abnormalities were also seen in the mass. The relation of these vascular abnormalities to etiological background of the syndrome and occurrence of the nodular lesion is discussed.