Hepatocellular carcinoma and myocardial sarcoidosis.--An autopsy case.

An autopsy case of a 65-year-old male who died of hepatocellular carcinoma superimposed on liver cirrhosis complicated with systemic sarcoidosis is presented. No organ metastasis of hepatocellular carcinoma was found except for a minute tumor embolus in the left upper lobe of the lung. Involved organs by sarcoidosis were the lymph nodes, lungs, heart, liver and spleen, but its presence was not noticed before death. Its cardiac involvement coincide with his clinical symptom of exertional dyspnea and the ECG finding of A-V block.     

HEPATOCELLULAR CARCINOMA AND MYOCARDIAL SARCOIDOSIS—AN AUTOPSY CASE—

An autopsy case of a 65-year-old male who died of hepatocellular carcinoma superimposed on liver cirrhosis complicated with systemic sarcoidosis is presented, No organ metastasis of hepatocellular carcinoma was found except for a minute tumor embolus in the left upper lobe of the lung. Involved organs by sarcoidosis were the lymph nodes, lungs, heart, liver and spleen, but its presence was not noticed before death. Its cardiac involvement coincide with his clinical symptom of exertional dyspnea and the ECG finding of A-V block.     

Sarcoidosis with selective involvement of a second liver allograft: report of a case and review of the literature.

A case of sarcoidosis recurrent in a patient's second liver allograft is described. There was no granulomatous disease seen in the patient's first liver allograft. After the second orthotopic liver transplantation (OLT), the patient was successfully treated for acute rejection, aspergillus infection, and cytomegalovirus viremia. Approximately 2 months after the second OLT, the patient was treated with long-term interferon-alpha for recurrent hepatitis C. Five years after the operation, he experienced liver failure secondary to recurrent hepatitis and underwent a third OLT. This is only the second reported case of sarcoidosis recurrent in the liver parenchyma of a transplanted organ and the first in which interferon-alpha might have played a role.     

Pituitary Adenoma with Tumoral Granulomatous Reaction

Herein, we report a unique case of an adult male with a corticotrophic pituitary adenoma of silent subtype 1 exhibiting conspicuous idiopathic tumoral noncaseating granulomatous inflammation. The lesion was unassociated with clinical or laboratory evidence of either systemic sarcoidosis or infection. Histochemical and polymerase chain reaction (PCR) studies revealed neither fungi nor tubercle bacilli. We suggest that tumoral production of an as yet uncharacterized antigen may have induced the granulomatous inflammatory reaction.     

Poorly differentiated hepatocellular carcinoma accompanied by anti‐Hu antibody‐positive paraneoplastic peripheral neuropathy

The anti‐Hu antibody is one of the most famous onco‐neural antibodies related to paraneoplastic neurological syndrome, and is associated with small cell lung carcinoma in most cases. Here, we report a case of poorly differentiated hepatocellular carcinoma accompanied by paraneoplastic peripheral neuropathy positive for the anti‐Hu antibody. Image inspection before operation revealed that no tumors were found in organs other than the liver, including lung, and that the liver tumor had no metastatic lesion. The liver tumor showed histological appearance of poorly differentiated carcinoma with cartilaginous metaplasia and partial blastoid cell appearance. Most tumor cells presented trabecular‐like structure lined by sinusoidal vessels. Immunohistochemically, the tumor cells were positive for low molecular weight cytokeratin and vimentin, partially positive for cytokeratin 19 and CD56, but negative for synaptophysin, chromogranin A and alpha‐fetoprotein. Based on the trabecular‐like morphology and the results of immunohistochemical staining, we concluded that the tumor was diagnosed as poorly differentiated hepatocellular carcinoma. Anti‐Hu antibody‐positive paraneoplastic peripheral neuropathy accompanied with liver tumor is extremely rare as far as is known. The presented case indicates that poorly differentiated carcinoma has the potential to be the responsible lesion of anti‐Hu antibody‐positive paraneoplastic neurological syndrome and systemic work‐up is important for the management of this neurological disorder.     

An Autopsy Case of Metastatic Foci of Hepatocellular Carcinoma in Adenomatous Hyperplasias of the Liver

Adenomatous hyperplasia of the liver is known as a preneoplastic or early developmental stage of hepatocellular carcinoma, in which overt malignant foci occasionally develop. We have recently experienced an autopsy case (a 70-year-old male) of liver cirrhosis with hepatocellular carcinoma and two nodules of adenomatous hyperplasia. The latter two nodules contained several microscopic foci of moderately differentiated hepatocellular carcinoma. There were a number of tumor microemboli in portal vein branches within areas of adenomatous hyperplasia in addition to areas surrounding cirrhotic liver, some of which grew into the parenchyma of adenomatous hyperplasia and cirrhotic regenerative nodules. These findings and the fact that adenomatous hyperplasia contained portal tracts including portal venous branches, suggest that malignant foci in adenomatous hyperplasia of the liver in this case might represent metastases from hepatocellular carcinoma in other parts of the liver via the intrahepatic portal venous system. Acta Pathol Jpn 41: 911 915, 1991.     

Isolated spinal cord neurosarcoidosis diagnosed by cord biopsy and thalidomide trial

We report a case of 54-yr-old woman who presented with 4-extremities weakness and sensory changes, followed by cervical spinal cord lesion in magnetic resonance imaging. Based on the suspicion of spinal tumor, spinal cord biopsy was performed, and the histology revealed multinucleated giant cells, lymphocytes and aggregated histiocytes within granulomatous inflammation, consistent with non-caseating granuloma seen in sarcoidosis. The patient was treated with corticosteroid, immunosuppressant and thalidomide for years. Our case indicates that diagnosis of spinal cord sarcoidosis is challenging and may require histological examination, and high-dose corticosteroid and immunosuppressant will be a good choice in the treatment of spinal cord sarcoidosis, and the thalidomide has to be debated in the spinal cord sarcoidosis.     

An autopsy case of metastatic foci of hepatocellular carcinoma in adenomatous hyperplasias of the liver.

Adenomatous hyperplasia of the liver is known as a preneoplastic or early developmental stage of hepatocellular carcinoma, in which overt malignant foci occasionally develop. We have recently experienced an autopsy case (a 70-year-old male) of liver cirrhosis with hepatocellular carcinoma and two nodules of adenomatous hyperplasia. The latter two nodules contained several microscopic foci of moderately differentiated hepatocellular carcinoma. There were a number of tumor microemboli in portal vein branches within areas of adenomatous hyperplasia in addition to areas surrounding cirrhotic liver, some of which grew into the parenchyma of adenomatous hyperplasia and cirrhotic regenerative nodules. These findings and the fact that adenomatous hyperplasia contained portal tracts including portal venous branches, suggest that malignant foci in adenomatous hyperplasia contained portal tracts including represent metastases from hepatocellular carcinoma in other parts of the liver via the intrahepatic portal venous system.     

Total necrosis of hepatocellular carcinoma due to spontaneous occlusion of feeding artery

Spontaneous total necrosis of hepatocellular carcinoma is extremely rare, with only 15 cases reported to date in the English literature, and the involved mechanism remains unresolved. This paper describes a case of spontaneous necrosis of hepatocellular carcinoma in a 70-year-old man with chronic hepatitis. The patient suffered epigastric pain on admission and computed tomography revealed a 4 cm mass with low density in the left lobe of the liver. Fine needle aspiration biopsy revealed a few scattered, naked and irregular nuclei exhibiting nuclear hyperchromasia in the dirty necrotic background, a finding highly suggestive of malignancy. The lobectomized liver revealed a 3.5 cm, well encapsulated, round, and nearly totally necrotic mass. On microscopic examination, the tumor was found to be composed of thick trabeculae of necrotic tumor cells, supporting the diagnosis of hepatocellular carcinoma. After surgery and throughout 13 months of follow up the patient has recovered well.     

A case of isolated metastatic hepatocellular carcinoma arising from the pelvic bone

Reports of metastatic hepatocellular carcinoma (HCC) without a primary liver tumor are rare. Here we present a case of isolated HCC that had metastasized to the pelvic bone without a primary focus. A 73-year-old man presented with severe back and right-leg pain. Radiological examinations, including computed tomography (CT) and magnetic resonance imaging (MRI), revealed a huge mass on the pelvic bone (13×10 cm). He underwent an incisional biopsy, and the results of the subsequent histological examination were consistent with metastatic hepatocellular carcinoma. The tumor cells were positive for cytokeratin (AE1/AE3), hepatocyte paraffin 1, and glypican-3, and negative for CD56, chromogranin A, and synaptophysin on immunohistochemical staining. Examination of the liver by CT, MRI, positron-emission tomography scan, and angiography produced no evidence of a primary tumor. Radiotherapy and transarterial chemoembolization were performed on the pelvic bone, followed by systemic chemotherapy. These combination treatments resulted in tumor regression with necrotic changes. However, multiple lung metastases developed 1 year after the treatment, and the patient was treated with additional systemic chemotherapy.     

Necrotizing Granulomatous Hypophysitis Presenting as a Sellar Mass

We report the case of a 45-year-old Colombian female with a 3-month history of headache, anorexia, fatigue, and diplopia in addition to left facial nerve palsy 2 weeks prior to presentation. On examination, visual fields and fundi were normal, but left abducens and facial nerve palsies were noted. An MRI scan disclosed a sellar mass with suprasellar but neither parasellar nor retrosellar extension. The mass was interpreted as a pituitary tumor and resected via the transsphenoidal approach. Histologic examination revealed necrotizing granulomas in a background of normal pituitary gland tissue. The differential diagnosis includes tuberculosis, sarcoidosis, fungal infection, syphilis, granulomatous autoimmune hypophysitis, Langerhans cell histiocytosis, and Erdheim-Chester disease. Staining for tubercle bacilli (acid fast and fite) as well as for fungi (GMS) was negative and PCR for mycobacteria showed the same result. Postoperative empiric treatment with antituberculous medication resulted in resolution of the cranial nerve palsies within a 1 month. The diagnosis of inflammatory/infectious granulomatous hypophysitis can be difficult to diagnose preoperatively and occasionally even postoperatively. A high index of suspicion should be maintained especially in those patients with a history of a systemic granulomatous disease or in regions endemic in granulomatous infectious diseases.     

Pulmonary infarction caused by sarcoidosis vascular involvement: A case report

Sarcoidosis is a systemic granulomatous disease. In pulmonary sarcoidosis, granulomatous vascular involvement is a common feature that occurs in all types of vessels, including large elastic arteries to venules, but sarcoidosis complicated with pulmonary infarction has not been reported. We report a case of a 60 years old female, who was operated on a clinical diagnosis of lung cancer, and histological examination revealed a pulmonary infarction and sarcoidosis. In the pulmonary elastic arteries, granulomas infiltrated the adventitia and media, and caused elastic fiber collapse and destruction. Arterial occlusion by granulomas was observed in the edge of the infarcted area. It was considered that the arterial sarcoidosis granuloma involvement was the cause of pulmonary infarction. Sarcoidosis is a significant risk factor for cardiovascular events. However, pulmonary infarction is an extremely rare complication of sarcoidosis. Our case suggests that sarcoidosis may cause vascular events in the lungs.     

Double cancer consisting of adenosquamous and hepatocellular carcinomas of the liver

A very rare case of a double cancer consisting of adenosquamous and hepatocellular carcinomas of the liver in a 65-year-old-man is discussed. The patient was hospitalized with epigastralgia in May 1997. Abdominal computed axial tomography revealed a tumor located in the left lobe of the liver and a left hepatic lobectomy was performed. The tumor recurred several months after surgery and the patient died on 4 June 1999. At autopsy, both a major tumor mass with extensive involvement, located in the surgical margin, and a small mass located in S7 were discovered. Microscopically, the major tumor was diagnosed as adenosquamous carcinoma and the small one in S7 as hepatocellular carcinoma. To our knowledge, this is the first case of a double cancer consisting of adenosquamous and hepatocellular carcinomas of the liver. The pathological findings support the hypothesis that this tumor developed as a squamous transformation of adenocarcinoma.     

NOD2-associated diseases: Bridging innate immunity and autoinflammation

NOD2 is an intracellular microbial sensor of the innate immune system that can act as a potent activator and regulator of inflammation. Mutations in the gene encoding NOD2 in humans have been associated with Crohn's disease (CD), Blau syndrome (BS), and early onset sarcoidosis (EOS). These diseases have in common features of dysregulated inflammation, but have very distinct phenotypes, which have been hypothesized to result from either loss-of-function (CD) or gain-of-function (BS/EOS) mutations. Here we describe an infant with early onset sarcoidosis who presented with systemic inflammation and disseminated granulomatous disease, including the triad of granulomatous arthritis, uveitis and dermatitis, as well as unusual gastrointestinal tract granulomas. The patient had a susceptibility polymorphism of NOD2 previously described in CD, but not in BS or EOS. We discuss the complex role of NOD2 in innate immunity to microbes and the clinical consequences of disturbances in this system.     

Leberparenchymknoten bei pathologischer hepatischer Vaskularisation/Perfusion

Nodular regenerative hyperplasia (NRH) is characterized by a non-cirrhotic micronodular transformation of the liver parenchyma. It is based on the obliteration of small portal veins. Macroregenerative nodules (MRN) develop in areas of favourable blood flow in otherwise hypoperfused liver tissue. Hypoperfusion is caused by obliteration of liver veins and/or large portal veins with the subsequent atrophy or extinction of parenchyma. The hyperperfused and sometimes rapidly growing MRN might simulate a malignant tumor in CT and MRT. Morphologically, MRN resemble FNH. In contrast to hepatocellular adenoma, they show a more or less nodular architecture with fibrous septa and ductular structures. NRH and cases of MRN without cirrhosis can indicate an extrahepatic/systemic disease causing altered liver perfusion. MRN in liver cirrhosis must be differentiated from dysplastic nodules and highly differentiated hepatocellular carcinoma by cytological and microarchitectural criteria. Focal nodular hyperplasia (FNH) can imitate liver cirrhosis, steatohepatitis, cholangitis or chronic hepatitis, if biopsy material does not include normal perilesional liver tissue. Telangiectatic FNH might resemble classic hepatocellular adenoma. Neoductular structures and septation argue for this rare subtype of FNH. Neoductular transformation of hypoperfused liver parenchyma might imitate cholangioma or cholangiocarcinoma.     

Dendritic cells in muscle lesions of sarcoidosis

Sarcoidosis is a chronic systemic granulomatous disorder of unknown etiology. The precise mechanism by which granulomatous lesions form is still obscure. Dendritic cells (DCs) are the most efficient antigen presenting cells; however, pathologic investigations of dendritic cells in the affected lesions of sarcoidosis are quite limited. We immunohistochemically examined the localization and phenotypes of dendritic cells and the expressions of CD40 and CD40L (CD154), which are key molecules in dendritic cell activation, in the muscles of 5 patients with muscular sarcoidosis, 8 patients with muscular disorders without inflammation, and 4 patients with histologically normal muscles as controls. In muscular sarcoidosis, CD1c-positive myeloid dendritic cells were scattered mainly in the lymphocyte layers of granulomas and the endomysium around the granulomas. Double immunostaining revealed that some CD1c-positive cells expressed the mature dendritic cell marker CD83, but immature dendritic cell marker CD1a-positive cells were not found. Smaller numbers of Blood dendritic cell antigen (BDCA)-2-positive plasmacytoid dendritic cells were found in the lymphocyte layers of granulomas. In the controls, small numbers of CD1c-positive cells were seen in the endomysium, whereas BDCA-2-positive cells were not observed except in 1 case. In muscular sarcoidosis, CD40 was expressed on mononuclear cells, on the interstitium around the muscle fibers and granulomas, and on the endothelium of vessels. CD40L was positive on mononuclear cells scattered within and around granulomas in 3 of 5 patients. In the controls, CD40 was expressed on the endothelium of the vessels and sparse mononuclear cells in the lesions of muscle fiber necrosis, whereas CD40L was not seen in any. In muscular sarcoidosis, recruitment of myeloid dendritic cells and less plasmacytoid dendritic cells and up-regulation of the CD40/CD40L system in affected muscles suggest that myeloid dendritic cells may be mainly involved in granulomatous inflammation through antigen presentation in a Th1 immune milieu.     

HEPATOCELLULAR CARCINOMA WITH METASTATIC GASTRIC CANCER SIMULATING BORRMANN TYPE 2 AND HYPERLIPIDEMIA

A case of hepatocellular carcinoma with metastasis to the stomach and hyperlipidemia as a paraneoplastic syndrome was presented. The patient, a 69-year-old man, was admitted to Kurobe City Hospital with a complaint of eplgastralgia. He was diagnosed as having hepatocellular carcinoma by an increased plasma AFP and the abnormalities of hepatic scintigram and abdominal angiography. Endoscopic examination of the stomach revealed an ulcerative lesion suggesting Borrmann type 2 gastric cancer and the gastric mucosal biopsy was interpreted as tubular adenocarcinoma. At autopsy, the liver was enlarged and weighed 4,170g without liver cirrhosis. Histologic finding of the liver tumor was hepatocellular carcinoma of Edmondson's grade 2 and the gastric tumor with bile production was identical to that of liver tumor. The tumor architecture of the stomach, however, was mixed with trabecular pattern and tubular pattern near the site of gastric mucosa, and was concordant with the findings of gastric mucosal biopsy. Multiple tumor thrombi in the portal system suggested that hepatocellular carcinoma retrogradely metastasized to the stomach through the portal system.     

Hepatocellular carcinoma with metastatic gastric cancer simulating Borrmann type 2 and hyperlipidemia

A case of hepatocellular carcinoma with metastasis to the stomach and hyperlipidemia as a paraneoplastic syndrome was presented. The patient, a 69-year-old man, was admitted to Kurobe City Hospital with a complaint of epigastralgia. He was diagnosed as having hepatocellular carcinoma by an increased plasma AFP and the abnormalities of hepatic scintigram and abdominal angiography. Endoscopic examination of the stomach revealed an ulcerative lesion suggesting Borrmann type 2 gastric cancer and the gastric mucosal biopsy was interpreted as tubular adenocarcinoma. At autopsy, the liver was enlarged and weighed 4,170 g without liver cirrhosis. Histologic finding of the liver tumor was hepatocellular carcinoma of Edmondson's grade 2 and the gastric tumor with bile production was identical to that of liver tumor. The tumor architecture of the stomach, however, was mixed with trabecular pattern and tubular pattern near the site of gastric mucosa, and was concordant with the findings of gastric mucosal biopsy. Multiple tumor thrombi in the portal system suggested that hepatocellular carcinoma retrogradely metastasized to the stomach through the portal system.     

Hepatocellular carcinoma arising from ectopic liver tissue in the spleen producing insulin-like growth factor II

We report a case of splenic tumor associated with severe hypoglycemia. The patient was a 69-year-old man with a large splenic tumor. He had suffered from relapsing hypoglycemic attacks and the lowest serum glucose level (4 mg/dl). He died 34 months after the onset of symptoms of left abdominal pain. Autopsy revealed large tumors in the spleen, 3 medium sized tumors in the lungs, and several small tumors in the liver. Microscopic studies of the splenic tumors revealed a hepatocellular carcinoma which showed a strongly positive reaction against anti-PIVKA-II and anti-“hepatocyte” antibodies. Several bile ductules thought to be heterotopic remnants of the liver tissues were found in the capsule of the spleen, adjoining the splenic tumor. It was suggested that the tumor originated from one of these ductules. Electron microscopic analysis showed numerous endocrine-like granules of every tumor cell, and 87-165 times stronger mRNA expression of insulin-like growth factor-II was measured in the tumor tissues when compared with normal liver tissue. Owing to these results, we believe that this is the first report of hepatocellular carcinoma that had developed from a liver tissue in the spleen.     

Collision tumors of hepatocellular carcinoma and malignant peritoneal mesothelioma

We report a case of synchronous hepatocellular carcinoma (HCC) and malignant peritoneal mesothelioma (MM-per). A 56-year-old man with no past history of asbestos exposure, chronic viral hepatitis, or alcoholic liver injury was admitted to our hospital with left flank pain and abdominal tumor. Partial hepatectomy, splenectomy, partial diaphragm resection, and partial gastrectomy were performed. The tumor in the lateral segment of the liver was gray to white, massive in appearance, and contained focal bile-producing nodules and extensive fibrous firm lesion. It had directly invaded the spleen and diaphragm. Liver cirrhosis was not found. The peritoneum contained multiple small nodules especially around the diaphragm, which mimicked carcinoma dissemination. After histological examination, the liver tumor was diagnosed as HCC. It had trabecular and scirrhous patterns and positive immunoreactivities for Hep-Par-1 and α-fetoprotein. The peritoneal nodules were diagnosed as MM-per, epithelioid type, with positive immunoreactivities for calretinin and cytokeratin 5/6. The two tumors collided around the diaphragm. Cases of MM synchronous with other primary malignant tumors have been reported, but most had a history of asbestos exposure unlike the present case. The carcinogenic background was unclear for two tumors in this case. This is an extremely rare and valuable case.