Repeated hepatectomies for recurrent follicular dendritic cell tumour of liver: a case report

Follicular dendritic cell tumour is a very rare tumour of unknown aetiology. We report a case of follicular dendritic cell tumour of liver which was treated with extended right hemihepatectomy but recurred twice in the remaining left lobe within 3 years. The recurrent tumours were removed by further liver resection. The mainstay of treatment for this rare tumour is surgical resection.     

Needle track seeding of primary and secondary liver carcinoma after percutaneous liver biopsy

Seeding of tumour in the needle track following percutaneous needle biopsy of liver neoplasms is rarely reported. We describe two such cases following the needle biopsy of an hepatocellular carcinoma and secondary colorectal carcinoma respectively. The risk of needle track recurrence of liver tumours should not be regarded as insignificant. The diagnosis of liver neoplasms may be achieved by non-invasive modalities, and their needle biopsy should be reserved for cases not amenable to surgical resection.     

Effusion cytology of hepatocellular carcinoma with in situ hybridisation for human albumin

While the cytological features of hepatocellular carcinoma on fine needle aspiration cytology are well described, cases of hepatocellular carcinoma with malignant cells in ascitic fluid and their characteristics are not. A patient is described with cirrhosis resulting from chronic hepatitis B virus infection, ascites, and hepatocellular carcinoma diagnosed by effusion cytology. The malignant cells in the effusion were shown to be positive for alpha fetoprotein using immunocytochemistry, and for human albumin using in situ hybridisation, confirming the diagnosis of hepatocellular carcinoma. Further investigations in a terminally ill patient were thus avoided.     

Degradation of annexin I in bronchoalveolar lavage fluid from patients with cystic fibrosis

BACKGROUND/AIMS: The number of perisinusoidal myofibroblasts has been shown to be increased in hepatocellular carcinoma, as compared to cirrhosis. This increase might suggest a cooperative relationship between tumour cells and myofibroblasts. To assess this relationship, we undertook: (a) an immunohistochemical study to confirm the existence of an increased number of perisinusoidal myofibroblasts in human hepatocellular carcinoma, as compared to cirrhosis with or without liver cell dysplasia, (b) an in vitro study testing the role of normal or tumoral human hepatocytes in myofibroblast proliferation. METHODS: Forty explanted cirrhotic livers, including 14 with hepatocellular carcinoma and 24 with liver cell dysplasia, were studied. Myofibroblasts were detected by immunohistochemistry using an antibody directed against alpha-smooth muscle actin. Hepatic myofibroblasts in culture were obtained by outgrowth from human liver explants. RESULTS: There was a progressive increase in the number of perisinusoidal myofibroblasts, from cirrhotic nodules without dysplasia to liver cell dysplasia and hepatocellular carcinoma. Conditioned medium from isolated normal human hepatocytes had only minor mitogenic effects on myofibroblasts, as assessed by measuring DNA synthesis and cell growth. In contrast, conditioned medium from a human hepatoma cell line (HepG2 cells) markedly stimulated the proliferation of human myofibroblasts. This mitogenic activity was stored in HepG2 cells and secreted in the extracellular medium rather than being simply released following cell lysis. CONCLUSIONS: These results suggest that the increased number of myofibroblasts in hepatocellular carcinoma might be due to a paracrine mechanism involving soluble mitogenic factor(s) secreted by tumour cells.     

The value of frozen section examination in planning surgery for follicular thyroid neoplasms

Frozen section examination of follicular neoplasms of the thyroid has been claimed to be of little value in planning the extent of surgery. Clinical factors such as age, sex and tumour size are said to be more accurate predictors of malignancy. The aim of this study was to examine the respective value of clinical factors and frozen section in the surgical management of follicular thyroid neoplasms. A retrospective study of 735 patients with follicular neoplasms treated at Royal North Shore Hospital was undertaken. Factors assessed included clinical features, such as age and sex of the patients and tumour size, as well as findings at frozen section examination. No significant difference in sex distribution was demonstrated when comparing follicular adenoma with follicular carcinoma. There was a significant difference with respect to patient age between the two groups, but the large overlap in the distribution made this difference of no clinical value. In addition, there was no significant difference in tumour size when comparing follicular adenoma with carcinoma. On the other hand, review of frozen section results showed that 40% of patients with follicular carcinoma were positively identified by frozen section examination at initial surgery, with a false positive rate of less than 0.2%. It appears that clinical factors, such as age, sex and tumour size, are of little assistance in differentiating benign from malignant follicular neoplasms. Frozen section examination remains the most definitive tool in planning intra-operatively the extent of surgery for follicular neoplasms of the thyroid.     

Cyclin D1, another molecule of the year?

AIM: Testicular germ cell tumours may present as metastases in cervical lymph nodes, yet the primary tumours remain clinically occult. The aim of the study is to alert pathologists and clinicians to this uncommon but important presentation and highlight the clues and the diagnostic adjuncts to its correct diagnosis. METHODS: The clinical, cytological, histological, and immunohistochemical features of two patients with germ cell tumour initially presenting as cervical lymphadenopathy were described and analysed. RESULTS: Both patients were young adult males, who were found to have metastatic undifferentiated carcinoma on fine needle aspiration of the enlarged cervical lymph nodes. The tumour cells in both cases were positive for placental alkaline phosphatase (PLAP) and negative for epithelial membrane antigen (EMA). CONCLUSIONS: Clinicians and pathologists should be aware of the possibility of germ cell tumour when encountering a young adult male with metastatic poorly differentiated carcinoma. Positivity for PLAP and negativity for EMA are helpful adjuncts in arriving at the correct diagnosis.     

Hepatocellular carcinoma presenting as a tumour of the hilar and extrahepatic bile ducts

A case of hepatocellular carcinoma extending within the large extra- and intrahepatic bile ducts is reported. No primary tumour was found in the liver parenchyma by abdominal ultrasound, spiral computed tomography or magnetic resonance, but transduodenal cholangioscopy showed tumour in the common hepatic ducts and the two main branches. Endoscopic biopsy showed highly differentiated hepatocellular carcinoma. The patient was treated with endoscopic biliary drainage and died at home 7 months after admittance.     

Carcinosarcoma of the adult kidney

Carcinosarcoma of the adult kidney is a very rare tumour and there are only a few well documented cases in the literature. In this report such a tumour is described from a 50-year-old white male, which progressed very rapidly with widespread metastases. Histologically, the tumour consisted of renal cell carcinoma and fibrosarcomatous components. The interesting features in this case were that both the carcinomatous and sarcomatous elements of the tumour exhibited metastases separately to various organs.     

Angiomyoid and follicular dendritic cell proliferative lesions in Castleman's disease of hyaline-vascular type: a study of 10 cases

Castleman's disease of hyaline-vascular type (HV CD) may rarely be associated with a confusing variety of stromal cell overgrowths and neoplasms. We report here on the pathologic and clinical findings of 10 such cases. In addition to the usual complex histoimmunophenotype of the stroma of HV CD and some unusual features that mimicked neoplasms, we observed focal proliferations of angiomyoid (five cases) and follicular dendritic cell type (five cases). The former were nonneoplastic growths featuring compact tangles of spindle cells, exhibiting immunoreactivity for smooth muscle actin and interpreted as vessel-related pericytes and myoid cells. The latter were neoplastic growths of oval to spindle cells intermixed with lymphocytes; the tumor cells grew in long, intersecting bundles, featured various degree of atypia, and expressed the markers of follicular dendritic cells (CD21, CD35, KiM4p). The two types were clinically distinct. Four of five patients with angiomyoid proliferations were young women, who presented with an abdominal mass and were cured by surgery; that is, they had a clinical profile similar to that of patients with the stroma-rich variant of HV CD. The follicular dendritic cell proliferations were in older patients of either gender presenting with masses at various sites, recapitulating the profile of follicular dendritic cell tumors arising independently from HV CD; in three patients with long-term follow-up, recurrences or metastases developed at various intervals from the initial diagnosis (1 1/6, 3 1/2, and 11 years), and one patient died as a result. This study confirms the potential for, and the variety of, stromal cell proliferations in HV CD. Because their biologic behavior differs, correct identification of these various proliferative lesions is clinically important.     

Coexistence of papillary and medullary carcinoma of the thyroid gland-mixed or collision tumour? Clinicopathological analysis of three cases

We present three thyroid carcinomas displaying medullary and papillary components. In two cases the papillary component was characterized by typical papillae with a fibrovascular core; in one a follicular variant of papillary carcinoma was found. The papillary component was dominant in two and the medullary in one case. One tumour showed clear-cut borders between the two components, the others displayed an intermingled pattern. Both tumour components were seen in lymph node metastases with immunostaining with antibodies to calcitonin, chromogranin A, carcinoembryonic antigen, other neuroendocrine markers and thyroglobulin. At least two of our cases are true mixed carcinomas probably arising from a common stem cell.     

Ultrafast contrast-enhanced 3D MR angiography of the aorta and renal arteries in apnea

Mixed medullary-follicular carcinomas (MMFC) of the thyroid are rare tumours showing the morphological and immunochemical properties of both parafollicular and follicular cell lineages. Their recognition is based on a classical WHO definition, although several other patterns have been described in recent years. We investigated 11 cases of MMFC by immunohistochemistry and in situ hybridization (ISH) to analyse the structural features, the immunophenotypic profile and the calcitonin (CT) and thyroglobulin (TG) gene expression of the neoplasm. Histologically, 10 cases had mixed parafollicular and follicular cell populations in the primary tumour and 1 only in the lymph node metastasis. All cases were immunoreactive for CT (in medullary areas) and TG (in follicular areas and also in the solid component of 8/11 cases). These findings were confirmed by ISH analysis. Combined ISH and immunostaining showed that most cases had separate CT and TG gene expression, although rare cells with concurrent CT and TG gene expression were identified in 2 tumours. We conclude that (a) MMFC display heterogeneous morphological patterns and are a special type of thyroid tumour undergoing divergent differentiation; (b) in MMFC, CT and TG genes are generally not simultaneously expressed by the same cell, although dual expression of CT and TG was present in rare neoplastic elements; and (c) the origin of MMFC, whether they are derived from the ultimo-branchial body or result from neoplastic transformation of different cell populations following common oncogenic stimuli, is unclear.     

Multidisciplinary treatment of hepatocarcinoma]

Radical treatment of the hepatocellular carcinoma (HCC) is complete surgical removal; it may be done by resection or total hepatectomy. Although multicentric carcinogenesis predicts that liver transplantation is likely adequate to treat both the hepatoma and the underlying cirrhosis, it doesn't seem justified in the advanced stages or in absence of end-stage liver disease and therefore liver resection remains the treatment of choice for radical cure of HCC. However, low resectability and high recurrence rate make surgery alone ineffective. Unresectable HCC may be converted to resectable by multimodality radiation/chemotherapy, and embolization of portal branch feeding tumour, improving the function of the nonembolized liver, can extend the surgical indications for HCC. Adjuvant chemoembolization has already shown to reduce recurrence rate after radical resection and it should be widely applied. In unresectable or not converted HCCs as well as in postoperative recurrence, alternative therapies, particularly as multimodality treatment, can improve survival rate. To date, multidisciplinary treatment of hepatocellular carcinoma, waiting for further studies on newer modalities (prevention and gene therapy, especially), represents the best way to improve long-term results.     

MRI and CT of metastatic hepatocellular carcinoma causing spinal cord compression

We report the imaging features in five patients with metastatic hepatocellular carcinoma causing spinal cord compression, three of which were biopsy proven and two were in patients with known diagnosis of hepatocellular carcinoma. The radiographic, magnetic resonance imaging (MRI) and computed tomography (CT) features are highlighted. Although the occurrence of metastatic disease in hepatocellular carcinoma is exceedingly rare, it may be increasingly encountered as survival of patients is improved with advancing methods of therapy, both surgical and palliative. It often accompanies local recurrence, and invariably signals a grave prognosis with extremely short life expectancy. Unusually, two of the five patients in this series presented initially with skeletal metastases which led to the diagnosis of hepatocellular carcinoma.     

Papillary and follicular thyroid carcinoma metastatic to the skin: a case report and review of the literature

Cutaneous metastases from thyroid cancers are rare. We report the case of an otherwise asymptomatic 81-year-old woman with an enlarging scalp lesion. Her solitary skin metastasis was the presenting feature of thyroid carcinoma. Routine histopathology of the lesion was notable for an atypical clear cell neoplasm. Immunohistochemistry was positive for thyroglobulin. Subsequent resection of the thyroid gland identified separate foci (< 1 cm) for both papillary and follicular carcinoma. Although such immunohistochemical staining has been used previously, it has never been reported to provide the definitive diagnosis for a solitary cutaneous metastasis from the thyroid. Previous tumors had anatomic features in a clinical context that permitted identification by routine light microscopy. Clear cell features found in the follicular focus of carcinoma in the thyroid suggest that it is the primary. A worldwide literature review reveals that follicular carcinoma has a greater preponderance than papillary carcinoma for cutaneous metastasis and that the majority of skin metastases from either papillary or follicular thyroid cancer are localized to the head and neck.     

Joint stress in inline skating--a biomechanical study

Mantle cell lymphoma (MCL) has been established as a clinicopathologic entity in 1991. A histopathologic and immunohistochemical study of 16 cases of MCL was performed in order to demonstrate differential diagnostic aspects. MCLs were composed of small and medium-sized B cells assuming the appearance of centrocytes. The growth pattern was diffuse in 9 cases and that of follicle mantle zone type within at least partially present nodular parts in 16 cases. The immunohistochemical staining for CD23 antigen was negative in tumour cells whereas the strong immunoreactivity of follicular dendritic cells (FDC) decorated residual FDC network. Seven cases of MCL were examined for the presence of translocation t(11;14)(q13;q32) using polymerase chain reaction. Despite histomorphological features compatible with a diagnosis of low-grade lymphoma, MCL has a worse prognosis and more aggressive behaviour than other types of small cell lymphomas, such as small lymphocytic lymphoma and follicle centre lymphoma.     

Wound botulism associated with black tar heroin

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) is thought to play an important role in cellular immunological reactions. Expression can be induced by inflammatory cytokines in a wide variety of cells, including hepatocytes. OBJECTIVE: To compare the behaviour of ICAM-1 in liver diseases. PATIENTS AND METHODS: We assayed serum ICAM-1 (sICAM-1) in patients with hepatocellular carcinoma-associated liver cirrhosis, and compared them with a group of cirrhotic patients and controls. sICAM-1 values were also correlated with some biochemical parameters of liver function. Moreover, immunohistochemical localization of ICAM-1 was performed on liver tissue sections of patients with hepatocellular carcinoma, liver cirrhosis and a sample of normal liver. RESULTS: sICAM-1 levels were significantly higher in the hepatocellular carcinoma patients than in controls (P < 0.0001) and the cirrhosis group (P < 0.001). sICAM-1 values directly correlated with alanine aminotransferase, total bilirubin, alkaline phosphatase and gamma-glutamyltranspeptidase serum values (P < 0.05), with an inverse correlation with albuminaemia values (P < 0.05). There was no correlation with alpha-fetoprotein values, but sICAM-1 values were higher in hepatocellular carcinoma patients with large tumours (> 3 cm) than in those with small tumours (< 3 cm) (P < 0.04). Immunohistochemical localization of ICAM-1 was negative in normal liver tissue; positive staining for endothelial cells was found in chronic liver disease, while in hepatocellular carcinoma tissues, positive membrane staining was observed in hepatocytes and, to a lesser extent, at the cytoplasmic level. CONCLUSION: These results suggest that high serum levels of sICAM-1 are associated with severe liver disease, such as liver cirrhosis and hepatocellular carcinoma, and that they tend to increase with deteriorating hepatic function and tumour size.     

Follicular and Hurthle cell carcinomas of the thyroid: a comparative study

University of Texas M. D. Anderson Cancer Center cases filed as Hurthle cell and follicular carcinoma were reviewed. Requirements for including a case in the study were that the diagnosis of Hurthle cell or follicular carcinoma be confirmed, that histologic material and clinical information be adequate, and that there be at least 9 years of follow-up. The study group included 18 cases of Hurthle cell carcinoma and 33 cases of follicular carcinoma. Ten of the Hurthle cell carcinomas had extrathyroid invasion, three had intrathyroid invasion, and five were encapsulated (i.e., they had intracapsular invasion only). In the follicular carcinoma group, 5 tumors had extrathyroid invasion, 14 had intrathyroid invasion, and 14 were encapsulated. When the cases were stratified according to extent of invasion in this manner, there was no statistically significant difference in rate of local recurrence, rate of metastasis (either regional lymph node or distant), or patient survival between Hurthle cell carcinoma and follicular carcinoma. Other variables including patient age and sex, treatment differences, tumor size, vascular invasion, predominant growth pattern (follicular versus solid-trabecular), nuclear size and pleomorphism, mitotic rate, and tumor necrosis did not provide significant additional prognostic information. Metastases of both Hurthle cell and follicular carcinoma were mostly distant and predominantly involved bone and lung. Behavioral differences between Hurthle cell and follicular carcinoma that were not statistically significant included a higher rate of local recurrence in Hurthle cell carcinoma with intrathyroid invasion, more frequent occurrence of regional lymph node metastasis in Hurthle cell carcinoma with extrathyroid invasion, and absence of distant metastasis and death caused by tumor in encapsulated Hurthle cell carcinoma. Five follicular carcinomas and one Hurthle cell carcinoma appeared to have arisen within an adenoma.     

Dedifferentiated liposarcoma: a report of nine cases with a peculiar neurallike whorling pattern associated with metaplastic bone formation

Nine cases of dedifferentiated liposarcoma with both a peculiar neurallike or meningeallike whorling pattern and metaplastic bone formation are reported. The tumors predominated in the retroperitoneum of elderly adults. All nine tumors were resected, and five of seven that were followed-up recurred locally, but none metastasized after a follow-up of 2 to 7 years. Grossly, most of the tumors were huge masses, ranging from 2.5 cm to 60 cm. Histologically, the tumors revealed, in addition to areas of well-differentiated liposarcoma, discrete nodules consisting of hypercellular, spindled to ovoid cellular proliferation arranged in tight, concentric whorls resembling neural tumors or meningiomas. Metaplastic, heterotopic ossification was present in seven of nine tumors and consisted of variable amounts of osteoblast-rimmed bone trabeculae situated at the periphery of the whorled areas or intimately mixed with the whorled cellular component. Immunohistochemical studies were inconclusive in determining the nature of the dedifferentiated, whorled element. Ultrastructural evaluation of one tumor disclosed neoplastic cells featuring thin, interdigitating cytoplasmic processes connected by desmosomes, similar to those described in follicular dendritic cell neoplasms. Although suggested by the light and electron microscopic features, the follicular dendritic cell differentiation of the dedifferentiated component could not be confirmed on immunohistochemical grounds, and the histogenesis of the intriguing neurallike or meningiomalike component in these dedifferentiated liposarcomas is unknown.     

Repair of DNA lesion O6-methylguanine in hepatocellular carcinogenesis

Evidence from both experimental carcinogenesis and studies in human cirrhotic liver suggest that defective repair of the promutagenic DNA base lesion, O6-methylguanine, is a factor in the multistep process of hepatocellular carcinogenesis. Ubiquitous environmental alkylating agents such as N-nitroso compounds can produce O6-methylguanine in cellular DNA. Unrepaired, O6-methylguanine can lead to the formation of G --> A transition mutations, a known mechanism of human oncogene activation and tumour suppressor gene inactivation. Combined treatment of rodents with an agent producing O6-methylguanine in DNA, and an agent promoting cell proliferation, leads to development of hepatic nodules and hepatocellular carcinoma (HCC), cell division, hence DNA replication, being required for the propagation of tumorigenic mutation(s) in hepatocyte DNA. The paramount importance of O6-methylguanine in hepatocellular carcinogenesis is indicated by the observation that transgenic mice engineered to have increased hepatic levels of repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) are significantly less prone to hepatocellular carcinogenesis following alkylating agent treatment. Cirrhosis is a universal risk factor for development of human HCC, and a condition that is characterized by increased hepatocyte proliferation as a result of tissue regeneration. Levels of the human repairing enzyme for O6-methylguanine were found to be significantly lower in cirrhotic liver than in normal tissue. In accord with findings from animal models, this suggested a mechanism in which persistence of O6-methylguanine due to defective DNA repair by MGMT, together with increased hepatocyte proliferation, might lead to specific gene mutation(s) and hepatocellular carcinogenesis. Screening for the presence and persistence of O6-methylguanine in human DNA presently involves formidable technical difficulty. Indications are that such limitations might be overcome by the use of an ultrasensitive method such as immuno-polymerase chain reaction (PCR). This approach should allow parallel measurement of DNA adduct and repair enzyme in routine liver biopsy samples. It might also enable investigation of O6-methylguanine in human genes specifically associated with hepatocellular carcinogenesis. Given the wide variation in human MGMT levels observed between individuals, tissues, and cells, this technology should be adapted to permit the ultrasensitive localisation and measurement of adducts and repairing enzyme in liver biopsy tissue sections. Ability to ultrasensitively measure O6-methylguanine, and its repair enzyme, should prove valuable in the risk assessment of cirrhotic patients for developing hepatocellular carcinoma.