[Hepatocellular carcinomas and their mimics]. / Hepatozelluläre Karzinome und leberzellähnliche Tumoren.

High resolution cross-sectional imaging techniques means that even small, well-differentiated hepatocellular tumors can also be diagnosed with biopsy. In cirrhotic liver tissue, macroregenerative and dysplastic nodules must be discriminated from hepatocellular cancer (HCC). In non-cirrhotic liver tissue the differential diagnosis includes hepatocellular adenoma, macroregeneratory nodules, fibrolamellar carcinoma, as well as primary tumors and metastases. The diagnostic procedure includes matrix diagnosis of the tumor-bearing liver tissue, cyto- and histomorphologic analysis including capillarization of vascular bed, and adapted immunohistological testing with antibodies which underline possible malignancy or hepatocellular differentiation. A flow chart for the diagnosis of hepatocellular carcinomas and their mimics on liver biopsies is presented.

Osseous hydatidosis of the proximal femur: a rare diagnosis in revision total hip arthroplasty.

Musculoskeletal hydatidosis is a rare but severe disease in central Europe. This case report presents the incidental finding of an osseous hydatidosis after cementless revision total hip arthroplasty in a patient without a preoperative history of hydatidosis or any clinical symptoms. Revision total hip arthroplasty had been necessary due to a septic osteonecrosis of the femoral head 2 years after osteosynthesis of a traumatic proximal femur fracture with a sliding hip screw. The positive sample was taken out of the greater trochanter in the area of the possible former entry point for the lag screw, which was macroscopic inconspicuous. Sero-analysis could afterwards confirm the suspected diagnosis. Postoperative chemotherapy with albendazole was performed for 6 months. A full-body MRI did not reveal any further cysts. This case demonstrates a possible impact of migration on the expected pathogens in revision arthroplasty. This demonstrates that in revision arthroplasty, an infection with this parasite also has to be taken into account, if the patients come from an area endemic for hydatidosis.

[Salmon-pink colored conjunctival tumor with amyloid deposits]. / Lachsfarbener Bindehauttumor mit Amyloidablagerung.

An 82-year-old male patient presented with a salmon-pink colored conjunctival tumor of the left eye. A circumscribed, dense and whitish portion was detected by clinical examination. The histophological and immunhistochemical examination of the biopsy tissue revealed a CD20+ marginal zone lymphoma of the conjunctiva with amyloid deposits. Extranodal marginal zone lymphoma at this site is the most common lymphoma of the ocular adnexa and accounts for 5-10% of malignant diseases. An association with amyloid production is very rare and according to the current state of knowledge has no known impact on the outcome.

[Hepatocellular tumours in noncirrhotic liver tissue]. / Hepatozelluläre Tumoren im nichtzirrhotischen Lebergewebe.

In recent years, the spectrum of tissue-based diagnostics of hepatocellular tumours has changed due to novel molecular pathological findings. Innovative radiographics filter out small lesions and ambiguous tumours for bioptical sampling. The spectrum of these tumours includes hepatocellular carcinoma, hepatocellular adenomas, focal nodular hyperplasia and macroregenerative nodules. Primarily, morphological analysis should identify the dignity of a lesion. After exclusion of HCC and reactive liver cell nodules, hepatocellular adenomas should be further subclassified based on immunohistochemical/molecular pathological criteria according to the WHO classification of liver tumours. This procedure provides significant additional information regarding the prognosis and therapeutic implications of hepatocellular adenomas.

Primary perivascular epitheloid cell tumour (PEComa) of the liver: case report and review of the literature.

PURPOSE: Perivascular epitheloid cell tumour [PEComa] is a rare neoplasm entity, characterized by perivascular epitheloid cells with a coexpression of smooth muscle and melanocytic markers. PEComas are found in a variety of localizations, though lesions within the liver are still scarcely found. Although the majority of these tumours are recognized as benign, there are some reports about advanced and aggressive tumours even with fatal outcome. By means of this case report and literary review including other 21 published cases, potential treatment modalities concerning clinical diagnostics, therapy and the follow-up care should be discussed. METHODS: The following report presents the case of a 53-year old woman with a known liver lesion, since four years under regularly sonographic controls. Finally, after a haemorrhage episode, the lesion was resected and the diagnosis found. For the literary review a systematic search for case reports published between January 1, 1999 and May 1, 2012 was performed on Pubmed. RESULTS: The only way, till now, of confirming the diagnosis is through immunohistochemical examinations. The already published Malignancy criteria by Folpe et al. must be taken carefully in question, as there are cases of malignant behaviour, that do not exactly coincide with these. CONCLUSION: Primary PEComa of the liver must be treated as potential malignant and therefore a close follow-up is demanded.

[Non-alcoholic steatohepatitis and cirrhosis in young adult patients with hypothalamic-pituitary dysfunction]. / Nichtalkoholische Steatohepatitis mit Zirrhose bei jungen Erwachsenen mit hypothalamisch-hypophysärer Dysfunktion.

BACKGROUND: In rare cases, hypothalamic-pituitary dysfunction can be associated with an extraordinarily active non-alcoholic steatohepatitis (NASH) and subsequent liver cirrhosis. CASE REPORT: The two young adult patients described in this report presented with NASH together with advanced liver fibrosis and cirrhosis 5 and 19 years, respectively after resection of a craniopharyngeoma. CONCLUSIONS: In young patients and children with active steatohepatitis, an association with hypothalamic-pituitary dysfunction should be excluded. Especially hypothalamic-pituitary-related NASH tends to develop rapidly into liver cirrhosis.

[Orbital invasion of a maxillary ameloblastoma]. / Orbitale Infiltration durch ein Ameloblastom der Maxilla.

A 66-year-old man with a history of repeated surgery, external radiation and brachytherapy for ameloblastoma presented with a recurrence of the tumor with sinus, intraorbital and skull base infiltration. Histopathologic examination of the resected orbital and sinus tissue confirmed the diagnosis of ameloblastoma. Immunohistochemical staining for CD56 was strongly positive in the tumor cells. Although ameloblastoma is usually a low-grade malignant tumor, it can be locally aggressive with invasion of the surrounding tissue. Maxillary ameloblastomas are more likely to infiltrate the orbit.

[Heterozygous alpha-1-antitrypsin deficiency (PiMZ): risk factor in the development of primary liver carcinoma in non-cirrhotic liver?]. / Heterozygoter Alpha-1-Antitrypsin-Mangel (PiMZ): Risikofaktor zur Entwicklung eines hepatozellulären Karzinoms in der nicht zirrhotischen Leber?

Here we report on a patient with a primary hepatocellular carcinoma in a non-cirrhotic liver, in whom heterozygosity for an AAT-deficiency allele was found (PiMZ). Based on this observation and the current literature, the possible mechanisms for an eventual contribution of a heterozygosity of a heterozygous AAT-deficiency for a hepatocellular carcinoma are discussed. Alpha-1-antitrypsin (AAT)-deficiency (Laurell-Eriksson syndrome) is a genetic disorder, in which individuals who are homozygous for a deficiency allele are at an increased lifetime risk for pulmonary emphysema, liver cirrhosis, and primary hepatocellular carcinoma. It has been controversially discussed whether the heterozygous form (PiMZ) is also associated with an increased risk for liver diseases. Hepatocarcinogenesis for AAT-deficiency is probably based on a series of toxic events. Precipitation of AAT aggregates in hepatocytes is the initial step. These accumulate in the endoplasmic reticulum and cannot be eliminated from all hepatocytes by proteasomal and non-proteasomal mechanisms. AAT aggregates induce proinflammatory pathways and may be a stimulus for hepatocarcinogenesis. This hypothesis is based mostly on studies of individuals homozygous for a deficiency allele (PiZZ). The mechanism may also play a role in heterozygous patients. Since not all patients with precipitates of AAT-aggregates are develop a hepatocellular carcinoma related comorbidities such as chronic hepatitis B, C, chronic alcohol abuse, or so far unknown genetic and environmental factors may be crucial.

Gene expression of oncogenes, antimicrobial peptides, and cytokines in the development of oral leukoplakia.

OBJECTIVE: The aim of this study was to investigate the expression pattern of oncogenes, antimicrobial peptides, and genes involved in inflammation in leukoplakia of the oral cavity compared with healthy gingiva. STUDY DESIGN: Biopsies of healthy gingiva (n=20) and leukoplakia (n=20), were obtained during routine surgical procedures. RNA was extracted according to standard protocols. Transcript levels of alpha-defensin (DEFA) 1/3, DEFA-4, S100-A7, deleted-in-oral-cancer (Doc) 1, interleukin (IL) 1beta, IL-6, IL-8, IL-10, tumor necrosis factor (TNF) alpha, cyclooxygenase (Cox) 2, epidermal growth factor (EGF), keratinocyte growth factor (KGF), transforming growth factor (TGF) beta1, TGF-alpha, collagen-IA1 (Col-1), and tenascin-c were analyzed by real-time reverse-transcription polymerase chain reaction. The proteins encoded by the different genes were visualized by immunostaining. RESULTS: Compared with healthy gingiva (set as 1), there was an increased gene expression of DEFA-4 (179.2-fold), S100-A7 (25.4-fold), EGF (24.8-fold), TGF-beta1 (25.2-fold), and tenascin-c (34.3-fold) in oral leukoplakia. The expression of IL-1beta and Doc-1 was decreased (0.01-fold and 0.2-fold, respectively). CONCLUSIONS: The combination of an increased expression of the antimicrobial peptide DEFA-4, the oncogene S100-A7, EGF, and tenascin-c, and a decreased Doc-1 expression in oral leukoplakia might characterize its potency of malignant transformation. Chronic inflammation seems not to be involved in the development of this lesion.

[Pressure-related dysphonia, recurring pneumonia and supraglottic tumor]. / Belastungsabhängige Dysphonie, rezidivierende Pleuropneumonie und supraglottische Raumforderung.

Urbach-Wiethe syndrome (hyalinosis cutis et mucosae) is an autosomal-recessive inherited disease. It often presents with typical symptoms such as skin lesions (especially in the face and neck area), dyspnea, and maldigestion. Hoarseness is a leading symptom in young children. These manifestations are caused by the assimilation of glycoproteins in mesenchymal tissue. Our case report shows that hoarseness does not necessarily appear only in children, but can also appear later. Furthermore, the assimilation of glycoproteins in the supraglottic area may also cause dysphonia. Due to the varied features of this disease, interdisciplinary check-ups are necessary at regular intervals.

[Conjunctival myxoma: two cases. Histopathological examination and clinical course]. / Konjunktivales Myxom - zwei Kasuistiken. Histopathologische Aufarbeitung und klinische Korrelation.

Conjunctival myxoma is a rare and benign tumour without tendency for recurrence. Here, we present the histological features and the clinical course of two cases. Removal of each tumour was followed by histopathological examination including immunohistochemistry as well as electron microscopy. Besides the expected findings characteristic of conjunctival myxoma some features reflecting the possible aetiology of this entity are shown.

Fatal acute liver failure due to reactivation of hepatitis B following treatment with fludarabine/cyclophosphamide/rituximab for low grade non-Hodgkin's lymphoma.

BACKGROUND: Reactivation of chronic hepatitis B in HBsAg carriers is a well known complication of chemo?therapy. The clinical spectrum ranges from asymptomatic hepatitis to fatal hepatic failure. Although it impairs the prognosis of cancer treatment, it may be overlooked due to other possible causes of liver damage. CASE REPORT: The patient presented with acute liver failure after 6 cycles of rituximab, fludarabine, and cyclophosphamide for low grade non-hodgkin's lymphoma. Differential diagnoses were chemotherapy-induced liver failure, autoimmune hepatitis, phenprocoumon-induced liver failure and infiltration of the liver by lymphoma. Finally, reactivation of hepatitis B with a fibrosing cholestatic pattern was identified. CONCLUSION: This case reminds clinicians that patients receiving high-intensive chemotherapy or immunosuppressive therapy should be screened for HBsAg. HbsAg positive patients should obtain prophylactic antiviral therapy with lamivudine or another substance active against HBV.

Nuclear hBD-1 accumulation in malignant salivary gland tumours.

BACKGROUND: Whereas the antimicrobial peptides hBD-2 and -3 are related to inflammation, the constitutively expressed hBD-1 might function as 8p tumour suppressor gene and thus play a key role in control of transcription and induction of apoptosis in malignant epithelial tumours. Therefore this study was conducted to characterise proteins involved in cell cycle control and host defence in different benign and malignant salivary gland tumours in comparison with healthy salivary gland tissue. METHODS: 21 paraffin-embedded tissue samples of benign (n = 7), and malignant (n = 7) salivary gland tumours as well as healthy (n = 7) salivary glands were examined immunohistochemically for the expression of p53, bcl-2, and hBD-1, -2, -3. RESULTS: HBD-1 was distributed in the cytoplasm of healthy salivary glands and benign salivary gland tumours but seems to migrate into the nucleus of malignant salivary gland tumours. Pleomorphic adenomas showed cytoplasmic as well as weak nuclear hBD-1 staining. CONCLUSION: HBD-1, 2 and 3 are traceable in healthy salivary gland tissue as well as in benign and malignant salivary gland tumours. As hBD-1 is shifted from the cytoplasm to the nucleus in malignant salivary gland tumours, we hypothesize that it might play a role in the oncogenesis of these tumours. In pleomorphic adenomas hBD-1 might be connected to their biologic behaviour of recurrence and malignant transformation.

[Liver biopsy at the intersection of clinical and pathological diagnosis]. / Die Leberbiopsie im Schnittpunkt von klinischer und pathologischer Diagnostik.

Liver biopsy plays an important role in the diagnosis of liver diseases. Nowadays, biochemical, immunological, functional and molecular tests allow the etiology of many liver diseases to be clarified. The liver biopsy contributes essential information about the stage and grade of inflammatory liver diseases on the basis of consensus criteria. These data influence treatment and help to assess the prognosis. In addition, the different patterns of fibrosis allow conclusions about the cause and progress of the underlying liver disease. Hepatitis C, autoimmune hepatitis, unexplained severe course of hepatitis B, differentiation of simple steatosis from steatohepatitis, the differential diagnosis of cholestatic diseases, unclear hepatopathy, transplant pathology and last but not least, hepatic masses are the focal points of liver biopsy diagnoses. Increased risk of hemorrhage due to coagulation defects can be minimized by a transjugular biopsy. Liver masses can be effectively located and identified by radiologically or ultrasound-guided biopsy. Regular periodic conferences between clinicians and pathologists help to clarify individual problematic cases and will promote the diagnostic competence of both partners in hepatology.

[Pathology along the liver sinusoids: endothelial and perisinusoidal findings]. / Pathologie entlang der sinusoidalen Wegstrecke: sinusendotheliale und perisinusoidale Befunde.

Sinusoidal alterations unrelated to primary hepatocellular damage present without characteristic clinical findings and in these cases the liver biopsy is particularly important. Capillarization of sinusoids is characterized by closing of fenestration, formation of a basal membrane and by the expression of CD34 and is typical for active cirrhosis. In nodular regeneratory hyperplasia, capillarization indicates a local or general disturbance of perfusion. In large regenerative nodules, focal nodular hyperplasia and liver cell adenoma CD34-positive capillaries reflect afferent parts and CD34-negative sinusoids the efferent parts of the parenchymal vascular bed. HCC generally have a completely capillarized CD34-positive vascular bed. Hepatic angiosarcomas and epithelioid hemangioendotheliomas can be easily overseen in liver biopsies, if they spread along the sinusoids without detoriation of the acinar architecture and without significant alteration of the surrounding liver cell plates. Toxic damage of endothelial cells, post-sinusoidal stasis and sinusoidal hyperperfusion are the underlying pathogenetic principles of sinusoidal injury. Rupture and loss of the perisinusoidal reticulin fibres lead to peliosis hepatis. In these cases liver biopsy might disclose occlusion of the terminal liver veins (VOD). Perisinusoidal fibrosis can be caused by intrasinusoidal accumulation of pathologic cells, advanced intrasinusoidal macrophagocytic storage diseases and by activation of the vitamin A-storing hepatic stellate cells. Perisinusoidal amyloidosis can be the first sign of an underlying B-cell neoplasia.

[Hereditary hemochromatosis, alpha-1-antitrypsin deficiency and Wilson's disease. Pathogenesis, clinical findings and pathways to diagnosis]. / Hereditäre Hämochromatose, Alpha-1-Antitrypsin-Mangel und Morbus Wilson: Pathogenese, Klinik und Wege zur Diagnose.

Primary hemochromatosis, alpha-1-antitrypsin (AAT) deficiency, and Wilson's disease are the most common hereditary causes of unclear hepatopathy. Classical primary hemochromatosis (type I) on the basis of a homozygous mutation of the HFE gene, usually presents in adults with increasing hepatocellular siderosis and chronic progressive necroinflammatory liver disease. Homozygous AAT deficiency type PiZZ becomes manifest in newborns as a giant cell hepatitis or findings similar to bile duct atresia, in adults as chronic hepatitis or "cryptogenic cirrhosis". The heterozygous PiZ mutation can lead to PAS-positive hepatocellular AAT deposits increasing over the life time. Immunohistochemical detection of AAT deposits by specific PiZ antibodies is a highly sensitive and specific supplementary method. Molecular analysis of AAT and HFE genes in paraffin-embedded tissue or blood can confirm the diagnosis and allows the zygosity status to be defined. Wilson's disease has to be considered in children and young adults with unexplained histologic findings of chronic hepatitis or steatohepatitis. Rhodanin staining is the most effective histochemical method to detect free copper deposits, but negative staining results do not exclude Wilson's disease. In cases suspected of Wilson's disease further clinical exploration must be initiated. The diagnosis is based on a combination of clinical and biochemical findings, which can be supplemented by mutation analysis of the ATP7B gene.

[Pathology along the liver sinusoids: intrasinusoidal findings]. / Pathologie entlang der sinusoidalen Wegstrecke: intrasinusoidale Befunde.

Pathological findings in the liver sinusoids are mostly caused by extrahepatic or systemic diseases. Unclear fever, hepatosplenomegaly, portal hypertension or a mild elevation of liver enzymes are reasons for a liver biopsy leading to path-breaking diagnoses. Reactive intrasinusoidal lymphocytosis, especially with Epstein-Barr virus infections, has to be differentiated from predominantly intrasinusoidal lymphoproliferative malignancies. Intrasinusoidal megakaryocytes can be the first sign of a myeloproliferative or myelodestructive disease. Intrasinusoidal carcinosis and melanomatosis might present radiologically without tumor lesions and are easily overlooked histologically, in particular, if the critical cells have a similar size to hepatocytes. This also applies for intrasinusoidal storing macrophages. Gaucher's disease type I, and some other subtypes of inborn storage diseases might present for the first time in adulthood by hepatomegaly and Kupffer cell hypertrophy. Accompanying perisinusoidal fibrosis and immunohistochemical staining (CD68) can help to detect the large pale intrasinusoidal macrophages. In immunocompromized patients with fever, particular attention must be paid to intracellular agents, especially atypical mycobacteria and yeasts in non-granulomatous nested or dispersed Kupffer cells. Leishmaniasis with amastigotes in macrophages is accompanied by reactive sinusoidal plasmocytosis.