Long-term survival after recurrent hepatocellular carcinoma in liver transplant patients: clinical patterns and outcome variables.

BACKGROUND: The objective of this trial was to analyze the clinical patterns and outcome variables of recurrent hepatocellular carcinoma (HCC) in liver transplant patients. PATIENTS AND METHODS: Sixty patients after liver transplantation (LT) for HCC were analyzed. All of them received initially a calcineurin-inhibitor based immunosuppressive regimen. Recurrent HCC was treated by surgical intervention, if eligible, or adjuvant therapies. Furthermore, patients were converted to a Sirolimus (SRL)-based immunosuppressive regimen after tumor relapse. The impact of clinical and histopathological variables on post-recurrence survival was analyzed in uni- and multivariate analysis. RESULTS: Sixteen liver recipients developed HCC recurrence between 4 and 58 months (median: 23 months) post-LT. Sites of first tumor recurrence were lung (n = 5), liver (n = 4), bone (n = 4), cerebrum (n = 1), adrenal gland (n = 1) and peritoneum (n = 1). Seven patients were amenable for surgical resection, while 9 patients were only suitable for adjuvant treatment (n = 4) or general medical support (n = 5). Median survival rate post-recurrence was 65 months (range: 12-136 months) in patients amenable for surgical therapy, and 5 months (range: 1-52 months) in patients unsuitable for surgical intervention (P = 0.01). Multivariate analysis identified late (>24 months) posttransplant tumor relapse (P = 0.039) and surgical therapy (P = 0.014) as independent predictors of long-term survival after tumor relapse. Five patients are tumour-free alive for a median of 65 months after surgical resection of recurrent HCC and conversion to SRL. CONCLUSION: Liver transplant patients with HCC recurrence should be treated surgically, if eligible, since this is an independent predictor of long-term survival.

[Solitary fibrous tumor and haemangiopericytoma: what is new?]. / Solitärer fibröser Tumor und Hämangioperizytom : Was ist neu?

Soft-tissue tumors with haemangiopericytoma (HPC)-like growth patterns can now be divided into three categories: (1) The solitary fibrous tumour (SFT) group with its variants; (2) lesions showing clear evidence of myoid/pericytic differentiation and corresponding to "true" HPCs (myopericytoma/glomangiopericytoma and a subset of sinonasal HPCs); (3) neoplasms that occasionally display HPC-like features (e.g. synovial sarcoma). In this study 268 intrathoracic and extrathoracic SFTs from the German consultation and reference center of soft tissue tumors in Jena were evaluated and analyzed immunohistochemically with antibodies CD34, Bcl-2, CD99, SMA, S100, PanCK and Ki-67. Furthermore, SFTs were categorized into the newly proposed SFT designation: Fibrous variant, cellular variant (more than 90% hypercellularity), fat-forming variant, giant cell-rich variant and malignant SFTs. This article should provide insights into the diagnosis of this entity with emphasis on the new international standard.

Increased 18F-FDG uptake of hepatocellular carcinoma on positron emission tomography independently predicts tumor recurrence in liver transplant patients.

The aim of this retrospective trial was to analyze the value of preoperative (18)F-fluoro-deoxyglucose positron emission tomography ((18)F-FDG PET) to predict parameters of tumor aggressiveness among liver transplant (OLT) patients with hepatocellular carcinoma (HCC). Fifty-five patients with HCC underwent (18)F-FDG-PET during evaluation for OLT. Nineteen patients demonstrated increased (18)F-FDG uptake on PET pre-OLT (PET(+)), and 36 patients revealed negative PET findings (PET(-)). PET(+) patients showed a relative risk of 9.5 and 6.4 for poor differentiation and for microvascular invasion (MVI) in the HCC at explant pathology, respectively. Of the 10 patients (18.2%) who developed HCC recurrences, 9 (90%) revealed increased (18)F-FDG uptake pre-OLT; only 1 (10%) showed a PET(-) status (P < .001). Apart from poor tumor differentiation, PET(+) status was identified as an independent predictor of tumor recurrence post-OLT (odds ratio, 23.9). Our study demonstrated that (18)F-FDG uptake on PET is a reliable preoperative predictor of tumor recurrence after OLT in patients with HCC, triggered by its high association with poor tumor differentiation and MVI.

18F-FDG-uptake of hepatocellular carcinoma on PET predicts microvascular tumor invasion in liver transplant patients.

Vascular invasion of hepatocellular carcinoma (HCC) is a major risk factor for poor outcome after liver transplantation (LT). The aim of this retrospective analysis was to assess the value of preoperative positron emission tomography (PET) using (18)F-fluorodeoxyglucose ((18)F-FDG) in liver transplant candidates with HCC for predicting microvascular tumor invasion (MVI) and posttransplant tumor recurrence. Forty-two patients underwent LT for HCC after PET evaluation. Sixteen patients had an increased (18)F-FDG tumor uptake on preoperative PET scans (PET +), while 26 recipients revealed negative PET findings (PET-) pre-LT. PET- recipients demonstrated a significantly better 3-year recurrence-free survival (93%) than PET + patients (35%, p < 0.001). HCC recurrence rate was 50% in the PET + group, and 3.8% in the PET-population (p < 0.001). PET + status was identified as independent predictor of MVI [hazard ratio: 13.4]. Patients with advanced PET negative tumors and patients with HCC meeting the Milan criteria had a comparable 3-year-recurrence-free survival (80% vs. 94%, p = 0.6). Increased (18)F-FDG uptake on PET is predictive for MVI and tumor recurrence after LT for HCC. Its application may identify eligible liver transplant candidates with tumors beyond the Milan criteria.

[Modern morphological diagnosis and current classification of soft tissue sarcomas]. / Moderne morphologische Diagnostik und aktuelle Klassifikation von Weichteilsarkomen.

Malignant soft tissue tumors are somewhat rare, and thus sufficient experience in diagnostics and therapy of these sarcomas is available as a rule only at specialist centers. The gold standard of morphological diagnosis is still represented by evaluation of HE-stained histological sections. However modern methods of examination are also helpful in diagnosis. Because immunohistochemistry is now used routinely, emphasis in this article is laid on molecular methods with special reference to fluorescence in-situ hybridization (FISH) and reverse transcriptase polymerase chain reaction. Principles of the WHO soft tissue tumor classification are explained, and the changed or expanded interpretation of some tumor entities is illustrated using the example of atypical lipomatous tumors, so-called malignant fibrous histiocytomas and hemangiopericytomas, fibrosarcomas, and inflammatory myofibroblastic tumors.

Plexiform angiomyxoid myofibroblastic tumour: differential diagnosis of gastrointestinal stromal tumour in the stomach.

Mesenchymal tumours other than gastrointestinal stromal tumours are rare in the stomach. Nevertheless it is important to incorporate them into the differential diagnosis. Plexiform angiomyxoid myofibroblastic tumour is a recently described new entity of a presumably benign mesenchymal gastric tumour. This report presents what is believed to be the third case of this tumour. The tumour is characterised by bland spindle cells in a plexiform pattern, a mucinous extracellular matrix and a network of thin blood vessels. These findings are completely in line with the two previous reported cases. There was a strong positivity for alpha-smooth muscle actin and a low proliferation index (<2%). The tumour had no C-KIT or CD34 expression and no mutation in the C-KIT and PDFGRalpha genes. Plexiform angiomyxoid myofibroblastic tumour may present a new mesenchymal tumour entity in the stomach.

[Gastrointestinal stromal tumors. Diagnosis and estimating aggressiveness]. / Gastrointestinale Stromatumoren. Diagnose und Malignitätseinschätzung.

A diagnosis of gastrointestinal stromal tumor must be considered if a mesenchymal tumor is localized in the gastrointestinal tract, especially in the stomach. In daily practice diagnosis is based on the histology (cellular features and histologic architecture) and immunohistochemistry (cellular positivity with antibodies to CD117 and often to CD34). Expression of CD117 indicates the autoactivation of a type-III-receptor tyrosine kinase mediated by mutation of the KIT gene. This is lacking in the roughly 5% of cases which instead show a mutation of the PDGF receptor alpha gene. The estimation of dignity is difficult and can be uncertain in some cases. A malignancy grading according to the procedure in soft tissue tumors is not possible. Nowadays, however, the general consensus is that size of the tumor and number of mitoses are the most important criteria for appraising tumor aggressiveness and risk of metastasis. The tumor localization was later added to these criteria. Recent years have shown that mutation analysis can also provide information for judging tumor aggressiveness and predicting possible metastasis and response to therapy.

[Problematic zones in the classification of soft tissue tumors]. / Problemzonen der Tumorklassifikation bei Weichgewebstumoren.

The classification of soft tissue tumors is based on the recognition of the resemblance to normal tissue or cells. Nowadays, molecular pathologic findings essentially may contribute to the diagnosis. In daily practice, however, the evaluation of HE sections and immunohistochemical findings are most important because these methods are widely available. Nevertheless, misinterpretations are possible if certain rules and limitations in data utilization for diagnosis are not considered. There are some problematic zones referring to this in which especial attention is mandatory. By means of examples difficulties are explained which may result from overlapping morphological features between soft tissue tumors, between nerve sheath tumors and melanocytic neoplasms, and between soft tissue tumors and sarcomatoid carcinomas. The necessity of a careful interpretation of immunohistochemical findings is underscored with selecting actin positivity as example. Finally, difficulties in determining the dignity of a soft tissue tumor are discussed. Moreover, tumor heterogeneity may under certain conditions render more difficult the classification of a soft tissue tumor.

Low-grade fibrosarcoma--report on 39 not otherwise specified cases and comparison with defined low-grade fibrosarcoma types.

AIMS: Low-grade fibrosarcomas are tumours that mainly affect the extremities and trunk of adults of either sex. Among these, low-grade fibromyxoid sarcoma (FMS), hyalinizing spindle cell tumour with giant collagen rosettes (HST) and sclerosing epithelioid fibrosarcoma (SEF) are well-established entities. In this study, our aim was to describe a group of low-grade fibrosarcomatous tumours, which could not be encompassed by these entities. These low-grade fibrosarcomas, not otherwise specified (FNOS) were provisionally designated as 'fibrosarcoma, low-grade fibroblastic type'. METHODS AND RESULTS: In the soft tissue tumour registry we found 39 FNOS (46%), 31 FMS (36%), 11 SEF (13%) and four HST (5%). FNOS occurred in older patients than FMS (mean age 56.3 years versus 33.7 years). They mainly showed fibrous features, but myxoid areas could also be seen. While cells tended to be loosely arranged in the myxoid areas, densely packed sheets with a storiform pattern, fascicular arrangements or regions without a defined growth pattern were observed in the fibrous areas. However, neither whirling nor swirling patterns were found. Arcade-like vessels were not visible; pseudolipoblasts did not occur. FNOS exhibited increased atypia and mitotic count compared with the other sarcomas studied [FNOS, mean value 4.6 mitoses/10 high-power field (HPF); FMS, 0.7/10 HPF). Follow-up data were available in 21 FNOS patients. In seven cases (33.3%), local recurrences were reported. Three patients (14.3%) developed metastases and all of them died of tumour. CONCLUSIONS: The term 'fibrosarcoma, low-grade fibroblastic type' should be used as a diagnosis of exclusion. Further studies should elucidate whether it represents a distinct fibrosarcoma type.

[Intramuscular nodular fasciitis--a clinicopathological study with emphasis on myogenic giant cells]. / Intramuskuläre Fasciitis nodularis : Klinikopathologische Ubersicht unter besonderer Berücksichtigung myogener Riesenzellen.

Nodular fasciitis is a frequently occurring pseudosarcomatous fibrous proliferation which usually affects the subcutaneous tissue. In the present study, we investigated tissue specimens from 26 patients with intramuscular nodular fasciitis. The median age of patients was 31 years, with the tumors occurring mainly in the extremities (11 patients) and the trunk (11 patients). These had an average size of 2.6 cm. Males predominated (male:female 9:4). Histological examination revealed a proliferation of myofibroblasts (positive for smooth muscle-actin) embedded in a myxoid or fibrous stroma. In 25/26 cases, myogenic giant cells were observed (positive for desmin, negative for smooth-muscle actin and CD 68). Less frequently (11/26 patients), osteoclastic giant cells were found (positive for CD 68, negative for desmin and smooth-muscle actin). In intramuscular nodular fasciitis, myogenic giant cells are encountered more often than previously described. They are relevant for the differential diagnosis of sarcoma and fibromatoses, since they can be misinterpreted as neoplastic giant cells. However, the uniformity of the myofibroblastic proliferate and the myogenic phenotype of the giant cells without proliferative activity (no mitoses, negativity for Ki-67) lead to a correct diagnosis.

[Simultaneous analysis of t(X;18) by FISH- und SYT/SSX-RT-PCR in synovial sarcoma]. / Diagnostik des Synovialsarkoms Simultane t(X;18) FISH- und SYT/SSX-RT-PCR-Analyse.

Synovial sarcoma diagnosis and differential diagnostic distinction from other spindle cell sarcomas may be difficult. In these cases the detection of the t(X;18) translocation by FISH and RT-PCR is diagnostically extremely helpful. This study was aimed at the question whether or not simultaneous use of both methods is required for evidence of t(X;18) translocation.Paraffin-embedded tumour specimens from 53 patients were included in the study which were considered to be possible synovial sarcomas on the basis of histological aspect and immunohistochemical profile. Detection of t(X;18) was performed using FISH and RT-PCR simultaneously. Nuclei and amplifiable RNA could be isolated from 39 of the 53 included cases (75%). In 72% of these 39 cases FISH and RT-PCR showed identical negative or positive results. The remainder of the cases (28%) showed either a typical PCR product or a positive FISH signal.In conclusions FISH could be confirmed by typical PCR products and is therefore qualified as an internal quality control. Nevertheless tumour biological and methodical reasons have an important influence on both methods. Consequently in difficult cases simultaneous FISH and RT-PCR analysis is necessary for a clear evidence of t(X;18) translocation.

[Dermal chondroid melanoma]. / Dermales chondroides Melanom.

This case describes the history of disease of a 53-year old man, who has been treated for a putative recurrent nailbed granuloma of the right big toe since 1996. In 2000 an enlarged inguinal lymph node was excised. The light microscopic examination showed a metastasis of a malignant melanoma. In 2003 we received a tumor of the right big toe for histopathological examination. The histological and immunohistochemical results proved a dermal chondroid melanoma. This extremely rare variant of malignant melanoma occurs particularly in subungual location and is possibly related to a previous trauma. We discuss the spectrum of differential diagnoses and the importance of immunohistochemistry.

[Low-malignant peripheral nerve sheath tumors of nasal and sinonasal mucous membranes]. / Niedrig-maligne periphere Nervenscheidentumoren der Nasen- und Nasennebenhöhlenschleimhaut. Bedeutung der S100-Protein-Reaktivität für Diagnose und Differenzialdiagnose.

Sinonasal malignant peripheral nerve sheath tumors (MPNST) are infrequent neoplasms. 16 cases of low-malignant MPNST in this localization were retrieved from the files of soft tissue tumors established in Jena. They were examined with regard to their morphology and immunohistochemistry. The importance of an only partial immunostaining by S100 protein antibodies for diagnosis and differential diagnostic discrimination to benign peripheral nerve sheath tumors (schwannomas and neurofibromas) is explained. Finally, the differential diagnosis of spindle cell tumors in the sinonasal region in general is briefly discussed.