[Histological classification of soft tissue tumors and staging according to the TNM system]. / Histologische Klassifikation von Weichgewebstumoren und Stadieneinteilung gemäß TNM-System.

The classification of soft tissue tumors is based on their resemblance to normal non-neoplastic tissues and provides an indication of how the tumor will behave in the further disease course. The current article presents the principles to be considered when classifying tumors into categories and discusses additional findings to be taken into account in the diagnosis. The importance of considering combinations of findings when classifying a tumor is underscored; individual (in particular immunohistochemical) findings can be misleading. A statement on the grade of malignancy of a soft tissue tumor requires its identification as a known entity, otherwise incorrect prediction of its biological behaviour is possible. The category of "intermediate malignancy" has been added to the categories of "benign" and "malignant", whereby locally aggressive and incidentally metastasizing tumors have been included in this new category. The staging of soft tissue tumors according to the TNM system is explained, emphasizing that one important feature compared with carcinomas is the inclusion of depth localisation and grade of malignancy.

[Update from the soft tissue tumour registry in Jena]. / Neues aus dem Jenaer Weichteiltumor-Register.

The Jena Institute of Pathology has been serving as a consultation and reference center for soft tissue tumors in Germany since 1978. The present study provides an overview of the clinicopathological data from a two-year period and an update on diagnostics and research. Retrospectively, 7043 cases sent to the institute in the years 2006 and 2007 were analyzed. The majority of cases (>77.7%) were soft tissue tumors, of which 49% were categorized as malignant, 11.4% as intermediate, 35% as benign and 4.6% as tumors of uncertain biological potential. Neoplasms with fibroblastic differentiation were the most frequent. The mean age of patients with a sarcoma was 63 years. The molecular pathological analysis of soft tissue tumors has attained a major role in diagnosis. This is further advanced at the Jena institute in the context of a German Federal Ministry of Education and Research (BMBF) project for molecular sarcoma diagnosis with the aim of developing and validating DNA probes for in situ hybridization detection of translocations and their associated chromosomal breaks on the one hand, and DNA chips for the detection of fusion transcripts on the other. Research projects relate to the analysis of specific biomarkers in large tumor collectives and the pathomechanisms in several sarcoma entities.

[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.

Recurrence of a laryngeal spindle cell sarcoma with a transformation into a higher grade of malignancy.

Primary malignant mesenchymal neoplasms of the larynx are rare. Sarcomas of the larynx account for <1% of all malignant laryngeal mesenchymal neoplasms. This report examines a case of a recurring laryngeal, initial benign-appearing mesenchymal tumour, which first changed its clinical phenotype without any histological signs of malignancy and later also its histological appearance with signs of malignancy. Finally, it even underwent a transformation into a higher grade of malignancy. In addition to this, the difficulties of allocating this tumour to the correct sarcoma subentity are shown.

[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.

[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.

Hibernoma-like brown fat in the bone marrow: report of a unique case.

We report on a bone-marrow biopsy of a 61-year-old female patient that was performed because of the clinical suspicion of a myeloproliferative disease. The trephine biopsy showed morphological features that were consistent with an essential thrombocythaemia (ET). The diagnosis of a myeloproliferative disease could be corroborated by demonstration of the V617F mutation of JAK2. Besides the histological features of ET, the marrow showed a peculiar infiltrate that consisted of multivacuolated cells that were immunohistochemically identified as brown adipose tissue with a hibernoma-like picture. To the best of our knowledge, this is the first report on brown adipose tissue in the bone marrow.

[Primary liposarcoma of the liver--a rare mesenchymal tumor]. / Primäres Liposarkom der Leber--ein seltener mesenchymaler Tumor.

Primary sarcoms of the liver are rare. Most often angiosarcomas have been reported. Primary liposarcoma of the liver is extremely rare. We report a case of primary liposarcoma of the liver in a 48-year-old woman and compare it with the 13 cases found in the literature. Histologic analysis showed a well differentiated liposarcoma. The treatment of choice is wide local tumor resection.

[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.

[Morphological variability of synovial sarcoma in childhood]. / Morphologische Variabilität des synovialen Sarkoms im Kindesalter.

We report on an unusual locally recurrent plantar soft tissue sarcoma in a 7-years-old boy. Due to an unusual morphology a clear diagnosis was initially not possible. The histologically different recurrent tumor was classified as synovial sarcoma by means of immunohistochemistry, ultrastructural and molecular analysis. This case demonstrates the variable morphological appearance of synovial sarcoma and the value of modern diagnostic procedures in such circumstances.

[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.

[Pathology and histology of soft tissue sarcomas in the upper extremity: adults]. / Pathologie und Histologie von Weichteilsarkomen der oberen Extremität: Erwachsene.

PURPOSE/BACKGROUND: Clinicopathologic characterization and demonstration of histologic findings in six common soft tissue sarcomas of the upper extremity in adult patients. RESULTS/CONCLUSION: Clinicopathologic findings and histologic features of the following malignant soft tissue tumours are compiled: epithelioid sarcoma, synovial sarcoma, clear cell sarcoma, liposarcoma, fibrosarcoma, and malignant fibrous histiocytoma (MFH). All these tumours show typical clinical presentations and characteristic histological findings.

Use of complementary and alternative medicine by patients with breast cancer: observations from a health-care survey.

GOALS OF THE WORK: The aim of this study was to assess the period prevalence and identify predictors of the use of complementary and alternative medicine (CAM) among women with breast cancer. PATIENTS AND METHODS: In a cross-sectional study, 263 women participating in a quality of life survey reported on CAM use. Differences between CAM users and nonusers were evaluated using logistic regression. RESULTS: About 3 years after diagnosis the period prevalence of CAM use among women with breast cancer was 36%. Younger women reported usage of CAM more often than older women. Associations between remote disease, pain and psychosocial variables were found. Involvement in self-help groups and active participation in leisure activities were associated with CAM use; this may indicate differences in the patients' ability to cope with the disease. Most patients were informed of CAM by a physician. CONCLUSIONS: Involvement in self-help groups and leisure activities were associated with CAM use, indicating differences in the patients' ability to cope. Further research is necessary to evaluate the safety of CAM and to determine the value of CAM in health care.

The impact of comorbidity on the survival of postmenopausal women with breast cancer.

PURPOSE: The aim was to assess the impact of comorbidity on survival of postmenopausal women with breast cancer diagnosis in the period 1995-1997. METHODS: The level of comorbidity was described by the methods suggested by Satariano and Charlson. Cox's proportional hazard models were used to explore the impact of comorbidity on all-cause mortality. RESULTS: After a median follow-up time of 52 months, an increasing level of comorbidity was associated with a higher all-cause mortality. Compared to patients with-out comorbid conditions, the hazard ration of death (HR) was 1.2 (95% CI: 0.8-1.7) for Satariano index 1 and HR 2.3 (95% CI: 1.5-3.5) for Satariano index >or=2, and HR 1.6 and 2.1 for the Charlson comorbidity index, respectively. Independent of comorbidity, the treatment pattern had a strong impact on survival. The level of comorbidity has an influence on the 3-year survival of postmenopausal women with breast cancer. CONCLUSIONS: Long-term follow-up is required to appraise these findings in relation to treatment strategies.

[Extranodal Rosai Dorfman disease (sinus histiocytosis with massive lymphadenopathy). Report of 5 cases]. / Extranodale Rosai-Dorfman-Erkrankung (Sinushistiozytose mit massiver Lymphadenopathie). Ein Bericht über fünf Fallbeobachtungen.

Sinus histiocytosis with massive lymphadenopathy (SHML) was described in 1969 by Rosai and Dorfman as an benign disorder of the lymph nodes. Involvement of extranodal sites by SHML may occur as part of a generalized disease involving lymph nodes as well as independently of the lymph node status. The clinical course is mostly benign and indolent, but in rare cases the SHML can cause death. We report 5 cases of extranodal Rosai Dorfman disease (ENSHML). The lesions were localized in the soft tissue of the extremities, the head and the skeleton. Histopathological examination revealed a lymphoplasmacellular infiltration and numerous histiocytes with an eosinophilic cytoplasma and vesicular nuclei with basophilic nucleoli. The histiocytes showed emperipolesis with multiple lymphocytes within the cytoplasm and occasionally phagocytosis of other inflammatory cells. The histiocytes were immunohistochemically positive for S 100 protein and macrophage-specific antibodies, but in paraffin material negative for CD1a. We briefly discuss aspects of differential diagnosis of this lesion, too.

[Sclerosing epithelioid fibrosarcoma]. / Sklerosierendes epitheloides Fibrosarkom.

The sclerosing epithelioid fibrosarcoma (SEF), defined as an entity by Meis-Kindblom et al. in 1995 [15] is now considered to be a variant of fibrosing fibrosarcomas. It is a rare tumor with an intermediate malignant potential leading to local recurrences in one third and to metastases in about 40% of the cases. We report six cases of this entity. At the time of diagnosis two patients of our series already showed metastases in the lungs. The tumors were located in the deep soft tissue and measured between 2.5 and 17 cm. The histology is characterized by small epithelioid cells that are arranged individually or in cords and nests and set typically in a hyaline sclerotic matrix. By immunohistochemistry, all cases were vimentin positive, however EMA positive cells are also possible. The differential diagnosis includes metastases of carcinoma, benign and malignant soft tissue tumors. The distinction of SEF from fibromatosis, fibrous histiocytomas, ossifying fibromyxoid tumors, clear cell sarcomas, epithelioid sarcomas, synovial sarcomas and extraskeletal osteosarcomas is discussed.