[Ectopic thymic tissue and ectopic thymic tumors]. / Ektopien des Thymus und ektope Thymustumoren.

Ectopic thymic tissue outside its core position in the antero-superior mediastinum is quite common owing to the complexity of embryonal thymus development, whereby reported prevalence values (1 to 90%) are heavily dependent on the method of investigation and the intensity of the workup. The debated prevalence and relevance of ectopic thymic tissue and its accessibility underlie the ongoing discussion whether modern, minimally invasive thymectomy strategies can match the proven benefit of the radical transsternal thymectomy procedure for the treatment of Myasthenia gravis. In this context, the following article covers the etiology, prevalence, and location of normal-looking, reactive, and neoplastic ectopic thymic tissue. Furthermore, ectopic tissues and tumors inside or adjacent to the thymus are mentioned.

Ki67 levels as predictive and prognostic parameters in pretherapeutic breast cancer core biopsies: a translational investigation in the neoadjuvant GeparTrio trial.

BACKGROUND: The proliferation marker Ki67 has been suggested as a promising cancer biomarker. As Ki67 needs an exact quantification, this marker is a prototype of a new generation of tissue-based biomarkers. In this study, we have systematically evaluated different cut points for Ki67 using three different clinical end points in a large neoadjuvant study cohort. PATIENTS AND METHODS: We have evaluated pretherapeutic Ki67 levels by immunohistochemistry in 1166 breast cancer core biopsies from the neoadjuvant GeparTrio trial. We used the standardized cutoff-finder algorithm for three end points [response to neoadjuvant chemotherapy (pCR), disease-free (DFS) and overall-survival (OS)]. The analyses were stratified for hormone receptor (HR) and HER2 status by molecular subtype radar diagrams (MSRDs). RESULTS: A wide range of Ki67 cut points between 3%-94% (for pCR), 6%-46% (for DFS) and 4%-58% (for OS) were significant. The three groups of Ki67 ≤ 15% versus 15.1%-35% versus >35% had pCR-rates of 4.2%, 12.8%, and 29.0% (P < 0.0005), this effect was also present in six of eight molecular subtypes. In MSRD, Ki67 was significantly linked to prognosis in uni- and multivariate analysis in the complete cohort and in HR-positive, but not triple-negative tumors. CONCLUSIONS: Ki67 is a significant predictive and prognostic marker over a wide range of cut points suggesting that data-derived cut point optimization might not be possible. Ki67 could be used as a continuous marker; in addition, the scientific community could define standardized cut points for Ki67. Our analysis explains the variability observed for Ki67 cut points in previous studies; however, this should not be seen as weakness, but as strength of this marker. MSRDs are an easy new approach for visualization of biomarker effects on outcome across molecular subtypes in breast cancer. The experience with Ki67 could provide important information regarding the development and implementation of other quantitative biomarkers.

[Primitive neuroectodermal tumor of the testis. Molecular analysis and discussion of genesis]. / Primitiver neuroektodermaler Tumor im Hoden. Molekulare Analyse und Diskussion der Entstehung.

We describe a case of a testicular primitive neuroectodermal tumor (PNET) with intratubular germ cell neoplasia of the adjacent testicular parenchyma. The occurrence of testicular PNET is rare because malignant transformation of testicular germ cell tumors into somatic malignancy is uncommon. Based on morphological, immunohistochemical and molecular pathological findings these tumors resemble central PNETs as they otherwise typically occur in children without rearrangement of the Ewing sarcoma breakpoint region (EWSR) gene on chromosome 22. This case also showed no evidence for a translocation.

[The bovine cartilage punch model: a tool for the in vitro analysis of biomaterials and cartilage regeneration]. / Das bovine Knorpelstanzenmodell : Ein Werkzeug zur In-vitro-Analyse von Biomaterialien und Knorpelregeneration.

BACKGROUND: The limited regeneration capacity of hyaline articular cartilage requires detailed studies concerning the tissue integration of cartilage transplants with meaningful but time and/or resource-consuming and in part ethically problematic animal models or, alternatively, with in vitro test systems for implant materials. MATERIAL AND METHODS: The present study describes a regeneration model with bovine cartilage rings (outer Ø 6 mm, central defect Ø 2 mm) for insertion, cultivation and biomechanical or histological testing of cartilage replacement materials (HE and safranin O staining). In this study, resorbable polymers composed of polyglycolic acid (PGA) were analyzed. RESULTS: Biomechanical testing showed a continuous decrease of the push-out force for the PGA inserts from the cartilage rings, probably due to the resorbability of the material. Histologically, clear immigration of cells into cell-free PGA was observed even after 4 weeks of culture, but in particular after 10 weeks. In addition, storage of proteoglycans was interpreted as an initial sign of the formation of new matrix. CONCLUSION: Thus, the new regeneration model is in principle suitable for the testing of biomaterials, but shows limitations in assessing the "lateral bonding" of resorbable materials.

[Infectious lymphadenitis]. / Infektiöse Lymphadenitiden.

Infectious lymphadenitis is often biopsied in the differential diagnoses of malignant disease. Since the repertoire of lymph nodes which react to exogenous stimuli is limited, malignant lymphomas may enter the clinical and morphological differential diagnosis. In a morphological sense, infectious lymphadenitis is defined as an infection of lymph node tissue. Therefore, the effector phase of the inflammatory reaction will act against lymphatic tissue, in contrast to common physiological hyperplasia. Follicular reactions, in addition to follicular hyperplasia, are seen in HIV-associated lymphadenopathy. Other viruses, such as infectious mononucleosis, give rise to a cytotoxic T-cell reaction. Most infections, however, induce a histiocytic reaction; depending on the microorganism, this varies morphologically from a small clustered epithelioid cell reaction or histiocytic abscesses to epithelioid necrotizing granulomata.

[Vascular proliferations of the spleen]. / Vaskuläre Tumoren der Milz.

Vascular proliferations of the spleen reflect the variability of vascular structures occurring in the normal spleen. Besides haemangiomas, there is a spleen-specific vascular neoplasm, littoral cell angioma, that often occurs as a paraneoplastic lesion and thus may require the differential diagnostic delineation of metastases to the spleen in patients with known neoplasms. The most common malignant vascular tumours of the spleen are angiosarcomas. A recently described vascular lesion of unknown pathogenesis, sclerosing angiomatoid nodular transformation (SANT) of the spleen, usually is an incidental finding detected in the course of imaging studies.

[Functional splenic pathology and differential diagnosis in splenectomy]. / Funktionelle Pathologie der Milz. Grundlagen und differenzialdiagnostische Erwägungen am Milzpräparat.

From a pathologic-anatomic perspective, the splenic parenchyma is divided into red and white pulp, which react to a certain extent independently from one another in the context of systemic and local processes. While the red pulp serves to filter blood, the white pulp, together with the perifollicular marginal zone, organizes immune reactions. In the marginal zone, innate and acquired immune responses are integrated. The vast majority of splenectomies serve therapeutic purposes in the context of already known disease. Therefore, only about 10% of splenectomy specimens are diagnostic challenges, including the diagnosis of haematological diseases, splenomegaly or splenic tumors. Differential diagnosis considerations are discussed based on the clinical presentation.

[Inflammatory reactions of the spleen]. / Entzündliche Reaktionstypen der Milz.

Inflammatory reactions of the spleen occur in the context of two pathophysiological settings. First, lymphoid hyperplasia of the spleen can be the result of a principally physiological production of immune effector cells e.g. due to systemic viral infections, autoimmune diseases and acquired or inherited immunodeficiencies. Second, the spleen itself may be the target of a pathological inflammatory reaction; this setting is exemplified by abscess formation due to septicopyemic spread of bacteria and by granulomatous inflammations, e.g. due to tuberculosis or sarcoidosis. Differential diagnostic considerations have to include splenic inflammatory pseudotumors, mycobacterial spindle cell tumors and lymphomas with granulomatous or histiocyte-rich reactive changes.

[Splenic vascular disturbances]. / Kreislaufstörungen der Milz.

Splenic vascular disturbances mainly affect the red pulp and can involve the venous or arterial blood flow. The venous blood flow may be impaired by congestion and morphologically shows dilated splenic sinuses. Disturbances of the arterial blood flow may occur in connection with anomalies of the erythrocyte membrane or in immune haemolysis and usually are characterized by narrow splenic sinuses. Infarction of the spleen is usually caused by arterial embolism.

[Lymphomas of the spleen]. / Lymphome der Milz.

The spleen is commonly affected by malignant lymphomas and the macroscopic findings of the spleen correlate with different lymphoma entities. However, most lymphomas are not primarily diagnosed in splenectomy specimens. Exceptions include splenic marginal zone lymphomas and hepatosplenic T-cell lymphomas that are typically diagnosed from histological findings. In addition, hairy-cell leukemia, LGL leukemia and T-cell prolymphocytic leukemia typically show characteristic patterns of infiltration in the spleen which may be diagnostically useful. The different infiltration patterns of these tumors are discussed here.

Differential diagnosis between classic Hodgkin's lymphoma, T-cell-rich B-cell lymphoma, and paragranuloma by paraffin immunohistochemistry.

There are significant difficulties in the differential diagnosis of lymphomas at the interface between classic Hodgkin's lymphoma and both paragranuloma and T-cell-rich B-cell lymphoma as well as at the interface between T-cell-rich B-cell lymphoma and paragranuloma. We therefore investigated 197 cases (155 classic Hodgkin's lymphomas, 32 T-cell-rich B-cell lymphomas, and 10 paragranulomas) by paraffin immunohistochemistry. Special interest was given to cases with a B-cell phenotype of tumor cells. The reactive inflammatory infiltrate in both classic Hodgkin's lymphoma and T-cell-rich B-cell lymphoma was rich in TIA-1-positive cytolytic lymphocytes, and CD57-positive cells were rarely encountered. In contrast, in paragranuloma CD57-positive cells and small B-lymphocytes predominated the background infiltrate. The tumor cells in cases of classic Hodgkin's lymphoma were positive for CD30 in 95%, for CD15 in 75%, and for CD20 in 22%. Apart from this, vimentin was expressed in >95% of the cases. All cases of T-cell-rich B-cell lymphoma were negative for vimentin, CD30, and CD15. The reactivity of the tumor cells for CD30, CD15, CD20, and vimentin together with the background reactivity for CD57 and TIA-1 seem to reliably discriminate between the entities and should therefore help to increase the interobserver reproducibility of diagnoses in the gray zone around Hodgkin's lymphoma.

Peripheral T-cell lymphoma with distinct perifollicular growth pattern: a distinct subtype of T-cell lymphoma?

Nine cases of peripheral T-cell lymphoma were identified in this study showing a distinctive growth pattern with partial distortion of the lymph node structure and prominent infiltration predominantly of marginal zones by medium-sized cells with clear cytoplasm and significant nuclear atypia. In the paracortical T-zone, there was a marked proliferation of high endothelial venules. Plasmocytosis and capsular fibrosis were other distinctive features. On immunohistochemistry, the lymphomas proved to be of T-helper cell origin (CD3+, CD4+, CD5+/-, CD8-, TIA1-) and proliferation was most prominent in the marginal zone of the regressive B-cell follicles. These cases have a characteristic morphology that may be sufficient to differentiate them as a variant from other peripheral T-cell lymphomas of the "not otherwise specified" group and to include them in the list of currently recognized lymphomas. Because of the distinct perifollicular growth pattern and incomplete effacement of the lymph node architecture, the differential diagnosis consists mainly of marginal zone B-cell lymphoma and reactive lesions.

What is CD4+CD56+ malignancy and how should it be treated?

CD4+CD56+ malignancy is a rare neoplasm with a typical clinical pattern, an aggressive course and high early relapse rate despite good initial response to chemotherapy. In this review, the impact of different therapeutic approaches on clinical outcome has been studied. We evaluated 91 published cases and our own six patients in terms of clinical features, immunophenotype/cytogenetics and treatment outcome. Treatment was divided into four groups: (A) chemotherapy less intensive than CHOP; (B) CHOP and CHOP-like regimens; (C) therapy for acute leukemia; (D) allogeneic/autologous stem cell transplantation. The median overall survival was only 13 months for all patients. Patients with skin-restricted disease showed no difference in the overall survival from patients with advanced disease (17 and 12 months, respectively). Age >/=60 years was a negative prognostic factor. Age-adjusted analysis revealed improved survival after high-dose chemo/radiotherapy followed by allogeneic stem cell transplantation when performed in first complete remission. This therapeutic approach should be recommended for eligible patients with CD4+CD56+ malignancy. For older patients the best treatment option is still unknown.

[Birt-Hogg-Dubé syndrome : bilateral oncocytic kidney tumors in a patient]. / Birt-Hogg-Dubé-Syndrom : Bilateraler onkozytischer Hybridtumor der Niere.

We report on a rare case of bilateral oncocytic kidney tumors in a patient with Birt-Hogg-Dubé syndrome (BHD). BHD is an autosomal inherited cancer syndrome associated with multiple kidney tumors, benign cutaneous tumors, and pulmonary cysts with spontaneous pneumothorax. To date about 50 BHD families have been described. Patients are best treated with nephron-sparing surgery. Close follow-up is mandatory because recurrence in previously operated kidneys and metastatic tumor progression can occur. Family members at risk should also early be screened for BHD.

[Uncommon presentation of cryptogenic organizing pneumonia with miliary pattern in the thorax]. / Ungewöhnliche Manifestation einer kryptogen organisierenden Pneumonie mit miliarem Verschattungsmuster im Thorax.

A 28-year-old female with worsening dyspnea showed miliary nodules of 2 mm in diameter on chest X-ray and high-resolution CT (HRCT). Histological evaluation and clinical outcome revealed an uncommon presentation of cryptogenic organizing pneumonia.

[Enteropathy type T-cell lymphomas: pathology and pathogenesis]. / Pathologie und Pathogenese des Enteropathie-assoziierten T-Zell-Lymphoms.

Enteropathy type T-cell lymphomas (ETL) are the most frequent T-cell lymphomas arising in the gastrointestinal tract. Commonly, the neoplasm is clinically associated with symptoms of malabsorption, and it frequently manifests as a spontaneous bowel perforation. Among ETL, two types can be distinguished by morphology, immunophenotype and, possibly, by pathogenesis. A total of 80% of ETL are characterized by a close association with celiac disease, pleomorphic cytomorphology and the rare expression of CD8 and CD56. In contrast, 20% of ETL show a monomorphic small to medium size cytomorphology and frequent expression of CD8 and CD56, an association with celiac disease is rare in the latter cases. Genetically, ETL is characterized by frequent and recurrent chromosomal gains of 9q33-q34.

[Cutaneous B-cell lymphoma. Classification and diagnostics]. / Kutane B-Zell-Lymphome. Klassifikation und Diagnostik.

Primary cutaneous B-cell lymphomas include cutaneous follicle centre lymphoma (PCFCL), cutaneous marginal zone B-cell lymphoma (PCMZL) and cutaneous diffuse large B-cell lymphoma (PCLBCL) "leg type" which are the three main types in the new WHO-EORTC classification for cutaneous lymphomas. PCFCL and PCMZL are indolent lymphomas with an excellent prognosis while PCLBCL shows an aggressive clinical course. All three types must be distinguished from a secondary skin involvement by systemic lymphomas. Since histological and immunohistochemical findings are not decisive, making this distinction requires appropriate staging procedures. In contrast, the pathologist can make an important contribution to the differential diagnosis between neoplastic and reactive cutaneous lymphoproliferations.

[Peripheral NK/T-cell lymphoma]. / Periphere NK/T-Zell-Lymphome.

Peripheral T-cell lymphomas comprise 8% of the malignant lymphomas in Germany. About 25% of these cases present primarily in extranodal localizations. Such localizations are typical for the respective disease and form the basis for the classification of extranodal peripheral T-cell lymphoma. The morphology, immunophenotype and lineage specificity of the tumor cells (originating from T- or NK-cells) is only secondary for the classification. Extranodal NK/T-cell lymphomas of the nasal type are characterized by an angiocentric growth pattern and large confluent areas of necrosis. In addition, there is a clonal infection by Epstein-Barr virus in the T-lymphocytes. In the differential diagnosis, B-cell lymphomas are more frequent at all localizations than T- or NK-cell lymphomas.