Pathologie und molekulare Pathologie des Hodgkin-Lymphoms

Hodgkin’s lymphoma comprises nodular lymphocyte-predominant Hodgkin’s lymphoma and classical Hodgkin’s lymphoma which are considered to be separate disease entities. The new WHO classification maintains the previously recognized subtypes of classical Hodgkin’s lymphoma which include the nodular sclerosis subtype, the mixed cellularity subtype and the lymphocyte-rich and lymphocyte-depleted subtypes. The tumor cells in classical Hodgkin’s lymphoma are the Hodgkin-Reed-Sternberg (HRS) cells, whereas LP cells are characteristic for nodular lymphocyte-predominant Hodgkin’s lymphoma. HRS cells are probably derived from pre-apoptotic germinal center B cells and LP cells also show many features of germinal center derivation. HRS cells are characterized by downregulation of the B cell expression program and activation of several potent signaling pathways. These include constitutive activation of NFκB, JAK/STAT and PI3 K signaling cascades as well as an increased expression of anti-apoptotic molecules. The recent identification of inactivating mutations of the TNFAIP3 gene coding for A20 in approximately 40% of classical Hodgkin’s lymphoma seems to indicate a central role for the NFκB cascade in the pathogenesis of this neoplasm.     

Pathologie des CUP-Syndroms

So-called CUP (carcinoma of unknown primary) syndrome challenges the diagnosing physician and the patient. By means of sophisticated pathohistological analyses, the morphology can be described and by immunohistochemistry further relevant characteristics can be identified, thus, possibly achieving a correlation to a tissue of origin. Thereby the search for a latent primary is facilitated and further therapeutic opportunities can be made available to the patient. As a last step, molecular analyses can augment the diagnostic repertoire.     

Pathologie des Hodgkin-Lymphoms

Zusammenfassung Hodgkin-Lymphome sind die häufigsten bösartigen Erkrankungen des Lymphknotens in Westeuropa. Anhand der Ausprägung von CD20 und CD30 durch die Tumorzellen unterscheidet man das lymphozytenreiche Hodgkin-Lymphom von den Subtypen des klassischen Hodgkin-Lymphoms. Die L&H-Zellen des lymphozytenreichen Hodgkin-Lymphom sind ebenso wie die Hodgkin- und Reed-Sternberg-Zellen des klassischen Hodgkin-Lymphoms klonale Proliferate. Sie stammen in der Regel von B-Zellen ab und stellen die eigentliche Tumorzellpopulation dar. Genexpressionsanalysen konnten zeigen, dass die Hodgkin- und Reed-Sternberg-Zellen des klassischen Hodgkin-Lymphoms einen globalen Verlust von typischen B-Zell-Genen zeigen und 6 verschiedene Rezeptortyrosinkinasen aberrant ausprägen. Die gleichzeitige Ausprägung verschiedener Rezeptortyrosinkinasen ist wahrscheinlich ein Transformationsmechanismus im Hodgkin-Lymphom. Die spezifische Hemmung dieser Kinasen ist ein möglicher Ansatz für eine neue Therapiestrategie.     

Pathologie der Weichgewebssarkome

This article is based on the latest (2002) classification of soft tissue tumors by the World Health Organization (WHO). The WHO currently distinguishes between soft tissue tumors with full malignancy and neoplasms with intermediate malignancy. The latter tumors are divided into locally aggressive forms without metastatic potential and neoplasms with rare metastases (in less than 2% of cases). Considering this classification, tumors of adipocytic, fibroblastic/myofibroblastic, so-called fibrohistiocytic, muscular, vascular, and uncertain differentiation are characterized. Tumors with nerve sheath differentiation have been eliminated from the category of soft tissue tumors. This article also includes some remarks concerning malignancy grading and the certainty of the morphological diagnosis if only very small biopsies are available.     

Pathologie des Magenkarzinoms

Die Onkologie - Die exakte histomorphologische und molekulare Charakterisierung der verschiedenen Subtypen des Magenkarzinoms wird im Hinblick auf personalisierte Therapieoptionen immer...     

Pathologie kleinzelliger Lungentumoren

Kleinzellige Lungentumoren haben, ebenso wie alle b?sartigen Lungen- tumoren, in den letzten 20 Jahren eine Zunahme in der H?ufigkeit erfahren. Die histomorphologische Abgrenzung kleinzelliger und nicht-kleinzelliger b?sartiger Lungentumoren erfolgt anhand relativ grober, ph?notypischer histologischer und zytologischer Parameter. Bei der zuvor nach lichtmikroskopischen Befunden relativ „homogenen” Gruppe kleinzelliger b?sartiger Lungentumoren, wird aufgrund neuerer Untersuchungsverfahren die Heterogenit?t immer deutlicher, soda? z. Z. die histogenetische Zuordnung in einer Gruppe „neuro-endokriner Tumoren” favorisiert wird. Die neuen elektronenmikroskopischen, immunhistochemischen und molekularbiologischen Untersuchungsverfahren haben wesentlich zum besseren Verst?ndnis der Genese und Progression der b?satigen Lungentumoren beige-tragen.     

Pathologie der malignen Kopf-Hals-Tumoren

Context

Tumors of the head and neck form a heterogeneous group of benign and malignant neoplasms that includes carcinomas, sarcomas and a variety of lymphomas. The somewhat confusing variety of these neoplasms requires profound knowledge of location-specific human tumor pathology to select of optimal treatment strategies for head and neck cancer patients.

Objective

This article gives a comprehensive overview on the epidemiology and histology of tumors in the head and neck region with an emphasis on location-specific tumor entities.

Material and methods

Relevant literature on the histology and epidemiology of head and neck cancers was screened with an emphasis on current World Health Organization (WHO) recommendations. Literature data was supplemented with up date epidemiological data for Germany from the Robert-Koch Institute.

Results

With respect to frequency and clinical importance, squamous cell carcinoma of the laryngopharyngeal region and oral cavity is clearly the most prominent malignant tumor in this anatomical region. Salivary gland neoplasms, although less frequent, constitute a second important pathologically and clinically complex group of tumors at this location. These two large tumor families are complemented by a distinct group of neoplasms which typically manifest in the head and neck region, such as nasopharyngeal carcinoma, olfactory neuroblastoma, NK/T-cell lymphoma of nasal type and by a variety of lymphomas and sarcomas which are morphologically indistinguishable from their counterparts elsewhere in the body. This article gives a comprehensive overview on the landscape of neoplasms in the head and neck region.

Conclusion

Knowledge on the histology and epidemiology of tumors in the head and neck region forms the basis for a profound differential diagnosis and therapeutic decision making and therefore constitutes the basis of oncological treatment strategies for patients with head and neck neoplasms.     

Pathologie des invasiven Mammakarzinoms

Invasive breast carcinoma is the most common malignant tumour in women. The pathologist’s diagnosis is of pivotal importance for local therapy as well as for establishing the prognostic and predictive factors of such a malignancy. Moreover, new cell biological and molecular findings have led to a better understanding of the numerous variants of breast carcinoma. The first part of our review is an attempt to explain the development of breast carcinomas against the background of cell biological and molecular principles and to place this malignancy into the context of benign proliferative breast disease and in situ neoplasia. The second part gives an account of some important subtypes of breast carcinoma, and the third part is dedicated to the currently accepted prognostic and predictive factors, the majority of which have to be assessed by the pathologist within the framework of his or her diagnostics.     

Pathologie und Molekularpathologie von Weichteilsarkomen

Background

Soft tissue sarcomas are rare compared to other malignancies such as carcinomas and represent approximately 1?% of all malignant neoplasms. The current World Health Organization (WHO) classification from 2013 defines more than 60 different entities.

Aim

This article describes the histomorphological and molecular findings which are important for the current diagnostics of sarcomas.

Results and conclusion

Most notably molecular diagnostic procedures have an increasing influence on the subtyping of sarcomas which requires a broad panel of molecular procedures and a sufficient number of sarcoma cases to be able to establish the correct diagnosis. Besides the relevance of molecular diagnostics to establish the correct diagnosis, the results are becoming increasingly more important to identify potential therapeutic targets. In the case of already existing specific inhibitors these may also be used in sarcoma patients. This implies that the sarcoma diagnosis has been done correctly and that patients with a specific sarcoma subtype can be identified through a central registry to be included in a clinical trial. A second opinion by a reference pathologist and the inclusion in such a registry should be the rule.     

Pathologie und Prognosefaktoren des Harnblasenkarzinoms

An der Entstehung von Harnblasenkarzinomen sind endogene und exogene Faktoren beteiligt. Wie bei den meisten anderen Tumoren scheinen genetische und Umwelteinflüsse zusammenzuwirken. W?hrend zu verschiedenen exogenen Faktoren gesicherte Erkenntnisse vorliegen, ist über die genetische Disposition und ihre Rolle bei der Entwicklung von Harnblasenkarzinomen noch wenig bekannt. Eine famili?re H?ufung, die allein auf genetische Faktoren zurückzuführen ist, konnte nicht beobachtet werden. Pathogenetisch führt die Einwirkung karzinogener Faktoren zu Ver?nderungen am genetischen Material des übergangsepithels. Bei den manifesten Tumoren sind prim?r papill?re Formen von flachen in situ abzugrenzen, die sich auch prognostisch und bezüglich des therapeutischen Vorgehens unterscheiden. Der folgende Beitrag gibt eine übersicht über die histopathologische Klassifikation von Harnblasentumoren sowie über tumorbiologische und prognostische Parameter.     

Anatomie und Pathologie des Gallengangskarzinom

Maligne Tumoren der Galleng?nge sind insgesamt relativ selten. Bei diesen Tumoren überwiegen die epithelialen Neubildungen (Karzinome), mesenchymale Tumoren sind noch weitaus seltener. Karzinome der extra- und intrahepatischen Gallenwege entstehen durch maligne Transformation des Epithels der extrahepatischen Galleng?nge sowie der gro?en und mittleren intrahepatischen Gangabschnitte. Dabei k?nnen die Karzinome intrahepatisch, als intrahepatische Gallengangskarzinome oder Cholangiokarzinome (CC), gelegen sein, aber auch die Ductus hepatici dexter/ sinister, Ductus hepaticus communis oder den extra- bzw. intraduodenalen Anteil des D. choledochus (extrahepatische Gallengangskarzinome) betreffen.     

Pathologie des Schilddrüsenkarzinoms

Thyroid carcinoma accounts for approximately 1% of all human malignancies and is thus a rather rare tumour. Both its differential diagnosis from benign lesions (thyroid hyperplasia and adenoma) and exact classification may cause substantial difficulties in daily routine diagnostic pathology. Due to their different biological behaviour the recently published WHO classification of thyroid tumours subdivides thyroid carcinomas of follicular cell origin into well-differentiated carcinomas (papillary and follicular carcinoma), poorly differentiated carcinomas and anaplastic carcinomas. Whereas papillary and follicular carcinomas are usually associated with good prognosis, poorly differentiated carcinoma shows a significantly less favourable and anaplastic carcinoma even a devastating outcome. Thyroid medullary carcinoma, originating from calcitonin-producing C cells, occurs in a sporadic and familial form; the familial type is inherited in an autosomal dominant manner and shows specific germ line mutations of the RET proto-oncogene.     

Pathologie und Staging des Nierenzellkarzinoms

Das Ziel einer histopathologischen Klassifikation ist, anhand morphologischer Kriterien biologisch unterschiedliche Entit?ten zu erfassen, um so letztendlich eine individuelle prognostische Aussage zu erm?glichen. Tumorentstehung und Tumorprogression sind jedoch eng an genetische Alterationen geknüpft, sodass mit zunehmendem Kenntnisstand hinsichtlich genetischer Ver?nderungen beim Nierenzellkarzinom bzw. dessen Subtypen eine zytopathologische Klassifikation und eine molekulargenetische Klassifikation existieren [12].     

Neue Aspekte der Pathologie des Nierenzellkarzinoms

New treatment options for renal cell cancer have increased the interest in the histogenesis and in molecular alterations of renal tumors. The current WHO classification of renal cancer is based on specific molecular alterations and characteristic biologic behavior. During recent years novel tumor types have been identified with immediate impact for the selection of new treatment modalities. In this review the current classification of renal cancer with special emphasis on novel renal tumor types will be discussed. Knowledge of Xp11 translocation carcinomas and renal tumors with characteristic cyst formation is diagnostically relevant. In addition this review focuses on reassessing the current TNM staging system for renal cell cancer. Retrospective studies have shown the relevance of renal sinus invasion for stage evaluation.     

Anatomie und Pathologie der zentralen Gallengangstumoren

Adenocarcinomas of the bile ducts (so-called cholangiocarcinomas) may originate from both intrahepatic and extrahepatic bile ducts and constitute a rare tumor entity. Carcinomas of the perihilar and central extrahepatic bile ducts (so-called Klatskin’s tumors) are demarcated as special tumor entities and patients with these carcinomas face a poor prognosis. As therapeutic options have improved with respect to both operative and conservative treatment strategies, sophisticated TNM classifications for the different parts of the bile duct system have been introduced in order to determine the anatomic spread as accurately as possible. The new classifications and modifications of the 7^th edition are based on data from Asia and the U.S. Application of the new classifications is mandatory as of 1^st January 2010.