[Rosai-Dorfman disease as a rare cause of a pancreatic mass]. / Die Rosai-Dorfman-Erkrankung als seltene Ursache für einen Pankreastumor.

The CT and MRI scans of a 70-year-old male patient revealed a mass in the pancreatic head and a 2.8-cm peripancreatic lymph node. Under steroid therapy the mass did not show regression. Finally, a pancreatoduodenectomy was performed. Histologically, Rosai-Dorfman disease (RDD) was diagnosed. RDD is a rare histiocytic disorder with usually nodal but sometimes also extranodal involvement. Herein we report a rare case of extranodal RDD with intrapancreatic localization.

[Genetic evolution of in situ follicular neoplasia to t(14;18)-positive aggressive B-cell lymphoma]. / Die genetische Evolution der in situ follikulären Neoplasie zum t(14;18)-positiven aggressiven B­Zell-Lymphom.

BACKGROUND: In situ follicular neoplasia (ISFN) is a t(14;18)(q32;q21)+ precursor lesion of follicular lymphoma (FL), which in turn can transform into diffuse large B­cell lymphoma (DLBCL). For DLBCL that arise de novo, no precursor lesion is known. Given the high frequency of the t(14;18) translocation in de novo DLBCL as well, we investigated whether they can also arise from ISFN without FL as an intermediate step. OBJECTIVES: To investigate the clonal evolution of ISFN to DLBCL - transformed from FL and de novo. MATERIALS AND METHODS: Identification of ISFN lesions in patients with DLBCL was performed by BCL2 staining of reactive lymphoid tissues. ISFN and DLBCL were subsequently analyzed by fluorescence in situ hybridization, clonality analyses, sequencing of the t(14;18) breakpoint, and targeted next-generation sequencing. RESULTS: 10 cases with paired ISFN and DLBCL samples were identified, 6 of which were de novo DLBCL and 4 transformed from FL. 3 DLBCL carried MYC-rearrangements in addition to the t(14;18) and were classified as high-grade B­cell lymphoma (HGBL). The clonal relationship of ISFN and DLBCL/HGBL was confirmed for all cases. CREBBP, KMT2D, EZH2, TNFRSF14, and BCL2 were the genes most frequently mutated, with the distribution of private and shared mutations pointing to 2 different scenarios of clonal evolution. In most cases, DLBCL/HGBL, ISFN, and, if also present, FL had evolved divergently from a common progenitor, whereas linear evolution was less frequent. CONCLUSION: We show for the first time that t(14;18)+ DLBCL/HGBL can arise directly from ISFN without FL as an intermediate step and that during this progression, divergent evolution is common.

Correction to: The natural course of pT2 prostate cancer with positive surgical margin: predicting biochemical recurrence.

In multivariate analysis, GS of the regular prostatectomy specimen was the only statistically significant parameter for pT2R1 prostate cancer.

[Aggressive B­cell lymphomas : Recommendations from the German Panel of Reference Pathologists in the Competence Network on Malignant Lymphomas on diagnostic procedures according to the current WHO classification, update 2017]. / Aggressive B­Zell-Lymphome : Empfehlungen des Deutschen Panels der Referenzpathologen im Kompetenznetz Maligne Lymphome e. V. zum diagnostischen Vorgehen nach der aktuellen WHO-Klassifikation, Update 2017.

The update of the 4th edition of the WHO classification for hematopoietic neoplasms introduces changes in the field of mature aggressive B­cell lymphomas that are relevant to diagnostic pathologists. In daily practice, the question arises of which analysis should be performed when diagnosing the most common lymphoma entity, diffuse large B­cell lymphoma. We discuss the importance of the cell of origin, the analysis of MYC translocations, and the delineation of the new WHO entities of high-grade B­cell lymphomas.

[Revised version of the 4th edition of the WHO classification of malignant lymphomas : What is new?] / Revidierte Fassung der 4. Ausgabe der WHO-Klassifikation maligner Lymphome : Was ist neu?

After 8 years, the WHO has now published the updated version of the 4th edition of the classification of hematopoietic and lymphoid tumors. This update provides a conceptual rewrite of existing entities as well as some new provisional entities and categories, particularly among the aggressive B­cell lymphomas. Important new diagnostic categories include the high-grade B­cell lymphomas, the large B­cell lymphoma with IRF4 rearrangement, and the Burkitt-like lymphoma with 11q aberrations. Of particular importance, new concepts concerning the taxonomy and classification of early lymphoid lesions or precursor lesions are included, such as the in situ follicular neoplasia or the in situ mantle cell neoplasia. In addition, the concept of indolent lymphoproliferations, such as breast-implant-associated anaplastic large cell lymphoma and the indolent T­cell lymphoproliferative disorder of the gastrointestinal tract, has been strengthened. Finally, diagnostic criteria for existing lymphoma entities have been refined.

[Clonal evolution of early lymphoproliferations]. / Klonale Evolution früher Lymphoproliferationen.

The identification and molecular characterisation of premalignant precursor lesions of lymphomas, such as monoclonal gammopathy of unknown significance (MGUS) and the so-called in situ lymphoproliferations, has made significant progress in the recent years. The in situ follicular neoplasia (ISFN), the best-characterised entity, is by definition not identifiable by morphology and represents a t(14;18)+ precursor lesion of follicular lymphoma with characteristic immunophenotype, low potential for progression, and already identifiable secondary genetic alterations. The use of high-throughput genetic techniques on microdissected tissues has generated novel insights into clonal evolution and biological progression of early lesions and documented that an isolated genetic analysis is insufficient to understand the complexity of proliferations.

First report of robot-assisted transperineal fusion versus off-target biopsy in patients undergoing repeat prostate biopsy.

PURPOSE: To clarify the value of targeted versus off-target biopsies in men with a suspicion of prostate cancer (PC) and a visible lesion in multi-parametric magnetic resonance imaging (mpMRI) using transperineal robot-assisted biopsy. METHODS: Fifty-five consecutive men with one non-palpable suspicious lesion in mpMRI after negative 12-core transrectal ultrasound-guided biopsy were enrolled in 2014-2015. Lesions were scored using the Prostate Imaging Reporting and Data System. A robot-assisted system was utilized to collect four robot-assisted targeted transperineal biopsy cores (RA-TB) within the lesion using mpMRI-TRUS elastic fusion. Untargeted transperineal 14-core biopsy was performed only outside the lesion (RA-UB). Histological grade was compared in biopsies and available prostatectomy specimens. RESULTS: Overall, 34 of 55 patients (62%) were diagnosed with PC based on biopsy. 85% of cancers were clinically significant PC (csPC) defined as GS ≥ 7. 85% of biopsy-proven cancers were detected with RA-TB alone. RA-UB identified only one additional patient with csPC and lead to upgrading in five biopsy cases (14.7%). Pathological evaluation of 14 prostatectomy specimens showed upgrading in 2 patients (14.3%), while all other patients were correctly classified by RA-TB without need of additional RA-UB. Mean procedure duration was 43 (±6) min, and only minor complications according to Clavien-Dindo were recorded during 30-day follow-up. CONCLUSIONS: This is the first report of transperineal robot-assisted elastic mpMRI-TRUS fusion biopsy. RA-TB of positive MR lesions enabled reliable detection of csPC, while RA-UB in MRI-negative regions is of minor importance.

[Malignant lymphomas of the eye]. / Maligne Lymphome des Auges.

The eye and the ocular adnexae are rare sites for malignant non-Hodgkin lymphoma (NHL). Based on their anatomical location, intraocular lymphomas must be discerned from NHL of adnexal structures including conjunctiva, lacrimal gland, and orbit. Whereas the latter group mostly consists of indolent extranodal marginal zone B­cell lymphomas of mucosa-associated lymphoid tissue (MALT) type or secondary manifestations of systemic NHL, most primary intraocular lymphomas are classified as diffuse large B­cell lymphomas (DLBCL) and are considered a variant of primary DLBCL of the central nervous system. The most common form is primary vitreoretinal lymphoma (PVRL), which presents with nonspecific symptoms and is difficult to discern from uveitis. Diagnosis of PVRL is usually made by cytological, immunocytochemical, and molecular analysis of vitreous aspirates. Degenerative changes, limited material, and the occurrence of pseudoclonality in the molecular analysis of B­cell clonality can hamper diagnostic assessment. Novel techniques such as detection of MYD88 mutations common in PVRL can increase diagnostic sensitivity. Close cooperation with clinical colleagues and rapid specimen processing are fundamental for successful diagnosis.

[Tumor of the mesosalpinx with unclear differentiation]. / Tumor der Mesosalpinx mit unklarer Differenzierung.

Female adnexal tumors of probable Wolffian origin (FATWO) are rare tumors, which are mostly localized in the broad ligament or the mesosalpinx. They show high intratumor and intertumor variability of histological patterns (e.g. solid, tubular, cribriform and cystic) with usually unremarkable cellular and nuclear morphology and a lower mitotic rate. In general, they behave in a benign fashion but there are rare cases with malignant transformation, so that careful examination and surveillance are necessary. Differential diagnoses include Sertoli-Leydig cell tumors, metastasized endometrioid carcinoma and the FATWO-like variant of the endometrioid carcinoma of the fallopian tubes. The FATWOs express pancytokeratin, CD10, vimentin, calretinin and inhibin A. Estrogen and progesterone receptors are expressed in a minority of cases, whereas epithelial membrane antigen (EMA) is not detectable.

The natural course of pT2 prostate cancer with positive surgical margin: predicting biochemical recurrence.

PURPOSE: To predict biochemical recurrence respecting the natural course of pT2 prostate cancer with positive surgical margin (R1) and no adjuvant/neoadjuvant therapy. METHODS: A multicenter data analysis of 956 patients with pT2R1N0/Nx tumors was performed. Patients underwent radical prostatectomy between 1994 and 2009. No patients received neoadjuvant or adjuvant therapy. All prostate specimens were re-evaluated according to a well-defined protocol. The association of pathological and clinical features, in regard to BCR, was calculated using various statistical tests. RESULTS: With a mean follow-up of 48 months, BCR was found in 25.4 %. In univariate analysis, multiple parameters such as tumor volume, PSA, Gleason at positive margin were significantly associated with BCR. However, in multivariate analysis, Gleason score (GS) of the prostatectomy specimen was the only significant parameter for BCR. Median time to recurrence for GS ≤ 6 was not reached; 5-year BCR-free survival was 82 %; and they were 127 months and 72 % for GS 3+4, 56 months and 54 % for GS 4 + 3, and 27 months and 32 % for GS 8-10. The retrospective approach is a limitation of our study. CONCLUSIONS: Our study provides data on the BCR in pT2R1-PCa without adjuvant/neoadjuvant therapy and thus a rationale for an individual's risk stratification. The data support patients and physicians in estimating the individual risk and timing of BCR and thus serve to personalize the management in pT2R1-PCa.

[Differential diagnostic specific skin infiltrates in chronic myelomonocytic leukemia]. / Differenzialdiagnose spezifischer Hautinfiltrate bei chronischer myelomonozytärer Leukämie.

A 72-year-old male patient presented with multiple erythematous plaques on the lower arms, lower legs and feet. The patient suffered from rheumatoid arthritis and accompanying interstitial granulomatous dermatitis under treatment with tocilizumab. Several months prior to presentation a chronic myelomonocytic leukemia (CMML) had been diagnosed. The skin biopsy showed a perivascular infiltration of medium-sized cells with positivity for CD123, CD303 and CD4 with a low proliferation activity so that a diagnosis of a CMML-associated proliferation of plasmacytoid dendritic cells was made. The differential diagnosis of specific cutaneous infiltrates in CMML is discussed.

[Erdheim-Chester disease and Rosai-Dorfman disease: Pathological, radiological and clinical features of adult non-Langerhans cell histiocytosis]. / Erdheim-Chester- und Rosai-Dorfman-Erkrankung : Klinisch-radiologisch-pathologische Diagnostik von Non-Langerhans-Zell-Histiozytosen des Erwachsenenalters.

Non-Langerhans cell histiocytoses (N-LCH) of adulthood are rare disorders with heterogeneous pathogenesis, morphology and clinical presentation. In this review two disorders are presented, which predominantly develop in extracutaneous sites in adults. Erdheim-Chester disease is a rare nonhereditary clonal disorder of lipid storing histiocytes most commonly presenting as osseous involvement of the long bones. Other organ manifestations include the central nervous system (CNS), the cardiovascular system, the retroperitoneum and kidneys and less commonly the skin and the lungs. Immunohistochemical staining reveals positivity for the macrophage markers CD163, CD68 and lysozyme but CD1a and langerin are negative, in contrast to Langerhans cell histiocytosis. Rosai-Dorfman disease is considered to be a reactive histiocytic proliferation occurring mainly in lymph nodes. Prominent sinuses filled with commonly multinucleated, S100-positive histiocytes with emperipolesis are a characteristic feature and develops particularly as extensive lymphadenopathy with massive sinus histiocytosis but can also occur extranodally. Painless bilateral cervical lymph node enlargement is the most common clinical presentation. This review summarizes the clinical, radiological and histopathological findings and discusses the recent molecular advances in these rare disorders.

[Predictive biomarkers for tumor-relevant signaling pathways in molecular pathology]. / Prädiktive Biomarker tumorrelevanter Signalwege in der molekularen Pathologie.

In the era of personalized medicine, targeted cancer treatments aim to improve therapy and overall survival. Specific therapies are individually customized for patients based on molecular alterations of the neoplastic cells. The pathologist has a central role in the identification and characterization of a variety of molecular markers that can be used to better predict outcome and assess therapeutic success of specific targeted approaches.

[Mesothelial proliferation in rectal cancer]. / Mesotheliale Proliferate bei Rektumkarzinom.

In an epiphrenic lymph node of a 55 years old female patient who underwent surgical resection of a rectal adenocarcinoma epitheloid proliferations with papillary and solid growth pattern were seen additional to a metastasis of the carcinoma. Adjacent vessels contained similar infiltrates. Immunohistochemically a co-expression of pan-keratin, calretinin and WT1 was seen, suggestive for a diagnosis of a metastasis of a malignant mesothelioma. However, radiologic examination yielded no morphologic correlate to this suspicion. Further immunohistochemical work-up showed positivity for desmin, negativity for EMA, GLUT1, p53 and a low ki67-fraction of 2-3 %. Therefore, a final diagnosis of benign mesothelial proliferations disseminated into the lymph node and the adjacent vessels was made.

[B-cell neoplasms with plasmacellular and plasmablastic differentiation]. / B-Zell-Neoplasien mit plasmazellulärer und plasmablastischer Differenzierung.

Plasma cell malignancies are tumors of terminally differentiated B-cells in which the neoplastic plasma cells are the dominant and proliferating tumor cell component. Plasma cell myeloma (PCM) is one of the most common hematological neoplasms and typically does not cause diagnostic problems. A morphologically and immunophenotypically detectable plasmacellular orplasmablastic differentiation is, however, commonly observed in a wide range of mature B-cell lymphomas. A confident separation of the distinct entities requires the integration of clinical and morphological findings as well as an adequate phenotyping of both the plasma cell and the B-cell component if present. Detection of lymphotropic viruses, specific translocations and novel molecular markers, such as the MYD88 L265P mutation occurring in the vast majority of lymphoplasmacytic lymphomas complement our diagnostic repertoire. In this review we describe the most commonly observed diagnostic problems in separating small B-cell lymphomas from PCM and high-grade B-cell non-Hodgkin lymphoma (B-NHL) with plasmablastic differentiation from extramedullary spread of aggressive PCM and provide helpful criteria for routine diagnostics.

[In situ lymphoma and other early stage malignant non-Hodgkin lymphomas]. / "In-situ-Lymphome" und andere Frühstadien maligner Non-Hodgkin-Lymphome.

The increasing use of immunohistochemical and molecular investigations of lymphatic tissues results in more frequent detection of early lymphoid proliferations. These show some but not all features of malignant lymphomas without fulfilling the diagnostic criteria for the diagnosis of lymphoid malignancy. In addition to well-known premalignant B-cell proliferations, such as monoclonal gammopathy of unknown significance (MGUS) and monoclonal B-cell lymphocytosis (MBL), so-called in situ lymphomas have recently been described with minimal infiltrates of clonal B-cells in morphologically reactive lymphoid tissues which show the phenotypic and genetic features of specific B-cell lymphoma subtypes and often show a characteristic topographical distribution. This article addresses a group of clonal lymphoproliferations with usually localized disease and excellent clinical prognosis, such as pediatric follicular lymphoma and nodal marginal zone lymphoma. Another group of early lesions not addressed in this review are virally induced lymphoproliferations which represent a grey zone between purely reactive lesions and malignant lymphomas and may pose significant diagnostic as well as clinical problems. In this review diagnostic criteria for early or in situ lesions and their distinction from partial infiltration by malignant lymphoma are described.

Allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia and pulmonary mucormycosis.

Mucormycosis is a serious invasive fungal infection in immunocompromised patients. Patients undergoing treatment for hematologic malignancies are predominantly prone to the pulmonary manifestation of mucormycosis. Historically, allogeneic hematopoietic cell transplantation (HCT) in patients suffering from pulmonary mucormycosis (PM) was considered contraindicated owing to mortality rates up to 90%. We present 3 patients with acute myeloid leukemia and PM who were treated with radical surgical debridement combined with high-dose liposomal amphotericin B (LAB), and subsequently underwent successful allogeneic HCT. To date, all 3 patients are in complete remission and show no signs of mucormycosis. Allogeneic HCT in patients with PM seems feasible provided that the infectious focus is completely removed surgically and adequate antifungal pharmacotherapy, such as high-dose LAB or posaconazole, is established.

Spontaneous hepatic rupture in amyloidosis - report of a case.

In systemic amyloidosis spontaneous rupture of the liver is a rare complication. Here we report on a patient with unrecognized systemic amyloidosis who presented to an outside hospital with unspecific abdominal pain. Under the signs of a hemorrhagic shock, distended abdomen and intraabdominal bleeding a laparotomy was performed. Due to uncontrollable hemorrhage of the ruptured right liver lobe a packing was performed. After being transferred to the reporting institution a CT scan was performed showing a grade IV laceration of the right liver. Therefore a transarterial embolization of the right hepatic artery was carried out. The following day an infection of the abdominal cavity and the abdominal wall with gas-producing bacteria was noticed and a relaparotomy, necrectomy and repacking due to diffuse bleeding were performed. The situation deteriorated and at the second relaparotomy the following day an almost completely necrotic liver was found. The patient deceased the following day. Life-threatening spontaneous liver rupture due to systemic amyloidosis might only successfully be cured by high urgency liver transplantation as presented in the literature. However, in two published cases interventional therapy by embolization of bleeding vessels has saved patients' life.