[Primary extra-axial chondroid chordoma of the anterior nasal septum: case report of a rare chordoma with literature review]. / Primäres extraaxiales chondroides Chordom des anterioren Nasenseptums: Fallbericht eines seltenen Chordoms mit Literaturübersicht.

An 87-year-old patient reported a nodular, progressively enlarging mass of the anterior nasal septum leading to partial obstruction of the nostrils. The tumor showed no infiltration of the subcutis, bone, or paranasal sinuses in imaging or intraoperatively. Histological examination revealed a chondroid tumor with lobular growth and physaliferous cell morphology. Immunohistochemistry revealed a brachyury-positive tumor without EWSR1 rearrangement, leading to the diagnosis of a chondroid chordoma. The reported case demonstrates the differential diagnostic considerations pertaining to this rare tumor, which can also have an untypical and very rare extra-axial location. Review of the literature identified 34 primary extraosseous chordomas of the nose, nasopharynx, and paranasal sinuses, and allowed the nasal chordoma presented herein to be included in this group of extra-axial chordomas.

U-CH17P, -M and -S, a new cell culture system for tumor diversity and progression in chordoma.

Chordoma is a rare bone tumor with a known intrinsic heterogeneity. Here, we address this tumor heterogeneity in a new cell culture model for tumor diversity and progression in chordoma. The three cell lines U-CH17P, U-CH17M, and U-CH17S were established from a primary sacral chordoma and its derived metastases, a soft tissue and a skin metastasis, respectively. The lesions had divergent differentiation patterns which are conserved in the derived cell lines making them a suitable in vitro model for the analysis of tumorigenesis in chordoma. A common feature of the three cell lines is the expression of typical chordoma markers, such as Brachyury, vimentin, cytokeratins, EMA and S100 protein. A comparison of the genomic aberrations by array comparative genomic hybridization of the cell lines and the corresponding parental tumor tissues revealed that the precursor cells of U-CH17P, U-CH17M and U-CH17S were already present in the primary tumor. Therefore, we show that clonal diversity of this chordoma exists in the primary tumor and that not all of these subclones tend to metastasize. All cell lines had a CDKN2A loss. A comparison of the gene expression profiles of the cell lines revealed significant differences in the expression of several genes like MAGEC2 and SEMA6A known to be associated with the tendency to metastasize or proliferation and migration. Since the underlying mechanisms of tumor progression in chordoma are still largely unclear, the three U-CH17 cell lines are a suitable in vitro model for elucidating chordoma oncobiology.

[New aspects on giant cell tumor of bone]. / Neue Aspekte zum Riesenzelltumor des Knochens.

A giant cell tumor of bone (GCTB) is one of the giant cell-rich lesions of bone and has to be differentiated from non-ossifying fibroma, aneurysmatic bone cyst, chondroblastoma, "brown tumor" and osteosarcoma containing giant cells. A hallmark of GCTB is the presence of the distinct histone 3 (H3F3A) mutation G34W and its detection either by sequencing methods or using immunohistochemistry with a novel antibody against this mutational site. Worrisome is the fact that under denosumab therapy a histological change of the lesions can be seen and there are first reports of sarcomas arising after therapy. When diagnosing giant cell-rich lesions, pathologists should be aware of the various differential diagnoses and morphological spectrum within GCTB.

[Notochordal tumors : Benign notochordal tumors and chordomas]. / Notochordale Tumoren : Benigne notochordale Tumoren und Chordome.

Benign notochordal tumors (BNCT) and chordomas are primary bone tumors of the spine with a predominant localization in the sacrum and clival region followed by the vertebral bodies. Besides the most common variant (NOS [not otherwise specified] with hepatoid or renal carcinoma cell-like differentiation) chordomas with chondroid, and polymorphic to anaplastic morphology are described. An unfavorable variant are pediatric chordomas with a loss of INI-1. BNCT and chordomas are characterized by the following immunohistological profile: vimentin+, cytokeratin+/-, epithelial membrane antigen (EMA)+/-, S100 protein+/-, brachyury+. This profile helps to distinguish these tumors from other lesions such as chondrosarcoma, chordoid meningioma, and metastases of carcinoma.

[Presacral lesion at the rima ani]. / Präsakrale Raumforderung an der Rima ani.

A 26-year-old woman presented with a painful bulge at the rima ani. The tumor was located in the presacral region. Histological examination revealed a well-circumscribed biphenotypical tumor with papillary configured myxoid areas and strongly sclerosing regions. This case of a myxopapillary ependymoma is a rare example of a myxoid neoplastic lesion in the sacral region.

[H3F3A mutated multicentric giant cell tumor of bone : A very rare primary bone disease]. / H3F3A-mutierter multifokaler Riesenzelltumor des Knochens : Eine äußerst seltene primär ossäre Erkrankung.

This article presents the case of a metachronic multicentric giant cell tumor of bone (GCTB). The patient obtained his first diagnosis of GCTB in the left humerus at the age of 47 years. Furthermore, he suffered from a GCTB in the head of his 4th left metacarpal bone and from a recurrence of the latter. All tumors carried the characteristic H3F3A mutation, which was proven by Sanger sequencing and a mutation specific antibody. The case is the first description of a multicentric H3F3A mutated GCTB.

Taking the next step forward - Diagnosing inherited infantile cholestatic disorders with next generation sequencing.

Identifying rare genetic forms of infantile cholestasis is challenging due to their similar clinical presentation and their diverse etiology. After exclusion of common non-genetic causes a huge list of rare differential diagnosis remains to be solved. More than 90 genes are associated with monogenic forms of infantile cholestasis, thus preventing routine genetic workup by Sanger sequencing. Here we demonstrate a next generation sequencing approach to discover the underlying cause in clinically well characterized patients in whom common causes of infantile cholestasis have been excluded. After validation of the analytical sensitivity massive parallel sequencing was performed for 93 genes in six prospectively studied patients. Six novel mutations (PKHD1: p.Thr777Met, p.Tyr2260Cys; ABCB11: p.Val1112Phe, c.611+1G > A, p.Gly628Trpfs*3 and NPC1: p.Glu391Lys) and two known pathogenic mutations were detected proving our multi gene panel for infantile cholestasis to be a sensitive and specific method overcoming the complexity of the phenotype-based, candidate gene approach. Three exemplary clinical cases of infants with cholestasis are presented and discussed in the context of their genetic and histopathological findings (autosomal recessive polycystic kidney disease, atypical PFIC and Niemann-Pick syndrome type C1). These case reports highlight the critical impact of integrating clinical, histopathological and genetic data during the process of multi gene panel testing to ultimately pinpoint rare genetic diagnoses.

[Detection of the BCR-ABL fusion: Comparative analysis of six commercially available FISH fusion probes]. / Detektion der BCR-ABL-Fusion : Vergleichende Analyse sechs kommerzieller FISH-Sondensätze.

Chronic myeloid leukemia (CML) is diagnostically defined by the reciprocal translocation t(9;22)(q34;q11). This aberration can be detected by the BCR-ABL fluorescence in situ hybridization (FISH) technique. This article presents a comparative analysis of different commercially available FISH probes and different FISH protocols in order to optimize this technique on formalin-fixed and paraffin-embedded bone marrow trephine biopsies.

[Manifestation of rheumatic diseases in the larynx]. / Erkrankungen des rheumatischen Formenkreis mit Manifestation im Larynx.

Rheumatic disorders (rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, Wegener's granulomatosis, relapsing polychondritis) may affect the larynx. The clinical symptoms are often unspecific, leading to delayed diagnosis. Malignant tumours should be considered in differential diagnosis with necessitating biopsy. Treatment may require interdisciplinary approach together with a specialist in internal medicine and rheumatology.

[Cystic echinococcosis and hepatocellular carcinoma--a coincidence? A case report]. / Zystische Echinokokkose und hepatozelluläres Karzinom--zufällige Koinzidenz? Ein Fallbericht.

INTRODUCTION: The coincidence of echinococcosis and hepatocellular carcinoma (HCC) is quite rare. We report the case of a 45-year-old man who was admitted to our hospital because of abdominal pain in the right upper quadrant and jaundice. Clinical features and diagnostics: There was no history of weight loss or fever. No abdominal mass was palpable. The laboratory reports showed increased transaminase levels. Ultrasonography revealed an inhomogenous, cystic lesion measuring 6 cm in diameter in the segments VI and VII. Serology for echinococcosis was negative, alpha-fetoprotein (AFP) was considerably increased. CT scan showed a solid mass of 3,7 cm in diameter adjacent to the cystic lesion. THERAPY AND COURSE: Anthelminthic therapy with albendazole caused a massive increase of cholestasis parameters and treatment had to be stopped. The simultaneous occurrence of serologically negative cystic echinococcosis and HCC was suspected and partial liver resection was performed. Histological examination confirmed both diagnoses and tumor resection in healthy tissue. 5 months after resection CT scan showed multicentric HCC affecting the whole liver. Palliative therapy with sorafenib was established. DISCUSSION: The coincidence of HCC and cystic echinococcosis in the non-cirrhotic liver of a young man is a rare event. Despite resection in healthy tissue multicentric HCC was diagnosed 5 months later. Only few cases of simultaneous occurrence of HCC and echinococcosis have been published so far. Some authors considered echinococcosis as a trigger for HCC. A causal link between both entities has not been demonstrated until now.

[Gastric lymphoma: still an interdisciplinary challenge]. / Das Lymphom im Magen: Eine persistierende interdisziplinäre Herausforderung.

Differentiation of chronic gastritis from marginal zone B-cell lymphoma (MZoL) of MALT type is often difficult for the pathologist. Diagnostic tools include CD20 stain to highlight lymphoepithelial lesions, Wotherspoon grading of the infiltrate, and clonality analysis of the B-cells. MZoL may partially transform into a diffuse, large B-cell lymphoma, which the authors have named blastic MZoL. Blastic MZoL may be present with or without small cell MZoL. Without this component, blastic MzoL, while being CD10-negative, is presently difficult to positively diagnose since specific immune markers are still lacking. Blastic MZoL has a very favourable outcome compared to conventional diffuse large B-cell lymphomas (DLBCL). Moreover, there are conventional DLBCL in the stomach, mostly in a setting of a secondary organ involvement. The biology of these gastric DLBCL is identical to their extragastric counterparts. This is also true for primary gastric Burkitt lymphoma and mucosal involvement in B-CLL or mantle cell lymphoma. Unfavourable outcomes are always observed for EBV-triggered lymphoproliferations in immunodeficiency and peripheral T-cell lymphomas which might also arise or be initially diagnosed in the stomach.

[Round robin test for detection of genomic aberrations in non-Hodgkin lymphoma by in situ hybridization]. / Ringversuch zum Nachweis genomischer Veränderungen bei Non-Hodgkin-Lymphomen mittels In-situ-Hybridisierung.

BACKGROUND: The detection of characteristic genomic aberrations by fluorescence in situ hybridization (FISH) has a high diagnostic impact on lymphomas according to the World Health Organization (WHO). To investigate the reproducibility of non-isotopic ISH results a multicenter trial was carried out involving eight institutes for hematopathology. MATERIAL AND METHODS: Analyses were performed on two diffuse large B-cell lymphomas (DLBCL) without known aberrations, on one follicular lymphoma with a IGH/BCL2 translocation and BCL6 split and on two B-cell lymphomas intermediate between DLBCL and Burkitt's lymphoma with c-MYC and BCL2 rearrangements, one with an additional BCL6 split. Break-apart probes for BCL6 and c-MYC, as well as fusion probes for the c-MYC/IGH and the IGH/BCL2 translocations were used. RESULTS: All aberrations were correctly detected by all centres and no false positive or false negative results were obtained. The numbers of positive cells varied from 25% to 94%. Pearson's correlation coefficient between the centres was always > 0.8. CONCLUSIONS: The ISH analysis of recurrent genomic aberrations in formalin-fixed paraffin-embedded (FFPE) tissue is a highly reproducible technique which yields substantial additive help for lymphoma diagnostics.

[Chordoma-An update]. / Chordome ­ Ein Update.

Chordomas are rare malignant tumors of the axial skeleton with notochordal differentiation. From a morphological point of view, chordomas display a broad spectrum ranging from the classical, conventional form not otherwise specified (NOS) to forms with hepatoid or renal carcinoma-like differentiation or even poorly or dedifferentiated variants. The detection of brachyury is highly characteristic, though not exclusive. The morphological differential diagnosis from a benign notochordal tumor (BNCT) requires integration of imaging since BNCT is limited to the vertebral bodies and is not osteolytic. Targeted therapy is a current research focus and cell lines as in vitro models are a precondition for the establishment and validation of this approach.

Acute Pancreatitis in a patient with hypercalcemia due to tertiary hyperparathyroidism.

Hypercalcemia represents an independent risk factor of acute pancreatitis and can result from hyperfunctioning parathyroid glands. Here, we report on a 35-year-old patient who was admitted to our hospital with abdominal pain six weeks after kidney transplantation. Based on laboratory tests and ultrasound imaging, acute pancreatitis with hypercalcemia due to tertiary hyperparathyroidism was diagnosed. Subsequently, the patient was treated by parathyroidectomy with autologous tissue transplantation. This constellation points to acute pancreatitis as a very rare and severe complication of patients developing tertiary hyperparathyroidism-related hypercalcemia from secondary hyperparathyroidism after kidney transplantation.

C-11 methionine positron emission tomography/computed tomography localizes parathyroid adenomas in primary hyperparathyroidism.

In patients with primary hyperparathyroidism (pHPT), positive preoperative localization studies enable to perform a minimally invasive approach for parathyroid surgery. However, current imaging techniques are not always successful. We therefore conducted a study to determine the sensitivity of C-11 methionine positron emission tomography/computed tomography (Met-PET/CT) in localizing parathyroid adenomas in pHPT. Met-PET/CT scans of the neck and mediastinum of 33 patients undergoing parathyroidectomy for primary HPT were compared with intraoperative and histological findings. Primary HPT was caused by a single gland adenoma in 30 patients, while another 3 patients had multiglandular disease. Met-PET/CT scan correctly located a single gland adenoma in 25 out of 30 (83%) patients with pHPT, among them 2 patients with persistent disease, 7 patients with prior neck surgery, and 8 patients with concomitant thyroid nodules. In 3 patients with multiglandular disease, Met-PET/CT showed only one enlarged parathyroid gland in two individuals and was negative in the third patient. Statistical analysis found a significant correlation between true-positive results and the weight (2.42+/-4.05 g) and diameter (2.0+/-1.18 cm) of parathyroid adenomas while the subgroup with false negative findings had significantly smaller (0.98+/-0.54 cm) and lighter (0.5+/-0.38 g) glands. Sensitivity was 83% for single gland adenomas and 67% for multiglandular disease. Met-PET/CT correctly localized 83% of single gland parathyroid adenomas in patients with pHPT. However, preoperative localization of multiglandular disease due to double adenomas or parathyroid hyperplasia remained difficult.

[Current aspects of the pathology and differentiation of extranodal marginal zone B-cell lymphoma, MALT-Type, and gastrointestinal diffuse large B-cell lymphoma]. / Aktuelle molekular-zytogenetische Aspekte zur Pathologie und Differenzierung von extranodalen Marginalzonen B-Zell-Lymphomen vom MALT-Typ und gastrointestinalen diffusen grosszelligen B-Zell-Lymphomen.

The marginal zone B-cell lymphoma, MALT-type (MZBL, MT) is a low-grade B-cell lymphoma which is predominantly localised in the stomach with a typical morphology and cytogenetic pattern. The coexistence of a diffuse large B-cell lymphoma (DLBCL) with an MZBL, MT in the gastrointestinal tract is defined as a composite lymphoma (ComL) and represents a fascinating model of lymphoma progression. In this review we focus on current aspects regarding the molecular characterisation of MZBL, MT and gastrointestinal DLBCL and their mutual relationships.

Difficult diagnosis of a large cystic retroperitoneal tumor mimicking a hepatic origin.

Schwannomas are rare tumors, usually benign, originating from the nerve sheath, and found only infrequently in the retroperitoneal space. We report on a 67-year-old woman who was initially misdiagnosed and treated for a liver hydatid cyst. After incomplete resection and recurrence of the tumor, we were able to diagnose a large retroperitoneal schwannoma that completely displaced the liver to the left abdomen. The patient underwent surgical resection of the schwannoma; pathological evaluation revealed a cystic tumor measuring 18.5 × 18 × 12.5 cm, with tumor cells staining strongly positive for S-100. Retroperitoneal schwannomas may mimic cystic hepatic tumors and should, therefore, be considered as a differential diagnosis in such cases. We describe the diagnostic modalities and difficulties in the approach of a cystic liver tumor.

Comparison of sonographically measured bowel wall vascularity, histology, and disease activity in Crohn's disease.

The purposes of this study was to provide a retrospective comparison of semiquantitatively measured bowel wall vascularity by power Doppler sonography, endoscopic-histopathological biopsy findings, and disease activity in patients with confirmed Crohn's disease. Thirty-two out of 1,332 patients with histologically confirmed Crohn's disease (18 female, 14 male; mean age 38.8 years) met the inclusion criteria: ileocolonoscopy with biopsy and power Doppler sonographic determination of bowel wall vascularity with assessment of disease activity within a period of 5 days. Sonographic determination of bowel wall vascularity was based on a semiquantitative score. Endoscopic bowel wall biopsy specimens were assessed using a self-developed inflammation score and the disease activity was calculated using Crohn's disease activity index (CDAI). A significant association (p < 0.05) was shown for results of histology and bowel wall vascularity in the terminal ileum (kappa = 0.66; sensitivity 95%; specificity 69%). There was no observed association between CDAI and histology, although there was an association between CDAI and bowel wall vascularity (sensitivity 82%). Increased bowel wall vascularity in the terminal ileum measured by power Doppler ultrasound reflects inflammatory activity in histologically examined bowel wall. Power Doppler ultrasound may be able to monitor activity changes of the bowel wall determined by pharmaceutical treatment.

Anorectal amelanotic melanoma.

OBJECTIVE: Anorectal melanoma is a rare, highly malignant tumour with a poor 5 year survival of 10%. Most anorectal melanomas have gross and/or histologic pigmentation, however about 30% of anorectal melanomas are amelanotic. METHOD: We report three cases of amelanotic anorectal melanomas and integrate our data with six case reports of amelanotic malignant melanoma from the literature. Further we compare clinicopathological data and clinical outcome with large series of anorectal melanomas (both, amelanotic and pigmentated). RESULTS: There were seven females and two males, of median age 62 years (range: 45-75 years). Rectal bleeding was the leading symptom in all cases with a mean duration of 4 months before diagnosis. Eight of nine patients developed distant metastases. Median survival was 14 months (range: 3-60 months). A tumour thickness of < 4 mm was correlated with long-term disease-free survival, whereas tumour thickness of 4 mm or more was correlated with systemic recurrence. CONCLUSION: Early diagnosis is key for efficient treatment and improved survival rate for patients with this unusual variant of melanoma. There is no difference in terms of age, time of diagnosis, stage and survival between pigmented and amelanotic anorectal melanoma.