Co-amplification of the HER2 gene and chromosome 17 centromere: a potential diagnostic pitfall in HER2 testing in breast cancer

Co-amplification of the centromere on chromosome 17 (CEP17) and HER2 can occur in breast cancer. Such aberrant patterns (clusters) on CEP17 can be misleading to calculate the HER2/CEP17 ratio, and thus underreporting of HER2 amplification. We identified 14 breast cancers retrospectively with HER2/CEP17 co-amplification and performed FISH (fluorescence in situ hybridization) with additional chromosome 17 probes (17p11.1-q11.1, 17p11.2-p12, TP53 on 17p13.1, RARA on 17q21.1-3 and TOP2 on 17q21.3-22) to characterize the spanning of the amplicon in these cases. Furthermore, the HER2 status was analyzed by means of HER2 silver in situ hybridization (SISH) and immunohistochemistry (IHC). The co-amplification of HER2/CEP17 was compared between the three institutions. TP53 was eusomic in all cases, 17p11.2-p12 in 79% (11/14), whereas 17p11.1-q11.1 showed chromosomal gain in all cases. RARA was amplified in 10/14 cases (71%) and TOP2 in 3/14 cases (21%). HER2 was amplified with FISH/SISH in all 14 cases. 9/14 tumors were 3+ IHC positive (64%) and 3 cases were 2+ IHC positive. In our cohort the CEP17 amplicon almost always involves the HER2 but not the TOP2 locus. Overall agreement on HER2/CEP17 ratio (when applying ASCO/CAP guidelines) was only 64% (9/14 cases) between the institutions. Discrepant ratios varied from 1.1 to 14.3. The HER2/CEP17 co-amplification is not defined in the ASCO/CAP guidelines, and may result in inaccurate HER2-FISH/SISH status, particularly if only the calculated HER2/CEP17 ratio is reported. It is recommended to report separate CEP17 and HER2 signals in complex HER2/CEP17 pattern

Predictive Value of Tumor Ki-67 Expression in Two Randomized Trials of Adjuvant Chemoendocrine Therapy for Node-Negative Breast Cancer

Several small studies have reported that having a high percentage of breast tumor cells that express the proliferation antigen Ki-67 (ie, a high Ki-67 labeling index) predicts better response to neoadjuvant chemotherapy. However, the predictive value of a high Ki-67 labeling index for response to adjuvant chemotherapy is unclear. To investigate whether Ki-67 labeling index predicts response to adjuvant chemoendocrine therapy, we assessed Ki-67 expression in tumor tissue from 1924 (70%) of 2732 patients who were enrolled in two randomized International Breast Cancer Study Group trials of adjuvant chemoendocrine therapy vs endocrine therapy alone for node-negative breast cancer. A high Ki-67 labeling index was associated with other factors that predict poor prognosis. Among the 1521 patients with endocrine-responsive tumors, a high Ki-67 labeling index was associated with worse disease-free survival but the Ki-67 labeling index did not predict the relative efficacy of chemoendocrine therapy compared with endocrine therapy alone. Thus, Ki-67 labeling index was an independent prognostic factor but was not predictive of better response to adjuvant chemotherapy in these studie

Giant intraosseous meningioma mimicking fibrous dysplasia

peer reviewedWe illustrate a case of a giant primary intraosseous meningiomas (PIMs) with optic nerve compression treated by partial resection. A 48-year-old female presented with visual disturbances exophthalmus, diplopia and eye pain due to optic nerve compression. The patient had a past history of fibrous dysplasia treated surgically with partial resection by ENT in 2010. Histology confirmed the diagnosis. Two years later she presented with further decrease in visual acuity and diffuse hyperostosis. In this context she underwent a neurosurgical procedure consisting in craniotomy and further partial resection of the lesion including optic canal decompression. The second pathological examination demonstrated an extensive meningioma (WHO grade I) of the skull base. We recommend that in cases of diffuse hyperostosis the differential diagnosis include diffuse intraosseous meningioma. If complete surgical resection is not achievable, a biopsy to confirm the diagnosis is recommended. Treatment options include complete or partial resection followed by adjuvant radiotherapy

Pulmonary Embolism in a Patient with Primary Renal Synovial Sarcoma: The Important Differential Diagnosis of Tumor Embolism and Its Therapeutic Implications

Pulmonary tumor embolism rarely occurs in epithelial-derived tumors, but it has been described in different tumor entities. Microscopic pulmonary tumor embolisms are often only discovered on autopsy. Pulmonary thromboembolism, on the other hand, is a frequent complication in cancer patients, and surgery in patients with a malignant tumor is an additional risk factor. The differential diagnosis between pulmonary thromboembolism and pulmonary tumor embolism can be challenging. In this case report, we describe the rare case of a patient with primary renal synovial sarcoma and the workup for a thrombus in the left pulmonary artery

Der Rücken tut aber noch immer weh!

Wir berichten über einen 39-jährigen Mann, der sich wegen lumbaler Rückenschmerzen in der Sprechstunde meldete. Trotz spezialärztlicher Beurteilung und entsprechender Therapie persistierten die Schmerzen. Im Verlauf kam es zu beidseitigen Schenkelhalsfrakturen, und aufgrund multipler Anreicherungen in der Szintigrafie wurde der Verdacht auf eine chronische multifokale (sterile) Osteomyelitis gestellt. Im weiteren Verlauf gelang aber der histologische Nachweis einer Osteomalazie mit laborchemischer Bestätigung eines Vitamin-D-Mangels, sodass eine adäquate Therapie mit Vitamin D erfolgen konnte. We present the case of a 39-year-old man who reported to the primary care physician for low back pain. Pain persisted despite extensive assessment and therapy. During the course, bilateral femoral neck fractures occurred and due to multiple enrichments in scintigraphy chronic multifocal (sterile) osteomyelitis was suspected. In the further follow-up the appropriate diagnosis of osteomalacia was established in bone biopsy and adequate treatment with Vitamin D was initiated. During therapy, the patient was free of pain or discomfort

Soft tissue sarcomas of the kidney

Soft tissue sarcomas are rare mesenchymal tumors. Amongst others, primitive neuroectodermal tumors (PNET) of the kidney and synovial sarcoma of the kidney belong to the group of soft tissue sarcomas. Synovial sarcomas can occur almost anywhere in the body, most frequently, however, in the lower (62%) or upper extremities (21%). Metastases occur in 50-70% of cases, and thus the prognosis is poor. PNETs are rare, highly aggressive neoplastic lesions which mainly occur in the torso or axial skeleton in young adults. The prognosis is poor with a 5-year disease-free survival rate of 45-55%. The primary therapeutic approach is surgical resection. Most randomized studies assessing adjuvant chemotherapy for all types of localized soft tissue sarcomas did not show statistically significantly better overall survival times after chemotherapy, although they did show longer progression-free survival. We report on two cases of primary renal synovial sarcoma and one case of PNET of the kidney

Soft tissue sarcomas of the kidney

Soft tissue sarcomas are rare mesenchymal tumors. Amongst others, primitive neuroectodermal tumors (PNET) of the kidney and synovial sarcoma of the kidney belong to the group of soft tissue sarcomas. Synovial sarcomas can occur almost anywhere in the body, most frequently, however, in the lower (62%) or upper extremities (21%). Metastases occur in 50-70% of cases, and thus the prognosis is poor. PNETs are rare, highly aggressive neoplastic lesions which mainly occur in the torso or axial skeleton in young adults. The prognosis is poor with a 5-year disease-free survival rate of 45-55%. The primary therapeutic approach is surgical resection. Most randomized studies assessing adjuvant chemotherapy for all types of localized soft tissue sarcomas did not show statistically significantly better overall survival times after chemotherapy, although they did show longer progression-free survival. We report on two cases of primary renal synovial sarcoma and one case of PNET of the kidney

Osteolytic changes around biodegradable cement restrictors in hip surgery

Background and purpose — Biodegradable cement restrictors are widely used in hip arthroplasty. Like others, we observed osteolytic reactions associated with a specific cement restrictor (SynPlug; made of PolyActive) and reviewed our patients. Patients and methods — We identified 703 patients with suitable radiographs from our database (2007 to 2012) who underwent cemented hip arthroplasty and received a SynPlug biodegradable cement restrictor. We reviewed all available radiographs to determine the incidence, severity, and progression of osteolysis. Mean postoperative follow-up was 1.8 (1–7) years Results — 1 year after implantation, the femoral cortex showed thinning by 12% in the anterior-posterior view and by 8% in the axial view. This had increased to 14% and 12%, respectively, at the latest available follow-up postoperatively (at a mean of 4 years). Cortical thinning of less than 10% was found in 37% of patients, but cortical thinning of 10–30% was found in 56% of patients. In the remaining 7%, a reduction of more than 30% of the original cortical thickness was observed. Interpretation — Osteolytic changes associated with the SynPlug biodegradable bone restrictors are inconsistent and highly variable. While some patients showed increased weakening of the femoral cortex with the potential risk of periprosthetic fracture, in others the degree of osteolysis only increased slightly or stabilized after 2 or more years. Any cortical bone loss after total hip replacement should be avoided, so the use of PolyActive biodegradable cement restrictors should be discontinued. Patients with a PolyActive cement restrictor in place should be followed up closely after surgery