N.A. Athanasou

An assessment of the histological criteria used to diagnose infection in hip revision arthroplasty tissues.

AIM: To characterise the number and nature of the inflammatory cells seen in cases of septic or aseptic loosening of hip arthroplasty, and to establish reliable histological criteria to distinguish between these two conditions. METHODS: Histological examination of paraffin sections of periprosthetic tissues (pseudocapsule, femoral and acetabular pseudomembranes) of 523 cases of aseptic loosening and 79 cases of microbiology culture proven septic loosening. The cellular composition of the inflammatory cell infiltrate was determined semiquantitatively. RESULTS: The finding of a 2+ or greater neutrophil polymorph infiltrate (one or more cells per high power field (x400) on average after examination of 10 fields) in arthroplasty tissues correlated strongly with the microbiological diagnosis of septic loosening: diagnostic sensitivity 100%, specificity 97%, accuracy 99%, positive predictive value 92%, negative predictive value 100%. The finding of a 3+ neutrophil polymorph infiltrate (five or more cells on average per high power field) had a diagnostic sensitivity of 72%, specificity 100%, accuracy 98%, positive predictive value 100%, and negative predictive value 97%. In some cases of septic loosening the finding of a heavy lymphocytic and plasma cell infiltrate was of low diagnostic sensitivity. A neutrophil polymorph infiltrate (generally less than one cell per 10 high power fields) was also seen in cases of aseptic loosening. CONCLUSIONS: The presence of 2+ or more (more than one neutrophil polymorph per high power field (x400) on average after examination of at least 10 high power fields) in periprosthetic tissues provides the most sensitive and accurate histopathological criterion for distinguishing between septic and aseptic loosening of hip arthroplasty.

Origin of marrow stromal cells and haemopoietic chimaerism following bone marrow transplantation determined by in situ hybridisation.

The origin and cell lineage of stromal cells in the bone marrow is uncertain. Whether a common stem cell exists for both haemopoietic and stromal cells or whether these cell lines arise from distinct stem cells is unknown. Using in situ hybridisation for detection of the Y chromosome, we have examined histological sections of bone marrow from seven patients who received marrow transplants from HLA-matched donors of the opposite sex. Stromal cells (adipocytes, fibroblasts, endothelial cells, osteoblasts and osteocytes) were identified in these recipients as being of host origin. This result is consistent with the concept of a distinct origin and separate cell lineage for cells of the haemopoietic and stromal systems. It also shows that engraftment of marrow stromal cell precursors does not occur and that host stromal cells survive conditioning regimens for marrow transplantation. With the exception of one case, with a markedly hypocellular marrow, mixed chimaerism was seen in haemopoietic cells, indicating that this is not a rare event after marrow transplantation.

Localized amyloid deposition in cartilage is glycosaminoglycans-associated

Localized amyloid deposition is known to occur commonly in the articular cartilage of elderly patients. Its pathogenesis is uncertain and it is not known if other cartilage‐containing tissues also contain amyloid deposits. Systemic amyloid deposits are known to contain highly sulphated glycosaminoglycans, a major constituent of cartilage. As the composition of articular cartilage glycosaminoglycans is known to change with age, we sought to identify whether localized amyloid deposition in cartilage was glycosaminoglycan‐related. We examined specimens of articular cartilage over a wide age range and also examined a variety of cartilaginous tumours and tumour‐like lesions for the presence or absence of amyloid deposits. Using mucin histochemistry (alcian blue: MgCl2 critical electrolyte concentration) and immunohistochemistry, we found that highly sulphated glycosaminoglycans (0.9 M and 1 M MgCl2), in particular keratan sulphate, localized to amyloid deposits in both articular cartilage and loose bodies derived from the articular surface. Other cartilaginous lesions (including loose bodies of primary synovial chondromatosis) were negative for amyloid and did not contain highly sulphated glycosaminoglycans. These findings suggest that changes in specific highly sulphated glycosaminoglycans may play a role in localized amyloid deposition in articular cartilage.

Osteoclast‐like giant cells in malignant melanoma

A 24-year-old woman presented with a pigmented nodule in the centre of her back. The lesion was clinically ulcerated and had recently bled. Histopathological assessment of the resected specimen showed a nodular, symmetrical collection of melanocytes in the dermis, many of which were epithelioid and some of which had 2-4 nuclei. There was mild cytological atypia and no mitotic figures were seen. The surface of the lesion was ulcerated. The lesion caused some diagnostic difficulty, but a diagnosis of Spitz naevus was favoured over nodular malignant melanoma. The patient had no other suspicious pigmented lesions. The patient returned 6 months later with axillary lymphadenopathy. A fine needle aspirate and a subsequent axillary clearance were performed.

Chondromyxoid fibroma of the nasal bone with extension into the frontal and ethmoidal sinuses.

Chondromyxoid fibroma is a rare benign tumour whose histological appearance may easily be misinterpreted as chondrosarcoma. It has a tendency to recur locally unless completely excised. A rare case of the tumour affecting the nasal bone with extension into the frontal and ethmoidal sinuses and impingement on the cribiform plate is presented. Complete excision was achieved by the craniofacial resection approach.

Osteosarcomatous differentiation in carcinoma of the breast: a case of 'metaplastic' carcinoma with osteoclasts and osteoclast-like giant cells

A case of carcinoma of the breast with osteosarcomatous differentiation and containing both osteoclasts and osteoclast-like giant cells is presented. The morphology, immunophenotype and clinical behaviour of this lesion support the concept that the sarcomatous areas represent ‘metaplasia’. The immunophenotype of the osteoclast-like giant cells and the behaviour of the tumour after injection into a nude mouse suggest that these cells are both phenotypically heterogeneous and represent a reactive infiltrate in the primary tumour. This case confirms the importance of recognition and classification of ‘metaplastic’ carcinomas in view of their relatively good prognosis.

Durable Response of Spinal Chordoma to Combined Inhibition of IGF-1R and EGFR.

Chordomas are rare primary malignant bone tumors arising from embryonal notochord remnants of the axial skeleton. Chordomas commonly recur following surgery and radiotherapy, and there is no effective systemic therapy. Previous studies implicated receptor tyrosine kinases, including epidermal growth factor receptor (EGFR) and type 1 insulin-like growth factor receptor (IGF-1R), in chordoma biology. We report an adult female patient who presented in 2003 with spinal chordoma, treated with surgery and radiotherapy. She underwent further surgery for recurrent chordoma in 2008, with subsequent progression in pelvic deposits. In June 2009, she was recruited onto the Phase I OSI-906-103 trial of EGFR inhibitor erlotinib with linsitinib, a novel inhibitor of IGF-1R/insulin receptor (INSR). Treatment with 100u2009mg QD erlotinib and 50u2009mg QD linsitinib was well-tolerated, and after 18u2009months a partial response was achieved by RECIST criteria. From 43u2009months, a protocol modification allowed intra-patient linsitinib dose escalation to 50u2009mg BID. The patient remained stable on trial treatment for a total of 5u2009years, discontinuing treatment in August 2014. She subsequently experienced further disease progression for which she underwent pelvic surgery in April 2015. Analysis of DNA extracted from 2008 (pre-trial) tissue showed that the tumor harbored wild-type EGFR, and a PIK3CA mutation was detected in plasma, but not tumor DNA. The 2015 (post-trial) tumor harbored a mutation of uncertain significance in ATM, with no detectable mutations in other components of a 50 gene panel, including EGFR, PIK3CA, and TP53. By immunohistochemistry, the tumor was positive for brachyury, the molecular hallmark of chordoma, and showed weak–moderate membrane and cytoplasmic EGFR. IGF-1R was detected in the plasma membrane and cytoplasm and was expressed more strongly in recurrent tumor than the primary. We also noted heterogeneous nuclear IGF-1R, which has been linked with sensitivity to IGF-1R inhibition. Similar variation in IGF-1R expression and subcellular localization was noted inu200915 further cases of chordoma. In summary, this exceptionally durable response suggests that there may be merit in evaluating combined IGF-1R/INSR and EGFR inhibition in patients with chordomas that recur following failure of local treatment.

Metastatic meningioma presenting as a malignant soft tissue tumour.

BackgroundExtracranial metastasis of malignant meningioma to soft tissues is extremely rare and its clinical, radiological and pathological features are not well-characterised.Case presentationWe report a case of a 58xa0year old man who presented with a mobile mass within the left trapezius muscle. The patient had previously undergone surgery for a right frontal lobe high grade anaplastic meningioma. Histology of the soft tissue lesion showed metastatic anaplastic meningioma with clumps of pleomorphic tumour cells which expressed epithelial membrane antigen, cytokeratin and P63 but were negative for other epithelial and mesenchymal markers. A PET-CT scan revealed additional metastatic lesions in the left pleura, liver and iliac bone.ConclusionsMetastatic malignant meningioma can very rarely present as a high grade pleomorphic malignant soft tissue tumour and needs to be distinguished from soft tissue sarcomas and metastatic carcinomas that express epithelial antigens.

Giant cell tumour of the distal radius/ulna: response to pre-operative treatment with short-term denosumab.

BackgroundTreatment of giant cell tumour of bone (GCTB) of the distal radius/ulna poses a surgical challenge, as complex reconstructive surgery may be required. This study evaluates the clinical, radiological and pathological findings in five cases of GCTB of the distal forearm where a 3xa0month course of denosumab was given prior to surgery.MethodsPatients with biopsy proven distal forearm GCTB, treated for 3xa0months with denosumab, followed by salvage surgery (curettage and cementation) were included. Wrist pain and function were assessed using the modified Mayo Wrist Score (MMWS). Plain radiographs, MRI and PET/CT were performed pre-treatment and 2xa0months after initiation of denosumab therapy. Histological comparison was made between the original biopsy and surgical curettage specimens.ResultsFive patients with an average age of 25xa0years were included in the study. Improvement in wrist pain and function was seen in all patients with the average MMWS increasing from 30 pre-treatment to 85 at 3xa0months. Plain radiographs demonstrated marginal sclerosis in all cases with reconstitution of cortical and subarticular bone by 2xa0months; internal matrix sclerosis and osseous consolidation was more variable. Increased tumour heterogeneity and low signal were observed on T2-weighted MR images. PET/CT revealed a decrease in average SUV from 14.8 pre-treatment to 4.7 at 2xa0months. Histology showed disappearance of osteoclasts and increased fibro-osseous tissue. Denosumab treatment has the potential to facilitate salvage surgery, thus avoiding bone resection and graft reconstruction. A good outcome was achieved apart from local recurrence in one case. Follow up ranged from 17 to 54xa0months.ConclusionDistal forearm GCTB responds clinically, radiologically and histologically to a short course of pre-operative denosumab therapy, which has the potential to facilitate salvage surgery.