Immunophenotypic expression of UCP1 in hibernoma and other adipose/non adipose soft tissue tumours.

BACKGROUND: Uncoupling protein 1 (UCP1) is a mitochondral protein transporter that uncouples electron transport from ATP production. UCP1 is highly expressed in brown adipose tissue (BAT), including hibernomas, but its expression in other adipose tumours is uncertain. UCP1 has also been found in other tissues (e.g. smooth muscle) but whether it is expressed in non-adipose benign and malignant soft tissue tumours is unknown. METHODS: Immunohistochemical staining of normal (axillary) BAT and subcutaneous/abdominal white adipose tissue (WAT) as well as a wide range of benign and malignant primary soft tissue tumours (n = 171) was performed using a rabbit polyclonal antibody to UCP1. BAT and hibernomas were also stained by immunohistochemistry with monoclonal and polyclonal antibodies to adipose/non-adipose tumour markers in order to characterise the immunophenotype of BAT cells. RESULTS: UCP1 was strongly expressed in the cytoplasm of brown fat cells in BAT and hibernomas, both of which also expressed aP2, S100, CD31, vimentin and calponin. UCP1 was not expressed in WAT or other adipose tumours with the exception a few tumour cells in pleomorphic liposarcoma. UCP1 was variably expressed by tumour cells in a few non-adipose sarcomas including leiomyosarcoma, rhabdomyosarcoma, alveolar soft part sarcoma, synovial sarcoma and clear cell sarcoma. CONCLUSIONS: UCP1 is strongly expressed in BAT but not WAT and is found in all hibernomas and a few pleomorphic liposarcomas but not in other adipose tumours. UCP1 expression in a few non-adipose soft tissue sarcomas may possibly reflect origin of tumour cells from a common mesenchymal stem cell precursor and/or developmental pathway.

Implant failure in bilateral metal-on-metal hip resurfacing arthroplasties: a clinical and pathological study.

Metal-on-metal hip resurfacing arthroplasties (MoMHRAs) have a high failure rate due to pseudotumour formation. It is not certain whether pseudotumours in bilateral MoMHRAs form on the basis of an adverse reaction to metal debris (ARMD) that is entirely due to a local innate and adaptive immune response to Cobalt-Chrome (Co-Cr) wear particles. To determine if there is a systemic component to ARMD in bilateral MoMHRAs, we examined the histology of ARMD in unilateral and bilateral MoMHRAs revised for pseudotumour and determined whether implant survival differed between these two groups. Periprosthetic tissue specimens from 119 hips revised for pseudotumour were examined. These were derived from 109 patients including 10 patients with bilateral MoMHRAs and 99 with sunilateral MoMHRAs including a cohort of 20 patients with bilateral MoMHRAs that had undergone only one MoMHRA revision for pseudotumour. The mean time to revision for pseudotumour of unilateral and bilateral MoMHRAs was determined. The histology of periprosthetic tissue was examined for evidence of the innate and adaptive immune response and scored semi-quantitatively. There was no significant difference in histological features of the innate / adaptive response between Group 1 bilateral pseudotumours and Group 2 and Group 3 unilateral pseudotumours. Histological features, including ALVAL scores, were similar in the periprosthetic tissues of right and left hips in Group 1 bilateral MoMHRAs. The mean time to first revision for pseudotumour of bilateral MoMHRAs (6.59 years) was not decreased compared with unilateral MoMHRAs (5.66 years) or bilateral MoMHRAs that had only one revision (7.05 years). Right and left hip pseudotumours in bilateral MoMHRAs exhibit similar histological features of the innate and adaptive immune response. Mean implant survival is not decreased in bilateral compared with unilateral MoMHRA cases. The findings suggest that pseudotumour formation is due more to a local than a systemic innate /adaptive immune response to components of metal wear.

Sclerostin expression in bone tumours and tumour-like lesions.

AIMS: To assess the immunophenotypic and mRNA expression of sclerostin in human skeletal tissues and in a wide range of benign and malignant bone tumours and tumour-like lesions. METHODS AND RESULTS: Sclerostin expression was evaluated by immunohistochemistry and quantitative polymerase chain reaction (PCR). In lamellar and woven bone, there was strong sclerostin expression by osteocytes. Osteoblasts and other cell types in bone were negative. Hypertrophic chondrocytes in the growth plate and mineralized cartilage cells in zone 4 of hyaline articular cartilage strongly expressed sclerostin, but most chondrocytes in hyaline cartilage were negative. In primary bone-forming tumours, including osteosarcomas, there was patchy expression of sclerostin in mineralized osteoid and bone. Sclerostin staining was seen in woven bone in fibrous dysplasia, in osteofibrous dysplasia, and in reactive bone formed in fracture callus, in myositis ossificans, and in the wall of solitary bone cysts and aneurysmal bone cysts. Sclerostin was expressed by hypertrophic chondrocytes in osteochondroma and chondroblasts in chondroblastoma, but not by tumour cells in other bone tumours, including myeloma and metastatic carcinoma. mRNA expression of sclerostin was identified by quantitative PCR in osteosarcoma specimens and cell lines. CONCLUSIONS: Sclerostin is an osteocyte marker that is strongly expressed in human woven and lamellar bone and mineralizing chondrocytes. This makes it a useful marker with which to identify benign and malignant osteogenic tumours and mineralizing cartilage tumours, such as chondroblastomas and other lesions in which there is bone formation.

Metastatic meningioma presenting as a malignant soft tissue tumour.

BACKGROUND: Extracranial metastasis of malignant meningioma to soft tissues is extremely rare and its clinical, radiological and pathological features are not well-characterised. CASE PRESENTATION: We report a case of a 58 year 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. CONCLUSIONS: Metastatic 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.

A multidisciplinary approach to giant cell tumors of tendon sheath and synovium--a critical appraisal of literature and treatment proposal.

Giant cell tumors deriving from synovium are classified into a localized (GCT of tendon sheath; GCT-TS) and diffuse form (diffuse-type GCT, Dt-GCT). We propose a multidisciplinary management based upon a systematic review and authors' opinion. Open excision for GCT-TS and open synovectomy (plus excision) for Dt-GCT is advised to reduce the relatively high recurrence risk. External beam radiotherapy should be considered in severe cases, as Dt-GCT commonly extends extra-articular.

Epidermal growth factor receptor signalling contributes to osteoblastic stromal cell proliferation, osteoclastogenesis and disease progression in giant cell tumour of bone.

AIMS: Epidermal growth factor receptor (EGFR) is implicated in bone remodelling. The aim was to determine whether EGFR protein expression contributes to the aggressiveness and recurrence potential of giant cell tumour of bone (GCTB), an osteolytic primary bone tumour that can exhibit markedly variable clinical behaviour. METHODS AND RESULTS: Immunohistochemical analysis on tissue microarrays (TMA) of 231 primary, 97 recurrent, 17 metastatic and 26 malignant GCTBs was performed using TMA analysis software and whole digital slides allowing validated scoring. EGFR expression was restricted to neoplastic stromal cells and was significantly more frequent in recurrent (71 of 92; 77%) than in non-recurrent GCTBs (86 of 162; 53%) (P = 0.002); and in clinicoradiologically aggressive (31 of 43; 72%) than latent (27 of 54; 50%) cases (P = 0.034). Detecting phosphotyrosine epitopes pY1068 and -pY1173 indicated active EGFR signalling, and finding EGFR ligands EGF and transforming growth factor-α restricted to cells of the monocytic lineage suggested paracrine EGFR activation in stromal cells. In functional studies EGF supported proliferation of GCTB stromal cells, and the addition of EGF and macrophage-colony stimulating factor promoted osteoclastogenesis. CONCLUSION: In GCTB, EGFR signalling in neoplastic stromal cells may contribute to disease progression through promoting stromal cell proliferation and osteoclastogenesis.

Immunophenotypic analysis of glomus coccygeum associated with coccygodynia.

OBJECTIVE: Glomus coccygeum is a glomus body which is found in the pericoccygeal soft tissue. This specialised arteriovenous anastomosis is a non-pathological vestigial structure usually larger than its equivalent in the distal extremities. Its prevalence is uncertain. Glomus coccygeum has been associated with coccygodynia and can cause diagnostic problems to pathologists unfamiliar with this entity. MATERIALS AND METHODS: The presence of a glomus coccygeum was sought in 40 coccygectomy specimens and correlated with clinical, radiological and histological findings. RESULTS: A glomus coccygeum was identified in 13 samples (35%). Glomus cells expressed smooth muscle actin (SMA) and were negative for desmin, S100, cytokeratin and a wide range of vascular markers. Proliferative activity was low. Pre-operative MRI did not identify these tiny lesions, and most patients with coccygodynia did not have a glomus coccygeum. CONCLUSION: Glomus coccygeum is a common microanatomical structure which can be distinguished from glomus and other tumours by its small size, SMA expression and low proliferative activity.

Local recurrence and assessment of sentinel lymph node biopsy in deep soft tissue leiomyosarcoma of the extremities.

BACKGROUND: Leiomyosarcoma of deep soft tissues of the extremities is a rare malignant tumour treated primarily by surgery. The incidence of local recurrence and lymph node metastasis is uncertain and it is not known whether a sentinel lymph node biopsy is indicated in these tumours. METHODS: A retrospective review of patients treated for extremity deep soft tissue leiomyosarcoma at our institution over a 10-year period was conducted. Patients developing local recurrence or lymph node metastasis were identified. The presence or absence of lymphatics in the primary tumours was assessed by immunohistochemical expression of LYVE-1 and podoplanin. RESULTS: 27 patients (mean age 62 years) were included in the study. 15 were female and 12 male. Lymph node metastasis was seen in only two cases (7%); intratumoural lymphatics were identified in the primary tumours of both these cases. Local recurrence occurred in 25.9% of cases despite complete excision and post-operative radiotherapy; the mean time to recurrence was 10.1 months. CONCLUSION: On the basis of this study, we do not advocate sentinel lymph node biopsy in this group of patients except in those cases in which intratumoural lymphatics can be demonstrated. Close follow up is important especially for high grade leiomyosarcomas, particularly in the first year, as these tumours have a high incidence of local recurrence.

A 10-year review of benign and malignant peripheral nerve sheath tumors in a single center: clinical and radiographic features can help to differentiate benign from malignant lesions.

BACKGROUND: Malignant peripheral nerve sheath tumors are rare, and their aggressive nature mandates treatment in specialist centers. In contrast, benign peripheral nerve sheath tumors are common and are treated by a variety of specialist surgeons, including plastic surgeons. The authors aimed to detect features in the clinical presentation of peripheral nerve sheath tumors that point toward a diagnosis of malignant peripheral nerve sheath tumor and therefore prompt referral to a specialist center. METHODS: All histologically diagnosed primary peripheral nerve sheath tumors from January of 1995 to December of 2004 were identified from histopathology records. Notes were reviewed and analyzed with regard to symptoms, signs, radiology, electrophysiology, surgery, and pathology. Statistical comparisons used Fisher's exact test and the Mann-Whitney test. RESULTS: During the study period, 32 cases of malignant peripheral nerve sheath tumor in 30 patients were treated. Factors in the clinical evaluation that significantly predicted the presence of malignant peripheral nerve sheath tumor included site, large size, depth in relation to the deep fascia, short duration of symptoms, and pain. Magnetic resonance imaging and computed tomography were sensitive and specific ways of confirming the clinical diagnosis. Interestingly, schwannomata were harder to distinguish from malignant peripheral nerve sheath tumors both clinically and radiologically. CONCLUSIONS: The authors have reviewed their institutional experience of peripheral nerve sheath tumors over a 10-year period. Their results will help to focus clinical and radiologic investigation of patients presenting with these tumors.