Pathology of intra-articular tumours and tumour-like lesions: pearls, pitfalls and rarities from a general surgical pathology practice.

Intra-articular tumours are uncommonly encountered in routine practice and may present diagnostic challenges to pathologists. Challenges unique to this site include distinction from more common reactive synovial conditions, which are far more common; histologic variability; superimposed reactive changes; and often, lack of provided clinicoradiological context. This article reviews the pathology of the synovial tumours and tumour-like lesions, including diagnostic pearls, pitfalls and rare entities.

Blau syndrome: a rare cause of exuberant granulomatous synovitis of the knee.

Blau syndrome (BS) is a rare autosomal dominant familial granulomatous inflammatory disease presenting in early childhood with dermatitis, arthritis and uveitis. Early-onset sarcoidosis represents the sporadic form, and both are characterised by mutations in the CARD15/NOD2 gene on chromosome 16. We describe a 38-year-old man with known BS who presented for orthopaedic review following right-sided patellar dislocation. MRI of the injured knee demonstrated diffuse synovitis and prominent fatty tissue resembling lipoma arborescens with evidence of recent patellar dislocation. Synovectomy was performed and confirmed granulomatous synovitis. Knee imaging findings are described for the first time. Combining distinct morphological bone changes with synovitis which resembles lipoma arborescens and histology which includes sarcoidal-type granulomatous synovitis should lead the radiologist and pathologist to consider the diagnosis of BS.

Thalidomide and neurotrophism.

BACKGROUND: Following the thalidomide disaster (1958-62), Henkel and Willert analysed the pattern of dysmelia in the long bones (J Bone Joint Surg Br. 51:399-414, 1969) and the extremities, Willert and Henkel (Z Orthop Ihre Grenzgeb. 107:663-75, 1970). Willert's material from deformed extremities is re-examined here asking "How does thalidomide reduce the skeleton?" MATERIALS AND METHODS: We reviewed the original data collection of Willert and Henkel (Z Orthop Ihre Grenzgeb. 107:663-75, 1970), comprising musculoskeletal histology slides from 30 children affected by thalidomide with radiographs of hands (19 cases) and feet (4 cases). RESULTS: All original observations by Willert and Henkel (Z Orthop Ihre Grenzgeb. 107:663-75, 1970), were verified. Radial rays of the hand disappeared early, but the foot was spared until late. Radiology confirms that bone reduction in the hand (aplasia or hypoplasia in the thumb and index finger) coincides with sensory segmental nerve C6. In the foot, reduction of the toes is rare, but mesenchymal excess (polydactyly) occurs in the hallux (L5 sclerotome), usually associated with absent tibia (L4 sclerotome). Histology confirms skeletal mesenchymal components to be unremarkable, contrasting with grossly abnormal bony architecture, a striking discordance between microscopic and macroscopic findings. No necrosis or vascular pathology was seen. CONCLUSION: The basic lesion was an abnormal quantity rather than quality of mesenchyme. Cell populations result from cellular proliferation, controlled in early limb bud formation by neurotrophism. Thalidomide is a known sensory neurotoxin in adults. In the embryo, sensorineural injury alters neurotrophism, causing increased or diminished cell proliferation in undifferentiated mesenchyme. Differentiation into normal cartilage occurs later, but within an altered mesenchymal mass. Reduction or excess deformity results, with normal histology, a significant finding. The primary pathological condition is not in the skeleton, but in the nerves.

Atypical Ewing sarcoma breakpoint region 1 fluorescence in-situ hybridization signal patterns in bone and soft tissue tumours: diagnostic experience with 135 cases.

AIMS: Recurrent Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangements characterize a select group of bone and soft tissue tumours. In our routine diagnostic practice with fluorescence in-situ hybridization (FISH), we have occasionally observed EWSR1 gene rearrangements in tumours not associated classically with EWSR1 translocations. This study aimed to review our institutional experience of this phenomenon and also to highlight the occurrence of unusual EWSR1 FISH signals (i.e. 5' centromeric region or 3' telomeric region signals) that do not fulfil the published diagnostic criteria for rearrangements. METHODS AND RESULTS: Using an EWSR1 break-apart probe, we performed FISH assays on formalin-fixed paraffin-embedded tissue sections from 135 bone and soft tissue specimens as part of their routine diagnostic work-up. EWSR1 gene rearrangements were identified in 51% of cases, 56% of which also showed an abnormal FISH signal pattern (in addition to classically rearranged signals). However, atypical FISH signals were present in 45% of the non-rearranged cases. In addition, we observed tumours unrelated to those described classically as EWSR1-associated that were technically EWSR1-rearranged in 6% of cases. Borderline levels of rearrangement (affecting 10-30% of lesional cells) were present in an additional 17% of these cases. CONCLUSIONS: While our study confirmed that FISH is a sensitive and specific tool in the diagnosis of EWSR1-associated tumours, atypical FISH signals and classical rearrangement in entities other than EWSR1-associated tumours can occur. Therefore, it is essential that the FISH result not be used as an isolated test, but must be evaluated in the context of clinical features, imaging, pathological and immunohistochemical findings.

Multifocal low-grade central osteosarcoma: a rare case.

Low-grade central osteosarcoma (LGCOS) is a rare variant of osteosarcoma. We present a rare case of multifocal LGCOS located in two distinct skeletal sites, initially noted as incidental findings on imaging for distant traumatic pathology. Both sites seemed small and innocuous on initial imaging, and were quiescent clinically, illustrating the value of close interval multimodal surveillance scanning.

Intraosseous hibernoma: characterization of five cases and literature review.

OBJECTIVE: To describe the imaging and histopathological findings and provide an overview of a recently described and rare cause of bone sclerosis. MATERIALS AND METHODS: Five cases of intra-osseous hibernoma of bone that presented over the last year. The imaging and histopathology is reviewed. RESULTS: All cases were identified in asymptomatic middle-aged to elderly adults as incidental findings with bone sclerosis in the axial skeleton. MRI showed lesions that were T1 hypointense to subcutaneous fat and hyperintense to skeletal muscle and one showed contrast enhancement. Glucose avidity was demonstrated on FDGPET in both cases tested and isotope bone scan performed in three cases showed strong positivity in two, but uptake was inconspicuous in one case. CONCLUSIONS: Intra-osseous hibernoma is a rare cause of sclerotic bone lesions, predominating in the axial skeleton of middle-aged and elderly adults. They have a non-aggressive appearance on CT and on MRI are T1 hypointense to subcutaneous fat and hyperintense to skeletal muscle. They are usually T2 hyperintense and may show peripheral contrast enhancement. They may show increased glucose avidity on FDGPET and may or may not be positive on isotope bone scans. We suspect that with ever-increasing use of a variety of imaging techniques, particularly in a setting of staging for malignant disease, more such cases will come to light. This diagnosis should be added to the differential diagnosis of sclerotic bone lesions.

MRI "row of dots sign" in gossypiboma: an enlarging mass 8 months after sarcoma resection.

The retention of foreign bodies after surgery is rare, but carries significant morbidity and mortality as well as financial and legal implications. Such retained items cause a foreign-body reaction, which in the case of cotton-based materials are called gossypibomas. We present the case of an 84-year-old woman with a pseudotumor secondary to a retained dressing gauze roll, presenting 5 months after resection of a gluteal sarcoma, which had raised concerns of local recurrence. We also outline the imaging modalities that may assist in diagnosis of a retained foreign body, and suggest the MRI "row of dots" sign as a useful radiological feature associated with gossypiboma. Awareness of the imaging appearances of retained foreign bodies allows the inclusion of this possibility in differential diagnosis of a mass in patients with a surgical history.

Periprosthetic tissues from third generation alumina-on-alumina total hip arthroplasties.

The histological features of periprosthetic tissues are related to the bioreactivity of particles generated by the prosthesis. This study analyzed synovial-like pseudocapsules collected from 21 patients with alumina ceramic-on-ceramic hip arthroplasties and correlated histological features with wear of the ceramic bearings, duration of implantation and clinical factors such as neck-to-rim impingement. A histopathological classification system was developed for this purpose. The pseudocapsules were viable, with few foreign body type giant cells and occasional lymphocytes. This differs from tissues in polyethylene containing hip arthroplasties which often have extensive foreign body type inflammatory changes or from metal-on-metal hip arthroplasties in which extensive necrosis is common. Soft-tissue inflammation was not associated with failure of the hip arthroplasties, and may be clinically insignificant in alumina-on-alumina total hip arthroplasties.

The Lateral Deltoid Originates From the Entire Lateral Wall of the Acromion: MRI and Histologic Cadaveric Analysis Regarding Vertical Lateral Acromioplasty.

PURPOSE: The aim of this study was to assess the nature of the middle deltoid muscle insertion onto the lateral acromion by macroscopic, MRI and histologic examination and to, therefore, assess the potential impact of a vertical lateral acromioplasty on the deltoid origin. METHODS: We assessed the acromial origin of the deltoid in 6 cadaver shoulders by macroscopic, MRI and histologic examination. The cadavers were scanned with T1 and proton density-weighted sequences. H&E- and Masson trichrome-stained histologic sections through the acromion were taken and visualized under polarized microscopy. RESULTS: The enthesis of the deltoid muscle consisted of dense birefringent bundles of collagen that blended with the bony endplate of the acromion at all points on its lateral wall. A prominent band of collagen was seen on both MRI and histologic slices, traversing the superior surface of the acromion. It was continuous with the deltoid origin and blended with the superficial fascia of the deltoid laterally. CONCLUSIONS: The middle deltoid muscle occupies the entire lateral acromion. CLINICAL RELEVANCE: A high critical shoulder angle is associated with rotator cuff tears. A lateral acromioplasty resects the lateral acromion and aims to normalize the critical shoulder angle. However, a vertical lateral acromioplasty may release the middle deltoid origin from the lateral acromion. The superior band of collagen may anchor the middle deltoid to the superior acromion and prevent retraction.

The role of intra-operative pathological evaluation in the management of musculoskeletal tumours.

A tissue biopsy is usually a critical aspect in guiding appropriate initial management in patients with musculoskeletal tumours. We have previously outlined the role of intra-operative frozen section in both the determination of adequacy of a biopsy and for its diagnostic utility. In this article, the options and techniques for intra-operative pathological evaluation, namely frozen section, fine needle aspiration cytology and touch imprint cytology are reviewed. Frozen section examination may be applicable in the following Sections, including (1) at core biopsy, (2) at surgical margins, (3) at confirming diagnosis prior to definitive treatment or to evaluate tumour spread, and (4) at establishing a diagnosis of a metastasis prior to intramedullary nailing. There are also situations in which frozen section is inappropriate. Pitfalls associated with frozen sections are also highlighted. There are also cost implications, which we have quantified, of performing frozen sections. In our experience that the use of intra-operative pathological evaluation reduces the non-diagnostic rate of bone and soft tissue sarcoma biopsies, eliminates the need for re-biopsy hence alleviating stress, and is a useful addition to the armamentarium in evaluating musculoskeletal tumours.

Osteolysis in third-generation alumina ceramic-on-ceramic hip bearings with severe impingement and titanium metallosis.

The most common cause of long-term failure of total hip arthroplasty is osteolysis and aseptic loosening secondary to wear debris. Combinations of hard materials such as ceramic-on-ceramic generate smaller volumes of particulate wear debris than traditional combinations such as metal-on-polyethylene. We describe 2 cases where osteolysis arose in hips with third-generation alumina ceramic-on-ceramic couplings. Periarticular tissue in both cases contained titanium wear debris due to impingement of the neck of the titanium femoral component against the rim of the titanium shell and ceramic debris from edge loading wear (stripe wear) of the ceramic. It is not clear whether the titanium debris, the ceramic debris, or both caused the osteolysis. These cases illustrate that the risk of osteolysis persists, even with third-generation alumina ceramics.

A robust assay for alternative lengthening of telomeres in tumors shows the significance of alternative lengthening of telomeres in sarcomas and astrocytomas.

PURPOSE AND EXPERIMENTAL DESIGN: Telomeres of tumor cells may be maintained by telomerase or by alternative lengthening of telomeres (ALT). The standard ALT assay requires Southern analysis of high molecular weight genomic DNA. We aimed to establish and validate an ALT assay suitable for archived paraffin-embedded tumors and to use it to examine the prevalence and clinical significance of ALT in various types of tumors that are often telomerase negative. RESULTS: To assay for ALT, we detected ALT-associated promyelocytic leukemia (PML) bodies (APBs) by combined PML immunofluorescence and telomere fluorescence in situ hybridization. APBs are PML nuclear domains containing telomeric DNA and are a known hallmark of ALT in cell lines. The APB assay concurred with the standard ALT assay in 62 of 62 tumors and showed that 35% of 101 soft tissue sarcomas (STS), 47% of 58 osteosarcomas (especially younger patients), 34% of 50 astrocytomas, and 0% of 17 papillary thyroid carcinomas were ALT positive (ALT+). The prevalence of ALT varied greatly among different STS subtypes: malignant fibrous histiocytomas, 77%; leiomyosarcomas, 62%; liposarcomas, 33%; synovial sarcomas, 9%; and rhabdomyosarcomas, 6%. ALT correlated with survival in glioblastoma multiforme and occurred more often in lower-grade astrocytomas, but ALT+ and ALT- sarcomas were equally aggressive in terms of grade and clinical outcome. CONCLUSION: The APB assay for ALT is suitable for paraffin-embedded tumors. It showed that a substantial proportion of STS, osteosarcomas, and astrocytomas, but not papillary thyroid carcinomas use ALT. APB positivity correlated strongly with survival of patients with astrocytomas.

A case of intradural osteosarcoma of the spine.

BACKGROUND CONTEXT: Intradural-extramedullary spinal tumors and extradural osteosarcomas are both rare entities. Only one case of primary intradural-extramedullary osteosarcoma of the spine has been previously reported. This is the second reported case. PURPOSE: To describe a case of primary intradural-extramedullary osteosarcoma of the spine associated with rapid clinical deterioration. STUDY DESIGN: Case report of a 70-year-old woman who presented with a constellation of neurologic symptoms. METHODS: Review of patient files, radiographic studies, surgical images, histopathology, and relevant literature. RESULTS: The patient underwent tumor debulking but exhibited rapid, postsurgical, functional deterioration and died within 6 weeks. This case and the only previous case of its kind both occurred in individuals with a remote history of iophendylate (Myodil) myelogram. CONCLUSIONS: Primary intradural-extramedullary extraosseous osteosarcoma of the spine is an exceedingly rare entity with no established management approach. Iophendylate myelography may be implicated in the etiology of this tumor type.

Optimising the management of soft tissue tumours.

The Royal College of Pathologists of Australasia is developing a series of protocols as an educational tool to assist pathologists in the reporting of relevant information for specific cancer specimens. The protocol for the management of soft tissue tumour resections has recently been released, and this document elaborates the relevant literature on which that protocol drew. Sarcoma is uncommon but is associated with significant morbidity and mortality, and its management is complex. Diagnostic errors are not uncommon and these can have disastrous effects on patient outcome. Sophisticated ancillary testing is often an important adjunct to diagnosis and prognostication. Referral to a specialist sarcoma unit is indicated for both adult and paediatric sarcoma.

Protuberant fibro-osseous lesion of the temporal bone: "Bullough lesion".

Primary tumors of the calvarium are infrequent, and with the exception of osteoma, lesions confined to the surface of the skull are very rare. The differential diagnosis includes benign and malignant matrix forming tumors, other mesenchymal tumors, and reactive lesions. Fibro-osseous lesions are characteristically centered within bone and surface fibro-osseous lesions always prompt consideration of parosteal osteosarcoma, which is rare but well documented in the calvarium. We present 2 cases of a distinctive lesion of the temporal bone intimately related to the occipito-mastoid suture and typically presenting as a retroauricular soft tissue mass with calcific densities, confined to the soft tissues on the outer table of the skull without intraosseous involvement. The lesion is characterized histologically by rounded and ovoid zones of ossification within a bland fibrous stroma. The first 2 cases were documented in 1999 as "Protuberant fibroosseous lesion of the temporal bone.:" We present a further 2 cases, 1 of 2 years duration and the other with a 10-year history. This distinctive entity, which must be distinguished from other fibro-osseous lesions, including subtle low-grade parosteal osteosarcoma, seems to behave in a benign fashion and thus far recurrence is not documented. Local excision seems adequate. The pathologic features in the original report were documented by Prof Peter Bullough. As these cases were recognized by him alone we propose calling this entity "Bullough lesion" or, better still, "Bullough's Bump!"

Epithelioid and spindle cell haemangioma of bone.

A case of epithelioid and spindle cell haemangioma of bone occurring in the proximal femur is presented. The tumour had typical microscopic features with a striking lobular pattern comprising spindled and epithelioid areas with admixed inflammatory cells. The case represents only the eighth reported example of this rare tumour, which appears to fit in the spectrum of epithelioid haemangioma. This is the first case to involve the proximal portion of a long bone. A review of the classification and features of similar vascular tumours of bone is presented.