Incidence and survival of soft tissue sarcoma in England between 2013 and 2017, an analysis from the National Cancer Registration and Analysis Service.

There is a paucity of population-based data detailing the incidence and survival of patients with soft tissue sarcoma (STS), in part due to the heterogeneity of disease and changes to classification. Here, the incidence and survival of all STS subtypes registered in England between 2013 and 2017 were analysed using cancer registry data held by the National Cancer Registration and Analysis Service. Age-standardised incidence rates were calculated per 1 000 000 using the 2013 European Standard Population. Net survival was computed using Brenner's alternative method, with the Ederer II estimator. Age-specific overall survival was assessed using Kaplan-Meier. The influence of age, sex, socioeconomic deprivation and diagnostic routes on survival was assessed using Cox proportional hazards modelling. In total, 19 717 patients were diagnosed with STS, an average of 3943 patients per year and representing approximately 0.8% of malignancies. The most common histological diagnoses were Gastrointestinal Stromal Tumours (GIST), leiomyosarcoma and undifferentiated sarcoma, accounting for 20.2%, 13.3% and 12.7% of all sarcomas, respectively. Five-year net survival for all malignant STS was 65.0%; and was lowest for patients with vascular tumours at 39%. Patients from most deprived cohorts had 23% greater chance of dying within 5 years than patients in least deprived areas. This population-based study has allowed us for the first time to define the incidence and survival rates of prevalent STS subtypes in England such as GIST, liposarcoma and leiomyosarcoma, as well as rare entities and groups with inferior outcome. This data is invaluable for service provision, benchmarking and addressing inequality.

Indolent T-Cell Lymphoproliferative Disorder of the Uterine Corpus: A Case Report.

Primary lymphoproliferative disorders of the uterus are rare, with the majority being B-cell diseases or aggressive T-cell disease. We present the case of a 31-yr old in whom an Indolent T-cell lymphoproliferative disorder (iTCLPD) was identified in resection chippings for a suspected fibroid, following presentation with menorrhagia. Laboratory investigations revealed an oligoclonal T-cell infiltrate with the immunophenotype of nonactivated cytotoxic T cells, and a proliferative fraction of 10% to 15%. There was no clinical or radiologic evidence of systemic disease, and the patient remained well with no indication of relapse 1 yr from resection and diagnosis. iTCLPD of the uterine corpus has features in common with the recently described iTCLPD of the gastrointestinal tract and primary cutaneous acral CD8 T-cell lymphoma. Recognition of these parallels is important as few other cases of iTCLPD have been described, and it suggests local resection rather than systemic treatment as the best therapeutic strategy.

Establishment and molecular characterisation of seven novel soft-tissue sarcoma cell lines.

BACKGROUND: Soft-tissue sarcomas (STS) are a diverse group of malignancies that remain a diagnostic and therapeutic challenge. Relatively few reliable cell lines currently exist. Rapidly developing technology for genomic profiling with emerging insights into candidate functional (driver) aberrations raises the need for more models for in vitro functional validation of molecular targets. METHODS: Primary cell culture was performed on STS tumours utilising a differential attachment approach. Cell lines were characterised by morphology, immunocytochemistry, proliferation assays, short tandem repeat (STR) and microarray-based genomic copy number profiling. RESULTS: Of 47 STS cases of various subtypes, half formed adherent monolayers. Seven formed self-immortalised cell lines, including three undifferentiated pleomorphic sarcomas, two dedifferentiated liposarcomas (one of which had received radiotherapy), a leiomyosarcoma and a myxofibrosarcoma. Two morphologically distinct yet genetically identical variants were established in separate cultures for the latter two tumours. All cell lines demonstrated genomic and phenotypic features that not only confirm their malignant characteristics but also confirm retention of DNA copy number aberrations present in their parent tumours that likely include drivers. CONCLUSIONS: These primary cell lines are much-needed additions to the number of reliable cell lines of STS with complex genomics available for initial functional validation of candidate molecular targets.

An aggressive case of pseudomyogenic haemangioendothelioma of bone with pathological fracture and rapidly progressive pulmonary metastatic disease: case report and review of the literature.

Pseudomyogenic haemangioendothelioma (PMH) is a rare recently described vascular tumour typically presenting with soft tissue disease in distal extremities of young adults. Multi-focal and multi-layered involvement is commonly recognised. The majority of cases described so far have shown an indolent clinical course and distant metastatic spread is rare. We report a case of PMH in an 82-year-old male diagnosed following a pathological fracture of the distal tibia. Further bone lesions were identified in the fibula, patella and distal femur. The patient was found to have multiple nodules suspicious for pulmonary metastases on a CT scan at the time of diagnosis that showed significant progression at a follow-up scan 4 weeks later. To our knowledge, this is the first reported case of PMH presenting with a pathological fracture. The rapid progression of bone and distant metastatic disease in this case is highly unusual given the typically indolent clinical course reported in the literature to date.

Angiogenic growth factor expression in benign and malignant vascular tumours.

Angiosarcomas are rare malignant vascular tumours. Angiosarcoma expression of vascular endothelial growth factor (VEGF) has previously been reported, but angiosarcoma expression of other angiogenic growth factors has not been systematically studied. Non-VEGF angiogenic growth factors are a potential mechanism of resistance to VEGF-targeted therapy, but they also represent potential therapeutic targets. Immunohistochemistry analysis evaluated the expression of 13 angiogenic growth factors and receptors in 27 separate benign and malignant archived human vascular tumour samples. The expression of 55 angiogenesis-related proteins was subsequently profiled in five fresh human angiosarcoma tumour samples using antibody arrays. Angiosarcomas expressed a variety of angiogenic growth factors. Significantly higher levels of Notch1 were detected compared with benign haemangiomas (p=0.033), but lower levels of basic fibroblast growth factor (bFGF) compared to benign haemangiomas (p=0.07) and inflammatory vascular lesions (p=0.009). Vascular tumour expression of FGF receptor (FGFR)-1 correlated with angiopoietin (Ang)-2, Tie2, hepatocyte growth factor (HGF) and Notch1 expression (p=0.001, p=0.001, p<0.001 and p<0.001 respectively). Notch1 also correlated with Tie2 expression (p=0.004). In conclusion, angiosarcomas express multiple angiogenic growth factors. Treatments could be targeted at individual angiogenic growth factors. However, our findings provide a rationale for combination therapy, or for treatments that target common downstream signalling intermediaries, such as Akt, mTOR or ERK.

MR imaging features of spindle cell lipoma.

OBJECTIVE: To assess the MR imaging features of spindle cell lipomas (SCL) and to compare these appearances directly with the histopathological findings. MATERIALS AND METHODS: A retrospective review of our soft tissue tumor database was performed. This yielded 1,327 histologically proven lipomas, of which 25 were confirmed as being SCLs. Fourteen of the 25 patients had MR examinations available for review and only these patients were included in our study. Lesions were assessed at MR examination for the degree of internal fat signal content with grade 0 representing 0 % fat signal and grade 4 100 % fat signal. The degree of fat suppression and contrast-enhancement pattern were also recorded. The excision specimens were independently reviewed by a consultant histopathologist. The histology specimens were assessed for the amount of internal fat and non-adipose tissue and graded using the same scale applied for the imaging. Where core needle biopsy (CNB) was performed, the CNB specimens were also examined for positive features of SCL. RESULTS: In our study, 93 % (13/14) of our patients were male and the average age was 58 years. 65 % (9/14) of the lesions presented in the upper back, shoulder, or neck. All lesions were subcutaneous. 35 % (5/14) of the SCLs demonstrated grade 3 (>75 %) or grade 4 (100 %) fat signal on MR examination. 35 % (5/14) of the lesions had grade 2 (25-75 %) fat signal and 29 % (4/14) of the lesions demonstrated grade 0 (0 %) or grade 1 (<25 %) fat signal. 43 % (6/14) of lesions demonstrated homogenous fat suppression, 28 % (4/14) showed focal areas of high internal signal, and 28 % (4/14) had diffuse internal high signal on fluid-sensitive fat-saturated sequences. 86 % (6/7) of the cases demonstrated septal/nodular enhancement. The diagnosis was evident on the CNB specimen in 100 % (9/9) cases. The histopathology fat content grade was in agreement with the imaging grade in 86 % (12/14) cases. CONCLUSIONS: The internal signal pattern of SCL can range broadly, with low fat content lesions seen almost as commonly as intermediate and high fat content lesions. We also found that the fat:non-fat internal MR signal pattern of these lesions is accurately reflected in their composition at histology.

Intramuscular mesenchymal chondrosarcoma surrounded by a split fat sign mimicking a benign lesion.

Mesenchymal chondrosarcoma (MCS) is an aggressive malignant mesenchymal tumour of uncertain differentiation. This is rare, accounting for 2%-4% of chondrosarcomas. Its peak incidence is in the second and third decades, though it can occur at any age. These tumours show a widespread distribution, mainly in bone, but with approximately 40% affecting somatic soft tissue. We present a case of MCS arising within the soleus muscle. The lesion was surrounded by a split-fat sign/fatty rind which is a typical feature of peripheral nerve sheath tumours or other benign intramuscular tumours. However, percutaneous biopsy showed MCS. We highlight how perilesional fat is not exclusive to benign intramuscular lesions and, although much less common, can be associated with malignant lesions. This is, to the best of our knowledge, the first reported case of MCS presenting with a split-fat sign at MRI.

Corrigendum to "Juxta-articular extraskeletal myxoid chondrosarcoma mistaken for a benign cyst presenting with multiple lung metastases" [Radiology Case Reports 19 (2024) 684-690].

[This corrects the article DOI: 10.1016/j.radcr.2023.10.075.].

Juxta-articular extraskeletal myxoid chondrosarcoma mistaken for a benign cyst presenting with multiple lung metastases.

Extraskeletal myxoid chondrosarcoma (EMC) is a malignant cartilage neoplasm usually encountered in the proximal extremities. We report the case of a 58-year-old male who presented initially with a 3-month history of cough. Initial staging demonstrated a right upper lobe mass with bilateral pulmonary nodules and moderate tracer uptake in the right lung mass and right groin on positron emission tomography imaging. Endobronchial ultrasound biopsy confirmed a histological diagnosis of EMC for which the patient underwent right upper lobe wedge resection. Pelvic MRI revealed a peripherally enhancing juxta-articular lesion within the region of the right obturator externus bursa, which was thought initially to represent either a ganglion or paralabral cyst. However, ultrasound-guided biopsy yielded identical histology to the resected lung mass leading to the diagnosis of primary EMC in the right groin with pulmonary metastases. The patient underwent surgical excision of the right groin mass with no local recurrence on the surveillance computed tomography at 5, 12, and 18 months but eventual disease recurrence in the right groin and further progression of the pulmonary metastases at 29 months. We emphasize that the contrast enhancement pattern of EMC can mimic a benign cystic lesion, in particular, when in a juxta-articular location, which has the potential to mislead radiologists and delay diagnosis and definitive treatment.

A Fibroblastic Reticular Cell Tumour Arising in the Oral Cavity: A Case Report and Review of the Literature.

BACKGROUND: Tumours of dendritic or histiocytic lineage are amongst the rarest tumours and probably account for < 1% of tumours affecting the lymph nodes or soft tissue. Because several of these entities were poorly recognised until recently, the true incidence is not determined. METHODS: We present what we believe is the first reported case report of a fibroblastic reticular cell tumour arising in the oral cavity as well as reviewing the current literature regarding this rare subset of tumours. RESULTS: We discuss the clinical and histopathological findings of our reported case and examine the literature regarding this entity. We discuss the key differential diagnoses to consider when making this diagnosis. CONCLUSION: Histiocytic and dendritic cell derived tumours are exceptionally rare within the head and neck region although a number of these tumours have been reported within the oral cavity. We present what we believe is the first reported case of a fibroblastic reticular cell tumour arising within the oral cavity.

What is the evidence for the management of urethral amyloidosis? A systematic review of the literature.

UNLABELLED: What's known on the subject? and What does the study add? Urethral amyloidosis is rare and urethrotomy has been proposed as a suitable treatment option. By reviewing the literature and comparing our own experiences, we have shown urethroplasty to have good medium term outcomes in patients with urethral amyloidosis, whereas urethrotomy may lead to recurrence. OBJECTIVE: • Urethral amyloidosis (UA) is a rare condition which may be encountered by an urological surgeon. We reviewed the literature regarding the presentation, investigation and management of UA. PATIENTS AND METHODS: • A systematic review of the English literature on PubMed was conducted and we identified 39 articles which reported 45 patients. We included our experience with four patients from our tertiary centre. RESULTS: • The majority of patients reported symptoms consistent with a urethral structure. Most patients were treated with urethrotomy, only two patients have been reported to have had a urethroplasty in the literature. Medium and long term outcome data is lacking for urethrotomy and urethroplasty. We found recurrence in our patients after urethromoty and incomplete resection of UA. We describe short (6 month) and medium term (18 month) outcomes in two patients who underwent augmentation urethroplasty. CONCLUSION: • Although urethrotomy and dilatation have been proposed in the past, we found these may still lead to disease progression and therefore urethroplasty may be the most appropriate long term management option.

Osteoprotegerin (OPG) and related proteins (RANK, RANKL and TRAIL) in thyroid disease.

BACKGROUND: Osteoprotegerin (OPG), receptor activator of nuclear factor kappaB (RANK), RANK ligand (RANKL), and TNF related apoptosis inducing ligand (TRAIL) are the key proteins in the development of bone metastases. Osteoprotegerin improves tumor cell survival and inhibits TRAIL induced apoptosis of cancer cell lines. It also binds to RANKL and inhibits its interaction with RANK (cell surface receptor), which influences osteoclast formation and function. The aim of the present study was to characterize the expression of OPG, RANK, RANKL, and TRAIL in benign and malignant thyroid tissue and thyroid cell lines. METHODS: Archived thyroid tissue from 79 patients (60 differentiated thyroid cancers and 19 benign thyroids) was stained for OPG, RANK, RANKL, and TRAIL by immunohistochemistry. Staining was assessed semiquantitatively and correlated with pathology. Western blots were performed on three human thyroid cell lines: Nthy-ori 3-1 (thyroid follicular epithelium), FTC-133 (follicular thyroid carcinoma), and K1E7 (subclone of papillary thyroid carcinoma). RESULTS: Osteoprotegerin and RANKL staining was cytoplasmic; RANK staining was nuclear; and TRAIL staining was predominantly cytoplasmic. All four proteins were expressed in benign and malignant tissue. There was significant difference in RANK expression between malignant and benign tissue (8 vs. 84%, respectively; Fisher's exact test; P < 0.001). RANKL expression was significantly increased in malignant tissue (Fisher's exact test; P = 0.04). Western blotting showed OPG expression in all cell lines and TRAIL in none. RANK and RANKL were not detected in papillary and follicular cell lines, respectively. CONCLUSIONS: Nuclear expression of RANK protein in thyroid tissue is paradoxical; it could be due to nuclear migration after ligand binding. Suppression of RANK and increased expression of RANKL in malignant tissue warrant further investigation.

Identification and Validation of ERK5 as a DNA Damage Modulating Drug Target in Glioblastoma.

Brain tumours kill more children and adults under 40 than any other cancer, with approximately half of primary brain tumours being diagnosed as high-grade malignancies known as glioblastomas. Despite de-bulking surgery combined with chemo-/radiotherapy regimens, the mean survival for these patients is only around 15 months, with less than 10% surviving over 5 years. This dismal prognosis highlights the urgent need to develop novel agents to improve the treatment of these tumours. To address this need, we carried out a human kinome siRNA screen to identify potential drug targets that augment the effectiveness of temozolomide (TMZ)-the standard-of-care chemotherapeutic agent used to treat glioblastoma. From this we identified ERK5/MAPK7, which we subsequently validated using a range of siRNA and small molecule inhibitors within a panel of glioma cells. Mechanistically, we find that ERK5 promotes efficient repair of TMZ-induced DNA lesions to confer cell survival and clonogenic capacity. Finally, using several glioblastoma patient cohorts we provide target validation data for ERK5 as a novel drug target, revealing that heightened ERK5 expression at both the mRNA and protein level is associated with increased tumour grade and poorer patient survival. Collectively, these findings provide a foundation to develop clinically effective ERK5 targeting strategies in glioblastomas and establish much-needed enhancement of the therapeutic repertoire used to treat this currently incurable disease.

Orbital lipofibromatosis in a child: a case report.

PURPOSE: Lipofibromatosis is a rare, benign, soft tissue tumor that typically involves extremities particularly in children. We report a young girl with lipofibromatosis involving the superotemporal quadrant of the left orbit. CASE REPORT: An 8-year-old girl presented with a history of a gradually expanding mass in the superotemporal quadrant of the left orbit over several years. Orbital imaging showed a soft tissue mass superolateral to the globe with possible infiltration into the lacrimal gland and lateral rectus muscle. The lesion was excised preserving adjacent structures. Histopathological examination revealed that the lesion consisted of adipose tissue with fibroblastic elements, being consistent with a diagnosis of lipofibromatosis. No recurrence of the lesion was seen in 18 months follow-up. COMMENT: Orbital involvement of lipofibromatosis as reported here is indeed a very rare entity. Diagnosis can be confirmed by histopathological analysis. As the lesion has a tendency to infiltrate into surrounding structures, surgical excision without hampering important structures is a treatment of choice.

Paraneoplastic granulomatous vitritis and retinitis as a presentation of recurrent classical Hodgkin's lymphoma.

We describe a unique case of a patient with an established diagnosis of Hodgkin's lymphoma in clinical remission who later presented with apparent vitreous inflammation. A vitreous biopsy (including fortuitously some peripheral retinal fragments) exhibited granulomatous inflammation. Since the latter can be a paraneoplastic phenomenon of active Hodgkin's lymphoma in distant organ sites, the haematologists were alerted to the possibility of recurrent lymphoma, despite the patient having no clinical symptoms. Repeat body imaging showed enlarged mediastinal lymph nodes, biopsy of which confirmed recurrent Hodgkin's lymphoma. The patient responded well to systemic chemotherapy with resolution of the visual symptoms. This case report illustrates the importance of vitreous biopsy in this clinical setting and how to interpret the significance of granulomas in this context, and outlines a unique vitreo-retinal paraneoplastic granulomatous presentation in the setting of recurrent Hodgkin's lymphoma and how this diagnosis triggered a prompt review of the patient who had no constitutional symptoms, with hopefully a favourable impact on prognosis given the early recurrent disease detection.

Microarray RNA expression analysis of cerebral white matter lesions reveals changes in multiple functional pathways.

BACKGROUND AND PURPOSE: White matter lesions (WML) in brain aging are linked to dementia and depression. Ischemia contributes to their pathogenesis but other mechanisms may contribute. We used RNA microarray analysis with functional pathway grouping as an unbiased approach to investigate evidence for additional pathogenetic mechanisms. METHODS: WML were identified by MRI and pathology in brains donated to the Medical Research Council Cognitive Function and Ageing Study Cognitive Function and Aging Study. RNA was extracted to compare WML with nonlesional white matter samples from cases with lesions (WM[L]), and from cases with no lesions (WM[C]) using RNA microarray and pathway analysis. Functional pathways were validated for selected genes by quantitative real-time polymerase chain reaction and immunocytochemistry. RESULTS: We identified 8 major pathways in which multiple genes showed altered RNA transcription (immune regulation, cell cycle, apoptosis, proteolysis, ion transport, cell structure, electron transport, metabolism) among 502 genes that were differentially expressed in WML compared to WM[C]. In WM[L], 409 genes were altered involving the same pathways. Genes selected to validate this microarray data all showed the expected changes in RNA levels and immunohistochemical expression of protein. CONCLUSIONS: WML represent areas with a complex molecular phenotype. From this and previous evidence, WML may arise through tissue ischemia but may also reflect the contribution of additional factors like blood-brain barrier dysfunction. Differential expression of genes in WM[L] compared to WM[C] indicate a "field effect" in the seemingly normal surrounding white matter.

Adult-Type Rhabdomyoma of the Larynx in Birt-Hogg-Dubé Syndrome: Evidence for a Real Association.

The autosomal dominant Birt-Hogg-Dubé syndrome is known to be associated with skin, lung and kidney lesions. It is caused by heterozygous germline mutations in the folliculin gene and has a high penetrance. We report the case of a 51 year old woman with Birt-Hogg-Dubé syndrome who presented with a laryngeal mass. Imaging confirmed a mass centered on the piriform sinus and following excision histological examination confirmed the lesion was composed of polygonal cells with abundant eosinophilic cytoplasm consistent with a rhabdomyoma. Laryngeal rhabdomyoma is rare condition and has not been previously described in association with Birt-Hogg-Dubé. In patients with Birt-Hogg-Dubé syndrome who develop upper aerodigestive tract symptoms secondary to mass lesion an adult-type rhabdomyoma might be considered as a differential, with endoscopic excision being the treatment of choice.

Two cases of spontaneous remission of primary hyperparathyroidism due to auto-infarction: different management and their outcomes.

Spontaneous remission of primary hyperparathyroidism (PHPT) due to necrosis and haemorrhage of parathyroid adenoma, the so-called 'parathyroid auto-infarction' is a very rare, but previously described phenomenon. Patients usually undergo parathyroidectomy or remain under close clinical and biochemical surveillance. We report two cases of parathyroid auto-infarction diagnosed in the same tertiary centre; one managed surgically and the other conservatively up to the present time. Case #1 was a 51-year old man with PHPT (adjusted (adj.) calcium: 3.11 mmol/L (reference range (RR): 2.20-2.60 mmol/L), parathyroid hormone (PTH) 26.9 pmol/L (RR: 1.6-6.9 pmol/L) and urine calcium excretion consistent with PHPT) referred for parathyroidectomy. Repeat biochemistry 4 weeks later at the surgical clinic showed normal adj. calcium (2.43 mmol/L) and reduced PTH. Serial ultrasound imaging demonstrated reduction in size of the parathyroid lesion from 33 to 17 mm. Twenty months later, following recurrence of hypercalcaemia, he underwent neck exploration and resection of an enlarged right inferior parathyroid gland. Histology revealed increased fibrosis and haemosiderin deposits in the parathyroid lesion in keeping with auto-infarction. Case #2 was a 54-year-old lady admitted with severe hypercalcaemia (adj. calcium: 4.58 mmol/L, PTH 51.6 pmol/L (RR: 1.6-6.9 pmol/L)) and severe vitamin D deficiency. She was treated with intravenous fluids and pamidronate and 8 days later developed symptomatic hypocalcaemia (1.88 mmol/L) with dramatic decrease of PTH (17.6 pmol/L). MRI of the neck showed a 44 mm large cystic parathyroid lesion. To date, (18 months later), she has remained normocalcaemic. Learning points: Primary hyperparathyroidism (PHPT) is characterised by excess parathyroid hormone (PTH) secretion arising mostly from one or more autonomously functioning parathyroid adenomas (up to 85%), diffuse parathyroid hyperplasia (<15%) and in 1-2% of cases from parathyroid carcinoma. PHPT and hypercalcaemia of malignancy, account for the majority of clinical presentations of hypercalcaemia. Spontaneous remission of PHPT due to necrosis, haemorrhage and infarction of parathyroid adenoma, the so-called 'parathyroid auto-infarction', 'auto-parathyroidectomy' or 'parathyroid apoplexy' is a very rare in clinical practice but has been previously reported in the literature. In most cases, patients with parathyroid auto-infarction undergo parathyroidectomy. Those who are managed conservatively need to remain under close clinical and biochemical surveillance long-term as in most cases PHPT recurs, sometimes several years after auto-infarction.

The management of deep-seated, lowgrade lipomatous lesions.

Deep-seated, low-grade lipomatous lesions detected on imaging often cause uncertainty for diagnosis and treatment. Confidently distinguishing lipomas from well-differentiated liposarcomas is often not possible on imaging. The approach to management of such lesions varies widely between institutions. Applying an evidenced-based approach set around published literature that clearly highlights how criteria such as lesion size, location, age and imaging features can be used to predict the risk of well-differentiated liposarcomas and subsequent de-differentiation would seem sensible. Our aim is to review the literature and produce a unified, evidence-based guideline that will be a useful tool for managing these lesions.