Background and purpose — Tenosynovial giant cell tumors (TGCT) are rare, benign tumors, arising in synovial lining of joints, tendon sheaths, or bursae. 2 types are distinguished: localized, either digits or extremity, and diffuse lesions. Current TGCT incidence is based on 1 single US-county study in 1980, with an incidence of 9 and 2 per million person-years in localized (including digits) and diffuse TGCT, respectively. We aim to determine nationwide and worldwide incidence rates (IR) in TGCT affecting digits, localized-extremity TGCT and diffuse-type TGCT.Material and methods — Over a 5-year period, the Dutch Pathology Registry (PALGA) identified 4,503 pathology reports on TGCT. Reports affecting digits were solely used for IR calculations. Reports affecting extremities were clinically evaluated. Dutch IRs were converted to world population IRs.Results — 2,815 (68%) digits, 933 (23%) localized-extremity and 390 (9%) diffuse-type TGCT were identified. Dutch IR in digits, localized-extremity, and diffuse-type TGCT was 34, 11 and 5 per million person-years, respectively. All 3 groups showed a female predilection and highest number of new cases in age category 40–59 years. The knee joint was most often affected: localized-extremity (46%) and diffuse-type (64%) TGCT, mostly treated with open resection: localized (65%) and diffuse (49%). Reoperation rate due to local recurrence for localized-extremity was 9%, and diffuse TGCT 23%.Interpretation — This first nationwide study and detailed analyses of IRs in TGCT estimated a worldwide IR in digits, localized-extremity and diffuse TGCT of 29, 10, and 4 per million person-years, respectively. Recurrence rate in diffuse type is 2.6 times higher, compared with localized extremity. TGCT is still considered a rare disease; however, it is more common than previously understood.

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BackgroundRecently, the phase III PALETTE study introduced pazopanib (Votrient®) as treatment for adult patients with locally advanced or metastatic non-liposarcoma soft tissue sarcoma after prior treatment with doxorubicin and/or ifosfamide. Pneumothorax was reported as adverse event in 8 of 246 treated patients (3.3%) in that study. This case series presents the incidence and clinic of this complication in the Leiden University Medical Centre.CasesForty-three patients were treated with pazopanib of which six patients (14.0%) developed a pneumothorax. These six patients were treated for malignant peripheral nerve sheath tumour, angiosarcoma, synovial sarcoma, fibromyxomatoid sarcoma, pleomorphic sarcoma and endometrial stromal sarcoma. All six patients had subpleural pulmonary or pleural metastases at the start of pazopanib and the pneumothorax developed during or shortly after treatment with pazopanib and was difficult to treat.DiscussionThe incidence reported by us is higher than the incidence in the PALETTE study. Trials with pazopanib in renal cell carcinoma, urothelial carcinoma and cervix carcinoma did not report pneumothorax as an adverse event, suggesting pneumothorax as a specific adverse event in soft tissue sarcoma patients treated with pazopanib. This may be related to the fact that there is often pleural metastatic involvement and cystic degeneration due to pazopanib treatment may add to the risk.ConclusionThe risk of an, often difficult to treat, pneumothorax during pazopanib therapy should be discussed with the patient before initiation of treatment for a pulmonary metastasized sarcoma and physicians should be alert to the occurrence of such an event.

Symptomatic gastrointestinal stromal tumours (GIST) are infrequent with an incidence of 12.7 per million inhabitants in the western population. We studied whether the incidence of GIST has further increased between 2003 and 2012 and assessed the frequency of mutations, risk groups, histological subtypes and immunohistochemistry results. From PALGA, the nationwide Dutch Pathology Registry, pathology excerpts from all patients with a GIST or GIST-like tumour between 2003 and 2012 were retrieved to calculate incidence rates. Full pathology reports were retrieved of resections in 2011 and 2012 to study the frequency of mutations, risk groups, histological subtypes and immunohistochemistry results. The incidence of GIST increased to 17.7 per million inhabitants in 2012 with a median age of 67 years. Mutational analysis was performed in 33.9% of patients with a resection between 2011 and 2012 (KIT mutation 67.5%, PDGFRA 16.3%, wild-type 11.4%). The percentage of high risk patients in the different risk classifications varied from 19.9% to 38.0% depending on the used classification. Only 35.9% of patients had diagnosis or revision of pathology diagnosis within three months in a designated GIST referral centre. No increase in proportion of central pathology reviews was found. Proportion of patients with mutational analysis increased over the years. The registered incidence of GIST, 17.7 per million inhabitants in 2012 in the Netherlands, is still rising. Despite incorporation in the ESMO GIST guidelines since 2008 for mutational testing and since 2010 for central review of pathology, both are performed in a minority of patients.Electronic supplementary materialThe online version of this article (10.1007/s00428-017-2285-x) contains supplementary material, which is available to authorized users.

Background and purpose — Giant cell tumors of bone (GCT-B) are rare, locally aggressive tumors characterized by an abundance of giant cells. Incidence studies for GCT-B are rare. This is the first study using a fully automated 100% covering pathology database, the nationwide Dutch Pathology Registry (17 million inhabitants), PALGA, to calculate incidence rates for GCT-B.Patients and methods — From PALGA, all pathology excerpts were retrieved for patients diagnosed with GCT-B, giant cell tumors of tenosynovium, and giant cell tumors of soft tissue between January 1, 2009 and December 31, 2013. The incidence of GCT-B was calculated.Results — In total, 8,156 excerpts of 5,922 patients were retrieved; these included 138 first GCT-B diagnosis. For GCT-B the incidence was 1.7 per million inhabitants per year with a male to female ratio of 1:1.38 and a median age of 35 years (9–77). Most common localization was the femur (35%), followed by the tibia (18%). No differences in localization according to age and sex were found. The incidence rate of local recurrence was 0.40 per million inhabitants per year.Interpretation — This is the first nationwide study reporting the incidence of GCT-B, based on a nationwide pathology database with 100% coverage of pathology departments. Current incidence calculations are based only on doctor-driven registries. We confirmed that GCT-B is a rare disease with an incidence that is slightly higher than previously published. The relatively young median age of patients and the high incidence of recurrence stresses the importance of developing more effective treatments for this disease.

Introduction Nonsurgical management of patients with desmoid-type fibromatosis (DF) is increasing. This study tries to provide insight on type, usage, and outcome of first-line nonsurgical management strategies. Patients and Methods From the Dutch Pathology Registry (PALGA), patients with extra-abdominal or trunk/abdominal wall DF, diagnosed between 1993 and 2013, were identified. First-line treatment was analyzed. Best response (BR) using RECIST criteria from start of treatment/surveillance until change of treatment or last follow-up was analyzed. Results Ninety-one of the 1141 identified patients had first-line nonsurgical management. The percentage of patients treated nonsurgically increased from 0.6% in 1993–1998 to 12.8% in 2009–2013. Thirty-seven patients had surveillance (41%), 35 radiotherapy (38%), and 19 systemic treatment (21%). BR for surveillance was complete response (CR) in 2/37, partial response (PR) in 4/37, stable disease (SD) in 21/37, progressive disease (PD) in 5/37, and unknown in 5/37 patients. BR for radiotherapy was CR in 4/35, PR in 11/35, SD in 16/35, and unknown in 4/35. BR for systemic treatment was CR in 1/19, PR in 1/19, SD in 10/19, PD in 2/19, and unknown in 5/19. Totally, 91% of patients did not progress. Discussion Given the low percentage (9%) of PD of nonsurgical management, these data can be used in shared decision making with the patient regarding optimal treatment.

Background: Home treatment of cancer-associated venous thromboembolism (VTE) is challenging due to the high risk of adverse events. While home treatment is quite agreeable to cancer patients, studies evaluating the safety of VTE home treatment in this setting are largely unavailable. Methods: This was an observational study in patients with cancer-associated VTE. The main outcomes were the proportion of patients treated at home (hospital discharge < 24 h after diagnosis) and the 3-month incidence of VTE-related adverse events (major bleeding, recurrent VTE and/or suspected VTE-related mortality) in patients managed in hospital versus at home. Results: A total of 183 outpatients were diagnosed with cancer-associated VTE: 69 had deep vein thrombosis (DVT) and 114 had pulmonary embolism (PE ± DVT). Of those, 120 (66%) were treated at home; this was 83% for patients with DVT and 55% for patients with PE ( ± DVT). The 3-month incidence of any VTE-related adverse event was 13% in those treated at home versus 19% in the hospitalized patients (HR 0.48; 95%CI 0.22-1.1), independent of initial presentation as PE or DVT. All-cause 3-month mortality occurred in 33 patients treated as inpatient (54%) compared to 29 patients treated at home (24%; crude HR 3.1 95%CI 1.9-5.0). Conclusions: Two-third of patients with cancer-associated VTE -including PE -were selected to start anticoagulant treatment at home. Cancer-associated VTE is associated with high rates of VTE-related adverse events independent of initial in hospital or home treatment. However, home treatment may be a good option for selected patients with cancer-associated DVT or PE.

This large retrospective database study shows that patients with advanced STSs treated with first-line chemotherapy with locally advanced disease, metastatic disease and both local and metastatic disease have different outcomes. This should be accounted for in future study design, interpretation and comparison of study results and daily practice.