Spindle cell neoplasms with novel LTK fusion - Expanding the spectrum of kinase fusion-positive soft tissue tumors.

AIMS: Kinase fusion-positive soft tissue tumors represent an emerging, molecularly defined group of mesenchymal tumors with a wide morphologic spectrum and diverse activating kinases. Here, we present two cases of soft tissue tumors with novel LTK fusions. METHODS AND RESULTS: Both cases presented as acral skin nodules (big toe and middle finger) in pediatric patients (17-year-old girl and 2-year-old boy). The tumors measured 2 and 3 cm in greatest dimension. Histologically, both cases exhibited bland-looking spindle cells infiltrating adipose tissue and accompanied by collagenous stroma. One case additionally displayed perivascular hyalinization and band-like stromal collagen. Both cases exhibited focal S100 staining, and one case had patchy coexpression of CD34. Targeted RNA-seq revealed the presence of novel in-frame MYH9::LTK and MYH10::LTK fusions, resulting in upregulation of LTK expression. Of interest, DNA methylation-based unsupervised clustering analysis in one case showed that the tumor clustered with dermatofibrosarcoma protuberans (DFSP). One tumor was excised with amputation with no local recurrence or distant metastasis at 18-month follow-up. The other case was initially marginally excised with local recurrence after one year, followed by wide local excision, with no evidence of disease at 10 years of follow-up. CONCLUSIONS: This is the first reported case series of soft tissue tumors harboring LTK fusion, expanding the molecular landscape of soft tissue tumors driven by activating kinase fusions. Furthermore, studies involving a larger number of cases and integrated genomic analyses will be warranted to fully elucidate the pathogenesis and classification of these tumors.

A single-cell atlas of conventional central chondrosarcoma reveals the role of endoplasmic reticulum stress in malignant transformation.

The transformation of benign lesions to malignant tumours is a crucial aspect of understanding chondrosarcomas, which are malignant cartilage tumours that could develop from benign chondroid lesions. However, the process of malignant transformation for chondroid lesions remains poorly understood, and no reliable markers are available to aid clinical decision-making. To address this issue, we conducted a study analysing 11 primary cartilage tumours and controls using single-cell RNA sequencing. By creating a single-cell atlas, we were able to identify the role of endoplasmic reticulum (ER) stress in the malignant transformation of conventional central chondrosarcomas (CCCS). Our research revealed that lower levels of ER stress promote chondrosarcoma growth in a patient-derived xenograft mouse model, while intensive ER stress reduces primary chondrosarcoma cell viability. Furthermore, we discovered that the NF-κB pathway alleviates ER stress-induced apoptosis during chondrosarcoma progression. Our single-cell signatures and large public data support the use of key ER stress regulators, such as DNA Damage Inducible Transcript 3 (DDIT3; also known as CHOP), as malignant markers for overall patient survival. Ultimately, our study highlights the significant role that ER stress plays in the malignant transformation of cartilaginous tumours and provides a valuable resource for future diagnostic markers and therapeutic strategies.

Novel MAP4::RAF1 Fusion in a Primary Bone Sarcoma: Expanding the spectrum of RAF1 Fusion Sarcoma.

Soft tissue tumors with RAF1 fusion had been emerging as a group of tumors with peculiar histology and immunoprofile. While a case series and rare case reports of RAF1 translocated sarcoma had been reported, to our knowledge a primary bone tumor with RAF1 translocation and fusion partner with MAP4 had not been described in the literature. The patient was a 60-year-old lady, with strong family history of breast cancer, who presented with pathological fracture of right humerus. X-ray revealed a 9.7 cm juxta-articular lesion of the proximal humerus, which was expansile and lytic with a non-sclerotic well defined border distally, radiologically suggestive of a giant cell tumor of bone. Excision was performed after initial biopsy. Histology showed a monomorphic low grade spindle cell lesion with prominent hyalinized stroma. Immunohistochemistry demonstrated diffuse CD34 staining, with focal staining for S100. Gene sequencing for histone 3 H3 genes was negative for hotspot mutation. Targeted RNA-seq sequencing revealed the presence of MAP4::RAF1 fusion, which was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) and fluorescence in-situ hybridization (FISH) break-apart probes involving both genes. The overall features were consistent with a primary bone sarcoma with RAF1 fusion. This report expanded the spectrum of RAF1 fusion sarcoma and was the first report documenting its primary occurrence in bone.

KRAS Mutation Testing on Endoscopic Ultrasound-Guided Fine-Needle Aspiration Samples Improves the Diagnostic Accuracy of Pancreatic Cancer.

OBJECTIVES: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) cytology was one of the investigations for pancreatic masses. While the specificity approached 100%, its sensitivity remained low because of high rate of indeterminate and false-negative results. Meanwhile, KRAS gene was frequently mutated in up to 90% of pancreatic ductal adenocarcinoma and its precursor lesions. This study aimed to determine whether KRAS mutation analysis could improve the diagnostic sensitivity in EUS-FNA samples for pancreatic adenocarcinoma. METHODS: The EUS-FNA samples from patients with a pancreatic mass obtained between January 2016 and December 2017 were reviewed retrospectively. The cytology results were classified as malignant, suspicious for malignancy, atypical, negative for malignancy, and nondiagnostic. KRAS mutation testing was performed using polymerase chain reaction followed by Sanger sequencing. RESULTS: A total of 126 EUS-FNA specimens were reviewed. The overall sensitivity and specificity by cytology alone were 29% and 100%, respectively. When KRAS mutation testing was performed in cases with indeterminate and negative cytology, the sensitivity increased to 74.2%, and the specificity remained at 100%. CONCLUSIONS: KRAS mutation analysis, especially when performed in cytologically indeterminate cases, improves the diagnostic accuracy for pancreatic ductal adenocarcinoma. This may reduce the need to repeat invasive EUS-FNA for diagnosis.

Case report on metastatic pelvic bone tumor treated with frozen autograft by liquid nitrogen.

INTRODUCTION AND IMPORTANCE: Frozen autograft recycling has been used for biological reconstruction of bone defects following tumor excision, more commonly in extremities. We report on the histological outcome of a pelvic recycled frozen autograft. CASE PRESENTATION: We investigated the pelvic frozen autograft removed in 2 years and 8 months after surgery because of soft tissue recurrence in pelvic floor. The autograft bone showed no evidence of revitalization and was non-viable with patchy inflammation, and no residual tumor. There was only fibrous union but the autograft bone remained mechanically stable. CLINICAL DISCUSSION: We confirmed the clearance of tumor cells with the treatment with liquid nitrogen. The union at the host-graft junction might be affected by the previous radiotherapy, the presence of infection, the small contact area limited by the anatomy, and the inadequate compression across the osteotomy interface with the fixation. CONCLUSION: Frozen autograft treated by liquid nitrogen can be used safely for biological reconstructions after pelvic tumor excision.

Imaging of intramuscular haemangiomas of the extremities.

Intramuscular haemangiomas are benign soft tissue tumours that are more frequently seen in children and young adults. As they may be difficult to diagnose clinically, imaging has an important role in the detection, diagnosis and preoperative planning of these lesions. Haemangiomas of the extremities may be classified into capillary, cavernous, venous and mixed types, with or without an arteriovenous shunt, depending on the predominant vascular channels. Nonvascular components such as fat, smooth muscle, fibrous tissue and thrombus may also be present. This pictorial essay highlights the imaging features of intramuscular haemangiomas, with an emphasis on magnetic resonance imaging.

Transfer of the anterior gluteus maximus to address abductor deficiency following soft tissue tumour excision.

Hip abductor deficiency is most commonly encountered in the context of degeneration of the hip, and techniques for reconstruction pioneered by arthroplasty surgeons. We adopted a local muscle transfer technique utilizing the anterior half of the gluteus maximus for abductor reconstruction following soft tissue tumour excision in a young female patient. The patient of concern had a solitary fibrous tumour located between the right gluteus medius and minimus detected as an incidental finding. Marginal excision of the mass resulted in removal of the gluteus medius. The anterior half of the gluteus maximus was transferred and attached to the decorticated lateral greater trochanter by means of suture anchors and transosseous sutures. The patient initially demonstrated a Trendelenburg gait and limited abduction against gravity. By 1-year post-operation, there was return of normal gait and recovery of hip abductor power. This is the first report of anterior gluteus maximus transfer being successfully applied for soft tissue reconstruction around the hip subsequent to tumour excision.

Co-existing malignant lesions in atypical ductal hyperplasia - Pathology, probability, predictors and prognosis.

BACKGROUND: Atypical ductal hyperplasia (ADH) is known to be associated with underlying malignant breast conditions. Previous studies have shown that up to 40% of ADH found in core needle biopsy of the breasts had undiagnosed malignant lesions after excision. METHODS: This is a retrospective study on a prospectively maintained database. From 1st January 2005 to 31st December 2014, a total of 262 excision or mastectomy specimens were identified to contain ADH. Clinical, radiological and pathological data were retrieved and analyzed. Correlating factors for the presence of co-existing pre-malignant or malignant conditions were analyzed. Overall survival in patients with or without co-existing malignant breast lesions were evaluated. RESULTS: 95 (36.3%) had co-existing malignant breast lesions within the same specimen. The median age at diagnosis was 49 (Range 17-85). Suspicious breast imaging features (BIRADS 4 or above) and lesions larger than 10 mm on breast imaging were independent risk factor for co-existing malignant pathology (p < 0.001 and 0.005 respectively). After median follow-up interval of 60 months (6-120 months), the overall survival was comparable between the groups of patients having ADH with or without co-existing malignant pathologies (98.2% and 97.9% respectively). CONCLUSION: Co-existing malignant lesions were present in up to 36.3% of the pathology specimens containing ADH, in which its presence could be predicted by pre-operative breast imaging.

Idiopathic granulomatous mastitis: a 10-year study from a multicentre clinical database.

Idiopathic granulomatous mastitis (IGM) is an uncommon, chronic inflammatory breast disease with elusive aetiology, simulating malignancy clinically and radiologically. Here we present our 10-year review on a region-wide multicentre IGM database. A retrospective study was performed on a prospectively maintained database from three University affiliated hospitals in Hong Kong and Shenzhen, China. All patients with biopsy proven IGM were included while patients with positive culture of Mycobacterium tuberculosis were excluded. Disease recurrence rate and its prognosticators were evaluated. A total of 102 patients were included between January 2007 and December 2017. Median age was 33 years (range 20-54). Most patients presented with painful inflammatory mass (n = 57); median size at presentation was 37 mm (6-92 mm). Sixty-three patients had bacterial culture performed on the pus sample: eight patients had Corynebacterium kroppenstedtii while four had Corynebacterium species not otherwise specified. Seventy-seven (75.5%) patients received conservative treatment with oral corticosteroid (±antibiotics) and drainage only, while 25 (24.5%) patients received breast lump excision after initial medical treatment. Twelve (11.8%) patients developed recurrence after a median follow-up interval of 14 months (4-51 months). Univariate analysis revealed that abscess on presentation, history of smoking, and presence of C. kroppenstedtii were significant prognosticators for recurrence. Subsequent multivariate analysis with logistic regression revealed cigarette smoking and isolation of C. kroppenstedtii as independent risk factors for disease recurrence (p < 0.05). In conclusion, IGM is uncommon with a recurrence rate of 12%, especially in patients with history of smoking and isolation of C. kroppenstedtii.

Genetic and clonal dissection of osteosarcoma progression and lung metastasis.

Osteosarcoma is a primary malignant bone tumor that has a high potential to metastasize to lungs. Little is known about the mechanisms underlying the dissemination of OS cancer cells to lungs. We performed whole exome sequencing of 13 OS primary tumors, with matched lung metastases and normal tissues. Phylogenetic analyses revealed that lung metastatic tumors often harbor clones that are nonexistent or rare in the matched primary OS tumors. Spatially and temporally separated lung metastases were from parallel seeding events with a polyphyletic pattern. Loss of TP53 or RB1 is among the early events during OS tumorigenesis, while loss of PTEN is involved at the later stages associated with lung metastases. Finally, KEAP1 was identified as a novel biomarker for increased metastatic risk. Patients whose primary tumors harbored KEAP1 amplification have significantly poorer lung-metastasis free survival. This finding was validated in two independent datasets. Further, in vitro experiments exhibited that KEAP1 depletion suppressed the invasion of OS cells. Our findings uncover the patterns of clonal evolution during OS progression and highlight KEAP1 as a novel candidate associated with the risk of lung metastasis in OS patients.

Factors affecting the under-diagnosis of atypical ductal hyperplasia diagnosed by core needle biopsies - A 10-year retrospective study and review of the literature.

INTRODUCTION: Due to the possibility of underestimation, surgical excision is usually offered to patients with atypical ductal hyperplasia (ADH) diagnosed with core needle biopsy (CNB). Here we review the 10-year data of patients with ADH diagnosed by CNB, aiming to identify the factors associated with under-diagnosis. METHODS: Retrospective review of database from 1st Jan 2005 to 31st Dec 2014 was performed; patients with ADH diagnosed by CNB were identified. Diagnosis upgrade rate and its risk factors were evaluated. RESULTS: 104 patients were found to have ADH on CNB, 101 patients received excisional biopsy while 3 patients refused operation. 34 patients had ductal carcinoma in situ (DCIS) after excision, 6 had invasive ductal carcinoma, 1 had lobular carcinoma in situ and 1 had angiosarcoma. CNB under-diagnosed up to 41.6% of malignant lesions. Breast mass on presentation and suspicious mammograms (BIRADS ≥ 4) are associated with diagnosis upgrade (P = 0.0005, 0.0001). Literature review of 39 studies between 1997 and 2017 revealed 3125 excision procedures performed for ADH diagnosed by CNB, the pooled median diagnosis upgrade rate was 25% (Range 4-54%). CONCLUSION: We recommend excision in all patients with ADH diagnosed by CNB, especially in patients with suspicious mammographic features.

Effect of Thyroid Remnant Volume on the Risk of Hypothyroidism After Hemithyroidectomy: A Prospective Study.

BACKGROUND: Hypothyroidism is a common sequel after a hemithyroidectomy. Although various risk factors leading to hypothyroidism have been reported, the effect of the contralateral lobe's volume has been understudied. This study aimed to examine the association between the preoperative contralateral lobe's volume and the risk of postoperative hypothyroidism. METHODS: During a 2-year period, 150 eligible patients undergoing a hemithyroidectomy were evaluated. The volume of the contralateral nonexcised lobe was estimated preoperatively by independent assessors on ultrasonography using the following formula: width (in cm) × depth (in cm) × length (in cm) × (π/6), adjusted for the body surface area (BSA). Postoperative hypothyroidism was defined as serum thyroid-stimulating hormone (TSH) exceeding 4.78 mIU/L. Any significant characteristics in the univariate analysis were entered into the multivariate analysis to determine independent factors. RESULTS: After a mean follow-up period of 53.5 ± 9.4 months, 44 patients (29.3 %) experienced postoperative hypothyroidism, and 10 of these patients required thyroxine replacement. Hypothyroidism was associated with a higher preoperative TSH level (p < 0.001), a smaller BSA-adjusted volume (p < 0.001), fewer ipsilateral nodules (p = 0.037), and the presence of thyroiditis (p = 0.050). After adjustment for thyroiditis, preoperative TSH (p < 0.001), number of ipsilateral nodules (p = 0.048), and BSA-adjusted volume (p < 0.001) were independent factors for hypothyroidism. Patients with a BSA-adjusted volume smaller than 3.2 ml had a threefold greater hypothyroidism risk than those with a BSA-adjusted volume of 3.2 ml or more (p < 0.001). CONCLUSIONS: A significant inverse association between the preoperative contralateral lobe's volume and hypothyroidism risk was observed after hemithyroidectomy. Together with a higher preoperative TSH level and fewer ipsilateral nodules, a smaller BSA-adjusted volume measured by preoperative ultrasonography independently predicted hypothyroidism.

Significance of Size of Persistent/Recurrent Central Nodal Disease on Surgical Morbidity and Response to Therapy in Reoperative Neck Dissection for Papillary Thyroid Carcinoma.

BACKGROUND: To balance the risk of disease progression, morbidity, and efficacy of reoperative central neck dissection (RCND) in papillary thyroid carcinoma, the latest clinical guidelines recommend early surgery over surveillance when the largest diseased node is >8 mm in its smallest dimension. However, the evidence remains scarce. To determine an appropriate size for first-time RCND, the relationship between size of largest diseased central node, morbidity, and response-to-therapy following RCND was examined. METHODS: A total of 130 patients who underwent RCND following initial surgery for persistent/recurrent nodal disease were reviewed. Patients with largest diseased central node measured preoperatively by ultrasonography were included. Eligible patients were categorized into three groups: largest central node <10 mm (group I), 10-15 mm (group II), and >15 mm (group III). Surgical morbidity and response to therapy at one year after RCND were compared between groups. To evaluate biochemical response, patients with structural incompleteness were excluded. RESULTS: Group III not only had significantly more high-risk tumors (by American Thyroid Association risk stratification) at initial therapy (64.5% vs. 44.4%, respectively; p = 0.038), but this group also a higher risk of extranodal extension (35.5% vs. 16.0%; p = 0.055), recurrent laryngeal nerve involvement (19.4% vs. 0.0%; p < 0.001), incomplete surgical resection (48.4% vs. 7.4%; p < 0.001), new-onset vocal cord paresis (16.7% vs. 2.5%; p = 0.017), overall surgical morbidity (22.6% vs. 7.4%; p = 0.021), and biochemical incompleteness (80.6% vs. 67.9%; p = 0.004) than groups I and II combined did. However, overall morbidity did not differ between groups I and II (5.7% vs. 8.7%; p = 0.694). After adjusting for American Thyroid Association risk stratification, only the size of the largest diseased central node ≥15 mm (odds ratio = 7.256 [confidence interval 1.302-40.434], p = 0.001) was an independent risk factor for biochemical incompleteness following RCND. CONCLUSIONS: Patients with larger diseased central node(s) had a significantly higher risk of local invasion, surgical morbidity, and biochemical incompleteness. Relative to nodal size <10 mm, size >15 mm in the largest disease central node was an independent risk factor for incomplete biochemical response, while nodal size 10-15 mm was not. These findings imply that the recommended threshold of 8 mm might be too stringent and could be raised to 15 mm without increasing the surgical morbidity from RCND.

The significance of unrecognized histological high-risk features on response to therapy in papillary thyroid carcinoma measuring 1-4 cm: implications for completion thyroidectomy following lobectomy.

BACKGROUND: Although lobectomy is an alternative to total thyroidectomy (TT) for 1-4 cm papillary thyroid carcinoma (PTC) without high-risk features (HRFs) such as aggressive histology, vascular invasion, lymphovascular invasion (LVI), microscopic extrathyroidal extension, positive margin, nodal metastasis >5 mm and multifocality, these HRFs are not recognized until after surgery. Therefore, the chance of completion TT being required following lobectomy might be high. We evaluated the frequency of unrecognized HRFs and how they affected the response to therapy following TT and radioiodine (RAI). METHODS: Altogether, 1513 patients were analysed. Only 1-4 cm PTCs without recognizable HRFs were included. For response-to-therapy evaluation, only patients who had TT and post-RAI-stimulated thyroglobulin were analysed. Patients without an excellent response were defined as having 'incomplete response'. A multivariate analysis for incomplete response was performed. RESULTS: Of the 600 patients eligible for lobectomy, 257 (42·8%) had ≥1 unrecognized histological HRF before surgery. The prevalence of unrecognized HRFs was similar between 1-2 cm and >2-4 cm PTCs (P = 0·393). Of the 330 patients eligible for response-to-therapy evaluation, 260 (78·8%) had an excellent response while 70 (21·2%) had an incomplete response. LVI was the only independent unrecognized HRF for incomplete response (P = 0·021). CONCLUSIONS: The prevalence of unrecognized histological HRFs under the current recommendations is relatively high among 1-4 cm PTCs. Among the unrecognized histological HRFs, LVI was the only one which independently associated with an incomplete response (i.e. posing an increased risk of persistent/recurrent disease after curative surgery). These findings may have implications for patients who undergo lobectomy for 1-4 cm PTCs with no clinically recognizable HRFs under the current recommendations.

The total number of tissue blocks per centimetre of tumor significantly correlated with the risk of distant metastasis in patients with minimally invasive follicular thyroid carcinoma.

BACKGROUND: Given that careful histological examination plays a pivotal role in follicular thyroid carcinoma categorization, we hypothesize that the number of blocks taken at initial specimen review may be associated with survival outcomes of patients initially diagnosed with minimally invasive follicular thyroid carcinoma. METHODS: A total of 162 patients with confirmed minimally invasive follicular thyroid carcinoma were analyzed. The number of tissue blocks taken from each patient was recorded and the number of blocks per each centimeter of tumor was calculated. A multivariate analysis was conducted to identify independent factors for distant metastasis-free survival. RESULTS: After a mean follow-up of 197.88 ± 155.39 months, 7 (4.3%) patients developed distant metastasis during follow-up (group II). Relative to those who remained disease-free (group I), group II were significantly older at initial operation (p = 0.022), had larger tumors (p = 0.002) and fewer number of blocks taken/cm of tumor (p = 0.001). However, after adjusting for age at initial operation and tumor size, total number of tissue blocks taken/cm of tumor was the only independent determinant for distant metastasis-free survival (p = 0.049). The 10-year distant metastasis-free survival was significantly better in those who had ≥ 4 blocks/cm of tumor (n = 82) than those with ≤ 3 block/cm of tumor (n = 80) (100 vs. 84.7%, p = 0.005, by log rank). CONCLUSIONS: Although our study was not able to identify the precise cause for the association between the total number of tissue blocks taken/cm of tumor and distant metastasis-free survival, our data support a more liberal approach in taking tissue blocks on thyroid nodules especially those showing well-differentiated follicular cell differentiation.

Does microscopically involved margin increase disease recurrence after curative surgery in papillary thyroid carcinoma?

BACKGROUND: The prognostic significance of microscopically involved margin in papillary thyroid carcinoma (PTC) following curative surgery remains unclear. We aimed to evaluate the impact of an involved margin and its location (anterior vs. posterior) on disease recurrence. METHODS: Of the 638 eligible patients, 538 (85.9%) did not have an involved margin (group I) while 100 (14.1%) did (group II). The latter group was further classified according to its location relative to the surface of the thyroid gland (anterior or posterior). A multivariate analysis was conducted to identify independent factors for recurrence risk. RESULTS: After a mean of 130.1 ± 93.5 months, 22 patients had disease recurrence. The 10-year disease-free survival (DFS) was significantly worse in group II (95.0% vs. 97.0%, P = 0.011). After adjusting other significant factors, involved margin was not an independent risk factor for disease recurrence (P = 0.358). Compared to a negative margin, an anterior involved margin did not pose increased recurrence risk (HR = 1.21, 95%CI = 0.93-500.00, P = 0.368), whereas a posterior involved margin had almost 23 times higher recurrence risk (HR = 22.95; 95%CI = 4.33-121.70, P < 0.001). CONCLUSIONS: Overall, a microscopically involved margin was not an independent factor for DFS. However, although an anterior involved margin itself did not increase disease recurrence, a posterior involved margin did. J. Surg. Oncol. 2016;113:635-639. © 2016 Wiley Periodicals, Inc.

Impact of microscopic extra-nodal extension (ENE) on locoregional recurrence following curative surgery for papillary thyroid carcinoma.

BACKGROUND: The presence of microscopic extra-nodal extension (ENE) may increase locoregional recurrence (LRR) in papillary thyroid carcinoma (PTC). We aimed to evaluate the association between microscopic ENE, response to initial therapy and LRR risk following total thyroidectomy, therapeutic neck dissection, and radioactive iodine (RAI) ablation in PTC. METHODS: Of the 369 eligible PTC patients, 264 (71.5%) did not have microscopic ENE (group I) while 105 (28.5%) did (group II). All presented with clinical nodal metastasis (cN1) and underwent therapeutic neck dissection and RAI ablation. Biochemical incompleteness meant post-ablation stimulated thyroglobulin (sTg) >10 ng/ml. Multivariate analyses were conducted to identify independent factors for LRR. RESULTS: Biochemical incompleteness was significantly more common group II (43.8% vs. 17.4%, P < 0.05). The 10-year locoregional free-survival was significantly worse in group II than I (52.0% vs. 86.2%, P = 0.005). After adjusting for other significant factors, age <45 (P < 0.05), multifocality (P < 0.05), presence of ENE (P = 0.027) were independent risk factors of LRR. The number and size of positive lymph nodes were not independent factors. CONCLUSIONS: Patients with microscopic ENE were significantly more likely to have biochemical incompleteness after initial therapy. After adjusting for other significant primary and nodal characteristics, microscopic ENE was an independent factor for LRR in patients with cN1. J. Surg. Oncol. 2016;113:526-531. © 2016 Wiley Periodicals, Inc.

Assessing the short- and long-term outcomes after resection of benign insulinoma.

BACKGROUND: Insulinoma is a rare functional pancreatic neuroendocrine tumour (NET) believed to have an excellent long-term outcome, but few studies have solely focused on this issue after apparently curative resection. This study aimed to assess post-operative and long-term outcomes after resection of benign insulinomas. METHODS: From 1998 to 2013, 36 consecutive patients with insulinomas underwent surgery. Three patients had multiple endocrine neoplasia type-1 (MEN-1). Demographics, operative findings, tumour grade (2010 World Health Organization (WHO) NET classification), post-operative pancreatic fistula (POPF) grade (International Study Group of Pancreatic Fistula (ISGPF)), complications and recurrence were analysed. RESULTS: Eighteen (50%) had enucleation while the rest underwent pancreatic resection. The majority (86.1%) of insulinomas belonged to WHO NET grade G1. POPF occurred in 58.3% of patients while clinical fistula (ISGPF grades B and C) occurred in 19.4%. One (2.8%) patient required reoperation. The occurrence of POPF was not related to type of resection or surgical approach. There was no perioperative mortality. After a mean follow-up of 83.6 months, two patients (5.7%) developed disease recurrence at 34.4 and 131.9 months after initial surgery. No patients developed distant metastasis. The 10- and 15-year disease-free rates were 95.6 and 85.4%, respectively. CONCLUSION: POPF occurred frequently and posed a significant morbidity after resection of insulinoma. However, it occurred independently of type of resection or surgical approach. Although the immediate cure rate after resection was high (100%), long-term disease recurrence in sporadic (non-MEN-1) cases was not insignificant. Regular long-term follow-up is recommended.

Giant cell tumor of the humeral head treated by denosumab: Implication to shoulder surgeons.

Giant cell tumor is a benign bone tumor that is commonly encountered. The optimal treatment of a giant cell tumor which causes extensive bony destruction is controversial. Recent studies on the receptor activator of nuclear factor κB ligand antagonist denosumab may offer a new treatment option for these patients. We presented a patient with giant cell tumor of the humeral head. He was initially treated with denosumab and subsequently with the operation. The shoulder joint was successfully salvaged. But there are potential difficulties that surgeons may face in patients treated with denosumab.