Treatments and prognostic factors for bone and soft tissue sarcoma in non-urban areas in Japan.

BACKGROUND: Although bone and soft tissue sarcoma is recognized as a rare cancer that originates throughout the body, few comprehensive reports regarding it have been published in Japan. PATIENTS AND METHODS: Bone and soft tissue sarcomas were tabulated from the Cancer Registries at eight university hospitals in the Chugoku-Shikoku region. Prognostic factors in cases were extracted in a single facility and have been analyzed. RESULTS: From 2016 to 2019, 3.4 patients with bone and soft tissue sarcomas per a general population of 100,000 were treated at eight university hospitals. The number of patients who underwent multidisciplinary treatment involving collaboration among multiple clinical departments has been increasing recently. In the analysis carried out at a single institute (Ehime University Hospital), a total of 127 patients (male/female: 54/73) with an average age of 67.0 y (median 69.5) were treated for four years, with a 5-year survival rate of 55.0%. In the analysis of prognostic factors by multivariate, disease stage and its relative treatment, renal function (creatinine), and a patient's ability of self-judgment, and a patient's mobility and physical capability were associated with patient prognosis regarding bone and soft tissue sarcomas. Interestingly, age did not affect the patient's prognosis (> 70 vs ≦ 70). CONCLUSIONS: Physical and social factors may affect the prognosis of patients with bone and soft tissue sarcomas, especially those living in non-urban areas.

Effective examination methods for identifying the primary origins of metastatic bone tumors of unknown primary origin during the initial visit: A retrospective chart review study.

Objective: To provide appropriate treatment for patients, early diagnosis of the primary origin of skeletal metastases of unknown primary origin is important. This study aimed to assess the examination strategy effective for identifying the primary origin of skeletal metastases of unknown primary origin. Methods: Sixty-one patients with skeletal metastases of unknown primary origin were reviewed. The primary origin was examined via physical examination, blood test including tumor markers, chest radiography, thoracoabdominal computed tomography scan, positron emission tomography-computed tomography scan, metastatic lesion biopsy, and other assessments. Examination methods considered effective for the diagnosis of the primary origin in a specific type of cancer were investigated. Results: The lung was the most common primary origin site, followed by the lymph nodes, prostate, and breast. Meanwhile, biopsy was the most effective examination, followed by positron emission tomography-computed tomography scan and thoracoabdominal computed tomography scan. Blood tests are useful for detecting hematological malignancies and prostate cancer. Computed tomography scans can be used to identify cancers in the lung, breast, and kidney, which are the common primary origins. Forty-one (67.2%) of the 61 patients with skeletal metastases of unknown primary origin were diagnosed via the first four steps, that is, physical examination, blood test, chest radiography, and thoracoabdominal computed tomography scan. Finally, two patients were diagnosed with skeletal metastases of unknown primary origin. Conclusion: The examination steps used in this study, including physical examination, blood test including tumor markers, chest radiography, thoracoabdominal computed tomography scan, positron emission tomography-computed tomography scan, biopsy, and other assessments were effective in determining the primary origin of skeletal metastases of unknown primary origin during the initial visit.

Serum lactate dehydrogenase levels predict the prognosis of patients with soft tissue sarcoma.

Several studies have reported the prognostic factors for soft tissue sarcoma. Although serum lactate dehydrogenase (LDH) levels are associated with poor prognosis in several types of cancer, their role in soft tissue sarcomas remains unclear. Therefore, the present study evaluated the association between serum LDH levels and the clinical characteristics and prognosis of soft tissue sarcoma. A total of 103 patients diagnosed with primary soft tissue sarcoma between 2003 and 2019 were retrospectively examined, and the association between serum LDH levels at the first visit and clinical characteristics were analysed. In high-grade soft tissue sarcoma, the association between survival and clinical characteristics, including stratified LDH levels, was also analysed. Serum LDH levels were stratified (>253 and ≤253 IU/l) according to the standard values used at our institution. High serum LDH levels were significantly associated with the presence of metastasis and histological grade (P<0.001 and 0.040, respectively). In both the univariate and multivariate analyses, disease-specific survival (DSS) was significantly worse in patients with high-grade soft tissue sarcoma and high serum LDH levels than in patients with normal serum LDH levels (univariate analysis: P=0.025; multivariate analysis: Hazard ratio, 4.60; 95% confidence interval, 1.16-18.2; P=0.030). In conclusion, high serum LDH levels at the first visit predicted the presence of distant metastasis, high histological grade and worse DSS in patients with high-grade soft tissue sarcoma. Therefore, in patients with high serum LDH levels at the first visit, these risks should be considered during pretreatment examinations and post-treatment follow-up.

Hand tumors: A review of 186 patients at a single institute.

PURPOSE: The spectrum of diagnoses and clinical features of hand tumors differ from those of tumors in other body parts. However, only a few reports have comprehensively referenced the diagnosis and clinical features of hand tumors. This study aimed to elucidate the diagnostic distribution and the clinical features of hand tumors undergone surgery in our institute. PATIENTS AND METHODS: A total of 235 lesions in 186 patients diagnosed with hand tumors between 1978 and 2020 were reviewed. Age at surgery, gender, chief complaint, tumor location, and pathological diagnosis were analyzed. RESULTS: There were 121 benign bone tumors, 98 benign soft tissue tumors, and 16 malignant tumors. Chondroma and tenosynovial giant cell tumor were common benign bone and soft tissue tumors at the proximal phalanx of the ring finger and the palm, respectively. Meanwhile, chondrosarcoma and synovial sarcoma were common malignant tumors at the dorsal part of the hand. Local pain and painless mass were the chief complaints in patients with benign bone and soft tissue tumors, respectively. Most patients with malignant tumors were referred after unplanned resection. When patients were classified into two categories by tumor size according to maximal diameter, tumors larger than 19 mm had a significantly higher risk of malignant (p = 0.031) despite being smaller than other tumors in different body parts. CONCLUSION: When a tumor malignancy is suspected, the patient should be referred to a specialist to avoid unplanned resection or delayed diagnosis due to misdiagnosis. Knowing the distribution and clinical features should help in diagnosing hand tumors.

Unilateral lower limb atrophy associated with glomus tumors: a case report.

BACKGROUND: Glomus tumors are soft tissue neoplasms comprised of glomus cells, vasculature, and smooth muscle cells, which occur commonly in a single subungual area of the digits, and their main clinical features include severe paroxysmal pain, localized tenderness, and cold hypersensitivity. CASE PRESENTATION: A 47-year-old Japanese man had suffered from chronic progressive paroxysmal shooting pain in his right leg since childhood. He avoided putting weight on his right foot whenever he walked. The frequency of paroxysmal pain and the number of tender points both gradually increased with age, and his right leg gradually atrophied. Magnetic resonance imaging of the lower extremity demonstrated multiple gadolinium-enhanced nodules that corresponded with his tender points. Excisional biopsy relieved his pain and provided a histopathological diagnosis of glomus tumors. CONCLUSION: This case suggests that small glomus tumors located in deep tissue may cause disuse atrophy because of their long delay before diagnosis. Clinicians should consider the potential for glomus tumors when patients exhibit unilateral lower limb muscular atrophy with pain.

Prediction of Soft Tissue Sarcoma from Clinical Characteristics and Laboratory Data.

The accurate diagnosis of soft tissue tumors may be difficult. Simple clinical characteristics or laboratory data that can predict tumor malignancy can be useful tools for diagnosing soft tissue tumors. Between 2003 and 2018, 588 patients with primary soft tissue tumors were retrospectively reviewed. Their clinical characteristics and laboratory data were evaluated to determine their association with the diagnosis of benign, intermediate, or malignant tumor. Multivariable analysis revealed that tumor size ≥ 5.6 cm (odds ratio (OR), 6.15; p < 0.001), white blood cell (WBC) count ≥ 5700/µL (OR, 2.49; p = 0.002), hemoglobin (Hb) count ≤ 12.4 g/dL (OR, 2.56; p = 0.004), C-reactive protein (CRP) level ≥ 0.17 mg/dL (OR, 2.64; p < 0.001), and lactate dehydrogenase (LDH) level ≥ 240 IU/L (OR, 4.94; p < 0.001) were significant predictive factors for sarcoma. The sensitivity and specificity in the presence of three or more predictive factors for detecting malignant tumors were 0.58 and 0.90 respectively, and it was an appropriate threshold with the maximum Youden's index of 0.49. Simple clinical and laboratory data were useful tools for predicting whether the tumor is malignant. Patients with soft tissue tumors that meet any three or more predictive factors should be referred to a specialist.

Intraosseous synovial sarcoma of the distal ulna: a case report and review of the literature.

BACKGROUND: Synovial sarcoma is a relatively rare type of soft tissue sarcoma. The commonly observed symptom is a deep-seated palpable mass accompanied by pain or tenderness. Thus, it is considered a soft tissue sarcoma and rarely occurs primarily in bone. However, only few studies have been reported on intraosseous synovial sarcoma, and reports on cases with cytogenetic or molecular confirmation are even rarer. We report a case of intraosseous synovial sarcoma of the distal ulna that has been confirmed using histopathological examination and molecular analysis. CASE PRESENTATION: A 77-year-old female was referred to our hospital with a 1-month history of right wrist pain after housework. Clinical and imaging findings suggested a benign bone tumor that was enhanced by Gd-DTPA. It was thought that the tumor was possibly an enchondroma. Initially, we planned to evaluate the benignancy of the tumor with intraoperative frozen section, followed by curettage and bone graft at one stage However, when considering carefully, characteristics of the tumor did not perfectly match those of any diagnostic categories including enchondroma. Therefore, an incisional biopsy was performed and revealed that the tumor was synovial sarcoma. Following an elaborate plan, the patient underwent a wide resection of the tumor at the distal part of the right ulna. Reverse transcription-polymerase chain reaction (RT-PCR) from the resected specimen and sequencing of RT-PCR products demonstrated a chimeric SYT-SSX1 transcript, confirming the diagnosis of synovial sarcoma. CONCLUSIONS: Synovial sarcoma is seldom considered in differential diagnosis of bone tumors because it is difficult to line up such an unusual diagnosis as a differential diagnosis. When the lesion does not perfectly fit into any diagnostic category, when the initial image diagnosis appears unconvincing, biopsy and pathology are indicated, recalling Jaffe's triangle. According to these diagnostic processes, the patient successfully completed the treatment for this rare intraosseous synovial sarcoma, following a careful plan based on the preoperative diagnosis.

Risk factors for neurological complications after operative treatment for schwannomas.

Schwannoma is a common benign soft tissue tumor. Although schwannomas can be theoretically enucleated without nerve damage, neurological complications occasionally develop following enucleation. The aim of this study was to elucidate the incidence of and risk factors for postoperative neurological complications following schwannoma enucleation. Ninety-eight schwannomas from 95 patients that were treated by surgical excision between January 2003 and December 2014 were included in this retrospective case series study. Patients were 49 men and 46 women with a median age of 60.5years (range, 22-87years). The incidence of postoperative neurological complications was evaluated in all the patients, and characteristics, such as age, tumor size, sex, preoperative symptoms, MRI findings, tumor location, and the nerve of origin, were compared between the cases with or without complications at the last follow-up. In our study population, postoperative neurological complications were observed in 18.4% of the cases. In univariate analysis, preoperative sensory disturbance, tumor location, and the nerve of origin were associated with the incidence of postoperative neurological complications (p<0.001, p=0.034, and p=0.003, respectively). In multivariate analysis, tumors showing preoperative sensory disturbance and tumors located in the proximal aspect of the limbs were identified as independent risk factors for postoperative neurological complications (p<0.001 and p=0.014, respectively). A certain percentage of schwannoma cases undergoing enucleation would show postoperative neurological complications. Therefore, patients with schwannoma, in particular, those with risk factors for postoperative neurological complications, should be informed regarding the possibility of postoperative complications. In cases of schwannoma enucleation, the procedure should be meticulously performed to minimize the damage to the affected nerve of origin.

New endoprosthesis suspension method with polypropylene monofilament knitted mesh after resection of bone tumors in proximal humerus.

BACKGROUND: Endoprosthetic reconstruction of the proximal humerus is one of the standard procedures after resection of tumors of the proximal humerus and has been considered a reliable method to reconstruct the proximal humerus in recent reports. However, instability of the shoulder joint caused by loss of the rotator cuff and deltoid muscle function is often observed after such an endoprosthetic reconstruction. METHODS: We performed the endoprosthesis suspension method with polypropylene monofilament knitted mesh. This suspension method, by which the endoprosthesis is suspended from the bone structure, was used after resection of tumors in 9 patients. We assessed postoperative stability of the shoulder joint by comparing these patients with 12 patients who underwent the conventional surgical technique, by which the mesh-wrapped endoprosthesis is attached only to soft tissue. RESULTS: In radiographic and physical evaluation, 4 of the 12 patients in the soft tissue reconstruction group showed shoulder joint instability. No patient in the suspension method group showed subluxation of the humeral prosthesis. The mean shoulder flexion was 35° and 65° and the mean shoulder abduction was 40° and 40° for the soft tissue reconstruction group and the suspension method group, respectively. DISCUSSION: Shoulder joint subluxation sometimes occurs because of elongation of the attached soft tissue in the conventional reconstruction with mesh, whereas no shoulder joint subluxation occurs after endoprosthetic reconstruction in the suspension method because the bone structure has no leeway for elongation. Excellent stability of our new method enables exercise of the surgical shoulder at an early stage, leading to improved range of shoulder joint motion.

Polyostotic fibrous dysplasia with gigantism and huge pelvic tumor: a rare case of McCune-Albright syndrome.

We report a rare case of polyostotic fibrous dysplasia on endocrine hyperfunction with elevated human growth hormone and normal serum level of prolactin. There were some differential points of gender, gigantism, endocrine function, and GNAS gene from McCune-Albright syndrome. Malignant transformation was suspected in the pelvic tumor from imaging because rapid growth of the tumor by imaging was observed; however, no malignant change occurred in this case.

Synovial hemangioma of the knee joint in a 3-year-old girl.

Synovial hemangioma has been reported to be relatively rare, and usually occurs in childhood and adolescence. However, there are a few reports of the disease in infants. In this report, we diagnosed synovial hemangioma in a 3-year-old girl who had swelling and pain in her left knee. Gadolinium-enhanced magnetic resonance imaging revealed abnormal intensity in an intra-articular lesion. We performed arthroscopy, and arrived at a final diagnosis based on a scopic biopsy. Synovial hemangioma should be considered as a possible diagnosis in infants with swelling and pain in the knee.

Reconstruction using a frozen bone method for osteosarcoma of the talus. A case report and review of the literature.

A case of osteosarcoma of the talus is reported. Osteosarcoma of the talus is very rare. The patient is alive and she has been continuously disease free for five years after surgery. This is the first case of osteosarcoma of the talus with reconstruction using a frozen bone method, an autograft containing tumor treated with liquid nitrogen. This is a rare case report of osteosarcoma of the talus without extrainvasion of the talus.

Diagnostic and therapeutic problems of giant cell tumor in the proximal femur.

Primaly giant cell tumor of bone (GCT) in the proximal femur is relatively rare, and can prove difficult to diagnose, and can require therapeutic methods. Subjects comprised 10 patients (8 males, 2 females). Mean patient age was 27.5 years, and mean follow-up was 89.9 months. Tumors in the present study were limited to H1 and H2 according to the International Society of Limb Salvage (ISOLS) system. All patients received surgical treatment only. Second surgery after preoperative open biopsy was performed for two patients, while the remaining eight patients received excisional biopsy to determine treatment methods using rapid intraoperative pathological examination of frozen sections. The mean functional score was 28.2 out of 30 (93.9%). Local recurrence was observed in two patients. The long-term follow-up reveals that one of the important problem is pre-operative diagnosis. Excisional biopsy is effective for surgery of GCT in the proximal femur.

A Small Ras-like protein Ray/Rab1c modulates the p53-regulating activity of PRPK.

PRPK phosphorylates serine-15 residue of p53 and enhances transcriptional activity. PRPK possesses a bipartite nuclear localization signal and localizes in nucleus when over-expressed in cells. However, intrinsic PRPK localizes mainly in the cytosol in situ. While studying the mechanisms in the distribution of intrinsic PRPK, we identified a PRPK binding protein, an ubiquitously expressed Small Ras-like GTPase, Rab1c, also named Ray or Rab35. The over-expressed Ray was distributed in the nucleus, cytosol, and cell membrane. Both Ray wild type and GTP-restrictively binding mutant Ray-Q67L, but not guanine nucleotide unstable binding mutant Ray-N120I, partially distributed the over-expressed PRPK to the cytosol and also suppressed the PRPK-induced p53-transcriptional activity profoundly. A Small Ras-like GTPase protein Ray was thus indicated to modulate p53 transcriptional activity of PRPK.

AIP1/WDR1 supports mitotic cell rounding.

The actin cytoskeleton plays a fundamental role in configuring cell shapes and movements. Actin interacting protein 1 (AIP1)/tryptophan-aspartate-repeat protein 1 (WDR1) induces actin severing and disassembly cooperating with ADF/cofilin. We found that mitotic cell flattening but not rounding was manifested by suppression of AIP1/WDR1 in cells. This mitotic cell flattening was not due to any changes in phosphorylation and distribution of cofilin in cells. We carried out a direct observation of actin filament severing/disassembly assay and found that phosphorylated cofilin still somewhat severs/disassembles actin filaments and that AIP1/WDR1 effaces this in vitro. We suggest that the phosphorylation of ADF/cofilin will be insufficient to completely inhibit actin turnover during mitosis, and that AIP1/WDR1 could abort the severing/disassembly activity somewhat still carried out due to phosphorylated ADF/cofilin. This mechanism could be required to induce cell morphologic changes, especially mitotic cell rounding.

A case of nodular-type muscular sarcoidosis: findings of imaging, histopathology, and polymerase chain reaction.

We report a case of nodular-type muscular sarcoidosis with no systemic symptoms. Thallium-201 scintigraphy showed intense uptake in the muscular lesion mimicking malignant soft tissue tumor. Magnetic resonance imaging (MRI) demonstrated characteristic signal patterns of peripheral high intensity with central low intensity ("three stripes" pattern). Microscopy revealed sarcoid granuloma with typical histopathological characteristics. Propionibacterium acnes was detected on polymerase chain reaction analysis of the excised tissue.

A 40-year-old gossypiboma (foreign body granuloma) mimicking a malignant femoral surface tumor.

The patient was a 61-year-old man who developed gossypiboma of the left thigh and femur resulting in the imaging appearances of a malignant surface tumor. He had a past history of surgery on the left femur for open fracture 40 years previously. Radiographs and CT showed a soft tissue mass with osteolysis and periosteal thickening of the left femur. On MRI, the mass showed heterogeneous signal intensity with contrast enhancement at the periphery, suggesting a malignancy. 99mTc-HMDP bone scintigraphy showed a faint ring-like uptake, but thallium -201 scintigraphy did not show any uptake in the tumor. An extensive intralesional excision was performed. Postoperative histopathological examination showed a fibrous foreign body with reactive changes. There were neither viable cells nor atypical giant cells around the foreign body. No malignant change was evident. Based on surgical and histopathological examinations, the tumor was finally diagnosed as gossypiboma related to a retained surgical sponge.