This paper reported a case of cervical intraspinal metastasis of alveolar rhabdomyosarcoma (ARMS). The clinicopathological features, surgical treatment, chemotherapy and prognosis were introduced and the current literature was reviewed. The diagnosis, differential diagnosis, treatment, molecular features and prognosis of the disease were comprehensively analyzed to improve clinicians' knowledge of this rare disease. The primary lesion appeared about 1 year ago which was painless mass of left hand whose size was about 2 cm×2 cm. After conservative treatment, the mass gradually enlarged and the mass was resected. Postoperative pathology revealed embryonic rhabdomyosarcoma. Postoperative chemotherapy with recombinant human endostatin, liposomal doxorubicin and ifosfamide was performed. The left neck mass was found about 3 months ago, and then the left neck mass was resected under general anesthesia. Postoperative pathological examination showed small round cell malignant tumors. Severe left upper extremity pain began about 2 weeks ago with nocturnal pain and supine pain. Non-steroidal anti-inflammatory drugs were needed to relieve pain which was accompanied by numbness and weakness of the left upper extremity. MRI showed a intraspinal tumor at C5. The left thumb and index finger were absent. Hypoesthesia, muscle atrophy and hypotonia of the left upper limb were confirmed. The muscle strength of biceps brachii and deltoid muscle of the left upper limb was grade 0, the muscle strength of extensor carpus and interphalangeal muscle was grade II, the muscle strength of intrinsic muscles of hands was grade I. The tendon reflex of the left upper limb disappeared. Intraspinal mass was removed and the pain was relieved. But there was no significant change in the muscle strength of the left upper limb. Pathological examination revealed small cell malignancies which were poorly differentiated with diffuse patchy distribution and disordered arrangement. The tumor cells had round, oval or irregular nuclei, and few cytoplasms were positive for Myogenin and MyoD1. FISH test of FOXO1 gene was positive. More than 50% of nuclei showed redgreen signal separation, and the distance between redgreen signals was larger than double diameter of the signal points, which supported ARMS. Total resection of intraspinal tumors was achieved and postoperative chemotherapy was admitted. But intraspinal disseminated metastasis occurred rapidly. ARMS was rare, aggressive tumor with poor prognosis. Subdural metastasis was rare. Correct diagnosis and classification can be made only with help of modern molecular diagnostic methods, which is effective to guide the treatment.
Humans ; Ifosfamide ; Muscle, Skeletal ; Myogenin ; Prognosis ; Rhabdomyosarcoma, Alveolar ; Spinal Neoplasms

OBJECTIVETo probe into the function of stem cell antigen-1 (Sca-1) in cell proliferation and differentiation.

METHODSSca-(1+) and Sca-(1-) muscle derived cells were separated from C57BU6 mice by fluorescence-activated cell sorting and then cultured in vitro. After 5 days cells proliferative curve were drawn according CCK-8 experimental results. Western blot also were done to detect Sca(-1), MyoD and Myogenin expression in cultured Sca(-1+) and Sca-(1-) muscle derived cells.

RESULTSThe difference of the proliferative curve of Sca-(1+) and Sca-(1-) muscle derived cells cultured 3 days in vitro was not apparent, but Sca-(1-) muscle derived cells had a accelerated division rate in the follow days compared to the Sca-(1+) muscle derived cells. Sca-1 expression in both cells was not obvious. MyoD and Myogenin expression were stronger in Sca-(1+) than Sca-(1-) muscle derived cells.

CONCLUSIONSca-1 expression in muscle derived cells takes a period of time that related to the beginning and ending of the cell cycle.

Animals ; Antigens, Ly ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Flow Cytometry ; Membrane Proteins ; Mice ; Muscle, Skeletal ; Myogenin ; Stem Cells

BACKGROUND: Breast cancer treatment with selective estrogen receptor modulators (SERMs) increases the incidence of uterine malignant mixed Müllerian tumors (uMMMTs). We examine clinicopathologic characteristics and prognosis of SERM-associated uMMMTs (S-uMMMTs) and discuss possible pathogenetic mechanisms. METHODS: Among 28,104 patients with breast cancer, clinicopathologic features and incidence of uMMMT were compared between patients who underwent SERM treatment and those who did not. Of 92 uMMMT cases that occurred during the same period, incidence, dose, and duration of SERM treatment, as well as overall survival rate, were compared for patients with breast cancer who underwent SERM treatment and those who did not (S-uMMMT vs NS-uMMMT) and for patients without breast cancer (de novo-uMMMT). Histopathological findings and immunophenotypes for myogenin, desmin, p53, WT-1, estrogen receptor (ER) α, ERβ, progesterone receptor, and GATA-3 were compared between S-uMMMT and de novo-uMMMT. RESULTS: The incidence of S-uMMMT was significantly higher than that of NS-uMMMT (6.35-fold). All patients with SERM were postmenopausal and received daily 20–40 mg SERM. Cumulative SERM dose ranged from 21.9 to 73.0 g (mean, 46.0) over 39–192 months (mean, 107). Clinicopathologic features, such as International Federation of Gynecology and Obstetrics stage and overall survival, were not significantly different between patients with S-uMMMT and NS-uMMMT or between patients with S-uMMMT and de novo-uMMMT. All 11 S-uMMMT cases available for immunostaining exhibited strong overexpression/null expression of p53 protein and significantly increased ERβ expression in carcinomatous and sarcomatous components. CONCLUSIONS: SERM therapy seemingly increases risk of S-uMMMT development; however, clinicopathologic features were similar in all uMMMTs from different backgrounds. p53 mutation and increased ERβ expression might be involved in the etiology of S-uMMMT.
Breast Neoplasms ; Breast ; Desmin ; Estrogens ; Gynecology ; Humans ; Incidence ; Myogenin ; Obstetrics ; Prognosis ; Receptors, Progesterone ; Selective Estrogen Receptor Modulators ; Survival Rate ; Tamoxifen

BACKGROUND: We analyzed whether thyroid stimulating hormone receptor (TSH-R) is expressed in a skeletal muscle cell line and if TSH has influence on the differentiation of muscle cells or on the determination of muscle fiber types. METHODS: TSH-R gene expression was detected with nested real-time polymerase chain reaction (RT-PCR) in C2C12, a mouse skeletal muscle cell line. The effect of TSH on myotube differentiation was assessed by microscopic examination of myotube formation and through the measurement of expression of muscle differentiation markers, i.e., myogenin and myoD, and muscle type-specific genes, i.e., MyHC1, MyHC2a, and MyHC2b, with quantitative RT-PCR before and after incubation of C2C12 myotube with TSH. RESULTS: TSH-R was expressed in the mouse skeletal muscle cell line. However, treatment with TSH had little effect on the differentiation of muscle cells, although the expression of the muscle differention marker myogenin was significantly increased after TSH treatment. Treatment of TSH did not affect the expression of muscle type-specific genes. CONCLUSION: TSH-R is expressed in a mouse skeletal muscle cell line, but the role of TSH receptor signaling in skeletal muscle needs further investigation.
Animals ; Antigens, Differentiation ; Cell Line ; Gene Expression ; Mice ; Muscle Cells ; Muscle Fibers, Skeletal ; Muscle, Skeletal ; Muscles ; Myogenin ; Real-Time Polymerase Chain Reaction ; Receptors, Thyrotropin ; Thyroid Gland ; Thyrotropin

OBJECTIVE: Granulocyte-macrophage colony-stimulating factor (GM-CSF) facilitates mammalian embryonic development and implantation. However, its biological function after implantation is not elucidated. The aim of this study is to assess the changes of gene expression by GM-CSF in human trophoblast obtained in early pregnancy. METHODS: Human trophoblast obtained in early pregnancy was cultured with or without GM-CSF. The difference of gene expression was evaluated with microarray and selected genes were reevaluated with real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Microarray analysis revealed that the expressions of 468 genes were increased while those of 40 genes were decreased by GM-CSF. These genes were evaluated according to the known biologic pathways. The regulation of actin cytoskeleton and focal adhesion pathways were mostly influenced by GM-CSF. Annexin A2, thymosin-like 3, vimentin, myogenin, ACK1, and tensin1 genes were selected for real-time RT-PCR. The increased expressions of of vimentin and ACK1, and decreased expressions of tensin1 were confirmed by real-time RT-PCR. CONCLUSION: GM-CSF activates focal adhesion pathway in human trophoblast by increasing the expression of vimentin and ACK1, and decreasing the expression of tensin1.
Actin Cytoskeleton ; Annexin A2 ; Embryonic Development ; Female ; Focal Adhesions ; Gene Expression ; Granulocyte-Macrophage Colony-Stimulating Factor ; Humans ; Microarray Analysis ; Myogenin ; Pregnancy ; Trophoblasts ; Vimentin

The effects of unilateral sciatic neurectomy on gastrocnemius muscle were studied in adult male rats. The morphological changes of both gastrocnemius muscles were observed by light and electron microscopy. Western blot analysis was performed to study the protein expression. Following the denervation, the affected muscle weights decreased significantly than normal. And the denervation led to a significant reduction in the area and diameter of muscle fibers on light microscopy. The affected muscle fibers showed the decreasing in size and the irregularity of myofibrilar arrangement on electron microscopy. On transverse view, the area of affected muscle fibers were smaller than normal. Their myofibrils were smaller and very irregular in size. The thin and thick myofilaments were not regular and partially lost. Mitochondria between myofibrils and subsarcolemmal area in affected muscle fibers were damaged and partially lost. The sacoplasmic reticulum and T-tubules were mostly lost and irregular. Some satellite cells were observed adjacent the muscle fiber, but they were inactive morphologically. On longitudinal view, most of myofibrils in affected muscle fibers were lost generally or partially although the their most sarcomeres were regularly arranged. Z line and myofilaments were lost partially and were partially irregularly arranged. The loss of thin myofilaments was more than that of thick myofilaments. Much debris of cell organelles were scattered among myofibrils. The expression of MyoD and myogenin were decrease significantly and the expression of p-mTOR and p-FOXO1 were decreased, too. On the other hand, MuRF1 was increased significantly. Taken together, the main effect of gastrocnemius muscle by sciatic neurectomy is the atrophy as a result of the loss of myofilaments and cell organelles through the decrease of protein synthesis and the increase of protein degradation.
Adult ; Animals ; Atrophy ; Blotting, Western ; Denervation ; Hand ; Humans ; Light ; Male ; Microscopy ; Microscopy, Electron ; Mitochondria ; Muscle, Skeletal ; Muscles ; Myofibrils ; Myogenin ; Organelles ; Proteolysis ; Rats ; Reticulum ; Sarcomeres ; Sciatic Nerve ; Weights and Measures

BACKGROUND: Primary breast sarcoma (PBS) is rare, comprising approximately 1% of breast malignancies. Rhabdomyosarcoma (RMS) accounts for an extremely small proportion of PBSs, often leading to delayed histologic confirmation. METHODS: Upon reviewing Asan Medical Center’s pathology database between 2000 and 2018, 41 PBS cases were retrieved, including three cases of primary RMS of the breast. Their clinicopathological features were analyzed, and the literature related to PBS and primary RMS of the breast was reviewed. RESULTS: We identified three primary breast RMS cases from our institution database, comprising 7.3% of PBS: one case each of spindle cell/sclerosing RMS (ssRMS), alveolar RMS (aRMS), and embryonal RMS (eRMS). All cases involved adolescents or young adults (14, 16, and 25 years, respectively) who underwent mastectomy or radiotherapy and were confirmed using immunohistochemical testing for myogenin, desmin, and myogenic differentiation. The ssRMS patient experienced recurrence at the operation site 4 months post-surgery despite undergoing concurrent chemoradiotherapy. The aRMS patient had multiple metastases at diagnosis and showed FAX3-FOXO1 fusion transcripts; she died 22 months after the diagnosis. The eRMS patient had enlarged axillary lymph nodes; post-radiotherapy, the lesion recurred as multiple metastases to the bone and lung. She died 18 months post-diagnosis. CONCLUSIONS: Our experience on RMS cases suggests that spindle cell or small round cell malignancy in breasts of young female should raise suspicion for the possibility of primary or secondary RMS. To our knowledge, this is the second report of primary breast ssRMS and it may help clinicians who encounter this rare disease in the future.
Adolescent ; Arm ; Breast ; Chemoradiotherapy ; Chungcheongnam-do ; Desmin ; Diagnosis ; Female ; Humans ; Lung ; Lymph Nodes ; Mastectomy ; Myogenin ; Neoplasm Metastasis ; Pathology ; Radiotherapy ; Rare Diseases ; Recurrence ; Rhabdomyosarcoma ; Sarcoma ; Young Adult

Fine-needle aspiration cytology(FNAC) has been used extensively in the diagnosis of metastatic malignancies. However, metastatic soft tissue sarcomas are often overlooked, primarily due to the low frequency with which they occur. Here, we report a rare case of metastatic rhabdomyosarcoma in both cervical lymph nodes, which was detected by FNAC. A 45-year-old woman presented with anosmia, postnasal drip, and sneezing, symptoms which had persisted for 1 month. The patient was found to have a tumorous lesion at the upper portion of the mid-turbinate, with multiple enlarged cervical lymph nodes, and this lesion was examined closely at our facility. FNA cytology smears obtained from both cervical lymph nodes revealed a high degree of cellularity, and displayed cohesive clusters with gland-like spaces, as well as single isolated cells with abundant karyorrhectic debris. The tumor cells exhibited round to oval nuclei containing fine chromatin, occasional small nucleoli, and scanty cytoplasm, or a total lack of cytoplasm. Some of the tumor cells were arranged in multinucleated forms and abundant dense eosinophilic cytoplasms, reminiscent of a rhabdomyoblast. The histological findings of the lymph nodes revealed an outstanding sinusoidal infiltration and a prominent alveolar growth pattern, interspersed with occasional typical rhabdomyoblasts. The immunohistochemical results [desmin(+), myoglobin(+), myogenin (+), pan CK(-), synaptophysin(-), neuron specific enolase(-)] supported a confirmative diagnosis of alveolar rhabdomyosarcoma. Alveolar rhabdomyosarcoma is a representative sarcoma, which typically manifests with nodal metastasis and carcinoma-like clustering. The cytopathologist should remain alert upon encountering unusual morphology, so that the possibility of this condition, although somewhat remote, should not be dismissed or overlooked.
Biopsy, Fine-Needle* ; Chromatin ; Cytoplasm ; Diagnosis ; Eosinophils ; Female ; Humans ; Lymph Nodes ; Lymphatic Metastasis ; Middle Aged ; Myogenin ; Neoplasm Metastasis ; Neurons ; Olfaction Disorders ; Rhabdomyosarcoma ; Rhabdomyosarcoma, Alveolar* ; Sarcoma ; Sneezing

OBJECTIVES: Rheumatoid arthritis (RA) is characterized by chronic inflammation of the synovium, progressive erosion of the articular cartilage, and joint destruction. RA also causes secondary osteoporosis and muscle wasting. We investigated the effects of ibandronate (IBN), a bisphosphonate; eldecalcitol (ELD), an active vitamin D3 derivative; and combination treatment with both agents on secondary osteoporosis and muscle wasting using adjuvant-induced arthritis rats. METHODS: Arthritis was induced in 8-week-old male Lewis rats. Rats were randomized into 4 treatment groups and an untreated normal control group: IBN (subcutaneously, once every 2 weeks, 10 µg/kg), ELD (orally, once daily, 30 ng/kg/day), IBN + ELD, vehicle, and control. Paw thickness measurements were performed for evaluation of arthritis. The femur was scanned using dual-energy X-ray absorptiometry. Cross-sectional areas of left tibialis and anterior muscle fibers and the expression of MuRF1, atrogin-1, MyoD, and myogenin in the gastrocnemius muscle were measured to evaluate muscle wasting. RESULTS: IBN and/or ELD increased bone mineral density (BMD) in the femur. In addition, there was an additive effect of combination treatment compared with single treatments for BMD. However, IBN and/or ELD did not inhibit muscle wasting in adjuvant-induced arthritis rats. CONCLUSIONS: Combination treatment with IBN and ELD may be effective for secondary osteoporosis associated with RA. Other treatments are necessary for muscle wasting associated with RA. Studies in humans are needed to confirm these findings.
Absorptiometry, Photon ; Animals ; Arthritis ; Arthritis, Rheumatoid ; Bone Density ; Cartilage, Articular ; Cholecalciferol ; Femur ; Humans ; Inflammation ; Joints ; Male ; Muscle, Skeletal ; Myogenin ; Osteoporosis ; Rats ; Synovial Membrane ; Vitamin D

Calbindin 2 ; metabolism ; Heart Neoplasms ; metabolism ; pathology ; surgery ; Humans ; Male ; Middle Aged ; MyoD Protein ; metabolism ; Myogenin ; metabolism ; Rhabdomyosarcoma, Embryonal ; metabolism ; pathology ; surgery