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

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

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

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

OBJECTIVETo investigate the effect of exogenous recombinant human basic fibroblast growth factor (rhbFGF) on the healing of muscles in rats after deep tissue injury of pressure ulcers.

METHODSForty-eight SD rats were randomly divided into normal control group, injury control group, post injury day (PID) 4 group, PID 7 group, PID 14 group, PID 21 group according to the random number table, with 8 rats in each group. The rats in normal control group did not receive any treatment, whereas the rats in the latter 5 groups were established the deep tissue injury of pressure ulcer model on both sides of the gracilis muscle on the hind limb. The rats in injury control group did not receive any treatment after injury, while the rats in the latter 4 groups were given subcutaneous injection of 0.1 mL rhbFGF to the left gracilis in a dosage of 100 µg/mL immediately after injury, and an equal volume of normal saline (NS) was injected to right gracilis, once every other day. The rats in injury control group were sacrificed immediately after injury, and the rats in normal control group were sacrificed at the same time point. The rats in the other 4 groups were sacrificed on PID 4, 7, 14, 21, and the gracilis muscles on both sides were harvested respectively. The morphology of the gracilis muscle was examined after HE staining. The expression of myogenin in the tissues was detected by immunofluorescence method. The levels of muscle structural proteins myosin heavy chain (MyHC), phosphorylated protein kinase B (Akt), and phosphorylated mammalian target of rapamycin (mTOR) were determined by Western blotting. Data were processed with one-way analysis of variance and LSD test.

RESULTS(1) In normal control group, the nuclei of graciles cells were in uniform size, and they were closely arranged with clear structure, and there were no significant infiltration of inflammatory cells. In injury control group, the nuclei of graciles cells showed signs of pyknosis, dissolution, fracture and structural disorder. Swelling of muscle cells, inflammation infiltration, structural disorder and other pathological signs of injury phenomena in graciles of PID 4 group, PID 7 group, PID 14 group, PID 21 group after rhbFGF treatment were milder compared with those after NS treatment. In addition, the numbers of regenerated myocytes in graciles of PID 4 group, PID 7 group, PID 14 group, PID 21 group after rhbFGF treatment were higher than those after NS treatment. (2) The numbers of graciles myogenin positive cells in normal control group and injury control group were respectively 28 ± 17 and 42 ± 28. The numbers of graciles myogenin positive cells in PID 4 group, PID 7 group, PID 14 group after NS treatment were 100 ± 50, 196 ± 87, 460 ± 110 respectively, while the numbers of graciles myogenin positive cells in PID 4 group, PID 7 group, PID 14 group after rhbFGF treatment were 174 ± 34, 717 ± 182, 613 ± 122 respectively, and the numbers of graciles myogenin positive cells after rhbFGF treatment were significantly higher than those after NS treatment in each group(P < 0.05 or P < 0.01). The number of graciles myogenin positive cells in PID 21 group after rhbFGF treatment was 109 ± 34, which was significantly lower than that after NS treatment (218 ± 71, P < 0.05). (3) The expression of MyHC in graciles in normal control group was high, which was decreased in injury control group. Both the expressions of MyHC in graciles in PID 4 group, PID 7 group, PID 14 group, PID 21 group after treatment of NS and rhbFGF showed a trend of gradual elevation, while the expressions of MyHC in graciles after rhbFGF treatment were significantly higher than those after NS treatment (P < 0.05 or P < 0.01). The expression of MyHC in graciles in PID 21 group showed a high level, and it was similar to that of the normal control group (P > 0.05). The expressions of phosphorylated Akt and phosphorylated mTOR in graciles of normal control group were low, and the expression of phosphorylated Akt in graciles increased in injury control group, while the expression of phosphorylated mTOR in graciles decreased in injury control group. The expressions of phosphorylated Akt and phosphorylated mTOR in graciles of PID 4 group, PID 7 group, PID 14 group, PID 21 group after treatment with rhbFGF showed a trend of elevation in the beginning but declined afterwards. The expressions of phosphorylated Akt and phosphorylated mTOR in graciles of PID 4 group after rhbFGF treatment were significantly lower than those after NS treatment (P <0 .05 or P < 0.01). The expressions of phosphorylated Akt and phosphorylated mTOR in graciles of PID 7 group, PID 14 group, PID 21 group after rhbFGF treatment were significantly higher than those after NS treatment (P < 0.05 or P < 0.01).

CONCLUSIONSExogenous rhbFGF may effectively facilitate the healing of muscle structure and accelerate the regeneration of muscles in rats after deep tissue injury of pressure ulcers, and its mechanism may be related to the improvement of the expression of myogenin and enhancement of the expression of protein of muscle growth-related signaling pathways.

Animals ; Disease Models, Animal ; Fibroblast Growth Factor 2 ; metabolism ; Humans ; Myogenin ; metabolism ; Phosphorylation ; Pressure Ulcer ; therapy ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases ; metabolism ; Wound Healing

OBJECTIVETo investigate the clinicopathologic characteristics, differential diagnosis and biological behavior of extracardiac rhabdomyoma.

METHODSNine cases of extracardiac rhabdomyoma diagnosed between January of 1997 and July of 2014 were reviewed. The clinical, pathologic and immunohistochemical profiles were evaluated.

RESULTSThere were 5 males and 4 females at diagnosis with age ranging from 2 years and three months to 59 years (mean, 37.6 years). Sites included the head and neck region (7 cases), chest (1 case ) and vagina wall (1 case). Clinically, most cases manifested as a subcutaneous nodule or as a submucosal polypoid lesion with a mean diameter of 3.2 cm. Histologically, 4 were adult-type rhabdomyoma characterized by tightly packed large round or polygonal rhabdomyoblasts with abundant eosinophilic to clear cytoplasm; 3 were myxoid variant of fetal rhabdomyoma composed of immature myofibrils, spindled and primitive mesenchymal cells embedded in a myxoid background, 1 was an intermediate form of fetal rhabdomyoma consisting of densely arranged differentiated myoblasts with little myxoid stroma; 1 was a genital rhabdomyoma composed of elongated or strap-like myoblasts scattered in loose fibrous connective tissue. By immunohistochemistry, they showed diffuse and strong positivity for desmin, MSA and myoglobin with variable expression of myogenin. A case of intermediate type also stained for α-smooth muscle actin. Follow up data (2 months ~ 17 years) showed local recurrence in one patient 6 months after surgery.

CONCLUSIONSRhabdomyoma is a distinctively rare benign mesenchymal tumor showing skeletal muscle differentiation, which may occassionally recur if incompletely excised. Familiarity with its clinical and morphological variants is essential to avoid misdiagnosing this benign lesion as embryonal rhabdomyosarcoma.

Adolescent ; Adult ; Cell Differentiation ; Child ; Child, Preschool ; Desmin ; analysis ; Diagnosis, Differential ; Female ; Head and Neck Neoplasms ; chemistry ; pathology ; Humans ; Immunohistochemistry ; Male ; Mesenchymoma ; pathology ; Middle Aged ; Myogenin ; analysis ; Neoplasm Recurrence, Local ; Rhabdomyoma ; chemistry ; pathology ; Rhabdomyosarcoma, Embryonal ; pathology ; Thoracic Neoplasms ; chemistry ; pathology ; Thoracic Wall ; pathology ; Vaginal Neoplasms ; chemistry ; pathology

OBJECTIVETo study the clinicopathological and immunohistochemical features, histogenesis and prognosis of pleuropulmonary blastoma (PPB) in children.

METHODSPPB specimens from 16 pediatric cases with an age ranging from 1 year and 7 months to 5 years and 3 months (mean age of 3 years) were retrieved and analyzed by routine histological, immunohistochemical and electron methods.

RESULTSAmong 16 patients, there were 2 type I, 7 type II and 7 type III PPB cases. Type I PPB as multilocular cystic structure, consisted of thin fibrous wall lining the respiratory epithelium, subepithelial primitive blastema or immature mesenchymal cells, with or without rhabdomyoblastic differentiation or cartilage; Type II PPB as cystic-solid tumor, comparing with type I, consisted of intracystic components with appearance of anaplastic tumor cells. Type III PPB consisted of completely solid mass, the same as the solid region of type II, had mixed pattern including blastema, undifferentiated spindle-cell proliferations and sarcomas. In addition, anaplastic tumor cells and intra-and extra- cytoplasmic eosinophilic globules were also commonly present. Epithelial components in PPB were benign. Immunohistochemical study showed primitive mesenchymal differentiation of tumors. All cases were positive for vimentin, desmin, myogenin and SMA in tumors with skeletal muscle differentiation, S-100 was positive in tumors with cartilage differentiation. All tumors were negative for synaptophysin, CD99, and CD117. Benign epithelial components were positive for AE1/AE3 and EMA. In 12 cases, electron microscopy revealed few organelles in the primitive mesenchymal cells and rich heterochromatin in mesenchymal cells, the latter also demonstrating cytoplasmic myofilament dysplasia. Nine cases had clinical follow-up ranging from 5 to 48 months, of which 4 patients died.

CONCLUSIONSPPB is a rare lung neoplasm of children under the age of 6 years, with distinct pathological morphology. PPB may arise from lung or pleura mesenchymal cells and has a poor clinical outcome.

Child, Preschool ; Cysts ; pathology ; Desmin ; analysis ; Female ; Humans ; Infant ; Lung Neoplasms ; chemistry ; pathology ; Male ; Microscopy, Electron ; Myogenin ; analysis ; Prognosis ; Pulmonary Blastoma ; chemistry ; pathology ; Sarcoma ; pathology ; Vimentin ; analysis

To clarify the function and molecular mechanism of miR-155 in myogenic differentiation of C2C12, we constructed adenovirus over-expression vector of miR-155, then C2C12 cells were infected by adenovirus and induced myogenic differentiation. First, we observed the morphology of C2C12 after differentiation. Then the mRNA and protein expressions of myogenic markers (MyoD, MyoG and MyHC) were detected by qPCR and western blotting. Subsequently, the dual luciferase reporter gene assay was carried out to validate putative target gene (TCF4) of miR-155. Meanwhile, mRNA level of TCF4 was analyzed after over-expressing miR-155. The results show that over-expressed miR-155 reduced myotubes formation. Moreover, the mRNA and protein expression of MyoG and MyHC decreased significantly (P < 0.01). Further research demonstrated miR-155 bound the one (4532-4538) of three putative sites (1487-1493,1516-1522, 4532-4583) of TCF4 by luciferase reporter gene assay and the mRNA level of TCF4 decreased notably (P < 0.05). The data suggest that miR-155 inhibited myogenic differentiation of C2C12 through targeted TCF4.
Animals ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; genetics ; Cell Differentiation ; Cell Line ; Genetic Vectors ; Mice ; MicroRNAs ; genetics ; Myoblasts ; cytology ; Myogenin ; genetics ; metabolism ; Myosin Heavy Chains ; genetics ; metabolism ; RNA, Messenger ; genetics ; Transcription Factor 4

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

OBJECTIVETo investigate the clinicopathologic characteristics, differential diagnosis and biologic behaviors of pleomorphic rhabdomyosarcoma (PRMS).

METHODSThe clinical findings, pathological features and immunophenotypes were reviewed in 44 cases of PRMS (encountered during the period from 2005 to 2012). The clinical outcome was analyzed.

RESULTSThere were 33 males and 11 females with age ranging from 2 to 85 years (mean, 51 years; median, 55 years). Of 44 tumors, 22 occurred in the extremities (50.0%), 16 in the trunk (36.4%), 5 in the internal organs (11.4%), and 1 in the head and neck (2.2%). Histologically, 40 tumors showed features of pleomorphic sarcoma with striking resemblance to undifferentiated pleomorphic sarcoma (UPS)/malignant fibrous histiocytoma(MFH). However, variable amount of pleomorphic rhabdomyoblasts (PRMB) were identified in most cases. The remaining 4 tumors were composed predominantly of fascicles of spindle cells with interspersed PRMBs. Immunohistiochemically, tumor cells showed diffuse staining of desmin (41/41,100%), with variable expression of myogenin (18/32, 56.3%), MyoD1 (10/21, 47.6%) and MSA (21/29, 72.4%), whereas α-SMA was negative in most cases. Follow-up data (range, 2 to 51 months) available in 29 cases showed 12 patients were alive with unresectable or recurrent disease and 17 patients were alive with no evidence of disease. The median disease-free and overall survivals was 6.0 months (mean, 9.1 months) and 8.0 months (mean, 11.2 months) respectively. Thirteen patients (44.8%) exhibited progression of disease with recurrence in 4 cases and metastasis in 9 cases. The median interval to progression was 6.0 months (mean, 5.9 months).

CONCLUSIONSThe presence of pleomorphic cells with strong eosinphilic cytoplasm in a pleomorphic sarcoma is suggestive of a PRMS. Diffuse, strong expression of desmin and negative staining for α-SMA further facilitate the diagnosis of PRMS and its differential diagnosis from pleomorphic leiomyosarcoma. Although PRMS may affect children or adolescents, it should be cautious not to misdiagnose anaplastic rhabdomyosarcoma as PRMS. PRMS is a high-grade sarcoma with a poor prognosis.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Chemoradiotherapy, Adjuvant ; Chemotherapy, Adjuvant ; Child ; Child, Preschool ; Desmin ; metabolism ; Diagnosis, Differential ; Extremities ; Female ; Follow-Up Studies ; Histiocytoma, Malignant Fibrous ; metabolism ; pathology ; Humans ; Lung Neoplasms ; secondary ; Male ; Middle Aged ; MyoD Protein ; metabolism ; Myogenin ; metabolism ; Neoplasm Recurrence, Local ; Retrospective Studies ; Rhabdomyosarcoma ; metabolism ; pathology ; secondary ; surgery ; therapy ; Survival Rate ; Young Adult