Objective: To investigate the clinicopathological characteristics, immunophenotype, molecular genetics and differential diagnoses of fibrocartilaginous lipomas which consist of adipose tissue, fibrocartilage and fibrous elements. Methods: The clinicopathological features, immunohistochemical profiles and molecular profiles in six cases of fibrocartilaginous lipomas diagnosed at Foshan Traditional Chinese Medicine Hospital, Fudan University Shanghai Cancer Center, the Fifth Affiliated Hospital of Zhengzhou University and the Fourth Affiliated Hospital of Harbin Medical University from January 2017 to February 2022 were included. The follow-up information, diagnosis and differential diagnoses were evaluated. Results: There were three males and three females with a median age of 53 years (range 36-69 years) at presentation. Tumors were located in the extremities, the head and neck region and trunk; and presented as painless masses that were located in the subcutaneous tissue or deep soft tissue. Grossly, three cases were well defined with thin capsule, one case was well circumscribed without capsule, two cases were surrounded by some skeletal muscle. The tumors were composed of fatty tissue with intermingled gray-white area. The tumors ranged from 1.50-5.50 cm (mean 2.92 cm). Microscopically, the hallmark of these lesions was the complex admixture of mature adipocytes, fibrocartilage and fibrous element in varying proportions; the fibrocartilage arranged in a nodular, sheet pattern with some adipocytes inside. Tumor cells had a bland appearance without mitotic activity. Immunohistochemical analysis using antibodies to SMA, desmin, S-100, SOX9, HMGA2, RB1, CD34, adipopholin was performed in six cases; the fibrocartilage was positive for S-100 and SOX9, adipocytes were positive for S-100, adipopholin and HMGA2; CD34 was expressed in the fibroblastic cells, while desmin and SMA were negative. Loss of nuclear RB1 expression was not observed. Other genetic abnormalities had not been found yet in four cases. Follow-up information was available in six cases; there was no recurrence in five, and one patient only underwent biopsy of the mass. Conclusions: Fibrocartilaginous lipoma is a benign lipomatous tumor with mature adipocytes, fibrocartilage and fibrous elements. By immunohistochemistry, they show the expression of fat and cartilage markers. No specific molecular genetics changes have been identified so far. Familiarity with its clinicopathological features helps the distinction from its morphologic mimics.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Desmin/analysis* ; China ; Lipoma/pathology* ; Fibroblasts/pathology* ; S100 Proteins/analysis* ; Diagnosis, Differential ; Fibrocartilage/pathology* ; Biomarkers, Tumor/analysis*

Aggressive angiomyxoma is a rare mesenchymal tumor. To discuss the clinicopathological characteristics, treatment and prognosis of aggressive angiomyxoma, four cases of aggressive angiomyxoma of soft tissue in abdominopelvic cavity were collected from January 2015 to August 2017 in Peking University International Hospital. The clinical data, imaging examination, histopathological features, immunophenotype, therapy and prognosis were analysed. The related literatures were reviewed. All of the patients were adult females, age range from 27 to 49 years and mean 33 years. The clinical complaint was abdominal distention with no definite predisposing factor, or occasional physical-exam finding with no obvious discomfort. Three cases were primary and one case was recurrent. Typical layered or swirled structural sign was presented by CT and MRI scanning of three cases. All tumors located in the pelvic cavity, and attached to the uterus, vagina, rectum, bladder or ureter. One case was involved in the abdominal cavity simultaneously,adhesive to the spine, inferior vena cava and spleen. The gross appearance of tumors was from 5 to 22 cm in maximum diameter. The sectioned surfaces were soft, solid, white or yellow-gray, focally accompanied by edema, mucoid degeneration or cystic change. Microscopic observation showed that tumor cells were short spindle shaped and little atypical, the stroma was loose like edematous mucus or collagen, and the vessels were rich in thin and thick-wall. Partially the vessel wall expressed hyaline degeneration. Also tumors might infiltrate surrounding tissue, such as fat or nerve. The immunohistochemistry results of all cases were estrogen receptor and progesterone receptor diffusely moderate positive, Desmin and smooth muscle actin mostly positive, whereas CD34 expressed only in vessel and S-100 protein, CD117 and Dog1 all negative. All the tumors were complete surgical excision. During follow-up, one case recurred the second time. Our conclusions are the diagnosis of aggressive angiomyxoma is based on pathological morphology supplemented by immunohistochemistry, and the tumor may relapse after surgical resection.
Adult ; Desmin/analysis* ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Myxoma/pathology* ; Neoplasm Recurrence, Local ; Receptors, Estrogen/analysis*

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

BACKGROUNDTissue-engineered bioartificial muscle-based gene therapy represents a promising approach for the treatment of heart diseases. Experimental and clinical studies suggest that systemic administration of insulin-like growth factor-1 (IGF-1) protein or overexpression of IGF-1 in the heart exerts a favorable effect on cardiovascular function. This study aimed to investigate a chronic stage after myocardial infarction (MI) and the potential therapeutic effects of delivering a human IGF-1 gene by tissue-engineered bioartificial muscles (BAMs) following coronary artery ligation in Sprague-Dawley rats.

METHODSLigation of the left coronary artery or sham operation was performed. Primary skeletal myoblasts were retrovirally transduced to synthesize and secrete recombinant human insulin-like growth factor-1 (rhIGF-1), and green fluorescent protein (GFP), and tissue-engineered into implantable BAMs. The rats that underwent ligation were randomly assigned to 2 groups: MI-IGF group (n = 6) and MI-GFP group (n = 6). The MI-IGF group received rhIGF-secreting BAM (IGF-BAMs) transplantation, and the MI-GFP group received GFP-secreting BAM (GFP-BAMs) transplantation. Another group of rats served as the sham operation group, which was also randomly assigned to 2 subgroups: S-IGF group (n = 6) and S-GFP group (n = 6). The S-IGF group underwent IGF-1-BAM transplantation, and S-GFP group underwent GFP-BAM transplantation. IGF-1-BAMs and GFP-BAMs were implanted subcutaneously into syngeneic rats after two weeks of operation was performed. Four weeks after the treatment, hemodynamics was performed. IGF-1 was measured by radioimmunoassay, and then the rats were sacrificed and ventricular samples were subjected to immunohistochemistry. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine the mRNA expression of bax and Bcl-2. TNF-α and caspase 3 expression in myocardium was examined by Western blotting.

RESULTSPrimary rat myoblasts were retrovirally transduced to secrete rhIGF-1 and tissue-engineered into implantable BAMs containing parallel arrays of postmitotic myofibers. In vitro, they secreted consistent levels of hIGF (0.4 - 1.2 µg×BAM(-1)×d(-1)). When implanted into syngeneic rat, IGF-BAMs secreted and delivered rhIGF. Four weeks after therapy, the hemodynamics was improved significantly in MI rats treated with IGF-BAMs compared with those treated with GFP-BAMs. The levels of serum IGF-1 were increased significantly in both MI and sham rats treated with IGF-BAM. The mRNA expression of bax was lower and Bcl-2 expression was higher in MI-IGF group than MI-GFP group (P < 0.05). Western blotting assay showed TNF-α and caspase 3 expression was lower in MI-IGF group than MI-GFP group after therapy.

CONCLUSIONSrhIGF-1 significantly improves left ventricular function and suppresses cardiomyocyte apoptosis in rats with chronic heart failure. Genetically modified tissue-engineered BAMs provide a method delivering recombinant protein for the treatment of heart failure.

Animals ; Apoptosis ; Caspase 3 ; analysis ; Desmin ; analysis ; Genetic Therapy ; Heart Failure ; pathology ; physiopathology ; therapy ; Insulin-Like Growth Factor I ; genetics ; secretion ; Myoblasts, Skeletal ; metabolism ; Myocytes, Cardiac ; pathology ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; secretion ; Retroviridae ; genetics ; Tissue Engineering ; Tumor Necrosis Factor-alpha ; analysis ; Ventricular Function, Left

OBJECTIVETo culture rat corpus cavernosum smooth muscle cells in vitro using a modified tissue culture method.

METHODSFifteen male rats were randomized into 3 equal groups, namely enzyme digestion group, tissue culture group, and modified tissue culture group. The penis of the rats was separated carefully and cut into small pieces, and seeded onto culture flasks and cultured in complete medium consisting of DMEM containing 20% fetal calf serum at 37 degrees C; in a humidified atmosphere with 5% carbon dioxide. The cells growth was observed under phase contrast microscope and the smooth muscle cell specific proteins alpha-SM-actin and desmin were identified immunohistochemically.

RESULTSThe alpha-SM-actin-positive cell rate was 96.3% in rat corpus cavernosum smooth muscle and 23.8% in the fibroblasts, and the corpus cavernosum smooth muscle contained 74.4% desmin-positive cells while the fibroblasts showed no desmin positivity. Significant difference was found in the positive cell rate for desmin among the 3 groups, with the highest positive cell rate occurred in modified tissue culture group.

CONCLUSIONDesmin may serve as a marker for identifying corpus cavernosum smooth muscle cells. The modified tissue culture method can result in highly purified corpus cavernosum smooth muscle cells with intact structure and functions.

Actins ; analysis ; Animals ; Biomarkers ; analysis ; Cell Proliferation ; Desmin ; analysis ; Male ; Muscle, Smooth ; cytology ; Penis ; cytology ; Rats ; Rats, Sprague-Dawley ; Tissue Culture Techniques

OBJECTIVETo profile the protein expression in activated rat hepatic stellate cells (HSCs).

METHODSPrimary rat HSCs were isolated and cultured in vitro. After 10 days in vitro culture, the HSCs were activated. Total protein extracted from these activated HSCs were digested, and the obtained peptides were analyzed by using online 2D nanoLC-MS/MS. The identified proteins were classified according to their distributions and functions.

RESULTS1014 proteins were identified from 50 microg HSCs protein extract, the molecular weights of these proteins ranged from 7832 Da to 588,364 Da. Most of these proteins resided in nucleus, cytoskeleton, mitochondrion and endoplasmic reticulum. And these proteins were mainly involved in nucleic acid metabolism, organelle organization, signal transduction and energy generation. Among these proteins, alpha-smooth muscle actin, vimentin and desmin were specifically expressed in activated HSCs.

CONCLUSIONTo the best of our knowledge, this is the most comprehensive protein expression profile of activated rat HSCs.

Actins ; analysis ; metabolism ; Animals ; Cell Nucleus ; metabolism ; Cells, Cultured ; Chromatography, High Pressure Liquid ; methods ; Desmin ; analysis ; metabolism ; Hepatic Stellate Cells ; metabolism ; Male ; Proteome ; analysis ; metabolism ; Proteomics ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; Vimentin ; analysis ; metabolism

BACKGROUNDIntermediate filament (IF) proteins have been thought to play a role in nuclear centration, organelle movement and maintenance of cell shape. dl-praeruptorin A (Pd-Ia), a novel Ca2+-influx blocker and K+-channel opener isolated from Chinese traditional herbal medicine Qian-Hu, has been demonstrated to inhibit expression of apoptosis related proteins and reduce the level of proinflammatory factors in ischemia/reperfusion myocardiocytes. Morphologically, whether Pd-Ia effects myocardiocyte IFs remains unclear. The purpose of this study was, for the first time, to evaluate the in vivo effects of Pd-Ia on IF desmin and vimentin content in order to further explore its cardioprotection against ischemia and elucidate its mechanism of action.

METHODSRats underwent a 30 minutes coronary occlusion followed by 120 minutes reperfusion. Assessment of desmin and vimentin content of myocardiocytes was performed by immunohistochemistry, Western blot, Hematoxylin-Eosin staining and densitometry.

RESULTSPretreatment with i.v. infusion of Pd-Ia prior to ischemia significantly increased desmin and vimentin content and alleviated defects caused by the ischemia/reperfusion insult, e.g. with Pd-Ia at a dose of 0.5 or 1.0 mg/kg, integrated density values of desmin were increased from 61 478 +/- 10 074 to 177 408 +/- 10 395 and 195 784 +/- 20 057, and vimentin from 59 189 +/- 19 853 to 164 781 +/- 19 543 and 185 696 +/- 20 957 (P < 0.01, vs placebo), respectively. The recovery of desmin seemed to be stronger and appeared earlier than that of vimentin.

CONCLUSIONPd-Ia protectively increased IF desmin and vimentin content in ischemia/reperfusion myocardiocytes, which might be partially responsible for its cardioprotection against ischemia.

Animals ; Blotting, Western ; Calcium ; metabolism ; Coumarins ; pharmacology ; Desmin ; analysis ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; pharmacology ; Female ; Immunohistochemistry ; Male ; Myocardial Ischemia ; drug therapy ; metabolism ; Myocardial Reperfusion Injury ; prevention & control ; Myocytes, Cardiac ; chemistry ; drug effects ; pathology ; Rats ; Rats, Wistar ; Vimentin ; analysis

Animals ; Desmin ; analysis ; genetics ; Female ; Immunohistochemistry ; Intermediate Filament Proteins ; analysis ; genetics ; Kidney Glomerulus ; chemistry ; Nephrosis ; metabolism ; Nerve Tissue Proteins ; analysis ; genetics ; Nestin ; Podocytes ; chemistry ; RNA, Messenger ; analysis ; Rats ; Rats, Inbred WKY ; Vimentin ; analysis ; genetics

BACKGROUNDPodocyte has inflammatory role in the development of diabetic nephropathy (DN). Mycophenolate mofetil (MMF), an anti-inflammatory agent, can suppress macrophage infiltration and reduce renal injury in streptozotocin-induced diabetic rats. Angiotensin II receptor blocker (ARB), another renal protecting agent, can decrease podocyte loss in DN. In this study, we detected the expression levels of monocyte chemoattractant protein-1 (MCP-1) and nephrin to evaluate podocyte's role in inflammatory reaction in DN, observe and compare the effect of MMF alone and in combination with valsartan, on preventing podocyte loss in streptozotocin (STZ) induced diabetic rats.

METHODSDiabetic model was constructed in uninephrectomized male Wistar rats by single peritoneal injection of STZ (65 mg/kg). The successfully induced diabetic rats were randomly divided into four groups: diabetes without treatment group (DM), valsartan treated group (DMV), MMF treated group (DMM), and combined therapy group (DMVM). Normal rats of the same sibling were chosen as control (NC). At the end of the 8th week, serum biochemistry, 24-hour urinary protein (UP) and the ratio of kidney weight/body weight (RWK/B) were measured. The rats were sacrificed for the observation of renal histomorphology through light and electron microscope. Nephrin, desmin and MCP-1 levels were detected by semi-quantitative immunohistochemical assays. Real-time quantitative PCR was used to detect the mRNA levels of nephrin and MCP-1.

RESULTSCompared with group NC, serum glucose level, 24-hour UP and RWK/B in group DM were significantly higher (P < 0.01), and the nephrin mRNA level in DM group was significantly lower (P < 0.05). The nephrin mRNA expression levels in group DMV, DMM and DMVM were all higher than that of DM group (P < 0.05) and no significant differences were found among the three treatment groups (P > 0.05). Treatment with MMF, valsartan or their combination could significantly decrease the 24-hour UP and RWK/B, and suppress glomerulosclerosis and interstitial fibrotic lesions in diabetic rats. In diabetic rats, the high expressions of desmin and MCP-1 in kidney were suppressed by valsartan, MMF or their combination.

CONCLUSIONSPodocytes are involved in the inflammatory reaction of diabetic rats. MMF could suppress MCP-1 and desmin expression, enhance nephrin expression, and attenuate proteinuria in diabetic rats. The combined therapy of valsartan and MMF did not show any superiority over monotherapies on renal protection. MMF may have renoprotective effect in early stages of diabetic nephropathy through preventing podocytes loss and anti-inflammatory activity.

Animals ; Chemokine CCL2 ; analysis ; Desmin ; analysis ; Diabetic Nephropathies ; drug therapy ; pathology ; Drug Therapy, Combination ; Immunohistochemistry ; Male ; Membrane Proteins ; analysis ; Mycophenolic Acid ; administration & dosage ; analogs & derivatives ; therapeutic use ; Podocytes ; drug effects ; pathology ; Rats ; Rats, Wistar ; Tetrazoles ; administration & dosage ; therapeutic use ; Valine ; administration & dosage ; analogs & derivatives ; therapeutic use ; Valsartan