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JFMS Open Reports 2024A 1-year-old castrated male domestic shorthair cat was suspected with myasthenia gravis (MG) based on neurological examination, complete blood count (CBC), serum...
CASE SERIES SUMMARY
A 1-year-old castrated male domestic shorthair cat was suspected with myasthenia gravis (MG) based on neurological examination, complete blood count (CBC), serum biochemistry, radiography and electrophysiological examination. In addition, a 9-year-old spayed female domestic shorthair cat was diagnosed with MG based on neurological examination, CBC, serum biochemistry, radiography, ultrasonography and increased acetylcholine receptor antibody titre. Positioning head tilt (PHT) was observed at the time of diagnosis in both cats.
RELEVANCE AND NOVEL INFORMATION
Although the pathophysiology of PHT in cats is not fully understood, the mechanism for PHT in cats with MG may be similar to that of cats with hypokalaemic myopathy, supporting our hypothesis that muscle spindle dysfunction causes PHT.
PubMed: 38357272
DOI: 10.1177/20551169231224534 -
International Journal of Molecular... Feb 2024Peripheral nerve injury denervates muscle, resulting in muscle paralysis and atrophy. This is reversible if timely muscle reinnervation occurs. With delayed...
Peripheral nerve injury denervates muscle, resulting in muscle paralysis and atrophy. This is reversible if timely muscle reinnervation occurs. With delayed reinnervation, the muscle's reparative ability declines, and muscle-resident fibro-adipogenic progenitor cells (FAPs) proliferate and differentiate, inducing fibro-fatty muscle degradation and thereby physical disability. The mechanisms by which the peripheral nerve regulates FAPs expansion and differentiation are incompletely understood. Using the rat tibial neve transection model, we demonstrated an increased FAPs content and a changing FAPs phenotype, with an increased capacity for adipocyte and fibroblast differentiation, in gastrocnemius muscle post-denervation. The FAPs response was inhibited by immediate tibial nerve repair with muscle reinnervation via neuromuscular junctions (NMJs) and sensory organs (e.g., muscle spindles) or the sensory protection of muscle (where a pure sensory nerve is sutured to the distal tibial nerve stump) with reinnervation by muscle spindles alone. We found that both procedures reduced denervation-mediated increases in glial-cell-line-derived neurotrophic factor (GDNF) in muscle and that GDNF promoted FAPs adipogenic and fibrogenic differentiation in vitro. These results suggest that the peripheral nerve controls FAPs recruitment and differentiation via the modulation of muscle GDNF expression through NMJs and muscle spindles. GDNF can serve as a therapeutic target in the management of denervation-induced muscle injury.
Topics: Rats; Animals; Glial Cell Line-Derived Neurotrophic Factor; Muscle, Skeletal; Cell Differentiation; Tibial Nerve; Adipogenesis; Denervation
PubMed: 38339124
DOI: 10.3390/ijms25031847 -
Diagnostics (Basel, Switzerland) Feb 2024Pseudomyogenic hemangioendothelioma (PMHE), a rare vascular neoplasm, was first described in 1992 asa fibroma-like variant of epithelioid sarcoma, and would be termed as...
Pseudomyogenic hemangioendothelioma (PMHE), a rare vascular neoplasm, was first described in 1992 asa fibroma-like variant of epithelioid sarcoma, and would be termed as epithelioid sarcoma-like hemangioendothelioma a decade later due to its significant histologic overlap with epithelioid sarcoma and diffuse cytokeratin expression. PHME is currently defined as a distinct, potentially intermediate malignant, rarely metastasizing neoplasm with vascular/endothelial differentiation. It is characterized by young age (typically less than 40 years old), extremity location (approximately ~80%), and t(7:19) SERPINE1::FOSB fusion as the most common molecular alteration. Herein, we report a case of a 59-year-old male presenting with multifocal lesions, including in the right temporalis muscle, right frontoparietal calvarium, right pterygoid muscles, and right mandibular condyle. Histologic examination of the right temporal lesion revealed a multinodular biphasic lesion composed of sheets and fascicles of elongated spindle and epithelioid cells infiltrating into the adjacent skeletal muscle. Admixed abundant neutrophilic infiltration is noted; however, areas of necrosis, increased mitosis, nuclear atypia, or rhabdomyoblast-like cells are absent. Immunohistochemical (IHC) staining showed that the tumor cells were diffusely and strongly positive for FOSB, pan-cytokeratin (AE1/AE3), CD31, and ERG. Molecular testing demonstrated a t(9:19) EGFL7::FOSB fusion mRNA. This constellation of morphological, IHC and molecular findings was consistent with a diagnosis of PMHE. This is the first reported case of multifocal PMHE with EGFL7::FOSB fusion in the head and neck area of a patient aged more than 50 years old. Since the differential diagnoses for PMHE includes high-grade malignancies with aggressive clinical behavior, coupled with the rare reports of PMHE in the head and neck region, awareness of this tumor in the head and neck region will avoid the misdiagnosis and overtreatment of this entity.
PubMed: 38337858
DOI: 10.3390/diagnostics14030342 -
Pediatric spindle cell/sclerosing rhabdomyosarcoma with fusion: a case report and literature review.Translational Pediatrics Jan 2024gene fusion is a recently identified and highly distinct molecular subtype of spindle cell/sclerosing rhabdomyosarcoma (RMS), with fewer than 40 cases being reported to...
BACKGROUND
gene fusion is a recently identified and highly distinct molecular subtype of spindle cell/sclerosing rhabdomyosarcoma (RMS), with fewer than 40 cases being reported to date. Due to its low incidence, clinical studies on this subtype are limited. Here, we report a new case of this rare entity to describe and summarize its unique clinical characteristics and treatment process, aiming to emphasize the importance of molecular testing for spindle cell/sclerosing RMS and increase the understanding of this subtype. By summarizing and comparing with previous reports on RMS with the fusion mutation, we hope to make some new hints for its management.
CASE DESCRIPTION
In this report, we describe a rare case of spindle cell/sclerosing RMS in a 13-year-old boy, who had a massive destructive lesion involving the mandible. Next-generation sequencing of tumor tissue revealing a fusion. The tumor was extremely aggressive and showed resistance to polychemotherapy, after 4 cycles of multi drug combined chemotherapy, the primary tumor still continued to grow, and suspicious chest metastasis occurred. Even after aggressive total resection of the primary tumor and postoperative chemotherapy, systemic metastasis to the vertebra and chest could not be prevented yet, ultimately with a fatal outcome within 6 months. We additionally summarize 37 cases of RMS with the fusion mutation reported in the literature. This subtype was found to be almost exclusively primary in bone and histologically showed a common origin of epithelium and muscle. The high aggressiveness made the conventional standard chemoradiotherapy ineffective. Because most tumors of this subtype express ALK protein, ALK inhibitors seem to be a new target for its therapy.
CONCLUSIONS
Spindle cell/sclerosing RMS with fusion has its unique clinical characteristics and progression. It shows a marked skeletal predilection and an aggressive clinical course, typically resistant to traditional standard treatments for RMS. Therefore, molecular detection is crucial in managing this subtype. Once the diagnosis is clear, a more aggressive treatment plan is needed. In addition, almost all cases were found to have a positive expression of ALK. So ALK inhibitors can be a choice of targeted therapy.
PubMed: 38323177
DOI: 10.21037/tp-23-603 -
Nucleic Acids Research Apr 2024The Wnt/β-Catenin pathway plays a key role in cell fate determination during development and in adult tissue regeneration by stem cells. These processes involve...
The Wnt/β-Catenin pathway plays a key role in cell fate determination during development and in adult tissue regeneration by stem cells. These processes involve profound gene expression and epigenome remodeling and linking Wnt/β-Catenin signaling to chromatin modifications has been a challenge over the past decades. Functional studies of the lysine demethylase LSD1/KDM1A converge to indicate that this epigenetic regulator is a key regulator of cell fate, although the extracellular cues controlling LSD1 action remain largely unknown. Here we show that β-Catenin is a substrate of LSD1. Demethylation by LSD1 prevents β-Catenin degradation thereby maintaining its nuclear levels. Consistently, in absence of LSD1, β-Catenin transcriptional activity is reduced in both MuSCs and ESCs. Moreover, inactivation of LSD1 in mouse muscle stem cells and embryonic stem cells shows that LSD1 promotes mitotic spindle orientation via β-Catenin protein stabilization. Altogether, by inscribing LSD1 and β-Catenin in the same molecular cascade linking extracellular factors to gene expression, our results provide a mechanistic explanation to the similarity of action of canonical Wnt/β-Catenin signaling and LSD1 on stem cell fate.
Topics: Animals; Histone Demethylases; Wnt Signaling Pathway; beta Catenin; Mice; Cell Self Renewal; Cell Nucleus; Spindle Apparatus; Cell Differentiation; Humans; Stem Cells
PubMed: 38321961
DOI: 10.1093/nar/gkae060 -
Journal of the Anus, Rectum and Colon 2024Inflammatory myofibroblastic tumors (IMTs) are neoplastic lesions characterized by the proliferation of spindle cells with myofibroblastic features and lymphocyte...
Inflammatory myofibroblastic tumors (IMTs) are neoplastic lesions characterized by the proliferation of spindle cells with myofibroblastic features and lymphocyte infiltration. Primary lesions can develop in several locations but rarely arise in the colon as described herein. The present case was that of a 69-year-old woman who visited our hospital with complaints of bloody bowel discharge and a prolapsed mass from the anus. A 20-mm tumor was identified on visual and digital examination. Lower gastrointestinal endoscopy revealed a pedunculated, elevated lesion above the dentate line, which showed contrast enhancement on abdominal computed tomography. The patient was preoperatively diagnosed with an anal polyp, which was resected transanally. During the procedure, a mobile tumor coated by anal epithelium was observed at the 11 o'clock position above the dentate line. Deeper parts of the tumor were contiguous with the internal anal sphincter (IAS) muscle. Suspecting a neoplastic lesion, we resected the mass with part of the IAS. Tumor histopathology after surgery led to a final diagnosis of an IMT of the anus. IMT is difficult to diagnose preoperatively. No adjuvant therapy has been formally established; thus, an adequate surgical margin and close monitoring are essential.
PubMed: 38313745
DOI: 10.23922/jarc.2022-043 -
Heliyon Jan 2024Fumarate hydratase (FH) deficient uterine leiomyomas account for only 0.4 % of all uterine leiomyomas. They are characterized by some distinct histological features and...
INTRODUCTION
Fumarate hydratase (FH) deficient uterine leiomyomas account for only 0.4 % of all uterine leiomyomas. They are characterized by some distinct histological features and may be associated with Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome.
METHODS
Herein we present a series of five cases of FH deficient uterine leiomyomas in patients with a mean age of 30 years. All five patients underwent myomectomy. Three of these cases had an outside histopathologic diagnosis ranging from Smooth muscle tumor of uncertain malignant potential (STUMP) to Leiomyosarcoma while two cases were operated at our centre. All five cases were reported as suggestive of FH deficient leiomyomas and were advised germline testing along with genetic counselling.
RESULTS
Immunohistochemically four of the cases showed moderate to strong positivity for 2-SC with a complete loss or reduced expression of FH while one case showed absence of 2-SC staining.
DISCUSSION
Mutations in FH lead to reduced enzyme activity and accumulation of fumarate leading to a complete loss or aberrant reduced expression seen on immunohistochemistry, which confirms the diagnosis. It is important to differentiate it from a leiomyosarcoma or other malignant spindle cell tumors as these tumors follow a benign course. Their association with HLRCC also needs to be established for a suitable follow up since HLRCC-associated RCCs are often aggressive.
CONCLUSION
Management of such leiomyomas is myomectomy or hysterectomy with advice of genetic testing to rule out HLRCC. Histomorphology and immunohistochemistry are imperative for a correct and timely diagnosis.
PubMed: 38293425
DOI: 10.1016/j.heliyon.2024.e24449 -
Radiology Case Reports Apr 2024Dendritic fibromyxolipoma (DFML) is a benign, very rare, and slow-growing soft tissue tumor commonly involving the muscular fascia of the foot, calf, shoulders, back, or...
Dendritic fibromyxolipoma (DFML) is a benign, very rare, and slow-growing soft tissue tumor commonly involving the muscular fascia of the foot, calf, shoulders, back, or head and neck muscles. Many authors consider dendritic fibromyxolipoma a variant of spindle cell lipoma composed of a plexiform vascular pattern, dendritic cytoplasmic processes, and keloidal collagen. Only a few cases have been reported in the shoulder region, and the presented case represents the second case in English literature whose histopathology showed intramuscular involvement. Recognition of such an entity is essential because it is considered a scarce type of benign tumor that can be mistaken for other aggressive neoplasms of myxoid pathology. We present a case of a dendritic fibromyxolipoma around the right shoulder with intramuscular involvement to the superficial fibers of the right trapezius muscle.
PubMed: 38292809
DOI: 10.1016/j.radcr.2023.12.035 -
Ear, Nose, & Throat Journal Jan 2024Solitary myofibroma or infantile myofibroma is a rare spindle cell neoplasm that generally affects infants before the age of 2 years but cases in young children and...
Solitary myofibroma or infantile myofibroma is a rare spindle cell neoplasm that generally affects infants before the age of 2 years but cases in young children and adults have been described. Although the location of infantile myofibroma in the oral and maxillofacial region has been described, the intramasseteric location of the lesion is very uncommon. A thorough assessment of histopathological and immunohistochemical characteristics is necessary to have a correct diagnosis. Treatment relies on surgical resection. In this article, we present a rare clinical case of a 15-year-old patient with a myofibroma of the masseteric muscle and its management.
PubMed: 38284156
DOI: 10.1177/01455613231223378 -
Therapeutic Advances in Urology 2024High-grade (HG) urothelial carcinoma (UC) with variant histology has historically been managed conservatively. The presented case details a solitary lesion of...
High-grade (HG) urothelial carcinoma (UC) with variant histology has historically been managed conservatively. The presented case details a solitary lesion of muscle-invasive bladder cancer (MIBC) with sarcomatoid variant (SV) histology treated by partial cystectomy (PC) and adjuvant chemotherapy. A 71-year-old male with a 15-pack year smoking history presented after outside transurethral resection of bladder tumor (TURBT). Computerized tomography imaging was negative for pelvic lymphadenopathy, a 2 cm broad-based papillary tumor at the bladder dome was identified on office cystoscopy. Complete staging TURBT noted a final pathology of invasive HG UC with areas of spindle cell differentiation consistent with sarcomatous changes and no evidence of lymphovascular invasion. The patient was inclined toward bladder-preserving options. PC with a 2 cm margin and bilateral pelvic lymphadenectomy was performed. Final pathology revealed HG UC with sarcomatoid differentiation and invasion into the deep muscularis propria, consistent with pathologic T2bN0 disease, a negative margin, and no lymphovascular invasion. Subsequently, the patient pursued four doses of adjuvant doxorubicin though his treatment was complicated by hand-foot syndrome. At 21 months postoperatively, the patient developed a small (<1 cm) papillary lesion near but uninvolved with the left ureteral orifice. Blue light cystoscopy and TURBT revealed noninvasive low-grade Ta UC. To date, the patient has no evidence of HG UC recurrence; 8 years after PC. Patient maintains good bladder function and voiding every 3-4 h with a bladder capacity of around 350 ml. Surgical extirpation with PC followed by adjuvant chemotherapy may represent a durable solution for muscle invasive (pT2) UC with SV histology if tumor size and location are amenable. Due to the sparse nature of sarcomatous features within UC, large multicenter studies are required to further understand the clinical significance and optimal management options for this variant histology.
PubMed: 38250697
DOI: 10.1177/17562872241226582