Unusual response to second-line single-agent gemcitabine in locally advanced primary leiomyosarcoma of the lung: a case report

Primary leiomyosarcomas (LMSs) of the lung are extremely rare malignancies that have been the subject of single or small series of case reports. Today, the gold standard of treatment in patients with locally advanced and metastatic disease includes one of the many possible regimens containing an anthracycline and/or ifosfamide. Few chemotherapy agents are active in the second-line setting. In particular, gemcitabine is considered quite ineffective in the treatment of first- as well as second-line chemotherapy of soft tissue sarcoma and responses to this agent are seldom reported. In this paper, we report a single patient with primary LMS of the lung previously treated with a combination of epirubicin and ifosfamide. The patient responded to second-line chemotherapy with gemcitabine 1250 mg/m2 given as a 30-minute infusion on days 1, 8, and 15 of a 28-day cycle and showed an 8-month response duration and negligible toxicity. Gemcitabine may represent an alternative to the best supportive care in patients affected with soft tissue sarcoma who fail first-line chemotherapy.     

Unusual Response to Second-Line Single-Agent Gemcitabine in Locally Advanced Primary Leiomyosarcoma of the Lung: A Case Report

Abstract

Primary leiomyosarcomas (LMSs) of the lung are extremely rare malignancies that have been the subject of single or small series of case reports. Today, the gold standard of treatment in patients with locally advanced and metastatic disease includes one of the many possible regimens containing an anthracycline and/or ifosfamide. Few chemotherapy agents are active in the second-line setting. In particular, gemcitabine is considered quite ineffective in the treatment of first- as well as second-line chemotherapy of soft tissue sarcoma and responses to this agent are seldom reported. In this paper, we report a single patient with primary LMS of the lung previously treated with a combination of epirubicin and ifosfamide. The patient responded to second-line chemotherapy with gemcitabine 1250 mg/m² given as a 30-minute infusion on days 1, 8, and 15 of a 28-day cycle and showed an 8-month response duration and negligible toxicity. Gemcitabine may represent an alternative to the best supportive care in patients affected with soft tissue sarcoma who fail first-line chemotherapy.     

Epigenetic signatures differentiate uterine and soft tissue leiomyosarcoma

Leiomyosarcomas (LMS) are diverse, rare, and aggressive mesenchymal soft tissue sarcomas. Epigenetic alterations influence multiple aspects of cancer, however epigenetic profiling of LMS has been limited. The goal of this study was to delineate the molecular landscape of LMS for subtype-specific differences (uterine LMS (ULMS) vs soft tissue LMS (STLMS)) based on integrated analysis of DNA methylation and gene expression to identify potential targets for therapeutic intervention and diagnosis. We identified differentially methylated and differentially expressed genes associated with ULMS and STLMS using DNA methylation and RNA-seq data from primary tumors. Two main clusters were identified through unsupervised hierarchical clustering: ULMS-enriched cluster and STLMS-enriched cluster. The integrated analysis demonstrated 34 genes associated with hypermethylation of the promoter CpG islands and downregulation of gene expression in ULMS or STLMS. In summary, these results indicate that differential DNA methylation and gene expression patterns are associated with ULMS and STLMS. Further studies are needed to delineate the contribution of epigenetic regulation to LMS subtype-specific gene expression and determine the roles of the differentially methylated and differentially expressed genes as potential therapeutic targets or biomarkers.     

Uterine sarcomas

Uterine sarcomas comprise a small percentage of uterine malignancies. The most common uterine sarcoma is leiomyosarcoma (LMS). Early stage uterine LMS is curable with complete hysterectomy with removal of an intact uterus. Patients with metastatic disease may achieve tumor responses with improvements in quality of life, but long-term remissions are rare. In this review article, I outline adjuvant therapies for early stage resected uterine LMS, as well as treatment of metastatic disease.     

Leiomyosarcoma of Nose a Very Rare Tumor Case Report: Unusual Case Leiomyosarcoma Inferior Turbinate

Leiomyosarcoma (LMS) accounts for approximately 7% of all soft tissue sarcomas and occurs most frequently in the gastrointestinal tract and uterus. In the head and neck, however, LMS makes up only 2.3%. LMS of the nasal cavity and Para nasal sinuses are very rare and only about 20 cases of LMS of the nose and Para nasal sinuses have been reported in the literature. Initially, LMS should be treated by extensive surgical excision, long-term follow-up is essential due to the high rate of local recurrence. Radiotherapy and chemotherapy are insufficient therapeutic approaches. Frequency of recurrence and prognosis depend on the tumor site.     

Optimal management of uterine leiomyosarcoma

Uterine leiomyosarcomas (LMSs) are rare tumors, comprising 1.3% of all uterine cancers. Primary therapy for localized disease entails complete surgical resection. The majority of patients recur within 2 years of primary therapy as these tumors tend to undergo early hematogenous spread. A randomized, controlled trial showed no improvement in the overall or disease-free survival with adjuvant radiotherapy, compared with observation, following resection of early-stage uterine LMS. A Phase II study of adjuvant chemotherapy following complete surgical resection of uterine LMS reported promising results. However, in the absence of Phase III randomized data demonstrating improved outcomes, the role of post-resection chemotherapy for early-stage disease remains experimental. For metastatic or unresectable LMS, systemic chemotherapy forms the mainstay of treatment. First-line treatment options include gemcitabine–docetaxel or doxorubicin with or without ifosfamide. Novel targeted therapies are under investigation in an attempt to devise more effective treatment strategies.     

Adult paratesticular sarcomas: A report of eight cases

Eight adult paratesticular sarcomas seen at a Regional Cancer Centre over a 7-year period are described. There were three cases of rhabdomyosarcoma (RMS), three cases of leiomyosarcoma (LMS), and two cases of liposarcoma (LS). The RMS occurred in a younger age group (3rd decade) than the LMS and LS (6th and 7th decades). Most of our patients presented with advanced disease after orchiectomy at other hospitals, three with recurrent or residual disease and four with metastasis. The single patient with RMS who received intensive adjuvant therapy is free of disease at 84 months in spite of the advanced stage at presentation. All three patients with LMS had an unfavourable clinical course. Both the patients with LS had well differentiated (WD) tumours and presented with recurrences, one over several years, following initial local excisions. The necessity for early adequate surgical and adjuvant therapy and the need for a uniform treatment policy are discussed. © 1994 Wiley-Liss, Inc.     

Experimental study of the treatment of uterine leiomyosarcoma in the mouse with progestogen

Because of its rare occurrence in the human, the endocrinologic and receptor-related aspects of an uterine leiomyosarcoma (LMS) are poorly understood when compared to what is known of, say, human endometrial cancer. Thus, to increase our understanding, we have succeeded, by the string method, in inducing an uterine LMS in the mouse and have studied the possibility of hormonal therapy as a method of treatment. The findings of our study are enumerated as follows: 1. The induced uterine LMS had an estrogen receptor, which was confirmed by a biochemical assay and, morphologically, by a PAP (the peroxidase anti-peroxidase technique); 2. The growth of this tumor was significantly inhibited by MPA (medroxyprogesterone acetate) therapy (100 mg/kg); 3. After MPA therapy, the estrogen receptor levels were increased, especially in the nucleus; and, 4. The growth of a secondary tumor, transplanted after the initial hormone therapy, was not inhibited by the readministration of MPA. Our results suggest that this experimentally-induced uterine LMS in the mouse provides a useful means to study therapeutic treatment, and may assist in furthering our understanding of human uterine LMS and lead to finding an effective therapy.     

Leiomyosarcoma of the skin: A case report

A middle-aged man presented with an ulcerated nodule of the right posterior thigh that was histologically evaluated as leiomyosarcoma of the skin. A wide excision of the tumor was followed by split-thickness skin grafting. Leiomyosarcomas of the skin and subcutaneous tissue are rare tumors, usually occurring in the proximal lower extremities. The treatment of choice is a wide local excision with a 3- to 5-cm margin including the subcutaneous tissue and fascia. The defect is covered by a split-thickness skin graft.     

A rare case of facial Candida albicans cellulitis in an uncontrolled diabetic patient

Facial cellulitis is defined as infections or inflammation of the skin or connective tissue in orbital, periorbital area and cheeks, and is known to be caused mainly by bacterial infections, for which treatment with proper antibiotics and incision and drainage are necessary. Candidal cellulitis is a rare disease and only two cases have been reported in the world to our knowledge. Candidal facial cellulitis is a non-haematogenous, deep-seated infection and we should figure out for known risk factors of candidal colonisation or overgrowth and possible routes of infection for candidiasis. We report one case of facial cellulitis caused by Candida albicans in an uncontrolled diabetic woman aged 50.     

1例转移性隐匿性乳腺癌的临床诊治

隐匿性乳腺癌(occult breast cancer, OBC), 是较少见的特殊类型乳腺癌, 指经临床体检和影像学检查未发现乳房内包块而以腋窝淋巴结转移或其他远处转移为首发症状, 并经病理证实来源于乳腺组织的乳腺癌。对转移淋巴结进行组织病理学检查是OBC诊断的关键。对于钼靶和超声阴性的OBC, 增强核磁共振(MRI)检查在寻找原发灶方面有重要作用, 且有助于OBC的术前定位和指导手术方案。其手术治疗方法的选择尚有争议。现介绍1例晚期转移性OBC, 经多学科联合诊治、予以个体化综合治疗的成功经验, 为OBC的诊治提供更多思路, 强调多学科协作诊疗模式。      

Using drug scheduling to manage adverse events associated with hedgehog pathway inhibitors for basal cell carcinoma

Basal cell carcinoma (BCC) is the most common malignancy and form of skin cancer worldwide; advanced BCC, either as locally advanced BCC (laBCC) or metastatic BCC (mBCC), can cause substantial tissue invasion and morbidity. Until the recent availability of the hedgehog pathway inhibitors (HHIs) sonidegib and vismodegib, treatment options for advanced BCC were limited. These agents demonstrate efficacy in patients with laBCC and mBCC; however, the adverse events (AEs) associated with these agents can lead to treatment interruption or discontinuation and reduced quality of life, all of which significantly impact long-term adherence to therapy, which might affect clinical outcome. Given that most AEs are class-related effects, switching HHIs does not appear to lead to a significantly different AE profile, underscoring the importance of maintaining patients on their first HHI. Interrupting treatment of sonidegib and vismodegib does not appear to undermine the efficacy of these agents and is therefore a practical option to manage AEs in order to maintain continued treatment and disease control.     

Thymic malignancies focusing on systemic treatment

Malignancies originating from thymic epithelial tissue are rare and treatment approach depends on the individual situation. There are no randomized trials that provide evidence of therapy for patients with thymoma and thymic carcinoma. Treatment includes surgery, radiation therapy, and systemic therapy. For early stage tumors, surgery is the treatment of choice. Long-term survival depends on histologic type, presence of invasion, and quality of surgical resection. For locally advanced thymomas and thymic carcinomas, multimodal treatment includes neoadjuvant chemotherapy and adjuvant radiation. Patients with metastatic tumors are mainly treated with palliative chemotherapy. The optimal chemotherapy combination has not yet been established, although platinum-based drug regimes show reasonable response rates. For patients with poor performance status, the somatostatin (SST) analog octreotide with high affinity for SST receptors could be a potential treatment alternative. Small trials showed tumor responses, especially in combination with prednisolone. In the last decade, an effort has been made to establish targeted agents in the treatment of thymomas and thymic carcinomas. Nevertheless, up to now these agents have had only limited activity in this rare malignancy.     

Primary head and neck reconstruction with a simultaneous ipsilateral pectoralis major myocutaneous flap and a deltopectoral flap

Patients with large advanced tumors of the head and neck that are resectable may be reconstructed by using the combination of an ipsilateral pectoralis major myocutaneous flap and an ipsilateral deltopectoral flap. Preoperative planning is necessary. The PM flap must be elevated and care taken not to interfere with the internal mammary perforating arteries. The lateral chest incision must be made low enough to provide adequate skin and soft tissue in the DP flap. These two flaps provide adequate tissue with a reliable blood supply to reconstruct these large defects.     

Gemcitabine in the treatment of soft tissue sarcomas

Soft tissue sarcomas (STS) are rare mesenchymal tumors with poor prognosis once they present as advanced or metastasized disease. Only few cytostatic drugs have been proven to be active in sarcoma patients and there is a clear need for further treatment options in patients with tumors refractory to standard chemotherapy. Gemcitabine, a nucleoside analogue, has shown activity in several epithelial tumors. Clinical data on the activity of gemcitabine in STS, however, are scarce and heterogeneous. In trials including all subtypes of sarcomas response rates observed with single and multiagent schedules are ranging from 3 to 53%. Histopathological subtypes which seem to exhibit an increased susceptibility to gemcitabine are uterine leiomyosarcomas and angiosarcomas. The synergistic role of other cytostatic drugs, e.g. the role of taxanes, still remains unclear and warrants further trials. We here review the available literature on gemcitabine in the treatment of STS.     

The ODAC Chronicles: Part 7. Tale of two goals

The soft-tissue sarcomas are a diverse group of rare malignancies of mesenchymal tissue. Surgery is the principle modality of treatment but chemotherapy is used for the treatment of advanced or metastatic tumors. However, the response to chemotherapy is poor. Genetic factors are known to be important in the development of soft-tissue sarcomas and also have a role in response to treatment. This review discusses known genetic abnormalities in soft-tissue sarcomas. Molecular targets for treatment are also discussed along with a review of treatments that have been developed to date.     

Molecular pathology and potential therapeutic targets in soft-tissue sarcoma

The soft-tissue sarcomas are a diverse group of rare malignancies of mesenchymal tissue. Surgery is the principle modality of treatment but chemotherapy is used for the treatment of advanced or metastatic tumors. However, the response to chemotherapy is poor. Genetic factors are known to be important in the development of soft-tissue sarcomas and also have a role in response to treatment. This review discusses known genetic abnormalities in soft-tissue sarcomas. Molecular targets for treatment are also discussed along with a review of treatments that have been developed to date.     

Gastrointestinal (GI) leiomyosarcoma (LMS) case series and review on diagnosis,management, and prognosis

This review of 76 gastrointestinal (GI) leiomyosarcoma (LMS) cases that include 11 cases from the American University of Beirut Medical Center represents, to our knowledge, the largest number of combined GI LMS cases reported. The age range of GI LMS is variable, and the presentation is non-specific, making pathological diagnosis essential. LMSs usually lack CD117 and CD 34 mutations and are usually positive for smooth muscle cell markers. The review highlights surgery as the mainstay of treatment with negative margins attained most of the times. Adjuvant chemotherapy is used in around 7–27 % of the cases mainly for small intestinal and colorectal LMS. The relatively small number of patients is a limitation on outcome analysis. However, LMS has a risk of recurrence reaching 39–80 % and secondary metastasis reaching 55–71 % in small intestinal and colorectal cases. In light of the high frequency of recurrence and metastasis, enrolling patients in clinical randomized trials to investigate the role of chemotherapy, radiation therapy, and targeted therapy is required for better control of this rare aggressive GI tumor.     

Integrated histologic and molecular analysis of uterine leiomyosarcoma and 2 benign variants with nuclear atypia

Uterine leiomyosarcoma (LMS) is a rare but deadly disease. Due to poor understanding of the molecular and genetic causes of the disease, the diagnosis of LMS has been based primarily on histology. Nuclear atypia is one of hallmarks in LMS, however, it also occurs in 2 clinically benign variants, including smooth muscle tumors with fumarate hydratase alteration (SMT-FH) and leiomyoma with bizarre nuclei (LM-BN). In addition to nuclear atypia, many well recognized biomarkers used for LMS are also frequently overexpressed in LM-BN, and the histogenesis and molecular natures for LM-BN and LMS remain largely unknown. To characterize the molecular profiling of LMS, SMT-FH, and LM-BN, we performed integrated comprehensive genomic profiling including whole-genome sequencing (WGS) and RNA sequencing and genomic microarray analyses to assess genome-wide copy number alterations (CNAs) and immunohistochemistry (IHC) in all 3 tumor types. We found that both LM-BN and LMS showed genomic instability and harbored extensive CNAs throughout the whole genome. By contrast, the SMT-FH presented its characteristic 1q43-44 deletions in all cases tested, with minimal CNAs in the rest of genomic regions. Further analyses revealed that LMS and LM-BN groups showed similar patterns of CNAs that are tended to cluster together and separated from the SMT-FH group. The integrated molecular profiling enabled the detection of novel and traditional biomarkers and showed excellent discrimination between LM-BN and LMS. Our study suggests that LM-BN, despite having similar nuclear atypia to SMT-FH, showed similar genomic instability but distinct genomic alterations with its malignant counterpart of LMS. The integrated molecular profiling is of clinical importance in characterizing these rare uterine smooth muscle tumors.