Expression of growth factor receptors,the focal adhesion kinase,and other tyrosine kinases in human soft tissue tumors

Background: The tyrosine kinases are a family of genes that includes many growth factor receptors and protooncogenes. They appear to have a role in many cancers, but have not been systematically studied in the pathogenesis and progression of human sarcomas. Methods: To characterize the protein tyrosine kinases that are expressed in human sarcomas, we used a polymerase chain reaction (PCR)-based method to construct kinase-specific cDNA libraries from low-grade and high-grade primary tumors. Thereafter, individual tyrosine kinase gene expression was assessed in a panel of sarcoma cell lines and primary tumors using Northern blotting and PCR. Results: We identified 19 species of tyrosine kinase genes, including many growth factor receptors, the human homolog of the focal adhesion kinase (FAK) gene, and a noveltrk-related kinase designated HGK2. Messenger RNA expression analyses showed relative overexpression of the two forms of the platelet-derived growth factor receptors (PDGFRs) with expression of the form restricted to a subgroup of high-grade and metastatic sarcomas. We were unable to demonstrate coexpression of the PDGF isoforms in primary tumors that overexpressed the receptors, suggesting that a PDGF/PDGFR autocrine pathway may not be a central mechanism in the malignant transformation of sarcomas in vivo. FAK expression was observed in a variety of sarcomas, with increased levels in several high-grade and metastatic leiomyosarcomas. Conclusions: When grouped together by histologic cell type and grade, the expression data of the 19 kinases in primary tumors described a greater degree of heterogeneity than is generally appreciated by clinicopathologic classification schemes. This diversity suggests that sarcomas, even those that appear to be clinically similar, arise through a variety of molecular pathways involving tyrosine kinases.Presented at the 46th Annual Cancer Symposium of the Society of Surgical Oncology, Los Angeles, March 18–21, 1993.     

Leiomyosarcoma: a rare pedal finding.

Leiomyosarcoma of the skin and subcutaneous tissue is a rare soft tissue neoplasm comprised of spindle-shaped smooth muscle cells. The statistical incidence of superficial leiomyosarcomas varies from 2.3% to 5.3% of malignant soft tissue tumors and from 4.0% to 6.5% of soft tissue sarcomas. Its occurrence in the foot is even more unusual. In a literature review extending from 1936-present, the authors have been able to locate only 12 known cases of leiomyosarcoma involving the foot and ankle. A presentation of the incidence, demographics of distribution, clinical characteristics, histopathologic features, prognosis, and treatment of leiomyosarcoma will be presented along with a unique case history involving a recalcitrant heel ulcer complicated by leiomyosarcoma.     

Inflammatory leiomyosarcoma of the head and neck: Case report

Introduction and importancePrimary sarcomas in the head and neck region are rare. Inflammatory leiomyosarcoma was first described in 1995. The case reported herein is the first reported inflammatory leiomyosarcoma occurring in the head and neck.Presentation of caseA 37-year-old male presented with a long history of an asymptomatic slowly enlarging neck mass. Examination revealed a firm mass in the lower third of the right sternocleidomastoid muscle. Computerized tomography and magnetic resonance imaging showed a lobulated, well-circumscribed tumour with malignant features. A wide local excision was performed and histopathological examination confirmed an inflammatory leiomyosarcoma.DiscussionInflammatory leiomyosarcoma is a recently described peculiar soft tissue tumour with histological features overlapping conventional leiomyosarcoma, and dense lymphocytic inflammation and immunohistochemical reactivity for both smooth and skeletal muscle markers. These are indolent tumours and wide local excision is curative.ConclusionThis case highlights the importance of considering primary sarcomas in the differential diagnosis of asymptomatic head and neck masses.     

Sarcomas in Teachers Using Three-Dimensional Printers: A Report of Three Patients and Literature Review

BackgroundWhile low-cost, small-scale, desktop three-dimensional (3D) printers are gaining popularity in the education sector, some studies have reported harmful emissions of particles and volatile organic compounds during the fused deposition modeling (FDM) process, posing a potential health risk. Sarcomas are rare tumors, constituting a group of diverse rare malignant tumors. While some genetic and environmental factors contribute to the development of sarcomas, most cases are idiopathic and sporadic.MethodsWe secured the medical records and statements about work environment from teachers diagnosed with sarcomas after frequent use of 3D printers in high schools, reviewed the cases, and described them in narrative format. Furthermore, popularization of FDM 3D printers, worrisome emissions released during the printing process, and related precautions and countermeasures were discussed through literature review.ResultsExceptionally, the cases of sarcomas, such as Ewing’s sarcoma, malignant peripheral nerve sheath tumor, and well-differentiated liposarcoma, arose in a common specific condition. All the teachers regularly operated 3D printers in poorly ventilated spaces for at least 2 years. They had no past or family history of relevant diseases.ConclusionsWe first reported three cases of sarcoma in teachers who used 3D printers in poorly ventilated conditions. Although a relationship between the use of 3D printers and the development of sarcomas has not been determined yet, it is important to come up with measures to protect teachers and students using 3D printers from the potential hazard.     

Testicular leiomyosarcoma: A case report and literature review

Introduction and importanceLeiomyosarcoma is a malignant mesenchymal tumor derived from the smooth muscle, it represents approximately 7% of all soft tissue sarcomas.Male genitourinary leiomyosarcomas are rare (Abdullazade et al., 2013 [1]).Primary testicular leiomyosarcoma is an exceptional entity with only 30 cases reported in the literature (Giridhar et al., 2011). Due to its rarity, additional studies are necessary to better define the optimal therapeutic management.Case presentationWe report a case of a 42-years-old male diagnosed in the urology department A of the University Hospital Ibn Sina in Rabat who complains of testicular swelling.The anatomopathological examination and immunohistochemical study revealed a leiomyosarcoma therefore, a radical inguinal orchiectomy with a primary ligation of the spermatic cord was performed for diagnostic and therapeutic purposes.The assessment of extension did not reveal any lymph node location or secondary appearance thus the decision of the multidisciplinary meeting opted for regular cancer check-ups without adjuvant treatment.DiscussionThe actual etiology of testicular leiomyosarcoma is still unknown added to its clinical presentation and radiological results that are non-specific.ConclusionLeiomyosarcoma of the testis is a very rare tumor and its clinical and radiological presentation remains similar to other testicular malignancies.     

Die Bedeutung von Referenzzentren in Diagnose und Therapie von Weichgewebssarkomen der Extremitäten

Correct histopathologic diagnosis is essential for adequate treatment of soft tissue sarcomas. Due to the disorder’s rarity, multitude of subgroups, sometimes varying histopathologic appearance, and occasionally inadequate biopsy specimens, diagnosis and grading are challenging. The records of 603 patients with soft tissue tumors of the extremities were reviewed concerning mismatches in primary and definite diagnoses relating to entity, evaluation of primary or recurrent tumor specimens, and the diagnosing pathology institution. For second opinions we referred to the Institute of Pathology of the Ruhr University at the Bergmannsheil Hospital in Bochum, Germany, and to the Pathology Institute of the University of Jena, also in Germany. Liposarcoma and malignant fibrous histiocytoma were the most often diagnosed subgroups at 24% and 22.6%, respectively. In the eight most frequent sarcoma types, malignant peripheral nerve sheath tumors and leiomyosarcoma had the highest rates of false primary diagnosis, 78.4% and 74.2% of cases, respectively. The diagnostic error ratio for nonspecialized pathologists in practice, community hospital pathologists, and academic medical centers was over 60%. For optimal treatment of soft tissue sarcomas, we suggest obtaining expert second opinion to ensure adequate surgical therapy and precise indications for radiation and chemotherapy.     

Clinical course of soft tissue sarcomas presenting as malignant wounds

BackgroundSoft tissue sarcomas can invade the skin and occasionally present as malignant wounds characterized by bleeding, exudate, odor, and infection. This study aimed to highlight the clinical problems associated with sarcomas with malignant wounds.MethodsThe patient group comprised 12 males and 1 female, with a median age at diagnosis of 75 (range 23–95) years old. The average follow-up was 28.3 months. Clinical information concerning the patients with soft tissue sarcomas presenting as malignant wounds was retrospectively investigated.ResultsEleven out of 13 malignant wounds cases were male and over 65 years old. Tumors were located in the chest wall in 4 patients and the thigh in 4, respectively. The histology was high-grade in 12 patients. Persistent bleeding from malignant wounds was observed in 6 patients. The patients' pre-operative hemoglobin level was 7.5 ± 1.9 g/dl. For the purpose of temporary hemostasis, Mohs' paste was applied in 1 case and zinc oxide starch was applied in 3. Surgical removal was done in 10 patients, and amputation in 2. Six patients needed skin reconstruction. Post-operative surgical site infection was found in 5 patients, but the infection did not occur in the patients who underwent skin reconstruction of musculocutaneous flaps. The 5-year survival rate was 25.4%.ConclusionsMassive bleeding from the tumor impairs patients' quality of life and can be life-threatening. To avoid exacerbating the systemic condition of elderly cancer patients, urgent surgical removal is recommended, especially in cases of exposed tumors with persistent bleeding. Orthopedic oncologists should be aware of surgical site infection as a potential post-operative complication.     

Malignant peripheral nerve sheath tumor of the vagus nerve in a teenager with the neurofibromatosis 1 gene mutation: a case report

Malignant peripheral nerve sheath tumors account for approximately 5% to 10% of all soft tissue sarcomas in which 25% to 50% are diagnosed in patients with neurofibromatosis 1 (NF1). Tumors are often located in the proximal portion of the upper and lower extremities and trunk, whereas cervical vagus nerve localizations are extremely rare, and the English literature is limited to isolated case reports. Malignant peripheral nerve sheath tumors usually affect adults. However, earlier presentation is described in patients with the NF1 mutation. The authors describe a very rare case of malignant peripheral nerve sheath tumor of the vagus nerve in a teenage patient with NF1 focusing on surgical management of this uncommon pathology and its histopathologic features to underline the importance of differential diagnosis and early treatment of this rare and aggressive tumor.     

Clinical features of bone and soft tissue tumors of the foot and ankle: Results from a retrospective single-center case-series

BackgroundThe malignant potential of the musculoskeletal tumors of the foot and ankle has often been underestimated because of their rarity. The current study reviewed the clinical features of the tumors of the foot and ankle, and evaluated the tumor size via imaging-based analysis to distinguish between benign and malignant lesions.MethodsA retrospective review was performed using the clinical records of all patients with histologically confirmed musculoskeletal tumors of the foot and ankle, treated between 1998 and 2020 at our institution. We examined the distribution of tumors, rate of unplanned excision for primary surgery, and subsequent outcomes. In addition, the tumor size was examined via magnetic resonance imaging, and the cut-off value was determined via receiver operating characteristic (ROC) curve.ResultsA total of 103 bone and soft tissue tumors of the foot and ankle were included, of which 78 were soft tissue tumors and 25 were bone tumors. Of the 14 cases of malignant bone and soft tissue tumors, 6 (42.9%) received unplanned excision in the primary surgery, followed by amputation in 3 cases. Tumor size of malignant soft tissue tumors was significantly larger than that of benign soft tissue tumors (47.6 mm vs. 31.0 mm, respectively, P < .001). However, the difference between benign and malignant bone tumors was not statistically significant with the numbers available. ROC curve determined that the optimum diagnostic cutoff value for soft tissue tumor size was 40 mm, with a high area under the ROC curve 0.816 (95% CI: 0.711–0.921, sensitivity 91.7%, specificity 70.5%)ConclusionsWe highlighted that bone and soft tissue tumors of the foot and ankle were often misdiagnosed and initially inadequately treated. We suggest that a cutoff value of 40 mm may be a useful index for prediction of malignancy in soft tissue tumors of the foot and ankle.Level of evidenceⅢ     

Endocervical fibroblastic malignant peripheral nerve sheath tumor (neurofibrosarcoma): report of a novel entity possibly related to endocervical CD34 fibrocytes

Primary cervical stromal sarcomas are rare neoplasms that have been poorly characterized. We report the clinical, histologic, and immunohistologic features of 3 primary endocervical S100 protein (S100p)-positive and CD34-positive sarcomas, herein designated as fibroblastic malignant peripheral nerve sheath sarcoma (endocervical neurofibrosarcoma), 2 of which occurred in women younger than 35 years of age. All tumors presented as a cervical polyp or mass lesion; 1 extended into the pelvic side wall and vaginal soft tissue. The tumors measured 2.0 to 8.0 cm, and were composed of compact fascicles of spindled cells arranged in herringbone, loose fascicular, or ill-defined storiform patterns. A focal whorled architecture was identified in all 3 tumors, but distinct Antoni A areas and Verocay bodies were absent. Ultrastructural examination in 1 case confirmed the presence of fibrocyte-like differentiation. Strong, diffuse, and in 1 case, patchy S100p expression was seen in all cases; strong and diffuse CD34 expression was also present in all tumors. Adjacent uninvolved endocervical stroma also showed CD34 positivity but expression was much less dramatic than in tumor cells. All other markers of neural, melanocytic, smooth muscle, endometrial stromal, and epithelial differentiation were negative. One of the tumors behaved extremely aggressively with extensive pelvic involvement, resulting in patient death within 16 months of diagnosis; another tumor was associated with pelvic recurrence 13 months after diagnosis; and the third tumor had an indolent course with no evidence of recurrence at 33 months after complete excision and local radiotherapy, although follow-up was limited. Review of large numbers of mesenchymal tumors in the uterus did not show similar tumors. Endocervical neurofibrosarcoma should be distinguished from solitary fibrous tumor, endometrial stromal sarcoma, leiomyosarcoma, melanoma, and other spindle cell neoplasms. The prominent fibroblastic endoneurial-like differentiation seen in this peripheral nerve sheath tumor may be related to the presence of a rich mucosal stromal fibrocyte network in the endocervix.     

Cutaneous Malignant Peripheral Nerve Sheath Tumor

Cutaneous malignant peripheral nerve sheath tumors (MPNSTs) are rare sarcomas of neuroectodermal origin arising in the dermis and/or subcutis. In contrast with their deep soft tissue and visceral counterparts, cutaneous MPNSTs are rarely associated with neurofibromatosis type 1. Two main subtypes of cutaneous MPNST can be distinguished histologically: conventional (ie, spindle cell) and epithelioid MPNST. The 2 subtypes also differ in predilection for deep versus superficial locations, association with preexistent benign peripheral nerve sheath tumors and S100 immunohistochemistry. Herein, we review current knowledge of cutaneous MPNST and discuss its differential diagnosis.     

Vascular Endothelial Growth Factor and Soft Tissue Sarcomas: Tumor Expression Correlates With Grade

Introduction: Vascular endothelial growth factor (VEGF), an endothelial–specific mitogen overexpressed in various epithelial malignancies is thought to be a potent regulator of angiogenesis. We hypothesized that some soft tissue sarcomas, due to their high propensity for hematogenous metastases (1) would overexpress VEGF, (2) that the degree of expression may represent a significant biologic predictor for disease-specific survival, and (3) that recurrent tumor would express as high or higher VEGF compared with the primary tumor.Methods: Selected paraffin-embedded tissue of surgical specimens from 79 patients with soft tissue sarcomas, treated between 1989 and 1995 were stained with a rabbit polyclonal anti-VEGF antibody at a concentration of 2 g/ml. Slides were assessed for VEGF expression as high or low by two investigators blinded to the clinicopathologic data. Twelve patients had VEGF expression of their primary tumors, and their recurrent tumors were compared. The Fishers exact test assessed for differences in VEGF expression; survival analyses were performed according to the methods of Kaplan and Meier.Results: Seventy-eight percent (29 of 37) of patients who died of disease had high VEGF expression. However, VEGF expression was not an independent predictor of either overall or disease-free survival. Tumor grade correlated with VEGF expression significantly. For the low-grade tumors, 7 of 13 expressed low VEGF, whereas for high-grade tumors, 53 of 66 expressed high VEGF (P = .016). Seven of the 12 paired tumor samples expressed identical VEGF immunostaining.Conclusions: The majority of high-grade soft tissue sarcomas in this study have high intensity VEGF expression. This finding may provide useful information on individual soft tissue sarcomas and offer the basis for therapeutic and biologic targeting in high-risk patients using anti-angiogenesis strategies. However, in our analysis, after accounting for tumor grade, VEGF does not seem to be an independent predictor of clinical outcome.Presented at the 53rd Annual Cancer Symposium of the Society of Surgical Oncology Poster Session, New Orleans, Louisiana, March 16-19, 2010434_2001_Article_260.     

Malignant peripheral nerve sheath tumor in a patient with Werner’s syndrome

Werner's syndrome is a rare autosomal recessive disorder characterized by features of premature aging. It is attributed to an autosomal recessive mutation on chromosome 8p12 where the Werner gene is located. This gene encodes a protein homologous to the RecQ-type DNA helicase, an enzyme that unwinds double-stranded DNA into single-stranded DNA. The association of Werner's syndrome with malignant tumors is widely reported in the literature. Both bone and soft tissue sarcomas have been described. We report a patient with Werner's syndrome who developed a malignant peripheral nerve sheath tumor of the left popliteal fossa.     

Buttock Soft Tissue Sarcoma: Clinical Features,Treatment, and Prognosis

Background: Primary buttock soft tissue sarcomas in adults are common entities that have been infrequently reported (three clinical series and isolated case reports). We present our experience of buttock sarcomas to better characterize and define the natural history of this condition.Methods: Buttock tumors occurring in adults (>16 years) between January 1990 and January 2002 were identified from the Royal Marsden Hospitals Sarcoma Unit prospective database.Results: Seventy-three buttock sarcomas were evaluated and treated at the Royal Marsden Hospital during this period. Liposarcoma (n = 19), leiomyosarcoma (n = 13), and synovial sarcoma (n = 9) were the most frequent histological types. There were 8 T1 and 61 T2 tumors, and size was not available in 4 patients. Most tumors (n = 64) were located deep to the deep fascia. There were 15 grade 1, 20 grade 2, and 37 grade 3 tumors, and grade was not available in 1 patient. There were 29 tumors contained within the gluteus maximus. Wide excision was performed in 50 patients. Local recurrence and distant metastasis occurred in 15 and 35 patients with a median time of 18 and 8 months, respectively. The rate of local recurrence at 2 years was 20.9% (SE, 6.8%). The 2-year overall and disease-free survival rates were 64.1% (SE, 6.7%) and 48.5% (SE, 6.4%), respectively.Conclusions: Buttock sarcomas present special surgical difficulties because of proximity of the sciatic nerve and the ability of tumors at this site to extend into the pelvis and perineum. Size and grade of the tumor were independent predictors for disease-free and overall survival.