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17 pages, 11988 KiB

Open AccessArticle

Gene Expression Landscape of SDH-Deficient Gastrointestinal Stromal Tumors

by Valentina Indio, Angela Schipani, Margherita Nannini, Milena Urbini, Alessandro Rizzo, Antonio De Leo, Annalisa Altimari, Valerio Di Scioscio, Daria Messelodi, Giuseppe Tarantino, Annalisa Astolfi and Maria Abbondanza Pantaleo

J. Clin. Med. 2021, 10(5), 1057; https://doi.org/10.3390/jcm10051057 - 4 Mar 2021

Cited by 13 | Viewed by 2694

Abstract

Background: About 20–40% of gastrointestinal stromal tumors (GISTs) lacking KIT/PDGFRA mutations show defects in succinate dehydrogenase (SDH) complex. This study uncovers the gene expression profile (GEP) of SDH-deficient GIST in order to identify new signaling pathways or molecular events actionable for a tailored [...] Read more.

Background: About 20–40% of gastrointestinal stromal tumors (GISTs) lacking KIT/PDGFRA mutations show defects in succinate dehydrogenase (SDH) complex. This study uncovers the gene expression profile (GEP) of SDH-deficient GIST in order to identify new signaling pathways or molecular events actionable for a tailored therapy. Methods: We analyzed 36 GIST tumor samples, either from formalin-fixed, paraffin-embedded by microarray or from fresh frozen tissue by RNA-seq, retrospectively collected among KIT-mutant and SDH-deficient GISTs. Pathway analysis was performed to highlight enriched and depleted transcriptional signatures. Tumor microenvironment and immune profile were also evaluated. Results: SDH-deficient GISTs showed a distinct GEP with respect to KIT-mutant GISTs. In particular, SDH-deficient GISTs were characterized by an increased expression of neural markers and by the activation of fibroblast growth factor receptor signaling and several biological pathways related to invasion and tumor progression. Among them, hypoxia and epithelial-to-mesenchymal transition emerged as features shared with SDH-deficient pheochromocytoma/paraganglioma. In addition, the study of immune landscape revealed the depletion of tumor microenvironment and inflammation gene signatures. Conclusions: This study provides an update of GEP in SDH-deficient GISTs, highlighting differences and similarities compared to KIT-mutant GISTs and to other neoplasm carrying the SDH loss of function. Our findings add a piece of knowledge in SDH-deficient GISTs, shedding light on their putative histology and on the dysregulated biological processes as targets of new therapeutic strategies. Full article

(This article belongs to the Special Issue Bone and Soft Tissue Sarcomas: A “Big” Family of “Rare” Tumors. A Multidisciplinary Targeted Approach and Emerging Topics)

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21 pages, 4456 KiB

Open AccessArticle

Skeletal Muscle Subpopulation Rearrangements upon Rhabdomyosarcoma Development through Single-Cell Mass Cytometry

by Lucia Lisa Petrilli, Federica Riccio, Giulio Giuliani, Alessandro Palma, Cesare Gargioli, Simone Vumbaca, Monika Faron, Graziana Palmieri, Luca Pasquini, Francesca Sacco, Gianni Cesareni, Luisa Castagnoli and Claudia Fuoco

J. Clin. Med. 2021, 10(4), 823; https://doi.org/10.3390/jcm10040823 - 17 Feb 2021

Cited by 4 | Viewed by 3254

Abstract

The embryonal rhabdomyosarcoma (eRMS) is a soft tissue sarcoma commonly affecting the head and neck, the extremities and the genitourinary tract. To contribute to revealing the cell types that may originate this tumor, we exploited mass cytometry, a single-cell technique that, by using [...] Read more.

The embryonal rhabdomyosarcoma (eRMS) is a soft tissue sarcoma commonly affecting the head and neck, the extremities and the genitourinary tract. To contribute to revealing the cell types that may originate this tumor, we exploited mass cytometry, a single-cell technique that, by using heavy-metal-tagged antibodies, allows the accurate monitoring of the changes occurring in the mononuclear cell composition of skeletal muscle tissue during tumor development. To this end, we compared cell populations of healthy muscles with those from spatiotemporal-induced eRMS tumors in a mouse model (LSL-Kras^G12D/+;Tp53^Fl/Fl) that can be used to develop rhabdomyosarcoma by means of infection with an adenovirus vector expressing Cre (Ad-Cre) recombinase. By monitoring different time points after tumor induction, we were able to analyze tumor progression and composition, identifying fibro/adipogenic progenitors (FAPs) as the cell type that, in this model system, had a pivotal role in tumor development. In vitro studies highlighted that both FAPs and satellite cells (SCs), upon infection with the Ad-Cre, acquired the potential to develop rhabdomyosarcomas when transplanted into immunocompromised mice. However, only infected FAPs had an antigen profile that was similar to embryonal rhabdomyosarcoma cells. Overall, our analysis supports the involvement of FAPs in eRMS development. Full article

(This article belongs to the Special Issue Bone and Soft Tissue Sarcomas: A “Big” Family of “Rare” Tumors. A Multidisciplinary Targeted Approach and Emerging Topics)

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10 pages, 738 KiB

Open AccessArticle

The Management of Radiation-Induced Sarcomas: A Cohort Analysis from a Sarcoma Tertiary Center

by Mateusz Jacek Spałek, Anna Małgorzata Czarnecka and Piotr Rutkowski

J. Clin. Med. 2021, 10(4), 694; https://doi.org/10.3390/jcm10040694 - 10 Feb 2021

Cited by 14 | Viewed by 2791

Abstract

(1) Background: Radiation-induced sarcomas (RIS) are rare diseases with poor prognoses. The aim of the study was to analyze outcomes and identify factors affecting survival in a cohort of patients with RIS. (2) Methods: We included consecutive patients with RIS that we found [...] Read more.

(1) Background: Radiation-induced sarcomas (RIS) are rare diseases with poor prognoses. The aim of the study was to analyze outcomes and identify factors affecting survival in a cohort of patients with RIS. (2) Methods: We included consecutive patients with RIS that we found in the available electronic medical records of a sarcoma tertiary center. We analyzed patients’ RIS characteristics, management of RIS, the occurrence of local recurrence and distant metastases, the date of disease progression, the date of death, and the date of the last follow-up. (3) Results: Fifty-eight patients met the inclusion criteria. The most frequent sites of RIS development were the thorax and pelvis. The majority of RIS were poorly differentiated, high-grade tumors. Forty patients underwent surgery or radiotherapy with curative intent. The others were referred to palliative chemotherapy. Median progression-free survival and overall survival were 15 and 21 months, respectively. Treatment with curative intent and tumor localization on breasts and upper extremities were associated with a lower risk of death in univariate analysis. (4) Conclusions: The study confirms the poor prognosis of RIS. Treatments with locally curative intent at the tumor site are of prognostic value. Secondary radiotherapy is rarely used in RIS. Full article

(This article belongs to the Special Issue Bone and Soft Tissue Sarcomas: A “Big” Family of “Rare” Tumors. A Multidisciplinary Targeted Approach and Emerging Topics)

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14 pages, 909 KiB

Open AccessArticle

Systemic Treatment for Advanced and Metastatic Malignant Peripheral Nerve Sheath Tumors—A Sarcoma Reference Center Experience

by Paweł Sobczuk, Paweł Teterycz, Anna M. Czarnecka, Tomasz Świtaj, Hanna Koseła-Paterczyk, Katarzyna Kozak, Sławomir Falkowski and Piotr Rutkowski

J. Clin. Med. 2020, 9(10), 3157; https://doi.org/10.3390/jcm9103157 - 29 Sep 2020

Cited by 13 | Viewed by 4235

Abstract

Malignant peripheral nerve sheath tumor (MPNST) is a rare type of soft tissue sarcomas. The localized disease is usually treated with surgery along with perioperative chemo- or radiotherapy. However, up to 70% of patients can develop distant metastases. The study aimed to evaluate [...] Read more.

Malignant peripheral nerve sheath tumor (MPNST) is a rare type of soft tissue sarcomas. The localized disease is usually treated with surgery along with perioperative chemo- or radiotherapy. However, up to 70% of patients can develop distant metastases. The study aimed to evaluate the modes and outcomes of systemic treatment of patients with diagnosed MPNST treated in a reference center. In total, 115 patients (56 female and 59 male) diagnosed with MPNST and treated due to unresectable or metastatic disease during 2000–2019 were included in the retrospective analysis. Schemes of systemic therapy and the outcomes—progression-free survival (PFS) and overall survival (OS)—were evaluated. The median PFS in the first line was 3.9 months (95% CI 2.5–5.4). Doxorubicin-based regimens were the most commonly used in the first line (50.4% of patients). There were no significant differences in PFS between chemotherapy regimens most commonly used in the first line (p = 0.111). The median OS was 15.0 months (95% CI 11.0–19.0) and the one-year OS rate was 63%. MPNST are resistant to the majority of systemic therapies, resulting in poor survival in advanced settings. Chemotherapy with doxorubicin and ifosfamide is associated with the best response and longest PFS. Future studies and the development of novel treatment options are necessary for the improvement of treatment outcomes. Full article

(This article belongs to the Special Issue Bone and Soft Tissue Sarcomas: A “Big” Family of “Rare” Tumors. A Multidisciplinary Targeted Approach and Emerging Topics)

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12 pages, 874 KiB

Open AccessArticle

The Long-Term Outcomes of Intensive Combined Therapy of Adult Patients with Localised Synovial Sarcoma

by Katarzyna Kozak, Paweł Teterycz, Tomasz Świtaj, Hanna Koseła-Paterczyk, Sławomir Falkowski, Tadeusz Morysiński, Ewa Bartnik, Anna M. Czarnecka, Michał Wągrodzki, Iwona Ługowska and Piotr Rutkowski

J. Clin. Med. 2020, 9(10), 3129; https://doi.org/10.3390/jcm9103129 - 28 Sep 2020

Cited by 1 | Viewed by 2544

Abstract

Introduction: Synovial sarcoma (SaSy) is a high-grade, malignant soft tissue sarcoma (STS) accounting for 5–9% of STS. The aim of this study was to analyse outcomes of patients with localised SaSy treated in a single institution with a uniform neo- and adjuvant-combined therapy [...] Read more.

Introduction: Synovial sarcoma (SaSy) is a high-grade, malignant soft tissue sarcoma (STS) accounting for 5–9% of STS. The aim of this study was to analyse outcomes of patients with localised SaSy treated in a single institution with a uniform neo- and adjuvant-combined therapy protocol. Methods: 171 patients with stage II/III SaSy were treated between 1997 and 2014. Chemotherapy consisted of 4 cycles of ifosfamide 12 g/m² and two cycles of a doxorubicin-based regimen 75 mg/m². With the exception of patients who underwent amputation, all patients received neoadjuvant radiotherapy. Results: Median age was 33 years (range 17–69). Tumours larger than 5 cm in size were found in 70% of patients. The 5-year overall survival (OS), local relapse-free survival (LRFS) and metastasis-free survival (MFS) rates were 75%, 80% and 60%, respectively. In multivariate Cox’s regression, age > 35 years, male sex, larger tumour size and histology other than monophasic were associated with worse OS. Conclusions: In adult patients with localised SaSy, long-term survival can be achieved in a significant proportion of cases with intensive combined therapy. The multivariate analysis identified age, sex, disease stage and histology subtype as independent prognostic factors of OS. Full article

(This article belongs to the Special Issue Bone and Soft Tissue Sarcomas: A “Big” Family of “Rare” Tumors. A Multidisciplinary Targeted Approach and Emerging Topics)

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12 pages, 1317 KiB

Open AccessArticle

Diagnostic and Clinical Impact of 18F-FDG PET/CT in Staging and Restaging Soft-Tissue Sarcomas of the Extremities and Trunk: Mono-Institutional Retrospective Study of a Sarcoma Referral Center

by Alessio Annovazzi, Sandra Rea, Carmine Zoccali, Rosa Sciuto, Jacopo Baldi, Vincenzo Anelli, Maria G. Petrongari, Edoardo Pescarmona, Roberto Biagini and Virginia Ferraresi

J. Clin. Med. 2020, 9(8), 2549; https://doi.org/10.3390/jcm9082549 - 6 Aug 2020

Cited by 22 | Viewed by 2922

Abstract

Background: Soft-tissue sarcomas (STS) represent a wide heterogeneous class of rare tumors. The exact role ¹⁸F-fluorodeoxyglucose positron emission/computed tomography (¹⁸F-FDG PET/CT) in the evaluation of STS is not well established. The aim of the present study was to evaluate how [...] Read more.

Background: Soft-tissue sarcomas (STS) represent a wide heterogeneous class of rare tumors. The exact role ¹⁸F-fluorodeoxyglucose positron emission/computed tomography (¹⁸F-FDG PET/CT) in the evaluation of STS is not well established. The aim of the present study was to evaluate how the use of ¹⁸F-FDG PET/CT in STS could influence patient therapy planning, looking for a possible added value over computed tomography and magnetic resonance imaging—the most used modalities in the study of STS. Differences in SUV_max according to histologic subtype and tumor grade were also considered. Methods: a total of 345 consecutive ¹⁸F-FDG PET/CT scans performed for initial staging (n = 171) or for suspected disease relapse (n = 174) in 282 patients with STS extracted from the local Information System database were retrospectively reviewed. Results: ¹⁸F-FDG PET/CT altered therapy planning in 80 cases (16.4% for staging and 29.9% in restaging), both for disease upstaging (58.8%) and downstaging (41.2%) Conclusions: ¹⁸F-FDG PET/CT could significantly influence management of patients with STS, particularly for restaging. Full article

(This article belongs to the Special Issue Bone and Soft Tissue Sarcomas: A “Big” Family of “Rare” Tumors. A Multidisciplinary Targeted Approach and Emerging Topics)

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15 pages, 1490 KiB

Open AccessArticle

The Real-Life Journey of Elderly Patients in Soft Tissue and Bone Sarcomas: A Retrospective Analysis from a Sarcoma Referral Center

by Virginia Ferraresi, Sabrina Vari, Barbara Rossi, Gabriella Maggi, Diana Giannarelli, Agnese Persichetti, Maria Grazia Petrongari, Maria Cecilia Cercato, Alessio Annovazzi, Vincenzo Anelli, Edoardo Pescarmona, Jacopo Baldi, Carmine Zoccali, Domenicangela Pellegrini, Francesco Cognetti and Roberto Biagini

J. Clin. Med. 2020, 9(8), 2503; https://doi.org/10.3390/jcm9082503 - 4 Aug 2020

Cited by 1 | Viewed by 2865

Abstract

The high complexity of multimodality treatment frequently results in undertreatment of elderly sarcoma patients, and this may be one of the factors that influence their prognosis. We describe the real-life approach to a population of patients aged over 70 with both soft tissue [...] Read more.

The high complexity of multimodality treatment frequently results in undertreatment of elderly sarcoma patients, and this may be one of the factors that influence their prognosis. We describe the real-life approach to a population of patients aged over 70 with both soft tissue (STS) and bone sarcomas (BS) followed by our Sarcoma Disease Management Team from 2012 to 2017. One-hundred and twenty-three patients with a median age of 77 years (range: 70–92) were identified. STS were the most common histological subtypes (94%) and the grade was high in 79/123 patients (64%). At diagnosis, 88% of patients had localized disease (LD) and 12% were metastatic (MD). Overall, 96% of patients with LD underwent surgery, 46/54 (85%) with high grade STS patients underwent complementary radiotherapy, and 10/54 (19%) received adjuvant treatments. Twelve out of 33 patients who relapsed (36%) underwent local therapies. Seventeen (52%) and eight (24%) patients were treated with first-line and second-line medical treatments, respectively. Tolerability to systemic treatments was fairly good. Overall, 21% of the patients with advanced disease were candidates for best supportive care alone. Our case series of elderly patients with both STS and BS shows that personalized multidisciplinary treatment can nevertheless be offered to this frail population in order to control the evolution of disease. Full article

(This article belongs to the Special Issue Bone and Soft Tissue Sarcomas: A “Big” Family of “Rare” Tumors. A Multidisciplinary Targeted Approach and Emerging Topics)

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14 pages, 1659 KiB

Open AccessFeature PaperArticle

Hypofractionated Radiotherapy in Locally Advanced Myxoid Liposarcomas of Extremities or Trunk Wall: Results of a Single-Arm Prospective Clinical Trial

by Hanna Koseła-Paterczyk, Mateusz Spałek, Aneta Borkowska, Paweł Teterycz, Michał Wągrodzki, Anna Szumera-Ciećkiewicz, Tadeusz Morysiński, Patrycja Castaneda-Wysocka, Andrzej Cieszanowski, Marcin Zdzienicki, Tomasz Goryń and Piotr Rutkowski

J. Clin. Med. 2020, 9(8), 2471; https://doi.org/10.3390/jcm9082471 - 1 Aug 2020

Cited by 21 | Viewed by 3192

Abstract

Introduction: Myxoid liposarcoma (MLPS) has been reported to be more radiosensitive compared with other soft tissue sarcomas. The main objective of the study was to assess the efficacy of hypofractionated radiotherapy (RT) in the preoperative setting in patients with locally advanced primary MLPS. [...] Read more.

Introduction: Myxoid liposarcoma (MLPS) has been reported to be more radiosensitive compared with other soft tissue sarcomas. The main objective of the study was to assess the efficacy of hypofractionated radiotherapy (RT) in the preoperative setting in patients with locally advanced primary MLPS. Methods: Single-arm prospective exploratory clinical trial enrolled MLPS patients for preoperative 5 × 5 Gy RT with delayed surgery. The endpoints of the study were the rate of early wound healing complications and 5-year local control rate. Results: 29 patients (pts) were included, all had tumors located on the lower limb. The median maximum size of the tumor was 13 cm (IQR 10–15 cm). Early RT tolerance was good. Postoperative wound complications occurred in 11 pts (37.9%), late complications concerned 13.8% of patients. A total of 27 patients were included for the efficacy analyses. The pathological features of response to RT were detected in all analyzed surgical specimens. In 25 patients R0 margins were achieved, two patients had an R1 resection. None of the patients had local recurrence. Conclusion: Preoperative hypofractionated RT with a prolonged gap between RT and surgery is a feasible method of the management of MLPS, providing a good local control and low rates of treatment toxicity. Full article

(This article belongs to the Special Issue Bone and Soft Tissue Sarcomas: A “Big” Family of “Rare” Tumors. A Multidisciplinary Targeted Approach and Emerging Topics)

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10 pages, 604 KiB

Open AccessArticle

Reorganization Tips from a Sarcoma Unit at Time of the COVID-19 Pandemic in Italy: Early Experience from a Regional Referral Oncologic Center

by Barbara Rossi, Carmine Zoccali, Jacopo Baldi, Alessandra Scotto di Uccio, Roberto Biagini, Assunta De Luca, Maria Grazia Petrongari and Virginia Ferraresi

J. Clin. Med. 2020, 9(6), 1868; https://doi.org/10.3390/jcm9061868 - 15 Jun 2020

Cited by 10 | Viewed by 2784

Abstract

Since the World Health Organization declared the novel coronavirus outbreak a global health emergency, Italy’s lockdown was declared on 9 March 2020. Elective orthopedic surgery was forced to stop to allow the healthcare system to face the emergency. However, many orthopedic oncology cases [...] Read more.

Since the World Health Organization declared the novel coronavirus outbreak a global health emergency, Italy’s lockdown was declared on 9 March 2020. Elective orthopedic surgery was forced to stop to allow the healthcare system to face the emergency. However, many orthopedic oncology cases could not be postponed. The aim of this study was to report the experience in managing sarcoma patients and the reorganization of a cancer center in an attempt to maintain it free from COVID-19. A Coronavirus Crisis Unit was established by the health directorate coordination in order to adopt specific procedures. General rules of screening and social distancing were applied in different health settings (entrance check point, hospital inward, outpatient clinic, operative room). Regarding oncologic orthopedics, priority was given to bone and soft tissue sarcomas, metastases and aggressive benign tumors at risk of impending or pathologic fracture. Precise indications were followed to manage first outpatient visits, patients undergoing surgery and follow-up. Meticulous adherence to rules among patients and personnel and collaboration between leadership and medical staff in order to continue to perform multidisciplinary treatment protocols, maintain the availability of infrastructural spaces and source protective equipment, swabs and screening samples have been successful in the aim towards a safe cure for cancer patients. Full article

(This article belongs to the Special Issue Bone and Soft Tissue Sarcomas: A “Big” Family of “Rare” Tumors. A Multidisciplinary Targeted Approach and Emerging Topics)

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11 pages, 427 KiB

Open AccessArticle

Impact of Antiretroviral Therapy on the Risk of Recurrence in HIV-1 Infected Patients with Kaposi Sarcoma: A Multicenter Cohort Experience

by Manuela Colafigli, Arturo Ciccullo, Alberto Borghetti, Iuri Fanti, Federico Melis, Sara Modica, Ilaria Uccella, Antonio Bonadies, Virginia Ferraresi, Enza Anzalone, Alfredo Pennica, Emilia Migliano, Barbara Rossetti, Giordano Madeddu, Roberto Cauda, Antonio Cristaudo, Simona Di Giambenedetto and Alessandra Latini

J. Clin. Med. 2019, 8(12), 2062; https://doi.org/10.3390/jcm8122062 - 23 Nov 2019

Cited by 6 | Viewed by 2960

Abstract

Kaposi sarcoma (KS) remains a relevant malignancy in human immunodeficiency virus (HIV)-infected patients with a non-standardized management; despite past suggestions that ritonavir-boosted protease inhibitor (bPI)-based regimens could be preferable, no combination antiretroviral therapy (cART) regimen was demonstrated to outperform the others and the [...] Read more.

Kaposi sarcoma (KS) remains a relevant malignancy in human immunodeficiency virus (HIV)-infected patients with a non-standardized management; despite past suggestions that ritonavir-boosted protease inhibitor (bPI)-based regimens could be preferable, no combination antiretroviral therapy (cART) regimen was demonstrated to outperform the others and the impact of new drugs, drug classes or paradigms was never investigated nor proven better than previous therapeutic regimes. In order to do this, we retrospectively collected data regarding HIV-infected patients with a diagnosis of KS last seen in six Italian centers after 1 January 2013. A total of 104 KS cases in 99 patients was analyzed for 945.34 patient-year follow-up (PYFU). Twenty-six patients had visceral localizations. Thirty-three patients were treated with chemotherapy, four with electrochemotherapy, and 12 with α-interferon (α-IFN). At censor, 22% received a bPI-based, 14% a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based, and 28% an integrase inhibitor (INI)-based standard cART, 24% a less drug regimen and 12% a mega-cART. Twelve recurrence episodes were observed in seven patients for an incidence of 1.27 per 100 PYFU. Two patients with no evidence of recurrence episodes died for other reasons. In our experience, KS recurrence episodes were infrequent. Despite the increasing use of new antiretroviral drug classes and new treatment paradigms, no excess of recurrence episodes was observed in patients receiving such cART regimens. Full article

(This article belongs to the Special Issue Bone and Soft Tissue Sarcomas: A “Big” Family of “Rare” Tumors. A Multidisciplinary Targeted Approach and Emerging Topics)

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Review

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18 pages, 19230 KiB

Open AccessReview

Chordoma—Current Understanding and Modern Treatment Paradigms

by Sean M. Barber, Saeed S. Sadrameli, Jonathan J. Lee, Jared S. Fridley, Bin S. Teh, Adetokunbo A. Oyelese, Albert E. Telfeian and Ziya L. Gokaslan

J. Clin. Med. 2021, 10(5), 1054; https://doi.org/10.3390/jcm10051054 - 4 Mar 2021

Cited by 53 | Viewed by 7729

Abstract

Chordoma is a low-grade notochordal tumor of the skull base, mobile spine and sacrum which behaves malignantly and confers a poor prognosis despite indolent growth patterns. These tumors often present late in the disease course, tend to encapsulate adjacent neurovascular anatomy, seed resection [...] Read more.

Chordoma is a low-grade notochordal tumor of the skull base, mobile spine and sacrum which behaves malignantly and confers a poor prognosis despite indolent growth patterns. These tumors often present late in the disease course, tend to encapsulate adjacent neurovascular anatomy, seed resection cavities, recur locally and respond poorly to radiotherapy and conventional chemotherapy, all of which make chordomas challenging to treat. Extent of surgical resection and adequacy of surgical margins are the most important prognostic factors and thus patients with chordoma should be cared for by a highly experienced, multi-disciplinary surgical team in a quaternary center. Ongoing research into the molecular pathophysiology of chordoma has led to the discovery of several pathways that may serve as potential targets for molecular therapy, including a multitude of receptor tyrosine kinases (e.g., platelet-derived growth factor receptor [PDGFR], epidermal growth factor receptor [EGFR]), downstream cascades (e.g., phosphoinositide 3-kinase [PI3K]/protein kinase B [Akt]/mechanistic target of rapamycin [mTOR]), brachyury—a transcription factor expressed ubiquitously in chordoma but not in other tissues—and the fibroblast growth factor [FGF]/mitogen-activated protein kinase kinase [MEK]/extracellular signal-regulated kinase [ERK] pathway. In this review article, the pathophysiology, diagnosis and modern treatment paradigms of chordoma will be discussed with an emphasis on the ongoing research and advances in the field that may lead to improved outcomes for patients with this challenging disease. Full article

(This article belongs to the Special Issue Bone and Soft Tissue Sarcomas: A “Big” Family of “Rare” Tumors. A Multidisciplinary Targeted Approach and Emerging Topics)

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14 pages, 304 KiB

Open AccessReview

Desmoid Tumors Characteristics, Clinical Management, Active Surveillance, and Description of Our FAP Case Series

by Lupe Sanchez-Mete, Virginia Ferraresi, Mauro Caterino, Aline Martayan, Irene Terrenato, Elena Mannisi and Vittoria Stigliano

J. Clin. Med. 2020, 9(12), 4012; https://doi.org/10.3390/jcm9124012 - 11 Dec 2020

Cited by 12 | Viewed by 2305

Abstract

(1) Background: desmoid tumors (DTs) are common in patients with familial adenomatous polyposis (FAP). An active surveillance approach has been recently proposed as a valuable alternative to immediate treatment in some patients. However, no clear indication exists on which patients are suitable for [...] Read more.

(1) Background: desmoid tumors (DTs) are common in patients with familial adenomatous polyposis (FAP). An active surveillance approach has been recently proposed as a valuable alternative to immediate treatment in some patients. However, no clear indication exists on which patients are suitable for active surveillance, how to establish the cut-off for an active treatment, and which imaging technique or predictive factors should be used during the surveillance period. (2) Results: we retrospectively analyzed 13 FAP patients with DTs. A surveillance protocol consisting of scheduled follow-up evaluations depending on tumor location and tissue thickening, abdominal computed tomography (CT) scan/Magnetic resonance imaging (MRI) allowed prompt intervention in 3/11 aggressive intra-abdominal DTs, while sparing further interventions in the remaining cases, despite worrisome features detected in three patients. Moreover, we identified a possible predictive marker of tumor aggressiveness, i.e., the “average monthly growth rate” (AMGR), which could distinguish patients with very aggressive/life-threatening tumor behavior (AMGR > 0.5) who need immediate active treatment, from those with stable DTs (AMGR < 0.1) in whom follow-up assessments could be delayed. (3) Conclusion: surveillance protocols may be a useful approach for DTs. Further studies on larger series are needed to confirm the usefulness of periodic CT scan/MRI and the value of AMGR as a prognostic tool to guide treatment strategies. Full article

(This article belongs to the Special Issue Bone and Soft Tissue Sarcomas: A “Big” Family of “Rare” Tumors. A Multidisciplinary Targeted Approach and Emerging Topics)

22 pages, 4113 KiB

Open AccessReview

Dermatofibrosarcoma Protuberans: Update on the Diagnosis and Treatment

by Xingpei Hao, Steven D. Billings, Fangbai Wu, Todd W. Stultz, Gary W. Procop, Gene Mirkin and Allison T. Vidimos

J. Clin. Med. 2020, 9(6), 1752; https://doi.org/10.3390/jcm9061752 - 5 Jun 2020

Cited by 91 | Viewed by 17628

Abstract

Dermatofibrosarcoma protuberans (DFSP) is a slow growing, low- to intermediate-grade dermal soft-tissue tumor. It has a high local recurrence rate but low metastatic potential. It is characterized by a uniform spindle cell arrangement, classically with a storiform pattern and CD34 immunoreactivity. The histomorphology [...] Read more.

Dermatofibrosarcoma protuberans (DFSP) is a slow growing, low- to intermediate-grade dermal soft-tissue tumor. It has a high local recurrence rate but low metastatic potential. It is characterized by a uniform spindle cell arrangement, classically with a storiform pattern and CD34 immunoreactivity. The histomorphology and immunophenotype overlap with a broad range of other neoplasms. The standard treatment is complete surgical excision. The surgical procedures include wide local excision (WLE) with tumor free margins, Mohs micrographic surgery (MMS) and amputation. Unresectable DFSPs are treated with radiation therapy and/or targeted therapy. DFSP has characteristic t(17; 22) (q22; q13), resulting in a COL1A1- PDGFB fusion transcripts in more than 90% of DFSPs. Molecular detection of the gene rearrangement or fusion transcripts is helpful for the diagnosis of patients with atypical morphology and for screening candidates for targeted therapy with tyrosine kinase inhibitors. The aims of the present review are to update the clinical presentation, tumorigenesis and histopathology of DFSP and its variants for diagnosis and differential diagnosis from other benign and malignant tumors, to compare the advantages and drawbacks of WLE and MMS, to propose the baseline for selecting surgical procedure based on tumor’s location, size, stage and relationship with surrounding soft tissue and bone structures, and to provide a biologic rationale for the systemic therapy. We further propose a modified clinical staging system of DFSP and a surveillance program for the patients after surgical excision. Full article

(This article belongs to the Special Issue Bone and Soft Tissue Sarcomas: A “Big” Family of “Rare” Tumors. A Multidisciplinary Targeted Approach and Emerging Topics)

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