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Background: Moderately hypofractionated, preoperative radiotherapy in patients with soft tissue sarcomas (HYPORT-STS; ClinicalTrials.gov identifier NCT03819985) investigated a radiobiologically equivalent, moderately hypofractionated course of preoperative radiotherapy (RT) 15 × 2.85 Gy in patients with soft tissue sarcoma (STS). Here, the authors report longer term follow-up to update local control and report late toxicities, as well as functional and patient-reported outcomes., Methods: HYPORT-STS was a single-center, open-label, single-arm, prospective phase 2 clinical trial that enrolled 120 eligible adult patients with localized STS of the extremities or superficial trunk between 2018 and 2021. Patients received a 3-week course of preoperative RT followed by surgery 4-8 weeks later. End points and follow-up were analyzed from the date of surgery., Results: The median follow-up was 43 months (interquartile range, 37-52 months), and the 4-year local recurrence-free survival rate was 93%. Overall RT-related late toxicities improved with time from local therapy (p < .001), and few patients had grade ≥2 toxicities (9%; n = 8 of 88) at 2 years. These included: 2% grade ≥2 skin toxicity, 2% fibrosis, 3% lymphedema, and 1% joint stiffness. Four patients (3%) had bone fractures. Both functional outcomes, as measured by the Musculoskeletal Tumor Society Rating Scale (p < .001), and quality of life, as measured by the Functional Assessment of Cancer Therapy-General (p < .001), improved with time from treatment, and both measures were better in follow-up at 2 years compared with baseline., Conclusions: Long-term follow up suggests that moderately hypofractionated preoperative RT for patients with STS is safe and effective. Higher grade late toxicities affect a minority of patients. Late toxicities decrease over time, whereas functional outcomes and health-related quality of life seem to improve with more time from combined modality treatment., (© 2024 American Cancer Society.)

PRRX1-fused mesenchymal neoplasm is a recently identified, rare subcutaneous soft tissue neoplasm that is characterized by fusion of PRRX1 (exon 1) with NCOA1 (exon 13) in the majority of reported cases. Although initially considered to be fibroblastic, a possibility of neural or neuroectodermal differentiation has been suggested in a subset of cases. We report a 26-year-old female with a 4.0 cm painless mass located in the subcutis of the left thigh. Microscopically, the tumor was well-circumscribed and multinodular and was composed of relatively monomorphic ovoid to spindle cells arranged in loose fascicles, trabeculae, and cords within alternating myxoid and fibrous matrix, and vascularized stroma. Mitotic figures were scarce and necrosis was not observed. By immunohistochemistry, the neoplastic cells demonstrated focal co-expression of S100 protein and SOX10 and were negative for epithelial membrane antigen, smooth muscle actin, desmin, CD34, STAT6, HMB45, Melan-A, and MUC4. The expression of Rb1 was retained. Targeted RNA-sequencing identified a novel transcript fusion of PRRX1 (exon 1)::NCOA1 (exon 15), which was further confirmed by reverse transcription polymerase chain reaction and Sanger sequencing. The tumor was narrowly excised and no tumor recurrence or metastasis was identified after 13 months of follow-up. In summary, we report a new case of PRRX1-fused mesenchymal neoplasm, expanding the molecular genetic spectrum and providing further support for possible neural or neuroectodermal differentiation of this emerging soft tissue tumor entity., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Neurotrophic receptor tyrosine kinase (NTRK)-rearranged spindle cell neoplasms are a recently described group of soft tissue tumors. They commonly present as a painless mass on the extremities of children and young adults. They are characterized microscopically by a heterogeneous spectrum of infiltrative spindle cell proliferations, which can morphologically mimic several other spindle cell neoplasms. Their identification is vital, as they may be amenable to treatment with tyrosine kinase-targeted therapy. This case report describes a rare NTRK3-rearranged spindle cell neoplasm in the groin of a 29-year-old female and provides further clinical and morphological features of this entity., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Calcified chondroid mesenchymal neoplasm is a recently recognized bone and soft tissue entity primarily found in the extremities and the temporomandibular joint. This neoplasm is typically driven by the fusion of the FN1 gene with a kinase. In this case report, we provide a detailed account of a rare superficial calcified chondroid mesenchymal neoplasm located on the left big toe, characterized by an FN1::FGFR2 fusion. The tumor exhibited a peripheral collarette and consisted of large intradermal histiocytoid to epithelioid cells with no mitotic activity. These cells displayed fine chromatin and abundant pale eosinophilic cytoplasm, forming a swirling syncytium. They were interspersed with localized areas of glassy chondromyxoid matrix containing randomly mineralized calcific material and isolated osteoclast-like giant cells. RNA sequencing confirmed the presence of an FN1 (exon 29)::FGFR2 (exon 7) gene fusion. Our report emphasizes the importance for dermatopathologists to consider this entity when evaluating superficial lesions displaying mesenchymal, chondroid, and calcified attributes., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Pleomorphic dermal sarcoma (PDS) is an uncommon malignant soft-tissue tumor that occurs mostly in elderly patients, with only 5% of cases occurring in children. However, pediatric patients with Li-Fraumeni syndrome (LFS) can develop several types of cancer, particularly sarcomas. Here, we describe a young LFS patient who presented with early-onset PDS and review the literature., (© 2023 Wiley Periodicals LLC.)

Background: The aim of this study was to assess the clinical impact of indeterminate pulmonary nodules (no more than four pulmonary nodules of less than 5 mm or one nodule measuring between 5 and less than 10 mm by computed tomography [CT]) in children and adolescents with adult-type non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) at diagnosis., Methods: Patients with NRSTS treated in 11 centers as part of the European paediatric Soft Tissue Sarcoma Study Group (EpSSG) were retrospectively assessed. Local radiologists, blinded to clinical information except for patients' age and tumor histotype, reviewed the chest CT at diagnosis and filled out a case report form. Because patients with or without indeterminate nodules in the EpSSG NRSTS 2005 study received the same type of treatment, event-free survival (EFS) and overall survival (OS) between groups by log-rank test were compared., Results: Overall, 206 patients were examined: 109 (52.9%) were without any nodules, 78 (38%) had at least one indeterminate nodule, and 19 (9.2%) had nodules meeting the definition of metastases, which were then considered to be misclassified and were excluded from further analyses. Five-year EFS was 78.5% (95% CI, 69.4%-85.1%) for patients without nodules and 69.6% (95% CI, 57.9%-78.7%) for patients with indeterminate nodules (p = .135); 5-year OS was 87.4% (95% CI, 79.3%-92.5%) and 79.0% (95% CI, 67.5%-86.8%), respectively (p = .086)., Conclusions: This study suggests that survival does not differ in otherwise nonmetastatic patients with indeterminate pulmonary nodules compared to nonmetastatic patients without pulmonary nodules., Plain Language Summary: Radiologists should be aware of the classification of indeterminate pulmonary nodules in non-rhabdomyosarcoma soft tissue sarcomas and use it in their reports. More than a third of patients with non-rhabdomyosarcoma soft tissue sarcoma can be affected by indeterminate pulmonary nodules. Indeterminate pulmonary nodules do not significantly affect the overall survival of pediatric patients with non-rhabdomyosarcoma soft tissue sarcoma., (© 2023 American Cancer Society.)

Fusion genes have been implicated in the development and progression of several types of sarcomas, serving as valuable diagnostic and prognostic markers, as well as potential therapeutic targets. We discovered a novel major facilitator superfamily domain-containing 7 (MFSD7) and adenosine triphosphate 5I (ATP5I) gene fusion from sarcomas. In this study, the MFSD7-ATP5I fusion transcript was screened using RNA sequencing in 55 sarcoma samples and sixteen normal samples. The MFSD7-ATP5I fusion transcript was detected in 58% of sarcoma samples. The correlation between the expression of MFSD7-ATP5I fusion transcript and clinicopathological information was analyzed, and MFSD7-ATP5I expression is associated with marked pleomorphism and lower tumor necrosis. Cell migration and invasion was significantly reduced by knock-down of MFSD7-ATP5I. Cell migration and invasion was increased by overexpression of MFSD7-ATP5I. A phosphokinase assay demonstrated that MFSD7-ATP5I is involved in the GSK-3 pathway. The current study found that MFSD7-ATP5I is associated with increasing pleomorphism and decreasing necrosis of tumors. And our gain and loss of function experiments prove that MFSD7-ATP5I promotes the invasiveness of tumor cells., (© 2023 Orthopaedic Research Society.)

Superficial CD34 fibroblastic tumors (SCD34FT) and PRDM10-rearranged tumors (PRTs) are mesenchymal tumors that have recently received increased scientific attention due to their irrefutable similarities yet debatable relationship. A 74-year-old male presented to the dermatology clinic with a violaceous, well-defined nodule on the left medial knee of 2-year duration. Shave biopsy demonstrated spindle cells arranged in a vaguely storiform pattern forming fascicles. Immunohistochemical stains were positive for vimentin, CD68, CD10, and CD34 diffusely. ERG, S-100, HMB45, and SOX-10 were negative. Molecular studies identified a mediator complex subunit 12 (MED12)-PR/SET Domain 10 (PRDM10) gene fusion thus favoring confirming the diagnosis of a PRT. Our patient underwent wide local excision with negative margins and had no complications. This case aims to provide context for considering SCD34FT and PRT as intersecting entities and to discuss a diagnostic approach when encountering these tumors., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Desmoplastic fibroblastoma (collagenous fibroma) is a rare soft tissue tumor that usually arises in the subcutis or skeletal muscle. Cases superficial to fascia are unusual and can cause diagnostic difficulty. We present 11 cases of superficial desmoplastic fibroblastoma involving a wide anatomic distribution., Methods: Archives were searched using the term "desmoplastic fibroblastoma" over a 10-year period (2012-2022). Cases superficial to fascia were retrieved, and available clinicopathologic features were recorded. Only cases involving the dermis were included., Results: Eleven cases were identified, all of which were received in consultation. Tumors involved the head and neck (2), lower extremity (2), back (2), foot (1), shoulder (1), axilla (1), hand (1), and breast (1). Each consisted of a hypocellular proliferation of bland stellate to spindled fibroblasts set in a collagenous to focally myxoid stroma. The immunohistochemical stains available for review demonstrated SMA positivity (4/7) and negative immunoreactivity for CD34 (0/6), EMA (0/3), desmin (0/3), and S100 (0/7)., Conclusions: Desmoplastic fibroblastoma may present superficially in the dermis to subcutis, posing a potential source of diagnostic difficulty. Recognition of the characteristic histopathologic features of desmoplastic fibroblastoma with judicial use of immunohistochemical stains should allow for accurate diagnosis., (© 2023 The Authors. Journal of Cutaneous Pathology published by John Wiley & Sons Ltd.)

Objective: Sarcoma diagnosis and its treatment trajectory may deeply affect the somatopsychic balance of patients and their caregivers. This systematic review aimed at deepening the understanding of sarcoma's impact on the entire family unit involved in the illness experience on a physical (e.g. fatigue), psychological (e.g. mental health, affective regulation, defense mechanisms), and interpersonal (e.g. social isolation, loneliness) level., Methods: The systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The literature search led to the identification and subsequent inclusion of 44 articles focused on sarcoma patients. Results were classified into seven categories: Quality of Life, worries and distress, anxiety and depression, suicide ideation, financial and occupational consequences, unmet needs, and coping strategies. Our search identified only one study focusing on informal caregivers, thus we could not perform a systematic review on these results., Results: Our findings underlined the traumatic impact of the sarcoma diagnosis. Patients can experience an impoverished emotional life, somatization, social withdrawal, difficulty in decision-making, increased feelings of discouragement and demoralization, and profound experiences of helplessness and vulnerability. Moreover, they seemed to display anxiety and depression and might present a higher suicide incidence than the general population., Conclusion: Our review highlighted that the psychosocial aftermath of sarcoma patients should guide institutions and healthcare professionals toward the design of assessment and intervention models that could contemplate the different dimensions of their suffering. Furthermore, it points out that there is still a lack of evidence regarding the psychosocial impact affecting sarcoma patients' caregivers., (© 2023 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.)

Background: Larotrectinib, a first-in-class, highly selective tropomyosin receptor kinase (TRK) inhibitor, has demonstrated efficacy in adult and pediatric patients with various solid tumors harboring NTRK gene fusions. This subset analysis focuses on the efficacy and safety of larotrectinib in an expanded cohort of adult patients with TRK fusion sarcomas., Methods: Patients (≥18 years old) with sarcomas harboring NTRK gene fusions were identified from three clinical trials. Patients received larotrectinib 100 mg orally twice daily. Response was investigator-assessed per RECIST v1.1. Data cutoff was July 20, 2021., Results: At the data cutoff, 36 adult patients with TRK fusion sarcomas had initiated larotrectinib therapy: two (6%) patients had bone sarcomas, four (11%) had gastrointestinal stromal tumors, and 30 (83%) had soft tissue sarcomas. All patients were evaluable for response and demonstrated an objective response rate of 58% (95% confidence interval, 41-74). Patients responded well to larotrectinib regardless of number of prior lines of therapy. Adverse events (AEs) were mostly grade 1/2. Grade 3 treatment-emergent AEs (TEAEs) occurred in 15 (42%) patients. There were no grade 4 TEAEs. Two grade 5 TEAEs were reported, neither of which were considered related to larotrectinib. Four (11%) patients permanently discontinued treatment due to TEAEs., Conclusions: Larotrectinib demonstrated robust and durable responses, extended survival benefit, and a favorable safety profile in adult patients with TRK fusion sarcomas with longer follow-up. These results continue to demonstrate that testing for NTRK gene fusions should be incorporated into the clinical management of adult patients with various types of sarcomas., Plain Language Summary: Tropomyosin receptor kinase (TRK) fusion proteins result from translocations involving the NTRK gene and cause cancer in a range of tumor types. Larotrectinib is an agent that specifically targets TRK fusion proteins and is approved for the treatment of patients with TRK fusion cancer. This study looked at how well larotrectinib worked in adult patients with sarcomas caused by TRK fusion proteins. Over half of patients had a durable response to larotrectinib, with no unexpected side effects. These results show that larotrectinib is safe and effective in adult patients with TRK fusion sarcomas., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: Giant cell tumor of soft tissue (GCT-ST) is a rare soft tissue neoplasm that is morphologically similar to but genetically distinct from giant cell tumor of bone. A novel keratin-positive GCT-ST (KPGCT-ST) harboring HMGA2::NCOR2 fusions was recently discovered. Fewer than 30 cases have been described; herein is reported an additional seven., Methods: Cases diagnosed as GCT-ST were retrieved from institutional archives and consultation files. The histopathologic characteristics were assessed, and the electronic medical record was reviewed., Results: Seven tumors were identified in six women and one man with a median age of 23 years. All patients underwent excision; no recurrences or metastases were noted during a median follow-up period of 7 months. Histopathologically, the tumors were characterized by a multinodular proliferation of keratin-positive mononuclear cells with evenly admixed osteoclast-like giant cells and absent neoplastic bone. A fibrous capsule with lymphoid cuffing was frequently seen. Foamy macrophages, inflammation, hemorrhage, and hemosiderin were variably present. The HMGA2::NCOR2 fusion was detected in all cases., Conclusions: Our findings support previously reported hypotheses that KPGCT-ST is a spectrum of the same entity as the recently described xanthogranulomatous epithelial tumor. Although follow-up data are limited, to date, KPGCT-ST appears to follow an indolent course., (© 2023 The Authors. Journal of Cutaneous Pathology published by John Wiley & Sons Ltd.)

Background: Elastofibroma dorsi (EFD) is a pseudotumor of the thoracic wall that can be difficult to diagnose due to its rarity. Prompt recognition can limit unnecessary workup and expedite treatment. This study retrospectively analyzed patients with a diagnosis of EFD, discussing clinical presentations and surgical outcomes., Methods: This is an IRB-approved single-center retrospective study of all patients with a diagnosis of elastofibroma at our institution between 2000 and 2022., Results: Ten patients were identified to have a pathologic diagnosis of EFD since 2000, with half presenting in the last 5 years. Our cohort had an average age of 56.8 years and was 50% female. The average age of male subjects was younger than females, 49.6-64.0 years, respectively (p = 0.10). Eighty percent (8/10) of patients had unilateral EFDs and symptoms lasted 27.1 months on average prior to diagnosis. Surgical resection was performed on 66.67% (8/12) of masses, with 87.5% (7/8) of patients who underwent surgery reporting complete resolution of their symptoms and none reporting recurrence., Conclusions: Although EFD is a rare pseudotumor, its incidence may be increasing. As such, surgeons should be aware of the typical clinical presentation; specifically, a slow growing, predominantly unilateral, painful, subscapular mass with an inhomogeneous pattern on imaging. Originally thought to predominantly affect elderly women, our study shows that younger men may be at risk as well. If patients present with EFD, complete surgical resection should be performed to achieve favorable outcomes and resolution of symptoms., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Limited data exist on the clinical behavior of pediatric non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) with distant metastases at onset, and a clear standard of care has not yet been defined., Methods: This cohort study reports on pediatric adult-type metastatic NRSTS enrolled in two concurrent prospective European studies, i.e., the randomized BERNIE study and the single-arm MTS 2008 study developed by the European paediatric Soft tissue sarcoma Study Group. Treatment programs were originally designed for patients with metastatic rhabdomyosarcoma, i.e., nine courses of multidrug chemotherapy (with or without bevacizumab in the BERNIE study), followed by 12 cycles of maintenance therapy, whereas radiotherapy and/or surgery (on primary tumor and/or metastases) were delayed until after seven courses of chemotherapy had been administered., Results: The study included 61 patients <21 years old treated from July 2008 to December 2016. The lung was the site of metastases in 75% of the cases. All patients received multi-agent chemotherapy, 44% had local therapy to primary tumor, and 18% had treatment of metastases. Median time to progression/relapse was 6 months. A high rate of tumor progression was observed during the initial part of the chemotherapy program. With a median follow-up of 41.5 months (range, 2-111 months), 3-year event-free survival and overall survival were 15.4% (95% confidence interval [CI], 7.6-25.7) and 34.9% (95% CI, 22.7-47.5), respectively. There were no statistically significant differences in outcome depending on the type of treatment administered., Conclusions: The study confirmed the overall poor outcome for patients with metastatic NRSTS, whose treatment remains a challenge., Plain Language Summary: Pediatric non-rhabdomyosarcoma soft tissue sarcomas form a heterogeneous group of rare tumors. Although recent international studies have defined the standard of care for patients with localized disease, limited data are available on the clinical behavior of patients with distant metastases. This study on 61 metastatic cases treated on two prospective European protocols confirms that the chances of survival of such patients are often dismal and a standard treatment is still lacking., (© 2023 American Cancer Society.)

Background: Selinexor (KPT-330) is a potent inhibitor of exportin 1 (XPO1), in turn inhibiting tumor growth. Selinexor enhances the antitumor efficacy of eribulin in triple-negative breast cancer (TNBC) in vitro and in vivo. Given the unmet medical need in TNBC and sarcoma, the authors explored the safety and efficacy of this combination., Methods: The authors conducted a phase 1b trial of combined selinexor and eribulin using a 3 + 3 dose-escalation design in patients who had advanced solid tumors and in those who had TNBC in a dose-expansion cohort., Results: Patients with TNBC (N = 19), sarcoma (N = 9), and other cancers (N = 3) were enrolled in the dose-escalation cohort (N = 10) and in the dose-expansion cohort (N = 21). The median number lines of prior therapy received was four (range, from one to seven prior lines). The most common treatment-related adverse events for selinexor were nausea (77%), leukopenia (77%), anemia (68%), neutropenia (68%), and fatigue (48%). One dose-limiting toxicity occurred at the first dose level with prolonged grade 3 neutropenia. The recommended phase 2 dose was 80 mg of selinexor orally once per week and 1 mg/m 2 eribulin on days 1 and 8 intravenously every 3 weeks. The objective response rate (ORR) was 10% in three patients. In the dose-escalation cohort, the ORR was 10%, whereas six patients with had stable disease. In the TNBC dose-expansion cohort (n = 18), ORR was 11%, and there were two confirmed partial responses with durations of 10.8 and 19.1 months (ongoing)., Conclusions: Selinexor and eribulin had an acceptable toxicity profile and modest overall efficacy with durable responses in select patients., Plain Language Summary: Effective therapies for advanced, triple-negative breast cancer and sarcoma represent an unmet need. Exportin 1 is associated with the transport of cancer-related proteins. Preclinical studies have demonstrated tumor growth inhibition and enhanced tumor sensitivity in patients who receive selinexor combined with eribulin. In this phase 1b study, the authors evaluated the safety profile and clinical activity of the combination of selinexor, a potent oral inhibitor of exportin 1, and eribulin in patients with advanced cancers enriched for triple-negative breast cancer or sarcoma. The combination was well tolerated; most adverse events were mild or moderate, reversible, and managed with dose modifications or growth factor support. The combination of selinexor and eribulin produced an antitumor response, particularly in some patients with triple-negative breast cancer. This work lays the foundation for prospective investigations of the role of selinexor and eribulin in the treatment of triple-negative breast cancer., (© 2023 American Cancer Society.)

Melanoma and benign histiocytic proliferations can sometimes show considerable clinical and histopathologic overlap. Recently, cases of melanomas resembling xanthogranuloma and Rosai-Dorfman disease have been reported, and herein we report a case of melanoma closely mimicking reticulohistiocytoma. An 84-year-old man presented with a 1 cm purple-red nodule on his arm concerning for squamous cell carcinoma. While the biopsy findings resembled reticulohistiocytoma, the clinical context and regression changes at the lesion perimeter raised stronger concern for melanoma, which was confirmed with immunohistochemistry. We review prior rare reports of melanomas resembling non-Langerhans cell histiocytic proliferations and summarize helpful clinical and histopathologic clues to avoid a diagnostic pitfall when confronted with this unusual quandary., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Lipofibromatosis-like neural tumors (LPF-NTs) are a recently discovered group of spindle cell tumors defined by the presence of a lipofibromatosis-like pattern, CD34 and/or S100 reactivity, and frequent neurotrophic receptor tyrosine kinase 1 (NTRK1) gene rearrangements. As new cases emerge, the spectrum of features observed in LPF-NTs continues to evolve. Here we describe the case of an 11-year-old with LPF-NT with a dermatofibrosarcoma protuberans-like honeycomb pattern, CD34 and S100 co-expression, and an NTRK1 rearrangement. We also review the clinical and molecular features of the 73 cases of LPF-NT previously described in the literature., (© 2023 Wiley Periodicals LLC.)

Myoepithelial neoplasms of the skin and soft tissue are rare and share histopathologic features with their salivary gland counterpart. We present a case of an atypical myoepithelial neoplasm from the back of a 72-year-old female. This lesion harbored an EWSR1::NR4A3 gene fusion, a genetic signature characteristically seen in extraskeletal myxoid chondrosarcoma. To our knowledge, this is a unique case of an atypical cutaneous myoepithelial neoplasm harboring EWSR1::NR4A3 fusion., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Cutaneous myoepithelioma is a rare benign soft tissue neoplasm of myoepithelial cells involving the skin and subcutis. These tumors can be diagnostically challenging. The plasticity of myoepithelial cells leads to wide variability in the cytomorphology, immunophenotype, and genetic features of myoepithelioma. Their protean presentations may mimic malignant neoplasms. Therefore, distinction from malignancy is essential. Herein, we report a case of cutaneous myoepithelioma presenting similarly to Ewing sarcoma, with small round blue cells and an EWSR1 rearrangement. Our case highlights the important morphologic, immunohistochemical, and cytogenetic features of this benign basaloid cutaneous tumor., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Superficial CD34-positive fibroblastic tumor (SCPFT) is a recently described rare superficial mesenchymal tumor. SCPFT has a distinctive morphologic appearance, marked by significant nuclear pleomorphism, low mitotic rate, and diffuse CD34 positivity. SCPFT is underdiagnosed because of its rarity and misdiagnosis as sarcoma, with very few reported cases of local recurrence or metastasis. Recognition and awareness of SCPFT are essential for accurate diagnosis and appropriate clinical management. We describe here the case of a 37-year-old male who presented with a right calf mass diagnosed as SCPFT with subsequent local recurrence of the tumor., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Sarcomas account for almost 11% of all cancers in adolescents and young adults (AYAs; 18-39 years). AYAs are increasingly recognized as a distinct oncological age group with its own psychosocial challenges and biological characteristics. Social functioning has been shown to be one of the most severely affected domains of health-related quality of life in AYA cancer survivors. This study aims to identify AYA sarcoma survivors with impaired social functioning (ISF) and determine clinical and psychosocial factors associated with ISF., Methods: AYAs from the population-based cross-sectional sarcoma survivorship study (SURVSARC) were included (n = 176). ISF was determined according to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 social functioning scale, and age- and sex-matched norm data were used as reference., Results: The median time since diagnosis was 6.2 years (range, 1.8-11.2). More than one-quarter (28%) of AYA sarcoma survivors experienced ISF. Older age, higher tumor stage, comorbidities, lower experienced social support, uncertainty in relationships, feeling less attractive, sexual inactivity, unemployment, and financial difficulties were associated with ISF. In a multivariable analysis, unemployment (OR, 3.719; 95% CI, 1.261-10.967) and having to make lifestyle changes because of financial problems caused by one's physical condition or medical treatment (OR, 3.394; 95% CI, 1.118-10.300) were associated with ISF; better experienced social support was associated with non-ISF (OR, 0.739; 95% CI, 0.570-0.957)., Conclusion: More than one-quarter of AYA sarcoma survivors experience ISF long after diagnosis. These results emphasize the importance of follow-up care that is not only disease-oriented but also focuses on the psychological and social domains., Plain Language Summary: Sarcomas account for almost 11% of all cancers in adolescents and young adults (AYAs; 18-39 years). The AYA group is increasingly recognized as a distinct oncological age group with its own psychosocial challenges and biological characteristics. Social functioning has been shown to be severely affected in AYA cancer survivors. A population-based questionnaire study to identify AYA sarcoma survivors with impaired social functioning (ISF) and determine factors associated with ISF was conducted. More than one-quarter of AYA sarcoma survivors experience ISF long after diagnosis. These results emphasize the importance of follow-up care that is not only disease-orientated but also focuses on the psychological and social domains., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Cutaneous VCL::ALK fusion spindle (ovoid) cell tumor is unique. Recently emerged RAS::MAP tyrosine kinase fusion sarcomas more commonly involve subcutis, skeletal muscle and even bone. We share our experience with a novel cutaneous VCL::ALK spindle cell tumor. An 11-year-old male presented with a back pedunculated pink-red papule thought to be a pyogenic granuloma. Biopsy histopathology revealed an epithelial collarette with pedunculated tumor extending to deep dermis/subcutis interface. The combination of spindled and epithelioid cells, an ovoid myopericytoid appearance within myxoid to collagenous stroma, low to moderate MIB1 and focal S100 protein without SOX10 immunostaining, were suggestive of a novel RAS::MAPK tyrosine kinase fusion sarcoma that is well described. ALK immunostain being positive, a next-generation sequencing comprehensive fusion panel was performed to reveal a VCL::ALK fusion. While epithelioid fibrous histiocytoma shares this fusion and similar dermal location and collarette pedunculation, this and other entities were excluded by older patient age, deeper dermal involvement, ovoid-to-spindled morphology, central pericytoid vasculature, myxoid stroma, moderate cellularity with low to moderate MIB1 expression, superficial ulceration, and focal S100 protein expression. Complete excision was performed with favorable follow-up to date. This novel VCL::ALK fusion spindle (ovoid) cell tumor of the dermis is best considered as part of the recently emerged RAS::MAP tyrosine kinase fusion sarcomas., (© 2023 The Authors. Journal of Cutaneous Pathology published by John Wiley & Sons Ltd.)

Introduction: Glomus tumors (GT) are rare, benign tumors that arise from glomus bodies and usually develop in digital areas. Extradigital GT are exceptional and thigh location is infrequent., Case Report: We report a case of a GT of the thigh in a 79-year-old male patient that measured 9.5 cm in maximum size. The GT lay above the muscular fascia without infiltrating it. Internal hypervascularity was seen by spectral Doppler ultrasound. Magnetic resonance image showed a heterogeneous mass with hyperintense and hypointense components and internal lobes with liquid-liquid levels. Histopathology revealed a monotonous round-cell proliferation with central nuclei without atypia or mitotic figures, around small-caliber vessels. These cells expressed smooth muscle actin and pericellular collagen IV. GT of uncertain malignant potential was diagnosed. The mass was completely removed. The patient did not experience local relapse nor distant metastasis., Conclusion: GT are rare soft tissue tumors whose diagnosis of unusual giant masses in uncommon locations may be delayed and misdiagnosed given the low suspicion., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Lipofibromatosis-like neural tumor is a recently described entity defined by a low-cellularity spindle cell infiltrate in the subcutaneous fat with admixed inflammatory cells. This tumor is histopathologically similar to lipofibromatosis, but unlike lipofibromatosis shows reactivity for S100 and has an NTRK-1 kinase fusion. These lesions are locally aggressive but appear to have a negligible metastatic potential. Subsequently, a more cellular variant has been described with generally low mitotic rate. This variant also displays S100 reactivity and kinase fusions (typically involving NTRK-1), but it has a low risk of metastasis. In this report, we describe a case that aligns with the more cellular variant of NTRK-1 kinase fusion tumors on histopathologic, immunohistochemical, and molecular grounds, but in addition has distinctive nodules with peripheral accentuation of cellularity, reminiscent of those present in epithelioid malignant peripheral nerve sheath tumors. This latter feature is previously undescribed in NTRK kinase fusion soft tissue tumors and offers further support for the presumed neural differentiation of this neoplasm., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Tumor-to-tumor metastases are an uncommon phenomenon and are very rare in the context of malignant melanoma. This case report describes a 73-year-old male who underwent an excision of a melanoma from his forehead. Six months later, he developed metastatic disease, including metastasis to a genetically confirmed angiofibroma of soft tissue of the abdominal wall. Angiofibroma of soft tissue is a relatively recently described benign fibrovascular soft tissue tumor, and there appear to be no previous reports of it being a recipient tumor for a metastasis. Awareness of the phenomenon of tumor-to-tumor metastasis and of the distinctive morphologic and molecular genetic features of angiofibroma are critical to avoid misdiagnosis of this very rare event as "dedifferentiated" melanoma., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Low-grade fibromyxoid sarcoma (LGFMS) typically involves deep soft tissue (beneath the fascia) of the proximal extremities and trunk. Long-term follow-up has shown a high rate of local recurrence, metastasis, and death. To the best of our knowledge, there is only one previous large series focusing on superficial LGFMS suggesting superficial tumors are disproportionately more common in children and may have a better prognosis. Our study's primary goals are to confirm these findings and increase general awareness that LGFMS may arise in superficial soft tissue., Methods: We retrieved our cases of superficial LGFMS diagnosed between 2008 and 2020. Available slides were reviewed, and clinical data and follow-up information were obtained., Results: The patients included nine males and 14 females with a median age of 29 years; eight (35%) were children (<18 years) and five (22%) were young adults (18-30 years). The majority involved the lower extremities (65%). The tumors were primarily centered in the subcutis (91%) and dermis (9%). Microscopically, they had typical features of LGFMS with alternating fibrous and myxoid zones composed of bland, slightly hyperchromatic spindled cells. All were positive for MUC4 by immunohistochemistry and/or FUS rearrangement by FISH. Follow-up on 14 cases ranged from 11 to 148 months (median 61 months) with no evidence of recurrences or distant metastases., Conclusions: Compared to conventional deep-seated counterparts, superficial LGFMS is more likely to occur in the extremities of children and young adults and may have a better clinical outcome. Further studies with longer follow-up will likely help support these findings., (© 2022 The Authors. Journal of Cutaneous Pathology published by John Wiley & Sons Ltd.)

Background: Soft tissue sarcoma (STS) is one of the most frequently diagnosed cancers among men younger than age 30 years and a leading cause of cancer death in men younger than age 40 years. The military may be more exposed to STS risk factors and have generally better health and health care access than the general population, which may relate to lower cancer risk and/or early detection. This study compared STS incidence between servicemen and men in the general U.S., Methods: Data were from the Department of Defense's Automated Central Tumor Registry (ACTUR) and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. Subjects were active-duty servicemen in ACTUR and men in SEER aged 18-59 years diagnosed with STS from 1990 to 2013. Age-adjusted rates, incidence rate ratios (IRR), and 95% CIs were calculated., Results: STS incidence rates were lower in ACTUR than SEER overall (IRR = 0.86 [0.78-0.93]), for 18- to 39-year-old men (IRR = 0.78 [0.70-0.86]), by race (White: IRR = 0.85 [0.77-0.95]; Black: IRR = 0.77 [0.63-0.94]), for sites other than skin/connective/soft tissue (IRR = 0.49 [0.37-0.63]), other specified histologies (IRR = 0.84 [0.71-0.98]), and unspecified histology (IRR = 0.57 [0.38-0.82]). Rates were lower in ACTUR for regional (IRR = 0.37 [0.28-0.47]) and distant metastases (IRR = 0.58 [0.43-0.76]), even when race and age stratified. However, rates were higher in ACTUR for 40- to 59-year-old men (IRR = 1.25 [1.04-1.48]) and localized tumors (IRR = 1.16 [1.04-1.29])., Conclusion: Lower STS rates among servicemen may relate to better health and early detection and treatment of STS-associated conditions within the military health system, which provides universal care. Higher rates among 40- to 59-year-old servicemen may result from greater cumulative military-related exposures., (© 2024 American Cancer Society.)

Background: Tumors and tumor-like lesions of the foot and ankle are relatively rare and their postoperative clinical outcome has not been well reported., Methods: This study retrospectively reviewed medical records of all patients who underwent excision of tumors and tumor-like lesions of the foot and ankle from 2008 to 2020. Preoperative and postoperative clinical outcomes were evaluated by the Japanese Society for Surgery of the Foot (JSSF) scales (pain, function, and alignment)., Results: A total of 117 consecutive patients were analyzed in this study. Bone lesions accounted for 51 patients (benign: 45, intermediate malignancy: 1, malignant: 5), and soft tissue lesions accounted for 66 patients (benign: 57, intermediate malignancy: 2, malignant: 7). Four patients (8%) presenting with bone tumor and six (9%) soft tissue tumors resulted in recurrence. Eight (67%) patients with malignant lesions were alive continuously disease free and followed for a median of 50.5 (range: 18 to 82) months. Amputation at the first operation was done for five cases (33%) of malignant or intermediate malignancy (below-knee amputation: 1, Chopart disarticulation: 1, forefoot amputation: 3). Postoperative JSSF scores resulted in a significant 'positive' increase (bone lesion, 75.9 ± 13.7 to 91.4 ± 14.9, p < 0.001; soft tissue lesion, 84.7 ± 14.8 to 91.9 ± 12.5, p < 0.001). The score improvement in bone lesions was significantly higher than in soft tissue lesions (p = 0.003)., Conclusion: The surgical management of tumors and tumor-like lesions of the foot and ankle showed good post-operative functional outcomes with bone lesions exhibiting better results when compared to soft-tissue lesions., (© 2022. The Author(s).)

For soft tissue sarcoma patients receiving preoperative radiation therapy, wound complications are common and potentially devastating. The purpose of this study was to assess the feasibility of intraoperative indocyanine green fluorescent angiography (ICGA) as a predictor of wound complications in these patients. A consecutive series of patients with soft tissue sarcoma of the extremities or pelvis who received neoadjuvant radiation and a subsequent radical resection received intraoperative ICGA with the SPY PHI device (Stryker Inc.) at the time of closure. Retrospective analysis of fluorescence signal along multiple points of the wound length was performed and quantified. The primary endpoint was wound complication, defined as delayed wound healing or wound dehiscence, within 3 months of surgery. Fourteen patients with preoperative irradiated soft tissue sarcoma were consecutively imaged. There were six patients with wound complications classified as "aseptic" in five cases. Using the ICGA, blinded surgeons correctly predicted wound complications in 75% of cases. During the inflow phase, a mean ratio of normal of 0.62 maximized the area under the curve (AUC = 0.90) for predicting wound complications with a sensitivity of 100% and specificity of 77.4%. During the peak phase, a mean ratio of normal of 0.55 maximized the AUC (0.95) for predicting wound complications with a sensitivity of 88.9% and a specificity of 100%. Intraoperative use of ICGA may help to predict wound complications in patients undergoing resection of preoperatively irradiated soft tissue sarcomas of the extremities and pelvis., (© 2022 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Sarcoma, the second common type of solid tumor in children and adolescents, has a wide variety of subtypes that are often not properly diagnosed at an early stage, leading to late metastases and causing serious loss of life and property to patients and families. It exhibits a high degree of heterogeneity at the cellular, molecular, and epigenetic levels, where DNA methylation has been proposed to play a role in the diagnosis of sarcoma subtypes. Thus, this study is aimed at finding potential biomarkers at the DNA methylation level to distinguish different sarcoma subtypes. A machine learning process was designed to analyse sarcoma samples, each of which was represented by lots of methylation sites. Irrelevant sites were removed using the Boruta method, and remaining sites related to the target variables were kept for further analyses. Afterward, three feature ranking methods (LASSO, LightGBM, and MCFS) were adopted to rank these features, and six classification models were constructed by combining incremental feature selection and two classification algorithms (decision tree and random forest). Among these models, the performance of RF model was higher than that of DT model under all three ranking conditions. The specific expression of genes obtained from the annotation of highly correlated methylation site features, such as PRKAR1B, INPP5A, and GLI3, was proven to be associated with sarcoma by publications. Moreover, the quantitative rules obtained by decision tree algorithm helped us to understand the essential differences between various sarcoma types and classify sarcoma subtypes, providing a new means of clinical identification and determining new therapeutic targets., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2022 Jingxin Ren et al.)

In medical research, it is often of great interest to have an accurate estimation of cure rates by different treatment options and for different patient groups. If the follow-up time is sufficiently long and the sample size is large, the proportion of cured patients will make the Kaplan-Meier estimator of survival function have a flat plateau at its tail, whose value indicates the overall cure rate. However, it may be difficult to estimate and compare the cure rates for all the subsets of interest in this way, due to the limit of sample sizes and curse of dimensionality. In the current literature, most regression models for estimating cure rates assume proportional hazards (PH) between different subgroups. It turns out that the estimation of cure rates for subgroups is highly sensitive to this assumption, so more flexible models are needed, especially when this PH assumption is clearly violated. We propose a new cure model to simultaneously incorporate both PH and non-PH scenarios for different covariates. We develop a stable and easily implementable iterative procedure for parameter estimation through maximization of the nonparametric likelihood function. The covariance matrix is estimated by adding perturbation weights to the estimation procedure. In simulation studies, the proposed method provides unbiased estimation for the regression coefficients, survival curves, and cure rates given covariates, while existing models are biased. Our model is applied to a study of stage III soft tissue sarcoma and provides trustworthy estimation of cure rates for different treatment and demographic groups., (© 2022 John Wiley & Sons Ltd.)

Soft-tissue sarcomas (STS) represent a group of rare and heterogeneous tumors associated with several challenges, including incorrect or late diagnosis, the lack of clinical expertise, and limited therapeutic options. Digital pathology and radiomics represent transformative technologies that appear promising for improving the accuracy of cancer diagnosis, characterization and monitoring. Herein, we review the potential role of the application of digital pathology and radiomics in managing patients with STS. We have particularly described the main results and the limits of the studies using radiomics to refine diagnosis or predict the outcome of patients with soft-tissue sarcomas. We also discussed the current limitation of implementing radiomics in routine settings. Standard management approaches for STS have not improved since the early 1970s. Immunotherapy has revolutionized cancer treatment; nonetheless, immuno-oncology agents have not yet been approved for patients with STS. However, several lines of evidence indicate that immunotherapy may represent an efficient therapeutic strategy for this group of diseases. Thus, we emphasized the remarkable potential of immunotherapy in sarcoma treatment by focusing on recent data regarding the immune landscape of these tumors. We have particularly emphasized the fact that the development of immunotherapy for sarcomas is not an aspect of histology (except for alveolar soft-part sarcoma) but rather that of the tumor microenvironment. Future studies investigating immunotherapy strategies in sarcomas should incorporate at least the presence of tertiary lymphoid structures as a stratification factor in their design, besides including a strong translational program that will allow for a better understanding of the determinants involved in sensitivity and treatment resistance to immune-oncology agents., (© 2022 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.)

Background: Phaeohyphomycosis is a fungal infection caused by heterogenous group of fungi known as phaeoid or dematiaceous fungi. It manifests in four clinical forms-cutaneous, subcutaneous, systemic and cerebral phaeohyphomycosis. The subcutaneous form is the most common presentation. Clinically these subcutaneous swellings resemble benign skin and soft tissue neoplasms like lipoma, sebaceous cyst or neurofibroma. Histopathology serves as a very useful tool in diagnosing these cysts by identifying the fungal elements., Methods: A retrospective review of all cases diagnosed as phaeohyphomycosis in the department of Pathology at a tertiary care centre in South India over 9 years (January 2009-December 2017) was done. The clinical, histopathological findings of these cases were reviewed and analysed., Results: Sixty-six cases of subcutaneous phaeohyphomycosis were reported during the 9 year period. Sixty-two per cent of these patients were diagnosed as skin and soft tissue neoplasms. In 94% cases, the extremities were affected. Multiple cysts were seen in 11% of patients. Fine needle aspiration cytology was done in 29 cases with fungal hyphae identified in all cases on cytology., Conclusion: Subcutaneous phaeohyphomycosis mimics benign skin and soft tissue neoplasms clinically. Histopathological examination along with cytology plays a major role in diagnosis of phaeohyphomycosis and thus helps in appropriate patient management.

Background: The European Organization for Research and Treatment of Cancer 22092-62092 STRASS trial failed to demonstrate the superiority of neoadjuvant radiotherapy (RT) over surgery alone in patients with retroperitoneal sarcoma. Therefore, an RT quality-assurance program was added to the study protocol to detect and correct RT deviations. The authors report results from the trial RT quality-assurance program and its potential effect on patient outcomes., Methods: To evaluate the effect of RT compliance on survival outcomes, a composite end point was created. It combined the information related to planning target volume coverage, target delineation, total dose received, and overall treatment time into 2 groups: non-RT-compliant (NRC) for patients who had unacceptable deviation(s) in any of the previous categories and RT-compliant (RC) otherwise. Abdominal recurrence-free survival (ARFS) and overall survival were compared between the 2 groups using a Cox proportional hazard model adjusted for known prognostic factors., Results: Thirty-six of 125 patients (28.8%) were classified as NRC, and the remaining 89 patients (71.2%) were classified as RC. The 3-year ARFS rate was 66.8% (95% confidence interval [CI], 55.8%-75.7%) and 49.8% (95% CI, 32.7%-64.8%) for the RC and NRC groups, respectively (adjusted hazard ratio, 2.32; 95% CI, 1.25-4.32; P = .008). Local recurrence after macroscopic complete resection occurred in 13 of 89 patients (14.6%) versus 2 of 36 patients (5.6%) in the RC and NRC groups, respectively., Conclusions: The current analysis suggests a significant benefit in terms of ARFS in favor of the RC group. This association did not translate into less local relapses after complete resection in the RC group. Multidisciplinary collaboration and review of cases are critical to avoid geographic misses, especially for rare tumors like retroperitoneal sarcoma., (© 2022 American Cancer Society.)

Objective: Soft tissue sarcomas (STS) and gastrointestinal stromal tumours (GIST) are a group of rare malignant tumours with a high and heterogenous disease burden. As evidence is scarce, we analysed the prevalence of increased emotional distress and identified distress-associated factors in these patients., Methods: The PROSa-study (Burden and medical care of sarcoma) was conducted between 2017 and 2020 in 39 study centres. Cross-sectional data from adult STS and GIST patients were analysed. Distress was measured with the Patient Health Questionnaire (PHQ-4). The relation of socioeconomic and clinical factors with distress was explored in adjusted logistic regression models., Results: Among 897 patients, 17% reported elevated anxiety and 19% reported depression. Unemployed patients (odds ratio [OR] 6.6; 95% CI 2.9-15.0), and those with a disability pension (OR 3.1; 95% CI 1.9-5.0) were more likely to experience distress compared to employed patients. Also, patients with a disability pass had higher odds of increased distress than those without (OR 1.8; 95% CI 1.2-2.7). Lowest distress was observed in patients 2 to <5 years and ≥5 years after diagnosis (comparison: <6 months) (OR 0.4; 95% CI 0.2-0.6) and (0.3; 95% CI 0.2-0.6). Patients with thoracic STS (vs. lower limbs) had twice the odds to experience distress (OR 2.0; 95% CI 1.1-3.6). Distress was seen almost twice as often in patients with progressive disease (vs. complete remission) (OR 1.7; 95% CI 1.1-2.8)., Conclusion: The prevalence of elevated distress in STS and GIST patients is high. In unemployed patients, in those with a disability pension and in newly diagnosed patients a noticeable increase was observed. Clinicians should be aware of these factors and consider the social aspects of the disease., (© 2022 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.)

Background: The incidence of different soft tissue sarcoma (STS) histotypes among ethnic and geographic populations has not been comprehensively investigated., Methods: Data from 2013 to 2016 were obtained from national cancer registry databases in France and Taiwan. Liposarcoma (LPS), leiomyosarcoma (LMS), angiosarcoma (AS), synovial sarcoma (SS), and malignant peripheral nerve sheath tumor (MPNST) were selected as index STSs to estimate the age-standardized incidence rates (ASRs) and other clinical features between patients., Results: In total, 9398 patients (7148 from France and 2250 from Taiwan) were included. The ASRs of AS (5.4 vs. 2.8) and MPNST (2.0 vs. 1.0) were significantly higher in Taiwan; France had significantly higher ASRs for LPS (12.0 vs. 10.0), LMS (9.7 vs. 7.6), and SS (1.7 vs. 1.2). Patients in Taiwan with LMS or LPS were younger than their French counterparts. With regard to the distribution according to primary anatomic site, French patients had higher odds for extremity and truncal LMS (odds ratio [OR], 2.84; p < .001), AS (OR, 2.67; p < .001), MPNST (OR, 1.55; p = .027), and LPS (OR, 1.38; p < .001) and for breast AS (OR, 10.58; p < .001). Taiwanese patients had higher odds for liver AS (OR, 10.72; p < .001) and uterine LMS (OR, 3.21; p < .001). SS age and distribution according to primary anatomic site did not differ significantly between the French and Taiwanese populations., Conclusions: Significant differences in the incidence and clinical characteristics of index STS suggested that geographic (environmental) and ethnicity factors likely play a vital role in the pathogenesis of STS., (© 2022 American Cancer Society.)

Background: Cellular and intrinsic markers of sarcoma immunogenicity are poorly understood. To gain insight into whether tumor-immune interactions correlate with clinical aggressiveness, the authors examined the prognostic significance of immune gene signatures in combination with tumor mutational burden (TMB) and cancer-testis antigen (CTA) expression., Methods: RNA sequencing and clinical data of 259 soft tissue sarcomas from The Cancer Genome Atlas project were used to investigate associations between published immune gene signatures and patient overall survival (OS) in the contexts of TMB, as computed from whole-exome sequencing data, and CTA gene expression. Multivariate Cox proportional hazards regression models and log-rank tests were used to assess survival associations., Results: Immune signature scores that reflected in part the intratumoral abundance of cytotoxic T cells showed significant positive associations with OS. However, the prognostic power of the T-cell signatures was highly dependent on TMB-high status, consistent with protective effects of tumor-infiltrating T cells in tumors with elevated antigenicity. In TMB-low tumors, a signature of infiltrating plasma B cells was significantly and positively associated with OS, independent of T-cell signature status. Although tumor subtypes based on differential expression patterns of CTA genes showed different survival associations within leiomyosarcoma and myxofibrosarcoma histologies, neither CTA nor histologic subtype interacted with the T-cell-survival association., Conclusions: Signatures of T-cell and plasma B-cell infiltrates were associated with a survival benefit in soft tissue sarcomas. TMB, but not CTA expression, influenced the prognostic power of T-cell-associated, but not plasma B-cell-associated, survival., Lay Summary: Clinical data and RNA analysis of 259 soft tissue sarcomas from The Cancer Genome Atlas project were used to investigate associations between five published gene immune cell expression signatures and survival in the context of tumor mutations. Activated T cells had a significant positive association with patient survival. Although high tumor mutation burden was associated with good survival, the prognostic power of T-cell signatures was highly dependent on tumor mutational status, consistent with protective effects of tumor-infiltrating T cells in tumors with high levels of antigens. In low tumor mutation-bearing tumors, plasma B cells were positively associated with survival., (© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Desmoid tumors (DTs) are rare soft tissue mesenchymal neoplasms that may be associated with impairments, disfigurement, morbidity, and (rarely) mortality. DT disease course can be unpredictable. Most DTs are sporadic, harboring somatic mutations in the gene that encodes for β-catenin, whereas DTs occurring in patients with familial adenomatous polyposis have germline mutations in the APC gene, which encodes for a protein regulator of β-catenin. Pathology review by an expert soft tissue pathologist is critical in making a diagnosis. Magnetic resonance imaging is preferred for most anatomic locations. Surgery, once the standard of care for initial treatment of DT, is associated with a significant risk of recurrence as well as avoidable morbidity because spontaneous regressions are known to occur without treatment. Consequently, active surveillance in conjunction with pain management is now recommended for most patients. Systemic medical treatment of DT has evolved beyond the use of hormone therapy, which is no longer routinely recommended. Current options for medical management include tyrosine kinase inhibitors as well as more conventional cytotoxic chemotherapy (e.g., anthracycline-based or methotrexate-based regimens). A newer class of agents, γ-secretase inhibitors, appears promising, including in patients who fail other therapies, but confirmation in Phase 3 trials is needed. In summary, DTs present challenges to physicians in diagnosis and prognosis, as well as in determining treatment initiation, type, duration, and sequence. Accordingly, evaluation by a multidisciplinary team with expertise in DT and patient-tailored management are essential. As management strategies continue to evolve, further studies will help clarify these issues and optimize outcomes for patients., (© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Epithelioid angioleiomyoma (EALM) is rare in the skin and subcutaneous tissues. To the best of our knowledge, only two previous cases of this tumor have been reported. We document here the case of an 83-year-old woman who underwent complete removal of a squamous cell carcinoma of the retromolar trigone and lymph node dissection of the neck. An incidental EALM was observed in the adipose tissue. The tumor formed a unilocular, poorly demarcated neoplasm measuring 0.3 cm, and showed cavernous angiomatous spaces with villiform growth of large epithelioid cells arranged in clusters. Besides the epithelioid cells of muscular origin, bundles of well-differentiated smooth muscle cells were observed. Epithelioid cells accounted for 70% of the total. The neoplasm originated in the wall of a medium-sized vein. Epithelioid and spindle cells were positive for alpha-smooth muscle actin, calponin, h-caldesmon, and muscle-specific actin. The endothelial cells lining the vascular spaces showed intense and diffuse positivity for CD31 and ERG. The main differential diagnosis includes metastatic carcinoma, melanoma, perivascular epithelioid cell neoplasm, myopericytoma, glomangiomyoma, epithelioid glomus tumor, and epithelioid leiomyosarcoma. This report expands the morphological spectrum of the EALM. Awareness of this uncommon morphologic variant of angioleiomyoma and the use of adequate techniques can avoid misdiagnosis., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Metastasis to the oral soft tissues and jaw is rare and accounts for 1%-3% of maxillofacial malignancies. These lesions usually occur in the context of an extensive malignant tumor with a poor prognosis., Materials and Methods: Archived cases from the Oral and Maxillofacial Pathology Department of the Faculty of Dentistry and two hospital centers of Mashhad University of Medical Sciences were examined. Inclusion criteria were cases with available records of pathologically confirmed metastatic lesions of the oral cavity with or without diagnosed primary malignancy., Results: Metastatic lesions in the oral cavity and jaw were found in 18 patients, including seven women and 11 men, with a mean age of 49.5 years. Metastatic lesions were more common in the jaw (66%) and particularly in the mandible (38%) than elsewhere. In the case of soft tissue metastases, the gingiva was more affected than other sites. The primary tumor was most commonly in the kidney in men and in the breast in women (36%-28%). In addition, the diagnosis of a metastatic lesion led to the detection of the primary tumor elsewhere in six out of 18 cases (33.3%)., Conclusions: Early diagnosis of the lesions is challenging, given the absence of specific signs or symptoms, which, in some cases, nonetheless resemble inflammatory, benign, reactive lesions. Therefore, dentists play a crucial role in diagnosing such lesions, as they lead to the discovery of hidden distant primary tumors. Biopsy should always be considered for suspicious lesions, even if the probability is very low., (© 2024 The Author(s). Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

Background and Objectives: This study aims to translate and culturally adapt the Toronto Extremity Salvage Score (TESS) for Latin American Spanish-speaking patients, enhancing the tool's accessibility for evaluating postsurgical functional outcomes in sarcoma patients across Latin America. Methods: The TESS questionnaires for lower extremity (LE) and upper extremity (UE) were translated and adapted following international guidelines. The process included forward and backward translation, expert committee review, and pretesting with cognitive interviewing. Patients treated for bone or soft tissue tumors in LE or UE were recruited to complete the adapted questionnaires. Test-retest reliability was evaluated by having participants complete the questionnaire again 2 weeks after the initial assessment. Results: A total of 89 participants completed the questionnaires. The study found high internal consistency, with Cronbach's alpha values reaching 0.9437 for LE and 0.9402 for UE. An agreement rate of 98.4% for the global score of TESS-LE (95% confidence interval [CI]: 0.909-1.059) and 93.9% for TESS-UE (95% CI: 0.882-0.995) was observed, demonstrating strong test-retest reliability. Conclusions: The Latin American Spanish version of TESS for both lower and upper extremities is a reliable and culturally appropriate tool for assessing physical function in limb sarcoma patients. Further validation across diverse Latin American populations is encouraged to strengthen its broad applicability., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Oscar Ceballos et al.)

A wide spectrum of tumors may affect the periungual spaces of the digits. Superficial acral fibromyxoma (SAF) is a rare, benign soft tissue tumor with diverse clinical presentations. We present a case of a 55-year-old woman with a 2-year history of a solitary periungual tumor on the left thumb, subjected to multiple episodes of trauma. Initially suspected to be a periungual squamous cell carcinoma (SCC) based on clinical and dermoscopic features, the tumor was confirmed to be a CD34 - SAF through histopathology and immunohistochemistry. Although CD34 immunoreactivity is common in SAF, one-third of these tumors, including this case, do not stain for this marker. Periungual SCC considered a "great mimicker of nail tumors," may resemble other benign nail tumors such as SAF. The patient underwent complete surgical excision with primary closure, resulting in no recurrence after 1 year. This case highlights SAF as an underrecognized benign entity that may manifest with features suspicious of malignancy, potentially leading to unnecessarily aggressive interventions. Recognizing SAF through accurate biopsy techniques and thorough histopathologic evaluation, even in the absence of CD34 reactivity, is crucial for appropriate treatment and preservation of hand function and appearance., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)