Subcutaneous Sarcoma Research Articles

Laser Capture Microdissection of Tertiary Lymphoid Structures from Formalin-Fixed Paraffin-Embedded Sections of Canine Cutaneous and Subcutaneous Sarcomas for NanoString Direct RNA Counting.

Laser capture microdissection (LCM) of formalin-fixed, paraffin-embedded sections is a way to analyze gene expression of morphologically distinct areas of tissue, as microscopically visualized with stained tissue sections. Herein, I describe a method for laser dissecting lymphoid aggregates in canine cutaneous and subcutaneous sarcomas and their adjacent sarcoma tissue to determine the differential expression of RNA as determined by NanoString® nCounter technology. Canine soft tissue sarcomas (STS) are diversely derived mesenchymal neoplasms that, regardless of exact histogenesis, behave similarly and thus have been grouped together as a diagnostic entity. The risk of recurrence and/or metastasis depends on the extent of surgical excision and histologic grade. Lymphoid aggregates are described in these tumors but have not been characterized. In humans, lymphoid aggregates characterized as tertiary lymphoid structures (TLS) improve the prognosis of several tumors, including sarcomas. We sought to determine if RNA expressed by lymphoid aggregates in canine sarcomas was compatible with TLS RNA expression. This chapter describes tissue preparation, staining, laser capture microdissection, and RNA isolation in preparation for digital RNA counting.

Lymphoid Aggregates in Canine Cutaneous and Subcutaneous Sarcomas: Immunohistochemical and Gene Expression Evidence for Tertiary Lymphoid Structures.

Canine cutaneous/subcutaneous soft-tissue sarcomas (STS) are diversely derived mesenchymal neoplasms with a risk of recurrence and/or metastasis depending on the extent of surgical excision and histologic grade. Lymphoid aggregates (LAs) are often described in these tumours but not characterised. In humans, LA characterised as tertiary lymphoid structures (TLSs) improve the prognosis of many tumours, including sarcomas. We sought to determine if LA meeting a size criterion (> 700 cells) in canine sarcomas met the criteria of TLS and the overall prevalence of LA of any size. RNA expression in large LAs versus aggregate-adjacent sarcoma tissue (AAS) was measured in laser capture microdissected tissue and compared to curl-derived RNA from aggregate-free sarcomas and lymph nodes. CD3, CD20, MUM-1 and PNAd expressions were measured using immunohistochemistry. CD20 and CD3 mRNA were more highly expressed in LA versus AAS (13.8 fold, p = 0.0003 and 2.3 fold, p = 0.043). This was supported by the IHC findings. The large LAs were also enriched in chemokine RNA expression characteristic of TLS (CXCR5 5.8 fold, p < 00001, CCL19 3.68 fold, p = 0.0209, CCL21 6.87 fold, p = 0.0209 and CXCL13 2.68 fold, p = 0.0924). Plasma cells and high endothelial venules were identified in LA containing tumours but not in control tissue. Large LAs were present in 12% of tumours, and LA of any size in 30%. We conclude that large LAs in canine STS are consistent with TLS.

Benefits of Collaboration Between the Wound, Ostomy, and Continence Nurse and Orthopedic Surgeon When Treating Skin Defects After Soft Tissue Sarcoma Resection: A Retrospective Case-Control Study.

The purpose of this study was to evaluate the benefits of collaborative management between orthopedic surgery and WOC nurses in patients undergoing resection of subcutaneous sarcomas. Retrospective case-control study. The sample comprised 25 patients who underwent wide resection for soft tissue sarcoma, followed by 2-stage split-thickness skin grafting. Data collection occurred between January 2015 and April 2021 in a university hospital based in Kagoshima, Japan. For comparison, we categorized these patients into 2 groups: intervention group participants were managed by an orthopedic surgeon and a WOC nurse; nonintervention group members were managed without WOC nurse participation. Patient background and treatment-related information was retrospectively collected from medical records and compared between the WOC nurse intervention group and the nonintervention group, including maximum tumor diameter, surgical time, maximum skin defect diameter, length of hospital stay, and time from surgery to complete wound healing. The average length of hospital stay was significantly shorter in the WOC nurse intervention group compared with the nonintervention group (38.3 days, SD = 8.0 vs 47.1 days, SD = 10.2; P = .023). Collaborative wound management with a WOC nurse resulted in a shorter hospital length of stay when compared to traditional management with WOC nurse involvement. Based on these findings, we assert that WOC nurses provide an important bridge between postoperative wound management in patients undergoing resection of subcutaneous sarcomas.

System describing surgical field extension associated with flap reconstruction after resection of a superficial malignant soft tissue tumor.

Flap reconstruction after resection of a superficial malignant soft tissue tumor extends the surgical field and is an indicator for potential recurrence sites. To describe a grading system for surgical field extension of soft tissue sarcomas. Grading system: CD-grading is a description system consisting of C and D values in the surgical field extension, which are related to the compartmental position of the flap beyond the nearby large joint and deeper extension for the pedicle, respectively. C1/D1 are positive values and C0/D0 are negative. With a known location, 1/0 values can be "p" (proximal), "d" (distal), and "b" (in the tumor bed), and the description method is as follows: flap type, CxDx [x = 0, 1, p, d or b]. Four representative patients with subcutaneous sarcomas who underwent reconstruction using fasciocutaneous flaps are presented. The cases involved a distal upper arm (elbow) synovial sarcoma reconstructed using a pedicled latissimus dorsi (pedicled flap: CpDp); a distal upper arm (elbow) pleomorphic rhabdomyosarcoma reconstructed using a transpositional flap from the forearm (transpositional flap: CdD0); an undifferentiated pleomorphic sarcoma in the buttocks reconstructed using a transpositional flap (transpositional flap: C0D0); and a myxofibrosarcoma in the buttocks reconstructed using a propeller flap from the thigh (pedicled flap: CdDd). The reconstruction method is chosen by the surgeon based on size, location, and other tumor characteristics; however, the final surgical field cannot be determined based on preoperative images alone. CD-grading is a description system consisting of C and D values in the surgical field extension that are related to the compartmental position of the flap beyond the nearby large joint and deeper extension for the pedicle, respectively. The CD-grading system gives a new perspective to the flap reconstruction classification. The CD-grading system also provides important information for follow-up imaging of a possible recurrence.

Clinical characteristics of primary cutaneous and subcutaneous Ewing sarcoma.

Given the rarity of cutaneous/subcutaneous Ewing sarcoma, their clinical characteristics remain poorly understood. In this study, we aimed to analyse the clinical characteristics of patients with cutaneous/subcutaneous Ewing sarcoma and review the treatment strategy. We reviewed the clinical data of 154 patients with Ewing sarcoma who were treated at our hospital between 2005 and 2019. Amongst these patients, 21 patients with cutaneous/subcutaneous Ewing sarcoma were analysed. As a basic strategy, patients with localized disease received intensive chemotherapy (vincristine-doxorubicin-cyclophosphamide/ifosfamide-etoposide), followed by definitive surgery with or without radiotherapy. In total, 15 patients underwent pre-diagnostic resection with macroscopic residue (seven patients) or non-macroscopic residue (eight patients) before intensive chemotherapy. The median tumour length of the measurable lesions was 3.2cm, and the ratio of metastasis was significantly lower than the Ewing sarcoma of other anatomical sites (10% vs. 37%, P=0.013). Despite the pre-diagnostic resection, local recurrence after additional resection and/or adjuvant radiotherapy did not occur in any of the patients with localized disease. Overall survival was significantly higher in patients with cutaneous/subcutaneous Ewing sarcoma than in patients with Ewing sarcoma of other anatomical sites (hazard ratio=0.33, P=0.013). The event-free survival rate of cutaneous/subcutaneous Ewing sarcoma was also superior to that of Ewing sarcoma of other anatomical sites (hazard ratio=0.35, P=0.01). Patients with cutaneous/subcutaneous Ewing sarcoma may have better prognosis than those with Ewing sarcoma at other anatomical sites. Although pre-diagnostic resection without appropriate investigations is not recommended, local control may be recovered by using a combination of additional resection, chemotherapy and radiotherapy.

Clinical update on cutaneous and subcutaneous sarcomas.

Cutaneous sarcomas are uncommon cancers that can have a wide range of clinical symptoms and lead to considerable cutaneous as well as systemic morbidity. The objective of this review article is to discuss epidemiology, clinical features, diagnosis, and therapy of different types of cutaneous sarcomas. Literature was screened to retrieve articles from PubMed/Medline and Google Scholar and related websites. Cross-references from the relevant articles were also considered for review. Review articles, clinical studies, systematic reviews, meta-analyses, and relevant information from selected websites were included. Cutaneous sarcomas have a negative effect on the quality of life. In their diagnosis, clinical presentation and histological evaluation are crucial. Complete surgical removal is the solution for more or less all cutaneous and subcutaneous sarcomas. The prognosis for cutaneous sarcomas is generally favorable since they tend to recur locally with distant metastases only on rare occasions. Patients having advanced disease should be treated in the setting of clinical trials if possible; choices include radiation therapy and systemic medicines. The value of innovative immunotherapy cannot be determined decisively at this time due to a paucity of relevant trials. As cutaneous sarcomas are rarely diagnosed based on clinical findings, histology plays an important role in the diagnosis. They have a relatively favorable prognosis if treated properly. Patients should be treated at specialized centres.

RETROSPECTIVE REVIEW OF MORBIDITY AND MORTALITY IN A POPULATION OF CAPTIVE BUDGERIGARS (MELOPSITTACUS UNDULATES).

This retrospective study reviews the diseases associated with morbidity and mortality in 221 budgerigars (Melopsittacus undulates) from a captive population from 2013 to 2019. The study aimed to evaluate the health status of a flock of budgerigars typical of today's zoologic collections. Based on previous literature, it was hypothesized that age-related conditions such as neoplasia would be common, whereas metabolic and nutritional disorders would be less common. Neoplasia was widespread among the population, affecting 34% of birds (75/221). Carcinomas made up most neoplastic processes and most commonly affected the renal system (n = 22), followed by the proventriculus (n = 7). Pituitary, adrenal, and hepatocellular carcinomas were less commonly diagnosed. Sarcomas affected the population less often than carcinomas and were found within the coelom (undifferentiated four cases), within the spleen (three cases), within the kidney (two cases), and one subcutaneous soft tissue sarcoma. There were five cases of multicentric lymphoma found most commonly affecting the spleen and liver. Benign neoplasms affected the pituitary most commonly (nine cases), followed by the reproductive system, with seminomas (seven cases) being most common. Macrorhabdus ornithogaster (MO) was found in 56 cases. The majority (38 cases) were found in conjunction with a range of comorbidities, but several birds experienced MO infections alone, and it was thought to have been the cause of death in these birds (22 cases). In contrast to our hypothesis, disease associated with nutritional or metabolic disorders impacted a substantial portion of the population; hepatic lipidosis (26 cases) was the most common along with obesity (26 cases), followed by atherosclerosis, xanthomas, and gout (8, 7, and 4 cases, respectively). Traumatic lesions were noted in 41 cases and were most commonly characterized by head trauma and cerebral hemorrhage. Toxicity was rare; five total cases caused by a single carbon monoxide event were identified.

Cutaneous and subcutaneous Kaposi's sarcoma lesions treated with electrochemotherapy.

Kaposi's sarcoma (KS) is a locally aggressive mesenchymal tumor that involves the lymphovascular system, with a tendency to become multifocal. Electrochemotherapy (ECT) is considered a valuable treatment option in selected patients with cutaneous and subcutaneous KS lesions. We report a retrospective study that included 14 classic and endemic KS patients that underwent ECT sessions for the treatment of KS cutaneous and subcutaneous lesions at our institution. According to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, our patients had an overall response rate (ORR) of 100% to the ECT treatment. A complete response (CR) was obtained in 92.8% of patients after one or more ECT sessions. Only one patient had a progressive disease (PD). The treatment was well tolerated with a low complication rate, mainly transitory local pain or skin ulceration. ECT represents a locoregional therapy for containment and symptomatic control of classic and endemic KS cutaneous and subcutaneous lesions. Further studies including different subtypes of KS patients should also be performed.

Quantifying Angiogenesis in Feline Cutaneous and Subcutaneous Soft Tissue Sarcomas via Semi-automated Endothelial Cell Detection and Digital Chalkley Counting

Quantifying Angiogenesis in Feline Cutaneous and Subcutaneous Soft Tissue Sarcomas via Semi-automated Endothelial Cell Detection and Digital Chalkley Counting

Acute toxoplasmosis mimicking metastatic lymphadenopathy of sarcoma

Abstract Introduction: Clear cell sarcoma is a rare malignant neoplasm with the potential to metastasize to lymph nodes. We report herein a case of acute toxoplasmosis that mimicked metastatic lymphadenopathy from treated clear cell sarcoma on 18F-fluorodeoxyglucose positron emission tomography/computed tomography. Toxoplasmosis is usually asymptomatic in immunocompetent hosts. Acute acquired toxoplasmosis clinically manifests as lymphadenopathy predominantly involving the cervical nodes. Patient concerns: A 45-year-old woman underwent resection of subcutaneous clear cell sarcoma of the right knee. PET/CT performed four years after surgery revealed multiple sites of lymphadenopathy with avid FDG uptake in the right neck, left axilla, left pulmonary hilum, and right inguinal regions. The patient was afebrile and asymptomatic. Metastases were suspected and excisional biopsy of a left axillary node was performed. Diagnoses: Histopathological examination revealed reactive lymphadenitis, suggesting toxoplasmic infection without evidence of malignancy. Serum levels of toxoplasmic immunoglobulin (Ig)M antibodies were high. Serum IgG antibodies were significantly elevated in six weeks from the PET/CT examination. The patient had a cat at home, which could have represented the source of infection. Interventions: The patient was carefully monitored using regular imaging examinations. Outcomes: FDG accumulations resolved spontaneously on follow-up examination one year later. Conclusion: We report a case in which toxoplasmic lymphadenitis mimicked malignant lymphadenopathy. Lymphadenopathy at a distant site from the primary malignancy with FDG avidity may be due to infectious or inflammatory conditions, creating false-positive results.

Low-Molecular-Weight Poly(ethylenimine) Nanogels Loaded with Ultrasmall Iron Oxide Nanoparticles for T1-Weighted MR Imaging-Guided Gene Therapy of Sarcoma.

Cancer metastasis is still a major obstacle in clinical cancer therapy and a paramount cause of cancer deaths. Designing multifunctional nanoplatforms with an enhanced diagnostic sensitivity and anti-metastasis efficiency against tumors represents a major trend in current cancer management. Herein, we report the preparation of low-molecular-weight poly(ethylenimine) (PEI)-poly(ethylene glycol) (PEG) nanogels (NGs) loaded with transforming growth factor-β1 (TGF-β1) siRNA and ultrasmall iron oxide nanoparticles (Fe3O4 NPs) for gene therapy and T1-weighted magnetic resonance (MR) imaging of tumors and tumor metastasis in a mouse sarcoma model. In this work, ultrasmall Fe3O4 NPs stabilized by sodium citrate were first prepared and then mixed with PEI (800 Da) and PEG (400 Da)-diacrylate as a cross-linker to form Fe3O4/PEI-PEG NGs with an average size of 76.3 nm via an inverse microemulsion method. The developed hybrid NGs display good cytocompatibility and enhanced MR imaging performance (r1 relaxivity = 1.0346 mM-1 s-1). The Fe3O4/PEI-PEG NGs can be further used to compact TGF-β1 siRNA through electrostatic interaction and efficiently deliver siRNA to cancer cells and a tumor model to silence the TGF-β1 gene, which inhibits the growth and invasion of cancer cell in vitro significantly, as well as the growth of a subcutaneous sarcoma tumor model and lung metastasis in vivo. The designed hybrid NG-ultrasmall iron oxide NPs may be extended for the delivery of other drugs or genes for theranostics of different biological systems.

Comorbidity: Chronic neurogenic pain affects malignant growth and changes balance of neurosteroids in brain of rats.

e23516 Background: Sex steroids in the brain regulate neurogenesis and the body's response to stress. Chronic neurogenic pain (CNP) and the tumor growth are stress factors that often accompany each other. The purpose of the study was to analyze levels of sex steroid hormones in white matter of the brain of rats with tumor development in presence of CNP. Methods: The study included white outbred male rats (n = 74). In the main groups, a CNP model was created by bilateral sciatic nerve ligation, and after 45 days, M1 sarcoma was transplanted subcutaneously (n = 11) or into the subclavian vein (n = 11). Two comparison groups (each n = 13) included sham operated animals with M1 sarcoma transplanted subcutaneously or into the subclavian vein. Control groups (each n = 13) included animals with CNP or sham operated rats. Levels of testosterone (T), estrone (E1), estradiol (E2), estriol (E3) and progesterone (P4) were measured by ELISA (Cusabio, China) in the brain tissues obtained on day 21 of the tumor growth. Results: Tumors transplanted subcutaneously with and without CNP grew in 100% of animals. Tumor volumes were 1.5 times (p&lt;0.05) greater in animals with CNP, compared with rats without CNP, while the survival in the groups was similar. Levels of all studied hormones, except for E1, in the brain tissue in subcutaneous sarcoma growth were lower in presence of CNP than without it: T and E3–on average by 1.4 times (p&lt;0.05), E2 and P4–by 3.5 times (p&lt;0.05). In rats with intravenous transplantation of M1, tumor nodes in the lungs were registered only in rats with CNP, and the survival of animals was 36 days shorter (p&lt;0.05) than in rats of the corresponding control group. Such specificity of selective neoplastic growth in the pulmonary tissue was combined with lower cerebral T and E3 levels than in the corresponding control–on average by 1.4 times (p&lt;0.05), E2–by 7.2 times, and higher levels of E1–by 1.3 (p&lt;0.05) and P4–by 2.0 times, compared to animals which did not develop the neoplastic process in the lungs without pain. Conclusions: The presence of CNP stimulates the growth of M1 sarcoma in standard subcutaneous inoculation and allows the development of tumors in the lung in intravenous inoculation. The specificity of malignant growth in presence of CNP is accompanied by changes in the brain levels of neurosteroids in rats.

Correlation between cytologic features and histologic grades in cutaneous and subcutaneous soft tissue sarcomas in dogs-A pilot study.

Currently, canine soft tissue sarcoma (STS) grading is based on histopathology. In humans, several studies have demonstrated concordance between cytologic grading systems for STS and histologic grade. The aim of this study was to correlate several cytologic parameters (smear cellularity, anisokaryosis, nucleolar malignancy score, multinucleation, and the number of mitotic figures per 200 cells) that form part of a human STS cytologic grading system, with histologic grades of canine cutaneous and subcutaneous STS. Three observers (blinded) reviewed the cytologic preparations independently from cases with confirmed histologic diagnoses of STS. A cytologic grading score was assigned for each parameter. Correlations between cytologic grading scores (averaged between observers) and histologic grades were assessed using Spearman's correlation coefficient, with statistical significance defined as P<.05. Twenty-one cases were included in the study (10 Grade I STS, nine Grade II STS, and two Grade III STS). The number of mitotic figures (≥3) per 200 cells was the only parameter that showed a significant but weak, positive correlation with histologic grade (rs =.469; P=.032). No Grade I tumors had ≥3 mitotic figures per 200 cells; however, ≥3 mitotic figures per 200 cells were only observed in 33% of Grade II tumors and 50% (one out of two) of the Grade III tumors. This pilot study suggests that an increased number of mitotic figures seen on cytology might correlate with higher grade STS; however, the sensitivity of this parameter for grading STS appears to be low.

Evaluation of the neoplastic infiltration of the skin overlying canine subcutaneous soft tissue sarcomas: An explorative study.

Studies regarding the neoplastic infiltration of the skin overlying canine subcutaneous soft tissue sarcoma (sSTS) are lacking. In case of the absence of tumor infiltration, there would be the possibility of leaving this unaffected skin in place, thus simplifying surgery. The aim of the study was to investigate whether the skin overlying sSTSs is infiltrated by neoplastic cells. Dogs with sSTSs treated surgically were prospectively enrolled. After excision, the skin was dissected from the tumor along the natural surgical plane of cleavage and histologically evaluated. Twenty-nine dogs with an sSTS were included (22 grade I, 6 grade II, and 1 grade III). The sSTS-overlying skin was not tumor-infiltrated in 14/29 cases (48.3%). A higher frequency of infiltration was observed in higher grade sSTSs (grades II and III, 100%; P=.006); nevertheless, 8/22 grade I sSTSs (36%) also showed cutaneous infiltration. This infiltration involved the dermis of the skin directly in contact with the tumor (multifocal in 11 and diffuse in four cases). Although the cutaneous tumor infiltration is less frequent in grade I sSTSs and a wide excision may still be the safest treatment for any sSTS for a greater possibility of local control, this study opens the possibility to a less aggressive cutaneous excision, but still with a local curative intent, as only the skin directly in contact with the sSTS has been proven to be tumor-infiltrated. Additional studies are warranted to confirm that excision of only this skin may guarantee a complete local control, especially in lower-grade sSTSs.

Prevalence of pulmonary nodules suggestive of metastasis at presentation in dogs with cutaneous or subcutaneous soft tissue sarcoma.

To investigate the prevalence of pulmonary nodules suggestive of metastasis at the time of initial presentation in dogs with cutaneous or subcutaneous soft tissue sarcomas (STSs) and no previous related thoracic diagnostic imaging. 146 client-owned dogs with a cutaneous or subcutaneous STS. Medical records were retrospectively searched to identify dogs with STSs that underwent initial thoracic diagnostic imaging when presented for referral examination between September 2014 and March 2018. Data collected included patient and tumor characteristics. Results were evaluated for dogs grouped on the basis of variables of interest (eg, STS grade, duration, or history). Initial thoracic imaging was performed with CT (131/146 [89.7%]) or radiography (15 [10.3%]). Although the presence or absence of pulmonary nodules suggestive of metastasis on thoracic imaging was uncertain in 9 dogs, it was certain in the remaining 137 dogs, with nodules present in 16 (11.7%) dogs (5/77 [6%] with grade 1 STSs, 2/36 [6%] with grade 2 STSs, and 9/24 [38%] with grade 3 STSs). The odds of such pulmonary nodules being present on initial examination were higher (OR, 10.8 and 3.14, respectively) for dogs with grade 3 STSs (vs grade 1 or 2 STSs) and for dogs with an STS duration > 3 months (versus ≤ 3 months). Results indicated that pulmonary staging was a low-yield diagnostic procedure for dogs with grade 1 or 2 cutaneous or subcutaneous STSs, especially when tumors had been present for ≤ 3 months.

Dual-agent fluorescent labeling of soft-tissue sarcomas improves the contrast based upon targeting both interstitial and cellular components of the tumor milieu.

Current practices for fluorescence-guided cancer surgery utilize a single fluorescent agent, but homogeneous distribution throughout the tumor is difficult to achieve. We hypothesize that administering a perfusion and a molecular-targeted agent at their optimal administration-to-imaging time will improve whole-tumor contrast. Mice bearing subcutaneous xenograft human synovial sarcomas were administered indocyanine green (ICG) (3 mg/kg) or ABY-029 (48.7 μg/kg)-an epidermal growth factor receptor-targeted Affibody molecule-alone or in combination. Fluorescence contrast and signal distribution were compared between treatment groups. Two commercial fluorescence imaging systems were tested for simultaneous imaging of ICG and ABY-029. ABY-029 has a moderate positive correlation with viable tumor (ρ = 0.2 ± 0.4), while ICG demonstrated a strong negative correlation (ρ = -0.6 ± 0.1). The contrast-to-variance ratio was highest in the ABY-029 +ICG (2.5 ± 0.8), compared to animals that received ABY-029 (2.3 ± 0.8) or ICG (2.0 ± 0.5) alone. Moreover, the combination of ABY-029 + ICG minimizes the correlation between viable tumor and fluorescence intensity (ρ = -0.1 ± 0.2) indicating the fluorescence signal distribution is more homogeneous throughout the tumor milieu. Dual-agent imaging utilizing a single channel in a commercial fluorescence-guided imaging system tailored for IRDye 800CW is a promising method to increase tumor contrast in a clinical setting.

Prognostic factors and proposed grading system for cutaneous and subcutaneous soft tissue sarcomas in cats, based on a retrospective study.

The objectives of this study included utilising a large database from a diagnostic laboratory to identify any breed, sex or age predilections for cutaneous and subcutaneous soft tissue sarcomas (STSs), and the most common anatomical locations. The second aim was to obtain clinical outcomes and to assess histological features of those tumours to identify any potentially useful prognostic indicators and propose a grading system. Records from the laboratory were searched for feline submissions received from January 2012 to December 2013 diagnosed with STSs; the breed, age, sex and neuter status of the cat and anatomical location of the tumour were recorded. Clinical outcomes were acquired using a questionnaire to submitting practices, and histological features of tumours from patients with known outcomes were assessed. No sex, neuter status or breed predispositions were found. Most STSs arise in middle-aged and older cats, and the most common anatomical location was the trunk. Forty-seven cases had a known clinical outcome and archived tissues allowing for histological assessment of the tumour. Significant differences in median survival time (MST), mitotic index and histological score were detected between those cats that died of tumour-related disease and those that did not. A novel grading system applied to these tumours produced significant differences in MST between cats with low (MST = 900.5 days), intermediate (MST = 514 days) and high grade tumours (MST = 283 days). This is the first study applying a histological grading system to these common tumours. Local recurrence is often the cause of a poor outcome, with metastatic disease apparently rare. The proposed grading system incorporates features that can be assessed on routine haematoxylin and eosin-stained sections; in this small study, the histological grade of the tumour appears to be associated with survival time.

Progesterone and estrogen receptor expression by canine cutaneous soft tissue sarcomas

ABSTRACT: Canine soft tissue sarcomas (STS) comprise a heterogeneous group of malignancies that share similar histopathological features, a low to moderate recurrence rate and low metastatic potential. In human medicine, the expression of estrogen receptors (ER) and progesterone receptors (PR) in sarcomas has been studied to search for prognostic factors and new treatment targets. Similar studies have yet to be conducted in veterinary medicine. The objective of this study was therefore to investigate by immunohistochemistry (IHC) the ER and PR expression in a series of 80 cutaneous and subcutaneous sarcomas in dogs with histopathological features of peripheral nerve sheath tumor (PNST) and perivascular wall tumor (PWT). All cases were positive for PR and negative for ER. Tumors of high malignancy grade (grade III) exhibited higher PR expression than low-grade tumors (grade I). Tumors with mitotic activity greater than 9 mitotic figures/10 high power fields also exhibited higher PR expression. In addition, there was a positive correlation between cell proliferation (Ki67) and PR expression. Therefore, it is possible that progesterone plays a greater role than estrogen in the pathogenesis of these tumors. Future studies should explore the potential for selective progesterone receptor modulators as therapeutic agents in canine STS, as well as evaluating PR expression as a predictor of prognosis.

Cutaneous Leiomyosarcoma: A SEER Database Analysis.

Cutaneous leiomyosarcoma is a rare dermal neoplasm usually arising from the pilar smooth muscle. It is considered a relatively indolent neoplasm, and there is debate whether designation as sarcoma is appropriate. Owing to some conflicting data in the literature, however, its behavior warrants further clarification. To determine the clinical behavior and demographic and pathologic characteristics of cutaneous leiomyosarcoma. The Surveillance, Epidemiology and End Results database was used to collect data on cutaneous leiomyosarcoma and 2 reference populations: cutaneous angiosarcoma (aggressive) and atypical fibroxanthoma (indolent). Demographic and oncologic characteristics were examined, and overall survivals (OS) and disease-specific survivals were compared. Leiomyosarcoma and atypical fibroxanthoma displayed lower stage (localized: 69.7% and 66.8% respectively), smaller size (<3 cm: 90.5% and 72%), and lower rates of disease-specific mortality (2.9% and 7.8%) compared with angiosarcoma. Patients with leiomyosarcoma had a 5-year disease-specific survival rate of 98% and OS rate of 85%. Cutaneous leiomyosarcoma shows outcomes similar to atypical fibroxanthoma. It is nearly always indolent and should be distinguished from more aggressive cutaneous and subcutaneous sarcomas. Clear communication of the biologic potential may be best achieved using alternate diagnostic terminology such as "atypical intradermal smooth-muscle neoplasm."

Direct Interstitial Treatment of Solid Tumors Using an Injectable Yttrium-90-Polymer Composite.

Purpose: Yttrium-90 (90Y)-polymer composite (radiogel) may be administered directly into cancerous tissues to deliver highly localized beta radiation for therapy. In a dose-escalation study, the authors investigated the feasibility of treating feline and canine soft-tissue sarcomas as a model for nonresectable solid tumors in humans to gain clinical experience and to identify optimal methods for placing the composite uniformly within target tumor tissue.Materials and Methods: Five cats (Washington State University) and three dogs (University of Missouri) were selected for treatment from among veterinary clinic patients presenting with subcutaneous soft-tissue sarcomas. The therapeutic radiogel composite comprised two parts that were combined before therapy: (1) a calibrated activity of highly insoluble 90Y(YPO4) particles in a sterile, phosphate-buffered saline solution and (2) a resorbable hydrogel delivery vehicle containing a dissolved copolymer of poly-(DL-lactic acid-co-glycolic acid) and poly-(ethylene glycol). Sarcomas of anesthetized animals (five cats and three dogs) were injected with the 90Y-radiogel (10%–15% by tumor volume) using a parallel-needle grid pattern with ∼4–5-mm spacings with or without ultrasound guidance. After injection, the composite solution gelled within tumor interstitial spaces to solid phase upon reaching body temperatures to constrain the 90Y activity intratumorally. The animals were then imaged with computed tomography (CT) or positron emission tomography (PET)/CT and placed in radiation isolation for overnight monitoring and follow-up.Results: Gelation of the composite within tumor extracellular spaces confined the 90Y(YPO4) particles in place to deliver a planned radiation absorbed dose (100–320 Gy) to target tissue through complete decay. Response of the tumor tissue to 90Y-radiation therapy postexcision was evaluated by imaging, tumor resection, and histology. Correlation was observed on histopathology between tumor destruction and radiation dose. With uniform placement at high dose, the authors achieved complete remission or stable disease (at 1–2 months posttreatment).Conclusions: This study demonstrated successful injection of 90Y-polymer composite (radiogel) without discernable radiation dose to normal organs or other detrimental side effects. Animal patients recovered quickly from the injection procedure. The better therapeutic responses were observed at mean doses at or above 300 Gy.