Pleomorphic Spindle Cell Sarcoma Research Articles

Neutrophil-to-lymphocyte ratio for the prediction of soft tissue sarcomas response to pre-operative radiation therapy

Purpose/ObjectiveThis study aims to assess the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in soft tissue sarcomas (STS) treated with pre-operative hypofractionated radiotherapy (HFRT). Materials/MethodsThis retrospective analysis included patients treated with pre-operative HFRT of 30 Gy in 5 fractions between 2016 and 2023. Clinical, demographic, and complete blood count (CBC) data were collected. NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. Only patients with CBCs conducted within 6 months after radiotherapy were included. Cox proportional-hazard regression models were used to assess the impact of NLR and different variables on outcomes. Kaplan Meier were used to illustrate survival curves. A p-value < 0.05 was considered significant, and 95 % confidence intervals (CI) were employed. ResultsA total of 40 patients received HFRT and had CBCs within 6 months after radiotherapy. There were 17 (42.5 %) females and 23 (57.5 %) males with a mean age of 66 years. The mean largest tumor size dimension was 7.1 cm, and the mean NLR post-RT was 5.3. The most frequent histological subtypes were myxofibrosarcoma (17.5 %), pleomorphic spindle cell sarcoma (10 %), leiomyosarcoma (7.5 %), and myxoid liposarcoma (5 %). The median follow-up period was 15.4 months. From all patients, 14 patients had disease progression, 12 metastatic disease and 3 died of disease. Multivariable Cox proportional-hazards regression analysis displayed that a higher post-RT NLR was associated with worse disease-free survival (DFS) (HR: 1.303 [1.098–1.548], p = 0.003), and distant metastasis-free survival (DMFS) (HR: 1.38 [1.115–1.710], p = 0.003). Moreover, post-NLR ≥ 4 as a single variable was associated with worse DFS, DMFS, but not worse local recurrence or overall survival. ConclusionThis study is the first to evaluate NLR as a prognostic biomarker in STS patients treated with pre-operative radiotherapy. A higher NLR after pre-operative radiotherapy was associated with increased disease progression.

Post-Hypofractionated Radiotherapy Neutrophil-to-Lymphocyte Ratio in Soft Tissue Sarcomas is a Prognostic Biomarker of Recurrence and Distant Metastases

The neutrophil-to-lymphocyte ratio (NLR) is a measure of systemic inflammation, and known to be prognostic of outcomes and treatment response across different cancer types, including soft tissue sarcomas (STS). Our study aims to determine if in patients with STS treated with pre-operative hypofractionated radiotherapy (HFRT), post-RT NLR is prognostic of recurrence, metastasis, and overall survival. We performed a single-center retrospective analysis of patients treated pre-operatively with 30 Gy in 5 fractions between 2016 and 2023. Clinical, demographic, radiation therapy (RT), and complete blood count (CBC) data were collected from medical records. The NLR calculation was performed by dividing the absolute neutrophils count by the absolute lymphocytes count. We dichotomized the variable into NLR ≤4 and >4. The CBC utilized to calculate NLR was only used if done <6 months post-RT. For post-RT NLR outcomes associations, we used univariable and multivariable logistic regression analyses adjusting for age, gender, tumor size, and histology. For continuous variables we used mean ± standard deviation. Analyses were done with SPSS. A p-value <0.05 was considered significant. We identified 40 patients that received HFRT and had a CBC within 6 months after RT. The mean age was 66 ± 17.5 years. There were 17 (42.5%) females and 23 (57.5%) males. The histologies were myxofibrosarcoma (17.5%), leiomyosarcoma (7.5%), pleomorphic spindle cell sarcoma (10%), myxoid liposarcoma (5%). Other histologies with n<2 accounted for 65%. The mean tumor size was 7.1cm (± 6.4) and the mean NLR 5.3 ± 0.6. The median follow-up was 15.4 ±2.2 months. The patients with recurrence and metastases were the same {n = 13 (32.5%)}, and 3 patients died of disease. Univariable analyses for NLR > 4 showed increased recurrence and metastases (Odds ratio (OR): 8, CI 95% = {1.48 - 43.4}, p = 0.016). The multivariable analyses also showed that post-RT NLR > 4, was associated with increased recurrence and metastases (OR: 7.73, CI 95% = {1.17- 50.9}, p- value = 0.034). Age, gender, histology, and tumor size were not significant variables (Table 1). In both univariable and multivariable analyses NLR > 4 was not associated with decreased overall survival (p = 0.998). To our knowledge, this is the first study assessing the immune response using neutrophil-to-lymphocyte ratio as a prognostic biomarker in STS treated with pre-operative hypofractionated radiotherapy. In this population, an NLR > 4 was prognostic for recurrence and distant metastasis, but not for overall survival. This study highlights the need for a better understanding of the immuno-biological effects of RT, which should be further addressed in the context of clinical trials due to its simplicity and potential prognostic value.

Hypofractionated Preoperative Radiotherapy 30Gy in Five Fractions for Soft Tissue Sarcoma of the Extremity

Hypofractionated preoperative radiotherapy (HypoRT) is being used with increasing frequency for soft tissue sarcomas (STS) of the extremities. Besides the social and economic advantages, HypoRT has a theoretical advantage in STS because of their low α/β ratio. The objective of this study is to review our experience using HypoRT to a dose of 30Gy in 5 fractions in STS of the extremities. This study is a retrospective review of patients with extremity STS treated at our center with preoperative HypoRT to a dose of 30Gy in 5 fractions given on alternate days over 2 weeks. Inclusion criteria were age ≥18 years, biopsy-proven primary STS in an extremity, and fitness for surgery. The primary endpoint was major wound complications (MWC) defined as the need for wound management or secondary operation under general or regional anesthesia within 120 days from surgery. Secondary objectives were: early toxicity grade ≥ 2 and clinical outcomes, including local control (LC), and metastasis-free survival (MFS). Descriptive statistics were used to evaluate patient and treatment characteristics. The Kaplan-Meier method was used to estimate survival. A total of 40 patients received preoperative HypoRT at our center between 2016 and 2022. The median age was 70 years (30 - 91). Males accounted for 57.5% of the patients. The most common primary site was the lower extremity (62.5%). The most prevalent histologic type was myxofibrosarcoma (27.5%), followed by pleomorphic spindle cell sarcoma (20%). All patients were treated with image-guided intensity modulated radiotherapy with margins for the CTV as tested in the RTOG 0630 study. Median follow-up was 14.8 months (5 - 86). Acute side effects were seen in 80% of the patients, all grade <3. The most common toxicity was dermatitis (37.5%), the second was fatigue (20%), and the third was pain (15%). Surgery was performed in all cases after a median interval from completion of HypoRT of 34 days (16-59). Amputation was performed in one patient with a fungating tumor, HypoRT having been aborted at only 24Gy because of worsening symptoms. On pathologic examination, positive margins were found in four cases (10%). The percentage of necrosis was ≥ 90% in 7 patients and 50%-90% in 10. MWC occurred in 13 patients (32.5%), including 10 who underwent a procedure with anesthesia. Sixteen patients were treated for a wound infection. Only one patient recurred locally. Two-year LC was 91.7%. MFS was 87.4% at 6 months and 60.8% at 2 years. DFS was 84.9% at 6 months and 64.8% at 2 years. The preoperative HypoRT regimen of 30Gy in 5 fractions given on alternate days for extremity STS is safe. Acute toxicity was not different from our previous experience using the conventional regimen of 50Gy in 25 fractions over 5 weeks and the MWC rate was comparable to that reported for the conventional regimen. Local control was excellent.

Anaplastic Kaposi Sarcoma: A Clinicopathologic and Molecular Genetic Analysis

Kaposi sarcoma (KS) is a human herpesvirus 8 (HHV8)-associated vascular proliferation that most often involves the skin. Rarely, KS shows marked nuclear atypia or pleomorphism; such examples are known as “anaplastic” KS. This poorly characterized variant often pursues an aggressive course; little is known of its genetic landscape. This study evaluated the clinicopathologic and genomic features of anaplastic KS. We identified 9 anaplastic KS cases from 7 patients and 8 conventional KS cases, including a matched conventional KS and primary metastasis anaplastic KS pair from a single patient (anaplastic KS diagnosed 9 years after conventional KS). All patients with anaplastic KS were men, aged 51 to 82 years, who had locally aggressive tumors predominantly affecting the soft tissue and bone of the lower extremities (5/7 patients). Four patients were known to be HIV positive (all on antiretrovirals), 2 were HIV negative, and 1 was of unknown HIV status. The tumors showed angiosarcoma-like or pleomorphic spindle cell sarcoma morphology. Plasma cell–rich chronic inflammation and hemosiderin deposition were commonly present. Single-nucleotide polymorphism–based chromosomal microarray analysis showed the anaplastic KS cohort to demonstrate highly recurrent whole chromosome (chr) gains of chr 7, 11, 19, and 21, which primarily affected olfactory and G protein–coupled receptor signaling and losses of chr6_q and chrY. Compared with conventional KS, anaplastic KS cases showed significantly more total copy number alterations and more frequent gains of chr7 and chr11_q13.1 (MARK2, RELA, and ESRRA, including high copy number gain in 1 case). Pathway analysis demonstrated that these gains preferentially affected genes that facilitate cyclin-dependent cell signaling. Furthermore, anaplastic KS cases were phylogenetically distinct from conventional KS cases, including the patient-matched primary metastasis anaplastic KS pair and conventional KS. Our study is the first to demonstrate that a more complex genome and distinct copy number alterations distinguish anaplastic KS from conventional KS. Gains of chr7 and chr11_q13.1 appear central to biological transformation.

The value of re-staging chest CT at first local recurrence of extremity and trunk soft tissue sarcoma

To determine the prevalence of pulmonary metastases on re-staging chest CT at the time of first local recurrence (LR) of trunk or extremity soft tissue sarcoma (STS). Retrospective review of all patients diagnosed with recurrent STS between May 2007 and April 2018. Data collected included patient age and sex, site of primary STS, time to LR, recurrence site, initial tumour grade, recurrent tumour grade, findings of initial staging chest CT, and prevalence of pulmonary metastases on re-staging chest CT. The study included 109 patients (males = 68, females = 41; mean age 56years, range 9-92years). The commonest tumour sub-types were myxofibrosarcoma (27.5%), undifferentiated pleomorphic/spindle cell sarcoma (20.2%), synovial sarcoma (10.1%), and malignant peripheral nerve sheath tumour (10.1%). Initial staging chest CT demonstrated pulmonary metastases in 1 of 77 (1.3%) patients for whom CT was available for review. The mean time to LR was 30.8months (range 3-224months). Pulmonary metastases were diagnosed on re-staging chest CT in 26 of 109 cases (23.9%), being commonest with grade 3 STS (36.1%). Pleomorphic sarcoma (85.7%) and undifferentiated spindle cell sarcoma (33.3%) were the 2 commonest tumour sub-types associated with pulmonary metastases at first LR. Re-staging chest CT at the time of first LR of STS identified a prevalence of 23.9% pulmonary metastases, which supports the need for chest CT at the time of LR in line with the UK guidelines for the management of bone and soft tissue sarcoma. • Pulmonary metastases were diagnosed in 1.3% of soft tissue sarcomas at presentation. • Pulmonary metastases were identified in ~ 24% of patients at first local recurrence of soft tissue sarcoma, most commonly with pleomorphic sarcoma and Trojani grade tumours. • No patient with a low-grade recurrence had pulmonary metastases.

Teaching NeuroImages: Intracranial DICER1 -associated spindle cell sarcoma in a child

An 8-year-old boy presented with a 2-week history of worsening right-sided headache and left-sided jerking movements. Symptoms were associated with vomiting, photophobia, phonophobia, and diplopia but no loss of consciousness. cEEG demonstrated increased voltage on the right but no evidence of seizures. Brain MRI demonstrated a large right frontoparietal mass (figure 1). The pathologic findings were compatible with DICER1 -associated pleomorphic spindle cell sarcoma (figure 2). Recently described, DICER1 mutation predisposes individuals to development of a subgroup of tumors termed “spindle cell sarcoma with rhabdomyosarcoma-like features, DICER1 mutant” although it may present as “primary intracranial sarcoma, DICER1 -mutant.”1,2

Prognostic role of % changes in longest tumor diameter (LTD) in localized high-risk soft tissue sarcoma (STS) treated with neoadjuvant chemotherapy in a randomized clinical trial.

11558 Background: We investigated the prognostic relevance of % change in LTD in patients (pts) with localized high-risk STS treated with neoadjuvant chemotherapy in a phase 3 randomized trial (NCT01710176), aimed at comparing 3 cycles of a neoadjuvant histology-tailored (HT) over 3 cycles of standard anthracycline + ifosfamide chemotherapy (S). Methods: Pts with localized high-risk STS of extremities or trunk wall, and a diagnosis of myxoid liposarcoma, leiomyosarcoma, synovial sarcoma, malignant peripheral nerve sheath tumors, undifferentiated pleomorphic sarcoma were randomly assigned to receive 3 cycles of S or HT. Pts affected by myxofibrosarcoma, pleomorphic liposarcoma, pleomorphic rhabomyosarcoma unclassified spindle cell sarcoma were prospectively registered and treated by S. Change of LTD was assessed comparing baseline dimension with that measured after 3 cycles of S or HT, before surgery. Only pts treated with neodjuvant chemotherapy alone were selected for the analysis. We first investigated Overall Survival (OS) from surgery of the groups identified by “any % reduction”, “no-change” or “increase” in LTD by Kaplan-Meier estimates and log-rank tests. Then we searched for cutoffs able to separate prognosis among pts with a LTD reduction applying the change-point method proposed by Contal - O’Quigley. Results: Of 325 pts who entered the study and evaluable for response, 181 received neoadjuvant chemotherapy alone (92 S and 89 HT group respectively) and were analyzed, while 144 received concurrent chemo-radiotherapy and were excluded. In the whole population, % changes in LTD were significantly associated (log rank p = 0.032) to OS. “Any % reduction in LTD (101/181pts) displayed a better prognosis compared to “no-change” (28/181 pts) or “any % increase” (52/181). The change-point analysis was applied to all, S and HT groups separately; a cutoff of = / &gt; 18.75% decrease in LTD was the optimal predictor of outcome for the S group (p = 0.031), while no size cut-off could be identified for the HT group. Conclusions: In our study, % change in LTD of pts treated with neoadjuvant chemotherapy for localized high-risk STS correlated with OS. However, a % decrease in LTD cut-off able to predict the best outcome could be identified only for pts treated in the S group, while no differences in outcome were found by any % LTD change in the HT group. Interestingly, the LTD cut-off identified in the S group was lower than the one selected to define a response by RECIST ( = / &gt; 18.75% decrease in LTD vs = / &gt; 30%). Clinical trial information: NCT01710176 .

Bilateral Anterior Uveitis in a Northern Saw-whet Owl (Aegolius acadicus) With a Metastatic Pectoral Malignant Mesenchymoma

A captive, adult, male northern saw-whet owl (Aegolius acadicus) was examined for blepharospasm of the left eye. The owl was diagnosed with bilateral anterior uveitis and a corneal ulceration in the left eye. It was treated with oral and topical nonsteroidal anti-inflammatory medications and a topical antibiotic. Multiple recheck examinations and medication adjustments were performed over the next 4 months, at the end of which time the bilateral anterior uveitis was controlled with a topical nonsteroidal anti-inflammatory applied 3 times per week to both eyes. The owl was re-examined 2 months later after 2 suspected neurologic episodes. On physical examination, the owl was quiet and had difficulty standing and ambulating. Five firm multilobular and immobile masses were identified overlying the pectoral muscle and sternum. Fine-needle aspiration from 1 mass revealed neoplastic cells consistent with a sarcoma. The owl was euthanatized. On the basis of results of histopathologic examination, the mass was diagnosed as a pleomorphic spindle cell sarcoma with features of rhabdomyosarcoma, liposarcoma, and osteosarcoma. Numerous tumor cells were immunopositive for myoglobin and desmin, indicating striated muscle origin. Although a metastatic lesion was present in 1 adrenal gland, lesions of inflammation or neoplasia were absent in either eye on histopathologic examination. This report describes an apparent ocular manifestation of systemic disease in an avian species with clinically diagnosed recurrent anterior uveitis.

Malignant Tenosynovial Giant Cell Tumor: The True “Synovial Sarcoma?” A Clinicopathologic, Immunohistochemical, and Molecular Cytogenetic Study of 10 Cases, Supporting Origin from Synoviocytes

We present our experience with ten well-characterized malignant tenosynovial giant cell tumors, including detailed immunohistochemical analysis of all cases and molecular cytogenetic study for CSF1 rearrangement in a subset. Cases occurred in 7 M and 3 F (mean age: 52 years; range: 26–72 years), and involved the ankle/foot (n = 1), finger/toe (n = 3), wrist (n = 1), pelvic region (n = 3), leg (n = 1), and thigh (n = 1). There were eight primary and two secondary malignant tenosynovial giant cell tumors. Histologically, all cases showed definite areas of typical tenosynovial giant cell tumor. The malignant areas varied in appearance. In some cases, isolated malignant-appearing large mononuclear cells with high nuclear grade and mitotic activity were identified within otherwise-typical tenosynovial giant cell tumor, as well as forming larger masses of similar-appearing malignant cells. Occasionally, these nodules of malignant large mononuclear cells showed transition to pleomorphic spindle cell sarcoma, with varying degrees of collagenization and myxoid change. One malignant tenosynovial giant cell tumor was composed of sheets of monotonous large mononuclear cells with high nuclear grade, growing in a hyalinized, osteoid-like matrix, with areas of heterologous osteocartilaginous differentiation. Mitotic activity ranged from 2 to 34 mitoses per 10 HPF (mean 18/10 HPF). Geographic necrosis was observed in four cases. The malignant-appearing large mononuclear cells were consistently positive for clusterin and negative for CD163, CD68, and CD11c. Desmin was positive in a small minority of these cells. Areas in malignant tenosynovial giant cell tumor resembling pleomorphic spindle cell sarcoma or osteo/chondrosarcoma showed loss of clusterin expression. RANKL immunohistochemistry was positive in the large mononuclear cells in eight cases. Two cases showed an unbalanced rearrangement of the CSF1 locus. Follow-up (nine patients; range 0.5–66 months; mean 20 months) showed three patients dead of disease, with three other living patients having lung and lymph node metastases; three patients were disease-free. We conclude that malignant tenosynovial giant cell tumors are highly aggressive sarcomas with significant potential for locally destructive growth, distant metastases, and death from disease. The morphologic and immunohistochemical features of these tumors and the presence of CSF1 rearrangements support origin of malignant tenosynovial giant cell tumor from synoviocytes.

Sarcomatoid Carcinoma of Renal Pelvis Involving Ureter and Renal Parenchyma with Heterologous Osteosarcomatous Differentiation: A Case Report and Review of Literature

Sarcomatoid carcinoma is a highgrade rare malignant tumor with both epithelial and mesenchymal components. Sarcomatoid carcinoma in the upper urinary tract is very rare. We reported here a case of sarcomatoid carcinoma of renal pelvis with osteosarcomatous differentiation, with involvement of the ureter and renal parenchyma in a 68-year-old female. Histologically, predominant pleomorphic spindle cell sarcoma component with osteoid production and urothelial carcinoma component with in situ areas were identified. Immunohistochemical analysis showed vimentin positivity in sarcomatous component and cytokeratin positivity in carcinomatous component.

Recurrent spindle cell sarcoma in pregnancy: a case report

Malignant Fibrous Histiocytoma (MFH) is a soft tissue sarcoma usually involving limbs and retroperitoneum. MFH of the anterior abdominal wall is rare with a high recurrence rate. Though wide surgical excision is the mainstay of treatment, it creates large abdominal wall defects that need reconstruction. The addition of chemotherapy and radiotherapy optimize the chances of survival and cure. We report a case of twice recurrent pleomorphic spindle cell sarcoma of the anterior abdominal wall in pregnancy, with adverse maternal and fetal outcome.

Malignant triton tumor: 2 sporadic cases and review

<h3>Background</h3> Malignant peripheral nerve sheath tumors (MPNST) are rare sarcomas commonly associated with neurofibromatosis. When MPNST coexists with rhabdomyoblasts: these lesions are termed malignant triton tumor (MTT); a subgroup of exceedingly rare, highly aggressive soft tissue tumors. <h3>Methods</h3> Two index cases of MTT. Case #1: An 80-year-old female presented with a right buttock mass. A 28 cm lobulated soft-tissue tumor arising from the sciatic nerve was excised. Case #2: A CT scan of a 27-year-old female with nasal polyps revealed opacification of the left nasal passage and maxillary, ethmoid, and frontal sinuses by a large mass that was excised. A 15-year retrospective surgical pathology review identified 21 cases of MPNST with six (29%) exhibiting transition from a neurofibroma. <h3>Results</h3> Histopathological examination of Cases #1 and #2 revealed the presence of SI00 positive pleomorphic spindle cell sarcoma admixed with plump strap/oval cells with linear striations and intense desmin reactivity on immunohistochemical staining confirming the diagnosis of malignant triton tumor. Both cases were not associated with neurofibromatosis-1. <h3>Conclusions</h3> Sporadic MTT is an extremely uncommon soft tissue tumor. Given the aggressive clinical course of such tumors, early and accurate diagnosis is critical for best patient management as complete tumor resection may improve patient survival.

Abstract No. 342 - Y-90 radioembolization of primary and metastatic soft tissue sarcomas of the liver

Purpose Soft tissue sarcomas (STS) are a group of uncommon neoplasms that are difficult to treat when unresectable. We present our initial data on Y-90 radioembolization (RE) of STS, both primary and metastatic to the liver. Materials and Methods Between November 2006 and June 2012, 11 patients with primary and metastatic STS involving the liver underwent 12 Y-90 RE treatments. Nine of 11 (81.8%) patients had prior unsuccessful treatments to control tumor progression in the liver including systemic chemotherapy, surgery, and locoregional therapies such as bland embolization or RFA. Eleven treatments were with resin and 1 treatment was with glass microspheres. Eight were whole liver treatments, and 4 were single lobar treatments. Sarcomas treated were 4 metastatic leiomyosarcomas (abdominal, retroperitoneal, uterine, and lower extremity in origin), 3 metastatic hemangiopericytomas, 1 metastatic prostatic rhabdomyosarcoma, 1 metastatic pleomorphic spindle cell sarcoma, 1 primary hepatic sarcoma, and 1 primary epithelioid hemangioendothelioma. Clinical and biochemical toxicities were recorded at baseline, 2 weeks, 4 weeks, and every 4 weeks thereafter. Radiographic response was recorded every 3 months. Results The median dose delivered was 1.68 GBq. The most common toxicities encountered were self-limited grade 1 fatigue in 6/11 (54.5%) and grade 1 abdominal pain in 4/11 (36.4%) patients. Follow up imaging was available in 11 cases. Partial (PR) or complete response (CR) was seen in 8/11 (72.7%) and 9/11 (81.8%) patients at 3 and 6 month imaging, respectively, according to mRECIST criteria. CRs were seen in 2 hemangiopericytomas, 1 uterine leiomyosarcoma, and 1 primary hepatic sarcoma. Median overall survival was 261 days with 5 (45.5%) patients surviving 491 days or longer. Two patients died within 50 days of treatment, though hepatic disease was not the cause of death in either patient. Conclusion Y-90 RE of advanced primary or metastatic STS of the liver appears to be a promising treatment option for patients who are poor surgical candidates or refractory to other salvage therapies.

Carcinosarcoma in dermoid cyst of ovary: An extremely rare malignant transformation

We report here a case of carcinosarcoma arising from dermoid cyst of ovary comprising of squamous cell carcinoma and pleomorphic sarcoma with focal myogenic differentiation.A 52-year-old female presented with left lower abdominal pain and a large pelvic mass. Ultrasonography revealed a large left adnexal cystic mass with fluid level and a small solid nodule [Figure 1]. Patient underwent total hysterectomy with bilateral salpingo-oophorectomy. The ovarian tumor was large measuring 18  12 10 cm. It was unilocular cystic mass filled with hair and yellow colored cheesy material. The thickness of cyst wall was 0.5-1.5 cm and a solid area measuring 3 cm in diameter was seen in one pole [Figure 2]. The left ovary appeared normal. The uterus was atrophic with keratinized cervix. Histopathological examination of the cyst wall showed a stratified squamous epithelial lining with focal dysplastic change and transition to infiltrating carcinoma with underlying dermal appendages. Hematoxylin and eosin stained sections from the solid area showed a malignant tumor with two distinct components. One of the components was epithelial showing diffuse squamous differentiation with extensive keratinization [Figure 3]. There was nuclear anaplasia and atypical mitosis. The other component revealed features of pleomorphic spindle cell sarcoma with marked pleomorphism and hyperchromasia, [Figure 3] frequent mitoses and necrosis. The epithelial and mesenchymal components were closely intermixed without well-demarcated boundaries. On immunohistochemistry, the malignant epithelial cells were reactive for high molecular weight keratin [Figure 4a] and P63 protein [Figure 4b] while the pleomorphic spindle cell sarcomatous component showed diffuse positivity for vimentin [Figure 4c] and focally for smooth muscle actin [Figure 4d]. Desmin, S100 protein and CD10 were negative in both components.The present case was a large ovarian cyst with characteristic squamous epithelial lining as described by Arora and Haldane who found adenocarcinoma in combination with sarcoma in dermoid cyst of ovary.

Pleomorphic spindle cell sarcoma (PSCS) formerly known as malignant fibrous histiocytoma (MFH): a complex malignant soft-tissue tumor

A presentation defining the nature, characteristics, causation, treatment and outcome of patients with lesions formerly known as malignant fibrous histiocytoma and now as pleomorphic spindle cell sarcoma is clearly a very difficult subject. Many authors do not believe that the tumor exists and instead describe them as forms of fibrosarcomas, fibromyxoid lesions, dedifferentiated chondrosarcomas or even leiomyosarcomas. The reasons for this confusion are presumably related to the fact that the malignant pleomorphic spindle cell sarcoma does not seem to be a distinct type of lesion with specific histologic and genetic characteristics. Instead, the tumor has at least four separate histologic variations and no specific gene signature and in fact does not seem to be either familial or ethnic in presentation. In view of the fact that the tumor was traditionally the most frequently encountered malignant soft-tissue neoplasm, the world of orthopedic oncology is clearly distressed by the problems that these patients have and is joined by the radiation oncologists and chemotherapists in seeking new solutions.

A Rare Cause of Scapular Pain

A 57-year-old male patient presented to an academic sports and spine clinic with acute scapular pain and what he described as “winging” of the scapula. Three weeks before his presentation, increasingly severe pain began to develop through his left shoulder; it radiated down the upper arm, and he had pain along his left ribcage. At the same time, a significant prominence of his left scapula abruptly developed. He experienced pain when leaning on the area and upon moving the extremity, and he felt weak when lifting objects. He denied numbness or any symptoms in his other extremities. He reported a previous history of chronic neck issues and an electrocution injury involving his cervical region and left arm that resulted in persisting upper back pain radiating down his left arm and intermittent tingling in the ring and long fingers; however, these symptoms were described as distinctly different and far milder than his presenting complaints. He had no other significant medical history other than a 30-pack-year smoking history. Upon examination, the patient appeared well and was in no apparent distress. The left scapular region protruded from the chest wall at rest (Figure 1). Palpation revealed a nontender prominence following the course of the scapula, but palpation of the scapular borders was difficult. Mild tenderness to palpation at the left lateral rib cage adjacent to the lower scapula was noted. His scapula did not wing further with resisted scapular protraction or a wall push-up. He had weak shoulder external rotation and shoulder abduction to a lesser degree with minimal pain. The results of a cervical spine examination and the remainder of the neurologic examination were normal. A workup was completed, including the images provided, magnetic resonance imaging, and computed tomography angiography (Figures 2 and 3, respectively), and open biopsy pathology results confirmed pleomorphic spindle cell sarcoma with evidence of myofibroblastic differentiation, high grade (Figure 4). Soft-tissue sarcomas (STS) are the most frequent sarcomas identified, with an incidence of 10,660 cases reported in the United States in 2009. They most commonly occur in the extremities (60%). At least 50 different histologic subtypes of STS exist; pleomorphic sarcoma (malignant fibrous histiocytoma) is one of the most common, with a predilection for the shoulder/shoulder girdle [1,2]. Surgery is the standard primary treatment for most sarcomas. Limb-sparing surgery is recommended for extremity STS to achieve local tumor control with minimal morbidity [1]. High-grade extremity sarcomas are at high risk for local recurrence and metastasis, and thus many patients are treated with radiation therapy and chemotherapy preoperatively or postoperatively [1,2]. Factors associated with decreased overall survival and local recurrence in patients are tumor characteristics, including stage, grade, size, depth, and anatomic location [3]. In a Mayo clinic study of 248 cases of intermediateor high-grade surgically treated STS of the extremities diagnosed between 1995 and 2008, the 5-year incidence of local recurrence was 4.1% [3]. Patients who had positive surgical margins or margins of less than 2 mm had 5-year survival rates of 47% versus 72% in patients with wide margins [3]. Cases of STS in the infraspinatus muscle itself are rare. Four previous cases of sarcoma located in the infraspinatus muscle were found in a review of the literature. The first case, published in 1897, was in an 8-year-old child who underwent excision of the scapula [4]. A second case published in 1938 described a 17-year-old male patient who underwent surgical excision of the tumor, as well as at least part of the scapula [5]. A more recent publication describes a 28-year-old Japanese woman who underwent surgical excision of the infraspinatus muscle, part of the teres minor and teres major, and near-complete resection of the scapular periosteum [2]. The fourth case was noted in a study of function after a subtotal scapulectomy for bony or soft-tissue tumors among patients presenting to a university musculoskeletal oncology unit

Histology and outcome in localized high-risk soft tissue sarcomas (STS) treated with preoperative chemotherapy (CHT) with or without radiation therapy (RT) within a phase III trial from the Italian Sarcoma Group (ISG) and the Spanish Sarcoma Group (GEIS).

10089 Background: We reported on a phase III trial comparing 3 versus 5 cycles of preoperative CHT in high-grade localized STS of the extremities and trunk wall. We explored to which extent histological subtype was prognostically relevant in such an adjuvant series. Methods: 311 pts were eligible. All received 3 cycles of preoperative Epirubicin + Ifosfamide, followed by surgery. Local RT was administered before or after surgery. 136 pts were randomized to receive 2 more cycles of adjuvant CHT. In 222 (71%) cases, centralized pathological review was performed. Histology was categorized into 4 groups: MFH/undifferentiated pleomorphic sarcoma and spindle cell sarcoma NOS (Group 1 = 125 pts), leiomyosarcoma (Group 2 = 41 pts), synovial sarcoma (Group 3 = 68 pts), other (Group 4 = 77 pts). The influence of histology OS and RFS was retrospectively assessed through a univariate Cox regression model. Besides, responses to the preoperative treatment according to RECIST (78% evaluated pts of those with measurable disease) and CHOI criteria (50% evaluated pts) were retrospectively recorded. Results: Group 1, Group 2 and Group 3 accounted for about 75% of cases. At a median follow-up of 60 months (range = 24-102), the OS probability was 0.76, 0.48, 0.64 and 0.73, and the RFS probability was 0.61, 0.48, 0.59 and 0.65, respectively, for Groups 1, 2, 3, 4. For both OS and RFS, a trend in favour of a better outcome was observed in Group 1. On the contrary, a diagnosis of leiomyosarcoma correlated with both a worse OS (Group 1 vs Group 2: HR 2.88, 95%CI 1.63 – 5.01) and a worse RFS (Group 2 vs Group 1: HR 1.72, 95%CI 1.03-2.88). Leiomyosarcoma was marked by the highest number of PD according to both RECIST and CHOI criteria, and Group 1 had the highest RR, when changes in tumor density were accounted for with CHOI criteria. Conclusions: In this series of localized high-risk limb and trunk wall STS, leiomyosarcoma performed worse than the other types. This may be the product of the combination of natural history and chemosensitivity. At least in part, the latter may correlate with the outcome.

Metastatic Malignant Melanoma of the Small Bowel—Report of Two Cases

We report two cases of malignant melanoma metastasizing to the ileum and jejunum in a 48-year-old female and 62-year-old male, respectively. The female patient was a known case of vaginal melanoma who on follow-up developed pain abdomen 4 years after excision of the primary, whereas the male patient who was initially referred as pleomorphic spindle cell sarcoma of the groin presented with complaints of bleeding per rectum and melena 6 years later. After preliminary investigations both underwent laparotomy and resection of segments of ileum and jejunum with tumor. Histopathological examination with immunohistochemistry showed features suggestive of metastatic malignant melanoma. Metastasis should be suspected in patients with malignant melanoma who develop gastrointestinal symptoms such as abdominal pain, anemia, melena, fatigue, constipation, small bowel obstruction, or perforation. This helps in avoiding a delay in the diagnosis and complications that arise due to metastatic disease. Our first patient with primary vaginal melanoma died of multiple metastases 11 months following surgery for the ileal metastasis while the second patient with jejunal metastasis developed recurrent disease in the small bowel and iliac lymph nodes 10 months after surgery. However, in a patient with isolated gastrointestinal metastasis, diagnosed early, with good general condition surgical management should be encouraged when a complete resection of the disease is feasible as no other treatment option is as good for relief of symptoms and prolongation of life.

Liposarcomas With Mixed Well-differentiated and Pleomorphic Features: A Clinicopathologic Study of 12 Cases

Pleomorphic liposarcoma (PL) is an undifferentiated pleomorphic sarcoma containing pleomorphic lipoblasts. PL almost always arises de novo without an associated low-grade precursor lesion [eg, well-differentiated liposarcoma (WDL)]. We have, however, observed rare cases of PL, which arose in association with WDL and have studied these cases to define their clinicopathologic features and their nosologic relationship to other forms of liposarcoma. Cases were retrieved from our consultation archives and from review of cases treated surgically at Mayo Clinic. Selected tumors were tested for MDM2/CPM amplification by fluorescence in situ hybridization when tumor blocks were available. Twelve tumors were identified, occurring in 7 men and 5 women (mean age 59 y, range: 35-84 y). Sites of origin included the retroperitoneum (7), scrotum (2), buttock (2), and abdominal cavity (1). Tumors consisted predominately of typical WDL, with an "abrupt" transition to pleomorphic spindle cell sarcoma containing pleomorphic lipoblasts. MDM2/CPM amplification was present in 10 of 11 (91%) cases, all of which consisted chiefly of PL in the studied blocks. Follow-up information was available for 7 of 7 patients with a postresection interval of >12 months (range: 14-165 mo, mean 44 mo). Four of these 7 patients are currently alive without disease (mean follow-up duration, 38 mo). Of the remaining 3 patients, 1 died of progressive disease 29 months after diagnosis, 1 suffered lung metastases and local recurrence 60 and 84 months after diagnosis, respectively, and was alive with unresectable disease 165 months after diagnosis, and 1 died 14 months after diagnosis, of unrelated causes. The 5 patients with a postoperative follow-up duration of <12 months are without evidence of disease. We conclude that PL arising in WDL is a rare phenomenon. The presence of MDM2/CPM amplification in the PL component of mixed WDL/PL suggests that a subset of PL may arise through tumor progression of WDL or may represent a "transitional" or partially differentiated step toward classic DL.

Ependymal Tumors With Sarcomatous Change (“Ependymosarcoma”): A Clinicopathologic and Molecular Cytogenetic Study

Gliosarcomas are uncommon primary tumors of the central nervous system defined as exhibiting both glial and sarcomatous components. Sarcomatous change occurring in ependymal tumors is rare. We identified 11 such examples. There were 6 female and 5 male patients (median age, 18 y; range, 2 to 63). The tumors were located in the parieto-occipital (n=2), temporal (n=1), parietal (n=1), frontal (n=1), and occipital lobes (n=1), as well as the lateral ventricles (n=2), insula (n=1), cerebellopontine angle (n=1), and fourth ventricle/cerebellopontine angle (n=1). At presentation, the sarcomatous component was noted in 6 (of 10) cases and the ependymal element was grade III in 7 and grade II in 3 tumors, respectively. The sarcomatous component consisted of a reticulin rich, glial fibrillary acidic protein-negative fibrosarcoma (n=5) or pleomorphic spindle cell sarcoma (n=3), and 2 examples with heterologous elements: osseous and cartilaginous (n=1) and osseous only (n=1). The single case involving the fourth ventricle/left cerebellopontine angle consisted of subependymoma and fibrosarcoma components in roughly equal proportions at presentation. Fluorescence in situ hybridization studies performed with probes targeting the NF2 gene and other members of the protein 4.1 gene family demonstrated similar alterations in the ependymal and sarcomatous components in the cases tested, including polysomies/polyploidy (n=3), gains of 1q (n=3), deletions of 22q (n=2) and 6q (n=1), and monosomy 18 (n=1). There was no evidence of MDM2 or CCND1 amplification in any of the cases tested. On follow-up, 5 patients expired 4 months to 18 years after initial resection and 4 to 11 months after development of the sarcomatous component (mean, 7.6 mo); 1 patient is alive at 5 years with recurrent disease, and 1 is alive without recurrence 12 years after initial gross total resection followed by radiation therapy. Although rare, ependymal neoplasms must be included among the gliomas prone to undergo sarcomatous change and we propose the term "ependymosarcoma" for these tumors.