Recurrent Soft Tissue Research Articles

Fraternal twins with job's syndrome and immune complex nephritis.

Job's syndrome or autosomal dominant hyperimmunoglobulin E syndrome (Hyper-IgE) is a rare disorder that results from a STAT3 gene mutation, which results in the absence of T-helper 17 (Th17) cells and manifests as a severe immunodeficiency. Affected individuals suffer recurrent soft tissue and pulmonary infections among other manifestations, and the spectrum of the disease is still being characterized. We describe 2 sisters with Job's syndrome each with variable expressivity. However, both patients developed proteinuric kidney disease and had biopsies confirming the presence of immune complex glomerulonephritis with staining for immunoglobulins and complement components. Previous reports link Job's syndrome and the development of systemic lupus erythematosus (SLE), but proliferative immune complex glomerulonephritis has not been described. We speculate that continual internal and external antigen exposure may induce an autoimmune process similar to SLE, which in turn may account for the immune complex disease in the kidney.

Phase II Trial of Dolastatin-10, a Novel Anti-Tubulin Agent, in Metastatic Soft Tissue Sarcomas.

Soft tissue sarcomas are uncommon malignancies with few therapeutic options for recurrent or metastatic disease. Dolastatin-10 (Dol-10) is a pentapeptide anti-microtubule agent that binds to tubulin sites distinct from vinca alkaloids. Based on the novel mechanism of action, limited activity of other anti-microtubular agents, and anti-neoplastic activity in pre-clinical screening of Dol-10, this multi-institutional phase II study was conducted to determine the objective response rate of Dol-10 in recurrent or metastatic soft tissue sarcomas that had not been treated with chemotherapy outside of the adjuvant setting. Dol-10 was given intravenously at a dose of 400 mug/m(2) and repeated every 21 days. Toxicities were assessed using the Common Toxicity Criteria (version 2.0). Radiographic studies and tumor measurements were repeated every two cycles to assess response [Miller AB, et al. Cancer 1981; 47(1): 207]. Dol-10 was associated with hematological toxicity and with some vascular toxicities. There was no significant gastrointestinal, hepatic or renal toxicity. There was one death on study due to respiratory failure. There were no objective responses in 12 patients treated with Dol-10. Based on this phase II trial, further study of Dol-10 on this schedule is not recommended in advanced or metastatic soft tissue sarcomas.

Prognostic factors and surgical tactics in patients with locally recurrent soft tissue sarcomas

The aim of this study was to identify prognostic indicators of survival in patients with locally recurrent soft tissue sarcoma through a long-term follow-up. We retrospectively assessed the relationship between post-recurrence survival (PRS) and potential predictive factors in 135 patients who had experienced local recurrence after surgical treatment. The median follow-up time after initial recurrence was 12.3 years (95% confidence interval [CI]: 10.4-14.2 years). The 5-year estimate of the PRS rate was 53.1% (95% CI: 44.3-61.2%) for the entire series. Synovial sarcoma and fibrosarcoma were associated with a significantly worse post-recurrence outcome compared with other STS histotypes. Patients with negative margins after the final surgery experienced improved survival compared with patients with positive margins (5-year survival: 46.7% [35.2-57.5%] vs. 35.5% [23.4-47.8%]; P=0.01). In a multivariate analysis, the significant prognostic indicators for PRS were histologic grade, tumour site, time to initial recurrence, the number of recurrences and the surgical margin status attained at the last resection. Complete surgical resection with microscopically clear margins is desirable in patients with locally recurrent STS. However, when achieving clear surgical margins will require major functional impairment of the extremity, a radical surgical approach should be carefully weighed out for the patient in each case.

Giant Cell Tumor of Distal Radius Treated by En-Bloc Resection and Reconstruction by Non Vascularized Fibular Graft

Giant cell tumor (GCT) of bone is a benign but locally aggressive tumor with tendency for local recurrence. Here we report a case of giant cell tumor of the right sided distal radius treated by en-bloc resection and reconstruction arthroplasty using autogenous non-vascularized ipsilateral proximal fibular graft. Early radiological union at host-graft junction was achieved at 12 weeks and solid incorporation with callus formation was observed at 20 weeks. Functional range of motion of the wrist was 20 degrees dorsiflexion and 20 degrees palmerflexion. Grip strength was moderate. Soft tissue recurrence and fibulo-carpal subluxation was not observed. Reconstruction arthroplasty of wrist following en-blocresection of GCT of the distal radius with non-vascularized proximal fibular graft was found useful in preserving the movements and functions as well as stability of the wrist.

A retrospective chart review of drug treatment patterns and clinical outcomes among patients with metastatic or recurrent soft tissue sarcoma refractory to one or more prior chemotherapy treatments.

BackgroundLimited clinical data on real-world practice patterns are available for patients with metastatic/relapsed soft tissue sarcomas (STS). The primary objective of this study was to evaluate treatment patterns in patients with metastatic/relapsed STS following failure of prior chemotherapy by examining data collected from 2000 to 2011 from a major tertiary academic cancer center in the United States.MethodsMedical records, including community-based referral records, from a tertiary cancer center for adult patients with metastatic/relapsed STS with confirmed disease progression who commenced second-line treatment between January 1, 2000 and February 4, 2011, and with at least 3 months of follow-up data following second-line treatment initiation, were retrospectively reviewed. Overall survival, time to progression, and clinician-reported tumor response were collected.ResultsA total of 99 patients (leiomyosarcoma, n = 48; synovial cell sarcoma, n = 7; liposarcoma, n = 5; or other histological subtypes, n = 39) received an average of four lines of treatment (maximum of 10). No consistent or dominant regimens were used in each treatment line beyond the second line. Median second-line treatment duration was 4.1 months (95% confidence interval, 3.0–5.0). Overall, 72 of 99 patients (73%) discontinued second-line treatment due to progressive disease. Median progression-free survival from initiation of second-line treatment varied across regimens from 2.0 to 6.6 months (overall median, 5.4 months).ConclusionsWide variations in treatment were evident, with no single standard of care for patients with metastatic/relapsed STS. Most patients discontinued second-line treatment due to progressive disease, often receiving additional systemic therapy with other drugs. These data suggest a high unmet need for more efficacious treatment options and improved data collection to guide practice among patients with relapsed/refractory STS.

Postoperative ultrasonography of the musculoskeletal system.

Ultrasonography of the postoperative musculoskeletal system plays an important role in the Epub ahead of print accurate diagnosis of abnormal lesions in the bone and soft tissues. Ultrasonography is a fast and reliable method with no harmful irradiation for the evaluation of postoperative musculoskeletal complications. In particular, it is not affected by the excessive metal artifacts that appear on computed tomography or magnetic resonance imaging. Another benefit of ultrasonography is its capability to dynamically assess the pathologic movement in joints, muscles, or tendons. This article discusses the frequent applications of musculoskeletal ultrasonography in various postoperative situations including those involving the soft tissues around the metal hardware, arthroplasty, postoperative tendons, recurrent soft tissue tumors, bone unions, and amputation surgery.

Comparison of stereotactic body radiotherapy and conventional external beam radiotherapy in renal cell carcinoma.

434 Background: Renal cell carcinoma (RCC) is considered a radiation-resistant histology, often with poor response to conventionally fractionated external beam radiotherapy (EBRT). We compared outcomes for patients treated with EBRT versus stereotactic body radiotherapy (SBRT) for RCC. Methods: From 2004 and 2012, a total of 89 patients were treated with either EBRT or SBRT and retrospectively reviewed. Patients with locally recurrent RCC, bone or soft tissue RCC metastases, or primary RCC in a solitary kidney were included. 51 patients received EBRT, while 38 patients received SBRT. The median biologically effective dose (BED), assuming an α/β ratio of 10, was 32.6 Gy10 for the EBRT group and 48.0 Gy10 for the SBRT group. Local failure (LC) was defined pathologically or by imaging according to RECIST 1.1 and toxicity reported according to CTCAE v4.0 guidelines. Univariable and multivariable analyses using Cox’s regression model was performed to determine predictors of local control. Results: Median follow up from RT was 9.8 mo (range: <1-73 mo) with EBRT and 19.7 mo (range: <1-61 mo) with SBRT (p=0.26). EBRT patients were younger (p=0.02) and more were M1 (p=0.04), yet other baseline features did not differ significantly. Total RT dose, dose/fraction, and BED10 were significantly higher in the SBRT group (p≤0.002 for each), while number of fractions was significantly fewer (p<0.001). The 1-year LC estimate was 88% (95% CI, 72-96%) with SBRT and 50% (95% CI, 32-65%) with EBRT (p=0.001), with no significant difference in rate of distant recurrences (p=0.37). The 1-year progression free survival (PFS) and overall survival (OS) between the EBRT and SBRT groups were 17% (95% CI, 8-29%) vs. 39% (95% CI, 24-54%) (p=0.06) and 39% (95% CI, 25-52%) vs. 82% (95% CI, 65-91%) (p=0.002), respectively. The use of SBRT was the most important independent factor significantly predictive of local control on multivariable analysis (p=0.001, LLR test; HR=0.29, 95% CI, 0.13-0.61), while neither age nor metastasis at diagnosis was predictive. No drade 3-4 toxicity was observed in either RT group. Conclusions: The data support that SBRT improves local control over standard fractionation schemes. Higher dose per fraction, with a BED in the range of 48 Gy10, is a safe and effective local treatment modality for RCC.

Trabectedin in patients with advanced soft tissue sarcoma: A retrospective national analysis of the French Sarcoma Group

AimThe French Sarcoma Group performed this retrospective analysis of the ‘RetrospectYon’ database with data of patients with recurrent advanced soft tissue sarcoma (STS) treated with trabectedin 1.5mg/m2 as a 24-h infusion every three weeks. MethodsPatients who achieved non-progressive disease after six initial cycles could receive long-term trabectedin treatment until disease progression. ResultsOverall, 885 patients from 25 French centres were included. Patients received a median of four trabectedin cycles (range: 1–28). The objective response rate was 17% (six complete/127 partial responses) and 50% (n=403) of patients had stable disease for a disease control rate of 67%. After a median follow-up of 22.0months, median progression-free survival (PFS) and overall survival (OS) were 4.4 and 12.2months, respectively. After six cycles, 227/304 patients with non-progressive disease received trabectedin until disease progression and obtained a significantly superior median PFS (11.7 versus 7.6months, P<0.003) and OS (24.9 versus 16.9months, P<0.001) compared with those who stopped trabectedin treatment. Deaths and unscheduled hospitalisation attributed to drug-related events occurred in 0.5% and 9.4% of patients, respectively. ConclusionThe results of this real-life study demonstrate that treatment with trabectedin of patients with STS yielded comparable or improved efficacy outcomes versus those observed in clinical trials. A long-term treatment with trabectedin given until disease progression is associated with significantly improved PFS and OS.

Recurrent furunculosis caused by a community-acquired Staphylococcus aureus strain belonging to the USA300 clone.

A 24-year-old female with recurrent skin and soft tissue infections (SSTI) was enrolled as part of a multicenter observational cohort study conducted by a practice-based research network (PBRN) on community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Strains were characterized by pulsed-field gel electrophoresis (PFGE), spa typing, and multilocus sequence typing. MRSA strains were analyzed for SCCmec type and the presence of the Panton-Valentine leukocidin (PVL) and arginine catabolic mobile element (ACME) using PCR. In the first episode, S. aureus was recovered from the wound and inguinal folds; in the second, S. aureus was recovered from a lower abdomen furuncle, inguinal folds, and patellar fold. Molecular typing identified CA-MRSA clone USA300 in all samples as spa-type t008, ST8, SCCmecIVa, and a typical PFGE pattern. The strain carried virulence genes pvl and ACME type I. Five SSTI episodes were documented despite successful resolution by antibiotic treatment, with and without incision and drainage. The source of the USA300 strain remains unknown. The isolate may represent a persistent strain capable of surviving extensive antibiotic pressure or a persistent environmental reservoir may be the source, possibly in the patient's household, from which bacteria were repeatedly introduced into the skin flora with subsequent infections.

Soft tissue recurrent ameloblastomas also show some malignant features: A clinicopathological study of a 15-year database.

BackgroundTo investigate the clinicopathological features of six cases of soft tissue recurrent ameloblastoma and explore the role of increased aggressive biological behavior in the recurrences and treatment of this type of ameloblastomas.Material and Methods In this study, we retrospectively reviewed recurrent ameloblastomas during a 15-year period; six cases were diagnosed as soft tissue recurrent ameloblastoma. The clinical, radiographic, cytological and immunohistochemical records of these six cases were investigated and analyzed.ResultsAll the six soft tissue recurrent ameloblastomas occurred after radical bone resection, and were located in the adjacent soft tissues around the osteotomy regions. In Case 4, the patient developed pulmonary metastasis, extensive skull-base infiltration and cytological malignancy after multiple recurrences and malignant transformation was diagnosed. In the other five cases, although there were no cytological signs are sufficient to justify an ameloblastoma as malignant, some malignant features were observed. In Case 1, the tumor showed moderate atypical hyperplasia and the Ki-67 staining percentage was 40% positive, which are strongly suggestive of potential malignance. In Case 5, the patient developed a second soft tissue recurrence in the parapharyngeal region and later died of tumor-related complications. All the remaining three patients showed cytology atypia of varying degrees and high expression of PCNA or Ki-67, which confirmed active cell proliferation.ConclusionsIncreased aggressiveness is an important factor of soft tissue recurrence. An intraoperative rapid pathological examination and more radical treatment are suggested for these cases. Key words: Ameloblastoma, soft tissue recurrence, aggressive biological behaviour.

Local administration of zoledronic acid for giant cell tumor of bone.

Giant cell tumor of bone is a locally aggressive tumor with a high local recurrence rate. Several adjuvant therapies have been employed to reduce the recurrence rate, but their effectiveness remains controversial. The authors attempted local administration of zoledronic acid, a nitrogen-containing bisphosphonate that strongly inhibits bone resorption, as an adjuvant treatment for histologically proven giant cell tumor of bone in 5 patients at their institution. After biopsy, 4 patients were treated with local administration of zoledronic acid with artificial bone and 1 was treated with zoledronic acid without artificial bone. Histologic response to the treatment was evaluated with surgically resected specimens. The 4 patients treated with artificial bone showed local control, with histologic tumor necrosis rates of 90%, 90%, 50%, and 10%. Magnetic resonance imaging showed poor gadolinium enhancement, and histologic examination after local zoledronic acid treatment showed tumor necrosis. One patient without artificial bone showed no histologic tumor necrosis and had local recurrence in soft tissue 18 months after tumor resection. A 3-week waiting period between biopsy and zoledronic acid treatment appears reasonable from the histological study. Complication of this therapy was delayed wound healing and it occurred in 2 cases. Taken together, this case series suggests that local administration of zoledronic acid with artificial bone is a potential adjuvant therapy for giant cell tumor of bone. On the other hand, effective local administration of zoledronic acid requires some bone matrix, including artificial bone. Campanacci's grading is important for predicting the effect of local administration of zoledronic acid.

Intraoperative Radiotherapy in the Management of Locally Recurrent Extremity Soft Tissue Sarcoma.

Purpose. To investigate the efficacy and morbidity of limb-sparing surgery with intraoperative radiotherapy (IORT) for patients with locally recurrent extremity soft tissue sarcoma (ESTS). Methods and Materials. Twenty-six consecutively treated patients were identified in a single institution retrospective analysis of patients with locally recurrent ESTS treated with IORT following salvage limb-sparing resection from May 2000 to July 2011. Fifteen (58%) patients received external beam radiotherapy (EBRT) prior to recurrence (median dose 63 Gy), while 11 (42%) patients received EBRT following IORT (median dose 52 Gy). The Kaplan-Meier product limit method was used to estimate disease control and survival and subsets were compared using a log rank statistic, Cox's regression model was used to determine independent predictors of disease outcome, and toxicity was reported according to CTCAE v4.0 guidelines. Results. With a median duration of follow-up from surgery and IORT of 34.9 months (range: 4 to 139 mos.), 10 patients developed a local recurrence with 4 subsequently undergoing amputation. The 5-year estimate for local control (LC) was 58% (95% CI: 36–75%), for amputation-free was 81% (95% CI: 57–93%), for metastasis-free control (MFC) was 56% (95% CI: 31–75%), for disease-free survival (DFS) was 35% (95% CI: 17–54%), and for overall survival (OS) was 50% (95% CI: 24–71%). Prior EBRT did not appear to influence disease control (LC, p = 0.74; MFC, p = 0.66) or survival (DFS, p = 0.16; OS, p = 0.58). Grade 3 or higher acute and late toxicities were reported for 6 (23%) and 8 (31%) patients, respectively. The frequency of both acute and late grade 3 or higher toxicities occurred equally between patients who received EBRT prior to or after IORT. Conclusions. IORT in combination with oncologic resection of recurrent ESTS yields good rates of local control and limb-salvage with acceptable morbidity. Within the limitations of small subsets, these data suggest that prior EBRT does not significantly influence disease control or toxicity.

Epiphyseal Sparing and Reconstruction by Frozen Bone Autograft after Malignant Bone Tumor Resection in Children.

Limb salvage surgery has become the standard treatment for malignant primary bone tumors in the extremities. Limb salvage represents a challenge in skeletally immature patients. Several treatment options are available for limb reconstruction after tumor resection in children. We report our results using the technique of epiphyseal sparing and reconstruction with frozen autograft bone in 18 children. The mean follow-up period for the all patients included in this study is 72 ± 26 m. Eight patients remained disease-free, seven patients lived with no evidence of disease, two were alive but with disease, and one patient died of the disease. Five- and ten-year rates of survival were 94.4%. Graft survival at 5 and 10 years was 94.4%. Functional outcome using the Enneking scale was excellent in 17 patients (94.4%) and poor in one patient (5.5%). Complications include 2 nonunions, 2 fractures, 2 deep infections, 1 soft tissue recurrence, and leg length discrepancy in 7 cases. This technique is a good reconstructive choice in a child with a nonosteolytic primary or secondary bone tumor, responsive to chemotherapy, without involvement of the articular cartilage. It is a straight forward, effective, and biological technique, which affords immediate mobilization of joints and possible cryoimmune effects, with excellent long term functional outcome and less complication.

A 35-year old woman with productive cough and breathlessness.

A 35-year-old lady was seen in the outpatient clinic owing to fever, cough with mucopurulent expectoration, and breathlessness for the duration of 1 month. She had history of similar episodes treated with antibiotics four times during last 2 years. There was no history of recurrent sinusitis, diarrhea, and skin or soft tissue infection. She had no history of diabetes mellitus or steroid intake. She denied any history of facial trauma or dental infection in the past. There was no history of tuberculosis in her or in the family. Radiograph and CT scan of the chest revealed right upper lobe consolidation. Flexible fibreoptic bronchoscopy revealed multiple nodules at opening of right upper lobe bronchus. This clinicopathological conference describes the details of differential diagnoses, difficulties in achieving the final diagnosis and management of such patient.

Forequarter Amputation Following Pre-Operative Embolization to Treat Two Upper Extremity Malignancies in a Previously Irradiated Tissue Bed: A Case Report

Forequarter amputations typically involve removing the entire upper extremity, scapula and part of, or the entire clavicle for palliative or curative purposes. Although the first forequarter amputation was performed in 1808 to treat a gunshot wound, currently the majority are performed to treat primary or recurrent soft tissue sarcomas of the proximal humerus or axilla. In the last two decades due to improved chemotherapy and radiotherapy treatments as well as improved surgical technique, there has been an increase in limb preserving surgeries at the expense of radical amputations. However major upper limb amputations remain a necessary treatment for aggressive or recurrent malignancies when limb preserving techniques have been exhausted. Forequarter amputations carry high complication rates including high local and distant recurrence, limb pain and wound complications often due to poor tissue quality, which can result from local radiation treatments. We present the case of a patient with recurrent upper extremity sarcoma and squamous cell carcinoma in a previously irradiated tissue bed that underwent a forequarter amputation with flap reconstruction following pre-operative embolization.

Recidiva de Ameloblastoma para Tecidos Moles após Tratamento Radical

Introduction: Ameloblastomas are locally aggressive jaw tumors with a high propensity for recurrence and believed to originate from remnants of dental lamina or odontogenic epithelium. Radical surgery still remains the first-choice therapy. Case Report: Herein we report the case of a 69-year-old patient admitted to the University Hospital Oswaldo Cruz in Pernambuco, Brazil, exactly eight years after undergoing hemi-mandibulectomy for treatment of a multicystic ameloblastoma. The patient complained of painful, well-delimited swelling measuring about 4 cm in submucosa next to a titanium bone plate that was used for reconstruction. Computed tomographic imaging and incisional biopsy were performed. The lesion was diagnosed as a ameloblastoma. The tumor was resected and histopathological analyses showed predominance of follicular and acanthomatous ameloblastoma within a highly fibrotic area, thus completing the diagnosis of soft-tissue recurrence. Considerations: This report shows the need of monitoring ameloblastomas for a long-term period even after radical treatment. DESCRIPTORS Neoplasm Recurrence Local. Ameloblastoma. Maxillofacial surgery.

Immunohistochemical and HPV-related features of laryngeal adenosquamous carcinoma

BackgroundAdenosquamous carcinoma (ASC) of the head and neck is a rare malignancy characterized by loco-regional and distant aggressiveness. At histology, ASC reveals two distinct, juxtaposed components, squamous cell carcinoma (SCC), and true adenocarcinoma. MethodsThe immunohistochemical expression of AE3, CK19 and CAM5.2, and HPV infection was tested in a case of laryngeal ASC. ResultsThe patient had no regional lymph node metastases, but developed a recurrence in neck soft tissues shortly after primary radical surgery. The laryngeal surgical specimen had the typical morphological features of ASC. The tumor's squamous and glandular components were both strongly and diffusely immunoreactive for AE3 and CK19, whereas CAM5.2 selectively stained only the gland-like part. We found no high- or low-risk HPV DNA (28 genotypes) in the specimens. The patient underwent salvage extended radical neck dissection and received postoperative radio-chemotherapy. At 4-month follow-up control, neck recurrence was found. Palliative chemotherapy was instituted. ConclusionsAn accurate histological and immunohistochemical diagnosis is mandatory to differentiate ASC from conventional SCC. Radical surgical excision is recommended for laryngeal ASC. Adjuvant postoperative therapy is administered in most cases, but there are no widely accepted indications for these treatments.

1598Risk Factors for Recurrent Skin and Soft Tissue Infections in HIV-Infected Patients Over a 5-Year Period

1598Risk Factors for Recurrent Skin and Soft Tissue Infections in HIV-Infected Patients Over a 5-Year Period

PO-0169 An Unusual Case Of Painful Purpura – Gardner-diamond Syndrome

We present the case of a 13 year old girl who presented with spontaneous, recurrent and painful soft tissue swellings affecting her extremities. On several occasions the degree of swelling and pain was enough to consider compartment syndrome. To date she has required ten fasciotomies. On two occasions she has also had haematuria. Baseline biochemical, haematological and radiological investigations were normal with no cause for symptoms identified. Skin biopsy showed no evidence of vasculitis. She underwent further extensive national investigations, including genetic testing for Type 4 Ehlers-Danlos syndrome. No pathological cause for purpura was found. Non-accidental and self inflicted injury were carefully considered, and excluded. Following wide-ranging investigations and on review of her complex presentation she was diagnosed with Gardner-Diamond Syndrome ( psychogenic purpura, autoerythrocyte sensitisation syndrome ). Gardner-Diamond Syndrome is a rare condition characterised by onset of spontaneous ecchymotic and painful lesions. The aetiology is not well understood but emotional stress is felt to be most common trigger for symptoms. Routine coagulation investigations are normal and the diagnosis is made clinically. It is therefore a diagnosis of exclusion. This interesting case highlights a rare cause of painful purpura. A high index of suspicion was necessary to make the diagnosis. Numerous medical treatments have been trialled without any clear benefit. In this case, early administration of DDAVP has been beneficial in decreasing the progression of bruising, although the mechanism remains unclear. Other cases have also reported some improvement in symptoms following psychotherapy once the underlying cause of emotional stress has been identified.

Abstract 4988: Clues for targeted therapies in inflammatory breast cancer (IBC)

Abstract Inflammatory breast cancer (IBC) is the most aggressive type of advanced breast cancer characterized by rapid proliferation, early metastatic development, and poor prognosis. The peculiar clinical presentation of IBC characterized by breast erythema and swelling is caused by the invasion of aggregates of tumor cells (tumor emboli) into the dermal lymphatics, causing an obstruction of the lymph channels. Although, tumor emboli are also occasionally demonstrated in non-IBC tumors, they are more frequently detected and more numerous in IBC. Tumor emboli expressed cell-cell adhesion molecules that maintain the tumor cells together. The high risk of disease recurrence in soft tissue and lymph nodes shortly after completion of multidisciplinary treatment particularly in patients with residual disease supports the hypothesis that these tumor emboli are critically related to the development of micro metastatic disease. We developed a new model of IBC derived from the pleural effusion of a woman with metastatic secondary IBC. FC-IBC02 cells are triple negative and form clusters in suspension that were strongly positive for E-cadherin, β-catenin, and TSPAN24, all adhesion molecules that play an important role in cell migration and invasion. The maintenance of cell-cell adhesions allow the migration of tumor cells through the lymphatic and blood vessels as clusters. FC-IBC02 cells shown a partial or incomplete epithelial-mesenchymal transition (EMT); these cells express some epithelial markers (EpCAM, E-cadherin) and also mesenchymal markers (VIM, FN1, Snai2, Twist1). Furthermore, circulating tumor cells (CTC) from IBC patients are present in the blood as single cells and clusters supporting the collective migration of tumor cells in IBC. FC-IBC02 cells were highly metastatic when injected in the fat mammary pad of SCID mice and these cells were able to produce brain metastasis in mice by intracardiac or intra-peritoneal injections. Genomic studies of FC-IBC02 and other IBC cell lines showed that IBC cells had important amplification of 8q24 where MYC, ATAD2 and the focal adhesion kinase FAK1 are located. MYC and ATAD2 showed between 2.5-7 copies in IBC cells. FAK1, which plays important roles in anoikis resistance and tumor metastasis, showed 6-4 copies in IBC cells. FAK1 is amplified, upregulated and phosphorylated (active) in inflammatory breast cancer. Additionally, FC-IBC02 showed amplification of ALK and NOTCH3. Our results indicate that MYC, ATAD2, CD44, NOTCH3, ALK and/or FAK1 may be used as potential targeted therapies against IBC. We are currently evaluating an ALK/FAK inhibitor using the novel established IBC model. Citation Format: Sandra V. Fernandez, Fredika M. Robertson, Sankar Addya, Zhaomei Mu, Massimo Cristofanilli. Clues for targeted therapies in inflammatory breast cancer (IBC). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4988. doi:10.1158/1538-7445.AM2014-4988