Search

Based on their distinctive histologic and genetic features, the latest WHO classification of soft tissue tumors includes four pathologic variants of rhabdomyosarcoma (RMS): embryonal (ERMS), alveolar (ARMS), spindle cell-sclerosing (SRMS-ScRMS) and pleomorphic RMS. The aim of this study focused on a detailed clinicopathologic and survival analysis of head and neck RMS (HNRMS) using the latest pathologic and molecular criteria reflecting this new subclassification in a large cohort.Patients managed for HNRMS in our institution (1996-2015) were analyzed. The presence of a FOXO1 fusion was required for the classification of ARMS. MYOD1 mutations in SRMS-ScRMS were tested when material available. Univariate and multivariate analyses were performed to evaluate variables related to overall survival (OS).Ninety-nine HNRMS patients (52 males and 47 females, mean of 16years) were included in the study after pathologic re-review. The most common location was parameningeal (PM) (n=64), followed by non-orbital/non-PM (n=25) and orbital (n=10). There were 53 ERMS, 33 fusion-positive ARMS and 13 SRMS-ScRMS [SRMS (8); ScRMS (5)]. The 5-year OS rate for ERMS patients was significantly higher (82%) compared to ARMS (53%) and SRMS-ScRMS (50%) [SRMS (75%); ScRMS (30%)]. Univariate analysis showed that survival was dependent on histology (P=0.012), tumor size5cm (P0.001), regional lymph node involvement (P=0.002), metastasis at initial presentation (P0.001), stage (P0.001), and recurrence (P=0.002). Multivariate analysis confirmed histologic subtype to be significant (P=0.043).Our findings reinforce that HNRMS is a heterogenous disease with ARMS and SRMS-ScRMS having an equally unfavorable outcome.

Osteoradionecrosis (ORN) remains an unintended debilitating complication of radiation therapy despite the advent of intensity-modulated radiation therapy (IMRT) which aims to deliver doses of radiation to the tumor site while minimizing doses to healthy tissues [[1], [2], [3], [4]. The etiopathogenesis of ORN has been attributed to the avascular effect of radiation to the bone resulting in hypoxia, hypovascularity, and hypocellularity [5], [6]. Radiation-induced fibrosis has also been implicated in the pathophysiology of ORN [7. Recent studies have placed reported incidences of ORN at 1–30% [2], [8], [9], [10], [11]. ORN of the jaw was defined as an area of exposed necrotic bone greater than 1 cm in an area of previous irradiation that failed to heal after 6 months [5]. This definition of ORN has been used for years and still remains the most widely used clinical criterion for the diagnosis of ORN though it fails to incorporate cases with radiologic evidence of necrosis with intact mucosa [5], [12], [13], [14], [15]. Although a report by Van Merkesteyn et al. described a case of ORN of the jaw with intact mucosa [16], subsequently only two series have likewise reported this condition. In 2000, Store and Boysen reported 17 patients with radiographic osteoradionecrosis of the jaw (rORN) with intact mucosa at initial diagnosis as did He et al. in a recent article where they described 16 patients presenting with rORN with intact mucosa [17], [18]Thus, it appears that rORN with intact mucosa is underdiagnosed. The objectives of this article are to: 1. Describe new cases of rORN with intact mucosa. 2. Correlate the dosimetric analyses of the involved area with the radiographic presentation and to determine the best predictor of rORN with intact mucosa. 3. Propose modification of Store and Boysen’s staging system of ORN. 4. Propose clinical guidelines for early identification of rORN with intact mucosa.

ObjectiveTo determine clinicopathologic factors on survival in patients with head and neck synovial sarcoma.Patients and methodsWe retrospectively identified patients with molecularly confirmed synovial sarcomas of the head and neck (SS-HN), either by the presence of SS18-SSX fusion transcript by RT-PCR or SS18 gene rearrangement by FISH, who were managed at our institution over a 20-year period (1996-2015). Kaplan-Meier survival analysis and log-rank test were performed to evaluate variables related to disease specific survival (DSS). Fisher exact test was performed to evaluate variables related to local recurrence.ResultsThirty-four patients (20 males and 14 females, mean of 31years) with SS18-SSX fusion-positive SS-HN were identified. The parapharyngeal region of the neck was the most common site. The mean tumor size was 4.8cm (0.8-10cm). Two-thirds (n=23) of cases had a monophasic histology. The 2, 5 and 10-year DSS rates were 97%, 79% and 68%. The 5-year DSS rates for the adult/pediatric cohort were 74%/88%. Recurrence showed significant effect on DSS (p=0.021). There was no significant effect on DSS with age, therapy modality, tumor site, surgical margin, tumor size (⩽5cm vs. >5cm) and histopathologic subtype. Tumor site (i.e. skull base/paranasal sinus region) was associated with local recurrence (p=0.003).ConclusionIn our cohort DSS rate was associated with recurrence. Tumors located in the skull base/paranasal sinus region were associated with a higher rate of local recurrence. Thus appropriate selection of high risk patients who can benefit from multimodality therapies might improve survival.

A 52-year-old male with history of metastatic melanoma of unknown primary, stage IV with metastases to the left iliac region as well as pancreatic head was diagnosed in early 2014. The metastatic melanoma to the iliac bone presented as a large painful lesion and radiologically as a large lytic lesion. He was treated with palliative radiotherapy, 27 Gy in 3 fractions completed in March 2014 and at about the same time started on Ipilimumab at 3 mg/kg intravenous (230 mg) every 3 weeks for a total of 4 doses, the last one in May 2014. Six days following the second dose of Ipilimumab, the patient presented with a gingival swelling on the lingual aspect of the right mandible. On examination, there was a swelling of the lingual gingiva adjacent to the right mandibular molars, localized bleeding on probing, mild discomfort, and a small amount of purulent discharge was expressed from the gingival sulcus on palpation (Fig. 1A). Panoramic and periapical radiographs showed no obvious radiopaque or radiolucent lesions. The area was irrigated with 0.12% chlorhexidine. He was advised to irrigate the area 3 times per day with chlorhexidine. One week later, he presented for a follow-up, at which time he said “it doesn't feel better”. On examination, the swelling had progressed, a fistula was noted from the lingual area of the right mandibular second molar to the mylohyoid space, and on palpation purulence was expressed from the fistula with slight discomfort. Nevertheless, the patient had excellent oral hygiene. He was prescribed Augmentin 875 mg bid for 7 days. A month later, he presented with a complaint of “my other doctor thought he saw some exposed bone in the area that we have been watching”. He stated that it was asymptomatic; however his tongue noticed something rough. On examination, there was a 2 × 2 mm exposed necrotic-appearing bone on the lingual aspect of the right mandibular second molar (Fig. 1B), there was slight purulence on palpation and the bone was mobile but no tenderness or sensitivity on manipulation. The patient was instructed to continue with the chlorhexidine rinse. In 3 weeks, he returned with the complaint of “the bone is moving around now and bothering my tongue”. There was no history of pain from that area. On examination, an area of exposed necrotic bone measuring 10 × 5 mm was present (Fig. 1C); the bone was very mobile and easily removed with cotton forceps with no associated pain or bleeding on removal. The patient was advised to continue the chlorhexidine rinse. The specimen was submitted for histopathologic evaluation (Fig. 1D), which was reported as a non-vital bone (sequestrum) with bacterial colonies consistent with actinomyces species associated with acute inflammatory cells (Fig. 1E). At his 2 month follow-up examination, the area had fully resolved and healed with no purulent discharge or pain on palpation (Fig. 1F). Fig. 1 Clinical picture at initial presentation showing a gingival swelling (A), clinical picture a month later showing a 2 × 2 mm area of exposed bone (B), clinical picture 3 weeks later showing a 10 × 5 mm area of exposed necrotic bone (C), ... The clinical findings of bone exposure of the jaw with histopathologic diagnosis of sequestrum with actinomyces and neutrophils are similar to osteonecrosis of the jaw (ONJ) in patients treated with anti-resorptive or antiangiogenic agents. With no history of radiation therapy to the jaw or metastasis of the tumor to the jaw, this can be termed medication related osteonecrosis of the jaw (MRONJ) [1]. Since 2003, there has been an increase in ONJ cases related to anti-resorptive medications such as Alendronate (oral bisphosphonate), Pamidronate and Zolendronate (intravenous bisphosphonate), Denosumab (humanized monoclonal antibody) and anti-angiogenic medications such as Sunitinib (tyrosine kinase inhibitor) and Bevacizumab (humanized monoclonal antibody), which targets the vascular endothelial growth factor pathway [[2], [3], [4], [5], [6], [7]]. This patient had not used any of the aforementioned class of medications. Ipilimumab was approved by the US Food and Drug Administration in March 2011 as an immunotherapy for the management of advanced (unresectable or metastatic) melanoma both in naive or post-chemotherapy treated patients. Ipilimumab is a humanized monoclonal antibody against cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 is expressed in activated T-cells and in suppressor T-regulatory cells which bind to antigen presenting cells thereby lessening T-cell responses. Blocking the CTLA-4 increases the antitumor responses by activated T-cells. Ipilimumab has demonstrated clinical benefits in the management of melanoma [[8], [9]]. The adverse toxicities of Ipilimumab have been attributed to increased immune-reactivity against normal tissues causing pruritus, diarrhea, vitiligo, hepatitis, and endocrinopathies [10]. Bone necrosis was not reported. We suggest that Ipilimumab may have been involved in the process of bone necrosis in this patient. Ipilimumab increases systemic activated T-cells presence. CTLA4 deficient activated T-cells have been shown to be associated with osteonecrosis, as activated T-cells may elicit osteoclastogenesis via osteoprotegerin ligand resulting in bone loss [11]. Trauma from regular oral activity (chewing or tooth brushing) could increase the demand on this vulnerable bone to mend itself, resulting in localized bone necrosis. To our knowledge, this is the first report of ONJ in a patient treated with Ipilimumab. Thousands of patients have been treated with Ipilimumab. If osteonecrosis is an associated complication, it is probably rare and maybe because patients are treated for a short time. As this is a relatively new medication with great promise for management of melanoma and other advanced-stage malignancy clinicians involved in the care of patients managed with Ipilimumab should be aware of this complication.