The Armed Forces Institute of Pathology.

European Organization for Research and Treatment of Cancer

Dedifferentiation is a well recognized, if sometimes controversial, form of tumor progression in certain types of soft tissue and bone sarcoma, and confers a worse prognosis when compared with the low-grade counterpart. To date, dedifferentiation has not been described in solitary fibrous tumor (SFT). Among 948 cases of both intrathoracic and extrathoracic SFTs in our files accessioned between 1988 and 2008, we identified 8 cases of conventional SFT with a discrete anaplastic component, which we believe represents dedifferentiation. These occurred in 3 men and 5 women, 40 to 76 years old (median 60 y), and measured 3.4 to 20.0 cm (median 8.5 cm). Two cases were intrathoracic, 2 were located in the deep soft tissue of thigh, and single cases were located in the omentum, scalp, retroperitoneum, and abdominal wall. In addition to typical features of benign-appearing SFT there was an abrupt transition to nondistinctive high-grade sarcoma in all cases. The latter included epithelioid, round cell, and/or spindle cell components with increased mitotic activity, necrosis, and cystic degeneration. By immunohistochemistry, 7 of 8 cases were CD34 positive in the usual SFT areas, whereas 5 showed loss of CD34 in the poorly differentiated component. Six of 7 cases stained for p53 and p16 showed either negative or scattered positive cells in well-differentiated SFT areas, in contrast to positive or stronger and more diffuse staining in the high-grade component. Follow-up information available in 7 patients ranged from 1 to 58 months (mean 24 mo). Three patients with the largest tumors (9.0, 17.0, and 20.0 cm) died of disease, whereas 3 patients whose tumors measured 8.0 cm or less were treated by surgical excision only, and show no evidence of disease but with only limited follow-up. One patient with an 11.5 cm intrathoracic tumor is alive with disease at 58 months after recurrence and metastasis. We describe, apparently for the first time, what seems, at least in our view, to be dedifferentiation in primary SFT. Our results demonstrate that dedifferentiation in SFT, comparable with that in other low grade/intermediate soft-tissue tumors, poses a higher risk of tumor recurrence and/or metastasis, most notably in large and deep-seated tumors. Similar to other dedifferentiated sarcomas, abrupt transition between low grade and high-grade areas is typically observed with loss of CD34 positivity. The p53 and p16 overexpression in the high-grade component is common as in other dedifferentiated lesions, perhaps pertaining to the underlying molecular mechanism.

Expanding the spectrum of malignant progression in solitary fibrous tumors: a study of 8 cases with a discrete anaplastic component--is this dedifferentiated SFT?

Importance Dual blockade of programmed death ligand 1 (PD-L1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) may overcome immune checkpoint inhibition. It is unknown whether dual blockade can potentiate antitumor activity without compromising safety in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) and low or no PD-L1 tumor cell expression. Objective To assess safety and objective response rate of durvalumab combined with tremelimumab. Design, Setting, and Participants The CONDOR study was a phase 2, randomized, open-label study of Durvalumab, Tremelimumab, and Durvalumab in Combination With Tremelimumab in Patients With R/M HNSCC. Eligibility criteria included PD-L1–low/negative disease that had progressed after 1 platinum-containing regimen in the R/M setting. Patients were randomized (N = 267) from April 15, 2015, to March 16, 2016, at 127 sites in North America, Europe, and Asia Pacific. Interventions Durvalumab (20 mg/kg every 4 weeks) + tremelimumab (1 mg/kg every 4 weeks) for 4 cycles, followed by durvalumab (10 mg/kg every 2 weeks), or durvalumab (10 mg/kg every 2 weeks) monotherapy, or tremelimumab (10 mg/kg every 4 weeks for 7 doses then every 12 weeks for 2 doses) monotherapy. Main Outcomes and Measures Safety and tolerability and efficacy measured by objective response rate. Results Among the 267 patients (220 men [82.4%]), median age (range) of patients was 61.0 (23-82) years. Grade 3/4 treatment-related adverse events occurred in 21 patients (15.8%) treated with durvalumab + tremelimumab, 8 (12.3%) treated with durvalumab, and 11 (16.9%) treated with tremelimumab. Grade 3/4 immune-mediated adverse events occurred in 8 patients (6.0%) in the combination arm only. Objective response rate (95% CI) was 7.8% (3.78%-13.79%) in the combination arm (n = 129), 9.2% (3.46%-19.02%) for durvalumab monotherapy (n = 65), and 1.6% (0.04%-8.53%) for tremelimumab monotherapy (n = 63); median overall survival (95% CI) for all patients treated was 7.6 (4.9-10.6), 6.0 (4.0-11.3), and 5.5 (3.9-7.0) months, respectively. Conclusions and Relevance In patients with R/M HNSCC and low or no PD-L1 tumor cell expression, all 3 regimens exhibited a manageable toxicity profile. Durvalumab and durvalumab + tremelimumab resulted in clinical benefit, with minimal observed difference between the two. A phase 3 study is under way. Trial Registration clinicaltrials.gov Identifier:NCT02319044

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Safety and Efficacy of Durvalumab With or Without Tremelimumab in Patients With PD-L1-Low/Negative Recurrent or Metastatic HNSCC: The Phase 2 CONDOR Randomized Clinical Trial.

Purpose Concurrent chemoradiotherapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN) increases both local tumor control and toxicity. This study evaluates clinical factors that are associated with and might predict severe late toxicity after CCRT. Methods Patients were analyzed from a subset of three previously reported Radiation Therapy Oncology Group (RTOG) trials of CCRT for locally advanced SCCHN (RTOG 91-11, 97-03, and 99-14). Severe late toxicity was defined in this secondary analysis as chronic grade 3 to 4 pharyngeal/laryngeal toxicity (RTOG/European Organisation for the Research and Treatment of Cancer late toxicity scoring system) and/or requirement for a feeding tube ≥ 2 years after registration and/or potential treatment-related death (eg, pneumonia) within 3 years. Case-control analysis was performed, with a multivariable logistic regression model that included pretreatment and treatment potential factors. Results A total of 230 patients were assessable for this analysis: 99 p...

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Factors Associated with Severe Late Toxicity After Concurrent Chemoradiation for Locally Advanced Head and Neck Cancer: An RTOG Analysis

Paracoccidioidomycosis is a fungal infection endemic to South American countries that affects the lungs, skin, and mucosae. Reports from Japan are limited by a long-term resident in South America. Some cases are incorrectly diagnosed because of a refractory buccal ulcer that resembles a malignant tumor. This is a disease that may not be correctly examined if we cannot suspect by a case history. We report the case of a Brazilian man who had a buccal ulcer with lung involvement, which mimicked pharyngeal cancer.

Case of oral paracoccidioidomycosis suspected to be pharyngeal cancer

Objective: The prognosis of patients with locally advanced squamous cell carcinoma (SCC) of the tongue is poor. Postoperative chemoradiotherapy (CRT) improves locoregional control and survival in high-risk patients. We investigated the prognostic factors for clinical T4a tongue SCC, and elucidated whether postoperative CRT has a benefit for patients with poor prognosis in terms of survival. Methods: We performed a retrospective analysis of 61 patients with stage T4a SCC of the tongue who underwent primary resection and neck dissection. Results: The median follow-up was 53.8 months. Multivariate analysis revealed a 4.26× relative risk of death for patients with the involvement of ≥5 regional lymph nodes (pN ≥5) compared with those with pN 0-4 (p = 0.002). In Kaplan-Meier analysis, patients with pN ≥5 who received CRT had longer overall survival rates than those who did not (hazard ratio = 0.31; p = 0.041). Conclusions: pN ≥5 is the most powerful prognostic factor for clinical T4a SCC of the tongue. Postoperative CRT is recommended in patients with pN ≥5.

Prognostic Factors and Multidisciplinary Postoperative Chemoradiotherapy for Clinical T4a Tongue Cancer

Squamous cell carcinoma (SCC) with rhabdoid features (SCCRF) is extremely rare in the oral cavity. We report herein a case of oral SCCRF. The patient was a 69-year-old Japanese woman who had been suffering from a mass in the right lower gingiva. Right hemi-mandibulectomy was performed. The gingival tumor was composed of pleomorphic, non-cohesive ovoid tumor cells with abundant cytoplasm and eccentric nuclei, which were positive for both pan-cytokeratin and vimentin. In another portion, moderately differentiated SCC and carcinoma in situ were also seen. A transition zone existed between the components. Finally, we diagnosed SCCRF. Four months after the operation, multiple bone metastases, lung and skin metastases and marked hypercalcemia were found. SCCRF, therefore, might be more aggressive than the usual type of oral SCC.

Squamous cell carcinoma with rhabdoid features of the gingiva: a case report with unusual histology

The 320-row multidetector computed tomography (MDCT) is now used by both cardiologists and neurosurgeons. It enables dynamic 3D-CT angiography, because the wide-area detector eliminates helical scanning, thus achieving very fast scanning times for single 3D-CT volume data. Some microvascular surgeons are familiar with 64-row MDCT for perforator studies, but there are few reports of studies using 320-row MDCT. This MDCT system was used to follow the dynamic blood flow of small vessels. It is considered to have a great potential in the clinical field of microvascular surgery.

Clinical application of 320-row multidetector computed tomography for a dynamic three-dimensional vascular study: imaging findings and initial experience

国立がんセンター頭頸科においては, 近年舌癌に対して手術を主体とした治療を施行してきた。今回その治療成績を検討し今後の治療に還元することを目的とし研究を行った。対象症例は1988年から1995年の間に一次治療を施行した舌扁平上皮癌241例とした。その結果5年累積生存率は66.8%ステージI, II, III, IVでは88.7%, 75.5%, 54.6%, 34.4%であった。5年累積局所制御率は81.6%であった。また頸部リンパ節再発は29.5%に認めた。舌深部の完全なる切除が局所制御率および生存率の向上につながると考えた。そして頸部郭清範囲, 病理組織学的転移部位および再発部位の検討を次なる課題と考えた。

Yoshiyuki Iida

Papers

Case of oral paracoccidioidomycosis suspected to be pharyngeal cancer

Prognostic Factors and Multidisciplinary Postoperative Chemoradiotherapy for Clinical T4a Tongue Cancer

Squamous cell carcinoma with rhabdoid features of the gingiva: a case report with unusual histology

Clinical application of 320-row multidetector computed tomography for a dynamic three-dimensional vascular study: imaging findings and initial experience

Result of surgical treatment for carcinoma of the tongue