Cases Of Sinonasal Undifferentiated Carcinoma Research Articles

IDH1/2 Mutations in Sinonasal Undifferentiated Carcinomas : Previously Undescribed IDH2 R172K and R140x Variants.

Sinonasal undifferentiated carcinoma (SNUC) is a rare, poorly defined sinonasal epithelial neoplasm from which several genetically defined entities are emerging. IDH1/2 mutations were recently identified in a subset of SNUC. However, the ideal method for the detection of these mutations remains to be established. Cases diagnosed as SNUC between 2010 and 2020 were retrieved. Immunohistochemistry was performed using IDH1/2 mutant-specific antibody MsMab-1. Quantitative real-time polymerase chain reaction (qPCR) was performed on genomic DNA extracted from formalin-fixed paraffin-embedded tissue using 2 kits to detect IDH1/2 mutations. Sanger sequencing was performed in a subset of cases. Thirty-eight cases of SNUC were identified, 18 of which showed IDH1/2 mutations by qPCR (47.4%). IDH2 R172K and R140x were most frequent, each seen in 6 cases (33.3%). Sanger sequencing identified IDH1/2 mutations in 4 out of 21 cases (19%) and did not detect mutations identified by qPCR in 7 cases. On immunohistochemistry, strong IDH positivity was present in 2 cases (5.3%), 1 of which had IDH2 mutation, while no mutation was detected in the other. Our results demonstrating IDH2 R172K and IDH2 R140x variants are a novel finding in SNUC. Immunohistochemistry and Sanger sequencing have low sensitivity for detection of IDH1/2 mutations, and qPCR-based assays may be utilized, particularly in resource-limited settings where access to sophisticated sequencing techniques are difficult.

A Case of Sinonasal Undifferentiated Carcinoma Sucessfully Responding to Chemoradiotherapy

A Case of Sinonasal Undifferentiated Carcinoma Sucessfully Responding to Chemoradiotherapy

SALL-4 and Beta-Catenin Expression in Sinonasal Teratocarcinosarcoma.

Sinonasal teratocarcinosarcoma (SNTCS) is a rare, aggressive malignancy that displays a heterogeneous combination of malignant blastema-like, epithelial and mesenchymal components. Its exact histogenesis is unknown with hypotheses ranging from true germ cell derivation to origin from pluripotent stem cells. However, despite this tumor's multiphenotypic histology, which includes frequent glandular, squamous, and neuroectodermal differentiation similar to adnexal germ cell tumors, SNTCS appears to have some differences from adnexal teratomas. For example, unlike adnexal teratomas, SNTCS has never been described as a component in a mixed germ cell tumor. Accurate recognition of SNTCS is difficult due to its rarity and histologic overlap with other sinonasal tumors. It is even more problematic on biopsy, since not all elements may be present in small samples. SNTCS can also share similar staining patterns with other neoplasms in the differential diagnosis. A recent study found nuclear β-catenin expression in a single TCS, but this has yet to be confirmed in additional cases. SALL-4, a marker of germ cell tumors, has not been examined. We performed β-catenin and SALL-4 immunohistochemistry on whole sections of 7 SNTCS and 19 other sinonasal neoplasms to assess whether β-catenin and SALL-4 are of utility in establishing a diagnosis of SNTCS. Intensity of expression and percentage of staining was noted for each tumor. For SNTCS, distribution of staining within each histologic component (immature neuroectodermal, epithelial, and mesenchymal) was also documented. Nuclear β-catenin expression was not identified in any SNTCS, with all cases demonstrating membranous expression (6 cases) or cytoplasmic and membranous expression (1 case). SALL-4 immunohistochemistry, however, was relatively sensitive (85.7%) and specific (89.5%) for SNTCS. SALL-4 expression was also identified in one poorly differentiated neuroendocrine carcinoma and one case of sinonasal undifferentiated carcinoma. SALL-4 appears to have utility in distinguishing SNTCS from other high grade sinonasal tumors.

Skin Biopsy in the Diagnosis of a Rare Case of Sinonasal Undifferentiated Carcinoma.

Skin Biopsy in the Diagnosis of a Rare Case of Sinonasal Undifferentiated Carcinoma.

A rare case report of sinonasal undifferentiated carcinoma of paranasal sinuses

<p>Sino nasal malignancies account for only 0.2-0.8% of all malignancies and undifferentiated carcinoma is rare malignant tumour of sinonasal tract, with extremely poor prognosis. We report a case of sinonasal undifferentiated carcinoma which we managed by surgery followed by post-operative radiotherapy with concomitant platinum-based chemotherapy. Although the overall survival is about 20% at 5 years and there are frequent recurrences combined modality treatment is the best management option available at present.</p>

Sinonasal undifferentiated carcinoma: Institutional trend toward induction chemotherapy followed by definitive chemoradiation

Recent reports have investigated the nascent role of induction chemotherapy for sinonasal undifferentiated carcinoma (SNUC). The goal of this study was to ascertain trends in treatment pattern changes for SNUC at a single institution and design a treatment algorithm utilized at our institution. Retrospective chart analysis of 21 cases of SNUC from 2010 to 2018. Of 21 patients in this cohort, 18 (85.7%) presented with T4 disease, 7 (33.3%) presented with nodal disease, and 3 (14.3%) presented with distant metastasis. Since 2016, patients have been managed by induction chemotherapy followed by concurrent chemoradiation. To this point, patients treated with TPF induction chemotherapy followed by concurrent chemoradiation show no evidence of disease; however, the average follow up time is 16.8 months. The multimodality treatment for SNUC continues to evolve, as highlighted by this study, toward increased use of induction chemotherapy followed by chemoradiotherapy.

Loss of SMARCB1 Expression Confers Poor Prognosis to Sinonasal Undifferentiated Carcinoma.

Background Due to the diverse histopathologic features and variable survival rates seen in sinonasal undifferentiated carcinoma (SNUC), it is likely that this diagnostic entity is comprised of a heterogonous group of morphologically undifferentiated tumors. As advancements in molecular testing have led to a better understanding of tumor biology, it has become increasingly evident that SNUC may actually encompass several tumor subtypes with different clinical behavior. As a result, it is also likely that all SNUC patients cannot be treated in the same fashion. Recent investigations have identified loss of the tumor suppressor SMARCB1 (INI1) expression in a subset of undifferentiated sinonasal tumors and extrasinonasal tumors and, studies have suggested that this genetic aberration may be a poor prognostic marker. The objective of this study was to identify differential expression of SMARCB1 in SNUC and to analyze and compare the survival outcomes in SNUC patients with and without SMARCB1 expression. Methods All cases of undifferentiated or poorly differentiated neoplasms of the sinonasal tract treated between 2007 and 2018 at a single tertiary care institution were selected. All cases of SNUC were tested for SMARCB1 status by immunohistochemistry (IHC). Clinical parameters were analyzed using Student's t -test and Fischer's test. Kaplan-Meier methods were used to estimate survival durations, while comparison between both the subgroups was done using the log-rank test. Statistical analysis was performed with the use of SPSS software, Version 25 (IBM, New York, NY, United States). Results Fourteen cases of SNUC were identified. Approximately two-thirds (64%; n = 9) of patients were male and the majority (79%; n = 11) were between fifth to seventh decade. Skull base and orbital invasion were seen in 79% ( n = 11) and 93% ( n = 13) of cases, respectively. Fifty-seven percent of tumors ( n = 8) retained SMARCB1 expression by IHC (SR-SNUC), while the remaining 43% ( n = 6) showed loss of SMARCB1 expression and, thus, were considered as SMARCB1 -deficient (SD-SNUC). Although clinicopathological features and treatment modalities were similar, SD-SNUC showed poorer (OS: p = 0.07; disease free survival [DFS]: p = 0.02) overall survival (OS) and DFS on Kaplan-Meier curves. Additionally, SD-SNUC showed higher recurrence (75 vs. 17%) and mortality (67 vs. 14%) (hazard rate = 8.562; p = 0.05) rates. Both OS (28.82 ± 31.15 vs. 53.24 ± 37.50) and DFS durations (10.62 ± 10.26 vs. 43.79 ± 40.97) were consistently worse for SD-SNUC. Five-year survival probabilities were lower for SD-SNUC (0.33 vs. 0.85). Conclusion SNUC represents a heterogeneous group of undifferentiated sinonasal malignancies. Based on the status of SMARCB1 expression, the two subgroups SD-SNUC and SR-SNUC appear to represent distinct clinical entities, with loss of SMARCB1 expression conferring an overall worse prognosis.

A case report of sinonasal undifferentiated carcinoma in a 60-year-old female in clinical practice

This was a rare case of sinonasal undifferentiated carcinoma (SNUC) in a 60-year-old female who presented with complaints of progressive right cheek swelling, associated headache, nasal obstruction, and mucopurulent nasal discharge. Conventional plane radiograph of the cranial paranasal air sinuses revealed opacification of the right maxillary sinus with erosion of the floor of the orbit. The cranial computed tomographic (CT) scan images revealed opacification of the right maxillary sinus, both ethmoidal sinuses and the entire right and medial half of the left frontal sinus. There was erosion of the floor of the anterior cranial fossa on the right side close to the midline. Furthermore, there was extensive and expansile mixed density mass lesion filling the entire right maxillary sinus, both ethmoidal sinuses, right sphenoidal sinus, frontal sinus, and both nasal cavities with medial displacement and infiltration of the right medial rectus muscle. A radiological assessment of extensive, locally advanced right antronasal mass was made on cranial CT scan. At surgery, a cheesy and friable tumor involving the roof, medial wall, and part of the floor of the maxillary sinus extending into the ethmoidal sinuses was seen with associated mucocele of the frontal sinus. Biopsy, histology, and immunohistochemistry of the mass showed SNUC.

Recurrent IDH2 R172X mutations in sinonasal undifferentiated carcinoma

Sinonasal undifferentiated carcinoma is a rare and aggressive malignancy. Sinonasal undifferentiated carcinoma has long been considered a diagnosis of exclusion; to date, the molecular pathogenetic basis for sinonasal undifferentiated carcinoma is unknown. To identify potential oncogenic drivers in sinonasal undifferentiated carcinoma, targeted next-generation sequencing of 300 cancer-related genes was performed on 11 cases of sinonasal undifferentiated carcinoma. We identified IDH2 R172X mutations in 55% of sinonasal undifferentiated carcinomas including R172S, R172T, and R172M. Multispecific mutant IDH1/2 immunohistochemistry was performed and identified mutant-specific protein expression in all cases with available tissue: 3/3 sinonasal undifferentiated carcinomas with R172 mutations were positive and 4/4 wild-type cases were negative. Review of sequencing data for our institutional head and neck cohorts (n=412) confirmed the absence of IDH-activating mutations in other tumor types. Alterations in the IDH2-wild-type sinonasal undifferentiated carcinomas included SMARCA4 loss-of-function with confirmed loss of immunohistochemical expression, NOTCH1 gain-of-function, and TET2 loss-of-function. We demonstrate that the majority of histologically defined sinonasal undifferentiated carcinomas are characterized by IDH2 R172X mutations and overexpression of mutant protein. IDH2 R172X mutations are specific to sinonasal undifferentiated carcinoma among carcinomas of the head and neck, confirming this tumor type as a distinct clinicopathologic entity. These findings have significant implications for diagnosis and therapy with IDH inhibitors for patients with this rare and poorly understood tumor.

Current management of sinonasal undifferentiated carcinoma.

The management of sinonasal undifferentiated carcinoma (SNUC) remains unclear. Low incidence and poor outcomes make treatment standardization difficult. The objective of this study was to review the used treatment and our outcomes. From 2001 to 2013, 17 cases of SNUC were treated at our department. Charts were reviewed for standard demographic, tumour size and extension, histological features, treatment strategies, surgical approach, adjuvant therapies, outcomes and complications. All patients presented with extensive local disease and 2 patients also had neck metastases. All patients were treated using a multimodality approach: 10 patients underwent surgery and postoperative chemoradiation, 1 patient was treated with surgery and adjuvant radiotherapy, 3 patients were treated with neoadjuvant chemotherapy, surgery and postoperative chemoradiation and the remaining 3 patients were treated with chemoradiotherapy. After median follow-up of 39 months 6 patients developed recurrences. The 3-year local control rate was 76% and the 5-year rate of overall survival was 58%. Management and outcomes of SNUC have improved due to advances in surgery and radiotherapy. Gross tumour resection followed by postoperative radiotherapy should be the standard of care in patients with SNUC. High-precision high-dose radiotherapy should be implemented to try to improve the outcomes.

Etoposide，Cisplatin療法が著効した鼻副鼻腔未分化癌の1例

鼻副鼻腔未分化癌（SNUC）は比較的稀な疾患である。現在未だ確立された治療はなく，診断された時点で進行癌の場合が多く予後不良である。今回我々は，SNUCに対してetoposide，cisplatin療法（EP療法）を施行し，完全寛解を得られた症例を経験したので報告する。症例は35歳男性。2013年5月から頭重感が出現し，同年6月に当科を紹介受診，精査の結果，SNUC（T4bN0M0）と診断された。導入化学療法としてEP療法施行したところ，1コース施行後に完全寛解が得られた。その後追加で1コース，合計2コースEP療法施行後，他院にて炭素イオン線治療が行われ，現在寛解継続中である。SNUCに対しては，現在確立された治療法は存在しないが，今後EP療法が治療の選択枝となる可能性が示唆された。

Current management of sinonasal undifferentiated carcinoma

The management of sinonasal undifferentiated carcinoma (SNUC) remains unclear. Low incidence and poor outcomes make treatment standardization difficult. The objective of this study was to review the used treatment and our outcomes. From 2001 to 2013, 17 cases of SNUC were treated at our department. Charts were reviewed for standard demographic, tumour size and extension, histological features, treatment strategies, surgical approach, adjuvant therapies, outcomes and complications. All patients presented with extensive local disease and 2 patients also had neck metastases. All patients were treated using a multimodality approach: 10 patients underwent surgery and postoperative chemoradiation, 1 patient was treated with surgery and adjuvant radiotherapy, 3 patients were treated with neoadjuvant chemotherapy, surgery and postoperative chemoradiation and the remaining 3 patients were treated with chemoradiotherapy. After median follow-up of 39 months 6 patients developed recurrences. The 3-year local control rate was 76% and the 5-year rate of overall survival was 58%. Management and outcomes of SNUC have improved due to advances in surgery and radiotherapy. Gross tumour resection followed by postoperative radiotherapy should be the standard of care in patients with SNUC. High-precision high-dose radiotherapy should be implemented to try to improve the outcomes.

Incidence and survival patterns of sinonasal undifferentiated carcinoma in the United States.

Objective To determine trends in sinonasal undifferentiated carcinoma (SNUC) survival patterns in the United States. Design Retrospective review of national database. Participants All cases of SNUC in the National Cancer Institute's Surveillance Epidemiology and End Results program from 1973 to 2010 were examined. Main Outcome Measures Age-adjusted incidence and survival rates were calculated and stratified by demographic information and treatment modality. Cohort analysis was performed to analyze survival patterns over time. Results A total of 318 SNUC cases were identified. Age-adjusted incidence rate (IR) was 0.02 per 100,000. Incidence was greater in males (IR: 0.03) than females (IR: 0.01; p = 0.03). Overall 5- and 10-year relative survival rate was 34.9% and 31.3%, respectively. Overall median survival was 22.1 months. Median survival following surgery combined with radiation was 41.9 months. Five-year relative survival rate following surgery, radiation, or surgery combined with radiation was 38.7%, 36.0%, and 39.1%, respectively. Median survival from 1973-1986 and 1987-2010 was 14.5 and 23.5 months, respectively. Conclusions This study provides new data regarding survival patterns of SNUC in the United States, confirming survival benefit with surgery and radiation as well as identifying a trend toward improved survival in recent decades.

Role of p40 and cytokeratin 5/6 in the differential diagnosis of sinonasal undifferentiated carcinoma.

Sinonasal undifferentiated carcinoma (SNUC) is an epithelial neoplasm of sinonasal region which does not exhibit a squamous or glandular differentiation. The challenge in diagnosis of this entity is the rarity of the disease, the varying morphology of the tumor which leads to gamut of differential diagnosis and the paucity of consistent immunohistochemical markers except pancytokeratin. Forty-one cases of sinonasal epithelial neoplasm consisting of 11 cases of SNUC and 10 cases each of high-grade (grade 3 and 4) esthesioneuroblastoma, undifferentiated nasopharyngeal carcinoma, and poorly differentiated squamous cell carcinoma of the sinonasal region were analyzed for morphology and immunoexpression of CK5/6 and p40. It was found that SNUC did not exhibit immunohistochemical expression of p40 and CK 5/6, suggesting that these could be useful negative immune markers for diagnosis of SNUC.

Esthesioneuroblastoma and Sinonasal Undifferentiated Carcinoma Recurring as Adenocarcinoma

Objective: We describe a case of esthesioneuroblastoma that recurred locally and a case of sinonasal undifferentiated carcinoma that recurred regionally. In both cases, the histopathology of the recurrence was interpreted as a nonintestinal type of adenocarcinoma.

Sinonasal malignancies with neuroendocrine differentiation: Case series and review of literature

Primary sinonasal tumors with neuroendocrine differentiation (SCND) are uncommon tumors with considerable overlap of histological features. Based on their neuroendocrine differentiation they can be sub categorized into sinonasal undifferentiated carcinoma (SNUC), sinonasal neuroendocrine carcinoma (SNEC), esthesioneuroblastoma (ENB) and small cell carcinoma (SmCC). The natural history and biological behavior varies in this group of tumors. Hence the histo-morphological diagnosis coupled with grading/staging is important for the prognostication of these tumors. Aim : To study the clinicopathological characteristics of sinonasal neuroendocrine malignancies at our institute. Material and Methods : We searched our institute's pathology database for the period from 2002 to 2007, for the four subcategories of sinonasal tumors with neuroendocrine differentiation. Morphological and immunohistochemical features were studied and, grading, staging was done in accordance with standard criteria. The clinical treatment and follow- up data were retrieved from the case files in available cases. Results : A total of 37 cases were retrieved from our database which include 14 cases of SNUC, 14 cases of ENB and nine cases of SNEC. The cases of SNUC were immunopositive for cytokeratin, epithelial membrane antigen and weakly for neuron-specific enolase. SNEC showed strong reactivity with epithelial and neuroendocrine markers whereas ENB demonstrated immunoreactivity to synaptophysisn and chromogranin strongly, with weak to negative expression of epithelial markers. All cases of SNUC and SNEC were of high grade and stage whereas 50% of ENB cases were of grade II but high stage tumors. Most of the SNUC and SNEC patients had been treated with multimodality treatment regimens including upfront chemotherapy followed by surgery and loco- regional radiation. In contrast, ENB patients had undergone surgical extirpation followed by radiation therapy in majority of cases. With limited follow-up data, it was observed that four out of five SNUC patients and three out of four SNEC patients developed either loco-regional (three of SNUC and two of SNEC) or distant metastasis (one patient each of SNUC and SNEC). ENB patients also had loco-regional recurrences (five out of seven patients) with a more protracted course but no distant metastases were observed during the follow up in available cases. Conclusion : Sino nasal tumors with neuroendocrine differentiation are a heterogenous group of tumors with overlapping histo-morphological features. They can be distinguished based on immunohistochemical characteristics. Pathological sub categorization is imperative for management and prognostication of these aggressive tumors.

부비동비강미분화암 1예

부비동비강미분화암 1예

A Case of Sinonasal Undifferentiated Carcinoma Originating from the Ethmoid Sinus

Sinonasal undifferentiated carcinoma (SNUC) is a rare, aggressive malignancy and commonly asymptomatic until the tumor has extensively progressed. Patients with SNUC usually show the involvement of multiple sinuses and the nasal cavity. In addition, the invasion of the orbit or cranial vault is a frequent finding. Most case series of SNUC report very poor prognosis despite aggressive multimodality therapy. We present a case of SNUC in a 19-year old female occurred from the right ethmoid sinus with invasion to the orbital content. (Korean J Otorhinolaryngol-Head Neck Surg 2009;52:536-40)

The Cytologic Features of Sinonasal Undifferentiated Carcinoma and Olfactory Neuroblastoma

Sinonasal undifferentiated carcinoma (SNUC) is a rare, aggressive malignancy of the sinonasal tract. Olfactory neuroblastoma (ONB) is an uncommon neuroectodermal tumor of the superior nasal cavity. Upon examining these lesions, a broad differential diagnosis of poorly differentiated round cell tumors must be considered. The cytologic features of SNUC and ONB have been rarely reported. We searched our cytology files for cases of SNUC and ONB and assessed the following: cellularity, architecture, cytoplasm, cell size, nuclear contours, nucleoli, chromatin, anisonucleosis/anisocytosis, mitotic activity, background, and nuclear crush. Seven cases of SNUC produced hypercellular smears with a single-cell-predominant pattern. Cells were intermediate-sized with irregular nuclear contours and small nucleoli. Nuclear crush and mitotic figures were noted. The background exhibited naked nuclei and karyorrhectic debris. Of 7 cases, 6 (86%) exhibited vacuoles or extracellular lumina. The 10 cases of ONB exhibited cellularity, cellular arrangement, and chromatin similar to SNUC. In contrast, ONBs demonstrated fibrillary cytoplasm and smooth nuclear contours; mitotic figures were generally absent. Homer Wright rosettes were encountered in 9 cases (90%). We believe that in the appropriate clinical context, a specific cytologic diagnosis should be possible.

Report of a case of sinonasal undifferentiated carcinoma arising in a background of extensive nasal gliomatosis

Sinonasal undifferentiated carcinoma (SNUC) is a relatively rare, aggressive malignancy of adulthood. Nasal glial heterotopia is a benign congenital condition in which mature benign brain tissue develops outside the central nervous system. A 37-year-old man was seen with right nasal obstruction, epistaxis, and headache. Imaging showed a radiologically malignant mass lesion. Biopsy and subsequent resection were performed in the evaluation and treatment of this lesion. Histologic and immunohistochemical assessments of the biopsy and resection specimens on the pathology material classified the lesional tissue. Histology and immunohistochemistry of the biopsy specimen demonstrated an SNUC that was subsequently resected following chemotherapy. In addition to SNUC, the resection specimen revealed extensive, multifocal nasal glial heterotopia (so called "nasal glioma"). This is the first known case in the literature in which these 2 relatively rare entities coincide.