SMARCB1(INI1)缺失的鼻腔鼻窦癌六例临床病理学特征

目的探讨SMARCB1(INI1)缺失的鼻腔鼻窦癌临床病理特征及其诊断和鉴别诊断。方法收集2016至2018年复旦大学附属眼耳鼻喉科医院手术切除SMARCB1(INI1)缺失的鼻腔鼻窦癌标本/活检病例6例,观察其临床特点、影像学特征、组织形态、免疫组织化学特征以及预后,并结合文献进行复习。结果5例男性,1例女性;年龄37~75岁(平均约56岁)。1例患者属于T2期,5例患者属于T4期,CT及MRI示鼻腔鼻窦占位伴骨质破坏。镜下观察:肿瘤境界不清,基底样细胞型4例,肿瘤细胞形态较单一,高核质比,细胞质稀少,呈巢状或片状分布于间质中;横纹肌样细胞型2例,肿瘤细胞呈巢状或条索状排列,细胞胞质丰富,嗜酸性,核偏位。免疫组织化学染色示6/6 INI1完全缺失,6/6弥漫强阳性表达广谱细胞角蛋白(CKpan),6/6均不表达S-100蛋白,6/6 EB病毒编码的小RNA(EBER)原位杂交阴性,4/6部分表达p63,1/5部分表达突触素,1/5部分表达p16,Ki-67阳性指数范围30%~70%。5例患者随访1~26个月,其中1例因广泛转移死亡,1例复发,2例淋巴结转移,1例无复发和转移。1例失访。结论SMARCB1(INI1)缺失的鼻腔鼻窦癌恶性程度高,病程进展快,预后差,组织形态主要为基底样细胞型和横纹肌样细胞型,细胞核INI1完全缺失有助于诊断及鉴别诊断。     

鼻窦SMARCA4缺失性癌1例

鼻窦未分化癌是一种在组织学及免疫组织化学染色证实缺乏腺性、鳞状或其他明显细胞谱系特征的恶性上皮性肿瘤。近年来,分化差的鼻窦癌相关分子发病机制引人关注,依据不同的遗传学特征将未分化癌进行重新命名,如中线癌（也称NUT癌）、SMARCB1（INI1）缺失性癌等。鼻窦SMARCA4缺失性癌是未分化癌的一种新认识的组织学类型,...     

Cytopathologic characteristics of SMARCB1 (INI‐1) deficient sinonasal carcinoma: A potential diagnostic pitfall

Tumors of the head and neck are extremely diverse and a subset are poorly differentiated and difficult to classify. Recently, a new entity has been described with rhabdoid and/or plasmacytoid cytologic features and a characteristic genetic signature—inactivation of the SMARCB1 (INI‐1) tumor suppressor gene. To date, only 16 cases of SMARCB1 (INI‐1) deficient sinonasal carcinoma have been described, and there are currently no reports of the cytopathologic features by fine needle aspiration (FNA) cytology. A case of a 77‐year‐old man who presented with a posterior ethmoid sinus lesion with invasion into the skull base and bone was reported. FNA cytology of a right retropharyngeal lymph node revealed relatively monomorphic, loosely cohesive clusters of plasmacytoid cells with occasional nucleoli, rare intranuclear cytoplasmic inclusions, and mitotic figures in a background of necrosis and absence of overt squamous or glandular differentiation. A diagnosis of metastatic myoepithelial carcinoma was made; however, retrospectively, the surgical excision showed loss of the SMARCB1 (INI‐1) tumor suppressor gene by immunohistochemistry. In summary, the cytomorphologic features of SMARCB1 (INI‐1) deficient sinonasal carcinoma are relatively nonspecific and overlap with other regional tumors, including myoepithelial neoplasms. As a result, this entity should be considered in the differential diagnosis for a plasmacytoid tumor arising in the sinonasal tract by FNA cytology. Diagn. Cytopathol. 2016;44:700–703. © 2016 Wiley Periodicals, Inc.     

Primary sinonasal neuroendocrine carcinoma invading the orbit

Primary sinonasal neuroendocrine carcinoma (SNEC) is a rare aggressive sinonasal malignancy which typically occurs in the ethmoidal or maxillary sinuses, with or without nasal cavity involvement, of middle-aged patients (median age 53 years), with a slight male preponderance. No risk factors have been identified. Most patients present at advanced stages due to the lack of significant symptoms.^1,4,5,8 Advanced tumours may invade the skull, orbit or brain. Staging is of limited value in predicting prognosis and recent literature clearly highlights the importance of histological diagnosis, particularly differentiation grade, in determining the prognosis and predicting treatment response. Nomenclature has been ambiguous, but broadly SNECs can be classified as well-, moderately- or poorly differentiated. The latter group includes sinonasal undifferentiated carcinoma and sinonasal small cell carcinoma. On histological examination, well-to-moderately differentiated tumours show medium-sized cells with large nuclei containing stippled or ‘salt/pepper’ chromatin and scant cytoplasm. Nuclear moulding, increased mitoses and apoptotic bodies are commonly seen. Immunohistochemistry reveals expression of neuroendocrine markers.^1,4–7 Poorly-differentiated tumours may lose expression of neuroendocrine markers and differentiation from other poorly differentiated malignancies can be extremely difficult.^1,4–7 Due to the limited number of reported cases, there is no clear consensus on management, although oncologists now advocate multimodal therapy. Combined surgery and radiotherapy is thought to beneficial in moderately and poorly-differentiated subtypes.^1,4–8 We describe a classical case of SNEC with secondary orbital involvement, with a review of the current literature.     

Activating KRAS mutations are characteristic of oncocytic sinonasal papilloma and associated sinonasal squamous cell carcinoma

Oncocytic sinonasal papillomas (OSPs) are benign tumours of the sinonasal tract, a subset of which are associated with synchronous or metachronous sinonasal squamous cell carcinoma (SNSCC). Activating EGFR mutations were recently identified in nearly 90% of inverted sinonasal papillomas (ISPs) – a related tumour with distinct morphology. EGFR mutations were, however, not found in OSP, suggesting that different molecular alterations drive the oncogenesis of these tumours. In this study, tissue from 51 cases of OSP and five cases of OSP‐associated SNSCC was obtained retrospectively from six institutions. Tissue was also obtained from 50 cases of ISP, 22 cases of ISP‐associated SNSCC, ten cases of exophytic sinonasal papilloma (ESP), and 19 cases of SNSCC with no known papilloma association. Using targeted next‐generation and conventional Sanger sequencing, we identified KRAS mutations in 51/51 (100%) OSPs and 5/5 (100%) OSP‐associated SNSCCs. The somatic nature of KRAS mutations was confirmed in a subset of cases with matched germline DNA, and four matched pairs of OSP and concurrent associated SNSCC had concordant KRAS genotypes. In contrast, KRAS mutations were present in only one (5%) SNSCC with no known papilloma association and none of the ISPs, ISP‐associated SNSCCs, or ESPs. This is the first report of somatic KRAS mutations in OSP and OSP‐associated SNSCC. The presence of identical mutations in OSP and concurrent associated SNSCC supports the putative role of OSP as a precursor to SNSCC, and the high frequency and specificity of KRAS mutations suggest that OSP and OSP‐associated SNSCC are biologically distinct from other similar sinonasal tumours. The identification of KRAS mutations in all studied OSP cases represents an important development in our understanding of the pathogenesis of this disease and may have implications for diagnosis and therapy. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Undifferentiated sinonasal carcinoma in a patient with nevoid basal cell carcinoma syndrome

Nevoid basal cell carcinoma syndrome is an autosomal dominant multisystem disorder characterized by developmental anomalies and occurrence of multiple basal cell carcinomas and other tumors in early childhood. In this article, the authors report a case of a 19-year-old African American male with nevoid basal cell carcinoma syndrome and a history of medulloblastoma at age 2, meningioma at age 14, thyroid follicular adenomas with papillary carcinoma at age 15, and 2 basal cell carcinomas at ages 16 and 18. Recently, he developed sinonasal undifferentiated carcinoma (SNUC). The radiology and pathology of the sinonasal carcinoma are presented in this report. Review of the literature reveals that this is the first case of SNUC occurring in a patient with nevoid basal cell carcinoma syndrome.     

Hybrid verrucous squamous cell carcinoma of sinonasal tract: a case report.

Verrucous carcinoma is a variant of squamous cell carcinoma and should be distinguished from benign papilloma and well-differentiated nonverrucous squamous cell carcinoma. It is rare tumor of the sinonasal tract. Occasionally, conventional squamous cell carcinomatous components may be seen in verrucous carcinoma. This entity is called a hybrid verrucous squamous cell carcinoma. We report a case of hybrid verrucous squamous cell carcinoma occurring in the nasal cavity and paranasal sinus of a 67-year-old male. The removed mass shows the typical feature of verrucous carcinoma, but focally conventional squamous cell carcinomatous area is also noted. The treatment of this case follows verrucous carcinoma, but close follow up is mandatory because it may potentially spread to regional lymph nodes in contrast to pure form of verrucous carcinoma.     

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.     

The international sinonasal microbiome study: A multicentre,multinational characterization of sinonasal bacterial ecology

The sinonasal microbiome remains poorly defined, with our current knowledge based on a few cohort studies whose findings are inconsistent. Furthermore, the variability of the sinus microbiome across geographical divides remains unexplored. We characterize the sinonasal microbiome and its geographical variations in both health and disease using 16S rRNA gene sequencing of 410 individuals from across the world. Although the sinus microbial ecology is highly variable between individuals, we identify a core microbiome comprised of Corynebacterium, Staphylococcus, Streptococcus, Haemophilus and Moraxella species in both healthy and chronic rhinosinusitis (CRS) cohorts. Corynebacterium (mean relative abundance = 44.02%) and Staphylococcus (mean relative abundance = 27.34%) appear particularly dominant in the majority of patients sampled. Amongst patients suffering from CRS with nasal polyps, a statistically significant reduction in relative abundance of Corynebacterium (40.29% vs 50.43%; P = .02) was identified. Despite some measured differences in microbiome composition and diversity between some of the participating centres in our cohort, these differences would not alter the general pattern of core organisms described. Nevertheless, atypical or unusual organisms reported in short-read amplicon sequencing studies and that are not part of the core microbiome should be interpreted with caution. The delineation of the sinonasal microbiome and standardized methodology described within our study will enable further characterization and translational application of the sinus microbiota.     

C-erbB-2和VEGF在鼻腔-鼻窦鳞状细胞癌中的表达及临床意义

目的研究原癌蛋白(C-erb B-2)及血管内皮生长因子(VEGF)在鼻腔、鼻窦鳞状细胞癌(SNSCC)中的表达及其临床意义。方法收集62例SNSCC组织、30例鼻息肉组织(NP组)以及25例正常鼻腔黏膜(正常组),用免疫组化及Western blot技术分别检测C-erb B-2和VEGF在三者中的表达情况。结果 C-erb B-2和VEGF在SNSCC组织中的表达明显高于鼻息肉及正常鼻腔黏膜中的表达(P0.05)。另外,C-erb B-2和VEGF的表达与病理类型、临床病理分期及淋巴结转移等临床病理特征呈正相关(P0.05),而与性别、年龄无关。结论 C-erb B-2和VEGF与SNSCC的发生、分化及细胞增殖密切相关,联合检测二者有助于对SNSCC的诊断与治疗。     

Selected epithelial sinonasal neoplasms: an update

Sinonasal neoplasms comprise 3% of all head and neck cancers and 1% of all malignancies. Malignant lesions are more common than benign ones and generally carry poor prognosis. Patients in most cases are asymptomatic and only present in advanced clinical stage with non-specific obstructive symptoms. Conventional squamous cell carcinomas are the most common carcinomas in the sinonasal tract; however, other there is an array of uncommon high grade malignancies, including poorly differentiated carcinomas, which present a diagnostic challenge due to overlapping microscopic findings in small biopsies. Distinguishing high-grade epithelial malignancies such as sinonasal undifferentiated carcinoma (SNUC), non-keratinizing squamous cell carcinoma, nuclear protein in testis (NUT) carcinoma, SMARCB1-deficiency carcinoma and HPV-related multiphenotypic sinonasal carcinoma can be difficult and almost invariably will require the use of ancillary studies to establish a definitive diagnosis.     

Primary sinonasal ameloblastoma

A case of primary ameloblastoma of the right sinonasal tract in a 66-year-old man is reported. The tumour presented as a radiographically solid mass filling the right nasal cavity and sinuses and without continuity with maxillary alveola. After radical surgery plus postoperative radiotherapy, the patient has pursued a non-aggressive clinical course after nine months of follow-up. The paper reviews the clinico-pathological features of this rare tumour and supports the theory of its sinonasal epithelium origin.     

Primary sinonasal choriocarcinoma

Primary choriocarcinoma of sinonasal tract has not been previously documented. The aim of the study was to report, for the first time, 2 cases of primary sinonasal choriocarcinoma. The differential diagnosis is discussed and also the theories concerning the histogenesis of this neoplasm are briefly reviewed. Two male patients of 44 and 49 years of age complained of epistaxis and nasal obstruction of 2-week duration. Computerized axial tomographic scan of the head revealed an opacity of the left nasal cavity in one patient and a destructive lesion of the maxillary sinus in the other. Histopathologically, the lesions disclosed a dual cell population composed of cytotrophoblastic cells with uniform, round nuclei, clear cytoplasm, admixed with large multinucleated syncytiotrophoblastic cells, with bizarre nuclei, and abundant eosinophilic cytoplasm. Immunohistochemically, the tumors were notable for strong keratin and β-chorionic gonadotrophin (HCG) positivity. The serum levels of HCG were 13 000 and 779 mIU/mL, respectively. One patient treated with maxillectomy, postoperative radiotherapy, and 5 courses of VIP chemotherapy (cisplatinum, etoposide, ifosfomide) died with brain metastases 10 months after diagnosis. The other patient received 4 courses of etoposide, and he is alive without tumor, 10 months after diagnosis. The serum levels of HCG are still negative. The present cases demonstrated the widespread distribution of germ cell tumors in the human body and lead to further support of the existence of primary choriocarcinomas in the sinonasal tract. Correct identification of this neoplasm is therefore important for institution of specific therapy.     

Secretory carcinoma of the sinonasal cavity and pharynx: A retrospective analysis of four cases and literature review

Secretory carcinoma (SC) is a recently recognized type of salivary gland tumor characterized by t(12;15) (p13;q25) translocation resulting in an ETV6-NTRK3 gene fusion. Most SCs are located in a main salivary gland, and primary sinonasal secretary carcinoma is rare. We describe three cases of primary SC in the sinonasal cavity with high-grade transformation (HGT) in one case, and the first case in the pharynx. All tumors comprised slightly atypical cells with solid, tubular, microcystic growth patterns. The case with HGT included two components with distinct sharp boundaries and comedo necrosis, high mitotic figures and obvious cellular atypia. Tumor cells were positive for vimentin, S100, and Gata-3 and negative for p63 and DOG-1. Three cases showed nuclear staining of pan-TRK and one showed cytoplasmic staining. All cases harbored ETV6 gene rearrangement, and ETV6-NTRK3 gene fusion was detected in three cases. Most patients were treated with radical resection and adjuvant therapy. After excision, all remained tumor-free for 65–164 months (medium 98.5 months). SC in the sinonasal cavity and pharynx is a low-grade malignant tumor with histologic features overlapping those of other salivary gland tumors. Immunohistochemical analysis and fluorescence in situ hybridization are useful techniques for its differential diagnosis.     

Association between carbonic anhydrase 9 expression and poor prognosis in sinonasal squamous cell carcinoma

ObjectivesCarbonic anhydrase 9 (CA9), as a member of the carbonic anhydrase enzyme family, was an endogenous marker of hypoxia. Previous studies suggested CA9 expression was correlated with poor prognosis in multiple types of malignancies. Therefore, this study was to evaluate the role of CA9 in sinonasal squamous cell carcinoma (SNSCC) and to determine whether this biomarker was associated with patient clinicopathologic characteristics and prognosis.MethodsWe assessed 63 patients diagnosed with SNSCC in 2013–2017 who underwent curative surgery. Tumor specimens was immunohistochemically analyzed for CA9 expression. The expression levels of CA9 was evaluated in relation to clinicopathological factors and prognosis.ResultsPositive expression of CA9 was observed in 21 (33.3%) patients and was significantly correlated with local recurrence (p = 0.016), overall survival (OS) (p = 0.003) and disease-free survival (DFS) (p = 0.002). In Cox's multivariate analysis, CA9 expression was an independent negative prognostic factor for OS (p = 0.048) and DFS (p = 0.019).ConclusionsOur findings demonstrated that CA9 overexpression could be used as an independent prognostic biomarker and therapeutic target in SNSCC.     

Inverted sinonasal papilloma : a molecular genetic appraisal of its putative status as a Precursor to squamous cell carcinoma

Inverted papilloma (IP) is a proliferative lesion of the epithelium lining the sinonasal tract. Although IP often recurs after surgical excision and is sometimes associated with squamous cell carcinoma of the sinonasal cavity (SNSCC), its presumed neoplastic nature and putative role as a precursor to squamous cell carcinoma have not been confirmed at the molecular genetic level. We analyzed the pattern of X chromosome inactivation in IPs from nine female patients. Inactivation of a single allele is seen in monoclonal proliferations and may be indicative of a neoplastic process. We also analyzed 28 IPs and 6 concurrent SNSCCs for loss of heterozygosity (LOH) on chromosomal arms 3p, 9p21, 11q13, 13q11, and 17p13. Losses at these loci occur frequently during neoplastic transformation of the upper respiratory tract and can be detected in squamous cell carcinomas and the progenitor lesions from which they arise. X chromosome analysis was informative in four of the nine IPs. All four lesions demonstrated a monoclonal pattern of inactivation. LOH was not detected in any nondysplastic areas from the 28 IPs, but LOH at one or more chromosomal loci was present in all six of the concurrent SNSCCs. We conclude that IPs are monoclonal proliferations, yet they do not fit the profile of a prototypic precursor lesion. Unlike squamous epithelial dysplasia, IPs do not routinely harbor several of the key genetic alterations that are associated with malignant transformation of the upper respiratory tract.