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B7-H4 (VTCN1), a member of the B7 family, is overexpressed in several types of cancer. Here we investigated the pattern of expression of B7-H4 in salivary gland carcinomas (SGC) and assessed its potential as a prognostic marker and therapeutic target. Immunohistochemistry (IHC) analyses were performed in a cohort of 340 patient tumors, composed of 124 adenoid cystic carcinomas (ACC), 107 salivary duct carcinomas (SDC), 64 acinic cell carcinomas, 36 mucoepidermoid carcinomas (MEC), 9 secretory carcinomas (SC), as well as 20 normal salivary glands (controls). B7-H4 expression was scored and categorized into negative (<5% expression of any intensity), low (5%-70% expression of any intensity or >70% with weak intensity), or high (>70% moderate or strong diffuse intensity). The associations between B7-H4 expression and clinicopathologic characteristics, as well as overall survival, were assessed. Among all tumors, B7-H4 expression was more prevalent in ACC (94%) compared with those of SC (67%), MEC (44%), SDC (32%), and acinic cell carcinomas (0%). Normal salivary gland tissue did not express B7-H4. High expression of B7-H4 was found exclusively in ACC (27%), SDC (11%), and MEC (8%). In SDC, B7-H4 expression was associated with female gender (P = .002) and lack of androgen receptor expression (P = .012). In ACC, B7-H4 expression was significantly associated with solid histology (P < .0001) and minor salivary gland primary (P = .02). High B7-H4 expression was associated with a poorer prognosis in ACC, regardless of clinical stage and histologic subtype. B7-H4 expression was not prognostic in the non-ACC SGC evaluated. Our comparative study revealed distinct patterns of B7-H4 expression according to SGC histology, which has potential therapeutic implications. B7-H4 expression was particularly high in solid ACC and was an independent prognostic marker in this disease but not in the other SGC assessed.

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BACKGROUND: Salivary duct carcinoma (SDC) is a rare and aggressive malignancy. Recently, biomarker studies found promising targetable alterations. In this study, we provide a descriptive analysis of tumor and immune biomarkers and survival associations. METHODS: We extracted clinical data and performed immunohistochemistry for AR, AR-V7, HER-2, PD-L1, LAG-3, and tumor-infiltrating immune cells. RESULTS: We included 17 patients. Age ranged from 42 to 85 years old; HER-2 was overexpressed or amplified in 65%. AR was positive in 88% of patients, while AR-V7 was positive in 13% by IHC. We found low scores of immune infiltration and a PD-L1 expression in 53%. We found no clinically significant association between biomarkers and survival outcomes. CONCLUSION: In this small series of SDC, biomarkers do not seem to correlate with disease biology, although they provide additional treatment options. SDC may harbor a different immune profile compared to other subtypes, with an indication of T-cell dysfunction.

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Abstract: Dural metastases are an unusual form of spread in treated sinonasal malignancies. An analysis is presented of 20 cases of dural metastases diagnosed during imaging follow-up in a selection of cases in which anterior craniofacial resection was performed. They included 12 undifferentiated sinonasal carcinomas, 7 olfactory neuroblastomas, and 1 adenoid cystic carcinoma case. Dural metastases appeared on an average of 7.3 years after treatment in olfactory neuroblastoma. The maximum distance from malignancy to dural metastases was 14 cm for olfactory neuroblastoma, and 4.3 cm for undifferentiated sinonasal carcinoma. Dural metastases in the Burr holes were observed in 50% of undifferentiated sinonasal carcinoma, and 29% of olfactory neuroblastomas. Dural metastases presented as a nodular (60%), multinodular (10%), cystic (15%), and plaque (15%) pattern. These are suggestive of a local venous spread mechanism related to tumour rupture during surgery of anterior cranial fossa. Long-term follow-up with cranial inclusion would be indicated, given the possible late and distant presentation of dural metastases.

Resumen: Presentamos las metástasis durales como forma inusual de diseminación de tumores nasosinusales malignos tratados; se revisan 20 casos diagnosticados durante el seguimiento imagenológico a un grupo tratado con resección craneofacial anterior. Evaluamos metástasis durales en 12 carcinomas nasosinusales indiferenciados, 7 neuroblastomas olfatorios y un carcinoma adenoquístico. En neuroblastomas olfatorios aparecieron metástasis durales en promedio 7,3 años postratamiento. La distancia máxima del tumor a la metástasis fue de 14 cm para neuroblastoma olfatorio y de 4,3 cm para carcinoma nasosinusal indiferenciado. Observamos metástasis durales en los agujeros de trepanación en el 50% de los carcinomas nasosinusales indiferenciados y en el 29% de los neuroblastomas olfatorios. Las metástasis durales presentaron patrón nodular (60%), multinodular (10%), quístico (15%) y en placa (15%). Proponemos un mecanismo venoso local de diseminación relacionado a disrupción tumoral o quirúrgica de la fosa craneal anterior. El seguimiento a largo plazo con inclusión craneal estaría indicado por la posible presentación tardía y distante de metástasis durales.

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Introduction Malignant sinonasal tumors comprise less than 1% of all neoplasms. A wide variety of tumors occurring primarily in this site can present with an undifferentiated or poorly differentiated morphology. Among them are esthesioneuroblastomas, sinonasal undifferentiated carcinomas, and neuroendocrine carcinomas. Objectives We will discuss diagnostic strategies, recent advances in immunohistochemistry and molecular diagnosis, and treatment strategies. Data Synthesis These lesions are diagnostically challenging, and up to 30% of sinonasal malignancies referred to the University of Texas MD Anderson Cancer Center are given a different diagnosis on review of pathology. Correct classification is vital, as these tumors are significantly different in biological behavior and response to treatment. The past decade has witnessed advances in diagnosis and therapeutic modalities leading to improvements in survival. However, the optimal treatment for esthesioneuroblastoma, sinonasal undifferentiated carcinoma, and neuroendocrine carcinoma remain debated. We discuss advances in immunohistochemistry and molecular diagnosis, diagnostic strategies, and treatment selection. Conclusions There are significant differences in prognosis and treatment for esthesioneuroblastoma, neuroendocrine carcinoma, and sinonasal undifferentiated carcinoma. Recent advances have the potential to improve oncologic outcomes but further investigation in needed.

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Introduction: Malignant sinonasal tumors comprise less than 1% of all neoplasms. A wide variety of tumors occurring primarily in this site can present with an undifferentiated or poorly differentiated morphology. Among them are esthesioneuroblastomas, sinonasal undifferentiated carcinomas, and neuroendocrine carcinomas. Objectives: We will discuss diagnostic strategies, recent advances in immunohistochemistry and molecular diagnosis, and treatment strategies. Data Synthesis: These lesions are diagnostically challenging, and up to 30% of sinonasal malignancies referred to the University of Texas MD Anderson Cancer Center are given a different diagnosis on review of pathology. Correct classification is vital, as these tumors are significantly different in biological behavior and response to treatment. The past decade has witnessed advances in diagnosis and therapeutic modalities leading to improvements in survival. However, the optimal treatment for esthesioneuroblastoma, sinonasal undifferentiated carcinoma, and neuroendocrine carcinoma remain debated. We discuss advances in immunohistochemistry and molecular diagnosis, diagnostic strategies, and treatment selection. Conclusions There are significant differences in prognosis and treatment for esthesioneuroblastoma, neuroendocrine carcinoma, and sinonasal undifferentiated carcinoma. Recent advances have the potential to improve oncologic outcomes but further investigation in needed...

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