ABSTRACT
Sinonasal cancer accounts for roughly only 3% of upper respiratory tract malignancies and generally presents as a primary malignancy. Although extremely rare, the sinonasal cavity is also a known location for metastasis, with 8% of these cases originating from primary breast cancer. When attempting to differentiate primary disease from metastasis, immunohistochemical analyses play a crucial role in reaching the correct diagnosis. To date, there are a handful of reports describing metastasis involving the paranasal sinuses but even fewer reporting primary sinonasal cancer with coexisting primary malignancy. Here we present a case of primary sinonasal adenocarcinoma in the setting of a long-standing history of breast cancer. The patient, a 73-year-old female, was diagnosed with T1cN1aM0, progesterone receptor positive and estrogen receptor negative ductal carcinoma in situ of the left breast in November 2019. She subsequently underwent bilateral mastectomy and treated with 3 cycles of chemotherapy and anastrozole, which were both discontinued due to intolerance. Of note, in March 2019, MRI of the head incidentally found a 3 x 2 cm mass in right nasal cavity extending into ethmoid sinus. One year later, she presented with mild right sided nasal obstruction and drainage, and biopsy revealed squamous and respiratory mucosa with chronic inflammation. The patient elected to cancel initial surgical resection of the mass due to the COVID-19 pandemic. The patient returned in March 2022 with complaints of eye pressure, double vision, headaches, and worsening nasal obstruction. PET/CT scan was negative for distant metastasis but demonstrated increased uptake in sinus cavity. MRI showed a larger 5 x 3.7 cm mass impressing on medial inferior margins of orbit. Imaging also suggested evidence of dehiscence of lamina and irregular neo-osteogenesis of the skull base. She underwent approach and resection of the mass with histology demonstrating a well differentiated, low grade non-intestinal mucinous adenocarcinoma. Immunohistochemistry was positive for pankeratin and CK7, favoring a primary sinonasal origin. It was estrogen receptor negative and negative for GATA3, a sensitive and fairly specific stain in mammary carcinoma. Adjuvant radiation was recommended postoperatively, however the patient declined this therapy. This case highlights the role of immunohistochemistry to discriminate a new primary cancer from metastasis in patients with a history of breast cancer. Clinically, patients with sinonasal metastasis can present with symptoms ranging from unilateral nasal obstruction, facial pain, diplopia, and decreased vision. On imaging, suspicion of malignancy is raised when there is evidence of destruction of bony boundaries and invasion of surrounding tissues such as the orbit and anterior skull base, as found in our patient. Notably, metastasis to the paranasal sinuses can mimic a primary cancer of the nasal cavity, with both tumors showing epithelial differentiation. However, primary tumors often show neoplastic changes in the overlying respiratory epithelium and do not express estrogen receptor, progesterone receptor, or HER2 positivity, which are known to be correlated with breast cancer. In this setting, GATA3 and estrogen receptor negativity allowed us to diagnose primary nasal cancer more confidently. Therefore, clinicians should be aware of metastatic disease and expand immunohistochemistry panels when appropriate.
ABSTRACT
The main focus in the course of COVID-19 goes on assessing the overall immune response. The role of mucosal immunity in this disease has not been studied sufficiently. The study aimed to analyze published data about secretory IgA as a significant indicator of the mucosal immune response of the respiratory tract in the context of the COVID-19 pandemic. Methods. Articles were identified via PubMed bibliographic database. The time-span of research was two years (2020, 2021). Results. The search identified 54 articles. There is evidence that secretory IgA (sIgA) is the main antibody isotype of the mucosal immunity. It is produced in quantities significantly higher than those of all other isotypes of immunoglobulins combined. sIgA antibodies are effective against various pathogens, including the SARS-CoV-2 virus, due to mechanisms such as neutralization, suppression of adhesion to the mucosal surface and invasion of epithelial cells, agglutination and facilitating the removal of pathogenic microorganisms with the mucosal secretions. Virus-specific IgA antibodies in the blood serum are detected in patients with COVID-19 as early as two days after the first symptoms, while IgM or IgG class antibodies appear only after 5 days. We accessed the efficacy of intranasal immunization as to induction of predominant production of sIgA in the upper and lower respiratory tract. Conclusion. The current information on the local immune response of the respiratory mucosa is important for understanding the pathophysiological mechanisms of the disease, diagnosis, and development of new methods of treatment and prevention of COVID-19.
ABSTRACT
INTRODUCTION: Otitis media is an umbrella term for middle ear inflammation; ranging from acute infection to chronic mucosal disease. It is a leading cause of antimicrobial therapy prescriptions and surgery in children. Despite this, treatments have changed little in over 50 years. Research has been limited by the lack of physiological models of middle ear epithelium. METHODS: We develop a novel human middle ear epithelial culture using an air-liquid interface (ALI) system; akin to the healthy ventilated middle ear in vivo. We validate this using immunohistochemistry, immunofluorescence, scanning and transmission electron microscopy, and membrane conductance studies. We also utilize this model to perform a pilot challenge of middle ear epithelial cells with SARS-CoV-2. RESULTS: We demonstrate that human middle ear epithelial cells cultured at an ALI undergo mucociliary differentiation to produce diverse epithelial subtypes including basal (p63+), goblet (MUC5AC+, MUC5B+), and ciliated (FOXJ1+) cells. Mature ciliagenesis is visualized and tight junction formation is shown with electron microscopy, and confirmed by membrane conductance. Together, these demonstrate this model reflects the complex epithelial cell types which exist in vivo. Following SARS-CoV-2 challenge, human middle ear epithelium shows positive viral uptake, as measured by polymerase chain reaction and immunohistochemistry. CONCLUSION: We describe a novel physiological system to study the human middle ear. This can be utilized for translational research into middle ear diseases. We also demonstrate, for the first time under controlled conditions, that human middle ear epithelium is susceptible to SARS-CoV-2 infection, which has important clinical implications for safe otological surgery. LEVEL OF EVIDENCE: NA.