Common Characteristics of Sinonasal Inflammation Associated with IgG4-Related Disease and Other Chronic Inflammatory Diseases: A Retrospective Observational Study.

INTRODUCTION: Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by elevated serum IgG4, tissue infiltration of IgG4-positive cells, and fibrosis. Although a number of IgG4-RD patients show sinonasal involvement, there is little known about sinonasal inflammation associated with IgG4-RD. This study aimed to describe the clinicopathological features of sinonasal inflammation associated with IgG4-RD and to compare with other inflammatory diseases, such as eosinophilic chronic rhinosinusitis (ECRS) and granulomatosis with polyangiitis (GPA). METHODS: A retrospective analysis of clinicopathological features of patients with sinonasal lesions and high serum IgG4 was performed. Patient data were reviewed to determine whether they fulfilled the diagnostic criteria for other inflammatory diseases. RESULTS: Six of 7 patients were diagnosed with IgG4-RD, while 1 patient was diagnosed with GPA. In the 6 patients with IgG4-RD, intranasal findings showed nasal polyps in 3 patients (50%) and nasal crusting in the 3 patients (50%). Computed tomography showed ethmoid sinus involvement in 5 patients (83%). Five of the 6 patients (83%) were diagnosed with IgG4-RD based on nasal biopsy, whereas 1 patient (17%) was diagnosed based on lacrimal gland biopsy. Four patients fulfilled the Japanese epidemiological survey of refractory ECRS (JESREC) criteria. However, none of the patients showed eosinophil infiltration. Although the patient with GPA showed high levels of serum IgG4 and tissue infiltration of IgG4-positive cells in the nasal biopsy, the patient showed common clinical features of GPA. CONCLUSION: Patients with sinonasal inflammation associated with IgG4-RD had similar clinical characteristics with ECRS and GPA. Histopathological findings of the nasal biopsy from clinically diagnosed GPA was consistent with that of IgG4-RD. Sinonasal inflammation associated with IgG4-RD should be diagnosed based not only on tissue infiltration of IgG4-positive cells but in conjunction with clinical findings such as local nasal characteristics, involvement of other organs, and serum antineutrophil cytoplasmic antibody levels. IgG4-RD should be ruled out in patients with eosinophilia without histopathological eosinophil infiltration.

Efficacy of Cetuximab Combined with Paclitaxel in Patients with Recurrent Salivary Gland Carcinoma: A Retrospective Observational Study.

INTRODUCTION: Due to the rarity and various histological types, a standard chemotherapy regimen for recurrent or metastatic salivary gland carcinoma (SGC) has not been established. Molecular-targeted therapy is a novel cancer therapy based on the expression of target molecules. However, few molecular-targeted therapy types have shown satisfactory efficacy for patients with SGC. Our study described promising results of epidermal growth factor receptor (EGFR)-targeting therapy with paclitaxel in patients with SGC. METHODS: The medical records of patients with recurrent SGC treated with weekly cetuximab combined with paclitaxel (Cmab-PTX) between December 2017 and December 2022 at our institutions were retrospectively analyzed. RESULTS: Seven patients with SGC received Cmab-PTX therapy. The median age was 76 years. All patients were high-grade histological types, and EGFR expression was positive in all examined patients. Cmab-PTX was administered for a median period of 20 months (range of 2-36 months). The overall responses were three with complete response, two with partial response, one with stable disease (>24 weeks), and one with progressive disease. The objective response and disease control rates were 71.4% and 85.7%, respectively. Progression-free survival ranged between 2 and 36 months (median 12 months), whereas overall survival ranged between 4 and 111 months (median 36 months). One patient experienced a grade 4 adverse event (neutropenia), which was conservatively manageable. CONCLUSION: Although the treatment sensitivity of SGC with high-grade histological types is usually poor, Cmab-PTX could be a promising treatment regimen for recurrent SGC. Due to the rarity and various histological types, a standard chemotherapy regimen for recurrent or metastatic salivary gland carcinoma (SGC) has not been established. Molecular-targeted therapy is a novel cancer therapy based on the expression of target molecules. However, few molecular-targeted therapy types have shown satisfactory efficacy in patients with SGC. Our study described promising results of cetuximab (Cmab), epidermal growth factor receptor (EGFR)-targeting therapy with paclitaxel (PTX) in patients with SGC. Seven patients with SGC received Cmab-PTX therapy. The median age was 76 years. All patients were high-grade histological types, and EGFR expression was positive in all examined patients. Cmab-PTX was administered for a median period of 20 months. The overall responses were three with complete response, two with partial response, one with stable disease (>24 weeks), and one with progressive disease. The objective response rate was 71.4%. Progression-free survival ranged between 2 and 36 months (median 12 months), whereas overall survival ranged between 4 and 111 months (median 36 months). One patient experienced a grade 4 adverse event (neutropenia), which was conservatively manageable. Our study revealed a preferable objective response rate of Cmab-PTX for patients with high-grade SGC. Although the treatment sensitivity of SGC with high-grade histological types is usually poor, Cmab-PTX could be a promising treatment regimen for recurrent SGC.

The efficacy of PD-1 inhibitors in patients with salivary gland carcinoma: A retrospective observational study.

Objective: Immune checkpoint inhibitors (ICIs) have been considered as novel therapeutic approaches for various cancers. ICIs were reportedly efficacious against rare cancers, including salivary gland carcinoma (SGC). We aimed to analyze the efficacy and safety of ICIs in patients with SGC. Methods: We retrospectively analyzed the oncologic outcomes and immune-related adverse events (irAEs) in patients with SGC treated with at least one cycle of nivolumab or pembrolizumab. Results: Among 12 patients, there were two with a complete response (CR), two with a partial response, five with stable diseases, and three with progressive diseases. The overall response rate was 33.3%. A CR was achieved in patients with poorly differentiated carcinoma (carcinoma ex pleomorphic adenoma) and salivary duct carcinoma. The progression-free survival ranged between 1 and 18 months (median, 4 months), while the overall survival ranged between 2 and 25 months (median, 13.5 months). An irAE was observed in only one patient who developed grade 3 erythema multiforme, and this patient's condition improved with withdrawal of pembrolizumab alone. Conclusion: Programmed death-1 blockade was an effective therapy for patients with SGC, including aggressive histologic types.

A case of primary histiocytic sarcoma arising from a neck lymph node.

Histiocytic sarcoma (HS) is an aggressive and rare hematological malignancy. Its treatment has not been established, and most patients die within 2 years of diagnosis. Resection can provide a favorable prognosis for solitary lesions. We present the case of an 80-year-old Japanese man with HS. He presented a history of a slow-growing painless mass in the lower part of his right jaw. Ultrasonography showed a swollen lymph node in the vicinity of the right submandibular gland. Contrast-enhanced computed tomography revealed a heterogeneous, low-contrast mass on the right of the neck. Magnetic resonance imaging revealed a heterogeneously enhanced mass in gadolinium-enhanced T1-weighted images. The fine needle biopsy showed spindle-shaped cells and HS was suspected. Fluorodeoxyglucose positron emission tomography revealed uptake by the tumor alone. The patient underwent right upper neck dissection and resection of the submandibular salivary glands. No postoperative adjuvant treatment was administered, but 2-year survival was achieved. Histopathological examination showed proliferation of large, pleomorphic atypical cells without differentiation into lymphocytes, which proved their differentiation into histiocytes. A bone marrow biopsy showed no evidence of monocytic leukemia. Thus, a diagnosis of HS was made. With local treatment alone, our patient achieved long-term survival, maintaining his quality of life.

Congenital cholesteatoma isolated to the mastoid presenting as stricture of the external auditory canal.

Congenital cholesteatoma may originate at various sites in the temporal bone. Congenital cholesteatoma of the mastoid origin shows a variable clinical presentation, although the least common site is the mastoid process. We report an extremely rare case of congenital cholesteatoma isolated to the mastoid presenting as stricture of the external auditory canal. A 10-year-old boy presented with stricture of the left-sided external auditory canal caused by bulging of the posterior wall of the external auditory canal. Computed tomography showed destruction of the posterior wall of the external auditory canal by a lesion of soft tissue density in the left mastoid cells. At surgery, cholesteatoma was observed in the mastoid cavity. Although destruction of the posterior wall of the external auditory canal was identified, the external auditory canal skin and tympanic membrane were intact, and the aditus ad antrum mucosa was normal. Congenital cholesteatoma isolated to the mastoid was diagnosed. Diagnosis of congenital cholesteatoma isolated to the mastoid should be based on clinical examination, radiological evaluation, and surgical findings. In addition, the possibility of congenital cholesteatoma isolated to the mastoid should be considered in patients with stricture of the external auditory canal.

[Three cases of methotrexate-associated lymphoproliferative disorder (MTX-LPD)].

Methotrexate (MTX) has been increasingly administered to patients with rheumatoid arthritis (RA), resulting in methotrexate-associated lymphoproliferative disorder (MTX-LPD) in patients. We reported three case of rheumatoid arthritis (RA) undergoing methotrexate (MTX) therapy who developed MTX-LPD. A 72-year-old woman treated with MTX since December 1997 (total dose 3684 mg) presented with swelling of the right tonsil in October 2006, and diffuse large B-cell lymphoma was diagnosed by tonsil biopsy and positive EBER1. When MTX therapy was interrupted, the tonsil was shrank and chemotherapy was not necessary. She followed a good clinical course for 12 months. Two other patients treated with MTX for RA for several years presented with enlarged neck lymph nodes and were diagnosed with MTX-LPD. Neck lymph nodes shrank upon MTX withdrawal in several weeks. There have been no signs of recurrence in these cases and they followed a good clinical course. The oncogenic potential of MTX and RA is reviewed.