Programmed Death-Ligand 1 Expression and Tumor-Infiltrating Lymphocytes in Temporal Bone Squamous Cell Carcinoma.

OBJECTIVES/HYPOTHESIS: The tumor immune microenvironment in temporal bone squamous cell carcinoma (TBSCC), including the programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs), has not been established. STUDY DESIGN: Retrospective cohort study. METHODS: We performed immunohistochemistry analyses to retrospectively analyze 123 TBSCC cases for PD-L1 expression and TILs and their prognostic significance. We also evaluated the prognostic correlations between these immunomarkers and the therapeutic responses to chemoradiotherapy (CRT). RESULTS: PD-L1 expression (≥1%) was detected in 62 (50.4%) TBSCC cases and was significantly associated with worse prognosis: progression-free survival (PFS), P < .0001; overall survival (OS), P = .0009. A high density of CD8+ TILs was significantly associated with better prognosis (PFS, P = .0012; OS, P = .0120). In contrast, a high density of Foxp3+ TILs tended to be associated with an unfavorable prognosis (PFS, P = .0148; OS, P = .0850). With regard to the tumor microenvironment subtypes defined by CD8+ TILs and PD-L1 expression, the CD8low /PD-L1+ group showed significantly worse prognosis. Among the 36 neoadjuvant CRT-treated cases, PD-L1 expression was significantly associated with worse OS (P = .0132). Among the 32 CRT-treated cases without surgery, a high density of CD8+ TILs tended to be more highly associated with complete response to CRT compared to a low density of CD8+ TILs (P = .0702). CONCLUSIONS: These results indicate that the evaluation of the tumor immune microenvironment may contribute to the prediction of prognoses and the selection of an individualized therapeutic strategy for patients with TBSCC. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2674-2683, 2021.

Cutaneous squamous cell carcinoma of the scalp in the immunocompromised patient: review of 53 cases.

OBJECTIVE: We analyzed outcomes from immunocompromised patients with scalp squamous cell carcinoma (SCC) treated with surgical excision with and without radiation in order to explore 3-year disease-free survival and overall survival. STUDY DESIGN: The study design was a retrospective chart review. SETTING: This study was conducted in a private practice setting. SUBJECTS AND METHODS: The study included 53 immunocompromised patients with an average age of 63.2 years, with scalp squamous cell carcinoma. Pre-operative imaging dictated the extent of resection. Patients with bony involvement received wide local excision including full-thickness craniectomy and cranioplasty. Patients without bony involvement underwent wide local excision and outer-table calvarial resection. All patients were recommended to have post-operative radiation. Patients were followed for a minimum of 3 years. RESULTS: A total of 53 patients were included in the study. Six patients had pre-operative CT showing bone involvement and were treated with full-thickness craniectomy along with post-operative radiation. Fourteen patients without bone involvement on pre-operative CT were found to have positive bone involvement on final pathology. Forty-five patients underwent post-operative radiation. Patients treated with adjuvant radiation demonstrated a 3-year survival of 80 % and the overall survival was 62 %. In the surgery-only group, the 3-year survival was 62.5 % and the overall survival was 32.5 %. CONCLUSIONS: Immunocompromised patients with scalp SCC have a poor prognosis. Early detection and treatment are crucial. Based on our results, we recommend wide local excision with at least outer-table calvarial resection, and post-operative radiation. Despite aggressive therapy, patients may still have distant, local, or regional recurrence. LEVEL OF EVIDENCE: level 2b (retrospective cohort).

L-carnitine treatment in a seriously ill cancer patient with severe hyperthyroidism.

OBJECTIVE: To report a case of vaccine-induced Graves' disease successfully managed with L-carnitine and propranolol and without antithyroid drugs (ATDs). ATDs sometimes need to be used at low doses or can be contraindicated/refused. One of the ancillary compounds available is L-carnitine. L-carnitine is a naturally occurring quaternary amine, which acts by impairing thyroid hormone access to the cell nucleus. REPORT: A 32-year-old Chinese woman with a synovial sarcoma received radiotherapy, chemotherapy and experimental immunotherapy. Two months after the start of immunotherapy, she developed autoimmune hyperthyroidism [thyroid-stimulating immunoglobulins (TSI)=152%, normal values <140]. Left untreated, hyperthyroidism worsened (TSI=248%), so that for 3 months she took L-carnitine (1-4 g/d) and propranolol (20-80 mg/d). Though the hyperthyroidism worsened biochemically (FT4>50 pg/ml, FT3>20 pg/ml, TSI=501%), it was tolerated very well clinically. Fearing a life-threatening thyroid storm, she agreed to have, while still hyperthyroid, total thyroidectomy. The operation was uneventful. CONCLUSIONS: This case expands previous observations involving two more patients who survived thyroid storms while being treated with L-carnitine (combined with low doses of ATD). Taking also into account that tissue concentrations of L-carnitine decrease in hyperthyroidism, there is room for wide therapeutic use of L-carnitine in several hyperthyroidism settings.

Characterization of a newly established malignant meningioma cell line of the human brain: IOMM-Lee.

A permanent malignant meningioma (MM) cell line of the human brain designated "IOMM-Lee" is reported. This cell line was successfully established from the tumor of a 61-year-old Chinese man with repeated recurrent primary intraosseous malignant meningioma of the skull. It has been subcultured for more than 60 passages during the past 30 months. The doubling time of cultured cells is approximately 62 hours. Tumorigenicity in athymic nude mice (Balb/c-nu/nu) who develop multiple pulmonary metastases was observed; the doubling time of tumor volume in vivo is approximately 5 days. Karyotypic analysis revealed this cell line to be of human origin and near-diploid, with a modal chromosome number of 49. The mesenchymal tumor marker vimentin and intracytoplasmic microfilaments were identified in the cytoplasm of tumor cells by indirect immunohistochemical peroxidase-anti-peroxidase assays and immunogold ultrastructural localization by transmission electron microscopy, respectively. Scanning electron microscopy of cultured cells and xenografted tumors revealed ellipsoidal or carrot-shaped tumor cells presenting a wrinkled surface with short sparse microvilli. Potential proliferating activity was determined by Ki-67 monoclonal antibody; the Ki-67 labeling index of cultured cells and xenografted tumors was approximately 36% and 30%, respectively. This newly established malignant meningioma cell line of the human brain may prove useful as a research model.

Solitary plasmacytoma of the skull revealed by a mononeuritis multiplex associated with immune complex vasculitis.

We describe a patient with solitary plasmacytoma of the skull, in whom mononeuritis multiplex was the presenting manifestation. Some features of the POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal [M] protein, skin changes), including thrombocytosis, were found. Muscle and nerve biopsies disclosed a small vessel hypersensitivity-type vasculitis and complement-fixing immune complex deposits in vessel walls. Removal of the plasmacytoma resulted in clinical improvement and clearance of the vasculitis and immune complex deposits.

Multiple myeloma: a study of 10 cases.

The clinical, radiographical, biochemical, microscopical and ultrastructural features of 10 cases of multiple myeloma were studied. The skull and jaw regions were frequently involved by the disease and although the diagnosis remains multidisciplinary, microscopical parameters differentiating a myelomatous bone marrow infiltrate from a reactive plasmacytosis are discussed. Biochemical and microscopical factors influencing the prognosis are highlighted and significant ultrastructural findings include erythrophagocytosis, cytoplasmic nuclear asynchrony of plasmablasts and intranuclear viral like inclusions.

Demonstration of cytokeratins and an epithelial membrane antigen in chondroid chordoma.

Chondroid chordomas are shown to possess cytokeratins and to stain with HMFG-2 as do ordinary chordomas. These findings support the concepts that these neoplasms are a variant of chordoma and that they are unrelated to myxoid chondrosarcoma.