Prognostic Significance of Systemic Inflammatory Response in Cases of Temporal Bone Squamous Cell Carcinoma.

OBJECTIVE/HYPOTHESIS: Squamous cell carcinoma (SCC) of the temporal bone is an extremely rare condition. This rarity has led to a delay in the establishment of a standard treatment protocol and adequate staging system. Identification of prognostic markers of this disease from a variety of fields is desirable in the establishment of treatment guidelines for temporal bone SCC. The aim of this study is to assess the prognostic role of inflammation-based prognostic scores in cases of temporal bone SCC. STUDY DESIGN: Case reries with chart review. METHODS: A total of 71 cases of primary malignancy eligible for curative treatment at a single tertiary medical institute were retrospectively analyzed. Univariate and multivariate regression analyzes were used to investigate the association between the inflammation-based scores and 5-year overall survival. RESULTS: Univariate Cox regression analyzes showed that a high neutrophil-to-lymphocyte ratio, high platelet-to-lymphocyte ratio, low lymphocyte-to-monocyte ratio, a Glasgow prognostic score of 2, and the systemic inflammation score of 2 were significantly associated with a poor prognosis, as well as a classification of T4 stage, presence of cervical lymph node metastasis, high white blood cell counts, and high C-reactive protein levels. The multivariate analysis showed that a clinical stage of T4 and a systemic inflammation score of 2 were independent prognostic markers. CONCLUSIONS: Inflammation-based prognostic markers are associated with the survival of patients with temporal bone SCC, as well as other head and neck SCCs. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1782-1789, 2021.

Benign leiomyoma with multiple metastases to vertebrae and calvarium: An index case with comprehensive review of endocrine targets.

"Benign" metastatic leiomyomas (BML) are indolently growing metastatic tumors which mostly associate with uterine leiomyomas in women in reproductive ages. The reason to define these lesions as "benign" despite metastasis is their pathological features with low mitotic counts, lack of or minimal nuclear atypia, pseudocyst formation, and coagulative necrosis unlike leiomyosarcomas. Despite lack of pathological malignant features, they may cause significant morbidity and even mortality. Here, we describe a BML case with metastases to vertebrae and skull bones. Vertebral and skull metastases of BMLs were very rarely reported. In treatment of these tumors, hysterectomy and GnRH modifier treatments are widely employed. GnRH agonists act by desensitization and downregulation of the GnRH receptors, while GnRH antagonists act via the canonical competitive blockage. These treatments reduce FSH and LH levels, thereby reducing the systemic levels of sex steroids which stimulate leiomyoma growth. However, leiomyomas inherently harbor aromatase activity and synthesize their own estrogen; hence, treatment with systemic estrogen antagonists may provide better tumor control. Another important factor in BML pathogenesis is progesterone, and both progesterone receptor antagonists and high-dose progesterone receptor agonists may reduce BML growth. Following surgical treatment of the calvarial mass and radiotherapy of the vertebral metastatic foci, our BML case was successfully managed with hysterectomy and anastrozole treatment. Higher awareness of BML cases and their molecular endocrinological features in the neurosurgical community may pave to develop better strategies for treatment of these tumors causing high morbidity.

Fibroblast Growth Factor 23-Producing Phosphaturic Mesenchymal Tumor with Extraordinary Morphology Causing Oncogenic Osteomalacia.

A possible cause of hypophosphatemia is paraneoplastic secretion of fibroblast growth factor 23 (FGF-23). Tumors secreting FGF-23 are rare, mostly of mesenchymal origin, usually benign, and may be located anywhere in the body, including hands and feet, which are often not represented in conventional imaging. A 50-year-old woman presented with diffuse musculoskeletal pain and several fractures. Secondary causes of osteoporosis were excluded. Laboratory analysis revealed hypophosphatemia and elevated alkaline phosphatase, parathyroid hormone, and FGF-23. Thus, oncogenic osteomalacia due to neoplastic FGF-23 secretion was suspected. FDG-PET-CT and DOTATATE-PET-CT imaging demonstrated no tumor. Cranial MRI revealed a tumorous mass in the left cellulae ethmoidales. The tumor was resected and histopathological examination showed a cell-rich tumor with round to ovoid nuclei, sparse cytoplasm, and sparse matrix, resembling an olfactory neuroblastoma. Immunohistochemical analysis first led to diagnosis of olfactory neuroblastoma, which was later revised to phosphaturic mesenchymal tumor. Following the resection, FGF-23 and phosphate levels normalized. In conclusion, we here describe a patient with an FGF-23-secreting phosphaturic mesenchymal tumor with an unusual morphology. Furthermore, we emphasize diagnostic pitfalls when dealing with FGF-23-induced hypophosphatemia.

A rare case of angiosarcoma with skull masses and erythropenia and thrombocytopenia: A case report and review of literature.

RATIONALE: Primary splenic angiosarcoma (PSA) is a rare, fatal neoplasm originating from sinusoidal vascular endothelial cells, and usually metastasizes and almost always has a poor prognosis. Surgical excision is the main treatment of this highly malignant disease. PATIENT CONCERNS: We reported a special case of a 68-year-old female who had a 6-month history of scalp masses. DIAGNOSIS: The patient was found to have 2 skull masses on computed tomography (CT). Laboratory findings revealed erythropenia and thrombocytopenia. Enhanced abdomen magnetic resonance imaging (MRI) showed multiple masses in liver and spleen. The pathological result of the skull masses was revealed to be metastatic angiosarcoma. INTERVENTIONS: The patient underwent surgical excision of skull masses, and no subsequent radiotherapy or chemotherapy was done. OUTCOMES: The patient died due to dyscrasia at August 12, 2015, with a survival of nearly 1 month. LESSONS: We highlight the importance for clinicians to be aware of this rare neoplasm, and to consider it in the differential diagnosis when encountering a skull mass. Early confirmation and treatment may improve the prognosis.

Single skull metastasis 15 years after primary treatment of prostate cancer and with undetectable PSA levels: a case report and review of the literature.

Prostate cancer is the first cause of skull metastases in men, accounting for 12-18% of all cases. This condition is generally a late event in the course of the disease, involving patients with disseminated lesions. Quite rarely is skull involvement the first and single site of distant recurrence. We report the case of a patient who developed a single skull lesion 15 years after primary treatment of prostate cancer, in the presence of undetectable PSA levels. Pathological assessment performed after resection of the lesion revealed a metastasis from prostate carcinoma. Basing on this experience the appearance of craniofacial pain or a nerve deficit in patients with a history of prostate cancer should alert the clinician to exclude distant recurrence of disease, even in the presence of undetectable PSA levels and even if many years have elapsed since the treatment of the primary tumor. Knowledge of these manifestations will reduce any diagnostic delay and lead to the effective delivery of appropriate treatment.

Tumor-induced osteomalacia originating from the temporal bone: a case report.

BACKGROUND: Tumor-induced osteomalacia (TIO) is a rare clinical entity in which secondary osteomalacia is induced by tumor-related products. Fibroblast growth factor 23 (FGF-23) mRNA is overexpressed in the tumor tissue, leading to impaired reabsorption of phosphorus in the renal tubules and hypophosphatemia. Curative treatment is considered to be total resection of the tumor. METHODS AND RESULTS: A 53-year-old woman had experienced systemic bone pain and muscle weakness for several years. She had refractory hypophosphatemia and marked elevation of serum FGF-23 level. Whole body imaging eventually revealed a hypervascular mass in the right temporal bone, leading to a diagnosis of TIO. She underwent skull-base surgery after embolization of the tumor. After the en bloc resection, FGF-23 became undetectable, phosphate reabsorption normalized, and all symptoms resolved. CONCLUSIONS: We discuss the clinical features and treatment options for this rare disease.

[A woman with low hemoglobin values]. / Een vrouw met een lage hemoglobinewaarde.

A 48-year-old woman presented with a low hemoglobin count and multiple lytic skull lesions caused by multiple myeloma.

Epithelioid hemangioendothelioma presenting with severe myelofibrosis and a high serum hyaluronan level.

Epithelioid hemangioendothelioma (EHE) is a rare tumor originating from the vascular endothelium; it has an intermediate malignant potential. EHEs affect all age groups and mostly originate from the soft tissues of the extremities, lungs, and liver. Spinal EHEs, especially those occurring in the bone marrow region, are extremely rare. We report a case of EHE with massive involvement of the liver, vertebrae, and cranial bones that caused severe myelofibrosis (MF) in a 67-yr-old-male patient. Hyaluronan deposits were diffusely observed in the tumor tissue biopsies obtained from both the liver and bone marrow. Furthermore, the serum hyaluronan level increased markedly along with rapid progression of the disease. To the best of our knowledge, this is the first report of MF occurring in an EHE; hyaluronan may have played an important role in the pathogenesis of fibrosis in this case.

Hypercalcemia in a patient with B-cell acute lymphoblastic leukemia: a role of proinflammatory cytokine.

The complication of hypercalcemia is reported to occur only in 2.5-4.8% of patients with acute lymphoblastic leukemia (ALL). We herein report a 53-year-old female patient with early B-cell ALL, complicated with extreme hypercalcemia (15.2 mg/dL). Bone X-ray revealed osteolytic changes in many locations. Serum 1,25(OH)2vitaminD3 and parathyroid hormone (PTH) levels were suppressed below normal ranges on admission. The circulating parathyroid hormone-related protein (PTHrP) value was within a normal range (< 1.1 pmol/L). Serum concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and soluble IL-2 receptor were increased to 72 pg/ml, 25.3 pg/ml, and 1469 U/ml, respectively. Following the induction chemotherapy, the serum calcium level was promptly normalized accompanied with decreases in serum TNF-alpha, IL-6 and soluble IL-2 receptor values to 34 pg/ml, 6.35 pg/ml, and 737 U/ml, respectively. Serum PTHrP values remained within detectable levels. To our knowledge, this is the first case of B-cell ALL in a patient who developed hypercalcemia with elevated concentrations of TNF-alpha, IL-6, and soluble IL-2 receptor, but not related to PTHrP. High circulating proinflammatory cytokines may have contributed to development of ALL-induced osteolysis and hypercalcemia in the present case.

Testing the hypothalamic-pituitary-adrenal axis in survivors of childhood brain and skull-based tumors.

The objective of this study was to determine whether a low dose of ACTH (0.2 microg/kg) improves the sensitivity of ACTH testing in detecting hypothalamic-pituitary-adrenal (HPA) axis abnormalities in survivors of childhood brain and skull-based tumors. Twenty-two children who had undergone treatment for brain or skull-based tumors were enrolled in a prospective study to extensively evaluate the HPA axis. Five tests of the adrenal axis were evaluated in each patient, including determination of basal serum cortisol, a standard ACTH test (250-microg i.v. bolus), a low dose ACTH test (0.2 microg/kg i.v. bolus), an insulin tolerance test, and a single dose metyrapone test. Cortisol responses to both ACTH tests were nearly identical. Two patients (9%) failed the low dose ACTH test, whereas three (14%) failed the standard ACTH test; five of the children (23%) failed the insulin tolerance test, and five (23%) had abnormal responses to metyrapone. One child who initially passed the metyrapone test failed the test 19 months later after becoming symptomatic. All children with abnormal metyrapone test results had low levels of basal cortisol secretion. In this study, the low dose ACTH test did not improve the sensitivity of ACTH testing for evaluation of the HPA axis. We conclude that a single morning basal cortisol level is a good screen for testing the HPA axis in children. We recommend confirming HPA axis dysfunction with the single dose metyrapone test, although this test also has limitations.

[Characteristics of the level of lipid-bound sialic acids in the blood of patients with brain tumors]. / Nekotorye osobennosti soderzhaniia lipidno-sviazannykh sialovykh kislot v krovi bol'nykh s opukholiami golovnogo mozga.

In hemispheric tumors, the highest blood levels of lipid-conjugated acid were found in patients with malignant tumors despite their histology. In the blood of patients with benign tumors of the same site, the content of lipid-conjugated acids was the same as the control ones. However, the blood of patients with chiasmal-cellar tumors did not show these features. The blood level of lipid-conjugated acids in these patients did not depend on tumor histogenesis, but it was generally high. In patients with benign tumours of the chiasmal-cellar region, the levels of lipid-conjugated acids were the same as in patients with malignant hemispheric tumors. This is suggested by the fact that patients with meningiomas or gliomas of the chiasmal-cellar site without anaplastic signs exhibit much higher blood levels of lipid-conjugated acids than those with the similar tumors of the hemispheric site.

AL kappa amyloid in a solitary extradural lymphoma.

A 68 year old man with a 10 year history of apparently benign IgM kappa paraproteinaemia presented with dysarthria, left hemiparesis, and a sensory peripheral neuropathy. A calcified right temporoparietal extradural mass was shown by scintigraphy with 123I-serum amyloid P component to contain amyloid. There were no extracranial amyloid deposits. Clinical improvement followed craniotomy and partial resection of tissue which consisted of amyloid and a mixed mononuclear cell infiltrate. The amyloid fibrils consisted of the framework 1 region of the variable domain of monoclonal kappa IV immunoglobulin light chains. There was a prominent B-cell clonal immunoglobulin gene rearrangement in the tumour tissue, supporting a diagnosis of lymphoplasmacytic lymphoma, but no sign of systemic lymphoma. Neurological state, tumour volume, and quantity of amyloid have remained static for two years after treatment with chlorambucil.

Melanotic neuroectodermal tumor of infancy in the skull associated with high serum levels of catecholamine. Case report.

The case of a 5-month-old boy with a left retromastoid melanotic neuroectodermal tumor of infancy is presented. The tumor extended from the subcutaneous tissue of the occiput to the cerebellar hemisphere. Histologically, the epidural part of the tumor was composed of undifferentiated neuroblasts, dense connective tissue, and glandular structures lined by melanin-containing cuboidal cells, whereas the subdural part contained differentiated neuroblasts and melanin-containing cells. The preoperative high serum levels of adrenaline, noradrenaline, vanillylmandelic acid, and neuron-specific enolase returned to normal after two operations and two cycles of chemotherapy; however, the dopamine level was mildly elevated. These data and immunohistochemical and ultrastructural findings strongly suggest that melanotic neuroectodermal tumor of infancy is derived from the neural crest.

A paraneoplastic syndrome associated with glomus tumors of the skull base? Early observations.

Independent secretion of vasoactive substances by glomus tumors of the skull base is widely recognized. Surgical removal of these tumors often results in an unexplained prolonged postoperative ileus, even in cases in which the vagus nerve is preserved. There is evidence that these tumors may secrete neuropeptides, such as cholecystokinin, in addition to catecholamines. A retrospective analysis of cases of glomus tumors of the skull base operated on at The Otology Group was carried out to correlate preoperative neuropeptide levels, vagus nerve status at surgery, and duration of postoperative ileus. High circulating levels of cholecystokinin associated with these tumors may be responsible for the unexplained phenomenon of prolonged postoperative ileus. The relevance of neuropeptides to the postoperative management of these patients is discussed. Preventive measures that may avert the potentially lethal complications of aspiration and negative nitrogen balance are described.

Plasma vasopressin, cortisol, and growth hormone concentrations in relation to surgery in the suprasellar region.

Posterior and anterior pituitary functions were assessed in 8 patients before, during, and after surgery for tumors in the suprasellar region. Preoperatively, all patients but one responded adequately to an osmotic stimulus with a rise in plasma vasopressin (AVP) and all but one showed adequate cortisol response to adrenocorticotropic hormone (ACTH) and hypoglycemia. During surgery a transient rise was seen in plasma levels of AVP (5 out of 8 patients), cortisol (7 out of 8 patients) and growth hormone (4 out of 8 patients). This response could be predicted from the preoperative stimulation tests. Postoperatively the AVP response to osmotic stimuli was impaired in 4 out of 5 patients, although urine volume had returned to normal after a transient polyuric phase. The response of plasma cortisol to ACTH was still adequate but lower than preoperatively.