Molecular heterogeneity of head and neck squamous cell carcinoma defined by next-generation sequencing.

Head and neck squamous cell carcinoma (HNSCC) can be divided into two different clinical entities based on their association with high-risk subtypes of human papilloma virus (HPV16 and HPV18). Dissimilarities in prognosis and molecular profiles have attracted much attention in recent years, in part because of increasing rates of HPV infection in HNSCC; however, the underlying mechanisms and detailed genetic profiles that set these tumors apart are still elusive. To elucidate oncogenic pathways in HNSCC with and without HPV infection, we used targeted next-generation sequencing to interrogate single-nucleotide polymorphisms (SNPs) in 50 cancer-related genes. We detected SNPs in 25 of these genes from HNSCC tissue specimens with and without HPV infection. In 5 of the 25 genes, variant patterns were similar regardless of HPV infection status. A greater number of sequence variants in genes from the tyrosine kinase receptors and their associated pathways were preferentially present in HPV(+) specimens. SNPs in genes related to tumor-suppressor functions were more prevalent in HPV(-) HNSCC specimens. The observations may help to elucidate mechanisms involved in the molecular pathogenesis of two clinically diverse subclasses of HNSCC. Over-representation of SNPs in either HPV(+) or HPV(-) HNSCC is another indicator of potentially actionable sequence variants for targeted therapy.

Complete regression of papillary tumor of the pineal region after radiation therapy: case report and review of the literature.

Papillary tumor of the pineal region (PTPR) is a rare neuroepithelial tumor that arises in the pineal region. The optimal treatment for PTPR remains controversial, as no definitive treatment strategy exists for this lesion. It is not clear whether aggressive surgical removal is superior to biopsy followed by radiotherapy. The majority of cases in the literature have undergone attempted gross total resection with a supracerebellar-infratentorial or a transcallosal-transventricular approach. In this report, we describe a case of PTPR in a 23 year-old male that presented as a third ventricular mass causing obstructive hydrocephalus. An endoscopic third ventriculostomy was performed followed by an endoscopic biopsy. Postoperative radiotherapy resulted in complete regression of the tumor with no evidence of tumor recurrence at 25 months. This case highlights a minimally invasive strategy for a rare neoplasm that resulted in a favorable response to radiation therapy, thereby avoiding the risks of aggressive surgical removal. We also review the radiographic and histopathologic features of PTPR and discuss various options of treatment reported in the literature.

Case of Anti-Single Recognition Particle-Mediated Necrotizing Myopathy After Influenza Vaccination.

Immune-mediated necrotizing myopathy is a very rare inflammatory disease affecting skeletal muscles. Immune-mediated necrotizing myopathy may be associated with myositis-specific autoantibodies including anti-single recognition particle and anti-3-hydroxy-3- methylglutaryl-coenzyme A reductase, infectious agents (HIV or hepatitis C), other connective tissue disorders (such as scleroderma), and malignancy. We reported a 28-year-old healthy woman presented with subacute onset ascending muscle weakness 2 weeks after an annual influenza vaccination. Cerebral Spinal Fluid study showed normal cell counts with elevated protein and nerve conduction study showed reduced diffuse compound muscle action potential amplitudes suggesting a diagnosis of Guillain-Barré syndrome. Despite treatment using intravenous immunoglobulin, her condition continued to get worse with new bulbar and respiratory muscle weakness. Eventually, the diagnosis of anti-single recognition particle-mediated necrotizing myopathy was made based on elevated creatine kinase, thigh magnetic resonance imaging, muscle biopsy, and positive antibody testing. Our patient responded to the combination of intravenous immunoglobulin, prednisone, and anti-CD20 monoclonal antibody, rituximab.

Sudden Death Associated With Incarcerated Small Bowel Due to Mesodiverticular Band.

Meckel's diverticulum is a congenital anomaly present in about 3% of the population and usually asymptomatic. Rarely, a mesodiverticular band extends from the tip of a Meckel's diverticulum to the mesentery, thought to be due to lack of involution of the left vitelline artery. The presence of this band creates a closed loop through which loops of bowel can become entrapped. Rare case reports have described incarceration of bowel and sudden death in children. We present such a case and discuss this entity.

Prognostic Differences: Epstein-Barr Virus-Associated Primary Leiomyosarcoma of the Spine Versus Spinal Leiomyosarcoma Metastases.

OBJECTIVE: The authors studied 6 cases of osseous leiomyosarcoma of the spine. Two of these cases were of immunocompromised human immunodeficiency virus (HIV)-positive patients with Epstein-Barr virus (EBV)-associated primary vertebral leiomyosarcomas. The remaining 4 cases were of patients with leiomyosarcoma metastases to the spine. METHODS: Each patient underwent surgical resection of their vertebral mass; however, the patients with the EBV-associated tumors had the best postoperative prognosis. RESULTS: The HIV-positive patients have had no further local recurrence, while the other 4 patients had rapid local recurrences requiring multiple surgical interventions. Furthermore, the patients living with HIV have lived longer with fewer leiomyosarcoma-related health complications. CONCLUSIONS: These findings suggest that EBV-associated vertebral leiomyosarcoma is of a less aggressive variety than metastatic leiomyosarcoma of the spine.

Fibroadenoma of the vulva. A report of two cases.

BACKGROUND: Vulvar fibroadenoma is a rare entity. It has been proposed that the tissue of origin is either ectopic breast tissue or vulvar mammarylike glands. Sporadic examples of benign and malignant vulvar tumors arising from such glands have been previously reported. CASES: We recently encountered two cases of vulvar fibroadenoma, one in a 29-year-old woman and one in a 42-year-old woman, with both neoplasms presenting clinically as vulvar cysts. CONCLUSION: Fibroadenoma of the vulva is an uncommon lesion histologically similar to fibroadenoma of the breast. Clinicians need to be aware that the lesion can occur in this location.

Progressive multifocal leukoencephalopathy: a rare cause of cerebellar edema and atypical mass effect. A case report.

Progressive multifocal leukoencephalopathy (PML) is an opportunistic demyelinating disease of the CNS caused by the JC papovavirus (JCV). Demyelination due to oligodendrocyte death leads to multifocal, asymmetric lesions. MRI is a valuable tool for detecting and differentiating PML from other neuropathies. Radiographically, PML classically presents as bilateral, subcortical white matter lesions with a lack of brain atrophy. As the disease progresses, lesions become larger and coalesce to become confluent. Minor edema and mass effect are infrequently described and the presence of significant mass effect suggests an alternative diagnosis. In our case, a patient demonstrated atypical marked infratentorial mass effect. Bilaterally, cerebellar lesions with associated mass effect were observed, as well as effacement of cerebellar folia and partial effacement of the fourth ventricle. The diagnosis of PML was confirmed with a biopsy of the right cerebellar lesion showing classic PML histology, with JCV DNA detection by polymerase chain reaction in the biopsy material.

Metastatic renal cell carcinoma, with a radiographically occult primary tumor, presenting in the operative site of a thoracic meningioma: long-term follow-up: Case report.

Lesions metastatic to the site of a meningioma resection from a different primary tumor are rare. Metastasis of a tumor without a known primary tumor is also rare. Metastasis of a renal cell carcinoma, without an identifiable primary tumor, to the bed of a meningioma resection has not been previously reported. The authors describe the case of a 54-year-old man who presented with decreased sensory and motor function in the lower extremities. He underwent T3-5 laminectomies and gross-total removal of an intradural, extramedullary meningioma. The postoperative course was uneventful, and the patient regained full neurological function. After a 3-year period, he developed progressive upper thoracic pain and lower-extremity paresthesias. Imaging studies showed an epidural mass at the T2-4 levels and what appeared to be blastic involvement of the T2-4 vertebrae. A metastatic workup was negative. Emergency revision laminectomies yielded a fibrous, nonvascular mass. Neuropathology was consistent with metastatic renal cell carcinoma. After 6 months, the patient's symptoms of pain and paresthesias recurred. Repeat excision, with decompression of the spinal cord, revealed tumor cells morphologically and immunophenotypically similar to those obtained from the prior surgery. Cytogenetic analysis confirmed the presence of metastatic renal cell carcinoma. A novel case of an epidural metastatic renal cell carcinoma, of unknown primary origin, in the same operative bed of a previously resected intradural, extramedullary meningioma of the thoracic spine is reported.

Giant suprasellar Rathke's cleft cyst mimicking craniopharyngioma: implications for a spectrum of cystic epithelial lesions of ectodermal origin.

Cystic epithelial lesions such as Rathke's cleft cysts (RCCs) and craniopharyngiomas may be difficult to distinguish on a clinical, radiographic, and sometimes histopathological basis. We describe a case of a giant 6.5 cm suprasellar cystic lesion that was presumed to be a craniopharyngioma based on the neuroimaging findings. The lesion extended from the anterior skull base and sella turcica to the lateral ventricle and sylvian fissure resulting in obstructive hydrocephalus. Complete surgical removal of the suprasellar lesion was achieved using an extended frontotemporal transbasal skull base approach. Intraoperatively, the cyst wall was thickened and partially calcified, resembling a craniopharyngioma. However, the histopathological examination revealed findings most consistent with a RCC with additional features of extensive squamous metaplasia, metaplastic bone formation, and chronic inflammation. The case raises the issue of whether there is a pathologic continuum of parasellar ectodermal lesions which may account for the overlap of features and transitional states. In this report, we discuss the possible spectrum between RCCs and craniopharyngiomas, and also emphasize the importance of complete resection of the cyst wall in RCCs that exhibit squamous metaplasia, inflammation, or ossification to minimize the probability of recurrence.

Vascular inflammation with eosinophils after the use of n-butyl cyanoacrylate liquid embolic system.

OBJECTIVE AND IMPORTANCE: Currently, n-butyl cyanoacrylate (n-BCA) is one of the most widely used liquid embolic agents in the treatment of intracranial arteriovenous malformations (AVMs). The cases of three patients are reported who underwent endovascular embolization with n-BCA, followed by resection in two and post-embolization hemorrhage with emergent evacuation in one, with histologic demonstration of an eosinophilic vasculitis found in resected AVM specimens. This is probably the first report of this tissue reaction, which may have theoretically serious clinical implications. CLINICAL PRESENTATION: In this series, three patients (2 women, 1 man) presented with intracranial AVMs (Spetzler-Martin I-III) with the lesions located in the frontal lobe in two of the patients and in the parietal lobe in one. All patients presented with headache, and one also had new-onset seizures. INTERVENTION: All patients underwent embolization with n-BCA before a planned, staged surgical resection of the embolized AVMs. One patient had four embolizations over a 5-month period, one had three embolizations over 3 months complicated by hemorrhage after embolization requiring emergent evacuation of the hematoma, and the third patient had a single embolization. In all three patients, surgical and autopsy specimens showed an inflammatory response within the embolized vasculature with a prominent eosinophilic infiltrate. CONCLUSION: The eosinophilic vasculitis seen in the pathology specimens may represent a previously undocumented hypersensitivity reaction following exposure to n-BCA, with the potential for adverse sequelae, including increased risk of hemorrhage as was seen in one of our patients.

Tumefactive Multiple Sclerosis presenting as Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) plaques appear as well-demarcated, homogenous small ovoid lesions on magnetic resonance imaging (MRI). Atypical radiographic features of MS lesions include size greater than 2 cm, mass effect, and edema. Tumefactive MS lesions can radiographically mimic intra-cranial neoplasms, infarction, as well as infections. In atypical cases of tumefactive demyelinating lesions, brain biopsy may be required for the diagnosis. METHODS: The authors describe the case of a 43 year old woman who presented with worsening right-gaze preference and left side weakness and was initially diagnosed with acute ischemic stroke. The patient underwent laboratory investigation and brain contrast-enhanced MRI before undergoing brain biopsy. RESULTS: Fluid attenuation inversion recovery (FLAIR) MRI showed an increase in signal intensity in the right frontal lobe sub-cortical region. Diffusion-weighted imaging showed an area of restricted diffusion involving the white matter of the right-frontal lobe. Cerebrospinal fluid studies were normal except for the presence of oligo-clonal bands. Magnetic resonance spectroscopy (MRS) demonstrated an elevated choline (Cho)/creatine ratio, increase lactate, and normal N-acetylaspartate (NAA)/creatine ratio, findings suggestive of an inflammatory or a demyelinating disease. A brain biopsy of the right frontal lesion was performed and revealed well-demarcated foci of demyelination with axonal preservation. Peri-vascular and parenchymal CD3(+) T-cells were also identified within the demyelinated foci, findings that further supported the diagnosis of active multiple sclerosis. CONCLUSION: Tumefactive MS can be radiographically misdiagnosed as one of several conditions, among which are infarction, infections, and tumors. Brain biopsy may be needed for diagnosing challenging cases of tumefactive MS.

Severe chronic aortic insufficiency requiring valve replacement: an infrequent complication of Takayasu's disease.

Takayasu's arteritis (TA) is a granulomatous vasculitis of medium and large arteries, which most often presents as pulseless disease due to widespread arterial stenoses. Only the minority of TA patients have aortic valve insufficiency, which is due to aortic root dilatation following aortitis and aneurysm formation. No other cardiac valve is involved. We report a case of Takayasu's disease-related severe aortic insufficiency (AI) in a Filipino woman, which necessitated aortic valve replacement. It is important to consider TA in the differential diagnosis of AI in young women, particularly those with early-onset systemic hypertension and pulse deficits. Early diagnosis and therapy of TA can improve outcomes.