Adrenocorticotropic hormone-producing pituitary carcinoma with intracranial metastases.

BACKGROUND: Pituitary carcinomas are rare and challenging clinical entities. Because of the paucity of cases, there is limited information in the literature on how best to diagnose and treat pituitary carcinomas. METHODS: We review the literature and describe a woman who presented with an adrenocorticotropic hormone (ACTH)-secreting pituitary macroadenoma that later evolved into a carcinoma with intracranial metastases. RESULTS: A 39-year-old woman presented at age 27 with classic findings of Cushing's syndrome and a pituitary macroadenoma. Her initial treatment was transsphenoidal surgery, during which we confirmed an ACTH-secreting pituitary neoplasm. For 5 years, she was asymptomatic before her first recurrence. During the next 6 years, she underwent four transsphenoidal surgeries and two craniotomies. After each surgery, there was some reduction in the size of the macroadenoma but the residual tumor mass would rapidly enlarge. Immunochemical staining was positive for ACTH, and a stain for Ki-67 antigen showed a high mitotic index. Eleven years after her initial presentation, magnetic resonance imaging revealed bilateral hippocampal and tempero-occipital masses. The patient's health continued to deteriorate, largely from complications of severe hypercortisolemia, and she died from sepsis. At postmortem, the hippocampus and tempero-occipital lobe masses proved to be a pituitary tumor with positive ACTH staining. CONCLUSIONS: Pituitary carcinomas are rare, may present many years after diagnosis of a primary pituitary adenoma, and should be suspected in patients with persistent or recurrent disease. Reliable histopathologic ways to distinguish between carcinoma and adenoma are difficult because the features of hypercellularity, nuclear pleomorphism, and mitotic figures are not always helpful.

Neurosarcoidosis: clinical features, diagnosis, and management.

Sarcoidosis is a multisystemic granulomatous disease, which uncommonly affects nervous system. However, when present, it may affect both central and peripheral nervous systems and potentially mimics other chronic diseases of the nervous system. Pathogenesis of neurosarcoidosis remains largely unknown, and its diagnosis and management pose serious challenges to clinicians. Early diagnosis and aggressive treatment of neurosarcoidosis are necessary to produce satisfactory clinical outcomes. This review discusses clinical manifestations, current diagnostic studies, and currently available modalities for management of neurosarcoidosis.

Acantholytic squamous cell carcinoma in upper aerodigestive tract: histopathology, immunohistochemical profile and epithelial mesenchymal transition phenotype change.

Acantholytic squamous cell carcinoma is a rare variant of squamous cell carcinoma in the mucosa of upper aerodigestive tract. Histomorphologically, acantholytic squamous cell carcinoma may lose the typical features of conventional squamous cell carcinoma and mimic other epithelial or mesenchymal malignancies due to advanced acantholysis and dyskeratosis. Because of its rarity, information of prognosis, pathologic features and immunohistochemical profiles is limited. We have studied clinicopathologic features and immunohistochemical profiles of four acantholytic squamous cell carcinoma cases arising from upper aerodigestive tract. Clinical results indicate an aggressive biologic behavior. Morphologically, all tumors revealed significant acantholysis with separation of tumor cells and intratumoral spaces. The tumor cells were highly pleomorphic and growth patterns were variable. In immunohistochemical studies, all tumor cells revealed positive reactions for AE1/AE3 and p63 supporting a squamous epithelial origin. In contrast to conventional aerodigestive squamous cell carcinoma, acantholytic squamous cell carcinoma showed significant reductions of cytokeratin19, E-cadherin and concomitant up-regulation of vimentin expression. Both morphologic features and immunohistochemical profiles indicate that acantholytic squamous cell carcinoma has acquired an epithelial mesenchymal transition phenotype. However, in contrast to other solid malignant tumors, the epithelial mesenchymal transition phenotype change in acantholytic squamous cell carcinoma is not limited to the invasive front of the peripheral tumor but, rather, diffusely involves entire neoplastic lesion. In addition, because cytokeratin 19 staining is attenuated, this would be an insensitive marker for following up and/or in detecting disseminated tumor cells in cases of acantholytic squamous cell carcinoma in upper aerodigestive tract.

Protothecosis: report of a case with 20-year follow-up, and review of previously published cases.

We present a Prototheca wickerhamii wound infection case that failed treatment with ketoconazole but was cured with amphotericin-B plus tetracycline. The patient was immunocompetent but had had local steroid injections. We reviewed another 159 cases from the literature. Prototheca has infected many areas of the human body, but most often skin, olecranon bursa, or wounds. Prior treatment with steroids and immune deficiencies are contributing factors. Itraconazole and fluconazole are reasonable initial treatments for patients with mild infections. For serious infections, or for infections that have failed azole treatment, amphotericin-B is the treatment of choice.

Sphenoid sinus basaloid squamous cell carcinoma presenting as a sellar mass: report a case with review of the literature.

Basaloid squamous cell carcinoma (BSCC) is a distinctive variant of squamous cell carcinoma (SCC) with more aggressive behavior. It occurs preferentially in the upper aerodigestive tract. Sinonasal tract BSCC is uncommon, and only limited studies have been reported in literature. In these studies, most BSCCs arose from the nasal mucosa with or without extension to the paranasal sinuses. Rare reported cases of BSCC involved only the paranasal sinus. In this report, we present a case of a female patient with a sphenoid sinus mass. Clinically, the patient had progressively decreasing vision and headache. Magnetic resonance imaging (MRI) and computerized tomographic (CT) scan showed an infiltrating tumor mass involving the sphenoid sinus and the sella with compression of the optic nerve. Pathologic examination revealed an invasive basaloid epithelial neoplasm that was arranged in lobules, nests and cords. The tumor also showed palisading of peripheral cells, focal abrupt squamous differentiation and in situ carcinoma in the surface mucosa. In the immunohistochemical studies, this tumor revealed a strongly positive nuclear staining for p63. The morphologic and ancillary studies indicated a BSCC. To the best of our knowledge, this is the first report of sinonasal tract BSCC that mainly involved the sphenoid bone and sella. In this region, BSCC should be distinguished from benign and malignant neoplasms that more often affect sella and base of skull, such as pituitary adenoma with extensive necrosis, small cell neuroendocrine carcinoma (SCNC), olfactory neuroblastoma, malignant germ cell tumor, paranasal adenoid cystic carcinoma (ACC), and a variety of metastatic malignancies.

Fine needle aspiration of parapharyngeal space adult rhabdomyoma: a case report.

BACKGROUND: Rhabdomyomas are rare benign tumors of striated muscle and include cardiac and extracardiac types. Extracardiac rhabdomyomas are divided in three subtypes (adult, fetal, genital). The adult type is usually found in the head and neck regions of elderly persons. Misinterpretations in initial diagnosis of adult rhabdomyomas on fine needle aspiration have been reported. CASE: A 64-year-old man presented with gurgling and difficulty swallowing for approximately 3 months. Computed tomography and magnetic resonance imaging showed a 5.8-cm solid mass located in the right parapharyngeal space. Fine needle aspiration smears were cellular, showing cohesive clusters of cells with scattered individual cells. Cells had abundant eosinophilic glassy cytoplasm, peripherally placed round nuclei, and prominent nucleoli. Many traversing vessels were noted, but cross-striations were not seen. The cell block demonstrated clusters of cells with abundant eosinophilic granular cytoplasm, some with clear and/or vacuolated cytoplasm, and possible cross-striations. Tumor cells were positive for desmin. The lesion closely resembled normal muscle tissue. Electron microscopy showed many cells containing actin and myosin filaments with Z-band material. CONCLUSION: Correct diagnosis can be achieved with a combination of awareness of the lesion, familiarity with the characteristic cytologic features, and application of appropriate immunohistochemistry markers. Classic electron microscopic findings can support the diagnosis.

Papillary tumor of pineal region: prolonged control rate after gamma knife radiosurgery - a case report and review of literature.

Papillary tumors of the pineal region (PTPR) are very rare. We describe the first report of a PTPR empirically managed with gamma knife radiosurgery. The patient was initially shunted and referred for empirical gamma knife radiosurgery. After initially showing some improvement, he had recurrence of tumor after 7 years. For recurrence he underwent a gross total resection and the biopsy established the diagnosis of PTPR. Further research needs to be done as to the efficacy of gamma knife surgery for PTPR. In addition, the role of stereotactic biopsy for eligible patients should be considered as the initial step to direct the treatment of choice.

Neurologic presentations of systemic vasculitides.

Vasculitis or angiitis refers to a group of inflammatory disorders of the blood vessels that cause structural damage to the affected vessel, including thickening and weakening of the vessel wall, narrowing of its lumen, and, usually, vascular necrosis. Systemic vasculitis is classified according to the vessel size and histopathologic and clinical features. Vasculitides with small vessel involvement typically include Henoch-Schönlein purpura and cryoglobulinemia. Polyarteritis nodosa and Wegener granulomatosis are small- and medium-sized vessel vasculitides, whereas temporal arteritis and Takayasu arteritis involve large vessels. In this article, the authors provide a review of the neurologic presentations of the major systemic vasculitides.

Increased expression of p53 protein correlates with the extent of myocyte damage in cardiac allograft rejection.

Acute cardiac allograft rejection (ACAR) has been associated with a poor prognosis. The early diagnosis of ACAR necessitates the accurate detection of myocyte damage. Nuclear damage activates p53, a transcription factor that initiates apoptosis and repair. Endomyocardial biopsies (n=25) from 10 cardiac allograft recipients were stained for nuclear p53. The biopsies were divided into rejection groups based on the grading of ACAR: group 1, grade 0; group 2, grade Ia and Ib; group 3, grades II and III. While clinical indices did not correlate with myocyte damage, significantly more myocytes in group 3 stained for nuclear p53 (2.48+/-0.60/mm(2)) compared with group 1 (0.22+/-0.12/mm(2)) and group 2 (0.43+/-0.18/mm(2)). Increased expression of p53 in cardiac myocytes with grade II or grade III rejection provides an objective quantification as an aid in the diagnosis of ACAR.

Amyloidoma presenting as a butterfly glioma on positron emission tomography scan and magnetic resonance-spectroscopy: a case report and review of the literature.

PURPOSE: Isolated amyloidoma rarely involves the nervous system. MATERIALS: We report a patient with progressively worsening triparesis and numbness in his extremities. RESULTS: Magnetic resonance imaging (MRI) of the brain revealed a mass lesion involving both hemispheres, which on positron emission tomography (PET) scan and magnetic resonance-spectroscopy (MR-SPECT) appeared to be a butterfly glioma. However, neuropathological examination revealed a large area with localized vascular amyloidosis. CONCLUSION: This is the first case of a localized central nervous system vascular amyloid to imitate a butterfly glioma on MRI and PET scan studies.

Brainstem astroblastoma: a case report and review of the literature.

BACKGROUND: Astroblastoma is a rare glial tumor that occurs mainly in the cerebral hemispheres of young adults. Our purpose in writing this article is to report one case of astroblastoma located within the medulla and review the literature on this infrequent tumor. METHODS: One case of astroblastoma was retrospectively reviewed. Presenting complaints, radiographic images, operative procedure, and histopathologic findings were recorded. RESULTS: Contrast-enhanced MRI scan revealed a well-defined, well-circumscribed, contrast-enhanced cystic lesion approximately 16 mm in diameter within the medulla oblongata. Light microscopy demonstrated a papillary neoplasm composed of mildly pleomorphic cells with indistinct cytoplasmic borders. The nuclei were generally round to oval in shape. Occasional rosettes of tumor cells were seen around blood vessels. Mitoses were not seen within the submitted specimen. One small area of necrosis was present. The tumor exhibited thickened but not hyalinized blood vessel walls. The tumor cells exhibited strong staining for EMA and vimentin throughout the tissue section. Neurofilament, CAM 5.2, and CK immunostains were negative, except for rare positive staining of CK between cells and within rare tumor cells. Ki-67 was positive in small numbers of tumor nuclei, with an overall reactivity of 7%. By electron microscopy, the tumor nuclei had irregularly round to oval nuclei with moderate clumping of the chromatin, especially at the nuclear margins. CONCLUSIONS: The combination of the radiologic and histopathologic characteristics of this tumor is necessary for making the diagnosis of astroblastoma. This article serves to summarize these characteristics as well as to report of an unusual location for this mainly hemispheric tumor.

Glioblastoma multiforme in two non-nuclear family members.

BACKGROUND: In spite of traditional and current epidemiological research, there have been few environmental risk factors identified for malignant brain tumors. It has been an equally difficult challenge to identify genetic causes for brain tumors because of the rarity of families with multiple affected individuals, which prevents the use of traditional methods of genetic analysis such as genetic linkage, sib-pair, or even population-based association studies. Thus, it is important to take advantage of rare occasions of familial brain tumors. METHODS: Identification and careful study of such families may provide important clues about the etiology of brain malignancies. We studied one family of which two nonnuclear family members were affected with pathologically diagnosed glioblastoma multiforme. Fluorescence in situ hybridization (FISH) assays were used on archival sections from each patient's tumor to investigate the loss and/or gain of important allelic endpoints. Tissue sections were prepared and processed for FISH. DNA probes for targeted gene loci were used to assess allelic gain/loss. FISH probes targeted regions including 19q13, 1p36, 10q/phosphate and tensin homolog (PTEN), chromosome 3, chromosome 7, chromosome 17/17q and p53/17p. RESULTS: FISH analyses identified distinct abnormalities in the two patients, suggesting that despite the familial connections and histologically similar tumors, genetic abnormalities are abundant and heterogeneous among these malignancies. CONCLUSION: These abnormalities, however, serve to contribute to valuable information regarding patient outcomes, albeit their precise roles in the etiology of this malignancy are yet to be determined.

Treatment of refractory temporal arteritis with adalimumab.

High-dose corticosteroids (CS) are the mainstay of treatment for temporal (giant cell) arteritis (TA). A usually required long-term treatment with CS, ranging from 1 to 5 years or more, frequently leads to serious side effects in about 60% of patients. There is no conclusive evidence about the role of immunosuppressive agents like methotrexate and azathioprine in the treatment of TA. There are few reports of treatment of refractory or steroid-dependent TA with tumor necrosis factor alpha (TNF-alpha) inhibitors including infliximab and etanercept. TA is characterized by infiltration of the vessel wall by macrophages, giant cells, and T lymphocytes, with production of several cytokines responsible for the acute phase response. TNF-alpha has been demonstrated in up to 60% of the cells in all areas of inflamed arteries by immunohistochemical techniques; hence, it could play a pivotal role in the pathogenesis of TA. We report the first case of resistant TA, which was treated successfully with adalimumab, a fully human recombinant IgG1, anti-TNF-alpha monoclonal antibody. The efficacy of TNF-alpha inhibitors in resistant TA should be studied in larger, controlled studies.

Central pontine myelinolysis, an update.

Central pontine myelinolysis (CPM) can be regarded as one of the demyelinating syndromes. First described by Adams et al. in 1959 in their chronic alcoholic patients, it has now been described in the malnourished, the chronically debilitated, the renal, the hepatic and the transplant patient among others. Pathologically, it is defined as a symmetric area of myelin disruption in the center of the basis pontis, although similar symmetric lesions have also been described occurring with CPM as well as independently in other brain areas (extrapontine myelinolysis or EPM) including the cerebellar and neocortical white/gray junctional areas, thalamus and striatum. Possible mechanisms include a hyperosmotically induced demyelination process resulting from rapid intracellular/ extracellular to intravascular water shifts producing relative glial dehydration and myelin degradation and/or oligodendroglial apoptosis. The process most often occurs during rapid rebalancing of the electrolyte parameters in the hyponatremic patient. Avoidance of CPM/EPM is dependent upon recognizing those patients with conditions pre-disposing them to osmotic myelinolysis and then moderating the rate of normalization of the electrolyte imbalance. The morbidity and mortality of CPM/EPM has been greatly reduced by recognition of pre-disposing conditions, increased understanding of the pathophysiology, intensive treatment, and rapid diagnosis and monitoring with advanced neuroimaging.

Regulation of dextran sodium sulfate induced colitis by leukocyte beta 2 integrins.

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders whose etiology remains unknown. Reports have shown that infiltration of leukocytes into intestinal tissue is a pathognomonic hallmark for this disease. Leukocyte beta(2) integrins are heterodimeric adhesion membrane proteins that are exclusively expressed on leukocytes and participate in immune cell adhesion and activation. In this study, we examined the pathophysiological role of the beta(2) integrins CD18, CD11a, and CD11b in the pathogenesis of dextran sodium sulfte (DSS)-induced experimental colitis. Disease activity was measured by daily assessment of clinical parameters including stool consistency, weight loss, occult blood, and gross rectal bleeding. Histopathological changes including severity of inflammation, surface epithelial/crypt damage, and depth of injury were also determined. The CD18 null and CD11a null mice had significantly lower disease activity and cumulative histopathological scores compared to wild-type mice. Interestingly, CD11b null mice did not show protection against DSS colitis and displayed increased disease activity compared to wild-type mice. Examination of specific leukocyte populations in the distal colon from various mice revealed significant attenuation of neutrophil and macrophage infiltrates in CD18, CD11a, and CD11b null mice. Surprisingly, the CD11b null mice showed a significant increase in plasma cell infiltration in response to DSS suggesting that this molecule may influence plasma cell function during colitis. This study demonstrates that genetic loss of CD18 or CD11a is protective during experimental colitis and that CD11b may serve a regulatory role during development of disease.

Concomitant choroid plexus papillomas involving the third and fourth ventricles: A case report and review of the literature.

Choroid plexus papillomas (CPP) are histopathologically benign and rare central nervous system (CNS) neoplasms arising from the epithelium of the choroid plexus. The most common site of presentation of these lesions is in the fourth ventricle in adults and lateral ventricles in children. Third ventricular CPP are uncommon. In this study, we present a case of a 66-year-old woman with complaints of progressive confusion, lethargy, and weakness who was found to have concomitant third and fourth ventricular masses on imaging studies. The patient underwent a biopsy of the third ventricular mass. The biopsy was followed by staged resections of the fourth and third ventricular masses, respectively. Pathology from the biopsy and both resections was benign CPP. Multifocal concomitant CPP is rare. Concomitant CPPs may be secondary to mere coincidental tumor occurrence or to biologic seeding of cerebrospinal fluid (CSF) from a primary CPP despite otherwise benign histopathology. The primary treatment for CPP is surgical resection. Post-operative chemotherapy or radiation for CPP is of controversial benefit.

Primary intracranial leiomyosarcoma: report of a case and review of the literature.

A 26-year old man presented with a 3-month history of a progressively enlarging palpable parieto-occipital mass. A CT scan indicated the lesion arose from the dura with bony destruction. A stealth assisted craniotomy was performed with the provisional diagnosis of osteoblastic meningioma. Further histopathologic analysis of the intracranial mass was consistent with leiomyosarcoma. Staging evaluation, including CT and PET scans, demonstrated no other sites of disease. Despite complete surgical resection and radiotherapy to the resection site, the disease recurred locally and systematically 5 months later. Primary intracranial mesenchymal tumors are rare and few cases have been previously reported. Outcomes have been universally poor and current therapeutic approaches appear to have only limited benefit.

Fever, chills, and weakness in a 61-year-old man.

A 61-year-old man presented to the emergency department of a community hospital with a 2-week history of fever, chills, and sudden extreme weakness of his right arm and lower extremities. He also had a cough, shortness of breath, nausea, abdominal pain, diarrhea, and myalgia. Though initially alert and cooperative, he quickly became unresponsive. In addition, he had hyponatremia, renal insufficiency, and compromised cardiopulmonary function. He was admitted to the intensive care unit for suspected bacterial infection and was started on broad-spectrum antibiotics. Chest radiograph revealed miliary infiltrates consistent with infectious emboli or metastatic carcinoma. Despite intensive resuscitation, the patient died 36 hours after admission. At autopsy multiple nodular lesions were observed on gross examination of the lungs, perihilar and paratracheal lymph nodes, and liver. Microscopic sections of the lung (Figure 1) and brain (Figures 2 and 3) are shown.

Anaplastic thyroid cancer and hyperthyroidism.

We report a rare case of thyrotoxicosis in a patient with anaplastic thyroid cancer. A 65-yr-old male presented with a 2-d history of rapidly enlarging neck mass and back pain. Physical examination revealed a large, hard thyroid mass and resting tachycardia. He did not have any symptoms suggestive of airway compression at presentation. Thyroid hormone levels were consistent with a hyperthyroid state. CT scan of the neck and thorax showed a heterogeneous mass replacing the thyroid, bilateral pulmonary nodules, and a metastasis with pathological fracture at the level of T-8. Technetium-pertechnetate scan failed to show any uptake in the region of the thyroid. Fine needle aspiration of the thyroid revealed anaplastic thyroid cancer. The patient was started on steroids and radiation therapy of his spine lesion. Brief surgical exploration of the thyroid revealed extensive local infiltration of adjacent neck tissues and marked tumor necrosis. Immunohistochemical stains of the tumor were positive for p53, thyroglobulin, and thyroid transcription factor-1. The tumor had an extremely aggressive course and the patient died of asphyxiation from severe airway compromise 11 d after his initial presentation.