Pediatric Atypical Teratoid/Rhabdoid Tumors of the Brain: Identification of Metabolic Subgroups Using In Vivo 1H-MR Spectroscopy.

BACKGROUND AND PURPOSE: Atypical teratoid/rhabdoid tumors are rare, aggressive central nervous system tumors that are predominantly encountered in very young children. Our aim was to determine whether in vivo metabolic profiles correlate with molecular features of central nervous system pediatric atypical teratoid/rhabdoid tumors. MATERIALS AND METHODS: Twenty confirmed patients with atypical teratoid/rhabdoid tumors who underwent MR spectroscopy were included in this study. In vivo metabolite levels of atypical teratoid/rhabdoid tumors were compared with molecular subtypes assessed by achaete-scute homolog 1 expression. Additionally, brain-specific creatine kinase levels were determined in tissue samples. RESULTS: In vivo creatine concentrations were higher in tumors that demonstrated achaete-scute homolog 1 expression compared with those without achaete-scute homolog 1 expression (3.42 ± 1.1 versus 1.8 ± 0.8 IU, P < .01). Additionally, levels of myo-inositol (mI) (9.0 ± 1.5 versus 4.7 ± 3.6 IU, P < .05) were significantly different, whereas lipids approached significance (44 ± 20 versus 80 ± 30 IU, P = .07) in these 2 cohorts. Higher brain-specific creatine kinase levels were observed in the cohort with achaete-scute homolog 1 expression (P < .05). Pearson correlation analysis showed a significant positive correlation of brain-specific creatine kinase with absolute creatine (P < .05) and myo-inositol (P < .05) concentrations. CONCLUSIONS: In vivo MR spectroscopy may predict key molecular features of atypical teratoid/rhabdoid tumors at initial diagnosis, leading to timely patient risk stratification and accelerating the development of targeted therapies.

Atypical teratoid/rhabdoid tumor of the central nervous system in an 18-year-old patient.

OBJECTIVE: Atypical teratoid/rhabdoid tumors are aggressive neoplasms of the central nervous system occurring mainly in the early childhood and rarely in adults. We described a case of this tumor in an 18-year-old male patient without previous medical history. MATERIAL AND METHODS: The neoplasm was localized in the right frontotemporal area of the brain and was totally excised. The specimen was fixed in formalin and embedded in paraffin. The histological and immunohistochemical features of the neoplasm were assessed, while sequencing analysis as well as interphase fluorescence in situ hybridization (FISH) were performed. RESULTS: Histological and immunohistochemical analysis demonstrated atypical rhabdoid cells strongly and diffusely positive for EMA and Vimentin as well as focally immunoreactive for SMA and GFAP. Additionally, though no abnormalities detected in the coding sequence of the INI1 gene, interphase FISH studies were consistent with a homozygous deletion of the INI1 gene in the majority of examined nuclei. INI1 immunostaining demonstrated diffuse loss of nuclear INI1 expression in tumor cells. Taken together, the results were consistent with a diagnosis of atypical teratoid/rhabdoid tumor (ATRT). CONCLUSIONS: 26 previous cases of ATRT have been reported in adults, thus far. To our knowledge, this is the eighth case of an ATRT reported in an adult patient having genetic confirmation and the first one in which the tumor is, partly, localized in the right temporal area of the brain. This unusual presentation underlines the necessity of considering this devastating neoplasm in the differential diagnosis of malignant brain tumors of young adults.

Dystrophic neuritic processes in epileptic cortex.

Cortical dysplasia is a frequent finding in cortical resections from children with refractory epilepsy. Diagnostic criteria and a classification scheme for cortical dysplasia has been proposed, though the relationship between specific cortical dysplasia features and their causal relationship with epilepsy is poorly understood. We reviewed 28 surgical resections from children and identified a common and easily recognized feature of cortical dysplasia: maloriented, misshapen and occasionally coarse neurofilament stained process forming a dystrophic neuritic background. The dystrophic neuritic background was associated with other features of cortical dysplasia in all 28 patients with cortical dysplasia, 26 with refractory epilepsy and 2 patients with other neurologic diagnoses. In seven children with refractory epilepsy due to other pathologic diagnosis such as vascular or glial lesions, the dystrophic neuritic background was only found in one patient with a ganglioglioma and other features suggestive of an associated cortical dysplasia. Our data indicate that a dystrophic neuritic background is a common and relatively specific neuropathologic finding in cortical dysplasia.

Dysplasia: a common finding in intractable pediatric temporal lobe epilepsy.

BACKGROUND: Risk factors for temporal lobe epilepsy (TLE) include history of CNS infection, family history of epilepsy, and history of febrile convulsions (FC). Pre-existing cortical dysplasia (CD) may also predispose to refractory TLE, independent of other risk factors for epilepsy. METHODS: The authors reviewed the neuropathologic features of surgical tissue from temporal lobectomies of 33 pediatric patients with refractory TLE, with and without a history of epilepsy risk factors. RESULTS: CD was found in 64% (21/33) of all patients with refractory TLE, including 73% (11/15) patients with a history of FC, 66% (2/3) patients with CNS infections, and 83% (5/6) patients with a family history of epilepsy. Disrupted cortical lamination, dystrophic and maloriented neurons, and balloon cells characterized the CD found in the temporal neocortex. CONCLUSION: CD was seen in 21 of 33 surgical specimens from children with refractory TLE, including those with and without other epilepsy risk factors.

Breast cancer: initial diagnosis and current treatment options.

Topics discussed in this article are breast cancer versus benign breast conditions, the importance of physical examination used in conjunction with screening mammography in the detection of abnormalities, imaging options, diagnosis, treatment options, and the importance of follow-up care.

Mycotic aneurysm and cerebral infarction resulting from fungal sinusitis: imaging and pathologic correlation.

SUMMARY: A 73-year-old man was admitted with invasive aspergillus of the sphenoid sinus. Endoscopic debridement of the sphenoid sinus was complicated by rupture of a mycotic cavernous carotid artery aneurysm with severe epistaxis. The aneurysm was closed emergently by endovascular coil placement. Subsequently, the mycotic aneurysm extended intradurally and caused fatal subarachnoid hemorrhage. The radiologic-pathologic data illustrate the mechanism of fungal mycotic aneurysm formation and growth. This case emphasizes the need for rapid diagnosis of potential fungal involvement of the central nervous system and suggests the necessity for aggressive treatment once fungal cerebrovascular involvement is identified.

Utility of immunohistochemistry in the evaluation of necrotic thyroid tumors.

We have previously shown that necrotic tumors retain their immunoreactivity for a range of cytokeratin antibodies. Some thyroid tumors undergo extensive necrosis after fine-needle aspiration (FNA) procedures. We evaluated the sensitivity of antibodies on necrotic thyroid tumors by examining a series of thyroid tumors consisting of 10 Hurthle cell neoplasms, 8 carcinomas, and 2 follicular adenomas (12 with post-FNA necrosis). These were stained with antibodies to AE1/3, PANCK, thyroglobulin and S100. Four of the cases of papillary carcinoma were also stained with antibodies to CK19. As a control for the specificity of thyroglobulin immunoreactivity in necrotic tissue, we also stained 11 nonthyroid tumors with extensive necrosis (7 carcinomas, 1 lymphoma, 2 melanomas, 1 sarcoma) for thyroglobulin. Six of 8 thyroid carcinomas were positive for AE1/3 and PANCK; AE1/3 reactivity was retained in necrotic areas of 4 of 6. AE 1/3 was positive in necrotic portions of 5 of 10 Hurthle cell lesions, whereas PANCKwas negative in all but 1. Thyroglobulin reactivity was present in 18 of 20 cases, and was preserved in necrotic portions of 5 of 6 carcinomas, as well as 8 of 10 Hurthle cell neoplasms. S100 cytoplasmic reactivity was present in 4 Hurthle cell neoplasms and 1 papillary carcinoma; this staining was lost in necrotic areas. No staining by thyroglobulin was observed in the viable or necrotic areas of nonthyroid neoplasms. The preservation of cytokeratin reactivity, measured by AE1/3, in thyroid neoplasms is a diagnostically useful feature in spontaneous and post-FNA infarction. PANCK is not a well-preserved marker in necrotic thyroid tissue. This difference may be due to detection of keratin 19 by AE1/3. Thyroglobulin is preserved in some necrotic thyroid carcinomas and in Hurthle cell lesions. Preservation of thyroglobulin reactivity in necrotic tissue is specific in that no staining was observed in nonthyroid neoplasms. These results suggest that thyroglobulin is useful in demonstrating thyroid lineage of both primary and metastatic necrotic tumor masses.

Neurosarcoidosis presenting in the pituitary gland with normal endocrine studies.

Two cases of neurosarcoidosis in the pituitary gland are presented with a review of past cases from the literature. Previous reported cases have always shown changes on the ondocrine exis clinically. These two cases, however, were endocrinologically normal prior to surgery. The evaluation of neurosarcoid in the pituitary, clinically and radiographically, is discussed.

Sensitivity and specificity of antibodies on necrotic tumor tissue.

Immunohistochemistry occasionally is used to determine the lineage of entirely necrotic tumors. However, the sensitivity and specificity of antibodies on necrotic tissue are unknown. To determine the usefulness of immunohistochemistry with necrotic lesions, a series of 24 known tumors consisting of 14 carcinomas, 2 lymphomas, 2 melanomas, and 6 sarcomas (all with extensive necrosis) was examined for reactivity with 6 cytokeratin antibodies, S100, and LCA. Carcinomas stained positively with at least 1 cytokeratin antibody in 78% of the cases. The cytokeratin antibodies with the highest sensitivity were AE1, AE1/3, S903, and PANCK. These antibodies also retained specificity for epithelial differentiation; no reactivity was observed in the 10 necrotic nonepithelial tumors. LCA retained its reactivity with necrotic lymphoma, but S100 reacted with only one third of the necrotic lesions. Unexpectedly, reactivity for LCA and S100 occurred in some necrotic carcinomas. Keratin markers can be used on necrotic tissue to determine epithelial differentiation, but the results obtained with S100 and LCA on necrotic tissue should be interpreted with caution.

A murine model of allergic rhinitis: studies on the role of IgE in pathogenesis and analysis of the eosinophil influx elicited by allergen and eotaxin.

BACKGROUND: Allergic rhinitis is a prevalent disease with significant morbidity. Studies of its pathophysiology in human subjects have been limited. Nasal biopsy specimens are difficult to obtain, and nasal secretions incompletely reflect the cellular and molecular events in the mucosa. IgE-mediated mast cell activation and the elaboration of factors promoting eosinophil development and chemotaxis are likely to participate in pathogenesis. OBJECTIVES: We sought to develop a murine model of allergic rhinitis, to use it to assess the role of IgE in pathogenesis, and to study the effects of IL-5 and eotaxin in the nasal mucosa. METHODS: A protein extract of Aspergillus fumigatus (Af) was instilled intranasally in mice. Histologic changes were examined in wild-type and IgE-deficient (IgE-/-) animals. The effect of eotaxin administration was assessed in wild-type and IL-5 transgenic mice. RESULTS: Af-treated mice developed a nasal mucosal eosinophil influx comparable to that described for humans. This histology was distinct from that observed in a murine model of Af-induced asthma. The pathology appeared over a time course similar to that reported for human subjects. There was no difference in the intensity of the mucosal inflammatory infiltrate of Af-treated IgE-/- mice compared with wild-type mice. Eotaxin was able to recruit eosinophils to the mucosa but only in IL-5 transgenic animals. CONCLUSION: We describe a murine model for allergic rhinitis with an eosinophilic infiltrate comparable to that found in human disease and have demonstrated that rhinitis can arise in the absence of IgE. We have shown that the eosinophil influx can be induced by eotaxin in the presence of IL-5.

Unique cytomegalovirus intracytoplasmic inclusions in ectocervical cells on a cervical/endocervical smear.

This case demonstrates unique cytomegalovirus (CMV)-associated intracytoplasmic inclusions in the intermediate squamous cells of a cervical/endocervical smear. These concentric, rod-shaped, perinuclear inclusions were stained for CMV by immunohistochemistry. Cytomegalovirus endocervicitis was also documented on a concurrent cervical biopsy. The finding of these characteristic inclusions on a routine endocervical/cervical smear may provide morphologic evidence for CMV infection in the absence of an adequate endocervical component.

Effects of lead on growth plate chondrocyte phenotype.

Lead toxicity is a major public health problem in the United States. The skeleton serves as the major reservoir for ingested lead, where it is incorporated into bone matrix during calcification. While lead in bone has been considered inactive, mounting clinical and epidemiological data has shown a strong correlation between lead exposure and adverse effects on stature in children. These epidemiologic data suggest a direct effect of lead on skeletal development, but whether it reflects a systemic effect, a specific effect on osteoblasts, or an effect on the epiphyseal growth plate is as yet unclear. This study examined the effects of lead on parameters of cartilage biology in isolated chondrocytes. Changes in growth plate chondrocyte phenotype were assessed utilizing an established avian growth plate chondrocyte model. Low, sublethal doses of lead caused specific and significant effects on a number of important markers of growth plate chondrocyte phenotype, including suppression of alkaline phosphatase and both type II and type X collagen expression at the protein and mRNA levels, and a decrease in thymidine incorporation. In contrast, proteoglycan synthesis was stimulated relative to controls in lead-treated cultures, suggesting that the alterations in collagen and DNA synthesis and alkaline phosphatase activity are not due to cytotoxity. The data demonstrate important regulatory effects of lead on growth plate chondrocytes in cell culture and suggest an inhibitory effect on the process of endochondral bone formation. The growth plate may be one of the key target tissues accounting for the adverse effects of chronic lead exposure on skeletal development.

Granular histiocytosis of pelvic lymph nodes following total hip arthroplasty. The presence of wear debris, cytokine production, and immunologically activated macrophages.

UNLABELLED: Infiltration of regional lymph nodes by macrophages has been demonstrated after total joint arthroplasty. Although lymph nodes regulate the immune response, neither cytokine production nor the degree of immunological activation of cells within these nodes after total joint arthroplasty has been investigated. Pelvic lymph nodes were obtained from five patients who had had a total of eleven arthroplasties in seven hips three to twenty years before a pelvic staging procedure for adenocarcinoma (of the prostate in four patients and of the endometrium in one). All lymph nodes had polyethylene or metal debris as well as effacement of the normal nodal architecture by a histiocytic infiltrate. These changes were bilateral in the patients who had had an arthroplasty of one hip. Analysis of specimens from pelvic lymph nodes on the side of the involved hip demonstrated intense immunohistochemical staining of histiocytes for the major histocompatibility complex class-II antigen HLA-DR, a marker of histiocyte immune activation. In contrast, staining was absent in specimens from the contralateral lymph nodes as well as in those from seven patients who had had a prostatectomy but not a hip arthroplasty. Immunohistochemical staining for interleukin-1beta, tumor necrosis factor-alpha, and interleukin-6 demonstrated a much greater expression of these cytokines in the involved lymph nodes. CLINICAL RELEVANCE: Additions improvements in total joint replacement will be facilitated by a more thorough understanding of the biological response to the components and materials of implants. While local biological factors leading to failure of prostheses are currently under intense investigation, the mechanisms and importance of regional and systemic immune responses to wear debris require further study.

Extension metacarpal osteotomy in the treatment of trapeziometacarpal osteoarthritis: a biomechanical study.

The biomechanical effects of extension metacarpal osteotomy on contact pressures in the trapeziometacarpal joint during lateral pinch were studied in 20 anatomic specimens using pressure-sensitive film. The gross appearance of joint surfaces was classified by severity of arthritic disease and correlated with specimen x-ray films taken before the osteotomy. Extension metacarpal osteotomy effectively unloaded the palmar contact area in nonarthritic and moderately arthritic specimens; primary contact areas and zones of peak pressure were shifted from the diseased palmar compartment to the normal dorsal compartment. In contrast, the pathologically congruent contact pattern seen in end-stage osteoarthritic joints was unaffected by osteotomy. The data demonstrate the efficacy of extension metacarpal osteotomy in unloading the palmar contact areas of normal and moderately arthritic joints but provide no biomechanical rationale for metacarpal osteotomy as originally described in treatment of advanced trapeziometacarpal osteoarthritis.

Primary lymphoma of bone. Correlation of magnetic resonance imaging features with cytokine production by tumor cells.

BACKGROUND: Primary lymphoma of bone is a rare, aggressive neoplasm that can present with a large, soft-tissue mass despite minimal evidence of cortical destruction on plain radiographs. METHODS: High resolution magnetic resonance imaging (MRI) examinations of four patients with primary lymphoma of bone were reviewed retrospectively, and in each case intramedullary tumors demonstrated "penetrating channels" extending through the cortex. The MRI studies were correlated with the histopathologic assessment of the tumor for each patient. Immunohistochemistry was performed for immunophenotyping and for cytokine expression by tumor cells. The cytokines that were investigated were interleukin-1, interleukin-6, and tumor necrosis factor-alpha, molecules known to regulate osteoclastic activity. RESULTS: The linear cortical foci noted on MRI correlated with the histopathologic findings of tumor-associated cutting cones, in proximity to osteoclastic bone resorption. Immunohistochemical stains showed a B-cell phenotype for each tumor and positive immunoreactivity in tumor cells for cytokine mediators that stimulate osteoclastic activation. CONCLUSIONS: These findings indicate that the tumor cells in these cases produce soluble cytokine mediators that may regulate extensive osteoclastic activity. In primary lymphoma of bone, tumor activation of osteoclastic resorption, with production of tumor tunnels through the cortex, may represent one of the mechanisms by which lymphoma escapes the intramedullary space and forms large, soft-tissue masses without extensive cortical destruction.

A model program for teaching nurses breast assessment and cancer screening.

The increasing incidence of breast cancer in the United States is well documented in the literature. Associated with this rise is a need for additional health care providers who are well versed in the detection of early breast cancer and who are dedicated public advocates of self-examination skills. To meet this challenge, approximately 300 nurses throughout the U.S. and Europe have attended a course designed at M.D. Anderson Cancer Center during the past decade. This article provides an overview of the program, including demographic data describing nurses who completed the course during 1989.

A health investment that may save your life.

Breast cancer need not continue to be the devastating, deadly disease it has been in the past. With early detection, there is a higher rate of cure. There are three components to good breast health. These include (a) annual physical exam by a physician, (b) mammography according to the prescribed guidelines, and (c) monthly breast self-examination (BSE). When a woman does all three of these things, she's doing everything she can to insure early detection of breast cancer. This article discusses location, description, and characteristics of tumors. It also includes a teaching protocol developed for Midwest Breast Care Center in St. Louis, Missouri by the writer that includes risk factors, signs, and symptoms of breast cancer. It also includes new, comprehensive examination techniques set forth by the University of Texas System Cancer Center M. D. Anderson Cancer Center. The protocol is set up in a step-by-step format for easier teaching and learning. New, more thorough examination techniques have also been established at M. D. Anderson for the woman who has had a mastectomy and needs to examine the surgical site each month as well as her remaining breast. The article encourages women to take responsibility for their breast health and wellness.

The breast self-examination practices of high risk women: implications for patient education.

The breast self-examination (BSE) behavior of 142 women referred to a large cancer center with malignant or benign breast disease was investigated. The women were interviewed about their BSE practices and variables that may have influenced their BSE behavior. Those reporting prior BSE practice were asked to demonstrate their breast examination to a trained nurse, who rated their performance against a set of standard criteria. Although it might be assumed that these women have had more opportunity to become educated about BSE, results showed the ratings of the women's performances were uniformly poor. Less than half reported having formal instruction by a medical professional. This is of particular consequence considering that those women taught by a doctor or nurse performed significantly more BSE steps than did those taught in other ways. Women who were encouraged to do BSE by friends or relatives also performed significantly more steps. Based on the study findings, specific recommendations are made, which can be applied to the improvement of BSE educational programs.