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T Tihan

Publications and source records attributed to T Tihan.

At least 19 recordsLinked to original sources
PubMed2006

Perfusion MR imaging of an intracranial collision tumor confirmed by image-guided biopsy.

We present a patient with a new intracranial mass lesion that was initially interpreted as a metastasis on conventional anatomic MR imaging. On dynamic, contrast-enhanced, susceptibility-weighted perfusion MR imaging, however, there were regional hemodynamic differences within the lesion. Image-guided open biopsy targeting these regions uncovered a collision tumor between a typical meningioma and a metastatic breast carcinoma. In cases where conventional anatomic MR imaging is ambiguous, physiology-based neuroimaging methods provide complementary physiologic information useful for discriminating between histologically unique tissue types.

Biopsy↗
PubMed2006

Comparison of microvascular permeability measurements, K(trans), determined with conventional steady-state T1-weighted and first-pass T2*-weighted MR imaging methods in gliomas and meningiomas.

BACKGROUND AND PURPOSE: The widely accepted MR method for quantitating brain tumor microvascular permeability, K(trans), is the steady-state T1-weighted gradient-echo method (ssT1). Recently the first-pass T2*-weighted (fpT2*) method has been used to derive both relative cerebral blood volume (rCBV) and K(trans). We hypothesized that K(trans) derived from the ssT1 and the fpT2* methods will correlate differently in gliomas and meningiomas because of the unique differences in morphologic and functional status of each tumor vascular network. METHODS: Before surgery, 27 patients with newly diagnosed gliomas (WHO grade I-IV; n = 20) or meningiomas (n = 7) underwent conventional anatomic MR imaging and 12 dynamic ssT1 acquisitions followed by 60 dynamic fpT2* images before and after gadopentate dimeglumine administration. The 3 hemodynamic variables-fpT2* rCBV, fpT2* K(trans), and ssT1 K(trans)-were calculated in anatomically identical locations and correlated with glioma grade. The fpT2* K(trans) values were compared with ssT1 K(trans) for gliomas and meningiomas. RESULTS: All 3 hemodynamic variables displayed distinct distributions among grades 2, 3, and 4 gliomas by using the Kruskal-Wallis test. Only K(trans) values, and not rCBV, could differentiate between grade 4 and lower-grade gliomas by using the Wilcoxon rank sum test. The fpT2* K(trans) was highly predictive of ssT1 K(trans) for gliomas, with an estimated regression coefficient of 0.49 (P < .001). For meningiomas, however, fpT2* K(trans) values correlated poorly with ssT1 K(trans) values (r = 0.26; P = .74). CONCLUSION: Compared with rCBV, K(trans) values derived from either ssT1 or fpT2* were more predictive of glioma grade. The fpT2* K(trans) was highly correlated with ssT1 K(trans) in gliomas but not in meningiomas.

Adolescent↗
PubMed2001

Subacute diencephalic angioencephalopathy: biopsy diagnosis and radiological features of a rare entity.

Subacute diencephalic angioencephalopathy (SDAE) is a rare and fatal disease of unknown etiology that involves the thalami bilaterally. To date, there have been four cases reported, in which the diagnosis was established only after post mortem examination of the brain. We report two male patients, ages 69 and 41 years, who presented with progressive dementia and somnolence. Radiological evaluation revealed enhancing lesions involving both thalami. The differential diagnosis included a number of neoplastic, inflammatory and vascular processes. In both cases, pathological evaluation of biopsy specimens suggested the diagnosis of SDAE. Despite supportive care, the disease progressed rapidly and both patients died within weeks after initial presentation. The diagnosis was confirmed at autopsy in both cases. SDAE is a rare cause of bithalamic disease that can be mistaken for a neoplasm as well as a number of conditions that necessitate different treatment choices. The histopathological findings can establish the diagnosis when combined with radiological and clinical information. This report emphasizes the utility of stereotactic biopsy in early diagnosis of SDAE.

Adult↗
PubMed2001

Apoptosis, neuronal maturation, and neurotrophin expression within medulloblastoma nodules.

Nodular/desmoplastic medulloblastomas are a well-established histopathological subtype containing reticulin-free nodules or "pale islands' that are comprised of cells with round "neurocytic" nuclei and abundant cytoplasm. Significant neuronal maturation occurs within nodules. We used immunohistochemistry to evaluate neuronal differentiation in the nodules of 6 of these tumors. The neuronal markers NeuN, synaptophysin, and MAP-2 were identified in the "pale islands" of all 6 nodular medulloblastomas examined, and high and medium molecular weight nonphosphorylated neurofilaments were detected in 2 of the 6 cases. We also observed collections of apoptotic cells within nodules. Given the known role of neurotrophin signaling in neuronal maturation and apoptosis, we analyzed immunohistochemically the distribution of neurotrophin receptors TrkA and TrkC and their primary ligands NGF and NT3 in 14 nodular medulloblastomas. TrkA and TrkC were detected in 13 and 10 cases, respectively, and were predominantly localized within nodules. NGF and NT3 were distributed diffusely with some nodular accentuation. The localized expression of Trk receptors within nodules of desmoplastic medulloblastomas suggests neurotrophin signaling is involved in the apoptosis and neuronal differentiation in medulloblastomas. We also examined expression of p53 and BCL-2 in these tumors; both were prominent in internodular regions but only weakly expressed within nodules. Trk receptors, p53, and BCL-2 are all expressed during development of the normal cerebellum. Interestingly, the immunohistochemical expression profile of these proteins in the differentiating nodules of medulloblastomas is in many ways similar to their expression in the developing cerebellum. Thus similar signaling pathways may be operational in cerebellar development and medulloblastoma tumor differentiation.

Adolescent↗
PubMed2001

Anasarca and small bowel obstruction secondary to endometriosis.

Intestinal involvement by endometriotic tissue occurs in up to 37% of patients with endometriosis. The vast majority of patients do not experience symptoms related to the gastrointestinal tract. In particular, the complications of intestinal obstruction and malabsorption secondary to endometriosis are exceedingly uncommon. We present a 42-year-old woman with intestinal obstruction, protein-losing enteropathy, and anasarca secondary to endometriosis. She had a 1-year history of watery diarrhea, bloating, and abdominal pain with a 30-lb weight-loss over 3 months. She had no previous history of endometriosis, and laboratory investigations showed severe hypoalbuminemia, hypokalemia, and metabolic acidosis. Abdominal x-rays revealed air-fluid levels and dilated loops of small bowel. She underwent surgical resection with primary anastomosis. Pathologic evaluation showed extensive endometriosis of the small bowel and appendix, which resulted in complete obstruction. Segments of ileum also demonstrated moderate-to-marked blunting of the villi. Postoperatively, the patient had a slow recovery with resolution of anasarca and a gradual increase in her weight. This report illuminates the rare, yet significant, complications of intestinal endometriosis, including small bowel obstruction, the development of a protein-losing enteropathy, and anasarca. One should consider the possibility of intestinal endometriosis in the differential diagnosis of bowel obstruction in women of childbearing age.

Adult↗
PubMed2001

Prognostic implications for gadolinium enhancement of the meninges in low-grade astrocytomas of childhood.

BACKGROUND: Persistent gadolinium enhancement on MRI of the meninges in some children with low-grade astrocytomas (LGA) is a widely recognized phenomenon. The relationship of this finding with the clinical course is unclear. METHODS: From a consecutive cohort of 282 children with pathologically confirmed LGA we identified all patients with asymptomatic gadolinium enhancement of the meninges found on surveillance MRI. A nested case-control study was performed, comparing patients with meningeal enhancement to controls without enhancement. RESULTS: Twenty-one children were identified with meningeal enhancement. The median follow-up was 5.2 years with enhancement noted for a median of 2.2 years. The 5-year overall survival for this cohort was 91.2% (Greenwood SE 8.0%), and the 5-year progression-free survival was 20.9% (SE 11.9%). Five patients are now free of disease, while 15 continue to have stable disease. The overall and progression-free survival was not significantly different compared to controls. CONCLUSIONS: Gadolinium enhancement of the meninges on MRI may occur in a significant number of children with LGA, particularly juvenile pilocytic astrocytoma, but does not appear to affect progression-free or overall survival. Change in management based on this finding alone is unwarranted.

Adolescent↗
PubMed2000

A clinicopathologic reappraisal of brain stem tumor classification. Identification of pilocystic astrocytoma and fibrillary astrocytoma as distinct entities.

BACKGROUND: Brain stem tumors in children have been classified pathologically as low grade or high grade gliomas and descriptively as diffuse gliomas, intrinsic gliomas, midbrain tumors, tectal gliomas, pencil gliomas, dorsal exophytic brain stem tumors, pontine gliomas, focal medullary tumors, cervicomedullary tumors, focal gliomas, or cystic gliomas. METHODS: To search for a simplified and prognostic clinicopathologic scheme for brain stem tumors, the authors reviewed a consecutive cohort of patients younger than age 21 years with tumors diagnosed from 1980 through 1997. Pathology specimens and neuroimaging were classified by masked review. Statistical and survival analysis along with Cox proportional hazards regression was performed. RESULTS: Seventy-six patients were identified, with initial diagnostic magnetic resonance imaging available for 51 and pathology specimens for 48 patients. Twenty cases were classified histologically as pilocytic astrocytoma (PA), 14 as fibrillary astrocytoma (FA), and 14 as other tumors or indeterminate pathology. For all tumors, characteristics significantly associated with a worse survival rate were: symptom duration less than 6 months before diagnosis (P = 0.004); abducens palsy at presentation (P < 0.0001); pontine location (P = 0.0002); and engulfment of the basilar artery (P = 0.006). Pilocytic astrocytoma was associated with location outside the ventral pons (P = 0.001) and dorsal exophytic growth (P = 0.013); Fibrillary astrocytoma was associated with symptoms less than 6 months (P = 0. 006), abducens palsy (P < 0.001), and engulfment of the basilar artery (P = 0.002). Pilocytic astrocytoma showed 5-year overall survival (OS) of 95% (standard error [SE], 5%) compared with FA 1-year OS of 23% (SE, 11%;P < 0.0001). CONCLUSIONS: Brain stem tumors can be succinctly and better biologically classified as diffusely infiltrative brain stem gliomas-generally FA located in the ventral pons that present with abducens palsy, often engulf the basilar artery, and carry a grim prognosis-and focal brain stem gliomas-frequently PA arising outside the ventral pons, often with dorsal exophytic growth, a long clinical prodrome, and outstanding prognosis for survival. Our findings emphasize the individuality of PA as a distinct clinicopathologic entity with an exceptional prognosis.

Adolescent↗
PubMed2000

Nuclear localization and mutation of beta-catenin in medulloblastomas.

The adenomatous polyposis coli (APC) gene, a member of the Wingless/Wnt signal transduction pathway, has been implicated in the development of medulloblastomas in Turcot's syndrome. beta-catenin also functions in this highly conserved signaling pathway and is instrumental in growth and development. Mutations in either APC or beta-catenin can stabilize beta-catenin protein. Stabilized beta-catenin complexes with Tcf/Lef transcription factors and moves from the cytoplasm into the nucleus where it regulates the transcription of c-Myc and other genes. Nuclear localization of beta-catenin therefore implies activation of the signaling pathway. We have analyzed the subcellular localization of beta-catenin in 51 sporadic medulloblastomas and in 1 medulloblastoma arising in a patient with Turcot's syndrome. Nuclear beta-catenin staining was present in 9 of the sporadic tumors (18%) and in the 1 medulloblastoma from a Turcot's patient. The remaining 41 cases did not show nuclear staining. This confirms earlier observations that Wingless/Wnt signaling is involved in a subset of sporadic medulloblastomas. We also examined 48 glial and meningeal CNS tumors, all of which were negative for nuclear beta-catenin. Exon 3 of beta-catenin was sequenced in 6 of the 9 sporadic medulloblastomas with nuclear beta-catenin staining. Five of the 6 tumors sequenced had mutations affecting highly conserved beta-catenin phosphorylation sites involved in protein stability. These data suggest a simple immunohistochemical method to screen for beta-catenin mutations in medulloblastomas.

Aged↗
PubMed2000

Pathology of diencephalic astrocytomas.

Pediatric gliomas span a spectrum of neoplasms ranging from the well-circumscribed, slowly growing lesions that can be totally removed by surgery to highly infiltrating, nonexcisable, rapidly growing tumors that resist any form of postoperative therapy. As part of this symposium, we discuss selected members of this group in the diencephalon, where lesions of both extremes are common in children. The report illustrates and contrasts the clinical, radiographic and pathological features of the two classic regional astrocytomas, pilocytic and fibrillary, as well as two less common but distinctive lesions, pilomyxoid astrocytoma and bithalamic astrocytoma.

Astrocytoma↗
PubMed2000

Practical value of Ki-67 and p53 labeling indexes in stereotactic biopsies of diffuse and pilocytic astrocytomas.

OBJECTIVE: Stereotactic biopsies are increasingly being used for the diagnosis and grading of astrocytomas, and there is a growing need to obtain maximum information from these tissue samples. In everyday practice, p53 protein and Ki-67 immunohistochemical analyses are the most frequently used ancillary studies to aid in diagnosis and grading, but their exact role is not clearly established. This study was undertaken to evaluate the practical value of these markers in stereotactic biopsy samples from diffuse astrocytomas as well as pilocytic astrocytomas. Methods/Results.-We analyzed the Ki-67 (MIB-1) and p53 labeling indexes in the stereotactic biopsy specimens from 11 pilocytic astrocytomas; 8 grade 2, 15 grade 3, and 16 grade 4 diffuse astrocytomas. Pilocytic astrocytomas and diffuse astrocytomas were evaluated as 2 separate groups. There was a strong correlation with poor outcome when both labeling indexes were higher than 15% in the same tumor for diffuse astrocytomas (P < 0.01). The indexes did not correlate with outcome in pilocytic astrocytomas. CONCLUSION: Combined Ki-67 and p53 labeling indexes higher than 15% indicated a worse outcome than suggested by the histologic grading. The analysis aided or improved histologic evaluation of stereotactic biopsies in our patients. We believe that a realistic prognostic upgrading of diffuse astrocytomas should be made only when labeling indexes for both markers are greater than 15%.

Adolescent↗
PubMed1999

Classification of small cell lung cancer and pulmonary carcinoid by gene expression profiles.

Small cell lung cancer is a common type of lung cancer that is generally classified within the spectrum of neuroendocrine lung neoplasms. Using high-density cDNA arrays, we profiled gene expression of small cell lung cancers and compared these expression profiles to those of normal bronchial epithelial cells and pulmonary carcinoids, which are classified as benign neuroendocrine tumors. We found the overall expression profiles of two small cell lung cancer cell lines, two microdissected tissue samples of primary small cell lung cancer, and cultured bronchial epithelial cells to be relatively similar to one another, with an average Pearson correlation coefficient for these comparisons of 0.63. However, we found the expression profiles of small cell lung cancers (and bronchial epithelial cells) to be surprisingly dissimilar to those of two samples of pulmonary carcinoid tumors, with an average correlation coefficient for these comparisons of 0.20. We then compared the pulmonary carcinoid expression profiles to those of two samples of infiltrating astrocytic brain cancers (oligodendroglioma and high-grade astrocytoma) and found similarity of gene expression among these four samples (average correlation coefficient, 0.57). These gene expression profiles suggest that small cell lung cancers are closely related to (and possibly derived from) epithelial cells, and that pulmonary carcinoids are related to neural crest-derived brain tumors. More generally, our results suggest that broad profiles of gene expression may reveal similarities and differences between tumors that are not apparent by traditional morphological criteria.

Carcinoid Tumor↗
PubMed1999

Pediatric astrocytomas with monomorphous pilomyxoid features and a less favorable outcome.

Among tumors classified as pilocytic astrocytoma (PA) in the Johns Hopkins Hospital Department of Pathology files, we identified 18 cases with a distinctive monomorphous pilomyxoid histological pattern and a higher recurrence rate than that of PA with classical histological features (classical PA). The majority of the tumors occurred in infants and young children and involved the hypothalamic/chiasmatic region. The tumors were histologically similar to PA, but they were more monomorphous and more myxoid. Rosenthal fibers were not seen and only 1 of 18 tumors had eosinophilic granular bodies. At the end of the follow-up period, 6 patients were dead and 12 were alive with evidence of disease. Progression free survival (PFS) at 1 year was 38.7%. In comparison, we identified a control group of 13 classical PAs in the same age range and location as the study group. In this group, PFS at 1 year was 69.2%, which was significantly better than that for pilomyxoid tumors (p = 0.04). There was no CSF dissemination or death due to tumor progression among patients with classical PA. Eight of these patients are alive with recurrent disease, and 4 have no evidence of disease. While the monomorphous pilomyxoid tumors have some resemblance to classical PA, our results suggest that the former is a more aggressive variant or a separate entity that needs to be recognized for prognostic purposes.

Astrocytoma↗
PubMed1998

Outcomes and failure patterns in childhood craniopharyngiomas.

Past studies of craniopharyngiomas in children have shown overall survival (OS) up to 95% at 5 years and 80% progression-free survival (PFS) at 5 years, although many of these series predate modern neuroimaging and current therapeutic management. Moreover, little mention has been made of failure patterns for craniopharyngioma in children. To obtain a contemporary assessment of outcome among pediatric craniopharyngioma patients, and also to determine the failure patterns for this tumor, we completed a retrospective study of a consecutive cohort of all children with craniopharyngioma diagnosed at the Johns Hopkins Hospital from 1980 to 1996. Resection was performed in 30 children, in 8 of whom gross total resection (GTR) was achieved. Initial treatment took the form of GTR followed by observation for 8, subtotal resection (STR) plus observation in 11, and STR followed immediately by radiotherapy in 8. The timing of radiotherapy following STR was unclear for 3. OS was 95.2% (SE= 4.7%) at 5 years, with only 2 children dying after 4 years from diagnosis. Five-year PFS was 59.4% (SE=10.2%). Before surgery, 19 children had visual loss and 15, endocrine deficits; after surgery, 21 children had visual loss and 29, endocrine deficits. Median time to relapse was 0.98 years (SD=2.5 years). Radiographic (n=4) and clinical (n=7) relapses did not differ in time to progression (P=0.32), but radiographic relapses were significantly associated with age at diagnosis less than 5 years (P=0.02). Degree of resection was not significantly associated with PFS (P=0.32) or with postoperative visual or endocrine deficits. Absence of calcification on diagnostic neuroimaging (n=8) was significantly associated with improved PFS [5-year PFS 100% vs. 42.9% (SE=14.7%), P=0.02], even when adjusted for extent of resection (P=0.03). Preoperative visual loss was predictive of postoperative visual loss (P=0.03). Survival for children diagnosed with craniopharyngioma in the current era is outstanding, even with relapse, although postoperative visual and endocrinological morbidities are high. Failures occurred both radiographically and clinically, typically in the first 3-4 years after surgery, suggesting a need for close surveillance initially with neuroimaging, particularly in younger children, and also clinical examination. The short times to relapse observed here may stem from a tendency to delay radiotherapy until recurrence. Lack of calcification at diagnosis is associated with a tendency to remain free of relapse.

Adolescent↗
PubMed1998

Clear cell papillary carcinoma of the liver: an unusual variant of peripheral cholangiocarcinoma.

Cholangiocarcinomas may be extrahepatic or intrahepatic; the latter are further divided into hilar and peripheral types. Peripheral cholangiocarcinomas often resemble adenocarcinomas arising in other organs. Although clear cell changes may occur in hepatocellular carcinoma and extrahepatic cholangiocarcinoma, peripheral cholangiocarcinomas with clear cell change are rare. In such cases, an extrahepatic primary carcinoma must be excluded. We present a patient with a large, clear cell papillary carcinoma in the liver. Extensive workup of the patient for other possible primary sites including kidneys, adrenals, thyroid, prostate, or urinary bladder failed to indicate any other neoplasm. The patient is alive without evidence of disease 30 months after complete resection. The histological, immunohistochemical, and electron microscopic results were most consistent with a neoplasm in the cholangiocarcinoma family. To the best of our knowledge, a clear cell papillary peripheral cholangio carcinoma has not been described previously. This neoplasm may be related to the recently described clear cell carcinomas of the gallbladder and extrahepatic bile ducts.

Adenocarcinoma, Clear Cell↗
PubMed1998

Atypical teratoid/rhabdoid tumor of the central nervous system: a highly malignant tumor of infancy and childhood frequently mistaken for medulloblastoma: a Pediatric Oncology Group study.

Fifty-five patients with atypical teratoid/rhabdoid tumors of the central nervous system were studied to define the clinical and pathologic features of this newly described neoplasm. The lesion occurred primarily in children younger than 2 (mean age at diagnosis, 17 months). The neoplasms were located in the posterior fossa (36 patients) and the supratentorial compartment (17 patients) or were multifocal in both compartments (2 patients) at presentation. Histologically, the tumors were composed of small cells and large, pale cells in a jumbled architectural arrangement. The small cell component resembled medulloblastoma and occasionally had cords of cells in a mucinous background, simulating chordoma. The cytoplasm of the larger cells was conspicuous with a somewhat "rhabdoid" appearance, although rhabdoid features were not always prominent. Epithelioid features in the form of poorly formed glands or Flexner-Wintersteiner rosettes were noted in a minority of lesions. The neoplasms showed striking polyphenotypic immunoreactivity, including that for vimentin, glial fibrillary acidic protein, epithelial membrane antigen, cytokeratins, synaptophysin, chromogranin, and smooth muscle actin. Using a probe for chromosome 22, seven of eight scorable cases showed a solitary signal by fluorescence in situ hybridization (FISH) consistent with monosomy 22. The eighth scorable case showed three signals by fluorescence in situ hybridization and had a translocation involving chromosome 22 reported by conventional cytogenetics. In contrast to patients with medulloblastoma, the neoplasm with which these lesions are often confused, the outcome of the patients was uniformly poor. The mean postoperative survival of patients with atypical teratoid/rhabdoid tumors was only 11 months. Local recurrence, seeding of the cerebrospinal fluid pathways, or both, were common terminal events. This study underscores the distinctive clinical, histopathologic, immunohistochemical, and cytogenetic character of this unusually aggressive tumor.

Brain Neoplasms↗
PubMed1998

Well-differentiated papillary adenocarcinoma arising in a supratentorial enterogenous cyst: case report.

OBJECTIVE AND IMPORTANCE: We report a case of a well-differentiated papillary adenocarcinoma arising in an supratentorial enterogenous cyst. The clinicopathological features of this case and a brief review of the literature are presented. CLINICAL PRESENTATION: A 45-year-old woman presented with abrupt onset of sensory seizures and abnormal sensation on the left side of her face, left leg, and left arm. Radiological studies showed a cystic extraaxial tumor with mass effect in the right parietal area. The initial clinical impression was a metastatic lesion, and a comprehensive metastatic workup revealed no evidence of tumor elsewhere. INTERVENTION: A gross total resection of the solid cystic tumor was achieved by a frontoparietal craniotomy. Sixteen months after the initial surgery, the patient presented with signs of increased intracranial pressure and a large parietal cyst. The cyst was fenestrated at the time of the second craniotomy. CONCLUSION: A pathological study of the initial surgical material revealed it to be a well-differentiated papillary adenocarcinoma in association with an enterogenous cyst. The second surgical specimen consisted only of the benign cyst wall. The patient recovered uneventfully from the second surgery and was free of symptoms 6 months postoperatively. The importance of recognizing the rare possibility of malignant progression of a benign enterogenous cyst in the central nervous system is discussed.

Adenocarcinoma, Papillary↗
PubMed1996

Coexistence of renal cell carcinoma and malignant lymphoma. A causal relationship or coincidental occurrence?

BACKGROUND: Secondary malignant neoplasms are increasingly being observed in cancer populations and a considerable amount of data have accumulated in the literature. Among the secondary malignant neoplasms that occur with a higher incidence in cancer patients are lymphomas and renal cell carcinoma (RCC), as well as melanoma, lung/bronchus carcinoma. METHODS: The authors analyzed the patient population at the Memorial Sloan-Kettering Cancer Center in New York City between 1985 and 1995 for coexisting carcinomas, and identified 15 patients who had both RCC and malignant lymphoma among a total of 1262 patients with RCC and 1660 patients with malignant lymphoma. The occurrence and time of diagnosis of both malignant neoplasms and their clinical features, types, and stages, as well as short term follow-up, results, are presented. RESULTS: The data show a greater than coincidental coexistence of RCC and malignant lymphoma (P < 0.01). In addition, there was a significant increase in the number of patients with both melanoma and RCC (P < 0.01), as well as melanoma and malignant lymphoma (P < 0.01). No significant increase was found in cases of coexisting RCC or malignant lymphoma with either lung/bronchus carcinoma or colorectal carcinoma (P > 0.05). CONCLUSIONS: Causes of this increased coexistence may include a genetic predisposition to cancer, similar immune mechanisms associated with these neoplasms, closer scrutiny of this group of patients, or a combination of these factors. Studies are underway to elucidate a common genetic component in these patients.

Adult↗