Thymic epithelial tumor progression in an SV40T transgenic mouse model. Cortical thymoma-thymic carcinoma sequence.

There have been several reports that thymoma in human is a progressive disease, and that thymoma and thymic carcinoma form a continuum. We established a stable line of SV40T transgenic mice, which consistently produced thymic epithelial tumours progressing to thymic carcinoma within a predictable time span. Using this animal model and a morphological approach, thymic epithelial tumour progression was studied with reference to sequential changes at different time points in animals aged from 3 to 32 weeks. At all ages, SV40T was expressed in the nuclei of thymic epithelial cells; in these transgenic mice we observed the entire spectrum from cortical type thymoma to thymic carcinoma. Thymic size tended to increase with ageing in SV40T TG mice. While younger mice had predominantly cortical (organoid) or cortical thymoma, older mice had well-differentiated thymic carcinoma (WDTC) or poorly differentiated thymic carcinoma. When SV40T TG mice (248 line) reached a certain age, carcinoma of the thymus was present in all of them. Cortical-type thymoma became malignant within a predictable time span, suggesting a cortical thymoma-carcinoma sequence. When the mice were 9 weeks of age, the thymuses formed gross masses compatible with cortical thymoma. At 14 weeks of age, WDTC appeared against the background of cortical thymoma. Poorly differentiated thymic carcinoma was found after 15 weeks and affected all animals over 23 weeks of age. Most thymic carcinomas coexisted in varying proportions with cortical-type thymoma. Medullary thymomas did not develop in the mice, and no transition from medullary-type thymomas to thymic carcinomas was observed. In this SV40T transgenic mouse model, thymic carcinoma is clearly preceded by cortical-type thymoma. These transgenic mice may provide an interesting model for the progression from cortical thymoma to WDTC and/or high-grade carcinoma.

Castleman's disease in the retropharyngeal space: CT and MR imaging findings.

We report CT and MR imaging findings in a case of Castleman's disease involving the retropharyngeal space in a middle-aged woman. On CT scans, a well-marginated, homogeneous, and densely enhancing mass was detected in the right retropharyngeal space. The mass was isointense to the muscle on T1-weighted MR images, hyperintense to the muscle on T2-weighted MR images, and showed homogeneous, strong enhancement on contrast-enhanced T1-weighted MR images. The linear hypointense signal in an arborizing pattern was observed within the mass on all pulse sequences.

Malignant peripheral nerve sheath tumor in the parapharyngeal space: tumor spread through the eustachian tube.

SUMMARY: We report the CT and MR findings in a patient with malignant peripheral nerve sheath tumor in the parapharyngeal space who had neither a family history nor stigmata of neurofibromatosis. A high-resolution CT scan of the temporal bone revealed bony erosion and widening of both the foramen ovale and the bony portion of the eustachian tube. A temporal bone MR image showed an intensely enhancing solid mass in the parapharyngeal space, which extended into the middle ear cavity via the eustachian tube.

Parapharyngeal second branchial cyst manifesting as cranial nerve palsies: MR findings.

SUMMARY: We report the MR findings of parapharyngeal branchial cleft cyst manifesting as multiple, lower cranial nerve palsies in a 35-year-old woman. On MR images, a well-marginated cystic mass was detected in the right parapharyngeal space, with displacement of both the right internal carotid artery and the right internal jugular vein on the posterolateral side. The cyst contained a whitish fluid that was slightly hyperintense on T1-weighted images and slightly hypointense to CSF on T2-weighted images. No enhancement on contrast-enhanced T1-weighted images was present. The right side of the tongue showed high signal intensity on T2-weighted images, suggesting denervation.

Supratentorial gangliocytoma mimicking extra-axial tumor: a report of two cases.

We report two cases of supratentorial gangliocytomas mimicking an extra-axial tumor. MR imaging indicated that the tumors were extra-axial, and meningiomas were thus initially diagnosed. Relative to gray matter, the tumors were hypointense on T1-weighted images and hyperintense on T2-weighted images. On contrast-enhanced T1-weighted images, homogeneous enhancement was observed, while CT scanning revealed calcification in one of the two cases.

Central nervous system tumors among Koreans--a statistical study on 697 cases.

A total of 697 cases of intracranial and intraspinal tumors was obtained from the pathology file of Seoul National University Hospital and Children's Hospital during the period of 8 years from 1980 to 1987. These tumors were classified according to WHO classification. This study was performed to understand the recent trend of the relative frequency of the central nervous system tumors among Koreans and to compare it with the previous studies in Korea and other countries. There were 663 intracranial tumors and 34 intraspinal tumors. More common intracranial tumors were pituitary adenoma, meningioma, astrocytoma and medulloblastoma, each representing 23.4%, 20.8%, 11.8%, and 5.6%, respectively. In juvenile age group (under 15 years of age), medulloblastoma, astrocytoma, ependymoma and craniopharyngioma were more commonly encountered to be 25.6%, 21.6%, 13.6% and 12%, respectively. Both sexes were equally affected among adult group, but male preponderance was observed among juvenile group (1.49:1). Nine cases of primitive neuroectodermal tumor, a unique tumor which is not listed in WHO classification, were observed and all of them occurred before the age of 20. There were 27 metastatic tumors. Our previous study encompassing previous 17 years, 1963 to 1979, showed similar overall results except for intraspinal tumors that were more commonly encountered in previous series.

An autopsy case of Adams-Oliver syndrome.

We report an autopsy case of a male fetus with Adams-Oliver syndrome. His mother was a healthy, 31-year-old woman and her family and past histories were unremarkable. Therapeutic termination was done at 28(+6) weeks gestational age due to oligohydramnios detected by antenatal ultrasonography. Chromosomal study revealed normal karyotype. On autopsy, characteristic transverse terminal defect of four extremities was found. Both feet were short and broad. All toes were rudimentary with no nails and fingers were irregularly short. On infantogram, all toe-bones were stubby and rudimentary. The middle and terminal phalanges of 2nd, 3rd & 5th fingers and the terminal phalange of 4th finger on the right hand were absent. The middle and terminal phalanges of 2nd & 5th fingers and terminal phalange of 3rd finger were defected on the left hand. His abnormalities were consistent with features of Adams-Oliver syndrome, which has not been reported in Korea.

Neonatal hemochromatosis--report of an autopsy case.

A case of neonatal hemochromatosis in a 3-hour-old male is described. He presented with hypotonia, mild jaundice, and respiratory difficulty immediately after birth. He had no evidence of congenital infection, immune-related hemolysis or exogenous iron uptake. Postmortem examination revealed abnormal facial features. The organs were of normal weight for his age except a small liver and lungs, and a large spleen. The most prominent changes were in the liver and pancreas. The liver was coarsely nodular and fibrotic. The lobular architecture was totally distorted by innumerable multinucleated giant cells, loss or collapse of the hepatocytes, and diffuse fibrosis. A large amount of hemosiderin was seen in the liver, pancreatic acini and thyroid follicular cells. Scanty amount of hemosiderin was also found in the myocardial fibers and renal tubular cells. The pancreas showed hyperplasia and hypertrophy of the islets. The spleen showed severe congestion and a moderate extramedullary hemopoiesis but no deposits of hemosiderin. This patient had three siblings died in neonatal period, one of which had clinical features of neonatal hemochromatosis.

A study on demyelinating effect of galactocerebroside in experimental allergic encephalomyelitis.

An experimental allergic encephalomyelitis was induced by bovine myelin basic protein (MBP) and bovine galactocerebroside (GC) on male guinea pigs. Animals were divided into five experimental and one control groups. Among the five experimental groups, three were inoculated with 75 micrograms, 150 micrograms and 300 micrograms of MBP, respectively, to see the dose dependency of demyelination. The fourth group was inoculated with mixture of 75 micrograms of MBP and 180 micrograms of GC and the fifth group with 180 micrograms GC. All inocula was injected intradermally in emulsion state mixed with equal amount of complete Freund adjuvant. Control group was injected with adjuvant only. Clinical symptoms began to appear from 15th day after inoculation and animals were sacrificed on maximum neurologic deficit or 4 to 5 days after the onset of symptoms. Demyelination was observed in 6 out of 8 animals inoculated with MBP/GC mixture, while only 3 out of 24 animals inoculated with various dosage of MBP showed demyelination. The difference was statistically significant. Serum antibodies to MBP and GC were measured by ELISA method. All of the eight animals inoculated with MBP/GC mixture and two animals inoculated with GC had low titer of anti-GC antibodies, while all animals inoculated with MBP, MBP alone or MBP/GC mixture, had high titer of anti-MBP antibodies. Therefor it is concluded that the demyelination is augmented by GC and is not significantly dose-dependent on MBP.

Histiocytic necrotizing lymphadenitis. A clinico-pathologic study of 45 cases with in situ hybridization for Epstein-Barr virus and hepatitis B virus.

Forty-five cases of histiocytic necrotizing lymphadenitis (HNL) or Kikuchi-Fujimoto disease were reviewed clinico-pathologically and studied for Epstein-Barr virus (EBV) and hepatitis B virus (HBV) by in situ hybridization to assess their causative role. Histologically, the lymph nodes typically showed relatively well defined paracortical lesions composed of large atypical mononuclear cells, histiocytes, and karyorrhectic nuclear debris. Mild to moderate degree of coagulation type necrosis was present in 24 cases. Clinical features did not vary greatly from previously described female preponderance, young age onset, subacute cervical lymphadenopathy, and frequent leukopenia, except for a few cases with recurrent disease over 8-9 years. Serologic tests revealed EBV IgG antibody in one case, HBV surface antibody in 11 cases and HBV surface antigen in 2 cases. In situ hybridization was performed on 41 cases using internal repeat 1 fragment DNA and EBV-coded small RNA (EBER-1) for EBV, and pan-HBV DNA probe for HBV detection, and showed that all cases were negative for EBV or HBV genome. Our results suggest EBV or HBV may not have causative role in the pathogenesis of HNL.

A case of myasthenia gravis proven by ultrastructural study.

Although light microscopic features of muscle are not pathognomonic in most cases of myasthenia gravis (MG), careful examination of neuromuscular junction by electron microscopy (EM) can reveal important clues for this disease. We report here a case of MG confirmed by EM study to emphasize that tissue diagnosis is still the best adjuvant to confirm the diagnosis. An 18-year-old female visited our hospital complaining of progressive muscle weakness for 3 years. She had difficulty in running, going upstairs and doing routine activities. Symptoms were aggravated with continuous work and resolved after rest. She had weakness of bilateral masseter and facial muscles and proximal portions of extremities without definite diurnal variation. Electromyography showed myopathic changes in proximal muscles of extremities. MG was considered but tensilon test was equivocal. Repetitive nerve stimulation tests revealed 20-30 percent decrease in responses to low and high rate stimulation. Muscle biopsy revealed selective type 2 atrophy. Ultrastructurally, abnormalities of neuromuscular junctions, i.e., wide primary synaptic cleft, and wide and shallow secondary synaptic clefts with mild myopathic features were present. These findings were pathognomonic for MG. Later, her symptoms were improved completely 3 months after thymectomy. The histologic finding of thymus was follicular hyperplasia.

Flow cytometric immunophenotyping in fine-needle aspiration of lymph nodes.

Fine-needle aspiration (FNA) of lymph nodes has been regarded as a useful method in the diagnosis of lymphadenopathy. However, this procedure has been shown to be of limited value in the diagnosis of low or intermediate grade malignant lymphomas in some studies. Immunophenotyping is an essential adjunct to cytomorphology for the diagnosis of lymphoma by FNA. Immunophenotyping using flow cytometry (FCM) is rapid, objective and reliable. Using FCM, multiparametric analysis of 33 FNA materials from lymph nodes was performed and profiles of surface markers of lymphoid cells were assessed. In reactive hyperplasia, patterns of cell surface markers were quite variable, but disclosed polyclonality. Most of the B-cell lymphomas showed immunophenotypes for B-cell lineages with their kappa: lambda or lambda: kappa ratio being over 3:1. In T-cell lymphomas, T-cell surface markers were predominantly expressed as well. In conclusion, our results suggest that immunophenotyping of lymph node aspirates is a valuable diagnostic adjunct for lymphoproliferative disorders, particularly in B-cell lymphomas because immunophenotyping can be easily and adequately performed by FCM.

Comparative study of mouse heart and heart-lung transplantations.

Heart transplantation in mice using a double anastomosis technique has become the standard method regardless of its technical difficulty. Heart-lung transplantation performed by single anastomosis in rats was also applied to mice, showing the identical operative result in addition to the advantage of easy applicability. We compared the heart transplant made by double anastomosis with the heart-lung transplantation using single aortic anastomosis in terms of graft survival and histologic features. The results were as follows: 1) During the follow-up period of 100 days after the transplantation in mice that survived 7 days after the operation, there were no deaths among the hosts and no evidence of nonfunction of the grafts in the six mice in each group. 2) In terms of monocyte infiltration perivascularily or interstitially, myocyte necrosis, interstitial hemorrhage, neutrophilic infiltration, and endocardial changes, histologic changes in the grafts were less in single anastomosis of heart-lung transplants than in double anastomosis. As a result, we can deduce that heart-lung transplantation using the single anastomosis technique is a good experimental model for the study of transplant reaction.

Sebaceous carcinoma of the eyelids: frequent expression of c-erbB-2 oncoprotein.

Ocular sebaceous carcinoma (OSC) is an uncommon malignancy with a potential to recur and metastasize. Some characteristics of sebaceous carcinoma, such as female preponderance, shown in the present series during 11-year period at Korea Cancer Center Hospital, led us to study their hormone receptors and c-erbB-2 expression. c-erbB-2 overexpression was very common (83%) in OSC, and was not associated with pathologic findings or clinical outcome. Interestingly, estrogen and progesterone receptor was detected in 4 and 2 cases, respectively, suggesting a role of hormonal influence on this neoplasm. Immunohistochemical and clinicopathologic features of 18 cases of OSC in Korea are presented.

5' CpG island methylation of p16 is associated with absence of p16 expression in glioblastomas.

Recent evidence shows that transcriptional silencing as a consequence of hypermethylation of CpG islands is an important mechanism in the inactivation of p16INK4 tumor suppressor gene. This study is designed to clarify the significance of p16INK4 hypermethylation in 23 cases of glioblastomas (GBMs) by methylation-specific polymerase chain reaction (PCR) and p16 immunostaining. Fourteen cases (60.9%) out of 23 GBMs revealed hypermethylation on p16. p16 immunostaining revealed that 13 (93%) of these 14 hypermethylation cases showed complete loss of immunoreactivity and only one (7%) case retained immunoreactivity. Among 9 methylation-negative cases, 4 were immunonegative, which might be related to mutations or deletions other than hypermethylation. The most significant finding was that of 17 cases with immunonegativity, 13 cases (76.5%) showed hypermethylation. We reconfirmed that p16 hypermethylation may be one of the major mechanisms of tumorigenesis of GBMs and the results between the methylation specific-PCR study and p16 immunostaining had a good correlation.

Mixed acinar-endocrine carcinoma of the pancreas--a case report.

A case of pancreatic carcinoma with both acinar and endocrine features is presented. The patient was a 52-year-old female presenting with jaundice of 3 weeks' duration. The tumor was a 6 x 6 cm-sized round solid mass in the head of pancreas, invading the superior mesenteric vein. Histologically, it was composed of monotonous ovoid cells with eosinophilic granular cytoplasm in solid nests and sheets with occasional acinar and glandular differentiation. Immunohistochemical study revealed coexpression of acinar and endocrine markers; amylase, chromogranin, neuron-specific enolase, glucagon, somatostatin, and gastrin in tumor cells. This is the first documented case of mixed acinar-endocrine carcinoma of the pancreas in Korea, and its amphicrine nature reflects a close histogenetic relationship between pancreatic exocrine and endocrine cells.

Clinicopathologic study of basaloid squamous carcinoma of the upper aerodigestive tract.

The clinicopathologic and immunohistochemical characteristics of nine cases of basaloid squamous carcinoma (BSC) of the upper aerodigestive tract are reported, along with the results of an in situ hybridization for human papilloma virus (HPV) DNA. The cases were selected through a review of 237 head and neck carcinomas, and were located in the supraglottic larynx (5), hypopharynx (2), and the base of tongue (2). The patients were 7 males and 2 females with the mean age of 62. BSCs were histologically characterized by lobules and nests of basaloid cells with scanty cytoplasm, comedonecrosis and adenoid features, and by concomitant presence of squamous cell carcinoma. Immunohistochemically, all BSCs showed positivity for high molecular weight cytokeratin (HMW CK) with heterogeneous or diffuse staining pattern, but lacked reactivity for neuroendocrine markers and bcl-2 oncoprotein. No HPV DNA was detected in BSCs. This study reaffirms that BSC is a rare carcinoma with a peculiar topographic distribution and distinct pathologic features.

Radiologic and histopathologic changes after Gamma Knife radiosurgery for acoustic schwannoma.

Gamma knife radiosurgery (GKRS) is a widely used treatment option for acoustic schwannomas, 3 cm in diameter or less. Between May 1990 and February 1998, 102 acoustic tumors in 101 patients were treated with GKRS. There are 77 patients with a follow-up period of more than six months (mean 55, range 7 to 90 months). Seventy (91%) of these tumors have remained unchanged or reduced in volume. After GKRS there was an increase in volume in seven cases. In four the volume increase affected solid tumour. Among these, three patients were in stable condition and are being observed. One of these patients developed brain stem compression symptoms and was operated. In another three cases, cysts with multiple septa developed medial to the tumor and compressed the brain stem and fourth ventricle, thus necessitating post-GKRS surgery. In these three patients, MRI had shown loss of central contrast enhancement followed by its return. Histological findings at surgery before and after GKRS were compared for these four tumours. In spite of the MRI changes, there were no definite histological findings after GKRS which could be attributed to radiation induced changes. The development of cysts occurred after the treatment of larger tumors.

Epstein-Barr virus-associated primary gastrointestinal lymphoma in non-immunocompromised patients in Korea.

We examined 81 cases of primary gastrointestinal lymphomas in Korea, including 64 gastric lymphomas and 17 intestinal lymphomas, for EBV expression by EBER-1 in situ hybridization (ISH) and EBNA-1 PCR. In EBER-1 positive cases, we performed immunohistochemistry for latent membrane protein-1 (LMP-1) and EBV diffuse early antigen (EA(D)) to compare EBV latent gene expression and lytic process. EBER-1 was detected in 15 of 81 cases of lymphomas. EBER-1 expression showed three different patterns on tumour cells; diffuse 4/81 (5%), localized 4/81 (8%), and a few scattered pattern 7/81 (9%). We regarded diffuse pattern and localized pattern as EBER-1 positive group (8/81: 10%). Diffuse pattern of EBER-1 was shown in all three T-cell lymphomas and one B-cell lymphoma. A localized pattern was seen all in B-cell lymphomas. The EBER-1 expression was 11% in the stomach (7/64) and 6% in the intestine (1/17). Five of the eight EBER-1 positive gastric lymphomas were histologically diffuse large B-cell lymphomas, and the other three were peripheral T-cell lymphoma, unspecified, one angiocentric lymphoma, and one intestinal T-cell lymphoma by REAL classification. Eight MALT type gastric B-cell lymphomas showed no EBV association. EBV nuclear antigen (EBNA-1) was detected in 15 of 45 resected cases (33%) by PCR. EBER-1 positive cases were all EBNA-1 positive. Twelve EBNA-positive/EBER-negative cases consisted of seven cases showing a few scattered EBER-1 positive lymphocytes. LMP-1 and diffuse early antigen (EA(D)) was detected in five and three cases, respectively. Although follow-up information in our series was incomplete, it seemed that there was no significant difference in their staging or prognosis between EBER-positive cases and EBER-negative group. It is concluded that EBV is associated with some lymphomas among Koreans without overt pre-existing immunodeficiency, especially in T-cell lymphomas.

Clinicopathologic analysis of 124 biopsy-proven peripheral nerve diseases.

We reviewed dinical, histological and ultrastructural findings of 124 cases of sural nerve biopsy specimens to delineate the trends of peripheral nerve diseases in our institute. Eighty-one were men and 43 were women. We categorized them into five groups: specific diagnosis (66 cases, 53.2%), axonal degeneration type (47 cases, 37.9%), demyelinating type (4 cases, 3.2%), mixed axonal degeneration-demyelinating type (6 cases, 4.8%) and normal (1 case, 0.9%). Cases with specific diagnosis included 21 inflammatory demyelinating polyneuropathy (15 chronic inflammatory demyelinating polyradiculoneuropathy, 6 Guillain-Barre disease), 13 hereditary motor and sensory neuropathy (7 Charcot-Marie-Tooth type I, 6 Charcot-Marie-Tooth type II), 10 vasculitis, 6 toxic neuropathy, 4 leprosy, 3 diabetic neuropathy, 2 alcoholic neuropathy, 1 Fabry's disease and other specific diseases (5 cases). In our cases, the proportion of specific diagnoses was higher, while the proportion of demyelinating peripheral neuropathies and normal were lower than those of Western series. The results of this study indicate that 1) a dose clinicopathologic correlation is important to make a precise diagnosis of peripheral nerve biopsy, 2) Biopsy under strict indication may reduce unnecessary histologic examination, 3) There is no difference in disease pattern of peripheral neuropathy between Western people and Koreans.