Increased ratio of FoxP3+ regulatory T cells/CD3+ T cells in skin lesions in drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms.

BACKGROUND: Drug-induced hypersensitivity syndrome/drug rash with eosinophilia with systemic symptoms (DIHS/DRESS) is a severe drug eruption accompanied by multiorgan disorders. Several unique aspects of DIHS/DRESS, including herpesvirus reactivation, liver dysfunction and hypogammaglobulinaemia, have similarities to graft-versus-host disease (GVHD). AIM: In this study, we focused on the dynamics of regulatory T cells (Tregs) infiltrating into the skin lesions of DIHS/DRESS and GVHD. METHODS: Skin biopsies were taken from patients with DIHS/DRESS, GVHD, or maculopapular drug eruption. Tregs were detected using immunostaining with anti-FoxP3. RESULTS: The ratio of FoxP3+ T cells to CD3+ T cells was significantly higher in the skin lesions of patients with DIHS/DRESS than in those of patients with GVHD, and was positively correlated with the number of days from disease onset in the acute phase. CONCLUSIONS: The dynamics of Tregs in skin lesions are different between DIHS/DRESS and GVHD, despite there being many similarities between these conditions.

Involvement of autoimmunity to REG, a regeneration factor, in patients with primary Sjögren's syndrome.

The regenerating gene (Reg) was isolated originally as a gene specifically over-expressed in regenerating pancreatic islets and constitute a growth factor family. Reg gene product (Reg) is important in the pathophysiology of various human inflammatory diseases. Recently, the possible involvement of human REG in the regeneration of salivary ductal epithelial cells of patients with primary Sjögren's syndrome (SS) was reported. However, the expression of the REG family genes in minor salivary glands (MSG) and the occurrence of anti-REG Iα autoantibodies in SS patients were obscured. In this study, we examined the expression of REG family genes in the MSG of SS and screened anti-REG Iα autoantibodies in SS. The mRNA levels of REG family genes in MSG were quantified using real-time reverse transcription-polymerase chain reaction (RT-PCR) and REG Iα expression in the MSG was analysed by immunohistochemistry. The mRNA level of REG Iα in the MSG of SS patients was significantly higher than that of control. REG Iα protein was expressed highly in SS ductal epithelial cells. Anti-REG Iα autoantibodies in the sera were found in 11% of SS. All the MSG in the anti-REG Iα autoantibody-positive group showed REG Iα expression, whereas only 40% showed REG Iα expression in the anti-REG Iα autoantibody-negative group. The anti-REG Iα autoantibody-positive group showed significantly lower saliva secretion and a higher ratio of grade 4 (by Rubin-Holt) in sialography. These data suggest strongly that autoimmunity to REG Iα might play a role in the degeneration of MSG ductal epithelial cells in primary SS.

Retinoblastoma protein and proliferating-cell nuclear antigen expression as predictors of recurrence in well-differentiated papillary thyroid carcinoma.

PURPOSE: We analyzed retinoblastoma protein (pRB) and proliferating-cell nuclear antigen (PCNA) expression in primary tumors and recurrent lesions of well-differentiated papillary thyroid carcinoma (PTC) to clarify the relationship between their expression and recurrent disease. PATIENTS AND METHODS: The study included 93 patients with PTC. No recurrent disease had developed in 60 patients within 10 years after surgery (group N). Thirty patients in whom recurrent disease had developed after surgery were enrolled in group R. Levels of pRB and PCNA expression were quantified using the CAS 200 system (Cell Analysis Systems, Elmhurst, IL) following immunohistochemical staining. RESULTS: Mean pRB expression level in the primary tumors in group R was significantly lower than that in group N (P < .0001). pRB expression in the tumors with a diameter up to 20 mm was significantly lower than that in tumors larger than 20 mm in group R (P < .01). There were no significant differences in the levels of expression of PCNA in the primary tumors between group N and group R. Univariate analysis demonstrated that the disease-free survival was significantly correlated with pN category, pRB, and PCNA expression level. The subgroup with high-level expression of pRB (> 25%) showed significantly long disease-free survival (P < .001). Furthermore, the subgroup with low-level expression of PCNA (< 35%) showed significantly longer disease-free survival (P < .05). Multivariate analysis showed pRB expression and pN category to be independent prognostic factors for disease-free survival in PTC. CONCLUSION: pRB expression level can be used as a reliable predictor for recurrence of PTC.

Immunohistochemical demonstration of thyrotropin (TSH)-receptor in normal and diseased human thyroid tissues using monoclonal antibody against recombinant human TSH-receptor protein.

We performed an immunohistochemical analysis of TSH-receptor in normal and diseased human thyroid tissues using a monoclonal antibody (T3-356) against the C terminal region of human TSH receptor. In normal human thyroid tissues, a positive staining was observed exclusively along the basal cell surface of the flattened follicular cells. In the tissues from adenomatous nodules, adenomas, and papillary carcinomas, a positive staining was also found along the basal cell surface of the follicular cells. In addition, a considerable cytoplasmic staining was observed. The apical and lateral cell surfaces of the follicular cells showed no staining. The foci of squamous cell metaplasia of papillary carcinomas, anaplastic carcinoma, and medullary carcinoma did not show a positive staining. In Graves' thyroids, the positive staining was also observed along the basal cell surface of the follicular cells. The staining was obviously intense in the Graves' thyroids, and the most intense staining was noted in the foci of papillary projection of the columnar follicular cells. These findings indicate that TSH receptor is preserved essentially in the basal cell surface of the thyroid follicular cells in neoplastic conditions and that the amount of TSH receptor protein is increased in Graves' thyroid.

Iodine-induced hypothyroidism: a clinical and histological study of 28 patients.

Thirty-three thyroid specimens obtained from 28 patients with clinically and laboratory-proven iodine-induced hypothyroidism were examined clinically, histologically, immunohistochemically, and ultrastructurally. Twenty-eight specimens obtained during the hypothyroid phase showed common histological changes in the thyroid thought to be specific for this disease; hyperplastic change in the follicles with some papillary folding, cuboidal to columnar change of follicular cells with clear and vesicular cytoplasm, scanty or absent colloid material in the large distended follicles, and occasional dilatation of capillary vessels. Lymphocytic infiltration was present in about half of the specimens. No specimens showed either stromal fibrosis or parenchymal atrophy. Immunohistochemical and electron microscopic examination revealed that severe interference with thyroid hormone biosynthesis occurs in the follicular cells. In two patients who had a follow-up biopsy in the recovery (euthyroid) phase after iodine restriction, the histological involvement seen in the hypothyroid phase was no longer present. The histological changes in the thyroid gland seen in patients with iodine-induced hypothyroidism are characteristic. This disease can be diagnosed from laboratory tests, but thyroid biopsy is also a useful tool to differentiate this condition from other diseases causing hypothyroidism. Not only clinicians, but also pathologists, must pay attention to this type of hypothyroidism, because thyroid function may revert to normal by iodine restriction alone.

Midcourse thallium-201 scintigraphy to predict tumor response in bone and soft-tissue tumors.

UNLABELLED: The purpose of this study was to assess the predictive power of 201TI scintigraphy in the midcourse of chemotherapy for the final tumor response to chemotherapy in malignant bone and soft-tissue tumors. METHODS: The 21 patients studied with 201TI scintigraphy were 14 males and 7 females (average age 39.8+/-22.1 yr; age range 8-74 yr). Planar scintigraphy was performed 15 min after injection of 111 MBq 201TI before chemotherapy, after the third chemotherapy cycle (midcourse) in all 21 patients and after the final chemotherapy cycle but before surgery in 11 patients. The 201TI uptake ratio was calculated by dividing the count density of the lesion by that of the contralateral normal area. The percent reduction of the 201TI uptake ratio calculated by 100 x [(prechemotherapy ratio - postchemotherapy ratio)/prechemotherapy ratio] in the midcourse was compared with that after the final course of chemotherapy, and it also was compared with the histologic response. RESULTS: In patients with histologically complete response [(CR), n=6] and with partial response [(PR), n=5], the percent reduction in 201TI uptake ratio after three cycles of chemotherapy was 64.1%+/-14.4% and 50.9% +/-10.5%, respectively. In patients with histologically no change [(NC), n=10], the percent reduction was 0.40%+/-18.2% after the third cycle; -5.3%+/-20.9% in four patients with full courses of chemotherapy (p < 0.0001 and p < 0.005 compared with the CR and PR groups, respectively). After the final cycle of chemotherapy, the percent reduction in 201TI uptake ratio was 68.6%+/-14.7%, 56.2%+/-6.1% and -0.3%+/-17.2% in the CR, PR and NC groups, respectively (NC versus CR, p < 0.0005; NC versus PR, p < 0.005). CONCLUSION: Thallium-201 scintigraphy performed in the midcourse of chemotherapy is predictive of the final response to chemotherapy that can be demonstrated histologically. Serial 201TI scintigraphy in the midcourse of chemotherapy is useful in assessing final chemotherapeutic response in the early stage of chemotherapy, and it helps clinicians when choosing the most appropriate treatment strategies in patients with bone and soft-tissue tumors.

Thallium-201 SPECT depicts radiologically occult lung cancer.

A case of radiologically occult lung cancer is presented in which 201TI SPECT of the chest clearly delineated the involved area. A 66-yr-old man underwent chest screening examinations for asymptomatic smokers and presented a positive sputum cytology for lung cancer. Conventional chest x-ray, tomography of computed radiography, and a CT scan failed to locate the lesion in the lung. Thallium-201 SPECT, however, was successful in depicting the area of the involvement.

Evaluating benign and malignant bone and soft-tissue lesions with technetium-99m-MIBI scintigraphy.

UNLABELLED: This study compares the ability of 201TI and 99mTc-MIBI to detect and assess tumor response to chemotherapy in malignant and benign bone and soft-tissue lesions. METHODS: Forty-two patients with various bone and soft-tissue pathologies (29 malignant and 13 benign lesions) were studied with 201TI and 99mTc-MIBI. Planar 201TI scintigraphy was performed 15 min after injection of 111 MBq of 201TI. Within 1 wk of the 201TI study, radionuclide angiography with 600-740 MBq of 99mTc-MIBI was performed and planar imaging was done 15 min later. RESULTS: In visual analysis, 31 of 42 patients showed similar uptake of both tracers, 8 showed more intense uptake of 99mTc-MIBI than 201TI and 3 showed more intense uptake of 201TI than 99mTc-MIBI. In quantitative analysis, similar 201TI and 99mTc-MIBI uptake ratios were obtained (1.96 +/- 1.25 versus 1.96 +/- 1.02, respectively; p = ns). The perfusion index derived from 99mTc-MIBI radionuclide angiography was higher than 99mTc-MIBI uptake ratio (2.33 +/- 1.23 versus 1.96 +/- 1.02, respectively; p < 0.005), but correlated well with 99mTc-MIBI uptake ratio (r = 0.75). In 11 patients with malignant tumors, 201TI and 99mTc-MIBI scintigraphy was repeated after chemotherapy and the uptake of both tracers was significantly suppressed in patients with complete response confirmed by histological evaluation. In patients with complete response (n = 3), the uptake ratio of both tracers was reduced by more than 50%, whereas, less than 20% reduction of uptake ratio was observed in patients with nonresponse (n = 6). CONCLUSION: The ability of 99mTc-MIBI to detect malignant and benign bone and soft-tissue lesions and to assess tumor response to chemotherapy was comparable to that of 201TI. In addition, blood flow could be assessed by radionuclide angiography with 99mTc-MIBI. Technetium-99m-MIBI is a promising radiopharmaceutical for the evaluation of bone and soft-tissue lesions.

Effect of thromboxane A2 antagonists on bronchial hyperresponsiveness induced immediately after interleukin-8 inhalation in guinea-pigs.

1. Although repeated intranasal administration of interleukin-8 (IL-8) causes bronchial hyperresponsiveness (BHR) mediated via thromboxane A2 (TXA2) and airway neutrophil accumulation in guinea-pigs, the acute effect of inhaled IL-8 is unclear. We performed this study to clarify the acute effect of IL-8 on bronchial responsiveness and the role of TXA2. 2. The effects of inhaled IL-8 on bronchial responsiveness and of the TXA2 antagonists, S-1452 (0.01 and 0.1 mg kg-1) and ONO-NT-126 (1.0 or 10 micrograms kg-1), on IL-8-induced BHR were examined by use of a modified Konzett-Rössler method in guinea-pigs. 3. Inhaled IL-8 at 100 ng ml-1, which failed to induce significant changes in Pao (pressure at the airway opening), enhanced an increase in Pao induced by subsequent inhalations of ascending doses (50-200 micrograms ml-1) of methacholine and histamine, suggesting the potentiating effect of IL-8 on bronchial responsiveness. No significant leukocyte infiltration was observed histologically sixteen minutes after the IL-8 inhalation. Both S-1452 and ONO-NT-126 reduced the IL-8-induced BHR. 4. In conclusion, IL-8 rapidly causes BHR via TXA2 release in guinea-pigs.

Fatal cardiac beta2-microglobulin amyloidosis in patients on long-term hemodialysis.

We report two long-term hemodialysis patients who developed severe congestive heart failure attributable to cardiac heavy amyloid deposition. Both patients became hypotensive during dialysis sessions, gradually making it difficult to continue hemodialysis, and they died of congestive heart failure. At autopsy, left ventricle walls in each case contained diffuse extensive deposits of amyloid. The distribution of amyloid was not localized to vessel walls but was widely disseminated throughout the left ventricle walls and replaced myocardial muscle fibers. Immunohistochemical examination showed positive staining for anti-human beta2-microglobulin antibody. We conclude that cardiac dialysis-related amyloidosis should also be considered in long-term hemodialysis patients with congestive heart failure as a life-threatening complication.

Immunohistochemical demonstration of epidermal growth-factor receptors in normal, benign and malignant thyroid tissues.

Human epidermal growth factor receptor (EGF-receptor) has been detected immunohistochemically in normal, benign and malignant human thyroid tissues. With a monoclonal antibody for EGF-receptor and avidin-biotin-peroxidase complex (ABC), the expression of EGF-receptor was evaluated in paraffin-embedded sections. Carcinomas of the thyroid showed a moderate to intense staining for EGF-receptor in most cases. Apical cell surface and cytoplasmic staining was the most common pattern of immunoreactivity. Adenomas showed a variable positivity in the cytoplasm of th tumor cells, and their apical cell surface staining was generally negative to borderline. The follicular cells in Hashimoto's thyroiditis showed a weak to moderate cytoplasmic staining, but those in Graves' disease and normal thyroids showed an essentially negative cytoplasmic staining. Apical cell surface staining was essentially negative or borderline in these benign lesions. There were no significant correlations between EGF-receptor expression and tumor size, degree of invasion or cervical metastases in the thyroid carcinomas. The apical surface expression of EGF-receptor was characteristic to thyroid carcinomas and this feature may be useful in the differentiation of thyroid carcinomas from benign thyroid lesions.

Hemosiderin deposition in portal endothelial cells: a novel hepatic hemosiderosis frequent in chronic viral hepatitis B and C.

We have recently noted a hitherto undescribed hepatic hemosiderosis confined to endothelial cells of the portal tract in chronic viral hepatitis. In this study, this lesion was surveyed in 156 liver biopsy specimens from patients with chronic hepatitis C and in 21 liver biopsy specimens from patients with chronic hepatitis B. As controls, we examined 110 liver biopsy specimens from patients with primary biliary cirrhosis (PBC), 36 from patients with alcoholic liver injury, nine from patients with autoimmune hepatitis (AIH), and five from patients with primary hemochromatosis. Hemosiderin deposition was found in the endothelial cells of venous vessels in portal tracts regardless of the presence or degree of hemosiderin deposition in hepatic parenchyma. This phenomenon was observed in 65 of 156 cases (42%) of chronic hepatitis C and in eight of 21 (38%) cases of chronic hepatitis B. In controls, this lesion was frequent in AIH (78%), but infrequent in PBC (8.1%) and alcoholic liver injury (11%). The incidence of this lesion showed significant differences between chronic hepatitis C, B, and AIH, and between PBC and alcoholic liver injury. There was a positive correlation between the progression of disease and the incidence of this feature in chronic viral hepatitis; the incidence was 18.3% and 11.1% in milder chronic hepatitis C and B, respectively, and 61.2% and 58.3%, respectively, in more severe cases. However, this correlation was not evident in either PBC or alcoholic liver injury. This hemosiderin deposition was positively correlated with the degree of piecemeal necrosis in chronic hepatitis C, and to a lesser degree, the positive correlation was shown in chronic hepatitis B. These findings suggest that the progression of chronic hepatitis and the piecemeal necrosis in chronic hepatitis C and B, followed by the release of hepatocellular iron to portal and periportal areas, are directly or indirectly responsible for endothelial hemosiderosis. Further studies focusing on this peculiar phenomenon in relation to choice of therapy and evaluation of chronicity of viral hepatitis are encouraged.

Thymic carcinoma involving the thyroid gland: report of two cases.

Two new cases of thymic carcinoma involving the thyroid gland and manifesting as thyroid tumors are presented. One tumor occurred within the thyroid gland and the other totally involved the thyroid gland. Microscopically they showed lobular architecture separated by fibrous bands and consisted of solid islands of squamoid to spindled epithelial cells with whorl formation resembling Hassall's corpuscle and variable amounts of lymphocytes. The squamoid to spindled epithelial cells were positive for cytokeratin but negative for thyroglobulin and calcitonin and the majority of lymphocytes showed a T-cell phenotype. One of the two cases had been diagnosed initially as squamous cell carcinoma of the thyroid. This type of thyroid carcinoma is relatively rare, but it should be differentiated from other types of thyroid carcinomas, especially squamous cell carcinoma, medullary carcinoma, or anaplastic carcinoma of the thyroid.

Distant metastases in differentiated thyroid carcinomas: a clinical and pathologic study.

Of 514 patients with differentiated thyroid carcinoma treated between 1970 and 1987, 34 (6.6%) had distant metastases. Twelve patients died of their distant metastases; eight of these patients died within 5 years from the time of initial diagnosis. Death from cancer was most frequent in the seventh decade. The metastases were most often found in the lungs and bones. In the fatal group, pleural, brain, and pericardial metastases were noted. Local recurrences were found only in 24% of these 34 patients. Histologic types of primary thyroid tumors and metastatic tumors were reexamined and classified using our criteria, which were mainly based on the World Health Organization nomenclature and currently obtained pathologic observations of thyroid tumors. In 31 thyroid tumors, the surgical specimens were available for review. Twenty-four tumors were papillary and seven were follicular. Of the 24 papillary carcinomas, nine were follicular, eight were well-differentiated, and seven were trabecular. On the other hand, the seven follicular carcinomas consisted of four well-differentiated, two solid, and one oxyphilic. The majority of the thyroid tumors showed an extrathyroidal extension; however, two were intrathyroidal carcinomas and two were encapsulated carcinomas, larger than 5 cm in diameter. Distant metastases were confirmed morphologically in 18 patients (11 by surgical or biopsy material, five by autopsy, and two by cytology). The histologic types of metastatic tumors were consistent with those of primary thyroid tumors. Diagnostic 131I uptake was examined in 32 patients and absorption of diagnostic 131I in metastatic tumors was demonstrated in 21 patients. The 10-year survival rate of patients with 131I accumulating metastases (70%) was significantly better than that of patients with metastases lacking such uptake (40%). Immunoreactivity for thyroglobulin in metastatic tumors was correlated with the 131I absorption. This finding indicated that immunostaining of thyroglobulin in metastatic tumors might be useful in the prediction of the effectiveness of 131I therapy.

Chronic thyroiditis: thyroid function and histologic correlations in 601 cases.

Six hundred one patients with histologically proven "chronic thyroiditis" were assessed for the correlation of thyroid function to histologic findings. The histology of chronic thyroiditis was classified into four groups (oxyphilic, mixed, focal, and hyperplastic), and the thyroid function of patients was divided into hyperthyroid, euthyroid, latent hypothyroid, and overt hypothyroid, based on the laboratory data of serum triiodothyronine (T3), thyroxine (T4), and thyrotropin (TSH) levels, as well as thyrotropin-releasing hormone (TRH) tests. In the oxyphilic group (137 cases), 116 (85%) of the patients were classified as hypothyroid: 52 (38%) as latent hypothyroid and 64 (47%) as overt hypothyroid. In the mixed group (161 cases), the thyroid function of the patients varied. Thirty-seven (23%) of the patients were classified as hyperthyroid, 61 (39%) as euthyroid, 54 (33%) as latent hypothyroid, and nine (5%) as overt hypothyroid. In this group thyroid function was intimately related to the ratio of replacement by hyperplastic-changed follicles and oxyphilic-changed follicles. In the focal group (149 cases), 123 (83%) of the patients were classified as euthyroid, while 22 (14%) were classified as latent hypothyroid. The frequency of latent hypothyroid patients increased in parallel with the severity of cell infiltration. In the hyperplastic group (154 cases), 130 (85%) of the patients were classified as hyperthyroid. In this series 19 patients under 10 years of age were included, and no difference in the distribution of histologic varieties was observed between juvenile and adult patients. Thyroid needle biopsy is a useful and safe tool, not only for the histologic diagnosis of chronic thyroiditis, but also for the evaluation of thyroid function and the identification of causes for hyperthyroidism or hypothyroidism.

Columnar cell carcinoma of the thyroid gland: a case report and review of the literature.

A rare case of columnar cell carcinoma of the thyroid gland is reported. The tumor was characterized by a predominantly papillary proliferation of tall columnar cells with marked nuclear stratification with associated focal areas showing solid or microfollicular growth. The nuclei of the tumor cells did not have the ground-glass appearance that characterizes papillary thyroid carcinoma; rather their nuclear features resembled follicular carcinoma. The tumor was found in an advanced stage and the patient died of lung metastases 2.5 years after surgery. The unique histopathological features and highly aggressive nature of columnar cell carcinoma require that this variant be differentiated from common papillary carcinoma of the thyroid. We also reviewed the literature emphasizing the lethal biological nature of this variant.

A clinicopathologic study of resected cases of adenosquamous carcinoma of the lung.

Adenosquamous carcinoma of the lung is an uncommon form of the lung cancer. Owing to the infrequent occurrence of this disease, no series reported to date (and to our knowledge) has been of adequate size for definitive statistical analysis. In this study, survival curves and background factors affecting prognosis in those with resected adenosquamous carcinoma of the lung were reviewed. In the period from 1973 to 1994, a total of 1,284 patients with primary lung cancer, including 44 cases (3.4%) of adenosquamous carcinoma, were surgically treated in our department. The cumulative 5-year postoperative survival rate, for all cases of adenosquamous carcinoma of the lung was 18.5%. When the survival rates were compared by histologic type, the outcomes of patients with adenosquamous carcinoma were statistically worse than for patients with squamous cell carcinoma and adenocarcinoma, owing to the highly aggressive pathologic stage of adenosquamous carcinoma. The background factors most closely associated with the survival rate in those with adenosquamous carcinoma, using Cox's proportional hazard model, were gender and the degree of nodal involvement. Five-year survival was obtained in seven patients as follows: T1N0M0 in one patient, T2N0M0 in three, T2N1M0 in two, and T3N0M0 in one. Of these seven patients, all had received complete resections, and five were N0 cases. Although our series is small, this study suggest that adenosquamous carcinoma of the lung is an aggressive tumor that grows rapidly.

Can tumor size be a guide for limited surgical intervention in patients with peripheral non-small cell lung cancer? Assessment from the point of view of nodal micrometastasis.

OBJECTIVE: We sought to determine the critical diameter of a peripheral non-small cell lung cancer tumor less than which no evidence of nodal micrometastasis is present. METHODS: Samples of 3081 lymph nodes from 181 patients with stage I peripheral lung cancer (155 with adenocarcinoma and 26 with squamous cell carcinoma) who had undergone complete resection with systematic lymphadenectomy were used in the study. In the samples immunohistochemical staining for cytokeratin was performed. The expression of vascular endothelial growth factor (VEGF) at primary sites was also immunohistochemically assessed. RESULTS: Nodal micrometastasis was detected in 44 patients. The mean tumor sizes were 2.2 +/- 1.3 cm (range, 1.0-7.0 cm) in nodal micrometastasis-positive adenocarcinoma, 2.1 +/- 0.9 cm (range, 0.5-6.0 cm) in nodal micrometastasis-negative adenocarcinoma, 4.8 +/- 2.3 cm (range, 2.2-10.0 cm) in nodal micrometastasis-positive squamous cell carcinoma, and 3.2 +/- 2.1 cm (range, 0-9.0 cm) in nodal micrometastasis-negative squamous cell carcinoma. The tumor size in the nodal micrometastasis-positive group tended to be greater than that in the nodal micrometastasis-negative group in squamous cell carcinomas, but there was no significant difference in adenocarcinomas. Nodal micrometastasis was not found in patients with squamous cell carcinoma of 2.0 cm or less in diameter. However, nodal micrometastasis was found in 20% (19/95) of the patients with adenocarcinoma of 1.1 to 2.0 cm in diameter and even in 4 of 11 patients with adenocarcinoma of 1.0 cm or less. Among the patients with nodal micrometastasis, survival of patients with vascular endothelial growth factor overexpression was worse than that of patients without it. The survival of patients with nodal micrometastasis without vascular endothelial growth factor overexpression was comparable with that of patients without nodal micrometastasis. CONCLUSION: A limited surgical intervention without lymphadenectomy is validated for squamous cell carcinoma of 2.0 cm or less without pleural involvement. In adenocarcinoma the tumor size itself is not a reliable guide for nodal micrometastasis status. In patients with nodal micrometastasis with vascular endothelial growth factor overexpression, the risk of systemic disease should be considered.

Extent of mediastinal node metastasis in clinical stage I non-small-cell lung cancer: the role of systematic nodal dissection.

OBJECTIVE: To determine the extent of lymph node metastasis in clinical stage I non-small-cell lung cancer (NSCLC). METHODS: We performed a retrospective review of 524 patients with clinical stage I NSCLC who underwent lobectomy with systematic nodal dissection. RESULTS: The nodal status was N0 in 409 patients (78%), N1 in 44 (8%), N2 in 67 (13%), and N3 in four (0.8%). Thirty-six patients had single-level mediastinal nodal metastases and 35 had multi-level metastases. The incidence of N2/3 disease in patients with adenocarcinoma/squamous cell carcinoma/other histologic types according to tumor size was 0/0/0%, respectively, in tumors < or = 10 mm in diameter, 12/0/0% in tumors 11-20 mm in diameter, 14/4/23% in tumors 21-30 mm in diameter, and 26/14/20% in tumors >30 mm in diameter. Nodal metastases to the upper mediastinum from middle or lower lobe lesions were frequently observed in 51 N2 adenocarcinomas, whereas those to the lower mediastinum from upper lobe lesions were rare. Of 10 N2 squamous cell carcinomas, seven had regional and three had non-regional nodal metastases. The 5-year survival rate was 68, 43, and 30% in N0, N1, and N2, respectively (P<0.01, N0 versus N1, N0 and N2). CONCLUSIONS: Systematic mediastinal nodal dissection should be routinely performed for clinical stage I lung cancer to ensure the correct nodal status, but it might be dispensable in the patients with peripheral squamous cell carcinoma < or = 20 mm in diameter, with central squamous cell carcinoma < or = 30 mm, and with adenocarcinoma < or = 10 mm. When systematic nodal dissection cannot be performed, the incidence and extent of nodal metastases should be taken account with respect to histologic type, size, and location of the tumor.

Borderline chondrosarcoma of long and flat bones.

We reviewed histological and clinical findings of six cases of borderline chondrosarcoma and examined the expression of collagen types I, II, III, V, and VI by immunohistochemical analysis of these tumors. Borderline chondrosarcoma is defined as a cartilaginous tumor of bone resembling enchondroma on the basis of histomorphology. Clinically the tumor causes intermittent vague pain unrelated to physical activities. On radiographs borderline chondrosarcoma is characterized by evidence of endosteal erosion. We observed local recurrences in two cases treated by intralesional excision and marginal excision, and one of those cases died of inoperable local tumor recurrence. In our histological analysis based on tissue patterns, there were enchondromatous patterns in five cases, and chondrosarcomatous patterns in four cases. In the second recurrent tumor in one case, a chondrosarcomatous pattern was newly observed, and the recurrent tumor was found to be a low-grade chondrosarcoma cytologically in the other case. In the tumor matrix immunoreactivity for collagen types II and VI was predominant, with collagen types I, III, and V showing heterogeneous expression in some cases. In all cases rimming of tumor lobules with collagen types I and V was absent. Immunoreactivity for collagen type II in the cytoplasm of tumor cells was found in four cases and all three recurrent tumors. Borderline chondrosarcoma, as defined by histology, clinical symptoms and radiological appearance, shows a collagen distribution pattern similar to that of low-grade chondrosarcoma. These findings are in accordance with the clinical outcome of borderline chondrosarcoma which parallels that of low-grade chondrosarcoma. Thus borderline chondrosarcoma may be best treated by wide en-bloc excision rather than curettage.