Epstein-Barr virus-associated inflammatory pseudotumor variant of follicular dendritic cell sarcoma of the liver: a case report and review of the literature.

BACKGROUND: Follicular dendritic cell sarcoma is a rare stromal tumor with no standard treatment. However, some reports have revealed that follicular dendritic cell sarcoma has an inflammatory pseudotumor variant associated with Epstein-Barr virus infection that has a relatively good prognosis. In this report, we present a case of a resected inflammatory pseudotumor variant of follicular dendritic cell sarcoma of the liver, and have reviewed the literature on the clinicopathological, molecular, and genomic features of this tumor. CASE PRESENTATION: The inflammatory pseudotumor variant of follicular dendritic cell sarcoma originates only in the liver or spleen, causes no symptoms, and is more common in middle-aged Asian women. It has no characteristic imaging features, which partially explains why the inflammatory pseudotumor variant of follicular dendritic cell sarcoma is difficult to diagnose. Pathologically, the inflammatory pseudotumor variant of follicular dendritic cell sarcoma has spindle cells mixed with inflammatory cells and is variably positive for follicular dendritic cell markers (CD21, CD23, and CD35) and Epstein-Barr virus-encoded RNA. On genetic analysis, patients with this tumor high levels of latent membrane protein 1 gene expression and extremely low levels of host C-X-C Chemokine Receptor type 7 gene expression, indicating that the inflammatory pseudotumor variant of follicular dendritic cell sarcoma has a latent Epstein-Barr virus type 2 infection. CONCLUSIONS: The inflammatory pseudotumor variant of follicular dendritic cell sarcoma is an Epstein-Barr virus-associated tumor and a favorable prognosis by surgical resection, similar to Epstein-Barr virus-associated gastric cancer.

Primary solitary fibrous tumour of the prostate: A case report and literature review.

INTRODUCTION: Solitary fibrous tumour (SFT) is a rare mesenchymal tumour with intermediate malignant potential. Although this tumour arises in several sites, prostatic SFT is an extremely rare neoplasm and may prove confusing owing to the lack of clinical experience because of tumour rarity. The diagnosis may be further difficult because SFTs can manifest positive immunoreactivity for CD34 and progesterone receptor, which are known markers of prostatic stromal tumours. Herein, we describe a case of prostatic SFT that was difficult to differentiate from a prostatic stromal tumour of uncertain malignant potential because of positive immunoreactivity to CD34 and progesterone receptor. CASE REPORT: A 40-year-old Japanese man presented with lower abdominal pain. Computed tomography revealed a prostatic mass; furthermore, prostate core needle biopsy revealed proliferating bland spindle cells, without necrosis or prominent mitoses. Tumour cells were positive for CD34 and progesterone receptor on immunohistochemical analysis; thus, a prostatic stromal tumour of uncertain malignant potential was initially suspected. However, as the tumour cells showed positive immunoreactivity for STAT6, the final diagnosis was an SFT of the prostate. The patient underwent tumour resection, and at the 6-month postoperative follow-up, neither local recurrence nor distant metastasis occurred. CONCLUSION: For an accurate diagnosis of an SFT of the prostate, STAT6 immunohistochemistry should be conducted for all mesenchymal tumours of the prostate. When STAT6 immunohistochemical analysis is unfeasible, pathologists should be aware that the morphological and immunohistochemical characteristics of SFT variable from case to case and diagnose with combined analysis of several immunohistochemical markers.

Histopathological study of carcinoma showing thymus-like differentiation (CASTLE).

INTRODUCTION: Carcinoma showing thymus-like differentiation (CASTLE) is a rare tumour that mainly arises from the thyroid gland, or occasionally, from the head and neck. Although the 10-year survival rate of patients with CASTLE is approximately 80%, local recurrence and distant metastasis are observed in some cases. A recent systematic review for CASTLE indicated that the prognostic factors are treatment-dependent, and postoperative radiotherapy significantly improves patient survival. CASE REPORT: Herein, we describe and compare three cases of CASTLE, including a case with distant metastasis despite administering postoperative chemotherapy. Thus, the mechanisms underlying metastasis of CASTLE are unclear. This case study helps to elucidate the histopathological risk factors of metastasis in CASTLE. DISCUSSION: We found that prominent lymphovascular invasion and higher proliferative activities might be risk factors of metastasis in CASTLE. In addition, we have summarised the cytological, morphological, and immunohistochemical features of CASTLE for an accurate diagnosis.

Radiographic and pathological analysis of small lung adenocarcinoma using the new IASLC classification.

AIM: To analyse the correlation between computed tomography (CT) findings of small lung adenocarcinomas and the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society Classification of Lung Adenocarcinoma. MATERIALS AND METHODS: A retrospective review of 300 lung adenocarcinoma lesions (size ≤20 mm) after surgical resection in 295 consecutive patients was performed. Tumours were defined as air-containing type if the ratio of the maximum dimension of the tumour on mediastinal windows to the maximum dimension of the tumour on lung windows was ≤50%, and as solid-density type if the ratio was >50%. The incidence between CT findings (air bronchogram, vascular involvement, pleural tags, notches, and spiculation) and pathological findings were investigated. RESULTS: Of the 142 air-containing lesions, 114 were adenocarcinoma in situ (AIS), 28 were minimally invasive adenocarcinoma (MIA), and none of the lesions were invasive adenocarcinoma. Of the 158 solid-density lesions, 30 were AIS, 24 were MIA, and 104 were invasive adenocarcinoma. Notches and pleural tags were commonly observed in cases of invasive adenocarcinoma (p < 0.05). CONCLUSIONS: In the air-containing type of small lung adenocarcinomas, AIS and MIA were observed but no cases of invasive adenocarcinoma were found. The presence of notches and pleural tags were a significant factor in invasive adenocarcinoma.

Increased visceral fat and impaired glucose tolerance predict the increased risk of metabolic syndrome in Japanese middle-aged men.

BACKGROUND: Impaired glucose tolerance (IGT) represents a stage of pre-diabetes and is a risk factor for future cardiovascular disease (CVD) which is a major cause of death in type 2 diabetes. The metabolic risk factors such as elevated blood pressure (elevated BP), abdominal obesity, dyslipidemia (elevated levels of total triglycerides [TG] and low levels of HDL cholesterol), and hyperglycemia precede the onset of the metabolic syndrome that increases the risk for CVD. This clustering is commonly associated with pre-diabetic hyperinsulinemia and it reflects peripheral insulin resistance. The present study documented that a visceral fat area (VFA) >/= 100 cm (2) can replace waist-to-hip ratios (WHR) associated with IGT or IFG/IGT as a critical risk for the development of the metabolic syndrome in Japanese middle-aged men. MATERIALS AND METHODS: A total of 575 middle-aged Japanese men with fasting plasma glucose levels of 6.1 - 6.9 mmol/l (impaired fasting glucose; IFG) were enrolled in the study. After a 75-g oral glucose tolerance test (OGTT), blood samples were collected 0 - 2 h later for determination of plasma glucose, insulin concentrations and other variables. Based on the results of an OGTT, the subjects were subgrouped into categories of glucose tolerance for further study. RESULTS: Subjects with IGT or IFG/IGT had significantly higher levels of metabolic abnormalities such as high BMI, increased AUC glucose, elevated HbA1c, high VFA, elevated BP, and increased TG levels when compared to NGT (normal glucose tolerance) (p < 0.001). Compensatory hyper-secretion of insulin was seen in all pre-diabetic subjects, and was higher in IFG/IGT subjects (681 +/- 33 pmol . h/l) than NGT (480 +/- 22 pmol . h/l) (p < 0.01). The metabolic clustering including abnormal VFA, TG, HDL-C, and BP was strongly associated with the development of metabolic syndrome. Interestingly, VFA >/= 100 cm (2) adjusted for the Japanese correlates strongly with the development of the metabolic syndrome in preclinical IGT or IFG/IGT subjects, with odds ratios of 2.7 and higher. CONCLUSION: VFA >/= 100 cm (2) strongly correlates with prediabetic IGT or IFG/IGT which is possibly associated with underlying insulin resistance, and is a critical risk factor linked to the development of metabolic syndrome in Japanese middle-aged subjects with IGT or IFG/IGT.

Prostate-specific antigen induces osteoplastic changes by an autonomous mechanism.

The high prevalence of osteoplastic bone metastasis in prostate cancer (PC) is believed to be attributable to the production of osteoblast-stimulating factors by PC cells. Prostate-specific antigen (PSA) is a serine protease and an important serological marker for PC. Exposure of osteoblasts to PSA in vitro was found to result in cell proliferation and marked upregulation of transforming growth factor-beta (TGF-beta) mRNA expression. This PSA-induced increase in osteoblast proliferation was inhibited by anti-TGF-beta antibodies and serine protease inhibitors. In vivo, PSA markedly enhanced osteoplastic changes in human adult bone implanted into NOD/SCID mice without PC cells, and alpha(1)-antichymotrypsin prevented the PSA-induced increase in bone volume. PSA promotes osteoplastic change by activating an osteoblast autonomous mechanism that is independent of the production of bone growth factors by PC cells.

Detection of early invasion on the basis of basement membrane destruction in small adenocarcinomas of the lung and its clinical implications.

To evaluate the correlation between the degree of basement membrane (BM) preservation and clinicopathological characteristics in the replacement-growth type (lepidic growth type) of small peripheral adenocarcinomas of the lung, the BM components of 72 surgically resected replacement-growth type adenocarcinomas of the lung, 2 cm or less in diameter, were evaluated immunohistochemically by using a monoclonal antibody to Type IV collagen and polyclonal antibodies to 7S collagen and laminin. The tumors were classified into the following three distinctive histological types according to the condition of the elastic framework: Type I, bronchioloalveolar carcinoma without fibrotic foci; Type II, sclerosing bronchioloalveolar carcinoma without elastic framework destruction; and Type III, sclerosing bronchioloalveolar carcinoma with elastic framework destruction. The BM was well preserved in the area of bronchioloalveolar spread along fully expanded alveoli in all tumor types; however, BM preservation was significantly lost in the areas of collapsed alveoli in Type III tumors. There were no BM component staining reactions in the scarred regions of Type III tumors. In addition, lymph node metastasis was significantly greater in Type III tumors and BM-destroyed tumors. We concluded that the BM was largely destroyed by tumor cell invasion in the scarred region of Type III adenocarcinomas. Type III tumors had discontinuous BMs in the area of collapsed alveoli, indicating that this BM-destructive pattern must be the first step in tumor invasion. Type I and II tumors were concluded to be noninvasive adenocarcinomas, because their BM components were well preserved and they had a good outcome.

Accumulation of losses of heterozygosity and multistep carcinogenesis in pulmonary adenocarcinoma.

Sixty-six replacing growth-type early lung adenocarcinomas, measuring 2 cm or less across their greatest dimension, were used to investigate allelic losses at eight loci on the eight chromosomes carrying the principal cancer-associated genes. In total, 2 (16.7%) of 12 type A tumors (localized bronchioloalveolar carcinoma, LBAC) and 11 (39.3%) of 28 type B tumors (LBAC with alveolar collapse), which correspond to early lung adenocarcinomas including cancers in situ, showed allelic losses in one or more of the regions examined. In contrast, 25 (96.2%) of 26 type C tumors (LBAC with active fibroblastic proliferation), which correspond to small but advanced tumors, showed allelic losses in one or more regions. The change in histology from type A to type C was characterized by a significant rise in the incidence of allelic losses (P < 0.01). Deletions of 3p, 17p, 18q, and 22q increased significantly during malignant progression. In type C tumors that showed heterogeneous histological features, the tumor cells in the central fibrotic areas exhibited more allelic losses than those in the peripheral bronchioloalveolar growths and were, therefore, considered to have progressed to a more advanced stage than the tumor cells in the peripheral regions.

Thymoma with osseous metaplasia.

A 69-year-old woman with a 15-year history of abnormal chest shadow was referred to our hospital. An enhanced chest CT scan of the anterior mediastinum revealed a mass containing a high-density area. The preoperative radiologic diagnosis was thymoma. Operation was performed in October 2000. Histologically, multiple ossified areas were observed within the tumor. Intratumoral ossification has never been reported in thymoma. Therefore, we report the first case of thymoma associated with multiple foci of osseous metaplasia.

Loss of heterozygosity on chromosomes 9q and 16p in atypical adenomatous hyperplasia concomitant with adenocarcinoma of the lung.

Atypical adenomatous hyperplasia (AAH) has recently been implicated as a precursor to lung adenocarcinoma. We previously reported loss of heterozygosity (LOH) in tuberous sclerosis (TSC) gene-associated regions to frequently be observed in lung adenocarcinoma with multiple AAHs. In this study, we analyzed LOH in four microsatellite loci on 9q, including the TSC1 gene-associated region, and four loci on 16p, including the TSC2 gene-associated region, in both 18 AAHs and 17 concomitant lung adenocarcinomas from 11 patients. Seven of 18 (39%) AAHs and 9 of 17 (53%) adenocarcinomas displayed LOH on 9q. Five (28%) AAHs and seven (41%) adenocarcinomas harbored LOH at loci adjacent to the TSC1 gene. Four of 18 (22%) AAHs and 6 of 17 (35%) adenocarcinomas displayed LOH on 16p. One (6%) AAH and five (29%) adenocarcinomas harbored LOH at loci adjacent to the TSC2 gene. These findings may indicate a causal relationship of LOH on 9q and 16p in a fraction of AAH lesions and adenocarcinomas of the lung. Especially, the frequencies of LOH on 9q and at the TSC1 gene-associated region were high. The TSC1 gene or another neighboring tumor suppressor gene on 9q might be involved in an early stage of the pathogenesis of lung adenocarcinoma.

Microvessel density predicts the radiosensitivity of metastatic head and neck squamous cell carcinoma in cervical lymph nodes.

Cervical lymph node metastasis is the most common recurrence pattern of head and neck squamous cell carcinoma (HNSCC), and it is usually treated with radiation therapy and/or neck dissection. There has long been a desire for markers useful in predicting radiosensitivity to enable assignment of patients with recurrent head and neck cancer to clinical trials to improve their survival rates and quality of life. A total of 43 cases of HNSCC treated with whole or elective neck irradiation (total dose, 26-70 Gy; median, 60 Gy) for recurrent metastatic SCC in neck lymph nodes after neck dissection between 1992 and 1999 were the subject of this study. The relationship between radiosensitivity and clinicopathological and histopathological factors, including the Ki-67-labeling index for cell proliferation, p53 immunoreactivity and microvessel density (MVD), in surgical neck lymph node specimens were investigated by univariate and multivariate analysis. Of the 43 patients, 31 had recurrent tumors in neck lymph nodes after radiotherapy. Univariate analysis revealed significant associations between radiosensitivity and both high grade of keratinization (p=0.033) and low MVD (p=0.004), and marginally significant associations between radiosensitivity and grade of differentiation of the cancer in the lymph nodes (p=0.070). Multivariate analysis showed that only MVD had predictive value (p=0.016). Tumors with a high MVD possessed a significantly better neck control rate than tumors with a low MVD (p=0.004) by Kaplan-Meier analysis. MVD can be used as a good predictive marker for radiosensitivity of metastatic HNSCCs in cervical lymph nodes after neck dissection.

Clinicopathologic and DNA cytometric analysis of carcinoid tumors of the thymus.

Twelve cases of carcinoid tumors of the thymus were reviewed in terms of clinicopathologic, histochemical, and immunohistochemical features and DNA ploidy patterns. The collective consisted of nine male and three female patients, aged 34 to 74 years, of whom five (42%) had symptoms. Eleven patients underwent surgical resection, and one with systemic metastases was autopsied. In the 11 resected patients, tumors had invaded surrounding structures in four cases, and mediastinal lymph node metastases were detected in six. Recurrence occurred in two of the resected patients (18%), and the 5-year survival rate was 82%. Histologically, all tumors showed an organoid growth pattern with delicate fibrovascular stroma. In addition, three tumors had unusual morphologic features such as combined features of carcinoid tumor and thymoma and solid growth pattern with occasional large tumor cells. Mitotic counts ranged from 1 to 14 per 10 high-power fields with a mean count of 4.9. Central necrosis within solid nests was observed in nine tumors. Classification of this series using the WHO histologic classification system resulted in categorization of all 12 tumors as atypical carcinoids. All tumors were positive for Grimelius staining and for cytokeratin. Immunohistochemical staining documented the presence of moderately to strongly positive neuroendocrine markers such as neuron-specific enolase, chromogranin A, synaptophysin, and neural cell adhesion molecule. No correlation between proliferative activity based on the Ki67 labeling index and prognosis or lymph node metastasis was found. Concerning DNA ploidy patterns, only one tumor with multiple lymph node metastases was considered to be aneuploid. In conclusion, although all of our cases were histologically classified as atypical carcinoid tumors of the thymus, most were diploid, and the patients enjoyed a relatively good prognosis.

p53 gene alteration in atypical epithelial lesions and carcinoma in patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is well known to be associated with lung cancer. Several atypical epithelial lesions are frequently observed in the fibrotic area in IPF patients, and they have been suspected to be related to lung carcinogenesis. Several studies have suggested that p53 protein accumulation and mutation occur in the early pathogenesis of squamous cell carcinoma of the lung, suggesting some abnormality of the p53 tumor-suppressor gene in interstitial lung diseases. To examine the cause of the high frequency of lung cancer in IPF, we examined the p53 changes in atypical epithelial lesions and carcinoma in patients with IPF by immunohistochemistry and mutational analysis. We examined 19 lung cancer patients with IPF who underwent surgical resection for lung cancer in our institute. Paraffin-embedded tissues were treated by microwave and stained with an anti-p53 antibody (RSP53) by the avidin-biotin-peroxidase complex method. Mutations in exons 5 through 8 of the p53 gene were also examined by polymerase chain reaction mediated single-strand conformation polymorphism (polymerase chain reaction-single-strand conformation polymorphism) analysis and DNA sequencing. p53 protein was immunohistochemically detected in 13 (62%) of 21 squamous cell carcinomas, 3 (60%) of 5 squamous metaplasia with atypia, 16 (54%) of 30 squamous metaplasia, and 1 (4%) of 26 other hyperplastic lesions. p53 mutation was detected in 12 (57%) of 21 squamous cell carcinomas, 2 (40%) of 5 squamous metaplasia with atypia, 7 (23%) of 30 squamous metaplasia, and 0 (0%) of 26 other hyperplastic lesions. In conclusion, there are frequent p53 gene alterations in squamous metaplasia, which is distributed in the peripheral zone of the fibrotic area in patients with IPF. The present findings might provide a clue to the molecular mechanisms underlying the high incidence of lung cancer, especially peripheral-type squamous cell carcinoma in IPF patients, and suggest that p53 gene alterations play an important role in the early stages of lung carcinogenesis in patients with IPF.

Atypical adenomatous hyperplasia of the lung in autopsy cases.

BACKGROUND: Atypical adenomatous hyperplasia (AAH) is a possible precursor lesion of adenocarcinoma of the lung, but very few reports of AAH have focused on the autopsy lung. METHODS: We intended to clarify the characteristics of AAH in the general population by using 207 autopsy cases, ranging in age from 0 to 90 years old. RESULTS: A total of 179 eligible cases (86.5%) and 1265 tissue slides (7.0 per case) was examined independently by two pathologists. One hundred seventy-nine autopsy cases consisted of 125 males and 54 females, whose median ages were 38 (range 0-90) and 31 (range 0-81) years old, respectively. AAH was microscopically found in five of 179 autopsy cases (2.8%). The male/female ratio was 5/0 and age distribution was 52-63 years of age (median 57). One of five cases with AAH harbored esophageal carcinoma, but the others had no present or previous malignant neoplasm. One of five lesions was high grade and the others were low grade. All five cases showed positive immunoreactivity for proSP-C, a type II pneumocytes marker, but not for p53, Ki-67 or CEA. CONCLUSIONS: The incidence of AAH was very low in the general autopsy cases, as compared with the previously reported surgically resected lung and senile autopsy cases, and AAH seems to occur after middle age in general.

Image analysis of microvessel surface area predicts radiosensitivity in early-stage laryngeal carcinoma treated with radiotherapy.

PURPOSE: The tissue oxygenation level, which is theoretically governed by distance from blood vessels, is one of the most important modulators of the radiosensitivity of carcinoma. A computed image analysis system for the detection of tissue oxygenation was developed to establish a method of predicting radiosensitivity in early-stage laryngeal carcinoma treated by curative radiotherapy. EXPERIMENTAL DESIGN: Microvessel structures labeled with CD31 antigen were investigated in 55 patients undergoing curative radiotherapy for T1 and T2 laryngeal carcinoma. We calculated (a) microvessel density [(MVD) vessels/field] under a microscope; (b) the ratio of the total microvessel number (TN):tumor area (TA) [TN:TA; vessels/mm2]; (c) the ratio of the total microvessel perimeter (TP):TA (TP:TA; mm/mm2); and (d) the ratio of tumor tissue area >150 microm from microvessels (hypoxic ratio; %) as parameters of tissue oxygenation in each whole biopsy specimen by using an image analyzer. We compared each of these factors with radiosensitivity. RESULTS: Mann-Whitney's U test revealed that tumors with a high MVD (median, 42 vessels/field), high TN:TA ratio (median=40.9 vessels/mm2), high TP:TA ratio (median, 2.92 mm/mm2), and low hypoxic ratio (median, 30.3%) had significantly greater radiosensitivity than tumors with a low MVD, low TN:TA ratio, low TP:TA ratio or high hypoxic ratio (P = 0.002, P = 0.0004, P < 0.0001, and P = 0.004, respectively). CONCLUSIONS: Prediction of radiosensitivity on the basis of the TP:TA ratio can be used as an efficient means of avoiding ineffective radiation, complications after salvage surgery, and prolonged hospital stays.

Occupational cancer genetics: infrequent ras oncogenes point mutations in lung cancer samples from chromate workers.

BACKGROUND: Chromium carcinogenicity and mutagenicity are no longer disputed. However, although chromium has various genetic effects that induce cancer, its mechanism of inducing lung cancer in humans is still not fully understood. p53, a tumor suppressor gene, was found to be infrequently mutated in samples of lung cancer in workers with long occupational exposure to chromium, suggesting other cancer-related genes to be targeted in such tumors. METHODS: To assess the contribution of the ras oncogenes in the pathogenesis of chromate-related lung cancer, we studied point mutations at the critical positions of codons 12, 13, and 61 of the Ha-ras and Ki-ras oncogenes in 38 lung cancer samples derived from Japanese patients who worked in the chromate industry for long periods. We used both radioactive isotope and non-radioisotope PCR-SSCP techniques. RESULTS: The results of this study demonstrated that activation of ras genes due to point mutations in chromate-related lung cancer is a rare event. CONCLUSIONS: Ras oncogenes activated by point mutations do not have a major role in the process of tumorigenesis of chromate-related lung cancer.

Establishment of a novel species- and tissue-specific metastasis model of human prostate cancer in humanized non-obese diabetic/severe combined immunodeficient mice engrafted with human adult lung and bone.

Bone is the most common site of metastasis in prostate cancer (PC), and to generate an animal model to investigate the basis of the unique organ tropism of PC cells for bone, we engrafted humanized non-obese diabetic/severe combined immunodeficient (NOD/SCID-hu) mice with human adult bone (HAB) and lung (HAL). Human PC cell lines LNCaP (1 x 10(7)) and PC-3 (5 x 10(6)) were injected into male NOD/SCID-hu mice via the lateral tail vein at 3-4 weeks after implantation. At 8 weeks after the injection, LNCaP and PC-3 cells had metastasized specifically to HAB in 35 and 65%, respectively, of the mice. The tumors formed by LNCaP appeared to be the osteoblastic type, whereas the PC-3 tumors consisted of osteolytic lesions without any surrounding osteogenic response. A feature of experimental metastasis of PC in NOD/SCID-hu mice was its specificity for HAB tissue. Human PC cells had no or very low metastatic potential in regard to implanted HAL, mouse bone, or native mouse bone. These findings indicate that metastasis of PC cells to HAB is both species and tissue specific. The availability of this small animal model could provide a useful tool for identifying and analyzing important features of the human PC metastatic process that cannot be addressed in conventional metastasis models.

A 7 mm lung adenocarcinoma with mediastinal involvement and lymphangiosis carcinomatosa: a case report.

We report a case of a 46-year-old man with a 7 mm lung adenocarcinoma with mediastinal nodal involvement and lymphangiosis carcinomatosa. The resected right middle lobe contained a 7 mm well-differentiated papillary adenocarcinoma and lymphatic vessels towards the hilum were severely involved. The disease was pathologically diagnosed as T1N2M0. Six months after the operation, malignant pleural effusion and multiple bone metastases developed and he died 21 months after the operation. This case indicates that even a very small-sized lung cancer, 1 cm or smaller, could be biologically highly malignant.

Atypical adenomatous hyperplasia of the lung: a clinicopathological study of 118 cases including cases with multiple atypical adenomatous hyperplasia.

BACKGROUND: Atypical adenomatous hyperplasia (AAH) of the lung is a putative precursor lesion of adenocarcinoma, according to many immunohistochemical and genetical studies, but few clinicopathological studies on a large number of cases have been reported. The aim of this study was to clarify the clinicopathological characteristics of lung cancer patients with AAH lesions. METHODS: A retrospective study was carried out on 508 consecutive primary lung cancer patients operated on at National Cancer Center Hospital East. The relationship between the number and location of AAH lesions and the clinicopathological features of the lung cancer patients was analysed statistically. RESULTS: A total of 311 AAH lesions were found in 118 (23.2%) of the 508 cases. AAH lesions were detected in 121 of 572 lobes examined, usually in both upper lobes, and occurred most frequently in patients with adenocarcinoma (OR 2.97; 95% CI 1.82 to 4.85). AAH lesions were more frequently detected in patients with multiple primary carcinomas than in those with a single carcinoma (OR 3.06; 95% CI 1.56 to 6.00). The presence of AAH lesions was not significantly correlated with sex, age, smoking status, familial history of malignancy, or preceding malignancy. Patients with multiple AAH lesions were found to have a significantly higher frequency of preceding malignancies. CONCLUSIONS: The present study highlights the clinicopathological characteristics of AAH lesions, showing them to be significantly associated with both adenocarcinoma and multiple primary carcinoma of the lung and suggesting common factors in the histogenesis of multiple AAH lesions and preceding malignancy.

Clinicopathological characteristics of surgically resected lung cancer associated with idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVES: Idiopathic pulmonary fibrosis (IPF) is well known to be associated with lung cancer. It is important to clarify the clinical and pathological features of lung cancer with IPF in understanding the pathogenesis of lung cancer in IPF patients. We compared clinicopathological factors of lung cancer in patients with and without IPF. METHODS: A retrospective study was conducted in 711 surgically resected lung cancer patients. Medical records were compared of IPF and non-IPF patients. RESULTS: Of the 711 patients, 53 (7.5%) were IPF patients. Lung cancer in IPF patients was more frequent in elderly male smokers. Most lung cancers in IPF (79%) arose in peripheral areas involving fibrosis (P < 0.01). The incidence of squamous cell carcinoma in the IPF patients (46%) was significantly higher than that in non-IPF patients (22%) (P < 0.01). The incidence of multiple lung cancer in IPF cases (17%) was also significantly higher. CONCLUSIONS: These results suggest that IPF has the potential to develop into lung cancer, especially peripheral squamous cell carcinoma. Further molecular analyses are necessary to clarify the relationship between IPF and lung cancer.