Utility of liquid-based cytology in endometrial pathology: diagnosis of endometrial carcinoma.

OBJECTIVE: The purpose of this study was to examine the utility of SurePath-liquid-based cytology (LBC) compared to conventional cytological preparations (CCP) in the identification of endometrial carcinoma. METHODS: During a 13-month period, direct endometrial samples were collected from 120 patients using the Uterobrush. The material comprised 30 cases each of endometrial carcinoma, proliferative endometrium, secretory endometrium and atrophic endometrium. The following points were investigated:(i) the frequency of cell clumps in endometrial carcinoma; (ii) the area of cell nuclei; (iii) overlapping nuclei. RESULTS: (i) Comparison of the frequency of cell clumps with irregular protrusion pattern and papillo-tubular pattern showed no statistically significant difference in either type of cell clump between CCP and LBC. (ii) Comparison of the nuclear area of cells showed a sequential decrease from endometrial carcinoma to secretory endometrium, to proliferative endometrium and to atrophic endometrium, which was significant in CCP and LBC. (iii) Nuclear area was significantly lower with LBC compared with CCP in endometrial carcinoma, secretory endometrium and proliferative endometrium but not atrophic endometrium. (iv) Comparison of the degree of overlapping nuclei showed a sequential decrease from endometrial carcinoma to proliferative endometrium, to secretory endometrium and to atrophic endometrium, which was significant in both CCP and LBC. (v) Comparison of the degree of overlapping nuclei between CCP and LBC showed no significant difference for normal types of endometrium, but LBC had significantly higher values (P < 0.0001) in endometrial carcinoma than in CCP. CONCLUSIONS: The results of this study revealed that applying diagnostic criteria used in CCP to LBC was easy to achieve, because LBC had excellent cytoarchitectural preservation and cells were well presented. Although we have not examined all cytological features of malignancy and have not considered atypical hyperplasia, we believe that this method may be a useful tool in the diagnosis of endometrial cytology.

Treatment outcome by risk group after radical prostatectomy in Japanese men.

BACKGROUND: North American investigators have suggested the usefulness of risk-group stratification based on prostate-specific antigen (PSA), clinical stage and biopsy Gleason score for predicting the biochemical outcome of prostate cancer after radical prostatectomy. There have been no reports of the application of this stratification to early biochemical outcome after radical surgery in Japanese men. METHODS: The study population consisted of 178 men treated with radical retropubic prostatectomy and bilateral pelvic lymph node dissection at Kitasato University Hospital (n = 110) and Kurashiki Central Hospital (n = 68) between October 1992 and May 1999. Pathologic and biochemical outcomes after radical prostatectomy were analyzed based on risk-group stratification. Risk groups were further analyzed according to detailed pathologic findings at biopsy. RESULTS: The median follow-up period for the 178 patients after radical surgery was 41.5 months (range, 2.0--82.0 months; mean, 40.9 months). Fifty-eight patients experienced PSA failure at a median of 8.0 months following surgery (range, 0.0--58.0). Risk-group stratification distinctly defined groups of pathologic findings in the radical prostatectomy specimens. The proportion of patients with PSA failure for low, intermediate and high-risk groups were 9.5%, 23.9% and 56.9%, respectively (P < 0.0001). Use of the number of cores with cancer and maximum cancer length in biopsy cores failed to improve risk stratification for PSA outcome in all risk groups. CONCLUSIONS: Risk-group stratification based on preoperative variables may significantly improve a physician's ability to counsel patients about PSA outcome after radical prostatectomy. Further improvement in risk stratification may call for use of variables other than the pathologic information in biopsy cores.

Reduced expression of hMLH1 and hMSH2 gene products in high-grade hepatocellular carcinoma.

We performed an immunohistochemical analysis of 2 major DNA mismatch repair proteins, human Mut L homologue-1 (hMLH1) and human Mut S homologue-2 (hMSH2), in hepatocellular carcinoma (HCC) using 33 biopsied and 58 surgically resected specimens, as well as 30 samples from non-cancerous livers. In well-differentiated HCCs, the immunoreactivity for these antigens was well preserved, and the staining intensity was stronger compared to the surrounding liver tissues. However, among 41 moderately-differentiated and 9 poorly-differentiated HCCs of the resected cases, hMLH1- and hMSH2-positive cells were significantly reduced in 19 (38%) and 9 (18%) cases, respectively. In 9 resected tumors, the expression of both of these antigens was reduced. Moreover, in 41 tumors of differing histological grades, 10 and 5 tumors for hMLH1 and hMSH2, respectively, contained a less-differentiated area with a reduced number of immunoreactive cells. The samples from non-cancerous biopsied liver and fetal autopsy tissue were well immunostained for both hMLH1 and hMSH2. We confirmed in this series that the hMLH1 and hMSH2 defect did commonly occur in high-grade HCCs, and that it might play a role in tumor progression.

Dynamic endorectal magnetic resonance imaging for local staging and detection of neurovascular bundle involvement of prostate cancer: correlation with histopathologic results.

OBJECTIVES: To assess the staging accuracy and detection of neurovascular bundle involvement by dynamic subtraction contrast-enhanced endorectal magnetic resonance imaging (MRI) in patients with localized prostate cancer. METHODS: In 38 patients with biopsy-proven prostate cancer, endorectal MRI was performed on a 1.5-Tesla magnetic resonance system using the dynamic technique with gadolinium-diethylenetriaminepentaacetic acid bolus enhancement. Two radiologists prospectively assessed the tumor involvement, localization, capsular penetration, seminal vesicle invasion, and neurovascular bundle involvement. All patients subsequently underwent radical prostatectomy, and the MRI findings were correlated with the histopathologic results. RESULTS: The overall accuracy of detecting cancer localization in the prostate was 72%. The detection of involvement in the peripheral zone had an 80% accuracy rate, but for lesions in the transition zone, the rate was 63%. The sensitivity and specificity of tumor detection was 81% and 79% for peripheral zone cancers and 37% and 97% for transition zone cancers, respectively. The accuracy rate, was 84%, 97%, and 97% for the detection of capsular penetration, seminal vesicle invasion, and neurovascular bundle involvement, respectively. CONCLUSIONS: Prostatic MRI with an endorectal surface coil using the dynamic technique more accurately detected tumor localization, capsular penetration, seminal vesicle invasion, and neurovascular bundle involvement than previously reported methods. The detection of tumor localization was more accurate in the peripheral zone than in the transition zone. This technique may be useful for the selection of patients for radical prostatectomy and, particularly, for identifying candidates for nerve-sparing surgery.

A study of pretreatment nomograms to predict pathological stage and biochemical recurrence after radical prostatectomy for clinically resectable prostate cancer in Japanese men.

BACKGROUND: Accurate pretreatment identification of the risks that prostate cancer has extended beyond the gland and that it will recur would significantly influence practice patterns. Preoperative nomograms to predict such risks have not been developed for the oriental male population. METHODS: Construction of nomograms to predict preoperatively pathological outcome and early biochemical failure following radical prostatectomy in Japanese males was based on logistic regression analysis, with predicted probabilities and 95% confidence intervals for the final model being obtained by repeating the analysis on 1000 bootstrap samples from the original cohort. RESULTS: Prostate-specific antigen level, clinical stage and biopsy Gleason score contributed significantly to the prediction of pathological stage and of biochemical failure in the univariate analysis (p < 0.001). Combined use of these three variables predicted these treatment outcomes better than any single variable (p < 0.001). Nomograms combining these three variables to predict final pathological findings and early biochemical failure were then developed. The medians and 95% confidence intervals of the predicted probabilities are presented in the nomograms. CONCLUSIONS: This information enables clinicians to use their nomograms when counseling Japanese patients, leading to more informed treatment decisions and helping to identify those with a high risk of early biochemical failure. The nomograms may also be used to assure comparability of different treatment modalities in investigational trials.

Solid-pseudopapillary tumor of the pancreas: immunohistochemical localization of neuroendocrine markers and CD10.

To clarify the neuroendocrine differentiation and CD10 expression in solid-pseudopapillary tumors (SPTs) of the pancreas, we performed immunohistochemical analysis in 19 such tumors, including one solid-pseudopapillary carcinoma (SPC), along with 20 pancreatic neuroendocrine tumors (PNTs), six acinar cell carcinomas (ACCs), and one pancreatoblastoma (PB). We used antisera directed against CD56, synaptophysin, protein gene product 9.5, the alpha-subunit of Go protein, chromogranin A, CD10, trypsin, chymotrypsin, various cytokeratins (CKs), CA19-9, vimentin, and alpha-1-antitrypsin (AAT). All SPTs exhibited immunoreactivity for CD56 and CD10, and 15 expressed other neuroendocrine markers focally with the exception of chromogranin A. Frequent clustering of synaptophysin-positive cells was noted. Two cases contained a peculiar nodule that cytomorphologically and immunohistochemically resembled PNT. CD10-positive cells were scarce in one SPC. PNTs were CD56-positive, but often with faint intensity, and staining for other neuroendocrine markers, including chromogranin A, was diffusely positive. CD10 was detected, mostly in a focal pattern, in five PNTs. Pan-CK, CK8, CK18, and CK19 were more frequently demonstrated in PNT than SPT. Vimentin and AAT were often identified in PNT as well and were not specific for SPT. ACCs were CD56-negative, with the exception of one case designated as a mixed acinar-endocrine carcinoma. PB was focally positive for CD56 at the periphery of the tumor nests. Four ACCs and one PB exhibited focal CD10 reactivity. This study demonstrated the unique immunohistochemical features of SPT. Our results also suggest that SPT exhibits, at least focally, neuroendocrine differentiation, and that these neuroendocrine markers and CD10 are diagnostically useful.

Familial cases of severe measles pneumonia.

We report two cases of severe measles pneumonia. Patient 1, a 17-year-old boy who contracted measles in the acute phase of infectious mononucleosis caused by Epstein-Barr virus (EBV), transmitted the disease to patient 2, his father. Both patients presented severe pneumonia with bilateral diffuse micronodular shadows. Diagnoses were established in both patients by antibody titers for measles and reverse transcriptase-polymerase chain reaction (RT-PCR) of blood and throat swab. Multinucleated giant cells with intranuclear inclusion bodies were revealed in the transbronchial lung biopsy (TBLB) specimen of patient 2. Both patients recovered with pulse steroid therapy.

Epithelioid trophoblastic tumor: morphological and immunohistochemical study of three lung lesions.

Epithelioid trophoblastic tumor (ETT) is a term proposed for an unusual variant of trophoblastic tumor that is closely related to choriocarcinoma but shows monomorphic growth of highly atypical trophoblastic cells instead of the typical dimorphic pattern of choriocarcinoma. We report here 3 cases of ETT, all of which were lung lesions probably originating from uterine trophoblastic disease. The antecedent pregnancies of the 3 cases were hydatidiform mole, invasive mole, and term pregnancy, respectively. The tumors were composed of highly atypical mononucleate cells, which mainly involved alveolar spaces, forming nests with central eosinophilic necrosis. Multinucleate giant cells were found within the nests, but they were fewer in number than in typical choriocarcinoma. The tumors were not associated with extensive hemorrhage or necrosis, except for 1 case, in which the ETT was combined with typical dimorphic choriocarcinoma. Immunohistochemically, multinucleate giant cells and occasional mononucleate tumor cells showed positivity for human chorionic gonadotropin. Staining for human placental lactogen was positive in rare multinucleate giant cells, and in 1 case, tumor cells showed diffuse positivity for placental alkaline phosphatase. Because ETT has a remarkably epithelioid appearance in cytological and architectural features, differentiation from the epithelial malignancies is problematic. Trophoblastic markers are frequently expressed in nontrophoblastic tumors, and reactivity for those markers alone is not sufficient for exclusion of other tumors. Rather, evidence of ETT comes from a combination of morphological features, immunohistochemical study, and clinical history.

Association of replication error positive phenotype with lymphocyte infiltration in endometrial cancers.

Microsatellite instability (MI) has been detected in certain sporadic cancers as well as in hereditary non-polyposis colorectal cancer (HNPCC). In order to determine the precise clinicopathological characteristics of MI in endometrial cancer, we examined 90 sporadic endometrial cancers (83 endometrioid adenocarcinomas, 3 adenosquamous carcinomas, 3 papillary serous carcinomas, and 1 clear cell carcinoma) and eight lesions of endometrial hyperplasia for replication error (RER) using polymerase chain reaction amplification of CA repeated microsatellite sequences at 15 loci. RER was observed in 23 (28%) of the 83 endometrioid adenocarcinomas at at least one locus and in 19 (23%) at two or more loci (RER+ phenotype) in the seven most commonly observed loci, but not in carcinomas of other histological types or in endometrial hyperplasia. Lymphocyte infiltration around carcinoma cells, which is one of the histological features seen in tumors from HNPCC, was severer in RER+ phenotype tumors (79%, 11/14) than in the RER- tumors (25%, 11/44) (marked/moderate infiltration versus slight, P < 0.001, chi 2 test), when 58 tumors with muscular invasion were examined. The RER+ phenotype was associated with a higher parity and gravidity (P < 0.05, Wilcoxon test). However, RER+ phenotype was not associated with tumor stage, histological grade, muscular invasion, lymph node metastasis or patient survival. In conclusion, MI occurs in a subset of endometrial cancers, which often show marked infiltration of lymphocytes around the tumor.

Etiological analysis of focal nodular hyperplasia of the liver, with emphasis on similar abnormal vasculatures to nodular regenerative hyperplasia and idiopathic portal hypertension.

Pathological studies were performed on 23 cases of focal nodular hyperplasia (FNH) under the hypothesis that FNH is a hyperplastic lesion caused by abnormal vasculatures of portal tracts within the nodule. For a comparison of the histological features of portal tracts, nodular regenerative hyperplasia (NRH), idiopathic portal hypertension (IPH), chronic hepatitis and so-called normal liver were used as control tissues. Extranodular areas of FNH nodules were also examined. Clinical data were briefly summarized. Most of the portal tracts within FNH nodules showed various abnormal findings, such as dilatation and/or stenosis of portal vein, muscular thickening of arterial wall with dilated or stenotic lumina, lymphocyte infiltration, and bile ductule proliferation. However, portal vein thrombi were not found. These findings were not thought to represent compensatory reaction to portal vein thrombosis. Similar abnormal features were also observed in extranodular areas of FNH although to a milder degree. These abnormal features resembled those of NRH and IPH. Moreover, the characteristic scar-like tissues within FNH nodules were proved to be abnormally large portal tracts including large feeding arteries, portal veins and bile ducts. It has been believed that septa and scar-like tissue within FNH nodules are not portal tracts and that arterial malformation independent of portal tracts are related to the development of FNH. In addition, venous structures within FNH modules have until now not been considered to be portal veins. However, this study revealed that severe anomaly of portal tracts including portal veins and hepatic arterial branches existed in FNH nodules. Moreover, portal tracts in extranodular areas were also abnormal. Clinically, only one patient had a history of oral contraceptives. Based on these findings, congenital anomaly of the portal tracts histologically resembling the abnormal portal tracts of NRH and IPH may be related to the pathogenesis of FNH.

Immunohistochemical expression of nm23 gene product, nucleotide diphosphate kinase, in pancreatic neoplasms.

CONCLUSION: Our findings suggest that contrary to the proposed role for the nm23 protein as a tumor metastasis suppressor, in pancreatic tumors, the nm23 protein does not play an important role as a suppressor against tumor metastasis. BACKGROUND: The nm23 gene product, nucleotide diphosphate kinase, is believed to suppress tumor metastasis. Although a number of studies on many kinds of tumors have examined the relationship between nm23 expression and metastatic potential, the antimetastatic activity of nm23 remains controversial. The expression of the nm23 protein has not been examined in pancreatic tumors, except for a few reports on pancreatic duct cell carcinomas. METHODS: We have investigated nm23 expression in pancreatic duct cell carcinomas, islet cell tumors, and ampullary carcinomas by immunohistochemical methods. RESULTS: In 73 cases of pancreatic duct cell carcinomas, the nm23 expression was increased when compared with the adjacent normal pancreatic ducts; diffuse immunostaining was detected in 21 (29%) cases, focally positive immunostaining in 47 (64%) cases, and negative immunostaining in 5 cases (7%). All five negative samples were obtained from distant metastatic regions. However, there was no significant difference in the nm23 expression between primary tumors and regional lymph node metastases. Furthermore, there was no significant correlation between nm23 expression and the prognosis of the 55 resected cases. In the 15 cases of ampullary carcinomas, all 15 tumors were positive for nm23 protein (6 diffuse and 9 focal), and the staining intensity was stronger than in normal pancreatic ducts. There was no significant difference in the nm23 expression in the primary regions between patients with and without lymph node metastasis (2 diffuse and 5 focal out of 7 patients with lymph node metastasis, and 4 diffuse and 4 focal out of 8 patients without lymph node metastasis). All 12 islet cell tumors showed strong and diffuse staining for the nm23 protein.

Case report: intraglomerular metastasis with neoplastic cell interposition.

A case is described of an 88-year-old man with lung cancer, nephrotic syndrome, and renal dysfunction who died suddenly of an acute myocardial infarction and whose autopsy revealed many adenocarcinoma cells stacked within glomerular capillary lumina of his kidney, entering into basement membrane zones (ie, neoplastic cell interposition). In addition, glomeruli showed a lobular transformation, doubling of glomerular basement membrane, and electron dense deposits along the glomerular basement membrane. These changes were similar to those of membraneoproliferative glomerulonephritis. The association of intraglomerular metastasis and membranoproliferative glomerulonephritis-like lesions led the authors to speculate that the latter glomerular change might have provided an attractive opportunity for circulating tumor cells to be trapped and grow within the glomerular lumina. This mode of metastasis has not been well-recognized. The authors describe the experience, review the literature, and discuss its possible pathogenesis.

[Multiple extra-osseous accumulation of 99mTc-phosphorous compounds bone scintigraphy in small cell lung cancer associated with hypercalcemia].

Bone scintigraphy was performed in a patient with lung cancer of small cell. On bone scintigraphy the increased accumulations in kidneys were observed, while no findings of multiple skeletal accumulations suspected of bone metastases were observed. Four weeks later, when hypercalcemia has been advanced, on repeated bone scintigraphy the extra-skeletal accumulations in such as lung, heart and stomach were shown. These findings indicated that the cause of hypercalcemia in this case was due to not bone metastases but humoral hypercalcemia which the osteolytic substance was produced from tumor. In present paper, the usefulness of bone scintigraphy in hypercalcemia with malignancy, and the mechanism of hypercalcemia have been described and discussed.

Imprint immunocytochemistry of estrogen receptors in breast carcinoma.

To clarify the accuracy of immunocytochemical detection of estrogen receptors (ER) in breast carcinomas using cytological materials, imprint specimens from tumor tissue were compared with frozen tissue sections and tumors analyzed by the dextran coated charcoal (DCC) method and enzyme immunoassay (EIA). Out of 50 cases examined by imprint immunocytochemistry, there were 39 ER positive cases (78.0% positivity). The positivity in the imprint materials agreed with that of the DCC in 36 out of 40 cases (85.0%), with 100% sensitivity and 60.0% specificity. The two methods statistically correlated with each other in their positivity and grade (p less than 0.001). The positivity and grades of imprint and frozen immunocytochemistry as well as those of imprint immunocytochemistry and the EIA agreed almost perfectly with each other. As a result of the present study, we concluded that immunocytochemical detection of ER is indeed reliable, as accurate as other procedures. We recommend that aspiration biopsy cytology (ABC) be used for morphological examination and ER immunocytochemistry when adequate materials are available and that imprint materials be used when ABC materials are inadequate and fresh tissue is available at the time of surgery.

Squamous cell carcinoma with cyst of the thyroid.

Two cases of primary squamous cell carcinoma associated with a thyroid cyst in the thyroid are described. The majority of squamous cell carcinomas reported so far have had some degree of co-existing adenocarcinoma, while the cases presented in this report had no glandular component at all. The histogenesis of squamous cell carcinoma is not clear, but at present, it is believed that most cases arise from the follicular epithelium. In our cases, in spite of an intensive examination of serially sectioned specimens, no areas of adenocarcinoma, squamous metaplasia from the follicular epithelium, or congenital squamous remnants could be found.

Mucin-producing carcinoma of the thyroid gland--a case report and review of the literature.

Mucin-producing carcinoma of the thyroid is rare and its histogenesis has been debated. The first case was reported by Diaz-Perez et al. (1976). We herein report the sixth case of mucin-producing carcinoma of the thyroid which was discovered in a 72-year-old Japanese woman. This patient was admitted with a 10-year history of a lump in the right anterior neck, which started to grow suddenly two months before diagnosis. The pathological diagnosis at biopsy was anaplastic carcinoma. A course of radiation therapy followed by chemotherapy resulted in no response. She died of two months after admission. At autopsy, the main tumor was found in the right lobe of the thyroid with metastasis to the lungs and liver. Histologically, the tumor was composed of mucin-secreting glandular cells and nests of epidermoid cells with keratinization and infrequent formation of intercellular bridges. Mucin was demonstrated both intracellulary and extracellulary.

[Divergent histology in the primary and metastatic lesions of thyroid carcinoma].

The metastatic lesions of malignant diseases tend to present similar histological findings as the primary tumor. However, thyroid carcinoma is one of the malignancies which may be an exception to this rule. We have reviewed 61 consecutive autopsies of thyroid cancer patients at the Ito Hospital and Kawasaki Medical School Hospital during a period between 1969-1982. Fifty-five of 61 cases of thyroid carcinoma were found to have metastatic spreads beyond the thyroid. The uniform pathological findings were present in 5 of 9 papillary adenocarcinomas, 14 of 15 anaplastic carcinomas, and 1 of two squamous cell carcinoma and one epidermoid carcinoma. The remaining 36 patients were found to have different histological findings in metastatic lesions from the primary tumor. The histological types in coexisting metastases varied from one lesion to the other; the primary tumor was adenocarcinoma, but one of the metastases was anaplastic and the others showed adenocarcinoma or its combination. Those histological divergence in the primary tumor and metastases can be considered as the results of anaplastic or squamous cell transformation from adenocarcinoma. Such alteration of the histological findings in thyroid carcinoma calls for the reassessment of the therapeutic strategy.

Dirofilarial infection in human lungs.

Two cases of dirofilarial infection in the human being were reported. Dirofilarial infection is common in dogs but rather rare in human. A review of Japanese literature disclosed 13 cases of human dirofilarial infection. Scarcity of symptoms and its morphological similarity to tuberculosis or infarction as well as the popularity in pets suggest that the true incidence of infection may actually be higher than the above figure. Our cases alert us for the recognition of human dirofilarial infection, and careful examination of multiple sections in granulomatous or nonspecific infarcted lesions is suggested.