Usefulness of estrogen receptor detection using archival Papanicolaou-stained smears.

OBJECTIVE: To examine estrogen receptor (ER) detection using cytologic specimens and to compare the results with those obtained by the dextran-coated charcoal (DCC) method and enzyme immunoassay (EIA). STUDY DESIGN: Immunocytochemical staining was conducted on 60 cases of breast cancer resected at our hospital between April 1993 and November 1997 in which ER had been measured by DCC or EIA. Specimens for immunocytochemical staining were prepared by a cell transfer method using archival Papanicolaou-stained imprint smears, and ER staining was performed by the labeled streptavidin method using an anti-ER monoclonal antibody. These results were compared with those obtained by DCC or EIA. RESULTS: In immunocytochemical staining for ER, positive staining was observed in the nuclei of tumor cells. A good correlation was obtained between the immunocytochemical staining results and biochemical results. Five cases were positive in anti-ER staining but negative in biochemical tests, and two cases were negative in anti-ER staining and positive in biochemical tests. CONCLUSION: Unlike biochemical assays, the immunocytochemical method does not necessitate use of fresh frozen materials and can be performed even using archival Papanicolaou-stained smears. Immunocytochemical study is a highly useful method for routine ER determination.

Intra-abdominal angiosarcomatosis after radiotherapy.

BACKGROUND: We report a case of a 61-year-old Japanese woman who developed intra-abdominal angiosarcomatosis 20 years after receiving radiotherapy for squamous cell carcinoma of the cervix. METHODS AND RESULTS: The surgically resected portion of the ileum showed diffuse proliferating angiosarcoma, with irregular channels lined by atypical vascular endothelial cells. Immunohistochemical studies showed that the tumour cells were positive for Factor VIII-related antigen and ulex europaeus agglutinin 1. At autopsy, the tumour had disseminated to the peritoneum and invaded into the right thoracic cavity. CONCLUSIONS: These findings were compatible with radiation-induced angiosarcomatosis.

Cytodiagnosis of malignant melanoma of soft tissue: report of a case with diagnosis by intraoperative cytology.

BACKGROUND: Malignant melanoma of soft tissue (MMST) is a rare tumor and consists of < 1% of all soft tissue neoplasms. There are few reports on its cytodiagnosis. CASE: A 14-year-old male attended the Department of Orthopedics, Juntendo University Urayasu Hospital, in August 1994 because of a painless tumor in the distal portion of the left thigh. Intraoperative imprint smear examination led to a diagnosis of malignant melanoma, and wide resection of the tumor, including the surrounding normal tissue, was performed. On cytologic examination, the background was relatively clean, with tumor cells distributing individually or in clusters. Under high magnification, the tumor cells were seen to contain a slightly enlarged, conspicuous nucleolus and large cell body. The cells varied in shape from polygonal to spindle shaped, with a few multinuclear giant cells. Melanin and glycogen were observed in varying degrees in the tumor cells. CONCLUSION: MMST can be diagnosed easily if melanin is observed in the cytoplasm. Even in the absence of melanin, the tumor has relatively characteristic cytomorphology. Intraoperative cytology is useful for an accurate diagnosis of the tumor.

[The intratumoral levels of thymidylate synthetase and folate in gastric and colon cancer].

Currently, biochemical modulation for 5-fluorouracil (5-FU) is one of the most successful chemotherapy for both colo-rectal and gastric cancer. The purpose of this study is to evaluate the significance of measuring intratumoral thymidylate synthetase (TS) and folate (FH4) levels as predictive parameters for the successful treatment. Samples were collected from 16 advanced colo-rectal and 21 advanced gastric cancer. TS and tetrahydrofolate levels in the specimens were measured by binding assay. Results showed that there were no significant difference in TS levels between the different pathologic types of carcinoma. On the other hand, well (3.94 +/- 1.75 p mol/g) and moderately (5.95 +/- 2.69 p mol/g) differentiated carcinoma showed lower FH4 levels compared to poorly differentiated carcinoma (9.58 +/- 5.27 p mol/g). In conclusion, biochemical modulation by cisplatin or leucovorin, which elevates intratumoral folate levels, is more needed for well and moderately differentiated carcinoma. Finally, measuring TS levels can also be important because two cases who responded to cisplatin/5-FU chemotherapy showed low TS levels compared to the others who had lower response.

[Cytopathology and histopathology of human papilloma virus].

Human papilloma viruses (HPV) have been regarded seriously not only as an important agent causing sexually transmitted disease, but also because of its association with malignant transformation. Over 70 types of HPV are known, of which 30 types have been detected in specimens from the cervix. These have been classified into a low risk group, a high risk group and an intermediate group according to their association with malignant transformation. Therefore, diagnosis of cervical HPV infection and to a certain extent the HPV type are extremely important. Diagnostic methods of HPV infection include morphological methods such as cytological, pathological and electron microscopical diagnoses; DNA hybridization methods such as Southern blot hybridization (SBH) and Dot blot hybridization (DBH); and a combination of the two methods such as in situ hybridization (ISH), in situ polymerase chain reaction (in situ PCR) and polymerase chain reaction-in situ hybridization (PCR-ISH). Morphological methods using koilocytosis as an indicator have a low detection rate for HPV. Although ISH, in situ PCR and PCR-ISH have lower sensitivity that SBH and DBH, they enable visual localization of the detected DNA in cells or tissues. These methods are therefore important for cytopathologists and histopathologists. In this study, we report the morphological characteristics of HPV, as well as the advantages, disadvantages and detection rates of the various diagnostic methods.

Cytodiagnosis of placental site trophoblastic tumor. A report of two cases.

BACKGROUND: Placental site trophoblastic tumor (PSTT) is a rare form of trophoblastic neoplasm. Approximately 100 cases of PSTT have been reported, but we found no report on its cytodiagnosis. CASES: Case 1, a 39-year-old female, came to the hospital because of abnormal genital bleeding. Case 2, a 36-year-old female came because of amenorrhea for a year. In both cases, endometrial smear and intrauterine curettage suggested trophoblastic disease, and hysterectomy was performed. Laboratory data revealed a mild increase in human chorionic gonadotropin (hCG) and beta-hCG but normal human placental lactogen (hPL). In the cytologic examination, the background contained some hemorrhagic and fibrinous areas but no necrosis. Most tumor cells stained light green, were round or polygonal, and contained abundant cytoplasm. Some were palely stained and had vacuoles. Some cells showed hyperchromatism, an irregular nucleus, fine-to-coarse chromatin granules and markedly different sizes. Most of the cells were hPL positive, and a few were hCG positive. CONCLUSION: Both cases were considered benign because of rare mitoses despite cellular pleomorphism. However, careful follow-up is required. The differential diagnosis of PSTT is difficult from cytologic and biopsy specimens alone but may be achieved with additional magnetic resonance imaging findings and positive staining of hPL and hCG.

Cytodiagnosis of vaginal endodermal sinus tumor. A case report.

BACKGROUND: Endodermal sinus tumor (EST) of vaginal origin is extremely rare, and few previously published reports have described the cytology of this tumor. CASE: A high serum alpha-fetoprotein (AFP) level and magnetic resonance imaging findings in a 10-year-old female suggested EST of the lower genital tract. Laparotomy revealed EST occupying the pelvic cavity. The patient died on the 17th postoperative day due to complications from disseminated intravascular coagulation. Autopsy was performed immediately after death. The tumor originated in the posterior vaginal wall directly below the ectocervical area. Both ovaries were involved, and the tumor proliferated to occupy the cavity of the pelvis minor. A vaginal smear, obtained on two occasions, revealed severe necrosis with few cells, and a diagnosis could not be made. An imprint smear of the tumor obtained during surgery showed relatively characteristic cytologic findings of EST. Immunocytochemical and immunohistochemical studies revealed staining positive for AFP. CONCLUSION: Vaginal EST usually occurs in patients under 3 years of age. This 10-year-old patient was the oldest among the reported cases. Vaginal EST is clinically similar to sarcoma botryoides and clear cell carcinoma, and a differential diagnosis is necessary. Immunocytostaining for AFP is essential for a definitive cytologic diagnosis of EST.

[Detection of HPV-DNA in the various uterocervical lesion by the in situ polymerase chain reaction].

The causal association of human papilloma virus(HPV) with cervical cancer has been supported by multiple lines of evidence. Therefore, in the case of dysplasia, the presence of HPV-DNA should be detected and its subtypes identified. This is important in the determination of the prognosis for cervical disease. We reported a study in which the localization and types of HPV in cervical diseases was identified by in situ polymerase chain reaction(PCR), using biotin-labelled DNA probes. The in situ PCR, used by us was modified of Nuovo's method. We used biopsy materials of 18 CIN and 9 SCC cases(total 27 cases), all of which had been detected HPV-DNA by Southern blot hybridization, but not detected by in situ hybridization. A positive intranuclear reaction was detected in 13 of 18 CIN cases and 6 of 9 SCC cases(total 19 positive cases). Molecular biological techniques are the most reliable methods for detecting specific tumor genes and virus DNA. In situ hybridization has the advantage of enabling recognition of the cellular localization of the DNA in histologic specimens, but its sensitivity in inferior to the other techniques such as Southern blot, Dot blot and PCR. In situ PCR method possesses the advantages of both PCR and in situ hybridization in being highly sensitive and enabling visualization of the cellular localization of the DNA. In our present study, we succeeded to detect HPV-DNA in cervical biopsies of CIN and SCC cases by the in situ PCR.

[Changes in folate levels after cisplatin treatment of gastric cancer].

Currently, biochemical modulation for 5-fluorouracil (5-FU) by cisplatin (CDDP) is one of the most successful forms of chemotherapy for gastric cancer. Although the mechanism of this modulation is thought to increase intracellular folate levels, it is still unknown how much CDDP is needed to elevate folate levels. The purpose of this study is to determine the appropriate volume of CDDP as a modulator for 5-FU. Either 5, 20, 100 mg/body of CDDP was administered intravenously to advanced gastric cancer patients just before operation. Four hrs later, the stomach was resected and folate levels were measured in the tumor and normal mucosa by thymidylate synthase binding assay. The results showed folate elevation only after administration of 100 mg/body of CDDP, both in the tumor and mucosa (p < 0.01). In conclusion, if CDDP is infused as a bolus, a relatively large amount is needed to modulate the intratumor folate level.