Rieko Nishimura

Background Human epidermal growth factor receptor 2 (HER2) testing of samples from recurrent or metastatic breast cancer is recommended by the 2013 update of the American Society of Clinical Oncology/College of American Pathologists guidelines. Although cytological analysis can be applied to several types of metastatic lesions, the practical method for HER2 testing of cytological specimens is yet to be resolved. We conducted immunohistochemical (IHC) staining for HER2 in breast cancer cell blocks (CBs) and compared the results with those from the corresponding histological specimens. In cases of discrepancy between the two types of specimen, the bright-field HER2 dual in situ hybridization (DISH) assay was performed. Methods CBs were prepared from 54 surgically excised breast cancers. The cells were fixed in 10% buffered formalin and embedded in paraffin. A Ventana BenchMark ULTRA (Roche Diagnostics) with anti-HER-2/neu (4B5) rabbit monoclonal primary antibody and INFORM HER2/neu Dual ISH DNA Probe Cocktail was used for the assays. Results Successful results were obtained in 52 of 54 CBs. Forty cases showed agreement between CBs and the histological specimens. No discrepancy was observed between the two types of specimens in cases where HER2 expression was positive. IHC results of CB in 12 discrepant cases were HER2 intermediate or negative. The DISH results of 11 of these cases were negative. Conclusion IHC staining of HER2 for breast cancer CBs can be used in the same way as that used for histological specimens, although the number of equivocal cases in CBs is greater than that in histological specimens. Diagn. Cytopathol. 2016;44:274–279. © 2016 The Authors Diagnostic Cytopathology Published by Wiley Periodicals, Inc.

HER2 testing for samples from recurrent or metastatic disease is recommended by the 2013 update of the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines and cytological analysis can be applied to several types of metastatic lesions. However, the practical method to assess the HER2 testing of breast cancer cytology specimens has yet to be resolved. Therefore, we conducted the bright-field HER2 dual in situ hybridization (DISH) assay on cell blocks (CBs) prepared from breast cancer cell samples as a validation study before clinical use.

While HER2 gene detection in cytological specimens using fluorescence in situ hybridization (FISH) has been reported, the appropriate criteria for such specimens remain controversial. Fine needle aspiration (FNA) samples collected from surgically resected breast cancer specimens were rinsed in a cytopreservative solution containing fixative. Then, slides of the FNA samples were prepared by liquid-based cytology (LBC) (ThinPrep system, Hologic) according to the manufacturer’s instructions, and a PathVision HER2 DNA probe kit (Abbott) was used for FISH staining. The results were evaluated using an automated MetaCyte imaging system (MetaSystems, Altlussheim, Germany). HER2 gene amplification was scored using the HER2/chromosome enumeration probe 17 (CEP17) signal count ratio as follows: amplified, >2.2; equivocal, 1.8–2.2; and unamplified, <1.8. The cytology results were compared with the histology results from concordant cases. Successful results were obtained in 98 of 100 cases, and results from the FNA specimens were in agreement with those from the histological sections in 97 of these 98 cases (accuracy rate, 99 %; kappa, 0.962). FISH-based assessment of the HER2 gene status is consistent between histological sections and cytological specimens of breast cancer.

Immunohistochemical (IHC) analysis of the hormone receptor (HR) in breast cancer cytology is an important issue nowadays. Several studies have shown discrepancy in the HR status between the primary tumor and metastases. Cytology can be used for patients with metastatic disease. Although cytological assessment of HR is an excellent method, it has not been routinely used because of the difficulty in consistently preparing multiple good quality slides. Liquid-based cytology (LBC) preparation is considered as the key to resolving the aforementioned problem; however, few studies have reported the HR assessment in breast cancer using LBC. Therefore, the HR status of LBC slides from 82 breast cancers was compared with that of the corresponding surgical specimens. The HR assay in both the LBC slides and surgical specimens was conducted by IHC using an autostainer. For the IHC staining, the protocol recommended by the manufacturer for paraffin-embedded sections was used for both the cytology and histology specimens. The HR results of the cytology agreed with those of the histology in 80 of the 82 cases (accuracy rate, 98%) for estrogen receptor, and in 78 of the 82 cases (accuracy rate, 95%) for progesterone receptor. The overall accuracy of the HR status on the cytology and the histology was 99% in 81 of the 82 cases. In conclusion, in HR analysis of breast cancers, LBC followed by IHC using an autostainer was useful for the standard processing of cytological specimens and showed a good correlation with the results of analysis on the histology specimens.

Breast cancer screening by mammography (MMG) has recently increased in Japan. Suspicious lesions are therefore being detected more and more by MMG and the number of benign biopsies is increasing. It is thus important to examine which pathologically benign lesions were read as suspicious on MMG to reduce the number of biopsies in the case of benign breast lesions. Of 299 category 3 or 4 lesions on MMG, 39 histologically benign lesions with calcification were reviewed and compared with the mammograms by a pathologist and a radiologist. The Japan Mammography Guidelines were used for MMG interpretation. In mastopathy lesions, small round segmental calcifications and pleomorphic clustered calcifications were assessed as suspicious. The suspicious type of calcification in fibroadenoma was small round clustered. The calcifications in fibroadenoma may be seen as small round when the fibroadenoma is rather young, and assessed as suspicious. Some types of calcifications in mastopathy and fibroadenoma were assessed as borderline by MMG. We should therefore collect data from more benign cases with suspicious calcifications on MMG and elucidate the diagnostic criteria in MMG findings of such calcifications.

Background Most of the discordant cases between biochemical and immunohistochemical (IHC) assays for hormone receptor (HR) status in breast cancers are due to negative findings from the biochemical...

Two cases of inflammatory pseudotumor (IPT) of the liver associated with gastrointestinal tract cancer are reported. In addition, the etiological correlation between IPT and abscesses of the liver in cancer patients is discussed. The first patient was a 63-year-old woman who underwent distal gastrectomy and partial hepatectomy under a diagnosis of stomach cancer with liver metastasis. The second patient was a 66-year-old man who had undergone surgery for rectal cancer 6 years previously and underwent partial hepatectomy under a diagnosis of metastasis of rectal cancer to the liver. The gastric cancer was a papillary adenocarcinoma limited to the mucosa, and the rectal cancer was a moderately differentiated adenocarcinoma limited to the subserosa. The resected liver tumor in the first case measured 5.5×5.0×4.0 cm and was 2.5×1.9×1.6 cm in the second. The cut surface showed that both masses were well circumscribed and divided into lobules by fibrous tissue. They were yellowish white in color and there was no evidence of necrosis or hemorrhage. Histologically the masses consisted of fibrous areas and cellular areas, and the cellular areas consisted of fascicles of plump spindle cells mingled with varying numbers of plasma cells, lymphocytes, and histiocytes. The masses were diagnosed as IPTs. Obliterating phlebitis suggesting infection via the portal vein was seen in the adjacent liver tissue in both cases. According to previous cases reported in the literature, there are three types of cancers associated with hepatic IPT: gastrointestinal tract cancer, biliary tract cancer, and cancers that need strong systemic chemotherapy. The underlying cancer types of IPT of the liver are almost similar to those associated with pyogenic liver abscesses suggesting the etiological correlation between IPT and abscesses of the liver.

A case of inflammatory pseudotumor (IPT) of the liver associated with early gastric cancer is reported. Intravenous contrast-enhanced computed tomography (CT) showed a large, irregularly shaped mass lesion in the left lobe of the liver. The lesion was characterized by peripheral rim-like or septal enhancement and an internal low density area in the delayed phase. The gastric cancer was a papillary adenocarcinoma limited to the mucosa. The resected liver tumor measured 5.5 × 5.0 × 4.0 cm, and its cut surface revealed a well-circumscribed mass divided into lobules by fibrous tissue. Histologically the mass was composed of fibrous areas and cellular areas, and the cellular areas consisted of fascicles of plump spindle cells intermingled with varying numbers of plasma cells, lymphocytes and histiocytes. Thus, the higher attenuation on the enhanced CT scan corresponded to the areas of intense fibrosis, and the areas of lower attenuation corresponded to the predominantly cellular areas. The CT findings of delayed peripheral rim-like or septal enhancement of the hepatic tumor may be a specific finding of IPT.