A quantitative evaluation method utilizing the homology concept to assess the state of chromatin within the nucleus of lung cancer.

Homology is a mathematical tool to quantify "the contact degree", which can be expressed in terms of Betti numbers. The Betti numbers used in this study consisted of two numbers, b0 (a zero-dimensional Betti number) and b1 (a one-dimensional Betti number). We developed a chromatin homology profile (CHP) method to quantify the chromatin contact degree based on this mathematical tool. Using the CHP method we analyzed the number of holes (surrounded areas = b1 value) formed by the chromatin contact and calculated the maximum value of b1 (b1MAX), the value of b1 exceeding 5 for the first time or Homology Value (HV), and the chromatin density (b1MAX/ns2). We attempted to detect differences in chromatin patterns and differentiate histological types of lung cancer from respiratory cytology using these three features. The HV of cancer cells was significantly lower than that of non-cancerous cells. Furthermore, b1MAX and b1MAX/ns2 showed significant differences between small cell and non-small cell carcinomas and between adenocarcinomas and squamous cell carcinomas, respectively. We quantitatively analyzed the chromatin patterns using homology and showed that the CHP method may be a useful tool for differentiating histological types of lung cancer in respiratory cytology.

Mesothelial cells facilitate cancer stem­like properties in spheroids of ovarian cancer cells.

Ovarian cancer is characterized by widespread peritoneal dissemination with ascites. Spheroids observed in the ascites of ovarian cancer patients are a mixture of cancer cells and mesothelial cells. In the present study, we evaluated whether mesothelial cells exfoliated from the peritoneum facilitate tumor spheroid formation and give rise to cancer stem­like properties in ovarian cancer cells. Spheroids from the CAOV3 and A2780 ovarian cancer cell lines grew much larger in co­culture with mesothelial cells than in monoculture under 3D conditions. The spheroids in co­culture displayed high Ki­67 expression in the peripheral zone and low expression in the central zone area. The expression of CD133 emerged in the inner portion of spheroids at later time­points (96 and 168 h), indicating that cancer cells expanded to the inner spheroid and acquired stem cell­properties. The mRNA levels of cancer stem cell markers Dclk­1, CD44 and Bmi­1 significantly increased in co­cultured CAOV3 and mesothelial cells compared to CAOV3 cells alone. Furthermore, the mesothelial cells promoted the tumorigenesis and growth of the CAOV3 cells in a mouse xenograft model compared to cancer cells alone. In conclusion, mesothelial cells promoted spheroid formation by ovarian cancer cells and facilitated cancer stem­like properties.

Retrospective cytological study of intraocular lymphoma using vitreous and intraocular perfusion fluid.

Intraocular lymphoma (IOL) is an extremely rare tumor. We carried out a retrospective cytopathological study with vitreous and intraocular perfusion fluid obtained on conducting a pars plana vitrectomy in 18 cases of IOL. In the 18 cases, nine were patients of Kansai Medical University Takii Hospital from 1991 to 2007, and the other nine had already been reported by other hospitals. Most patients were male, and the average age at onset was 60.4-year-old. The main symptoms were vitreous opacity, amblyopia, and blurred vision. Cases of primary intraocular lymphoma numbered 8/15 (53%), while cases of infiltration of malignant lymphoma from the brain numbered 2/15 (13%). Although IOL contains various subtypes of lymphoma, the most frequent subtype is diffuse large B-cell type lymphoma. It has been reported that making a definite diagnosis of IOL is difficult because the clinical symptoms and examinations are similar to chronic uveitis, and so IOL is called "masquerade syndrome." Recently, serological and molecular pathological studies have been carried out in addition to morphological examination. However, a cytological diagnosis based on the clinical background and/or image findings is important for the diagnosis of IOL, because of the volume limit of the vitreous fluid and difficulty of obtaining specimens from the inside of the eyes.

Diagnostic utility of vitreous humor fluid cytology for intraocular sarcoidosis: a clinicopathologic study of 7 cases.

Sarcoidosis is an enigmatic multisystem sarcoid disease occurring mainly in the lungs, skin, and eyes. Sarcoidosis of the eyes (intraocular sarcoidosis) has been proposed as one of the causes of uveitis. We carried out a clinicopathological study involving seven patients with intraocular sarcoidosis based on vitreous humor fluid cytology. In the seven patients, the sex ratio was 4:3, and the average age at onset was 65.6-years-old. Vitreous opacity was noted in all patients and snowball-like vitreous opacity in 85.7%. Nerve papilloedema was noted in 42.9%. Diagnostic vitrectomy and adrenocortical hormone therapy were performed in all patients. As a result, the symptoms were improved. Vitreous perfusion fluid cytology revealed multinucleate giant cells in 85.7% and lymphocytes and epithelioid cells in all cases. Cytological diagnosis is not included in the current criteria for sarcoidosis, but its value in the diagnosis of intraocular sarcoidosis was suggested based in present study.

Indeterminate calcification and clustered cystic lesions are strongly predictive of the presence of mucocele-like tumor of the breast: a report of six cases.

Mucocele-like tumor (MLT) of the breast is a mucinous disorder that is generally difficult to distinguish from mucinous carcinoma. Moreover, MLT is often accompanied by atypical ductal hyperplasia (ADH) or ductal carcinoma in situ (DCIS), and preoperative diagnosis is very confusing. In this paper, we summarize the clinicopathological characteristics of six cases of MLTs, comparing them with mucinous carcinoma. MLTs were characterized by clustered, coarse calcification on mammography and clustered, hypoechoic lesions with or without echogenic spots on ultrasonography. On fine-needle aspiration cytology (FNAC), three cases were correctly diagnosed and three cases were judged to be indeterminate, or insufficient material was present. Ultimately, excisional biopsies were performed to obtain a correct diagnosis in all cases. Immunohistochemical staining of MLTs accompanied by ADH or DCIS (malignant MLTs) revealed the presence of MUC6, while MLTs without ADH or DCIS (benign MLTs) were MUC6-negative. At present, as it is difficult to detect small areas of DCIS adjacent to the MLT by FNAC, excisional biopsy is essential. Immunohistochemical staining for MUC6 may be useful in differentiating between benign MLTs and malignant MLTs, although further investigation is needed.

Accuracy of imprint cytology for intraoperative diagnosis of sentinel node metastases in breast cancer.

OBJECTIVE: The aim of this study was to determine the accuracy of imprint cytology for the intraoperative diagnosis of sentinel node metastases in patients with breast cancer. SUMMARY BACKGROUND DATA: Accurate intraoperative diagnosis of sentinel node metastases enables the selection of patients who need axillary lymph node dissection during the same operation. METHODS: This study included 631 patients with clinical T1 breast cancer with clinically negative nodes. Sentinel nodes were serially sectioned at 2-mm intervals. Imprint cytologic samples were made from all cut surfaces and stained with Papanicolaou staining. Patients with positive sentinel nodes underwent immediate axillary lymph node dissection. Those with negative sentinel nodes diagnosed by intraoperative imprint cytology, but positive by final pathologic results, underwent subsequent axillary lymph node dissection. The results of imprint cytology were compared with the final pathologic results using hematoxylin and eosin staining and immunohistochemistry. RESULTS: In 110 of 130 patients with positive sentinel nodes diagnosed by final pathology, imprint cytology of at least one sentinel node was positive. In 17 of 501 patients with tumor-negative sentinel nodes diagnosed by final pathology, imprint cytology of at least one sentinel node was positive. The sensitivity, specificity, and overall accuracy of imprint cytology for the diagnosis of sentinel node metastases were 84.6%, 96.6%, and 94.1%, respectively. Only 20 (3.2%) patients required a second axillary operation in the present study. CONCLUSION: Intraoperative imprint cytology is a useful method for evaluating sentinel node metastasis in patients with breast cancer.

Intraoperative imprint cytology for the diagnosis of sentinel node metastases in breast cancer.

Accurate intraoperative diagnosis of sentinel node metastases enables the selection of patients for axillary lymph node dissection, thus avoiding an unnecessary additional operation in patients with false-negative results. The main reason for false-negative results of imprint cytology was poor quality of the imprint samples because of sampling error. False-positive imprint cytology results that lead to an unnecessary axillary lymph node dissection are very rare. Imprint cytology can be recommended for the intraoperative examination of sentinel nodes in breast cancer patients.

Sentinel node biopsy for breast cancer: technical aspects and controversies.

Sentinel node biopsy has rapidly emerged as a minimally invasive, highly accurate method of axillary staging, and has replaced routine axillary lymph node dissection as the new standard of care in breast cancer. However, many practical problems remain and details of the technique have not been standardized yet. Guideline recommendations help us to perform appropriate sentinel node biopsy and pathological examination. We should perform sentinel node biopsy without deviation from such consensus guidelines. The technical controversies of sentinel node biopsy are discussed in this article and the results of our studies about sentinel node biopsy in breast cancer are reviewed.

Three-axillary lymph node sampling for the prediction of nonsentinel node metastases in breast cancer patients with sentinel node metastases.

BACKGROUND: In half of breast cancer patients with positive sentinel nodes, the sentinel nodes are the only metastatic nodes. Such patients have no more metastatic nonsentinel nodes and do not need to undergo axillary lymph node dissection. The purpose of this study was to investigate whether three-axillary lymph node sampling after sentinel node biopsy predicts the status of nonsentinel nodes in patients with sentinel node metastases. METHODS: Sentinel node biopsy was performed with dye and radioisotope. When the sentinel nodes were diagnosed as metastasis positive by using intraoperative imprint cytology, three-axillary lymph node sampling was performed, followed by axillary lymph node dissection. RESULTS: Of 47 cases with positive imprint cytology, 43 (91%) were diagnosed as metastasis positive on their final histological examination and were analyzed. The status of the sampled nodes was significantly associated with the status of nonsentinel nodes (P < .0001). Six (43%) of 14 patients with positive sampled nodes had at least 1 positive remaining node. Only 2 (7%) of 29 patients whose sampled nodes were negative were found to have additional nodal metastases. The sensitivity, specificity, and accuracy of the sampled nodes for the prediction of nonsentinel node metastases were 87.5%, 100%, and 95.3%, respectively. CONCLUSIONS: We demonstrated that three-node sampling may be useful for predicting the status of nonsentinel nodes and avoiding axillary lymph node dissection in patients with only sentinel node metastases.

Controversies in sentinel node biopsy for breast cancer.

Sentinel node biopsy for breast cancer patients has recently been applied as a less invasive, highly accurate alternative to axillary lymph node dissection. Numerous studies have shown that sentinel nodes accurately diagnose axillary staging. However, many problems remain to be answered and must be addressed before sentinel node biopsy becomes the standard surgical procedure for patients with breast cancer. We reviewed and discussed here three of these problems; axillary sampling as an alternative to sentinel node biopsy, dye method vs. combination of dye and radiocolloid for sentinel node biopsy, and intraoperative sentinel node examination. Further investigation will continue to be necessary as we learn how to better provide procedure of sentinel node biopsy.

Sentinel node biopsy to avoid axillary lymph node dissection in breast cancer.

The role of sentinel node biopsy in breast cancer has increased over the last few years. Sentinel nodes can predict the status of all axillary lymph nodes precisely and select patients with negative nodes for whom axillary dissection is unnecessary. Many problems remain, such as the ideal injection technique, ideal agents, and ideal histological detection of sentinel node metastases, and must be addressed before sentinel node biopsy becomes the standard of care for patients with breast cancer.

Intraoperative lavage cytologic analysis of surgical margins as a predictor of local recurrence in pulmonary metastasectomy.

HYPOTHESIS: Cytologic analysis of intraoperative lavage at the surgical margin during wedge or segmental resection for pulmonary metastatic lesions predicts postoperative local failure at the surgical margin of the pulmonary parenchyma. DESIGN: Prospective nonrandomized trial. SETTINGS: Institution-based study. PATIENTS: Fifty-one consecutive patients undergoing wedge or segmental resection for 87 pulmonary metastatic lesions of various primary tumor types from November 1, 1997, through January 31, 2001, were prospectively enrolled. INTERVENTIONS: An intraoperative lavage cytologic technique at the surgical margin for each pulmonary metastasis was performed as described previously. MAIN OUTCOME MEASURES: Incidence of positive cytologic findings and postoperative local recurrence at the surgical margin. RESULTS: Of the examined lesions, 10 (11%) showed positive cytologic results at the surgical margin, despite a macroscopically safe margin in the attempted resection. Of these, metastasectomy was converted to segmentectomy in 3. An additional wedge resection and evaporation using an Nd:YAG laser in the surgical margin were performed in 1 and 4 lesions, respectively. Complications precluded further treatment in 2 lesions. By July 2001, although no local recurrence at the surgical margin area was found among the lesions with negative cytologic results, recurrence at the surgical margin occurred in 2 with positive cytologic results, including 1 receiving no treatment and 1 receiving Nd:YAG laser evaporation, indicating that a significant difference in the recurrence rate according to lavage cytologic status (P<.001). CONCLUSIONS: This intraoperative lavage cytologic technique in wedge or segmental resection of pulmonary metastases of various primary tumors may be a useful predictor of local recurrence at the surgical margin. With these test results, local recurrence at the surgical margin may be controllable in patients undergoing pulmonary metastasectomy.