Immunohistochemical distribution of tumor-associated antigen CA6 in gynecological neoplasms as detected by monoclonal antibody DS6.

DS6 is a murine monoclonal antibody developed using ovarian papillary serous adenocarcinoma as the immunogen. DS6 immunohistochemically reacts with a tumor-associated antigen, CA6, which has a limited range of expression in normal human tissues and is not expressed by benign mesothelium. We have studied the spectrum of immunohistochemical reactivity of antibody DS6 in 293 formalin-fixed, paraffin-embedded human gynecological neoplasms. The CA6 antigen shows strong expression in serous adenocarcinomas of the ovary (56/58 cases) and endometrium (6/6). CA6 is also expressed by the majority of ovarian endometrioid adenocarcinomas and Brenner tumors and by the majority of endometrioid adenocarcinomas, mucinous adenocarcinomas, and clear cell adenocarcinomas of the endometrium. CA6 is detected in 14% of ovarian clear cell carcinomas and is not detected in ovarian mucinous cystadenomas (0/7), mucinous intestinal-type borderline tumors (0/8), mucinous adenocarcinomas (0/10), or in malignant mesotheliomas (0/8). In neoplasms with papillary or glandular growth patterns, CA6 is detected along luminal cell membranes. CA6 is also seen along peripheral cell membranes and focally in the cytoplasm in some epithelial neoplasms. There is heterogeneity in immunohistochemical staining for DS6 both within an individual neoplasm and between neoplasms. Reactivity is not detected in neoplasms of sex cord-stromal, mesenchymal or germ cell origin.

Multicenter trial of sentinel node biopsy for breast cancer using both technetium sulfur colloid and isosulfan blue dye.

OBJECTIVE: To determine the factors associated with false-negative results on sentinel node biopsy and sentinel node localization (identification rate) in patients with breast cancer enrolled in a multicenter trial using a combination technique of isosulfan blue with technetium sulfur colloid (Tc99). SUMMARY BACKGROUND DATA: Sentinel node biopsy is a diagnostic test used to detect breast cancer metastases. To test the reliability of this method, a complete lymph node dissection must be performed to determine the false-negative rate. Single-institution series have reported excellent results, although one multicenter trial reported a false-negative rate as high as 29% using radioisotope alone. A multicenter trial was initiated to test combined use of Tc99 and isosulfan blue. METHODS: Investigators (both private-practice and academic surgeons) were recruited after attending a course on the technique of sentinel node biopsy. No investigator participated in a learning trial before entering patients. Tc99 and isosulfan blue were injected into the peritumoral region. RESULTS: Five hundred twenty-nine patients underwent 535 sentinel node biopsy procedures for an overall identification rate in finding a sentinel node of 87% and a false-negative rate of 13%. The identification rate increased and the false-negative rate decreased to 90% and 4.3%, respectively, after investigators had performed more than 30 cases. Univariate analysis of tumor showed the poorest success rate with older patients and inexperienced surgeons. Multivariate analysis identified both age and experience as independent predictors of failure. However, with older patients, inexperienced surgeons, and patients with five or more metastatic axillary nodes, the false-negative rate was consistently greater. CONCLUSIONS: This multicenter trial, from both private practice and academic institutions, is an excellent indicator of the general utility of sentinel node biopsy. It establishes the factors that play an important role (patient age, surgical experience, tumor location) and those that are irrelevant (prior surgery, tumor size, Tc99 timing). This widens the applicability of the technique and identifies factors that require further investigation.

Myxoid chondrosarcoma of the sphenoid sinus and chondromyxoid fibroma of the iliac bone: cytomorphologic findings of two distinct and uncommon myxoid lesions.

Myxoid chondrosarcoma (MCS) and chondromyxoid fibroma (CMF) are two uncommon myxoid cartilaginous neoplasms with distinct cytologic features, histologic patterns, and immunoprofiles. Because these neoplasms have characteristic biological behaviors and management, their correct diagnosis is crucial to avoid debilitating and unnecessary surgical procedures. We report the imprint cytology (IC) preparation findings along with the differential diagnosis in one case each of myxoid chondrosarcoma and chondromyxoid fibroma of the splenoid sinus and iliac bone, respectively. The two great mimickers for these neoplasms, chordoma and chondrosarcoma, represent difficult diagnostic challenges, especially when MCS and CMF occur in unusual locations. IC in conjunction with the clinical and radiologic findings can provide a rapid preliminary intraoperative diagnostic interpretation which can aid in planning the immediate surgical management, as well as guide specific tissue triage for key ancillary studies such as electron microscopy and cytogenetic analyses. To the best of our knowledge, there have been no cytologic reports of MCS of the sphenoid sinus and CMF of the iliac bone.

Diagnostic utility of MIC-2 immunocytochemical staining in the differential diagnosis of small blue cell tumors.

Ewing's sarcoma (ES) and peripheral neuroectodermal tumor (PNET) are considered in the differential diagnosis of small round blue cell tumors of infancy and childhood which includes neuroblastoma, rhabdomyosarcoma and malignant lymphoma. Fine-needle aspiration diagnosis of these neoplasms can be particularly difficult when the neoplasms are composed of poorly differentiated cells or fail to produce a stroma. MIC-2 is a highly sensitive and specific marker for the PNET/ES group of neoplasms and has been studied extensively in surgical pathology. Other small blue cell neoplasms including rhabdomyosarcoma, blastemal Wilm's tumor, and lymphoblastic lymphoma have also shown positivity, but the staining reactions are usually weak and focal. The utility of this marker in the differential of small blue cell neoplasms in cytologic material has not been examined. Twenty cases of small blue cell neoplasms obtained by fine-needle aspiration (FNA) were studied. MIC-2 antibody was applied retrospectively to formalin-fixed cell block material and destained alcohol-fixed and air-dried cytologic preparations. These cases include primitive neuroectodermal tumor (five cases), Ewing's sarcoma (two cases), neuroblastoma (four cases), Wilms's tumor (four cases), lymphoblastic lymphoma (two cases), and small-cell carcinoma (three cases). The cases were judged positive when the majority of the cells showed cytoplasmic staining. Diffuse cytoplasmic staining was observed in all seven cases of PNET/ES. Staining could be seen on the destained air-dried smears (three cases), fixed smears (two cases), or the cell block material (two cases). None of the other 13 small blue cell neoplasms showed positive staining. We conclude that MIC-2 is a sensitive and specific marker for the PNET/ES group of neoplasms in specimens from formalin-fixed cell block, air-dried, and alcohol-fixed cytologic material and is useful in the differential diagnosis of small blue cell tumors.

Fine-needle aspiration cytology of amyloid associated with nonneoplastic and malignant lesions.

To assess the value of fine-needle aspiration (FNA) cytology for the diagnosis of amyloid, we retrospectively studied all FNA cases diagnosed as having amyloid during a 6-yr period (1990-1996). FNA was performed on both superficial and deep locations. A total of 6 cases containing amyloid was studied, including primary medullary thyroid carcinoma, metastatic medullary thyroid carcinoma to a vertebrae, multiple myeloma, squamous-cell carcinoma of the lung metastatic to a hilar lymph node, primary pulmonary amyloid, and amyloid tumor in a vertebral body in a patient with primary systemic amyloidosis. Despite the location or disease association, the cytologic appearance of amyloid in all cases was similar. On Diff-Quik stain, amyloid appeared as amorphous, irregular, waxy basophilic to metachromatic clumps of material. Papanicolaou stain revealed cyanophilic to organophilic clumps of material with occasional prominent fissures. In all 6 cases, amyloid was confirmed by Congo red stain and in 3 cases by a thioflavin T stain. In 4 of the 6 cases (67%), amyloid was associated with an underlying malignancy. In 3 cases malignant cells were admixed with the amyloid, and in another case malignancy was present at a distant site. We conclude that FNA biopsy is a helpful initial procedure for the evaluation of patients with amyloid deposits. The clinical implications of amyloid found in any particular body site include both benign and malignant conditions. The presence of an associated neoplasm must be especially considered in the differential diagnosis of amyloid deposits.

Diagnostic accuracy of an international static-imaging telepathology consultation service.

Static-image and dynamic- (real-time) image telepathology are competing technologies. Although some studies suggest that the diagnostic accuracy of the dynamic-image telepathology approaches the accuracy of light microscopy, few reports have documented the diagnostic accuracy of static-image telepathology as used in the setting of an actual surgical pathology consultation practice. We report the results of an analysis of 171 telepathology consultation cases submitted to the Arizona-International Telemedicine Network (AITN). Digital images were submitted by pathologists from six participating institutions in Arizona, Mexico, and China. Telepathologists could render a telepathology diagnosis (TP) or defer rendering a diagnosis to obtain additional video images, glass slides for detailed analysis, or to obtain tissue blocks for special studies such as immunohistochemistry. The telepathologists rendered diagnoses for 144 cases and deferred 27 cases. Two pathologists retrospectively evaluated-glass slides from each case and rendered a consensus glass slide (GS) "truth" diagnosis. There was 88.2% concordance between TP and GS diagnoses (127 of 144 diagnoses). Concordance of 96.5% was achieved for clinically important diagnoses (139 of 144 diagnoses). Telepathologists deferred making a diagnosis to obtain glass slides for conventional light microscopy in 14 cases (8.1%) and for results of immunohistochemistry studies in 13 cases (7.6%). Thus, correct diagnoses were rendered by static-image telepathology in 127 of 171 cases (74.3%) at the time of telepathology diagnostic sessions. Inappropriate field selection and sampling biases of referring pathologists, as well as a tendency of static-image telepathologists to underestimate the complexity of some cases, may reduce the value of consultations based on the viewing of static images.

Case triage model for the practice of telepathology.

OBJECTIVE: To implement and evaluate a practice model for telepathology. METHODS: A case triage practice model was devised in which general pathologists review all cases and refer them to subspecialists only when necessary. In 1993, the Arizona-International Telemedicine Network (AITN), a high-resolution static imaging telepathology diagnostic network, linking six sites to the University of Arizona in Tucson, began testing the model. Work flow through the network was analyzed, and diagnostic concordance was assessed in 150 surgical cases by comparing the diagnoses of the referring (transmitting) pathologists with diagnoses of the consulting (receiving) telepathologists as well as by comparing the referring pathologists' diagnoses with the consensus diagnoses reached by an independent review panel. Data analysis was controlled for subspecialty case type. Telepathologists had access to the referring pathologists' preliminary diagnoses, and the review panel had access to the original glass slides and the surgical pathology reports prior to rendering their respective diagnoses. RESULTS: The triage pathologist completed the telepathology consultation without the assistance of a subspecialty pathologist in 66% of the cases. The review panel examined the original glass slides from 134 cases by light microscopy. Concordance rates of the telepathologists' or review panel's diagnoses with the referring pathologists' diagnoses were not statistically different (93.1% v 83.6%, respectively; P > 0.05). CONCLUSION: The case triage model is suitable for the practice of telepathology. It significantly reduces the need for subspecialty pathologists. Static imaging telepathology is useful and reasonably efficient for rendering diagnostic opinions in the majority of referred cases. Tissue sampling limitations imposed by static imaging occasionally resulted in diagnostic errors.