Cytological and cyst fluid analysis of small (< or =3 cm) branch duct intraductal papillary mucinous neoplasms adds value to patient management decisions.

BACKGROUND/AIM: Management of patients with small (1-3 cm) branch duct intraductal papillary mucinous neoplasms (IPMN) is a challenge. Symptoms, dilated duct, mural nodule or positive cytology have been proposed as parameters for resection. The aim of our study was to compare this proposed algorithm to one that incorporates cytology with less than malignant epithelial cells and cyst fluid carcinoembryonic antigen (CEA). METHODS: A retrospective study was conducted. RESULTS: There were 14 nonmalignant and 6 malignant cysts with 3 invasive IPMN. None were associated with a dilated duct and none had positive cytology. Only a mural nodule was significant by univariate analysis for the detection of malignancy (p = 0.01) and invasion (p = 0.009). The detection of atypical epithelial cells or a cyst fluid CEA of >2,500 ng/ml was more accurate for the detection of malignancy than using the recommended algorithm. CONCLUSIONS: The presence of a mural nodule in a small branch duct IPMN is a predictor of malignancy and invasion by univariate analysis. Recognition of an atypical epithelial cell component in contrast to positive cytology or a cyst fluid CEA of >2,500 ng/ml is more accurate than the recommended algorithm and adds value to the preoperative assessment of clinically diagnosed small branch duct IPMN. and IAP.

Fine-needle aspiration biopsy of secondary neoplasms of the thyroid gland: a multi-institutional study of 62 cases.

BACKGROUND: Secondary neoplasms of the thyroid gland (SNTGs) are uncommon, and it is important to recognize them in thyroid fine-needle aspiration biopsy (FNAB). METHODS: The authors report a cohort of 62 SNTGs from 7 institutions in the United States and Europe. Patients were identified retrospectively by searching through medical records of the respective institutions. All initial diagnoses were rendered by FNAB. RESULTS: SNTGs represented 0.16% of all thyroid FNABs and were more frequent among women (ratio of women to men, 1.2:1.0). The mean patient age was of 59 years (range, 7-84 years), the mean tumor size was 3 cm (range, 0.9-7 cm), and the mean interval from diagnosis of the primary tumor was 45 months (range, 0-156 months). Eighty-seven percent of SNTGs were diagnosed as malignant by FNAB, and there was a specific SNTG diagnosis in 93% of patients. Immunocytochemistry and flow cytometry, which were used in 30% of patients, were useful ancillary studies. Adenocarcinomas (n = 23; 37%) and squamous cell carcinomas (SCCs) (n = 22; 35.5%) represented the majority of SNTGs, followed by lymphoma (n = 5; 8%), melanoma (n = 5; 8%), adenoid cystic carcinoma (n = 3; 5%), and various sarcomas (n = 3; 5%). Adenocarcinomas originated from the kidney (n = 9; 39%), lung (n = 6; 26%), breast (n = 5; 22%), and colon (n = 3; 13%). SCCs originated mostly from the head and neck (n = 13; 59%), followed by lung (n = 3; 13%), esophagus (n = 3; 14%), and unknown primary sites (n = 3; 14%). CONCLUSIONS: Adenocarcinomas from the kidney, lung, breast, and colon along with SCCs represent the majority of SNTGs. The current results indicate that FNAB is a sensitive and accurate method for diagnosing SNTG; however, diagnostic difficulties can occur. Knowledge of clinical history and the judicious application of ancillary studies can increase the sensitivity and accuracy of FNAB for detecting SNTGs.

Internet teleconferencing method for telepathology consultations from lung and heart transplant patients.

Current Internet-based teleconferencing techniques allow a referring pathologist to transmit real-time images from a microscope to a consultant, while maintaining a verbal conversation using Internet telephony. In our study, 50 randomly selected transbronchial biopsies from lung allograft recipients and 58 randomly selected endomyocardial biopsies from heart transplant patients were diagnosed by consultant pathologists using Internet-based teleconferencing methods. The referring pathologists acquired the real-time video images from the biopsies using a light microscope equipped with a phototube adapter and a video camera. The consultant pathologists viewed the processed images on a video monitor at 800 x 600 resolution, using a standard microcomputer equipped with Netmeeting software, and directed the referring pathologist to move the slide under the microscopy and/or change image magnification. The validity of telepathology diagnoses was assessed with kappa coefficients. Consultations were completed in 5 to 15 minutes per case. Sound transmission was unreliable, and in approximately 25% of consultations the referring pathologist needed to "call back" to reestablish verbal communication. In all but 2 transbronchial biopsies there was agreement between the original diagnosis and the diagnosis by telepathology (kappa = 0.92). In 48 of 58 endomyocardial biopsies there was concordance between the 2 diagnoses (kappa = 0.692). Only 3 out of 10 of these discrepancies were clinically significant (kappa = 0.897). Internet-based teleconferencing techniques provide effective and relatively inexpensive tools for real time telepathology consultations. The technology is probably best suited for the study of small specimens from patients that require rapid diagnosis by a consultant.

Humoral rejection in cardiac transplantation: risk factors, hemodynamic consequences and relationship to transplant coronary artery disease.

BACKGROUND: Acute cellular rejection is the mechanism of most immune-related injury in cardiac transplant recipients. However, antibody-mediated humoral rejection (HR) has also been implicated as an important clinical entity following orthotopic heart transplantation. Humoral rejection has been reported to play a role in graft dysfunction in the early post-transplant period, and to be a risk factor for the development of transplant coronary artery disease. Some involved in transplantation pathology doubt the existence of clinically significant humoral rejection in cardiac allografts. Those who recognize its existence disagree on its possible role in graft dysfunction or graft coronary artery disease. In this study, we report clinical features of patients with the pathologic diagnosis of HR at our institution since July 1997, when we began systematic surveillance for humoral rejection. METHODS: We reviewed medical records of patients with the pathologic diagnosis of HR without concurrent cellular rejection between July 1997 and January 2001. Diagnosis was based on routine histology ("swollen cells" distending capillaries, interstitial edema and hemorrhage) and immunofluorescence (capillary deposition of immunoglobulin and complement with HLA-DR positivity), or immunoperoxidase staining of paraffin-embedded tissue (numerous CD68-positive macrophages and fewer swollen endothelial cells distending capillaries). RESULTS: A total of 44 patients (4 to 74 years old) showed evidence of HR without concurrent cellular rejection at autopsy or on one or more biopsies. Although females comprised only 26% of our transplant population, 23 patients (52%) with HR were female. A positive peri-operative flow cytometry T-cell crossmatch was observed in 32% of HR patients compared with 12% of controls (p = 0.02). Hemodynamic compromise consisting of shock, hypotension, decreased cardiac output/index and/or a rise in capillary wedge or pulmonary artery pressure was observed in 47% of patients at the time of diagnosis of HR. Six patients (5 females) died (14% mortality) with evidence of HR at or just before autopsy, 6 days to 16 months after transplantation. The incidence of transplant coronary artery disease was 10% greater at 1 year, and 36% greater at 5 years, in patients with HR when compared with non-HR patients. CONCLUSIONS: Humoral rejection was associated with acute hemodynamic compromise in 47% of patients, and was the direct cause of death in 6 patients (13%). Humoral rejection is a clinicopathologic entity with a high incidence in women and is associated with acute hemodynamic compromise, accelerated transplant coronary artery disease and death.

Intraductal papillary mucinous neoplasm of the pancreas: cytologic features predict histologic grade.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is an increasingly recognized cystic neoplasm of the pancreas, histologically classified by the degree of epithelial atypia and by the presence or absence of invasion of the cyst wall. To the authors' knowledge, the cytologic features of this neoplasm are poorly characterized, especially with respect to tumor grade. METHODS: Thirty-three endoscopic ultrasound (EUS)-guided pancreatic fine-needle aspiration biopsy (FNAB) samples and 1 pancreatic duct brush specimen from 25 patients with a histologically confirmed IPMN were retrospectively reviewed. Blinded to tumor grade, background mucin, inflammation, necrosis, overall cellularity, the presence of gastrointestinal-contaminating epithelium, architecture of cell clusters, and nuclear and cellular morphology were evaluated. In cases in which special stains for mucin were performed, the diagnostic utility of these stains was assessed. These cytologic features were subsequently correlated with the histologic diagnosis. RESULTS: The 34 cytology samples represented 4 adenomas, 15 IPMN-moderate dysplasias, 7 intraductal carcinomas, and 8 IPMNs with invasive carcinoma. Extracellular mucin was present in 97% of all cases; 53% had thick, viscous, "colloid-like" mucin. Special stains for mucin were positive in 6 of 11 cases (54%), helping to identify thin mucin in only 2 cases. Gastrointestinal contamination did not appear to create diagnostic difficulty due to an apparent dual (dysplastic-nondysplastic) epithelial population, but only 4 adenomas were evaluated in this study. Necrosis distinguished IPMN with carcinoma from IPMN-adenomas and IPMN with moderate dysplasia (P < .00001), and was more often observed with invasion than IPMN-carcinoma in situ (P < .05). Tight epithelial cell clusters with hyperchromatic nuclei and a high nuclear to cytoplasmic ratio was more significant in IPMN of at least moderate dysplasia (P = .03). Pale nuclei with parachromatin clearing was found to be a nuclear feature that was suspicious for at least carcinoma in situ (P < .001). In addition, significant background inflammation (neutrophils and histiocytes) was found to be more characteristic of IPMN with at least carcinoma in situ (P = .002). CONCLUSIONS: The presence of thick, "colloid-like" mucin is noted in half of the IPMN cases, but was not found to be specific to grade. The absence of such mucin does not exclude an IPMN. The presence of tight epithelial cell clusters is consistent with a neoplasm of at least moderate dysplasia, and abundant background inflammation and parachromatin clearing correlated with the presence of at least carcinoma in situ. Necrosis was the only feature found to be strongly suggestive of invasion.

Humoral rejection of human organ transplants.

Although T-cell mediated rejection has remained the most common form of acute rejection, humoral rejection now accounts for a substantial fraction in patients with kidney or heart allografts, and probably causes the majority of acute graft losses. The frequency, variously estimated at 20-30%, is attributed to improved methods of detection, including staining for C4d in tissues, which is more sensitive and specific than histological features. Detection of circulating anti-donor reactive antibody (usually to donor HLA antigens) confirms the diagnosis. The clinico-pathological entity of acute humoral rejection is well accepted in kidney and increasingly in heart transplantation. Recent evidence points to a new category of chronic humoral rejection, which accounts for about 60% of chronic rejection of kidneys. Importantly, the hallmark of humoral rejection, C4d, can be detected in the grafts before development of histological evidence of chronic rejection. Humoral rejection is generally not responsive to the usual anti-T cell immunosuppressive agents, but small, non-controlled trials suggest humoral rejection can be reversed with plasmapheresis, intravenous immunoglobulin, anti-CD20 and other treatments, all of which deserve formal clinical evaluation. Prophylaxis for chronic rejection is expected to require donor-specific serological monitoring and protocol biopsies.