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Context.—Recognizing the difficulty in applying the concept of critical values to anatomic pathology diagnoses, the College of American Pathologists and the Association of Directors of Anatomic and Surgical Pathology have chosen to reevaluate the concept of critical diagnoses.Objective.—To promote effective communication of urgent and significant, unexpected diagnoses in surgical pathology and cytology.Design.—A comprehensive literature search was conducted and reviewed by an expert panel.Results.—A policy of effective communication of important results in surgical pathology and cytology is desirable to enhance patient safety and to address multiple regulatory requirements.Conclusions.—Each institution should create its own policy regarding urgent diagnoses and significant, unexpected diagnoses in anatomic pathology. This policy should be separate from critical results or panic-value policies in clinical pathology, with the expectation of a different time frame for communication. Urgent diagnosis is defined as a medical condition that, in most cases, should be addressed as soon as possible. Significant, unexpected diagnosis is defined as a medical condition that is clinically unusual or unforeseen and should be addressed at some point in the patient's course. Further details of this statement are provided.

Providing the best treatment options and appropriate prognostic information to patients with cartilaginous neoplasms of long bones depends on distinguishing benign from malignant lesions. Correlative interpretation of imaging, histopathology, and clinical information is the current method for making this distinction, yet the reliability of this approach has not been critically evaluated. This study quantifies the interobserver reliability of the determination of grade for cartilaginous neoplasms among a group of experienced musculoskeletal pathologists and radiologists.Nine recognized musculoskeletal pathologists and eight recognized musculoskeletal radiologists reviewed forty-six consecutive cases of cartilaginous lesions in long bones that underwent open biopsy or intralesional curettage. All diagnosticians had a bulleted history and preoperative conventional radiographs for review. Pathologists reviewed the original hematoxylin and eosin-stained glass slides from each case. Radiologists reviewed any additional imaging that was available, variably including serial radiographs, magnetic resonance imaging, and computed tomography scans. Each diagnostician classified a lesion as benign, low-grade malignant, or high-grade malignant. Kappa coefficients were calculated as a measure of reliability.Kappa coefficients for interrater reliability were 0.443 for the pathologists and 0.345 for the radiologists (p0.0001 for both). Kappa coefficients for a subgroup of cases determined to be high risk by subsequent clinical course were poorer at 0.236 and 0.206, respectively (p0.0001 for both). Slightly improved agreement among radiologists was noted for the twenty lesions that had magnetic resonance imaging available (Kappa = 0.437, p0.0001), but not for the lesions analyzed with serial plain radiographs or computed tomography scans.This study demonstrates low reliability for the grading of cartilaginous lesions in long bones, even among specialized and experienced pathologists and radiologists. This included low reliability both in differentiating benign from malignant lesions and in differentiating high-grade from low-grade malignant lesions, both of which are critical to the safe treatment of these neoplasms. This may explain in part the wide variation in outcomes reported for chondrosarcomas treated in different medical centers. New diagnostic and grading strategies linked to protocol-driven treatments are needed, but they must be measured against the long-term gold standard of patient outcomes.

Two adult patients are described with multifocal osteolytic lesions radiologically simulating a vascular tumor. One patient had multiple bones involved. Histologically, the individual lesions had the features of the nidus of osteoid osteoma/osteoblastoma. A review of the English language medical literature yielded only one other reported case with similar features. The process is designated as osteoblastomatosis to indicate its bone-forming character, prominent osteoblast proliferation, and multiplicity. The cases are distinguished from multifocal/multicentric osteoid osteoma and osteoblastoma, and from benign and malignant vascular tumors.

Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that is activated by integrin clustering. There are limited data regarding the functional role of FAK in ovarian cancer migration and invasion. In the current study, FAK expression was evaluated in ovarian cell lines (nontransformed and cancer), 12 benign ovarian samples, and in 79 invasive epithelial ovarian cancers. All three ovarian cancer cell lines overexpressed FAK compared to the nontransformed cells. The dominant-negative construct called FAK-related nonkinase (FRNK) was introduced into two ovarian cancer cell lines (SKOV3 and 222). FRNK promoted FAK dephosphorylation without changing total FAK levels in these cell lines. Furthermore, FRNK decreased the in vitro invasive ability of ovarian cancer cells by 56 to 85% and decreased migration by 52 to 68%. FRNK-transfected cells also displayed poor cell spreading. Immunohistochemical analysis revealed that the surface epithelium from all benign ovarian samples had weak FAK expression. In contrast, 68% of invasive ovarian cancers overexpressed FAK. FAK overexpression was significantly associated with high tumor stage, high tumor grade, positive lymph nodes and presence of distant metastasis (all P values 1 cm were independent predictors of poor survival. These data indicate that FAK is overexpressed in most invasive ovarian cancers and plays a functionally significant role in ovarian cancer migration and invasion. Thus, FAK may be an important therapeutic target in ovarian carcinoma.

Expression of the telomerase reverse transcriptase subunit telomerase reverse transcriptase gene is associated with most human malignancies. Because telomerase reverse transcriptase is rarely expressed in normal tissue, its presence in pathologic specimens is considered a marker of transformed cells. Moreover, high levels of expression have been correlated with poor prognosis in many cancers. Although telomerase activity has been found in chondrosarcomas, its prognostic significance in these malignant cartilage tumors is unknown. Malignancy in cartilage-derived tumors is assessed routinely by histomorphologic grading, but even well differentiated, low-grade lesions can metastasize. This unpredictable behavior greatly complicates the clinical treatment of cartilage tumors, making better prognostic indicators desirable. To address this issue we used immunohistochemistry to compare telomerase reverse transcriptase expression in a collection of 61 tumors consisting of malignant chondrosarcomas of varying grade and benign enchondromas. Associated case histories were reviewed to test the hypothesis that telomerase reverse transcriptase expression levels correlated with subsequent tumor recurrence. We found that the relative abundance of telomerase reverse transcriptase-expressing cells correlated significantly with grade and recurrence. These findings indicate that telomerase reverse transcriptase immunostaining may be a useful adjunct to the conventional three-level grading system.

The term lipoblastoma was first used by Jaffe in 19261 to refer to a tumor of immature fat cells. It was not consistently applied to the benign embryonal adipose tumors that now bear its name until Chung and Enzinger established the initial morphological criteria for its diagnosis in 19732. In doing so, they expanded on the descriptions provided by Vellios et al. in 19583 and by Shear in 19674 in their reports on the diffuse form of the tumor, called lipoblastomatosis. Despite their infrequent occurrence in the overall population and their rare discussion in the literature, lipoblastoma and lipoblastomatosis represent >15% of all benign soft-tissue neoplasms that present in the extremities of children who are five years of age or less5. The typical—almost exclusive—presentation of lipoblastoma as described in the literature is that of a painless soft-tissue mass, with or without progressive enlargement and with or without mass-effect symptoms when located near vital structures. Between February 1999 and October 2002, three children presented to the orthopaedic clinic at our institution for evaluation of thigh dimples; each was found to have a lipoblastoma. The families of our three patients were informed that data concerning the cases would be submitted for publication. Case 1. A thirty-nine-month-old girl presented with a three to four-month history of an enlarging dimple on the proximal part of the lateral aspect of the left thigh. The defect was noticed when it was approximately 7 mm in size, and it had grown to 25 mm in size by the time of presentation to the orthopaedic clinic. No history of trauma or pain was reported. Gestation, birth, development, and the medical history were unremarkable. Physical examination revealed a 2.5-cm, nontender deficit of the subcutaneous fat overlying the left greater trochanter. No …

Mandates for pathology training are a topic sure to surface “hot button” issues whatever the venue or whatever the combination of viewpoints gathered around the water cooler. A national pathology fellowship match administered by the National Residency Matching Program (NRMP) is the latest in a series of controversies affecting residents preparing for a future in our discipline and the programs entrusted with their education and professional development. Crawford and coauthors,1 representing the Association of Pathology Chairs (APC) and its program directors section (PRODS), argue in this issue of the Journal that a pan-pathology fellowship match is the best solution for problems exacerbated by changes in credentialing requirements for board certification in pathology. Other opinion leaders and organizations, including the Association of Directors of Anatomic and Surgical Pathology (ADASP), are unconvinced. The primary rationale for a pan-pathology fellowship match offered by Crawford and colleagues1 is the perception of “widespread dissatisfaction” among affected residents driven primarily by a single event in 2007 at which only a small fraction of the national resident pool was present and fewer still accounted for the residents sufficiently motivated to “overrun” the microphone. More inclusive data drawn from American Society for Clinical Pathology (ASCP) Resident In-Service Examination surveys showed that, in fact, only a minority of pathology residents were in favor of a fellowship match when asked in 2007 (39%), 2008 (26%), and 2010 (47%).1 Paradoxically, the same survey results showed that a consistent majority supported having a uniform fellowship application timeline. In an independent survey targeting members of the College of American Pathologists (CAP) Residents Forum and the ASCP Resident Liaison Network, only 43% of resident respondents were in favor of a match despite also identifying absence of clear and consistent application deadlines as an issue for fellowship applicants.2 These results resonate …

Background: There have been several reports in the literature of dermatofibromas with granular cells. Here we report a granular cell tumor with the architecture of a dermatofibroma. This is the first report of this histological variant of granular cell tumor. The lesion was a 2.5-cm oval, hyperpigmented plaque present for “years” on the back of a 60-year-old African-American woman. Methods: The specimen was processed using formalin fixation and paraffin embedding. Tissue sections were stained with hematoxylin and eosin. Immunohistochemical studies were performed with antibodies directed against S-100 protein, neuron-specific enolase, and factor XIIIa. Results: Histopathologic examination revealed granular cells, some of which were spindle shaped, distributed singly and in small groups between collagen bundles resembling a dermatofibroma. Immunohistochemical studies showed the tumor cells to be positive for S-100 and neuron-specific enolase and negative for factor XIIIa. Conclusion: The immunohistochemical findings support the diagnosis of a granular cell tumor with a dermatofibroma-like pattern.

Extranodal Hodgkin disease presenting as a primary localized neoplasm is uncommon, with rare case reports describing primary sites other than lymph nodes. The gastrointestinal tract is the most frequent site of involvement by extranodal Hodgkin disease, typically involving the stomach or small bowel. To date, we have been able to find only one fully documented case of Hodgkin disease of the sigmoid colon confirmed by immunohistochemical studies. We report a case of extranodal Hodgkin disease involving the transverse colon, presenting as inflammatory bowel disease and documented by light microscopic, immunohistochemical, cytogenetic, and molecular studies.

Differentiating between primary tumors of the liver and metastatic lesions can, at times, be difficult. Various histochemical and immunohistochemical methods have been used in an effort to better delineate between hepatocellular carcinoma (HCC), especially the microglandular variant, primary cholangiocarcinoma, and metastatic adenocarcinoma; these ancillary studies can yield less than satisfactory results. Recently, anti-MOC31, a monoclonal antibody directed against a cell surface glycoprotein, has been shown to be helpful in distinguishing between adenocarcinoma and mesothelioma. This study addresses whether this antibody might be helpful in distinguishing between HCC, primary cholangiocarcinoma, and metastatic adenocarcinoma in the liver. Formalin-fixed, paraffin-embedded tissue sections from 15 HCC (including 10 microglandular variants), 14 primary cholangiocarcinomas, and 33 metastatic adenocarcinomas (7 colon, 1 lung, 8 breast, 4 GE jct/gastric, 9 pancreas, 2 small intestine, 1 renal, 1 ovary) were immunostained with anti-MOC 31 (1:40, Dako) after protease digestion and biotin block using a modified ABC technique. Positive staining was limited to membrane based reactivity; controls stained appropriately. Immunoreactivity for MOC31 was observed in 14 of 14 cholangiocarcinomas and 33 of 33 metastatic tumors. Staining was diffuse, intense, and readily interpretable, with rare exceptions. All 15 cases of HCC were negative. We conclude that cholangiocarcinoma and metastatic adenocarcinoma from a variety of sites express MOC31; HCC is uniformly negative for this marker. Anti-MOC31 may prove useful in the evaluation of liver neoplasms where primary hepatocellular and adenocarcinoma enter the differential diagnosis; it is not useful in separating primary cholangiocarcinoma from metastatic adenocarcinoma.

Angiosarcoma is a rare malignancy that is characterized by endothelial cell differentiation. In the head and neck area, most of these lesions arise in the scalps of elderly individuals. Less commonly, angiosarcomas can be found within bone. The purpose of this report is to describe an example of angiosarcoma involving the floor of the mouth and right body of the mandible. The histopathologic and immunopathologic features of these lesions are also reviewed.

CD31 has been shown to be a sensitive and specific marker for endothelial differentiation among epithelioid and spindled-pleomorphic human neoplasms. However, the role of this marker in the evaluation of small round cell tumors has not been evaluated. Formalin-fixed, paraffin-embedded tissue sections from 276 small round cell tumors, including 85 Ewing's sarcoma/primitive neuroectodermal tumors (ES/PNET), 52 rhabdomyosarcomas, 10 extraabdominal polyphenotypic small cell tumors, six desmoplastic small cell tumors, 11 neuroblastomas, 23 Wilms' tumors, 20 retinoblastomas, 13 esthesioneuroblastomas, and 56 small cell malignant lymphomas were stained with CD31 (JC/70A, 1:40), using a modified avidinbiotin-peroxidase complex technique, after citrate buffer microwave epitope retrieval. Among nonlymphoid small round cell tumors, four of 85 ES/PNET were at least focally reactive. No other lesion in this group was positive. In contrast, the majority of well-differentiated (11 of 17), intermediately differentiated (two of three), and lymphoblastic lymphomas (three of three) were positive. Small cleaved lymphomas (three of 13 follicular, one of 13 diffuse) were less often reactive, whereas small noncleaved lesions were negative. Although reactivity for CD31 in ES/PNET is uncommon, the presence of platelet/endothelial cell adhesion molecule in a small cell neoplasm should not in isolation be taken as evidence of hematopoietic origin. These results further define the utility of CD31 in the evaluation of human neoplasms.

After curative resection for pancreatic cancer, only 10% of patients survive disease for 5 years. These dismal results suggest the presence of occult tumor at the time of initial operation. This phase I/II study was conducted to compare traditional exploratory laparotomy with radioimmunoguided surgery (RIGS) in the assessment of disseminated pancreatic cancer.Ten patients with the diagnosis of adenocarcinoma of the pancreas were injected intravenously with 1 mg CC49 monoclonal antibody radiolabeled with 2 mCi iodine 125. All patients were evaluated by a standard abdominal exploration followed by RIGS. Tumor identified by each technique was documented and categorized as neoplasm disseminated to viscera or lymphatics.There were 25 visceral sites of disease that were traditionally discovered at the time of exploration including pancreas, omentum, small bowel, pelvis, liver, and other. All 25 sites of disease were positive by RIGS plus an additional four sites of visceral tumor for a total of 29 RIGS positive sites of disease. Six lymphatic sites of disease were discovered by traditional examination; however, 44 sites of lymphatic sites were documented by RIGS (p0.001). In addition, nine traditionally and pathologically negative/RIGS positive nodes were subjected to cytokeratin and MOC 31 immunohistochemistry. Six of nine nodes were positive by cytokeratin immunohistochemistry, and five of the six cytokeratin positive nodes were MOC 31 positive.These data suggest that the RIGS technique detected significantly more foci of visceral spread of tumor than traditional exploratory laparotomy and significantly more sites of lymphatic dissemination were identified by RIGS than by standard exploration.

This is the first report (to our knowledge) that describes a patient with massive polyostotic fibrous dysplasia involving the calvaria and facial skeleton that subsequently underwent transformation to a malignant mesenchymoma with elements of chondrosarcoma, osteosarcoma, and rhabdomyosarcoma arising in the maxilla. Malignant transformation occurred in the absence of prior radiation exposure, osteomyelitis, or known bony infarction. A review of the literature did not reveal any similar cases of massive fibrous dysplasia of the maxilla degenerating to multiple simultaneous malignant histotypes. Arch Otolaryngol Head Neck Surg. 1997;123:106-109

Chondrosarcomas are among the most malignant skeletal tumors. Dedifferentiated chondrosarcoma is a highly aggressive subtype of chondrosarcoma, with lung metastases developing within a few months of diagnosis in 90% of patients. In this paper we performed comparative analyses of the transcriptomes of five individual metastatic lung lesions that were surgically resected from a patient with dedifferentiated chondrosarcoma. We document for the first time a high heterogeneity of gene expression profiles among the individual lung metastases. Moreover, we reveal a signature of “multifunctional” genes that are expressed in all metastatic lung lesions. Also, for the first time, we document the occurrence of massive macrophage infiltration in dedifferentiated chondrosarcoma lung metastases.

A 42-year-old woman presented with right leg pain of 4 years' duration without a palpable mass. Magnetic resonance imaging showed a soft tissue mass adjacent to the posterior aspect of the proximal fibula that appeared to arise from the belly of the gastrocnemius muscle. Excisional biopsy showed a well-circumscribed tumor mass composed of fascicles of spindled smooth muscle cells intimately admixed with islands of larger, epithelioid cells in an extracellular basophilic matrix reminiscent of immature cartilage. Other areas resembled maturing hyaline cartilage. Immunohistochemical staining and electron microscopy were utilized to verify the presence of the two distinct cell types within this tumor. Review of the literature suggested that this case represents the first well documented case of cartilaginous metaplasia in a deeply situated soft tissue leiomyoma. Int J Surg Pathol 1(4):235-238, 1994

This study investigated the effect of sildenafil citrate on micro-recanalization and neovascularization, which were previously demonstrated in a rat model using biodegradable grafts (BGs) for vas deferens reconstruction. A total of 24 male rats underwent bilateral vasectomy with removal of a 0.5-cm vasal segment and were randomly assigned to four groups. Groups 1 and 2 underwent immediate vasovasostomy. Groups 3 and 4 underwent interposition of a 0.5-cm BG in the vasal gap. Groups 1 and 3 were given 5 mg kg(-1) day(-1) oral sildenafil. Other groups were given placebo. Rats were housed with females 12 weeks postoperatively. Reconstructed vasal segments were harvested 16 weeks postoperatively and analyzed histologically. Fluid from the distal vasal stump was analyzed for motile sperm. Urine samples obtained 16 weeks postoperatively were analyzed for cGMP levels. cGMP levels in rats treated with sildenafil were significantly higher than in control rats. No pregnancies were sired by grafted groups. In all, 5/6 rats in group 1 and 3/6 rats in group 2 sired litters. No motile sperm were noted in the vasal fluid of the grafted groups. Motile sperm were noted in all rats in group 1 and in 5/6 rats in group 2. In addition, 29 and 4 microcanals were detected in the sildenafil and placebo groups, respectively (P = 0.023). No microcanal exceeded 3 mm in length. An average of 12 and 28 blood vessels per graft were noted in the placebo and sildenafil groups, respectively (P0.0001). In conclusion, sildenafil enhances micro-recanalization and neovascularization in BG used for vas deferens reconstruction, but does not increase the microcanal length after 16 weeks.

The implementation and enforcement of the College of American Pathologists Survey Checklist ANP 22432 has renewed attention on the issue of outdating of antibodies used for immunohistochemical analysis. The current study examined the staining patterns of 26 recently acquired primary antibodies and their expired counterparts. Two reviewers examined sequential sections of formalin-fixed, paraffin-embedded tissue samples for staining intensity and percentage of positivity. Appropriate positive and negative control studies were performed. Of the 26 antibodies, 20 exhibited no difference in percentage of positivity or staining intensity. Of the remaining 6, 3 showed better performance with the expired cohort and 3 with nonexpired antibodies. However, no antibody staining characteristics varied by more than 1 step, and in no case was positive staining lost after antibody expiration. Negligible differences exist in immunostaining between outdated and current antibodies. Thus, exemption for primary antibodies from existing regulations would conserve resources without adversely impacting patient care.

Summary The teaching of pathology and the face of pathology as a career are changing rapidly. A short questionnaire was constructed covering key areas impacted by curricular change to collect data for a workshop to be held at the Annual Meeting of the West and Mid-West Region of the Association of Pathology Chairs. Questions included the ongoing existence of pathology as a separate discipline, the degree of ‘control' exercised by pathology faculty, the length of the course (hours), the use of microscopes, and selected outcomes data, specifically National Board of Medical Examiners graphs of comparative performance of disciplines and US Medical Licensing Examination Step 1 data. The written responses and discussion by attendees at the meeting are presented with preliminary analysis and commentary. It was concluded that ‘evidence-based education' represents something of a novelty, worthy of further study.

Background Somatostatin receptor scintigraphy (SRS) has been successfully used in imaging PBTs and, as a functional imaging modality, may be better able to differentiate tumor from scar/necrosis. This retrospective study evaluates the role of SRS in post-treatment surveillance of PBTs. Procedure Twenty children (age range: 7 months to 24 years, mean: 9 years) with known brain malignancies underwent serial SRS and MRI. The sensitivity and specificity of SRS and MRI were compared for surveillance scanning using patient outcome as the reference standard. Somatostatin receptors (sstrs) expression was determined by immunohistochemistry (IHC) of available tumor specimens. Results SRS was true positive (TP) in 15 of 16 patients with proven disease found post-resection (n = 5) or during follow-up (n = 11). In contrast, MRI was positive in 12 of these 16 patients and equivocal in another two patients where it could not distinguish between radiation necrosis and tumor recurrence. The two patients with false negative (FN) MRI and proven disease were positive by SRS. SRS was negative in all four patients with no evidence of disease by follow-up (mean follow-up = 58 months). The only patient with a FN SRS (TP by MRI) was one without IHC evidence of sstrs. SRS was TP in 7/7 tumors with IHC documented sstrs. Conclusions SRS is a useful adjunct to MRI for post-treatment surveillance of sstr-positive PBTs, particularly when MRI is equivocal. Pediatr Blood Cancer 2008;50:561–566. © 2007 Wiley-Liss, Inc.

Antibodies directed against alpha-inhibin have been previously reported as staining both sex cord-stromal neoplasms as well as adrenal cortical tumors. This relatively restricted immunoreactivity pattern is useful in the assessment of retroperitoneal masses, especially in a setting of limited tissue (e.g., needle biopsy). However, no study to date has evaluated alpha-inhibin immunoreactivity in soft-tissue neoplasms, which frequently enter the differential diagnosis of retroperitoneal masses. We investigate the incidence of alpha-inhibin staining in a variety of soft-tissue neoplasms by using formalin-fixed, paraffin-embedded tissue sections from 282 previously classified soft-tissue neoplasms with anti-alpha-inhibin (Serotec, 1:75). A modified avidin-biotin complex method was used after heat-induced epitope retrieval. Cytoplasmic granular staining was considered positive. Of the 282 tumors studied, a total of 8 (2.8%) demonstrated positive staining with anti-alpha-inhibin antibody. These included 4 of 25 liposarcomas (16%), 2 of 18 angiosarcomas (11%), 1 of 48 lipomas (2.1%), and 1 of 1 rhabdomyoma (100%). Negative staining was noted among hemangiomas (0/28), schwannomas (0/32), leiomyomas (0/16), fibrosarcomas (0/2), fibromas (0/11), dermatofibromas (0/9), neurofibromas (0/6), synovial sarcomas (0/15), rhabdomyosarcomas (0/10), Triton tumors (0/2), and malignant fibrous histiocytomas (0/59). We conclude that rare soft-tissue tumors, especially those exhibiting either lipomatous or vascular differentiation, demonstrate alpha-inhibin immunoreactivity. These findings re-emphasize the need for a well-construed antibody panel when immunohistochemical methods are employed in the evaluation of retroperitoneal neoplasms. However, the rarity of alpha-inhibin expression by soft-tissue neoplasms provides further support for its overall specificity as a marker of adrenal cortical differentiation in the biopsy evaluation of a retroperitoneal mass.

Objective Tumor microvessel density, measured by CD31 immunohistochemistry, correlates with survival in patients with ovarian cancer. CA 125 is secreted by most ovarian cancers, and we have previously shown that the rate of decline of CA 125 is also predictive of ovarian cancer survival. Because increased tumor vascularity may allow metastases on one hand, while facilitating the delivery of chemotherapy on the other, we investigated the relationship of tumor microvessel density to preoperative CA 125, residual disease, and the initial response to treatment. Methods FIGO stage, grade, age, residual disease, and CD31 microvessel density count were correlated with consecutive patients ( n = 202) diagnosed with epithelial ovarian cancer who met entry criteria. The relationship of CD31 staining to preoperative CA 125, and the rate of decline in CA 125 (slope) as a measure of initial response to therapy, was also evaluated based on complete CA 125 data. Spearman correlation and the Wilcoxon rank sum test were used for bivariate analyses. Linear and logistic regression was used for multivariate analysis. Results There were 21 stage I, 14 stage II, 125 stage III, and 42 stage IV patients diagnosed with epithelial ovarian cancer included in the study. More than half ( N = 126) of the patients were optimally cytoreduced. Elevated microvessel density was associated with advanced stage of disease ( P = 0.0453), grade ( P = 0.0002), and an increased amount of residual disease ( P = 0.0144). CA 125 values were higher in patients with residual disease versus patients without residual disease ( P = 0.0357), and the decline in the CA 125 (slope) was less steep in patients without residual disease versus patients with residual disease ( P = 0.0003). However, the initial response to chemotherapy was unrelated to the microvessel density count as measured by CD31 antibody staining ( P = 0.7911). In multivariate analyses, CD31 counts remained significant in relationship to grade. Nonideal slopes, indicating decreased response, were associated with increasing age ( P = 0.0008) and residual disease ( P = 0.0035). Conclusion Elevated ovarian cancer microvessel density count is related to advanced stage and grade of disease, and compromised potential for cytoreduction. Residual disease is associated with higher CA 125 levels and faster CA 125 decline rates. The rate of decline of CA 125 during the initial response to treatment cannot be predicted based on CD31 counts, confirming a complex relationship between tumor vascularity, metastasis, and response to treatment.

Sulindac sulfone (Exisulind), a metabolite of the non-steroidal anti-inflammatory drug, sulindac, was evaluated for its effects on the development of rectal polyps in patients with familial adenomatous polyposis. Three cohorts of 6 patients each were given doses of 200, 300, or 400 mg Exisulind twice daily. Hepatotoxicity, shown by elevation in blood transaminase levels, was the dose-limiting toxicity and occurred at the 400 mg bid dose. Due to this toxicity, all patients treated with the 400 mg dose were subsequently reduced to the 200 mg dose level. Subsequently, 2 of the 6 patients were dose-escalated to 400 mg bid dose. The patients were treated with Exisulind for a period of six months. Sixteen of 18 patients had regression of small polyps (≥6mm in diameter) characterized by a flattening of the polyps and a macular “halo” appearance. Histopathologic examination of the polyp biopsy specimens showed a marked increase in the proportion of mucin producing cells in the glands after treatment with Exisulind at all dose levels. Ki-67 staining, a measure of cell proliferation, was higher in the polyps than in normal mucosa. There was no significant change in the proliferation index between baseline and six month values in any of the groups treated with Exisulind or in normal tissues. The median apoptotic labeling index, as determined by the TUNEL technique, was higher in the polyps than in normal-appearing mucosa. Overall, there was no significant change in the apoptotic labeling index between baseline and 6 months in normal-appearing mucosa however, the index in polyps was increased. These results suggest that treatment of FAP patients with Exisulind for a period of six months may lead to regression of small polyps, and that the mechanisms of Exisulind—induced regression appear to be through stimulation of mucus differentiation and apoptosis in glandular epithelium.

The human Na+/I- symporter (hNIS) is the plasma membrane protein that mediates active iodide uptake into several tissues, such as the thyroid and salivary glands. To study the distribution and cellular localization of the hNIS protein, we have generated a polyclonal antibody that could detect the hNIS protein by immunohistochemical staining on tissue sections. In normal thyroids, hNIS expression is heterogeneous, and it is only detected in sporadic thyrocytes of a given follicle. The hNIS protein was not detected in thyroid carcinomas, yet it was detected in the majority of thyrocytes in Graves' thyroids. In salivary glands, hNIS protein was not detected in acinar cells, but it was detected in ductal cells. The hNIS proteins are clustered in the basal and lateral membranes in cells stained positive for hNIS.

Castleman disease, or angiofollicullar hyperplasia, is a rare cause of lymph node enlargement. This most commonly occurs within the thorax, although rare extrathoracic presentations have been described. Only two cases with hepatic localization have been reported. We present a case of Castleman disease within the porta hepatis masquerading as a hepatic neoplasm.

To study if HER-2 overexpression by locally advanced esophageal cancers increase the chance of brain metastasis following esophagectomy.We retrospectively reviewed the medical records of esophageal cancer patients who underwent esophagectomy at University of Iowa Hospitals and Clinics between 2000 and 2010. Data analyzed consisted of demographic and clinical variables. The brain metastasis tissue was assayed for HER-2 overexpression utilizing the FDA approved DAKO Hercept Test(®).One hundred and forty two patients were reviewed. Median age was 64 years (36-86 years). Eighty eight patients (62%) received neoadjuvant chemoradiotherapy. Pathological complete and partial responses were achieved in 17 (19%) and 71 (81%) patients. Cancer relapsed in 43/142 (30%) patients. The brain was the first site of relapse in 9/43 patients (21%, 95% CI: 10%-36%). HER-2 immunohistochemistry testing of the brain metastasis tissue showed that 5/9 (56%) cases overexpressed HER-2 (3+ staining).HER-2 overexpression might be associated with increased risk of brain metastasis in esophageal cancer patients following esophagectomy. Further studies will be required to validate this observation.

Objectives To describe the characteristics of head and neck leiomyosarcoma and to identify factors associated with survival. Design Retrospective population-based study. Patients The 17-registry Surveillance, Epidemiology, and End Results database was used to identify 578 patients with leiomyosarcoma of the head and neck. Interventions Surgery and primary and adjuvant radiotherapy. Main Outcome Measures Patient demographics and tumor characteristics were examined. Treatment modalities were compared, and survival was assessed using the log-rank test. Results The mean age at diagnosis was 64 years. Most tumors were smaller than 5 cm in greatest dimension (87%) and high grade (44% were moderately differentiated and 39% were poorly differentiated). The primary tumor demonstrated deep extension in 39% of cases, and 2% had lymph node metastases. The most common primary site was the skin and soft tissue of the head and neck (83%). Surgical treatment was provided to 89% of patients, 14% received adjuvant radiotherapy, and 4% received radiotherapy alone. The median observed survival was 84.7 months. The 5-year disease-specific survival rate was 87.6% in patients with well-differentiated tumors, 85.7% in patients with moderately differentiated tumors, and 52.7% in patients with poorly differentiated tumors (P Conclusions Leiomyosarcoma typically presents in older patients; it is often poorly differentiated; and improved survival is associated with surgical treatment.

e14572 Background: BM is historically an uncommon relapse pattern of EC. HER2 is a membrane tyrosine kinase that is overexpressed in various cancers as EC and breast cancer (BC). BM in BC patients ...

e21102 Background: Previous analyses have demonstrated that a neuroendocrine tumor's site of origin correlates with tumor biology, clinical presentation, and oftentimes prognosis. There is however ...

e14585 Background: Previous analyses have demonstrated that neuroendocrine tumor (NET) grade correlates well with OctreoScan positivity, SST2, and Chromogranin-A immunohistochemical (IHC) staining....