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Abstracts and Case Studies From the College of American Pathologists 2006 Annual Meeting (CAP '06)

Posted on: Wednesday, 13 September 2006, 15:00 CDT

By Anonymous

Abstract and case study poster sessions will be conducted during the College of American Pathologists' Annual Meeting (CAP '06), which is scheduled for September 10 to 13, 2006. The meeting will occur at the Manchester Grand Hyatt Hotel, San Diego, Calif. The poster sessions will occur in the Connection Caf & Exhibits area. Specific dates and times for each poster session are listed below. Also shown below each poster session listing are the subject areas that will be presented during each session.

POSTER SESSION 100: SUNDAY, SEPTEMBER 10, 2006, 9:30 AM-1:00 PM

Autopsy and Forensic Pathology; Bone & Soft Tissue Pathology; Breast Pathology; Cardiovascular Pathology

An Unusual Case of Primary Pulmonary Hypertension Associated With HIV

(Poster No. 1)

Puja K. Puri, MD (puripuja@gwu.edu); Jan M. Orenstein, MD. Department of Pathology, George Washington University, Washington, DC.

Context: A 31-year-old African American man with asthma presented to the George Washington University Hospital (GWUH) with a week- long history of shortness of breath, increasing left-sided chest pressure, and lower extremity edema. Two months prior he was treated elsewhere for nephrotic syndrome, renal failure, and hypertension and was found to have cardiomegaly and to be HIV positive. A CD4 T- cell count and viral load were not obtained, and treatment was not initiated. On admission to GWUH, the patient was found to have pulmonary hypertension con- firmed by Swan-Ganz catheter.

Design: Despite medical treatment, he developed respiratory failure and died within 12 hours of admission. A full gross and microscopic autopsy was performed.

Results: Primary pulmonary hypertension (PPH) was diagnosed on the basis of histology. PPH occurs in low frequency in patients with HIV/ AIDS. The pulmonary findings fell into the less common category of medial hypertrophy and medial and intimal fibrosis, without plexiform changes. Inexplicably, the patient had prominent chronic inflammation involving his lungs, liver, heart, kidneys and leptomeninges. Despite a normal CD4 T-lymphocyte count, his lymph nodes were atrophic and fibrotic. Lung culture grew Mycobacterium mucogenicum.

Conclusions: This case is unusual because the patient was documented to be HIV positive for less than 10 months and was only diagnosed with PPH at the time of his death. This is much more rapid than the average of 33 months between HIV diagnosis and the onset of PPH and the 6- month average between the diagnosis and death.

Hepatocellular Carcinoma, Hepatitis C, and Cirrhosis: A Retrospective Study of Immediate Cause of Death in 100 Autopsies

(Poster No. 2)

John J. Cangelosi, MD (jjcangel@utmb.edu); Daniel F. Cowan, MD; Vicki J. Schnadig, MD. Department of Pathology, University of TexasMedical Branch, Galveston.

Context: The incidence of hepatocellular carcinoma (HCC) in the United States has increased from 1.5 to 3.0 per 100 000 during the past 2 decades and is often associated with cirrhosis. The course for these patients is often long, complicated, and challenging to the physician as to extension of life. This study reviews the immediate cause of death (ICD), found at autopsy, for 100 patients with HCC.

Design: A database search of 5070 consecutive autopsies from 1993 through 2005 was done and identified 100 cases with final autopsy diagnoses of HCC. Further inquiry was done to determine the ICD in these cases using both autopsy and antemortem clinical data. Analysis as to whether the ICD could be attributed to HCC, cirrhosis, and/or HCV was made.

Results: Review of all 100 cases revealed 58% of the ICDs fell into 6 diagnoses: nonspecific ''complications from HCC'' (14%), ''exsanguination from esophageal varices'' (10%), ''hemoperitoneum due to rupture of HCC'' (9%), ''hepatic encephalopathy'' (9%), ''end stage liver disease'' (9%), and ''acute bronchopneumonia'' (7%). After further analysis, it was apparent that pulmonary complications and blood loss/shock accounted for 55% of the ICDs in patients with HCC (22% and 23% of the cases, respectively), with bronchopneumonia representing 50% of all pulmonary- related deaths. Esophageal/ gastric bleeds accounted for almost 50% of all blood loss/shock related deaths.

Conclusions: Common causes of death in patients with HCC include respiratory failure and hemorrhage. Further investigation is needed to identify how this knowledge can translate into better use of time and resources for prolonging survival.

CD117 Positivity in a Primary Peritoneal Papillary Serous Carcinoma

(Poster No. 3)

Marisa Mammarappallil, MD (Marisa.Mammarappallil@ttuhsc.edu); Elizabeth Miller, MD. Department of Pathology, Texas Tech University Health Sciences Center, Lubbock.

Context: We present a case of primary peritoneal papillary serous carcinoma that stained positively for CD117. Primary peritoneal carcinoma is a rare entity that has been shown to be immunoreactive for B72.3, Ber- EP4, and CA 19-9. There are no previously reported cases of CD117 positivity in this tumor.

Design: Review of medical records reveals that the patient was a 77- year-old woman who presented in a hypercoagulable state with multiple embolic events. A CT scan revealed a large pelvic mass. She also was found to have an elevated CA 125. The patient had a strong family history of ovarian carcinoma.

Results: Autopsy revealed a 13 11 3.5 cm soft, friable mass in the mesentery. The large and small bowel were unremarkable. The bilateral adnexae were in place and unremarkable. Microscopically, the tumor was composed largely of papillae lined by columnar cells with pleomorphic, enlarged nuclei. Immunohistochemical studies for CD117 and Ber-EP4 were positive, while those for B72.3, calretinin, and CA 19-9 were negative.

Conclusions: Immunohistochemistry for differentiating primary peritoneal carcinoma from mesothelioma and from ovarian carcinoma has been minimally studied. Positive staining with CD117, which has not previously been reported, may potentially be of use in the diagnosis of this tumor. A literature review and comparison with our immunohistochemical findings will be discussed.

Sudden Death in a 42-Year-Old Man Due to Cerebral Cavernoma

(Poster No. 4)

Ralph Matthews,MD (ralph.matthews@vtmednet.org); Steven Shapiro, MD. Department of Pathology, Fletcher-Allen Healthcare, Burlington, Vt.

Context: Venous angiomas are benign vascular malformations and are the most common vascular malformation in the central nervous system. These lesions are rarely symptomatic and seldom hemorrhage. To our knowledge, there are no published reports of sudden death caused by a cerebral cavernoma.

Design: The autopsy was performed by the chief medical examiner. The neuropathologic examination was performed by our institution's neuropathologist. The patient's clinical records were reviewed to assess for comorbidities.

Results: A 42-year-old man with no significant past medical history collapsed suddenly while walking with his son in the woods. He was transported emergently to a local hospital, where despite resuscitative efforts, he died approximately 45 minutes after the incident. At autopsy, a 1.5 1.5-cm area of black-brown discoloration with cystic change and dilated blood vessels was identified in the right medial temporal lobe during gross examination of the brain. Histologically, this area was composed of numerous dilated, thin-walled vessels surrounded by marked gliosis and pigmented macrophages. Many of the vessels were necrotic. Elastin von Giesen stain demonstrated no elastic tissue within the thinwalled vessels, confirming the venous vascular nature of the lesion.

Conclusions: This case represents the first report of sudden death due to a cerebral cavernoma.

Hepatocellular Carcinoma, Hepatitis C, and Cirrhosis: A Retrospective Study of Metastatic Patterns in 100 Autopsies

(Poster No. 5)

John J. Cangelosi, MD (jjcangel@utmb.edu); Daniel F. Cowan, MD; Vicki J. Schnadig, MD. Department of Pathology, University of TexasMedical Branch, Galveston.

Context: The incidence of hepatocellular carcinoma (HCC) in the United States has increased from 1.5 to 3.0 per 100 000 during the past 2 decades, attributed to an increased prevalence of long- standing hepatitis C virus infection (HCV). Intravascular spread and periportal lymph node metastases are common; however, bone and extra- abdominal metastases, once relatively rare, are increasing. This study reviews 100 autopsies performed on patients with HCC, with focus on metastatic sites and correlation with HCV infection and presence of cirrhosis.

Design: A database search of 5070 consecutive autopsies from 1993 through 2005 was done and identified 100 cases with a final diagnosis of HCC. Clinical records and histologic and gross photographic material were also reviewed.

Results: Of the 100 cases reviewed, 87% had cirrhosis, 86% had documented HCV infection, and 76% had combined cirrhosis and HCV. Portal/ hepatic vein (53%) and lung (47%) metastasis were common. Of note were metastases to diaphragm (9%), bone (7%), heart (5%), and esophageal submucosa (3%). The cardiac metastases included HCC extension from the IVC into the right atrium, transmural invasion of the right ventricle, adventitial invasion of the aorta, and fat/ lymphatic invasion of the pericardium.

Conclusions: This study supports previous findings that blood vessels and lungsare common sites of metastatic HCC; however, other sites were commonly seen at autopsy as well. Whether this is related to longer survival of HCC patients from improved medical care or a new trend emerging in HCV-associated liver disease requires further exploration.

Diagnostic Yield of Perinatal Autopsy in a Community Hospital

(Poster Number 6)

Abstract Withdrawn

Integration of Demographic Database of Hospital Records With Mortality and Autopsy Database by a Barcode Identification System and Microsoft Access Interface

(Poster No. 7)

Avneesh Gupta, MD; Dan X. Cai, MD; Sandra Cota, BS; Joseph F. Tomashefski, MD. Department of Pathology, MetroHealth Medical Center, Cleveland, Ohio.

Context: Maintenance of an accurate and complete mortality and autopsy database is of crucial importance to health care quality assurance, graduate medical education, and continuous quality improvement. The purpose of this study is to introduce a barcode identification system that imports demographic data from the database of hospital records to our Microsoft Access-based mortality and autopsy database and to demonstrate the advantages of such integration in reducing data entry errors and in improving the efficiency and accountability of mortality personnel.

Design: A barcode scanning mechanism is used to import demographic data from the main hospital records to the mortality and autopsy database. The prevention of decedent misidentification is achieved by standardization of decedent identification barcode placement by nursing staff and standardization of decedent ID verification during body acceptance, autopsy, and release of body. The employee ID barcodes are included in the process to track persons responsible for handling of the cases.

Results: The integration of data along with barcode identification resulted in reduction in database entry errors and increased accountability of the personnel. The standardization of decedent ID barcode placement was 95% achieved during first 3 months of use. Our Microsoft Access- based mortality and autopsy database is searchable and convenient for statistical and epidemiologic studies.

Conclusions: Utilizing commonly available barcode scanners and a database management program, we have built a complete, low-cost, accurate, and efficient mortality and autopsy database, which serves well in our health care practice and graduate medical education programs.

Horseshoe Lung With Pulmonary Hypoplasia, Anomalous Pulmonary Vasculature, and Congenital Pulmonary Airway Malformation

(Poster No. 8)

Manali Bendre, MD (Manali.S.Bendre@uth.tmc.edu); Reenu Malhotra, MD; Harvey Rosenberg. Department of Pathology, University of Texas at Houston.

Context: Horseshoe lung is a rare congenital anomaly characterized by an isthmus of pulmonary parenchyma that extends from the base of one lung to the other. Of the approximately 40 reported cases, most have been associated with the scimitar syndrome, composed of varied combinations of anomalies including pulmonary hypoplasia, pulmonary vascular anomalies, and anomalies of the bronchial tree in addition to horseshoe lung. Infants with these anomalies usually have severe cardiorespiratory distress with systemic to suprasystemic pulmonary arterial pressures.

Design: We present a case of a 1480 g, 32-week gestational age female infant born to a mother with preeclampsia. The infant had multiple external facial anomalies and clenched fists. At birth, the infant had poor respiratory effort, with chest radiograph suggestive of pulmonary hypoplasia. The infant died approximately 14 hours after delivery.

Results: Autopsy findings included horseshoe lung, posteriorly displaced hypoplastic right lung with anomalous venous return from right lower lobe to inferior vena cava, and systemic arterial blood supply from thoracic aorta to left lower lobe. The left lower lobe also had a congenital pulmonary airway malformation (CPAM) type 2. The heart was in situs solitus but dextroposed to the right side of the thoracic cavity. The karyotype was 46XX.

Conclusions: This case showed association of horseshoe lung with some pulmonary vascular anomalies of scimitar syndrome. We found no prior reports of association of CPAM with either horseshoe lung or scimitar syndrome. Speculations on the as-yet-unknown pathogenesis of horseshoe lung focus on disturbances in pulmonary development early in embryogenesis.

Expression of D2-40 in Kaposi Sarcoma and Other Vascular Tumors

(Poster No. 9)

Yasser M. El-Gohary, MD1 (yelgohar@msmc.com); Robert J. Poppiti, MD1; Yulin L. Liu, MD2; Jan F. Silverman, MD2; Reda S. Saad, MD.2 1Department of Pathology, Mount Sinai Medical Center, Miami Beach, Fla; 2Department of Pathology, Allegheny General Hospital, Pittsburgh, Pa.

Context: Previous studies have failed to definitely establish the cell of origin in Kaposi sarcoma (KS), contributing to the controversy about its lymphatic or blood vessel endothelial histogenesis. D2-40 is a novel monoclonal antibody that reacts with lymphatic endothelium. In this study, we investigated the expression of D2-40 in KS and compared it with the findings for other endothelial immunohistochemical markers.

Design: Thirty cases of KS were retrieved. One tissue block from each case was submitted for the immunohistochemical markers CD31, CD34 (Dako, Carpinteria, Calif), CD105 (endoglin) (Cell Marque, Hot Springs, Ariz), and D2-40 (Signet, Dedham, Mass). Anatomic sites of the KS spec- imens included 21 cutaneous, 4 gastrointestinal, 2 lymph node, 2 lung, and 1 palate. Nine of the 30 patients had documented acquired immunodeficiency syndrome (AIDS). Twenty cases of angiosarcoma and 10 cases of capillary hemangiomas were also included as a control group. Immunostains were performed on an automated immunostainer with appropriate positive and negative controls.

Results:

Please see the table. D2-40 was strongly expressed by cells lining irregular vascular spaces in early KS lesions (4 cases) and areas of solid tumor in advanced KS (24 cases); the other 2 negative cases had focal (<10%) patterns of staining mainly highlighting vascular channels without staining solid tumor areas. There was no difference in staining pattern between cases associated with AIDS and other, classic cases.

Conclusions: KS may be derived from lymphatic endothelium. D2-40 is a sensitive marker for KS. D2-40 can be added to immunohistochemical panels for vascular neoplasms.

Expression of Bcl2/bax Ratio and p53 in Synovial Sarcoma

(Poster No. 10)

Dariusz Borys, MD1 (borysd01@med.nyu.edu); Jerome B. Taxy, MD2; Herman Yee, MD1; Andre Kajdascy Balla, MD3; Roberto Garcia, MD1; Sharon Lang, PhD4; Thomas Krausz, MD2; Jonathan Melamed, MD1; M. Alba Greco, MD.1 1Department of Pathology, NYU School of Medicine, New York, NY; 2Department of Pathology, University of Chicago, Ill; 3Department of Pathology, University of Illinois at Chicago; 4Pathology, Biogenex, San Ramon, Calif.

Context: Bcl-2 oncoprotein is overexpressed in synovial sarcoma and is known as an apoptosis suppressant. bax protein is a homolog of Bcl- 2, and promotes cell death by apoptosis. p53 may induce apoptotic cell death via bax. The objective of this study is to investigate roles of p53 and Bcl-2/bax ratio in synovial sarcoma on the susceptibility of sarcoma to apoptotic stimuli.

Design: A tissue micro array was created using paraffin-embedded samples from 16 synovial sarcoma cases. Immunohistochemistry was done with monoclonal anti-Bcl-2, anti-p53, and polyclonal anti-bax antibodies. Immunoreactive scoring was based on a direct visual count of 400 cells and a calculated percentage of Bcl-2-, bax-, and p53-positive cells.

Results: The ages of the patients ranged from 12 to 55 years (mean 38 years). Ten patients had monophasic and 6 biphasic synovial sarcomas. A 2-year followup was available in 10 patients. Five patients had pulmonary metastasis; 1 had a recurrence in the primary site. Two patients with pulmonary metastasis and 1 with local recurrence were previously treated with adjuvant therapy. The table shows results of percentage immunoreactivity of Bcl-2, bax, and p53 in 16 cases.

Conclusions: These results show increased expression of Bcl-2 with decreased expression of bax and p53 in cases with synovial sarcoma. These data would suggest a potential mechanism by which p53 regulates apoptosis in synovial sarcoma, possibly a subject for a larger study.

Steroid Hormone Receptor Expression by Immunohistochemistry in Fibromatosis Cases

(Poster No. 11)

Ozlen Saglam, MD (osaglam@hotmail.com); Richard J. Zarbo, MD. Department of Pathology, Henry Ford Hospital, Detroit, Mich.

Context: Fibromatosis is a locally infiltrative myofibroblastic lesion. The growth of these proliferations from various sites has been related to steroid hormone receptors, resulting in recent clinical attempts to treat these cases with antiestrogen and/or nonsteroidal anti-inflammatory drugs.We aim to corroborate these findings regarding hormone receptors in the etiology of fibromatosis by examining our recent institutional experience.

Design: Twenty-three fibromatosis cases were retrieved from the surgical pathology files of Henry Ford Hospital between 1995 and 2005. Ten cases were classified as abdominal fibromatosis. Other anatomical sites of involvement were upper and lower extremities, chest wall, and penis. The patient cohort of 12 female and 11 male patients ranged in age from 14 to 74 years. Formalin-fixed, paraffin- embedded sections were subjected to immunohistochemical staining for estrogen, progesterone, and androgen receptors using mouse monoclonal antibodies. (DAKO; dilutions, 1:100 for estrogen and progesterone receptors, and 1:25 for androgen receptor with avidin- biotin peroxidase technique). Any nuclear staining was accepted as positive.

Results: All 23 cases were negative for estrogen, progesterone, and androgen receptor immunostaining except 1 case. A penile localized fi- bromatosis case w\as stained positive only for androgen receptor.

Conclusions: Antiestrogen (eg, tamoxifen) treatment has been proposed as an alternative first-line treatment for desmoid tumors instead of surgery. However, nearly all fibromatosis cases in this series, including abdominal desmoid tumors, were steroid hormone receptor negative. It has yet to be evaluated in a controlled clinical trial whether responsiveness to antihormonal therapy can be predicted by immunohistochemical definition of hormone receptor status.

Alveolar Rhabdomyosarcoma With Neuroendocrine Differentiation

(Poster No. 12)

Amy Y. Lin, MD1 (alin@uic.edu); M. Adib Houreih, MD2; Brian Eyden, PhD2; Robert Folberg, MD1; Gregorio Chejfec, MD1; D. Barker, MD3; S. S. Banerjee, MD.2 1Department of Pathology, University of Illinois-Chicago; 2Department of Histopathology, Christie Hospital NHS Trust,Manchester, United Kingdom; 3Department of Histopathology, Royal Albert Edward Infirmary NHS Trust, Wigan, United Kingdom.

Context: Neuroendocrine/neuronal variants of epithelial and nonepithelial tumors, including embryonal rhabdomyosarcoma (ectomesenchymoma), have been reported. However, to our knowledge, neuroendocrine differentiation in alveolar rhabdomyosarcoma (ARMS) has not previously been described.

Design: This is a case series of 2 patients with ARMS showing neuroendocrine differentiation. Histologic, immunohistochemical, and ultrastructural features are presented.

Results: The patients are a 20-year-old man with recurrent orbital ARMS and a 61-year-old woman with ARMS of the omentum. Microscopically, both cases showed solid components with areas of necrosis and hemorrhage and numerous mitoses. The omental tumor also showed alveolar architecture. Rosette-like structures were identified in the orbital tumor. By immunohistochemistry, the following markers were positive: desmin (2 of 2), myogenin (2 of 2), synaptophysin (2 of 2), chromogranin (1 of 2). Ultrastructurally, the orbital tumor cells had prominent sarcomeres without neurosecretory granules, whereas the omental tumor showed scattered small neurosecretory granules and poorly defined Z-material.

Conclusions: Neuroendocrine differentiation in ARMS is rare. These 2 cases demonstrate the spectrum of phenotypes in this tumor.

Phosphaturic Mesenchymal Tumor Without Oncogenic Osteomalacia

(Poster No. 13)

Sharon Bihlmeyer (sharon.bihlmeyer@vtmednet.org); Kumarasen Cooper, MD. Department of Pathology, University of Vermont/Fletcher Allen Health Care, Burlington.

Context: Phosphaturic mesenchymal tumor (mixed connective tissue variant) (PMT-MCT) is an underrecognized and poorly understood, rare distinctive histopathologic entity. It is frequently associated with osteogenic osteomalacia and manifested clinically by hyophosphatemic hyperphosphaturia.

Design: A 53-year-old man presented with a 4-month history of a protuberant and painful mass in the left anterior pretibial region. Eleven years prior, the patient had an excision of a similar mass in the same location. Metabolic laboratory studies were within normal limits including a phosphorous level of 4.4 mg/dL.

Results: An excisional biopsy was performed, revealing a multilobated tan-yellow firm gritty mass that measured 5.0 cm in greatest dimension. The well-circumscribed lesion was located within the subcutis and contained large portions of a calcified matrix with a flocculent or grungy pattern. Bland-appearing spindle cells with normochromic, small nuclei and indistinct nucleoli admixed within a thin-walled capillary network predominated the rest of the mass. Numerous osteoclast-like giant cells and regions of woven bone were also identified. High-power examination revealed focal infiltration of the surrounding connective tissues. The diagnosis of PMT was rendered and confirmed in consultation by an outside institution (Figure 1).

Conclusions: PMTs are rare tumors with a usual clinical association with oncogenic osteomalacia. This case is unusual as it is one of few in the English literature without metabolic manifestations, but with identical histologic features of a prototypical PMT. Clinicians and pathologists alike need to have a heightened awareness of this tumor in the setting of a normal phosphorous level.

Granular Cell Tumor of the Breast: A Series of 8 Cases in a Women's Hospital and Review of the Literature

(Poster No. 14)

Gloria J. Carter, MD1 (gcarter@mail.magee.edu); Syed Ahmed, MD1; Akosua B. Domfeh, MD1; Joseph Kelley, MD.2 Departments of 1Pathology and 2Obstetric and Gynecologic Oncology,MageeWomen'sHospital, Pittsburgh, Pa.

Context: Granular cell tumor of the breast is a rare entity that typically is clinically and radiologically mistaken for a carcinoma.

Design: The English literature was reviewed, summarized, and compared to 8 cases of granular cell tumor of the breast identified from the anatomic pathology files of our institution from 1993 to 2003.

Results: The neoplasm has never been reported to have occurred in the lower outer quadrant, and there was no predilection for the right or left breast. Mammographic and sonographic abnormalities were nearly always suspicious for a malignancy. Fine-needle aspiration cytology was sometimes diagnostic but in other instances supported the suspicion of malignancy. Histologically, polygonal cells with abundant eosinophilic granular cytoplasm having small round to oval, uniform basophilic and eccentrically located nuclei were seen. Mitoses were usually not identified. Immunohistochemical studies were comparable to previous reports and support neural origin. There were no recurrences in the 16 cases where follow-up was reported.

Conclusions: Granular cell tumors can easily be mistaken for a carcinoma clinically and radiologically. Fine-needle aspiration biopsy may or may not be helpful; histologic examination of the lesion is often required to establish the diagnosis. The diagnosis of this usually benign entity requires a collaborative effort of astute clinicians, radiologists, and pathologists to arrive at the appropriate diagnosis and prevent disfiguring surgeries and legal repercussions.

The Utility of Select Breast Cancer Characteristics and the Predictive Value in Determining Extent and Progression of Sentinel Lymph Node Involvement: A Direct Correlation

(Poster No. 15)

Steven Drury, MD (stevendrury@hotmail.com); Jonathan F. Lara, MD. Department of Pathology, Saint Barnabas Medical Center, Livingston, NJ.

Context: Sentinel node (SN) evaluation is standard practice in the management of breast cancer. It is used to determine tumor nodal status ranging from in situ to invasive. Understanding the significance of SN involvement relative to certain tumor characteristics can refine the use of SN examination.

Design: A 1-year retrospective study of 318 SN biopsies was conducted to determine whether type and extent of SN involvement relate to certain primary tumor characteristics. The size and the presence of lymphovascular invasion of the primary tumor were correlated with the number of positive and negative nodes, size of metastasis, and axillary involvement.

Results: Three hundred eighteen patients had SN biopsy for tumors ranging from Tis to T3; 94 were positive, 224 negative. Tis to T1c cases progressively increased and decreased beyond T2. There was a progressive increase in the number of SN-positive cases from T1c through T3 and in the percentage of lymphovascular invasion. Positive axillary nodes after positive SN increased from T1c to T3. Mean size of metastasis and number of involved lymph nodes rose with increasing tumor size.

Conclusions: Extent and frequency of SN involvement are directly proportional to tumor size and lymphovascular invasion. Tis through T1b cases had low incidence of positive SN while T1c through T3 had high incidence. SN status is more predictable toward either extreme of breast cancer stage, while the presence and extent of lymphovascular invasion are more useful with larger tumors. Refinement of selection criteria for SN analysis can be predicted from primary tumor characteristics.

Papillary Neoplasms of the Breast-A Clinico-Pathologic Correlation Between Core Needle Biopsy and Surgically Resected Specimens: A 5-Year Study at Danbury Hospital (2000 to 2005)

(Poster No. 16)

Rhea J. Birusingh,MD (rhea.birusingh@danhosp.org); Juan A.Merayo- Rodriguez, MD; German Escudero; Frank Braza, MD. Department of Pathology, Danbury Hospital, Danbury, Conn.

Context: Core needle biopsies of the breast are becoming increasingly common as the first-line surgical intervention, and the validity of the histopathologic diagnoses made on such specimens are the backbone of further clinical management; however, some pathologic entities are challenging due to the small size of the specimen obtained and are well-recognized pitfalls of breast core needle biopsies.

Design: A retrospective review of papillary lesions detected on core needle breast biopsies from January 2000 to December 2005 was performed, and subsequent surgical excisions were identified. A total of 592 breast core needle biopsy results were reviewed. Papillary lesions were identified in 24 cases, representing 4% of all breast core biopsies. Subsequent follow-up of these 24 cases was classified into 6 diagnostic categories: no surgical intervention, 11 cases (46%); papilloma without evidence of carcinoma, 4 cases (17%); carcinoma, 3 cases (13%); atypia without evidence of carcinoma, 2 cases (8%); fibrocystic changes, nonproliferative/ benign, 4 cases (17%).

Results: Out of the 13 cases with surgically resected specimens, 3 (23%) of 13 cases had a diagnosis of carcinoma (ductal carcinoma in situ, invasive ductal carcinoma, micropapillary and apocrine types) and 2 (15%) of 13 cases had atypical ductal hyperplasia. These results show that papillary lesions may have underlying malignancy or atypia in approximately 38% of follow-up surgical specimens.

Conclusions: Careful follow-up of papillary le\sions identified on core needle breast biopsy specimens is suggested including complete surgical excision of the lesion, as these papillary lesions may have an underlying malignancy.

A Study of 945 Invasive Breast Carcinoma Cases Comparing HER-2/ neu FISH Amplification Status With Tumor Grade and Tumor Type

(Poster No. 17)

Ronald J. Paler, MD (teri.oldaker@genzyme.com); Lydia Balatian- Flores, MD; Steven Kargas, MD; Eduardo Gabriel, BA; Teri Oldaker, BA; Moacyr Da Silva, MD. Pathology, Genzyme Genetics, Los Angeles, Calif.

Context: FISH testing for HER-2/neu amplification status is a frequently performed test for treatment options in breast carcinoma. We hypothesized that there was a significant difference between both tumor type and tumor grade with respect to HER-2/neu FISH amplification status. Based on the findings we sought to establish the clinical utility of routinely performing HER-2/neu FISH testing in all types of breast carcinoma.

Design: Nine hundred forty-five consecutive invasive breast carcinoma cases submitted to our laboratory for HER-2/neu FISH testing were classified by tumor type, tumor grade, and amplification status.

Results: The invasive ductal carcinoma type showed a statistically significant difference from the invasive lobular carcinoma type when comparing amplified to nonamplified cases (P = .04). The invasive ductal carcinoma type had 1.889 times more risk to be HER-2/neu FISH gene amplified than the invasive lobular tumor type. The mucinous (colloid) type showed a difference in amplification status in comparison to the invasive ductal type as well; however, due to the small number of mucinous cases, reliable statistical data could not be determined. After controlling for tumor grade across both invasive ductal and invasive lobular cases, no significant statistical difference was noted.

Conclusions: Although invasive lobular carcinoma of the breast showed a significantly lower incidence of amplification, 11% of lobular carcinomas as a whole showed amplification. Therefore, elimination of HER-2/neu FISH testing for invasive lobular carcinoma is not recommended. Testing recommendations for mucinous tumors will require additional studies.

Microcalcifications of the Breast-Size Matters: A Mammographic- Histologic Correlation Study

(Poster No. 18)

Xiaoying Liu, MD1; Marc Inciardi, MD2; Fang Fan, MD1; Patricia Thomas, MD1; William Smith, MD2; Ossama Tawfik,MD1 (otawfik@kumc.edu). Departments of 1Pathology and Laboratory Medicine and 2Diagnostic Radiology, Kansas University Medical Center, Kansas City, Mo.

Context: Core needle biopsies (CNBs) of the breast are highly sensitive techniques for sampling of mammographic calcifications. Currently, there is no standardized protocol for evaluating such samples. This study was undertaken to attempt to standardize the procedure of CNB program in correlating histologic findings with mammographically detectable calci- fication.

Design: 113 CNBs with mammographic evidence of calcification were first reviewed and categorized into 2 main groups based on the presence or absence of microcalcifications. Biopsy specimens with microcalcifications were divided into <100 m and >100 m subgroups based on the microcalcifications' aggregate largest diameter. Tissue blocks from discrepant biopsy specimens (negative and <100 m microcalcifications) were radiographed. Deeper sectioning into the blocks was performed for discrepant biopsy specimens.

Results: One hundred two of 113 CNBs (90.2%) had microcalcifications on primary review; 11 were negative and 21 had microcalcifications (<100 m) considered below the limit of mammographic detectability. Following tissue block radiology and deeper sectioning, large microcalcifications >100 m were identified in 12 discrepant biopsy specimens (1 negative and 11 <100 m). Without careful evaluation 10 discrepant biopsy specimens would have been erroneously reported as ''false'' positive and 1 as ''false'' negative for microcalcifications.

Conclusions: Tissue block radiography and deeper sectioning are required to assess microcalcifications in all discrepant cases.We recommend a systematic approach to standardize reporting of microcalcifications in CNBs. Pathologists should routinely report the size of microcalcifications in their reports and correlate their findings with the tissue block radiologic findings. Discrepant ''false-positive with <100 m microcalcifications'' biopsy specimens should be considered nondiagnostic and should be handled clinically the same way as negative biopsy specimens.

Angiosarcoma of the Breast: A Clinicopathologic Analysis of Cases in Our Institution From the Last 10 Years

(Poster No. 19)

Xiao Yun Wang, MD (xwang2@kumc.edu); Marilyn K. Davis, BS; Ossama W. Tawfik, MD; Patricia A. Thomas, MD; Fang Fan, MD. Department of Pathology, University of Kansas, Kansas City, Mo.

Context: Breast angiosarcoma may occur de novo or as a complication of radiation therapy for mammary carcinoma. In our effort to determine whether radiation therapy has increased the incidence of breast angiosarcoma, we reviewed all cases of angiosarcoma from the files of the University of Kansas Medical Center.

Design: A search for breast angiosarcoma cases was performed in the University of Kansas Medical Center archives from 1995 to 2005. Clinical histories and follow-up data for identified patients were reviewed. The tumors were graded histologically according to the Rosen method and also studied with antibodies against Ki-67.

Results: Only 5 angiosarcomas were identified among 2555 malignant breast neoplasms (0.20%) for the last 10 years. Three cases (2 high-grade, 1 low-grade) were identified as postradiation angiosarcoma (postradiation time interval 4 to 9 years), and 2 cases were identified as primary angiosarcomas (1 high grade, 1 low grade). The histologic grade correlatedwell with the proliferation index Ki-67 (high-grade > 15%; low grade 15%). Follow-up (median 36 months) revealed that 2 cases of postradiation angiosarcoma recurred as skin and/or chest wall lesions and 1 case of primary angiosarcoma developed liver metastases.

Conclusions: Angiosarcomas of the breast are rare. From our data, one cannot tell whether or not radiation therapy has significantly increased the incidence of angiosarcoma. The Rosen method for grading breast angiosarcoma is easy to implement and correlates well with Ki-67 and clinical outcome. There are no distinct clinical or histologic differences between primary and postradiation breast angiosarcomas.

Determination of the Number of Slides Necessary to Detect Significant Lesions in Breast Lumpectomies Based on a Core Biopsy Diagnosis of Atypical Ductal Epithelial Hyperplasia or Ductal Carcinoma In Situ

(Poster No. 20)

Mamatha Chivukula, MD (mchivukula@mail.magee.edu); Raj Hari, MD; William E. Gooding, PhD; David Dabbs, MD. Department of Pathology, Magee Women's Hospital of UPMC, Pittsburgh, Pa.

Context: The incidence of upstaging to ductal carcinoma in situ (DCIS) or invasive carcinoma (IC) in follow-up lumpectomies (FUL) given a core biopsy (cbx) diagnosis of atypical ductal epithelial hyperplasia (ADH) is up to 25%. There is no guidance in the literature as to what quantity of lumpectomy tissue should be submitted for histologic examination when no gross lesion is present in FUL. The aim of this study is to quantify the appropriate number of sections needed to be submitted on grossly normal FUL to identify significant lesions.

Design: All cbxs diagnosed with ADH were retrieved from MWH Pathology files from 2004-2005. Hematoxylin-eosin slides from FUL were reviewed. The significant lesion on the slides and the number of slides required to identify this lesion with high probability were quantified and calculated using statistical analysis.

Results: The average number of slides needed from FUL for diagnosing ADH was 11, and 7 for DCIS. Probabilities were calculated for a range from the average number of slides per case to maximum per case. To achieve a 90% probability of a positive diagnosis required 24 slides for ADH and 16 slides for DCIS (Table).

Conclusions: We conclude that to identify DCIS in FUL without gross lesions, enough FUL tissue to prepare at least 16 slides should be submitted.

Probability of a Positive Diagnosis of ADH and DCIS: Predictive Markers and Morphologic Changes After Systemic Therapy in Locally Advanced Breast Cancers

(Poster No. 21)

Linda R. Varghese, MD1 (varg0053@umn.edu); Evin H. Gulbahce,MD1; Adeka McIntosh, MD2; Jennifer Presthus, BS3; Colleen Forster, BS1; Ying Zhang, PhD.3 Departments of 1Pathology, 2Radiology, and 3Statistics, University of Minnesota, Minneapolis.

Context: Neoadjuvant therapy (NT) for breast cancer allowsmonitoring of the response to a specific agent with a better chance of reaching pathologic complete response (pCR). We analyzed tumor markers to identify tumors with more likelihood to respond to NT and assess morphologic changes following NT.

Design: Biopsies and post-treatment lumpectomy/mastectomy specimens from locally advanced breast cancers were reviewed. Stains for Ki- 67, caspase-cleaved cytokeratin 18, and p53 were performed. Response to NT, measured with 4 Tesla MRI, was correlated to the tumor characteristics. Post-treatment changes in tumor morphology were assessed.

Results: Thirty-five patients with stage I to III locally advanced breast cancer were identified. Average age was 47.6 years. Sixteen had grade 3, 15 grade 2, 2 grade 1 carcinoma. In 2 patients the tumor was too small to allow grading. Information on the MRI- determined tumor size was available in 24; average: 6.2 cm. pCR was achieved in 8 (22.8%) of 35. Residual disease in 15 of 25 patients had lower Ki-67 staining when compared to pretreatment biopsy specimens. Six of 22 patients with residual disease had a decrease in Nottingham grade following NT. Two patients with residual disease had ''pseudolobular'' morphology following t\reatment for ductal carcinoma. Four had viable tumor limited to vessels.

Conclusions: Locally advanced breast cancers that are ER negative and have higher Ki-67+ cells are more likely to achieve pCR after NT. Morphologic changes are observed post-NT including increased nuclear pleomorphism, pseudolobular change, and decrease in Nottingham grade.

Correlations Between Clinical Characteristics, Hormone Receptor Status, and Proliferative Index in Mucinous Carcinoma of the Breast

(Poster No. 22)

Adebowale J. Adeniran, MD (debodee@hotmail.com); Toni M. Robinson- Smith, MD; John W. Bishop, MD. Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio.

Context: Increased proliferative activity and overexpression of p53 in ductal carcinoma correlate significantly with adverse hormone receptor status. Mucinous breast carcinoma (MBC) has a relatively better prognosis, but little is known about cell proliferation and p53 expression in MBC. This study correlates proliferative activity in MBC with other clinical and prognostic characteristics.

Design: Thirty-two cases were studied (27 pure and 5 mixed). Clinical and pathologic materials were reviewed. Microscopic sections of the primary tumor were examined. The immunohistochemical expressions of ER, PR, and p53 protein were evaluated. MIB-1 labeling index and Her-2/ neu expression were performed using the Chromavision ACIS system.

Results: Patients with pure tumor had a median age of 72 years as compared with 63 years for patients with mixed tumor. Racial origin and location were similar in both groups. Two (9%) of 23 cases had positive lymph nodes. Disease-free survival at 5 years was 100%. The average MIB- 1 labeling index was 5.08 in the mixed group, 4.52 in the pure group, 4.51 in tumors less than 2 cm and 5.67 in tumors 2 cm or larger. Four of the 5 mixed tumors had strong p53 expression.

Conclusions: MIB-1 labeling index was higher in the mixed group and in larger tumors. There were no statistically significant differences in MIB- 1 expression in relation to age, racial origin, hormone receptor status, and disease-free survival time. There was positive correlation between p53 overexpression and mixed tumors. Lymph node involvement was not associated with increased Mib-1 labeling index or p53 protein overexpression.

Basal-Like Subtype of Invasive Mammary Carcinoma Arising in Ectopic Breast Tissue of the Axilla

(Poster No. 23)

Shuko Harada (Shuko.Harada@DrexelMed.edu); Suganthi Soundararajan, MD; Marian M. Haber, MD; Fernando U. Garcia, MD; Xiaoli Chen, MD. Department of Pathology and Laboratory Medicine, Drexel University College of Medicine, Philadelphia, Pa.

Context: Primary carcinoma of ectopic axillary breast tissue is uncommon. For pathologists, the diagnosis of ectopic mammary carcinoma can be difficult, especially in the axilla, where carcinoma of adnexal origin and metastatic carcinomas of breast and other origins must be excluded. To our knowledge, this is the first case report of basal-like subtype of invasive mammary carcinoma arising in ectopic axillary breast tissue.

Design: Histologic and immunohistochemical examination was performed.

Results: A 49-year-old woman presented with a 3-month history of right axillary mass. Incisional biopsy revealed a 4 cm firm mass located close to the skin and not immediately adjacent to the breast. Microscopic examination revealed a high-grade invasive carcinoma showing ribbonlike architecture associated with geographic necrosis and focal stromal lymphocytic response. Immunohistochemically, the tumor was negative for estrogen receptor (ER), progesterone receptor (PR), HER-2, GCDFP, p63, CK20 and carcinoembryonic antigen (CEA) but positive for epidermal growth factor receptor (EGFR), CK5/6, CAM5.2, CK7, and vimentin. Initially, adnexal origin was favored because of the expression of EGFR. After submitting the entire specimen, residual mammary glandular tissue was identified interspersing among adnexal glands. In comparison with the recently described morphologic and immunophenotypic features of basallike subtype of invasive breast carcinoma, our case was found to be consistent with this entity. Subsequent bilateral mammogram was negative. A wide excision and adjuvant therapy are planned.

Conclusions: This case underlines the importance of recognition of the basal-like subtype of invasive mammary carcinoma and a careful search for ectopic benign breast tissue in the context of axillary carcinoma.

Columnar Cell Lesions and Pseudoangiomatous Hyperplasia-Like Stroma: Is There an Epithelial-Stromal Interaction?

(Poster No. 24)

Rosemary A. Recavarren Asencios, MD (recavarrenra@upmc.edu); Mamatha Chivukula, MD; David J. Dabbs, MD. Department of Pathology, Magee-Women's Hospital of University of Pittsburgh Medical Center, Pittsburgh, Pa.

Context: Columnar cell lesions (CCL) arise in the terminal duct lobular unit (TDLU). If CCLs present cytologic/architectural atypia, they deserve the diagnosis of atypical ductal hyperplasia or ductal carcinoma in situ (DCIS). Studies suggest CCLs are nonobligate precursors of low-grade DCIS. Pseudoangiomatous hyperplasia (PASH) is a pseudovascular-stromal proliferation of unknown etiopathogenesis. A subset of CCLs is intimately associated with PASH-like-stroma (CCPLS). This study intends to search for PLS vascular/hormonal factors that might contribute to CCLs progression.

Design: Eight core biopsy specimens with CCPLS (6 with simple changes, 1 hyperplasia, and 1 atypia) were examined by IHC with antibodies to CD117 (c-kit), CD34, angiogenic factors CD105 and bFGF, AR, ER-beta, and MIB-1. The results were compared to normal TDLU.

Results: C-kit positivity in normal TDLU-epithelium was noted to be markedly decreased in CCLs. A subset of PLSs were c-kit positive. CD34 intensely stained PLS due to greater cellularity than normal TDLU stroma. CD105 showed increase-activated vascularization around CCLs. The positive bFGF stroma surrounding CCLs gave a ''halo'' effect. AR and ERbeta showed strong nuclear positivity in both CCL and PLS. MIB-1 showed higher expression in CCPLS compared to normal breast.

Conclusions: (1) A molecular alteration is signified by c-kit loss in CCL, (2) activated blood vessels predominate in CCPLS, (3) ER-beta and AR positivity indicate CCPLS are hormonally responsive. Hence, there is intimate vascular and hormonal stromal-epithelial interface interaction in CCPLS lesions. As proposed on animal models, our results suggest potential growth-stimulating factors released by PLS cells are necessary for CCL progression.

Lymphoid Neoplasms Involving the Breast: A Clinicopathologic Study of 77 Cases

(Poster No. 25)

Sameer S. Talwalkar, MD1 (drsameerst@hotmail.com); Jose Valbuena, MD2; George Z. Rassidakis, MD2; Carlos Bueso-Ramos, MD2; L. Jeffrey Medeiros, MD.2 1Department of Pathology and Lab Medicine, University of Louisville, Louisville, Ky; 2Department of Hematopathology, UT M.D. Anderson Cancer Center, Houston, Tex.

Context: Lymphoid neoplasms involving the breast are uncommon, accounting for approximately 2% of extranodal lymphomas and less than 1% of all non-Hodgkin lymphomas. These neoplasms either may be localized, presumably arising in the breast, or a part of disseminated disease (presumably secondary involvement). Information is lacking relating to the prognostic differences between patients with primary (PBL) and secondary breast lymphomas (SBL).

Design: The clinicopathologic features of 77 cases of breast lymphoma were assessed. The neoplasms involved the left breast in 36, right breast in 32, were bilateral in 6, and side unspecified in 3. Thirty-four patients had PBL, 39 patients had SBL, and staging information was not available in 4 patients. The neoplasms were classified using theWHO system. Overall survival (OS) was calculated using the Kaplan-Meier method.

Results: There were 28 diffuse large B-cell lymphomas (DLBCL), 23 MALT lymphomas, 11 follicular lymphomas, 7 precursor lymphoblastic leukemia/lymphomas (6 B and 1 T cell), 3 anaplastic large cell lymphomas, 2 classical Hodgkin lymphomas, and 1 case each of mantle cell lymphoma, Burkitt lymphoma, and peripheral T-cell lymphoma unspecified (PTCL-U). PBLs (67.6%) were more commonly high-grade than SBLs (51.5%), but this difference was not significant (P = .21). Follicular lymphomas occurred exclusively as secondary neoplasms (P < .001). Patients with primary neoplasms had better OS than patients with secondary neoplasms (P = .02).

Conclusions: Lymphoid neoplasms involving the breast are a heterogenous group with a broad morphologic spectrum. The present study, one of the largest, reveals a significant difference in the survival between PBL and SBL.

Human Umbilical Cord Blood Cell Administration's Reduction of Atherosclerotic Plaques in the Ld^sup lrtm1Her^ Mouse Without Immunosuppression

(Poster No. 26)

Norman Ende, MD1 (endeno@umdnj.edu); Milton Ende, MD2; R. Chen, MD1; K. Coakley, BA1; A. Reddi, MD.3 1Department of Pathology and Laboratory Medicine, UMDNJ, Newark, NJ; 2Department of Medicine, Southside Regional Medical Center, Petersburg, Va; 3Department of Medicine, UMDNJ, Newark, NJ.

Context: Congenic bone marrow transplantation can alleviate plaque formation in the apolipoprotein E-deficient mouse. Similar to bone marrow transplantation, human umbilical cord blood (HUCB) cell administration and human breastmilk (hBM) have been shown to have therapeutic effects on other murine disease models. This study examined the extent of atherosclerosis following HUCB cell and hBM administration in male homozygous mice that develop atherosclerosis through the targeted mutation 1 in the low-density lipoprotein receptor (Ld^sup lrtm1Her^).

Design: Four groups of mice were studied. One group (N = 8) received 200 10^sup 6^ HUCB cells retro-orbitally. Another group (N = 6) received hBM. The third group (N = 6) received HUCB cells and hBM\, and the fourth group (N = 10) received no treatment. Treatment was started at 7 weeks, and mice were killed at 30 months of age. The extent of atherosclerosis in the ascending aorta, above the aortic valve, and the thoracicabdominal aorta was evaluated by a grading system from 1+ to 4+; 1+ being the least and 4+ the most significant lesion involving the entire circumference of the vessel.

Results: In the ascending aorta, HUCB cell treatment significantly ameliorated atherosclerosis treated vs. untreated (mean SEM: 2.75 0.37 vs. 3.93 0.07; P < .02). Combined treatment significantly improved atherosclerosis of the ascending aorta; however, hBMalone was suggestive of improvement but showed no statistical difference from untreated mice. There was no treatment effect on atherosclerosis in the thoracic-abdominal aorta.

Conclusions: HUCB cell treatment has the potential to reduce plaque formation in the Ld^sup lrtm1Her^ mouse.

Autopsy Pathology in Lymphomas: Impact of the Introduction of Rituximab Treatment

(Poster No. 27)

Steve M. Vanderwerf, MD (vand0190@umn.edu); Stefan Pambuccian, MD; Adina Cioc, MD. Department of Pathology, University of Minnesota, Minneapolis.

Context: Rituximab is a monoclonal antibody against CD20 antigen that was approved for use in treating B-cell non-Hodgkin lymphomas in 1997. Although many patients have received rituximab therapy, very few serious complications have occurred. To date, there has not been a study to compare immediate causes of death in patients who have and have not received rituximab.

Design: We reviewed our institution's autopsy database from 1988 to 2006, searching for B-cell lymphomas that had been treated with conventional chemotherapy with or without rituximab. We reviewed slides and reports for residual lymphoma, immediate causes of death, age, lymphoma type, and bone marrow transplant status.

Conclusions: We found similar distributions of lymphoma types among the 2 patient groups. However, there were significantly more patients treated with bone marrow transplant in the rituximab group. Our results show significantly (P = .004) fewer patients with residual lymphoma at death in the rituximab group (20% vs 65%). In addition, although not statistically significant, there were relatively more immediate causes of death due to infectious etiologies in the rituximab group (90% vs 65%). Within the infectious etiologies, there were relatively more deaths due to viral and possibly fungal organisms. A confounding factor in these results, however, may be the significant percentage of patients receiving bone marrow transplant in the rituximab group.

SESSION 200: SUNDAY, SEPTEMBER 10, 2006, 2:00 PM-5:30 PM

Clinical Chemistry; Cytopathology; Dermatopathology; Endocrine Pathology; Gynecologic and Placental Pathology; Pathology Education

Differentiation of Bone Marrow Mesenchymal Stem Cells Toward the Smooth Muscle Cell Lineage by Blocking Elk-1 Signaling

(Poster No. 1)

Kenichi Tamama, MD (kjtamama@hotmail.com); Alan Wells, MD. Department of Pathology, University of Pittsburgh, Pittsburgh, Pa.

Context: Smooth muscle cells (SMCs) are major components of hollow visceral organs, including blood vessels. For tissue engineering and regeneration of blood vessels, an accessible autologous cell source for SMCs would be ideal. This study aims to evaluate whether adult bone marrow mesenchymal stem cells (BMMSCs) could be used. Unfortunately, there is no established protocol for differentiating BMMSCs into SMCs. Elk-1 is a transcriptional factor that represses myogenesis through antagonizing myocardin, a very potent myogenic factor. We hypothesize that the blocking Elk-1 signaling would drive BMMSC differentiation into the SMC lineage.

Design: Primary human BMMSCs were provided by the courtesy of Dr. Prockop (Tulane University). To block Elk-1 signaling, we employed PD98059, an inhibitor of MEK, the upstream activator of Elk-1, and siRNA for direct knockdown of Elk-1. We used reverse transcriptase polymerase chain reaction (RT-PCR) to evaluate SMC specific marker gene expression.

Results: Undifferentiated BMMSCs express most SMC marker genes except smooth muscle myosin heavy chain, the most definitive marker of differentiated SMC. PD98059 blocked Elk-1 phosphorylation in BMMSCs in low serum condition; this treatment induced smooth muscle myosin heavy chain expression in BMMSCs. In accord with our hypothesis, knockdown of Elk-1 with siRNA also induced smooth muscle myosin heavy chain expression in BMMSCs.

Conclusions: Inhibition of Elk-1 signaling drives BMMSCs into the SMC lineage. This finding could be utilized for bioengineering of SMCrich organs, such as blood vessels or urinary bladder.

A Comparison of Preservatives in Fine-Needle Aspiration Cytology of Pleuropulmonary Lesions

(Poster No. 2)

Timothy Craig Allen, MD (timothy.allen@uthct.edu); Charlotte M. Myers; Marsha L. Moler, BS. Department of Pathology, University of Texas Health Center at Tyler.

Context: While studies have evaluated the efficacy of various preservatives in gynecologic cytology, the comparison of preservatives in nongynecologic cytology has not been fully examined. We compared the conventional Saccomanno and alcohol cytologic preservatives with the newer CytoRich Red and SurePath preservatives for use with pleuropulmonary lesion fine-needle aspirations.

Design: Fine-needle aspirations were preformed on 15 primary pleuropulmonary masses received fresh as frozen section specimens (13 malignant neoplasms, 2 pneumonia). Separate aspirations were performed and cytologic material was obtained for 4 preparations: fresh smears for 95% alcohol fixation and needle rinses for Saccomanno, CytoRich Red, and SurePath fixation. Standard processing was preformed with each. Preparations were reviewed by 2 experienced cytotechnologists and a cytopathologist experienced in pulmonary cytology for differences in the quality of the preparations, including artifact, background, and cellular characteristics, specifically nucleus, nucleolus, and cytoplasm. In all cases, the cellular characteristics were scored for each fixative from 1 to 4 respectively as poor, fair, good, or excellent.

Results: Saccomanno fixation overall yielded greater air-drying artifact than the other fixatives. SurePath-preserved preparations scored highest overall for all cellular characteristics. Ninety- five percent alcohol-preserved and CytoRich Red-preserved preparations scored poorest overall for nucleolar detail. No major differences among the preservatives were identified with regard to background, including cases with necrotic backgrounds.

Conclusions: In our preliminary study, the best cytologic detail from fine-needle aspirations of malignant and reactive pleuropulmonary lesions was obtained using SurePath preservative. Further evaluation of nongynecologic fine-needle aspirations is needed to fully evaluate the benefits of these preservatives.

Ordering Patterns in Combined High-Risk HPV and Pap Smear Screening: Time and Experience Show Improved Clinical Compliance with Guidelines

(Poster No. 3)

Miriam D. Post, MD (mdpost@partners.org); Diane Kuebler; Rosemary H. Tambouret, MD; David C.Wilbur, MD. Department of Pathology, Massachusetts General Hospital, Boston.

Context: In 2004, the US Food and Drug Administration approved high-risk HPV (hrHPV) testing in conjunction with the Pap test for the >30 years population, which has a lower prevalence of transient HPV infection. Hence, detection of hrHPV in this group is a greater risk factor for persistent infection and neoplasia. A negative result indicates low risk of high-grade disease and allows a shift to triennial screening. Adherence to this age requirement should enhance utility and cost effectiveness of the test.

Design: All hrHPV tests ordered with a Pap test were analyzed for a period of 2 years. Data were compiled by quartile and included patient age and hrHPV and Pap test results. During this period, clinicians received education on appropriate test use via educational bulletins, clinical presentations, and direct vendor interactions.

Results: The data for number of tests ordered, percentage in each age category, and percentage of tests positive within the age group are shown in the Table.

Conclusions: Overall, 62% of orders were appropriate in the >30 age group with a trend toward more correct ordering over time. However, many tests in the <30 age group are found throughout. As expected,more hrHPV-positive cases are noted in the <30 age group, limiting the value of testing within this group. The high rate of hrHPV positivity in the >30 group (14%) suggests an ordering bias toward higher-risk patients. The results show improvement in appropriate ordering practice but with significant noncompliance remaining. Potential causes and strategies to improve performance are being analyzed.

Mastocytosis Diagnosed Using Endoscopic Ultrasound- Guided Fine- Needle Aspiration Biopsy

(Poster No. 4)

Nilesh P. Patel, MD1 (nipatel@wfubmc.edu); James O. Cappellari, MD1; Girish Mishra, MD.2 1Department of Pathology; and 2Department of Internal Medicine, Section on Gastroenterology,Wake Forest University Baptist Medical Center, Winston-Salem, NC.

Context: Systemic mastocytosis (SM) is a hematopoietic disease derived from an abnormal monoclonal proliferation of mast cells involving extracutaneous organs. It is divided into clinicopathologic subtypes correlating with clinical presentation and disease progression. Today, gastroenterologists routinely implement the use of endoscopic ultrasound-guided fineneedle aspiration biopsies (EUS-FNABs). To our knowledge, we present the first case report of SM diagnosed using EUS-FNAB.

Design: A 69-yr-old man underwent endoscopy using a linear echoendoscope with dopplers for evaluation of an abnormal abdominal CT scan. During endoscopy, a conglomerate of lymph nodes was seen in the gastrohepatic area, including a 3 3-cm hepatoduodenal lymph n\ode, which was sampled via EUS-FNAB. The on-site smears were air- dried and stained using Diff-Quik. The second smears were fixed in 95% ethanol and stained using the Papanicolaou method, as was the cytocentrifuged 0.9% saline rinse. Cell block material was stained using hematoxylineosin.

Results: Cytologic examination showed numerous mononuclear cells consistent with mast cells displaying reniform, oval, spindled, or even rare bilobed nuclei with granulated cytoplasm. The cytoplasmic granules displayed minimal-to-metachromatic staining using toluidine blue. The cell block material displayed lymphocytes, histiocytes, and multiple aggregates of mast cells that were intensely positive for immunohistochemical staining with CD117 and mast cell tryptase (DakoCytomation, Carpinteria, Calif).

Conclusions: EUS-FNAB is a safe, efficient, and cost- effectivemodality for sampling lesions such as hepatoduodenal lymph nodes that would otherwise require operative intervention. This approach provides ample tissue for diagnosing hematopoietic malignancies, including SM, and can serve as an adjunct to BM biopsy.

Cytologic Features of Pseudomyxoma Peritonei in Liquid-Based Preparations

(Poster No. 5)

Bo Wang, MD (BoWang@creighton.edu); Zoran Gatalica, MD; Chhanda Bewtra, MD. Department of Pathology, Creighton University Medical Center, Omaha, Neb.

Context: Pseudomyxoma peritonei (PMP) has been recently classified into disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and peritoneal mucinous carcinomatosis with intermediate or discordant features (PMCA-I/D). We compared the cytologic features of DPAM and PMCA in liquid-based preparations.

Design: Peritoneal fluids (18 ascites, 28 washes, 3 others) from 49 PMP cases (16 DPAM, 33 PMCA) were processed by SurePath liquid- based technique and stained with Pap stain. Forty-three cases also had hematoxylineosin- stained cell blocks. The 2 groups were compared for age, sex, gross appearance, nuclear size, chromasia, cell arrangement, overall cellularity, intracellular and extracellular mucin, nucleoli, and mitotic figures. DNA ploidies of the tissue samples were also obtained.

Results: The average age of the patients with PMP was 52.4 years (range, 28-76 years), with 10:9 male-female distribution. Grossly mucinous appearance of the specimens was noted in 17 cases, mostly in ascites (14 cases). Microscopically, the presence of some mucin was seen in most cases (43). Fifty percent of PMCA and 0% of DPAM were aneuploid. Cytologically, the background mucin was often sparse in liquid preparations and cellularity was low in DPAM cases. Cell blocks were found helpful in these cases. Also noted were mitotic figures-PMCA 76% vs. DPAM 19% and prominent nucleoli-PMCA 45% vs. DPAM 0%.

Conclusions: DPAM may be difficult to diagnose in liquid preparations due to lack of cellularity and sparse background mucin. Cell blocks and direct smears are helpful in these cases. Compared to DPAM, PMCA shows increased mitosis, aneuploidy, and prominent nucleoli.

Cytologic Findings on Reexamining Thin-Prep Slides of Women Aged 30 Years and Older With a Cytologic Diagnosis of Negative for Intraepithelial Lesions and Malignancy and Positive High-Risk HPV DNA Discovered by Hybrid Capture 2 for Primary Screening for Cervical Cancer

(Poster No. 6)

Susan Zacharizh, BS1; Dwight Oliver, MD2; Jing Liu, MD2 (Jing.Liu.1@uth.tmc.edu). 1Cytology Laboratory,MemorialHermannHospital, Houston, Tex; 2Pathology and Laboratory Medicine, University of Texas at Houston Medical School.

Context: Cytologic findings on reevaluating the Thin-Prep slides of women (≤30 years old) with an initial cytologic interpretation of negative for intraepithelial lesions and malignancy (NILM) and a concurrent positive HR-HPV DNA testing result have not been well documented in the literature.

Design: From our cytopathology archives, we found 296 women (<30 years old) with an initial interpretation of NILM on Thin-Prep, who subsequently had HR-HPV DNA testing by Hybrid Capture 2 using the same liquid sample.

Results: Of the 296 cases, 16 (5.4%) were positive for HR-HPV DNA. On reviewing the original Thin-Prep slides of the 16 cases, 1 was reclassified as LGSIL and 6 as ASC; 6 had very mild atypia (insufficient for a diagnosis of ASC or AGUS) in endocervical components (immature squamous metaplastic/glandular cells); and 3 had no additional findings. The atypical cells were very scant in all 7 cases reclassified as

Conclusions: This study showed that it is important to reevaluate the cytologic slides in cases with an initial interpretation of NILM but a positive HR-HPV DNA result. The positive HR-HPV DNA result is valuable in picking up cases with scant atypical cells or atypical cells masked by other conditions. A significant number (37.5%) of cases with very mild atypia in endocervical components (insufficient for ASC or AGUS) were identified by careful reexamination in this study. The clinical implication of this finding remains to be studied.

Cytologic Diagnosis of Metastatic Pleomorphic Rhabdomyosarcoma in Pleural Effusion in Conjunction With Immunocytochemistry

(Poster No. 7)

Kathy Szelei-Stevens, MD; Alberto G. Ayala, MD; Jing Liu, MD (Jing.Liu.1@uth.tmc.edu). Department of Pathology an

Source: Archives of Pathology & Laboratory Medicine

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