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Biomedical subjects

Yun Gong

Publications and source records attributed to Yun Gong.

At least 19 recordsLinked to original sources

Membrane activation: selective vesicle fusion via small molecule recognition.

We report herein the induction of selective vesicle fusion with biological recognition motifs not natively associated with lipid bilayer fusion, thus broadening the scope of recognition-guided membrane activation. Our system employs vancomycin glycopeptide, coupled to the antimicrobial peptide magainin, and D-Ala-D-Ala-OH dipeptide coupled to a phospholipid derivative, as surface-bound fusogens. Fusion was characterized by dynamic light scattering and FRET experiments with lipid bound fluorophores. We have demonstrated here that appropriately designed membrane anchored molecular recognition motifs have the biomimetic ability to activate specific membrane mergers; this principle has resonance with goals in targeted chemical delivery and nanoscale compartmentalized chemistry.

Cell Membrane↗

Fine-needle aspiration of pancreatic serous cystadenoma: cytologic features and diagnostic pitfalls.

BACKGROUND: The preoperative diagnosis of pancreatic serous cystadenoma (SCA) is important because as a typically benign tumor it can be treated expectantly, whereas many other cystic tumors require excision. This study examines the cytology, clinical and radiologic features, diagnostic accuracy of fine-needle aspiration (FNA), and potential pitfalls associated with this rare tumor. METHODS: Cytomorphologic features were retrospectively reviewed from 28 FNAs of SCA from 21 patients. FNA biopsies were guided by percutaneous computed tomographic or ultrasonographic imaging in 10 cases and by endoscopic ultrasonographic imaging in 18 cases. Corresponding histology (14 tumors) and clinical/imaging findings were also evaluated. RESULTS: Patients typically presented with upper abdominal discomfort or asymptomatically. Radiologically, a well-demarcated, multiloculated cystic mass involving the pancreatic head or uncinate process was common. Aspirates were sparsely cellular against a clean or granular, proteinaceous background. Tumor cells formed loose clusters or monolayered sheets composed of cuboidal cells with indistinct cell borders and granular or clear cytoplasm that was often stripped from the nucleus. Nuclei were small, round, with fine chromatin and indistinct nucleoli and devoid of mitotic activity. Seven (25%) of the aspirates were initially classified as "consistent with SCA," 6 (21%) as "no malignant cells," 3 (11%) as "nondiagnostic specimen," 3 (11%) as "suspicious for malignancy," 3 (11%) as "rare atypical cells," and 6 (21%) as "probably or consistent with mucinous cystic neoplasm." Features causing diagnostic difficulty were scant cellularity, papillary groups, nuclear atypia, and columnar cells mimicking those of mucinous neoplasms. Gastrointestinal (GI) epithelium and mucin also caused confusion. The detection of intracytoplasmic glycogen (3 of 6 cases) and cyst fluid analysis (2 of 2 cases) showing low viscosity and low or undetectable levels of carcinoembryonic antigen, CA 19.9, and amylase enhanced diagnostic confidence. CONCLUSIONS: Diagnosing SCA by FNA is challenging. Familiarity with its morphologic spectrum, use of ancillary studies, and correlation with clinical/radiologic findings greatly improves diagnostic accuracy. Contaminating GI epithelium and mucin should be distinguished from components of a mucinous neoplasm.

Adult↗

Decreased expression of thyroid receptor-associated protein 220 in temporal lobe tissue of patients with refractory epilepsy.

PURPOSE: TRAP220 (thyroid hormone receptor-associated protein) functions as a coactivator for nuclear receptors and stimulates transcription by recruiting the TRAP mediator complex to hormone responsive promoter regions. Thus, TRAP220 enhances the function of thyroid/steroid hormone receptors such as thyroid hormone and oestrogen receptors. This study investigated the expression of TRAP220 mRNA and protein level in epileptic brains comparing with human control. METHODS: We examined the expression of TRAP220 mRNA and protein levels in temporal lobes from patients with chronic pharmacoresistant epilepsy who have undergone surgery. RESULTS: Expression of TRAP220 mRNA and protein was shown to be decreased significantly in the temporal cortex of the patients with epilepsy. CONCLUSIONS: Our work showed that a decrease in TRAP220 mRNA and protein levels may be involved in the pathophysiology of epilepsy and may be associated with impairment of the brain caused by frequent seizures.

Adolescent↗

Transformation from a low-dimensional framework to a high-dimensional architecture based on different metal ions: syntheses, structures, and photoluminescences.

Five novel metal pamidronates (3-ammonium-1-hydroxypropylidene-1,1-bisphosphonate, APD) formulated as Ni2(C3NH10P2O7)4.4H2O (1), M(C3NH9P2O7).H2O (M = Co (2), Mn (3), Zn (4)) and Cu3(C3NH8P2O7)2.2H2O (5) have been hydrothermally synthesized under similar conditions. Compound 1 is a molecular binuclear nickel cluster. Compounds 2 and 3 exhibit similar one-dimensional ladderlike structures. Compound 4 possesses a novel two-dimensional gridlike framework. Compound 5 shows an unusual three-dimensional architecture, in which two-dimensional layers with a parquet motif are pillared by {CuO4} planar squares. Different dinuclear secondary building units (SBUs) are observed in compounds 1-5, depending on the different coordination modes of APD. They also exhibit different photoluminescence properties.

Journal Article↗

Reproducibility of gene expression signature-based predictions in replicate experiments.

PURPOSE: The goals of this analysis were to (a) determine concordance of gene expression results from replicate experiments, (b) examine prediction agreement of multigene predictors on replicate data, and (c) assess the robustness of prediction results in the face of noise. PATIENTS AND METHODS: Affymetrix U133A gene chips were used for gene expression profiling of 97 fine-needle aspiration biopsies from breast cancer. Thirty-five cases were profiled in replicates: 17 within the same laboratory, 11 in two different laboratories, and 15 to assess manual and robotic labeling. We used data from 62 cases to develop 111 distinct pharmacogenomic predictors of response to therapy. These were tested on cases profiled in duplicates to determine prediction agreement and accuracy. To evaluate the robustness of the pharmacogenomic predictors, we also introduced random noise into the informative genes in one half of the replicates. RESULTS: The average concordance correlation coefficient was 0.978 (range, 0.96-0.99) for intralaboratory replicates, 0.962 (range, 0.94-0.98) for between-laboratory replicates, and 0.971 (range, 0.93-0.99) for manual versus robotic labeling. The mean % prediction agreement on replicate data was 97% (95% CI, 0.96-0.98; SD, 0.006), 92% (95% CI, 0.90-0.93; SD, 0.009), and 94% (95% CI, 0.92-0.95; SD, 0.008) for support vector machines, diagonal linear discriminant analysis, and k-nearest neighbor prediction methods, respectively. Mean accuracy in the test set was 77% (95% CI, 0.74-0.79; SD, 0.014), 66% (95% CI, 0.63-0.73; SD, 0.015), and 64% (95% CI, 0.60-0.67; SD, 0.016), respectively. CONCLUSION: Gene expression results obtained with Affymetrix U133A chips are highly reproducible within and across two high-volume laboratories. Pharmacogenomic predictions yielded >90% agreement in replicate data.

Biopsy, Needle↗

Correlation of cytologic findings and chromosomal instability detected by fluorescence in situ hybridization in breast fine-needle aspiration specimens from women at high risk for breast cancer.

Cytologic evaluation of ductal lavage or random periareolar fine-needle aspiration (FNA) specimens has been proposed to improve risk stratification of women at high risk for breast cancer. However, cytologic assessment of morphologic changes is subjective. To assess the utility of fluorescence in situ hybridization (FISH) in the categorization of breast lesions, we prospectively evaluated 32 random periareolar FNA specimens from 27 women at high risk for breast cancer. Cytologic specimens were prepared using the thin preparation technique, and diagnoses were made on the basis of previously published criteria. Specimens were also evaluated by FISH for chromosomes 1, 8, 11, and 17. Monosomy was defined as the loss of one signal or both signals in >20% of cells, and polysomy was defined as the presence of > or = 3 signals in >6% of cells. Cytologic smears from seven invasive ductal carcinomas and nine benign breast specimens from women at low risk for breast cancer were included for comparison. In the high-risk group, cytologic findings were nonproliferative epithelium (NPE) in 16 cases and hyperplasia in 16 cases. Chromosomal aberrations were detected in 11 (69%) of 16 NPE cases, 14 (89%) of 16 hyperplasia cases, seven (100%) of seven carcinoma cases, and none of the low-risk cases. High-risk cases had significantly more monosomy of chromosomes 1, 11, and 17 and polysomy of chromosome 8 compared to low-risk cases and significantly less polysomy of chromosomes 1, 8, 11, and 17 compared to patients with cancer. There were no significant differences in monosomy or polysomy of individual chromosomes or a combination of chromosomes between the NPE and hyperplasia groups. This study shows that aberrations of chromosome number are common in high-risk women irrespective of cytologic findings. Studies evaluating the association between specific patterns of chromosomal polysomy and progression to malignancy may be warranted.

Adult↗

Metastatic ductal adenocarcinoma of the prostate: cytologic features and clinical findings.

We retrospectively reviewed the cytologic features of metastatic prostatic ductal carcinoma (PDC) in 23 cases, clinical manifestations, and clinical outcomes. Cytologic smears typically showed tumor cells with abundant cytoplasm and oval nuclei arranged in papillary groups or flat and folded sheets, some of which showed peripheral nuclear palisading. However, these features could be focal, subtle, and even indistinguishable from those of acinar carcinoma, particularly when the ductal component was predominantly of a cribriform and solid pattern or coexisted with acinar carcinoma. A determination of a prostatic origin of a metastatic PDC, based on cytomorphologic features alone, could be difficult. Immunostaining for prostate-specific antigen and prostatic acid phosphatase proved helpful in determining a definitive diagnosis. The median followup of patients was 82 months, the median overall survival was 77 months, and the 5-year overall survival rate was 72%. Tumor growth pattern did not correlate with prognosis, but visceral metastasis conveyed a poor prognosis. The correlation with clinical and radiologic findings, a high index of suspicion, and the use of immunoperoxidase studies are important in making an accurate diagnosis.

Acid Phosphatase↗

Fine-needle aspiration of adrenal cortical carcinoma: cytologic spectrum and diagnostic challenges.

We reviewed the cytologic features of 20 adrenal cortical carcinomas (ACCs; 9 primary and 11 metastatic) from 19 patients and highlighted diagnostic pitfalls. The mean size of primary ACCs was 11.9 cm, and that of metastatic ACCs was 3.0 cm. The metastatic sites were liver, lung, lymph node, soft tissue, and bone. Primary and metastatic ACCs were cytologically similar and showed a wide range of features varying from well-differentiated tumor resembling a benign cortical lesion or low-grade neuroendocrine tumor to poorly differentiated pleomorphic tumor mimicking poorly differentiated carcinoma, melanoma, or high-grade sarcoma. The common cytologic features were hypercellularity (70% of cases), necrotic debris in the background (70%), moderate to marked nuclear pleomorphism (80%), mitotic figures (90%), and prominent nucleoli (60%). Twenty percent of cases exhibited all 5 features; 40% exhibited 4 features, and 40% exhibited 3 features. Necrosis and/or mitosis were found in all cases, even in tumors with bland cytologic features. Cytologic, immunophenotypic, and ultrastructural findings should be correlated with clinical and radiologic information for achieving a proper cytologic diagnosis.

Adolescent↗

Downregulation of the cyclin-dependent kinase inhibitor p27kip1 might correlate with poor disease-free and overall survival in inflammatory breast cancer.

PURPOSE: The objective of this study was to evaluate whether p27kip1 downregulation is a prognostic factor in patients with inflammatory breast carcinoma (IBC). PATIENTS AND METHODS: Fifty-eight patients with IBC were treated between January 1994 and July 2002. Median age was 49 years. Thirty-eight patients had baseline biopsy specimens. Patients received preoperative chemotherapy with FAC (5-fluorouracil/doxorubicin/cyclophosphamide; 34%) or FAC followed by a taxane (66%). All patients underwent mastectomies. All patients received radiation therapy and hormonal treatment when indicated. Expression level of p27kip1 was evaluated by indirect immunoperoxidase procedure. The p27kip1 was considered downregulated if nuclear staining was present in < 50% of the neoplastic cells. RESULTS: Thirty-two patients (84%) had p27kip1-downregulated tumors, and 6 patients (17%) had p27kip1-normal tumors. Six patients (16%) exhibited a pathologic complete response. At a median follow-up of 43 months, 25 recurrences (66%) and 27 deaths (71%) occurred. Patients with p27kip1-downregulated tumors had fewer pathologic complete responses (9% vs. 50%; P = 0.03) and had lower 4-year recurrence-free survival (23% vs. 83%; P = 0.03) and overall survival rates (36% vs. 83%; P = 0.01). CONCLUSION: The p27kip1 deregulation manifested by low protein cellular concentration might represent an adverse prognostic marker in IBC and could provide a valuable tool for selecting treatment for this aggressive disease.

Adult↗

Transthoracic fine-needle aspiration vs concurrent core needle biopsy in diagnosis of intrathoracic lesions: a retrospective comparison of diagnostic accuracy.

To assess the value and limitations of fine-needle aspiration (FNA) and core needle biopsy (CNB) in the diagnosis of intrathoracic lesions, we retrospectively compared the diagnostic accuracy of 362 FNA and concurrent CNB procedures performed on 350 patients. Based on the final diagnoses that were determined based on combined information from biopsy, resection, clinical, radiologic, and microbiologic findings, the study cases were grouped into 188 malignant, 161 benign, and 13 inconclusive lesions. FNA and CNB yielded similar diagnostic accuracy for malignant tumors (85.1% vs 86.7%) and epithelial malignant neoplasms (86.4% vs 85.2%), whereas CNB yielded better diagnostic accuracy (96%) than FNA (77%) for nonepithelial malignant neoplasms. Combined FNA and CNB substantially improved the rate of malignancy diagnosis (95.2%). Of 161 benign cases, 50 were proven to be benign-specific lesions; FNA provided specific diagnosis in 20 (40%) and CNB in 46 (92%). The remaining 111 benign lesions yielded benign-nonspecific findings on both specimens. These results indicate that CNB should be obtained when clinical or radiologic findings do not match the cytologic findings or nonepithelial lesions and benign lesions are considered likely.

Adolescent↗

Validation of commonly used immunostains on cell-transferred cytologic specimens.

BACKGROUND: Immunocytochemical staining (ICC) is often limited by the lack of cell blocks that contain diagnostic cells or by the unavailability of smear materials. The cell-transfer technique, in which original smear material is divided into several pieces and then transferred to multiple slides, can facilitate multiple ICC on limited materials. However the reliability of the staining results has not been systematically evaluated. METHODS: The authors validated 21 commonly used antibodies (cytokeratin [CK] 7, CK 20, TTF-1, panCK, vimentin, HMB-45, Mart-1, leukocyte common antigen, chromogranin, synaptophysin, estrogen receptor, progesterone receptor, prostate-specific antigen, prostatic acid phosphatase, calretinin, CK5/6, WT-1, BerEP4, MOC-31, p63, and thyroglobulin) on the cell-transferred materials of various tumor samples (n = 20) and reactive effusion samples (n = 2). The staining results were compared with the previously available ICC results (performed either on cell block sections or on smears) of the same specimens. RESULTS: One hundred pieces of transferred materials were immunostained, of which 5 (5%) were lost during the staining procedure. Of the remaining 95 pieces, 92 (97%) showed staining results that agreed with those of the previous ICC, whereas 3 (3%) showed results that disagreed. The original ICC in the latter three specimens was performed on cell block sections and showed focally positive synaptophysin staining in a sample with a neuroendocrine tumor, focally positive CK5/6 staining in a pleural effusion sample with mesothelioma, and positive TTF-1 staining in a lymph node sample with metastatic lung carcinoma. Their corresponding ICC of cell-transferred materials showed negative results. An increase in background staining was observed in 1 of the 95 tissue pieces, but no false-positive results were observed. CONCLUSIONS: In general, ICC can be reliably performed on cell-transferred tissue specimens for markers tested. However, caution should be taken when interpreting ICC results in tissue specimens with limited cellularity and heavy background staining.

Biopsy, Needle↗

Comparison of HER-2 status determined by fluorescence in situ hybridization in primary and metastatic breast carcinoma.

BACKGROUND: Accurate assessment of HER-2 status is necessary prior to anti-HER-2 antibody (trastuzumab) therapy for metastatic breast carcinoma. However, controversy exists regarding whether to assess HER-2 status in the primary tumor or in metastatic lesions. It is also unclear whether HER-2 status can change during disease progression or after chemotherapy. METHODS: Breast carcinoma samples from 60 women with known HER-2 status in both primary tumors and paired metastases (locoregional disease, n = 43 patients; distant disease, n = 17 patients) were reviewed retrospectively. Thirty-two patients underwent chemotherapy before their metastatic lesions were sampled, including 18 patients who received neoadjuvant chemotherapy and 14 patients who received adjuvant chemotherapy. The HER-2 gene was examined by fluorescence in situ hybridization either in paraffin-embedded tissue samples (48 primary tumors and 9 metastatic tumors) or in fine-needle aspirates (12 primary tumors and 51 metastatic tumors). HER-2 gene amplification was defined as a HER-2:chromosome 17 signal ratio >/= 2.0. RESULTS: The HER-2 status of primary and metastatic tumors agreed in 58 of 60 patients (97%), including 18 (30%) amplified tumors and 40 (67%) nonamplified tumors. A discrepancy in HER-2 status was observed in specimens from two patients in which HER-2 amplification was detected in the primary tumor but not the metastatic tumors. In one patient, three foci of tumor nodules were found in the same breast; the HER-2 status was assessed in only one of them, which showed amplification; however, HER-2 amplification was not detected in the axillary lymph node metastasis. In another patient, the HER-2 gene was amplified in the primary tumor but not in the liver metastasis. No metastases showed HER-2 amplification without amplification in the primary tumor. Locoregional and distant metastases demonstrated similar concordance rates with their corresponding primary tumors (98% and 94%, respectively). Complete concordance of HER-2 status was found between primary tumors prior to chemotherapy and metastases that were sampled after chemotherapy. CONCLUSIONS: The HER-2 status in breast carcinoma generally was stable during metastasis, whether to locoregional or distant sites. Chemotherapy did not modify the HER-2 status in metastatic lesions. Therefore, HER-2 amplification can be evaluated reliably in material from either primary or metastatic tumors in most patients. Further study with larger series is warranted to elucidate the significance of discordant results.

Adult↗

Fine-needle aspiration cytology of a liver metastasis of follicular dendritic cell sarcoma.

Follicular dendritic cell sarcoma (FDCS) is an uncommon neoplasm derived from FDCs in lymphoid tissue. Metastatic FDCS to the liver is rare. We present a case of a 65-yr-old woman who was referred to our institution 1 mo after splenectomy for FDCS of the spleen. An abdominal CT scan revealed a 2.0-cm liver lesion, which led to fine-needle aspiration (FNA) biopsy. Smears of the aspiration obtained were hypercellular showing a pleomorphic population of large oval to spindle-shaped tumor cells against a background of small mature lymphocytes, plasma cells, and necrotic debris. Tumor cells were arranged singly, in syncytial or fascicular patterns, and had a moderate amount of cytoplasm and indistinct cell borders. Nuclei had irregular nuclear membranes, finely granular to vesicular chromatin, and prominent nucleoli. Multinucleated and binucleated cells resembling Reed-Sternberg cells were noted occasionally. Mitotic figures, including atypical forms, were frequently identified. The diagnosis of "pleomorphic malignant spindle-cell neoplasm consistent with metastatic FDCS" was rendered and later confirmed by histological review and immunohistochemical staining of the subsequent liver resection specimen. Although cytological features of FDCS are characteristic, they are overlapping with those of many other tumors. We review the literature on this entity with emphasis on FNA cytomorphology, differential diagnosis, and immunohistochemical findings.

Aged↗

Fine-needle aspiration of an unusual case of poorly differentiated insular carcinoma of the thyroid.

Poorly differentiated insular carcinoma of the thyroid is a rare thyroid malignancy that is intermediary in biological behavior between well-differentiated and undifferentiated thyroid carcinoma. We used fine-needle aspiration (FNA) to diagnose a poorly differentiated insular carcinoma with unusual cytological features in a 53-yr-old woman with a history of goiter and hypothyroidism, who presented with a massively enlarged thyroid gland and a large liver metastasis. The hypercellular aspirates were comprised predominantly of individually dispersed tumor cells. The tumor cells were small, monotonous, round to oval, and often plasmacytoid with eccentric hyperchromatic nuclei and occasional binucleation; finely granular, ill-defined cytoplasm; and smooth nuclear contours, with hyperchromasia, and small to inconspicuous nucleoli. There were no identifiable microfollicles, necrosis, and mitotic figures. The differential diagnosis included poorly differentiated insular carcinoma, medullary carcinoma of the thyroid, and low-grade lymphoma. Immunocytochemical staining for thyroglobulin, calcitonin, and CD45 yielded negative findings. The insular pattern and scattered microfollicles were appreciated only focally in the specimen from the total thyroidectomy, which also showed other histological patterns including solid, trabecular, and papillary forms. In addition to small, uniform cells, Hurthloid, columnar, and clear cells were focally noted. Thyroglobulin immunoreactivity was recognized only in areas with well-formed follicles. In view of the aggressive nature of insular carcinoma, preoperative recognition is important in planning appropriate therapy. Familiarity with the cytomorphological features, a high index of suspicion, and consideration of appropriate differential diagnoses can greatly aid in reaching a definitive preoperative diagnosis. The limitations of FNA in the sampling of a large tumor with heterogeneous patterns should be kept in mind when interpreting the cytomorphological and immunocytochemical results.

Biopsy, Fine-Needle↗

Reliability of chromogenic in situ hybridization for detecting HER-2 gene status in breast cancer: comparison with fluorescence in situ hybridization and assessment of interobserver reproducibility.

Accurate determination of HER-2 status is important in the management of patients with breast cancer, especially in determining their eligibility for trastuzumab therapy. Fluorescence in situ hybridization (FISH) has been regarded as the gold standard method for detecting HER-2 gene amplification. Recently, chromogenic in situ hybridization (CISH), in which HER-2 is detected by a peroxidase reaction and the gene copies are determined by regular bright-field microscopy, has emerged as a potential alternative to FISH. However, this method requires validation before it can be adopted into clinical practice. In this study, we evaluated 80 cases of invasive breast carcinoma by CISH, compared the results with those obtained by FISH, and assessed interobserver reproducibility among three observers. We found that agreement among the three pathologists on the CISH-determined HER-2 status was achieved in 73 cases (91%), all of which had results matching the corresponding FISH results: 54 nonamplified and 19 amplified. Of the 19 amplified cases, 13 were scored unanimously as high-level amplification; six had a minor scoring discrepancy (ie, low-level vs high-level amplification). A major scoring discrepancy (ie, nonamplification vs amplification) was found in the remaining seven cases, three of which were amplified and four of which were nonamplified by FISH. Two of the latter cases had a polysomy of chromosome 17. The cases that caused scoring difficulty were those with an equivocal or borderline signal number against a high background. Overall, there was nearly perfect agreement between the CISH and corresponding FISH results, and interpretation of CISH results were highly reproducible among the three pathologists. We conclude that, in general, HER-2 status can be reliably assessed by CISH. Confirmatory FISH is recommended in cases with equivocal or borderline CISH copy numbers.

Breast Neoplasms↗

Optimal fixation conditions for immunocytochemical analysis of estrogen receptor in cytologic specimens of breast carcinoma.

BACKGROUND: The techniques for immunostaining estrogen receptor (ER) in cytologic specimens have varied, as have the detection rates. The authors compared various fixation methods for their effect on ER detection in cytologic smears of breast carcinoma. METHODS: Smears were prepared by gently scraping the cut surfaces of 47 resected breast carcinoma specimens and placing immediately in 1 of the following conditions: 1) a sequence of 10% formalin-methanol-acetone fixatives at -20 degrees C (Abbott method); 2) 10% formalin at room temperature; and 3) Carnoy's fixative at room temperature and then Papanicolaou stained (Carnoy's-Pap). Destaining of Carnoy's-Pap smears (Carnoy's-dPap) was initially attempted before ER staining. One set of smears was also air-dried for 3 minutes before using the Abbott method. Smears and corresponding tissue sections were immunostained with anti-ER antibody 6F11 using a similar protocol except for antigen retrieval, which was not initially applied on cytologic slides. All the ER-negative smears that had been fixed with 10% formalin or Carnoy's-Pap were restained after antigen retrieval. Agreement between cytologic and histologic findings was expressed by both concordance and the kappa coefficient. RESULTS: ER detection in smears processed with the Abbott method correlated best with findings from tissue samples, with an overall correlation of 91.5% (kappa = 0.80). Findings from air-dried smears were less optimal (concordance, 84.4%; kappa = 0.65), followed by Carnoy's-Pap (concordance, 71.4%; kappa = 0.45), formalin (concordance, 31%; kappa = 0.05), and Carnoy's-dPap (concordance, 29.4%; kappa = 0.04). Antigen retrieval converted most of the ER-negative smears to positive (18 of 20 smears in formalin and 6 of 8 smears in Carnoy's-Pap), leading to a final concordance of 93% and kappa = 0.83 for both conditions. Antigen retrieval also led to stronger staining intensity without causing false positivity. CONCLUSIONS: Antigen retrieval was found to greatly improve ER immunodetectability and staining intensity in formalin-fixed and Carnoy's-Pap smears. The former may offer an alternative to the Abbott method because of its easiness and the latter can be reliably used in archival Pap-stained smears for retrospective analysis of ER. Air-drying, destaining Pap smear, and fixation in formalin or Carnoy's-Pap without antigen retrieval are not recommended.

Adenocarcinoma↗

Post-transplant plasma cell myeloma and polymorphic lymphoproliferative disorder with monoclonal serum protein occurring in solid organ transplant recipients.

Post-transplant lymphoproliferative disorders are mostly Epstein-Barr virus-related, B-cell tumors that develop as a consequence of immunosuppressive therapy in recipients of solid organ or bone marrow transplants. These disorders range from reactive, polyclonal plasmacytic hyperplasia to those that are morphologically and genotypically indistinguishable from typical non-Hodgkin's lymphomas. Plasma cell myeloma occurring after solid organ transplantation is rare. We report three plasma cell myeloma post-transplant lymphoproliferative disorder cases and one polymorphic, monoclonal post-transplant lymphoproliferative disorder case associated with a monoclonal serum protein. All three plasma cell myeloma post-transplant lymphoproliferative disorder cases had clinical, radiologic, and pathologic features of conventional plasma cell myeloma. The one polymorphic post-transplant lymphoproliferative disorder case was associated with an IgM monoclonal serum protein and was morphologically indistinguishable from a lymphoplasmacytic lymphoma. Three of the four cases, including the one polymorphic post-transplant lymphoproliferative disorder case, were positive for Epstein-Barr virus encoded small RNA by in situ hybridization. One patient died of plasma cell myeloma post-transplant lymphoproliferative disorder. The remaining three patients are alive: two are completely free of post-transplant lymphoproliferative disorder, and one has shown partial response to therapy. We compare the clinicopathologic features of these cases with those in the literature.

Aged↗