Pathologic Response of Hepatocellular Carcinoma Treated with Yttrium-90 Glass Microsphere Radiation Segmentectomy Prior to Liver Transplantation: A Validation Study.

PURPOSE: To evaluate the pathologic outcomes of hepatocellular carcinoma (HCC) treated with Yttrium-90 radiation segmentectomy using glass microspheres prior to liver transplantation and explore parameters associated with pathologic necrosis. MATERIALS AND METHODS: A single-institution retrospective analysis of HCC patients who received radiation segmentectomy prior to liver transplantation from November 2016 to May 2020 was performed. Patients were included if the treatment angiosome encompassed the entire tumor and could be correlated with available gross pathology. Archived histology slides were reviewed for percentage of pathologic necrosis. Thirty-three patients with 37 tumors were evaluated. The median tumor size was 2.3 cm (range, 1-6.7 cm). RESULTS: All tumors received a single treatment. The median time from radiation segmentectomy to transplantation was 206 days (range, 58-550 days). Objective response per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) was 92% (complete response, 76%; partial response, 16%). A total of 68% (n = 25) of tumors demonstrated ≥99% pathologic necrosis. Complete pathologic necrosis was present in 53% and 75% of tumors treated with >190 Gy (n = 18) and >500 Gy (n = 8) single-compartment Medical Internal Radiation Dose, respectively. Complete response per mRECIST, posttreatment angiosome T1 hypointensity, dose >190 Gy, microsphere specific activity >297 Bq, and a longer time between treatment and transplant were associated with ≥99% tumor necrosis (P < .05). No posttransplant tumor recurrences occurred within a median follow-up of 604 days (range, 138-1,223 days). CONCLUSIONS: Radiation segmentectomy can serve as an ablative modality for the treatment of HCC prior to liver transplant.

Taurine Is Covalently Incorporated into Alpha-Tubulin.

Taurine is the most abundant free amino acid in the human body. It is found in relatively high concentrations (1-10 mM) in many animal tissues but not in plants. It has been studied since the early 1800s but has not been found to be covalently incorporated into proteins in any animal tissue. Taurine has been found in only one macromolecular complex as a post-transcriptional modification to mitochondrial tRNA. Tubulin is the subunit of microtubules found in all eukaryotic species and almost all eukaryotic cells and subject to numerous post-translational modifications (PTMs). An important PTM on α-tubulin is the removal and re-ligation of the final carboxyl residue, tyrosine. We here demonstrate that taurine can be covalently incorporated at the C-terminal end of alpha-tubulin in avian erythrocytes in a reaction that requires the de-tyrosination PTM and prevents the re-tyrosination PTM. Further, this is, to our knowledge, the first instance of taurine incorporation into a large protein.

Immunolabeling of Cleared Human Pancreata Provides Insights into Three-Dimensional Pancreatic Anatomy and Pathology.

Visualizing pathologies in three dimensions can provide unique insights into the biology of human diseases. A rapid and easy-to-implement dibenzyl ether-based technique was used to clear thick sections of surgically resected human pancreatic parenchyma. Protocols were applicable to both fresh and formalin-fixed, paraffin-embedded tissue. The penetration of antibodies into dense pancreatic parenchyma was optimized using both gradually increasing antibody concentrations and centrifugal flow. Immunolabeling with antibodies against cytokeratin 19 was visualized using both light sheet and confocal laser scanning microscopy. The technique was applied successfully to 26 sections of pancreas, providing three-dimensional (3D) images of normal pancreatic tissue, pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasms, and infiltrating pancreatic ductal adenocarcinomas. 3D visualization highlighted processes that are hard to conceptualize in two dimensions, such as invasive carcinoma growing into what appeared to be pre-existing pancreatic ducts and within venules, and the tracking of long cords of neoplastic cells parallel to blood vessels. Expanding this technique to formalin-fixed, paraffin-embedded tissue opens pathology archives to 3D visualization of unique biosamples and rare diseases. The application of immunolabeling and clearing to human pancreatic parenchyma provides detailed visualization of normal pancreatic anatomy, and can be used to characterize the 3D architecture of diseases including pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm, and pancreatic ductal adenocarcinomas.

Mass spectrometry imaging of lipids: untargeted consensus spectra reveal spatial distributions in Niemann-Pick disease type C1.

Mass spectrometry imaging (MSI) is a tool to rapidly map the spatial location of analytes without the need for tagging or a reporter system. Niemann-Pick disease type C1 (NPC1) is a neurodegenerative, lysosomal storage disorder characterized by accumulation of unesterified cholesterol and sphingolipids in the endo-lysosomal system. Here, we use MSI to visualize lipids including cholesterol in cerebellar brain tissue from the NPC1 symptomatic mouse model and unaffected controls. To complement the imaging studies, a data-processing pipeline was developed to generate consensus mass spectra, thereby using both technical and biological image replicates to assess differences. The consensus spectra are used to determine true differences in lipid relative abundance; lipid distributions can be determined in an unbiased fashion without prior knowledge of location. We show the cerebellar distribution of gangliosides GM1, GM2, and GM3, including variants of lipid chain length. We also performed MALDI-MSI of cholesterol. Further analysis of lobules IV/V and X of the cerebellum gangliosides indicates regional differences. The specificity achieved highlights the power of MSI, and this new workflow demonstrates a universal approach for addressing reproducibility in imaging experiments applied to NPC1.

Intraoperative PTH May Not Be Necessary in the Management of Primary Hyperparathyroidism Even with Only One Positive or Only Indeterminate Preoperative Localization Studies.

BACKGROUND: Intraoperative PTH (IOPTH) monitoring has been widely used to confirm the removal of the culprit lesion during operation. However, the true benefit of IOPTH in patients with preoperatively well-localized single adenoma has been questioned. The aim of this study was to examine how or if IOPTH changes the surgical management and outcomes in patients with only one positive or only indeterminate localization studies. METHODS: This is a retrospective review of data from a parathyroid surgery database and patient records from July 2004 to June 2014, including patients with primary hyperparathyroidism with a planned MIP by two experienced endocrine surgeons after ≥1 positive/indeterminate preoperative localization study by ultrasound and/or sestamibi. RESULTS: A total of 482 patients with positive (342: 259 only 1, 83 with ≥2) or indeterminate (140: 105 only 1, 35 with ≥2) preoperative imaging studies were included. IOPTH changed the management in only 16 (3%) patients, with an additional lesion found in 12 of them. Surgical cure was achieved in 471 (98%) of patients (98% in the positive vs. 97% in the indeterminate group, p 0.58). With or without IOPTH, the cure rate would not have been significantly different in patients with only 1 positive preoperative imaging (96 vs. 98%, p 0.12). Similar results were seen in those with ≥2 indeterminate (100% cure rate with or without IOPTH). CONCLUSION: Our study suggests that MIP may be safely and successfully performed without IOPTH for patients with ≥1 positive or ≥2 indeterminate preoperative imaging studies. This study is retrospective within inherent biases, and future prospective study is warranted.

ProteinProcessor: A probabilistic analysis using mass accuracy and the MS spectrum.

Current approaches to protein identification rely heavily on database matching of fragmentation spectra or precursor peptide ions. We have developed a method for MALDI TOF-TOF instrumentation that uses peptide masses and their measurement errors to confirm protein identifications from a first pass MS/MS database search. The method uses MS1-level spectral data that have heretofore been ignored by most search engines. This approach uses the distribution of mass errors of peptide matches in the MS1 spectrum to develop a probability model that is independent of the MS/MS database search identifications. Peptide mass matches can come from both precursor ions that have been fragmented as well as those that are tentatively identified by accurate mass alone. This additional corroboration enables us to confirm protein identifications to MS/MS-based scores that are otherwise considered to be only of moderate quality. Straightforward and easily applicable to current proteomic analyses, this tool termed "ProteinProcessor" provides a robust and invaluable addition to current protein identification tools.

High prevalence of TERT promoter mutations in primary squamous cell carcinoma of the urinary bladder.

TERT promoter mutations (TERT-mut) are detectable in the majority of urothelial carcinomas. The detection of TERT-mut in urine is under investigation as a potential urine-based molecular-screening assay for bladder cancer. A small but significant number of bladder carcinomas are pure squamous cell carcinoma. We sought to assess the incidence of TERT-mut in squamous cell carcinoma of the urinary bladder. A retrospective search of the institutional pathology archives yielded 15 cystectomy specimens performed for squamous cell carcinoma (2000-2014). Histologic slides were reviewed by a senior urologic pathologist to confirm the diagnosis and select a representative formalin-fixed paraffin-embedded tissue block for mutational analysis. All cases yielded adequate material for DNA analysis. Sequencing for TERT-mut was performed using previously described SafeSeq technique. We detected TERT-mut in 12/15 (80%) of bladder squamous cell carcinomas. TERT promoter mutations, commonly found in conventional urothelial carcinoma, are also highly prevalent in urinary bladder squamous cell carcinoma suggesting a common tumorigenesis and potential utility as a molecular urine-based-screening assay.

Clinical presentation of patients with a thyroid follicular neoplasm: are there preoperative predictors of malignancy?

BACKGROUND: Studies examining differences in presentation of patients with benign [follicular adenoma (FA)] and malignant follicular thyroid neoplasms [follicular thyroid carcinoma (FTC) or follicular variant papillary thyroid carcinoma (FVPTC)] include only one or two of these subtypes, and none has considered clinical, cytological, and sonographic features together. We therefore examined presenting clinical features of all benign and malignant follicular neoplasm subtypes in an attempt to identify predictors of malignancy. METHODS: Consecutive patients with a surgically resected follicular thyroid neoplasm at a tertiary hospital from 2005 to 2013 were reviewed. Age, gender, symptoms, history, physical findings, nodule size, sonographic, cytologic, and final pathologic results were recorded. Multivariate logistic regression was used to determine variables that contributed to a diagnosis of malignant follicular neoplasm. RESULTS: A total of 616 patients (163 males, 453 females) presented with 441 FAs, 17 FTCs, and 158 FVPTCs. On multivariate analysis, male sex [odds ratio (OR) 1.87, p = 0.008], family history of thyroid cancer (OR 5.16, p < 0.001), and history of head and neck radiation (OR 2.01, p = 0.04) were associated with an increased odds of malignancy; age >45 (OR 2.03, p = 0.001), dysphagia (OR 3.48, p = 0.001) or pressure sensation (OR 3.00, p = 003), concomitant hyperthyroidism (OR 4.76, p = 0.01), nodules ≥4 cm (OR 3.68, p < 0.001), and multinodularity on physical examination (OR 1.93, p = 0.004) were associated with an increased odds of a benign lesion. CONCLUSIONS: Independent clinical predictors exist that might be helpful in preoperative differentiation of benign and malignant follicular neoplasms. A combination of these predictors with both FNA and molecular results may help us to improve the clinical management of patients with follicular thyroid lesions.

The impact of molecular testing on the surgical management of patients with thyroid nodules.

BACKGROUND: The use of molecular tests as an adjunct to FNA diagnosis of thyroid nodules has been increasing. However, the true impact of these tests on surgical practice has not been demonstrated. This study examines the usefulness of molecular testing on surgical management decisions in patients referred for thyroid surgery at a tertiary care center. METHODS: Clinical information was collected from patients who presented to Johns Hopkins Hospital for surgical consultation regarding a thyroid nodule and who underwent molecular testing between August 2009 and March 2013. Tests included an RNA-based gene expression classifier, a DNA-based somatic mutation panel, BRAF, NRAS, and/or RET/PTC translocation. A surgical management algorithm was created by consensus of four thyroid surgeons. Postsurgical pathology analysis in each case was then used to judge the appropriateness of the surgical decision-making and the usefulness of preoperative molecular testing, in guiding surgical planning. RESULTS: Of 114 patients assessed by preoperative molecular testing, 87 (72 %) underwent surgery. Surgical management was altered in nine (10 %) patients on the basis of molecular testing. Of these, surgical management change was appropriate, relative to the postoperative pathology analysis, for three patients and inappropriate for six patients. CONCLUSIONS: In this study, molecular testing of thyroid nodule did not alter the surgical management of the majority of patients with thyroid nodules. These results indicate that molecular testing may be overused in patients for whom the results would not change surgical management. Furthermore, our data question the usefulness of the molecular tests examined in guiding preoperative surgical decision-making.

Cytotechnologist performance for screening microfollicular atypia in indeterminate thyroid fine-needle aspirates.

INTRODUCTION: We previously identified a high level of accuracy among our cytotechnologists (CTs) for identifying nuclear atypia in thyroid fine-needle aspiration (FNA) specimens. Herewith, we present our CT performance at screening for microfollicular atypia. METHODS: 8,814 thyroid FNA specimens were identified in our archives, all screened by 1 of 11 CTs and signed out by a cytopathologist. A subsample of cases was categorized either as atypia of uncertain significance (AUS) with microfollicular proliferation (AUS-F) or suspicious for a follicular neoplasm (SFN). RESULTS: The agreement rate was low between CTs and cytopathologists for SFN and AUS-F. Only 55.8% of SFN screening diagnoses were upheld; 27.9% were downgraded to AUS, 10.4% were downgraded to benign, and 5% were upgraded. Of AUS-F screening diagnoses, 35.5% were upheld, 33.7% were downgraded to benign, and 20.2% were upgraded to SFN. Among all cases, two-step discrepancies were uncommon. CONCLUSION: Most disagreements were one-category discrepancies between AUS-F and SFN. The evaluation of microfollicular atypia is challenging given that certain follicular lesions cannot be definitively diagnosed on cytology, a high level of subjectivity is involved in the interpretation of such lesions, and the presence of nuclear or Hurthle cell atypia may complicate the diagnosis.

Cytotechnologist performance for detecting nuclear atypia in indeterminate thyroid fine needle aspirates.

INTRODUCTION: The thyroid gland is arguably the fastest growing anatomic site for fine needle aspiration (FNA). With the increase of thyroid cases, a reevaluation of cytotechnologist screening quality metrics in terms of thyroid FNA is called for. We present our institutional cytotechnologist performance at screening for nuclear atypia by applying established quality metrics. MATERIALS AND METHODS: Information on 8,814 consecutive thyroid cytopathology cases over a 10-year period was retrieved from computerized records. A subsample of cases categorized either as atypia of uncertain significance with nuclear atypia or suspicious for malignancy with features suspicious for papillary thyroid carcinoma. The cytotechnologist and cytopathologist diagnoses were compared using step discrepancies and Δ-ratios. RESULTS: Overall discrepancy between the cytotechnologist and cytopathologist diagnoses existed in <10% of all thyroid cases. One-category discrepancies were the most common (7.8%), while two-category discrepancies were rare (0.5%). The one-category discrepancy rate correlated with cytotechnologist experience. One-category under calls were twice as common as over calls (5.3 vs. 2.5%, p < 0.0001). CONCLUSIONS: We identified a high level of quality in the screening for nuclear atypia in thyroid FNA. The one-category discrepancy rate is suited to tracking individual cytotechnologist performance, identifies outliers and appears to correlate with cytotechnologist experience.

'Suspicious for papillary thyroid carcinoma' before and after The Bethesda System for Reporting Thyroid Cytopathology: impact of standardized terminology.

BACKGROUND: The high-risk 'suspicious for papillary thyroid carcinoma' (SPTC) is a clinically relevant diagnosis in the cytological interpretation of thyroid aspirates. While The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has provided invaluable terminology standardization, a performance comparison for this diagnostic category has not been performed. Therefore, this study evaluates the SPTC diagnosis before and after the introduction of TBSRTC in a large meta-analysis and at a single institution. MATERIALS AND METHODS: The meta-analysis analyzed publications of SPTC or similar diagnoses before and after the introduction of TBSRTC. Similarly our own institutional experience was analyzed for the 8 years surrounding the introduction of TBSRTC. A correlation of the cytopathology and surgical pathology diagnoses was performed. RESULTS: The introduction of TBSRTC coincided with a significant decrease in the fraction of cases called SPTC in the meta-analysis (4.5-3.1%, p < 0.00001) and in the institutional review (1.7-0.9%, p = 0.005). Meanwhile, the malignancy risk for those cases increased significantly in the meta-analysis from 62.5 to 80.5% (p < 0.00001) and trended upwards in the institutional review from 69 to 79% (p = 0.4). The follow-up rate was similar in both time periods in the meta-analysis and the institutional review. CONCLUSIONS: The introduction of TBSRTC coincided with a decrease in the fraction of cases called SPTC and an increase in the malignancy risk associated with that diagnosis.

Alternative calibration strategies for the clinical laboratory: application to nortriptyline therapeutic drug monitoring.

BACKGROUND: The addition of a calibration curve with every run is both time-consuming and expensive for clinical mass spectrometry assays. We present alternative calibration strategies that eliminate the need for a calibration curve except as required by laboratory regulations. METHODS: We measured serum nortriptyline concentrations prospectively in 68 patients on 16 days over a 2-month period using a method employing calibration schemes that relied on the measurement of the response ratio (RR) corrected by the response factor (RF), i.e., a measurement of the RR for an equimolar mixture of the analyte and internal standard. Measurements were taken with contemporaneous RF (cRF) measurements as well as sporadic RF (sRF) measurements. The measurements with these alternative calibration schemes were compared against the clinical results obtained by interpolation on a calibration curve, and those differences were evaluated for analytical and clinical significance. RESULTS: The differences between the values measured by cRF and sRF calibration and interpolation on a calibration curve were not significant (P = 0.088 and P = 0.091, respectively). Both the cRF- and sRF-based calibration results demonstrated a low mean bias against the calibration curve interpolations of 3.69% (95% CI, -15.8% to 23.2%) and 3.11% (95% CI, -16.4% to 22.6%), respectively. When these results were classified as subtherapeutic, therapeutic, or supratherapeutic, there was categorical agreement in 95.6% of the cRF calibration results and 94.1% of the sRF results. CONCLUSIONS: cRF and sRF calibration in a clinically validated liquid chromatography-tandem mass spectrometry assay yields results that are analytically and clinically commensurate to those produced by interpolation with a calibration curve.

Pancreatic metastasis from a solitary fibrous tumor of the kidney: a rare cause of acute recurrent pancreatitis.

Solitary fibrous tumors are unusual spindle cell neoplasms that uncommonly originate from the kidney. We report a case of a 43-year old male who presented with acute recurrent pancreatitis secondary to a mass in the head of the pancreas. Endoscopic ultrasound with fine needle aspiration (EUS-FNA) was performed. Cytology revealed solitary fibrous tumor of the kidney. This is the first reported case of solitary fibrous tumor metastasizing to the pancreas and presenting as acute recurrent pancreatitis.

The differential diagnosis of squamous cells in pancreatic aspirates: from contamination to adenosquamous carcinoma.

BACKGROUND: This study was conducted to describe the frequency and significance of squamous cells in fine needle aspiration (FNA) specimens of the pancreas in benign and malignant processes. METHODS: A retrospective review was performed of 102 patients with squamous cells in their pancreatic FNA specimens from 1986 to 2012. The malignant cases were classified as adenosquamous carcinoma (ASqC) or metastatic squamous cell carcinoma, and a double institutional review of the ASqC cases was undertaken to characterize the clinical and pathological features and survival statistics of patients who present with unresectable or metastatic ASqC and have no follow-up surgery. Survival analyses were performed. RESULTS: Of the 4,094 pancreas FNA procedures performed in the study, squamous features were found in 102 (2.5%) of all cases, and 48% of these cases represented ASqC. The other cases were contamination (52%) or atypical (<1%). ASqC constituted 4.5% (46/1,025) of all primary pancreatic exocrine malignancies. When compared with conventional adenocarcinoma, ASqC demonstrated a significantly poorer overall median survival (11.0 vs. 6.51 months; p = 0.023), and this difference was also seen in patients presenting with metastatic disease (median survival of 9.1 vs. 4.2 months; p = 0.025). CONCLUSIONS: Squamous cells in FNA specimens from the pancreas have a broad differential diagnosis that ranges from contamination to ASqC.

Malignant pleural effusion resulting from metastasis of thyroid primaries: a cytomorphological analysis.

BACKGROUND: Malignant serous cavity effusion caused by primary thyroid cancer is extremely rare in routine clinical practice. Therefore, it is often not included in the differential diagnostic workup of patients presenting with positive effusion cytology. METHODS: The clinical features were reviewed for 6 patients seen at our institution over the last 26 years for malignant effusion resulting from metastatic thyroid cancer. The cytomorphology from 4 of these cases was also reviewed. RESULTS: All of the patients found in this study presented with malignant pleural effusion - other serous cavity effusions resulting from metastatic thyroid carcinoma were not seen. These comprised 0.25% of all patients with a known history of thyroid carcinoma and 0.67% of all malignant pleural effusions. One patient had a history of bone metastases, but all the others had no pathological evidence of distant metastatic disease prior to the pleural effusion. CONCLUSIONS: Malignant pleural effusion rarely results from a thyroid carcinoma after some latency. The diagnosis requires immunohistochemical staining as well as the pertinent clinical context.

Impact of flow cytometry in thyroid cytopathology.

BACKGROUND: Fine-needle aspiration (FNA) is a useful diagnostic tool for preoperative evaluation of thyroid nodules. However, cytomorphology alone has poor accuracy for the diagnosis of lymphoproliferative disorders involving the thyroid. This study reviews our experience with flow cytometry on thyroid FNA and correlation with surgical follow-up at The Johns Hopkins Hospital. METHODS: The 11,118 thyroid FNAs performed over a 20-year period were reviewed for clinical flow cytometry data (n = 62) or a subsequent diagnosis of lymphoma in the thyroid without flow cytometry data (n = 2). RESULT: Sixty-four cases (0.6%) were included out of 11,118 thyroid FNAs collected over a 20-year period. Lymphoma was diagnosed 13 times. In 8 cases, both cytomorphology and flow cytometry arrived at the correct diagnosis. Cytomorphology alone made the correct diagnosis twice in the absence of flow cytometric results; flow cytometry made the diagnosis once in the absence of suspicious morphology. Neither flow cytometry nor cytomorphology made the correct diagnosis in 2 sparsely cellular cases. CONCLUSION: The combination of cytomorphology and flow cytometry is a useful diagnostic modality for the work-up of lymphocyte-rich thyroid nodules that show atypical lymphocyte populations.

'Suspicious for a follicular neoplasm' before and after the Bethesda System for Reporting Thyroid Cytopathology: impact of standardized terminology.

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) standardized the terminology for indeterminate diagnoses, but the performance of the indeterminate categories before and after TBSRTC has not been compared. This study evaluates the 'suspicious for a follicular or Hürthle cell neoplasm' (SFN/HCN) category before and after the introduction of TBSRTC at a single institution and in a meta-analysis of the literature. METHODS: A meta-analysis compiled findings from publications on SFN/HCN or similar diagnoses before and after the introduction of TBSRTC. The pathology database at our institution identified all SFN/HCN or similar diagnoses in the 8 years surrounding the introduction of TBSRTC, and those cases were correlated with the surgical follow-up. RESULTS: In the meta-analysis, the fraction of cases called SFN/HCN or the equivalent increased from 6.1 to 7.4% (p = 0.0002); the surgical follow-up rate increased from 55 to 61% (p < 0.00001), and the histological malignancy rate among the cases that were resected increased from 22 to 28% (p = 0.03) after TBSRTC. In our institutional experience, the introduction of TBSRTC did not coincide with any significant changes. CONCLUSION: Standardized terminology clearly coincided with increases in follow-up and the malignancy rate of SFN/HCN. A change in the same statistics was not seen in our institutional experience.

Metastases to the pancreas diagnosed by fine-needle aspiration.

BACKGROUND: Metastatic cancer infrequently involves the pancreas. When the pancreas hosts a metastatic tumor, cytopathological evaluation of fine-needle aspirate material is a crucial part of the diagnostic process. In this study, we show two institutions' experience with cytopathological diagnosis of pancreatic metastasis. METHODS: Databases of institutional experience at The Johns Hopkins Hospital and Ohio State University Medical Center were queried for cases of metastatic tumors in the pancreas that underwent fine-needle aspiration. Demographic and pathological features were compiled and the cytomorphology was reviewed. RESULTS: Forty-two cases of tumor metastasis to the pancreas were found. Over the time of this review, 5,495 aspirates were performed, and 43% (2,389/5,495) had malignant cytological findings. Thus, the 42 cases of metastatic disease to the pancreas comprised 0.8% of all pancreas aspirates and 1.8% of the malignant ones. Renal cell carcinoma was the most common metastasis, followed by melanoma and non-small cell lung carcinoma. Among the other tumors in this series, 2 cases each of rare metastases such as the fibrolamellar variant of hepatocellular carcinoma and solitary fibrous tumor were also seen. CONCLUSION: The pancreas is rarely involved with metastatic disease, but when it is involved the most common tumor is renal cell carcinoma followed by melanoma and non-small cell lung cancer. Clinical history and awareness of the primary pancreatic mimickers are necessary for arriving at the correct diagnosis. As conventional pancreatic adenocarcinoma is uncommon in children and young adults, history of other tumors - even ones that usually follow an indolent course - is essential.

Cribriform morular variant of papillary thyroid carcinoma: clinical and cytomorphological features on fine-needle aspiration.

BACKGROUND: Cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is a rare tumor that may arise in patients with familial adenomatous polyposis (FAP), although sporadic instances of this tumor have been reported. When it arises in FAP, CMV-PTC may present before colonic manifestations are apparent, so proper identification and classification are essential for prompt assessment of the colonic disease status and genetic and familial counseling. METHODS: Nine cases of PTC with cribriform morular cytomorphology were identified at 2 large tertiary-care hospitals; 6 were true CMV-PTC with positive ß-catenin and 3 were CMV-like PTC with negative ß-catenin. A review of the cytomorphology and a cytology-histology correlation were performed. RESULTS: Only 1 patient presented with a known history of FAP. Patients presented with a median age of 41 years (range 19-64 years). There was a clear female predilection; 8 of 9 patients (89%) were female. All cases demonstrated the classical nuclear and architectural features of PTC. In addition, the most salient features were large tissue fragments with cribriform architecture and dense cellular morules. The elongated cellular shape of the tumor cells led to the misclassification of one tumor as a tall-cell variant of PTC on the FNA material. CONCLUSION: CMV-PTC or CMV-like PTC demonstrate cytomorphological features that overlap with classic PTC. ß-Catenin immunostaining plays an important role in making a definitive diagnosis.