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Beckwith-Wiedemann syndrome (BWS) is a genetic overgrowth and cancer predisposition syndrome that can be associated with a spectrum of clinical features including isolated lateralized overgrowth, macrosomia, macroglossia, organomegaly, omphalocele/umbilical hernia, and distinct facial features. Because of a range of clinical presentations and molecular defects involving Chromosome 11p15, many cases will fall within what is now being defined as the Beckwith-Wiedemann spectrum (BWSp). Cushing syndrome (CS) in infants is a rare neuroendocrinological disease associated with hypercortisolism that has rarely been reported in patients with BWS. Here, we describe the first case of a 5-month-old male with CS secondary to paternal uniparental disomy of Chromosome 11p without additional clinical signs or symptoms of BWS. This case continues to expand the phenotypic spectrum of BWSp.

Objectives Manufacturer recalls and altered supply chains during the coronavirus disease 2019 (COVID-19) pandemic caused a nationwide shortage of blue-top tubes (BTTs). Most non–point-of-care coagulation tests use these tubes, leaving laboratories and health care facilities in short supply. The Department of Pathology and Laboratory Medicine at Cedars-Sinai Medical Center implemented interventions to conserve supply without sacrificing patient safety. Methods In a retrospective quality improvement analysis, we examined coagulation testing and BTT utilization over the 3-month interval during which our interventions were applied. Our study assessed the interventions’ effectiveness by evaluating changes in BTT utilization, coagulation testing volume, and patient impact. Results Average daily use (ADU) of BTT before and after the intervention were 476 and 403, respectively—a 15.2% reduction. Notably, the Emergency Department had a reduction in ADU of 43.3%. Average daily volumes of coagulation assays performed decreased from 949 to 783—a 17.5% reduction. No adverse events from the Pharmacy Department were identified during the study period. Conclusions Interventions resulting in significant reductions were in divisions with effective management and supervision. Success in navigating the BTT shortage stemmed from timely announcements, action, and effective communication. Our recommendations established more effective coagulation assay utilization, decreased overall BTT use, and prevented patients with coagulopathic disorders from experiencing adverse consequences.

Nail unit melanocytic lesions present a unique set of diagnostic challenges because of the unfamiliarity with clinical assessment and the lack of experience with histologic examination. Because the first surgical specimen received in the pathology laboratory is typically small, sometimes suboptimal biopsy, the distinction between melanoma and its histologic mimics can be difficult. For this reason, there has been a continued interest in the development of ancillary markers that may assist in the differential diagnosis of nail unit melanocytic lesions. Upregulation of preferentially expressed antigen in melanoma (PRAME) has been reported to be a common event in melanomas, and PRAME immunohistochemistry has been shown to be helpful in evaluating various melanocytic neoplasms. In this study, we evaluated PRAME protein expression in a series of nail unit melanocytic lesions. Twenty-five nail unit melanomas (including small biopsy and amputation specimens) and 32 control benign melanocytic lesions were retrospectively retrieved. Nuclear PRAME staining was scored as percentage and intensity labeling. All melanoma cases showed the nuclear expression of PRAME, which was usually diffuse and strong. In specimens where the neoplastic cells are limited in number, the staining was restricted to the tumor cells, corresponding to the initial HE impression. All control cases were negative for PRAME expression. PRAME expression is helpful in distinguishing between melanomas and other nail unit melanocytic lesions. This antibody also proved to be diagnostically valuable in detecting melanoma cells in small specimens with minimal disease.

The distinction among cutaneous basaloid neoplasms such as trichoepithelioma (TE), desmoplastic trichoepithelioma (DTE), morpheaform basal cell carcinoma (MBCC), and microcystic adnexal carcinoma (MAC) can be difficult, especially in superficial biopsies. As the treatment plan of each entity is different, accurate characterization is important for appropriate management. While TE and DTE are benign neoplasms with indolent behavior, MBCC and MAC are typically locally aggressive. The expression of several recently described immunohistochemical (IHC) markers, including p40, IMP3, and ProEx C, has not been adequately established in cutaneous neoplasms. We explored the potential utility of a broad IHC panel, including previously reported and novel markers to differentiate TE, DTE, MBCC, and MAC.A total of 35 archival cases [TE (n=14), DTE (n=9), MBCC (n=6), and MAC (n=6)] were stained with 9 IHC markers: p40, IMP3, ProEx C, p16, CK20, Ki-67, androgen receptor, D2-40, and beta-catenin. Tumors with5% immunoreactivity were scored as positive. The intensity was scored on a scale from 1+ to 3+. The pattern of positivity- nuclear, cytoplasmic, membranous, or in combination; peripheral or central distribution with lesion was also recorded.CK20 (in contrast to prior studies) and IMP3 were negative in all cases. Likewise, with the exception of one case of TE, androgen receptor showed no immunoreactivity in all categories. No significant difference was observed in the expression of beta-catenin, p16, ProEx C, and p40 among the four groups of cutaneous neoplasms. The mean Ki-67 labeling index for MBCC (8%) was slightly higher than DTE (3%). Interestingly, the proliferation index for TE (15%) was significantly higher than that of MBCC. All six cases of MAC and 36% of TEs expressed D2-40; neither the MBCC nor DE cases showed D2-40immunoreactivity. Also, we confirmed the previously published observation of scattered CK20 positive Merkel cells in the epidermis of all cases of DTE; whereas, no Merkel cells were identified in MBCC and MAC cases.Except Ki-67, our IHC panel showed no significant added diagnostic utility of IHC in discriminating among TE, DTE, MBCC, and MAC. Among the four cutaneous neoplasms, DTE and MBCC show a small but discernible difference in Ki-67.

Microphthalmia-associated transcription factor (MiTF) is used as a marker of melanocytic differentiation. However, MiTF immunoexpression has also been observed in histiocytes, macrophages, smooth muscle cells and fibroblasts, which raise the concern of fibrohistiocytic (FH) lesions being misdiagnosed as melanoma based on MiTF immunoreactivity. MiTF has been known to be positive in FH tumors, but this is the first study evaluating ninety-three fibrohistiocytic neoplasms to understand and delineate the staining pattern of MiTF in these tumors. Ninety-three cases of FH, 30 cases of melanocytic lesions, and 20 miscellaneous cases were studied. The FH cases included benign fibrous histiocytoma (BFH, n = 29), angiofibroma (AF, n = 11), fibromatosis (FM, n = 14), keloid (KE, n = 10), atypical fibroxanthoma (AFX, n = 7), dermal scar (DS, n = 9), dermatofibrosarcoma protuberans (DFSP, n = 12), and pigmented DFSP (Bednar tumor, n = 1). Benign fibrous histiocytoma were sub-categorized into dermatofibroma (n = 15) and epithelioid fibrous histiocytoma (n = 14). The melanocytic lesions included desmoplastic melanoma (DM, n = 8), melanoma in-situ (MIS, n = 5), re-excision-free of melanoma (RFM, n = 10), blue nevus (BN, n = 5), and spitz nevus (SN, n = 3). The miscellaneous category included osteosarcoma (OS, n = 3), pigmented basal cell carcinoma (PBCC, n = 5), spindle cell squamous cell carcinoma (SCA, n = 2), and giant cell tumor of tendon sheath (GCTTS, n = 10). All BFH, AF, AFX, KE, and DS cases showed a positive MiTF staining of variable extent and intensity. MiTF positivity was observed in 86% (n = 12) cases of FM and 17% (n = 2) cases of DFSP. Amongst the miscellaneous category, all cases of PBCC and GCTTS and 50% (n = 1) cases of SCA were immunoreactive for MiTF. All melanocytic lesions were positive for MiTF. None of the OS and pigmented DFSP showed positive labeling. Because of the promiscuity of MiTF labeling, awareness of its pattern in FH proliferations may avoid potential pitfalls in the diagnosis of spindle cell lesions.

Initial investigations reported GATA3 to be a sensitive and relatively specific marker for mammary and urothelial carcinomas. Recently, GATA3 expression has been described in several other epithelial tumors. However, there has been only limited investigation of GATA3 expression in cutaneous epithelial tumors. The objective of this study was to examine the immunohistochemical expression of GATA3 in a wide variety of cutaneous epithelial neoplasms. GATA3 expression was evaluated in 99 benign and 63 malignant cutaneous epithelial tumors. GATA3 was consistently and usually strongly expressed in clear cell acanthoma, trichofolliculoma, trichoepithelioma, trichilemmoma, sebaceous adenoma, sebaceoma, apocrine hidrocystoma, apocrine tubular papillary adenoma, hidradenoma papilliferum, and syringocystadenoma papilliferum. Hidradenomas exhibited variable positive staining. Most poromas, syringomas, chondroid syringomas, cylindromas, and spiradenomas were negative or only focally and weakly positive. Focal staining was present in all pilomatrixomas. Thirteen of 14 basal cell carcinomas, 21 of 24 squamous carcinomas, and all 6 sebaceous carcinomas exhibited positive staining. The 1 apocrine carcinoma, both mucinous carcinomas, and 2 of 3 microcystic adnexal carcinomas also exhibited positive staining, whereas the 1 eccrine porocarcinoma and the 1 adenoid cystic carcinoma were negative. One of 11 Merkel cell carcinomas exhibited focal weak staining. Our findings demonstrate that GATA3 is expressed in a wide variety of benign and malignant cutaneous epithelial neoplasms. In addition to carcinomas of breast and urothelial origin and other more recently described GATA3-positive tumors, the differential diagnosis of a metastatic tumor of unknown primary origin that expresses GATA3 should also include a carcinoma of cutaneous epithelial origin.

Background: The Paris System (TPS) acknowledges the need for more standardized terminology for reporting urine cytopathology results and minimizing the use of equivocal terms. We apply TPS diagnostic terminologies to assess interobserver agreement, compare TPS with the traditional method (TM) of reporting urine cytopathology, and evaluate the rate and positive predictive value (PPV) of each TPS diagnostic category. A survey is conducted at the end of the study. Materials and Methods: One hundred urine samples were reviewed independently by six cytopathologists. The diagnosis was rendered according to TPS categories: negative for high-grade urothelial carcinoma (NHGUC), atypical urothelial cells (AUC), low-grade urothelial neoplasm (LGUN), suspicious for high-grade urothelial carcinoma (SHGUC), and high-grade urothelial carcinoma (HGUC). The agreement was assessed using kappa. Disagreements were classified as high and low impacts. Statistical analysis was performed. Results: Perfect consensus agreement was 31%, with an overall kappa of 0.362. Kappa by diagnostic category was 0.483, 0.178, 0.258, and 0.520 for NHGUC, AUC, SHGUC, and HGUC, respectively. Both TM and TPS showed 100% specificity and PPV. TPS showed 43% sensitivity (38% by TM) and 70% accuracy (66% by TM). Disagreements with high clinical impact were 27%. Of the 100 cases, 52 were concurrent biopsy-proven HGUC. The detection rate of biopsy-proven HGUC was 43% by TPS (57% by TM). The rate of NHGUC was 54% by TPS versus 26% by TM. AUC rate was 23% by TPS (44% by TM). The PPV of the AUC category by TPS was 61% versus 43% by TM. The survey showed 33% overall satisfaction. Conclusions: TPS shows adequate precision for NHGUC and HGUC, with low interobserver agreement for other categories. TPS significantly increased the clinical significance of AUC category. Refinement and widespread application of TPS diagnostic criteria may further improve interobserver agreement and the detection rate of HGUC.

An accurate and complete pathology report is critical for the optimal management of cutaneous melanoma patients. Protocols for the pathologic reporting of melanoma have been independently developed by the Royal College of Pathologists of Australasia (RCPA), Royal College of Pathologists (United Kingdom) (RCPath), and College of American Pathologists (CAP). In this study, data sets, checklists, and structured reporting protocols for pathologic examination and reporting of cutaneous melanoma were analyzed by an international panel of melanoma pathologists and clinicians with the aim of developing a common, internationally agreed upon, evidence-based data set. The International Collaboration on Cancer Reporting cutaneous melanoma expert review panel analyzed the existing RCPA, RCPath, and CAP data sets to develop a protocol containing “required” (mandatory/core) and “recommended” (nonmandatory/noncore) elements. Required elements were defined as those that had agreed evidentiary support at National Health and Medical Research Council level III-2 level of evidence or above and that were unanimously agreed upon by the review panel to be essential for the clinical management, staging, or assessment of the prognosis of melanoma or fundamental for pathologic diagnosis. Recommended elements were those considered to be clinically important and recommended for good practice but with lesser degrees of supportive evidence. Sixteen core/required data elements for cutaneous melanoma pathology reports were defined (with an additional 4 core/required elements for specimens received with lymph nodes). Eighteen additional data elements with a lesser level of evidentiary support were included in the recommended data set. Consensus response values (permitted responses) were formulated for each data item. Development and agreement of this evidence-based protocol at an international level was accomplished in a timely and efficient manner, and the processes described herein may facilitate the development of protocols for other tumor types. Widespread utilization of an internationally agreed upon, structured pathology data set for melanoma will lead not only to improved patient management but is a prerequisite for research and for international benchmarking in health care.

Background Endoscopic ultrasound guided fine needle aspiration (EUS-FNA) is the procedure of choice to investigate and sample pancreatic masses for the preoperative diagnosis of pancreatic ductal adenocarcinoma (PDAC). The role of 18 fluoro-deoxyglucose positron emission tomography/computed tomography (PET/CT) in PDAC is debated. This study evaluates the role of EUS-FNA as compared to PET/CT in the preoperative evaluation of PDAC. Methods Preoperative evaluation by PET/CT and EUS-FNA was performed on 25 patients with pancreatic solid lesions, who underwent a subsequent Whipple procedure or partial pancreatic resection. Results This series included 19 PDACs and 6 non-PDACs including 1 metastatic breast ductal adenocarcinoma, 2 low grade neuroendocrine tumors, 2 chronic pancreatitis and 1 gastrointestinal tumor abutting the pancreas. EUS-FNA correctly diagnosed 18 of 19 PDACs, 1 metastatic breast ductal adenocarcinoma and all 5 of the other non-PDAC cases. One case of well differentiated PDAC was negative on EUS-FNA. PET/CT provided excellent size and was positive in 14 of 19 PDACs and the metastatic breast ductal adenocarcinoma. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy for EUS-FNA in diagnosis of selected pancreatic tumors were 91%, 100%, 100%, 50% and 92%, respectively, while they were 65%, 100%, 100%, 20% and 68% for PET/CT, respectively. Conclusions Compared to PET/CT, EUS-FNA has a higher sensitivity and accuracy for preoperative diagnosis of PDAC. However, PET/CT provides excellent size, volume and stage information. A combination of both PET/CT and EUS will better help guide diagnosis and treatment of pancreatic adenocarcinoma.

Aim Retrieval of a minimum of 12 lymph nodes has been recommended for adequately staging a node-negative colorectal cancer (CRC). This study was designed to determine whether the extra effort expended to recover more nodes for histological examination improves the accuracy of staging. Method Pathology reports, histology worklists, and haematoxylin and eosin (H&E) slides of 334 CRC resections were reviewed. The total number of nodes and the number of positive nodes harvested from the first and additional searches were recorded for each patient. Results The number of nodes retrieved from the 334 resections at the first search ranged from 0 to 57 (mean: 14.2), with 195 patients (58.4%) having ≥ 12 nodes. Nodal metastasis was found in 122 (33.6%) patients. Additional searches were performed on 115 patients, including 91 with

Background and Aim: Hepatocellular carcinoma (HCC) is unique in that the presence of vascular invasion significantly changes tumor stage. Even though searching for vascular invasion is a common practice in surgical pathology, there appears to be a great variation among pathologists in its recognition. This study was designed to assess whether HCC could be accurately staged using vascular invasion as a staging parameter. Methods: The interobserver and intraobserver agreement for vascular invasion was analyzed in 126 liver resections for HCC. Selected slides were circulated twice among six pathologists for independent review using their own criteria. One to three representative images from 26 equivocal cases selected by one of the authors were re-evaluated by the pathologists. The presence or absence of vascular invasion on each slide or image was recorded as yes or no. The results were analyzed using unweighted kappa statistic analysis for multiple raters. Results: The interobserver agreement was moderate on two slide circulations with kappa values of 0.50 (95% confidence interval 0.45–0.55) and 0.43 (0.38–0.47), respectively. The kappa value dropped significantly to 0.19 (0.09–0.29) on selected images photographed from controversial cases. The intraobserver agreement was moderate, with kappa values ranging from 0.23 to 0.56 (mean = 0.45). Conclusions: Pathologists can reproducibly recognize vascular invasion in many HCC cases but may have difficulty in equivocal cases, which may lead to either understaging or overstaging of the tumors. This may have a significant impact on prognostic assessment and therapeutic decision making. Our observations indicate the need for improved definition for vascular invasion in HCC.

Although grading has been demonstrated to be an important prognostic factor in ovarian serous carcinoma, there is no system universally used to perform this task. A few years ago, we proposed a two-tier system for grading ovarian serous carcinoma that is based primarily on the assessment of nuclear atypia (uniformity vs. pleomorphism) in the worst area of the tumor. Tumor grade in this two-tier system is correlated with survival. After being used by numerous pathologists and trainees at The University of Texas M.D. Anderson Cancer Center (MDACC) for 15 years, we have observed that this system is user-friendly and reproducible. We undertook this study to evaluate the interobserver and intraobserver variability among a group of 7 gynecologic pathologists and 2 general surgical pathologists using this grading system. A total of 80 cases of ovarian serous carcinoma, 40 low-grade and 40 high-grade, were circulated twice among these pathologists. Slides with examples of low-grade and high-grade serous carcinoma were sent with the unknowns. A website was used to provide diagnostic criteria, images of examples of ovarian low-grade and high-grade carcinoma, and a log form to facilitate data entry. Statistical analysis demonstrated an overall kappa statistic among the different observers of 0.909. The intergrader kappa's ranged from 0.717 to 1.000 in the first round of the review and from 0.701 to 1.000 in the second round. Eight of the participants had an intragrader kappa ranging from 0.775 to 1.000 (excellent agreement), whereas a single participant had an intragrader kappa of 0.725 (good agreement). This study demonstrates that the two-tier grading system (the MDACC grading system) for ovarian serous carcinoma on the basis of the assessment of nuclear atypia is easy to learn and is highly reproducible. These findings would support its universal use, which would be beneficial for the standardization of clinical trials and protocols, thus facilitating the understanding of this disease and investigation into the treatment of patients affected by these tumors.

ContextThe labeling of paraffin blocks and microscopic glass slides in the practice of surgical pathology varies from institution to institution and introduces potential risk of preanalytic error. Currently there are no evidence-based guidelines regarding the uniform labeling of these materials.ObjectiveTo develop recommendations that will address the need for adequate patient identification and provide a consistent method of identifying slides originating from a particular block.DesignThe College of American Pathologists Pathology and Laboratory Quality Center and the National Society for Histotechnology convened a panel of pathologists and histotechnologists with expertise in histology laboratory quality practices to develop labeling recommendations. A systematic evidence review was conducted to address 6 main key questions. Recommendations were derived from strength of evidence, open comment feedback, and expert panel consensus.ResultsTwelve guideline statements were established to assist pathology laboratories in developing standardized block and slide labeling practices. These guidelines call for the use of 2 patient identifiers, 1 of which includes the accession number and case type, on all paraffin blocks and slides. Recommendations were also developed to address the order and format in which identifying elements should appear.ConclusionsUniform labeling of paraffin blocks and slides derived from patient specimens will provide an important enhancement to patient safety by assuring that all preparations derived from a patient's tissue can be uniquely and unambiguously linked to that patient. Adoption of standardized practices additionally will improve patient care by facilitating interpretation of histologic sections when they are referred in consultation to a second institution.

Small intestinal lipomatosis is a distinctly uncommon lesion that primarily affects the distal ileum and frequently presents with signs of obstruction or intussusception. The affected segment is often carpeted by numerous, generally submucosal, lipomas. Radiologic imaging is helpful in making the diagnosis preoperatively, and surgical cure can be obtained by resection of the involved area. This case report highlights this unusual entity, discusses the preoperative and operative management, and reviews the available literature.

Although rare, congenital malignant melanoma (CMM) should be considered in the differential diagnosis of congenital skin lesions. We report a case of CMM in a 4-month-old infant presenting with an enlarging scalp mass, initially thought to be a hemangioma. Incisional biopsy of the lesion showed a compound congenital nevus with atypical cells suggestive of a proliferative nodule versus malignancy on histopathology. Subsequent excisional biopsy revealed malignant melanoma, and further workup confirmed extensive disease with distant metastases. Cytogenetic analysis of both the tumor sites showed highly abnormal karyotypes including pseudotetraploidy, telomere associations, and evidence of gene amplification, all consistent with malignancy. Fluorescence in situ hybridization demonstrated amplification of the MYC gene, with no copy number changes in CDKN2A (INK4/ARF), PTEN, or Cyclin D1. Our report details the cytogenetic and molecular studies of CMM, which provide insight into the biologic behavior of the lesions and may confirm diagnosis when histopathology is not determinant.

Nodules of the thyroid gland are common and frequently problematic specimens encountered by the diagnostic surgical pathologist. It is estimated that 4–7% of adults have a palpable thyroid nodule, and several times that many have nodules which are detectable at autopsy or by ultrasound. Of the estimated 10–20 million clinically detectable thyroid lesions in the United States, approximately 5–30% will be malignant. Thyroid nodules are more common in women, in people with a history of radiation exposure, and in those with goitrogenic-rich diets or iodine-deficient diets (Faquin, Arch Pathol Lab Med 132:622–632, 2008). Carcinomas of follicular cell origin are the most common and greatly outnumber carcinomas of C-cell origin. Secondary malignancies and lymphomas are far less common than follicular origin tumors, but they do occur and must be considered in the differential diagnosis of both benign and malignant thyroid abnormalities. The majority of carcinomas of follicular origin are indolent, with approximately 90% 10-year survival rates.

Our previous study utilizing the 2008 NCI six-category system (also known as The Bethesda System) for reporting thyroid fine-needle aspirations (FNA) identified considerable overlap in diagnosis and in assigned malignancy risk estimates for the “follicular lesion of undetermined significance (FLUS)” and “follicular neoplasm (FN)” categories and for the “suspicious for malignancy (Susp)” and “malignant” categories. We proposed a simplified Bethesda System for reporting thyroid FNAs that provided four non-overlapping, statistically significant, and more clinically relevant diagnostic categories: unsatisfactory, benign, FLUS/FN, and Susp/malignant. In the current study, six cytopathologists participated in a blinded retrospective review of 60 thyroid FNAs and kappa statistics were utilized to compare the intra- and inter-observer diagnostic agreements obtained using the six-category and the simplified four-category schemes. Surgical follow-up was used to determine which scheme provided more discrete malignancy risk estimates. Use of the simplified four-category scheme significantly improved intra- and inter-observer diagnostic agreement levels, significantly increased the sensitivity of FNA for a diagnosis of carcinoma in the subsequently resected thyroid glands, and provided non-overlapping malignancy risk estimates for each diagnostic category. Diagn. Cytopathol. 2012;40:E62–E68. © 2011 Wiley Periodicals, Inc.

To present an unusual case of multiple endocrine neoplasia type 2A (MEN 2A) syndrome and to describe how this case differs from the typical clinical features and usual genetic variations seen in classic MEN 2A syndrome.We describe the work-up, diagnosis, and treatment course of a patient who presented with multi-focal pheochromocytomas, parathyroid adenoma, thyroid abnormalities, and a RET mutation.A 65-year-old man with previously treated pheochromocytoma presented with a parathyroid adenoma, multiple thyroid nodules, and a RET polymorphism. C-cell hyperplasia (CCH) or medullary thyroid carcinoma (MTC) occurs with nearly 100% penetrance in patients with MEN 2A syndrome. Our patient did not have CCH or frank MTC, but he expressed the other manifestations of the MEN 2A syndrome.MEN 2A syndrome is characterized by the occurrence of MTC, pheochromocytomas, and parathyroid hyperplasia or adenomas. It is inherited in an autosomal dominant fashion, and more than 80% of patients with MEN 2A have a specific substitution on codon 634 of the RET proto-oncogene. Despite the nearly 100% penetrance of MTC or CCH in patients with MEN 2A, our patient did not have this. Additionally, he exhibited a RET mutation that is uncommonly seen in classic MEN 2A syndrome. Our patient may have a MEN 2A variant or a pseudo-MEN 2A syndrome.

Hepatocellular carcinoma (HCC) is unique in that the presence of vascular invasion significantly changes tumor stage. Even though searching for vascular invasion is a common practice in surgical pathology, there appears to be a great variation among pathologists in its recognition. This study was designed to assess whether HCC could be accurately staged using vascular invasion as a staging parameter.The interobserver and intraobserver agreement for vascular invasion was analyzed in 126 liver resections for HCC. Selected slides were circulated twice among six pathologists for independent review using their own criteria. One to three representative images from 26 equivocal cases selected by one of the authors were re-evaluated by the pathologists. The presence or absence of vascular invasion on each slide or image was recorded as yes or no. The results were analyzed using unweighted kappa statistic analysis for multiple raters.The interobserver agreement was moderate on two slide circulations with kappa values of 0.50 (95% confidence interval 0.45-0.55) and 0.43 (0.38-0.47), respectively. The kappa value dropped significantly to 0.19 (0.09-0.29) on selected images photographed from controversial cases. The intraobserver agreement was moderate, with kappa values ranging from 0.23 to 0.56 (mean = 0.45).Pathologists can reproducibly recognize vascular invasion in many HCC cases but may have difficulty in equivocal cases, which may lead to either understaging or overstaging of the tumors. This may have a significant impact on prognostic assessment and therapeutic decision making. Our observations indicate the need for improved definition for vascular invasion in HCC.

A National Cancer Institute (NCI) “Thyroid Fine-Needle Aspiration (FNA) State of the Science Conference” recently proposed standardized nomenclature and “risks of malignancies” associated with various diagnostic categories. We evaluated the evidence levels of the data used by NCI to predict malignancy risks and whether those estimates had clinical validity in our patient population. Eight hundred seventy-nine patients underwent thyroid FNA during 2006. FNA diagnoses were translated into NCI diagnostic categories, and 2-year follow-up retrospective information was obtained. Four percentages of malignancies were calculated for each diagnostic category using follow-up information from FNA, thyroidectomy, both, and all patients as denominators. 95% confidence intervals (CI) were estimated for all proportions, and results were analyzed with chi-square statistics. “Relative risk” calculations were performed using the percentage of malignancies in the entire population under study as a denominator. Most of the studies cited by the NCI provided incomplete and variable level III evidence based mainly on surgical follow-up. Among our patients, the percentages of malignancies calculated with follow-up data from all patients as the denominator were similar to the “risk estimates” proposed by the NCI, but estimates based on surgical follow-up overestimated the probability of thyroid malignancy for patients with FNA diagnosis of “benign” and “follicular lesions of undetermined significance” (FLUS). Relative risk and 95% CI calculations suggested that the NCI classification could be simplified into three categories: “benign,” “FLUS + neoplasm,” and “suspicious + malignant.” Diagn. Cytopathol. 2010. © 2009 Wiley-Liss, Inc.

A case of recurrent rhabdomyosarcoma in an adult is reported. The primary disease at presentation was in the maxillary sinus with metastatic spread to regional lymph nodes. A complete response (CR) and a 14-month disease-free interval (DFI) were obtained with combination therapy. The sole site of relapse was an intratesticular mass. Management implications are discussed.

Background: Transverse sections of human scalp biopsy specimens can provide both qualitative and quantitative information about follicular histopathology not readily available in vertically sectioned specimens. Objective: We propose a method for making the processing and interpretation of such specimens easier. Methods: All scalp biopsy specimens obtained during the past 18 months in our institution for the evaluation of alopecia were processed for transverse sections by means of a technique employing trisection or quadrisection (rather than the standard bisection), and maintaining all sections in the same anatomic orientation (deep to superficial) in all tissue pieces on microscopic slides. Results: More than 120 transversely sectioned specimens from more than 75 patients have been processed with this technique. The typical number of slides cut per specimen decreased from between 12 and 20 to between 1 and 4, with no loss of clinical information. Conclusion: This technique allows transverse sections for evaluation of alopecia to be processed in a more cost-effective manner and compares favorably with previously published techniques in providing diagnostic information.

Verruciform xanthoma is a rare benign lesion. The majority of the cases occur on the oral mucosa. However, other sites, particularly the anogenital region, may be involved. We report the eleventh case in the literature of verruciform xanthoma of the penis. Genital verruciform xanthoma is significant because it can simulate verrucous carcinoma or invasive squamous cell carcinoma. Proper diagnosis by clinical recognition, adequate but limited biopsy and histopathological examination will avoid unnecessarily aggressive surgical procedures. The pertinent clinical and histological features of our case are described and the literature on penile verruciform xanthoma is reviewed.

Introduction: Colloid carcinoma (CC) is a rare invasive carcinoma of the pancreas believed to arise from intestinal type intraductal papillary mucinous neoplasm (IPMN). The cytologic features of CC are not well described because previous cytology descriptions of invasive carcinomas arising from IPMN do not consistently subtype the invasive carcinoma. Furthermore, current diagnostic criteria may not have been used to diagnose the histologic correlates for prior descriptions of CC. We describe fine needle aspiration (FNA) findings for CC using histologically confirmed cases meeting current diagnostic criteria. Materials and Methods: We searched our archive for ultrasound-guided FNAs of the pancreas with histologic correlation showing CC defined by containing >80% extracellular mucin and reviewed corresponding cytology and histology. The following morphologic parameters were evaluated: cellularity, quantity and quality of mucin, cytoarchitecture, cell size, shape, and nuclear features. Results: Six FNA cases from resected CCs were identified. In 4/6 patients an associated IPMN of predominantly intestinal type was identified with the CC component comprising

Background Radioactive iodine (RAI) is a treatment for patients with thyroid carcinoma after thyroidectomy. The Na+/I- symporter (NIS) plays a role in this ability to concentrate iodide within tumor cells. Recent studies have shown a correlation between immunohistochemical staining of NIS and the ability to concentrate iodide mainly in tumors > 1.0 cm. Here only papillary thyroid microcarcinomas (PTMC) with or without LN metastasis (LNM) are evaluated to observe NIS expression. Design A retrospective study involved 47 cases of PTMC (24 with and 23 without LNM). Immunostains were performed using two different monoclonal anti-NIS antibodies: clone SPM186 from Abeam and clone FP5A from Millipore. Results The findings were very similar using two different monoclonal antibodies. One out of 24 cases with LNM displayed focal expression of NIS while two cases showed several NIS-positive cells. None of 23 cases without LNM and none of metastatic tumors showed NIS expression. Ten benign nodules with Hiirthle cell features exhibited moderate membranous stain. Conclusion PTMC with or without LNM show minimal to no expression of NIS. NIS expression and function may not be the same in PTMC vs a non-PTMC and RAI therapy may not be effective in treating PTMC due to lack of NIS.

Papillary fibroelastomas comprise approximately 7.9% of benign primary cardiac tumors. Although papillary fibroelastomas were at first discovered incidentally at autopsy or during heart surgery, these tumors are increasingly being identified by echocardiography. This article reviews those papillary fibroelastomas detected by transthoracic or transesophageal echocardiography and discusses the echocardiographic features of these tumors, associated symptoms, and management. Echocardiography is important in influencing management decisions regarding excision, valve replacement, and valve repair.

A 26-year-old female pediatric nurse was referred to the dermatology service from the emergency department with a 4-day history of fever, malaise, and sore throat. Two days earlier, numerous oral lesions developed along with painful blistering digital lesions, one on each hand. She denied a history of recurrent oral or genital lesions and was taking no medications. Physical examination revealed a mildly toxic-appearing white woman with an oral temperature of 38.2°C. There were numerous 3- to 8-mm erosions of the lower labial mucosa with surrounding erythema and areas of coalescence ( Figure 1 ). The patient also had scattered erosions of the attached gingiva, dorsum of the tongue, and the posterior pharynx. The cervical lymph nodes were enlarged and painful. Additionally, the patient had two paronychial vesicopustules, one on the left thumb, the other on the right index finger. These lesions were deep-seated, unilocular, and exquisitely tender ( Figure 2 ). Tzanck smears were