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Introduction: Cytologic screening for urothelial carcinoma is fraught with low sensitivity, a high indeterminate rate, and until recently, poor standardization of terminology. The Johns Hopkins Hospital John K. Frost Cytopathology Laboratory has recently developed and published a template for reporting urine cytopathology; herein, we evaluate its interobserver reproducibility., Materials and Methods: Two sets of 100 cases each were deidentified; each set was reviewed by 5 of 10 observers in a randomized order at the direction of computerized data collection software that tracked observation time as well as observer classification of the atypia-no atypia, atypia (AUC-US), or atypia suggestive of high-grade urothelial carcinoma (AUC-H). Specific morphologic features were also recorded. Cases were grouped into low-, intermediate-, and high-agreement based on the number of observers who made the assessment. The findings were correlated against clinical outcomes., Results: High agreement among observers about the presence or absence of high-grade features was possible in approximately two-thirds of indeterminate urine cases. Time and order did not factor significantly into observer propensity for identifying atypical features or favoring either AUC-US or AUC-H, and cases with high agreement about the presence of high-grade features were more likely to have a malignant follow-up. Furthermore, AUC-H diagnoses based on 2 or more high-grade features had a significantly higher malignancy risk than AUC-US diagnoses did., Conclusions: AUC-H is a valid diagnostic category with specific, reproducibly identified features that portend a higher risk of malignancy than the findings of AUC-US., (Copyright © 2014 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Objectives: The tall cell variant of papillary thyroid carcinoma (TCV-PTC) is an aggressive variant of PTC requiring accurate cytopathologic diagnosis for early aggressive management., Study Design: Twenty-five cases of TCV-PTC in which the tall cells comprised at least 30% of surgically resected tumor were included in the study. The direct smears from a preoperative fine needle aspiration (FNA) and available hematoxylin and eosin cell block sections were reviewed. Ten cases of TCV-PTC were randomly selected and blinded with an equal number of conventional PTC cases. Representative slides were independently reviewed by 7 cytologists., Results: In a majority of the cases, the FNA direct smears were hypercellular and displayed flat monolayer sheets of cells. Tall columnar cells with cytoplasmic tails were seen in 56% of cases. The presence of large polygonal follicular cells with abundant granular oncocytic cytoplasm and distinct cell borders was the most common feature seen in all cases. Seventeen (68%) cases displayed intranuclear pseudoinclusions in cells with abundant granular cytoplasm. A correct diagnosis of TCV-PTC was made in 30-40% of cases by 7 study participants., Conclusions: The correct recognition of TCV-PTC features in preoperative FNA is important for clinical management, and reporting these features in a cytopathology report is suggested.

Pancreatic neuroendocrine tumors (PanNETs) are typically solid neoplasms but in rare instances may present as cystic lesions. This unusual presentation can make clinical diagnosis challenging. In addition, the clinical and histopathologic characteristics of cystic PanNETs are poorly defined. We identified 53 cystic PanNETs in our single-institution experience of 491 surgically resected PanNETs. Similar to solid PanNETs, cystic PanNETs developed with an equal sex distribution and over a wide age range (23 to 91 y; mean, 52 y). The unusual cystic appearance made radiologic differentiation from other cystic pancreatic neoplasms difficult with a misdiagnosis in 23 of 53 (43%) cases. An association between cystic PanNETs and multiple endocrine neoplasia type 1 or multifocal disease [5 of 53 (9%) and 7 of 53 (13%), respectively] was not observed as compared with solid PanNETs (P=0.34 and P=0.31, respectively). Grossly, cystic PanNETs were predominantly located in the tail of the pancreas (n=28, 53%) and were similar in size (mean, 3.3 cm) to solid PanNETs (mean, 4.1 cm; P=0.12). All cysts were unilocular (n=53, 100%) and filled with clear to straw-colored fluid. Larger cysts were sometimes noted to be hemorrhagic. Histologically, the cysts were lined by a thin fibrous band that separated the cyst from the neoplastic cells. In comparison with their solid counterparts, cystic PanNETs were less likely to demonstrate tumor necrosis (6%; P=0.04), perineural invasion (8%; P<0.001), vascular invasion (4%; P<0.001), regional lymph node metastasis (13%; P<0.001), and synchronous distant metastasis (4%; P=0.015). The neoplastic cells of the cystic PanNETs were well differentiated (n=53, 100%) with a low mitotic rate and low Ki-67 proliferation index (range, 0.2% to 11%; mean, 1.8%). On the basis of both the American Joint Cancer Committee and European Neuroendocrine Tumor Society staging systems, the majority of cystic PanNETs presented at a lower pathologic stage as compared with solid PanNETs. In summary, cystic PanNETs are a distinctive subgroup of PanNETs with unique clinical, radiographic, and pathologic features.

Background: Intrapancreatic accessory spleen (IPAS) is a rare benign lesion of the pancreas that frequently clinically and radiographically mimics a solid neoplasm. Very rarely, epidermoid cysts may form in IPAS and be mistaken for a cystic neoplasm of the pancreas on radiographic imaging. IPAS and epidermoid cyst involving intrapancreatic cyst (ECIPAS) are benign, and, if recognized, do not require surgical intervention. There are few reports of the cytopathologic features of IPAS diagnosed by fine-needle aspiration (FNA)., Methods: Here we report a series of 6 cases of endoscopic ultrasound (EUS)-guided FNA of IPAS, 3 of which had histological confirmation, including 1 case of histologically confirmed ECIPAS., Results: Cytomorphologic features of IPAS include a polymorphous population of hematopoietic cells, including lymphocytes, eosinophils, histiocytes, plasma cells, and red blood cells, admixed with numerous small blood vessels representing splenic sinusoids. CD8 immunostaining of cell block or core biopsy material highlights splenic endothelial cells and confirms the diagnosis. FNA of ECIPAS reveals predominantly macrophages and proteinaceous debris., Conclusions: Diagnostic pitfalls include pancreatic neuroendocrine tumor. If IPAS is recognized as a diagnostic consideration on EUS-FNA, unnecessary surgical resection may be avoided., (Copyright © 2012 American Cancer Society.)

Background: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), a rare subtype of Hodgkin lymphoma, is an indolent tumor with frequent instances of disease recurrence but a favorable prognosis. To the best of the authors' knowledge, there are only limited descriptions of NLPHL in the cytology literature because it was only formally recognized as a distinct entity in 1994., Methods: In the current study, all cases of NLPHL diagnosed on excisional biopsy (n = 6 cases) at the study institution between 2000 and 2011 that had undergone previous fine-needle aspiration (FNA) were reviewed, with a focus on cytomorphologic features., Results: Four of 6 cases were termed benign on FNA; however, there was retrospective recognition of characteristic LP cells in all cases. Unlike classical Hodgkin lymphoma, the tumor cells of NLPHL were often found to be mononucleate and presented in a background of small lymphocytes. Other features identified included epithelioid histiocytes and numerous bare atypical nuclei., Conclusions: Cases of NLPHL are commonly misdiagnosed as benign reactive lymphoid tissue and therefore a careful search using high magnification for LP cells is recommended in the evaluation of lymph node FNAs., (Copyright © 2012 American Cancer Society.)

The use of human papillomavirus DNA testing plus Papanicolaou (Pap) testing (cotesting) for cervical cancer screening in women 30 years and older has been recommended since 2006. However, few studies have detailed the adoption of such cotesting in clinical practice. We examined the trends in monthly percentage of Pap tests ordered as cotests in our laboratory over a 2.5-year period and used joinpoint regression to identify periods in which there was a change in the average monthly proportion of cotests. Cotesting of patients 30 years and older increased from 15.9% in January 2008 to 39.4% in June 2010. In patients aged 18 to 29 years, cotesting initially increased, but showed a downward trend in the last 14 months of the study, ending at 7.7% in June 2010. Our study highlights increased adoption of age-appropriate cotesting as well as the persistence of age-inappropriate cotesting.

Background: Signet ring carcinoma is an exceedingly rare and aggressive variant of primary bladder carcinoma. The cytomorphologic features of this rare entity in urinary specimens have not been well characterized., Methods: Twenty-seven cases of signet ring cell carcinoma of the urinary bladder were identified from the pathology archives of The Johns Hopkins Hospital (1989-2011). Of these, 6 cases with prior urinary cytology specimens were studied., Results: There were 5 males and 1 female, with a mean age of 62 years. The presenting complaints included hematuria with or without symptoms of bladder irritation. Histopathologically, there were 5 cases of primary bladder carcinoma and 1 case of metastatic colonic signet ring cell carcinoma. The salient cytomorphologic features included scattered malignant epithelial cells, displaying distinct cell borders, abundant cytoplasm with a single large, discrete mucin vacuole, and eccentric irregular nuclei with prominent nucleoli. Primary adenocarcinoma additionally revealed a few intact malignant glandular epithelial fragments. Metastatic colonic signet ring cell carcinoma displayed predominantly singly dispersed malignant cells with eccentrically placed, oval nuclei with occasional small nucleoli and a moderate amount of vacuolated cytoplasm., Conclusion: Signet ring cell carcinomas are rarely encountered in urinary cytology. The differential diagnosis includes distended histiocytes or degenerated urothelial cells, primary signet ring cell carcinoma, and metastatic adenocarcinoma., (Copyright © 2012 S. Karger AG, Basel.)

Cutaneous angiosarcoma can sometimes mimic other benign and malignant lesions, thereby presenting a difficult differential diagnosis. In the two cases of cutaneous angiosarcoma presented herein, extensive foamy cell alteration of tumor cells resembled a reactive xanthogranulomatous process. Foamy cell angiosarcoma is an unusual and deceptively benign morphologic variant of cutaneous angiosarcoma. Critical features for diagnosis include the presence of a deep, permeative, sometimes 'scaffolding' growth pattern and subtle areas of vascular formation.

Numerous methods exist for monitoring residual disease in multiple myeloma using peripheral blood, urine, and bone marrow (BM) techniques. This study was conducted in a cohort of 83 patients to compare residual disease detection using serum protein electrophoresis (SPE) and urine protein electrophoresis (UPE) with immunofixation with immunoperoxidase staining of BM tissue sections. Of the 83 patients, 49 had a positive SPE and/or UPE result and all had BM involvement shown by immunohistochemical analysis. The results for SPE and UPE were negative in 17 patients, and all 17 had a negative immunohistochemical BM result for a negative predictive value for SPE/UPE of 100%. In addition, SPE and UPE detected residual disease in 17 patients with negative BM biopsy studies. SPE and UPE can be used to screen patients for residual disease, and negative results for both can obviate the need for BM biopsy for the detection of residual disease by immunohistochemical analysis.

Cutaneous focal mucinosis has been rarely reported in association with follicular induction of the epidermis. We present 2 cases of focal mucinosis with follicular induction and describe the histopathologic findings to create awareness of this association and to prevent confusion with other diagnoses such as dermatofibroma with follicular induction or superficial basal cell carcinoma.

Objectives: Expression of transcription factors that mediate epithelial-mesenchymal transition (EMT), such as Twist and Slug, is correlated with poor prognosis in many tumor types. Selected EMT markers were studied in a series of pancreatic ductal adenocarcinomas (PDAs) and benign pancreatic tissues to determine whether expression levels correlated with diagnosis, histologic grade, or patient outcome., Methods: Immunohistochemical stains for Twist, Slug, and N-cadherin were performed using a tissue microarray containing 68 PDAs and 38 samples of normal pancreas or chronic pancreatitis tissues., Results: Twist and Slug were identified in both the nucleus and cytoplasm of benign pancreatic ductal epithelium, chronic pancreatitis, and PDA. Compared with normal ductal epithelium, nuclear levels of Twist are decreased in PDA. None of the other EMT markers showed significant differences in staining indices among the diagnostic groups. There were no correlations between EMT marker expression and histologic grade. Epithelial-mesenchymal transition marker expression was not associated with N-cadherin expression, patient outcome, or duration of survival., Conclusions: Decreased expression of nuclear Twist is observed in malignant pancreatic epithelium. However, use of Twist as a diagnostic marker is precluded because decreased expression is also seen in chronic pancreatitis. None of the markers studied were predictive of patient outcome.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a clinically effective neurosurgical treatment for Parkinson disease. Tissue reaction to chronic DBS therapy and the definitive location of active stimulation contacts are best studied on a postmortem basis in patients who have undergone DBS. The authors report the postmortem analysis of STN DBS following 5 years and 11 months of effective chronic stimulation including the histologically verified location of the active contacts associated with bilateral implants. They also describe tissue response to intraoperative test passes with recording microelectrodes and stimulating semimacroelectrodes. The results indicated that 1) the neural tissue surrounding active and nonactive contacts responds similarly, with a thin glial capsule and foreign-body giant cell reaction surrounding the leads as well as piloid gliosis, hemosiderin-laden macrophages, scattered lymphocytes, and Rosenthal fibers; 2) there was evidence of separate tracts in the adjacent tissue for intraoperative microelectrode and semimacroelectrode passes together with reactive gliosis, microcystic degeneration, and scattered hemosiderin deposition; and 3) the active contacts used for approximately 6 years of effective bilateral DBS therapy lie in the zona incerta, just dorsal to the rostral STN. To the authors' knowledge, the period of STN DBS therapy herein described for Parkinson disease and subjected to postmortem analysis is the longest to date.