bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of a Phonological Intervention on EEG Connectivity Dynamics in Dyslexic Children
Authors: Bedo Nicolas , Ender-Fox Dikla , Chow Janet , Siegel Linda , Ribary Urs , M. Ward Lawrence
Published: February 2021

We examined the brain networks and oscillatory dynamics, inferred from EEG recordings during a word-reading task, of a group of children in grades 4 and 5 (ages 9–11), some of whom were dyslexic. We did this in order to characterize the differences in these dynamics between typical and dyslexic readers, and to begin to characterize the effect of a phonological intervention on those differences. Dyslexic readers were recorded both before and after they participated in a FastForWord (FFW) reading training program for approximately six months and typical readers were recorded once during this period. Before FFW dyslexic readers showed (i) a bottleneck in letter recognition areas, (ii) expansion in activity and connectivity into the right hemisphere not seen in typical readers, and (iii) greater engagement of higher-level language areas, even for consonant string stimuli. After FFW, dyslexic readers evinced a significant reduction in the engagement of language processing areas, and more activity and connectivity expanding to frontal areas, more resembling typical readers. Reduction of connectivity was negatively correlated with gains in reading performance, suggesting an increase in communication efficiency. Training appeared to improve the efficiency of the alternative (bilateral) pathways already used by the dyslexic readers, rather than inducing them to create new pathways more similar to those employed by typical readers.
Emergency Management of Acute Pancreatitis
Authors: Karaali Rezan , Topal Firdes
Published: February 2021

Acute pancreatitis (AP) is the sudden inflammation of the pancreas, and it may be confined to the pancreas, or more life-threatening, affecting all organs and systems. AP is a common gastrointestinal condition Worldwide and is associated with cost to the health care system. It progresses mildly in 80% of patients and resolves with treatment, but in cases of severe AP, with mortality of around 30% recorded. In this section, we will discuss the first management of the AP in the emergency department. Because this is the period when management decisions can change the course of the disease and the length of stay in the hospital. In the management AP, approaches regarding the utility and timing of antibiotics, the timing and type of nutritional support, endoscopic retrograde cholangiopancreatography (ERCP) and cholecystectomy approaches are constantly being updated. Treatment is mainly related to the severity of the disease. With early diagnosis and treatment, most of the patients can be discharged, and the development of complications and mortality can be reduced. Therefore, emergency management is important in acute pancreatitis.
AgNano, the Construction of Occupational Health Standards: A Status Update
Authors: Foladori Guillermo , Invernizzi Noela
Published: February 2021

The regulation of chemical substances involves a negotiation between social actors to translate controversial scientific evidence about risks into legal norms. This chapter addresses the discussion elicited by a public consultation on a voluntary regulation guide on silver nanoparticles (AgNP) in workplaces. It examines the comments made from 2016 to 2018 by diverse social actors – business representatives, non-governmental organizations (NGO), and independent researchers – to two successive draft versions of a Recommended Exposure Limit (REL) in working environments with AgNP. The REL is a voluntary guideline on permissible exposure limits elaborated by the NIOSH in the U.S. The methodology used was a qualitative content analysis, structured upon a historical and sociotechnical contextualization of nanotechnologies carried out through literature review. The findings show how different social actors position themselves in the controversy, revealing a pattern of behavior consistent with their position in the research, production, and commercialization of this new nanomaterial. While a group of actors, aligned with the interests of AgNP producers, proposed the restriction of mandatory and AgNP-specific regulation, another group of more heterogeneous actors, identified with the interests of workers and consumers, demanded more scientific and technical information and stricter health protection measures.
Physician Satisfaction With Surgical Pathology Reports: A 2-Year College of American Pathologists Q-Tracks Study
Authors: Nakhleh Raouf E. , Souers Rhona , Ruby Stephen G.
Published: February 2021

Context.—There are multiple elements that can be measured to assess the quality of a surgical pathology laboratory. Overall customer satisfaction is an excellent “global” measure, because it highlights the unique insight of laboratory performance from the users' perspective.

Objective.—To measure customer satisfaction with surgical pathology reports.

Design.—This study was based on a subscription Q-Tracks study. Voluntary participants were asked to distribute and collect a minimum of 25 surveys per quarter from their clients. Four parameters were graded, which included overall satisfaction, report turnaround time (TAT), completeness, and style on a scale of 1 (poor) to 5 (excellent). Each laboratory submitted quarterly data to the College of American Pathologists, where the data were tabulated and analyzed. Each laboratory could compare their performance in all 4 measures against the entire cohort or a selected subgroup of laboratories. Overall customer satisfaction with surgical pathology reports and 3 subcategories of report TAT, completeness, and style were the main outcome measures.

Results.—This study ran during 2004 and 2005, with 41 and 33 participant laboratories, respectively. The median score for overall satisfaction, TAT, completeness, and style were 4.57, 4.31, 4.62, and 4.64 in 2004, and 4.64, 4.56, 4.65, and 4.68 in 2005, respectively. Most laboratories reported results for 4 quarters or fewer. There was no statistically significant change in overall satisfaction over time.

Conclusions.—Overall satisfaction scores for surgical pathology reports as well as satisfaction with report TAT, completeness, and style were high. Report TAT received the lowest scores of all parameters.
Prostatic Stromal Hyperplasia With Atypia: Follow-up Study of 18 Cases
Authors: Hossain Deloar , Meiers Isabelle , Qian Junqi , MacLennan Gregory T. , Bostwick David G.
Published: February 2021

Context.—Prostatic stromal hyperplasia with atypia is a rare lesion that can be mistaken for sarcoma because of the presence of atypical, bizarre, degenerative myocyte nuclei.

Objective.—To determine the diagnostic criteria and clinical significance of prostatic stromal hyperplasia with atypia.

Design.—Eighteen cases of prostatic stromal hyperplasia with atypia were reviewed from the consultation file of one of the authors (D.G.B.).

Results.—Prostatic stromal hyperplasia with atypia consists of 1 or more ill-defined, uncircumscribed, hyperplastic stromal nodules, with variable numbers of atypical, bizarre giant cells, with vacuolated nuclei, smudged chromatin, and frequent multinucleation infiltrating around benign acini. There was a hypocellular, loose, myxoid stromal matrix, with ectatic hyalinized vessels and mild to moderate chronic inflammation. Stromal cells displayed intense immunoreactivity for androgen receptors and vimentin, but moderate reactivity for desmin and actin. There were 3 local recurrences, with a mean follow-up of 6.3 years (range, 0.5–14 years), but none developed evidence of sarcomatous transformation or malignancy.

Conclusions.—Prostatic stromal hyperplasia with atypia is a rare, benign lesion, composed of degenerative myocytes with atypia that is histologically and clinically reminiscent of benign counterparts in the myometrium, breast, vulva, vagina, and elsewhere. Recognition of this distinctive entity should allow separation from phyllodes tumor and sarcoma of the prostate. The phrase stromal tumor of uncertain malignant potential is inappropriate for this benign tumor, and its use is discouraged.
Gastroduodenitis Associated With Yttrium 90–Microsphere Selective Internal Radiation: An Iatrogenic Complication in Need of Recognition
Authors: Ogawa Fumihiro , Mino-Kenudson Mari , Shimizu Michio , Ligato Saverio , Lauwers Gregory Y.
Published: February 2021

Context.—Selective internal radiation (SIR) therapy (SIRT) with yttrium 90 microspheres is increasingly used as an alternative therapeutic modality for patients with inoperable liver tumors. During administration of microspheres via the hepatic artery branches, some may on occasion be misdirected and be caught in the capillary bed of the duodenal and/or stomach.

Objective.—To better characterize the histopathologic features of these complications.

Design.—We report herein our experience with 3 patients who received SIR and developed gastroduodenal complications.

Results.—SIR-microsphere–induced gastroduodenitis was diagnosed from 10 days to 5 months after treatment. In all 3 cases, purple particles measuring about 40 ;gmm in diameter were observed. An array of changes ranging from mucosal ulceration to epithelial changes were seen. Fibrinopurulent exudate was admixed with granulation tissue and reactive stromal cells. Epithelial changes included apoptosis and mucin depletion. Glandular cystic dilatation and epithelial flattening were also common as well as foveolar hyperplasia, suggestive of reparative changes in one case. Capillary ectasia and prominent plump endothelial cells were also present.

Conclusion.—The spectrum of the alterations is consistent with radiotherapy-induced changes. Given the recent approval by the US Food and Drug Administration for the use of SIRT, it is anticipated that more patients will be treated with this modality. Pathologists should become aware of the adverse effects associated with its use.
Immunohistochemical Evaluation of Androgen Receptor, HER-2/neu, and p53 in Benign Pleomorphic Adenomas
Authors: DeRoche Tom C. , Hoschar Aaron P. , Hunt Jennifer L.
Published: February 2021

Context.—Immunohistochemical stains for androgen receptor (AR), HER-2/neu, and p53 are used as diagnostic markers associated with malignancy in several histologic types of salivary gland tumors. These markers may be useful in differentiating pleomorphic adenoma with cytologic atypia from intracapsular carcinoma ex pleomorphic adenoma (CXPA), as these tumors are often difficult to distinguish on the basis of morphology alone.

Objective.—To determine whether AR, HER-2/neu, and p53 expression can be seen in entirely benign pleomorphic adenomas.

Design.—Androgen receptor, HER-2/neu, and p53 immunoreactivity was assessed in 41 histologically and clinically benign pleomorphic adenomas.

Results.—A total of 3 of 41 pleomorphic adenomas exhibited multifocal areas with moderate staining for HER-2/ neu and AR. The positive staining was mainly confined to the epithelial component, where the ductal epithelium showed no cytologic atypia. Immunoreactivity for p53 was observed in the epithelial component of 5 of 41 cases, none of which stained for HER-2/neu and AR. Mean mitotic rate and Ki-67 index were 1 per 10 high-powered fields and 2.7% in HER-2/neu– and AR-positive cases and 1 per 10 high-powered fields and 2.2% in p53-positive cases.

Conclusions.—HER-2/neu, AR, and p53 are expressed in a subset of histologically and clinically benign pleomorphic adenomas. These markers cannot be used to reliably predict early carcinomatous transformation in pleomorphic adenoma.
Sister Mary Joseph Nodule as a First and Only Sign of Extraovarian Carcinoma: A Case Report and Review of the Literature
Authors: Kolwijck Eva , Kruitwagen Roy F. , Massuger Leon F.
Published: February 2021

Sister Mary Joseph nodule is one of the less well-known signs of intra-abdominal metastatic disease. The primary tumor site is nearly always detected because of specific morphologic and immunohistochemical features of the umbilical tumor. We describe a case of a 74-year-old woman with a Sister Mary Joseph nodule, which appeared most likely to be metastatic from a primary serous papillary ovarian carcinoma based on the histologic examination and the immunohistochemical analysis. Despite an extensive workup, no primary tumor could be detected and therefore we ultimately diagnosed the tumor as an extraovarian carcinoma with primary site at the umbilicus. After a literature search we concluded that a primary adenocarcinoma of the umbilicus is extremely rare and to our knowledge has never been described with both morphologic and immunohistochemical features of a serous ovarian carcinoma.
Granular Cell Astrocytoma
Authors: Shi Yan , Morgenstern Nora
Published: February 2021

Granular cell astrocytoma (GCA) is a rare type of malignant brain tumor with distinct morphologic features and aggressive clinical behavior. Almost all GCAs occur in the cerebral hemispheres. It is characterized by a prominent component of bland-looking granular cells. The tumor cells are usually positive for glial fibrillary acidic protein, S100, CD68, and epithelial membrane antigen. The most important differential diagnoses include a number of reactive lesions such as cerebral infarction, multiple sclerosis, and progressive multifocal leukoencephalopathy. Electron microscopic study reveals that the granules of GCA correspond to an increased number of intracytoplasmic lysosomes. The histogenesis of GCA is still unclear, but most people believe it originates from astrocytes. Loss of 9p and 10q were identified in almost all cases of GCA, but they are not specific for this tumor. Surgical excision plus postoperative chemotherapy or radiotherapy is the choice for most patients with GCA.
Intracranial Lesions Mimicking Neoplasms
Authors: Cunliffe Clare H. , Fischer Ingeborg , Monoky David , Law Meng , Revercomb Carolyn , Elrich Susan , Kopp Michael Jered , Zagzag David
Published: February 2021

Context.—A broad spectrum of nonneoplastic conditions can mimic a brain tumor, both clinically and radiologically. In this review we consider these, taking into consideration the following etiologic categories: infection, demyelination, vascular diseases, noninfectious inflammatory disorders, and iatrogenic conditions. We give an overview of such diseases, which represent a potential pitfall for pathologists and other clinicians involved in patient care, and present selected cases from each category.

Objective.—To illustrate the radiologic and pathologic features of nontumoral intracranial lesions that can clinically and radiologically mimic neoplasia.

Data Sources.—Case-derived material and literature review.

Conclusions.—A variety of nonneoplastic lesions can present clinically and radiologically as primary or metastatic central nervous system tumors and result in surgical biopsy or resection of the lesion. In such situations, the pathologist has an important role to play in correctly determining the nature of these lesions. Awareness of the entities that can present in this way will assist the pathologist in the correct diagnosis of these lesions.
Flow Cytometric Immunophenotyping of Anaplastic Large Cell Lymphoma
Authors: Muzzafar Tariq , Wei Eric X. , Lin Pei , Medeiros L. Jeffrey , Jorgensen Jeffrey L.
Published: February 2021

Context.—Anaplastic large cell lymphoma (ALCL) is usually diagnosed by histologic and immunohistochemical analysis. However, fine-needle aspiration is becoming a popular alternative to lymph node biopsy, and flow-cytometric immunophenotyping is often used to analyze fine-needle aspiration specimens.

Objective.—To review our experience using flow-cytometric immunophenotyping to assess cases of ALCL and to evaluate the diagnostic utility of this technique.

Design.—Each case of ALCL was assessed by flow cytometry with 3-color or 4-color antibody panels, and data were reanalyzed by cluster analysis using Paint-a-Gate for cases with retrievable flow cytometry data files. Anaplastic lymphoma kinase (ALK) was assessed by using immunohistochemistry.

Results.—Twenty-three ALCL cases were analyzed by flow cytometry. In 4 cases, neoplastic cells could not be identified. In the remaining 19 cases (11 ALK+, 8 ALK−), all were positive for CD30 and CD45. Anaplastic large cell lymphoma cells were large and usually CD45 bright, with many or most cells falling in the region of monocytes on the CD45/side scatter plot. The frequencies of T-cell antigen expression in ALK+ cases were CD2, 67%; CD7, 60%; CD3, 45%; CD4, 33%; CD5, 14%; and CD8, 14%. In ALK− cases, the frequencies of the T-cell antigen expression were CD2, 100%; CD3, 50%; CD4, 40%; CD7, 40%; CD5, 25%; and CD8, 20%.

Conclusions.—Flow cytometry can be used to immunophenotype ALCL cases. Neoplastic cells may be few, and they may fall outside of the lymphocyte gate. Cluster analysis using software like Paint-A-Gate is often helpful because it allows for flexible, sequential gating strategies to identify and characterize the neoplastic cells.
Can GEWF Solution Improve the Retrieval of Lymph Nodes From Colorectal Cancer Resections?
Authors: Gregurek Steven F. , Wu Howard Her-Juing
Published: February 2021

Context.—Lymph node status is an important prognostic factor in colorectal cancer staging.

Objective.—To determine whether the use of GEWF solution (glacial acetic acid, ethanol, distilled water, formaldehyde) increases the yield of lymph nodes (LNs) from colorectal cancer specimens.

Design.—A prospective study investigated the usefulness of GEWF in identifying LN from colorectal cancer resection specimens. After standard formalin fixation, approximately half of the specimens were placed in GEWF solution, and the remainder were used as a control. The number of LNs, patient sex, length of specimen, site of the specimen, tumor staging, and the number of positive LNs were analyzed. The numbers of retrieved and metastasis-positive LNs were recorded and compared with specimens from the previous year, in which no GEWF solution was used. Residents were educated on the importance of LN status before the study. Data were analyzed using independent-sample t tests. The residents also completed a subjective survey at the conclusion of the study.

Results.—A total of 85 specimens, 45 (53%) with GEWF and 40 (47%) without GEWF, were examined by 11 residents. The mean number of retrieved LNs using GEWF was slightly higher than the control group (19.96 vs 18.30); however, there was no statistical significance (P = .53). The mean number of LNs from the current study (2004– 2005) is significantly higher than that from the previous year (2003–2004) (19.17 vs 11.51, P < .001).

Conclusions.—GEWF did not increase the yield of LNs from colorectal cancer specimens. However, application of the guideline for a minimum of 12 LNs significantly increased the LN retrieval.
Phenotyping Studies of Clonotypic B Lymphocytes From Patients With Multiple Myeloma by Flow Cytometry
Authors: Conway E. Joseph , Wen Jianguo , Feng Yongdong , Mo Albert , Huang Wan-Ting , Keever-Taylor Carolyn A. , Hari Parameswaran , Vesole David H. , Chang Chung-Che
Published: February 2021

Context.—Clonotypic B lymphocytes, monoclonal B lymphocytes sharing identical, rearranged IGH-CDR3 sequences with the patient's myeloma cells, have been detected in the peripheral blood of patients with multiple myeloma. These cells have been postulated to act as a therapy-resistant tumor reservoir that drives recurrence.

Objective.—To characterize clonotypic B lymphocytes for future investigation of their role in myeloma pathogenesis.

Design.—Harvests of cryopreserved peripheral blood stem-cells from 20 myeloma patients were enriched for clonotypic B lymphocytes. Cytoplasmic immunoglobulin light chain and surface immunophenotype were analyzed by flow cytometry. IGH-CDR3 gene-rearrangement pattern was performed to determine clonality. Posttransplant remission rate was compared with the percentage of clonotypic B lymphocytes.

Results.—Clonotypic B lymphocytes expressing CD34±, CD38+, CD184+, CD31±, CD50±, CD138−, CD19−, CD20−, and the same immunoglobulin light chain as the patients' known myeloma cells were identified in 12 of 20 patients (60%). Progenitor B lymphocytes expressing similar surface immunophenotype but opposite light chains were identified in the same patients. Polymerase chain reaction for IGH rearrangement showed clonal rearrangement pattern in clonotypic lymphocytes but not in B lymphocytes expressing light chains opposite to myeloma cells. There was no statistically significant correlation between the percentage of clonotypic B lymphocytes and response to autologous transplant.

Conclusions.—Clonotypic B lymphocytes expressing CD34, but not CD19, were identified in stem cell harvests from patients with myeloma and could represent progenitor cells of neoplastic plasma cells. However, the same or similar immunophenotyping can be detected in both clonotypic B lymphocytes and benign progenitor B cells, suggesting clonality analysis might be needed to determine clonotypic B lymphocytes in patients with myeloma. Further studies are warranted to study the role of clonotypic B lymphocytes in the pathogenesis of myeloma.
Detection of Chromosomal Aberrations in Renal Tumors: A Comparative Study of Conventional Cytogenetics and Virtual Karyotyping With Single-Nucleotide Polymorphism Microarrays
Authors: Monzon Federico A. , Alvarez Karla , Gatalica Zoran , Bridge Julia A. , Nelson Marilu , Kim Hyun-Jung , Hagenkord Jill M.
Published: February 2021

Context.—Renal epithelial neoplasms have characteristic chromosomal imbalances, and we have shown previously that virtual karyotypes derived from single-nucleotide polymorphism microarrays can be performed on formalin-fixed, paraffin-embedded tissue.

Objective.—To perform a direct comparison of virtual and conventional karyotypes to evaluate concordance of results.

Design.—Twenty archival formalin-fixed, paraffin-embedded tumor samples with preexisting, conventional cytogenetic results were analyzed with Affymetrix 10K 2.0 or 250K Nsp single-nucleotide polymorphism microarrays.

Results.—Nineteen samples yielded adequate virtual karyotypes for interpretation. Eight samples showed complete agreement between the 2 techniques, and 8 samples showed partial agreement. The disease-defining lesions (eg, loss of 3p for clear cell carcinoma) were identified in all 19 cases by virtual karyotypes and in 15 cases by conventional karyotypes. Virtual and conventional karyotypic findings were concordant in the identification of these disease-defining lesions in 86% (13 of 15) of cases. In 3 cases, virtual karyotypes identified lesions consistent with the morphologic diagnosis, whereas the conventional karyotypes were unsuccessful because of insufficient tumor representation or stromal overgrowth. Two cases with acquired uniparental disomy were identified by single-nucleotide polymorphism arrays, and 5 cases with translocations were identified by conventional karyotype.

Conclusions.—Our results show that both techniques are able to identify the characteristic chromosomal abnormality for renal tumor subtypes in most cases. Discrepancies can be explained by inherent limitations of each technique, inadequate tumor sampling, and tumor heterogeneity. We conclude that virtual karyotyping is a robust alternative to conventional cytogenetics for the evaluation of chromosomal anomalies in formalin-fixed, paraffin-embedded tissues from renal epithelial neoplasms.
Pigmented Perivascular Epithelioid Cell Tumor of the Kidney
Authors: Fukunaga Masaharu , Harada Tohru
Published: February 2021

A case of pigmented perivascular epithelioid cell tumor of the kidney in a 57-year-old woman with a clinically indicated tuberous sclerosis is presented. The lesion was a 3.0-cm, well-demarcated, black-colored mass. The tumor was histologically characterized by an epithelioid arrangement of round to polygonal cells with round nuclei and clear cytoplasm containing abundant melanin. Tumor cells showed mild atypia and low mitotic activity. A spindle cell proliferation was focally observed. There were no adipose elements or thick-walled vascular vessels. The stroma demonstrated intervening, thin, fibrovascular septa. Immunohistochemically, the tumor cells were strongly positive for HMB-45 but negative for epithelial and muscle markers, vimentin, and S100 protein. The patient had no evidence of disease 3 months after surgery. Pathologists and clinicians should know about the existence of pigmented perivascular epithelioid cell tumor of the kidney. This type of tumor should be differentiated from clear cell renal cell carcinoma or malignant melanoma.
Spermatocytic Seminoma
Authors: Aggarwal Nidhi , Parwani Anil V.
Published: February 2021

Spermatocytic seminoma is a rare germ cell tumor distinct from classical seminoma, both clinically and pathologically. It affects older men, has not been associated with a history of cryptorchidism, and has no known counterpart in ovary or any other site. Pathologically, it is characterized by 3 distinct cell types, lack of cytoplasmic glycogen, and scant to absent lymphocytic infiltrate. Gain of chromosome 9 is the most consistent genetic abnormality. There have been few case reports of sarcomas arising in spermatocytic seminoma and only an occasional report of metastasis. It is important to differentiate this condition from its frequent mimics, such as classic seminoma and embryonal carcinoma, because patients with spermatocytic seminoma may not require further treatment after surgery.
Adult Orbital Xanthogranulomatous Disease: Review of the Literature
Authors: Guo Jin , Wang Jun
Published: February 2021

This article provides an overview of the pathologic features of adult orbital xanthogranulomatous disease, a rare heterogeneous group of disorders that includes 4 clinical syndromes: adult-onset xanthogranuloma, necrobiotic xanthogranuloma, adult-onset asthma and periocular xanthogranuloma, and Erdheim-Chester disease. The diagnosis is made by biopsy of the lesion, demonstrating tissue infiltration by the hallmarks of xanthoma cells and Touton giant cells. The differential diagnosis is broad, including syndromes within the adult xanthogranulomatous disease category as well as other entities involving the eyelid and the orbital tissues. Because of its rarity and sometimes close similarity to other disease entities, it is often misdiagnosed initially. This article focuses on the morphology and immunohistochemical patterns in diagnosis of adult orbital xanthogranulomatous disease with emphasis on adult-onset asthma and periocular xanthogranuloma in particular, its clinical features and associated systemic manifestations in differential diagnosis, as well as the current management strategy.
Advances in the Biology and Genetics of the Podocytopathies: Implications for Diagnosis and Therapy
Authors: Barisoni Laura , Schnaper H. William , Kopp Jeffrey B.
Published: February 2021

Context.—Etiologic factors and pathways leading to altered podocyte phenotype are clearly numerous and involve the activity of different cellular function.

Objective.—To focus on recent discoveries in podocyte biology and genetics and their relevance to these human glomerular diseases, named podocytopathies.

Data Sources.—Genetic mutations in genes encoding for proteins in the nucleus, slit diaphragm, podocyte cytoplasm, and cell membrane are responsible for podocyte phenotype and functional abnormalities. Podocyte injury may also derive from secondary stimuli, such as mechanical stress, infections, or use of certain medications. Podocytes can respond to injury in a limited number of ways, which include (1) effacement, (2) apoptosis, (3) arrest of development, and (4) dedifferentiation. Each of these pathways results in a specific glomerular morphology: minimal change nephropathy, focal segmental glomerulosclerosis, diffuse mesangial sclerosis, and collapsing glomerulopathy.

Conclusions.—Based on current knowledge of podocyte biology, we organized etiologic factors and morphologic features in a taxonomy of podocytopathies, which provides a novel approach to the classification of these diseases. Current and experimental therapeutic approaches are also discussed.
The Effectiveness of Inking Needle Core Prostate Biopsies for Preventing Patient Specimen Identification Errors: A Technique to Address Joint Commission Patient Safety Goals in Specialty Laboratories
Authors: Raff Lester J. , Engel George , Beck Kenneth R. , O'Brien Andrea S. , Bauer Meagan E.
Published: February 2021

Context.—The elimination or reduction of medical errors has been a main focus of health care enterprises in the United States since the year 2000. Elimination of errors in patient and specimen identification is a key component of this focus and is the number one goal in the Joint Commission's 2008 National Patient Safety Goals Laboratory Services Program.

Objective.—To evaluate the effectiveness of using permanent inks to maintain specimen identity in sequentially submitted prostate needle biopsies.

Design.—For a 12-month period, a grossing technician stained each prostate core with permanent ink developed for inking of pathology specimens. A different color was used for each patient, with all the prostate cores from all vials for a particular patient inked with the same color. Five colors were used sequentially: green, blue, yellow, orange, and black. The ink was diluted with distilled water to a consistency that allowed application of a thin, uniform coating of ink along the edges of the prostate core. The time required to ink patient specimens comprising different numbers of vials and prostate biopsies was timed. The number and type of inked specimen discrepancies were evaluated.

Results.—The identified discrepancy rate for prostate biopsy patients was 0.13%. The discrepancy rate in terms of total number of prostate blocks was 0.014%. Diluted inks adhered to biopsy contours throughout tissue processing. The tissue showed no untoward reactions to the inks. Inking did not affect staining (histochemical or immunohistochemical) or pathologic evaluation. On average, inking prostate needle biopsies increases grossing time by 20%.

Conclusions.—Inking of all prostate core biopsies with colored inks, in sequential order, is an aid in maintaining specimen identity. It is a simple and effective method of addressing Joint Commission patient safety goals by maintaining specimen identity during processing of similar types of gross specimens. This technique may be applicable in other specialty laboratories and high-volume laboratories, where many similar tissue specimens are processed.
Chronic Pancreatitis and the Differential Diagnosis Versus Pancreatic Cancer
Authors: Klöppel Günter , Adsay N. Volkan
Published: February 2021

Context.—Distinguishing chronic pancreatitis from pancreatic ductal adenocarcinoma (PDAC) is a well-known challenge, at both the clinical and the morphologic level.

Objective.—To focus on the histopathologic findings that are diagnostic or suggestive of PDAC.

Data Sources.—Findings that are specific to PDAC are the presence of duct structures in perineural and vascular spaces and (“naked”) ducts in fatty tissue. However, these findings are only observed in specimens containing extrapancreatic tissue. The features that are suggestive of PDAC in specimens from the pancreas include haphazard distribution of ductlike structures (ie, loss of a lobular pattern), markedly irregular ductal contours, ruptured ducts, nuclear enlargement, pleomorphism and hyperchromatism, and mitotic figures. Immunohistologic markers that are helpful are carcinoembryonic antigen, MUC1, p53, and Ki-67/ MIB1.

Conclusions.—There are a few features that are diagnostic and a number that are suggestive of PDAC. Therefore, a combination of several features may be required to clearly distinguish chronic pancreatitis from invasive PDAC.
Problems and Controversies in the Histopathology of Thyroid Carcinomas of Follicular Cell Origin
Authors: Ghossein Ronald
Published: February 2021

Context.—Despite past and recent efforts, many problems and controversies remain in the classification of thyroid carcinomas of follicular cell origin. These controversies have an impact on the prognosis and therapy of patients with thyroid carcinoma as well as on the development of robust cutting-edge research aimed at better outcome and quality of life.

Objective.—To focus on 3 contentious areas with significant clinical value: the follicular variant of papillary thyroid carcinoma, the extent of invasion in follicular carcinoma, and the poorly differentiated thyroid carcinomas.

Data Sources.—The published English language literature was reviewed.

Conclusions.—Recent data show that prognosis and therapy for many disease entities can be better delineated if a meticulous microscopic examination is performed. An accurate assessment of the extent of invasion (especially vascular) is crucial. Proliferative grading (ie, mitosis and necrosis) is of high prognostic value and should be looked for in every specimen. In addition, molecular data gathered to date can help reassess these tumors at the histologic level. Classification proposals based on personal experience rather than adequate and careful clinical follow-up should be discouraged.
Recommended Principles and Practices for Validating Clinical Molecular Pathology Tests
Authors: Jennings Lawrence , Van Deerlin Vivianna M. , Gulley Margaret L.
Published: February 2021

Context.—The use of DNA- and RNA-based tests continues to grow for applications as varied as inherited disease, infectious disease, cancer, identity testing, human leukocyte antigen typing, and pharmacogenetics. Progress is driven in part by the huge growth in knowledge about the molecular basis of disease coupled with advancements in technologic capabilities. In addition to requirements for clinical utility, every molecular test also may have limitations that must be carefully considered before clinical implementation. Analytic and clinical performance characteristics as well as test limitations are established and documented through the process of test validation.

Objective.—To describe the established principles of test validation, along with relevant regulations in the United States, in order to provide a rational approach to introducing molecular tests into the clinical laboratory.

Data Sources.—PubMed review of published literature, published guidelines, and online information from national and international professional organizations.

Conclusions.—These resources and recommendations provide a framework for validating clinical tests.
Number of Lymph Nodes Examined and Associated Clinicopathologic Factors in Colorectal Carcinoma
Authors: Shen Steven S. , Haupt Bisong X. , Ro Jae Y. , Zhu Jijiang , Bailey H. Randoph , Schwartz Mary R.
Published: February 2021

Context.—Nodal metastasis is one of the most important prognostic factors in colorectal carcinoma. The number of lymph nodes recovered and examined in resection specimens has been recently shown to be critical for proper staging and is associated with survival.

Objective.—To assess the clinicopathologic factors that may be associated with the number of lymph nodes harvested from surgical resections.

Design.—Clinicopathologic factors of 434 consecutive cases of colorectal cancers treated by surgical resection from a single tertiary medical center were retrospectively reviewed and correlated with number of lymph nodes recovered.

Results.—Our data show that patient age, tumor location, and length of resected bowel segment were associated with number of lymph nodes harvested in surgical resections of colorectal cancer. The average number of lymph nodes was 18.2 and 17.8 for patients younger than 50 years and aged 50 through 60 years, respectively, whereas it was 14.4, 15.1, and 14.9 for patients aged 61 through 70 years, 71 through 80 years, and 80 years and older, respectively. More lymph nodes were present in resection specimens of cecum/ascending colon and descending colon cancers than in those of transverse colon, sigmoid colon, and rectal cancers. There was a linear increase in number of lymph nodes examined with increasing length of bowel resection specimens. In multivariate regression analysis, the factors that remained independent predictors of removal of 12 or more lymph nodes from resection specimens were tumor location and length of resected bowel segment.

Conclusions.—The number of lymph nodes obtained in resection specimens for colorectal cancer was significantly associated with the length of resected segments of bowel, patient age, and location of the tumor.
Basal-like Breast Carcinoma: From Expression Profiling to Routine Practice
Authors: Rakha Emad , Reis-Filho Jorge S.
Published: February 2021

Context.—Advances in the understanding of the molecular and genetic mechanisms of breast cancer have led to realization of the heterogeneity of the disease and the promise of a new era of individualized management for patients with breast cancer. The advent and use of high-throughput molecular methods for the study of breast cancer have brought to the forefront the existence of the so-called basal-like breast cancers, which have been shown to have distinct biologic and clinical characteristics.

Objective.—To critically assess the clinicopathologic features of basal-like breast cancer, discuss the morphologic and immunophenotypic features of basal-like cancer, and explore the criteria that can be used to identify these tumors in routine practice.

Data Sources.—A Medline/PubMed search was conducted using the terms “basal-like,” “(basal OR basaloid OR basal-like) AND breast cancer.” All articles in English language were retrieved and critically reviewed.

Conclusions.—Basal-like breast cancers constitute a distinct, yet heterogeneous, class of neoplasms associated with specific histologic features and poor prognosis despite high response rates to neoadjuvant chemotherapy. Basal-like breast cancers have features that recapitulate those of tumors arising in BRCA1 mutation carriers, and the majority of patients with BRCA1 germline mutations develop basal-like breast cancers. At the molecular level, basal-like cancers harbor a transcriptome that is distinct from that of hormone-receptor–positive or HER2-amplified tumors, being characterized by the expression of genes usually found in basal/myoepithelial cells of the breast. However, translating the new concepts about basal-like cancer into clinical practice has proven a Herculean task, given the lack of an internationally accepted definition for these tumors and for the method of identification in routine practice.
Histopathologic Risk Factors in Retinoblastoma in India
Authors: Gupta Roshmi , Vemuganti Geeta K. , Reddy Vijay Anand P. , Honavar Santosh G.
Published: February 2021

Context.—The presence of histopathologic risk factors is associated with development of metastasis in a patient with retinoblastoma. Adjuvant chemotherapy administered to such patients decreases the risk of metastasis.

Objective.—To analyze the incidence of histopathologic risk factors in our patient population and the clinical predictors of such risk factors.

Design.—This is a retrospective case series, with review of clinical data and histopathologic slides, in 142 consecutive eyes enucleated for retinoblastoma between 1996 and 2002.

Results.—Histopathologic risk factors were present in 54.2% of 142 eyes enucleated for retinoblastoma and included infiltration of iris (7%), ciliary body (9%), choroid (40%), optic nerve lamina cribrosa (11%), retrolaminar optic nerve (17%), optic nerve to the line of transection (8%), sclera (9%), and extrascleral structures (6%). On univariate analysis, histopathologic risk factors correlated with age greater than 24 months at presentation and with glaucoma and iris neovascularization at presentation. On multivariate logistic regression analysis, age greater than 24 months and iris neovascularization correlated with infiltration of the choroid, while iris neovascularization correlated with infiltration of the retrolaminar optic nerve.

Conclusion.—Histopathologic risk factors are present in a significant proportion of patients enucleated for retinoblastoma and have identifiable clinical predictors.
Variation of Monosomy 3 Status Within Uveal Melanoma
Authors: Schoenfield Lynn , Pettay James , Tubbs Raymond R. , Singh Arun D.
Published: February 2021

Context.—Determining the most significant prognostic variables in uveal melanoma is important for stratifying patients for metastasis surveillance and possible initiation of chemotherapy or immunotherapy. Monosomy 3, one such variable, can be determined using fluorescence in situ hybridization, either on enucleated samples, fine-needle aspiration biopsy, or tumor sample obtained by vitrector.

Objective.—To evaluate possible regional discordance in chromosome 3 by sites likely to be sampled by different biopsy methods.

Design.—Eighteen consecutive patients with uveal melanoma who underwent primary enucleation were studied. Representative paraffin blocks were selected based on review of hematoxylin-eosin stained sections, and the apex and base of each tumor was demarcated. Unstained paraffin sections, 4 μm in thickness, were prepared, and fluorescence in situ hybridization, looking for monosomy 3, was performed. The chromosomal analysis was also correlated with histologic evaluation for melanoma cell type (spindle vs epithelioid cell), ciliary body involvement, presence of positive periodic acid–Schiff vascular mimicry patterns, scleral or extrascleral spread and size. One case was excluded because of necrosis.

Results.—Ten of the 17 remaining cases (59%) demonstrated monosomy 3 (in either the base or both base and apex of the tumor) with 7 cases (41%) showing disomy. Seven cases (70%) with monosomy 3 demonstrated this in both the apex and the base locations, whereas 3 cases (30%) showed monosomy in one location only (always at the base). Fourteen of the 17 cases (82%) revealed concordance in chromosome 3–monosomy 3 (7 of 14, 50%) or chromosome 3–disomy 3 (7 of 14, 50%). All 3 discordant cases demonstrated the monosomy 3 at the base with disomy at the apex. Lack of concordance between the base and apex did not correlate with melanoma cell type.

Conclusions.—Prognostic variables are important in management of neoplasms, and this study points out that the site of tissue biopsy for prognostication in uveal melanoma could affect the results obtained, at least for the presence of monosomy 3.
Intraocular Lymphoma: Diagnostic Approach and Immunophenotypic Findings in Vitrectomy Specimens
Authors: Raparia Kirtee , Chang Chung-Che(Jeff) , Chévez-Barrios Patricia
Published: February 2021

Context.—Diagnosis and classification of primary intraocular lymphoma can be challenging because of the sparse cellularity of the vitreous specimens.

Objective.—To classify and clinically correlate intraocular lymphoma according to the World Health Organization (WHO) classification by using vitrectomy specimens.

Design.—Clinical history, cytologic preparations, flow cytometry reports, and outcome of 16 patients diagnosed with intraocular lymphoma were reviewed.

Results.—The study group included 10 women and 6 men. The mean age of the patients was 63 years (range, 19–79 years). Eleven patients had central nervous system involvement and 6 patients had systemic involvement. All cases were adequately diagnosed and classified according to the WHO classification by using combination of cytologic preparations and 4-color flow cytometry with a limited panel of antibodies to CD19, CD20, CD5, CD10, and κ and λ light chains. The cases included 9 primary diffuse large B-cell lymphomas of the CNS type; 2 diffuse large B-cell lymphomas, not otherwise specified; 1 extranodal, low-grade, marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT); 1 precursor B-lymphoblastic lymphoma; and 3 peripheral T-cell lymphomas, not otherwise specified. Of note, all 11 cases of diffuse large B-cell lymphoma were CD10−. All the patients received systemic chemotherapy and radiation therapy. Only 4 patients were free of disease at last follow-up (range, 18 months to 8 years), with severe visual loss.

Conclusions.—Intraocular lymphoma cases can be adequately classified according to the WHO classification. Diffuse large B-cell lymphoma, CD10− and most likely of non–germinal center B-cell–like subgroup, is the most common subtype of non-Hodgkin lymphoma in this site, in contrast to ocular adnexal lymphoma for which MALT lymphoma is the most common subtype.
Bilateral Massive Retinal Gliosis Associated With Retinopathy of Prematurity
Authors: Houston S. K. Steven , Bourne T. David , Lopes M. Beatriz S. , Ghazi Nicola G.
Published: February 2021

Massive retinal gliosis (MRG) is a rare, benign intraocular condition that may develop in association with long-standing eye conditions including chronic inflammation, vascular disorders, glaucoma, trauma, or congenital abnormalities. It is thought to represent a nonneoplastic reactive tissue response to retinal injury. Here, we describe an unusual case of bilateral MRG in association with retinopathy of prematurity. To our knowledge, this may be the first report of such an occurrence. The differential diagnosis of MRG is discussed with specific emphasis on its relationship to vasoproliferative tumor of the retina and presumed acquired retinal hemangiomas. In addition, we hypothesize that MRG, vasoproliferative tumor of the retina, and presumed acquired retinal hemangiomas may represent different phenotypes along a spectrum of the same disease process.
Performance of Candida—Fungal-Induced Atypia and Proficiency Testing: Observations From the College of American Pathologists Proficiency Testing Program
Authors: Moriarty Ann T. , Darragh Teresa M. , Fatheree Lisa A. , Souers Rhona , Wilbur David C.
Published: February 2021

Context.—Candida may elicit cellular changes on otherwise negative screening Papanicolaou tests that may be misinterpreted as atypical squamous cells of undetermined significance. Although these changes have been correctly interpreted in the educational program of the College of American Pathologists, the Interlaboratory Comparison Program in Gynecologic Cytology, the performance of negative slides with Candida faltered when the same field validated slides were included in proficiency testing (PT).

Objective.—To identify the performance differences of negative for intraepithelial lesion (NILM) Candida challenges before and after PT.

Design.—We compare the performance of NILM College of American Pathologists slides with Candida as a single reference diagnosis, prior to PT (1991–2006) and after PT (2006–2007).

Results.—There were 147 186 responses for slides with NILM Candida from the College of American Pathologists programs from 1991 through 2007. After PT, 79.7% of incorrect participant responses identified Candida as Category C (low-grade squamous intraepithelial lesion), whereas prior to PT only 59.5% of the incorrect diagnoses were low-grade squamous intraepithelial lesion (P < .001) in the field-validated component of the program. Validated Candida slides performed significantly more poorly in PT (97.2%) than prior to PT (98.3%) (P < .001). Candida challenges performed better in the educational component post-PT (98.3% versus 97.2%; P < .001). Cytotechnologists (97.9%) identified Candida more frequently than pathologists (97.3%) (P < .001) and ThinPrep preparations performed the best of all preparation types.

Conclusions.—Proficiency testing adversely affects the performance of participants in the identification of NILM Candida. Slides with Candida are more likely to be identified as low-grade squamous intraepithelial lesion in a PT exercise. Misidentification is not due to lack of recognition but most likely an attempt of test takers to optimize their likelihood of passing the examination.