bluuebunny/crossref_metadata_2025 huggingface dataset:
Limited Sampling of Radical Prostatectomy Specimens With Excellent Preservation of Prognostic Parameters of Prostate Cancer
Authors: Kim Kyungeun , Pak Pil June , Ro Jae Y. , Shin Dongik , Huh Soo-Jin , Cho Yong Mee
Published: February 2021

Context.—The widespread use of the serum prostate-specific antigen test has increased the early detection of prostate cancer and consequently reduced grossly definable prostate cancers.

Objective.—To find the most efficient gross sampling method for radical prostatectomy specimens not only preserving important prognostic factors but also being cost effective.

Design.—We initially analyzed clinicopathologic features of the entire prostate sections from 148 radical prostatectomy specimens, which then were used to examine the impact of 5 partial sampling methods on tumor stage, Gleason score, extraprostatic extension, resection margin status, and paraffin block numbers. The methods included submission of (1) alternative slices, (2) alternative slices plus biopsy-positive posterior quarters, (3) every posterior half, (4) every posterior half plus one midanterior half, and (5) alternative slices plus peripheral 3-mm rim of the remaining prostate.

Results.—Prostate cancers and their extraprostatic extension and resection margin involvement were commonly located in the right posterior portion of the prostate. Method 5 was most efficient, detecting all cases with extraprostatic extension and resection margin involvement and reducing 25% of paraffin blocks compared with the entire sampling of the prostate. The Gleason scores were retained in most of cases, except reversal of the primary and secondary Gleason grade component in only 2 cases (1%). Only 4 cases (3%) were downstaged within the same T2 stage.

Conclusions.—These results demonstrate that sampling of alternative slices plus peripheral rim of the remaining prostate is the most efficient partial sampling method for radical prostatectomy specimens.
Primary Leiomyosarcoma of Extragnathic Bone: Clinicopathologic Features and Reevaluation of Prognosis
Authors: Adelani Muyibat A. , Schultenover Stephen J. , Holt Ginger E. , Cates Justin M. M.
Published: February 2021

Context.—Leiomyosarcoma most commonly involves the female genital tract and occasionally arises within the retroperitoneum, abdominal cavity, or the soft tissues of the extremity. Presentation as a primary bone tumor is extraordinarily uncommon, potentially leading to misdiagnosis. The prognosis is traditionally thought to be dismal. However, this conclusion is largely based on individual case reports and small series, in some of which the pathologic diagnosis is not well documented.

Objective.—To review the clinicopathologic features of well-established cases of primary skeletal leiomyosarcoma and reevaluate the prognostic implications thereof.

Data Sources.—A National Center for Biotechnology Information PubMed search of the English language literature identified 104 authenticated cases of primary leiomyosarcoma of extragnathic bone. An additional 3 cases are reported and illustrated herein.

Conclusions.—Approximately half of all patients with primary skeletal leiomyosarcoma either presented with metastatic disease or developed metastases within 1 year of diagnosis. The 5-year overall and disease-free survival rates were 59% and 41%, respectively, comparable to that of other skeletal sarcomas. As for other bone and soft tissue sarcomas, high histologic grade and tumor stage are predictive of poor outcome.
Segmental Tandem Triplication of the MLL Gene in an Intravascular Large B-Cell Lymphoma With Multisystem Involvement: A Comprehensive Morphologic, Immunophenotypic, Cytogenetic, and Molecular Cytogenetic Antemortem Study
Authors: Deisch Jeremy , Fuda Franklin“Buddy” , Chen Weina , Karandikar Nitin , Arbini Arnaldo A. , Zhou Xin J. , Wang Huan-You
Published: February 2021

An association between intravascular large B-cell lymphoma (IVLBCL) and the mixed lineage leukemia (MLL) gene has never been demonstrated. Here, we report an IVLBCL in a 47-year-old Asian man. Morphologically, the atypical lymphoid infiltrate was entirely confined in the lumina of capillaries, small vessels, and sinusoidal space. Within the kidney, the neoplastic lymphoid cells exhibited both the glomerular and peritubular capillary distribution pattern. Conventional cytogenetic analysis from the bone marrow aspirates displayed a complex karyotype, with a notable triple tandem repeat at band segment q22–q25 of chromosome 11. Fluorescence in situ hybridization with an MLL probe set, performed on both interphase cells and metaphase spreads, confirmed the presence of 3 copies of the MLL gene on the derivative chromosome 11. From this finding and 3 other IVLBCL cases reported in the literature, we conclude that MLL may play an important role in the lymphomagenesis of IVLBCL at least in a subset of cases.
Mixed Epithelial and Stromal Tumors of the Kidney: An Overview
Authors: Mohanty Sambit K. , Parwani Anil V.
Published: February 2021

Mixed epithelial and stromal tumor of the kidney is a recently recognized distinct neoplasm that should be distinguished from other renal neoplasms. These tumors are relatively rare with a female preponderance. Imaging studies are not diagnostic but reveal a solid or solid and cystic mass in most cases. Histopathologically, these tumors reveal biphasic growth pattern comprising mesenchymal and epithelial elements with characteristic estrogen and progesterone receptor immunoreactive mesenchyme reminiscent of ovarian stroma. Malignant transformation, recurrence, and metastasis are rare; however, recently a few cases of malignant mixed epithelial and stromal tumors have been reported in the literature. Recently a case with translocation t(1;19) has been described. This article provides a brief overview of the current knowledge of mixed epithelial and stromal tumor of the kidney.
High-Resolution Computed Tomography Screening for Lung Cancer: Unexpected Findings and New Controversies Regarding Adenocarcinogenesis
Authors: Chirieac Lucian R. , Flieder Douglas B.
Published: February 2021

Context.—Recent advances in human imaging technologies reawakened interest in lung cancer screening. Although historic and current preliminary and noncontrolled studies have not shown a decrease in lung cancer mortality in screened populations, many explanations have been proffered while the lung cancer community awaits the results of several large controlled population studies.

Objective.—To critically review the current model of adenocarcinoma development against the background of lung cancer screening results combined with observational pathologic and radiographic studies.

Data Sources.—Published articles pertaining to lung cancer screening, lung adenocarcinoma pathology, and radiology accessible through PubMed form the basis for this review.

Conclusions.—The current adenocarcinogenesis model is probably valid for many but not all lung adenocarcinomas. Screening data combined with radiographic and pathologic studies suggest that not all lung adenocarcinomas are clinically aggressive, and it is uncertain whether all aggressive adenocarcinomas arise from identified precursors.
Primary Pancreatic Sinus Histiocytosis With Massive Lymphadenopathy (Rosai-Dorfman Disease): An Unusual Extranodal Manifestation Clinically Simulating Malignancy
Authors: Podberezin Mark , Angeles Ronald , Guzman Grace , Peace David , Gaitonde Sujata
Published: February 2021

Sinus histiocytosis with massive lymphadenopathy (SHML), also called Rosai-Dorfman disease, is a rare entity. Its etiology and pathogenesis are still essentially unclear. The histologic hallmark of this disease is proliferation of distinctive histiocytes within lymph node sinuses and in extranodal sites. Approximately 23% of patients with SHML, documented in the SHML Registry, presented with disease primarily in extranodal sites, and very few cases of SHML (<1%) involving the gastrointestinal system have been described in the literature. We report an unusual case of primary pancreatic SHML with infiltration of the process into peripancreatic, perinephric, and perisplenic adipose tissue, simulating malignancy.
Pseudoneoplasms of the Gastrointestinal Tract
Authors: Petris Giovanni De , Leung Stanley T.
Published: February 2021

Context.—The pathologist plays the leading role in distinguishing pseudoneoplasms from truly neoplastic lesions in the gastrointestinal tract.

Objective.—This review was conducted to heighten awareness of pseudoneoplasms, to help differentiate among the various types of pseudoneoplasms, and to help distinguish pseudoneoplasms from malignancies.

Data Sources.—This review is based on the medical literature on pseudoneoplasms in MEDLINE and the authors' own experiences. Reference lists of retrieved articles were also reviewed to identify additional articles.

Conclusions.—A classification of pseudoneoplasms, according to the mechanism of injury to the gastrointestinal tract, morphologic patterns, and heterotopia, may be useful in providing a diagnostic framework in which ancillary techniques often have a diagnostic role. Several pseudoneoplasms may be closely associated with true neoplasms (eg, malakoplakia, prolapsetype lesions) because of the nonspecific nature of the response of the intestine to injury.
Pseudoneoplastic Lesions of the Female Genital Tract
Authors: Medeiros Fabiola , Bell Debra A.
Published: February 2021

Context.—Numerous benign, proliferative, or reactive processes, often related to hormone stimulation or inflammation, occur throughout the female genital tract and may mimic benign or malignant tumors. Several of the more common pseudoneoplastic lesions are discussed in this article, including microglandular hyperplasia of the cervix mimicking well-differentiated endometrial adenocarcinoma, reactive epithelial changes in the fallopian tubes mimicking adenocarcinoma or carcinoma in situ, and pregnancy changes in the ovary including pregnancy luteoma and large solitary luteinized follicular cyst of pregnancy and puerperium that may mimic ovarian neoplasms.

Objectives.—To discuss and illustrate several common lesions of the female genital tract that mimic neoplasms.

Data Sources.—Material derived from consultation cases and review of the literature.

Conclusions.—Many benign hyperplastic or reactive processes that occur in the female genital tract may be mistaken for neoplasms both clinically and pathologically. Awareness of the features of such lesions will aid in their correct diagnosis and prevent overtreatment of benign processes.
Pseudoneoplasms of the Nervous System
Authors: Donev Kliment , Scheithauer Bernd W.
Published: February 2021

Context.—Pseudoneoplasms of the nervous system vary greatly in nature. Ranging from inflammatory to autoimmune, infectious, malformative, reactive, degenerative, and radiation induced, they all mimic true tumors. Thus, they have the potential to mislead clinicians, radiologists, and pathologists alike. Their clinical and/or neuroimaging and histologic features are readily misinterpreted as tumor. Knowledge of the pitfalls is essential to avoid mismanagement, specifically overtreatment. In such instances, pathologists must take the entire clinical picture into consideration, acquainting themselves with presenting symptoms, physical findings, and neuroimaging.

Objective.—To present 10 examples of pseudoneoplasms of the nervous system, analyze the basis for their mimicry, and discuss their differential diagnosis.

Data Sources.—Review of the pertinent literature related to pseudoneoplasms of the nervous system and review of the consultation files of one of the authors (B.W.S.).

Conclusions.—The identification of tumor mimics may be difficult under the best of circumstances, and maintaining a broad differential diagnosis as well as application of a variety of immunocytochemical and occasionally ultrastructural and/or molecular genetic methods is essential to arrive at a correct diagnosis.
The Pittsburgh Cervical Cancer Screening Model: A Risk Assessment Tool
Authors: Austin R. Marshall , Onisko Agnieszka , Druzdzel Marek J.
Published: February 2021

Context.—Evaluation of cervical cancer screening has grown increasingly complex with the introduction of human papillomavirus (HPV) vaccination and newer screening technologies approved by the US Food and Drug Administration.

Objective.—To create a unique Pittsburgh Cervical Cancer Screening Model (PCCSM) that quantifies risk for histopathologic cervical precancer (cervical intraepithelial neoplasia [CIN] 2, CIN3, and adenocarcinoma in situ) and cervical cancer in an environment predominantly using newer screening technologies.

Design.—The PCCSM is a dynamic Bayesian network consisting of 19 variables available in the laboratory information system, including patient history data (most recent HPV vaccination data), Papanicolaou test results, high-risk HPV results, procedure data, and histopathologic results. The model's graphic structure was based on the published literature. Results from 375 441 patient records from 2005 through 2008 were used to build and train the model. Additional data from 45 930 patients were used to test the model.

Results.—The PCCSM compares risk quantitatively over time for histopathologically verifiable CIN2, CIN3, adenocarcinoma in situ, and cervical cancer in screened patients for each current cytology result category and for each HPV result. For each current cytology result, HPV test results affect risk; however, the degree of cytologic abnormality remains the largest positive predictor of risk. Prior history also alters the CIN2, CIN3, adenocarcinoma in situ, and cervical cancer risk for patients with common current cytology and HPV test results. The PCCSM can also generate negative risk projections, estimating the likelihood of the absence of histopathologic CIN2, CIN3, adenocarcinoma in situ, and cervical cancer in screened patients.

Conclusions.—The PCCSM is a dynamic Bayesian network that computes quantitative cervical disease risk estimates for patients undergoing cervical screening. Continuously updatable with current system data, the PCCSM provides a new tool to monitor cervical disease risk in the evolving postvaccination era.
Immunohistochemical Profile and Fluorescence In Situ Hybridization Analysis of Diffuse Large B-Cell Lymphoma in Northern China
Authors: Li Ting , Medeiros L. Jeffrey , Lin Pei , Yin Hongfang , Littlejohn Martin , Im Whan , Lennon P. Alan , Hu Peter , Jorgensen Jeffrey L. , Liang Mei , Guo Hua , Yin C. Cameron
Published: February 2021

Context.—Gene expression profiling of diffuse large B-cell lymphoma using complementary DNA microarrays has revealed 2 major prognostic groups in Western countries: germinal center B-cell–like and nongerminal center B-cell–like lymphomas. Immunohistochemical analysis using antibodies specific for CD10, BCL6, and MUM1 has been proposed as a surrogate for gene expression profiling.

Objective.—To study the immunohistochemical features of diffuse large B-cell lymphoma cases from northern China because geographic differences for this disease are known to exist.

Design.—Morphologic, immunohistochemical, and fluorescence in situ hybridization analyses of 63 cases of diffuse large B-cell lymphoma from northern China.

Results.—There were 38 men and 25 women with a median age of 57 years (range, 12–87 years). CD10 was positive in 19 cases (30%), BCL6 was positive in 22 cases (35%), and MUM1 was positive in 32 cases (51%). Twenty-one (33%) cases were germinal center B-cell–like lymphoma, and 42 (67%) were nongerminal center B-cell–like lymphoma. BCL2 was expressed more often in nongerminal center B-cell–like disease versus germinal center B-cell–like disease (60% versus 24%, P  =  .01) and in nodal versus extranodal (64% versus 30%, P  =  .01) cases. Fluorescence in situ hybridization analysis showed BCL6, MYC, and BCL2 rearrangements in 11 of 32 (34%), 8 of 27 (30%), and 11 of 50 (22%) cases, respectively.

Conclusions.—These results add to what is known about the geographic variation of diffuse large B-cell lymphomas. In northern China, the frequency of the germinal center B-cell–like type and BCL6 expression and/or BCL6 rearrangement is less and the frequency of MYC rearrangement is greater than have been reported in Western countries.
Do Eosinophil Numbers Differentiate Eosinophilic Esophagitis from Gastroesophageal Reflux Disease?
Authors: Genevay Muriel , Rubbia-Brandt Laura , Rougemont Anne-Laure
Published: February 2021

Context.—Although the healthy esophageal mucosa contains no eosinophils, eosinophilic infiltration is observed in 2 major clinicopathologic settings: gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EE). The prevalence of EE is increasing in many countries, and this increase seems only partly to be due to a better awareness of the pathology, following the relatively recent description of EE. Gastroesophageal reflux disease and EE represent 2 entities that do not respond to the same treatment modalities and, thus, need to be distinguished. However, diagnostic criteria of EE have been defined arbitrarily, and the more recent articles tend to prove that the overlap with GERD is probably greater than initially believed, leading the authors to advise strict exclusion of GERD before considering the diagnosis of EE.

Objectives.—To provide pathologists with the currently proposed histologic criteria of GERD and EE, to stress the need to combine these criteria with clinical data and endoscopic findings, and to outline the remaining controversies.

Data Sources.—This review is based on selected articles identified by a PubMed (US National Library of Medicine, Bethesda, Maryland) search of the literature in English for GERD and EE, a recent review by the American Gastroenterological Association (Bethesda), the Proceedings of the First International Gastrointestinal Eosinophil Research Symposium, and the authors' experience.

Conclusions.—Proper identification of the etiology of eosinophilic infiltration of the esophagus allows accurate medical or surgical treatment and follow-up. Eosinophilic esophagitis and GERD diagnoses require integration of the histologic findings with the clinical and endoscopic data.
Immunoexpression of Multidrug-Resistance Protein 2 and Cyclooxygenase 2 in Medullary Thyroid Carcinomas
Authors: Ruggeri Rosaria Maddalena , Sciacchitano Salvatore , Vitarelli Enrica , Trimarchi Francesco , Barresi Gaetano , Trovato Maria
Published: February 2021

Context.—Chemoresistance is due to the expression of multidrug-resistance proteins (MRPs). Cyclooxygenase 2 (COX2), a key enzyme in prostaglandins synthesis, upregulates MRP1. MRP1 is overexpressed in medullary thyroid carcinomas (MTCs), but it is not involved in resistance to doxorubicin and cisplatin, which are commonly used in MTC treatment. MRP2 is specifically involved in resistance to both chemotherapeutic agents, but no data exist on the expression of MRP2 and COX2 in MTC.

Objective.—To evaluate MRP2 and COX2 expressions in MTC.

Design.—We analyzed immunohistochemical expression of MRP2 and COX2 in 12 MTCs and in 6 lymph node metastases. Results were correlated with pTNM and clinical stage.

Results.—MRP2 and COX2 expressions were observed only in tumor samples and metastases. Nine MTCs, all pTNM stage T4, were positive for MRP2, whereas 3 MTCs, pTNM stages T2 and T3, were unreactive for MRP2. Six metastatic MTCs at stage T4 showed higher proportion of MRP2+ cells, compared with primary tumors. All 12 MTCs were positive for COX2. Three MTCs, pTNM stage T2 and T3, showed COX2 positivity in all cells. The proportion of COX2+ cells decreased with increased pTNM stage. Four out of 6 metastatic MTCs, stage T4, showed a lower proportion of COX2+ cells, compared with primary tumors. The proportion of MRP2+ cells was inversely related to the proportion of COX2+ cells.

Conclusions.—MRP2 and COX2 expression correlated with pTNM stage. High MRP2 and low COX2 expression may explain resistance to doxorubicin and cisplatin, which is observed in advanced stage MTC. Evaluation of the expression pattern of these 2 proteins may be useful to predict chemosensitivity of these types of tumors.
Atypical Small Acinar Proliferation in the Prostate: Clinical Significance in 2006
Authors: Bostwick David G. , Meiers Isabelle
Published: February 2021

About 2% of contemporary prostate needle biopsy specimens contain collections of small acini that are suspicious for cancer but that fall below the diagnostic threshold and are reported as atypical small acinar proliferation suspicious for but not diagnostic of malignancy. Prostate cancer has been identified in specimens from subsequent biopsies in up to 60% of cases of atypical small acinar proliferation, indicating that this finding is a significant predictor of cancer. Identification of atypical small acinar proliferation warrants repeat biopsy for concurrent or subsequent invasive carcinoma.
The Utility of Immunohistochemistry and In Situ Hybridization in Placental Pathology
Authors: Nuovo Gerard
Published: February 2021

It has long been recognized that routine histologic examination of the placenta has limitations, especially with regard to the diagnosis of infectious diseases and the concomitant cytokine response that may cause severe in utero fetal damage. Immunohistochemical testing of the placenta in such situations can be very useful in terms of identifying the infectious agent as well as in demonstrating a marked increase in cytokines such as tumor necrosis factor α and interleukin 8, produced primarily by cells native to the villi and fetal membranes. One hundred placentas (20 normal childbirths, 20 with severe neonatal morbidity of known cause, 25 idiopathic stillbirths where autopsy material was available, 35 with severe idiopathic neonatal morbidity) were examined for a wide variety of infectious diseases and cytokine production. An infectious agent was evident in 19 (76%) of 25 placentas from stillbirths and 28 (80%) of 35 placentas associated with idiopathic severe neonatal morbidity. No infectious agent was noted in the placentas from normal childbirths or cases of known neonatal morbidity. The most common infectious agent was coxsackie virus (51% of infections) followed by bacterial infections (24% of infections). The same infectious agent found in the placenta was found in the corresponding autopsy material from the stillbirths, with the spleen containing the greatest number of infected cells. There was a strong correlation between the number of cells demonstrating cytokine expression (tumor necrosis factor α and interleukin 8) and the presence of an infectious disease in the placenta and stillborn. No histologic feature was associated with an in utero infection. Immunohistochemical testing of placentas gives much insight into their structure and function, including, besides infectious disease detection, the marked diversity of function of trophoblasts, the rarity of committed B cell response, and the strong potential of contractility of villi.
Grading of Follicular Lymphoma: Comparison of Routine Histology With Immunohistochemistry
Authors: Martinez Antonio E. , Lin Li , Dunphy Cherie H.
Published: February 2021

Context.—Follicular lymphoma (FL) grading is based on the average number of large transformed cells in 10 neoplastic follicles at ×40 high-power field (×10–40 high-power field) examination (grade 1, 0–5 centroblasts per high-power field; grade 2, 6–15 centroblasts per high-power field; grade 3, >15 centroblasts per high-power field).

Objective.—Since there may be significant interobserver variability, we analyzed the usefulness of immunohistochemical stains in grading FLs more reliably.

Design.—Forty-three FLs initially graded by World Health Organization criteria (grade 1, 12; grade 2, 18; grade 3, 13) were reviewed and stained with CD3, CD20, Ki-67, CD30, CD68, PAX-5, and BCL-6. Retrospective review was performed for the average number of large cells, of large lymphoid cells, of large cells staining with CD3, CD20, BCL-6 (40 cases), and PAX-5, and of all cells staining with CD68, Ki-67, and CD30.

Results.—By histologic review, 8 of 43 FLs had a significant grade change (4 cases upgraded and 4 cases downgraded). CD3 and CD30 stained only 0 to 3 large cells and 0 to 3 cells, respectively, in neoplastic follicles. CD68+ cells represented the large nonlymphoid cells. Increasing FL grades demonstrated increases in Ki-67+ cells. The original grade showed substantial agreement with CD20 and moderate agreement with PAX-5 and BCL-6. The original histologic grade agreed with immunohistochemical-based grade using 2 or more antibodies in 5 of 8 discordant cases (4 by CD20 or BCL-6 and PAX-5; 1 by CD20, PAX-5, and BCL-6).

Conclusions.—Interobserver variability of histologic FL grading may be significant; we showed low-end “substantial agreement.” Immunohistochemical stains (ie, CD20, PAX-5, and BCL-6) may more reliably determine the number of large transformed cells in neoplastic follicles; Ki-67 staining correlates with higher FL grades. Immunohistochemical stains may be evaluated in clinical trials of FL patients to determine prognostic significance.
Utility of MIB-1 (Ki-67) in Evaluating Diminutive Colorectal Polyps With Cautery Artifact
Authors: Groisman Gabriel M. , Amar Mary , Meir Alona
Published: February 2021

Context.—Accurate interpretation of colorectal polyp histology is essential in the decision-making process during treatment and surveillance following polypectomies. However, interpretation of diminutive colorectal polyps removed by thermal electrocoagulation (hot biopsy technique) is often problematic as a result of cautery artifact.

Objective.—To evaluated the usefulness of the proliferation marker MIB-1 (Ki-67) as an aid in the differential diagnosis of diminutive colorectal polyps with cautery artifact, as adenomatous and nonadenomatous polyps display different patterns of epithelial proliferation.

Design.—Seventy-five diminutive colorectal polyps with extensive cautery artifact displaying at least the upper portions of 3 adjacent crypts with the corresponding surface epithelium were evaluated and immunolabeled with MIB-1. They included 25 cases in which a definitive or presumptive diagnosis could not be reached (indeterminate polyps), 25 cases diagnosed as compatible with adenomatous polyp, and 25 cases diagnosed as compatible with nonadenomatous polyp.

Results.—MIB-1 immunoreactivity was well preserved in the cauterized areas. Among indeterminate polyps, MIB-1 stained upper crypts and surface epithelium in 14 cases (adenomatous polyp staining pattern) and revealed minimal or absent staining in these areas in 11 cases (nonadenomatous polyp staining pattern). All cases diagnosed as compatible with adenomatous polyp displayed the adenomatous polyp staining pattern. In contrast, all cases diagnosed as compatible with nonadenomatous polyp revealed the nonadenomatous polyp staining pattern.

Conclusions.—Immunoreactivity for MIB-1 may be used as a beneficial adjunctive test to help diagnose diminutive colorectal polyps with extensive cautery artifact.
Expression of p63 Differs in Peritoneal Endometriosis, Endometriomas, Adenomyosis, Rectovaginal Septum Endometriosis, and Abdominal Wall Endometriosis
Authors: Poli Neto Omero B. , Ferreira; Hebert M. , Ramalho Leandra N. Z. , Rosa e Silva Júlio C. , Candido dos Reis Francisco J. , Nogueira Antonio A.
Published: February 2021

Context.—Although there is evidence that endometriosis results from basal endometrium dislocation, the underlying biology is not fully understood. One protein that plays an important role in regulating epithelial proliferation and differentiation is the 63-kDa membrane protein (p63), which is also a marker of basal and reserve cells in the female genital tract.

Objective.—To determine whether p63 is expressed differently in peritoneal endometriosis, endometriomas, and adenomyosis, as well as in deep endometriotic nodules of the rectovaginal septum and abdominal wall.

Design.—This study includes a prospective series of consecutive patients (Canadian Task Force classification II-2) from a tertiary care university hospital. Specimens collected from 83 patients (15 peritoneal endometriosis specimens, 22 endometrioma specimens, 36 adenomyosis specimens, and 10 rectovaginal septum/abdominal wall specimens) were evaluated. Diagnostic and operative laparoscopies or laparotomies were performed, and tissue samples were obtained. Immunohistochemistry was used to evaluate p63 expression.

Results.—Positivity for p63 was detected in 93.3% of the peritoneal endometriosis specimens, 81.8% of the endometrioma specimens, 36.1% of the adenomyosis specimens, and none of the rectovaginal/abdominal wall endometriosis specimens (P < .001). Distribution of p63 immunostaining in the positive specimens was homogeneous.

Conclusions.—Endometriotic lesions express p63 differently, and some retain the basal/reserve cell immunophenotype. Nevertheless, it remains unclear whether the lack of p63 expression in some lesions is related to the extent of the disease, to its clinical behavior, or to exacerbation of the accompanying symptoms.
Histologic Variants of Infiltrating Urothelial Carcinoma
Authors: Zhai Qihui J. , Black Jennifer , Ayala Alberto G. , Ro Jae Y.
Published: February 2021

Context.—The spectrum of urothelial carcinoma is broad, and variant morphologies are being reported continually. Many of these variants have been extensively documented and even established as subclasses of urothelial carcinoma.

Objective.—To review the established and more recently described variants of urothelial carcinoma. The significance of recognizing these variants is discussed.

Data Sources.—The literature is reviewed in conjunction with our experience pertaining to urothelial carcinomas of the bladder and ureters.

Conclusions.—Urothelial carcinoma displays many forms, and some of these variant morphologies may introduce diagnostic difficulties because of their similarity to other malignancies and/or benign lesions. Additionally, it is important to recognize variants that are associated with different outcomes from conventional urothelial carcinoma. For these reasons, familiarity with the diverse morphology of urothelial carcinoma is not simply an academic exercise but is important in providing quality care for patients affected by this disease.
Prostatic Intraepithelial Neoplasia: Recent Advances
Authors: Ayala Alberto G. , Ro Jae Y.
Published: February 2021

Context.—There have been 2 putative prostatic cancer precursors, prostatic intraepithelial neoplasia (PIN) and atypical adenomatous hyperplasia (adenosis), but PIN remains as a well-known precancerous condition.

Objective.—To describe recent advances in knowledge of PIN and to better define the diagnostic criteria and differential diagnosis of PIN.

Data Sources.—Review of the pertinent literature and our experience.

Conclusions.—The presence of ductal/acinar epithelial changes including nuclear enlargement, prominent nucleoli, chromatin alterations, and luminal complexity is an easy way to identify the disorder. Four main patterns of high-grade PIN (HGPIN) have been described: tufting, micropapillary, cribriform, and flat. In addition, variants of HGPIN have also been described. Both HGPIN and prostatic carcinoma share an increased incidence and severity with advancing age and with high rates of occurrence in the peripheral zone of the prostate. Furthermore, HGPIN and prostate cancer share genetic and molecular markers as well, with PIN representing an intermediate stage between benign epithelium and invasive carcinoma. The clinical significance of HGPIN is that it identifies patients at risk for prostatic carcinoma. With the increased use of extended biopsy protocols, clinicians are more likely to identify HGPIN and less likely to miss concurrent carcinoma.
An Overview of the Histology of Skeletal Substitute Materials
Authors: Bauer Thomas W.
Published: February 2021

Context.—Orthopedic and spine surgeons are in frequent need of bone for skeletal reconstruction. The amount of autograft is limited, and conventional allograft has some disadvantages, so surgeons are now using increasing amounts of demineralized allograft and a variety of synthetic materials to replace or “extend” autograft.

Objective.—To provide an overview of the composition and histology of the materials most likely to be seen by pathologists today.

Data Sources.—The review is based on published literature and the author's experience with preclinical studies and human biopsies.

Conclusions.—Pathologists are likely to find these skeletal substitute materials in biopsy and resection specimens from patients who have undergone prior treatment, and recognizing a synthetic bone substitute can help explain an otherwise confusing specimen. Pathologists also play an important role in helping define the safety and efficacy of new bioactive materials.
Goblet Cell Mimickers in Esophageal Biopsies Are Not Associated With an Increased Risk for Dysplasia
Authors: Younes Mamoun , Ertan Atilla , Ergun Gulchin , Verm Ray , Bridges Margaret , Woods Karen , Meriano Frank , Schmulen A. Carl , Colman Ronald , Johnson Craig , Barroso Alberto , Schwartz Jim , McKechnie John , Lechago Juan
Published: February 2021

Context.—Identification of intestinal-type goblet cells (ITGCs) in hematoxylin-eosin–stained sections of esophageal biopsies is essential for the diagnosis of Barrett metaplasia. However, we have seen cases diagnosed as Barrett metaplasia based solely on cells that pose morphologic similarity to ITGCs on hematoxylin-eosin staining or stain positive with Alcian blue.

Objective.—To determine the clinical significance of goblet cell mimickers.

Design.—Initial biopsies from 78 patients with original diagnosis of Barrett metaplasia negative for dysplasia and a mean follow-up of 72 months were reviewed and reclassified into 3 categories: (1) ITGCs, (2) goblet cell mimickers, or (3) neither. Sections from available paraffin blocks were stained with Alcian blue at pH 2.5. The presence of the different types of cells and positive Alcian blue staining were correlated with each other and evaluated for their significance as predictors of progression to dysplasia.

Results.—Goblet cell mimickers were present in 35 cases and were associated with ITGCs in the same biopsy in 23 (66%) of these cases. Intestinal-type goblet cells were present in 56 cases, and the remaining 10 cases, although called Barrett on the original report, did not show either ITGCs or goblet cell mimickers. Only the presence of ITGCs was associated with significant risk for dysplasia (P = .008). Positive Alcian blue staining was not associated with a significant risk for dysplasia.

Conclusions.—Our results indicate that the diagnosis of Barrett metaplasia should be rendered with confidence only when ITGCs are identified on routine hematoxylin-eosin–stained sections.
Primary Skull Lesions in the Pediatric Population: A 25-Year Experience
Authors: Gibson Sarah E. , Prayson Richard A.
Published: February 2021

Context.—Primary skull lesions are rare in the pediatric population. The differential diagnosis of these lesions is broad and includes both congenital and acquired lesions. Previous studies of skull lesions in the pediatric population suggest that dermoid/epidermoid tumors are the most common childhood skull tumors.

Objective.—To review the clinicopathologic features of primary skull lesions identified within the pediatric population of an academic tertiary medical center.

Design.—A retrospective review of surgical pathology reports during a 25-year period identified 19 primary skull lesions occurring in the pediatric population. Lesions were excluded if they were of known soft tissue or intracranial origin with secondary calvarial involvement, or if they represented a metastasis from a known primary malignancy.

Results.—Nineteen primary skull lesions were identified in 11 male (58%) and 8 female (42%) patients, with a median age at diagnosis of 9.5 years. These lesions were usually benign and most commonly presented as a painless mass (n = 8). The lesions were located in the occipital bone (n = 7), frontal bone (n = 5), parietal bone (n = 2), and temporal bone (n = 1). Diagnoses included epidermoid/ dermoid cyst (n = 8), Langerhans cell histiocytosis (n = 6), intraosseous hemangioma (n = 2), osteoblastoma (n = 1), infantile myofibroma (n = 1), and fibroma (n = 1). Intracranial extension was identified in 1 case, and recurrence was found in only 2 cases.

Conclusions.—Epidermoid/dermoid cysts and Langerhans cell histiocytosis are the most commonly encountered skull lesions in the pediatric population at our institution. Intracranial extension of these lesions is rare, and recurrence is uncommon following complete surgical resection.
Accuracy of ThinPrep Imaging System in Detecting Low-Grade Squamous Intraepithelial Lesions
Authors: Zhang Fred Fangyuan , Banks Helen Whitler , Langford Shanna Maria , Davey Diane Davis
Published: February 2021

Context.—The ThinPrep Imaging System (Imager) for cervical cytology is used in many US laboratories, but the ability of the system to identify classic changes of low-grade squamous intraepithelial lesion (LSIL) has not been independently reported.

Objective.—To evaluate the accuracy of this system in detecting classic LSIL cells.

Design.—A total of 114 imaged ThinPrep LSIL cases from April to June 2005 were reviewed to determine whether the most diagnostically relevant cells were present in the 22 fields selected by Imager. Those LSIL specimens from January to June 2005 that were initially screened by the Imager and classified as “negative” in the 22 fields were also reviewed. The average number of classic koilocytes per slide was compared among cases that had koilocytes within 22 fields with cases upgraded during full review.

Results.—Twelve (10.5%) of 114 LSIL cases from April to June 2005 did not show diagnostic LSIL cells within the initial 22 fields. Full manual rescreening was performed on 1025 cases from January to June (20.4% of negative cases). Nine cases that were initially negative in the 22 fields were revised to LSIL (2.4% of all 381 LSIL cases reported from January to June 2005). An average of 10 to 11 koilocytes were present in these 2 groups, which was significantly lower than the average of 75 koilocytes in cases in which the 22 Imager-selected fields showed LSIL.

Conclusions.—Although the ThinPrep Imager finds abnormal cells in most LSIL cases, the system may have limitations in detecting koilocytes in the 22 Imager-selected fields. When 10% quality control rescreening is performed as required by federal regulations, full manual rescreening will provide the most accurate results.
Activated Protein C Resistance and Factor V Leiden: A Review
Authors: Rosendorff Adam , Dorfman David M.
Published: February 2021

Context.—Factor V Leiden (FVL) is the most common heritable cause of venous thrombosis. It is caused by a single nucleotide substitution resulting in an R506Q missense mutation, resulting in factor V resistance to activated protein C (APC) inactivation. Carriers of FVL have an increased susceptibility to venous thrombosis, which is further increased in the presence of other genetic or environmental risk factors.

Objective.—To review the biology, clinical findings, laboratory detection methods, and screening recommendations for patients with the FVL mutation.

Data Sources.—PubMed review of published literature and online information.

Conclusions.—FVL remains an important heritable cause of hypercoagulability since its discovery more than 10 years ago. Clinical suspicion should be high in cases of unexplained venous thrombosis. APC resistance and FVL mutation can be diagnosed with high sensitivity and specificity with use of clotting time–based functional assays and genetic assays, respectively, allowing for evidence-guided clinical decision making regarding the benefit of long-term anticoagulation.
Reduced Annexin II Protein Expression in High-Grade Prostatic Intraepithelial Neoplasia and Prostate Cancer
Authors: Yee David S. , Narula Navneet , Ramzy Ibrahim , Boker John , Ahlering Thomas E. , Skarecky Douglas W. , Ornstein David K.
Published: February 2021

Context.—Annexin II is a calcium-dependent phospholipid-binding protein that plays a role in many cellular functions, including apoptosis, signal transduction, and cellular motility. The protein is strongly expressed in normal prostatic epithelial glands, but its expression in benign prostatic lesions has not been reported. Although commonly underexpressed in prostate cancer, the association of reduced expression with pathologic grade and stage is unknown.

Objective.—To compare annexin II expression in benign prostatic lesions with expression in high-grade prostatic intraepithelial neoplasia and prostate cancer, as well as to correlate expression levels with pathologic grade and stage.

Design.—A semi-quantitative assessment of annexin II expression was performed in radical prostatectomy specimens from 74 patients and prostate needle core biopsy specimens from 13 patients. Foci with normal prostatic glands, atrophic glands, basal cell hyperplasia, high-grade prostatic intraepithelial neoplasia, and prostatic adenocarcinoma were evaluated.

Results.—Annexin II expression was present in more than 50% of glands in most (>85%) samples of benign prostatic epithelium, atrophic glands, and basal cell hyperplasia. In high-grade prostatic intraepithelial neoplasia, annexin II staining was markedly reduced in epithelial cells but not in basal cells. Annexin II was absent or focally present in moderately differentiated adenocarcinoma but was retained in poorly differentiated adenocarcinomas.

Conclusions.—Reduced annexin II expression may be a useful diagnostic biomarker to help identify small foci of moderately differentiated adenocarcinoma on needle core biopsy specimens since it is consistently expressed in benign prostatic glands. Re-expression of annexin II in poorly differentiated adenocarcinoma may provide prognostic information.
Sarcomas Arising in Paget Disease of Bone: A Clinicopathologic Analysis of 70 Cases
Authors: Deyrup Andrea T. , Montag Anthony G. , Inwards Carrie Y. , Xu Zhiheng , Swee Ronald G. , Krishnan Unni K.
Published: February 2021

Context.—Sarcomatous transformation is a rare complication of Paget disease of bone. Prognosis in patients with other types of sarcomas arising in bone has improved in the last several decades because of therapeutic advances. However, because of the rarity of Paget sarcoma, outcome studies in these patients are limited.

Objective.—To determine whether prognosis for Paget sarcoma has improved.

Design.—Seventy cases of sarcomas arising in the setting of Paget disease were collected, and the histologic and clinical findings were reviewed. Clinical follow-up was obtained in 67 cases.

Results.—Sarcoma arising in Paget disease tended to arise in older men (46 men, 24 women; age range, 31–88 years; mean age, 66 years) and predominated in the axial skeleton (n = 37), especially in the pelvis. Thirty-three patients had a clinical history of Paget disease ranging in duration from 16 months to 30 years (mean, 15 years). No significant difference in incidence between monostotic (n = 33) and polyostotic (n = 36) disease was noted. Most tumors were osteosarcomas (88%). All tumors were high grade. Follow-up information was obtained in 67 of 70 cases (range of follow-up, 1–252 months). Survival ranged from 1 month to 20 years, with a 5-year survival rate of 10%.

Conclusions.—Prognosis remains poor in patients with Paget sarcoma. There is no significant correlation between the number of bones involved with Paget disease or the duration of disease and development of Paget sarcoma. Poor prognosis in Paget sarcoma is unrelated to site or stage at presentation.
Sertoliform Endometrioid Carcinoma of the Ovary: A Potential Diagnostic Pitfall
Authors: Misir Anil , Sur Monalisa
Published: February 2021

Sertoliform endometrioid carcinoma of the ovary (SEC) is an uncommon variant that bears histologic similarity to Sertoli and Sertoli-Leydig cell tumors (SLTs). Clinically, SEC affects an older population (60–70 years), while patients with SLT have an average age of 25 years and may exhibit endocrine manifestations. A number of histologic features can be used to distinguish the 2 entities, the most important ones being (1) the presence of areas with the usual pattern of endometrioid carcinoma, and (2) the presence of mucin at the apical borders of the tumor cells. Cytokeratin stains positively, while inhibin and calretinin stain negatively in SEC; the converse is true for SLTs. Based on the clinicopathologic behavior of this entity, SEC should be considered a well-differentiated carcinoma with relatively good prognosis if limited to the ovary.
Practice of Forensic Medicine and Pathology in Sri Lanka
Authors: Balachandra A. Thambirajah , Vadysinghe Amal N. , William Anita L.
Published: February 2021

The practice of forensic medicine and pathology in Sri Lanka is based on the British model. Medical students during their third and fourth years receive approximately 50 hours of lectures and tutorials in forensic medicine and pathology and then undergo an examination. After completing an internship, these doctors are sent to various hospitals throughout Sri Lanka where they may be asked to perform medicolegal examinations on victims and suspects in rape cases, persons suspected of being under the influence of drugs and/or alcohol, and, injured live patients. As well, they may be asked to perform medicolegal autopsies. Depending upon their experience, some medical officers may be designated as judicial medical officers and appointed full time to do medicolegal work. Up until 1980, judicial medical officers with at least 2 years of work experience were allowed to obtain their postgraduate qualifications in the United Kingdom. However, since 1981 and the establishment of its own Postgraduate Institute of Medicine in Colombo, Sri Lanka, medical officers are offered 2 postgraduate programs in forensic medicine and pathology, a diploma in legal medicine and a doctorate in medicine (forensic medicine). After completing the doctorate in forensic medicine, doctors are allowed to train abroad for a further year in an approved center. Upon return they can then be appointed as consultant judicial medical officers. The practice of forensic medicine and pathology in Sri Lanka is unique and vibrant. However, due to the country's prevailing civil war, the practice of forensic medicine and pathology is suboptimal.
Expression of JL1 Is an Effective Adjunctive Marker of Leukemia Cutis
Authors: Park Young Soo , Park So Hyung , Park Seo-Jeong , Kim Youngji , Jang Kee-Taek , Ko Young Hyeh , Lee Mi-Woo , Huh Joo Ryung , Park Chan-Sik
Published: February 2021

Context.

Specific differentiation of leukemia cutis (LC) from nonleukemic dermatoses is crucial to ensure proper treatment for the disease. Because of the exceptionally variable histologic features of LC and the frequent nonleukemic dermatoses in leukemia patients, identification of leukemic cells that infiltrate skin lesions is important. Here, we introduce JL1, a novel leukemia-associated surface antigen, which is not expressed in mature human tissue but in cortical thymocytes and small subpopulations of bone marrow hematopoietic precursors.

Objectives.

To assess the expression pattern of JL1 in LC and compare it with other commonly used markers. Also, to evaluate the expression of JL1 in other cutaneous lesions that need differential diagnoses.

Design.

Immunohistochemical staining with anti-JL1 and other commonly used markers for LC was performed on paraffin-embedded skin biopsies from 32 cases of LC with acute lymphoblastic leukemia/lymphoma and acute myelogenous leukemia. Immunohistochemical staining score was evaluated in each case according to the proportion of positive tumor cells found. JL1 staining was also done on 96 reactive or neoplastic cutaneous lesions.

Results.

JL1 was detected in 7 of 11 acute lymphoblastic leukemia/lymphoma LC (63.6%) and 7 of 21 acute myelogenous leukemia LC (33.3%), with invariably high-staining scores. None of the other cutaneous lesions or normal tissues expressed JL1. The expression pattern of JL1 was not altered in 2 patients with follow-up biopsies.

Conclusions.

Our finding that JL1 is expressed exclusively and stably by leukemic cells suggests that it can be used as a useful adjunctive marker for initial diagnosis and follow-up biopsy of LC, particularly in cases of scarce infiltrates.