bluuebunny/crossref_metadata_2025 huggingface dataset:
Papillary Carcinomas of the Gallbladder: Analysis of Noninvasive and Invasive Types
Authors: Albores-Saavedra Jorge , Tuck Matthew , McLaren Bernadette K. , Carrick Kelley S. , Henson Donald Earl
Published: February 2021

Context.—Although papillary carcinomas have been recognized as distinct morphologic variants of gallbladder neoplasms, they have been lumped together in a single group despite the recognition of noninvasive and invasive types. As a result, the biologic behavior of each type remains undescribed.

Objective.—To compare the biologic behavior of noninvasive and invasive papillary carcinomas of the gallbladder.

Design.—The clinical and morphologic features of 16 noninvasive papillary carcinomas (>1 cm) of the gallbladder were analyzed, and their clinical behavior was compared with that of 370 invasive papillary carcinomas recorded in the Survey Epidemiology and End Results (SEER) Program of the National Cancer Institute from 1973 through 2001. The biologic behavior of invasive papillary carcinomas was compared with that of invasive nonpapillary carcinomas of the gallbladder recorded in SEER. Hematoxylin-eosin–stained sections were available for review in the 16 noninvasive papillary carcinomas. The number of slides examined per case varied from 3 to 16, with an average of 7.

Results.—The 16 patients with noninvasive papillary carcinomas included 11 women and 5 men, aged 34 to 83 years (mean age, 61 years). Thirteen patients had cholelithiasis. Laparoscopic cholecystectomy was performed on 12 patients and open cholecystectomy on 4. The tumors measured from 1.3 to 8.6 cm and were well to moderately differentiated. Fourteen noninvasive papillary carcinomas showed biliary phenotype, and 2 showed intestinal phenotype. Follow-up was obtained in 11 patients; 6 were asymptomatic 5 to 11 years after surgery, 2 were symptom free 9 months to 4 years following cholecystectomy, and 3 died of unrelated causes 2 to 3 years after surgery. Three hundred seventy cases of invasive papillary carcinomas were recorded in SEER. The 10-year relative survival rate for 225 patients with invasive papillary carcinomas confined to the gallbladder wall was 52%, while the 10-year relative survival rate for 83 patients with papillary carcinomas that had spread to the lymph nodes was less than 10%. Of the remaining 62 invasive papillary carcinomas, 58 had distant metastases and 4 were not staged. The 10-year relative survival rate for invasive nonpapillary carcinomas confined to the gallbladder wall was 30%.

Conclusion.—Noninvasive papillary carcinomas of the gallbladder—regardless of size, cell phenotype, and degree of differentiation—do not metastasize, and a simple cholecystectomy appears to be a curative procedure. In contrast, invasive papillary carcinomas do metastasize and are associated with a poor prognosis (10-year relative survival rate for tumors confined to the gallbladder wall was 52%, while the 10-year relative survival rate for tumors with lymph node metastasis was <10%). The separation of papillary carcinomas into noninvasive and invasive types is clinically relevant and therefore fully justified.
Expression Patterns of Markers for Type II Pneumocytes in Pulmonary Sclerosing Hemangiomas and Fetal Lung Tissues
Authors: Yoo Seong Ho , Jung Kyeong Cheon , Kim Joo Hyun , Sung Sook Whan , Chung Jin-Haeng , Shim Young Soo , Lee Soong Deok , Chung Doo Hyun
Published: February 2021

Context.—Although the histogenesis of sclerosing hemangioma is currently not well understood, the tumor has been characterized by its 2 histologically different types of cells, namely, surface and polygonal cells.

Objective.—To elucidate the origin of these cells, we analyzed samples from 15 cases of sclerosing hemangioma and 15 specimens of fetal lung tissue.

Design.—We immunostained specimens from 15 cases of sclerosing hemangioma and 15 samples of fetal lung tissue using antibodies against thyroid transcription factor 1, MUC1, Thomsen-Friedenreich antigen, and CD44v6, known as markers for type II pneumocytes, and a panel of antibodies against cytokeratin, epithelial membrane antigen, synaptophysin, CD56, estrogen receptor, and progesterone receptor.

Results.—In fetal lung tissue, MUC1 and thyroid transcription factor 1 were expressed throughout all developmental stages of airway epithelium, whereas Thomsen-Friedenreich antigen and CD44v6 were expressed by type II pneumocytes of saccular and alveolar origin. Thomsen-Friedenreich antigen was expressed in the bronchial bud of the pseudoglandular stage. MUC1, thyroid transcription factor 1, and epithelial membrane antigen were observed in both surface and polygonal cells of sclerosing hemangioma. Only the surface cells in all cases of sclerosing hemangioma showed positivity for cytokeratin and CD44v6. Thomsen-Friedenreich antigen was expressed in the surface cells of 11 of 15 cases of sclerosing hemangioma. Epithelial membrane antigen was expressed in both types of tumor cells, whereas cytokeratin was not detected on polygonal cells, but was reactive with surface cells.

Conclusions.—Our results suggest that the 2 types of cells in sclerosing hemangioma may derive from a common precursor cell through divergent differentiation toward the type II pneumocyte during tumorigenesis.
Acute Lymphoblastic Leukemic Transformation in a Patient With Chronic Idiopathic Myelofibrosis and Paroxysmal Nocturnal Hemoglobinuria: A Case Report and Review of the Literature
Authors: Shaheen Saad Paul , Talwalkar Sameer S. , Simons Ruth , Yam Lung
Published: February 2021

Leukemic transformation of chronic idiopathic myelofibrosis (CIMF) to acute lymphoblastic leukemia (ALL) is rare. We report a case of a patient with CIMF who developed paroxysmal nocturnal hemoglobinuria (PNH) 2 years after initial presentation. His disease eventually transformed to ALL of precursor B-cell type. In that CIMF and PNH are clonal stem cell disorders with different pathogeneses, there may be an association between them. However, leukemic transformation is a rare sequel of both disorders. Coexistence of CIMF and PNH and subsequent transformation to ALL have, to our knowledge, never been previously reported in the world literature. The simultaneous presentation of CIMF and PNH, complicated by the rare sequela of leukemic transformation, raises important issues with regard to diagnosis and treatment.
Storage and Transfusion of Infected Autologous Blood or Components: A Survey of North American Laboratories
Authors: Shulman Ira A. , Osby Melanie
Published: February 2021

Context.—Many patients request that autologous blood or components be collected and available for use during scheduled surgical or invasive medical procedures to avoid exposure to human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) from allogeneic transfusions. Some patients from whom autologous blood is collected are themselves infected with HIV, HBV, or HCV. However, unlike HIV-, HBV-, or HCV-infected allogeneic blood and components, which must be excluded from the community blood supply, infected autologous blood and components are allowed to be stored in hospitals and transfused back to the patients (autologous donors) from whom the blood was collected. Although the transfusion of HIV-, HBV-, or HCV-infected autologous blood or components does not present a risk to the autologous donor, such a transfusion presents a risk to other patients, considering that at least 1 in every 25 000 transfusions are administered to the wrong individual.

Objective.—To determine if hospital transfusion services store and/or transfuse autologous blood or components infected with HIV, HBV, and/or HCV.

Design.—An educational enhancement subsection of a College of American Pathologists Proficiency Testing Survey (J-C 2003) assessed transfusion service practices for storing and/or transfusing HIV-, HBV-, and HCV-infected autologous blood and components.

Setting and Participants.—A total of 4251 participants were asked whether they stored and/or transfused autologous blood or components and whether these stored blood products included those that were infected with HIV, HBV, or HCV.

Results.—Of the 4251 survey respondents, 3561 provided data regarding their autologous blood and component storage and/or transfusion practices. A total of 2988 participants reported that they store and/or transfuse autologous blood or components. A total of 2390 respondents reported that they do not test autologous donations collected in their own institution for evidence of infection with HIV, HBV, or HCV. Most survey participants reported that even if an autologous donation is tested and found to be infected they would still be willing to store and transfuse the blood component, according to which agent was causing the infection: HIV (n = 1867), HBV (n = 2158), or HCV (n = 2233).

Conclusion.—Most North American hospitals do not test autologous blood donations that they collect in their own institution for evidence of infection with HIV, HBV, or HCV, leading to the conclusion that infected autologous blood components are being stored and transfused. Even when autologous donations are tested and found to be infected with HIV, HBV, or HCV, most North American hospitals would be willing to store and/or transfuse the infected autologous blood components.
Performance Characteristics of Several Rules for Self-interpretation of Proficiency Testing Data
Authors: Carey R. Neill , Cembrowski George S. , Garber Carl C. , Zaki Zohreh
Published: February 2021

Context.—Proficiency testing (PT) participants can interpret their results to detect errors even when their performance is acceptable according to the limits set by the PT provider.

Objective.—To determine which rules for interpreting PT data provide optimal performance for PT with 5 samples per event.

Design.—We used Monte Carlo computer simulation techniques to study the performance of several rules, relating their error detection capabilities to (1) the analytic quality of the method, (2) the probability of failing PT, and (3) the ratio of the peer group SD to the mean intralaboratory SD. Analytic quality is indicated by the ratio of the PT allowable error to the intralaboratory SD. Failure of PT was defined (Clinical Laboratory Improvement Amendments of 1988) as an event when 2 or more results out of 5 exceeded acceptable limits. We investigated rules with limits based on the SD index, the mean SD index, and percentages of allowable error.

Results.—No single rule performs optimally across the range of method quality.

Conclusions.—We recommend further investigation when PT data cause rejection by any of the following 3 rules: any result exceeds 75% of allowable error, the difference between any 2 results exceeds 4 times the peer group SD, or the mean SD index of all 5 results exceeds 1.5. As method quality increases from marginal to high, false rejections range from 16% to nearly zero, and the probability of detecting a shift equal to 2 times the intralaboratory SD ranges from 94% to 69%.
Current Management of the Myeloproliferative Disorders: A Case-Based Review
Authors: Rice Lawrence , Baker Kelty R.
Published: February 2021

Context.—Properly managed, the myeloproliferative disorders are generally compatible with prolonged survival. Challenges to the hematologist include knowing when and how best to intervene to prevent and manage complications. The cytoreductive agent of choice for these disorders is currently hydroxyurea, emerging from randomized trials beginning with those of the Polycythemia Vera Study Group.

Objective.—To examine the roles and shortcomings of interventions (including hydroxyurea, antiplatelet agents, anagrelide, interferon, thalidomide, alkylating agents, cell cytopheresis, erythropoietins, splenectomy, bone marrow transplantation, and imatinib) for myeloproliferative disorders.

Data Sources.—This report uses actual case histories to illustrate the roles and shortcomings of these interventions.

Conclusions.—Beyond phlebotomy for polycythemia vera, patients with polycythemia vera and essential thrombocythemia can be stratified by their risk for thrombosis, which guides the institution of cytoreductive therapies. High-risk patients generally benefit from cytoreductive therapy, and hydroxyurea has emerged as the agent of choice, because alkylating agents (and P32) have high leukemogenic potentials. Anagrelide and interferon are second-line agents. The addition of low-dose aspirin is beneficial for most, helping to prevent arterial thrombotic complications. Therapy in any of these disorders should be tailored to the unique characteristics of the individual patient. With myelofibrosis, therapeutic options run the gamut from observation, erythropoietic stimulators, cytotoxic agents, splenectomy, and bone marrow transplantation. Thalidomide and imatinib have shown some utility. Future challenges are the refinement of individualized treatment strategies and the development of targeted therapies based on rapidly expanding understanding of the molecular perturbations in these disorders.
Quality Improvement to Decrease Specimen Mislabeling in Transfusion Medicine
Authors: Quillen Karen , Murphy Kate
Published: February 2021

Context.—Proper specimen identification and labeling is a critical preanalytic step in pretransfusion compatibility testing.

Objective.—To gather baseline data for specimen mislabeling, specifically targeting major mislabeling events, and to design and implement a plan of corrective action.

Design.—All mislabeled specimens received by the transfusion service for a type and screen were recorded and classified into minor and major mislabeling categories. Major mislabeling events were tracked by origin of the specimen. Locations with a high proportion of major mislabeling were given timely feedback (within 1 week) of the events as they arose.

Setting.—A university hospital.

Main Outcome Measures.—The incidence of major mislabeling.

Results.—The incidence of mislabeling in the transfusion service was 0.5% (243/49 955) during 21 months of data collection. Of these mislabeling events, 47% were classified as major events (unlabeled, mismatched specimen/ requisition, ABO/Rh result on current specimen not matching historical record on file). The emergency department accounted for a high proportion of these major mislabeling events. After the intervention of providing weekly feedback to emergency department staff, their contribution to major mislabeling fell from 47% in 1 year (23/49) to 14% (4/29) in the subsequent 3 quarters.

Conclusions.—Collecting and trending data on mislabeled samples with timely feedback to patient care areas can change phlebotomy practice and reduce specimen mislabeling.
Malignant Neoplasm of Perivascular Epithelioid Cells of the Liver
Authors: Parfitt Jeremy R. , Bella Anthony J. , Izawa Jonathan I. , Wehrli Bret M.
Published: February 2021

Neoplasms of perivascular epithelioid cells (PEComas) have in common the coexpression of muscle and melanocytic immunohistochemical markers. Although this group includes entities with distinct clinical features, such as angiomyolipoma, clear cell sugar tumor of the lung, and lymphangioleiomyomatosis, similar tumors have been documented in an increasing diversity of locations. The term PEComa is now generally used in reference to these lesions that are not angiomyolipomas, clear cell sugar tumors, or lymphangioleiomyomatoses. While most reported PEComas have behaved in a benign fashion, malignant PEComas have occasionally been documented. We present a case of hepatic PEComa with benign histologic features, which nonetheless presented with metastases to multiple sites nearly 9 years later. This case represents the second documented malignant PEComa of the liver, as well as the longest follow-up of a surviving patient with a malignant PEComa, emphasizing both the need for criteria that more accurately predict the behavior of PEComas and the necessity of long-term follow-up of patients with PEComas.
Meckel-Gruber Syndrome: Pathologic Manifestations, Minimal Diagnostic Criteria, and Differential Diagnosis
Authors: Alexiev Borislav A. , Lin Xiaoqing , Sun Chen-Chih , Brenner David S.
Published: February 2021

This article provides an overview of the major pathologic manifestations of Meckel-Gruber syndrome, current knowledge about its pathogenesis, minimal diagnostic criteria, and differential diagnosis. Typical sonographic findings (occipital encephalocele, postaxial polydactyly, and cystic enlargement of the kidneys) allow for diagnosis of most cases before the 14th week of gestation, but the pathologist may encounter clinically unsuspected or atypical cases that require morphologic confirmation. In these cases, a meticulous autopsy is necessary to establish the diagnosis of Meckel-Gruber syndrome.
Elder Maltreatment: A Review
Authors: Collins Kim A.
Published: February 2021

Context.—Elder maltreatment is not a new entity but is one that is recently recognized as a widespread and growing social problem. Unfortunately, few physicians are trained to recognize the different forms of elder maltreatment including physical abuse, sexual abuse, and neglect. The elder, age 65 years or older, is also a unique individual with respect to pathophysiology. The natural changes of aging must be considered when assessing any physical or laboratory findings.

Objective.—The practicing pathologist and resident/fellow in training must be familiar with the 6 forms of elder abuse, in particular the 3 forms that are seen in general and forensic pathology: physical abuse, sexual abuse, and neglect. Naturally occurring conditions must also be recognized so that these are not erroneously interpreted as trauma or neglect. Furthermore, the victims and perpetrators, scenarios and risk factors, common anatomic and clinical findings, the pathophysiology of aging, and possible imitators of abuse must be understood.

Data Sources.—This review explores the current medical and psychological understanding of elder maltreatment. Current scientific literature including peer-reviewed journal publications and texts is cited.

Conclusions.—As a prevalent form of domestic violence, we can only expect to see more cases of elder maltreatment as the number and percentage of elders in our population increase. The correct interpretation of physical and laboratory findings is needed to adequately classify these cases, certify the cause and manner of death, and prevent future incidents.
Low-Grade Fibromyxoid Sarcoma: A Brief Review
Authors: Vernon Stephen E. , Bejarano Pablo A.
Published: February 2021

Low-grade fibromyxoid sarcomas are uncommon deep soft tissue neoplasms first described by Evans in 1987. They exhibit a deceptively benign appearance, with a whorled or linear arrangement of spindle-shaped cells showing few to absent mitoses. A characteristic, but not specific, feature is the presence of areas of myxoid stroma. Recurrences are common, and late metastases have been recorded. A closely related but morphologically distinct tumor, the so-called hyalinizing spindle cell tumor with giant rosettes, has also been described; both neoplasms share the same cytogenetic abnormality, a balanced translocation resulting in a FUS/CREB3L2 fusion gene. Because of similar clinical behavior and the common cytogenetic abnormality, some authors prefer to consider both lesions as a single entity within the spectrum of low-grade sarcomas.
Interlaboratory Comparison of Immunohistochemical Testing for HER2: Results of the 2004 and 2005 College of American Pathologists HER2 Immunohistochemistry Tissue Microarray Survey
Authors: Fitzgibbons Patrick L. , Murphy Douglas A. , Dorfman David M. , Roche Patrick C. , Tubbs Raymond R.
Published: February 2021

Context.—Correct assessment of human epidermal growth factor receptor 2 (HER2) status is essential in managing patients with invasive breast carcinoma, but few data are available on the accuracy of laboratories performing HER2 testing by immunohistochemistry (IHC).

Objective.—To review the results of the 2004 and 2005 College of American Pathologists HER2 Immunohistochemistry Tissue Microarray Survey.

Design.—The HER2 survey is designed for laboratories performing immunohistochemical staining and interpretation for HER2. The survey uses tissue microarrays, each consisting of ten 3-mm tissue cores obtained from different invasive breast carcinomas. All cases are also analyzed by fluorescence in situ hybridization. Participants receive 8 tissue microarrays (80 cases) with instructions to perform immunostaining for HER2 using the laboratory's standard procedures. The laboratory interprets the stained slides and returns results to the College of American Pathologists for analysis. In 2004 and 2005, a core was considered “graded” when at least 90% of laboratories agreed on the result—negative (0, 1+) versus positive (2+, 3+). This interlaboratory comparison survey included 102 laboratories in 2004 and 141 laboratories in 2005.

Results.—Of the 160 cases in both surveys, 111 (69%) achieved 90% consensus (graded). All 43 graded cores scored as IHC-positive were fluorescence in situ hybridization-positive, whereas all but 3 of the 68 IHC-negative graded cores were fluorescence in situ hybridization-negative. Ninety-seven (95%) of 102 laboratories in 2004 and 129 (91%) of 141 laboratories in 2005 correctly scored at least 90% of the graded cores.

Conclusion.—Performance among laboratories performing HER2 IHC in this tissue microarray–based survey was excellent. Cores found to be IHC-positive or IHC-negative by participant consensus can be used as validated benchmarks for interlaboratory comparison, allowing laboratories to assess their performance and determine if improvements are needed.
Grading of Soft Tissue Sarcomas: Review and Update
Authors: Coindre Jean-Michel
Published: February 2021

Context.—Histologic grading is the most important prognostic factor and the best indicator of metastatic risk in adult soft tissue sarcomas. The most commonly used systems are the French grading and the National Cancer Institute grading. Both are 3-grade systems and are mainly based on histologic type and subtype, tumor necrosis, and mitotic activity. Rules for using grading should be strictly respected and limitations of grading should be known to obtain the best performance. The most controversial point is the respective values of histologic typing and grading. Histologic typing should be clearly defined before any attempt at grading, and grading should not be used on tumors of intermediate malignancy such as atypical fibroxanthoma and on some sarcomas such as dedifferentiated liposarcoma. However, grading is useful in more than 90% of adult soft tissue sarcomas and has been adapted to pediatric nonrhabdomyosarcomatous sarcomas. Current grading is not suitable for core needle biopsies.

Objective.—To review the current value and limitations of histologic grading in soft tissue sarcomas.

Data Sources.—The reviews on grading and original studies on prognostic factors in soft tissue sarcomas were analyzed.

Conclusions.—Grading is the best predictor of metastasis outcome in adult soft tissue sarcomas and should be part of the pathologic report. Grading should be adapted to the modern management of patients and complemented by radiologic and molecular parameters.
Rhabdomyosarcomas in Adults and Children: An Update
Authors: Parham David M. , Ellison Dale A.
Published: February 2021

Context.—Rhabdomyosarcomas comprise a relatively common diagnostic entity among childhood cancers and a relatively rare one among adult tumors. They may possess a variety of histologies that generally differ among age groups. These lesions appear to be separate biologic entities as well as morphologic categories, with embryonal tumors having genetic lesions related to loss of heterozygosity and aberrant parental imprinting, alveolar tumors containing genetic fusions between PAX and forkhead genes, and pleomorphic tumors showing an accumulation of genetic lesions similar to other adult high-grade sarcomas.

Objective.—To present guidelines for diagnosis of rhabdomyosarcoma and recent finding concerning the biology and classification of these lesions.

Data Sources.—Review of recent and older published literature and distillation of the authors' experience.

Conclusions.—Infants and young children tend to have embryonal rhabdomyosarcomas, adolescents and young adults tend to have alveolar rhabdomyosarcomas, and older adults tend to have pleomorphic rhabdomyosarcomas, although there is some overlap. Newer rare entities, including spindle cell rhabdomyosarcoma and sclerosing rhabdomyosarcoma, have been described in children and adults. Fusion-positive tumors have a distinct molecular signature with downstream activation of a number of myogenic and tumorigenic factors. Genetic testing may be successfully used for diagnosis and may guide therapy in future clinical trials. Differential diagnosis has become simpler than in previous years, because of use of myogenic factors in immunohistochemistry, but classification based solely on histologic features remains challenging.
Lymphomas Involving the Pleura: A Clinicopathologic Study of 34 Cases Diagnosed By Pleural Biopsy
Authors: Vega Francisco , Padula Anthony , Valbuena Jose R. , Stancu Mirela , Jones Dan , Medeiros L. Jeffrey
Published: February 2021

Context.—Pleural involvement by lymphoma is relatively common. However, there are very few clinicopathologic studies reported in the literature of lymphomas involving the pleura.

Objective.—To characterize the clinicopathologic features of lymphomas involving the pleura.

Design.—We reviewed the clinicopathologic features of 34 patients with lymphoma involving the pleura proven by biopsy and classified these neoplasms using the World Health Organization classification.

Results.—There were 22 men and 12 women, with an average age of 62 years (range, 22–82 years). Nine (26.5%) patients had pleural involvement as the only site of disease, 22 (64.7%) had other sites of involvement, and 3 (8.8%) had inadequate staging data. Eighteen (56.2%) of 32 patients with adequate clinical data had a history of lymphoma (including 3 patients with pleural involvement as the only disease site). In 29 (85.3%) cases, a specific diagnosis according to the World Health Organization classification could be made: 17 (58.6%) diffuse large B-cell lymphoma, 5 (17.2%) follicular lymphoma (including a case with areas of diffuse large B-cell lymphoma), 2 (6.9%) small lymphocytic lymphomas/chronic lymphocytic leukemia, 2 (6.9%) precursor T-cell lymphoblastic lymphoma/leukemia, 1 (3.4%) mantle cell lymphoma, 1 (3.4%) posttransplant lymphoproliferative disorder, and 1 (3.4%) classical Hodgkin lymphoma. The other 5 cases were B-cell lymphomas that could not be further classified. Cytologic examination of pleural fluid was performed in 15 cases and was positive for lymphoma in 8 (53.3%) cases.

Conclusions.—Most patients with lymphoma involving the pleura have simultaneous evidence of systemic involvement. The most frequent type is diffuse large B-cell lymphoma, followed by follicular lymphoma. Cytologic examination can have negative results in patients with pleural involvement by lymphoma.
Mucinous Expression in Benign and Neoplastic Glandular Lesions of the Uterine Cervix
Authors: Baker Allyson C. , Eltoum Isam , Curry Rebecca O. , Stockard Cecil R. , Manne Upender , Grizzle William E. , Chhieng David
Published: February 2021

Context.—Mucins are glycoproteins produced by both normal and neoplastic glandular epithelial cells including endocervix.

Objective.—To determine the expression of mucins in uterine cervical glandular lesions and whether mucin expression correlates with the nature and origin of the glandular lesions.

Design.—Antibodies to MUC1, MUC2, MUC4, and MUC5AC were applied on 52 cases including 14 endocervical adenocarcinomas (including 4 adenosquamous carcinomas), 9 endometrial carcinomas (8 endometrioid adenocarcinomas and 1 adenosquamous carcinoma), 8 adenocarcinoma in situ (AIS), 2 glandular dysplasias, 6 tubal metaplasias, 10 microglandular hyperplasias, and 3 normal endocervix. The presence of any staining was considered positive.

Results.—All benign endocervical epithelia, including tubal metaplasia and microglandular hyperplasia, expressed MUC1, MUC4, and MUC5AC but not MUC2. Almost all endocervical AIS and carcinomas and all endometrial adenocarcinomas expressed MUC1; the exceptions were 2 cases of endocervical adenocarcinoma and 1 case of adenosquamous carcinoma of the endocervix. MUC2 staining was noted in 25%, 40%, and 22% of AIS, endocervical adenocarcinomas, and endometrial adenocarcinomas, respectively. About 38% of AIS, 75% of endocervical adenocarcinomas, and 44% of endometrial adenocarcinomas expressed MUC4. Half of AIS, most of endocervical adenocarcinomas, and 22% of endometrial adenocarcinomas expressed MUC5AC. The difference in MUC4 and MUC5AC expression between benign endocervical lesions and AIS and the difference in MUC5AC expression between endocervical and endometrial neoplasms were statistically significant.

Conclusions.—Mucin expressions differed among benign endocervical lesions and AIS and among endocervical and endometrial malignancies. These results suggest that mucin staining may potentially be helpful in differentiating various uterine cervical glandular lesions.
Expression of the Intestinal Transcription Factor CDX2 in Carcinoid Tumors Is a Marker of Midgut Origin
Authors: Jaffee Ian M. , Rahmani Mahdis , Singhal Maria G. , Younes Mamoun
Published: February 2021

Context.—Carcinoid tumors are classified according to their site of origin into foregut, midgut, or hindgut carcinoids, which have different presentations and prognosis. The intestinal transcription factor CDX2 has been found to be expressed in most intestinal adenocarcinomas but in less than one half of the gastrointestinal carcinoids according to 1 study.

Objective.—To determine whether CDX2 expression in carcinoid tumors varies by the site of origin and whether CDX2 expression is retained in metastatic disease.

Design.—Sections of formalin-fixed and paraffin-embedded tissue from 36 primary carcinoid tumors and 5 cases of metastatic carcinoid to the liver were immunohistochemically stained for CDX2. The percent of cells with nuclear immunoreactivity and the intensity of staining were assessed.

Results.—All 18 foregut carcinoids (10 pulmonary and 8 gastric) were negative (0%) for CDX2. All 11 midgut carcinoids (100%) were positive for CDX2 with moderate to strong staining in more than 50% of the cells. Only 2 (29%) of 7 of hindgut carcinoids were CDX2-positive with the 2 positive cases showing weak to moderate staining intensity in less than 10% of the cells. Expression of CDX2 in more than 50% of tumor cells was seen only in midgut carcinoids (P < .001). CDX2 expression in metastatic tumors was consistent with the site of origin.

Conclusions.—Midgut carcinoid tumors and their metastases are distinct from foregut and hindgut carcinoids in that they express high levels of CDX2. Additional studies are needed to determine whether CDX2 immunostaining may be helpful in determining the primary site of metastatic carcinoid tumors of unknown origin.
Subinvolution of the Placental Site as an Anatomic Cause of Postpartum Uterine Bleeding: A Review
Authors: Weydert Jamie A. , Benda Jo Ann
Published: February 2021

Context.—Subinvolution of the placental site is an anatomic cause of delayed postpartum uterine bleeding that may be underrecognized by general surgical pathologists.

Objective.—To review the physiology of uteroplacental arterial development and normal postpartum involution, and to present the characteristic clinical and histopathologic features of subinvolution.

Data Sources.—Literature review (MEDLINE via PubMed and Ovid) regarding the pathology and pathophysiology of placental site subinvolution. Review of the clinical and pathologic characteristics of our own institution's previously diagnosed cases of subinvolution from hysterectomy and endomyometrial curettage specimens.

Conclusions.—Surgical pathologists must be aware of the cardinal histopathologic findings of subinvolution, and this diagnosis must be considered in every postpartum curettage or hysterectomy specimen presented to the surgical pathologist. Subinvolution of the placental site is an important diagnosis, as this process implies an idiopathic cause, rather than an iatrogenic cause, of postpartum uterine bleeding. The etiology of placental site subinvolution remains poorly characterized.
Primary Angiosarcoma of the Bladder
Authors: Seethala Raja R. , Gomez Jose A. , Vakar-Lopez Funda
Published: February 2021

Context.—Primary bladder angiosarcomas are extremely rare, and their clinical and pathologic features are not well described.

Objective.—To further refine the clinical features of primary bladder angiosarcomas and define their pathologic spectra.

Data Sources.—Relevant sources were identified using MEDLINE and a subsequent bibliographic search of all pertinent reports and reviews. We also searched the M. D. Anderson pathology archives.

Study Selection.—After excluding 4 cases that likely secondarily involved the bladder, we identified 9 true primary bladder angiosarcomas.

Data Extraction.—Data were extracted on the following: demographics, clinical presentation, predisposing factors, gross pathology, microscopic pathology, immunophenotype, therapy, and outcomes.

Data Synthesis.—Primary bladder angiosarcomas were found at a mean age of 64.2 years, with a male-female ratio of 8:1. Two cases arose in a postirradiation setting. Primary bladder angiosarcomas typically presented with hematuria and were grossly hemorrhagic, raised masses (mean size, 6.7 cm) of the trigone and/or dome. Histologically, most showed classic anastomosing channels lined by plump hyperchromatic cells, though many showed variant histology such as solid growth and epithelioid cytology. Three (43%) of 7 patients died within a year, but only 1 patient died with evidence of disease. The remaining patients were alive at the time of publication of their respective cases (mean, 22 months).

Conclusions.—Primary angiosarcomas of the bladder are typically rare tumors of middle-aged and elderly men that present with locally advanced disease and show a wide histologic spectrum. However, their prognosis may be better than previously thought.
Hamartomatous Polyps of the Colon: Ganglioneuromatous, Stromal, and Lipomatous
Authors: Chan Owen T. M. , Haghighi Parviz
Published: February 2021

Intestinal ganglioneuromas comprise benign, hamartomatous polyps characterized by an overgrowth of nerve ganglion cells, nerve fibers, and supporting cells in the gastrointestinal tract. This polyposis has been divided into 3 subgroups, each with a different degree of ganglioneuroma formation: polypoid ganglioneuroma, ganglioneuromatous polyposis, and diffuse ganglioneuromatosis. The ganglioneuromatous polyposis subgroup is not known to coexist with systemic disorders that often have an associated intestinal polyposis, such as multiple endocrine neoplasia type IIb, neurofibromatosis type I, and Cowden syndrome. We report a case of ganglioneuromatous polyposis plus cutaneous lipomatosis in a 41-year-old man with no established systemic disease. However, he possessed unique anatomic findings in addition to his ganglioneuromatosis, suggesting that the ganglioneuromatosis-lipomatosis in our patient may represent an unrecognized syndrome. This case report and brief review of the literature provide an overview of intestinal ganglioneuromatosis in relation to the hereditary polyposis syndromes and describe the individual ganglioneuromatosis subgroups.
Distinguishing Carcinoid Tumor of the Mediastinum From Thymoma: Correlating Cytologic Features and Performance in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology
Authors: Renshaw Andrew A. , Haja Jennifer C. , Neal Margaret H. , Wilbur David C.
Published: February 2021

Context.—The cytologic features of carcinoid tumor in mediastinal fine-needle aspiration are well described. Nevertheless, this tumor may be difficult to distinguish from thymoma in this site.

Objective.—We sought to correlate the cytologic features of carcinoid tumor of the mediastinum in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology with the frequency of misclassification as thymoma.

Design.—We reviewed 446 interpretations from 18 different cases of carcinoid tumor in mediastinum and correlated the cytologic features with performance.

Results.—Cases were more frequently classified as thymoma (158 responses, 35%) than as carcinoid tumor (126 responses, 28%). The best-performing case was classified as carcinoid tumor only 56% of the time. Three cytologic patterns were identified. Four cases consisted of isolated round cells with salt-and-pepper chromatin. Four cases consisted of isolated spindle and round cells with salt-and-pepper chromatin. The remaining 10 cases consisted of cohesive fragments of crowded cells with finely granular chromatin showing numerous pyknotic cells mimicking lymphocytes. Prominent vasculature patterns were not a feature of any of the cases. There was no correlation between any pattern and the rate of classification as carcinoid tumor or thymoma (P > .05).

Conclusions.—Carcinoid tumor of the mediastinum is frequently misclassified as thymoma in this program. Although some cytologic patterns resemble thymoma, the lack of correlation of these patterns with performance suggests that at least part of the reason for misclassification may be failure to consider the correct diagnosis or a lack of familiarity with discriminating cytologic criteria.
Extensively Necrotic Retinoblastoma Is Associated With High-Risk Prognostic Factors
Authors: Chong Eva-Marie , Coffee Robert E. , Chintagumpala Murali , Hurwitz Richard L. , Hurwitz Mary Y. , Chévez-Barrios Patricia
Published: February 2021

Context.—Retinoblastoma is the most common malignant intraocular tumor in children. It has been shown that adjuvant therapy following enucleation in patients with high-risk histopathologic features significantly decreases the mortality. We describe the association of extensive necrosis of tumor and intraocular structures with 2 of the major risk factors: optic nerve invasion and choroidal invasion. This may alert the pathologist who makes the observation of extensive necrosis to carefully search for histologic features associated with adverse outcome.

Objective.—To determine whether extensively necrotic retinoblastoma is associated with high-risk histologic prognostic factors for metastatic disease and patient survival.

Design.—Retrospective case series. Forty-three eyes of 43 patients with retinoblastoma who underwent enucleation between 1990 and 2001 were evaluated. Medical records, histopathology specimens, pathology reports, and clinical photographs were reviewed. Tumors were designated as exhibiting extensive necrosis if more than 95% of tumor cells and intraocular tissues were necrotic. The main outcome measure was the association of extensive tumor necrosis with 3 high-risk histopathologic features: extraocular extension, optic nerve invasion, or choroidal invasion. Metastatic disease, patient survival, and associations with pathologic findings were also analyzed.

Results.—Optic nerve head invasion (P < .001), post-lamina-cribrosal invasion (P < .001), and choroidal invasion by tumor (P = .004) were observed more frequently in eyes with extensive necrosis compared with eyes without extensive necrosis. Two of the 11 patients with extensively necrotic intraocular retinoblastoma died from metastatic disease (P = .06). None of the 32 patients without extensive necrosis developed metastatic disease or died.

Conclusions.—Extensive ocular tissue and tumor necrosis is associated with histologic high-risk prognostic factors for tumor metastasis and mortality.
Hospital Nursing Satisfaction With Clinical Laboratory Services: A College of American Pathologists Q-Probes Study of 162 Institutions
Authors: Jones Bruce A. , Walsh Molly K. , Ruby Stephen G.
Published: February 2021

Context.—Monitoring customer satisfaction is an important and useful quality improvement tool and is required of most clinical laboratories in the United States.

Objective.—To survey the level of nursing satisfaction with hospital clinical laboratory services.

Design.—Participating laboratories provided information regarding laboratory demographics and practices. These laboratories then surveyed hospital nursing personnel regarding their level of satisfaction with defined aspects of laboratory service.

Setting.—College of American Pathologists Q-Probes laboratory quality improvement study in 162 hospital laboratories.

Main Outcome Measures.—Nursing overall satisfaction score (ranging from 1, not satisfied, to 5, very satisfied) and satisfaction scores for 13 specific aspects of clinical laboratory services.

Results.—One hundred sixty-two institutions submitted data from a total of 7033 nursing surveys. The overall satisfaction score for all institutions ranged from 2.5 to 4.6. The median overall score for all participants was 3.9 (10th percentile, 3.2; 90th percentile, 4.2). Nursing personnel were most satisfied with the accuracy of test results, phlebotomy courtesy toward patients and nursing staff, and notification of abnormal results. They were least satisfied with stat test turnaround time, laboratory management responsiveness and accessibility, phlebotomy responsiveness to service requests, and routine test turnaround time. The most important aspect of laboratory service reported by nursing personnel was stat test turnaround time.

Conclusions.—Most nursing personnel are satisfied with the clinical laboratory services that are provided to the patients in their care. Although test result accuracy is very highly regarded, there is room for improvement in several aspects of service, particularly in test turnaround time and laboratory management accessibility and responsiveness.
Odontogenic Myxoma: A Clinicopathologic Study of 25 Cases
Authors: Li Tie-Jun , Sun Li-Sha , Luo Hai-Yan
Published: February 2021

Context.—Odontogenic myxoma is an uncommon tumor that has the potential for extensive destruction of the jaws.

Objective.—To document the clinical, pathologic, and behavioral features of odontogenic myxomas.

Design.—Histologic and immunocytochemical examinations were performed on odontogenic myxomas from 25 Chinese patients. Clinical and available follow-up data were analyzed.

Results.—In the present series, 13 were male and 12 female. The age at diagnosis ranged from 6 to 66 years, with a mean age of 28.8 years. Twelve tumors involved the mandible and 13 occurred in the maxilla, with a predilection for posterior areas. The posterior maxillary tumors frequently (9/10) involved the maxillary sinus. Of the 23 cases with radiographic records, 22 lesions presented with a multilocular appearance. Although 80% of the mandibular lesions showed a well-defined border, only 33.3% of the maxillary tumors were well-defined. Histologically, odontogenic myxomas were mainly composed of spindled or stellate-shaped cells in a mucoid-rich intercellular matrix. Tumors containing noticeable fibrous components were evident in 13 cases. Apart from 5 cases treated conservatively by enucleation, the remaining 20 cases were treated by relatively radical procedures, including block/segmental resection and partial or total maxillectomy or mandibulectomy. Follow-up data were available on 22 patients and only 1 patient initially treated by enucleation had a recurrence.

Conclusions.—Odontogenic myxomas have a very bland histologic appearance that lacks atypia and may easily lead to misdiagnosis. The tumors are infiltrative with no capsulation and may recur after inadequate surgery.
Comparative Analysis of Routine Histology, Immunohistochemistry, Reverse Transcriptase Polymerase Chain Reaction, and Fluorescence In Situ Hybridization in Diagnosis of Ewing Family of Tumors
Authors: Jambhekar Nirmala A. , Bagwan Izhar N. , Ghule Prachi , Shet Tanuja M. , Chinoy Roshni F. , Agarwal Sandhya , Joshi Rupali , Amare Kadam Pratibha S.
Published: February 2021

Context.—The Ewing family of tumors are often difficult to distinguish from other malignant small round cell tumors, but more than 90% have EWS-FLI1 chimeric transcript, which acts as a potential molecular diagnostic marker.

Objective.—To do a comparative analysis of 32 cases with EWS-FLI1: Ewing family of tumors (n = 30), desmoplastic small round cell tumor (n = 1), and undifferentiated sarcoma (n = 1).

Design.—The initial diagnosis was made on core biopsy (n = 22) and open biopsy (n = 4) specimens by using morphology and immunohistochemistry and on fine-needle aspiration cytology ([FNAC], n = 6) specimens. EWS-FLI1 was detected by reverse transcriptase polymerase chain reaction on all 32 fresh FNAC samples and by fluorescence in situ hybridization on 16 paraffin blocks.

Results.—The 19 male and 13 female patients had bone (n = 19) or soft tissue (n = 13) tumors. Histologic groups were typical Ewing sarcoma (n = 15), atypical Ewing sarcoma (n = 4), Askin Rosai tumors (n = 5), desmoplastic small round cell tumor (n = 1), undifferentiated sarcoma (n = 1), and cases diagnosed as malignant small round cell tumors on FNAC (n = 6). All tumors except desmoplastic small round cell tumor and undifferentiated sarcoma were CD99 positive. EWS-FLI1 by reverse transcriptase polymerase chain reaction was noted in 15 cases of typical Ewing sarcoma, 4 cases of atypical Ewing sarcoma, 5 cases of Askin Rosai tumor, and no cases of desmoplastic small round cell tumor or undifferentiated sarcoma. With use of fluorescence in situ hybridization, EWS break was detected in 10 of 11 paraffin blocks used and was negative in desmoplastic small round cell tumor.

Conclusions.—The excellent correlation of routine histologic findings in Ewing family of tumors with results on immunohistochemistry and fluorescence in situ hybridization on archival material and reverse transcriptase polymerase chain reaction on fresh FNAC specimens underscores that the traditional observation on routine histologic examination is a time-tested tool. The diagnosis of Ewing family of tumors can be validated on archival material or fresh biopsy samples, including those obtained by FNAC.
Does Physiologic Breakdown Mask Significant Pathology in Endometrial Biopsies? A Retrospective Case-Control Study
Authors: Galan Mark , Kim Young Bae , Hecht Jonathan L.
Published: February 2021

Context.—Adequacy criteria for endometrial biopsy samples do not exist.

Objective.—To assess the sensitivity of endometrial sampling for detecting neoplasia in the setting of extensive glandular and stromal breakdown.

Design.—Retrospective case-control study. Surgical pathology records between 1996 and 2005 at Beth Israel Deaconess Medical Center (Boston, Mass) were searched for endometrial samples with diagnoses containing the key words “menstrual” or “extensive breakdown.” Hospital records for these women were parsed for demographics, clinical indications, and follow-up with rebiopsy within 6 months. Age cutoffs enriched the population for women at higher risk for carcinoma. A control group, consisting of 2 age-matched control patients for each test patient, was also studied; each control patient had an endometrial sample taken within a 6-month period and was not diagnosed with extensive breakdown, menstrual endometrium, or neoplasia on initial sampling.

Results.—Fifty-four cases were identified. The primary biopsy reports had benign descriptive diagnoses (ie, proliferative, secretory, polyp). Follow-up biopsies showed benign pathology in all cases and specific causes of bleeding—including polyp, leiomyoma, or endometritis—in 28 (52%) of 54. In the control group, neoplasia was found in 2 of the 108 follow-up biopsies. Only 5 other controls had specific diagnoses; all were polyps.

Conclusions.—Extensive breakdown or menstrual-pattern endometrium may mask other specific benign pathologies but does not commonly mask cancer.