bluuebunny/crossref_metadata_2025 huggingface dataset:
Ensuring Timely Completion of Type and Screen Testing and the Verification of ABO/Rh Status for Elective Surgical Patients
Authors: Saxena Sunita , Nelson Janice M. , Osby Melanie , Shah Mrugesh , Kempf Raymond , Shulman Ira A.
Published: February 2021

Context.—A blood bank can provide compatible blood for an elective surgical procedure, provided a blood sample is received by the laboratory with sufficient time to allow pretransfusion testing and acquire enough compatible red blood cell units. With the push for same-day admission surgical procedures, a patient's pretransfusion blood sample is often collected the morning of surgery. However, if blood is needed, compatible units might not be immediately available.

Objective.—To define and improve the process of completing presurgical/preadmission type and screen testing and verifying the ABO/Rh status of scheduled surgical patients before they receive a transfusion.

Study Design.—A list of surgical procedures that might necessitate blood transfusion was created. A checklist was used to ensure that the preoperative clinic nurse collects a baseline pretransfusion blood sample for type and screen testing from patients scheduled for a listed procedure. A new pretransfusion specimen was received on the day of surgery, if needed, so that a current specimen would be available for compatibility testing and to verify the accuracy of the patient's ABO/Rh status in case blood was requested.

Results.—During the 1-year study period, 666 patients qualified for baseline type and screen testing. Cholecystectomy was the most commonly scheduled surgery. In 99% of cases, a baseline type and screen specimen was received in the laboratory at least 1 day before surgery. The interval between the preoperative clinic visit and date of surgery varied from same day (6 patients) to 3 months.

Conclusion.—Timely receipt of a presurgical specimen for type and screen testing and verification of a patient's ABO/Rh status can be ensured when clinical services collaborate and when the hospital blood utilization committee provides oversight to improve compliance.
Clinical Laboratory Specimen Rejection—Association With the Site of Patient Care and Patients' Characteristics: Findings From a Single Health Care Organization
Authors: Stark Azadeh , Jones Bruce A. , Chapman Deborah , Well Karen , Krajenta Richard , Meier Frederick A. , Zarbo Richard J.
Published: February 2021

Context.—Programs to track laboratory quality have reported aggregated specimen rejection rates ranging from 0.30% to 0.83%. Because the performance of the laboratory, rather than errors, has been the focus, reasons for specimen rejection or demographic characteristics of individuals at risk for specimens of poor quality may not be fully understood.

Objective.—To calculate the proportions of rejected specimens stratified by point of collections and demographic information of patients.

Design.—Retrospective cross-sectional study. Data were retrieved from the intrainstitutional electronic databases.

Results.—The proportions of specimens that were rejected in the emergency department and inpatient services were 2-fold and more than 5-fold higher, respectively, than for the outpatient services. Assessment of data by patients' ethnic heritages yielded no significant differences among African Americans (0.38%), Caucasians (0.38%), or “Others” (0.35%) in the outpatient services (P = .07). In the emergency department, the proportions of rejected specimens for African Americans (2.24%) were almost twice that of Caucasians (1.39%) and 30% higher than for Others (1.70%). A similar finding was observed for the inpatient services.

Conclusions.—The effect of ethnicity on the proportions of rejected specimens was significant for samples that were collected in the emergency department and inpatient services, even after adjusting for the total number of specimens. A constellation of factors, that is, disease severity and seriousness, practice of blood sample collection, and lesser proficiency of the nursing staff in phlebotomy may be reasons for this observation. However, the likelihood of differential care, although unlikely, cannot be refuted by the present data.
Perineurioma: A Distinctive and Underrecognized Peripheral Nerve Sheath Neoplasm
Authors: Macarenco Ricardo S. , Ellinger Fred , Oliveira Andre M.
Published: February 2021

Context.—Perineuriomas are benign peripheral nerve sheath neoplasms composed of perineurial cells with characteristic immunohistochemical and ultrastructural features. They have been traditionally classified into two main types according to their location—intraneural and extraneural—and overlap histologically with many other tumors, which may be diagnostically challenging to general surgical pathologists.

Objective.—To review the clinical, morphologic, immunohistochemical, ultrastructural, cytogenetic, and molecular genetic aspects of perineurioma, as well as to discuss its clinicopathologic variants and differential diagnosis.

Data Sources.—English-language literature published between 1966 and 2005 was reviewed.

Conclusions.—The correct identification of perineuriomas is important to avoid unnecessary overtreatment. The histologic diagnosis should be confirmed through immunohistochemical studies (including epithelial membrane antigen, S100 protein, and more recently described antibodies such as claudin-1 and GLUT1) or electron microscopy. Cytogenetic and molecular genetic studies are still of limited value for the diagnosis of perineuriomas but may play a fundamental role in excluding important differential diagnoses and also in helping elucidate the biology of these poorly known neoplasms.
Transfusion Medicine for the Practicing Pathologist/Physician With Responsibilities for the Transfusion Service
Authors: Sazama Kathleen
Published: February 2021

Transfusion medicine is a challenging and complex medical practice that occurs in virtually every hospital, except perhaps rehabilitation and mental health facilities, on a frequent, often daily, basis. The knowledge base required to effectively meet the standard of care for transfusion practice is increasing at a rapid pace. It is not unusual for patients with successful ABO changes due to bone marrow or stem cell transplantation to be treated in their local community hospital or even to receive such transplantations much closer to home than previously. Routine transfusions for patients with anemia, hemoglobinopathies, elective surgeries, and trauma, as well as the special needs of neonates and geriatric patients, are provided in hospital transfusion services of all sizes. In some hospitals, there are board-certified physician specialists in transfusion medicine who provide hands-on consultative services to their colleagues, whereas in other facilities, the technical specialists (including blood banking and specialist in blood banking certified personnel) shoulder much of the burden of providing these services.
Measurement of PTEN Expression Using Tissue Microarrays to Determine a Race-Specific Prognostic Marker in Breast Cancer
Authors: Winter Jerald Luke , Stackhouse Bodiford L. , Russell Gregory B. , Kute Timothy E.
Published: February 2021

Context.—African American women with breast cancer have worse prognoses than non–African Americans and might benefit with a race-specific prognostic marker such as PTEN (phosphatase and tensin homologue), a tumor suppressor protein. Reduced PTEN expression is associated with worse outcomes and resistance to trastuzumab in human epidermal growth factor receptor 2–positive breast cancers. Standardized PTEN evaluation is therefore needed.

Objective.—To assess PTEN as a race-specific prognostic marker in breast cancer by using a novel semiquantitative score and a percent staining assessment.

Design.—Between 1991 and 1996, 146 patients with invasive ductal adenocarcinoma were grouped by race and recurrence; there was a median follow-up of 7.2 years with 63 recurrences. Immunostaining of PTEN in tissue microarrays was correlated with race, recurrence, node positivity, stage, size, age, estrogen/progesterone receptor status, grade, and DNA ploidy.

Results.—No significant racial difference was detected in mean PTEN values using either the semiquantitative score (P = .46) or the percent staining (P = .54). Unrelated to race, the percentage of tumor cells with positive PTEN expression correlated with longer time to recurrence (P = .047), positive estrogen receptor status (P = .009), and lower tumor grade (P = .005). The semiquantitative score correlated with positive estrogen receptor status (P = .01) and lower tumor grade (P = .001).

Conclusions.—PTEN expression is not a race-specific biologic prognostic marker for invasive ductal adenocarcinoma. Increased PTEN expression correlates with longer time to recurrence, positive estrogen receptor status, and lower tumor grade. The novel semiquantitative score may be used to evaluate PTEN expression, but the approximate percentage of tumor cells with any PTEN staining may be the most useful measure of PTEN expression.
Typing of Amyloidosis in Renal Biopsies: Diagnostic Pitfalls
Authors: Satoskar Anjali A. , Burdge Kelly , Cowden Daniel J. , Nadasdy Gyongyi M. , Hebert Lee A. , Nadasdy Tibor
Published: February 2021

Context.—Amyloidosis represents a group of diseases with extracellular deposition of congophilic fibrils of similar morphology but differing chemical composition. The types commonly involving the kidney are AL (light chain amyloid) and AA (serum amyloid A). Familial amyloidosis can also affect the kidney, but we have not encountered such a case during the study period. Distinguishing between the AL and AA forms of amyloid is clinically important because of the different treatments and outcomes. The classification of amyloidosis is made by immunostaining with antibodies to κ and λ immunoglobulin light chains and for serum amyloid A protein.

Objective.—To draw attention to the nonspecific immunofluorescence staining patterns in renal biopsies with amyloidosis, causing potential diagnostic pitfalls.

Design.—Renal biopsies from 15 patients, including 13 cases of AL and 2 cases of AA amyloidosis, were studied. Immunofluorescence staining with routine antibody panel and immunoperoxidase staining for amyloid A were performed.

Results.—Of the 13 cases of AL amyloidosis, 2 cases showed little difference in staining intensity between κ and λ light chains (2+ and 3+, respectively) and 4 cases showed only moderate intensity (2+) of the predominant light chain. The 2 cases diagnosed as AA amyloidosis also exhibited staining for light chains. One case had strong (3+) signal for κ and moderate (2+) for λ light chain, while the other showed weaker staining.

Conclusions.—Immunofluorescence staining for immunoglobin light chains on renal biopsy, as the first step to differentiate between AL and AA amyloidosis, may sometimes be inconclusive or even misleading. Applying amyloid A immunostain on a routine basis and detailed clinical history are essential to avoid misclassification.
Sarcomatoid Carcinoma of the Lung: Histologic Criteria and Common Lesions in the Differential Diagnosis
Authors: Franks Teri J. , Galvin Jeffrey R.
Published: February 2021

Context.—Sarcomatoid carcinoma of the lung is a subset of poorly differentiated non–small cell lung cancers that are diagnostically challenging because they are uncommon, may reveal little of their parent cell of origin, and overlap morphologically with other anaplastic epithelioid and spindle cell tumors that can be primary in, or metastatic to, the lung and pleura.

Objective.—To review the current histologic classification and diagnostic criteria that identify the 5 subtypes of sarcomatoid carcinoma of the lung and to discuss the most common tumors in the differential diagnosis.

Design.—Published classification systems from the World Health Organization and pertinent peer-reviewed articles indexed in PubMed (National Library of Medicine) form the basis of this review.

Conclusions.—Identification of sarcomatoid carcinoma of the lung requires knowledge of specific histologic criteria that define the 5 subgroups, targeted immunohistochemical studies, and correlation with chest imaging to assess distribution of disease and to avoid misdiagnosis.
Is the Epidermal Growth Factor Receptor Status in Lung Cancers Reflected in Clinicopathologic Features?
Authors: Inamura Kentaro , Ninomiya Hironori , Ishikawa Yuichi , Matsubara Osamu
Published: February 2021

Context.—Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are molecular-targeted drugs that are innovatively effective for non–small cell lung carcinomas with EGFR mutations. Epidermal growth factor receptor is a transmembrane receptor forming dimers on ligand binding. These then stimulate signals by activating receptor autophosphorylation through tyrosine kinase activity. Autophosphorylation triggers intracellular pathways facilitating malignant conversion. The most clinically advanced EGFR inhibition strategies include small-molecule inhibition of the intracellular tyrosine kinase domain (gefitinib and erlotinib) and monoclonal antibody–mediated blockade of the extracellular ligand-binding domain (cetuximab). Lung cancers with EGFR mutations are prevalent among patients who are female, of Asian ethnicity, and nonsmokers; thus, they can obtain benefit from EGFR tyrosine kinase inhibitors.

Objective.—To survey histopathologic findings and examine correlations with EGFR mutations. We mainly focused on component cell types (hobnail, columnar, and polygonal) and presence or absence of bronchioloalveolar carcinoma elements and a micropapillary pattern. Although EGFR mutations can be detected by various methods, including polymerase chain reaction–Invader assay or direct sequencing, these are inconvenient.

Data Sources.—Review of the published literature.

Conclusion.—Detailed pathologic examination showed significant genotype-phenotype correlations between EGFR mutations and presence of a bronchioloalveolar carcinoma component, a micropapillary pattern, and the hobnail cell type. We conclude that these characteristic histologic features are good predictors of EGFR mutations, and patients with these features might be good candidates for and could benefit from therapy with EGFR tyrosine kinase inhibitors.
Basaloid Follicular Hamartoma
Authors: Mills Omie , Thomas L. Brannon
Published: February 2021

Basaloid follicular hamartoma is a benign lesion of important consideration because it can be mistaken both clinically and histologically for basal cell carcinoma. The formation of basaloid follicular hamartoma has been linked to a mutation in the patched gene, which is part of the same pathway implicated in nevoid basal cell carcinoma syndrome. While these hamartomas are considered benign lesions, malignant growths have been reported to arise within them, which raises the question, “Is basaloid follicular hamartoma a premalignant lesion?” Correct identification allows for periodic monitoring for malignant transformation, while sparing patients unnecessary surgery. Treatment strategies, including experimental therapies, are reviewed.
The Small Cell Variant of Anaplastic Large Cell Lymphoma
Authors: Summers Thomas A. , Moncur Joel T.
Published: February 2021

Anaplastic large cell lymphomas constitute a heterogeneous group of hematopoietic neoplasms that are characterized by immunopositivity for CD30 and the presence, in varying degrees, of large, pleomorphic “hallmark” cells. Primary systemic anaplastic lymphoma kinase-positive anaplastic large cell lymphomas are a subset of this group. Numerous heterogeneous histomorphologic patterns have been described in anaplastic lymphoma kinase-positive anaplastic large cell lymphomas, and all patterns tend to have a better prognosis than that found in anaplastic lymphoma kinase-negative cases. We provide a short review of the small cell variant of anaplastic large cell lymphoma to facilitate the diagnosis of this difficult-to-recognize entity, which may be confused with reactive processes, commonly presents with disseminated disease, and pursues an aggressive clinical course.
Do Liquid-Based Preparations of Urinary Cytology Perform Differently Than Classically Prepared Cases? Observations From the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology
Authors: Laucirica Rodolfo , Bentz Joel S. , Souers Rhona J. , Wasserman Patricia G. , Crothers Barbara A. , Clayton Amy C. , Henry Michael R. , Chmara Beth Anne , Clary Karen M. , Fraig Mostafa M. , Moriarty Ann T.
Published: February 2021

Context.—The cytomorphology of liquid-based preparations in urine cytology is different than classic slide preparations.

Objectives.—To compare the performance of liquid-based preparation specimens to classically prepared urine specimens with a malignant diagnosis in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology.

Design.—Participant responses between 2000 and 2007 for urine specimens with a reference diagnosis of high-grade urothelial carcinoma/carcinoma in situ/dysplasia (HGUCA), squamous cell carcinoma, or adenocarcinoma were evaluated. ThinPrep and SurePath challenges were compared with classic preparations (smears, cytospins) for discordant responses.

Results.—There were 18 288 pathologist, 11 957 cytotechnologist, and 8086 “laboratory” responses available. Classic preparations comprised 90% (n = 34 551) of urine challenges; 9% (n = 3295) were ThinPrep and 1% (n = 485) were SurePath. Concordance to the general category of “positive-malignant” was seen in 92% of classic preparations, 96.5% of ThinPrep, and 94.6% of SurePath challenges (P < .001). These results were statistically different for the exact reference interpretation of HGUCA (P < .001) but not for adenocarcinoma (P = .22). Cytotechnologists demonstrate statistically better performance for the general category of “positive-malignant” compared with pathologists for all urinary slide types and for the exact reference interpretation of HGUCA (94% versus 91.1%; P < .001) but not adenocarcinoma (96.3% versus 95.8%; P = .77) or squamous cell carcinoma (93.6% versus 87.7%; P = .07).

Conclusions.—Liquid-based preparations performed significantly better in urinary cytology challenges when evaluating malignant categories in the College of American Pathologists interlaboratory comparison program. The liquid-based preparation challenges also performed better for the exact reference interpretation of HGUCA, but no difference was observed for adenocarcinoma challenges. Cytotechnologists perform better than pathologists for all slide types, as well as those demonstrating HGUCA. These results suggest that liquid-based preparations facilitate a more accurate diagnosis than conventional preparations.
Clinical Utility of Adjunctive High-Risk Human Papillomavirus DNA Testing in Women With Papanicolaou Test Findings of Atypical Glandular Cells
Authors: Zhao Chengquan , Florea Anca , Austin R. Marshall
Published: February 2021

Context.

Atypical glandular cell (AGC) Papanicolaou (Pap) test interpretations are challenging. Most biopsy findings are benign, but AGC results may also reflect highly significant noninvasive neoplastic and malignant histologic outcomes. High-risk human papillomavirus (hrHPV) test use with AGC Pap test results is evolving.

Objective.

To further evaluate the utility and limitations of hrHPV testing with AGC Pap tests.

Design.

Hospital records were searched for AGC Pap tests results from June 1, 2005, to August 31, 2007. Cases of AGC with hrHPV tests and histopathologic follow-up were included.

Results.

Of the 662 women with AGC Pap test results and follow-up analyzed, hrHPV results were available for 309 (46.7%) and were positive in 75 cases (24.3%). Among the 75 cases with hrHPV+ AGC results, 13 (17.3%) had cervical intraepithelial neoplasia grades 2/3, 10 (13.3%) had adenocarcinoma in situ, and 3 (4.0%) had cervical invasive adenocarcinoma, whereas for 234 women with hrHPV− results, 1 (0.4%) had cervical intraepithelial neoplasia grades 2/3, 1 (0.4%) had adenocarcinoma in situ, 1 each (0.4%) had cervical adenocarcinoma and ovarian carcinoma, and 8 (3.4%) had endometrial carcinoma.

Conclusions.

Positive hrHPV AGC results were most strongly associated with cervical intraepithelial neoplasia grades 2/3 and adenocarcinoma in situ in women younger than 50 years. Positive hrHPV AGC results were also present in all 3 cases of invasive cervical adenocarcinoma in women younger than 50 years. Of note, hrHPV− AGC results were present in 10 of 13 carcinomas (76.9%) detected after AGC Pap tests, all in women 40 years or older with endometrial adenocarcinomas (n  =  8), ovarian carcinoma (n  =  1), and cervical adenosquamous carcinoma in a woman (n  =  1) in her 50s. Testing for hrHPV after AGC Pap testing was most helpful in the detection of cervical intraepithelial neoplasia grades 2/3, adenocarcinoma in situ, and invasive cervical adenocarcinomas in women younger than 50 years.
Well-Differentiated Neuroendocrine (Carcinoid) Tumors of the Extrahepatic Biliary Ducts
Authors: Noronha Yvonne Saldanha , Raza Anwar Sultana
Published: February 2021

Primary, well-differentiated neuroendocrine (carcinoid) tumors of the extrahepatic biliary ducts are an uncommon cause of biliary obstruction. As compared to cholangiocarcinomas, which are more commonly seen at this location, these tumors tend to behave less aggressively, and only one-third metastasize. Tumor size (>2 cm) appears to be the best predictor of aggressive behavior. Surgery is the mainstay of treatment and complete resection offers prolonged disease-free survival. Accurate preoperative diagnosis is therefore important and can be made by examining brush cytology specimens obtained during endoscopic retrograde cholangiopancreatography and/or endoscopic ultrasound-guided fine-needle aspiration. It is important to keep this entity in mind, especially when examining cytologic or small biopsy specimens, so that appropriate immunohistochemical stains can be used to arrive at the correct diagnosis.
Variation in Human Erythrocyte Membrane Unsaturated Fatty Acids: Correlation With Cardiovascular Disease
Authors: Sepulveda Jorge L. , Tanhehco Yvette C. , Frey Monica , Guo Lida , Cropcho Lorna J. , Gibson K. Michael , Blair Harry C.
Published: February 2021

Context.—Whether cell membrane fatty acid (FA) composition is a useful indicator of vascular disease is unclear.

Objective.—To study variation of erythrocyte (RBC) membrane FA in samples from healthy volunteers, hospitalized patients, and cardiac troponin I–elevated patients with myocardial damage without a priori assumptions as to FA composition.

Design.—We separated FAs extracted from RBCs by gas chromatography and identified them by mass spectrometry. Fatty acids with abundance greater than 1% of total were quantified and compared: hexadecanoic (C16:0), octadecadienoic (C18:2), cis- and trans-octadecenoic (C18:1), and eicosatetraenoic (C20:4) acids. Deuterated standards established proportionality of FA recovery. The cis- and trans-C18:1 identification was verified by comparison with standards.

Results.—In troponin-positive samples, C18:2 to C18:1 ratios were increased 30% compared with healthy controls or with random patient samples. Erythrocyte trans-C18:1 had a wide variation, ∼10-fold, in all groups but without differences between groups. Replicates showed that the wide range of RBC trans-FA load is not due to analytic variation. In healthy subjects, the RBC content of lower– molecular weight FAs (C16-C18) correlated with serum low-density lipoprotein cholesterol, but despite the established relationship between dietary trans-FA and increased low-density lipoprotein cholesterol, lipid profiles had no correlation with RBC trans-FA content.

Conclusions.—Erythrocyte accumulation of unsaturated FA may be a useful indicator of vascular disease, whereas the wide range in trans-FAs suggests that both diet and genetic variation affect RBC trans-FA accumulation. Unsaturated FAs increase membrane fluidity and may reflect a natural response to subclinical vascular changes, which may in turn reflect increased risk of clinical disease.
Trastuzumab as Adjuvant Therapy for Early Breast Cancer: The Importance of Accurate Human Epidermal Growth Factor Receptor 2 Testing
Authors: Hicks David G. , Kulkarni Swati
Published: February 2021

Context.—Overexpression of human epidermal growth factor receptor 2 (HER2) is an adverse prognostic parameter for patients with breast cancer. Patients with HER2-positive tumors are, however, likely to gain significant benefit from targeted therapy with trastuzumab. Four large-scale trials have assessed the efficacy and safety of adjuvant trastuzumab. In all 4 trials, disease-free survival and overall survival were significantly improved with adjuvant trastuzumab (36%–52% and 33%–41%, respectively), and improvements were observed in all patient subgroups.

Objective.—To describe, in detail, the clinical benefits of using trastuzumab in the adjuvant setting, and to emphasize the importance this places on the pathologist to correctly identify all patients with HER2-positive tumors with a high degree of accuracy.

Data Sources.—Published literature on both HER2 testing and the adjuvant use of trastuzumab.

Conclusions.—Immunohistochemistry and/or fluorescence in situ hybridization are routinely used to determine HER2 status. Maintaining quality assurance throughout a standardized testing process is essential to achieve accurate and reproducible assay results. Adherence to the new American Society of Clinical Oncology/College of American Pathologists HER2 testing guidelines will help to ensure correct identification of all patients who may benefit from adjuvant trastuzumab and has significant implications for patient outcomes.
Practical Pituitary Pathology: What Does the Pathologist Need to Know?
Authors: Asa Sylvia L.
Published: February 2021

Context.—The sellar region is the site of frequent pathology. The pituitary is affected by a large number of pathologic entities arising from the gland itself and from adjacent anatomical structures including brain, blood vessels, nerves, and meninges. The surgical pathology of this area requires the accurate characterization of primary adenohypophysial tumors, craniopharyngiomas, neurologic neoplasms, germ cell tumors, hematologic malignancies, and metastases as well as nonneoplastic lesions such as cysts, hyperplasias, and inflammatory disorders.

Objective.—To provide a practical approach to the diagnosis of pituitary specimens.

Data Sources.—Literature review and primary material from the University of Toronto.

Conclusions.—The initial examination requires routine hematoxylin-eosin to establish whether the lesion is a primary adenohypophysial proliferation or one of the many other types of pathology that occur in this area. The most common lesions resected surgically are pituitary adenomas. These are evaluated with a number of special stains and immunohistochemical markers that are now available to accurately classify these tumors. The complex subclassification of pituitary adenomas is now recognized to reflect specific clinical features and genetic alterations that predict targeted therapies for patients with pituitary disorders.
Expression of Melanoma Antigens in Epithelioid Gastrointestinal Stromal Tumors: A Potential Diagnostic Pitfall
Authors: Guler Mehmet L. , Daniels Jason A. , Abraham Susan C. , Montgomery Elizabeth A.
Published: February 2021

Context.—Most gastric gastrointestinal stromal tumors (GISTs) express CD117/c-kit, as do a subset of metastatic melanomas, leading to a diagnostic dilemma in some cases.

Objective.—To further differentiate GISTs from melanoma, we investigated expression of melanoma markers in GISTs using a well-characterized set of gastric lesions on tissue microarrays.

Design.—Tissue microarrays from paraffin-embedded tissue cores from 38 patients were stained with S100 protein, HMB-45, and Melan-A antibodies. All cases had been previously stained with CD117/c-kit and CD34 antibodies. All were reactive with CD117/c-kit, and 88.2% expressed CD34.

Results.—S100 protein was focally expressed in 2 (5.3%) of 38 GISTs; these lesions lacked HMB-45 and Melan-A labeling. No tumor labeled with HMB-45, but 4 (10.6%) of 38 cases labeled with Melan-A antibodies. The Melan-A–reactive cases were all S100 negative and CD34 positive. The S100-reactive cases were spindle cell neoplasms, whereas the Melan-A–reactive cases were epithelioid neoplasms (4/9; 44%). An additional 15 standard sections of separate cases of epithelioid GISTs were then labeled with Melan-A, and 5 (33%) of 15 showed at least focal labeling.

Conclusions.—Melan-A staining can be encountered in a subset of epithelioid GISTs, a finding that can suggest a differential diagnosis of melanoma. In this series, the Melan-A–reactive cases lacked S100 protein and expressed CD34, both of which would be unlikely in melanoma. As such, a panel approach is best in differentiating epithelioid GISTs from melanoma.
How Much Tissue Sampling Is Required When Unsuspected Minimal Prostate Carcinoma Is Identified on Transurethral Resection?
Authors: Trpkov Kiril , Thompson Jenny , Kulaga Andrew , Yilmaz Asli
Published: February 2021

Context.—When minimal prostate cancer is detected in the initial transurethral resection of the prostate (TURP) sample, it is uncertain how extensively the remaining tissue should be sampled for accurate grading and staging.

Objective.—To identify whether additional partial or complete sampling is required to accurately evaluate TURP samples with minimal cancer (stage T1a).

Design.—We prospectively examined all TURP samples in our institution during 1 year. All specimens were sampled randomly in 6 cassettes. When minimal cancer was found, we performed additional partial sampling (1 block per 5 g of remaining tissue), followed by complete submission of all remaining tissue. All samples were evaluated separately to identify possible changes in Gleason score and tumor volume. We performed a cost analysis for the additional tissue sampling.

Results.—Of 747 TURP samples evaluated on the initial 6 cassettes, 125 (16.7%) contained prostate cancer. Minimal cancer involving less than 5% of sampled tissue was found in the initial submission in 26 (3.5%) patients. Additional partial examination required 3.5 blocks per case (median; range, 1–23), while complete processing required an additional 5.5 blocks per case (median; range, 2–25). Initial Gleason scores and tumor volumes were not changed in any of the studied cases after evaluating the additional partial and complete samples. In our laboratory, we calculated a cost of $4336 per year for the additional sampling of TURPs with minimal cancer ($1681 for partial and $2655 for complete sampling).

Conclusions.—When minimal cancer was found in the first 6 cassettes of transurethral resections, additional partial and complete sampling did not change the initial Gleason scores and tumor volumes.
The Impact of Gene Expression Microarrays in the Evaluation of Lung Carcinoma Subtypes and DNA Copy Number
Authors: Sanchez-Cespedes Montserrat
Published: February 2021

Context.—The development of targeted therapies creates a need to accurately classify tumors. Among the more pressing needs are the identification of the complete catalog of genes that are altered in cancer and the accurate discrimination of tumors based on their genetic background.

Objectives.—To discuss the use of gene expression profiles to recapitulate the pathology and to distinguish the genetic background of non–small cell lung cancer. Also, to comment on using global analysis of gene expression to identify chromosomal regions carrying clusters of highly expressed genes, likely due to gene amplification. Gene amplification at these regions may target the activation of an oncogene critical to tumor development and potentially important in therapy.

Data Sources.—Review of relevant, recent literature on molecular alterations and expression analysis in lung cancer.

Conclusions.—The complexity of genetic and epigenetic alterations and the cell type of origin confer marked patterns of gene expression to lung tumors, which differentiate different tumor entities.
Reporting Guidelines for Clinical Laboratory Reports in Surgical Pathology
Authors: Goldsmith Jeffrey D. , Siegal Gene P. , Suster Saul , Wheeler Thomas M. , Brown Richard W.
Published: February 2021

Context.—The surgical pathology report (SPR) is an essential part of patient care because it documents the pathologic findings in tissues removed from patients for diagnostic or therapeutic reasons. Despite the importance of the SPR, exhaustive guidelines outlining the various elements of the SPR have not, to our knowledge, been published.

Objectives.—To outline recommendations delineating the required, preferred, and optional elements that should be included in the SPR. These guidelines, if implemented, will bring uniformity to the reporting of surgical pathology specimens.

Data Sources.—The Surgical Pathology Resource Committee of the College of American Pathologists compiled and prioritized the elements that have been included in various institutional SPRs. Additional data sources include the College of American Pathologists Laboratory Accreditation Program checklists and the recommendations of the Association of Directors of Anatomic and Surgical Pathology. Each element was assigned a priority of required, preferred, or optional. These priorities were discussed and consensus was reached. This report does not address issues of formatting or style substantively.

Conclusions.—These recommendations afford a framework for the creation of an SPR containing all of the components that are required or optimal for patient care.
Hepatic Angiomyolipoma
Authors: Petrolla Amber A. , Xin Wei
Published: February 2021

Hepatic angiomyolipoma is a rare, benign, hepatic mesenchymal neoplasm found in both males and females, and most commonly in adult females. Angiomyolipoma occurs most commonly in the kidneys. The liver represents the second most frequent site of involvement. Hepatic angiomyolipomas are composed of varying amounts of smooth muscle cells, adipose tissue, and vessels. The smooth muscle cell component is the most specific to the diagnosis. The smooth muscle cells can have varying morphologies and are positive for homatropine methylbromide–45 but are negative for hepatocyte paraffin 1 and S100 protein. The definitive diagnostic study remains the histologic examination of the surgically resected lesion coupled with immunohistochemical stains. The differential diagnosis includes hepatocellular carcinoma, hepatic adenoma, leiomyoma, hepatoblastoma, melanoma, and gastrointestinal stromal tumor. The immunohistochemical staining pattern differentiates this lesion from other malignant and benign liver lesions. If the diagnosis of hepatic angiomyolipoma has been made, it can be followed conservatively or surgically resected.
National HER2 Proficiency Test Results Using Standardized Quantitative Controls: Characterization of Laboratory Failures
Authors: Vani Kodela , Sompuram Seshi R. , Fitzgibbons Patrick , Bogen Steven A.
Published: February 2021

Context.—An important component in fostering test standardization for HER2 testing by immunohistochemistry is an appropriate positive control. We developed a new standardized, quantitative immunohistochemical HER2 control using a HER2 peptide covalently attached to glass microscope slides. The peptide controls can be formalin fixed or unfixed, providing the new capability of distinguishing errors associated with antigen retrieval from errors associated with the staining process itself.

Objective.—To investigate the causes of variability in HER2 immunohistochemistry staining performance. By comparing laboratory performance with both formalin-fixed and unfixed analyte controls, we aimed to distinguish problems associated with antigen retrieval from reagent or staining protocol deficiencies.

Design.—HER2 peptide analyte controls were printed on 2 slides that also contained unstained sections of invasive breast carcinomas and were mailed with the College of American Pathologists' 2006 HER2-B proficiency testing survey. Laboratory participants were asked to stain the 2 slides and return them for central review and quantification. This study is unique in combining central review with new quantitative HER2 controls.

Results.—Of 109 participants who returned evaluable stained slides, staining was suboptimal in 20 (18.3%) as judged by quantification of the peptide analyte controls and review of tissue sections. Of those, 35% failed due to antigen retrieval errors, 20% failed due solely to antibody or staining protocol problems, and the remainder failed due to a combination of the two.

Conclusions.—In practice, errors in HER2 testing are caused by variables associated with antigen retrieval and the reagents and staining protocol, as well as interpretive error. Analyte controls help distinguish these different causes.
Intraoperative Consultation/Final Diagnosis Correlation: Relationship to Tissue Type and Pathologic Process
Authors: White Valerie A. , Trotter Martin J.
Published: February 2021

Context.—The correlation of the diagnosis made at intraoperative consultation (IC) with the final diagnosis is one of the cornerstones of quality assurance in the anatomic pathology laboratory.

Objective.—To review correlation of IC diagnoses with final diagnoses during a 1-year period in a regionalized, multisite hospital setting in a major Canadian city.

Design.—One pathologist reviewed all surgical pathology cases at Calgary Laboratory Services from June 2004 through May 2005 that had an IC to extract the following data points: intraoperative diagnoses, final diagnoses, correlation between the two, anatomic site of the tissue on which the IC was requested, pathologic procedure requested of the IC, types of disagreements encountered, reasons for disagreement, and deferrals.

Results.—Intraoperative consultations occurred for 2812 specimens, of which 87 were discordant and 135 were deferred. Percent agreement was 96.75% (95% confidence interval, 96.08–97.42) with a κ statistic of 0.94 (95% confidence interval, 0.92–0.95). Lymph nodes for evaluation for metastases (427), thyroid/parathyroid (401), and central/peripheral nervous system (378) specimens were sent most frequently for IC, and the latter 2 tissue types accounted for the greatest number of disagreements. The most common assessments requested were the presence/ typing of a neoplasm (1161) and assessment of margins (730), which also accounted for the largest number of disagreements. Disagreements were most frequently due to interpretive (53) and gross sampling (23) errors; false-negative disagreements were nearly 3 times as common as false positives.

Conclusions.—The IC was an excellent diagnostic test. Agreement and deferral rates varied by specimen site and by type of assessment requested.
The Pathology of Pulmonary Disorders Due to Aspergillus spp
Authors: Kradin Richard L. , Mark Eugene J.
Published: February 2021

Diagnosing the range of pulmonary disorders caused by Aspergillus spp can be challenging. In instances of hypersensitivity responses to Aspergillus spp (ie, allergic bronchopulmonary aspergillosis, bronchocentric granulomatosis, and hypersensitivity pneumonitis), the surgical pathologist must be cognizant of their relationship to infection, as fungal organisms may be rare or absent from the biopsy specimens. Within the spectrum of opportunistic infection, it is critical to distinguish Aspergillus spp from other fungal mimics, as well as to discern whether infection is limited, progressive, or immanently life threatening. However, the surgical pathologist who establishes expertise in this area will be rewarded by the satisfaction of having contributed primarily to an important area of patient care. This article reviews the spectrum of pulmonary disorders due to infection by Aspergillus spp, with emphasis on the clinical implications of diagnosis.
Interface Dermatitis
Authors: Crowson A. Neil , Magro Cynthia M. , Mihm, Jr Martin C.
Published: February 2021

Interface dermatitis can be classified based upon the cell type that dominates the infiltrate (ie, neutrophilic, lymphocytic, or lymphohistiocytic) or by the intensity of the interface inflammation. Regarding lymphocytic interface dermatitis, there are 2 broad categories: cell-poor interface dermatitis, when only a sparse infiltrate of inflammatory cells is present along the dermoepidermal junction, or cell rich, which typically occurs as a heavy bandlike infiltrate that obscures the basal layers of the epidermis. In the case of lymphocytic interface dermatitis, the latter is often termed a lichenoid interface dermatitis. This review focuses upon the mononuclear cell-predominant forms of interface dermatitis.
Lesions of the Bones of the Hands and Feet: A Study of 50 Cases
Authors: Uppin Shantveer G. , Sundaram C. , Umamahesh Matapathi , Chandrashekar P. , Rani Y. Jyotsna , Prasad V. B. N.
Published: February 2021

Context.—The bones of the hands and feet constitute more than half of the bones in the human skeleton (106/ 206), but lesions occurring in them are infrequently reported. Although many of the lesions that occur in the rest of the skeletal bones can occur in bones of the hands or feet, their distribution and frequency differ.

Objective.—To study lesions involving bones of the hands or feet.

Design.—Retrospective study of all lesions involving bones of the hands or feet during the period from January 2000 to September 2006 from a university hospital in southern India. Clinical, radiologic, and pathologic features were reviewed.

Results.—The 50 lesions encountered included 23 (46.0%) infections/inflammatory lesions, 16 (32.0%) benign tumors, 6 (12.0%) malignant tumors, and 5 (10.0%) tumorlike lesions. Giant cell tumor was the most common benign tumor. Malignant tumors involved the nonphalangeal bones, with chondrosarcoma the most common.

Conclusions.—Lesions of the bones of the hands or feet are uncommon. Awareness and correlation of clinical, radiologic, and pathologic features help in making correct diagnoses.
Clinicopathologic Significance of Nuclear Grooves and Inclusions in Renal Cell Carcinoma: Image Database Construction and Quantitative Scoring
Authors: Lee Ju-Han , Han Eun Mee , Lin Zhen-Hua , Wu Zheng-Sheng , Lee Eung-Seok , Kim Young-Sik
Published: February 2021

Context.—Nuclear grooves and inclusions are major features of cancer. However, the nuclear irregularities in renal cell carcinoma (RCC) have not yet been well characterized.

Objective.—To determine the clinicopathologic significance of nuclear grooves and inclusions in RCC.

Design.—The frequencies or scores of nuclear grooves and inclusions were compared with the histologic subtype, nuclear grade, and TNM stage, as well as overall survival of RCC patients. For objective counting of nuclear irregularities, a relational image database was constructed and used for quantitative assessment.

Results.—Nuclear grooves and inclusions were seen in 96% and 65% of 110 RCC cases, respectively. The intranuclear inclusions were found more frequently in chromophobe and papillary types than in clear cell carcinoma (P < .001). The nuclear scores, the sum of grooves or inclusions per 5000 tumor cells, were highly related to the histologic subtype (P < .001). Clear cell RCCs with high inclusion scores (2 or more) were correlated with poorer overall survival in comparison to clear cell carcinomas with low inclusion scores (P = .04). The groove scores were highly associated with Fuhrman grade (P = .003) but not with overall survival of clear cell RCC patients (P = .65). In multivariate analysis, higher inclusion scores and advanced tumor stages (III/IV) were correlated with worse outcomes of clear cell RCC.

Conclusions.—Nuclear grooves and inclusions are histologic components of RCCs, especially chromophobe and papillary carcinomas. Furthermore, nuclear inclusions might be an independent prognostic factor for clear cell RCC.
Pancreatic Manifestations of von Hippel-Lindau Disease
Authors: Safo Anthony-Osei F. , Pambuccian Stefan E.
Published: February 2021

Von Hippel-Lindau disease is an uncommon, multisystem, multitumor disorder that can present in sporadic form but is more commonly inherited as an autosomal-dominant disease with high penetrance. Affected patients are at increased risk for developing multiple synchronous or metachronous benign or malignant, cystic, and vascular neoplasms of various organs. The characteristic neoplasms associated with von Hippel-Lindau are hemangioblastoma of the central nervous system and retina, clear cell renal cell carcinoma, and pheochromocytoma, but other lesions are well recognized. Pancreatic lesions, both primary and metastatic, are common, and several differential diagnostic possibilities must be considered.
MicroRNAs in Benign and Malignant Hematopoiesis
Authors: Bhagavathi Sharathkumar , Czader Magdalena
Published: February 2021

MicroRNAs (miRNAs) are a family of 19- to 24-nucleotide noncoding RNAs that regulate messenger RNA function at the posttranscriptional and translational level. Recent literature demonstrates a significant role of miRNAs in normal and malignant hematopoiesis. Specific miRNAs have been shown to regulate each step of hematopoiesis starting at the level of multipotent progenitors through terminal stages of myeloid and lymphoid differentiation. Similarly, individual miRNAs and miRNA signatures have been associated with specific hematologic malignancies. There is accumulating evidence that miRNAs can be used for diagnostic, prognostic, and therapeutic purposes. This review highlights the current status of knowledge on miRNA in normal and malignant hematopoiesis.
Legal Aspects of Laboratory Medicine and Pathology for Residents and Fellows: A Curriculum for Pathology Training Programs
Authors: Otte Kimberly K. , Zehe Sharon C. , Wood Angela J. , Hernandez James S. , Karon Brad S.
Published: February 2021

Context.—Preparing residents and fellows to manage laboratories and pathology practices increasingly requires awareness of the law and a framework within which to manage legal risk in dealing with compliance, malpractice, and human resources issues.

Objectives.—To describe a curriculum for pathology and laboratory medicine residents and fellows that highlights activities most likely to result in adverse legal outcomes and to help trainees understand when the services of an attorney may be required.

Design.—The 3-hour course evolved as part of a comprehensive leadership and management curriculum designed to help meet systems-based practice and professionalism requirements. Didactic lectures and interactive case scenarios were presented, and participants then evaluated the course content and speakers on a 5-point scale (5  =  high). Short-term knowledge accumulation was assessed by comparison of performance on the laboratory administration section of the Resident In-Service Examination between junior residents who had not taken the course and senior residents who did take the course.

Results.—The course was evaluated by 72 trainees during a 5-year period (2004–2008); the mean overall rating was 4.6 (range, 3.5–5.0). Senior residents (n  =  37) had a mean (SD) score on the Resident In-Service Examination laboratory administration section of 521 (67) for 2004 through 2008. Junior residents (n  =  51), who had not yet completed the course, scored 470 (70) (P < .001) for the same period.

Conclusions.—This curriculum met the needs of professionals entering careers in laboratory medicine and pathology and can be modified for other pathology and laboratory medicine training programs.