bluuebunny/crossref_metadata_2025 huggingface dataset:
Total Long-term Within-Laboratory Precision of Cortisol, Ferritin, Thyroxine, Free Thyroxine, and Thyroid-Stimulating Hormone Assays Based on a College of American Pathologists Fresh Frozen Serum Study: Do Available Methods Meet Medical Needs for Precision?
Authors: Steele Bernard W. , Wang Edward , Palmer-Toy Darryl E. , Killeen Anthony A. , Elin Ronald J. , Klee George G.
Published: February 2021

Context.—It is important that the total long-term precision of laboratory methods meet the medical needs of the patients being served.

Objectives.—To determine the long-term within- and between-laboratory variation of cortisol, ferritin, thyroxine, free thyroxine, and thyroid-stimulating hormone measurements using commonly available methods and to determine if these variations are within accepted medical needs.

Design.—Two vials of pooled frozen serum were mailed 6 months apart to laboratories participating in 2 separate College of American Pathologists surveys. The data from those laboratories that analyzed an analyte in both surveys were used to determine for each method the total variance and the within- and between-laboratory components.

Setting.—The study included the A mailing of the 2003 College of American Pathologists Ligand Survey and the C mailing of the Chemistry Survey.

Main Outcome Measures.—For each analyte, total variance was partitioned into within- and between-laboratory components for each analytic method. The within-laboratory variations were then compared with imprecision criteria based on biological variation.

Participants.—The laboratories that reported results on the same analyte using the same method in both surveys.

Results.—For each analyte, the median of the long-term within-laboratory variances of each peer group was 78% to 95% of its total-survey variance, and the median long-term within-laboratory coefficients of variation varied from 5.1% to 7.6%. The number of methods that met within-laboratory imprecision goals based on biological criteria were 5 of 5 for cortisol; 5 of 7 for ferritin; 0 of 7 for thyroxine and free thyroxine; and 8 of 8 for thyroid-stimulating hormone.

Conclusions.—For all analytes tested, the total within-laboratory component of variance was the major source of variability in this study. In addition, there are several methods, especially for thyroxine and free thyroxine, that may not meet analytic goals in terms of their imprecision.
Comparison of Fresh Frozen Serum to Proficiency Testing Material in College of American Pathologists Surveys: α-Fetoprotein, Carcinoembryonic Antigen, Human Chorionic Gonadotropin, and Prostate-Specific Antigen
Authors: Schreiber William E. , Endres David B. , McDowell Geraldine A. , Palomaki Glenn E. , Elin Ronald J. , Klee George G. , Wang Edward
Published: February 2021

Context.—Most proficiency testing materials (PTM) contain an artificial matrix that may cause immunoassays to perform differently with this material than with clinical samples. We hypothesized that matrix effects would be reduced by using fresh frozen serum (FFS).

Objective.—To compare the performance of an FFS pool to standard PTM for measurement of α-fetoprotein, carcinoembryonic antigen, human chorionic gonadotropin (hCG), and prostate-specific antigen (PSA).

Design.—One FFS specimen and 4 different admixtures of PTM were distributed in the 2003 College of American Pathologists K/KN-A (for α-fetoprotein, carcinoembryonic antigen, hCG, and total and free PSA) and C-C (hCG only) Surveys.

Participants.—The number of laboratories that participated in the surveys varied from a low of 288 (free PSA, K/KN-A Survey) to a high of 2659 (hCG, C-C Survey).

Main Outcome Measures.—Method imprecision and method bias were compared between the FFS specimen and the standard PTM specimen with the closest value. Method imprecision was determined by calculating the coefficients of variation for each method and for all methods combined. Bias was defined as the proportional difference between peer-group mean and the median of all method means.

Results.—The FFS specimen gave significantly higher imprecision than PTM for the analytes α-fetoprotein, carcinoembryonic antigen, total PSA, and free PSA. For hCG, no substantial imprecision differences were observed in both surveys. Bias was significantly greater for the α-fetoprotein, carcinoembryonic antigen, and total PSA assays and significantly lower for the hCG and free PSA assays when comparing the FFS with the PTM.

Conclusions.—Fresh frozen serum did not provide consistently lower imprecision or bias than standard PTM in a survey of commonly ordered tumor markers.
Perineural and Vascular Invasion in Oral Cavity Squamous Carcinoma: Increased Incidence on Re-review of Slides and by Using Immunohistochemical Enhancement
Authors: Kurtz Kevin A. , Hoffman Henry T. , Zimmerman M. Bridget , Robinson Robert A.
Published: February 2021

Context.—Perineural invasion and vascular invasion may be adverse prognostic factors in patients with oral cavity squamous cell carcinoma. However, the incidence of perineural and vascular invasion varies in the literature, and the use of immunohistochemistry to enhance their detection has not been evaluated in oral cavity squamous cell carcinomas.

Objective.—To determine if the previously assessed incidence of perineural and vascular invasion in cases of oral cavity squamous cell carcinoma would be increased by re-review of the original routinely hematoxylin-eosin–stained sections as well as review of slides stained immunohistochemically with S100 and CD31 to enhance visualization of nerves and vessels.

Design.—Forty cases of oral cavity squamous cell carcinoma in which the status of perineural and vascular invasion had been part of the original pathology report were reviewed. All original routinely stained slides were reviewed as well as S100- and CD31-stained sections of each case's tissue blocks that contained tumor.

Results.—Perineural invasion was identified in 30% (12/ 40) of tumors in the original reports, 62% (25/40) of the authors' re-review of the same slides, and 82% (33/40) when cases were stained with S100. Vascular invasion was identified in 30% (12/40) of tumors in the original reports, 35% (14/40) of the authors' re-review of the same slides, and 42% (17/40) when cases were stained with CD31. False-positive and false-negative results were common in the original reports. The number of foci of both types of invasion was related to its discovery in the original reports. Vascular invasion, but not perineural invasion, was significantly associated with death at 5-year follow-up.

Conclusions.—Although careful re-review of routinely stained slides will detect a significant number of cases of perineural and vascular invasion, immunohistochemical enhancement further improves the accuracy of the determination.
Copy Number Analysis of c-erb-B2 (HER-2/neu) and Topoisomerase IIα Genes in Breast Carcinoma by Quantitative Real-Time Polymerase Chain Reaction Using Hybridization Probes and Fluorescence In Situ Hybridization
Authors: Murthy Sabita K. , Magliocco Anthony M. , Demetrick Douglas J.
Published: February 2021

Context.—The Topoisomerase IIα (TOP2A) protein is the target of the anthracycline class of chemotherapeutic agents. TOP2A is frequently coamplified with c-erb-B2 and consequently might be a prognostic and/or predictive factor for breast cancer patients when anthracycline-based chemotherapy is a consideration. A total of 20% to 35% of breast carcinomas show amplification of the erb-B2 gene, some of which also have coamplification of the TOP2A gene. Investigation of the prognostic or predictive significance of these gene amplifications requires a reliable and sensitive method for the measurement of gene copy number in clinical tumor samples.

Objective.—To assess 2 different assay methods that might allow accurate, reproducible, quantitative, and high-throughput estimation of gene copy number in fresh, frozen, or paraffin-embedded breast cancer specimens.

Design.—We developed an assay and analyzed the gene copy numbers of the erb-B2 and TOP2A genes in 8 breast cancer cell lines, 6 fresh frozen samples, and 38 paraffin-embedded breast tumor specimens by a novel real-time polymerase chain reaction (PCR) assay using hybridization probes. The results were compared with standard fluorescence in situ hybridization.

Results.—We discovered a 100% concordance between assessment of gene copy number of erb-B2 and TOP2A between quantitative PCR and fluorescence in situ hybridization (FISH). Quantitative PCR also had the additional feature of uncovering an erb-B2 gene polymorphism. Finally, we observed that TOP2A amplification only occurred in conjunction with erb-B2 amplification in our paraffin-embedded cases of invasive breast carcinoma and that this event was present in 5 (42%) of 12 erb-B2 amplified cases.

Conclusions.—We conclude that the potentially automatic, real-time PCR analysis using hybridization probes is an efficient method to perform copy number analysis, with results that appear identical to the FISH technique and with the benefit of identifying HER-2 polymorphisms.
Cytologic Features of High-Grade Squamous Intraepithelial Lesion in Conventional Slides: What Is the Difference Between Cases That Perform Well and Those That Perform Poorly?
Authors: Renshaw Andrew A. , Prey Marianne U. , Hodes Lori , Weisson Maggie , Haja Jennifer , Moriarty Ann T.
Published: February 2021

Context.—Previous studies have suggested that cases of high-grade squamous intraepithelial lesion in conventional smears and in ThinPrep specimens that are frequently misinterpreted as normal have relatively few small and hypochromatic dysplastic cells.

Objective.—To determine the cytologic differences between conventional Papanicolaou slides of high-grade squamous intraepithelial lesion that perform poorly and those that perform well.

Design.—We compared the cytologic features of 22 cases of conventional smears with high-grade squamous intraepithelial lesion that performed poorly in the College of American Pathologists Interlaboratory Comparison Program in Gynecologic Cytology with 45 cases of conventional smears that performed extremely well.

Results.—Cases that performed poorly were significantly more likely to have 50 or fewer single dysplastic cells (P = .003) and to have only small dysplastic cells (P = .01). Cases that performed well were also more likely to have more than 500 dysplastic cells (P = .002), to exhibit the presence of large dysplastic cells (P < .001), and to be keratinized (P = .03). Hypochromasia and the number of groups of dysplastic cells were not correlated with performance.

Conclusions.—Conventional smears with high-grade squamous intraepithelial lesion with 50 or fewer single dysplastic cells, no large dysplastic cells, and lacking keratinization are highly associated with poor performance in this program.
Thromboelastographic and Hemostatic Characteristics in Pediatric Patients With Sickle Cell Disease
Authors: Yee Donald L. , Edwards Rachel M. , Mueller Brigitta U. , Teruya Jun
Published: February 2021

Context.—Patients with sickle cell disease suffer from a variety of vaso-occlusive events that may be related to activation of the hemostatic system. Thromboelastography assesses the functionality of this system from a global standpoint and has demonstrated some utility in detecting hypercoagulable states in varied clinical settings, but it has not been systematically evaluated in patients with sickle cell disease.

Objective.—To characterize the findings of thromboelastography in patients with sickle cell disease during periods of steady state and illness, to compare these results with those of healthy controls, and to correlate these profiles with other measured hemostatic parameters.

Design.—In this cross-sectional study, we obtained thromboelastographic and other hemostatic data on specimens from 46 patients with sickle cell disease (35 with hemoglobin SS, 7 with hemoglobin SC, and 4 with hemoglobin S-β thalassemia) and 20 healthy race-matched controls. Data were obtained from patients with sickle cell disease at baseline conditions (n = 41) and in the setting of acute illness (n = 5).

Results.—Patients with hemoglobin SS had lower reaction time and higher angle, maximum amplitude, and coagulation index values on thromboelastography than the control group. Hemoglobin SC patients had higher angle, maximum amplitude, and coagulation index values than controls. Hemoglobin S-β thalassemia patients showed no significant differences compared with controls. Five hemoglobin SS patients with recent or current illness demonstrated increased maximum amplitude and coagulation index compared with hemoglobin SS patients at baseline conditions.

Conclusions.—Patients with sickle cell disease demonstrated a significant hypercoagulable state in thromboelastography profiles, with the degree of abnormality dependent on the type of sickle cell disease and perhaps the presence of acute illness. Continued follow-up of this patient cohort, as well as further study of larger and more homogeneous patient groups, is required to adequately assess the utility of thromboelastography in predicting complications of sickle cell disease.
A Rare Case of Periosteal Osteoblastoma Located in the Frontal Cranial Bone
Authors: Lin Yun Chyi , Commins Deborah L. , Fedenko Alexander N. , Pinsky Gregory S.
Published: February 2021

Periosteal osteoblastoma is an extremely rare bone-forming neoplasm located on the surface of cortical bone. Of the fewer than 30 cases of periosteal osteoblastomas found in the literature, 2 have been reported to be located in cranial bone, and these have not been documented in detail with clinical history, radiographic findings, macroscopic features, and microscopic findings. Although the differential diagnoses of periosteal lesions include parosteal and periosteal osteosarcoma, periosteal chondroma and chondrosarcoma, osteochondroma, osteoid osteoma, periostitis ossificans, and myositis ossificans, an important differential diagnosis both radiologically and pathologically of such a lesion in the cranium is meningioma. We report an unusual case of periosteal osteoblastoma located in the frontal cranial bone that was radiologically consistent with a meningioma. The differential diagnosis of metaplastic meningioma with differentiation toward bone is discussed.
Sentinel Node Status and Tumor Characteristics: A Study of 234 Invasive Breast Carcinomas
Authors: Cao Ying , Paner Gladell P. , Rajan Prabha B.
Published: February 2021

Context.—Axillary lymph node status is the most important prognostic factor in patients with breast cancer. Tumor size and lymph node status, the most reliable pathologic bases of the tumor staging system, are practical parameters for estimating survival status. With the advent of lymphatic mapping and sentinel node (SN) identification, there is potential for a more efficient and sensitive evaluation of the axillary lymph node status.

Objective.—To correlate SN status with tumor size, grade, and lymphovascular invasion.

Design.—We examined 234 patients with unifocal breast carcinomas measuring 25 mm or less as detected by preoperative ultrasound during the period May 1998 through December 2002. Sentinel nodes were examined by frozen section and paraffin section as per protocol.

Results.—Of the 234 patients, SN was identified in 221 (94.5%). An average of 1.38 SNs were examined per patient. Seventy-seven of 221 patients were SN positive on paraffin section. Sixty-six (85.7%) of these 77 cases could be correctly diagnosed as positive for metastatic carcinoma on frozen section. Two cases reported as positive on paraffin section were reported as suspicious on frozen section. Logistic regression indicated that tumor size, grade, and lymphovascular invasion were all significantly associated with SN status (P < .001).

Conclusions.—Tumor size, grade, and lymphovascular invasion were significantly associated with SN status in unifocal invasive breast carcinoma.
Analysis of Red Cell Mass and Plasma Volume in Patients With Polycythemia
Authors: Lorberboym Mordechai , Rahimi-Levene Naomi , Lipszyc Helena , Kim Chun K.
Published: February 2021

Context.—Polycythemia describes an increased proportion of red blood cells in the peripheral blood. In absolute polycythemia, there is increased red cell mass (RCM) with normal plasma volume, in contrast with apparent polycythemia, in which there is increased or normal RCM and decreased plasma volume. In order to deliver the appropriate treatment it is necessary to differentiate between the two.

Objective.—A retrospective analysis of RCM and plasma volume data are presented, with special attention to different methods of RCM interpretation.

Design.—The measurements of RCM and plasma volume in 64 patients were compared with the venous and whole-body packed cell volume, and the incidence of absolute and apparent polycythemia was determined for increasing hematocrit levels. Measurements of RCM and plasma volume were performed using chromium 51–labeled red cells and iodine 125–labeled albumin, respectively. The measured RCM of each patient was expressed as a percentage of the mean expected RCM and was also defined as being within or outside the range of 2 SD of the mean. The results were also expressed in the traditional manner of mL/kg body weight.

Results.—Twenty-one patients (13 women and 8 men) had absolute polycythemia. None of them had an increased plasma volume beyond 2 SD of the mean. When expressed according to the criteria of mL/kg body weight, 17 of the 21 patients had abnormally increased RCM, but 4 patients (19%) had a normal RCM value. Twenty-eight patients had apparent polycythemia. The remaining 15 patients had normal RCM and plasma volume.

Conclusions.—The measurement of RCM and plasma volume is a simple and necessary procedure in the evaluation of polycythemia. In obese patients, the expression of RCM in mL/kg body weight lacks precision, considering that adipose tissue is hypovascular. The results of RCM are best described as being within or beyond 2 SD of the mean value.
Atypical Regenerative Hyperplasia of the Esophagus in Endoscopic Biopsy: A Mimicker of Squamous Esophagic Carcinoma
Authors: Arista-Nasr Julián , Rivera Irene , Martinez-Benitez Braulio , Bornstein-Quevedo Leticia , Orozco Héctor , Lugo-Guevara Yadira
Published: February 2021

Context.—Atypical regeneration can mimic carcinoma in various epithelia. On endoscopic biopsies, atypical regenerative hyperplasia of the esophagus may show pleomorphism and atypia, simulating esophageal squamous cell carcinoma.

Objective.—To establish the most useful histologic features to distinguish atypical regenerative hyperplasia from esophageal carcinoma in endoscopic biopsies.

Design.—To study the frequency and histologic appearance of atypical regenerative hyperplasia, which simulate carcinoma, we reviewed 600 endoscopic biopsies (555 with chronic esophagitis and 45 with carcinomas of the esophagus). We selected those cases in which the differential diagnosis included regenerative atypical hyperplasia versus esophageal carcinoma and cases of atypical regenerative hyperplasia that were mistaken for carcinoma. For comparative purposes, we studied 10 cases of esophageal carcinoma from endoscopic biopsies that were confirmed by esophagectomy.

Results.—Among the cases with chronic esophagitis, we found 10 biopsies (1.8%) in which atypical regenerative hyperplasia mimicked carcinoma. In 7 cases, there were 4 to 12 years of follow-up, and no patient developed esophageal neoplasm. The remaining 3 patients were submitted to esophagectomy. None of these patients had carcinoma or dysplasia in the esophageal resection (false-positive biopsies). The most useful architectural changes in squamous carcinoma included stromal infiltration by nests, cords, or thin prongs of neoplastic keratinocytes, palisading desmoplasia, and in situ carcinoma in the adjacent epithelium. Malignant keratinocytes showed variable degrees of differentiation with differently shaped and sized cells, squamous epithelial pearls, individual keratinization, and atypical mitosis. In contrast, biopsies with atypical hyperplasia showed detached nests or irregular fragments without stroma and were made up of immature and relatively monotonous medium or small keratinocytes that were intermixed with inflammatory cells. Individual keratinization was rare, and no squamous pearls were seen. Other features of atypical hyperplasia included granulated tissue with atypical endothelial cells, nonatypical mitosis, lymphoid hyperplasia, and the absence of dysplasia or carcinoma in situ. Two biopsies showed stromal pseudoinfiltration as a result of tangential sectioning and were characterized by thick, round prongs composed of keratinocytes that penetrated regions with granulation or the inflamed tissues of esophageal ulcers.

Conclusions.—Atypical esophageal regenerative hyperplasia may mimic carcinoma in a small percentage of esophageal biopsies. If the histologic changes are not sufficient to establish an accurate diagnosis, medical treatment and subsequent biopsies should be performed, particularly if there are no endoscopic or radiologic data to support the presence of a neoplasm.
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma With Trisomy 12 and Focal Cyclin D1 Expression: A Potential Diagnostic Pitfall
Authors: O'Malley Dennis P. , Vance Gail H. , Orazi Attilio
Published: February 2021

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma usually are distinctly different in regard to clinical presentation, morphology, immunophenotype, and molecular/genetic findings. In spite of this, select cases may show overlapping characteristics and represent a diagnostic challenge. Cyclin D1 immunohistochemical staining is usually envisioned as a definitive method for resolving this differential diagnosis, with positivity supporting a diagnosis of mantle cell lymphoma. We report a case involving a 58-year-old man with a diagnosis of CLL/SLL for several years. A lymph node excision was performed after increased adenopathy was noted in the cervical region. The excised lymph node showed typical morphologic findings of CLL/SLL, including the presence of characteristic proliferation centers. Cyclin D1 staining, using 3 different antibodies, was present in scattered prolymphocytes and paraimmunoblasts, mostly within proliferation centers. Fluorescence in situ hybridization and conventional cytogenetics demonstrated trisomy 12 and an absence of t(11;14) in lymph node tissue. Focal cyclin D1 expression by immunohistochemistry in nodal CLL/SLL is quite unusual and is discussed as a potential diagnostic pitfall.
Mantle Cell Lymphoma Disguised as Marginal Zone Lymphoma
Authors: Jacobson Erica , Burke Peter , Tindle Barbara H.
Published: February 2021

We report a case of mantle cell lymphoma histologically indistinguishable from marginal zone lymphoma. An 83-year-old man presented with a 9.0-cm, slowly enlarging axillary mass. Microscopically, the neoplastic process was largely interfollicular, surrounding residual follicular centers, some of which had discernible small lymphocyte mantles. Overall, the morphologic pattern was highly suggestive of marginal zone lymphoma. However, flow cytometric and immunohistochemical results, including cyclin D1 positivity, revealed an immunophenotype that fit with mantle cell lymphoma. The differential diagnosis of mantle cell lymphoma is broad, and it is well known that mantle cell lymphoma can assume a number of histologic appearances, including, infrequently, that of more indolent B-cell non-Hodgkin lymphomas. Although not pathognomonic, cyclin D1 positivity is highly specific for mantle cell lymphoma and is key in distinguishing these clinically dissimilar malignant lymphomas. In recent years, detection of cyclin D1 has expanded the recognizable histologic spectrum of mantle cell lymphoma.
Patient With Double Bence Jones Proteinuria After Hematopoietic Cell Transplantation
Authors: Méndez-Arredondo Jose-Antonio , Rodríguez-López Inés , González-Morales Isabel , Debén-Ariznavarreta Guillermo , Fernández-Rodríguez Fernando , Sánchez-Mozo Pilar
Published: February 2021

About two thirds of patients with multiple myeloma and M-component in serum also have light chains in urine. However, the simultaneous presence of 2 Bence Jones proteins of different immunologic types in the same patient is rare. We describe the case of a 58-year-old woman with multiple myeloma, having 2 monoclonal light chains of both types (κ and λ) and an immunoglobulin G-λ monoclonal protein in urine. The quantitative determination of light chains in urine was carried out using nephelometry, and Bence Jones proteinuria was confirmed by agarose gel immunofixation. To the best of our knowledge, this is the first reported case of double Bence Jones proteinuria after hematopoietic cell transplantation.
North American Pretransfusion Testing Practices, 2001–2004: Results From the College of American Pathologists Interlaboratory Comparison Program Survey Data, 2001–2004
Authors: Shulman Ira A. , Maffei Lieta M. , Downes Katharine A.
Published: February 2021

Context.—Pretransfusion testing of whole blood and red blood cell recipients is regulated by the federal government under the authority of the Clinical Laboratory Improvement Amendments of 1988. Regulated tests include determination of ABO group, Rh D type, antibody detection, antibody identification, and crossmatching. A wide variety of methods and reagents are available for these regulated tests. During 2001–2004, the College of American Pathologists (CAP) Interlaboratory Comparison Program (Proficiency Testing) J-Survey collected data from more than 4000 laboratories regarding their pretransfusion testing practices. Those data are presented in this report.

Objective.—To assess current testing practices for ABO grouping, Rh D typing, antibody detection, and crossmatching in North America.

Design.—Data collected for the CAP Interlaboratory Comparison Program (Proficiency Testing) J-Survey were analyzed for trends in laboratory testing practice during 2001– 2004. The data were grouped for analysis by peer group (testing method used) for ABO grouping, Rh D typing, antibody detection, and crossmatching and then analyzed.

Setting, Patients, or Other Participants.—Subscribers to the CAP Interlaboratory Comparison Program Transfusion Medicine J-Series.

Results.—The most common testing schemes used in North America during 2001–2004 are as follows: ABO grouping (most laboratories perform tube testing: 97.6% in 2000 and 91.1% in 2004); Rh D typing (most laboratories perform tube testing: 97.7% in 2001 and 91.1% in 2004); antibody detection (most laboratories perform tube testing: 69.7% in 2001 and 55% in 2004, most frequently with the low ionic strength solution anti-human globulin [AHG] method, 48.3% in 2001 and 39.9% in 2004; as of 2004 slightly more laboratories use the gel AHG method [42%] than the low ionic strength solution AHG tube method); crossmatching for alloimmunized patients (most laboratories perform tube testing using a low ionic strength solution AHG method; 55.8% in 2001 and 47.6% in 2004); and crossmatching for nonalloimmunized patients (tube testing using an immediate spin method; 42% in 2001 and 40.4% in 2004).

Conclusions.—Most North American laboratories currently favor tube methods when performing ABO grouping, Rh typing, antibody screening, and crossmatching. However, there has been a significant increase in the use of gel-based methods in recent years, especially for antibody detection and crossmatching. Data collection and data analysis of CAP Interlaboratory Comparison Program Survey results allow for assessment of laboratory proficiency and provide insights into current North American practice trends in pretransfusion compatibility testing.
Activation Status of the JAK/STAT3 Pathway in Mantle Cell Lymphoma
Authors: Yared Marwan A. , Khoury Joseph D. , Medeiros L. Jeffrey , Rassidakis George Z. , Lai Raymond
Published: February 2021

Context.—Signal transducer and activator of transcription 3 (STAT3) is oncogenic, and we previously found evidence of constitutive STAT3 activation in a relatively small number of frozen mantle cell lymphoma (MCL) cell tumors.

Objectives.—To comprehensively survey the activation and phosphorylation status of STAT3 in MCL and to assess if STAT3 activation in these tumors is due to cytokine stimulation by examining the phosphorylation and activation status of Janus kinase (JAK), the physiologic activator of STAT3.

Design.—We evaluated 43 formalin-fixed, paraffin-embedded MCL tumors using immunohistochemistry and phospho-specific antibodies against STAT3 and JAK.

Results.—There were 37 small cell and 6 blastoid cases. There was heterogeneous expression of phospho-STAT3 (pSTAT3), with 23 negative cases (53%), 12 weakly positive cases (28%), and 8 strongly positive cases (19%). JAK3 was the only member detectable in 3 MCL cell lines, and immunoprecipitation data showed a relatively low level of tyrosine phosphorylation of JAK3 in these cells. Using immunohistochemistry, phospho-JAK3 (pJAK3) was detectable in 18 (44%) of 41 MCL tumors examined, and pJAK3 expression correlated with that of pSTAT3 (P = .008). A notable exception to this correlation was seen in the blastoid variant, since 4 (67%) of 6 blastoid cases were pSTAT3 positive but pJAK3 negative.

Conclusions.—We have confirmed our previous finding that STAT3 is constitutively activated in MCL tumors, with an overall frequency of 47% in this series. STAT3 activation in the small cell but not the blastoid variant of MCL is likely mediated by JAK3.
Intracranial Peripheral Primitive Neuroectodermal Tumors of the Cavernous Sinus: A Diagnostic Peculiarity
Authors: Idrees Muhammad , Gandhi Chirag , Betchen Simone , Strauchen James , King Wesley , Wolfe David
Published: February 2021

Peripheral primitive neuroectodermal tumors (pPNETs) are aggressive, poorly differentiated neoplasms that occur in children and young adults. These tumors are associated with a peak incidence in the second decade and a slight male preponderance. Recently, Ewing sarcoma and pPNET tumors have been proven to carry identical translocations, the most common being t(11;22)(q24;q12). Intracranial Ewing sarcoma/pPNETs have rarely been described in the literature. We studied a case of intracranial pPNET arising in the right cavernous sinus of a 46-year-old man. On imaging, the tumor had both sellar and suprasellar components and was centered within the right parasellar region. Histologically, the tumor was composed of intermediate to large cells with round to oval hyperchromatic nuclei with distinct nucleoli. The cells contained a moderate amount of slightly basophilic cytoplasm. The tumor was markedly fibrotic and had collagen bands surrounding both individual and groups of cells. A large immunohistochemical panel was positive only for CD99 and vimentin. Fluorescence in situ hybridization did not show translocations associated with Ewing sarcoma/pPNET. However, a small percentage of these tumors can be negative for this translocation. In these cases, histology and immunohistochemical techniques in the absence of an alternative diagnosis are the only tools available to establish the diagnosis.
Ileal Ulcers and Cytomegalovirus Infection in a Case of Churg-Strauss Syndrome
Authors: Hayashi Kazuhiko , Horie Yasushi , Takahata Hiroyuki , Adachi Youshin , Kitamura Yukisato , Kato Masako
Published: February 2021

Churg-Strauss syndrome, or allergic granulomatous angiitis, is an uncommon vasculitic syndrome. We describe a 53-year-old man with Churg-Strauss syndrome and subsequent opportunistic cytomegalovirus enterocolitis. During intensive care, including steroid-pulse therapy, the patient developed rapidly progressive anemia caused by active bleeding from his small intestine, resulting in resection of 20 cm of ileum. Diagnosis of Churg-Strauss syndrome was confirmed both by characteristic clinical features and by histology. Histologic examination also revealed multiple shallow ulcers accompanied by cytomegalovirus infection. Characteristic angiitis was found in the ileum with normal-like mucosa, and it was not necessarily associated with ileal ulcers. This finding suggests that cytomegalovirus infection may be one of the causes or exacerbating factors for ileal ulcers in Churg-Strauss syndrome, although ulcers of the intestine have usually been considered to be caused by ischemia resulting from angiitis.
Basaloid Squamous Carcinoma of the Hypopharynx With an Extensive Spindle Cell Component Exhibiting a Pedunculated Polypoid Mass
Authors: Kimura Tokuhiro , Mukai Makio , Shiotani Akihiro , Moro Kazuhisa , Ikeda Asako , Okada Yasunori
Published: February 2021

We report a case of basaloid squamous carcinoma of the hypopharynx with an extensive spindle cell component in an 82-year-old man. The tumor (4.0 × 2.5 × 2.2 cm) was a pedunculated polypoid mass that was attached to the left pyriform sinus. Histologically, most (70%) of the tumor was composed of malignant spindle cell proliferation, and the rest (30%) was basaloid squamous carcinoma. Some of the spindle cells were positive for cytokeratins. The preoperative histologic diagnosis was difficult because the endoscopic biopsy specimens showed only spindle cell proliferation. This is an unusual presentation of basaloid squamous carcinoma of the head and neck.
Pseudofungi in Pericolic Lymph Nodes
Authors: Song Dong Eun , Kahn Andrea G. , Khang Shin Kwang , Ro Jae Y.
Published: February 2021

We report a case of extensive pseudofungi in the pericolic lymph nodes. A 45-year-old man presented with lower abdominal discomfort, and large solid and cystic masses were discovered in the pelvic cavity by computed tomography. Debulking of the masses (by means of a Hartmann operation) was performed under the clinical impression of a pelvic sarcoma, and histologically the masses demonstrated features of a malignant gastrointestinal stromal tumor. All pericolic lymph nodes demonstrated multiple septate hyphae–like structures with pigmentation, particularly in the subcapsular sinuses. These structures showed positive staining with periodic acid–Schiff, but Gomori methenamine silver staining was negative. The structures appeared to be composed of iron, phosphorus, and calcium by Perls iron and von Kossa stains and revealed deposition of electron-dense granules on electron microscopic examination. Energy-dispersive radiographic micro-analysis showed the structures to contain phosphorus, sulfur, potassium, calcium, and iron. Pseudofungi can be misinterpreted as true fungi with septate hyphae; therefore, a careful morphologic examination with appropriate special stains is mandatory.
Composite Lymphocyte-Rich Hodgkin Lymphoma and Peripheral T-Cell Lymphoma Associated With Epstein-Barr Virus: A Case Report and Review of the Literature
Authors: Sanchez Steven , Holmes Houston , Katabi Nora , Newman Joe , Domiatti-Saad Rana , Stone Marvin , Netto George
Published: February 2021

We report a case of a 65-year-old black man with combined Hodgkin lymphoma and T-cell lymphoma. The patient presented with diffuse lymphadenopathy, fever, weight loss, and night sweats. Subsequent biopsy of an axillary lymph node revealed a composite lymphoma composed of classic Hodgkin lymphoma and a peripheral T-cell lymphoma. A needle biopsy of the liver also showed involvement by the composite lymphoma. In situ hybridization studies revealed positive Epstein-Barr virus in Reed-Sternberg cells. Development of T-cell lymphoma following chemotherapy for Hodgkin lymphoma has been reported, but synchronous composite occurrence of both lesions is very rare. Furthermore, this is the first report of such occurrence in a black patient. We present a review of the literature and a discussion of the potential pathophysiologic role of Epstein-Barr virus in the early stages of T-cell lymphomagenesis.
Extranodal Rosai-Dorfman Disease of the Kidney and Coexistent Poorly Differentiated Prostatic Adenocarcinoma
Authors: Harik Lara , Nassar Aziza
Published: February 2021

We present a case of a patient who was initially diagnosed with poorly differentiated prostatic adenocarcinoma on prostate needle core biopsy. Upon staging workup, a computed tomographic scan showed a 9-cm left renal mass involving mainly the pelvicalyceal system. Positron emission tomographic scan showed increased uptake in para-aortic, paracaval, and retrocaval lymph nodes suspicious for metastatic disease. Left nephrectomy revealed involvement with extranodal Rosai-Dorfman disease. Lymphadenectomy revealed metastatic prostatic adenocarcinoma; however, the lymph nodes did not show evidence of Rosai-Dorfman disease. Isolated involvement of the kidney by Rosai-Dorfman disease is very rare. The combination of prostatic adenocarcinoma and isolated extranodal Rosai-Dorfman disease of the kidney makes this case unique.
Fatal Splenic Rupture in a Pregnant Woman With Hemoglobin C/β-Thalassemia and Myeloid Metaplasia
Authors: Boldorini Renzo , Bozzola Cristina , Gallarotti Eleonora , Ribaldone Raffaella
Published: February 2021

Splenic rupture with intraperitoneal hemorrhage is a fatal condition that is rarely encountered during the third trimester of pregnancy; its pathogenetic mechanisms and causes are largely unknown. We report a case of splenic rupture in a pregnant woman that caused the death of the mother and child. The patient was a carrier of double heterozygosis for hemoglobin C/β-thalassemia. Spleen and liver enlargement due to extramedullary hematopoiesis was found at autopsy. Our data suggest that rare and hidden hematologic disorders should be considered as possible causes of splenic enlargement and rupture during pregnancy.
Assessing Performance, Productivity, and Staffing Needs in Pathology Groups: Observations From the College of American Pathologists PathFocus Pathology Practice Activity and Staffing Program
Authors: Martin Scott A. , Styer Patricia E.
Published: February 2021

Context.—The PathFocus program affords the opportunity for participating pathology practices to be compared with other practices that have similar characteristics.

Objectives.—To demonstrate variability in workload among different pathology practice settings and to determine practice characteristics that influence staffing levels.

Design.—Among 228 group practices in the PathFocus database, group practice settings were analyzed. The practice characteristics that were highly correlated with staffing levels are presented.

Results.—Activities that showed significant variation include surgical pathology (P = .003), cytopathology (P = .006), miscellaneous (P = .006), and professional development (P = .003). Group practices report up to 4% of hours devoted to clinical pathology consultation, on average, and from 20% to 25% to administration and management. There are strong positive associations with staffing levels for lower-complexity Current Procedural Terminology code volumes (P < .001) and higher-complexity Current Procedural Terminology code volumes (P = .006).

Conclusion.—The settings of pathology practices carry specific commitments of time that are different and not equally distributed among all practice settings and strongly influence staffing requirements.
Hypothermia and Hyperthermia Medicolegal Investigation of Morbidity and Mortality From Exposure to Environmental Temperature Extremes
Authors: Nixdorf-Miller Allison , Hunsaker Donna M. , Hunsaker III John C.
Published: February 2021

Context.—The determination of the cause of death from exposure to extreme temperatures is a diagnosis of exclusion. Because both clinical and autopsy findings are nonspecific, a thorough investigation of the background and scene, evaluation of temporally relevant environmental conditions, and assessment of the victim's underlying state of health with appropriate laboratory studies, which frequently include autopsy, are essential to establish the cause of injury and/or death with reasonable medical probability. Individuals may encounter environmental extremes in many settings during any season. Both constitutional and external factors exacerbate the stress brought about by extreme temperature.

Objective.—This article reviews guidelines for forensic investigation into environmental temperature extremes that contribute to an important seasonal grouping of morbidity and mortality in the United States.

Data Sources.—Articles on clinical and pathologic aspects of hyperthermia and hypothermia were collected and reviewed.

Conclusions.—Recognition of multiple risk factors predisposing humans to both cold-related and heat-related morbidity and mortality enhances prevention. Awareness of the susceptibility of these exposed at-risk individuals is crucial to investigations by both clinicians and medicolegal death investigators.
CD10 Expression in Cutaneous Adnexal Neoplasms and a Potential Role for Differentiating Cutaneous Metastatic Renal Cell Carcinoma
Authors: Bahrami Soon , Malone Janine C. , Lear Sheron , Martin Alvin W.
Published: February 2021

Context.—Recent investigations have demonstrated the utility of CD10 as a marker for renal cell carcinoma (RCC). Cutaneous metastases occur in up to 11% of patients with RCC and may be the presenting sign of widespread disease. The differential diagnosis in histopathologic evaluation of these cases includes cutaneous adnexal neoplasms, and describing the expression of CD10 in these tumors may be helpful in delineating the differential diagnosis.

Objective.—To determine CD10 expression in a variety of adnexal lesions and to determine the diagnostic utility of CD10 in an immunohistochemical panel differentiating metastatic cutaneous renal cell carcinoma from cutaneous adnexal neoplasms.

Design.—We studied 57 primary adnexal neoplasms of eccrine (n = 31), apocrine (n = 16), and sebaceous (n = 10) differentiation as well as normal skin (n = 3) and RCC metastatic to the skin (n = 4). A CD10 monoclonal antibody was applied to formalin-fixed, paraffin-embedded tissue. Specimens were randomized and categorized as immunopositive or immunonegative by a pathologist with expertise in immunohistochemistry who was blinded to the diagnoses.

Results.—Two (6.5%) of 31 eccrine, 1 (6%) of 16 apocrine, and 4 (40%) of 10 sebaceous neoplasms demonstrated CD10 immunopositivity. Four (100%) of 4 RCC were CD10 immunopositive. CD10 expression was significant for eccrine and apocrine neoplasms (P < .001) compared to metastatic RCC, but not for sebaceous neoplasms (P = .08).

Conclusion.—Based on these results, CD10 is a useful additional immunostain for the discrimination of RCC metastatic to the skin and cutaneous adnexal neoplasms with eccrine and apocrine differentiation, but not with sebaceous differentiation.
Diagnostic Molecular Pathology: An Increasingly Indispensable Tool for the Practicing Pathologist
Authors: Netto George J. , Saad Rana Domiati
Published: February 2021

Context.—Diagnostic molecular pathology is rapidly becoming an indispensable tool for anatomic pathologists. Familiarity with some of the technologic principles and current, as well as upcoming, molecular diagnostic applications is greatly advantageous for today's practice of pathology.

Objectives.— To provide a discussion of the most common techniques currently used in molecular pathology laboratories and review their essential applications to diagnosis and management of neoplastic diseases.

Data Sources.—A literature review and illustrative cases from the authors' molecular diagnostic practices.

Conclusions.—Applications such as clonality assays, molecular cytogenetics, and chimerism analysis are providing us with accurate tools to resolve difficult diagnostic and management decisions in hemato-oncology. This should serve as a future model to expand molecular applications into the wider field of solid tumors.
Decreased Fragile Histidine Triad Gene Protein Expression Is Associated With Worse Prognosis in Oral Squamous Carcinoma
Authors: Guerin Leana A. , Hoffman Henry T. , Zimmerman M. Bridget , Robinson Robert A.
Published: February 2021

Context.—Fragile histidine triad (FHIT) gene is thought to be a tumor suppressor; abnormalities in expression have been reported in a variety of neoplasms.

Objective.—To determine whether abnormalities of FHIT protein expression or loss of heterozygosity in the FHIT gene were correlated with survival or other clinical parameters in patients with oral cavity squamous cell carcinoma.

Design.—Fifty-three patients with initial surgical treatment of oral cavity squamous cell carcinoma were followed a minimum of 5 years or until death. The FHIT protein expression was studied by immunohistochemistry in all patients, and a subset of 20 patients was studied for allelic loss of heterozygosity and microsatellite instability using formalin-fixed, paraffin-embedded tissue.

Results.—Sixty-one percent of patients whose tumors had reduced FHIT expression were dead of disease, and 37% of patients whose tumors exhibited preserved FHIT expression were dead of disease at 5-year follow-up. Log-rank analysis showed that patients retaining FHIT expression had a longer overall survival (P = .03) and disease-free survival (P = .01). The FHIT expression was not correlated with node status or clinical stage. Loss of heterozygosity was seen in 10 (50%) of 20 tumors, low levels of microsatellite instability in 4 (20%) of 20 tumors, and high levels of microsatellite instability in 1 (5%) of 20 tumors tested.

Conclusions.—The FHIT gene was associated with a worse survival outcome when its expression was reduced in patients with oral cavity squamous cell carcinoma. Loss of heterozygosity in the gene was common, but no correlation with protein expression was found. Neither loss of heterozygosity nor microsatellite instability was found to correlate with survival. Because genomic alterations involving loss of heterozygosity of the FHIT gene were not associated with protein expression in these tumors, the presence or absence of FHIT expression may be controlled by other factors.
Aggressive Clear Cell Chondrosarcomas: Do Distinctive Characteristics Exist?: A Report of 4 Cases
Authors: Corradi Domenico , Bacchini Patrizia , Campanini Nicoletta , Bertoni Franco
Published: February 2021

Context.—Clear cell chondrosarcoma (CCC) is commonly considered to be a low-grade subtype of chondrosarcoma. However, a few cases of CCC behave as high-grade lesions (with early metastases or multiple/synchronous locations).

Objective.—To investigate morphologic features that can help predict the aggressiveness of these CCCs.

Design.—To investigate possible hallmarks of this aggressiveness, we are presenting the clinicopathologic features of 6 cases of CCC, 4 of which presented aggressive features and 2 low-grade behavior. The patients were 5 men and 1 woman; their ages ranged from 22 to 47 years. Histologic appearance, ultrastructure, and immunohistochemical expression of metalloproteinase 1 and 2 and their inhibitors were evaluated in all 6 cases.

Results.—Pain was the most common symptom; the lesions were located in the femur (4), humerus (2), and vertebral body (1), with 1 patient presenting a double/synchronous lesion. Although no major differences were detected using conventional light microscopy, an ultrastructural analysis—at variance with usual cases—showed a lack of superficial microvilli in more than 50% of neoplastic cells in the aggressive cases, therefore suggesting a less differentiated phenotype. In addition, metalloproteinase 2 was more diffusely expressed in the aggressive tumors than in the conventional CCCs, whereas p53 labeling was always negative.

Conclusions.—The aggressive behavior of some CCCs may be, at least in part, correlated to a lesser degree of cell differentiation and to the expression of tumor cell proteins, such as metalloproteinase 2, which are able to favor neoplastic spreading.