bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinguishing Carcinoid Tumor From Small Cell Carcinoma of the Lung: Correlating Cytologic Features and Performance in the College of American Pathologists Non-Gynecologic Cytology Program
Authors: Renshaw Andrew A. , Haja Jennifer , Lozano Richard L. , Wilbur David C.
Published: February 2021

Context.—The cytologic features of carcinoid tumor of the lung are well described. Nevertheless, some carcinoids may be difficult to distinguish from small cell carcinomas.

Objective.—To correlate the cytologic features of individual cases of carcinoid tumor of the lung in fine-needle aspiration specimens in the College of American Pathologists Non-Gynecologic Cytology Program with the frequency of misclassification as small cell carcinoma.

Design.—We reviewed 1100 interpretations from 26 different cases of carcinoid tumor in lung fine-needle aspiration specimens in the College of American Pathologists Non-Gynecologic Cytology Program and correlated the cytologic features with the performance in the program.

Results.—Cases were divided into those that were frequently misclassified as small cell carcinoma (at least 20% of the responses, 19 cases) and those that were infrequently misclassified as small cell carcinoma (<10% of all responses, 7 cases). All cases had areas with classic features of carcinoid tumor. Cases were reviewed independently by 3 cytopathologists specifically looking for cytologic features that might be responsible for misclassification as small cell carcinoma. All 7 cases that were infrequently misclassified consisted of numerous monotonous well-preserved tumor cells that were either entirely round or were a mixture of round and spindle-shaped cells. Six of 7 cases showed a prominent streaming vascular pattern with tumor cells attached to the endothelial cell core. In contrast, cases that were frequently misclassified had 1 of 6 patterns that were not seen in cases that were rarely misclassified. These 6 patterns were: (1) poorly preserved and pale-staining cells with fine chromatin and a suggestion of molding (5 cases); (2) numerous large, well-preserved, spindle-shaped cells (2 cases); (3) numerous cells varying markedly in both size and shape (both round and spindle-shaped cells), with a common finding of degenerated, smudgy, small round and spindle-shaped cells (9 cases); (4) hypocellular specimens (8 cases); (5) obscuration of cells by blood (2 cases); and (6) tumor cells present predominantly in groups, with few isolated cells (8 cases). In none of these cases were mitoses or true necrosis identified.

Conclusions.—Frequent misclassification of carcinoid tumor as small cell carcinoma in lung fine-needle aspiration specimens in this program correlates strongly with specific cytologic features, some of which are common in small cell carcinoma (fine chromatin, molding, smudgy chromatin) and others that are not (spindle-shaped cells). In addition, hypocellular specimens or specimens with cellular obscuration performed poorly, along with specimens exhibiting absence of the commonly described carcinoid feature of streaming vascularity. Awareness of these patterns may aid in avoiding misdiagnosis.
Automatic 3-Dimensional Visualization of Peripheral Blood Slides: A New Approach for the Detection of Infection/Inflammation at the Point of Care
Authors: Urbach Joseph , Rogowski Ori , Shapira Itzhak , Avitzour Daniel , Branski David , Schwartz Shepard , Berliner Shlomo , Mardi Tamar
Published: February 2021

Context.—The identification and quantitation of the intensity of the acute-phase response at the point of care might be of clinical relevance.

Objective.—To report the possibility of automatic screening of unstained peripheral blood slides by using a 3-dimensional image analysis system.

Design.—Peripheral venous blood was obtained from children with acute inflammation/infection and examined by an automatic 3-dimensional image analyzer to detect the number of white blood cells as well as to reveal the degree of erythrocyte aggregation, a marker of the humoral phase response.

Results.—We included 66 children with acute bacterial infections and 59 with nonbacterial inflammation/infection; mean ages of the 2 groups were 4.3 ± 3.9 years and 4.2 ± 3.7 years, respectively (P = .91). The percentages of correct classifications based on discriminant analysis in predicting between bacterial and nonbacterial inflammation/infection were 61.3% by using the white blood cell count, 64.5% by using the percentage of granulocytes, 61.6% by using the degree of erythrocyte aggregation, and 59.2% by using the number of leukocytes counted on the unstained slides. The results of the receiver-operated characteristic curve analysis yielded an area under the curve of 0.714 (P < .001) for the number of granulocytes, 0.699 (P < .001) for the white blood cell count, 0.685 (P < .001) for the number of leukocytes on the slides, and 0.685 (P = .001) for the degree of erythrocyte aggregation. The correlation between the number of leukocytes by the electronic cell analyzer and the number of cells counted on the slides was highly significant (r = 0.85, P < .001).

Conclusions.—It is feasible to use an automatic 3-dimensional image analyzer to reveal the different intensities of the acute-phase response between a group of children with an acute bacterial infection and another with nonbacterial inflammation/infection. These findings might be relevant for potential application at the point of care.
Immunohistochemical Detection of Glucose Transporter GLUT1 in Benign and Malignant Fallopian Tube Epithelia, With Comparison to Ovarian Carcinomas
Authors: Kalir Tamara , Rahaman Jamal , Hagopian George , Demopoulos Rita , Cohen Carmel , Burstein David E.
Published: February 2021

Context.—Enhanced expression of GLUT1, a facilitative glucose transporter found on red blood cells, blood-brain barrier, and perineurium, has been described in a large spectrum of epithelial malignancies.

Objective.—We present an immunohistochemical survey of GLUT1 expression in benign and malignant fallopian tube epithelia, and compare serous carcinomas of the fallopian tube and ovary.

Design.—One hundred two routinely fixed and processed archival specimens (36 benign fallopian tubes, 29 primary tubal adenocarcinomas, and 37 primary ovarian adenocarcinomas) were immunostained with rabbit anti-GLUT1 and developed with streptavidin-biotin/diaminobenzidine. Only distinct membrane staining was scored positively (1+ to 3+).

Results.—Benign tubes (n = 36) were either negatively stained (58.3%) or displayed rare weak staining (0.5+ to 1+, rarely 2+; 41.7%); of the latter, 4 specimens showed chronic salpingitis, and 6 showed hyperplasia (epithelial tufting and stratification). A case of florid hyperplasia with atypia in a BRCA1-positive patient was GLUT1 negative. Twenty-three (79.3%) of 29 tubal carcinomas were positively stained. Staining ranged from focal/scattered foci (n = 15) to multifocal/extensive (n = 8). Of the 6 nonstaining tubal carcinomas, 3 were undifferentiated. Nineteen tubal carcinoma sections showed residual benign epithelium, which was consistently nonstaining. Very frequently, GLUT1 staining intensified in cells furthest from stroma/ stromal capillaries and/or bordering necrotic zones. On average, GLUT1 staining in primary fallopian tube cancers was less extensive than in primary ovarian adenocarcinomas.

Conclusions.—GLUT1 immunostaining of fallopian tube adenocarcinomas was substantially stronger and more extensive than staining of benign tubal epithelium, consistent with previously described findings in carcinomas versus benign tissues from many primary sites. The frequent localization of GLUT1 positivity to regions most distal from stroma/stromal capillaries is consistent with known activation of GLUT1 expression by hypoxia-sensing cellular pathways and may constitute a survival advantage under hypoxic conditions present in malignancy. The difference in extent of GLUT1 staining between primary tubal and primary ovarian serous adenocarcinomas is discussed.
Ellis-van Creveld Syndrome and Dyserythropoiesis
Authors: Scurlock Deven , Ostler Daniel , Nguyen Andy , Wahed Amer
Published: February 2021

Ellis-van Creveld (EVC) syndrome or chondroectodermal dysplasia is a rare autosomal recessive disorder characterized by a variable spectrum of clinical findings. Classical EVC syndrome comprises a tetrad of clinical manifestations of chondrodystrophy, polydactyly, ectodermal dysplasia, and cardiac defects. In several case reports, dysplasia involving other organs has also been identified. Hematologic abnormalities have been rarely reported in patients with EVC syndrome. Here, we report a case of a 3-year-old Hispanic boy with EVC syndrome and marked dyserythropoiesis. The dyserythropoiesis may be part of an isolated myelodysplastic change or a primary myelodysplastic syndrome and likely represents an unusual EVC syndrome association. To our knowledge, this association has not been previously reported.
Myeloid Sarcoma of Appendix Mimicking Acute Appendicitis
Authors: Palomino-Portilla Eugenio Americo , Valbuena Jose R. , Quinones-Avila Mariadel Pilar , Medeiros L. Jeffrey
Published: February 2021

Context.—Myeloid sarcoma is a neoplasm of immature myeloid cells involving an extramedullary anatomic site that is usually, although not always, associated with acute myeloid leukemia. Any extramedullary site can be involved by myeloid sarcoma, but involvement of the cecal appendix is uncommon, and symptoms mimicking acute appendicitis as a result of appendiceal involvement are rare.

Objective.—To describe the clinicopathologic features of 2 patients with myeloid sarcoma involving the appendix who presented with right lower quadrant pain suggestive of acute appendicitis and prompting appendectomy.

Design.—Clinical information for both patients was obtained from the medical record. Routine hematoxylin-eosin–stained slides, naphthol-ASD-chloroacetate stain, and immunohistochemical stains for myeloid, B-cell, and T-cell antigens were prepared.

Results.—Peripheral blood and bone marrow were infiltrated by coexistent acute myeloid leukemia in case 1 but were negative for leukemia in case 2. In case 2, the patient had a history of acute myeloid leukemia that had been treated by an allogenic bone marrow transplant 7 months earlier. Histologic examination of the appendix revealed poorly differentiated myeloid sarcoma in both cases. Each neoplasm was positive for chloroacetate esterase, myeloperoxidase, lysozyme, and CD43 and was negative for CD3 and CD20.

Conclusions.—Myeloid sarcoma involving the appendix can rarely cause pain or other symptoms mimicking acute appendicitis. A high index of suspicion combined with the use of cytochemical and immunohistochemical studies are helpful in establishing the diagnosis.
Autoimmune Pancreatitis: More Than Just a Pancreatic Disease?A Contemporary Review of Its Pathology
Authors: Deshpande Vikram , Mino-Kenudson Mari , Brugge William , Lauwers Gregory Y.
Published: February 2021

Context.—Autoimmune pancreatitis (AIP) is a chronic inflammatory condition of the pancreas constituting one quarter of Whipple resections performed for benign conditions in North America.

Objective.—We review the clinical, radiologic, and characteristic histopathologic patterns of this disease and discuss the extrapancreatic manifestations of AIP.

Design.—We searched the literature using MEDLINE and OVID, related conference abstracts, and bibliographies of selected studies.

Results.—Autoimmune pancreatitis predominantly affects elderly individuals, frequently presenting as obstructive jaundice and occasionally in association with other autoimmune diseases. The histology is characterized by a collar of periductal inflammation, obliterative phlebitis, and the absence of stigmata of alcoholic pancreatitis. A prepancreatectomy diagnosis can be rendered using a combination of clinical findings, radiologic features, elevated immunoglobulin G4 levels, endoscopic ultrasound-guided fine-needle aspiration biopsy, and response to steroids. The disease can involve the bile ducts (sclerosing cholangitis), gallbladder (lymphoplasmacytic sclerosing cholecystitis), and kidney (interstitial nephritis) and can form inflammatory masses in the lungs.

Conclusions.—Despite significant evolution in our understanding of AIP, a prepancreatectomy diagnosis remains a challenge in the North American and European population.
Max Brödel: Illustrating Healed Valve Ring Abscesses
Authors: Lucey Brendan P. , Thomas Caroline Bedell , Hutchins Grover M.
Published: February 2021

A 14-year-old adolescent girl presented with severe congestive heart failure, progressive throughout 3 months. A precordial thrill, machinery-like murmur, and right bundle branch block were noted. Death occurred despite digitalis and diuretic therapy and removal of pleural and ascitic fluid. The autopsy revealed 2 multilocular cystic structures in the interventricular septum consistent with being spontaneously drained valve ring abscesses. One of these lesions formed a fistulous communication that penetrated through the interventricular septum between the right aortic sinus of Valsalva and the crista supraventricularis that connected to the right ventricle. Another lesion, an adjacent separate but similar cystlike structure, communicated only with the left ventricular cavity. Although the cause of these lesions is uncertain, it seems probable that they are the residue of spontaneously drained and healed valve ring abscesses. Max Brödel, a medical illustrator and the first director of the Department of Art as Applied to Medicine at The Johns Hopkins University, drew previously unpublished figures of this patient's cardiac lesions. These illustrations exhibit Brö del's superb command of both art and medicine essential to his ability to make complex anatomic relationships demonstrable. We discuss Brödel's career and his influence on both the art and science of medicine.
An Indolent Case of T-Prolymphocytic Leukemia With t(3;22)(q21;q11.2) and Elevated Serum β2-Microglobulin
Authors: Moid Farah , Day Estella , Schneider Marta A. , Goldstein Kenneth , DePalma Louis
Published: February 2021

We report a novel case of T-prolymphocytic leukemia, small cell variant, associated with complex cytogenetic findings including t(3;22)(q21;11.2) and elevated serum β2-microglobulin. The diagnosis is based on morphologic, immunophenotypic, cytogenetic, and molecular analysis of peripheral blood and bone marrow. In contrast to most reported cases of T-prolymphocytic leukemia, this patient did not present with lymphadenopathy or organomegaly. Moreover, only a moderate leukocytosis (25.3 × 103/μL) was evident at presentation. In the absence of any specific treatment, the patient is doing well, with a stable white blood cell count 12 months following presentation. Further investigation may be warranted to determine whether the unusual cytogenetic findings and elevated serum β2-microglobulin are associated with the indolent clinical course in this patient.
Pathology of the NovaSure (Radio-Frequency) Impedance-Controlled Endometrial Ablation System
Authors: Fadare Oluwole , Qin Lihui , Martel Maritza , Tavassoli Fattaneh A.
Published: February 2021

The widespread use of increasingly novel diagnostic and neoadjuvant therapeutic modalities necessitates that contemporary pathologists familiarize themselves with the spectrum of tissue derangements that may be seen in the eventual surgical specimens. In the management of endometrial lesions, for example, a variety of endometrial ablation technologies, such as cryosurgery, balloon therapy, microwave, hot circulating saline, and bipolar impedance technology, have been introduced in the past decade and are being utilized with increasing frequency. We describe herein pathologic changes associated with one such technology, the NovaSure impedance-controlled endometrial ablation system. The US Food and Drug Administration approved NovaSure in 2001 for ablation of the endometrial lining in premenopausal women with menorrhagia. The ablation is accomplished by the delivery of radio-frequency energy for a period of approximately 90 seconds through a device inserted transcervically into the endometrial cavity. Our patient, a 54-year-old with menorrhagia, had undergone the NovaSure ablative treatment 38 days prior to her eventual hysterectomy. The resultant changes were quite distinctive: in a uterine wall that was 20 to 30 mm thick, a 3- to 6-mm-thick, hyalinized, subendometrial bandlike zone was apparent throughout the uterus even on macroscopic examination of the slides. This zone was sharply demarcated from the subjacent myometrium and from the endometrium; the latter displayed severe stromal fibrosis, some myxoid change, and sparse glands that were largely confined to the basalis. Paradoxically, scattered aggregates of stromal cells in the endometrium remained relatively viable. Adenomyotic aggregates and leiomyomata in the myometrium beneath the hyalinized zone were unaffected by this treatment. Practitioners evaluating hysterectomy specimens should be aware of changes such as those described herein, not only to better understand the specimens they evaluate but to avoid potentially misinterpreting grotesque alterations caused by benign processes.
Frozen Section of the Gastrointestinal Tract, Appendix, and Peritoneum
Authors: Younes Mamoun
Published: February 2021

Context.—Intraoperative consultation is frequently requested by surgeons operating on the gastrointestinal tract, appendix, and peritoneum. In this setting, the pathologist's diagnosis plays a central role in determining whether a resection is needed, and if so, how much to resect and whether it was adequate. There is no room for errors in the frozen section laboratory, because a small mistake can have serious consequences. To my knowledge, no recent books or publications in the literature have dealt with this important topic.

Objective.—To review the intraoperative consultation of the gastrointestinal tract, appendix, and peritoneum.

Data Sources.—The MEDLINE database was queried for keywords, including gastrointestinal, esophagus, stomach, esophageal, gastric, small intestine, and all other names of the gastrointestinal tract, peritoneum, and appendix in combination with frozen section. All suitable articles were retrieved and reviewed. This literature search and my personal experience formed the basis of this review.

Conclusions.—The role, value, and limitations of frozen section and gross consultation are different for different areas of the gastrointestinal tract, even for the same types of lesions. Close interaction with the surgeon and knowing what is intended from the frozen section, what will be done following a certain diagnosis, and what is the minimal information needed from the pathologist at the time of frozen section are essential for proper patient management.
Frozen Section of Lung Specimens
Authors: Sienko Anna , Allen Timothy Craig , Zander Dani S. , Cagle Philip T.
Published: February 2021

Context.—Frozen section of lung tissue is performed to guide the surgeon in subsequent therapy.

Design.—Practical experience in frozen section of the lung was reviewed in the medical literature and from the records of several academic hospitals.

Results.—Most frozen sections of the lung are performed for evaluation of a solitary nodule, a mass, or the surgical margins of a resection. Frozen section may also be used to assess the adequacy of a lung wedge biopsy taken for later diagnosis of a condition.

Conclusion.—The pathologic evaluation of intraoperative pulmonary lesions is indicated for the differential diagnosis of pulmonary nodules and masses, both neoplastic and nonneoplastic, surgical resection margins, and mediastinal lymph nodes. The most worrisome pitfalls involve differentiating benign reactive atypia from malignancy on frozen section.
Frozen Section Diagnosis and Indications in Ophthalmic Pathology
Authors: Chévez-Barrios Patricia
Published: February 2021

Context.—Frozen sections for ophthalmic tissues require very precise indications.

Objective.—To describe indications and procedures for frozen sections in ophthalmic pathology based on review of my experience and reports in the literature.

Design.—Frozen sections received by the ophthalmic pathology service at The Methodist Hospital from 1996 to 2004 were reviewed. A review of the literature also was performed.

Results.—Of the 277 specimens received, most were eyelid lesions (138, 49.8%), followed by orbital (106, 38.3%), temporal artery (17, 6.1%), optic nerve (9, 3.2%), and conjunctival (7, 2.5%) lesions. A review of appropriate indications for intraoperative diagnosis is presented and a description of tissue handling and procedures to obtain better results in ophthalmic pathologic lesion cases is discussed.

Conclusions.—The most frequent indications for frozen sections in ophthalmic abnormalities are for margin control in eyelid and orbital lesions. At my institution, the second most frequent indications for ophthalmic frozen sections are the evaluation of adequacy of tissue sampling and triaging for flow cytometry and molecular techniques, especially in childhood malignancies.
Fine-Needle Aspiration of Pulmonary Hamartoma: A Common Source of False-Positive Diagnoses in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology
Authors: Hughes Jonathan H. , Young Nancy A. , Wilbur David C. , Renshaw Andrew A. , Mody Dina R.
Published: February 2021

Context.—We use data from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology to evaluate the accuracy of fine-needle aspiration (FNA) biopsy for diagnosing pulmonary hamartoma (PH).

Objective.—To use the performance characteristics of the PH cases in the Nongynecologic Cytology Program to determine the accuracy of FNA for identifying these lesions and to determine potential sources of interpretative errors.

Design.—A retrospective review of the College of American Pathologists Nongynecologic Cytology cumulative data from 1997 to 2003 was performed to identify the overall accuracy of FNA for diagnosing PH and to determine the most common interpretative pitfalls. The slides from each of the cases of PH in the Nongynecologic Cytology Program were then reviewed in an effort to identify the cytologic characteristics that contributed to the poor performance of these cases.

Results.—A total of 766 participant responses for 19 PH FNA specimens were reviewed. The specificity of FNA for making the correct general reference interpretation of benign was 78%. The false-positive rate was 22%, with the most common false-positive diagnoses being carcinoid tumor, adenocarcinoma, and small cell carcinoma. The overall accuracy for making the correct specific reference diagnosis of PH was 26%. Microscopic review of the individual cases revealed possible explanations for some of the interpretative errors and the most frequent false-positive interpretations.

Conclusions.—Cytologists should be aware of the potential false-positive interpretations that can occur in FNAs of PH and the potential reasons for these inaccuracies in order to minimize clinically significant diagnostic errors.
Comparison of Pooled Fresh Frozen Serum to Proficiency Testing Material in College of American Pathologists Surveys: Cortisol and Immunoglobulin E
Authors: Palmer-Toy Darryl Erik , Wang Edward , Winter William E. , Soldin Steven J. , Klee George G. , Howanitz Joan H. , Elin Ronald J.
Published: February 2021

Context.—The College of American Pathologists (CAP) provides proficiency testing (PT) surveys to laboratories around the world.

Objectives.—To compare diagnostic assay methods for serum/plasma cortisol and immunoglobulin (Ig) E in terms of their bias and precision, to determine how well CAP PT specimens simulate human serum, and to reassess proficiency test grading criteria in light of these findings.

Design.—A participant-blinded, prospective trial. One vial of pooled fresh frozen serum (FFS) and 4 different admixtures of PT material (PTM) were sent to laboratories participating in PT surveys.

Participants.—Laboratories providing cortisol (>1000) or IgE (>230) results among the subscribers to the CAP surveys, Ligand (General) 2003, set K/KN-A and Chemistry 2003, set C-C.

Main Outcome Measures.—The main outcome measures were (1) bias among laboratories using the same method (peer groups), defined relative to the median of method means (MedMM); (2) imprecision as measured by the SD and coefficient of variation (CV) about each method mean; and (3) total error across laboratories for the FFS cortisol results, defined as |Bias Relative to Reference Method| + 2 SD.

Results.—Cortisol method biases, relative to MedMM, ranged from −22% to 9% for the FFS challenge and from −24% to 36% for comparable PTM challenges. The method biases, relative to the reference method, ranged from −3% to 19% for the FFS challenge. The cortisol method CVs ranged from 4.2% to 13.6% for the FFS challenge and from 4.7% to 12.7% for comparable PTM challenges. Total error across laboratories ranged from 1.4 to 6.9 μg/dL (39 to 190 nmol/L) for the FFS challenge. Immunoglobulin E method biases, relative to MedMM, ranged from −8% to 9% for the FFS challenge and from −7% to 5% for comparable PTM challenges. The IgE method CVs ranged from 3.6% to 6.7% for the FFS challenge and from 3.4% to 9.8% for comparable PTM challenges.

Conclusions.—The bias for cortisol results was less with FFS than with PTM, but imprecision was comparable. The FFS MedMM was 8.5% higher than the reference value. Fresh frozen serum and PTM bias and imprecision for IgE methods were each less than 10%. Because some of the methods demonstrated greater bias when analyzing PTM than FFS, peer group grading of both these analytes is appropriate.
Giant Cell Tumors: Inquiry Into Immunohistochemical Expression of CD117 (c-Kit), Microphthalmia Transcription Factor, Tartrate-Resistant Acid Phosphatase, and HAM-56
Authors: Ramos Rolando Y. , Haupt Helen M. , Kanetsky Peter A. , Donthineni-Rao Rakesh , Arenas-Elliott Carmen , Lackman Richard D. , Martin Anne-Marie
Published: February 2021

Context.—Osteoclast-like giant cells (GCs) in giant cell tumors (GCTs) are thought to derive from a monocyte-macrophage lineage. Microphthalmia transcription factor (MITF) is necessary for osteoclast gene expression and tartrate-resistant acid phosphatase (TRAP) activation; c-Kit plays a role in regulation of MITF.

Objective.—To gain insight into the differentiation of GCTs of bone (GCTBs) and GCTs tendon sheath (GCTTSs) by investigating immunohistochemical staining for c-Kit, MITF, TRAP, and HAM-56 in the GCs and stroma.

Design.—Immunoreactivity for CD117 (c-Kit), MITF, TRAP, and HAM-56 was studied in 35 GCTBs, 15 GCTTSs, and 5 foreign-body GC controls.

Results.—Across tumors, MITF and TRAP but not c-Kit were generally expressed in GCs; TRAP was variably expressed in stromal cells. The MITF was expressed more consistently in stromal cells of GCTTSs than GCTBs (P < .001). The GCTBs showed more intense MITF stromal (P < .001) and TRAP GC staining (P = .04) than GCTTSs. HAM-56 staining by stromal cells was associated with MITF stromal staining (r2 = 0.6, P < .001).

Conclusions.—Results suggest that MITF and TRAP are expressed during osteoclast differentiation and that a proportion of mononuclear cells in GCTs express the macrophage marker HAM-56. Both GCTBs and GCTTSs show similar patterns of immunohistochemical expression.
Usefulness of Cutaneous T-Cell Clonality Analysis for the Diagnosis of Cutaneous T-Cell Lymphoma in Patients With Erythroderma
Authors: Cordel Nadege , Lenormand Bernard , Courville Philippe , France Helot Marie , Benichou Jacques , Joly Pascal
Published: February 2021

Context.—Demonstration of a dominant T-cell clone in skin biopsy specimens by a molecular assay constitutes an additional diagnostic criterion to differentiate cutaneous T-cell lymphomas (CTCLs) from inflammatory dermatoses.

Objective.—To determine which patients, depending on their clinical presentations, could most benefit from a cutaneous T-cell clonality analysis in addition to histopathologic analysis for the diagnosis of CTCL.

Design.—Comparison of sensitivity and specificity of histopathologic analysis and a combination of this method and the detection of a T-cell receptor γ chain gene rearrangement by polymerase chain reaction denaturing gradient gel electrophoresis performed on skin biopsy specimens obtained at initial presentation.

Patients.—One hundred forty consecutive patients were classified into 4 groups, depending on their clinical presentation: (1) eczematous patches suggestive of early-stage mycosis fungoides (MF) (IA and IB of the TNM classification) (n = 42); (2) plaques, nodules, or tumors that arise on or are associated with plaques suggestive of late-stage MF (IIB and III of the TNM classification) (n = 16); (3) erythroderma (n = 50); and (4) nodules or tumors that arise in normal skin, suggestive of non-MF CTCL (n = 32).

Results.—When compared with histopathologic examination, the addition of clonality analysis increased the sensitivity of CTCL diagnosis in all groups of patients except those with cutaneous lesions suggestive of late-stage MF, because the diagnosis was made based on histopathologic analysis alone in 100% of these cases. The main increase in sensitivity of CTCL diagnosis was observed in patients with erythroderma: 62% with histopathologic analysis alone to 87% with the combination of both methods (P = .04). Diagnostic specificity of molecular assays decreased from 100% to 76% (P = .01) in patients with patch lesions and from 100% to 70% (P = .04) in patients with nodules that occurred in normal skin due to the detection of a T-cell clone in 6 patients with follicular mucinosis without a histologic pattern of MF and in 5 of 20 cases of T-cell pseudolymphoma (25%), respectively. In contrast, a T-cell clone was not detected in the 34 patients with erythroderma of inflammatory origin.

Conclusion.—Polymerase chain reaction analysis of cutaneous T-cell clonality could be useful for the diagnosis of CTCL in patients who present with erythroderma.
Epstein-Barr Virus in Breast Carcinoma in Argentina
Authors: Preciado María Victoria , Chabay Paola Andrea , De Matteo Elena Noemí , Gonzalez Pedro , Grinstein Saúl , Actis Andrea , Daniel Gass Hugo
Published: February 2021

Context.—Because the etiology and progression of breast carcinoma remain unclear, novel mechanisms of disease pathogenesis need to be considered. Recent interest has focused on Epstein-Barr virus (EBV), an oncogenic ubiquitous herpesvirus. Investigations of this association could not only broaden understanding of breast cancer etiology but also have implications regarding early detection, treatment, and prevention.

Objective.—To assess EBV presence in breast carcinoma in an Argentine series.

Design.—Breast biopsy specimens of 69 women with breast carcinoma and fresh tumor tissue of 39 of these women were collected. As controls, 17 biopsy specimens of fibroadenomas, 9 of benign epithelial proliferation, 4 of atypical ductal hyperplasia, and 10 of usual ductal hyperplasia and 8 normal breast tissues from women were studied. The EBV-infected cells were identified by means of immunohistochemical analysis, using a monoclonal antibody against Epstein-Barr virus–encoded nuclear antigen 1 (EBNA-1). Polymerase chain reaction (PCR) was used to amplify EBV DNA, with primers that cover the EBV encoded RNA (EBER) and BamHIW regions.

Results.—Nuclear expression of EBNA-1 was observed in tumor epithelial cells in 24 (35%) of the 69 cases. We confirmed both positive and negative immunohistochemical results by PCR in those cases where good quality DNA was also available, detecting amplification fragments of 108 base pairs (bp) from the EBER region and 122 bp from the BamHIW region. Neither immunohistochemical analysis nor PCR detected any positive EBV results in the control samples.

Conclusions.—Our results demonstrate the presence and expression of EBV restricted to epithelial tumor cells in a subset of breast carcinomas studied. However, no significant association was observed between EBV expression and worse clinical and pathologic patient characteristics.
Hairy Cell Leukemia Variant With Features of Intrasinusoidal Bone Marrow Involvement
Authors: Ya-In Charin , Brandwein Joseph , Pantalony Dominic , Chang Hong
Published: February 2021

Hairy cell leukemia variant (HCL-V) is a rare lymphoproliferative disorder. We report a case of HCL-V with an intrasinusoidal pattern of bone marrow involvement without interstitial or diffuse infiltration that is typical of HCL and its variant. The peripheral blood and bone marrow aspirates demonstrated abnormal lymphoid cells with cytoplasmic projections that were weakly positive for tartrate-resistant acid phosphatase cytochemical staining. Immunostaining of the bone marrow biopsy specimen showed that these cells were strongly positive for CD20, located within bone marrow sinusoids, and weakly positive for DBA44. By flow cytometry, these cells were positive for CD19, CD20, CD11c, and CD103, exhibited λ light chain restriction, and were negative for CD25. The patient was initially diagnosed as having splenic lymphoma with villous lymphocytes (SLVL) or splenic marginal zone lymphoma (SMZL) (World Health Organization designation) and treated with fludarabine followed by splenectomy with simultaneous liver biopsy. The pathologic analysis of the spleen revealed infiltration of red pulp by the critical cells without white pulp involvement, which is characteristic of HCL and HCL-V but not of SLVL (SMZL). This case illustrates an atypical marrow presentation of HCL-V and emphasizes the need to correlate all clinical and pathologic data, including tissue biopsy, in reaching a diagnosis.
Staffing Benchmarks for Clinical Laboratories: A College of American Pathologists Q-Probes Study of Staffing at 151 Institutions
Authors: Valenstein Paul N. , Souers Rhona , Wilkinson David S.
Published: February 2021

Context.—Inadequate staffing of clinical laboratories may compromise quality and throughput, whereas excess staff unnecessarily increases the cost of testing.

Objectives.—To measure productivity of technical staff and management span of control in a large number of laboratories and to determine factors associated with favorable staffing ratios.

Design.—A total of 151 clinical laboratories provided information about technical and management staffing and output (workload) for 4 laboratory sections: anatomic pathology, chemistry/hematology/immunology, microbiology, and transfusion medicine.

Results.—For each laboratory section, there was wide variation in labor productivity (output per nonmanagement full-time equivalent) and in management span of control (nonmanagement full-time equivalent per manager). Productivity ratios for the 10th- and 90th-percentile laboratories varied more than 3-fold. Except in histology, laboratory sections with higher test volumes had higher labor productivity (P < .001 for cytology, chemistry/hematology, and transfusion medicine; P = .003 for microbiology). Even within peer groups composed of sections with similar volume, there was wide variation in labor productivity. A number of variables other than test volume were associated with labor productivity and management span of control. Staffing ratios for each laboratory section and for sections of different sizes are presented.

Conclusions.—Despite standardization of testing methods in the clinical laboratory industry, there is wide variation in staffing level among institutions. This variation suggests opportunities to improve staff productivity in many facilities.
Results of a Survey of Hospital Coagulation Laboratories in the United States, 2001
Authors: Shahangian Shahram , Stanković Ana K. , Lubin Ira M. , Handsfield James H. , White Mark D.
Published: February 2021

Context.—Coagulation and bleeding problems are associated with substantial morbidity and mortality, and inappropriate testing practices may lead to bleeding or thrombotic complications.

Objective.—To evaluate practices reported by hospital coagulation laboratories in the United States and to determine if the number of beds in a hospital was associated with different practices.

Design.—From a sampling frame of institutions listed in the 1999 directory of the American Hospital Association, stratified into hospitals with 200 or more beds (“large hospitals”) and those with fewer than 200 beds (“small hospitals”), we randomly selected 425 large hospitals (sampling rate, 25.6%) and 375 small hospitals (sampling rate, 8.8%) and sent a survey to them between June and October 2001. Of these, 321 large hospitals (75.5%) and 311 small hospitals (82.9%) responded.

Results.—An estimated 97.1% of respondents reported performing some coagulation laboratory tests. Of these, 71.6% reported using 3.2% sodium citrate as the specimen anticoagulant to determine prothrombin time (81.3% of large vs 67.7% of small hospitals, P < .001). Of the same respondents, 45.3% reported selecting thromboplastins insensitive to heparin in the therapeutic range when measuring prothrombin time (59.4% of large vs 39.8% of small hospitals, P < .001), and 58.8% reported having a therapeutic range for heparin (72.9% of large vs 53.2% of small hospitals, P < .001). An estimated 96.3% of respondents assayed specimens for activated partial thromboplastin time within 4 hours after phlebotomy, and 89.4% of respondents centrifuged specimens within 1 hour of collection. An estimated 12.1% reported monitoring low-molecular-weight heparin therapy, and to do so, 79% used an assay for activated partial thromboplastin time (58% of large vs 96% of small hospitals, P = .001), whereas 38% used an antifactor Xa assay (65% of large vs 18% of small hospitals, P = .001).

Conclusions.—Substantial variability in certain laboratory practices was evident. Where significant differences existed between the hospital groups, usually large hospitals adhered to accepted practice guidelines to a greater extent. Some reported practices are not consistent with current recommendations, showing a need to understand the reasons for noncompliance so that better adherence to accepted standards of laboratory practice can be promoted.
A Procedure for Rapid Issue of Red Cells for Emergency Use
Authors: Weiskopf Richard B. , Webb Mary , Stangle Deena , Klinbergs Gunter , Toy Pearl
Published: February 2021

Context.—A College of American Pathologists Q-Probe revealed that the median turnaround times for emergency requests for red blood cells from the operating room were 30 minutes to release of cells from the blood bank and 34 minutes to delivery to the operating room. These times may not be adequate to permit the red cells to provide sufficiently rapid delivery of oxygen in massively bleeding patients.

Objective.—To improve the time from emergency request for red cells to delivery to the operating room.

Design.—A new emergency issue program was implemented for only the operating rooms; emergency issue to all other hospital locations remained unchanged. Six units of group O Rh-negative red blood cells (RBCs) are maintained in the blood bank in a separate basket with transfusion forms containing the unit numbers and expiration dates and a bag with one blood tubing segment from each unit. The times to issue and to delivery to the operating room suite were compared with time to issue of 2 group O Rh-negative RBCs for other hospital locations using the older system during the same time period and with the time to issue of 2 units to all other hospital locations during the preceding 2 years.

Setting.—A university hospital.

Main Outcome Measures.—Time between emergency request for red cells and delivery to the operating room.

Results.—The time between blood bank notification and arrival in the operating room of the 6 units of RBCs was significantly shorter than the time required to just issue (not including delivery time) 2 units of RBCs to other hospital locations. With the new procedure, 82% of units issued reached the operating room within 2 minutes of request, 91% arrived within 3 minutes, and 100% arrived within 4 minutes. These percentages are significantly higher than those for only issue of blood (without delivery) using the older issuing procedure for all hospital locations during the previous 2 years (37%, 49%, and 66%, respectively; P = .007, .009, and .02, respectively) and for other locations during the same 7-month period (29%, 46%, and 73%, respectively; P = .004, .01, and .09, respectively). Time (mean [95% confidence interval]) from blood bank notification to delivery of RBCs to the operating room suite (2.1 [1.6–2.6] minutes, of which approximately 50–60 seconds is attributable to delivery time) was less than issue times (not including delivery times) using the older issuing procedure for other hospital locations during the same period (4.1 [3.1–5.0] minutes; P = .007).

Conclusions.—An emergency issue procedure can be used to issue several units of RBCs within 1 minute and have them delivered to the operating room within 2 minutes while maintaining sufficient controls and providing required information to satisfy patient and blood bank requirements.
Histomorphologic Assessment of Formalin Substitute Fixatives for Diagnostic Surgical Pathology
Authors: Titford Michael E. , Horenstein Marcelo G.
Published: February 2021

Context.—In 1987, the Formaldehyde Standard became law in the United States, alerting laboratory workers to the potential carcinogenicity of formaldehyde. As a result, a variety of proprietary fixatives were developed for use in surgical pathology.

Objective.—To assess histomorphology with different formalin substitute fixatives.

Design.—Four experienced board-certified surgical pathologists examined 7 specimens (hepatocellular carcinoma, ovarian sex cord/stromal tumor, myxoid liposarcoma, uterine endometrioid adenocarcinoma, splenic follicular hyperplasia, infiltrating mammary carcinoma, and cecal signet ring carcinoma) fixed with formalin and 5 proprietary fixatives advertised as formalin replacements. In a blind study, the pathologists rated cellular outlines, cytoplasmic detail, nuclear detail, erythrocyte integrity, lymphocyte integrity, overall morphology, and overall staining in each case.

Results.—Formalin received the highest overall morphology and staining scores, followed by Glyo-Fixx, STF-Streck, Omnifix, Histochoice, and Histofix. Formalin also received the highest scores in cellular outline and erythrocyte integrity. Individually, some fixatives performed better in different areas than others. Glyo-Fixx performed as well as formalin for overall morphology and provided highest nuclear detail and lymphocyte appearance scores. Omnifix II gave best results for cytoplasmic detail.

Conclusion.—In this blind study, formalin fixation provided the highest histomorphologic quality for tissue stained with hematoxylin-eosin and examined for diagnostic surgical pathology. Should the use of formalin be discontinued, pathologists will have to familiarize themselves with a different set of microscopic details associated with the replacement fixatives.
Intravascular Papillary Endothelial Hyperplasia of Renal Vein: Report of 2 Cases
Authors: Akhtar Mohammed , Aslam Muhammed , Al-Mana Hadeel , Bamefleh Hana , Al-Khateeb Sultan S. , Lindstedt Eric
Published: February 2021

Intravascular papillary endothelial hyperplasia is a benign intravascular process thought to arise from an organizing thrombus. The lesion may present clinically as an abnormal mass and, depending on the location, may be confused with benign or malignant neoplasms. It has been described in a variety of locations. Involvement of the renal vein by papillary endothelial hyperplasia is extremely rare, with only 4 cases reported in the literature. We describe 2 additional cases. In both cases, the radiologic examination revealed a well-circumscribed mass in the hilar region of the kidney, which was considered to be a renal neoplasm. Nephrectomy specimen in each case revealed characteristic features of intravascular papillary endothelial hyperplasia. It is suggested that intravascular papillary endothelial hyperplasia should be included in the differential diagnosis of a hilar renal mass.
Gallbladder Paraganglioma: A Case Report With Review of the Literature
Authors: Mehra Shveta , Chung-Park Moonja
Published: February 2021

We report a case of gallbladder paraganglioma that was discovered during nonrelated surgery. Retrospective study disclosed a family history of pheochromocytoma. The occurrence of gallbladder paraganglioma in the presence of family history of endocrine neoplasia supports that gallbladder paraganglioma may indeed occur as a part of the multiple endocrine neoplasm syndrome. Gallbladder paraganglioma is a rare tumor, and so far to our knowledge only 6 cases have been reported in the literature. Three cases were discovered incidentally during cholecystectomy for cholelithiasis, 2 presented with right upper quadrant pain, and 1 manifested with gastrointestinal bleeding. We herein review all reported cases of paraganglioma of gallbladder and biliary system.
Small Cell Carcinoma of the Ovary With Hypercalcemia and Ectopic Parathyroid Hormone Production
Authors: Chen Lei , Dinh Tri A. , Haque Abida
Published: February 2021

Small cell carcinoma of the ovary is a rare malignant tumor of the ovary. It is the most common undifferentiated ovarian carcinoma in young women. Approximately two thirds of patients with ovarian small cell carcinoma have hypercalcemia. The mechanism of development of hypercalcemia is unclear, although parathyroid hormone–related protein has been found in some of the cases. Parathormone expression in tumor cells, rarely reported, was seen in this case, suggesting that ectopic parathyroid hormone production by the tumor cells may be the cause of hypercalcemia.
Plexiform Neurofibroma of the Uterine Cervix: A Case Report and Review of the Literature
Authors: Wei Eric X. , Albores-Saavedra Jorge , Fowler Marjorie R.
Published: February 2021

The female genital system is rarely affected in von Recklinghausen neurofibromatosis. The vulva is the most frequent genital location, but vaginal, cervical, uterine, and ovarian neurofibromas have rarely been reported. We describe a case of plexiform neurofibroma affecting the uterine cervix in a patient with chronic pelvic pain and menorrhagia who had multiple cutaneous neurofibromas and 1 large paraspinal neurofibroma. A small plexiform neurofibroma, which was not grossly visible, was confined to the uterine cervix and coexisted with a uterine leiomyoma and adenomyosis. There were no neurofibromas in the myometrium, fallopian tubes, or ovaries. Plexiform neurofibroma is a neoplasm that should be considered in the differential diagnosis of spindle cell neoplasms of the uterine cervix, especially in specimens from patients with neurofibromatosis.
Subcutaneous Phaeohyphomycosis Caused by Cladophialophora bantiana
Authors: Hussey Sean M. , Gander Rita , Southern Paul , Hoang Mai P.
Published: February 2021

Primary subcutaneous phaeohyphomycosis can rarely be caused by Cladophialophora bantiana, and we present the histologic and culture findings of such a case. A 32-year-old African American woman with systemic lupus erythematosus presented with a 2-year history of multiple, recurrent, tender, and ulcerated skin nodules with purulent drainage on her upper back. Histologic sections of the excision demonstrated features of phaeohyphomycosis. Culture findings were characteristic of C bantiana. Of interest, at age 10 she had sustained traumatic implantation of wood splinters into this area during a tornado, yet clinical symptoms of a subcutaneous infection did not manifest until she developed lupus erythematosus at age 27. Our case highlights the role of trauma and immunosuppression in the pathogenesis of subcutaneous phaeohyphomycosis.