bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Method for Simultaneous Analysis of p53 and K-ras Mutations and p53 Protein Expression in Single Histologic Sections
Authors: Yamashita Kazuya , Yoshida Tsutomu , Shinoda Hiroshi , Okayasu Isao
Published: January 2021

Background and Objective.—Abnormal protein expression and gene mutation should be examined on exactly identified lesions. To perform simultaneous analyses of oncogene or tumor suppressor gene mutations and related protein expression in single histologic sections, we have developed a novel method using an antigen-retrieval solution for a polymerase chain reaction template before immunohistochemical staining.

Methods.—Using 20 cases of sporadic colorectal carcinoma, several kinds of antigen-retrieval solutions were tested after heating rehydrated, 4-μm-thick, formalin-fixed, paraffin-embedded histologic sections at 96°C for 20 minutes. Polymerase chain reaction–single-strand conformation polymorphism analysis was conducted for p53 (exons 5 through 9) and K-ras (exons 1 and 2), and the histologic sections were then immunostained with monoclonal antibody against p53.

Results.—DNA analysis of antigen-retrieval solutions was possible in all 20 cases and revealed completely consistent results (100%) with fresh cancer tissue and microdissected cancer tissue of paraffin-embedded histologic sections. With this method, K-ras mutations were positive in 10 of 20 cases (exon 1 in 9 cases and exon 2 in 1 case) and p53 mutations were positive in 9 of 20 cases (exon 5 in 4 cases, exon 6 in 1, exon 7 in 3, and exon 8 in 1 case), with 8 of the 9 p53 mutation cases showing diffuse p53 protein expression on immunostaining. Base alterations of all abnormal conformers were confirmed with direct sequencing. For polymerase chain reaction–single-strand conformation polymorphism analysis, sodium citrate buffer (pH 6.0) was found to be the optimal antigen-retrieval solution.

Conclusions.—This newly developed method can be used for routine immunostaining and genetic analysis with single histologic sections.
Goblet Cell Carcinoids of the Appendix
Authors: Kanthan R. , Saxena A. , Kanthan S. C.
Published: January 2021

Background.—Goblet cell carcinoids of the appendix are rare neoplasms with uncertain biological behavior.

Objective.—The aims of our study were to evaluate the immunophenotype of this neoplasm with cell cycle/cell proliferation markers and to understand their histogenesis with ultrastructural analysis using conventional carcinoids as a frame of reference.

Methods.—Clinical data and archival pathologic material of all goblet cell carcinoids of the appendix recorded by the Saskatchewan Cancer Registry between 1970 and 1998 were reviewed and evaluated by light microscopy, histochemistry, immunohistochemistry, and electron microscopy.

Results.—Seven cases of goblet cell carcinoids were identified among 110 cases of conventional carcinoids of the appendix. Histopathology revealed widespread infiltration of the periappendiceal fat in all cases, with extensive perineural invasion. The cells stained strongly positive for mucicarmine, periodic acid–Schiff, periodic acid–Schiff diastase, Alcian blue, cytokeratin, and carcinoembryonic antigen. Most cases were positive for synaptophysin. Increased expression of cell proliferation markers and cell cycle markers was observed. Expression of p53 was strong in one case. Electron microscopy demonstrated the presence of mucinous vacuoles of varying sizes and occasional membrane-bound neuroendocrine granules.

Conclusions.—Goblet cell carcinoids of the appendix arise from a pluripotent cell with divergent neuroendocrine and mucinous differentiation. These neoplasms are widely invasive; they demonstrate a high cellular proliferation rate and dysregulation of the cell cycle with up-regulation of cyclin D1 and p21, and down-regulation of p16. Complete removal of the tumor is recommended because of the unpredictable biological behavior of this tumor, which includes delayed local recurrences and lung metastases.
Morphometry and Histology of Gonads From 13 Children With Dysgenetic Male Pseudohermaphroditism
Authors: Scolfaro Márcia Ribeiro , Cardinalli Izilda Aparecida , Stuchi-Perez Eliana Gabas , de Mello Maricilda Palandi , de Godoy Assumpção Juliana , Baptista Maria Tereza Matias , Silva Joaquim Murray Bustorff , Maciel-Guerra Andréa Trevas , Júnior Gil Guerra
Published: January 2021

Background.—Dysgenetic male pseudohermaphroditism (DMP) is a sexual differentiation disorder characterized by bilateral dysgenetic testes, persistent müllerian structures, and cryptorchidism in individuals with a 46,XY karyotype. However, the histologic criteria for the diagnosis of DMP are poorly established.

Objective.—To determine gonadal histology in children with DMP.

Patients and Methods.—Between 1996 and 1998, 13 patients with DMP were evaluated on our service. The clinical diagnosis of DMP was based on a 46,XY karyotype, sex ambiguity, high levels of follicle-stimulating hormone and low levels of antimüllerian hormone, a decreased testosterone response to human chorionic gonadotropin stimulation without accumulation of testosterone precursors, and the presence of müllerian structures. Molecular sequencing the HMGbox region of the SRY gene did not reveal any mutations. Biopsies were performed for 22 of 26 gonads (patient age at the time of biopsy, 16 months to 10 years). Conventional microscopy was used to evaluate mean tubular diameter, tubular fertility index, and number of Sertoli cells per tubular profile.

Results.—All 26 gonads were located outside of the labioscrotal folds. Their histologic features varied from only a reduction in tubular size to features of a streak gonad. Five of the 22 gonads grossly resembled a streak gonad. The mean tubular diameter was severely reduced (>30% reduction relative to the normal tubular diameter for the patient's age) in 4 gonads, markedly reduced (10%–30%) in 11 gonads, slightly reduced (<10%) in one gonad, and normal in one gonad. The tubular fertililty index, expressed as the percentage of tubular profiles containing germ cells, was severely reduced (<30% of normal values) in 9 gonads, markedly reduced (50%–30%) in 2 gonads, and normal in 6 gonads. The number of Sertoli cells per tubular profile was elevated in 16 gonads and normal in one gonad. Thin tubules surrounded by fibrous tissue were occasionally observed.

Conclusion.—The histologic findings confirmed the clinical diagnosis of DMP in every patient in the present series. However, gonadal histology was variable, and careful morphometric evaluation may be necessary to establish the diagnosis.
Nasal Natural Killer Lymphoma Associated With Epstein-Barr Virus in a Patient Infected With Human Immunodeficiency Virus
Authors: Canioni Danielle , Arnulf Bertrand , Asso-Bonnet Marianne , Raphael Martine , Brousse Nicole
Published: January 2021

Nasal natural killer (NK) lymphoma associated with Epstein-Barr virus (EBV) is a rare lymphoma that has not yet been reported in patients with human immunodeficiency virus (HIV). This report describes the first case, to our knowledge, of nasal NK cell lymphoma in an HIV-positive patient. A 50-year-old African man presented with an obstructive nasopharyngeal tumor, leading to the diagnosis of HIV infection. Nasal biopsy specimens showed NK cell lymphoma, confirmed on nasal tissues by morphologic, immunohistochemical, and polymerase chain reaction studies using a denaturing gradient gel electrophoresis technique that showed no T-cell receptor γ rearrangement. The EBV was detected by in situ hybridization. The patient received chemotherapy but died from infection. To our knowledge, this is the first reported case of nasal NK cell lymphoma associated with EBV in an HIV patient. Involvement of EBV in HIV non–B-cell lymphomas may represent a further manifestation of opportunistic EBV infection arising in these patients.
Blastomyces dermatitidis With Large Yeast Forms
Authors: Hussain Zakir , Martin Anita , Youngberg George A.
Published: January 2021

Yeast forms of Blastomyces dermatitidis typically range from 8 to 20 μm in largest diameter. We report a rare case of primary pulmonary blastomycosis with an unusual morphology, in which we found significant numbers of large yeast forms ranging from 30 to 35 μm in diameter. To our knowledge, this is only the second reported case of giant forms of B dermatitidis. We also review the literature and discuss the possible association of this unusual morphology with immunosuppression in general and glucocorticoid use in particular.
Pigmented Cardiac Paraganglioma
Authors: Mikolaenko Irina , Galliani Carlos A. , Davis Gregory G.
Published: January 2021

A pigmented left atrial paraganglioma was found at autopsy in a 40-year-old black man who died unexpectedly. The cause of death was ascribed to coronary artery disease. The atrial mass was sharply demarcated and polypoid, measured 4 cm in greatest dimension, and had a cut surface that revealed dark red-brown soft tumor tissue. Histopathologically, the neoplasm exhibited a classic organoid clustering of cells (zellballen) with a prominent capillary network. The chief cells contained a brown-black pigment with histochemical characteristics of melanin. We report a case of pigmented cardiac paraganglioma because of its rarity. To our knowledge, no mention has been made of the presence of pigment in previously reported cases of cardiac paragangliomas.
Squamous Carcinoma in a Major Salivary Gland
Authors: Taxy Jerome B.
Published: January 2021

Context.—Squamous carcinoma in a major salivary gland has several possible sources: (1) high-grade mucoepidermoid carcinoma, (2) metastasis or direct invasion from a primary skin carcinoma, (3) metastasis from a distant primary carcinoma, or (4) a primary malignant neoplasm. The latter is conventionally regarded as a diagnosis of exclusion after a history of squamous carcinoma elsewhere has been obtained or there is a positive mucin stain.

Design.—Eleven cases of squamous carcinoma in a major salivary gland are presented and the literature reviewed.

Results.—Two cases, 1 metastatic from a histologically identical squamous carcinoma from the ipsilateral tonsil and 1 with in situ squamous carcinoma in a duct, demonstrated positive mucicarmine stains. Two cases were high-grade mucoepidermoid carcinomas, also with positive mucin stains. Five cases represented metastases from cutaneous squamous carcinomas. Only 2 cases were regarded as primary carcinomas. There were no histologic clues as to correct subclassification. Six patients died, 4 from their disease. Three of the 5 still alive had recurrence or metastasis.

Conclusion.—The occurrence of squamous carcinoma in a major salivary gland exhibits a histologic sameness that precludes accurate subclassification and assignation of origin. Also irrespective of tumor origin, the clinical approach to diagnosis and treatment is similar. Adjuvant therapy (eg, radical neck dissection, radiation, chemotherapy) is not uniformly applied. Most patients present with a sizable (>3-cm) mass for which total excision is attempted. The natural evolution of the tumor is aggressive, irrespective of clinical context. The traditional subclassification of squamous carcinoma in a major salivary gland may not be clinically relevant.
Varicella-Zoster Virus Infections of the Nervous System
Authors: Kleinschmidt-DeMasters B. K. , Gilden Donald H.
Published: January 2021

Background.—Diseases that present with protean manifestations are the diseases most likely to pose diagnostic challenges for both clinicians and pathologists. Among the most diverse disorders caused by a single known toxic, metabolic, neoplastic, or infectious agent are the central and peripheral nervous system complications of varicella-zoster virus (VZV).

Methods.—The pathologic correlates of the neurologic complications of VZV infection, as well as current methods for detecting viral infections, are discussed and presented in pictorial format for the practicing pathologist.

Results.—Varicella-zoster virus causes chickenpox (varicella), usually in childhood; most children manifest only mild neurologic sequelae. After chickenpox resolves, the virus becomes latent in neurons of cranial and spinal ganglia of nearly all individuals. In elderly and immunocompromised individuals, the virus may reactivate to produce shingles (zoster). After zoster resolves, many elderly patients experience postherpetic neuralgia. Uncommonly, VZV can spread to large cerebral arteries to cause a spectrum of large-vessel vascular damage, ranging from vasculopathy to vasculitis, with stroke. In immunocompromised individuals, especially those with cancer or acquired immunodeficiency syndrome, deeper tissue penetration of the virus may occur (as compared with immunocompetent individuals), with resultant myelitis, small-vessel vasculopathy, ventriculitis, and meningoencephalitis. Detection of the virus in neurons, oligodendrocytes, meningeal cells, ependymal cells, or the blood vessel wall often requires a combination of morphologic, immunohistochemical, in situ hybridization, and polymerase chain reaction (PCR) methods. The PCR analysis of cerebrospinal fluid remains the mainstay for diagnosing the neurologic complications of VZV during life.

Conclusions.—Varicella-zoster virus infects a wide variety of cell types in the central and peripheral nervous system, explaining the diversity of clinical disorders associated with the virus.
Induction of Human Immunodeficiency Virus 1 Replication by Human Herpesvirus 8
Authors: Mercader Maria , Nickoloff Brian J. , Foreman Kimberly E.
Published: January 2021

Background.—Human immunodeficiency virus 1 (HIV-1)–infected individuals are commonly infected with herpesviruses, including cytomegalovirus, herpes simplex virus, varicella-zoster virus, and human herpesvirus 8 (HHV-8, also known as Kaposi sarcoma–associated herpesvirus [KSHV]). Previous studies have demonstrated that coinfection with herpesviruses can modulate HIV-1 replication. This can occur either through direct interaction between the 2 viruses or through secondary effects resulting from the release of cellular factors in response to infection.

Objective.—To investigate HIV-1 replication in the presence and absence of HHV-8.

Design and Methods.—HIV-1 replication was analyzed following culture of HIV-1–infected CD4+ T cells in the presence of HHV-8 infected B-cell lines or control, uninfected B-cell lines. To confirm and extend the results of these in vitro studies, HIV-1–infected T cells were injected into human skin transplanted onto severe combined immunodeficient mice. The human skin was also injected with purified HHV-8 or phosphate-buffered saline as a control and HIV replication measured in biopsy specimens taken 5 to 8 days later.

Results and Conclusions.—The results demonstrated a significant increase in HIV-1 replication in the presence of HHV-8 in both the in vitro and in vivo model systems. Although the mechanism responsible for HHV-8 induction of HIV-1 replication remains to be identified, the results indicate that these 2 viruses may interact at the molecular level in coinfected patients, resulting in increased HIV-1 viral load.
Osteosarcoma of the Urinary Bladder Occurring Simultaneously With Prostate and Bowel Carcinomas
Authors: Ghalayini Ibrahim F. , Bani-Hani Ibrahim H. , Almasri Nidal M.
Published: January 2021

Osteosarcoma is a very rare tumor of the urinary bladder, with only 28 well-documented cases reported in the literature to date. The tumors have characteristically been large and polypoid and most commonly have been located in the trigone. An abdominal mass has occasionally been palpated, and rectal examination has frequently revealed a mass in the region of the bladder. The prognosis for this tumor is very poor. In this report, a 75-year-old man with hematuria was found to have a primary osteosarcoma of the urinary bladder with superficial invasion. Radical cystoprostatectomy and ileal conduit urinary diversion were performed. During surgery, a synchronous mucinous adenocarcinoma of the ascending colon was found, and a right hemicolectomy was performed. Prostatic adenocarcinoma was discovered from the histology. The patient died 7 months after surgery with systemic spread of the osteosarcoma. Osteosarcoma of the bladder should be distinguished from other bladder tumors that may be associated with bone formation, such as carcinosarcomas and transitional cell carcinomas with osseous metaplasia of their stroma, both of which have a better prognosis than osteosarcoma.
Small Cell Carcinoma of the Kidney
Authors: González-Lois Carmen , Madero Santiago , Redondo Pilar , Alonso Isabel , Salas Ana , Montalbán M. Angeles
Published: January 2021

Small cell carcinoma is a malignant tumor composed of small cells with a diffuse growth pattern. It has immunohistochemical and ultrastructural features of both neuroendocrine and epithelial neoplasms. These tumors constitute 10% to 20% of malignant tumors in the lung, which is their most frequent site. They have been described in other extrapulmonary sites, where they are defined using the same criteria as used in the lung. These tumors are rarely found in the genitourinary tract. Fewer than 30 cases have been reported in the kidney. The differential diagnosis mainly includes other small round cell tumors and metastatic small cell lung carcinoma. We present and discuss a primary small cell carcinoma of the kidney (to our knowledge the 9th to be reported in the literature), which we studied with light microscopy, immunohistochemistry, electron microscopy, and, for the first time, flow cytometry.
Glassy Cell Carcinoma of the Endometrium
Authors: Mhawech Paulette , Dellas Athanassios , Terracciano Luigi M.
Published: January 2021

Endometrial glassy cell carcinoma (GCC) is a rare neoplasm, with 11 cases reported in the literature. Although GCC is considered to be a poorly differentiated variant of adenosquamous carcinoma, its real nature is still debatable. We report a case of GCC of the endometrium in a 60-year-old woman and review the literature. The patient presented with vaginal bleeding, and pelvic computed tomographic scan showed a polypoid lesion in the uterine fundus. Histologically, the tumor showed 2 components: a moderately differentiated adenocarcinoma with extensive areas of squamous metaplasia (adenoacanthoma) and a GCC. The clinical stage of the patient's disease was IB as classified by the International Federation of Gynecology and Obstetrics. She was treated by a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic radiation therapy. The patient was still alive and free of disease at 5 years of follow-up.
Physician Satisfaction and Emergency Department Laboratory Test Turnaround Time
Authors: Steindel Steven J. , Howanitz Peter J.
Published: January 2021

Objectives.—To determine the length of time for the components of the emergency department (ED) turnaround time (TAT) study in 1998 and to ascertain physician satisfaction concerning laboratory services to the ED.

Methods.—Using forms supplied by the College of American Pathologists Q-Probes program, participants conducted a self-directed study of ED TAT over a 4-week period. Data requested included various times of day associated with the ordering, specimen collection, laboratory receipt, and result-reporting stages of stat ED TATs for potassium and hemoglobin. Additionally, practice-related questions associated with the laboratory were asked. Participating laboratories also provided a physician satisfaction survey for up to 4 physicians who were users of ED services. Results of both the TAT study and the physician satisfaction survey were returned by mail. Participants were drawn from the 952 hospital laboratories enrolled in the 1998 College of American Pathologists Q-Probes study on ED TAT. The main outcome measures included the components of the ED TAT process, factors associated with decreases in ED TAT, and the results of the physician satisfaction survey.

Results.—Six hundred ninety hospital laboratories (72.4% response rate) returned data on up to 18 230 hemoglobin and 18 259 potassium specimens. Half of these laboratories responded that 90% of potassium tests were ordered and reported in 69 minutes or less, whereas the TAT for 90% of hemoglobin results was 55 minutes or less. Comparison of the components of TAT for both potassium and hemoglobin with similar studies done in 1990 and 1993 showed no change. Factors found to statistically contribute to faster TATs for both tests were laboratory control of specimen handling and rapid transport time. When whole blood specimens were used for potassium determination, TAT improved. Emergency department physicians chose the study-defined lower satisfaction categories of Often, Sometimes, Rarely, and Never for the questions concerning the laboratory being sensitive to stat testing needs (39.1%) and meeting physician needs (47.6%). Many of the physicians surveyed believed that laboratory TAT caused delayed ED treatment more than 50% of the time (42.9%) and increased ED length of stay more than 50% of the time (61.4%) when compared with other specialty users of the ED.

Conclusions.—Laboratory ED TATs have remained unchanged for almost a decade. Emergency department physicians are not satisfied with laboratory services. Although it appears that one issue may relate to the other, the interaction between the laboratory and the ED is quite complex and has been evolving for at least 30 years. Improvement in interoperability between the departments is essential for operational efficiency and patient care. Effective communication channels need to be established to achieve these goals.
Three-Dimensional Morphology of c-Kit–Positive Cellular Network and Nitrergic Innervation in the Human Gut
Authors: Nemeth Laszlo , Puri Prem
Published: January 2021

Context.—c-Kit–positive interstitial cells of Cajal (ICC) appear to play a key role in the normal motility function and development of intestine. Nitric oxide is considered to be the most important messenger of inhibitory nonadrenergic, noncholinergic nerves in the enteric nervous system.

Objectives.—The aims of this study were to examine the distribution of nitrergic innervation and ICCs in normal human bowel and to demonstrate interconnections between ICCs and nitrergic nerves and smooth muscle fibers using histochemical and immunohistochemical double-staining methods with a whole-mount preparation technique and confocal laser scanning microscopy.

Methods.—Full-thickness small and large bowel specimens were obtained at autopsy from 18 children who died of nongastrointestinal diseases. A whole-mount preparation was performed for all specimens, and double staining was carried out with nicotinamide adenine dinucleotide phosphate (reduced form, NADPH)-diaphorase and c-Kit immunohistochemistry. Double immunofluorohistochemistry with neuronal nitric oxide synthase and c-Kit using confocal laser scanning microscopy was also performed in all specimens.

Results.—The whole-mount preparation facilitated 3-dimensional visualization of the meshlike network of NADPH-diaphorase–positive nerve fibers in the myenteric plexus surrounded by a reticular network of c-Kit–positive ICCs. The dense c-Kit–positive cellular network located between longitudinal and circular muscle layers and at the innermost part of circular muscle layer intermingled with the myenteric plexus. Short, fine processes of ICCs made connections with the muscle fibers and c-Kit–positive cells.

Conclusions.—The development of double–NADPH-diaphorase histochemistry and c-Kit immunohistochemistry staining technique in a whole-mount preparation provides an easy and useful method for investigating the association between c-Kit–positive cellular network and nitrergic neuronal network in the human bowel wall. The characteristic profiles of the c-Kit–positive cellular network and nitrergic neuronal network and their relationship with the smooth muscle fibers provide a morphologic basis for investigating intestinal motility disorders.
Declining Clinical Autopsy Rates Versus Increasing Medicolegal Autopsy Rates in Halifax, Nova Scotia
Authors: Wood Marnie J. , Guha Ashim K.
Published: January 2021

The downward trend in the rate of clinical autopsies has been extensively documented in the literature. This decline is of concern when the benefits of the clinical autopsy are considered. In contrast, the rate of medicolegal autopsies has not been studied in such detail. What little reference there is to medicolegal autopsy rates suggests an absence of the same downward trend. A retrospective review of autopsy data over a 13-year period from the Queen Elizabeth II Health Sciences Centre in Halifax, Nova Scotia, and from the Office of the Chief Medical Examiner of Nova Scotia was conducted. This review showed a difference between the rates of clinical and medicolegal autopsies for the metro Halifax area. The clinical autopsy rate was consistently less than 30% and declined to 15% in 1999, while the medicolegal autopsy rate was consistently greater than 40% and rose to 62% in 1999. The literature proposes many reasons for the decline in the clinical autopsy rate, but none for this difference between rates. The explanation proposed here is the changing and currently uncertain purpose of the clinical autopsy versus the clear, and consistent over time, purpose of the medicolegal autopsy.
Pulmonary Valve Papillary Fibroelastoma
Authors: Saad Reda S. , Galvis Colleen O. , Bshara Wiam , Liddicoat John , Dabbs David J.
Published: January 2021

Papillary fibroelastomas are rare and benign cardiac tumors that typically affect the cardiac valves. To the best of our knowledge, the English literature contains only 1 case report of pulmonary valve fibroelastoma diagnosed by echocardiogram and confirmed by surgical resection. There is a paucity of pathology literature on this subject. We describe an additional case of pulmonary valve fibroelastoma diagnosed by transesophageal echocardiography and magnetic resonance imaging confirmed by pathologic examination in a patient who also had a thymoma.
Papillary Carcinoma of Thyroid Metastatic to the Pituitary Gland
Authors: Bell C. David , Kovacs Kalman , Horvath Eva , Smythe Harley , Asa Sylvia
Published: January 2021

We describe a 35-year-old woman who presented with diabetes insipidus caused by metastatic papillary carcinoma of the thyroid involving the pituitary gland, 25 years after treatment for a papillary carcinoma of thyroid and 17 years after treatment for multiple pulmonary metastases. The literature contains 10 previously described cases of metastatic thyroid carcinoma involving the sella, but only 2 of these cases had unequivocal metastases to the pituitary gland, making the present case, to our knowledge, the third reported case of unequivocal hematogenous metastasis of thyroid carcinoma to the pituitary gland. The pituitary tumor was removed by transsphenoidal surgery, and the tissue was examined by conventional histology, extensive immunohistochemistry, and electron microscopy. The findings confirmed the tumor to be papillary thyroid carcinoma. To our knowledge, this is the first report citing use of thyroid transcription factor-1 to establish a thyroid source of a pituitary metastasis.
Vertebral Metastases From Pineoblastoma
Authors: Charafe-Jauffret Emmanuelle , Lehmann Gilbert , Fauchon François , Michiels Jean-François , Paquis Philippe , Maraninchi Dominique , Hassoun Jacques
Published: January 2021

Two male patients aged 26 and 18 years presented with vertebral metastases originating from pineoblastomas on which surgery had been performed 8 years and 5 months earlier, respectively. In the first case in which the metastasis developed in the T8 corpus, the disease is presently under control after high-dose chemotherapy and autologous blood stem cell transplantation. The second patient (sacral metastasis), despite aggressive adjuvant therapy, died 2 years after the last operation because of spinal seeding. These uncommon cases are discussed with reference to the literature on extraneural metastases that originate from neuroepithelial tumors of the central nervous system.
Allergic Granulomatosis Secondary to a Limited Form of Churg-Strauss Syndrome
Authors: Cualing Hernani , Schroder Louis , Perme Charles
Published: January 2021

Allergic granulomatosis is a disorder of obscure etiology characterized by infiltration of lymph nodes with histiocytic granulomas and eosinophils. In this report, we describe a case of allergic granulomatosis that is consistent with Churg-Strauss disease limited to lymph nodes. The histologic findings of this patient's lymph nodes demonstrated eosinophilic abscesses and ring-shaped necrotizing and nonnecrotizing granulomas surrounding hyperplastic germinal centers. We report herein a rare type of reactive lymphadenopathy and present its histologic, immunohistochemical, and flow cytometric findings, which may allow its distinction from other lymphadenopathies.
Adequate Histologic Sampling of Breast Core Needle Biopsies
Authors: Renshaw Andrew A.
Published: January 2021

Objective.—To determine the degree of histologic sampling necessary for adequate examination of breast core needle biopsy specimens.

Design.—The results of all breast core needle biopsies (11 and 14 gauge) with a diagnosis of atypical small acinar proliferation or atypical ductal hyperplasia and subsequent excisional biopsies, for a 50-month period were reviewed. Blocks of all cores were sectioned entirely in 8 slides to determine the amount of sectioning needed to detect these foci, and the results were correlated with those from the excision specimen.

Setting.—Large community hospital practice.

Results.—Of 3026 cases, 216 (7.1%) were diagnosed as atypical ductal hyperplasia or atypia not otherwise specified. Subsequent resections were available in 105 (49%) cases, and after review, 95 (92%) qualified as atypical ductal hyperplasia and 2 were determined to be atypical small acinar proliferations. The 2 small acinar proliferations were first detected on the second and fourth slides. Of the atypical ductal hyperplasia cases, 43% were detected on the first slide, 17% on the second, 23% on the third, 8% on the fourth, and 8% on the fifth. No lesions were initially detected after this level. Ductal carcinoma in situ was detected in the excision specimens from 1 case each of those detected initially on the fourth and fifth slides.

Conclusion.—Five sections of breast core needle biopsy specimens are necessary to ensure that all atypical small acinar proliferations and atypical ductal hyperplasia lesions are sampled.
Inflammatory Pseudotumor of the Submandibular Gland
Authors: Kojima Masaru , Nakamura Shigeo , Itoh Hideaki , Suchi Taizan , Masawa Nobuhide
Published: January 2021

We report a rare case of inflammatory pseudotumor arising in the submandibular gland, which presented with autoimmune disease–like clinical manifestations. A 70-year-old Japanese man developed masses in both submandibular regions. Laboratory tests revealed polyclonal hypergammaglobulinemia, high titers of antinuclear antibody, and a positive thyroid test. Histologically, the lesion was composed of multiple nodules separated by thick fibrous bands and contained a few atrophic lymphoid follicles and residual ductal structures. At higher magnification, the nodules contained numerous mature plasma cells mixed with myofibroblasts, lymphocytes, and histiocytes. Occasionally, the myofibroblasts were arranged in poorly formed fascicles and in a storiform pattern. Polymerase chain reaction analysis failed to demonstrated the rearrangement of the immunoglobulin heavy-chain gene. The patient was free of disease after 72 months follow-up. Marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type arising from salivary glands occasionally showed prominent plasma cell differentiation. The present case indicates that inflammatory pseudotumor should be added to the list of different diagnoses for mucosa-associated lymphoid tissue–type lymphoma of the salivary glands.
Confidentiality of Health Information Postmortem
Authors: Maixner Andrew H. , Morin Karine
Published: January 2021

Context.—Recent discussions of health care privacy have prompted new concerns over the control of private health information after a patient's death. The importance of confidentiality protections postmortem is compounded as genetic technologies and research capabilities advance and public interest in this information increases.

Objective.—The Council on Ethical and Judicial Affairs of the American Medical Association developed this report to guide physicians in the management of patients' health information postmortem.

Participants.—This report was developed by the 9 physician members of the Council on Ethical and Judicial Affairs with the assistance of staff from the Ethics Standards Group at the American Medical Association.

Evidence.—Literature searches in the MEDLINE and BIOETHICSLINE databases using the search terms postmortem and health information qualified with confidentiality or privacy yielded a combined total of 129 references. Additional references were culled from policies of a number of health care organizations.

Consensus Process.—The Council on Ethical and Judicial Affairs solicited suggestions from the federation of state medical and specialty societies before drafting this report. A copy of the report was sent to the College of American Pathologists for comment. It was then adopted by a majority vote of the House of Delegates of the American Medical Association.

Conclusions.—The report emphasizes the importance of maintaining confidentiality for information held within a deceased patient's medical record. However, these protections are subject to certain exceptions. Confidentiality can be upheld when such information is used for educational or research purposes by removing individual identifiers. For disclosures in which the identity of the deceased patient is known, a number of considerations are provided to assess when disclosure would be ethically permissible.
Unexpected Autopsy Findings Arising From Postmortem Ocular Examination
Authors: Butnor Kelly J. , Proia Alan D.
Published: January 2021

Background.—A full autopsy at our institution includes removal of the eyes for pathologic examination. To our knowledge, the rate of ophthalmic findings at autopsy has not been documented previously.

Design.—We retrospectively reviewed 277 consecutive autopsies conducted between 1995 and 1999 in which the eyes were removed for examination. Ophthalmic findings were placed in the following categories: I, major findings included those that contributed to the patient's death, would have changed patient management, and/or may have important medical implications for close relatives; II, expected findings after ophthalmologic surgery and minor findings that may have eventually required treatment; and III, incidental findings.

Results.—Major findings (category I) were found in 32% of autopsies. Minor findings (category II) and incidental findings (category III) were documented in 62% and 34% of autopsies, respectively. Only 14% of autopsies revealed no ophthalmologic diagnoses.

Conclusion.—In our series, postmortem ocular examination revealed a number of important findings, including several heritable and rare conditions. Eighty-six percent of autopsies disclosed at least one pathologic ophthalmologic finding, approximately one third of which demonstrated findings significant enough to have likely required management. Diabetic retinopathy was the most frequent major finding. Malignant melanoma of the choroid was the most commonly found intraocular neoplasm. Chronic uveitis was the most common minor finding. We conclude that important, often unexpected ophthalmic findings are frequently encountered at autopsy, underscoring the relevance of routine postmortem examination of the eyes.
Aberrant Expression of Tumor Suppressor Proteins in the Ewing Family of Tumors
Authors: Maitra Anirban , Roberts Helen , Weinberg Arthur G. , Geradts Joseph
Published: January 2021

Background.—Deregulation of tumor suppressor gene function and abrogation of cell cycle control are common features of malignant neoplasms, but corresponding data on Ewing sarcomas and primitive neuroectodermal tumors are relatively scarce. We studied the expression of 4 tumor suppressor proteins in the Ewing family of tumors (EFTs).

Design.—We examined a series of 20 pediatric EFTs for abnormal expression of p16INK4a, p14ARF, p21WAF1, and pRB by immunohistochemical analysis of pretreatment, nondecalcified archival specimens. Clinical follow up was available in all cases (median, 21 months; range, 5–103 months). Five patients presented with metastatic disease, 8 had no evidence of disease at last follow up, and 12 had an adverse outcome (death or progressive tumor posttherapy).

Results.—Twelve cases (60%) demonstrated abnormal expression of at least one tumor suppressor protein. There were 11 cases (55%) with loss of p21WAF1 expression, 4 (20%) with down-regulation of p16INK4a, 2 (10%) with absence of pRB, and one case (5%) with loss of p14ARF expression. Loss of p16INK4a expression correlated with metastatic disease at presentation (P = .026), and showed a trend toward shortened survival (P = .20). The p21WAF1, p14ARF, and pRB status was not significantly correlated with either metastatic disease at presentation or outcome.

Conclusion.—Abrogation of the G1 checkpoint was common in this series of EFTs, and down-regulation of p21WAF1 and p16INK4a were the most frequent findings. Loss of p16INK4a expression may identify a subset of cases with a more aggressive phenotype.
The Effect of Changes in Laboratory Practices on the Rate of False-Positive Cultures for Mycobacterium tuberculosis
Authors: Breese Peter E. , Burman William J. , Hildred Mary , Stone Barbara , Wilson Michael L. , Yang Zhenhua , Cave M. Donald
Published: January 2021

Context.—False-positive cultures for Mycobacterium tuberculosis have been found in nearly all DNA fingerprinting studies, but the effectiveness of interventions to reduce cross-contamination has not been evaluated.

Objective.—To evaluate whether changes in laboratory policies and procedures reduced the rate of false-positive cultures.

Design.—Retrospective study of isolates with matching DNA fingerprints.

Setting.—A mycobacteriology laboratory serving an urban tuberculosis control program and public hospital system.

Patients.—All M tuberculosis isolates processed from July 1994 to December 1999.

Methods.—Isolates were fingerprinted using IS6110; pTBN12 was used to fingerprint isolates having fewer than 6 copies of IS6110. We further evaluated all patients having only one positive culture whose DNA fingerprint matched that of another isolate processed in the laboratory within 42 days.

Interventions.—We changed laboratory policy to reduce the number of smear-positive specimens processed and changed laboratory procedures to minimize the risk of cross-contamination during batch processing.

Main Outcome Measure.—The rate of false-positive cultures.

Results.—Of 13 940 specimens processed during the study period, 630 (4.5%) from 184 patients and 48 laboratory proficiency specimens grew M tuberculosis. There were no cases (0/184) of probable or definite cross-contamination, compared with the 4% rate (8/199) identified in our previous study (P = .008). We also fingerprinted a convenience sample of isolates from other laboratories in Denver; 13.6% (3/22) of these were false-positive, a rate similar to the 11.9% rate (5/42) identified for other laboratories in our previous study (P = .84).

Conclusions.—Laboratory cross-contamination decreased significantly after relatively simple, inexpensive changes in laboratory policies and practices. Cross-contamination continued to occur in other laboratories in Denver.
Ganglioneuroma of Parapharyngeal Region
Authors: Albonico Giuseppe , Pellegrino Giovanna , Maisano Maurizio , Kardon David E.
Published: January 2021

In this article, we describe a case of ganglioneuroma observed in a 27-year-old woman. The tumor was found in an unusual location, the parapharyngeal space. The lesion was asymptomatic and was surgically excised after a fine-needle aspiration biopsy that was considered inadequate. The lesion measured 4 × 3 cm and was capsulated. Two distinct cells groups were identified: ganglion cells and Schwann cells placed in a loose myxoid stroma. Immunohistochemical stains (performed with the following monoclonal antibodies: high-molecular-weight cytokeratins, vimentin, neuron-specific enolase, neurofilaments, and S100) confirmed the diagnosis of ganglioneuroma. The pathologic findings and a review of recent literature are discussed.
CD15+ Acute Lymphoblastic Leukemia and Subsequent Monoblastic Leukemia
Authors: Dunphy Cherie H. , Gardner Laura J. , Evans H. Lance , Javadi Nader
Published: January 2021

The abnormality in the translocation of chromosomes 4 and 11 (t[4;11]) has been characteristically associated with calla-negative CD15+ acute lymphoblastic leukemia (ALL) of early pre–B-cell origin. Transformation of a lymphoblastoid to a monoblastoid morphologic structure has rarely been described at relapse in these cases; however, these cases have lacked flow cytometric immunophenotyping (FCI) and genotypic studies (GS) to define the immunophenotype of and the presence of a B-cell gene rearrangement in the monoblastoid component. We report a case of CD15+, CD10− ALL of early pre–B-cell origin defined by morphologic testing and FCI with the t(4;11) abnormality. At relapse, the morphologic testing, enzyme cytochemistry, and FCI data were characteristic of monoblastic leukemia. The t(4;11) abnormality persisted with associated additional chromosomal abnormalities, and the monoblasts contained a B-cell gene rearrangement by GS. These findings support the concept that both processes arose from a multipotential progenitor cell.
Solitary Blood Cultures
Authors: Novis David A. , Dale Jane C. , Schifman Ron B. , Ruby Stephen G. , Walsh Molly K.
Published: January 2021

Objective.—To determine the frequency with which solitary blood culture samples were submitted to laboratories serving small hospitals and to ascertain whether certain hospital practices relating to the performance of blood cultures were associated with lower solitary blood culture rates (SBCRs).

Design.—Participants in the College of American Pathologists Q-Probes laboratory quality improvement program collected data prospectively on the numbers of solitary blood culture sets from adult patients submitted to their laboratories and answered questions about their institutions' practice characteristics relating to the collection of blood culture specimens.

Setting and Participants.—Three hundred thirty-three public and private institutions with a median occupied bed size of 57. Participants were located in the United States (n = 329), Canada (n = 3), and Australia (n = 1).

Main Outcome Measure.—The solitary blood culture rate was defined as the number of instances in which only 1 blood culture venipuncture was performed on an individual patient during a 24-hour period divided by the total number of blood culture venipunctures that were performed during the study period.

Results.—Participants submitted data on 132 778 adult patient blood culture sets. The SBCRs were 3.4% or less in the top-performing 10% of participating institutions (90th percentile and above), 12.7% in the midrange of participating institutions (50th percentile), and 42.5% or more in the bottom-performing 10% of participating institutions (10th percentile and below). In half the participating institutions, the SBCRs for inpatients were 8.3% or less and for outpatients, 22% or less. Solitary blood culture rates were lower for institutions in which phlebotomists rather than nonphlebotomists routinely collected blood culture specimens, in which internal policies required drawing at least 2 blood culture sets, in which hospital personnel contacted clinicians when their laboratories received requests for solitary blood culture sets, and in which quality control programs monitored SBCRs routinely.

Conclusions.—Hospitals can achieve SBCRs under 5%. Those hospitals with particularly high SBCRs may lower their rates by altering certain institutional practices.
Preventing Medical Errors in Point-of-Care Testing
Authors: Kost Gerald J.
Published: January 2021

Objective.—To prevent medical errors, improve user performance, and enhance the quality, safety, and connectivity (bidirectional communication) of point-of-care testing.

Participants.—Group A included 37 multidisciplinary experts in point-of-care testing programs in critical care and other hospital disciplines. Group B included 175 professional point-of-care managers, specialists, clinicians, and researchers. The total number of participants equaled 212.

Evidence.—This study followed a systems approach. Expert specifications for prevention of medical errors were incorporated into the designs of security, validation, performance, and emergency systems. Additional safeguards need to be implemented through instrument software options and point-of-care coordinators. Connectivity will be facilitated by standards that eliminate deficiencies in instrument communication and device compatibility. Assessment of control features on handheld, portable, and transportable point-of-care instruments shows that current error reduction features lag behind needs.

Consensus Process.—Step 1: United States national survey and collation of group A expert requirements for security, validation, and performance. Step 2: Design of parallel systems for these functions. Step 3: Written critique and improvement of the error-prevention systems during 4 successive presentations to group B participants over 9 months until system designs stabilized into final consensus form.

Conclusions.—The consensus process produced 6 conclusions for preventing medical errors in point-of-care testing: (1) adopt operator certification and validation in point-of-care testing programs; (2) implement security, validation, performance, and emergency systems on existing and new devices; (3) require flexible, user-defined error-prevention system options on instruments as a prerequisite to federal licensing of new diagnostic tests and devices; (4) integrate connectivity standards for bidirectional information exchange; (5) preserve fast therapeutic turnaround time of point-of-care test results; and (6) monitor invalid use, operator competence, quality compliance, and other performance improvement indices to reduce errors, thereby focusing on patient outcomes.

(Arch Pathol Lab Med. 2001;1307–1315)
Obliterative Muscularization of the Small Bowel Submucosa in Crohn Disease
Authors: Koukoulis G. , Ke Y. , Henley J. D. , Cummings O. W.
Published: January 2021

Context.—The pathology of small bowel obstruction in Crohn disease has not been studied extensively. Stricture formation has been attributed mainly to fibrosis, although muscularization of the submucosa has been discussed previously.

Objective.—To identify additional pathologic changes in Crohn disease that could be involved in the formation of strictures.

Design.—We reviewed 50 ileal resections from patients with Crohn disease. The histopathologic slides were reviewed initially without knowledge of the macroscopic or clinical findings. We identified an unusual muscular proliferation that we refer to as obliterative muscularization of the submucosa, defined as a thick and continuous muscle layer from the mucosal base to the muscularis propria that is at least 1 cm in length. Subsequently, histopathologic findings were correlated with macroscopic and clinical findings.

Results.—Obliterative muscularization of the submucosa was present in 14 specimens, and in 11 of these 14 it was topographically restricted to strictures. Submucosal fibrosis was observed in sections from adjacent regions. Obliterative muscularization of the submucosa, including thick-walled vessels and hyperplastic nerves but not prominent scarring, was more common in specimens with strictures; the difference was statistically significant (P < .001).

Conclusions.—Obliterative muscularization of the submucosa may be pathogenetically involved in the formation of strictures either directly by causing a sustained spasm, or indirectly by minimizing the vasoprotective role of the submucosa, impairing repair and enhancing scarring.