bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative Microbiologic Study of Blood Salvaged by Intraoperative Membrane Filtration
Authors: Nosanchuk Jerome S.
Published: January 2021

Objective.—To evaluate the sterility of blood salvaged intraoperatively by a new membrane filtration system for transfusion.

Design.—Quantitative microbiologic cultures were prospectively collected from units of blood acquired by intraoperative membrane filtration from 18 patients undergoing elective spinal surgery. Medical records were reviewed for adverse events.

Setting.—A 204-bed, medical school–affiliated community hospital.

Results.—Quantitative blood cultures were sterile in 12 of 31 units of recovered blood. Of the 19 positive units, 17 units grew only 1 colony-forming unit (CFU)/mL, 1 unit grew 2 CFU/mL, and 1 unit grew 5 CFU/mL. The only organisms isolated were diphtheroids, coagulase-negative staphylococci, and micrococci. No patient experienced postoperative sepsis.

Conclusions.—Blood recovered by intraoperative membrane filtration is microbiologically equivalent to blood salvaged by continuous flow. Because no perfusionist and no expensive capital equipment are required, the technique is amenable to small and medium-sized hospitals that otherwise might financially be unable to provide intraoperative blood salvage.
Bcl-2, Bcl-x, and Bax Expression by Immunohistochemistry in Inclusion Body Myositis
Authors: Prayson Richard A. , Yu Albert C.
Published: January 2021

Context.—Bcl-2, Bcl-x, and Bax are among the variety of proteins that have been described as being involved in the regulation of apoptotic cell death. Bcl-2 and Bcl-xL inhibit apoptosis, and Bax is proapoptotic.

Objective.—To evaluate the expression of Bcl-2, Bcl-x, and Bax in inclusion body myositis (IBM).

Design.—We examined muscle specimens from 27 patients (17 men, 10 women) with IBM to evaluate Bcl-2, Bcl-x, and Bax expression by immunohistochemistry.

Results.—Patient ages ranged from 29 to 80 years (mean 62.2 years). All biopsies were marked by endomysial chronic inflammation, muscle fiber necrosis, and regeneration. Rimmed (autophagic) vacuoles were present in all cases. Ragged red fibers were noted in 4 biopsies (15%), and cytochrome oxidase–deficient fibers were found in 10 biopsies (37%). Ultrastructural evidence of intranuclear or cytoplasmic tubulofilamentous inclusions, confirming the diagnosis of IBM, were noted in all cases. Paracrystalline mitochondrial inclusions were seen in 5 biopsies (18.5%). Inflammatory cells stained positively with Bcl-2 in all biopsies, Bax in 26 biopsies (96%), and Bcl-x in 8 biopsies (30%). Degenerating muscle fibers were highlighted with Bax in 24 biopsies (89%), Bcl-2 in 2 biopsies (7%), and Bcl-x in 3 biopsies (11%). Regenerative muscle fibers were noted to stain with Bax in 24 muscles (89%), Bcl-2 in 21 muscles (78%), and Bcl-x in 4 muscles (15%). Rimmed vacuoles were highlighted by Bax in 24 biopsies (89%) and only rarely by Bcl-2 (n = 2, 7%) and Bcl-x (n = 3, 11%). A subsarcolemmal staining pattern was observed in 21 biopsies (78%) with Bax, 6 biopsies (22%) with Bcl-2, and only 1 biopsy (4%) with Bcl-x.

Conclusions.—(1) Bax (proapoptotic) immunostaining highlighted most autophagic vacuoles; (2) subsarcolemmal Bax and Bcl-2 immunoreactivity may be associated with mitochondrial defects that are commonly noted in IBM; (3) Bcl-2 and Bax immunoreactivity were not confined to degenerating muscle fibers and in fact appeared to be expressed more commonly in regenerating fibers, suggesting that their expression may be independent of apoptosis in the setting of IBM.
Expression of Thyroid Transcription Factor-1 and Other Markers in Sclerosing Hemangioma of the Lung
Authors: Illei Peter B. , Rosai Juan , Klimstra David S.
Published: January 2021

Context.—Sclerosing hemangioma of the lung is well characterized histologically, but the line of differentiation expressed by the tumor cells has been unclear. Despite the implication by its name of a vascular neoplasm, sclerosing hemangioma is considered by most authorities to be an epithelial tumor, possibly related to the pulmonary epithelium.

Objectives.—To determine the line of differentiation of the tumor cells with immunohistochemistry and to review the related literature.

Design.—Nine cases of histologically typical pulmonary sclerosing hemangioma were studied with pan-epithelial (epithelial membrane antigen [EMA] and CAM 5.2), endothelial (CD31), neuroendocrine (chromogranin A), and pulmonary epithelial markers (thyroid transcription factor-1 and PE10). Staining intensity was separately evaluated in the pale cells of the solid areas and the cells lining the papillary structures.

Results.—Both cell types were positive for thyroid transcription factor-1 and EMA in all cases (100%). Thyroid transcription factor-1 showed diffuse strong staining, and EMA staining varied from focal weak to diffuse strong. The pale cells showed focal staining for keratin (CAM 5.2) in 2 (28%) of 7 cases, and for PE10 in 5 (62%) of 8 cases. The papillary lining cells were at least focally positive with CAM 5.2 and PE10 in all cases (100%). Reactions for chromogranin and CD31 were negative in both cell types in every case. The number of PE10- or CAM 5.2–positive papillary lining cells was less than the number of EMA-positive papillary lining cells.

Conclusion.—The uniform positivity for EMA is consistent with the notion that the tumor cells of sclerosing hemangioma are epithelial, and the strong thyroid transcription factor-1 positivity suggests differentiation toward pulmonary epithelium. The papillary lining cells expressing EMA as well as PE10 or CAM 5.2 likely represent entrapped metaplastic alveolar epithelium, whereas the papillary lining cells expressing only EMA more likely constitute true neoplastic cells similar to those in the solid areas.
Rosai-Dorfman Disease of the Parotid Gland
Authors: Juskevicius Ridas , Finley James L.
Published: January 2021

Rosai-Dorfman disease is a rare histiocytic proliferative disorder of unknown origin and a distinct clinicopathologic entity also known as sinus histiocytosis with massive lymphadenopathy. The disease can involve extranodal tissues and rarely can present as salivary gland enlargement without significant lymphadenopathy. Involvement of the extranodal head and neck sites appears to be more common in patients with immunologic abnormalities. The disease was first described in 4 patients in 1969, and with later descriptions of more patients, the disease was established as a well-defined clinicopathologic entity. The characteristic pathologic feature of this disease is proliferation of distinctive histiocytic cells that demonstrate emperipolesis in the background of a mixed inflammatory infiltrate, consisting of moderately abundant plasma cells and lymphocytes. Fine-needle aspiration biopsy can be helpful in establishing the correct diagnosis, since surgical treatment is not necessary other than obtaining tissue for definitive diagnosis. We describe cytologic, histopathologic, and immunohistochemical features of a case of Rosai-Dorfman disease that involved a major salivary gland without significant lymphadenopathy in a 48-year-old patient with systemic lupus erythematosus. We also briefly discuss possible causes and pathogenesis and review the literature.
Allergic Mucin With and Without Fungus
Authors: Lara Jonathan F. , Gomez J. Daniel
Published: January 2021

Context.—Allergic mucin, a lamellated collection of inspissated inflammatory debris, has been a hallmark of allergic fungal sinusitis. While its identification is a clue for pathologists to search for fungi, and directs clinicians toward specific therapy and follow-up, recent reports describe cases with allergic mucin but without concomitant fungus. The absence of such organisms in otherwise typical allergic mucin brings into question the role of fungi in allergic fungal sinusitis.

Objectives.—To study clinical and pathologic differences between patients with allergic mucin in surgical nasal resection specimens and to elucidate the role of fungus in allergic sinusitis.

Design.—Patients with histologic evidence of allergic mucin, with and without fungus, were identified and retrieved from the surgical pathology files of a tertiary-care institution. The patients were separated into 2 groups for analysis, and their clinical and pathologic findings were reviewed and compared.

Setting.—Tertiary-care institution.

Patients.—All patients who underwent sinus mucosal resection between 1992 and 1998.

Results.—Clinical presentation and radiographic findings were similar in both groups. Incidence, age, and gender distribution were similar to data reported previously. However, the amount of allergic mucin was much greater in the group with fungus than in the group without fungus, which to our knowledge is an unreported observation to date.

Conclusion.—The presence of allergic mucin is not unique to allergic fungal sinusitis, but rather is the result of a process that could have other etiologies. While perhaps not always causative to the disease, the fungus continues to fuel the process and is likely an entrapped bystander. Allergic fungal sinusitis is more appropriately termed allergic mucinous sinusitis or eosinophilic mucinous rhinosinusitis.
Fine-Needle Aspiration Biopsy of Vertebral and Intervertebral Disc Lesions
Authors: Phadke Dattatreya M. , Lucas David R. , Madan Shashi
Published: January 2021

Background and Objectives.—Fine-needle aspiration biopsy (FNAB) is used extensively in the clinical workup of radiologically detected bony lesions. The aims of this study were to evaluate the diagnostic utility of FNAB of such radiologically detected vertebral and intervertebral disc lesions in patients with and without a known primary malignancy, to establish criteria for specimen adequacy, and to evaluate the diagnostic pitfalls.

Design.—The cytologic material obtained by FNAB performed under computed tomographic guidance of 78 cases comprising 66 vertebral and 12 intervertebral disc lesions was reviewed and analyzed. The initial cytologic diagnosis was compared with the diagnosis after review in all 78 cases.

Results.—Thirty-five cases (45%) were positive for malignancy, 1 case (1.3%) was suspicious for malignancy, 9 (11.5%) consisted of normal cellular elements with no evidence of malignancy, 21 (27%) were unsatisfactory/inadequate for diagnosis, and 12 (15.2%) were benign nonneoplastic lesions. Nonneoplastic lesions diagnosed included fracture callus, discitis/osteomyelitis, degenerative disc disease, and Paget disease. In 11 cases, FNAB gave the initial diagnosis of malignancy (8 occult carcinomas and 3 plasmacytomas). In 23 out of 36 cases with a clinical history of a known primary tumor, FNAB established the diagnosis of metastases, and in 1 case, a second primary was detected.

Conclusions.—Fine-needle aspiration biopsy of radiologically suspected vertebral and intervertebral disc lesions in patients with a history of a known malignancy is useful to confirm the presence of metastases. In cases without any history of malignancy, FNAB can provide additional clues to aid in the subsequent workup and treatment of cases diagnosed with an unsuspected malignancy and other nonneoplastic lesions. Through assessment of the specimen adequacy, correct interpretation of the cytologic material available, and correlating with the clinical and radiologic findings, a definitive diagnosis can be made in most cases.
Heterotopic Ovarian Splenoma
Authors: Cualing Hernani , Wang Guangsheng , Noffsinger Amy , Fenoglio-Preiser Cecilia
Published: January 2021

We present a case of ovarian splenoma, a form of heterotopicsplenic hamartoma consisting of red pulp tissue.The hamartoma was located in ovarian stroma in an otherwisenormal ovary. The histology showed interanastomosingvascular channels of splenic sinusoidal red pulplined by cells that were immunoreactive for antibodies tovon Willebrand antigen and CD8, findings consistent withsplenic lining cells. The sinuses were lined by cuboidal toflattened cells with ovoid and grooved bland-looking nuclei.Ultrastructurally, the tumor cells showed Weibel-Paladebodies and lysosomes. To our knowledge, this is thefirst case of splenic tissue arising in an ovary, and it underlinesthe trend noted in the literature that splenic hamartoma,although a rare entity, can arise in many retroperitonealorgans, including the ovary.
Intussusception Due to Yersinia enterocolitica Enterocolitis in a Patient with β-Thalassemia
Authors: Hansen Marilyn G. , Pearl Gary , Levy Marc
Published: January 2021

Patients who are homozygous for thalassemia major are at risk for Yersinia enterocolitica infections. We present a case of a 4-year-old child with intussusception of the terminal ileum whose past medical history was significant for β-thalassemia. His monthly blood transfusions for this condition may have put him at risk for Y enterocolitica enterocolitis. The pathogenesis of this disease relates to the role of iron as an essential growth factor for Yersinia, and this patient's transfusions left him in an iron-overloaded state, despite treatment with Desferal. Our patient's unusual presentation of intussusception was secondary to the mass effect caused by lymphoid hyperplasia, specifically hypertrophied Peyer's patches in the ileum caused by Y enterocolitica infection. To our knowledge, this is the first such case of intussusception caused by Yersinia to be reported.
Coexistence of Acute Cellular Rejection and Lymphoproliferative Disorder in a Lung Transplant Patient
Authors: Longchampt Elisabeth , Achkar Antoine , Tissier Frederique , Rabbat Antoine , Audouin Josee , Molina Thierry Jo
Published: January 2021

We report the case of a 37-year-old man who underwent bilateral lung transplantation for end-stage cystic fibrosis. Two months after his operation, a computed tomographic scan showed multifocal nodules throughout both lungs. Endobronchial biopsies revealed an Epstein-Barr virus–associated B-cell lymphoproliferation. Transbronchial biopsies revealed perivascular lymphoid infiltrates composed of predominantly small T lymphocytes. These perivascular infiltrates were retrospectively considered to be an acute cellular rejection rather than the periphery of the lymphoproliferative disorder. This opinion was based on several arguments: (a) a decrease in dosage of maintenance immunosuppression led to total regression of the lymphoproliferation but did not affect the perivascular lymphoid infiltrates; (b) the treatment of the acute cellular rejection temporarily induced the disappearance of the perivascular infiltrates; (c) the expression of Epstein-Barr virus was not detected in the perivascular infiltrates; and (d) on autopsy, performed 1 year later, severe obliterative bronchiolitis lesions were discovered, for which acute cellular rejection is the main risk factor. These observations point to the possibility that acute cellular rejection and an Epstein-Barr virus–associated lymphoproliferative disorder may coexist.
Metastatic Angiosarcoma Masquerading as Diffuse Pulmonary Hemorrhage
Authors: Adem Camilo , Aubry Marie-Christine , Tazelaar Henry D. , Myers Jeffrey L.
Published: January 2021

Context.—Diffuse pulmonary hemorrhage is an uncommon presenting manifestation of angiosarcoma.

Objective.—To review the clinical, radiologic, and pathologic findings of patients with metastatic angiosarcoma who presented with diffuse pulmonary hemorrhage.

Design.—Patients fulfilling inclusion criteria were identified from the consultation files. Clinical and radiologic data were obtained from referring pathologists. Histologic slides were reviewed in all patients.

Results.—Our patients included 6 men and 1 woman, aged 31 to 73 years; 4 patients were younger than 40 years. Six patients presented with hemoptysis, and all had diffuse abnormalities on radiographic studies. Clinical considerations prior to biopsy included pulmonary hemorrhage syndrome (n = 2), acute respiratory failure (n = 1), and infection (n = 1). Metastatic disease was included in the differential diagnosis in only 1 patient. None had a diagnosis of malignancy prior to lung biopsy. All biopsies showed hemorrhage associated with atypical epithelioid and spindle cells, forming anastomosing vascular channels, distributed along and within lymphatics and arteries. Neoplastic cells were immunoreactive for factor VIII–related protein or CD31 in all cases for which special stains were available. Three patients with complete follow-up died of their disease. Primary sites were discovered in all 3 patients who underwent autopsy examination. Two tumors arose in the heart and 1 in the pelvic soft tissues. One additional patient had a likely primary site identified in the right atrium by cardiac ultrasound and was subsequently lost to follow-up.

Conclusion.—Angiosarcoma should be included in the differential diagnosis of diffuse pulmonary hemorrhage, especially in young adults.
Sialadenoma Papilliferum of the Hard Palate
Authors: Ubaidat Manaf A. , Robinson Robert A. , Belding Paul J. , Merryman Don J.
Published: January 2021

This study reports on the clinical and histologic features of 2 previously unreported cases of sialadenoma papilliferum. Immunohistochemical analysis of one of the cases demonstrated that the ductal cell component shows both epithelial and myoepithelial differentiation.
Pulmonary Adenocarcinoma Simulating Malignant Mesothelioma
Authors: Tang Ping , Vatsia Sheel K. , Teichberg Saul , Kahn Ellen
Published: January 2021

Adenocarcinoma of the lung with pleural involvement frequently resembles pleural epithelioid mesothelioma clinically as well as macro- and microscopically. Special stains, immunohistochemical studies, and electron microscopic studies are needed to differentiate these 2 tumors. We report a case of pleural involvement by adenocarcinoma, mimicking in the hematoxylin-eosin stain an epithelioid mesothelioma, correctly identified only after immunohistochemical and electron microscopic examinations.
Coincident Choroid Plexus Carcinoma and Adrenocortical Carcinoma With Elevated p53 Expression
Authors: Wang Lina , Cornford Marcia E.
Published: January 2021

We describe a young patient with no known family history of cancer who presented at 18 months with 2 advanced primary tumors, choroid plexus carcinoma and adrenal cortical carcinoma. Immunohistochemical studies demonstrated high levels of nuclear p53 protein expression in both tumors, as well as in the adjacent normal-appearing adrenal cortical cell nuclei of the adrenal gland. The immunohistologic distribution of elevated p53 expression suggests that this individual has a de novo germline mutation affecting p53 gene expression.
Bilateral Paget Disease of the Nipple Associated With Lobular Carcinoma In Situ
Authors: Sahoo Sunati , Green Ileana , Rosen Paul P.
Published: January 2021

We report synchronous bilateral Paget disease derived from lobular carcinoma in situ in a 53-year-old woman who underwent bilateral mastectomy. The epidermis of both nipples contained small cells with a moderate amount of pale-staining cytoplasm. The nuclei had fine chromatin and identifiable nucleoli. The cells were strongly immunoreactive with cytokeratin 7 and displayed nuclear estrogen receptor reactivity. The underlying mammary gland showed involvement by lobular carcinoma in situ with pagetoid spread into lactiferous ducts, which was confirmed by lack of immunoreactivity for E-cadherin.
A103 Immunostaining in the Diagnosis of Adrenal Cortical Tumors
Authors: Loy Timothy S. , Phillips Roy W. , Linder Chadwick L.
Published: January 2021

Context.—The monoclonal antibody A103 recognizes an antigen on melanoma cells known as Melan-A or MART-1. Recent studies have shown that A103 also reacts with adrenal cortical cells and may be useful in the diagnosis of adrenal cortical tumors. However, only small numbers of some of the tumors in the differential diagnosis of adrenal cortical neoplasms have been studied.

Objective.—To study the specificity of A103 immunohistochemistry in a large number of tumors in the differential diagnosis of adrenal cortical neoplasms.

Design.—Formalin-fixed, paraffin-embedded tissue from 21 adrenal cortical tumors, 16 cases of metastatic carcinoma to the adrenal, 10 pheochromocytomas, and 269 extra-adrenal carcinomas was evaluated for A103 immunoreactivity using a commercially available antibody (Novocastra, Newcastle, UK).

Results.—Positive staining was seen in all of the adrenal cortical tumors but in none of the adrenal metastases or pheochromocytomas. In the 269 extra-adrenal carcinomas, A103 immunoreactivity was limited to a single ovarian serous carcinoma.

Conclusion.—A103 immunostaining is useful in distinguishing adrenal cortical neoplasms from other carcinomas and pheochromocytoma.
Detection of Microsatellite Instability From Archival, Hematoxylin-Eosin–Stained Colorectal Cancer Specimen
Authors: Trojan Joerg , Raedle Jochen , Herrmann Guenter , Brieger Angela , Zeuzem Stefan
Published: January 2021

Microsatellite instability (MSI) is characteristic of hereditary nonpolyposis colorectal cancer (HNPCC). Owing to early onset of colorectal cancer before the age of 50 years and/or familial clustering of HNPCC-related malignancies, the diagnosis of HNPCC was suspected in 2 patients. Because no paraffin-embedded tumor tissue was available, we used archival 5-μm, hematoxylin-eosin–stained tumor specimen slides for direct MSI analysis. Tissue was microdissected and cells were lysed using 1% Triton. Fluorescence polymerase chain reaction amplification of a panel of 7 microsatellite markers, including all markers of the current international reference panel (BAT-25, BAT-26, D2S123, D5S346, and D17S250), demonstrated MSI in one patient and excluded MSI in the other. In conclusion, this study demonstrates the feasibility of MSI analysis by direct fluorescence polymerase chain reaction amplification using hematoxylin-eosin–stained tissue specimens without the need for prior DNA extraction.
Cholesterol Granuloma of the Maxillary Sinus
Authors: Leon Marino E. , Chavez Carlos , Fyfe Billie , Nagorsky Matthew J. , Garcia Fernando U.
Published: January 2021

Cholesterol granuloma is usually associated with chronic middle ear disease and is common in the mastoid antrum and air cells of the temporal bone. It has also been reported in other parts of the skull, such as the frontal and maxillary sinuses and orbit. Cholesterol granuloma is rare in the paranasal sinuses. We report a new case of cholesterol granuloma in the maxillary sinus of a 38-year-old man who underwent surgical excision. We also review the literature and discuss the mechanism of development for this lesion. The resected specimen showed fragments of respiratory mucosa with cholesterol clefts surrounded by multinucleated foreign-body giant cells. Some multinucleated foreign-body giant cells showed asteroid bodies. Hemorrhagic areas, hemosiderin-laden macrophages, chronic inflammatory cells, and dilated lymphatics vessels were seen as well. Increased intrasinus pressure due to drainage obstruction may affect venous and lymphatic drainage from the sinus cavity, leading to venule microhemorrhages while still allowing arterial blood into the sinus mucosa and further contributing to a large localized hemorrhage. Lymphatic drainage may be insufficient to completely remove the lipid components of the red blood cells, and the lipid accumulation may contribute to the formation of cholesterol crystals and their esters.
Glial Cell–Derived Neurotrophic Factor Expression in Normal Human Lung and Congenital Cystic Adenomatoid Malformation
Authors: Fromont-Hankard Gaelle , Philippe-Chomette Pascale , Delezoide Anne-Lise , Nessmann Catherine , Aigrain Yves , Peuchmaur Michel
Published: January 2021

Context.—It has been recently suggested that dysregulation of developmental factors and disruption of cell turnover could play a role in the pathogenesis of congenital cystic adenomatoid malformation of the lung (CCAM). The glial cell–derived neurotrophic factor (GDNF) is a growth factor involved in organogenesis, and the temporal pattern of GDNF expression suggests that this factor may play a role in lung development.

Design.—We studied GDNF expression by immunohistochemistry in postnatally resected CCAM of the lung (n = 10), normal fetal lung (n = 5), and normal postnatal lung (n = 5). We also studied the association between GDNF expression and both cell proliferation and apoptosis.

Results.—GDNF was expressed in both epithelial and endothelial compartments of normal fetal lung, whereas no expression was found in normal postnatal lung. In contrast, in CCAM tissue, there was strong GDNF immunostaining that was restricted to epithelial cells. The percentage of proliferating epithelial cells was higher in CCAM tissue than in normal postnatal lung (6.3% vs 1.7%, P < .005). Apoptotic bodies were found in the mesenchyme of both normal fetal lung and CCAM tissue, whereas virtually no apoptotic bodies were detected in normal postnatal lung.

Conclusions.—Abnormal GDNF expression in CCAM suggests a dysregulation of the GDNF signaling pathway and argues in favor of a focal arrest in maturation during development. GDNF expression in lung tissue seems to be correlated with cell proliferation, suggesting that this factor could play a role in the growth of both fetal lung and CCAM.
Clonality of Combined Tumors
Authors: Huang Jiaoti , Behrens Carmen , Wistuba Ignacio I. , Gazdar Adi F. , Jagirdar Jaishree
Published: January 2021

Context.—Tumors with mixed morphologic patterns (combined tumors) are sometimes encountered, and questions often arise regarding the mechanism of molecular pathogenesis of each component and their relationships.

Objective.—To determine whether different components of combined tumors contain the same or different genetic alterations, thus providing evidence for their clonality.

Materials and Methods.—Six combined tumors with 2 components (in each case, both components showed epithelial differentiation morphologically) were studied by microdissecting tumor cells from each morphologic area followed by loss of heterozygosity analysis.

Results.—In 1 of the cases studied, the different morphologic areas contained different patterns of genetic alterations. In the remaining 5 cases, the different morphologic areas harbored identical genetic changes in the chromosome regions studied. The latter group, interestingly, included a colonic tumor with an area of tubulovillous adenoma and an area of neuroendocrine carcinoma, and 2 lung tumors with squamous carcinoma and small cell carcinoma components.

Conclusions.—Our results suggest that in the majority of combined tumors, cells with different phenotypes share similar genotype and may arise from a single precursor cell. However, in a minority of these tumors, different areas may be derived from different precursor cells.
Expression of Cyclin D1 in Normal, Metaplastic, Hyperplastic Endometrium and Endometrioid Carcinoma Suggests a Role in Endometrial Carcinogenesis
Authors: Quddus M. Ruhul , Latkovich Predrag , Castellani William J. , Sung C. James , Steinhoff Margaret M. , Briggs Robert C. , Miranda Roberto N.
Published: January 2021

Context.—Endometrioid carcinoma is often preceded by characteristic histopathologic lesions known as endometrial hyperplasia. Estrogen appears to be involved in the development of endometrioid carcinoma. Other mechanisms of endometrial carcinogenesis include mutations in p53 and PTEN tumor suppressor genes and overexpression of cyclin D1. However, the pattern of cyclin D1 expression is not well defined in normal, hyperplastic, neoplastic, and metaplastic endometrium.

Design.—Cyclin D1 immunohistochemical analysis was used to evaluate 108 fixed, paraffin-embedded endometrial biopsy specimens and uterine resections obtained from 108 patients. Specimens included proliferative and secretory endometria, simple and complex hyperplastic lesions, and endometrioid adenocarcinoma. Normal and metaplastic surface epithelia were also evaluated independently of glandular morphologic features.

Results.—Cyclin D1 was significantly overexpressed in glands with complex hyperplasia and endometrioid adenocarcinoma compared with proliferative or secretory endometrium and simple hyperplasia. Significant overexpression was also noted in papillary, syncytial, and squamous metaplasias compared with normal surface epithelium or epithelium with tubal metaplasia.

Conclusion.—Overexpression of cyclin D1 increases from normal endometrium to hyperplasia and carcinoma, suggesting that it may play a role in endometrial carcinogenesis. Overexpression of cyclin D1 in endometrial glands was independent from overexpression of cyclin D1 in surface metaplastic epithelium.
American Cutaneous Leishmaniasis
Authors: Royer Michael , Crowe Mark
Published: January 2021

We present 3 cases of American cutaneous leishmaniasis occurring in soldiers of a unit of US Army Rangers who parachuted into the jungles of Panama. Shortly after returning to the United States, these 3 soldiers each developed a crusted, indurated papule, which slowly enlarged during the following 6 weeks. Routine microscopy of skin biopsies revealed a dermal granulomatous inflammation and a predominantly lymphoid infiltrate. Numerous histiocytes contained small oval organisms with bar-shaped paranuclear kinetoplasts, morphologically consistent with leishmanial parasites. Cultures grew Leishmaniasis brasiliensis, subspecies panamensis. The soldiers were treated with intravenous pentavalent antimonial therapy daily for 20 days with good clinical improvement. Epidemics of leishmaniasis occur periodically in tropical regions of the world, and leishmaniasis has emerged in new settings, for example, as an acquired immunodeficiency syndrome–associated opportunistic infection. With an increasingly mobile society, it is important to be familiar with the clinical and histopathologic appearance of conditions such as leishmaniasis, which are common in tropical and subtropical regions and are increasingly significant in other regions of the world.
Pulmonary Abscesses in Congenital Syphilis
Authors: Bell Carrie , Taxy Jerome
Published: January 2021

Congenital syphilis remains a public health concern in the United States. Infants whose mothers are treated in the third trimester without adequate prenatal care have an increased risk of morbidity and mortality in the immediate perinatal period. The identification of Treponema pallidum in tissue is definitive confirmation of infection. We report the case of a 32-week gestational age infant born to a mother treated for syphilis 7 days prior to delivery. The infant died 12.5 hours after birth. At autopsy, there was extensive acute hyaline membrane disease. In addition, there were bilateral pulmonary abscesses with spirochetes. The onset of maternal disease was unknown, but was probably early in or prior to the pregnancy. This is an unusual case of pulmonary involvement in congenital syphilis.
Lack of HER-2/neuExpression in Hodgkin and Non-Hodgkin Lymphoma
Authors: Bairey Osnat , Pazgal Idit , Okon Elimelech , Shaklai Matityahu , Morgenshtern Sarah
Published: January 2021

Objective.—Overexpression of HER-2/neu oncoprotein, a tyrosine kinase receptor, occurs in a variety of human cancers and has been shown to play a critical role in their development. This overexpression is usually associated with poor clinical outcome. The significance of HER-2/neu in lymphomas is unknown. The aim of this study was to evaluate the expression of HER-2/neu in the malignant lymphomas: non-Hodgkin and Hodgkin lymphomas.

Methods.—We studied formalin-fixed, paraffin-embedded tissue from 50 patients with lymphoma. Forty-two specimens were from patients with various types of non-Hodgkin lymphoma, and 8 were from patients with Hodgkin lymphoma. HER-2/neu expression was examined by an immunohistochemical technique using the HercepTest.

Results.—None of the specimens demonstrated overexpression or even any expression of HER-2/neu. Reactive plasma cells showed cytoplasmic staining, which was not found in malignant plasma cells from patients with multiple myeloma.

Conclusions.—Non-Hodgkin and Hodgkin lymphomas do not express the HER-2/neu oncoprotein. This finding suggests that HER-2/neu does not play a role in these diseases.
Continuous-Specimen-Flow, High-Throughput, 1-Hour Tissue Processing
Authors: Morales Azorides R. , Essenfeld Harold , Essenfeld Ervin , Duboue Maria Carmen , Vincek Vladimir , Nadji Mehrdad
Published: January 2021

Context.—Current conventional tissue-processing methods employ fixation of tissues with neutral buffered formalin, dehydration with alcohol, and clearing with xylene before paraffin impregnation. Because the time required for this procedure is usually 8 hours or longer, it is customary to process tissues in automated instruments throughout the night. Although this time-honored method continues to serve histology laboratories well, it has a number of shortcomings, such as a 1-day delay of diagnosis, the need to batch specimens, the relatively large volumes and toxicity of reagents used, and the extent of RNA degradation.

Objective.—To describe a rapid new method of tissue processing using a continuous-throughput technique.

Design.—We used a combination of common histologic reagents, excluding formalin and xylene, as well as microwave energy, to develop a rapid processing method. The effect of this method on the quality of histomorphology, histochemistry, immunohistochemistry, and RNA content of processed tissue was compared with that of adjacent tissue sections processed by the conventional processing technique. We also assessed the impact of this rapid processing system on our practice by comparing the turnaround times of surgical pathology reports before and after its implementation.

Results.—The new processing method permitted preparation of paraffin blocks from fresh or prefixed tissue in about 1 hour. The procedure allowed continuous flow of specimens at 15-minute intervals. It eliminated the use of formalin and xylene in the processing and used considerably lower volumes of other chemical reagents. Histomorphologic, histochemical, and immunohistochemical results were comparable to the parallel sections prepared by the conventional method. The new technique, however, preserved higher quality RNA. Use of the new methodology led to the diagnosis and reporting of more than one third of surgical pathology specimens on the same day that they were received, as compared to 1% of same-day reporting before the implementation of the rapid processing system.

Conclusion.—The quality of hematoxylin-eosin, histochemical, and immunohistochemical tissue sections provided by the new system is comparable to that obtained following the conventional processing method. The new system preserves RNA better than the conventional method. It also shortens the processing time to about 1 hour from the receipt of fresh or prefixed tissue, eliminates the need for formalin and xylene, and reduces the volume of other chemicals. Most importantly, it impacts overall patient management by allowing for considerably shorter turnaround times for completion of surgical pathology reports.
Excisional Biopsy Should Be Performed if Lobular Carcinoma In Situ Is Seen on Needle Core Biopsy
Authors: Shin Sandra J. , Rosen Paul Peter
Published: January 2021

Context.—Percutaneous image-guided core biopsy is increasingly becoming the method of choice to evaluate impalpable breast lesions presenting with mammographically detected calcifications or as a mammographically detected mass. Infrequently, a diagnosis of a primary lobular lesion is rendered by needle core biopsy. Although lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH) are not themselves detectable by mammography, they can be associated with calcifications. The management of patients with a primary diagnosis of LCIS or ALH on needle core biopsy is uncertain. Recommendations include excisional biopsy, tamoxifen citrate therapy, mammographic surveillance, or a combination of these approaches.

Objective.—The purpose of this study was to report the histologic findings of excisional biopsies performed after ALH or LCIS was found in a needle core biopsy.

Design.—Hematoxylin-eosin–stained slides of 20 needle core biopsy specimens from patients with a primary diagnosis of LCIS or ALH were retrieved from the consultation and surgical pathology files of New York Presbyterian Hospital–Weill Medical College of Cornell University. Histologic diagnoses were confirmed in all cases.

Results.—Fourteen cases of primary LCIS and 6 cases of ALH found on needle core biopsy were identified. Subsequent excisional biopsy of the 14 LCIS cases revealed the following: LCIS, ductal carcinoma in situ, invasive carcinoma (1 patient; 7%); LCIS, infiltrating lobular carcinoma (1 patient; 7%); LCIS, ductal carcinoma in situ (1 patient; 7%); LCIS (8 patients; 57%); and ALH with or without atypical ductal hyperplasia (3 patients; 21%). Among the 6 patients with ALH on needle core biopsy, 1 had infiltrating lobular carcinoma and LCIS and 2 had LCIS in subsequent excision; other excisions for ALH were benign. Overall, 3 (21%) of 14 patients with a primary diagnosis of LCIS on needle core biopsy had a more significant lesion (ductal carcinoma in situ or invasive carcinoma) in a subsequent excisional biopsy.

Conclusions.—Data obtained in this study and in previously published reports lead us to conclude that excisional biopsy may be indicated and should be considered when LCIS is found on needle core biopsy in order to more fully examine the biopsy site for coexistent, clinically inapparent intraductal or invasive carcinoma that may be present in about 25% of these patients. The small number of ALH cases studied produced inconclusive results. We recommend that excisional biopsy be considered if atypical ductal hyperplasia is present with ALH in a needle core biopsy or if the diagnosis of the biopsy specimen is discordant with the mammographic findings.
Tyrosinase Expression in Malignant Melanoma, Desmoplastic Melanoma, and Peripheral Nerve Tumors
Authors: Boyle Jenny L. , Haupt Helen M. , Stern Jere B. , Multhaupt Hinke A. B.
Published: January 2021

Context.—Pathologists may encounter problems in the differential diagnosis of malignant melanoma, spindle and epithelioid neoplasms of peripheral nerves, and fibrohistiocytic tumors. Tyrosinase has been demonstrated to be a sensitive marker for melanoma.

Objective.—To determine the specificity of tyrosinase expression in the differential diagnosis of melanoma, desmoplastic melanoma, and peripheral nerve sheath tumors.

Design.—Immunoreactivity for tyrosinase, HMB-45 (anti-gp100 protein), S100 protein, CD34, and vimentin was studied in 70 tumors, including 15 melanomas (5 desmoplastic, 4 amelanotic, 6 melanotic), 13 malignant peripheral nerve sheath tumors; 10 schwannomas (1 pigmented), 12 neurofibromas (4 pigmented), and 20 fibrohistiocytic tumors (10 dermatofibrosarcoma protuberans and 10 dermatofibromas). Microwave-based antigen retrieval was performed in 10mM citrate buffer, pH 6.0, for 20 minutes at 121°C.

Results.—All melanomas demonstrated positive immunostaining for tyrosinase, HMB-45, and S100 protein. Immunoreactivity for HMB-45 was generally stronger than that for tyrosinase in amelanotic lesions and significantly stronger in 1 of the desmoplastic lesions. The 4 pigmented neurofibromas were focally positive for tyrosinase, but did not stain for HMB-45. The pigmented schwannoma was focally positive for both tyrosinase and HMB-45. The malignant peripheral nerve sheath tumors, dermatofibrosarcoma protuberans, and dermatofibromas were nonreactive for tyrosinase and HMB-45.

Conclusions.—Our results support the sensitivity of tyrosinase expression and demonstrate the relative specificity of tyrosinase as a marker for melanocytic lesions, including desmoplastic melanoma, although pigmented peripheral nerve tumors may demonstrate focal positive staining. Immunoreactivity for tyrosinase and HMB-45 may have been enhanced by the microwave-based antigen-retrieval technique used in this study.
Immunohistochemical Study of Myofibroblasts in Normal Colonic Mucosa, Hyperplastic Polyps, and Adenomatous Colorectal Polyps
Authors: Adegboyega Patrick A. , Mifflin Randy C. , DiMari John F. , Saada Jamal I. , Powell Don W.
Published: January 2021

Context.—Myofibroblasts are distinct cells with characteristics of both smooth muscle cells and fibroblasts. Through their ability to secrete cytokines, chemokines, prostaglandins, growth factors, and matrix components, they are thought to play critical roles in inflammation, growth, repair, and neoplasia.

Objective.—The goal of this study was to identify the distinct cell populations of the lamina propria of normal colon and colorectal polyps.

Design.—We studied the expression of α-smooth muscle actin (αSMA), smooth muscle myosin (SMM), desmin, vimentin, and c-kit by intestinal mesenchymal (stromal) cells in the normal colonic mucosa (n = 5), as well as in hyperplastic polyps (n = 5), sporadic colorectal adenomas (n = 47), and adenomas from patients with familial polyposis (n = 36).

Results.—In the normal colonic mucosa, the pericryptal stromal cells were αSMA+, SMM+, desmin−, and vimentin+, defining them as myofibroblasts. In contrast, cells of the muscularis mucosae were αSMA+, SMM+, desmin+, and vimentin−, defining them as smooth muscle cells. α-Smooth muscle actin also highlighted direct connections between the muscularis mucosae and the pericryptal myofibroblasts, and vimentin immunostaining showed a network of connections between the αSMA+ pericryptal myofibroblasts and the αSMA− fibroblasts in the interstitium. In all hyperplastic polyps and adenomatous polyps, the interstitial stromal cells (fibroblasts) now also express αSMA and form a syncytium of αSMA+ networklike connections throughout the lamina propria. Stromal cells of sporadic adenomas demonstrated the same immunohistochemical staining characteristics displayed by adenomas from patients with familial polyposis and by hyperplastic polyps.

Conclusions.—These findings indicate that in normal colon, αSMA− fibroblasts are the predominant cell type in the lamina propria. However, the pericryptal (subepithelial) stromal cells are a distinct cell type (αSMA+ myofibroblast) that is immunophenotypically different from muscularis mucosae smooth muscle cells and are connected to the interstitial, nonpericryptal fibroblasts with which they exist as a network throughout the lamina propria of the normal colon. Furthermore, in both hyperplastic and neoplastic polyps, there are changes in nonpericryptal fibroblasts from vimentin+, αSMA−, and SMM− to vimentin+, αSMA+, and SMM+; thus, the interstitial fibroblasts are replaced by myofibroblasts. The factors that cause these changes and the origin of the myofibroblasts need to be determined to clarify the biology of colorectal tumorigenesis.
Undifferentiated Sarcoma of the Parotid Gland With Osseous Metaplasia
Authors: Wajstaub Sandra , Deb Pratima , Chorneyko Katherine A.
Published: January 2021

Malignant spindle cell tumors of the parotid gland are a diagnostic challenge. We present an unusual case of such a tumor that occurred in the right parotid gland of a 53-year-old man. The clinical and histologic assessments were consistent with a primary sarcoma of the parotid gland. The tumor was composed of sheets of pleomorphic, spindle-shaped cells with an area of bone formation. By immunohistochemistry, the tumor cells were positive for vimentin and negative for epithelial markers. Electron microscopy revealed mesenchymal cells containing moderate amounts of rough endoplasmic reticulum. The major differential diagnostic considerations were spindle cell carcinoma, carcinosarcoma, and primary undifferentiated sarcoma with osseous metaplasia. The lack of epithelial features and the benign appearance of the bone formation led to a diagnosis of undifferentiated sarcoma of the parotid gland.
Altered Distribution of Interstitial Cells of Cajal in Hirschsprung Disease
Authors: Rolle Udo , Piotrowska Anna Piaseczna , Nemeth Laszlo , Puri Prem
Published: January 2021

Context.—Constipation or recurrent intestinal dysmotility problems are common after definitive surgical treatment in Hirschsprung disease (HD). c-Kit–positive interstitial cells of Cajal (ICCs) play a key role in the motility function and development of the gastrointestinal tract. Interstitial cells of Cajal that carry the tyrosine kinase receptor (c-Kit) develop as either myenteric ICCs or muscular ICCs under the influence of the kit ligand, which can be provided by neuronal and nonneuronal cells, for example, smooth muscle cells.

Objective.—To investigate the distribution of myenteric and muscular ICCs in different parts of the colon in HD.

Methods.—Resected bowel specimens from 8 patients with rectosigmoid HD were investigated using combined staining with c-Kit enzyme and fluorescence immunohistochemistry and acetylcholinesterase and nicotinamide adenine dinucleotide phosphate (NADPH) histochemistry in whole-mount preparations and conventional frozen sections.

Results.—In the normal bowel, ICCs formed a dense network surrounding the myenteric plexus and at the innermost part of the circular muscle. Myenteric ICCs were absent or sparse in the aganglionic bowel and sparse in the transitional zone. The expression of myenteric ICCs in the ganglionic bowel in HD was reduced compared to that in the normal bowel, and they formed only sparse networks. Muscular ICCs were found in the aganglionic bowel, transitional zone, and normoganglionic bowel of HD in a reduced density compared to the normal bowel.

Conclusion.—This study demonstrates altered distribution of ICCs in the entire resected bowel of HD patients. This finding suggests that persistent dysmotility problems after pull-through operation in HD may be due to altered distribution and impaired function of ICCs.
Prevalence of the 20210 G→A Prothrombin Variant and Its Association With Coronary Artery Disease in a Middle Eastern Arab Population
Authors: Abu-Amero Khaled K. , Wyngaard Carol A. , Kambouris Marios , Dzimiri Nduna
Published: January 2021

Background.—No reports are available on the distribution of the 20210 G→A prothrombin variant among Middle Eastern Arabs. Additionally, to date, studies that attempt to establish this polymorphism as an independent risk factor or as a predictor for coronary artery disease (CAD) have yielded conflicting results.

Objective.—To determine the prevalence of the 20210 G→A prothrombin variant among Middle Eastern Arabs and to evaluate the potential relevance of this variant to Arab patients with angiographically documented CAD.

Methods and Results.—We used the polymerase chain reaction and restriction enzyme digestion to determine the prevalence of this polymorphism in 613 individuals from Arabic ethnic origin with CAD and from 593 healthy blood donors (BDs) from an identical ethnic background. Within the BD group (n = 593), 10 individuals (1.7%) were heterozygous, 583 individuals (98.3%) were normal, and none were homozygous for the 20210 G→A prothrombin variant. Within the CAD group (n = 613), 13 individuals (2.1%) were heterozygous, 600 individuals (97.9%) were normal, and none were homozygous for the 20210 G→A prothrombin variant. A χ2 analysis was used to evaluate any significance in the distribution of genotypes. A value of 1.23 was obtained. Values less than 3.84 indicate no statistically significant difference between the heterozygous carriers of the 20210A allele in both study groups.

Conclusion.—In our population of Middle Eastern Arabs, the presence of the 20210 G→A prothrombin variant is not associated with patients with angiographically documented CAD. Therefore, this variant cannot be considered as an independent risk factor or as a predictor for CAD in this population.