bluuebunny/crossref_metadata_2025 huggingface dataset:
Malignant Melanoma Presenting as an Intrathymic Tumor
Authors: Alli P. M. , Crain B. J. , Heitmiller R. , Argani P.
Published: January 2021

The identification of malignant melanoma in a visceral organ of nonepidermal origin is not an uncommon occurrence. Frequently, these cases are solitary metastases that present years after a thin epidermal melanoma has been diagnosed (and sometimes forgotten). However, primary visceral melanomas have been reported that have not been preceded by an epidermal lesion. We describe herein a unique case of melanoma presenting as a primary intrathymic tumor. The patient had no previous history of epidermal melanoma, and extensive workup did not reveal evidence for an alternative primary site. The tumor exhibited histologic features characteristic of melanoma, including an abundance of large pleomorphic cells with eosinophilic cytoplasm, prominent nucleoli, and occasional intranuclear inclusions. Tumor cells stained for HMB-45 and S-100 protein and ultrastructural analysis revealed stage II and stage III melanosomes. The patient remained free of disease until intrathoracic recurrence was detected on a computed tomographic scan 14 months later. The lack of clinical history and physical findings of melanoma at presentation, the intrathymic location of the tumor, and the pattern of recurrence suggest that this case likely represents a primary thymic melanoma, a previously unreported entity.
Pleomorphic Giant Cell Carcinoma of the Esophagus With Coexpression of Cytokeratin and Vimentin and Neuroendocrine Differentiation
Authors: Mosnier Jean-Francois , Balique Jean-Gabriel
Published: January 2021

A pleomorphic (giant cell) carcinoma of the esophagus is reported in a 52-year-old man who had dysphagia and weakness. The 8-cm-high vegetating tumor consisted of solid sheets of poorly cohesive epithelioid cells broken into clusters by strands of stroma. Numerous giant cells showing phagocytic phenomenon were present. Immunochemical analyses demonstrated the epithelial origin of the neoplasm, although most of the tumor cells strongly expressed vimentin. Numerous tumor cells expressed synaptophysin. Neurosecretory granules were detected in some tumor cells on electron microscopic examination. The patient died 4 months after he became symptomatic. As far as we can ascertain, this is the first case report describing a pleomorphic carcinoma arising in the esophagus. This poorly differentiated carcinoma might be of neuroendocrine differentiation. In the esophagus, pleomorphic carcinoma must be distinguished from polypoid tumors such as carcinosarcoma and malignant melanoma.
Diagnosis of Papillary Carcinoma in a Thyroglossal Duct Cyst by Fine-Needle Aspiration Biopsy
Authors: Yang Yi Jun , Haghir Shahandeh , Wanamaker John R. , Powers Celeste N.
Published: January 2021

The incidence of papillary thyroid carcinoma arising in a thyroglossal duct cyst is rare and occurs in about 1% of thyroglossal duct cysts. Only 17 such cases diagnosed with fine-needle aspiration biopsy have been previously reported in the English-language literature, with a diagnostic rate of 53%. In this article, the cytologic features of the current case are emphasized and those of the previous reported cases are briefly reviewed. Diagnostic pitfalls of papillary carcinoma arising in thyroglossal duct cysts diagnosed by fine-needle aspiration biopsy are also discussed.
Lobular Carcinoma of the Breast Metastatic to the Oral Cavity Mimicking Polymorphous Low-Grade Adenocarcinoma of the Minor Salivary Glands
Authors: Nicol Kathleen K. , Iskandar Samy S.
Published: January 2021

The oral cavity is a rare site of metastatic lesions; however, metastatic breast carcinoma must be included in the differential diagnosis of tumors of that site in women. We describe a 54-year-old woman who presented with a lesion of the floor of the mouth that histologically resembled polymorphous low-grade adenocarcinoma of the minor salivary glands, which was eventually established to represent metastatic lobular breast carcinoma. The final diagnosis was based on comparison with a primary tumor resected 13 years earlier and immunohistochemical reactivity with antibodies to steroid receptors. Relevant aspects of lobular breast carcinoma, polymorphous low-grade adenocarcinoma, and metastatic oral cavity lesions are discussed.
Esophageal Small Cell Carcinomas
Authors: Lam King Y. , Law Simon , Tung Peter H. M. , Wong John
Published: January 2021

Objective.—To evaluate the clinicopathologic features and the roles of p53 and MIB-1 in esophageal small cell carcinoma.

Method.—Twenty patients (14 men and 6 women) with esophageal small cell carcinoma treated in our hospital from 1982 through 1996 were studied. The clinicopathologic features, treatment received, and survival data of these patients were documented. Representative tissue was collected from each tumor, and immunohistochemical preparations for p53 protein and MIB-1 were made.

Results.—Small cell carcinoma accounted for 1.3% of all esophageal malignant tumors. The median age of patients at presentation was 60 years. On gross examination, the tumors were large ulcerative lesions (median length, 7.5 cm). In 17 patients in whom p53 immunohistochemical study was performed, p53 protein was detected in 65% (9 of 17). All stage IV tumors were negative for p53 expression. The median tumor cell MIB-1 score was high at 855 (range, 810–964) positive cells per 1000. Overall median survival was 3.4 months. In patients who underwent chemotherapy, there was significant response.

Conclusions.—Esophageal small cell carcinoma is an aggressive tumor. Overexpression of p53 is associated with early stages of carcinogenesis. The high proliferative index, as defined by the MIB-1 immunohistochemical method, may be related to aggressive behavior and high sensitivity to chemotherapy and radiotherapy.
Optic Nerve Damage in Shaken Baby Syndrome
Authors: Gleckman Aaron M. , Evans Richard J. , Bell Michael D. , Smith Thomas W.
Published: January 2021

Background.—Rapid acceleration-deceleration of an infant's head during intentional shaking should in theory exert stretch or shear forces upon the optic nerves sufficient to cause axonal injury. β-Amyloid precursor protein (β-APP) immunohistochemistry recently has been shown to be a highly effective method for identifying diffuse axonal injury in the brains of infants with shaken baby syndrome. In this study, we investigated the utility of β-APP in identifying optic nerve damage in infants who have sustained fatal whiplash shaking.

Materials and Methods.—β-Amyloid precursor protein immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections of eyes (including optic disc and distal optic nerve) from infants less than 1 year of age with shaken baby syndrome (5 cases), combined shaken baby syndrome/blunt head trauma (3 cases), and “pure” blunt head trauma (1 case). Nontraumatic control cases included infants who died of suffocation (1 case), sudden infant death syndrome (1 case), and positional asphyxia (1 case) and an enucleation from a child with a retinoblastoma (1 case). Matched hematoxylin-eosin–and neurofilament-stained sections were used for comparison.

Results.—Three of the 5 shaken baby cases and all 3 combined shaken baby/blunt head trauma cases had optic nerve axonal injury identified by the presence of strongly β-APP–immunoreactive beaded or swollen axonal segments. Axonal injury could not be detected in the corresponding hematoxylin-eosin–or neurofilament-stained sections. Optic nerve axonal injury was not seen in the case involving pure blunt head trauma or in the nontraumatic control cases.

Conclusions.—Optic nerve axonal injury is a prominent feature of intentional fatal whiplash head trauma in infants less than 1 year of age. β-Amyloid protein precursor immunohistochemistry appears to be the most effective method for demonstrating axonal damage in the optic nerve.
Fibromatosis of the Breast
Authors: Devouassoux-Shisheboran Mojgan , Schammel David P. , Man Yan-Gao , Tavassoli Fattaneh A.
Published: January 2021

Objective.—To predict if antiestrogenic agents are useful in the treatment of breast fibromatoses, we undertook an immunohistochemical study of sex steroid hormone receptors (estrogen receptor, progesterone receptor, and androgen receptor) and protein pS2 in 33 cases.

Methods.—The morphologic and immunohistochemical findings were correlated to patient menstrual status, which was categorized as childbearing age (n = 15), perimenopausal (n = 8), and postmenopausal (n = 10).

Results.—Fibromatoses in women of childbearing age were more cellular, more mitotically active, and displayed a larger proportion of cells with mild atypia than those in perimenopausal and postmenopausal women. The hormonal status of these 3 groups does not explain the morphologic variations observed in these groups, inasmuch as no immunostaining for any of the hormone receptors was detected in the tumors.

Conclusions.—The absence of estrogen receptor and pS2 in breast fibromatoses suggests that antiestrogenic agents are unlikely to be beneficial in the management of these tumors. Assessment of the hormone receptor profile is a useful adjunct in the diagnosis of spindle cell lesions of the breast. Although most spindle cell carcinomas as well as fibromatoses of the breast do not express estrogen or progesterone receptors, the absence of androgen receptor reactivity would favor a diagnosis of fibromatosis over that of myofibroblastoma.
Amyloid Goiter With Parathyroid Involvement
Authors: Villamil C. F. , Massimi G. , D'Avella J. , Cole S. R.
Published: January 2021

Although involvement of the thyroid gland by amyloid is a relatively common phenomenon, diffuse enlargement of the gland secondary to infiltration by amyloid is infrequent. We report the pathologic findings in a case of primary amyloid goiter with involvement of a parathyroid gland in an euthyroid patient who presented to his physician with an enlarged thyroid, upper airway obstructive symptoms, and dysphagia. The clinical features of amyloid goiter, including difficulties in preoperative diagnosis and management, are discussed.
A Mouse Model of Aerosol-Transmitted Orthopoxviral Disease
Authors: Martinez Mark J. , Bray Michael P. , Huggins John W.
Published: January 2021

Objectives.—To determine the morphologic changes and disease progression of aerosolized cowpox virus infection in BALB/c mice and to ascertain the suitability of cowpox virus–infected BALB/c mice as a model of aerosol-transmitted, orthopoxviral respiratory disease.

Methods.—BALB/c mice were inoculated with cowpox virus, Brighton strain, by aerosol or intranasal route. Mice were killed at specified times after inoculation, necropsied, and tissues were collected for routine histology, immunohistochemistry, and electron microscopy.

Results.—Inoculation by both routes resulted in disease and death. Immunolabeled viral antigen and lesions predominated in the tissues associated with the inoculation route, that is, lungs, airways, trachea, and nasal passages and sinuses. Tracheitis was evident in the intranasally infected group only. Lesions were generally necrotizing and hemorrhagic, neutrophilic, and increased in extent and severity in a time-dependent fashion. Viral intracytoplasmic inclusion bodies, immunolabeled viral antigen, or virions were readily seen in epithelial tissues, smooth muscle cells of airways and vessels, fibroblasts, periosteal cells, perineural cells, and macrophages. Although the extension of infection appeared to be primarily direct, lesions suggesting hematogenous dissemination were occasionally noted in bone marrow and skin. Transmission electron microscopy demonstrated features of cell injury or death, virion assembly and maturation, and both A-type and B-type inclusions.

Conclusions.—Aerosol inoculation of BALB/c mice with cowpox virus provides a reliable and facilitative model of aerosol-transmitted, orthopoxviral respiratory disease.
Clinical Usefulness of Telomerase Assay for the Detection of Lymph Node Metastasis in Patients With Oral Malignancy
Authors: Sumida Tomoki , Hamakawa Hiroyuki , Kayahara Hiroaki , Zen Hirofumi , Sogawa Kenichi , Tanioka Hiroaki , Ueda Norifumi
Published: January 2021

Objective.—Telomerase is considered a diagnostic marker of malignancy. We investigated the usefulness of telomerase assay for the detection of lymph node micrometastasis.

Methods.—Sixteen cervical lymph nodes with metastasis of oral cancer and 20 benign lymph nodes were studied. The oral cancer cell line was used to estimate the sensitivity for telomerase assay. Telomerase activity was measured by semiquantitative telomeric repeat amplification protocol.

Results.—There was a significant difference between malignant and benign lymph nodes. The telomerase activity of 50 mg of lymph nodes with 103 or more cancer cells differed from that of control lymph nodes. Lymph nodes with 102 or fewer tumor cells expressed similar levels as benign lymph nodes.

Conclusions.—In addition to routine histologic examination, telomerase assay is considered a useful tool for the detection of lymph node metastasis in patients with oral malignancy.
Angiectatic Nasal Polyps That Clinically Simulate a Malignant Process
Authors: Yfantis Harry G. , Drachenberg Cinthia B. , Gray William , Papadimitriou John C.
Published: January 2021

Background.—Approximately 5% of inflammatory or allergic sinonasal polyps develop extensive vascular proliferation and ectasia with deposition of pseudoamyloid. These so-called angiectatic nasal polyps (ANPs) can grow rapidly and exhibit an aggressive clinical behavior that could simulate malignancy preoperatively.

Objective.—To systematically address the differential histologic diagnosis of ANPs.

Methods.—We evaluated by light microscopy, immunohistochemistry, and electron microscopy biopsy and resection specimens from 2 large ANPs (8 and 10 cm in diameter) that presented in 2 adult men with life-threatening epistaxis and facial deformity, respectively.

Results.—The tumors were firm, lobulated, and covered by smooth, partially ulcerated mucosa. Histologically, clusters of dilated, thin-walled blood vessels embedded in pools of Congo red–negative eosinophilic material, associated with patchy necrosis and atypical stromal spindle cells, were seen. Electron microscopy and immunohistochemistry (CD34, factor VIII) confirmed the endothelial nature of the cells lining the spaces, whereas the atypical stromal cells were classified as myofibroblasts.

Conclusions.—These 2 cases represent extreme examples of ANPs that clinically simulate a malignant process. Awareness of the histological features of ANPs should prevent confusion of such lesions with other vascular or spindle cell lesions of the nasopharynx that would require different treatment and carry a different prognosis.
Transformation of Monocytoid B-Cell Lymphoma to Large Cell Lymphoma Associated With Crystal-Storing Histiocytes
Authors: Thorson Phataraporn , Hess Jay L.
Published: January 2021

We report a case of crystal-storing histiocytosis associated with large cell lymphoma in a patient with a history of monocytoid B-cell lymphoma 10 years previously. The cervical lymph node biopsy showed a diffuse proliferation of large lymphocytes with vesicular nuclear chromatin and distinct nucleoli. These lymphocytes were associated with numerous immunoglobulin λ light-chain crystal-storing histiocytes, which morphologically resembled rhabdomyoblasts. Occasional lymphoid cells also showed large immunoglobulin crystals. This case establishes the association of crystal-storing histiocytes with lymphomas of mucosa-associated lymphoid tissue and emphasizes the need for immunophenotyping to distinguish these unusual cases from other tumors, particularly adult rhabdomyomas.
Angiotensin-Converting Enzyme Polymorphism and the Risk of Coronary Heart Disease in the Saudi Male Population
Authors: Dzimiri Nduna , Basco Chona , Moorji Azadali , Meyer Brian F.
Published: January 2021

Objective.—To determine the relevance of angiotensin I–converting enzyme (ACE) gene polymorphism for coronary artery disease (CAD) in the Saudi population.

Methods and Results.—DNA of 84 male Saudi patients with established CAD, 36 male controls who underwent angiography, and 327 healthy Saudi male blood donors was amplified by polymerase chain reaction, using oligonucleotide primers flanking the insertion (I)/deletion (D) sites in the polymorphic region of intron 16 of the ACE gene. Polymerase chain reaction amplification resulted in 490-bp (II), 190-bp (DD), or 490- and 190-bp (ID) fragments. The genotype II distribution was 16.7% in the control group, 7.3% in the blood donor group, and 7.2% in the patients with CAD, and the distribution for DD was 58.3%, 47.1%, and 41.0%, respectively. Notably, 61.9% (P < .0001) of CAD patients presented with angina on admission, and 52.4% had diabetes mellitus.

Conclusions.—The results show no increased risk of CAD in association with either the II or DD genotypes in the Saudi population. However, further investigation of genotype II as a predictor for atherosclerosis rather than increased risk of coronary heart disease may be indicated.
Effects of pH on Glucose Measurements With Handheld Glucose Meters and a Portable Glucose Analyzer for Point-of-Care Testing
Authors: Tang Zuping , Du Xiaogu , Louie Richard F. , Kost Gerald J.
Published: January 2021

Objectives.—To determine pH effects on glucose measurements obtained with the latest generation of glucose devices, to quantitate changes in glucose measurements obtained over a wide pH range, and to assess the potential clinical risks of pH effects with use of point-of-care glucose testing.

Design.—Paired differences of glucose measurements between pH-altered and parallel control samples with target pH 7.40 were calculated.

Setting.—A pH range of 6.94 to 7.84 was used to evaluate pH effects on glucose measurements in vitro with 6 handheld glucose meters and a portable glucose analyzer at both normal, 4.81 mmol/L (86.6 mg/dL), and high, 11.16 mmol/L (201 mg/dL), glucose levels.

Main Outcome Measures.—Glucose measurements obtained from test samples and control samples were compared by calculating paired differences, which were plotted against pH to show pH effects on glucose meter measurements.

Results.—At the normal glucose level, different pH levels did not interfere significantly with glucose measurements. At the high glucose level, a trend whereby low pH decreased and high pH increased glucose measurements was observed on the Precision G and the Precision QID glucose meters.

Conclusion.—Because of potential risk in diabetic patients with ketoacidosis and in other patients with acid-base disorders, we recommend that clinicians choose glucose devices carefully and interpret the measurements cautiously when point-of-care glucose testing is performed in critically ill patients with acidemia, alkalemia, or changing acid-base status.
Primary Hepatic Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue Type in a Patient With Primary Biliary Cirrhosis
Authors: Ye Ming Q. , Suriawinata Arief , Black Candice , Min Albert D. , Strauchen James , Thung Swan N.
Published: January 2021

Primary lymphoma of the liver is rare. Recently, marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type have been described in the liver. Most of these cases occurred without known underlying liver disease, while others were seen in patients with chronic hepatitis. A case of primary hepatic MALT lymphoma in a patient with primary biliary cirrhosis was reported recently. Some authors have proposed that chronic persistent immunogenic stimulation causes development of acquired MALT and subsequently MALT lymphoma, based on the observation of MALT lymphoma in association with infectious agents, such as Helicobacter pylori and hepatitis C virus, and autoimmune diseases, such as Hashimoto thyroiditis and Sjögren syndrome. Primary biliary cirrhosis is a chronic, progressive, cholestatic liver disease characterized by destruction of intrahepatic small to medium-sized bile ducts; this disease is mediated by a cytotoxic T-cell reaction. The prolonged immune activation in primary biliary cirrhosis may play a role in the lymphomagenesis of hepatic MALT lymphoma. We describe another case of primary hepatic MALT lymphoma, which was found incidentally in a patient with end-stage primary biliary cirrhosis. This case further supports the role of immunogenic stimulation in the pathogenesis of this particular low-grade B-cell lymphoma.
Quality Management in Gynecologic Cytology Using Interlaboratory Comparison
Authors: Jones Bruce A. , Davey Diane D.
Published: January 2021

Objective.—To describe a comprehensive integrated laboratory quality management plan for gynecologic cytology.

Design and Setting.—Cytopathology laboratory performance monitors with interlaboratory comparison.

Results.—Utilizing College of American Pathologists Q-Probes studies, the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology, and other published data, a quality management program for gynecologic cytology involving diagnostic statistics, screening limits and competency assessment, retrospective rescreening, real-time rescreening, cytology-biopsy correlation, follow-up of patients with abnormal cytology results, turnaround time, examination of unknown slides (survey programs), and new technology is described.

Conclusion.—Regular coordinated monitoring of performance, with longitudinal and interlaboratory comparison utilizing the methods described, provides an opportunity to optimize gynecologic cytology service.
Fas (APO-1/CD95) Ligand and Fas Expression in Renal Cell Carcinomas
Authors: Kim Young-Sik , Kim Kwang Hee , Choi Jung-Ah , Lee Ju Han , Kim Han Kyeom , Won Nam Hee , Kim Insun
Published: January 2021

Background and Objective.—Fas ligand (FasL, CD95L) is a type II transmembrane protein of the tumor necrosis factor family that induces cells to send an apoptotic signal to cells expressing Fas (CD95, APO-1). It has been shown that cancers have a dysregulated expression of Fas and FasL system, conferring a survival advantage. It is important to understand FasL and Fas expression in tumors, because the growth of cancer might be controlled by Fas-mediated apoptosis.

Methods.—The expressions of FasL and Fas were studied by immunohistochemical analyses in 51 cases of renal cell carcinomas and the adjacent normal renal tissues, respectively. In addition, their expressions were compared with prognostic factors, such as tumor size, nuclear grade, TNM stage, and histologic types.

Results.—In nonneoplastic renal tissues, FasL was expressed in all nephron segments, whereas Fas also expressed in all tubules, except for glomeruli. In renal cell carcinomas, FasL protein was detected in 50 (98.0%) of 51 cases, whereas Fas expressed in 38 (74.5%) of 51 cases. In fact, the immunostaining of Fas was less intense than that in the adjacent normal segments of all cases. The staining pattern showing both high expression of FasL and low expression of Fas was found in 36 (70.6%) (P = .04) of 51 cases, most of which were Fuhrman grade 2 or 3 tumors. However, the expression pattern did not correlate statistically with the tumor size, histologic type, or clinical stage. On the other hand, most grade 4 tumors displayed high expression of both FasL and Fas (P < .001).

Conclusion.—These data indicate that high expression of FasL and low expression of Fas protein in renal cell carcinomas may play a role in evading surveillance of the immune system. In addition, the FasL and Fas expressions appear to have a therapeutic implication for high-grade tumors rather than a prognostic one.
Liposarcoma of the Pleural Cavity
Authors: Okby Nader T. , Travis William D.
Published: January 2021

Background.—Primary liposarcomas of the pleura are extremely rare malignancies, and relatively few reports appear in the world literature.

Design.—We compiled a small series of 4 cases of primary pleural liposarcoma from the files of the Armed Forces Institute of Pathology (Washington, DC) and compared the histopathologic and clinical features of these 4 cases with those of 9 previously published cases.

Results.—Our investigation included the case studies of 9 men and 4 women, aged 19 to 80 years (average, 49 years). Histologic subtypes in the 9 cases with available information included 5 myxoid liposarcomas, 1 well-differentiated liposarcoma, and 3 liposarcomas with mixtures of histologic types. Surgical resection with or without chemotherapy appeared to be the most common form of treatment, although radiation therapy was used in some cases and seemed beneficial. Survival information was available for 11 cases; 4 patients died of disease at 7, 9, 12, and 19 months; 1 died of heart failure 2 days after presentation; 1 died of unknown causes 16 months after presentation; and 3 patients were alive without tumor at 5, 16, and 66 months after diagnosis. One patient had local recurrence at 2 years. A second surgical resection in this patient failed, and he died of disease 9 years after initial presentation. A second patient experienced recurrence at 4 years and was free of disease 4 years after the second surgical resection.

Conclusions.—Primary pleural liposarcomas occur predominantly in older men, and the myxoid histologic subtype is the most common. Radiographic or surgical evaluation is important to distinguish primary pleural liposarcoma from chest wall or mediastinal sarcomas, as well as metastases from other sites. Although further investigation is needed, evidence from the cases reviewed here indicates that surgical resection with adjuvant radiation therapy may benefit patients with primary pleural liposarcoma.
Pyogenic Spondylodiskitis
Authors: Lucio Emmanuel , Adesokan Adekunle , Hadjipavlou Alexander G. , Crow Wayne N. , Adegboyega Patrick A.
Published: January 2021

Background.—Intervertebral disk tissue is resistant to hematogenous infection because of its avascularity. However, spondylodiskitis is being diagnosed with increasing frequency because of advancement in magnetic resonance imaging technology. There is a dearth of information regarding the bacteriology, histomorphologic features, and radiopathologic correlation of spondylodiskitis.

Design.—The study population consisted of 20 patients diagnosed as having spondylodiskitis by magnetic resonance imaging with and without gadolinium 67 enhancement and bone scans with technetium Tc 99m or gallium citrate Ga 67. Twenty-seven biopsy and debridement specimens were obtained from these patients. The specimens were cultured for microorganisms and also processed for histopathologic testing. Tissue sections were examined with hematoxylin-eosin and stains for infectious agents (Gomori's methenamine-silver, Gram, and Ziehl-Neelsen stains).

Results.—Where intervertebral disk tissue was present (23 of 27 cases), the morphologic changes included vascularization (with or without granulation tissue), myxoid degeneration, and necrosis. Chronic osteomyelitis was present in all 27 specimens and was associated with acute osteomyelitis in 7 cases (25%). Twenty-one of 27 cases had positive culture results (mostly pyogenic bacteria), but special stains revealed microorganisms in sections of the disk in only 4 cases (3 cases with gram-positive cocci and 1 with yeast consistent with Blastomyces). Florid acute inflammation was present in all the 4 cases.

Conclusion.—Histopathologic features of acute spondylodiskitis include vascular proliferation, myxoid degeneration, and necrosis of the disk tissue with adjacent chronic osteomyelitis. Acute inflammation is variable and when florid is usually associated with identifiable organisms on histologic examination. At biopsy, tissue should be submitted for culture, since culture has a high sensitivity and specificity for detecting the etiologic organism.
Lymphoepithelioma-like Carcinoma of the Uterine Cervix
Authors: López-Ríos Fernando , Miguel Pilar San , Bellas Carmen , Ballestín Claudio , Hernández Lucía
Published: January 2021

Lymphoepithelioma-like carcinomas have been reported outside the nasopharynx in many sites, including the uterine cervix. The association with the Epstein-Barr virus in the latter site is still controversial. To date, Epstein-Barr virus genome has only been demonstrated in Asian patients. We report a case of lymphoepithelioma-like carcinoma of the uterine cervix in a white woman in whom the Epstein-Barr virus infection was tested for by in situ hybridization and polymerase chain reaction. The results of both techniques were negative. Our case and a review of the literature support the contention that cervical lymphoepithelioma-like carcinoma is not associated with Epstein-Barr virus infection in non-Asian patients.
Solitary Fibrous Tumor of the Orbit With a t(9;22)(q31;p13)
Authors: Havlik Dean M. , Farnath Denise A. , Bocklage Therese
Published: January 2021

Solitary fibrous tumors are well-described neoplasms found predominantly in the subpleural region but also in many other body sites. They generally behave in a benign fashion, although a few cases that exhibit a malignant course have been reported. Genetic information on solitary fibrous tumors is sparse. This case illustrates a previously unreported finding of a tumor-specific t(9;22)(q31;p13) in a solitary fibrous tumor of the orbit of a 58-year-old man.
Primary Meningeal Rhabdomyosarcoma in a Child With Hypomelanosis of Ito
Authors: Xu Fushen , De Las Casas Luis E. , Dobbs Larry J.
Published: January 2021

Intracranial rhabdomyosarcomas are rare neoplasms, and those thought to be primary meningeal tumors are even more rare. Hypomelanosis of Ito is a neurocutaneous disorder believed to involve a defect in cells of neural crest origin. We report the case of a 15-month-old boy with hypomelanosis of Ito who developed a primary meningeal rhabdomyosarcoma. The patient initially presented with hydrocephalus and 2 months later developed neurologic signs localizing to the spinal cord. Radiologic studies revealed widespread leptomeningeal enhancement with compression of the spinal cord at C5-C7. A brain biopsy revealed a tumor diffusely involving the meninges. Microscopically, the tumor was composed of rhabdomyoblasts, many of which showed prominent cross-striations on routine hematoxylin-eosin staining. To the best of our knowledge, this is the first reported case of meningeal rhabdomyosarcoma in a patient with hypomelanosis of Ito and the fourth reported case of a primary meningeal rhabdomyosarcoma reported in the world literature.
College of American Pathologists Conference XXXV: Solid Tumor Prognostic Factors—Which, How and So What?
Authors: Hammond M. Elizabeth H. , Fitzgibbons Patrick L. , Compton Carolyn C. , Grignon David J. , Page David L. , Fielding L. Peter , Bostwick David , Pajak Thomas F.
Published: January 2021

The College of American Pathologists convened a prognostic factor conference in June 1999 to consider prognostic and predictive factors in breast, colon, and prostate cancer, and to stratify these factors into categories reflecting the strength of published evidence. Because so little progress in prognostic factor clinical utility has been made in the last 5 years, the conference participants focused their attention on decreasing variation in methods, interpretation, and reporting of these factors so that greater clarity of value could be achieved. The conference was organized to promote discussion, broad input, and future planning. An initial plenary session provided an overview of the status of tumor marker research, the impact of variation in medicine and pathology, and statistical issues related to prognostic factor research. In working group sessions for each cancer type, participants interactively evaluated and refined the documents created by the expert panels. A second plenary session dealt with issues common to all 3 groups, including the problem of micrometastases in lymph nodes in these sites; statistical issues that arose during the breakout discussions; and issues of variation in methods, interpretation, and reporting of immunohistochemical assays. A faculty session brainstormed strategies that could be used to implement the changes recommended. This session included invited representatives of the Food and Drug Administration, Health Care Financing Administration, Centers for Disease Control and Prevention, National Cancer Institute, American Joint Committee on Cancer, and International Union Against Cancer. Cancer site and general recommendations were presented and discussed during a final session to achieve consensus of the conference participants and to address feasibility of implementation of these recommendations. A final discussion focused on future initiatives that might lead to implementation of the changes proposed in the conference by the various organizations represented. This report summarizes the general conference recommendations, cancer working group recommendations, and plans for implementation of the recommendations.
Prognostic Factors in Breast Cancer
Authors: Fitzgibbons Patrick L. , Page David L. , Weaver Donald , Thor Ann D. , Allred D. Craig , Clark Gary M. , Ruby Stephen G. , O'Malley Frances , Simpson Jean F. , Connolly James L. , Hayes Daniel F. , Edge Stephen B. , Lichter Allen , Schnitt Stuart J.
Published: January 2021

Background.—Under the auspices of the College of American Pathologists, a multidisciplinary group of clinicians, pathologists, and statisticians considered prognostic and predictive factors in breast cancer and stratified them into categories reflecting the strength of published evidence.

Materials and Methods.—Factors were ranked according to previously established College of American Pathologists categorical rankings: category I, factors proven to be of prognostic import and useful in clinical patient management; category II, factors that had been extensively studied biologically and clinically, but whose import remains to be validated in statistically robust studies; and category III, all other factors not sufficiently studied to demonstrate their prognostic value. Factors in categories I and II were considered with respect to variations in methods of analysis, interpretation of findings, reporting of data, and statistical evaluation. For each factor, detailed recommendations for improvement were made. Recommendations were based on the following aims: (1) increasing uniformity and completeness of pathologic evaluation of tumor specimens, (2) enhancing the quality of data collected about existing prognostic factors, and (3) improving patient care.

Results and Conclusions.—Factors ranked in category I included TNM staging information, histologic grade, histologic type, mitotic figure counts, and hormone receptor status. Category II factors included c-erbB-2 (Her2-neu), proliferation markers, lymphatic and vascular channel invasion, and p53. Factors in category III included DNA ploidy analysis, microvessel density, epidermal growth factor receptor, transforming growth factor-α, bcl-2, pS2, and cathepsin D. This report constitutes a detailed outline of the findings and recommendations of the consensus conference group, organized according to structural guidelines as defined.
Increased Expression of Vascular Endothelial Growth Factor and Angiogenesis in the Early Stage of Multistep Hepatocarcinogenesis
Authors: Park Young Nyun , Kim Young-Bae , Yang Kyung Moo , Park Chanil
Published: January 2021

Background.—Hepatocellular carcinoma (HCC) is known to receive its blood supply principally from the hepatic arteries. Recent studies have reported differences in the vascular supply, especially arterial supply among low- and high-grade dysplastic nodules (DNs) (also referred to as adenomatous hyperplasia and macroregenerative nodules) and HCCs. Increased expression of vascular endothelial growth factor (VEGF) has been reported in HCC. In addition, VEGF may play an important role in the early phases of hepatocarcinogenesis.

Methods.—We immunohistochemically stained 7 low-grade DNs, 8 high-grade DNs, 11 early HCCs, 17 small HCCs, and 21 advanced HCCs with antibodies against VEGF, α-smooth muscle actin (to identify unpaired arteries, ie, arteries not accompanied by bile ducts, indicative of angiogenesis), CD34 (as a marker of sinusoidal capillarization), and proliferation cell nuclear antigen.

Results.—Expression of VEGF was found in the hepatocytes and HCC cells. The degree of VEGF expression increased gradually according to the stepwise development of hepatocarcinogenesis. It was higher in high-grade DNs and early HCCs than in low-grade DNs. The hepatocytes and HCC cells adjacent to peliosis and fibrous septa showed stronger VEGF expression. Angiogenesis, unpaired arteries, and sinusoidal capillarization developed from low-grade DNs and gradually increased. It was highest in HCCs. The proliferation cell nuclear antigen labeling indexes of hepatocytes and HCC cells also increased gradually as hepatocarcinogenesis progressed. Small HCCs showed a higher status of neoangiogenesis and cell proliferation activity than advanced HCCs. The degree of VEGF expression was correlated with angiogenesis and cell proliferation activity.

Conclusion.—We conclude that VEGF plays a significant role in angiogenesis, growth, and development of HCC.
Malignant Mesothelioma With CD30-Positivity
Authors: Dunphy Cherie H. , Gardner Laura J. , Bee Christopher S.
Published: January 2021

The activation marker CD3O is useful in the diagnosis of Hodgkin and non-Hodgkin lymphomas. It has also been described in nonhematopoietic tumors, including pancreatic carcinomas, salivary gland tumors, and embryonal carcinomas. We report a case of malignant mesothelioma with intense CD30 positivity. This finding has not previously been described and is important in broadening the differential diagnosis of a CD30+ cohesive large cell malignancy.
Carcinosarcoma of the Urinary Bladder—An Aggressive Tumor With Diverse Histogenesis
Authors: Baschinsky Dmitry Y. , Chen Janny H. , Vadmal Manjunath S. , Lucas Joel G. , Bahnson Robert R. , Niemann Theodore H.
Published: January 2021

Objective.—Carcinosarcomas of urinary bladder are rare malignant neoplasms. Seventy-eight cases have been previously described. The histologic composition of these tumors is variable, but diagnosis requires the presence of both epithelial and mesenchymal malignant components. We report 4 additional cases, with an emphasis on unusual histologic features.

Methods.—Histologic and immunohistochemical examinations were performed on bladder tumors from 4 patients. Clinicopathologic features of previously reported and current cases were reviewed and summarized.

Results.—Four patients (3 men, 1 woman) age 54 to 77 years were found to have polypoid masses in the urinary bladder. In all cases, histologic examination showed biphasic neoplasms with distinct mesenchymal and epithelial components. The morphologic and immunohistochemical characteristics of the tumors varied. One of the cases was remarkable for the presence of liposarcoma, malignant peripheral nerve sheath tumor, and micropapillary urothelial carcinoma. Two of the patients died 2 years after diagnosis, which is consistent with the previously reported aggressive nature of urinary bladder carcinosarcomas.

Conclusions.—Carcinosarcomas of the urinary bladder are rare, aggressive malignant neoplasms. To our knowledge, a liposarcomatous component has been reported in only 1 case previously, and components of micropapillary urothelial carcinoma and malignant peripheral nerve sheath tumor have not been reported previously in carcinosarcomas of the urinary bladder. Because of the aggressive biologic behavior of these tumors, they should be identified promptly and treated appropriately.
Ciliocytophthoria in Clinical Virology
Authors: Hadziyannis Emilio , Yen-Lieberman Belinda , Hall Gerri , Procop Gary W.
Published: January 2021

Direct immunofluorescence assays (DFAs) are used in the clinical virology laboratory for the rapid detection of viruses. An assessment of the cellularity of specimens submitted for DFA is necessary for the most effective use of this assay. This assessment ensures that an adequate number of the appropriate cells are present for examination. During this assessment, clinical virologists may encounter unfamiliar cellular elements or cellular fragments. One of these elements, ciliocytophthoria, has been misinterpreted as a parasite in specimens submitted for cytologic testing. We describe a similar case in which a technologist thought that ciliocytophthoria possibly represented a ciliated parasite in a nasopharyngeal specimen sent for respiratory syncytial virus DFA. After a thorough morphologic examination, the staff dismissed the possibility of a ciliated parasite. We confirmed this entity as ciliocytophthoria using morphologic criteria and the Diff-Quik stain. This near misidentification of ciliocytophthoria as a ciliated parasite affords us the opportunity to raise the awareness of clinical virologists about ciliocytophthoria. Additionally, we briefly review useful features for differentiating ciliocytophthoria from the only ciliate parasitic for humans, Balantidium coli. Finally, we present the utility of a commonly used cytologic stain, the Diff-Quik stain, for the confirmation of ciliocytophthoria.
Primary Bilateral Mucosa-Associated Lymphoid Tissue Lymphoma of the Breast With Atypical Ductal Hyperplasia and Localized Amyloidosis
Authors: Gupta Dilip , Shidham Vinod , Zemba-Palko Vlasta , Keshgegian Albert
Published: January 2021

Primary non-Hodgkin lymphoma of the breast is a rare disease. Primary mucosa-associated lymphoid tissue lymphoma is even rarer, and bilateral involvement is exceptional. We describe a case of primary bilateral breast mucosa-associated lymphoid tissue lymphoma with bilateral atypical ductal hyperplasia and bilateral localized amyloidosis in a 64-year-old woman with a history of arthritis and systemic lupus erythematosus and its clinical, histologic, and immunohistochemical features. Microscopic examination of the breast lesion showed dense periductal and perilobular small and plasmacytoid lymphocytes with eosinophilic amyloid in the vessels and the stroma. Bilateral single foci of atypical ductal hyperplasia were also noted. Fine needle aspiration showed small and large lymphocytes and plasma cells. Molecular analysis demonstrated a heavy chain immunoglobulin H gene rearrangement. Flow cytometry studies showed an abnormal B-cell population. The combined histologic, paraffin immunohistochemistry, flow cytometry, and molecular results were considered diagnostic for low-grade mucosa-associated lymphoid tissue lymphoma. The patient underwent bilateral local breast radiation without other organ or site involvement.
Undesirable Cytokeratin Immunoreactivity of Native Nonepithelial Cells in Sentinel Lymph Nodes From Patients With Breast Carcinoma
Authors: Xu Xiaowei , Roberts Shelley A. , Pasha Theresa L. , Zhang Paul J.
Published: January 2021

Context.—Use of cytokeratin immunohistochemistry on histologically negative sentinel lymph nodes (SLNs) in patients with breast carcinoma has been shown to be efficient in detecting false-negative nodes. Several recent studies have shown that micrometastases detected by immunohistochemistry constitute an independent predictor of disease-free period and overall survival for breast cancer patients. It has been demonstrated that the fibroblastic type of reticulum cells in lymph nodes also express cytokeratin, and unawareness of such cytokeratin reactivity in SLNs could result in difficulty in the interpretation of the results of immunohistochemistry.

Objectives.—To study the incidence of undesirable cytokeratin reactivity in reticulum cells and other native nonepithelial cells of SLNs and to compare the immunoreactivity of 3 commonly used cytokeratin antibodies (AE1/AE3, pancytokeratin [pan-CK], and CAM5.2).

Design.—Immunohistochemistry with pan-CK, AE1/AE3, and CAM5.2 antibodies was performed on paraffin sections of SLNs from patients with breast cancer. Correlation of undesirable cytokeratin reactivity with size and metastatic status of the SLNs was also analyzed.

Patient Material.—Paraffin sections of 84 SLNs from 38 consecutive patients with breast cancer in our tertiary-care, teaching hospital.

Results.—Cytokeratin reactivity was found in reticulum cells and plasma cells in 29 (35%) and 9 (10%) of the 84 SLNs, respectively, with pan-CK and CAM5.2 but not with AE1/AE3 (P < .001). The presence of cytokeratin-positive reticulum cells did not correlate with the size and metastatic involvement of the SLNs.

Conclusions.—The incidence of undesirable keratin reactivity in SLNs from breast cancer patients could be limited by using an AE1/AE3 antibody cocktail. The AE1/AE3 antibody cocktail is a sensitive epithelial marker and appears to be more specific in recognizing epithelial cells in SLNs.
Proportion Positive for Epstein-Barr Virus, Cytomegalovirus, Human Herpesvirus 6,Toxoplasma,and Human Immunodeficiency Virus Types 1 and 2 in Heterophile-Negative Patients With an Absolute Lymphocytosis or an Instrument-Generated Atypical Lymphocyte Flag
Authors: Tsaparas Yotis F. , Brigden Malcolm L. , Mathias Richard , Thomas Eva , Raboud Janet , Doyle Patrick W.
Published: January 2021

Objectives.—To determine the proportion of patients with evidence of an acute infection due to Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), Toxoplasma, or human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) in heterophile-negative patients with an absolute lymphocytosis or an instrument-generated atypical lymphocyte flag, and to develop a cost-effective testing algorithm for managing such heterophile-negative patients.

Design.—We conducted a prospective investigation of 70 selected outpatients who tested negative for heterophile antibody in association with an absolute lymphocytosis or instrument-generated atypical lymphocyte flag. The control population consisted of 50 patients who were heterophile negative and had a normal absolute lymphocyte count and no instrument-generated atypical lymphocyte flag.

Setting.—A large outpatient laboratory system.

Intervention.—Viral serology for HHV-6 was performed by immunofluorescence, and all other serologies were performed by enzyme-linked immunoassay. All testing was for immunoglobulin (Ig) M antibodies, except in the case of HIV.

Results.—The proportion of study patients positive for EBV was 40% (28/70); for CMV, 39% (27/70); for HHV-6, 25% (16/65); for Toxoplasma, 3% (2/70); and for HIV, 0% (0/70). All 50 control patients were negative for EBV IgM antibodies. When patients with more than 1 positive viral test were excluded from analysis, positivity was 20% (9/45) for EBV, 22% (10/45) for CMV, 9% (4/45) for HHV-6, and 2% (1/45) for Toxoplasma. Utilizing hypothesis-generating logistic regression models, Downey type II atypical lymphocytes were significantly associated with EBV positivity (P = .006), while Downey type III lymphocytes were significantly associated with HHV-6 positivity (P = .016), and there was a trend for the association of Downey type I lymphocytes with CMV positivity (P = .097).

Conclusions.—A positive viral serology was identified in 70% of study patients. Multiple positive serologies complicate establishing a definitive diagnosis. Potential cost savings may be associated with the use of an appropriate testing algorithm.