1. health and fitness
2. disease

Abstracts of Papers
abstracts of papers
Check Sample Abstracts
The following abstracts are compiled from Check Sample exercises published in 2010. These peer-reviewed case studies assist
laboratory professionals with continuing medical education and are developed in the areas of clinical chemistry, cytopathology,
forensic pathology, hematology, microbiology, surgical pathology, and transfusion medicine.
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Vitamin D: An Overview
Clinical Chemistry No. CC 10-1 (CC-383)
Evrim Erdogan, PhD, and A. Wayne Meikle, MD. University of
Utah, Salt Lake City.
Anticoagulation Clinic: Point-of-Care Testing
Clinical Chemistry No. CC 10-3 (CC-385)
Amy Schmidt, MD, PhD, and Charles S. Eby, MD. Department of
Pathology and Immunology, Washington University, St Louis, MO.
Vitamin D, a fat-soluble vitamin, is involved in mineral and
bone metabolism. The two most functionally important metabolites
are 25-hydroxyvitamin D (25[OH]D) and 1,25-dihydroxyvitamin D
(1,25[OH]2D). Many disorders are associated with abnormally low
plasma concentrations of these metabolites resulting from insufficient dietary intake, altered synthesis, and altered sensitivity of target
tissue. Vitamin D deficiency is associated with impaired bone deposition and increased bone resorption, particularly in osteoporosis,
and deficiency results in defective bone mineralization, especially
in osteomalacia and rickets. Even though vitamin D deficiency is
not the primary cause of osteoporosis, it is one of the major risk
factors associated with the condition, particularly in postmenopausal
women. This overview of vitamin D includes its biochemistry, metabolic action, association with health conditions, clinical laboratory
testing, and reference intervals.
Warfarin is a commonly used anticoagulant. Its use necessitates
monitoring the anticoagulant effect due to the narrow therapeutic
window and wide therapeutic dose range. Anticoagulation clinics
specialize in testing the international normalized ratio (INR) and
making dose changes. Many of these clinics, as well as other outpatient clinics, use point-of-care (POC) testing devices. Moreover,
POC testing is used in rural areas as well as in home monitoring
by patients. This exercise discusses the issues affecting INR POC
testing, such as antiphospholipid syndrome, anemia, heparin/lowmolecular-weight heparin, thromboplastin reagent, and test strips.
Additionally, variables that affect warfarin metabolism, ie, drugs,
foods, supplements, and genotype, are examined.
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Alpha-1 Antitrypsin Deficiency: Which Test? When?
Clinical Chemistry No. CC 10-2 (CC-384)
Vijaya Nagabhushanam, MD, PhD, Ronald J. Harbeck, PhD, and
Robert A. Sandhaus, MD, PhD. National Jewish Health, Denver,
CO.
Testing for alpha-1 antitrypsin deficiency (AATD) appears
straightforward, but physicians and laboratory personnel may not
appreciate the differences between the testing methods currently
available. As a genetic condition causing precocious emphysema
and otherwise unexplained liver disease, among others, improper
choice of test method may lead to misdiagnosis, failure to diagnose,
and even paternity/maternity questions. With growing pressure to
identify the large undiagnosed majority of individuals with AATD,
a thorough understanding of the strengths and weaknesses of each
testing method is essential.
© American Society for Clinical Pathology
Beckwith-Wiedemann Syndrome: The Role of Molecular
Diagnostic Testing in Patient Care
Clinical Chemistry No. CC 10-4 (CC-386)
Bijal A. Parikh, MD, PhD,1 and Barbara Zehnbauer, PhD,
FACMG.2 1Department of Pathology and Immunology,
Washington University School of Medicine, St Louis, MO; and
Laboratory Practice Evaluation and Genomics Branch, Centers
for Disease Control and Prevention, Atlanta, GA.
Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder with characteristic features, including macroglossia, macrosomia, and abdominal wall defects. Pathogenesis has
been correlated with inappropriate expression of several genes
at chromosomal locus 11p15.5. The most common mechanism
involves transcriptional regulation of imprinted genes—genes normally expressed only from one parent or the other. Methods to
diagnose BWS currently include mutational analysis of an implicated
gene—CDKN1C, karyotype analysis for 11p15.5 rearrangements,
short tandem repeat analysis for uniparental disomy, and methylation
analysis of 2 imprinted transcripts—H19 and LIT1. However, these
Am J Clin Pathol 2011;135:313-326
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methods fail to detect 100% of affected individuals, and, therefore,
a thorough clinical evaluation remains essential. The need for accurate and early diagnosis is underscored by the higher frequency of
embryonal tumors and other comorbidities in the affected children.
Understanding the genetic basis of BWS for each case is necessary
to counsel parents about recurrence risks.
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Hemoglobin A1c and Estimated Average Glucose Levels
Clinical Chemistry No. CC 10-5 (CC-387)
Christopher N. Chapman, MD, and James H. Nichols, PhD,
DABCC, FACB. Baystate Health, Springfield, MA.
Hemoglobin A1c (HbA1c) has been the standard for monitoring the treatment of patients with diabetes for many years, because
HbA1c can trend glucose levels over the previous 3 months.
However, confusion over differences between HbA1c percentages
and correlation of HbA1c results with the patient’s self-monitoring
glucose levels have led to the development of a calculation to estimate the patient’s average glucose concentration from the HbA1c
result. This estimated average glucose level is endorsed by the
American Diabetes Association as a means of educating and counseling patients about diabetes control. The article reviews the study that
derived the estimated average glucose calculation and discusses the
role of the calculation in current patient care, the limitations of this
estimation, and requirements for future diabetes research in improving the current equation.
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Application of Point-of-Care Measurement of Creatinine
Clinical Chemistry No. CC 10-6 (CC-388)
Joely A. Straseski, PhD, William Clarke, PhD, and Lori J. Sokoll,
PhD. Johns Hopkins Medical Institutions, Baltimore, MD.
Patients with renal insufficiency are at increased risk for developing complications following administration of contrast agents used
for imaging studies. Ineffective renal clearance of contrast agents
such as gadolinium may result in nephrogenic systemic fibrosis in
these patients. This chronic, debilitating, and potentially fatal disease
has no known treatment or cure. Identifying at-risk patients is critical
to preventing morbidity and mortality. Determination of creatinine
level and the estimated glomerular filtration rate are recommended
as an approach to identify these patients. Point-of-care testing of
creatinine levels is a potential option for efficiently determining renal
function in patients prior to imaging with contrast agents. In addition,
studies have shown that point-of-care creatinine testing may benefit
patients in emergency or critical care departments and during longterm monitoring of chronic diseases.
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The Genetics of Familial Thoracic Aortic Aneurysm and
Dissection
Clinical Chemistry No. CC 10-7 (CC-389)
Katrina Kotzer, MS, and Linnea M. Baudhuin, PhD. Department of
Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Predisposition to thoracic aortic aneurysm and dissection
(TAAD) can be associated with a genetic syndrome such as Marfan
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syndrome or Loeys-Dietz syndrome. In the absence of a syndromic
condition, dominantly inherited TAAD is termed familial TAAD
(FTAAD). Defined as a confirmed diagnosis of TAAD in a person
with a positive family history and absence of a syndromic genetic
condition, FTAAD is characterized by reduced penetrance and a
high degree of variable expression, as well as genetic heterogeneity.
The genes identified as causing FTAAD include TGFBR2, TGFBR1,
FBN1, MYH11, ACTA2, and COL3A1. Genetic testing and genetic
counseling are useful tools in the identification and management of
families with FTAAD.
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Hyperviscosity Syndrome: Analytic Challenges and Diagnosis
Clinical Chemistry No. CC 10-8 (CC-390)
Christopher R. McCudden, PhD, DABCC, NRCC, FACB, Andrew
Laramore, MD, and Yuri Fedoriw, MD. University of North
Carolina, Chapel Hill.
Hyperviscosity syndrome (HVS) is a rare, potentially lifethreatening disorder caused by a myriad of underlying conditions,
including plasma cell neoplasms, autoimmune diseases, and lymphoproliferative disorders. The diagnosis of HVS depends on clinical symptoms and an array of laboratory and other diagnostic tests.
Acute treatment focuses on lowering blood viscosity and includes
fluids, diuretics, and plasmapheresis. Long-term management of
HVS depends on treating the underlying disorder. Laboratorians
play a critical role in identifying hyperviscous specimens when they
handle and process blood. Samples from patients with HVS can
cause multiple error flags on automated instruments, or the samples
can appear thick and can be difficult to pipette for manual tests.
Education of laboratory personnel is essential to catch these rare
specimens and alert treating physicians to consider immediate treatment of symptomatic patients.
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Bile-Duct-Brushing Cytologic Examination
Cytopathology No. C 10-1 (C-427)
Robert E. Emerson, MD. Department of Pathology and
Laboratory Medicine, Indiana University School of Medicine,
Indianapolis.
Laboratories are receiving specimens collected from the
extrahepatic bile ducts for cytopathologic examination with
increasing frequency, and interpretation of these specimens is
challenging, even for cytotechnologists and pathologists who
examine these specimens on a regular basis. The specimens are
usually collected at the time of endoscopic retrograde cholangiopancreatography during the evaluation of patients with biliary
strictures in order to confirm or exclude the presence of malignancy. Sensitivity is only moderate and is limited primarily by the
adequacy of specimen sampling. Specificity is generally high, but
false positives may occur, particularly in the setting of primary
sclerosing cholangitis or other inflammatory conditions. A definitive diagnosis may be impossible for a small percentage of cases,
and, for these cases, an atypical or suspicious diagnosis may be
appropriate. A variety of ancillary tests have been investigated for
their usefulness in the evaluation of bile-duct-brushing specimens,
but, in many cases, increases in sensitivity come at the expense of
decreased specificity.
© American Society for Clinical Pathology
Abstracts of Papers
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The Recognition of Extrauterine Malignancies in Pap Smears
Cytopathology No. C 10-2 (C-428)
Xin Gao, MD. Emory University School of Medicine, Grady
Memorial Hospital, Atlanta, GA.
As a screening test for cervical neoplasia, the Pap smear is not
a sensitive tool to detect metastatic malignancies in the cervix. If
malignant extrauterine cells are identified in Pap smears, the malignancy is usually already widespread and the diagnosis is straightforward. Less commonly, however, the Pap smear can be the first test
to diagnose an extrauterine malignancy. Therefore cytopathologists
should be familiar with the cytomorphologic features of some common extrauterine malignancies involving the cervix. Metastatic carcinomas usually appear as foreign “floaters” to the smear; cells are
obviously malignant; the background is clean. Differential diagnoses
with endocervical and endometrial adenocarcinomas are discussed.
Features of some uncommon metastases, including metastatic melanoma and malignant lymphoma, are also described.
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Diagnostic Pitfalls in Fine-Needle Aspiration Biopsy of the
Spleen
Cytopathology No. C 10-3 (C-429)
Maria A. Friedlander, MPA, CT(ASCP), and Andre L. Moreira,
MD, PhD. Department of Pathology, Memorial Sloan Kettering
Cancer Center, New York, NY.
Fine-needle aspiration (FNA) of splenic lesions is increasing
in frequency. FNA of spleen may be warranted in a defined subset
of patients with splenic lesions, namely those patients with diffuse
large-cell lymphoma and metastatic tumors. FNA is less invasive
than splenectomy, and a positive diagnostic result can aid in patient
management and may prevent further unnecessary surgery. While
FNA of spleen is rare, many of the diseases encountered represent
conditions diagnosed by FNA in other sites. To avoid misdiagnosis,
it is important to be familiar with the normal cytology of this uncommonly biopsied organ in order to successfully identify neoplastic
processes. Circumstances in which FNA might produce misleading
or nondiagnostic results include primary splenic vascular lesions and
hyperplastic lymphoid lesions. The use of ancillary studies is important in the definitive classification of both primary and metastatic
splenic lesions.
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Human Papillomavirus and Cervical Cancer Screening
Cytopathology No. C 10-4 (C-430)
Joel S. Bentz, MD. Laboratory Medicine Consultants, Las Vegas,
NV.
The Papanicolaou test is the most effective tool we have to
prevent cervical cancer. In addition, women 30 years of age and
older should also undergo testing for human papillomavirus (HPV).
Using both tests in combination for women in this age group further
increases the chances of identifying precancerous changes. Testing
for high-risk (oncogenic) HPV DNA has proven utility in a growing number of applications in gynecologic cytology, cervical cancer
screening, and clinical management. Circumstances in which HPV
testing is considered appropriate, and when such testing is generally
not appropriate, are reviewed in the exercise. A summary of clinical
© American Society for Clinical Pathology
indications based on consensus guidelines and the natural history and
epidemiology of HPV and cervical cancer is provided.
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Endoscopic Ultrasound–Guided Fine-Needle Aspiration of
Pancreatic Endocrine Neoplasms: Diagnostic Challenges and
the Role of Immunocytochemistry
Cytopathology No. C 10-5 (C-431)
Lee-Ching Zhu, MD,1 and Annette Peck, MD.2 1Group Health
Cooperative and 2University of Washington Medicine Pathology,
Seattle.
Endoscopic ultrasound (EUS) has become the standard of practice for diagnosis and staging of pancreatic neoplasms. The application of fine-needle aspiration (FNA) guided by EUS (EUS-FNA) has
proven to be a safe and effective procedure with a low complication
rate. Pancreatic endocrine neoplasms (PENs) are rare neoplasms of
a heterogeneous group of neuroendocrine gastroenteropancreatic
tumors that originate from totipotential stem cells or preexisting
endocrine cells within the pancreas. The morphologic spectrum of
PENs is variable, but typical cytological features usually allow a
preoperative diagnosis. A panel of immunocytochemical studies
can facilitate the differential diagnosis. By carefully applying the
laboratory techniques (scraping the direct smears into a cell block,
immunostaining over Papanicolaou-stained monolayer slides, or
applying different antibodies to different areas of one smear slide),
immunocytochemical studies are often achievable with limited aspiration materials. EUS-FNA cytology thus offers the possibility of a
relatively specific preoperative, less-invasive diagnosis of PENs.
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Tall Cell Variant of Papillary Thyroid Carcinoma
Cytopathology No. C 10-6 (C-432)
Ann E. Walts, MD. Department of Pathology & Laboratory
Medicine, Cedars-Sinai Medical Center, Los Angeles, CA.
Papillary thyroid carcinomas comprise approximately 80%
of thyroid malignancies. The cytologic features of conventional
papillary thyroid carcinoma have been well described. The exercise
illustrates the cytologic, histologic, and clinical features associated
with the tall cell variant of papillary thyroid carcinoma, an uncommon and clinically more aggressive tumor. It provides a context for
a brief discussion of the molecular alterations recently described in
thyroid tumors and their potential role in improving the diagnosis
and management of aggressive thyroid tumors.
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Diagnostic Approach to Hyperchromatic Cell Clusters on
Conventional and Liquid-Based Papanicolaou Tests
Cytopathology No. C 10-7 (C-433)
Krisztina Z. Hanley, MD,1 and Marina B. Mosunjac, MD.2
1University of Virginia Health System, Charlottesville; and
2Emory University, Grady Memorial Hospital, Atlanta, GA.
The Papanicolaou test is the most widely used primary screening tool for cervical squamous cell carcinoma and its precursors.
The primary diagnosis of several cases of relatively uncommon
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primary and metastatic tumors of the gynecologic tract has been
made on cervicovaginal smears. Due to the diagnostic limitations
of the Papanicolaou smear, specific diagnoses in the setting of these
uncommon tumors can only rarely be made, and ancillary studies are often required for exact classification of these lesions. The
diagnostic challenge of these smears is twofold: (1) to recognize
the abnormality and (2) to distinguish a neoplastic process from its
benign mimickers. Familiarity with the cytomorphologic features
of some uncommon tumors of the gynecologic tract can enable the
cytopathologist to play a valuable role in further clinical management of these patients.
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Ocular Proliferations in the Context of Cytologic Evaluation
Cytopathology No. C 10-10 (C-436)
Lourdes Ylagan, MD, FIAC. Department of Pathology and
Laboratory Medicine, Roswell Park Cancer Institute, Buffalo, NY.
Tumors of the ocular adnexae are uncommon and may represent 1% to 2% of all tumors in general surgical pathology. A variety
of lesions originate in the ocular adnexae, and a variety of lesions
metastasize to this area. The exercise discusses the most common
malignant ocular neoplasms, some esoteric lesions of the ocular
adnexa, as well as some common metastatic lesions to the eye. The
clinical presentation, diagnostic approach, and treatment modalities
specific to these tumors are explained.
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Biliary Brush Cytologic Diagnosis With FISH Correlation
Cytopathology No. C 10-8 (C-434)
Trynda N. Oberg, MS, CT(ASCP)CM, Benjamin R. Kipp,
PhD, Kevin C. Halling, MD, PhD, and Amy C. Clayton, MD.
Department of Laboratory Medicine and Pathology, Mayo Clinic,
Rochester, MN.
Diagnostic sampling of pancreatobiliary strictures is a challenge
due to the difficult anatomic location and desmoplastic tumor cells.
Biliary-brushing specimens obtained through endoscopic retrograde
cholangiopancreatography provide material for evaluation by routine cytology and fluorescence in situ hybridization (FISH). The
specimens can be difficult to interpret by routine cytology. Routine
cytologic examination has a relatively low sensitivity for the detection of malignancy in these specimens. FISH has an increased sensitivity with biliary brush specimens compared with routine cytology.
Incorporation of both routine cytology and FISH results can improve
patient care through a more definitive diagnosis of equivocal cytologic interpretations. Bile-duct-brushing cytologic examination with
FISH testing aids in the diagnosis of cholangiocarcinoma, pancreatic
adenocarcinoma, and other tumors of the pancreatobiliary tract.
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Diagnosis of Mesothelioma by Endoscopic Ultrasound–Guided
Fine-Needle Aspiration Biopsy
Cytopathology No. C 10-11 (C-437)
Darshana Jhala, MD, B MUS,1,2 and Nirag Jhala, MD, MIAC.1
1University of Alabama at Birmingham; and 2Auburn University,
Montgomery, AL.
The evaluation of mediastinal lesions is morphologically
challenging. Endoscopic ultrasound–guided fine-needle aspiration
(EUS-FNA) biopsy has enabled deep tissue to be sampled from the
thoracic and abdominal cavities. EUS-FNA is minimally invasive,
cost-effective, and is increasingly used in the diagnosis of mediastinal lesions. A morphology-based algorithm is useful. Malignant
mesothelioma is a rare neoplasm encountered as a mediastinal mass.
The use of EUS-FNA in the diagnosis of a mesothelioma reinforces
the pivotal role the cytopathologist plays in triaging specimens for
ancillary studies that lead to the correct diagnosis.
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Discriminating Hepatocellular Carcinoma From Metastatic
Adenocarcinoma: The Utility of the Immunohistochemical
Panel
Cytopathology No. C 10-9 (C-435)
Husain Saleh, MD, FIAC, FASCP, MBA. Sinai Grace Hospital/
DMC and Wayne State University, Detroit, MI.
Endobronchial Ultrasound–Guided Transbronchial Needle
Aspiration
Cytopathology No. C 10-12 (C-438)
Monika Roychowdhury, MD, Charanjeet Singh, MD, and Stefan
E. Pambuccian, MD. Department of Laboratory Medicine &
Pathology, University of Minnesota, Minneapolis.
Hepatocellular carcinoma (HCC) is a relatively common cancer
worldwide and has a poor prognosis. At the same time, the majority of liver malignancies are metastatic adenocarcinoma (MAC).
Distinction between these 2 tumors is important because of different
biologic behavior and treatment approaches. Fine-needle aspiration
biopsy (FNAB) has an important role in evaluating liver masses;
however, distinction between poorly differentiated HCC and MAC
and between well-differentiated HCC and benign liver lesions can be
difficult and challenging in FNAB samples because of less-apparent
cytologic architecture, limited material, and obscure clinical history.
The search for helpful ancillary tests continues, and immunocytochemical markers enhance diagnostic accuracy and distinction.
Several cases of HCC and MAC diagnosed by FNAB are discussed.
The value of a panel of immunostains including new markers such
as glypican-3 and CD10 is highlighted.
An 81-year-old man with chronic cough, hemoptysis, and
a right suprahilar mass on computed tomography was diagnosed
as having pN2 squamous cell carcinoma on endobronchial
ultrasonography–guided fine-needle aspiration (EBUS-FNA) of
the mass and station 7 lymph node. EBUS-FNA is a minimally
invasive procedure for staging and on-site evaluation of non–
small cell bronchogenic carcinomas. Alternatively, it is used for
restaging bronchogenic carcinomas postchemoradiation and for
evaluation of granulomatous thoracic lesions. Specimen triaging
is the goal of on-site EBUS-FNA. A cytopathologist can identify
the adequacy of a specimen based on lymphocytes and tingible
body macrophages, and a diagnosis can be based on cytomorphologic features, but caution is warranted because false-positive
results can potentially adversely affect the patient more than falsenegative results.
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© American Society for Clinical Pathology
Abstracts of Papers
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Thyrotoxicosis and Postmortem Diagnosis of Thyroid Disease
Forensic Pathology No. FP 10-1 (FP-352)
Daniel C. Lingamfelter, DO,1,2 Gregory G. Davis, MD, MSPH,3
and Amy C. Gruszecki, MSFS, DO.1,2 1Southwestern Institute of
Forensic Sciences, Dallas, TX; 2University of Texas Southwestern
Medical Center, Dallas; and 3Jefferson County Coroner/ME
Office, and University of Alabama at Birmingham.
Diagnosis of Bacterial Meningitis at Autopsy
Forensic Pathology No. FP 10-4 (FP-355)
Kristin A. Olson, MD,1and Michelle Barry, MD.2 1Department
of Pathology, 2Office of the Medical Investigator, University
of New Mexico School of Medicine, University of New Mexico,
Albuquerque.
Thyrotoxicosis, a hypermetabolic state produced by elevated
levels of thyroid hormone, is most often caused by Graves disease,
toxic multinodular goiter, subacute thyroiditis, or toxic adenoma.
Typically, hyperthyroidism occurs in women between the ages of 20
and 40 years, with a lower incidence in the black population. Signs
and symptoms are related to the patients’ hypermetabolism, and
poorly treated cases may progress to thyroid storm, a physiologic
collapse marked by stupor, coma, hypotension, and death in up to
75% of cases. Other complications of thyrotoxicosis include highoutput cardiac failure and, specifically, both ophthalmopathy and
dermopathy in individuals with Graves disease. In cases of suspected
hyperthyroidism for which no antemortem blood is available for
laboratory analysis, postmortem blood should be collected for both
thyroid-stimulating hormone (TSH) and thyroxine (T4) level determination. Both enzyme levels have been shown to be of potential
worth even when collected after the patient’s death.
Although the incidence of bacterial meningitis continues to
decline with the use of antibiotics and vaccines, this infectious condition remains an important cause of morbidity and mortality worldwide. The majority of cases occur in adults, are community acquired,
and are caused by Streptococcus pneumoniae. Predisposing host
factors include immunocompromise, infection, exposure to an
individual with meningitis, injection drug use, head trauma, otorrhea or rhinorrhea, and travel to areas with endemic meningococcal
disease. Gross examination of the brain with histologic correlation is
typically sufficient to render the diagnosis, but postmortem bacterial
cultures of blood, lung, and cerebrospinal fluid should be secured
in suspected cases to identify the causative organism. If obtaining
cerebrospinal fluid proves difficult, a swab of the purulent meninges
can be cultured instead. Other potentially fatal conditions in the
clinical differential diagnosis of bacterial meningitis—such as herpes encephalitis, cerebral toxoplasmosis, meningeal carcinomatosis,
stroke, sepsis, bacterial endocarditis, and pneumonia—must be considered in the postmortem examination.
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Polypharmacy, Hyperthermia, and Sudden Death
Forensic Pathology No. FP 10-2 (FP-353)
Thomas A. Andrew, MD,1 and Rebecca L. Andrew, MD.2 1Office
of the Chief Medical Examiner and 2New Hampshire Hospital,
Concord.
Two young men on multiple medications presented with altered
mental status, hyperthermia, and neuromuscular irritability with
death ensuing within hours of presentation. Drug-related hyperthermia syndromes in general and serotonin syndrome specifically
are discussed in relation to these case studies. Presenting features,
clinical course, differential diagnosis, and autopsy findings in fatal
cases are examined.
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Radiograph Limitations in the Recovery of Firearm Projectiles
With Radiolucent Features
Forensic Pathology No. FP 10-3 (FP-354)
Joseph J. Pavelites, PhD,1 Ray Wolfenbarger,2 and Joseph A.
Prahlow, MD.1,3 1Indiana University School of Medicine, 2South
Bend Police Department, and 3South Bend Medical Foundation,
South Bend.
The uses and limitations of plain radiographs in firearm projectile recovery is examined, particularly with regard to certain
ammunition types. The common pitfalls of using plain radiographs
in the determination of the number of bullets expected or found in
a shooting victim’s body, bullet caliber, and bullet migration are
discussed. Understanding the limitations of plain film radiographs in
the determination of caliber size, projectile number, and migration,
as well as knowledge of commonly encountered radiolucent materials like aluminum are critical in forensic investigations of firearmgenerated trauma.
© American Society for Clinical Pathology
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Cardiomyopathy in Survivors of Childhood Cancers
Forensic Pathology No. FP 10-5 (FP-356)
Karen Cline-Parhamovich, DO, DABP, ASCP,1,2 and Cecilia Wu,
MD.3 1James H. Quillen College of Medicine, East Tennessee
State University; 2William L. Jenkins Forensic Center, Johnson
City, TN; and 3University of New Mexico School of Medicine,
Albuquerque, NM.
An autopsy was performed on a 12-year-old girl who suddenly
collapsed at home. Her history was significant for acute lymphoblastic leukemia diagnosed at age 3 years. She was subsequently treated
with a chemotherapy regimen that included doxorubicin. A partial
autopsy (restricted to head, chest, and liver) revealed dilated cardiomegaly, ventricular wall thinning, and myocardial hypertrophy and
fibrosis. These features are consistent with anthracycline-induced
cardiomyopathy. Despite well-documented cardiotoxic effects of
anthracyclines, they continue to be a popular chemotherapy agent
in the treatment of childhood cancers because of their efficacy in
achieving remission. As an increasing number of childhood survivors of cancers reach adulthood, it will be important to recognize
the signs, symptoms, and autopsy findings of anthracycline-induced
cardiomyopathy.
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Hypereosinophilic Syndrome With Loeffler Endocarditis:
Diagnostic Criteria, Characteristic Findings, and Appropriate
Laboratory Workup
Forensic Pathology No. FP 10-6 (FP-357)
Roger W. Stone, MD, and Nicholas I. Batalis, MD. Department of
Pathology and Laboratory Medicine, Medical University of South
Carolina, Charleston.
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Loeffler endocarditis is a restrictive cardiomyopathy characterized by eosinophilic myocarditis, endomyocardial fibrosis, clinical
manifestations of acute thromboembolism, and acute heart failure. It
is associated with eosinophilia that is often of unknown etiology and
further characterized as hypereosinophilic syndrome if the patient
meets specific criteria. Death usually results from congestive heart
failure with multiorgan dysfunction. In this article, a fatal case of
Loeffler endocarditis is reported in a 71-year-old woman who had a
history of asthma and peripheral eosinophilia. Following a detailed
description of the autopsy findings, the pathophysiology of Loeffler
endocarditis is reviewed, and potential underlying disease processes
that may result in profound eosinophilia are discussed.
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Anaphylaxis: Fatal Hypersensitivity Reaction to Carboplatin
Forensic Pathology No. FP 10-7 (FP-358)
Mary H. Dudley, MD, MS, RN,1,2 Steven W. Fleming, MS, DFTCB,3
Raja M. Gidwani, MD,4 William R. Porter, MD,5 Uttam Garg, PhD,
DABFT, DABCC, FACB,2,3 C. Clinton Frazee III, MBA, NRCC-TC,3
and Kamal D. Sabharwal, MD.1,6 1Office of the Jackson County
Medical Examiner, Kansas City, MO; 2University of Missouri Kansas
City School of Medicine, Kansas City, MO; 3Children’s Mercy
Hospitals and Clinics, Kansas City, MO; 4Detroit Medical Center/
Wayne State University, Detroit, MI; 5Kaleida Health, Williamsville,
NY; and 6St Louis County Medical Examiner’s Office, St Louis, MO.
A 65-year-old woman died suddenly and unexpectedly during
chemotherapy for ovarian cancer. Autopsy findings were significant
for pharyngeal edema, diffuse alveolar damage, shock kidney, and
splenic congestion. There was no evidence of coronary artery disease, pulmonary emboli, stroke, or any pathologic findings causing
her death. Postmortem samples were sent for toxicologic analysis
and were significant for an elevated tryptase concentration indicating a hypersensitivity reaction to carboplatin. Chemotherapy is not
generally known to be associated with hypersensitivity reactions.
However, carboplatin has been shown to cause anaphylaxis during
later rounds of chemotherapy. Due to the medical history, autopsy
findings, and an elevated postmortem tryptase concentration, the
cause of death was ruled anaphylactic reaction to chemotherapy. The
manner of death was ruled an accident.
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Fatal Fall of a Nine-Month-Old Infant
Forensic Pathology No. FP 10-8 (FP-359)
Mary H. Dudley, MD,1 and Anaïs N. Parker.2 1Jackson County
Medical Examiner Office, Kansas City, MO; and 2Boston
University, Boston, MA.
A 9-month-old infant died after a fall from a height of 13 feet.
The infant’s injuries were inconsistent with the provided history
and raised suspicions. Was the cause of death truly an accident or
was it due to inflicted head trauma in addition to a fall? A review
of the circumstances revealed several factors that supported both
nonaccidental and accidental trauma as the cause of injury. The
uncertainty of the cause of death necessitated the use of the multidisciplinary forensic team approach and accident reconstruction. The
use of forensic experts and accident reconstruction help to answer
important questions about the cause and manner of death. The case
example illustrates the need for thorough scene investigation, use of
a forensic team approach, and accident reconstruction in investigation of child fatalities.
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Manifestations of Ethylene Glycol Poisoning
Forensic Pathology No. FP 10-9 (FP-360)
Emily F. Gorman, MD,1 and Gregory G. Davis, MD, MSPH.1,2
1University of Alabama at Birmingham, and 2Jefferson County
Coroner/ME Office, Birmingham, AL.
Ethylene glycol is a bittersweet odorless and colorless dihydric
alcohol that is the major ingredient of many radiator fluid products in
the United States. Fluorescein dye, which fluoresces under ultraviolet
light, is often added to antifreeze to help automobile mechanics identify radiator fluid leaks. Readily absorbed from the gastrointestinal
tract, ethylene glycol can be maximally absorbed in humans within
1 to 4 hours and typically has a half-life of between 3 and 8 hours.
Laboratory findings of ethylene glycol intoxication can include
metabolic acidosis, increased serum osmolality, increased anion gap,
decreased calcium concentration, and the presence of calcium oxalate
crystals in the urine. Due to the variability of absorption and metabolism of ethylene glycol, urine may or may not fluoresce to visibly
detectable levels following ingestion of ethylene glycol. The absence
of findings in urine studies and/or microscopic examination of the
kidney cannot rule out ethylene glycol intoxication because crystals
may not be present if death occurred before crystals were formed.
30
Hydrops Fetalis Due to Hemoglobin Barts
Forensic Pathology No. FP 10-10 (FP-361)
Marianne Hamel, MD, PhD. Office of Chief Medical Examiner of
the City of New York, New York, NY.
Hydrops fetalis due to hemoglobin Barts (Hb Barts) is the most
clinically severe form of α-thalassemia and a common cause of intrauterine fetal demise in Southeast Asia. Affected fetuses show marked
edema, organomegaly, and widespread extramedullary hematopoiesis. Failure to express normal α-chains due to gene deletions causes
formation of unstable γ-chain tetramers. Such tetramers, called Hb
Barts, have abnormal oxygen dissociation curves and are the root of
disease-associated chronic intrauterine hypoxia. The exercise presents
a case of fetal demise shortly after delivery due to complications of
unsuspected Hb Barts. The molecular genetics of Hb Barts and other
α-thalassemias is outlined. The gross pathology, microscopic findings, methods of diagnosis, and current modalities of treatment for 4
α-globin gene deletion hemoglobinopathies are discussed.
31
Kikuchi Histiocytic Necrotizing Lymphadenopathy
Hematology No. H 10-1 (H-332)
Charles Blake Hutchinson, MD,1 Chuanyi M. Lu, MD, PhD,2,3 and
Endi Wang, MD, PhD.1 1Duke University Medical Center, Durham,
NC; 2University of California San Francisco; and 3San Francisco
Veterans Administration Medical Center, San Francisco, CA.
Kikuchi histiocytic necrotizing lymphadenitis, also known as
Kikuchi-Fujimoto disease (KFD), is an uncommon, self-limited
condition characterized by benign lymphadenopathy with associated fevers and, sometimes, other systemic symptoms. It is most
commonly seen in adults younger than 40 years of age and of Asian
descent. Histologically, involved lymph nodes demonstrate paracortical patchy areas of coagulative necrosis with abundant karyorrhectic
debris and proliferation of histiocytes, plasmacytoid monocytes, and
CD8-positive T cells in the absence of neutrophils and sparse plasma
cells. Based on histologic features, KFD is thought to have 3 evolving phases: proliferative, necrotizing, and xanthomatous. The etiology
© American Society for Clinical Pathology
Abstracts of Papers
of KFD is unknown, though viruses, such as Epstein-Barr virus, and
autoimmune mechanisms have been proposed as causes. No specific
laboratory tests are contributory to the diagnosis. A correct diagnosis
depends on careful histopathologic examination and effective exclusion of other differential diagnoses by using ancillary studies such
as flow cytometry, serologic tests, and molecular diagnostic studies.
Special attention should be paid to rule out systemic lupus erythematosus before diagnosis of KFD, given the overlapping clinical
and histologic features as well as the essentially different therapeutic
approach. Treatment of KFD involves supportive measures, and the
symptoms usually resolve spontaneously within 4 months.
32
Vitamin K–Deficiency Bleeding in an Infant: Clinical Features
and Laboratory Diagnosis
Hematology No. H 10-2 (H-333)
Benjamin Robert Koch, MD, and Nancy S. Rosenthal, MD.
Department of Pathology, University of Iowa Hospitals and
Clinics, Iowa City.
Vitamin K–deficiency bleeding (VKDB), also known as hemorrhagic disease of the newborn, is a rare but serious disease primarily
seen in infants who have not received prophylactic vitamin K administration after birth. Laboratory findings include both a prolonged
prothrombin time and a prolonged partial thromboplastin time,
although these findings are not specific. The diagnosis is confirmed
by normalization of these laboratory abnormalities after administration of vitamin K. VKDB can be divided into 3 different subsets
depending on the time of onset: early-onset VKDB, classic VKDB,
and late-onset VKDB. Clinical findings include gastrointestinal and/
or internal bleeding. Late-onset VKDB usually presents with acute
intracranial hemorrhage. The prognosis is excellent for infants with
VKDB in the absence of acute intracranial hemorrhage. For those
infants who develop acute intracranial hemorrhage, the prognosis
depends on the location and extent of hemorrhage.
Natasha Savage, MD, Elizabeth Manaloor, MD, Michelle ReidNicholson, MBBS, and Preetha Ramalingam, MBBS. Department
of Pathology, Medical College of Georgia, Augusta.
Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a B-cell neoplasm that
is typically localized and often involves the gastrointestinal tract.
Numerous etiologies have been postulated, including certain microbial infections and autoimmune disorders. Distinguishing between
MALT lymphoma and a reactive process can sometimes be challenging, particularly on small biopsies, and may require molecular studies to make the correct diagnosis. Furthermore, other small B-cell
lymphomas must be excluded before the diagnosis of MALT lymphoma can be rendered. MALT lymphomas usually have an excellent prognosis and may occasionally respond to simple therapeutic
regimens such as antibiotics. Several cytogenetic abnormalities have
been described and often correlate with the site of involvement.
35
A Case of Intracellular Red Blood Cell Parasites
Hematology No. H 10-5 (H-336)
Christina Wojewoda, MD, Jeffery Bailey, MD, PhD, and Linda M.
Sandhaus, MD. Department of Pathology, University Hospitals of
Cleveland, Cleveland, OH.
Human babesiosis is a tick-borne disease that is caused by the
protozoa Babesia. Babesia microti is endemic in the northeastern and
midwestern United States. Babesiosis can be asymptomatic or present with fever, malaise, headache, nausea, and generalized weakness for weeks to months. It is diagnosed primarily on clinical history
and blood smear evaluation and should be considered in patients
with persistent or recurring fevers who have a history of exposure
to ticks or hemolytic anemia. The differential diagnosis includes
Plasmodium, which can be difficult to differentiate on blood smear.
Treatment includes atovaquone plus azithromycin or clindamycin
plus quinine for patients who are symptomatic.
33
Mantle Cell Lymphoma, Pleomorphic Variant, Involving the
Bone Marrow
Hematology No. H 10-3 (H-334)
Natasha Savage, MD, and Elizabeth Manaloor, MD. Medical
College of Georgia, Augusta.
Mantle cell lymphoma is a malignancy of mature clonal B cells.
Morphologic variants exist; however, only the blastoid and pleomorphic variants are considered clinically significant because they
confer a worse prognosis. Although diagnostically mantle cell lymphoma, blastoid and pleomorphic variants, are distinguished from
common mantle cell lymphoma by morphologic means only, other
distinguishing features exist. Immature hematopoietic neoplasms
can morphologically mimic mantle cell lymphoma, blastoid variant; therefore immunohistochemistry for cyclin D1 and cytogenetic
analysis including fluorescent in situ hybridization for t(11;14) must
be performed for confirmation of the diagnosis.
34
Extranodal Marginal Zone B-Cell Lymphoma of MucosaAssociated Lymphoid Tissue Involving the Stomach
Hematology No. H 10-4 (H-335)
© American Society for Clinical Pathology
36
Anaplastic Large-Cell Lymphoma, ALK-Positive
Hematology No. H 10-6 (H-337)
Ari B. Molofsky, MD, PhD, and Chuanyi M. Lu, MD, PhD.
Department of Laboratory Medicine, University of California San
Francisco.
A 24-year-old man with diffuse lymphadenopathy, B symptoms, and lytic bone lesions was diagnosed with anaplastic largecell lymphoma, anaplastic lymphoma kinase–positive (ALCL,
ALK+). ALCL, ALK+ is a T-cell lymphoma of children and
young adults that expresses chimeric ALK fusions. The classical variant (“common pattern”) of ALCL is characterized by
an infiltrate of large cells with abundant cytoplasm and nuclear
pleomorphism, including “hallmark cells,” and sinusoidal and
paracortical nodal invasion. The neoplastic cells express CD30,
cytotoxic proteins (TIA-1, granzyme B, and perforin), epithelial
membrane antigen, and variable levels of T-cell antigens. ALCL,
ALK+ expresses 1 of a variety of ALK fusion proteins, most
commonly nucleophosmin (NPM)-ALK due to a t(2;5)(p23;q35)
translocation, and carries a favorable prognosis. ALCL, ALK– is
a distinct clinicopathologic entity of adults that lacks ALK expression and confers an intermediate prognosis. Treatment of ALCL,
Am J Clin Pathol 2011;135:313-326
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ALK+ with conventional chemotherapy is generally successful,
although experimental approaches targeting ALK and/or CD30
hold promise for improved outcomes in the future.
37
Primary Mediastinal (Thymic) Large B-Cell Lymphoma
Hematology No. H 10-7 (H-338)
Endi Wang, MD, PhD. Duke University Medical Center, Durham,
NC.
Primary mediastinal (thymic) large B-cell lymphoma (PMBL)
is a subtype of diffuse large B-cell lymphoma (DLBCL). At
diagnosis, it commonly appears as a bulky lesion in the anterior
mediastinum. The symptoms are often related to local invasion or
compression. Histologic examination typically shows a proliferation
of medium-large lymphoid cells that are entrapped in compartments
surrounded by collagen fibrosis, forming “alveolar compartmentalizing fibrosis.” The neoplastic cells are positive for CD20, CD79a,
Pax-5, and other B-cell markers. CD30 is commonly seen but shows
heterogeneous staining. CD15 is constantly negative. The lymphomagenesis of PMBL remains unclear. It is hypothesized to arise
from B cells within the thymic medulla. Of the lymphomas occurring in mediastinum, nodular sclerosis Hodgkin lymphoma needs to
be differentiated from PMBL. Rare cases with overlapping features
have been recently described as mediastinal gray zone lymphoma.
PMBL carries a relatively favorable prognosis in comparison with
conventional DLBCL. The optimal treatment is unknown, although
better outcomes with third-generation chemotherapy regimens have
been documented.
38
Acquired von Willebrand Syndrome
Hematology No. H 10-8 (H-339)
A. Victoria McKane, MD. Esoterix Coagulation, Englewood, CO.
von Willebrand disease is a fairly common cause of inherited
bleeding diathesis. However, acquired von Willebrand syndrome,
a nonheritable disorder associated with a number of medical indispositions, symptomatically similar or identical to the congenital
disease, is significantly less common and usually seen in adults
with concomitant illnesses. Diagnosis is achieved primarily through
analysis of von Willebrand factor antigen and activity—by ristocetin cofactor or collagen binding activity—and confirmed by
multimeric analysis, most often demonstrating loss of the highest
molecular weight multimers. The phenomenon is incompletely
understood. Several pathophysiologic mechanisms have been proposed, including autoantibody development, increased proteolysis
of von Willebrand factor, adsorption by neoplastic cells or activated
platelets, or mechanical destruction of the higher molecular weight
multimers. Therapeutically, maneuvers to increase circulating von
Willebrand factor or to suppress either the suspected syndromic
mechanism or ameliorate the underlying associated condition may
be sequentially or simultaneously undertaken.
39
Coccidioides Infection in a Pediatric Patient
Microbiology No. MB 10-1 (MB-366)
320
320
Am J Clin Pathol 2011;135:313-326
Dennis L. Murray, MD, FAAP, FIDSA,1 John C.H. Steele Jr,1
Saudiqa Hoosairy,1 and Margaret F. Guill, MD.1,2 Medical
College of Georgia, Augusta; and 2Dartmouth Medical School,
Hanover, NH.
Coccidioidomycosis is a fungal disease typically acquired in
the southwestern United States. Erythema nodosum may periodically
occur in patients infected with Coccidioides spp. We present a case
of an adolescent girl residing in Georgia who developed erythema
nodosum after experiencing mild respiratory symptoms. The girl
was found to have an abnormal chest radiograph and, later, a cavitary
nodular lesion on computerized tomography scan. No travel history
was initially obtained, and the patient was given antituberculosis
medications. Subsequently, after a history of prior travel to Arizona
was obtained, the girl was found to have a positive serological test
for Coccidioides, and Coccidioides immitis was isolated from a
bronchoalveolar lavage. The exercise reviews the pathogenesis and
clinical symptoms of coccidioidomycosis in pediatric patients, the
differential diagnosis of solitary nodules and cavitary lesions, and
how the clinical laboratory can assist in the diagnosis of infections
due to Coccidioides spp.
40
Herpes Simplex Virus Hepatitis Presenting in the Second
Trimester of Pregnancy
Microbiology No. MB 10-2 (MB-367)
William DePond, MD,1 and Anirudha Halder, MD.2 1MedLab,
Terre Haute, IN; and 2Chariton Laboratory Services, Kirksville,
MO.
A 32-year-old woman presented to the emergency department with fever of unknown origin and hepatomegaly. She was 23
weeks’ pregnant. Her laboratory data showed high levels of hepatic
enzymes, bilirubin, ammonia, and prothrombin time. Her condition deteriorated despite antibiotic therapy. She further developed
disorientation and coma. An antibody screen for herpes simplex
was strongly positive. Cesarian section was performed, and a 600-g
male infant was delivered. Liver biopsy performed during the
cesarian section revealed microvesicular steatosis, scattered areas
of hepatocellular necrosis, and large intranuclear inclusions in the
hepatocytes surrounding the areas of necrosis. Electron microscopic
examination confirmed the presence of herpes nucleocapsids. She
slowly responded to acyclovir therapy. Her hepatic coma eventually
decreased, and the patient recuperated.
41
Mansonella ozzardi Infection: Potential Inadvertent Diagnosis
Microbiology No. MB 10-3 (MB-368)
Joanne Salmon, MD, FRCP(C). Division of Infectious Diseases,
University of Alberta Hospital, Edmonton, Canada.
A previously healthy 48-year-old man was diagnosed with a
microfilarial worm infection after the organism was found inadvertently on his routine blood smear. Based on epidemiology and the
microscopic characteristics of the worm, he was subsequently diagnosed with a Mansonella ozzardi infection. M ozzardi is transmitted
only in the Caribbean and South America by black flies and midges.
Numerous symptoms have been associated with the infection, but
the characteristic clinical presentation is unclear because the areas
of high endemicity tend to have limited access to regular medical
© American Society for Clinical Pathology
Abstracts of Papers
care. Many reports describe an asymptomatic presentation. Some
advanced molecular diagnostics have been reported, but the diagnosis is predominantly based on history and the microscopic characteristics of the worm. M ozzardi has a benign prognosis compared with
other microfilarial infections but can be treated, if symptomatic, with
ivermectin therapy.
42
Infections Due to Kluyvera Species
Microbiology No. MB 10-4 (MB-369)
Gitika Aggarwal, MBBS, and John C.H. Steele Jr, MD, PhD.
Medical College of Georgia, Augusta.
The potential virulence of Kluyvera species is a relatively recent
area of study. Reported clinical infections have been limited in number. We report a case of asymptomatic bacteriuria and urinary tract
infection in a 73-year-old man with an ileal conduit for bladder cancer. Based on a literature review, we report the importance of early
identification and antibiotic susceptibility testing for this organism.
We emphasize the need for appropriate treatment decisions based on
the clinical presentation and severity of the infection.
43
Algae Gone Wild: When Plants Become Pathogens
Microbiology No. MB 10-5 (MB-370)
Philippe R.S. Lagacé-Wiens, MD, DTM&H, FRCPC, and Paulette
F. Pang, RT. Diagnostic Services of Manitoba, Saint-Boniface
General Hospital, Winnipeg, Canada.
A case of protothecosis in an otherwise healthy 46-year-old
man is described. The presentation and diagnosis of protothecosis
are presented. The discussion includes when localized or disseminated infection by algal pathogens should be considered, and
the microbiologic and microscopic characteristics of the algae
Prototheca wickerhamii and Prototheca zopfii are identified.
Acknowledging the controversies that exist in the management of
this rare disease, the treatment options for localized and disseminated disease are also discussed.
44
Trichosporon Species: Classification, Identification, and Clinical
Relevance
Microbiology No. MB 10-6 (MB-371)
Kennard Tan, MD, and Jennifer Grant, MDCM, FRCPC.
University of British Columbia, Vancouver, Canada.
Trichosporon are yeast-like fungi, characterized by the production of arthroconidia, blastoconidia, true hyphae, and pseudohyphae.
The taxonomy can be confusing. Trichosporon beigelii, the species
classically implicated in human infections, has been reclassified into
6 species: Trichosporon asahii, Trichosporon inkin, Trichosporon
mucoides, Trichosporon cutaneum, Trichosporon ovoides, and
Trichosporon asteroides. These different species have different
pathogenicities, but speciation is not routinely done in most laboratories. Trichosporon spp may be normal human flora; infections are
rare and range from benign superficial infections and white piedra
to invasive infections known as trichosporonosis. Trichosporonosis
© American Society for Clinical Pathology
may be localized or disseminated and is almost exclusively found
in patients who are immunocompromised. Disseminated disease in
people who are severely neutropenic is frequently fatal. Trichosporon
are intrinsically resistant to echinocandins and have variable susceptibilities to amphotericin-B, flucytosine, and fluconazole. Due to its
rarity and evolving taxonomy, clinical data and treatment recommendations for trichosporonosis remain unclear.
45
Q Fever Over 75 Years: What Have We Achieved?
Microbiology No. MB 10-7 (MB-372)
Adnan Alatoom, MD, PhD, Rhea Sumpter, Jr, MD, PhD, Jessica
N. Ricaldi, MD, PhD, and Rita M. Gander, PhD, D(ABMM).
Departments of Pathology and Internal Medicine and Infectious
Diseases, University of Texas Southwestern Medical Center,
Dallas.
Q fever is a zoonotic infection with a worldwide distribution.
It is caused by Coxiella burnetii, an obligate intracellular gramnegative bacterium. The microorganism possesses many unique
features, including phase variation, pleomorphism, and sporogenic
differentiation. Since Q fever became a reportable disease in the
United States in 1999, the number of cases has been increasing dramatically. The disease has many acute and chronic manifestations.
Pneumonia and hepatitis are common in the acute disease, whereas
endocarditis is the most common manifestation of chronic disease.
Serology, performed by indirect immunofluorescence, detecting
antibodies against phase I and phase II antigens of C burnetii is the
reference method used for diagnosis. Polymerase chain reaction is in
the experimental phase, and it offers less sensitivity than serologic
methods. Different treatment regimens including doxycycline, cotrimoxazole, hydroxychloroquine, macrolides, and fluoroquinolones
are used. Q fever should be included in the differential diagnosis
of atypical pneumonia with hepatitis, fever of unknown origin, and
culture-negative endocarditis.
46
Respiratory Syncytial Virus in Adults
Microbiology No. MB 10-8 (MB-373)
Sherif B. Mossad, MD, and Belinda Yen-Lieberman, PhD.
Cleveland Clinic and Cleveland Clinic Lerner College of
Medicine, Cleveland, OH.
Respiratory syncytial virus (RSV) is the single most important
cause of acute respiratory tract infections in all ages and is the
most common cause of lower respiratory tract illness in infants and
children worldwide. A nonspecific upper respiratory tract infection,
manifesting as cough and rhinorrhea, is the most common presentation. Patients who are elderly and patients who are immunocompromised are at highest risk for respiratory failure. The major
pathologic feature is obstruction with alveolar collapse. Qualitative
and quantitative molecular methods based on reverse transcriptase–
polymerase chain reaction have proven to be extremely useful
diagnostic tools for the detection of RSV in various samples, such
as nasopharyngeal or throat swabs and bronchoalveolar lavage.
Supportive measures, including supplemental oxygen, are the
mainstay of therapy. Inhaled ribavirin is a broad-spectrum antiviral agent that is active against RSV. Its use, however, should be
restricted to selected high-risk patients.
Am J Clin Pathol 2011;135:313-326
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47
Pleomorphic Xanthoastrocytoma in the Right Temporal Lobe
Surgical Pathology No. SP 10-1 (SP-369)
Colby Fernelius, MD, Zachary S. Hoffer, MD, PhD, and Kerry
O’Brien, MD. Department of Pathology, Madigan Army Medical
Center, Tacoma, WA.
A 33-year-old man presented with headache, visual symptoms,
and a temporal lobe mass. His history was notable for resection of a
right temporal-parietal lobe pleomorphic xanthoastrocytoma (PXA).
Resection of the mass showed a recurrence of the PXA with anaplastic features.
PXA is a rare, low-grade glial neoplasm classified by the
World Health Organization (WHO) as a grade II glial tumor. It is
usually diagnosed in adolescents and has a favorable prognosis.
PXAs are histologically composed of multinucleate giant cells and
large pleomorphic astrocytes, often with bizarre nuclei and intracellular inclusions. Large cells with intracellular lipids give the tumor
its xanthomatous appearance, and intensely staining eosinophilic
granular bodies are distributed throughout the tumor. An aggressive
anaplastic variant with a high mitotic rate and necrosis resembling
high-grade gliomas has been categorized as a WHO grade III tumor.
WHO grade III PXAs can spontaneously arise de novo, but in some
circumstances, incompletely excised low-grade PXAs can progress
to high-grade tumors. Ultrastructural features, tumor markers, and
the molecular genetics of PXAs are discussed.
48
Primary Mucosal Malignant Melanoma of the Head and Neck
Surgical Pathology No. SP 10-2 (SP-370)
Kerry L. O’Brien, MD, Novae Simper, MD, and Marc Hohman,
MD. Madigan Army Medical Center, Tacoma, WA.
A 59-year-old woman with an unremarkable medical history
presented for care after experiencing 6 months of clear nasal drainage from her left naris that eventually became bloody without acute
hemorrhage. On examination, clotted blood was noted in the naris,
and a reddish mass on the anterior face of the inferior turbinate nearly
occluded the nasal cavity. Histological examination showed large,
pleomorphic, epithelioid cells with prominent, eosinophilic nucleoli
and numerous mitotic figures. Immunohistochemical stains were
positive for S100, HMB-45, MART-1, CD117, and vimentin. The
histologic appearance and immunohistochemical pattern supported
a diagnosis of malignant melanoma. A full body skin examination
and positron emission tomography were negative, and a diagnosis of
primary intranasal mucosal malignant melanoma was made. Primary
mucosal melanoma of the head and neck mucosa is an extremely
rare and very aggressive entity. The natural history, most common
sites, patient population, and treatment options for this neoplasm are
discussed.
49
Axillary Mass in a Middle-Aged Man: Unexpected Diagnosis
Surgical Pathology No. SP 10-3 (SP-371)
Jeffrey T. Bunning, MD, and Victor G. Prieto, MD, PhD.
Department of Pathology, University of Texas M. D. Anderson
Cancer Center, Houston.
Ossifying fibromyxoid tumor of soft parts (OFMT) is an
extremely rare, soft tissue neoplasm of uncertain histogenesis. The
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Am J Clin Pathol 2011;135:313-326
exercise describes the clinical, radiographic, and histologic characteristics of OFMT in the context of an unusual case. Special emphasis is given to the histomorphologic comparison of OFMT with other
soft tissue tumors in the differential diagnosis. Although OFMT is a
low-grade lesion that usually has an excellent prognosis with simple
surgical excision, there are well-documented examples of OFMTs
that behave aggressively. Much debate surrounds the characterization of prognostic factors applicable to patients who harbor OFMTs.
The current debate regarding tumor classification, risk assessment,
and predictive histologic features is summarized to enable pathologists to guide clinicians in their treatment of patients with OFMT.
50
Malignant Mesothelioma and Extrapleural Pneumonectomy
Surgical Pathology No. SP 10-4 (SP-372)
Cesar A. Moran, MD. Department of Pathology, M. D. Anderson
Cancer Center, Houston, TX.
Primary malignant tumors of the pleura are unusual, and one
of the most common is malignant mesothelioma. In recent years,
the treatment for these tumors has changed considerably. The use of
extrapleural pneumonectomy has become a common surgical treatment, and considerable stress has been placed on accurate diagnosis.
Immunohistochemical studies considered positive markers for the
diagnosis of mesothelioma are also in widespread use. However,
care must be emphasized not only in the interpretation of these
immunohistochemical stains, but also in the different patterns in
which these ancillary tools are more helpful. An understanding of the
different histopathologic growth patterns of these tumors is essential
to a proper diagnostic workup. Histologic, immunohistochemical,
and radiologic aspects must be considered in the diagnosis of mesothelioma.
51
Differential Diagnosis and Workup of Myxoid Adipocytic
Tumors of the Retroperitoneum
Surgical Pathology No. SP 10-5 (SP-373)
Priya Rao, MD,1 Victor Prieto, MD, PhD,1 Martin P. Powers,
MD,2 and Dolores Lopez-Terrada, MD, PhD.2 1M. D. Anderson
Cancer Center, 2Texas Children’s Hospital and Baylor College of
Medicine, Houston.
A 56-year-old woman had a 30-cm retroperitoneal mass. After
resection, histologic examination revealed a tumor composed of
atypical cells with hyperchromatic nuclei embedded in an abundantly
myxoid background. This led to an initial diagnosis of myxoid liposarcoma. Examination of the resection specimen showed the presence
of a neoplasm with an extensively myxoid background. The tumor
was largely devoid of adipocytic tissue and focally showed delicate
staghorn vasculature. Other areas of the tumors were more cellular
with a prominent fibrous background. Individual tumor cells were
small with hyperchromatic nuclei and demonstrated mild nuclear
pleomorphism. Mitotic figures were rare. Fluorescence in situ
hybridization studies showed amplification of the 12q15 locus, thus
supporting the diagnosis of atypical lipomatous tumor. The case illustrates that atypical lipomatous tumor/well-differentiated liposarcoma
can occasionally demonstrate a prominently myxoid background and
mimic myxoid liposarcoma. In cases where the distinction is difficult
on histologic grounds, molecular tests to demonstrate amplification
of the 12q15 locus or CHOP-DDIT3 gene fusion help to arrive at the
© American Society for Clinical Pathology
Abstracts of Papers
accurate diagnosis. The diagnosis of primary myxoid liposarcoma in
the retroperitoneum should always be questioned, and a meticulous
clinical workup must be performed to exclude a primary tumor at an
extra-abdominal site.
52
Small Cell Carcinoma of the Endometrium
Surgical Pathology No. SP 10-6 (SP-374)
Irina Lytvak, MD, Neil Fuehrer, MD, and Philip Valente, MD.
Department of Pathology, University of Texas Health Science
Center at San Antonio.
Small cell carcinomas of the endometrium are very rare. Most
patients are postmenopausal and present with vaginal bleeding.
Microscopically, these lesions are composed of small cells with
scant cytoplasm, a high nuclear/cytoplasmic ratio, evenly dispersed
chromatin, and inconspicuous nucleoli. Immunohistochemical
stains demonstrate positivity for 1 or more neuroendocrine markers. Electron microscopy shows neurosecretory granules. We
present a 60-year-old who was postmenopausal and had vaginal
spotting. Endometrial biopsy was diagnostic for a small cell carcinoma. The patient was surgically staged IV (FIGO) due to intraabdominal spread.
53
Adenoid Cystic Carcinoma of the Larynx
Surgical Pathology No. SP 10-7 (SP-375)
Jeremy Stuelpnagel, MD, Tiffany Harper, MD, and H. James
Williams, MD. Robert C. Byrd Health Sciences Center, West
Virginia University School of Medicine, Morgantown.
The authors report an uncommon presentation of adenoid
cystic carcinoma (ACC) in the larynx of a 29-year-old man with
hoarseness and unintentional weight loss. The patient underwent
a total laryngectomy. While ACC is the most common malignant
minor salivary gland tumor and the second most common laryngeal
malignant neoplasm, it is still very rare, comprising fewer than 1%
of laryngeal malignancies after squamous cell carcinoma. ACC has
an indolent but relentless clinical course with frequent perineural
involvement, late regional recurrences, and distant metastases.
The long-term prognosis for ACC of the larynx is poor. Treatment
consists of total laryngectomy and radiation therapy with long-term
follow-up. The histologic features of ACC and the differential diagnosis for tumors in this location are discussed. Common tumors of
the larynx are differentiated.
54
Ganglioneuroma in the Adrenal Gland
Surgical Pathology No. SP 10-8 (SP-376)
Qi-Hui “Jim” Zhai, MD, FCAP,1 and Lindsay Waters, MD.2
1University of Cincinnati, Cincinnati, OH; and 2The Methodist
Hospital, Houston, TX.
Ganglioneuromas are rare, benign, differentiated tumors derived
from neural crest cells most often presenting in childhood or young
adulthood. These tumors rarely arise in the adrenal gland, but rather
occur in various locations along the paravertebral sympathetic plexus, including the posterior mediastinum, retroperitoneum, and neck.
© American Society for Clinical Pathology
The clinical presentation ranges from asymptomatic to local mass
effect, cough, abdominal pain, dyspnea, flushing, diarrhea, sweating,
and hypertension. Grossly, ganglioneuromas are firm, white to yellow, trabeculated or whorled, and histologically these tumors contain
ganglion cells in a schwannian stroma. Immunohistochemical stains
such as S100, neurofilament, and synaptophysin may be used to
confirm neural differentiation. Surgical excision is typically curative,
although rare cases of metastatic ganglioneuromas exist in patients
with previous regressive metastatic neuroblastomas. Differential
diagnoses include other neuroblastic tumors, including ganglioneuroblastoma and neuroblastoma, as well as pheochromocytoma. An
understanding of ganglioneuromas is essential to accurate diagnosis
and optimal patient care.
55
Adrenal Gland Leiomyosarcoma and Metastasis to the Lung
Surgical Pathology II No. SPII 10-1 (SPII-333)
Maria Dirlei Begnami, MD,1 and Martha Quezado, MD.2 1A.
C. Camargo Cancer Hospital, Sao Paulo, Brazil; and 2National
Institutes of Health, Bethesda, MD.
Leiomyosarcomas of the adrenal gland are exceedingly uncommon. They most likely arise from the smooth muscle wall of the
central adrenal vein and its branches. They are commonly invasive
diseases that include venous thrombosis, adjacent organ invasion,
and distant metastases, with poor prognosis. The treatment is based
on surgical resection. Histologically, conventional leiomyosarcomas are composed of interlacing fascicles of spindle cells with a
moderate degree of atypia and low mitotic index. Poorly differentiated tumors show pleomorphic neoplastic cells. In those tumors, the
typical features of smooth muscle tumors are not seen. Conventional
leiomyosarcomas commonly show immunoreactivity for smooth
muscle markers such as smooth muscle actin and/or muscle actin
and desmin. The differential diagnoses are metastatic carcinoma,
sarcomatoid renal cell carcinoma, adrenocortical carcinoma, direct
extension of a primary retroperitoneal sarcoma, malignant fibrous
histiocytoma, malignant melanoma, epithelioid angiosarcoma, and
pleomorphic rhabdomyosarcoma.
56
Granular Cell Tumor of the Tongue
Surgical Pathology II No. SPII 10-2 (SPII-334)
Anirudha Halder, MD, FCAP,1 Maria L. Evans, MD,1 and Tara
N. Hoftiezer, DO.2 1A. T. Still University of Health Sciences, and
2North East Regional Medical Center, Kirksville, MO.
Granular cell tumor, also known as Abrikossoff tumor, most
commonly occurs in the head and neck region, and more than half
of these are located in the tongue. It develops in the second and
sixth decades of life, more frequently in African American women.
Most granular cell tumors are benign. Only about 2% are malignant.
Metastatic granular cell tumors must be distinguished from local
recurrences and various benign multifocal tumors. The case example
is a 55-year-old white man with a 1.5-cm nodule on the dorsum of his
tongue. Clinically, the lesion was suspicious for a squamous cell carcinoma. Biopsy showed marked pseudoepitheliomatous hyperplasia
along with subepithelial sheets of granular cells that strongly marked
with periodic acid–Schiff without diastase and S-100 protein. The
morphology was diagnostic of a granular cell tumor.
Am J Clin Pathol 2011;135:313-326
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323
Abstracts of Papers
57
Acute Hemorrhagic Leukoencephalitis (AHL or Hurst Disease)
Surgical Pathology II No. SPII 10-3 (SPII-335)
Sarah Ondrejka, DO, and Richard Prayson, MD. Cleveland
Clinic, Cleveland, OH.
Acute hemorrhagic leukoencephalitis (AHL), also known as
Hurst disease, is a rare demyelinating disease of the central nervous system. Characterized by rapid onset and a fulminant course,
this process is thought to be a severe variant of acute disseminated
encephalomyelitis (ADEM). Similar to ADEM, AHL typically presents approximately 1 to 3 weeks following systemic viral infection
or vaccination. The clinical features and appearance of the lesions
on imaging create diagnostic difficulty in distinguishing AHL from
other causes of demyelination and from infectious and neoplastic
causes of neurologic decline. The classic histologic appearance is
that of perivascular myelin loss with fibrinoid necrosis of blood
vessels and inflammatory infiltrate composed predominantly of
mononuclear cells and neutrophils. A favorable clinical outcome
is uncommon but may be aided by early diagnosis and aggressive
management.
58
Mucoepidermoid Carcinoma, Oncocytic Type
Surgical Pathology II No. SPII 10-4 (SPII-336)
Muhammad Adeel Raza, MD, and Basim M. Al-Khafaji, MD. St
John Hospital and Medical Center, Detroit, MI.
Mucoepidermoid carcinoma (MEC) with extensive oncocytic
metaplasia (mucoepidermoid carcinoma, oncocytic variant) arose in
a parotid gland in an 82-year-old woman. The patient had a 1-year
history of a painless mass behind her left ear. The left parotid gland
was excised. A diagnosis of an oncocytic neoplasm was rendered on
frozen section. Additionally, permanent sections revealed prominent
oncocytic change with phosphotungstic acid hematoxylin (PTAH)positive intracytoplasmic granularity corresponding to the mitochondria of the oncocytes. However, a mucicarmine stain also showed
mucocytes to contain mucin-positive intracytoplasmic material. The
final diagnosis was MEC, low-grade, oncocytic type. MEC is the
most common salivary gland malignancy. Meanwhile, oncocytic
mucoepidermoid carcinoma (OMEC) is a rare neoplasm; reported
cases show it to be a low-grade neoplasm with a favorable prognosis.
Oncocytic neoplasms of the salivary glands include oncocytoma,
Warthin tumor, and oncocytic carcinoma. Most salivary lesions with
oncocytic change are benign. Therefore, it is important to distinguish MEC from other entities that may show prominent oncocytic
change.
benign chest wall lesions is mesenchymal hamartoma of the chest
wall, which most commonly presents in neonates or in early infancy.
These lesions are most commonly identified on a routine chest
radiograph, but they can cause respiratory distress secondary to
mass effect. The treatment for a symptomatic mass is wide excision.
Asymptomatic lesions are treated surgically or with observation.
60
Secretory Breast Carcinoma
Surgical Pathology II No. SPII 10-6 (SPII-338)
George Jour, MD, and Nebras Zeizafoun, MD. Department
of Pathology, St Luke’s-Roosevelt Hospital Center, Columbia
University College of Physicians and Surgeons, New York, NY.
Secretory breast carcinoma (SBC) is a rare malignancy. Often
a painless mass at diagnosis, SBC is more common in women than
men. Although most of the reported cases are in adults, it is the most
common breast malignancy in children. Microscopically, microcystic and glandular spaces are filled with eosinophilic periodic acid–
Schiff–positive vacuoles and lined by neoplastic cells with relatively
bland cytologic features. The differential diagnosis includes collagenous spherulosis and acinic cell carcinoma. The absence of myoepithelial marker (SMMS1 and p63) reactivity and the presence of
chromosomal translocation t(12;15)(p13;q25) assist in reaching the
correct diagnosis. Secretory breast carcinoma is a low-grade tumor
with a favorable prognosis. Treatment includes simple mastectomy
or excisional biopsy with negative margins.
61
Histologic Presentation of a Two- and Three-Vessel Umbilical
Cord: A Potential Case of Fused Umbilical Arteries
Surgical Pathology II No. SPII 10-7 (SPII-339)
Douglas W. Lynch, MD, and Wes D. Putnam, MD. Sanford School
of Medicine, University of South Dakota, Sioux Falls.
Cases of both fused umbilical artery (FUA) and single umbilical
artery (SUA) have been documented in the literature. These diagnoses are made by sonographic or histologic examination of the umbilical cord, and the congenital anomaly rate varies in cases of FUA vs
SUA. A correct diagnosis is critical in fetuses suspected of having
either condition. In the case example, a 28-year-old gravida 2 para 1
aborta 1 woman was closely followed sonographically for a 2-vessel
umbilical cord. The neonate was delivered via cesarean section without evidence of congenital anomalies. Gross and microscopic evaluation of the placenta revealed the presence of 3 vessels at the fetal end
and 2 vessels at the placental end of the umbilical cord. A point of
fusion was not identified; however, the clinical and histologic evaluation was most consistent with fused umbilical arteries.
59
Mesenchymal Hamartoma of the Chest Wall
Surgical Pathology II No. SPII 10-5 (SPII-337)
Brooks Smith, MD, and Shadi Qasem, MD. Wake Forest
University Baptist Medical Center, Winston Salem, NC.
A chest wall mass in an asymptomatic child is most commonly
secondary to a normal anatomic variant. Even so, the differential
for a chest wall mass in an infant is broad. Primary abnormalities
of the chest wall in infants include a fractured clavicle, benign bone
lesions, primary bone malignancies, malignant teratoma, congenital
neuroblastoma, and vascular malformations. Among the rare and
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Am J Clin Pathol 2011;135:313-326
62
Clear Cell Papillary Renal Cell Carcinoma and the Differential
Diagnosis of Renal Neoplasms With Clear Cytoplasm and
Papillary Architecture
Surgical Pathology II No. SPII 10-8 (SPII-340)
Sean R. Williamson, MD, and David J. Grignon, MD, FRCP(C).
Department of Pathology and Laboratory Medicine, Indiana
University, and Clarian Pathology Laboratory, Indianapolis.
© American Society for Clinical Pathology
Abstracts of Papers
Clear cell papillary renal cell carcinoma is an interesting renal
neoplasm, recently recognized as distinct from clear cell renal cell
carcinoma (RCC) and papillary RCC. Originally identified in endstage kidneys, tumors have also developed in patients without prior
renal disease and likely are more common than otherwise appreciated. Microscopically, the neoplasm shows branching, folded fibrovascular cores protruding into cystic spaces. Both cysts and papillae
are lined by cuboidal cells with clear cytoplasm and low-grade cytologic features. A distinct pattern of positivity for cytokeratin 7 and
carbonic anhydrase IX, with negativity for alpha-methylacyl-CoA
racemase and CD10 contrasts this lesion to both clear cell and papillary RCC. Molecular and genetic abnormalities also appear distinct.
We examine the differential diagnosis of renal neoplasms with clear
cytoplasm and papillary architecture through the case of a 57-yearold man with a previous diagnosis of clear cell RCC, now presenting
with 2 discrete renal tumors.
63
Bacterial Detection of Platelets
Transfusion Medicine No. TM 10-1 (TM-317)
Marcia D. Haimowitz, MD. American Red Cross Blood Services,
Southern California Region, Pomona.
There are accreditation requirements in the United States for
bacterial detection in platelet components to reduce the risk of transfusion-transmitted sepsis. Methods to detect and limit bacteria in
platelets, data published from US blood centers since implementing
bacterial detection, and issues related to managing donors with positive bacterial results are discussed. Guidance has been developed for
collection facilities, transfusion services, and transfusing physicians
when platelet component with a positive result has been transfused.
Though bacterial detection methods have been introduced, residual
risks remain for septic reactions following platelet transfusion.
64
Warfarin Coagulopathy Monitoring and Treatment Strategies
Transfusion Medicine No. TM 10-2 (TM-318)
Kari-Elise T. Codispoti, MD,1 and Elsie Lee, MD.2 1Johns
Hopkins University School of Medicine, Baltimore, MD; and 2The
George Washington University Medical Center, Washington, DC.
Anticoagulant therapy is widely used in various clinical situations. The vitamin K antagonists, of which warfarin is the most
commonly used, have been the basis for oral anticoagulant regimens.
Despite the broad usage and ample experience with warfarin, it
remains a challenging drug to administer with an increased risk for
bleeding. The discussion briefly reviews the clinical indications and
varied uses of vitamin K antagonists, highlights the role the laboratory plays in monitoring anticoagulation therapy, and reviews the
management and treatment of supratherapeutic anticoagulation.
65
Streptococcus pneumoniae–Induced Hemolytic Uremic
Syndrome and T Activation: Pathogenesis and Treatment
Transfusion Medicine No. TM 10-3 (TM-319)
Christine Moung, MD, Shan Yuan, MD, and Alyssa Ziman, MD.
Department of Pathology and Laboratory Medicine, University of
© American Society for Clinical Pathology
California, Los Angeles, and David Geffen School of Medicine,
Los Angeles.
A nondiarrheal form of hemolytic uremic syndrome (HUS) is
seen in children infected with Streptococcus pneumoniae. A unique
phenomenon called T activation is frequently seen in S pneumoniae–
induced HUS. T activation occurs when neuraminidase, elaborated
by pneumococci, cleaves terminal N-acetylneuraminic acid residues on the surface of RBCs, as well as glomerular epithelial and
endothelial cells. The exposure of the T antigen on RBCs results in
polyagglutinability, while the interaction between autologous naturally occurring anti-T and T antigens on the glomerular epithelial
and endothelial cells is speculated to contribute to the pathogenesis
of S pneumoniae–induced HUS. There may be a role for plasma
exchange to remove autologous anti-T antibodies and reduce levels
of neuraminidase in severe cases.
66
Prenatal Diagnosis and Management of Hemolytic Disease of
the Fetus and Newborn
Transfusion Medicine No. TM 10-4 (TM-320)
Marie Sohsman, MD, Shan Yuan, MD, Alyssa Ziman, MD, and
Qun Lu, MD. David Geffen School of Medicine at UCLA, Los
Angeles, CA.
While RhD immunoglobulin prophylaxis has significantly
decreased the incidence of RhD hemolytic disease of the fetus and
newborn (HDFN), HDFN due to RhD and non-RhD alloantibodies
continues to occur. A type and screen of a 37-year-old gravida 2 para
1 woman at 11 weeks’ gestation demonstrated anti-D, anti-G, and
anti-E alloantibodies with titers of 32, 8, and 4, respectively. After
an episode of mild vaginal bleeding, titers increased significantly for
all 3 antibodies. Doppler ultrasound examination showed a fetus with
hydrops. After multiple intrauterine transfusions, a live infant was
delivered. Strategies for prenatal management of alloimmunization,
methods for monitoring fetal anemia and diagnosing HDFN, and
criteria for starting intrauterine transfusion are discussed. Special
requirements for blood products for intrauterine transfusion are
presented. The case example demonstrates that minor trauma/injury
during pregnancy in a previously alloimmunized woman can cause
severe HDFN, and careful management can successfully prevent
potentially fatal complications.
67
Chagas Disease: A Potential Concern for Transfusion and
Transplantation in the United States
Transfusion Medicine No. TM 10-5 (TM-321)
Brit S. Shackley, MD, Sheeja T. Pullarkat, MD, Diana TanakaMukai, and Qun Lu, MD. David Geffen School of Medicine at
UCLA, Los Angeles, CA.
A case of transplant-associated Chagas disease occurred in
a 64-year-old man with idiopathic dilated cardiomyopathy who
underwent orthotopic cardiac transplantation. The patient initially
did well. Less than 2 weeks following surgery, however, he returned
to the emergency department complaining of acute onset of diarrhea
and intermittent fevers. A routine blood smear showed flagellated
parasites consistent with Trypanosoma cruzi parasitemia. A posttransplantation endomyocardial biopsy showed rare myocardial
fibers containing small round basophilic structures, consistent with
Am J Clin Pathol 2011;135:313-326
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325
Abstracts of Papers
amastigotes of T cruzi. IgG and IgM antibodies for T cruzi remained
negative; however, the polymerase chain reaction result was positive,
indicating recent infection. The organ donor was a Hispanic male
with a history of travel to Guadalajara, Mexico. He was seropositive for T cruzi antibodies by radioimmunoprecipitation assay and
borderline-positive by immunofluorescence assay.
68
Neonatal Alloimmune Thrombocytopenia, Assuring Timely
Diagnosis and Treatment
Transfusion Medicine No. TM 10-6 (TM-322)
Marigny Roberts, MD, and Susan Roseff, MD. Department of
Pathology, Virginia Commonwealth University, Richmond.
Neonatal alloimmune thrombocytopenia (NAIT) is the platelet
equivalent to hemolytic disease of the fetus and newborn. NAIT
is a syndrome characterized by thrombocytopenia and bleeding
in an otherwise healthy infant. It is caused by maternal antibodies
directed against paternally derived antigens present on fetal platelets.
Assuring timely diagnosis and treatment is important to prevent
severe bleeding, especially intracranial hemorrhage and subsequent
neurologic damage. While detection of the offending antibody is
important, treatment must usually proceed prior to full workup.
Postnatal treatment consists of platelet transfusion and administration of intravenous immunoglobulin, while prenatal treatment might
require intrauterine platelet transfusion. The feasibility of prenatal
screening programs continues to be debated.
69
A protocol for complex antibody identification is provided.
The protocol includes a complete RBC phenotype, antibody
screening, selected cell panel testing, neutralization testing, and
differential adsorption of plasma. The prewarm technique, which
determines the clinical significance of typically room-temperature
reactivity, is included. The P1 antigen and related blood group
systems are discussed.
The reactivity of anti-P1 may vary with reagent RBCs, particularly when tested at AHG. The possibility of cold-reactive antibodies
reacting at AHG should be considered when antibody specificity is
not clear-cut.
70
Umbilical Cord Blood: A Hematopoietic Stem Cell Goldmine
Transfusion Medicine No. TM 10-8 (TM-324)
Jennifer Daniel-Johnson, MD,1 and Susan D. Roseff, MD.2 1New
York Presbyterian Hospital, New York, NY; and 2VCU School of
Medicine, Richmond, VA.
Umbilical cord blood transplantation was first successfully performed in 1988 on a 6-year-old boy with Fanconi anemia using his
sibling’s umbilical cord blood (UCB) stem cells. The authors present
the case of a healthy 25-year-old primigravida woman in early labor
who was approached about a UCB donation. The case illustrates
important criteria for eligibility for donation, the process of obtaining informed consent, required testing of maternal and cord blood,
collection methods available, shipping, processing and storage, and
criteria that need to be met for a unit to be banked. Important differences between public and private cord blood banks and ethical issues
in cord blood banking are highlighted.
Confounding Antibody Identification: Don’t Forget the Obvious
Transfusion Medicine No. TM 10-7 (TM-323)
Susanne Bishop, MT(ASCP)SBB, Kerry Burright-Hittner,
MT(ASCP)SBB, and Ramakrishna Reddy, MD. American Red
Cross, Omaha, NE.
A delay in providing blood for transfusion can occur when reactivity is not clear-cut. Most antibody identification protocols detect
clinically significant antibodies reactive at 37°C. Reactivity observed
at the antihuman globulin (AHG) phase of testing, however, might
be due to the presence of an alloantibody reactive preferentially at
room temperature.
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Am J Clin Pathol 2011;135:313-326
© American Society for Clinical Pathology
To advertise, call Terri Berkowitz 847.375.4763 or email tberkowitz@connect2amc.com
DEPARTMENT OF PATHOLOGY,
DIVISION OF ANATOMIC PATHOLOGY
UNIVERSITY OF ALABAMA AT BIRMINGHAM
Academic Surgical Pathologist
Asst/Assoc/Full-Professor applications are invited for a Surgical Pathology
faculty position. The University of Alabama at Birmingham is an outstanding
tertiary care institution currently processing more than 40,000 surgical
pathology specimens per year. The successful candidate will be a dynamic
physician eager to work with a large surgical pathology faculty headed
by Margaret Brandwein-Gensler, M.D. with a rich and diverse program
in diagnostic service, basic, clinical and translational research, and
teaching. Specialized training in GU and/or breast pathology would be a
definite advantage. There is ample opportunity for the teaching of house
staff and undergraduate health professional students and our graduate
[Ph.D], residency and fellowship programs are thriving. Opportunities for
collaborative research abound. Minimum requirements include an M.D.
degree, license to practice in Alabama, and eligibility for board certification
in Anatomic Pathology. Salary, rank, and tenure-status are commensurate
with experience and background.
Interested candidates should submit a cover letter that includes research
interest/experience, curriculum vitae, and the names of three references to
the attention of Gene P. Siegal, MD, Ph.D, Robert W. Mowry Endowed
Professor of Pathology, Director, Division of Anatomic Pathology,
Department of Pathology, University of Alabama at Birmingham,
path-aprecruits@mail.ad.uab.edu. All applications will
be accepted until position is filled.
The University of Alabama at Birmingham is an Affirmative Action/Equal
Opportunity Employer and encourages applications from qualified
women and minorities.
The James J. Peters
VA Medical Center
The James J. Peters VA Medical Center, Bronx NY is a full
service tertiary care hospital,affiliated with the Mt.Sinai School
of Medicine. We currently seek the following candidates:
MEDICAL TECHNOLOGIST (Generalist)
(SIGN ON BONUS)
Must have a BS degree and at least 3 years of demonstrated
experience performing a full range of emergency and nonroutine tests in the areas of chemistry, toxicology, urinalysis,
hematology, bacteriology and blood bank. ASCP or similar
certification required.
MICROBIOLOGIST TECHNOLOGIST
(SIGN ON BONUS)
Must have a BS degree and at least 3 years of demonstrated
experience/training in Molecular Biology techniques, e.g.
Western Blot, Genotyping, PCR, Sequencing etc. with
demonstrated experience in Bacteriology and Immunology
is required. Experience in Virology, Parasitology,
Mycobacteriology, and Mycology are desirable. ASCP or
similar certification required.
Qualifying candidates will receive Competitive Salary &
Benefits package, free parking, and may be eligible for
our (EDRP) Education Debt Reduction Program.
Interested candidates may forward resumes to:
Department of Veterans Affairs
James J. Peters VA Medical Center
Fax: 718-741-4598
Or Email to Cheryl.Carrington@va.gov
U.S. Citizenship is required. The VA is an EOE M/F/V/H.
All Veterans must submit Form DD 214.
DEPARTMENT OF
VETERAN AFFAIRS
© American Society for Clinical Pathology
MEDICAL DIRECTOR, LABORATORY
UNIVERSITY OF ARIZONA
The Department of Pathology at the University of Arizona College of
Medicine is seeking a Medical Director, Laboratory at the Associate or
Full Professor on Clinical Educator or Tenure Track level. The successful
candidate will possess a Doctor of Medicine or Doctor of Osteopathy and
will be board certified in Clinical Pathology or Anatomic Pathology with a
preference of 5 years of experience in a clinical laboratory.
The qualified candidate will be responsible for the overall operation,
leadership, direction, and administration of the Clinical Laboratory. The
successful candidate must be knowledgeable of academic medical settings
and a proven track record of successfully working in such settings.
Service responsibilities may include primary or back up and on-call
duties in specific areas of the laboratory depending on the expertise of the
candidate. Favored areas of expertise include: Cytogenetics, Informatics,
Transfusion Medicine, Molecular Pathology, Chemistry, Point of Care Testing.
The Department of Pathology is seeking an individual who is able
to work with diverse students, trainees and colleagues, and who has
experience with a variety of teaching methods and curricular perspectives.
The Arizona Health Sciences Center includes the Arizona Cancer Center, the
Sarver Heart Center, and the Steele Children’s Research Center, all premier
programs in the Southwest.
Salary is commensurate with experience and academic qualification.
The benefits package is excellent. For more information, see https://www.
uacareertrack.com. Applicants should apply on-line to Job # 46525 and
attach a current Curriculum Vitae.
Applications will be reviewed beginning January 24, 2011,
and will continue until position is filled.
The University of Arizona is an EEO/AA Employer – M/W/D/V
Am J Clin Pathol 2011;135:327 327
THE
PATH OLOGY
TO TREATMENT
BEGINS WITH YOU.
Your expertise has always contributed to an oncologist’s treatment decision.
Recent studies have shown that you now have an even bigger role to play in
advanced non-small cell lung cancer (NSCLC).1
Specialists treating these patients are leaning on you more and more because
of your understanding of tumor histology.
We recognize the value of the work you do and, more importantly, the positive
impact it can have on the lives of so many patients.
Lilly Oncology
Reference: 1. Hirsch FR, et al. J Thorac Oncol. 2008;3(12):1468-1481.
Images Copyright © 2007 Asterand PLC
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SUSPECT AND CONFIRM: PLAY A CRITICAL
ROLE IN THE DIAGNOSIS OF GIST
c-KIT (CD117) STAINING IS ESSENTIAL
GISTs are complex and
a challenge to diagnose
Gastrointestinal stromal tumors (GISTs) are complex
neoplasms with about 4000 to 6000 new cases annually
in the US.1-3 GISTs can occur anywhere along the GI
tract but are usually found in the stomach and small
intestine.4 Variability of symptoms at presentation can
mask GIST and lead to misdiagnosis.5-7
Cell morphology alone is insufficient
for a diagnosis of GIST — c-KIT staining
is confirmatory
About 95% of GISTs stain positive for the c-KIT (CD117)
protein.4,11 The KIT staining pattern is usually cytoplasmic,
although a globular/dot-like perinuclear or membranous
appearance may be seen.3,12,13
Contributing to the complexity and misidentification
of GIST is its microscopic appearance, which often
overlaps with other GI cancers.5,8 GISTs exhibit 2 major
histologic cell types: spindle cells (70%) and
epithelioid (20%). Others have mixed morphology.3
Cytoplasmic
Globular/dot-like
Membranous
Images courtesy of Brian Rubin, MD, PhD, Cleveland Clinic.
Assessment of prognostic factors is necessary4
Spindle cell (70%)3,9
Prognostic factors in GIST include mitotic rate, tumor size
and location, tumor rupture, and mucosal invasion.4,6,7
Epithelioid (20%)3,9
Reprinted from Am J Pathol 1998, 152:1259-1269 with permission
from the American Society for Investigative Pathology.9
GISTs have malignant potential, making
early diagnosis pivotal in management
GISTs should not automatically be considered benign.3
Once GISTs become metastatic or have recurred, prognosis
is poor.4,10 Therefore, diagnosis of GIST at early stages and
proactive follow-up may influence patient outcomes.
Accurate mitotic rate is a critical piece of information
obtained during the microscopic evaluation and may
play an important role in patient management decisions
made by the multidisciplinary team.7 NCCN recommends
a multidisciplinary approach in managing GIST.4
To assess the mitotic rate, the CAP Protocol recommends
counting the number of mitoses in 50 high-power fields
(HPFs) totaling 5 mm2.14*
Playing an active role in early diagnosis may influence patient outcomes
■
Always consider GIST in the evaluation
■
Test for c-KIT (CD117) and assess key prognostic factors
■
Collaborate with the multidisciplinary team
Stay up-to-date on the CAP Cancer Protocol for GIST at http://www.cap.org.
The College of American Pathologists Cancer Protocols are a resource to pathologists to aid in
effectively reporting surgical pathology findings necessary to provide quality patient care. The
CAP electronic Cancer Checklists (CAP eCC) offer a standardized way to manage information
and report cancer data electronically.
* It is important to note that the CAP Protocol indicates that the required total count of mitoses is per 5 mm2 on the glass slide section. With the use of older model microscopes, 50 HPF is equivalent to
5 mm2. Most modern microscopes with wider 40X lenses/fields require only 20 HPFs to embrace 5 mm2. If necessary, please measure field of view to accurately determine actual number of fields
required to be counted on individual microscopes to count 5 mm2.14
References: 1. What are the key statistics about gastrointestinal stromal tumors? American Cancer Society (ACS) Web site. http://www.cancer.org. Updated August 24, 2010. Accessed October 29,
2010. 2. Blanke C, Eisenberg BL, Heinrich M. Epidemiology of GIST. Am J Gastroenterol. 2005;100(10):2366. 3. Fletcher CDM, Berman JJ, Corless C, et al. Diagnosis of gastrointestinal stromal tumors:
a consensus approach. Hum Pathol. 2002;33(5):459-465. 4. The NCCN Soft Tissue Sarcoma Clinical Practice Guidelines in Oncology (Version 2.2010). ©2010 National Comprehensive Cancer
Network, Inc. http://www.nccn.org. Accessed April 15, 2010. To view the most recent and complete version of the guidelines, go online to www.nccn.org. 5. Demetri GD. Gastrointestinal stromal
tumors. In: DeVita VT Jr, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. Vol 1. 8th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2008:
1204-1217. http://www.cancerppo8.com. Accessed November 15, 2010. 6. Sepe PS, Brugge WR. A guide for the diagnosis and management of gastrointestinal stromal cell tumors. Nat Rev
Gastroenterol Hepatol. 2009;6(6):363-371. 7. Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of
1765 cases with long-term follow-up. Am J Surg Pathol. 2005;29(1):52-68. 8. Nickl NJ. Gastrointestinal stromal tumors: new progress, new questions. Curr Opin Gastroenterol. 2004;20(5):482-487.
9. Kindblom L-G, Remotti HE, Aldenborg F, Meis-Kindblom JM. Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial
cells of Cajal. Am J Pathol. 1998;152(5):1259-1269. 10. DeMatteo RP, Lewis JJ, Leung D, Mudan SS, Woodruff JM, Brennan MF. Two hundred gastrointestinal stromal tumors: recurrence patterns and
prognostic factors for survival. Ann Surg. 2000;231(1):51-58. 11. Joensuu H. Current perspectives on the epidemiology of gastrointestinal stromal tumours. Eur J Cancer Suppl. 2006;4(suppl 1):4-9.
12. Corless CL, Heinrich MC. Molecular pathobiology of gastrointestinal stromal sarcomas. Annu Rev Pathol. 2008;3:557-586. 13. Rubin BP, Blanke CD, Demetri GD, et al; for the Members of the Cancer
Committee, College of American Pathologists. Protocol for the examination of specimens from patients with gastrointestinal stromal tumor. Arch Pathol Lab Med. 2010;134(2):165-170. 14. Protocol for the
Examination of Specimens From Patients With Gastrointestinal Stromal Tumor (GIST). ©2010 College of American Pathologists. http://www.cap.org. Published October 8, 2010. Accessed October 26, 2010.
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