bluuebunny/crossref_metadata_2025 huggingface dataset:
Clear Cell Adenocarcinoma of the Urinary Bladder: A Short Review
Authors: Adeniran Adebowale J. , Tamboli Pheroze
Published: February 2021

In this short review, we discuss clear cell adenocarcinoma of the urinary bladder, a rare tumor that primarily affects women. The histogenesis of this neoplasm is uncertain; in some tumors the clinicopathologic and histologic features are suggestive of a müllerian origin. Clear cell adenocarcinoma consists of cells with abundant clear cytoplasm, arranged in solid, glandular, or tubulocystic patterns. These tumors are positive for pancytokeratin, cytokeratin 7, and CA 125 immunohistochemical stains. Patients typically present with gross hematuria, dysuria, and discharge. The natural history is poorly understood and patient outcomes remain unclear. Currently, surgery is the treatment of choice. Nephrogenic adenoma is the most important differential diagnostic consideration, followed by metastatic clear cell carcinoma.
Nonneoplastic Kidney Diseases in Adult Tumor Nephrectomy and Nephroureterectomy Specimens: Common, Harmful, Yet Underappreciated
Authors: Henriksen Kammi J. , Meehan Shane M. , Chang Anthony
Published: February 2021

Context.—Nonneoplastic kidney diseases, such as arterionephrosclerosis and/or diabetic nephropathy, are commonly encountered in tumor nephrectomy and nephroureterectomy specimens. Although any nonneoplastic kidney disease may be encountered in these resection specimens by chance, additional diseases that may be related to the underlying neoplasm or its treatment regimen include thrombotic microangiopathy, Amyloid A amyloidosis, membranous nephropathy, immunoglobulin A nephropathy, membranoproliferative glomerulonephritis, pauci-immune crescentic glomerulonephritis, focal segmental glomerulosclerosis, minimal-change disease, acute interstitial nephritis, and xanthogranulomatous pyelonephritis. Given the morbidity of chronic kidney disease and the relatively favorable 5-year survival rates for urothelial and renal cell carcinomas, accurate evaluation of the nonneoplastic kidney parenchyma is important.

Objectives.—We will discuss our approach for evaluating the nonneoplastic kidney parenchyma in tumor nephrectomy and nephroureterectomy specimens. The pathologic features of the aforementioned kidney diseases as well as pertinent references will be reviewed. The identification of glomerular abnormalities, including mesangial sclerosis or hypercellularity, segmental sclerosis, crescent formation, glomerulitis, or glomerular basement membrane alterations, should lead to additional immunofluorescence and electron microscopic studies. Safeguards to ensure that the nonneoplastic parenchyma is not overlooked include adding this important parameter to synoptic reports and obtaining periodic acid–Schiff and/or Jones methenamine silver stains prior to microscopic evaluation of the neoplasm.

Data Sources.—Relevant literature and University of Chicago Medical Center pathology archives.

Conclusions.—The practicing surgical pathologist should be aware of the importance of both correctly classifying the resected renal or urothelial neoplasm and the concomitant nonneoplastic kidney disease that may be present in these specimens.
Molecular Biology Underlying the Clinical Heterogeneity of Prostate Cancer: An Update
Authors: Mackinnon A. Craig , Yan Benjamin C. , Joseph Loren J. , Al-Ahmadie Hikmat A.
Published: February 2021

Context.—Recent studies have uncovered a number of possible mechanisms by which prostate cancers can become resistant to systemic androgen deprivation, most involving androgen-independent reactivation of the androgen receptor. Genome-wide expression analysis with microarrays has identified a wide array of genes that are differentially expressed in metastatic prostate cancers compared to primary nonrecurrent tumors. Recently, recurrent gene fusions between TMPRSS2 and ETS family genes have been identified and extensively studied for their role in prostatic carcinoma.

Objective.—To review the recent developments in the molecular biology of prostate cancer, including those pertaining to the androgen receptor and the newly identified TMPRSS2-related translocations.

Data Sources.—Literature review and personal experience.

Conclusions.—Prostatic adenocarcinoma is a heterogeneous group of neoplasms with a broad spectrum of pathologic and molecular characteristics and clinical behaviors. Numerous mechanisms contribute to the development of resistance to androgen ablation therapy, resulting in ligand-independent reactivation of the androgen receptor, including amplification, mutation, phosphorylation, and activation of coreceptors. Multiple translocations of members of the ETS oncogene family are present in approximately half of clinically localized prostate cancers. TMPRSS2:ERG gene rearrangement appears to be an early event in prostate cancer and is not observed in benign or hyperplastic prostatic epithelium. Duplication of TMPRSS2:ERG appears to predict a worse prognosis. The relationship between TMPRSS2:ERG gene rearrangement and other morphologic and prognostic parameters of prostate cancer is still unclear.
Recent Developments in Liver Pathology
Authors: Yan Benjamin C. , Hart John A.
Published: February 2021

Context.—Hepatocellular carcinoma is the sixth most common malignancy and the third leading cause of cancer deaths worldwide, making pathologic identification of precursor lesions essential. Recent molecular genetic, pathologic, and clinical data have led to the stratification of hepatic adenomas into subgroups with unique molecular profiles and varying potential for malignant transformation, as well as to the reclassification of telangiectatic focal nodular hyperplasia as telangiectatic adenoma. Clinical, morphologic, and molecular genetic studies have also established juvenile hemochromatosis and pediatric nonalcoholic steatohepatitis as entities distinct from their adult counterparts.

Objective.—To review the recent molecular genetic characterization of telangiectatic hepatic adenomas and juvenile hemochromatosis, as well as the recent clinicopathologic characterization of pediatric nonalcoholic steatohepatitis.

Data Sources.—Literature review, personal experience, and material from the University of Chicago.

Conclusions.—Basic science and translational research have led to the classification of many pathologic entities of the liver according to molecular genetic and protein expression profiles that correspond to traditional morphologic categories. Insights into signal transduction pathways that are activated in, and protein expression patterns unique to, an individual disease may lead to the development of new therapeutic agents and novel diagnostic biomarkers.
Proceedings of the Consensus Meetings From the International Retinoblastoma Staging Working Group on the Pathology Guidelines for the Examination of Enucleated Eyes and Evaluation of Prognostic Risk Factors in Retinoblastoma
Authors: Sastre Xavier , Chantada Guillermo L. , Doz François , Wilson Matthew W. , de Davila Maria T. G. , Rodríguez-Galindo Carlos , Chintagumpala Murali , Chévez-Barrios Patricia
Published: February 2021

Retinoblastoma is the most common intraocular malignant childhood tumor in need of prospective clinical trials to address important unanswered questions about biology, treatment, and prognostic factors. Currently, there is controversy about the definitions for choroidal invasion and an inconsistency in the handling of eyes with retinoblastoma. The International Retinoblastoma Staging Working Group (IRSWG) composed of 58 participants from 24 countries on 4 continents had a series of Internet meetings to discuss the staging and tissue handling guidelines to reach consensus for adequate processing, establishing definitions of histopathologic risk factors, and reporting of enucleated eyes with retinoblastoma to serve as the basis for clinical trials and studies to validate the proposed criteria. The meetings were facilitated by the International Outreach Program of the St. Jude Children's Research Hospital through Cure4Kids. The retinoblastoma guidelines from the Children's Oncology Group, the French Society for Pediatric Cancers, the Association of Directors of Anatomic and Surgical Pathology, and some published data were the basis for this consensus document. Discussions of the feasibility, practicality, and efficacy of the guidelines and criteria resulted in this report. The consensus definitions reached included definition of massive choroidal invasion stated as a maximum diameter of invasive tumor focus of 3 mm or more that may reach the scleral tissue. Focal choroidal invasion is defined as a tumor focus of less than 3 mm and not reaching the sclera. Optic nerve invasion is classified as prelaminar, laminar, retrolaminar, or tumor at surgical margin, and the measurement of the depth of invasion should also be recorded. These guidelines also address handling of the enucleated eye with retinoblastoma in an efficient, practical, and feasible manner for a meaningful diagnosis. The consensus criteria reached by the IRSWG should be validated through prospective clinical trials and studies.
High-Risk Features and Tumor Differentiation in Retinoblastoma: A Retrospective Histopathologic Study
Authors: Eagle Jr Ralph C.
Published: February 2021

Context.—Certain histopathologic risk factors in enucleated eyes are important indicators for adjuvant chemotherapy in patients with retinoblastoma.

Objectives.—To determine the frequency of histopathologic risk factors in a large series of retinoblastomas treated by enucleation on file in the pathology laboratory of a large American eye hospital, assess the relationship between tumor differentiation and age at enucleation, and investigate the frequency of photoreceptor differentiation and the role of retinoma/retinocytoma as retinoblastoma precursor.

Design.—Retrospective histopathologic review of 387 eyes with retinoblastoma treated by enucleation including 297 with no prior treatment.

Results.—Fifty-five of 297 untreated eyes (18.5%) had high-risk features. Retrolaminar optic nerve invasion was present in 31 (10.4%), and 24 (8.1%) had massive uveal invasion (defined as >3 mm in diameter). Of the high-risk eyes, 70.9% had iris neovascularization and 60% had neovascular glaucoma. There was a statistically significant inverse relationship between age at enucleation and the degree of tumor differentiation, evidenced by the presence of rosettes. Tumors in older children tended to be poorly differentiated, while rosettes were often numerous in the tumors of younger infants. In all, 20.4% of tumors contained foci of photoreceptor differentiation, which localized in the base of a predominantly endophytic tumor in about one-fourth. Lack of correlation between photoreceptor differentiation and age at enucleation is consistent with early or prenatal malignant transformation. Both preceding observations provide evidence for the hypothetical role of retinoma as a retinoblastoma precursor.

Conclusions.—Slightly less than 1 in 5 infants with retinoblastoma treated by enucleation at a large American eye hospital would require adjuvant chemotherapy on the basis of existing high-risk histopathologic features. Retinoblastomas become progressively less differentiated with time and may be spawned by precursor retinomas.
Primary Intraocular Lymphoma
Authors: Faia Lisa J. , Chan Chi-Chao
Published: February 2021

Primary intraocular lymphoma, recently suggested to be renamed primary retinal lymphoma, is a subset of primary central nervous system lymphoma and is usually an aggressive diffuse large B-cell lymphoma. Between 56% and 85% of patients who initially present with primary intraocular lymphoma alone will develop cerebral lesions. Patients typically complain of decreased vision and floaters, most likely secondary to the chronic vitritis and subretinal lesions. The diagnosis of primary intraocular lymphoma can be difficult to make and requires tissue for diagnosis. The atypical lymphoid cells are large and display a high nuclear to cytoplasmic ratio, prominent nucleoli, and basophilic cytoplasm. Flow cytometry, immunohistochemistry, cytokine analysis, and gene rearrangements also aid in the diagnosis. Local and systemic treatments, such as chemotherapy and radiation, are employed, although the relapse rate remains high.
Prognostic Value of E-Cadherin, β-Catenin, CD44v6, and HER2/neu in Metastatic Cutaneous Adenocarcinoma
Authors: Pozdnyakova Olga , Hoang Mai M. P. , Dresser Karen A. , Mahalingam Meera
Published: February 2021

Context.—Our recent experience with a patient developing cutaneous metastases within 3 months of diagnosis of esophageal adenocarcinoma suggests that altered expression of the cellular adhesion molecules, E-cadherin and CD44v6, may have had a role to play in the rapid onset of metastases.

Objective.—To corroborate these findings, we designed a cross-sectional study to investigate the expression of select molecules involved in the metastatic cascade.

Design.—E-cadherin, β-catenin, CD44v6, and HER2/neu immunohistochemical stains were performed on archival materials of metastatic adenocarcinoma to the skin from 27 patients and the available corresponding primary tumors in 10 patients. The primary sites included breast (n = 10; 37%), gastrointestinal tract (n = 10; 37%), ovary (n = 1; 4%), thyroid (n = 2; 7%), lung (n = 1; 4%), and unknown primary (n = 3; 11%).

Results.—Expression of all markers was noted with the most significant increases observed in β-catenin (26 of 27 cases; 96%), followed by CD44v6 (24 of 27 cases; 89%), E-cadherin (22 of 27 cases; 82%), and HER2/neu (11 of 27 cases; 41%). Contrasting expression of these molecules in the primary versus the metastatic tumors, enhanced expression of CD44v6 was observed in the cutaneous metastases relative to the primary in 6 of 10 (60%) cases. Of interest, 2 of these 6 cases (33%) also showed reduction in E-cadherin—a member of the cadherin family functioning as an invasion suppressor molecule.

Conclusions.—These findings reinforce the complexities of the metastatic cascade and imply that the variation in adhesive properties of tumor cells is, perhaps, a consequence of the difference in density of the molecules mediating this process.
Evaluation of Microbiologic and Hematologic Parameters and E-Selectin as Early Predictors for Outcome of Neonatal Sepsis
Authors: El Sayed Zaki Maysaa , El Sayed Hesham
Published: February 2021

Context.—Early diagnosis of neonatal sepsis is mandatory. Various markers are used to diagnose the condition.

Objective.—To evaluate the diagnostic value of various clinical data and hematologic parameters, such as total leukocyte count, absolute neutrophil count, immature to total neutrophil ratio, and soluble E-selectin (sE-selectin) in identification and outcome of neonatal sepsis.

Design.—Newborn infants with a clinical diagnosis of sepsis in the neonatal intensive care unit at Mansoura University Children's Hospital during the period between July 2007 and December 2007 were eligible for study. In addition, 30 healthy neonates were included in the study. Complete hematologic and microbiologic laboratory investigations were performed, and serum E-selectin was measured.

Results.—Plasma sE-selectin levels were significantly higher (P < .001) in infected infants (mean [SD], 156.9 [77.0] ng/mL) than in noninfected (mean [SD], 88.8 [47.1] ng/mL) and healthy infants (mean [SD], 8.67 [3.74] ng/ mL). Infants with gram-negative sepsis had higher sE-selectin levels than did those with gram-positive sepsis (P = .04). C-reactive protein was the best laboratory test for diagnosis of neonatal sepsis, with an overall sensitivity and specificity of 86% and 97%, respectively. Performing sE-selectin with C-reactive protein or immature to total ratio tests increased the specificity, but reduced the sensitivity, of the tests for the determination of neonatal sepsis. Plasma sE-selectin levels were higher in nonsurvivors than in survivors (P = .01) and were higher in those with hemodynamic dysfunction than in those without hemodynamic dysfunction (P < .001).

Conclusions.—We conclude that plasma sE-selectin levels are elevated in neonatal sepsis. Significant elevation was associated with gram-negative sepsis. Plasma sE-selectin had low diagnostic value when used alone or in combination with other tests; however, it can be used as a prognostic indicator for the outcome of neonatal sepsis.
Arteriosclerosis: Rethinking the Current Classification
Authors: Fishbein Gregory A. , Fishbein Michael C.
Published: February 2021

Context.—Arteriosclerosis is the vascular disease that is the leading cause of mortality in industrialized countries. Currently, there are 3 lesions within the broader category of arteriosclerosis: atherosclerosis, Mönckeberg medial calcific sclerosis, and arteriolosclerosis.

Objective.—In this review, we discuss the history of the terminology and current classification of arteriosclerosis and problems with the current classification. We also discuss recently described new arterial lesions that are not in the current classification.

Data Sources.—In spite of the prevalence and importance of arteriosclerotic vascular disease, and the widespread use of the current terminology, there are major problems with the current classification: (1) the current classification has an inconsistent naming convention, (2) the classification fails to use terms that accurately describe the lesions, and (3) important arterial lesions are absent from the classification. In addition, although the terms arteriosclerosis and atherosclerosis describe different lesions, these terms are often used interchangeably.

Conclusion.—Consideration should be given for a new more inclusive and accurate classification of “arteriosclerotic” lesions that more accurately reflects the pathology of these important vascular lesions.
Pseudoangiomatous Stromal Hyperplasia of the Breast
Authors: AbdullGaffar Badr
Published: February 2021

Pseudoangiomatous stromal hyperplasia is a relatively common lesion of the breast. In general, it is less commonly found as a clinically palpable mass and is more commonly found as incidental microscopic foci. It is a benign proliferative, probably neoplastic, hormonally driven process of the mammary stromal myofibroblasts. The clinical, radiologic, and cytologic findings can resemble those of fibroadenoma. Histologically, it can be confused with low-grade angiosarcoma. The exact etiology of pseudoangiomatous stromal hyperplasia is still controversial, but a neoplastic process of the stromal myofibroblasts, with a hormonal stimulus in its development and progression, is the favored theory. Most lesions can be cured by complete surgical excision, and patients undergoing the excision have a good prognosis.
Rare Nerve Lesions of Non–Nerve Sheath Origin: A 17-Year Retrospective Series
Authors: Strom Tobin , Kleinschmidt-DeMasters Bette K. , Donson Andrew , Foreman Nicholas K. , Lillehei Kevin O.
Published: February 2021

Context.—Peripheral nerve masses are frequently encountered in surgical pathology practice. However, once a peripheral nerve mass is determined not to be a nerve sheath neoplasm, differential diagnostic considerations drop off sharply.

Objective.—To review our experience with surgically resected nerve masses.

Design.—Retrospective search of pathology database. Rare neoplasms were studied by cytogenetic analysis or gene microarray.

Results.—Four hundred fifty-eight cases were identified. After elimination of common lesions (mostly nerve sheath tumors), 37 cases (8%) remained, almost all of which were of non–nerve sheath origin: for example, hemangioma, metastatic neuroendocrine pancreatic carcinoma, meningiomas invading nerve fascicles, and primary extrarenal rhabdoid tumor and Ewing sarcoma of nerve. The latter showed rearrangement of the EWSR1 locus (22q12). The gene expression pattern of an undifferentiated sarcoma, presenting as ropelike nerve enlargement, clustered with malignant peripheral nerve sheath neoplasms but not other sarcomas or neuroepithelial tumors.

Conclusions.—Diverse benign and malignant conditions can affect peripheral nerve.
Crossword Puzzles: Active Learning in Undergraduate Pathology and Medical Education
Authors: Saxena Anurag , Nesbitt Raenelle , Pahwa Punam , Mills Sheryl
Published: February 2021

Context.—Second-year medical students are introduced to many new terms and concepts in a short time frame in the hematology system and the neoplasia section of the undergraduate pathology course. It is a challenge to provide adequate practice and necessary repetition to reinforce key concepts.

Objective.—To determine student perceptions of the usefulness of crosswords as a quick and effective way to reinforce essential concepts and vocabulary.

Design.—Crosswords with ensured content validity built on a free Internet resource were completed by the students in collaborative and cooperative groups of 6 to 7 with a reward for the first group to successfully complete the puzzle. Student perceptions of the value of crosswords for their learning were examined in 2003 (39 students) with a survey of yes or no responses and in 2004 (41 students) with a survey using questions with a 5-point Likert scale.

Results.—Many students (37 of 39 in 2003 and 24 of 41 in 2004) indicated that crosswords were useful and contributed to their learning. Specifically, crosswords were found to be useful for identifying key concepts and vocabulary and for their collaborative and competitive aspects. Written and informal comments indicated student enthusiasm for and a desire to participate in more of these exercises. Students have transferred this review strategy to other classes and the peer teachers have expressed an interest in it as an adjunct teaching tool.

Conclusions.—The judicious use of crosswords was useful for near transfer content and provided an opportunity to discuss and recall essential concepts, think critically, and collaborate in small groups.
Mixed Adenocarcinomas of the Lung: Place in New Proposals in Classification, Mandatory for Target Therapy
Authors: Chilosi Marco , Murer Bruno
Published: February 2021

Context.—Lung cancer is one of the most frequent and lethal malignant neoplasms, but knowledge regarding the molecular basis of its pathogenesis is far from complete due to the striking diversity of different forms. The current lung cancer classification (World Health Organization 2004) can efficiently distinguish clinically relevant major subtypes (small cell and non–small cell carcinomas), but its results are partly inadequate when facing prognostic and therapeutic decisions for non–small cell carcinomas, especially for the group of tumors classified as adenocarcinoma. Lung adenocarcinoma comprises a heterogeneous group of tumors characterized by diverse morphologic features and molecular pathogenesis. The category of mixed adenocarcinomas includes most adenocarcinomas (approximately 80%) and, according to World Health Organization criteria, is defined by the occurrence of a mixed array of different patterns (acinar, papillary, bronchioloalveolar, solid with mucin). The histologic recognition of mixed adenocarcinoma is subjective and cannot consistently discriminate between responders and nonresponders to new targeted therapies (eg, tyrosine kinase inhibitors). Diagnostic problems are mainly related to the poor reproducibility of histologic criteria, especially when applied in small biopsies and cytology, and to the difficulty in assigning each form to a precisely defined entity, as needed by updated therapeutic approaches. In this evolving scenario, pathologists face new challenging diagnostic roles that include not only the precise morphologic definition of carcinoma subtypes but also their molecular characterization.

Objective.—To use a comprehensive critical analysis reconciling the overwhelming variety of biologic, morphologic, molecular, and clinical data to define new classification schemes for lung adenocarcinoma.

Data Sources.—Scientific literature and personal data were used.

Conclusions.—A new classification approach should redefine lung adenocarcinoma heterogeneity reconciling classic morphology, immunophenotypic and molecular features of neoplastic cells, and also relevant information provided by stem cell biology. This approach, which has been already successfully applied in World Health Organization classification of other tumors, could improve the recognition of new reproducible profiles for adenocarcinomas, more closely and reproducibly related to clinical features and response to specific therapies, limiting the use of “wastebasket” categories such as mixed adenocarcinoma.
Orthokeratinized Odontogenic Cyst: A Clinicopathologic Study of 61 Cases
Authors: Dong Qing , Pan Shuang , Sun Li-Sha , Li Tie-Jun
Published: February 2021

Context.—Orthokeratinized odontogenic cyst (OOC) is a relatively uncommon developmental cyst comprising about 10% of cases that had been previously coded as odontogenic keratocysts. Odontogenic keratocyst was designated as keratocystic odontogenic tumor (KCOT) in the new World Health Organization classification and OOC should be distinguished from KCOT for differences in histologic features and biologic behavior.

Objective.—To analyze the clinicopathologic features of 61 cases of OOC in a Chinese population.

Design.—Clinicopathologic analysis was performed on 61 cases of OOC. Immunohistochemical expression of Ki-67 and p63 was evaluated in 15 OOCs and 15 typical KCOTs.

Results.—The 61 patients with OOC ranged from 13 to 75 years (average, 38.93 years). The lesions developed mainly in the third and fourth decades (57.38%) with a distinct predilection for males (72.13%). Six (9.84%) lesions were found in the maxilla and 55 (90.16%) in the mandible. The most common sites were in the mandibular molar and ramus region. Of the 54 cases with radiographic record, 47 (87.04%) were unilocular and 7 (12.96%) were multilocular radiolucencies. Twenty-seven of the 54 cysts were associated with an impacted tooth. Follow-up of 42 patients revealed no recurrence during an average period of 76.8 months after surgery. Compared with KCOTs, expression level of Ki-67 and p63 was significantly lower in OOCs, suggesting a lower proliferative activity.

Conclusion.—Orthokeratinized odontogenic cyst is clinicopathologically distinct from KCOT and should constitute its own clinical entity.
Practices of Participants in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology, 2006
Authors: Eversole Galen M. , Moriarty Ann T. , Schwartz Mary R. , Clayton Amy C. , Souers Rhona , Fatheree Lisa A. , Chmara Beth A. , Tench William D. , Henry Michael R. , Wilbur David C.
Published: February 2021

Context.—Liquid-based preparations (LBPs) and human papillomavirus testing have led to changes in cervical cytology practices. The College of American Pathologists attempts to track practice patterns using a supplemental questionnaire, which allows laboratories to report diagnostic practices.

Objective.—To analyze the 2006 reporting practices and to compare the results with the 2003 survey data.

Design.—Questionnaire was mailed to 1621 laboratories. Participants included laboratories enrolled in the 2006 College of American Pathologists Gynecologic Proficiency Testing Program or the educational Interlaboratory Comparison Program in Gynecologic Cytology.

Results.—Of the 679 responding laboratories (response rate, 42%), most (97.8%; n  =  664) had implemented the Bethesda 2001 terminology. The median rate for all preparations with low-grade squamous intraepithelial lesions was 2.5% (2.9% for LBPs) compared with a 2003 median rate of 2.1%; the increase was confined to LBPs. Rates for high-grade squamous intraepithelial lesions (median, 0.5%) and atypical squamous cells have changed little. High-grade squamous intraepithelial lesions and unsatisfactory rates varied at statistically significant levels between types of LBPs. Most atypical squamous cell cases were subclassified as undetermined significance (median, 4.3%). The median ratio of atypical squamous cells to squamous intraepithelial lesions and carcinomas for all specimen types combined was 1.5, similar to the 2003 median ratio of 1.4. The median rates for findings of squamous cell abnormalities for 2006 were significantly higher for LBPs than for conventional smears.

Conclusions.—Most responding laboratories have implemented the Bethesda 2001 terminology. There is an increase in LBP low-grade squamous intraepithelial lesion rates when compared with 2003 data. Liquid-based preparations have higher median squamous intraepithelial lesion and atypical squamous cell rates.
Pseudoneoplastic Lesions: General Considerations
Authors: Wick Mark R. , Tazelaar Henry D.
Published: February 2021

Pseudoneoplastic lesions (“pseudotumors”) can be seen in virtually all anatomic locations. Some organ sites, such as the lungs and skin, are overrepresented for unknown reasons, and the histologic images seen in pseudoneoplastic lesions are partially overlapping in disparate locations. More than occasionally, the degree of histologic likeness to true neoplasms—often malignant ones—is striking. This overview outlines the spectrum of pseudoneoplastic lesions and divides them into etiologic categories, including reparative, developmental, functional (usually endocrine), iatrogenic, infectious, and idiopathic. Side-by-side pictorial comparisons of selected pseudoneoplastic lesions and their neoplastic mimics are included.
Cardiovascular Pseudoneoplasms
Authors: Miller Dylan V. , Tazelaar Henry D.
Published: February 2021

Context.—Primary cardiac tumors are rare and the great majority are benign neoplasms. Mass-forming reactive and pseudoneoplastic growths are less common, but recognizing and distinguishing these lesions from the neoplasms they resemble is critical to appropriate patient care.

Objective.—The general clinical, imaging, gross pathologic, and histologic features of 5 important pseudoneoplasms (inflammatory myofibroblastic tumor, hamartoma of mature cardiac myocytes, mesothelial/monocytic cardiac excrescences, calcified amorphous tumor, and lipomatous hypertrophy of the atrial septum) are discussed, with an emphasis on features differentiating them from other benign and malignant tumors.

Data Sources.—Pertinent citations of the literature and observations from the authors' experience are drawn upon.

Conclusions.—While lacking malignant potential, these lesions can be associated with considerable morbidity and occasional mortality. Their recognition is important in guiding patient management, providing both guidance for appropriate therapy and avoidance of inappropriately aggressive and toxic treatments.
Amyloidosis—Where Are We Now and Where Are We Heading?
Authors: Picken Maria M.
Published: February 2021

Context.—Amyloidoses are disorders of diverse etiology in which deposits of abnormally folded proteins share distinctive staining properties and fibrillar ultrastructural appearance. Amyloidosis ultimately leads to destruction of tissues and progressive disease. With recent advances in the treatment of systemic amyloidoses the importance of an early diagnosis of amyloid, and a correct diagnosis of its type, has been realized.

Objective.—To summarize current recommendations for the diagnosis of amyloidosis.

Data Sources.—Presentation given at the 4th Annual Renal Pathology Society Satellite meeting in Istanbul based on discussions and recommendations formulated during an interactive diagnostic session held at the XIth International Symposium on Amyloidosis in Woods Hole, Massachusetts.

Conclusions.—Congo red stain is currently the gold standard for amyloid detection and the goal is to detect amyloid early. Diagnosis of the amyloid type must be based on the identification of amyloid protein within the deposits and not solely by reliance on clinical or DNA studies. However, the latter are recommended for confirmation of the amyloid type based on evaluation of the protein in deposits. Immunohistochemistry must be performed and interpreted with caution and inconclusive results must be evaluated further using the more sophisticated methods available in referral centers. An adequate amount and quality of tissue must be available for amyloid diagnosis and typing with emphasis on the use of fresh tissue and greater use of abdominal fat biopsy. The development of new technologies underscores the need for regular review of recommendations and standards for the clinical diagnosis of amyloidosis.
The Classification of Renal Cystic Diseases and Other Congenital Malformations of the Kidney and Urinary Tract
Authors: Bonsib Stephen M.
Published: February 2021

Context.—Renal cystic diseases and congenital abnormalities of the kidney and urinary tract comprise a heterogeneous group of lesions whose pathogenesis has eluded physicians for centuries. Recent advances in molecular and genetic understanding of these diseases may provide the solution to this riddle.

Objective.—The formulation of an effective classification system for these disorders has been elusive but is needed to introduce order while providing a conceptual framework for diagnosis.

Data sources.—This review discusses the evolution, beginning in the 19th century, of postulates regarding the pathogenesis of cystic and developmental renal diseases. Selected classification systems proffered during this period are discussed in pursuit of an ideal classification schema that would account for morphologic features and their clinical importance, with logical links to pathogenesis and treatment. Although this remains an elusive target, its general outline is becoming clearer. A classification approach favored by the author is presented, which incorporates many of the strengths contained in several previous classifications.

Conclusions.—Genetic-and molecular-based postulates regarding the pathogenesis of the renal cystic and developmental diseases have implicated mutated master genes and the modification of genes that are crucial in renal development and genes that are central to the sensory effects of the renal tubular primary cilium on cell physiology. These scientific advances provide pathogenetic links between morphologically and genetically distinct entities and certain cystic and neoplastic entities, associations that seemed implausible not long ago. These advances may eventually provide the basis for future classification systems while suggesting targets for therapeutic approaches in the prevention and treatment of these diseases.
Granulomatous Lung Disease: An Approach to the Differential Diagnosis
Authors: Mukhopadhyay Sanjay , Gal Anthony A.
Published: February 2021

Context.—Granulomas are among the most commonly encountered abnormalities in pulmonary pathology and often pose a diagnostic challenge. Although most pathologists are aware of the need to exclude an infection in this setting, there is less familiarity with the specific histologic features that aid in the differential diagnosis.

Objective.—To review the differential diagnosis, suggest a practical diagnostic approach, and emphasize major diagnostically useful histologic features. This review is aimed at surgical pathologists who encounter granulomas in lung specimens.

Data sources.—Pertinent recent and classic peer-reviewed literature retrieved from PubMed (US National Library of Medicine) and primary material from the institutions of both authors.

Conclusions.—Most granulomas in the lung are caused by mycobacterial or fungal infection. The diagnosis requires familiarity with the tissue reaction as well as with the morphologic features of the organisms, including appropriate interpretation of special stains. The major noninfectious causes of granulomatous lung disease are sarcoidosis, Wegener granulomatosis, hypersensitivity pneumonitis, hot tub lung, aspiration pneumonia, and talc granulomatosis.
Interpretation and Utility of Drug of Abuse Immunoassays: Lessons From Laboratory Drug Testing Surveys
Authors: Melanson Stacy E. F. , Baskin Leland , Magnani Barbarajean , Kwong Tai C. , Dizon Annabel , Wu Alan H. B.
Published: February 2021

Context.—To assist with patient diagnosis and management, physicians from pain services, drug treatment programs, and the emergency department frequently request that urine be tested for drugs of abuse. However, urine immunoassays for drugs of abuse have limitations.

Objective.—To use data from the College of American Pathologists Proficiency Testing Surveys to determine and summarize the characteristics, performance, and limitations of urine immunoassays for drugs of abuse.

Design.—Six years of urine drug testing proficiency surveys were reviewed.

Results.—Lysergic acid diethylamide and methaqualone are infrequently prescribed or abused and, therefore, testing may be unnecessary. However, implementation of more specific testing for methylenedioxymethamphetamine and oxycodone may be warranted. Each drug of abuse immunoassay exhibits a different cross-reactivity profile. Depending on the cross-reactivity profile, patients with clinically insignificant concentrations of drugs may have false-positive results, and patients with clinically significant concentrations of drugs may have false-negative results.

Conclusions.—Laboratory directors should be aware of the characteristics of their laboratories' assays and should communicate these characteristics to physicians so that qualitative results can be interpreted more accurately. Furthermore, manufacturer's claims should be interpreted with caution and should be verified in each organization's patient population, if possible.
Practical and Molecular Evaluation of Colorectal Cancer: New Roles for the Pathologist in the Era of Targeted Therapy
Authors: De Hertogh Gert , Geboes Karen Paula
Published: February 2021

Context.—Colorectal cancer is the third most common cancer and the fourth most common cause of cancer death worldwide. Patient cases are discussed in multidisciplinary meetings to decide on the best management on an individual basis. Until recently, the main task of the pathologist in such teams was to provide clinically useful reports comprising staging of colorectal cancer in surgical specimens. The advent of total mesorectal excision and the application of anti-epidermal growth factor receptor (EGFR)–targeted therapies for selected patients with metastasized colorectal cancer have changed the role of the pathologist.

Objectives.—To present the traditional role of the pathologist in the multidisciplinary team treating patients with colorectal cancer, to address the technique of total mesorectal excision and its implications for the evaluation of surgical specimens, to offer background information on the various EGFR-targeted therapies, and to review the currently investigated tissue biomarkers assumed to be predictive for efficacy of such therapies, with a focus on the role of the pathologist in determining the status of such biomarkers in individual tumors.

Data Sources.—This article is based on selected articles pertaining to biopsy evaluation of colorectal carcinoma and reviews of EGFR-targeted therapies for this cancer. All references are accessible via the PubMed database (US National Library of Medicine and the National Institutes of Health).

Conclusions.—Pathologists play an increasingly important role in the diagnosis and management of colorectal cancer because of the advent of new surgical techniques and of targeted therapies. It is expected that this role will increase further in the near future.
Virtual Surgical Pathology in Underdeveloped Countries: The Zambia Project
Authors: Pagni Fabio , Bono Francesca , Di Bella Camillo , Faravelli Agostino , Cappellini Anna
Published: February 2021

Only 1 surgical pathology laboratory is available in Zambia, a country with a population of 12 million people. Since 2004 the Italian association of pathologists Patologi Oltre Frontiera has been working to create a virtual laboratory through the use of telemedicine. The project has involved staining histologic preparations on site, with the interpretation of imaged slides performed abroad through telepathology. Starting in April 2007, all surgical specimens obtained in Mtendere Mission Hospital, Chirundu, Zambia, were submitted for microscopic examination through whole-slide scans. Two independent Italian pathologists evaluated the cases by means of satellite connection and the final diagnoses were sent to Zambian clinicians via the internet. This article describes the spectrum of diagnoses made via telepathology for the Zambian population. Also, we analyze the concordant and discordant data between this telepathology method and traditional microscopy in a developing country. Moreover, we provide possible solutions for providing pathology services in other underdeveloped countries.
Inflammatory Myofibroblastic Tumor With Thrombocytosis and a Unique Chromosomal Translocation With ALK Rearrangement
Authors: Cole Bonnie , Zhou Holly , McAllister Nancy , Afify Zeinab , Coffin Cheryl M.
Published: February 2021

We describe a case of inflammatory myofibroblastic tumor with an unusual constellation of clinical, pathologic, and genetic findings. A 7-year-old girl had an 11-cm abdominopelvic mass accompanied by thrombocytosis, anemia, elevated erythrocyte sedimentation rate, and elevated C-reactive protein. The inflammatory myofibroblastic tumor displayed unusual histologic features of zonal coagulative necrosis, high cellularity with a herringbone pattern, and tumor-associated osteoclast-like giant cells. The complex tumor karyotype included a translocation t(1;2)(q21; p23). Following resection, the laboratory abnormalities resolved. The patient is well and free of recurrence at 3 years following resection. This case raises interesting questions about clinical, pathologic, prognostic, and molecular genetic interrelationships in inflammatory myofibroblastic tumor.
Commonly Encountered Difficulties in Pathologic Staging of Lung Cancer
Authors: Flieder Douglas B.
Published: February 2021

Context.—Lung cancer is the leading cause of cancer mortality worldwide. Despite technological, therapeutic, and scientific advances, most patients present with incurable disease and a poor chance of long-term survival. For those with potentially curable disease, lung cancer staging greatly influences therapeutic decisions. Therefore, surgical pathologists determine many facets of lung cancer patient care.

Objective.—To present the current lung cancer staging system and examine the importance of mediastinal lymph node sampling, and also to discuss particularly confusing and/or challenging areas in lung cancer staging, including assessment of visceral pleura invasion, bronchial and carinal involvement, and the staging of synchronous carcinomas.

Data Sources.—Published current and prior staging manuals from the American Joint Committee on Cancer and the International Union Against Cancer as well as selected articles pertaining to lung cancer staging and diagnosis accessible through PubMed (National Library of Medicine) form the basis of this review.

Conclusions.—Proper lung cancer staging requires more than a superficial appreciation of the staging system. Clinically relevant specimen gross examination and histologic review depend on a thorough understanding of the staging guidelines. Common sense is also required when one is confronted with a tumor specimen that defies easy assignment to the TNM staging system.
Cytodiagnosis in the Autopsy Suite: A Tool for Improving Autopsy Quality and Resident Education
Authors: Schnadig Vicki J. , Molina Claudia P. , Aronson Judith F.
Published: February 2021

Context.—Despite several publications attesting to its accuracy and value, cytology is rarely used for preliminary autopsy diagnosis in the United States. Postmortem cytodiagnosis has the potential to increase the accuracy and specificity of the provisional and final autopsy diagnoses, increase resident interest in cytodiagnostic techniques, and direct pathologists to request pertinent special studies, such as microbial cultures and special stains.

Objective.—To assess and illustrate the value of cytodiagnostic techniques for improving autopsy quality assurance and resident education.

Design.—Eighty-five samples were evaluated from 49 nonconsecutive autopsies. Sixty-five focal lesions were sampled by direct scraping. Diffuse lung consolidation was sampled by fine-needle aspiration (20 samples). Smears and cytocentrifuge preparations of fine-needle aspirations were routinely stained by both Papanicolaou and Romanowski methods. Cytologic diagnoses were compared with final autopsy diagnoses, and both cytology and pertinent histology were reviewed.

Results.—Clinical or radiographic antemortem site-specific diagnoses had been made in 28 (33%) of the 85 samples. A definite diagnosis was made by postmortem cytology in 68 (80%) of 85 samples, and these diagnoses could contribute to provisional autopsy diagnosis in 46 instances (68%). Resident and faculty enthusiasm for the use of cytology in the autopsy suite has increased during the 7 years following the study. Case examples illustrating the benefits of postmortem cytology are provided.

Conclusions.—Postmortem cytology benefits both autopsy quality and resident education.
Major Histocompatibility Complex Class I and II Detection as a Diagnostic Tool in Idiopathic Inflammatory Myopathies
Authors: Jain Ayushi , Sharma Mehar Chand , Sarkar Chitra , Bhatia Rohit , Singh Sumit , Handa Rohini
Published: February 2021

Context.—Muscle biopsy is at present the gold standard for the diagnosis of idiopathic inflammatory myopathies (IIMs), which include dermatomyositis, polymyositis, and inclusion body myositis. Currently, there is no definite diagnostic marker that helps in the discrimination of different subgroups of IIMs and the discrimination of IIMs from other clinical and morphologic mimics. Major histocompatibility complex (MHC) class I and II antigens are not expressed on normal muscle fibers.

Objective.—To determine the diagnostic utility of MHC class I and II antigen expression on the muscle biopsies from patients with various neuromuscular disorders and to validate its addition in the existing diagnostic armamentarium.

Design.—Expression of MHC class I and II antigen was studied on 126 muscle biopsies, of which 62 were IIMs and 64 were controls (taken from patients with other neuromuscular disorders).

Results.—When compared with controls, the sensitivity of MHC class I expression for diagnosis of IIMs was 88.7% (100%, 81.6%, and 100% for dermatomyositis, polymyositis, and inclusion body myositis, respectively), with a specificity of 89.1%. The specificity of MHC class II expression was 100% for all IIMs.

Conclusion.—Detection of MHC class I and II antigen expression is extremely helpful in the diagnosis of IIMs and has high sensitivity and specificity, especially in dermatomyositis. This expression can be used as a diagnostic tool in discriminating IIMs from other muscle diseases in which it is either absent or weakly expressed.