Showing papers in "Advances in Anatomic Pathology in 2010"

IgG4-related sclerosing disease: a critical appraisal of an evolving clinicopathologic entity.

Abstract: An elevated serum titer of immunoglobulin G4 (IgG4), the least common (3% to 6%) of the 4 subclasses of IgG, is a surrogate marker for the recently characterized IgG4-related sclerosing disease. The syndrome affects predominantly middle-aged and elderly patients, with male predominance. The patients present with symptoms referable to the involvement of 1 or more sites, usually in the form of mass lesions. The prototype is IgG4-related sclerosing pancreatitis (also known as autoimmune pancreatitis), most commonly presenting as painless obstructive jaundice with or without a pancreatic mass. Other common sites of involvement are the hepatobiliary tract, salivary gland, orbit, and lymph node, but practically any organ-site can be affected, such as retroperitoneum, aorta, mediastinum, soft tissue, skin, central nervous system, breast, kidney, prostate, upper aerodigestive tract, and lung. The patients usually have a good general condition, with no fever or constitutional symptoms. Common laboratory findings include raised serum globulin, IgG, IgG4, and IgE, whereas lactate dehydrogenase is usually not raised. Some patients have low titers of autoantibodies (such as antinuclear antibodies and rheumatoid factor). The disease often shows excellent response to steroid therapy. The natural history is characterized by the development of multiple sites of involvement with time, sometimes after many years. However, the disease can remain localized to 1 site in occasional patients. The main pathologic findings in various extranodal sites include lymphoplasmacytic infiltration, lymphoid follicle formation, sclerosis and obliterative phlebitis, accompanied by atrophy and loss of the specialized structures of the involved tissue (such as secretory acini in pancreas, salivary gland, or lacrimal gland). The relative predominance of the lymphoplasmacytic and sclerotic components results in 3 histologic patterns: pseudolymphomatous, mixed, and sclerosing. Immunostaining shows increased IgG4+ cells in the involved tissues (>50 per high-power field, with IgG4/IgG ratio >40%). The lymph nodes show multicentric Castleman disease-like features, reactive follicular hyperplasia, interfollicular expansion, or progressive transformation of germinal centers, with the unifying feature being an increase in IgG4+ plasma cells on immunostaining. The nature and pathogenesis of IgG4-related sclerosing disease are still elusive. Occasionally, the disease can be complicated by the development of malignant lymphoma and possibly carcinoma.

Uterine smooth muscle tumors other than the ordinary leiomyomas and leiomyosarcomas: a review of selected variants with emphasis on recent advances and unusual morphology that may cause concern for malignancy.

Abstract: Uterine smooth muscle tumors are classified according to their morphologic features that include architecture, growth pattern, cellular characteristics and constituents of the intercellular stroma. While terminologies used for the pathologic diagnosis of various subtypes may be eloquent and histologically accurate, some of these are confusing for the clinician and may also be open to interpretation by different pathologists: the labeling of atypical leiomyomas epitomizes this intricate system. Clinically, it is probably more useful to classify them as either tumors with or tumors without recurrent and/or metastatic potential. The term "atypical leiomyoma" has been used to label tumors that have a low risk of recurrence and is synonymous with benign tumors. The latter are known variously as leiomyoma with bizarre nuclei, symplastic leiomyoma, or pleomorphic leiomyoma. Variants of benign uterine smooth muscle tumors, such as mitotically active leiomyoma, cellular and highly cellular leiomyoma, epithelioid leiomyoma, and myxoid leiomyoma each have distinctive hallmarks that enable subclassification. Nevertheless, they may occasionally possess one or more unusual features that are cause for alarm. Tumors that have a dissecting growth pattern, with or without extrauterine extension, may mimic malignancy both grossly and microscopically. The current review discusses the pathologic diagnosis of and terminology applied to selected variants of uterine smooth muscle tumors other than the ordinary leiomyomas and leiomyosarcomas with emphasis on unusual reported features that may indicate malignancy. This includes an update on uterine smooth muscle tumor of uncertain malignant potential (STUMP), intravenous leiomyomatosis, benign metastasizing leiomyoma, and diffuse leiomyomatosis. Their clinicopathologic features, differential diagnoses, and management options based on findings in the previously reported cases will also be reviewed.

Mullerian adenosarcoma of the female genital tract.

Abstract: Mullerian adenosarcoma is an uncommon, but not rare, mixed tumor containing a neoplastic but benign or mildly atypical epithelial element and a sarcomatous, usually low-grade, stromal component. The most common site is the uterine corpus but adenosarcoma also occurs in the cervix and ovary and more

KRAS mutation testing in human cancers: The pathologist's role in the era of personalized medicine.

Abstract: A number of studies have shown that although antiepi- dermal growth factor receptor (EGFR) monoclonal antibodies are effective treatments for metastatic colorectal cancer (mCRC), only patients with wild-type KRAS tumors derive clinical benefit from these therapies. The anti-EGFR monoclonal antibodies panitumu- mab and cetuximab are approved in the United States for treatment of mCRC refractory to chemotherapy but are not recommended for use in patients with mutations in KRAS codons 12 or 13. Similarly, panitumumab is approved for the treatment of mCRC only in patients with wild-type KRAS in Europe and Canada. It is clear that KRAS mutational analysis will become an important aspect of disease management in patients with mCRC. Consequently, it will be important for pathologists and oncologists to develop and agree on standardized KRAS testing and reporting procedures to ensure optimum patient care. Pathol- ogists will be central to this process because of their crucial role in selecting appropriate tumor specimens for testing, choosing the molecular diagnostic laboratory to be used, assisting in the selection of a suitable KRAS test, and interpreting the results of KRAS mutational analysis. Guidelines for KRAS testing that address these and other important points of consideration have recently been proposed in the United States and the European Union.

A pathologist's road map to benign, precancerous, and malignant intraepithelial proliferations in the fallopian tube.

Abstract: The fallopian tube has recently emerged as an important site of origin for not only early serous cancer in women with inherited mutations in BRCA1/BRCA2 but as a source of many pelvic serous carcinomas. With this increased attention has come the inevitable need to sort out what epithelial abnormalities are clinically important and how they should be reported by the practicing pathologist. This review addresses 4 categories of tubal epithelial change: (1) metaplasias; (2) nonmalignant atypias; (3) potential precursors, including secretory cell outgrowths and p53 signatures; and (4) tubal intraepithelial carcinomas. A modified protocol for sectioning the fallopian tube (SEE-FIM) is discussed and each of the above topics is covered in the context of its differential diagnosis and recommendations for reporting are included. Finally, the rationale for close inspection of the tube, both in presumed benign and malignant disease, is discussed, with reference to an ongoing multi-institutional web-based project (Pelvic-ovarian Cancer Interception project).

Human papillomavirus detection in head and neck squamous cell carcinomas.

Abstract: Squamous cell carcinomas of the head and neck (HNSCC) are a frequent diagnosis in anatomic pathology practice. Tobacco use and heavy alcohol consumption are known risk factors for HNSCC but in other cases human papillomavirus (HPV) is linked to carcinogenesis. HPV proteins E6 and E7 promote oncogenesis by blocking the action of p53 and pRB, respectively. An absence of p53 mutations in addition to expression of p16 are part of the distinct molecular profile identified in the subset of HNSCCs because of HPV. Various methods are available for HPV detection but polymerase chain reaction and in situ hybridization techniques are commonly used. Both methods are amenable for testing formalin-fixed paraffin-embedded tissue that is a sample type readily available to the pathologist. HPV is detectable in approximately a quarter of all HNSCCs, and is particularly prevalent in the oropharynx in which the positivity rates approach 40%. A vast majority of HPV-related HNSCCs are owing to HPV type 16 with types 18, 31, and 33 accounting for almost all of the remaining cases. HPV-related HNSCCs are associated with better prognosis for both recurrence and survival. This group of tumors has also been shown to respond well to radiation treatment. As the clinical relevance of HPV in HNSCCs continues to emerge, anatomic pathologists are likely to receive increasing requests for testing. Herein, the authors review the biological and clinical aspects of HPV-associated HNSCC and review techniques for HPV detection.

Oncogene-induced cellular senescence.

Abstract: Oncogene-induced senescence (OIS) is a robust and sustained antiproliferative response brought about by oncogenic signaling resulting from an activating mutation of an oncogene, or the inactivation of a tumor-suppressor gene. The pathways mediating OIS are complex and incompletely elucidated but, the proliferative arrest involves activation of both the RB and p53 pathways. In addition, whereas there are indications that at least in some situations, negative feedback loops abolish the increased mitogenic signaling resulting from the oncogenic mutations, also an unexpected contribution of interleukin-mediated signaling has recently been found. OIS brings about cessation of growth of some benign tumors, including melanocytic nevi and several other lesions, including pituitary and thyroid adenomas. It protects against progression to cancer, and in this way complements oncogene-induced apoptosis. Perhaps, OIS has evolved as an alternative to apoptosis especially regarding long-lived cell types that are not replaceable in large numbers. Contrary to the earlier belief, OIS is not entirely irreversible, at least in some well documented in vitro systems. This means that its induction does not entirely eliminate the oncogenic threat resulting from the mutated cell. It also means that OIS, or related phenomena that may affect a proportion of the tumor cells of some cancers, may have an influence on responsiveness to cytotoxic cancer therapies, because OIS is associated with an antiapoptosis phenotype.

Ocular adnexal lymphomas: a review.

Abstract: Ocular adnexal lymphomas comprise 1% to 2% of all non-Hodgkin lymphomas and about 8% of extranodal lymphomas. They are a heterogeneous group of malignancies, the majority of which are primary extranodal lymphoma with most (up to 80%) of the marginal zone of mucosa associated lymphoid tissue type (MALT lymphoma). This review will encompass the incidence, histology, immunophenotyping, recent advances in molecular and cytogenetics, clinical features including outcome, and prognostic factors. The association with Chlamydia psittaci and the very recently recognized occurrence in the context of IgG4-related sclerosing disease will be discussed. Finally, traditional (surgery, radiotherapy, chemotherapy) and newer forms of therapy (immunotherapy and radioimmunotherapy) will be reviewed.

The utility of discovered on gastrointestinal stromal tumor 1 (DOG1) antibody in surgical pathology-the GIST of it.

Abstract: DOG1 (discovered on GIST 1), known also as TMEM16A and ANO1, has emerged in recent years as a promising biomarker for gastrointestinal stromal tumors (GIST). It was originally discovered through microarray expression profiling analysis as gene that is highly expressed in GIST, and subsequent immunohistochemical studies have shown its use in its diagnosis. The results from several series have shown a high overall sensitivity and specificity for DOG1 in the detection of GISTs and about 6% of GISTs overall exhibiting a DOG1+/KIT-immunoprofile. DOG1 antibodies are more sensitive than KIT antibodies in detecting tumors of gastric origin, tumors with epithelioid morphology, and tumors harboring PDGFRA mutation. Furthermore, DOG1 immunoreactivity is rarely observed in other mesenchymal and nonmesenchymal tumor types. These results support the use of DOG1 as a diagnostic biomarker for GIST. When used in combination with KIT, this panel of diagnostic biomarkers can help pathologists and clinicians to identify more patients who may benefit from targeted therapies.

Cystic renal tumors: new entities and novel concepts.

Abstract: Cystic renal neoplasms and renal epithelial stromal tumors are diagnostically challenging and represent some novel tumor entities. In this article, clinical and pathologic features of established and novel entities are discussed. Predominantly cystic renal tumors include cystic nephroma/mixed epithelial and stromal tumor, synovial sarcoma, and multilocular cystic renal cell carcinoma. These entities are own tumor entities of the 2004 WHO classification of renal tumors. Tubulocystic carcinoma and acquired cystic disease-associated renal cell carcinoma are neoplasms with an intrinsically cystic growth pattern. Both tumor types should be included in a future WHO classification as novel entities owing to their characteristic features. Cysts and clear cell renal cell carcinoma frequently coexist within the kidneys of patients with von Hippel-Lindau disease. Sporadic clear cell renal cell carcinomas often contain cysts, usually as a minor component. Some clear cell renal cell carcinomas have prominent cysts, and multilocular cystic renal cell carcinoma is composed almost exclusively of cysts. Recent molecular findings suggest that clear cell renal cancer may develop through cyst-dependent and cyst-independent molecular pathways.

State of the art, nomenclature, and points of consensus and controversy concerning benign melanocytic lesions: outcome of an international workshop.

Abstract: The following communication summarizes the proceedings of a one-day International Workshop focusing on the histology of benign melanocytic nevi. Areas of controversy identified in 6 focus sessions were the nomenclature and relationships among common nevi including nevi with halo reactions, traumatiz

Using LEAN principles to improve quality, patient safety, and workflow in histology and anatomic pathology.

Abstract: Histology and anatomic pathology have historically been slow to accept many of the process changes that have been widely accepted in the clinical laboratory. In this article, we describe the application of the Toyota Production System (LEAN) to histology and anatomic pathology as implemented at the Avera McKennan Hospital laboratory. Avera McKennan is the flagship hospital of the Avera Health System, a faith based, not for profit healthcare system based in South Dakota. Comprised of 235 hospitals, clinics, and physicians, with over 12,000 employees, Avera Health is one of the largest healthcare systems in the region. Beginning in 2004, Avera McKennan's laboratory began its "LEAN journey" and in the intervening years has expanded it throughout all areas of the laboratory. Following the example set by the laboratory, many other areas of the hospital have joined in the LEAN Process Improvement journey. In January 2009, the Avera McKennan Laboratory became the first hospital laboratory in the US to achieve the CAP ISO-15189 accreditation in both clinical and anatomic pathology.

New Insights Into Merkel Cell Carcinoma

Abstract: Merkel cell carcinoma (MCC) is a rare aggressive cutaneous malignancy of the elderly and immunocompromised populations The clinical presentation of MCC is nonspecific, with the majority of cases presenting as localized skin involvement Histologically and immunophenotypically, MCC is defined by both neuroendocrine and epithelial differentiation Recently, the Merkel cell polyomavirus has been implicated in the pathogenesis of MCC In addition, there have been numerous studies evaluating the histologic and immunohistochemical characteristics of MCC as they relate to diagnosis and prognosis The purpose of this paper is to review the most salient and clinically relevant updates in the pathogenesis and histologic features of MCC Specific attention is given to the clinical and histologic predictors of prognosis, staging, and the controversies concerning sentinel lymph node biopsy and therapy

The Use of Immunohistochemistry in the Diagnosis of Metastatic Clear Cell Renal Cell Carcinoma: A Review of PAX-8, PAX-2, hKIM-1, RCCma, and CD10

Abstract: The diagnosis of metastatic clear cell renal cell carcinoma may be difficult in some cases, particularly in the small image-guided biopsies that are becoming more common. As targeted therapies for renal cell carcinoma are now standard treatment, the recognition and diagnosis of renal cell carcinoma has become even more critical. Many adjunctive immunohistochemical markers of renal epithelial lineage such as CD10 and RCCma have been proposed as aids in the diagnosis of metastatic renal cell carcinoma, but low specificities often limit their utility. More recently described markers (PAX-2, PAX-8, human kidney injury molecule-1, hepatocyte nuclear factor-1-β, and carbonic anhydrase-IX) offer the potential for greater sensitivity and specificity in this diagnostic setting; however, knowledge of their expected staining in other neoplasms and tissues is critical for appropriate use. In this review, we discuss the most widely used immunohistochemical markers of renal lineage with an emphasis on their sensitivity and specificity for metastatic clear cell renal cell carcinoma. Subsequently, we present a variety of organ-specific differential diagnostic scenarios in which metastatic clear cell renal cell carcinoma might be considered and we propose immunopanels for use in each situation.

Paratesticular mesothelioma. Report of a case with comprehensive review of literature.

Abstract: Paratesticular mesotheliomas are rare tumors with 223 cases described so far. The sole plausible causative factor so far ascertained in the pathogenesis of these tumors is asbestos, which however is found in only around 30% to 40% of such cases. The age range of affected individuals is wide, mostly adults and the elderly, but also includes young people and children. The most common presenting symptom is either hydrocele of unknown origin or intrascrotal mass. When hydrocele is the presenting symptom, these tumors are often clinically overlooked and the diagnosis is delayed. Most paratesticular mesotheliomas arise in the tunica vaginalis, but primary tumors of the spermatic cord and epididymis are also on record. Tumors arising from the peritoneal mesothelium of a hernia sac are excluded from this group. The correct diagnosis is almost always made after histologic examination of the operative specimen. Immunohistochemistry and electron microscopy are always helpful and sometimes necessary tools for diagnosis. So far very few cases have been identified or suspected preoperatively on cytologic examination. Three clinicopathologic types of malignant mesotheliomas of the male genital tract are recognized: diffuse tubulo-papillary mesothelioma, well-differentiated papillary mesothelioma, and multicystic mesothelioma. The histologic subtypes are almost always pure epithelial or biphasic. The differential diagnosis is mainly with serous papillary tumors arising from Mullerian vestiges, but several diverse primary or secondary tumors also need to be considered. A clinicopathologic evaluation of a case of tunical diffuse mesothelioma in a 74-year-old male from the AMR Series is the starting point for this general review.

Endometrial Stromal Sarcomas: A Review of Potential Prognostic Factors

Abstract: Endometrial stromal tumors are uncommon mesenchymal tumors of the uterus. The classification of these tumors has evolved and the most current World Health Organization classification (2003) divides these neoplasms into: endometrial stromal nodule, low-grade endometrial stromal sarcoma, and undifferentiated endometrial sarcoma. The salient clinicopathologic features of these tumors are described, and a comprehensive review of literature pertaining to potential prognostic factors in endometrial stromal sarcomas is provided. Clinical factors, including age, race, parity and menopausal status, and pathologic factors, including tumor size, tumor stage, nuclear atypia, mitotic activity, tumor necrosis, lymphovascular space invasion, DNA ploidy and proliferative activity, and expression of hormone receptors, have been explored with varying outcomes. Surgicopathologic stage seems to be the most important prognostic factor in low-grade endometrial stromal sarcomas. The impact of other prognostic factors on survival is unclear or controversial, especially in patients with stage I tumors.

Telepathology for patient care: what am I getting myself into?

Abstract: The vast advancements in telecommunications and converting medical information to a digital format have increased the number of applications within telemedicine. Telepathology, in simplest terms, is the practice of formally rendering a pathologic diagnosis based upon examination of an image rather than of a glass slide through traditional microscopy. The use of telepathology for clinical patient care has so far been limited to relatively few large academic institutions. Although a number of challenges remain, there is increasing demand for the use of information technology in pathology as a whole owing to the expansion of health care networks and the opportunity to enhance the quality of service delivered to patients. The software used to acquire, display, and manage digital images for clinical patient care may be subject to national and federal regulations just as is any other electronic information system. Despite the barriers, telepathology systems possess the capability to help manage pathology cases on a global scale, improve laboratory workload distribution, increase standardization of practice and enable new classes of ancillary studies to facilitate diagnosis and education even in the most remote parts of the earth.

Glioma diagnosis: immunohistochemistry and beyond.

Abstract: Clinicians and pathologists have been inundated by published reports of new and potentially interesting diagnostic, prognostic, and putative predictive "markers" whose expression (or loss) holds great promise for more enlightened diagnoses and ultimately better patient care. Although an understanding of therapeutically (and possibly diagnostically) relevant pathways of glioblastoma may be at hand, significant challenges remain. Many immunohistochemical and genetic tests have proven to be useful in the stratification of clinical trials, whereas the utility of many others for the day-to-day practice of pathology awaits further study and validation. The importance of critical literature review and careful consideration of practical issues such as test standardization, compliance, cost-effectiveness, and availability must all be considered before implementing any new diagnostic test. This review will focus on the role of immunohistochemistry in the routine diagnosis of astrocytic and oligodendrocytic tumors and in assisting with the diagnosis of some less common gliomas that have ependymal-like features. It will conclude with a summary of molecular and genetic studies, which not only hold great promise for improved diagnosis, but also reveal prognostic information on disease outcome and predict response to treatment or provide biologic targets for novel therapies.

Immunohistology--past, present, and future.

Abstract: The rapid development of immunohistochemistry, a morphology-based technique, has come about through refinements in detection systems and an increasing range of sensitive and specific antibodies that have allowed application of the technique to formalin-fixed, paraffin-embedded tissues. The introduction of heat-induced antigen retrieval has been a significant milestone to compliment these developments so that the immunohistochemistry is firmly entrenched as an indispensable adjunct to morphologic diagnosis. Although this ancillary stain was initially used in a qualitative manner, problems surrounding the many variables that influence antigen preservation in formalin-fixed, paraffin-embedded tissues were not a major issue and laboratories strived to optimize their staining protocols to the material they accessioned and processed. The advent of personalized medicine and targeted cancer treatment has imposed the need to quantitate the stain reaction product and has resulted in calls to standardize the process of immunostaining. A closer examination of the variables that influence the ability to show antigens in formalin-fixed, paraffin-embedded tissues revealed many important variables, particularly in the preanalytical phase of the assay, that are beyond the control of the accessioning laboratory. Although analytical factors have the potential to be standardized, the actions of many pivotal procedures including fixation and antigen retrieval are not completely understood. Postanalytical processes including threshold and cut-off values require consensus and standardization and it is clear that some of these goals can be achieved through the direction of national and international organizations associated with cancer diagnosis and treatment. With the ability to serve as a surrogate marker of many genetic abnormalities, immunohistochemistry enters a new era and the need to better understand some of the mechanisms fundamental to the technique become more pressing and the development of true quantitative assays is imperative. There is also an increasing appreciation that the technique highlights patterns of staining that reflect exquisite localization to organelles and tissue structures that are not appreciable in routine stains, adding a further dimension to morphologic diagnosis.

Small Cell Tumors of Bone

Abstract: Bone tumors are fortunately rare, but small cell tumors of bone are a relatively common subset of these lesions. They comprise of a diverse group of primary and metastatic neoplasms in both children and adults. The most common small cell tumors of bone include Ewing sarcoma/primitive neuroectodermal tumor, small cell osteosarcoma, multiple myeloma, lymphoma, leukemia, neuroblastoma, rhabdomyosarcoma, and Langerhans cell histiocytosis. Although each entity has its distinctive features, the differential diagnosis of this group of tumors is still challenging because they are all "small, blue, and round cell tumors", histologically. The correct diagnosis of small cell tumors of bone depends on an evaluation of clinical, radiologic, pathologic, and genetic features. Patients' age and sex are very important, as are the signs and symptoms at presentation. Radiologically, which bone is involved, the specific portion of the bone (epiphysis, metaphysis, or diaphysis; cortex vs. medulla) involved, and the radiographic manifestations (lytic, blastic, or mixed lytic and blastic) are also often critical parameters for the diagnosis. In recent years, with a better understanding of the molecular and cytogenetic background of several small cell tumors, more accurate diagnoses have been supported by the clinicopathologic criteria and by a panel of immunohistochemical studies. In this review we will provide an overview of the clinical, radiologic, pathologic, and genetic characteristics of these tumors.

The Clinical Relevance of Molecular Genetics in Soft Tissue Sarcomas

Abstract: Bone and soft tissue sarcomas are an infrequent and heterogeneous group of mesenchymal tumors including more than a hundred different entities attending to histologic patterns Research into the molecular aspects of sarcomas has increased greatly in the last few years This enormous amount of knowledge has allowed, for instance, to refine the classification of sarcomas, improve the diagnosis, and increase the number of therapeutical targets available, most of them under preclinical evaluation However, other important key issues, such as sarcomagenesis and the cell of origin of sarcomas, remain unresolved From a molecular point of view, these neoplasias are grouped into 2 main types: (a) sarcomas showing relatively simple karyotypes and translocations, which originate gene fusions (eg, EWS-FLI1 in Ewing sarcoma) or point mutations (eg, c-kit in the gastrointestinal tumors) and (b) sarcomas showing unspecific gene alterations, very complex karyotypes, and no translocations The discovery of the early mechanisms involved in the genesis of sarcomas, the more relevant signaling pathways, and the development of genetically engineered mouse models could also provide a new individualized therapeutic strategy against these tumors This review describes the clinical application of some of the molecular alterations found in sarcomas, some advances in the field of sarcomagenesis, and the development of animal models

The non-neoplastic kidney in tumor nephrectomy specimens: what can it show and what is important?

Abstract: Surgical nephrectomy is a procedure that has been performed for nearly 100 years. In the presence of a normal contralateral kidney, such as in a renal transplant donor or child with Wilms tumor, it is a benign procedure without deleterious consequences on the remaining kidney. However, many adults and some children postnephrectomy will develop chronic kidney disease. The non-neoplastic kidney in tumor resections may harbor a large number of developmental and acquired diseases predictive of this outcome or that convey other medically significant information. Examination of the non-neoplastic kidney is a fertile opportunity to identify these unsuspected conditions that may ultimately dictate the subsequent clinical course and influence the medical care provided. This review discusses the consequences of unilateral and partial nephrectomy, and illustrates many conditions that may be encountered in the non-neoplastic cortex with a discussion of their clinical implications.

Thyroid cancer of follicular cell origin in inherited tumor syndromes.

Abstract: Well-differentiated thyroid cancer accounts for 95% of thyroid malignancies. In contrast to medullary thyroid carcinoma, in which about 25% are familial, only 5% of follicular cell-derived thyroid carcinomas are a component of a familial cancer syndrome. The familial follicular cell-derived tumors or nonmedullary thyroid carcinoma encompass a heterogeneous group of diseases, and are classified into 2 distinct groups: syndromic-associated tumors, occurring in syndromes in which nonmedullary thyroid carcinomas are the predominant tumor encountered, and nonsyndromic tumors, those occurring in tumor syndromes in which thyroid involvement is a minor component. The first group, syndromic-associated tumors, includes phosphase and tensin (PTEN)-hamartoma tumor syndrome/Cowden syndrome, familial adenomatous polyposis/Gardner syndrome, Carney complex type 1, Werner syndrome, and Pendred syndrome. Other syndromes, as McCune Albright syndrome, Peutz-Jeghers syndrome, and Ataxia-teleangiectasia syndrome may be associated with the development of follicular cell-derived tumors, but the link is less established than the above syndromes. The syndromic-associated tumors are the focus of this review. The second group of familial follicular cell-derived tumors syndromes or nonsyndromic tumors, in which nonmedullary thyroid carcinomas are the major findings, include pure familial papillary thyroid carcinoma, with or without oxyphilia, familial papillary thyroid carcinoma with papillary renal cell carcinoma, and familial papillary thyroid carcinoma with multinodular goiter. This review will discuss the clinical and pathological findings of the patients with familial syndrome-associated tumors: PTEN-hamartoma tumor syndrome/Cowden syndrome, familial adenomatous polyposis syndrome, Carney complex type 1, Werner syndrome, and Pendred syndrome.

Detection and classification of diagnostic discrepancies (errors) in surgical pathology.

Abstract: Detecting and classifying error in a surgical pathology (SP) practice is an important part of a comprehensive quality assurance program. There are a number of mechanisms to detect error, including secondary review, examination of amended reports, correlation studies (cytology-histology and frozen-final diagnosis correlation). These different detection methods are reviewed in this paper. Additionally, the most common methods for error classification are also reviewed, along with the benefits and limitations of each. Although there is presently no gold standard for detecting or classifying errors in SP, based on this review of the literature, it is clearly good practice to consistently apply a standard method. Most importantly, these data should be incorporated into quality assurance and quality improvement activities, such that departments strive to reduce errors, and to help improve overall quality in SP.

Emerging Concepts in Micropapillary Urothelial Carcinoma

Abstract: Micropapillary urothelial carcinoma is a relatively uncommon variant of urothelial carcinoma, but its recognition carries important prognostic and treatment implications. Micropapillary morphology occurs in neoplasms arising in many different organ systems and displays aggressive biologic behavior regardless of its site of origin. On account of this association, micropapillary features in urothelial carcinoma should be reported regardless of whether the pattern is focal or dominant. The overall prognosis for micropapillary urothelial carcinoma is poor and recent studies suggest that early treatment with cystectomy could improve outcome, as these tumors are unlikely to respond to chemotherapy when used as a secondary treatment modality. This review discusses the histologic features required for diagnosis and the clinical significance of rendering a diagnosis of micropapillary urothelial carcinoma.

Smoking-related Small airway disease--a review and update.

Abstract: The term "small airway disease" has been used in reference to abnormalities occurring secondary to cigarette smoking in the context of chronic obstructive pulmonary disease (COPD), and the small airways are the major site of obstruction in patients with COPD The histologic features associated with smoking-related small airway disease are largely nonspecific and overlap with those of other bronchiolitides The pathogenesis of smoking-related small airway disease is poorly understood; however, insights into the development of airway remodeling and matrix production continue to evolve The aim of this article will be to review the histologic findings and pathogenesis of smoking-related small airway disease in the context of COPD, and review other small airway disorders affecting cigarette smokers, namely respiratory bronchiolitis and Langerhans cell histiocytosis, and a newly described entity of respiratory bronchiolitis with fibrosis and associated issues with this entity

Adenocarcinoma of the upper aerodigestive tract.

Abstract: Although squamous cell carcinoma is the most frequent malignant diagnosis made with upper aerodigestive tract specimens, a myriad of neoplasms can occur throughout the area. Very uncommonly, one encounters adenocarcinomas that cannot be better classified as salivary gland-type neoplasia. This manuscript reviews these tumors, including sinonasal intestinal-type adenocarcinomas, sinonasal low-grade and high-grade nonintestinal adenocarcinomas and nasopharyngeal papillary adenocarcinomas. Clinical, histologic, and immunohistochemical features and differential diagnoses are discussed.

Mixed Medullary-follicular-derived Carcinomas of the Thyroid Gland

Abstract: Tumors of the thyroid are subclassified based on the cell of origin and commonly include follicular-derived tumors and C-cell-derived tumors. The most common follicular-derived tumors are papillary carcinoma and follicular carcinoma, whereas the malignant C-cell-derived tumor is medullary thyroid carcinoma. Rare cases in the literature describe patients who have follicular-derived and C-cell-derived tumors in the same thyroid gland. These can be synchronous but anatomically separate carcinomas, or they can show some mixing of the 2 components. The mixture may be at an interface, as in collision tumors, or can be throughout the entire lesion, as in true mixed medullary-follicular-derived carcinomas. The clinical, histologic, and molecular features of these mixed tumors and the classification guidelines are reviewed.

Histiocytic disorders of the lung.

Abstract: Histiocytic proliferations involving the lung span a broad spectrum. Some proliferations are primary; others represent a histiocytic response secondary to conditions in which there may be isolated lung involvement or the lung may be involved as part of a systemic process. Primary histiocytic lung disorders, particularly those of uncertain histogenesis are a heterogeneous and intriguing group of disorders. Although they have been the focus of attention by clinicians and pathologists alike, much is unknown about their etiopathogenesis. Owing to this uncertainty, our understanding of these processes is in a state of flux, and is likely to change as more information is brought to light. This review will focus on pulmonary histiocytic proliferations of uncertain histogenesis. Other histiocytic lesions will be dealt with in brief.

Novel immunohistochemical markers in the diagnosis of nonglial tumors of nervous system.

Abstract: Immunohistochemistry (IHC) has become an important adjunct tool in diagnostic neuro-oncology practice enabling immunophenotypic characterization of tumor cells. There have been several recent publications regarding new IHC markers that are useful for diagnosis of brain tumors. To introduce the latest advances in IHC in this field, we review the features of novel IHC marker antibodies applicable to selected nonglial tumors in the nervous system, based on recently published reports and our own experiences. We discuss (1) aquaporin-1 and alpha-inhibin for hemangioblastoma, (2) beta-catenin for craniopharyngioma, (3) brachyury for chordoma, and (4) INI-1 for hereditary schwannomas. All the markers presented here are used primarily for supporting or confirming the histologic diagnosis, with the exception of (4), which may be of help in identification of inherited forms in schwannomas. As with other surgical pathology practices, the judicious use of a panel of IHC antibodies selected on the basis of the histologic findings is important for an accurate diagnosis of brain tumors. Of note is that IHC results should be always interpreted in the histopathologic context.