Unknown primary tumors.

An unknown primary tumor (UPT) is defined by the presence of a metastatic cancer without a known primary site of origin despite a standardized diagnostic workup. Clinically, UPTs show rapid progression and early dissemination, with signs and symptoms related to the metastatic site. The molecular bases of their biology remain largely unknown, with no evidence as to whether they represent a distinct biological entity. Immunohistochemistry remain the best diagnostic tool in term of cost-effectiveness, but the time-consuming "algorithmic process" it relies on has led to the application of new molecular techniques for the identification of the primary site of UPTs. For example, several microarray or miRNA classifications of UPTs have been used, with an accuracy in the prediction of the primary site as high as 90%. It should be noted that validating a prediction of tissue origin is challenging in these patients, since most of them will never have a primary site identified. Moreover, prospective studies to determine whether selection of treatment options based on such profiling methods actually improves patient outcome are still missing. In the last few years functional imaging (i.e. FDG-PET/CT) has gained a main role in the detection of the site of origin of UPTs and is currently recommended by the European Association of Nuclear Medicine. However, despite recent refinements in the diagnostic workup, the site of origin of UPT often remains elusive. As a consequence, treatment of patients with UPT is still empirical and inadequate.

Neuroendocrine tumors diagnosed at the Antonio Cardarelli hospital (Naples, Italy) between 2006-2009: a single-institution analysis.

Neuroendocrine tumors (NETs) are rare, with an incidence of about 5 per 100,000 inhabitants. As no study on NETs has ever been specifically conducted on the population of Campania, we performed a retrospective analysis of all newly diagnosed NETs at the Antonio Cardarelli hospital between 2006-2009. A search of the registry of the Pathology Department of the Antonio Cardarelli hospital was carried out to retrieve available data on all newly diagnosed NET cases. Two hundred and ninety-nine NET tumors were diagnosed at our Institution from January, 2006 to December, 2009. Globally, 121 patients (40% of the population) had a lung NET, while 92 patients (30% of the population) presented a GEP-NET. The most common primary tumor site varied by sex, with female patients being more likely to have a primary NET in the lung, breast or colon, and male patients being more likely to have a primary tumor in the lung. Also, twenty-three cases of breast NETs were identified, and clinical information regarding therapy and response was available for 22 patients. Our study represents a pioneering effort to provide the medical community in Campania with basic information on a large number of patients with different types of NETs. The Antonio Cardarelli hospital could greatly benefit from cooperation with other hospitals in order to become a highly specialized center for NETs in the region and Southern Italy.

A National Quality Assurance program for breast immunohistochemistry: an Italian perspective.

A national project for the quality assessment of breast immunohistochemistry, involving 155 pathology laboratories distributed all over the Italian territory ( 19 regions), was carried out. The Project lasted one year from December 2014 to December 2015 and it was strongly supported by the Italian Society of Anatomic Pathology (SIAPEC/IAP). Proficiency tests were carried out by the Nordic Immunohistochemical Quality Control (NordiQC) organization. The main aim of the project was to investigate on the general performance of immunohistochemistry (ER, PR and HER2) in the field of breast cancer in the Italian territory, in order to emphasize any difference and give practical support to laboratories in daily practice.The present review article focused on the description of this extraordinary pioneer Italian experience. Besides NordiQC results, further analysis concerning epidemiology and geographical distribution were done.Aim of the study was to analyze the general results and to discuss on the benefits that a national quality control program may have if it became a mandatory service provided by the National Health Care System.In general, the Italian data were in accordance with the general results obtained from the "official" NordiQC HER2, PR and ER assessments. A HER2 scoring consensus between labs and assessor group was achieved in 80% of cases.Interestingly, what emerges from our study is that no substantial differences exist among the three Italian macro-areas (North, Center and South) in the quality of Immunohistochemistry performed for breast cancer. No statistically significant difference was even found between laboratories that perform more or less than 100 tests/year.

Pseudovascular adenoid squamous cell carcinoma of the skin. A neoplasm that may be mistaken for angiosarcoma.

The adenoid variant of squamous cell carcinoma has been well-documented in several anatomic sites, including the skin. This tumor is characterized by acantholytic arrays of neoplastic keratinocytes that form pseudoglandular profiles. Although it is typically confused with adenocarcinomas, adenoid squamous cell carcinoma also may be mistaken for malignant vascular proliferations. This report concerns six acantholytic cutaneous squamous cell carcinomas that closely simulated angiosarcomas on conventional histologic examination. They arose in sun-exposed skin areas in middle-aged or elderly patients (mean age, 60 years), five of whom were men. In contrast to the typical clinical appearance of angiosarcoma, pseudovascular adenoid squamous cell carcinoma presented itself as a discrete cutaneous ulcer or crusted tanpink nodule. Microscopically, this lesion was characterized by interanastomosing cordlike arrays of polygonal or flattened tumor cells, with internal pseudolumina that contained detached tumor cells. A connection between the dermal neoplasm and the epidermis was apparent in three cases, but it was focal. Erythrocytes were seen in pseudovascular spaces in five tumors. Immunohistochemically, all examples of pseudovascular adenoid squamous carcinoma were reactive with antibodies to cytokeratin and epithelial membrane antigen (EMA). In addition, three expressed vimentin, two exhibited blood group antigen-positivity, and two bound Ulex europaeus I agglutinin. None of them was immunoreactive for Factor VIII-related antigen, and two of three studied for CD34-reactivity were likewise negative. A control group of six cutaneous angiosarcomas was uniformly nonreactive for cytokeratin and EMA, but they showed positivity for vimentin, Ulex binding, and CD34 positivity in all instances. Pseudovascular adenoid squamous cell carcinoma may be distinguished effectively from angiosarcoma of the skin by attention to its clinical features and by appropriate immunohistochemical studies. These two tumors differ in biologic behavior; three patients with pseudovascular adenoid squamous cell carcinoma died of their tumors, whereas all angiosarcomas in this series proved fatal.

Renal cell carcinoma with rhabdoid features.

Neoplasms with rhabdoid features have been reported at many anatomic sites. In the kidney, rhabdoid tumors are typically found in children, whereas only rare examples have been reported in adults. Little is known of renal cell carcinomas (RCCs) that exhibit rhabdoid features. The objective of this study was to determine the incidence of RCC with rhabdoid attributes and characterize the histologic, immunophenotypic, and ultrastructural features by retrospective analysis of 480 consecutively identified cases of RCC in radical nephrectomy specimens. Immunohistochemical evaluation was performed in cases with rhabdoid foci using a panel of antibodies to pancytokeratin (pan-CK), CK7, CK20, epithelial membrane antigen (EMA), S-100 protein, desmin, vimentin, neuron-specific enolase (NSE), muscle-specific actin (MSA), smooth muscle actin (SMA), human melanoma, black-45 (HMB-45), and glial fibrillary acidic protein (GFAP). Electron microscopy was also performed in selected cases. The presence and extent of rhabdoid foci in relation to pathologic stage and grade were assessed. Twenty-three of 480 cases of RCC (4.7%) exhibited rhabdoid features. The 23 patients were all adults with a mean age of 61.8 years (age range, 33-84 yrs). Fifteen of the patients were men and eight were women. Histologically, the rhabdoid foci were typified by sheets and clusters of variably cohesive, large epithelioid cells with vesicular and often eccentric nuclei, prominent nucleoli, and large, paranuclear intracytoplasmic hyaline globules (inclusions). The presence of these rhabdoid features was related to high histologic Fuhrman grade of the nonrhabdoid carcinoma component, with an incidence of 0 of 84 grade I cases, eight of 300 grade 2 cases (2.6%), six of 70 grade 3 cases (8.9%), and nine of 26 grade 4 cases (34.6%; p = 3 x 10(-9)). The rhabdoid foci were all high grade. The presence of rhabdoid foci was also found in higher stage carcinomas. A total of 52% (12 of 23) of RCC cases with rhabdoid features exhibited extrarenal extension compared with 28% (24 of 92) of contemporary RCCs without rhabdoid features (p = 0.03). The size of the rhabdoid component ranged from 1 mm to more than 2 cm and comprised 1% to 50% of the renal mass. Immunoreactivity for vimentin (100%), NSE (79%), and panCK (56%) was present in the majority of cases. Substantial percentages of cases were immunopositive for EMA (47%) and S-100 protein (37%), with minimal to no immunohistochemical reactivity for CK7 (5%), SMA (5%), CK20 (0%), desmin (0%), MSA (0%), HMB-45 (0%), and GFAP (O%). A distinctive globular, paranuclear reaction pattern was found for the cytokeratin, EMA, and vimentin immunostains. Ultrastructurally, the rhabdoid cells had paranuclear intermediate filament aggregates or paranuclear condensation of organelles, often associated with peripheral vacuolization. Adult RCCs may harbor a rhabdoid component, and these neoplasms can be regarded as "composite" tumors. Rhabdoid elements are important to identify because of their high-grade nature, and association with high stage. Adult RCC with rhabdoid elements should be distinguished from pure rhabdoid tumors of kidney, in light of their clinicopathologic differences. Rhabdoid differentiation in adult renal cell carcinoma may represent clonal divergence and/ or evolution, and emergence of a particularly aggressive element.

Pseudovascular adenoid squamous cell carcinoma of the lung: clinicopathologic study of three cases and comparison with true pleuropulmonary angiosarcoma.

Pseudovascular adenoid squamous cell carcinoma (PASCC) is a variant epithelial neoplasm with the ability to simulate the growth pattern of angiosarcoma. It has been documented in the breast, skin, and, recently, lung. We describe three additional examples of pulmonary PASCC occurring in two men and one woman. The patients' ages ranged from 47 to 54 years at diagnosis, and all patients had radiographically and macroscopically typical squamous carcinomas of the lung. Histologically, the tumors showed the presence of interanastomosing pseudoluminal spaces that were lined by obviously atypical epithelioid cells and focally contained erythrocytes. Overtly carcinomatous growth was apparent only very focally. A comparison case of true pleuropulmonary angiosarcoma in a 57-year-old man showed closely similar microscopic features, but it lacked areas that resembled conventional carcinomas. Immunohistologic studies revealed uniform reactivity for keratin in PASCC of the lung. Two cases also stained positively for epithelial membrane antigen and vimentin, but all of them were negative for von Willebrand factor, CD31, CD34, and binding of Ulex europaeus I lectin. Electron microscopic examination of the three cases showed the presence of intercellular desmosomes and cytoplasmic tonofibrils. The example of true pleuropulmonary angiosarcoma demonstrated an endothelial immunophenotype. Two of three patients with pulmonary PASCC survived for at least 20 months, whereas the individual with true angiosarcoma died within 3 months. Together with prior reports on such lesions, these data suggest that angiosarcoma-like carcinomas of the lung differ pathologically and behaviorally from primary pulmonary endothelial malignancies.

Inflammatory sarcomatoid carcinoma of the lung: report of three cases and clinicopathologic comparison with inflammatory pseudotumors in adult patients.

Although the capacity for some pulmonary carcinomas to mimic sarcomas is well recognized, their potential resemblance to selected benign lesions of the lung is currently underappreciated. The authors herein report three examples of sarcomatoid bronchogenic carcinoma with a deceptively bland appearance and an investment of reactive inflammation, such that they resembled pseudotumors histologically. These lesions occurred in two men and one woman who were 44, 61, and 63 years old, respectively, at diagnosis. All patients presented with a productive cough, hemoptysis, or chest pain. Their pulmonary masses were irregularly marginated radiographically, and ranged in size from 2.5 to 5.5 cm. Two were treated with lobectomy, and one underwent a wedge excision, followed by radiotherapy to the thorax. Despite these measures, each patient with inflammatory sarcomatoid carcinoma (ISC) died of disease or is likely to do so. Microscopically, ISCs were composed of uniform spindle cell proliferations with only modest nuclear pleomorphism, limited mitotic activity, and an arrangement in fascicles, storiform configurations, or haphazard arrays. Lymphocytes and plasma cells were interspersed throughout each of them, and keloidal stromal collagen was apparent internally in two examples. Two of the neoplasms also invaded pulmonary blood vessels or bronchi. A comparison group of 10 adults with pulmonary inflammatory pseudotumors (IPs) of the fibrous histiocytoma type shared several clinical attributes with ISC and showed closely similar histological features, except that the IPs lacked mitoses and invasiveness, and contained xanthoma cells or multinucleated elements in some cases in this series. Immunohistochemical analyses showed consistent dissimilarities between ISC and IP; keratin and epithelial membrane antigen were present in ISC but not IP, whereas actin was observed only in the proliferating spindle cells of IP. In summary, the potential clinicopathologic overlap between ISC and IP suggests that caution should be exercised in the separation of these two lesions. In particular, it is unwise to attempt to make this distinction in an intraoperative frozen section setting.

Biphasic and monophasic sarcomatoid carcinomas of the lung. A reappraisal of 'carcinosarcomas' and 'spindle-cell carcinomas'.

To address the premise that pulmonary "carcinosarcomas" and spindle-cell carcinomas are part of a single clinicopathologic continuum, the authors studied 21 examples of such lesions as defined by World Health Organization criteria. Two biphasic tumors demonstrated an admixture of overt carcinoma with other foci showing partial rhabdomyogenic differentiation; 15 others were histologically similar but lacked "heterologous" sarcoma-like elements; and four lesions were monophasic spindle-cell sarcomatoid carcinomas. One of the latter also contained rhabdomyosarcoma-like areas by light microscopy. Sarcomatoid components were reactive for keratin and/or epithelial membrane antigen (EMA) in 18/21 cases. In addition, desmin and muscle-specific actin were co-detected in the same spindle cells that were keratin-positive in 4 tumors, 3 of which were those with partially myogenic histologic features. Vimentin was present in keratin- or EMA-reactive sarcomatoid cells in 12 neoplasms, and all cases were labeled with an antibody to collagen type IV. Survival was poor in this group of patients; only 1 was alive at last contact. These data support the contention that "carcinosarcoma" of the lung is part of a spectrum with "spindle-cell carcinoma." It is proposed that the terms "biphasic sarcomatoid carcinoma" and "monophasic sarcomatoid carcinoma" are more apt descriptors for such tumors.

Angiomatoid carcinoma and 'angiosarcoma' of the thyroid gland. A spectrum of endothelial differentiation.

The existence of angiosarcoma of the thyroid gland and its relation to angiomatoid carcinoma have been debated. The authors reviewed eight angiomatoid thyroid neoplasms. Controls consisted of six sarcomatoid thyroid carcinomas without angiomatoid features and an angiosarcoma metastatic to the thyroid gland. All eight angiomatoid neoplasms consisted of epithelioid cells with prominent eosinophilic cytoplasm lining vascularlike spaces. All eight expressed vimentin. Four tumors were predominantly angiosarcomalike neoplasms, based on staining for factor VIII-related antigen (three of four), CD31 (four of four), CD34 (one of four), and Ulex europaeus I lectin (four of four); they lacked epithelial markers other than cytokeratin (two of four). Four tumors were designated as angiomatoid carcinomas, based on staining for multiple epithelial markers: cytokeratin (four of four), epithelial membrane antigen (three of four), thyroglobulin (three of four). Three angiomatoid carcinomas also expressed or labeled with one or more vascular markers: CD34 (one of four), CD31 (two of four), Ulex europaeus I lectin (one of four), factor VIII-related antigen (one of four). The metastatic angiosarcoma to the thyroid gland labeled for factor VIII-related antigen, vimentin, CD31, and with Ulex europaeus I lectin. It did not express CD34. The six sarcomatoid carcinomas without angiomatoid features stained for cytokeratin (four of six), epithelial membrane antigen (one of six), and vimentin (six of six). None labeled for thyroglobulin, factor VIII-related antigen, CD31, CD34, or with Ulex europaeus I lectin. Angiomatoid carcinomas of the thyroid gland exhibit both epithelial and endothelial features. "Angiosarcoma" may represent the extreme in this spectrum of endothelial differentiation. All tumors behaved in a similar clinical fashion characterized by persistent local disease, widespread metastases and poor prognosis.

Gastric carcinoma with osteoclast-like giant cells. Report of four cases.

Four cases of gastric carcinoma are described that are associated with an osteoclast-like giant cell (OGC) stromal component. The patients were all middle-aged men (range 53-63 years). Microscopically, the tumors were characterized by a bland cytologic appearance, and an either solid or cribriform pattern. Osteoclast-like giant cells were found adjacent to, or intimately intermixed with, the neoplastic cells in the primary gastric masses and in the lymph nodal metastases and were often associated with lymphocytes, histiocytes, and desmoplastic stroma. By immunohistochemistry, mononuclear cells and OGCs showed diffuse positivity for alpha-1-antichymotrypsin, alpha-1-antitrypsin, and CD68. Neoplastic cells that were positive for keratin and CEA, also showed reactivity for vimentin and the latent membrane protein of Epstein-Barr virus in one case. At follow-up, three patients had died at 13, 15, and 24 months after diagnosis, and one is still alive, without evidence of disease, after 120 months. This report describes a novel variant of gastric carcinoma with distinctive and histologic features.

Primary rhabdomyosarcoma of the ileum in an adult.

We report a case of primary rhabdomyosarcoma of the ileum occurring in a 45-year-old man. The rhabdomyoblastic nature was immunohistochemically confirmed by positivity with anti-myoglobin and anti-striated actin antisera. We discuss the differential diagnosis with similar tumors. To our knowledge, ileal rhabdomyosarcomas have not been previously reported in adults.

Sarcomatoid neoplasms of the respiratory tract.

Sarcomatoid carcinomas (SCAs) of the respiratory tract are uncommon neoplasms of adults, most of whom are men in late middle-age who have a long history of tobacco usage. These tumors may be observed in the paranasal sinuses, nose, naso-oropharynx, larynx, trachea, central bronchi, or peripheral lung parenchyma. They may assume a polypoid configuration, with projection into luminal spaces, or show an infiltrative growth pattern like that of typical high-grade carcinoma. Histologically, both biphasic and monophasic variants of SCAs are recognized. The former include tumors with foci of overt carcinoma admixed with areas of divergent differentiation into "committed" mesenchymal tissues, such lesions have usually been termed "carcinosarcomas" in the past. On the other hand, monophasic SCAs lack obviously epithelial foci on light microscopy. Ultrastructural and immunohistological studies support the notion that SCA represents a continuum that embraces carcinosarcomas and spindle-cell carcinomas, all of which are basically epithelial neoplasms. Tumor behavior is site-dependent; SCAs of the nose, sinuses, pharynx, and lungs usually pursue an aggressive course, whereas histologically similar lesions in the larynx are usually found at an earlier stage and, therefore, are associated with a better prognosis.

Oxyphilic proliferations of the respiratory tract and paranasal sinuses.

Neoplasms of the upper respiratory comprised primarily of eosinophilic cells are, in general, rare, and they include a diverse group of lesions. Low-grade oncocytic neuroendocrine neoplasms (so-called oncocytic carcinoids) can be encountered in several locations throughout the respiratory tract. The oncocytoma and related entities, lesions that presumably arise from minor gland tissue, can likewise be seen from the nasal cavity to the lung; differences in clinical significance may relate to the location of such lesions, and are discussed herein. Granular cell tumor is another entity that can involve both the upper respiratory tract and lungs, and specific features of this lesion in different anatomic sites are highlighted. The oncocytic variant of Schneiderian papilloma is an important nasal lesion to recognize, because of important therapeutic and prognostic implications of that diagnosis. Finally, unique oncocytic variants of glomus tumor and pulmonary alveolar adenoma are discussed, as well as eosinophilic varieties of pulmonary carcinomas and mesotheliomas.

Neoplasms composed of eosinophilic polygonal cells: an overview with consideration of different cytomorphologic patterns.

Neoplasms that are composed of large eosinophilic cells present a distinctive and challenging image to the diagnostic pathologist. Potential lineages for such lesions include several types of epithelial tissue, as well as melanocytic, lymphoid, germ-cell, and mesenchymal proliferations. Attention to morphological details represents a useful first step in the further evaluation of eosinophilic large-cell tumors. These tumors can usually be segregated into one of four cytological categories, including granular eosinophilic (oncocytic and oncocytoid), fibrillary eosinophilic (myoid), globular eosinophilic (rhabdoid and gemistocytic), and diffusely eosinophilic (hyaline-cell and deeply eosinophilic, not further specified). Correlation with anatomic locations, nuances of clinical presentation, and results of electron microscopic and immunohistochemical studies provides additional data that can be used for a specific interpretation, especially if it is applied in an algorithmic fashion.

Hemangiopericytoma: histopathological pattern or clinicopathologic entity?

The tumor designated by Stout and Murray as "hemangiopericytoma" (HPC) more than 50 years ago continues to represent a source of uncertainty and disagreement among pathologists. In particular, questions exist regarding the synonymity of a hemangiopericytomatous growth pattern--defined by a monomorphic population of compact polygonal or bluntly fusiform cells and a branching stromal vascular pattern with a "staghorn" configuration--and the presence of a reproducible biological entity. It has been shown repeatedly that these same histologic features may be observed at least focally in a diversity of neoplasms, including "true" hemangiopericytomas, synovial sarcomas, mesenchymal chondrosarcomas, infantile fibrosarcomas, malignant fibrous histiocytomas, malignant peripheral nerve sheath tumors, leiomyosarcomas, endometrial stromal sarcomas, solitary fibrous tumors, myofibromas, malignant mesotheliomas, thymomas, sarcomatoid carcinomas, malignant melanomas, and "phosphaturic mesenchymal tumors." Despite their potential sharing of the microscopic attributes in question, such neoplasms have individualistic clinical features and can also be distinguished from one another by specialized pathologic analyses. HPC is "defined" in that context by reactivity for vimentin, with or without CD34 and CD57, but it lacks other immunodeterminants of epithelial, neural, and myogenous differentiation. Paradoxically, this phenotype is indeed associated with the presence of myogenous-type cytoplasmic filaments in ultrastructural evaluations of HPC. Other lesions that may resemble "true" HPC--but which possess dissimilar subcellular and clinical characteristics--include solitary fibrous tumors, hemangiopericytomalike tumors of the sinonasal tract, and "infantile (congenital) hemangiopericytomas." Such observations suggest that the hemangiopericytoma is both a pathologic entity and a morphological pattern, and they emphasize the utility of adjuvant pathologic studies in this diagnostic context.

Angiosarcoma-like neoplasms of epithelial organs: true endothelial tumors or variants of carcinoma?

Past experience has shown the existence of tumors in various viscera that assume growth patterns that are usually associated with angiosarcomas of skin and soft tissue. The lineage of differentiation pursued by the former of these proliferations has been the subject of controversy, with some investigators concluding that "angiosarcomatoid" neoplasms of solid organs were, in actuality, variants of high-grade carcinomas. The latter statement does appear to have partial validity, inasmuch as immunohistologic, ultrastructural, and clinical data on "pseudovascular carcinomas" do support their basic identity with high-grade epithelial malignancies of the breasts, skin, and lungs. Those lesions show uniform reactivity for keratin and epithelial membrane antigen, but they fail to express von Willebrand factor, CD31, or CD34, which are regarded as endothelial determinants. On the other hand, however, angiomatoid neoplasms of the thyroid gland are more complex; some represent indisputable carcinomas, others manifest seemingly "pure" mesenchymal phenotypes, and still others display a mixture of epithelial and endothelial phenotypes at ultrastructural and protein-chemical levels of specialized investigation. At present, it must be acknowledged that the distinction between angiomatoid thyroid carcinomas and "true" thyroid angiosarcomas is an academic one, because the prognoses and treatments for these lesions are essentially identical.

Clear cell tumors of unknown nature and origin: a systematic approach to diagnosis.

Not infrequently, surgical pathologists encounter malignant neoplasms composed of clear cells, the sources and natures of which are indeterminate on the basis of conventional morphological study. In this context, it is frustrating that tumors of completely dissimilar lineage can show strikingly similar microscopic appearances; moreover, anatomic location provides few if any definitive clues to the likely final diagnosis in many cases of clear cell neoplasia. Because of these factors, it is necessary to systematically pursue the same approach to the pathological assessment of clear cell tumors, routinely considering not only clinical and radiologic details but also the possible application of immunohistology, electron microscopy, and cytogenetics. This review provides algorithmic schemes by which such techniques can be applied, as well as their potential drawbacks and limitations.

Clear cell neoplasms of the endocrine system and thymus.

Clear cell tumors of the endocrine system and thymus are rare lesions with which surgical pathologists have only infrequent contact. As a result, these neoplasms may be misinterpreted and incorrectly classified. This review considers the histological, immunohistochemical, and ultrastructural features of clear cell pituitary adenomas, parathyroid tumors, pancreatic endocrine neoplasms, adrenocortical proliferations, and thymic malignancies. Emphasis is placed throughout on differential diagnosis with microscopically-similar lesions. Clear cell endocrine tumors and thymic lesions manifest a variety of potential lineages, including examples with epithelial, neural, germ cell, and lymphoid differentiation. Because of the wide differences in behavior and recommended treatment in this group, accuracy in diagnosis is essential.

Clear cell tumors of the alimentary tract and abdominal cavity.

Clear cell neoplasms of the abdominal organs are represented by a variety of epithelial and mesenchymal neoplasms, of varying malignant potential. Several varieties of clear cell carcinomas, including those with tubulopapillary, hepatoid, colloid, or neuroendocrine features, have been described, as well as several benign epithelial neoplasms. These epithelial tumors have been reported in the gastrointestinal hollow viscera, as well as the liver, pancreas, and biliary tract. A second major consideration is the mesenchymal-derived gastrointestinal stromal tumors, which also may feature clear cells, and comprise a spectrum of biological behavior. Miscellaneous lesions include clear cell variants of melanoma and mesothelioma. This review includes histological details of the various entities, as well as important histochemical, immunohistological, and ultrastructural features. Pertinent differential diagnostic points are stressed, including distinction of the primary clear lesions from relevant metastatic neoplasms.

Lymphoepithelioma-like carcinoma of the lung. Two cases diagnosed in Caucasian patients.

Lymphoepithelioma-like carcinoma is a non-nasopharyngeal undifferentiated carcinoma with prominent lymphoid infiltration. Ten cases arising in the lung have been reported so far; seven cases were diagnosed in Orientals, with the Epstein-Barr virus (EBV) genome demonstrated in neoplastic cells by in situ hybridization; the remaining three cases affected Caucasian patients and showed no evidence of hybridized viral genome. The present study describes two additional cases of lymphoepithelioma-like carcinoma of the lung in Caucasians, with reference to the differential diagnosis versus other thoracomediastinal malignancies. The neoplastic nuclei, blast-like in appearance, together with the immunohistochemical profile of the neoplastic cells (positivity for cytokeratins, and negativity for CD antigens, S100 protein, placental alkaline phosphatase, and neuroendocrine markers) represent the basic pathologic features of a lymphoepithelioma-like carcinoma and allow its recognition even on small bioptic fragments, in which the typical biphasic, Regaud-like morphology might be inapparent. In accordance with the previously reported cases of pulmonary lymphoepithelioma-like carcinoma in Caucasian patients, the present study found no evidence of the Epstein-Barr virus genome in neoplastic cells with in situ hybridization.